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  • 1. Abedini, Sadollah
    et al.
    Holme, Ingar
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jardine, Alan
    Cole, Ed
    Maes, Bart
    Holdaas, Hallvard
    Cerebrovascular events in renal transplant recipients2009Ingår i: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 87, nr 1, s. 112-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The incidence of stroke and risk factors for different subtypes of cerebrovascular (CBV) events in renal transplant recipients have not been examined in any large prospective controlled trial. METHODS: The Assessment of Lescol in Renal Transplantation was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg) daily on cardiovascular, and renal outcomes in renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study. We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years. RESULTS: The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm. A total of 184 (8.8%, 95% confidence interval 4.6-12.9) of 2102 patients experienced a CBV event during follow-up, corresponding to an incidence of 1.3% CBV event per year. The mortality for patients experiencing a hemorrhagic stroke was 48% (13 of 27), whereas the mortality for ischemic strokes was 6.0% (8 of 133). Diabetes mellitus, previous CBV event, age, and serum creatinine were independent risk factors for cerebral ischemic events. The risk of a hemorrhagic cerebral event was increased by diabetes mellitus, polycystic kidney disease, left ventricular hypertrophy, and systolic blood pressure. INTERPRETATION: Risk factors for CBV events in renal transplant recipients differ according to subtype.

  • 2. Abedini, Sadollah
    et al.
    Holme, Ingar
    März, Winfried
    Weihrauch, Gisela
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jardine, Alan
    Cole, Edward
    Maes, Bart
    Neumayer, Hans-Hellmut
    Grönhagen-Riska, Carola
    Ambühl, Patrice
    Holdaas, Halvard
    Inflammation in renal transplantation2009Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 4, nr 7, s. 1246-1254Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated. RESULTS: The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049). CONCLUSIONS: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.

  • 3. Abedini, Sadollah
    et al.
    Meinitzer, Andreas
    Holme, Ingar
    März, Winfried
    Weihrauch, Gisela
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jardine, Alan
    Holdaas, Halvard
    Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients2010Ingår i: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 77, nr 1, s. 44-50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients.

  • 4.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Brekkan, Einar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Lönnemark, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Periprocedural outcome after laparoscopic partial nephrectomy versus radiofrequency ablation for T1 renal tumors:: A modified R.E.N.A.L nephrometry score adjusted comparison.2018Ingår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, nr 2, s. 260-268Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Comparable oncological outcomes have been seen after surgical nephrectomy and thermal ablation of renal tumors recently. However, periprocedural outcome needs to be assessed for aiding treatment decision.

    Purpose: To compare efficacy rates and periprocedural outcome (technical success, session time, hospitalization time, and complications) after renal tumor treatment with laparoscopic partial nephrectomy (LPN) or radiofrequency ablation (RFA).

    Material and Methods: The initial experience with 49 (treated with LPN) and 84 (treated with RFA) consecutive patients for a single renal tumor (diameter ≤ 5 cm, limited to the kidney) during 2007-2014 was evaluated. Patient and tumor characteristics, efficacy rates, and periprocedural outcome were collected retrospectively. The stratified Mantel Haenzel and Van Elteren tests, adjusted for tumor complexity (with the modified R.E.N.A.L nephrometry score [m-RNS]), were used to assess differences in treatment outcomes.

    Results: Primary efficacy rate was 98% for LPN and 85.7% for RFA; secondary efficacy rate was 93.9% for LPN and 95.2% for RFA; and technical success rate was 87.8% for LPN and 100% for RFA. Median session (m-RNS adjusted P < 0.001; LPN 215 min, RFA 137 min) and median hospitalization time were longer after LPN (m-RNS adjusted P < 0.001; LPN 5 days, RFA 2 days). Side effects were uncommon (LPN 2%, RFA 4.8%). Complications were more frequent after LPN (m-RNS adjusted P < 0.001; LPN 42.9%, RFA 10.7%).

    Conclusion: Both methods achieved equivalent secondary efficacy rates. RFA included several treatment sessions, but session and hospitalization times were shorter, and complications were less frequent than for LPN. The differences remained after adjustment for renal tumor complexity.

  • 5.
    Adamo, Hanibal
    et al.
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Hammarsten, Peter
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Hägglöf, Christina
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Scherdin, Tove Dahl
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Egevad, Lars
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bergström, Sofia Halin
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Bergh, Anders
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome2019Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, nr 5, s. 435-445Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

    Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

    Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

  • 6.
    Adamo, Hanibal Hani
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Hägglöf, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Scherdin, Tove Dahl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Egevad, Lars
    Stattin, Paer
    Halin Bergström, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome2019Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, nr 5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

    Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

    Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

  • 7. Ahlén Bergman, Emma
    et al.
    Hartana, Ciputra Adijaya
    Johansson, Markus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden..
    Linton, Ludvig B
    Berglund, Sofia
    Hyllienmark, Martin
    Lundgren, Christian
    Holmström, Benny
    Palmqvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgery, Urology Section, Östersund County Hospital, Östersund, Sweden.
    Hansson, Johan
    Alamdari, Farhood
    Huge, Ylva
    Aljabery, Firas
    Riklund, Katrine
    Winerdal, Malin E
    Krantz, David
    Zirakzadeh, Ali A .
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Marits, Per
    Sjöholm, Louise K
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Winqvist, Ola
    Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients.2018Ingår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, artikel-id 102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.

    RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.

    CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.

  • 8.
    Ajalloueian, Fatemeh
    et al.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Lemon, Greg
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Chronakis, Ioannis S.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Fossum, Magdalena
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden; Karolinska Inst, Ctr Mol Med, CMM 02, Stockholm, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Paediat Surg, Sect Urol, Stockholm, Sweden.
    Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder2018Ingår i: Nature reviews. Urology, ISSN 1759-4812, E-ISSN 1759-4820, Vol. 15, nr 3, s. 155-174Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.

  • 9.
    Akre, Olof
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Garmo, Hans
    Regional Oncological Center, Uppsala, Sweden.
    Adolfsson, Jan
    Oncological Center, CLINTEC Department, Karolinska Institutet, Stockholm, Sweden.
    Lambe, Mats
    Oncological Center, CLINTEC Department, andDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bratt, Ola
    Department of Urology, Helsingborg Hospital, Lund University, Sweden.
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden2011Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 3, s. 554-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment.

    Objective

    To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent.

    Design, setting, and participants

    We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis.

    Measurements

    We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics.

    Results and limitations

    The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA < 4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status.

    Conclusions

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 10. Akre, Olof
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Lambe, Mats
    Bratt, Ola
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Mortality among men with locally advanced prostate cancer managed with noncurative intent: a nationwide study in PCBaSe Sweden2011Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 3, s. 554-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 11.
    Al Ahmadi, Ibrahim
    et al.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Abasi, Amira
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Syed, Raza
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Broering, Dieter-C.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Biglarnia, Ali-Reza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Initial Experience From Implementation of Hand-Assisted Retroperitoneoscopic Live Donor Nephrectomy in Saudi Arabia2013Ingår i: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, nr 2, s. S58-S59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Donor risks and morbidity are consequences of the invasiveness of donor nephrectomy procedure. The flank incision is currently the default donor nephrectomy procedure at the King Faisal Hospital in Saudi Arabia. In order to minimize the surgical-related trauma, we are implementing the hand-assisted retroperitoneoscopic live donor nephrectomy (HARS), which previously has been shown to promote donor safety. Here, we present our initial experience with this procedure. Material and Methods: The HARS technique was implemented at our center in 2010. We present a survey of our data regarding operative characteristics as well as donor/recipient outcome. Given the small number of cases, data are presented as median with range. Results: Between 2010 and 2013, 18 left -sided HARS nephrectomy procedures were performed. The median donor age and BMI were 26.5 (18-43) and 24.1 (18.7-30.7), respectively. The median hospitalization was 4 days (3-5). One donor presented wound seroma in the pfannenstiell incision with no need for intervention. Another donor presented unspecific thoracoabdominal pain on postoperative day 2. No intra-and postoperative bleeding was observed. The median creatinine at the current follow-up was 90 mu mol/L with 100% graft survival. Conclusion: HARS is a feasible and safe technique. However, for implementation of HARS as the default donor nephrectomy procedure more practice is needed.

  • 12. Albiges, Laurence
    et al.
    Powles, Tom
    Staehlerr, Michael
    Bensalan, Karim
    Giles, Rachel H.
    Horag, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Volpe, Alessandro
    Abu-Ghanem, Yasmin
    Dabestani, Saeed
    Fernndez-Pello, Sergio
    Hofmann, Fabian
    Kuusk, Teele
    Tahbaz, Rana
    Bex, Axel
    Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 2, s. 151-156Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies.

    Patient summary: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naive). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria.

  • 13.
    Aldenbratt, Annika
    et al.
    Sahlgrens Univ Hosp, Dept Nephrol, Gothenburg, Sweden.
    Lindberg, Christopher
    Sahlgrens Univ Hosp, Dept Neurol, Neuromuscular Ctr, Gothenburg, Sweden.
    Svensson, Maria K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Reduced renal function in patients with Myotonic Dystrophy type 1 and the association to CTG expansion and other potential risk factors for chronic kidney disease2017Ingår i: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, nr 11, s. 1038-1042Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Myotonic dystrophy type 1 (DM1) affects several organs. Disease severity and age at onset are correlated to the CTG repeat expansion. The aim of this study was to assess renal function and the association to numbers of CTG repeat expansion in patients with DM1. Ninety-eight patients with DM1 were included. Glomerular filtration rate (measured GFR) was measured using iohexol clearance. Data on CTG repeats were available in 83/98 (85%) patients. The overall mGFR was 74 (16) ml/min/1.73 m(2) (range 38-134). Sixty-four patients (69%) had a mild and sixteen patients (17%) a moderate decrease in renal function (mGFR 60-89 and 30-59 ml/min/1.73 m(2), respectively). No correlations were found between CTG repeats and mGFR (r = 0.10, p = 0.4) or between CTG repeats and serum cystatin C (r = 0.12, p = 0.29). CTG repeats was positively correlated to creatinine-based estimates of GFR (eGFR) (modified diet in renal disease r = 0.49, p < 0.001, CKD-EPI creatinine equation; r = 0.50, p < 0.001), but analyses using Structural Equation Modeling showed no correlation. The correlation was explained by an indirect effect via serum creatinine and skeletal muscle mass index. In conclusion, patients with DM1 seem to have a slight decrease in renal function but there is no association between renal function and the number of CTG repeats, a marker of disease severity.

  • 14.
    Alderson, Helen V.
    et al.
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Ritchie, James P
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Middleton, Rachel
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institute, Stockholm, Sweden..
    Kalra, Philip A
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    FGF-23 and Osteoprotegerin but not Fetuin-A are associated with death and enhance risk prediction in non-dialysis chronic kidney disease stages 3-52016Ingår i: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 21, nr 7, s. 566-573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: Numerous biomarkers have been shown to associate with clinical endpoints in chronic kidney disease (CKD). There is limited evidence whether biomarkers improve risk prediction in relation to clinical outcomes. Our study investigates whether a small suite of key chronic kidney disease-mineral and bone disorder biomarkers could be used to enhance risk assessment in CKD.

    METHODS: Fetuin-A, fibroblast growth factor-23 and osteoprotegerin were measured on baseline plasma samples from 463 patients recruited to the Chronic Renal Insufficiency Standards Implementation Study. The biomarkers were analysed in relation to progression to end stage kidney disease, death and major cardiovascular events.

    RESULTS: Over a median follow up of 46 months (interquartile range 21-69), fibroblast growth factor-23 was associated with risk for renal replacement therapy (hazard ratio (HR) 1.35, P = 0.05, 95% confidence interval (CI) 1.001-1.820), cardiovascular events (HR 1.74 P < 0.001, 95% CI 1.303-1.305) and death (HR 1.4 P = 0.005, 95% CI 1.109-1.767). Osteoprotegerin was associated with risk for death (HR 1.06, P = 0.03, 95% CI 1.006-1.117). There was no clear association between Fetuin-A and any of the clinical endpoints. The addition of biomarkers to risk models led to marginal improvement in model discrimination and reclassification.

    CONCLUSION: Biomarkers are often associated with clinical endpoints, and we observed such associations in our study of patients with advanced CKD. However, the markers analysed in our study were of limited benefit in improving the prediction of these outcomes. Any extra information biomarkers may provide to improve risk prediction in clinical practice needs to be carefully balanced against the potential cost of these tools.

  • 15.
    Alexeyev, Oleg
    et al.
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Olsson, Jan
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Elgh, Fredrik
    Örebro universitet, Hälsoakademin.
    Is There Evidence for a Role of Propionibacterium acnes in Prostatic Disease?2009Ingår i: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 73, nr 2, s. 220-224Artikel, forskningsöversikt (Refereegranskat)
  • 16.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.

    Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.

    Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.

    Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

  • 17.
    Aljabery, Firas
    et al.
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Lindblom, Gunnar
    Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Skoog, Susann
    Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Shabo, Ivan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015Ingår i: BMC urology, ISSN 1471-2490, Vol. 15, nr 1, s. 87-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

  • 18.
    Al-Mashhadi, Ammar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Läckgren, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlstrom, Mattias
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Changes of arterial pressure following relief of obstruction in adults with hydronephrosis2018Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, nr 4, s. 216-224Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.

    Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.

    Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.

    Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.

  • 19.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Checa, Antonio
    Karolinska Institute.
    Wåhlin, Nils
    Karolinska Institute.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Fossum, Magdalena
    Karolinska institute.
    Wheelock, Craig E.
    Karolinska Institute.
    Karanikas, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlström, Mattias
    Karolinska Institute.
    Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children2018Ingår i: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 33, nr 4, s. 639-649Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.

    Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.

    Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).

    Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.

    Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction 

  • 20.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Karanikas, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlstrom, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Wahlin, Nils
    Department of Pediatric Surgery, Astrid Lindgren Hospital, Karolinska Institutet, Stockholm, Sweden.
    Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis2015Ingår i: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 11, nr 2, s. 91.e1-91.e6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Patients and methods Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. Results As shown in the summary figure, postoperative systolic (103 +/- 2 mmHg) and diastolic (62 +/- 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 +/- 4 and 69 +/- 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Discussion Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. Conclusion This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.

  • 21. Anand, Aseem
    et al.
    Morris, Michael J.
    Larson, Steven M.
    Minarik, David
    Josefsson, Andreas
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Helgstrand, John T.
    Oturai, Peter S.
    Edenbrandt, Lars
    Røder, Martin Andreas
    Bjartell, Anders
    Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide2016Ingår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 6, artikel-id 23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.

    METHODS: Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall's tau (τ) was used to assess the correlation of BSI with other blood-based biomarkers. Concordance index (C-index) was used to evaluate the discriminating strength of automated BSI in predicting OS.

    RESULTS: Eighty mCRPC patients with baseline bone scans were included in the study. There was a weak correlation of automated BSI with PSA (τ = 0.30), with HgB (τ = -0.17), and with ALP (τ = 0.56). At baseline, the automated BSI was observed to be predictive of OS (C-index 0.72, standard error (SE) 0.03). Adding automated BSI to the blood-based model significantly improved the C-index from 0.67 to 0.72, p = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change alone (C-index 0.73), p = 0.041.

    CONCLUSIONS: The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated with enzalutamide.

  • 22.
    Anderberg, S. B.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Luther, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury2017Ingår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, nr 3, s. 575-590Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram-negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI-AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI-AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI-AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI-AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.

  • 23.
    Andersson, Ellen
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Albertsson, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Holmqvist, Annica
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs2017Ingår i: Clinical Practice, ISSN 2044-9038, E-ISSN 2044-9046, Vol. 14, nr 3, s. 175-182Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.

  • 24.
    Andersson, Gunnel
    et al.
    Örebro universitet, Institutionen för klinisk medicin. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro universitet, Institutionen för klinisk medicin. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Sahlberg-Blom, Eva
    Örebro universitet, Institutionen för vårdvetenskap och omsorg.
    Pettersson, Nicklas
    Department of Public Health, O¨ rebro County Council, O¨ rebro, Sweden.
    Nilsson, Kerstin
    Örebro universitet, Institutionen för klinisk medicin. Centre for Evidence Based Medicine and Assessment of Medical Technology, O¨ rebro, Sweden; Department of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Urinary incontinence - why refraining from treatment?: a population based study2005Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, nr 4, s. 301-307Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate why persons with urinary incontinence (UI) refrain from seeking care and treatment.

    MATERIAL AND METHODS: A population-based study was undertaken in which a public health survey and a specific UI questionnaire were sent to 15 360 randomly selected residents (age 18-79 years) of Orebro County, Sweden. For all persons reporting UI, the expressed wish for treatment or no treatment was analyzed in relation to relevant variables from both inquiry forms using binary logistic regression analysis.

    RESULTS: The response rate was 64.5%. UI was reported by 2194 persons, 1724 of whom comprised the study population. A statistically significant association was found between the degree of UI and a desire for treatment. Persons who did not experience daily leakage and those who did not perceive the leakage as troublesome or having an affect on their daily life mostly stated that they did not desire treatment. Socioeconomic or other health-related factors were not associated with desiring or not desiring treatment for UI.

    CONCLUSIONS: Our results show that it is the perceived severity of UI that determines whether afflicted persons desire treatment or not. Other factors, relating to seeking healthcare in general, were not found to be of importance. Interventions to identify those in need of treatment for UI should primarily be directed towards those with severe symptoms.

  • 25. Andersson, Gustav
    et al.
    Wennersten, Christoffer
    Gaber, Alexander
    Boman, Karolina
    Nodin, Bjorn
    Uhlen, Mathias
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Jirstrom, Karin
    Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts2014Ingår i: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 14, s. 36-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.

  • 26.
    Andersson, Patiyan
    et al.
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Kolaric, Aleksandra
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, nr 5, s. 2030-2034Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 27.
    André, Malin
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Rules of Thumb and Management of Common Infections in General Practice2004Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis deals with problem solving of general practitioners (GPs), which is explored with different methods and from different perspectives. The general aim was to explore and describe rules of thumb and to analyse the management of respiratory and urinary tract infections (RTI and UTI) in general practice in Sweden. The results are based upon focus group interviews concerning rules of thumb and a prospective diagnosis-prescription study concerning the management of patients allocated a diagnosis of RTI or UTI. In addition unpublished data are given from structured telephone interviews concerning specific rules of thumb in acute sinusitis and prevailing cough.

    GPs were able to verbalize their rules of thumb, which could be called tacit knowledge. A specific set of rules of thumb was used for rapid assessment when emergency and psychosocial problems were identified. Somatic problems seemed to be the expected, normal state. In the further consultation the rules of thumb seemed to be used in an act of balance between the individual and the general perspective. There was considerable variation between the rules of thumb of different GPs for patients with acute sinusitis and prevailing cough. In their rules of thumb the GPs seemed to integrate their medical knowledge and practical experience of the consultation. A high number of near-patient antigen tests to probe Streptococcus pyogenes (Strep A tests) and C-reactive protein (CRP) tests were performed in patients, where testing was not recommended. There was only a slight decrease in antibiotic prescribing in patients allocated a diagnosis of RTI examined with CRP in comparison with patients not tested. In general, the GPs in Sweden adhered to current guidelines for antibiotic prescribing. Phenoxymethylpenicillin (PcV) was the preferred antibiotic for most patients allocated a diagnosis of respiratory tract infection.

    In conclusion, the use of rules of thumb might explain why current practices prevail in spite of educational efforts. One way to change practice could be to identify and evaluate rules of thumb used by GPs and disseminate well adapted rules. The use of diagnostic tests in patients with infectious illnesses in general practice needs critical appraisal before introduction as well as continuing surveillance. The use of rules of thumb by GPs might be one explanation for variation in practice and irrational prescribing of antibiotics in patients with infectious conditions.

  • 28.
    Andrén, Ove
    Örebro universitet, Hälsoakademin.
    Natural history and prognostic factors in localized prostate cancer2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects.

    The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden.

    Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer.

    The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment.

    Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.

  • 29.
    Andrén, Ove
    et al.
    Örebro universitet, Institutionen för klinisk medicin.
    Fall, Katja
    Franzén, Lennart
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Rubin, Mark A.
    How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden2006Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, nr 4, s. 1337-1340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment.

    Materials and Methods

    We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death.

    Results

    Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%.

    Conclusions

    Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.

  • 30. Angenete, E
    et al.
    Angerås, U
    Börjesson, Mats
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Åstrandlaboratoriet, Björn Ekbloms forskningsgrupp.
    Ekelund, J
    Gellerstedt, M
    Thorsteinsdottir, T
    Steineck, G
    Haglind, E
    Physical activity before radical prostatectomy reduces sick leave after surgery - results from a prospective, non-randomized controlled clinical trial (LAPPRO).2016Ingår i: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 16, nr 1, artikel-id 50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Studies have reported that early physical rehabilitation after surgical procedures is associated with improved outcome measured as shorter hospital stay and enhanced recovery. The aim of this study was to explore the relationship between the preoperative physical activity level and subsequent postoperative complications, sick-leave and hospital stay after radical prostatectomy for prostate cancer in the setting of the LAPPRO trial (LAParoscopic Prostatectomy Robot Open).

    METHODS: LAPPRO is a prospective controlled trial, comparing robot-assisted laparoscopic and open surgery for localized prostate cancer between 2008 and 2011. 1569 patients aged 64 or less with an occupation were included in this sub-study. The Gleason score was <7 in 52 % of the patients. Demographics and the level of self-assessed preoperative physical activity, length of hospital stay, complications, quality of life, recovery and sick-leave were extracted from clinical record forms and questionnaires. Multivariable logistic regression, with log-link and logit-link functions, was used to adjust for potential confounding variables.

    RESULTS: The patients were divided into four groups based on their level of activity. As the group with lowest engagement of physical activity was found to be significantly different in base line characteristics from the other groups they were excluded from further analysis. Among patients that were physically active preoperativelly (n = 1467) there was no significant difference between the physical activity-groups regarding hospital stay, recovery or complications. However, in the group with the highest self-assessed level of physical activity, 5-7 times per week, 13 % required no sick leave, compared to 6.3 % in the group with a physical activity level of 1-2 times per week only (p < 0.0001).

    CONCLUSIONS: In our study of med operated with radical prostatectomy, a high level of physical activity preoperatively was associated with reduced need for sick leave after radical prostatectomy compared to men with lower physical activity.

    TRIAL REGISTRATION: The trial is registered at the ISCRTN register. ISRCTN06393679 .

  • 31.
    Arthur, R.
    et al.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
    Williams, R.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Malmstrom, H.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum, Stockholm, Sweden.
    Lambe, M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;AstraZeneca, Global Med Dev Med Evidence & Observat Res, Stockholm, Sweden.
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Robinsson, D.
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Jungner, I.
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Van Hemelrijck, M.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study2018Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, nr 11, s. 2254-2262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.

  • 32.
    Asad, Danna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    A prospective evaluation of visual staging by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 33.
    Asklund, Ina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Nyström, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sjöström, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Umefjord, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Samuelsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Mobile app for treatment of stress urinary incontinence: a randomized controlled trial2017Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 36, nr 5, s. 1369-1376Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To evaluate the effect of a mobile app treatment for stress urinary incontinence (SUI) in women.

    METHODS: Randomized controlled trial, conducted 2013-2014 in Sweden. Community-dwelling adult women with ≥1 SUI episode/week recruited through our website and randomized to app treatment (n = 62) or control group (postponed treatment, n = 61). One participant from each group was lost to follow-up. Intervention was the mobile app Tät(®) with a treatment program focused on pelvic floor muscle training (PFMT), and information about SUI and lifestyle factors. Primary outcomes, 3 months after randomization: symptom severity (International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form [ICIQ-UI SF]); and condition-specific quality of life (ICIQ Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]).

    RESULTS: One hundred and twenty-three women were included (mean age 44.7), with moderate/severe SUI (97.5%, 120/123), mean ICIQ-UI SF score 11.1 (SD 2.8) and mean ICIQ-LUTSqol score 34.4 (SD 6.1) at baseline. At follow-up, the app group reported improvements in symptom severity (mean ICIQ-UI SF score reduction: 3.9, 95% confidence interval 3.0-4.7) and condition-specific quality of life (mean ICIQ-LUTSqol score reduction: 4.8, 3.4-6.2) and the groups were significantly different (mean ICIQ-UI SF score difference: -3.2, -4.3to -2.1; mean ICIQ-LUTSqol score difference: -4.6, -7.8 to -1.4). In the app group, 98.4% (60/61) performed PFMT at follow-up, and 41.0% (25/61) performed it daily.

    CONCLUSIONS: The mobile app treatment was effective for women with SUI and yielded clinically relevant improvements. This app may increase access to first-line treatment and adherence to PFMT.

  • 34. Assel, Melissa
    et al.
    Dahlin, Anders
    Ulmert, David
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Lilja, Hans
    Vickers, Andrew J.
    Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 6, s. 961-967Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening. Objective: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time. Design, setting, and participants: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3-10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available. Outcome measurements and statistical analysis: Multivariable logistic regression was used to predict high-grade (Gleason grade group >= 2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age. Results and limitations: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10-1.16; p < 0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28-0.64; p < 0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation. Conclusions: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa. Patient summary: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis.

  • 35.
    Assel, Melissa
    et al.
    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Dahlin, Anders
    Lund University.
    Ulmert, David
    Lund Univerity; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Bergh, Anders
    Umeå University.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umeå University.
    Lilja, Hans
    Lund University; University of Oxford; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Vickers, Andrew J.
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 6, s. 961-967Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening.

    OBJECTIVE: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time.

    DESIGN, SETTING, AND PARTICIPANTS: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3-10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age.

    RESULTS AND LIMITATIONS: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10-1.16; p<0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28-0.64; p<0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation.

    CONCLUSIONS: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa.

    PATIENT SUMMARY: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis.

  • 36. Augsten, Martin
    et al.
    Hägglöf, Christina
    Olsson, Eleonor
    Stolz, Claudia
    Tsagozis, Panagiotis
    Levchenko, Tetyana
    Frederick, Mitchell J.
    Borg, Åke
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Egevad, Lars
    Östman, Arne
    CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth2009Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, nr 9, s. 3414-3419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.

  • 37.
    Austin, Paul F.
    et al.
    Washington Univ, St Louis Childrens Hosp, Div Urol, St Louis, MO 63110 USA..
    Bauer, Stuart B.
    Harvard Univ, Childrens Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA..
    Bower, Wendy
    Skejby Univ Hosp, Pediat Nephrol Sect, Aarhus, Denmark..
    Chase, Janet
    Cabrini Hosp, Childrens Ctr, Melbourne, Vic, Australia..
    Franco, Israel
    New York Med Coll, Valhalla, NY 10595 USA..
    Hoebeke, Piet
    Ghent Univ Hosp, Pediat Urol & Nephrol, Ghent, Belgium..
    Rittig, Soren
    Skejby Univ Hosp, Pediat Nephrol Sect, Aarhus, Denmark..
    Vande Walle, Johan
    Ghent Univ Hosp, Pediat Urol & Nephrol, Ghent, Belgium..
    von Gontard, Alexander
    Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Saarbrucken, Germany..
    Wright, Anne
    St Thomas Hosp, Evelina Childrens Hosp, Pediat, London, England..
    Yang, Stephen S.
    Buddhist Med Fdn, Taipei Tzu Chi Hosp, Div Urol, New Taipei, Taiwan.;Buddhist Tzu Chi Univ, Sch Med, Hualien, Taiwan..
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the standardization committee of the International Children's Continence Society2016Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 35, nr 4, s. 471-481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AimThe impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function. MethodsA variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited. ResultsFollowing a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback. ConclusionsThe present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children.

  • 38. Baigent, C
    et al.
    Blackwell, L
    Emberson, J
    Holland, LE
    Reith, C
    Bhala, N
    Peto, R
    Barnes , EH
    Keech, A
    Simes, J
    Collins, R
    Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials2010Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 376, nr 9753, s. 1670-1681Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy.

    Methods

    We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation.

    Findings

    In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9), even at low LDL cholesterol concentrations.

    Interpretation

    Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%.

    Funding

    UK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation.

  • 39.
    Bandhede, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    The recurrence rate of urinary bladder cancer (TaG3- and carcinoma in situ tumors) in relation to lead times from first documented symptom to the first trans-urethral resection of bladder2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 40.
    Barbour, Sean J.
    et al.
    Univ British Columbia, Div Nephrol, 2775 Laurel St,Fifth Floor, Vancouver, BC V5Z 1M9, Canada;BC Renal, Vancouver, BC, Canada.
    Coppo, Rosanna
    Regina Margherita Childrens Univ Hosp, Turin, Italy.
    Zhang, Hong
    Peking Univ, Inst Nephrol, Beijing, Peoples R China.
    Liu, Zhi-Hong
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China.
    Suzuki, Yusuke
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Matsuzaki, Keiichi
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Katafuchi, Ritsuko
    Natl Fukuoka Higashi Med Ctr, Fukuoka, Fukuoka, Japan.
    Er, Lee
    BC Renal, Vancouver, BC, Canada.
    Espino-Hernandez, Gabriela
    BC Renal, Vancouver, BC, Canada.
    Kim, S. Joseph
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Reich, Heather N.
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Feehally, John
    Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England.
    Cattran, Daniel C.
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Russo, M. L.
    Fdn Ric Molinette, Turin, Italy.
    Troyanov, S.
    Hop Sacre Coeur Montreal, Dept Med, Div Nephrol, Montreal, PQ, Canada;Hop Sacre Coeur Montreal, Dept Med, Div Nephrol, Montreal, PQ, Canada.
    Cook, H. T.
    Imperial Coll, Dept Med, Ctr Complement & Inflammat Res, London, England.
    Roberts, I.
    Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Cellular Pathol, Oxford, England.
    Tesar, V.
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Maixnerova, D.
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Lundberg, S.
    Karolinska Inst, Dept Clin Sci, Nephrol Unit, Stockholm, Sweden.
    Gesualdo, L.
    Univ Bah Aldo Moro, Dept Nephrol Emergency & Organ Transplantat, Foggia, Italy.
    Emma, F.
    Bambino Gesu Pediat Hosp, IRCCS, Dept Pediat Subspecialties, Div Nephrol, Rome, Italy.
    Fuiano, L.
    Bambino Gesu Pediat Hosp, IRCCS, Dept Pediat Subspecialties, Div Nephrol, Rome, Italy.
    Beltrame, G.
    San Giovanni Bosco Hosp, Nephrol & Dialysis Unit, Turin, Italy;Univ Turin, Turin, Italy.
    Rollino, C.
    San Giovanni Bosco Hosp, Nephrol & Dialysis Unit, Turin, Italy;Univ Turin, Turin, Italy.
    Amore, A.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy;Univ Turin, Regina Margherita Childrens Hosp, Nephrol Dialysis & Transplantat Unit, Turin, Italy.
    Camilla, R.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy.
    Peruzzi, L.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy.
    Praga, M.
    Hosp 12 Octubre, Nephrol Unit, Madrid, Spain.
    Feriozzi, S.
    Belcolle Hosp, Nephrol Unit, Viterbo, Italy.
    Polci, R.
    Belcolle Hosp, Nephrol Unit, Viterbo, Italy.
    Segoloni, G.
    Univ Turin, Turin, Italy;Citta Salute & Sci Hosp, Dept Med Sci, Div Nephrol Dialysis & Transplantat, Turin, Italy.
    Colla, L.
    Univ Turin, Turin, Italy;Citta Salute & Sci Hosp, Dept Med Sci, Div Nephrol Dialysis & Transplantat, Turin, Italy.
    Pani, A.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Piras, D.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Angioi, A.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Cancarini, G.
    Spedali Civili Univ Hosp, Nephrol Unit, Brescia, Italy.
    Ravera, S.
    Spedali Civili Univ Hosp, Nephrol Unit, Brescia, Italy.
    Durlik, M.
    Med Univ Warsaw, Dept Transplantat Med Nephrol & Internal Med, Warsaw, Poland.
    Moggia, E.
    Santa Croce Hosp, Nephrol Unit, Cuneo, Italy.
    Ballarin, J.
    Fdn Puigvert, Dept Nephrol, Barcelona, Spain.
    Di Giulio, S.
    San Camillo Forlanini Hosp, Nephrol Unit, Rome, Italy.
    Pugliese, F.
    Policlin Umberto Univ Hosp, Dept Nephrol, Rome, Italy.
    Serriello, I.
    Policlin Umberto Univ Hosp, Dept Nephrol, Rome, Italy.
    Caliskan, Y.
    Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Nephrol, Istanbul, Turkey.
    Sever, M.
    Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Nephrol, Istanbul, Turkey.
    Kilicaslan, I.
    Istanbul Univ, Istanbul Fac Med, Dept Pathol, Istanbul, Turkey.
    Locatelli, F.
    ASST Lecco, Alessandro Manzoni Hosp, Dept Nephrol & Dialysis, Lecce, Italy.
    Del Vecchio, L.
    ASST Lecco, Alessandro Manzoni Hosp, Dept Nephrol & Dialysis, Lecce, Italy.
    Wetzels, J. F. M.
    Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands.
    Peters, H.
    Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands.
    Berg, U.
    Dept Clin Sci Intervent & Technol, Div Pediat, Huddinge, Sweden.
    Carvalho, F.
    Hosp Curry Cabral, Nephrol Unit, Lisbon, Portugal.
    da Costa Ferreira, A. C.
    Hosp Curry Cabral, Nephrol Unit, Lisbon, Portugal.
    Maggio, M.
    Hosp Maggiore Lodi, Nephrol Unit, Lodi, Italy.
    Wiecek, A.
    Silesian Univ Med, Dept Nephrol Endocrinol & Metab Dis, Katowice, Poland.
    Ots-Rosenberg, M.
    Tartu Univ Clin, Nephrol Unit, Tartu, Estonia.
    Magistroni, R.
    Policlin Modena & Reggio Emilia, Dept Nephrol, Modena, Italy.
    Topaloglu, R.
    Hacettepe Univ, Dept Pediat Nephrol & Rheumatol, Ankara, Turkey.
    Bilginer, Y.
    Hacettepe Univ, Dept Pediat Nephrol & Rheumatol, Ankara, Turkey.
    D'Amico, M.
    St Anna Hosp, Nephrol Unit, Como, Italy.
    Stangou, M.
    Aristotle Univ Thessaloniki, Hippokrat Gen Hosp, Dept Nephrol, Thessaloniki, Greece.
    Giacchino, F.
    Ivrea Hosp, Nephrol Unit, Ivrea, Italy.
    Goumenos, D.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Kalliakmani, P.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Gerolymos, M.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Galesic, K.
    Univ Hosp Dubrava, Dept Nephrol, Zagreb, Croatia.
    Geddes, C.
    Western Infirm Glasgow, Renal Unit, Glasgow, Lanark, Scotland;Western Infirm & Associated Hosp, Renal Unit, Glasgow, Lanark, Scotland.
    Siamopoulos, K.
    Univ Ioannina, Med Sch, Nephrol Unit, Ioannina, Greece.
    Balafa, O.
    Univ Ioannina, Med Sch, Nephrol Unit, Ioannina, Greece.
    Galliani, M.
    S Pertini Hosp, Nephrol Unit, Rome, Italy.
    Stratta, P.
    Piemonte Orientale Univ, Maggiore Carita Hosp, Dept Nephrol, Novara, Italy.
    Quaglia, M.
    Piemonte Orientale Univ, Maggiore Carita Hosp, Dept Nephrol, Novara, Italy.
    Bergia, R.
    Infermi Hosp, Nephrol Unit, Biella, Italy.
    Cravero, R.
    Infermi Hosp, Nephrol Unit, Biella, Italy.
    Salvadori, M.
    Careggi Hosp, Dept Nephrol, Florence, Italy.
    Cirami, L.
    Careggi Hosp, Dept Nephrol, Florence, Italy.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Smerud, Hilde Kloster
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Ferrario, F.
    San Gerardo Hosp, Nephropathol Unit, Monza, Italy;San Gerardo Hosp, Nephropathol Unit, Monza, Italy;San Carlo Borromeo Hosp, Renal Immunopathol Ctr, Milan, Italy.
    Stellato, T.
    San Gerardo Hosp, Nephropathol Unit, Monza, Italy.
    Egido, J.
    Fdn Jimenez Diaz, Dept Nephrol, Madrid, Spain.
    Martin, C.
    Fdn Jimenez Diaz, Dept Nephrol, Madrid, Spain.
    Floege, J.
    Univ Aachen, Med Klin 2, Nephrol & Immunol, Aachen, Germany.
    Eitner, F.
    Univ Aachen, Med Klin 2, Nephrol & Immunol, Aachen, Germany.
    Lupo, A.
    Univ Verona, Dept Nephrol, Verona, Italy.
    Bernich, P.
    Univ Verona, Dept Nephrol, Verona, Italy.
    Mene, R.
    S Andrea Hosp, Dept Nephrol, Rome, Italy.
    Morosetti, M.
    Grassi Hosp, Nephrol Unit, Ostia, Italy.
    van Kooten, C.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Rabelink, T.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Reinders, M. E. J.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Boria Grinyo, J. M.
    Bellvitge Hosp, Dept Nephrol, Barcelona, Spain.
    Cusinato, S.
    Borgomanero Hosp, Nephrol Unit, Borgomanero, Italy.
    Benozzi, L.
    Borgomanero Hosp, Nephrol Unit, Borgomanero, Italy.
    Savoldi, S.
    Civile Hosp, Nephrol Unit, Cirie, Italy.
    Licata, C.
    Civile Hosp, Nephrol Unit, Cirie, Italy.
    Mizerska-Wasiak, M.
    Med Univ Warsaw, Dept Pediat, Warsaw, Poland.
    Martina, G.
    Chivasso Hosp, Nephrol Unit, Chivasso, Italy.
    Messuerotti, A.
    Chivasso Hosp, Nephrol Unit, Chivasso, Italy.
    Dal Canton, A.
    San Matteo Hosp, Nephrol Unit, Pavia, Italy.
    Esposito, C.
    Maugeri Fdn, Nephrol Unit, Pavia, Italy.
    Migotto, C.
    Maugeri Fdn, Nephrol Unit, Pavia, Italy.
    Triolo, G.
    Nephrol Unit CTO, Turin, Italy.
    Mariano, F.
    Nephrol Unit CTO, Turin, Italy.
    Pozzi, C.
    Bassini Hosp, Nephrol Unit, Cinisello Balsamo, Italy.
    Boero, R.
    Martini Hosp, Nephrol Unit, Turin, Italy.
    Bellur, S.
    Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Cellular Pathol, Oxford, England.
    Mazzucco, G.
    Univ Turin, Pathol Dept, Turin, Italy.
    Giannakakis, C.
    Sapienza Univ, Pathol Dept, Rome, Italy.
    Honsova, E.
    Inst Clin & Expt Med, Dept Clin & Transplant Pathol, Prague, Czech Republic.
    Sundelin, B.
    Karolinska Univ Hosp, Karolinska Inst, Dept Pathol & Cytol, Stockholm, Sweden.
    Di Palma, A. M.
    Aldo Moro Univ, Nephrol Unit, Foggia, Italy.
    Gutierrez, E.
    Univ Autonoma Madrid, Fdn Jimenez Diaz, Fdn Inst Invest Sanitarias, Renal Vasc & Diabet Res Lab, Madrid, Spain.
    Asunis, A. M.
    Brotzu Hosp, Dept Pathol, Cagliari, Italy.
    Barratt, J.
    Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England;Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England.
    Tardanico, R.
    Univ Brescia, Spedali Civili Hosp, Dept Pathol, Brescia, Italy.
    Perkowska-Ptasinska, A.
    Med Univ Warsaw, Dept Transplantat Med Nephrol & Internal Med, Warsaw, Poland.
    Arce Terroba, J.
    Fundacio Puigvert, Pathol Dept, Barcelona, Spain.
    Fortunato, M.
    S Croce Hosp, Pathol Dept, Cuneo, Italy.
    Pantzaki, A.
    Hippokrateion Hosp, Dept Pathol, Thessaloniki, Greece.
    Ozluk, Y.
    Istanbul Univ, Istanbul Fac Med, Dept Pathol, Istanbul, Turkey.
    Steenbergen, E.
    Radboud Univ Nijmegen, Med Ctr, Dept Pathol, Nijmegen, Netherlands.
    Soderberg, M.
    Dept Pathol Drug Safety & Metab, Huddinge, Sweden.
    Riispere, Z.
    Univ Tartu, Dept Pathol, Tartu, Estonia.
    Furci, L.
    Univ Modena, Pathol Dept, Modena, Italy.
    Orhan, D.
    Hacettepe Univ, Fac Med, Div Rheumatol, Dept Pediat, Ankara, Turkey.
    Kipgen, D.
    Queen Elizabeth Univ Hosp, Pathol Dept, Glasgow, Lanark, Scotland.
    Casartelli, D.
    Manzoni Hosp, Pathol Dept, Lecce, Italy.
    Ljubanovic, D. Galesic
    Univ Hosp Zagreb, Nephrol Dept, Zagreb, Croatia.
    Gakiopoulou, H.
    Univ Athens, Dept Pathol, Athens, Greece.
    Bertoni, E.
    Careggi Hosp, Nephrol Dept, Florence, Italy.
    Cannata Ortiz, P.
    UAM, IIS Fdn Jimenez Diaz, Pathol Dept, Madrid, Spain.
    Karkoszka, H.
    Med Univ Silesia, Nephrol Endocrinol & Metab Dis, Katowice, Poland.
    Groene, H. J.
    German Canc Res Ctr, Cellular & Mol Pathol, Heidelberg, Germany.
    Stoppacciaro, A.
    Sapienza Univ Rome, Osped St Andrea, Dept Clin & Mol Med, Surg Pathol Unit, Rome, Italy.
    Bajema, I.
    Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
    Bruijn, J.
    Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
    Fulladosa Oliveras, X.
    Bellvitge Univ Hosp, Nephrol Unit, Barcelona, Spain.
    Maldyk, J.
    Med Univ Warsaw, Childrens Clin Hosp, Div Pathomorphol, Warsaw, Poland.
    Loachim, E.
    Univ Ioannina, Med Sch, Dept Pathol, Ioannina, Greece.
    Bavbek, N.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Cook, T.
    Imperial Coll, London, England.
    Alpers, C.
    Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
    Berthoux, F.
    CHU St Etienne, Hop Nord, Dept Nephrol Dialysis & Renal Transplantat, St Etienne, France.
    Bonsib, S.
    LSU Hlth Sci Ctr, Dept Pathol, Shreveport, LA USA.
    D'Agati, V
    Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA.
    D'Amico, G.
    Fdn DAmico Ric Malattie Renali, Milan, Italy.
    Emancipator, S.
    Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
    Emmal, F.
    Bambino Gesu Childrens Hosp & Res Inst, Dept Nephrol & Urol, Div Nephrol & Dialysis, Rome, Italy.
    Fervenza, F.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Florquin, S.
    Univ Amsterdam, Acad Med Ctr, Dept Pathol, Amsterdam, Netherlands.
    Fogo, A.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Groene, H.
    German Canc Res Ctr, Dept Cellular & Mol Pathol, Heidelberg, Germany.
    Haas, M.
    Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA.
    Hill, P.
    St Vincents Hosp, Melbourne, Vic, Australia.
    Hogg, R.
    Scott & White Med Ctr, Temple, TX USA.
    Hsu, S.
    Univ Florida, Coll Med, Div Nephrol Hypertens & Renal Transplantat, Gainesville, FL USA.
    Hunley, T.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Hladunewich, M.
    Jennette, C.
    Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA.
    Joh, K.
    East Natl Hosp, Clin Res Ctr Chiba, Div Immunopathol, Chiba, Japan.
    Julian, B.
    Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
    Kawamura, T.
    Jikei Univ, Sch Med, Div Nephrol & Hypertens, Tokyo, Japan;Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Lai, F.
    Chinese Univ Hong Kong, Hong Kong, Peoples R China.
    Leung, C.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med, Hong Kong, Peoples R China.
    Li, L.
    Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing, Jiangsu, Peoples R China.
    Li, P.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med, Hong Kong, Peoples R China.
    Liu, Z.
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China;Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing, Jiangsu, Peoples R China.
    Massat, A.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Mackinnon, B.
    Western Infirm & Associated Hosp, Renal Unit, Glasgow, Lanark, Scotland.
    Mezzano, S.
    Univ Austral Chile, Escuela Med, Dept Nefrol, Valdivia, Chile.
    Schena, F.
    Policlinico, Renal Dialysis & Transplant Unit, Bari, Italy.
    Tomino, Y.
    Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo, Japan.
    Walker, P.
    Nephropathol Associates, Little Rock, AR USA.
    Wang, H.
    Peking Univ, Inst Nephrol, Hosp 1, Renal Div, Beijing, Peoples R China.
    Weening, J.
    Erasmus MC, Rotterdam, Netherlands.
    Yoshikawa, N.
    Wakayama Med Univ, Dept Pediat, Wakayama, Japan.
    Zeng, Cai-Hong
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China.
    Shi, Sufang
    Peking Univ, Inst Nephrol, Beijing, Peoples R China.
    Nogi, C.
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Suzuki, H.
    Juntendo Univ, Fac Med, Tokyo, Japan;Juntendo Univ, Fac Med, Tokyo, Japan.
    Koike, K.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Hirano, K.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Yokoo, T.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Hanai, M.
    Kurume Univ, Sch Med, Dept Med, Div Nephrol, Fukuoka, Fukuoka, Japan.
    Fukami, K.
    Kurume Univ, Sch Med, Dept Med, Div Nephrol, Fukuoka, Fukuoka, Japan.
    Takahashi, K.
    Fujita Hlth Univ, Sch Med, Dept Nephrol, Toyoake, Aichi, Japan.
    Yuzawa, Y.
    Fujita Hlth Univ, Sch Med, Dept Nephrol, Toyoake, Aichi, Japan.
    Niwa, M.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Yasuda, Y.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Maruyama, S.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Ichikawa, D.
    St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Suzuki, T.
    Juntendo Univ, Fac Med, Tokyo, Japan;St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Shirai, S.
    St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Fukuda, A.
    Miyazaki Univ, Fac Med, Dept Internal Med 1, Miyazaki, Japan.
    Fujimoto, S.
    Univ Miyazaki, Fac Med, Dept Hemovasc Med & Artificial Organs, Miyazaki, Japan.
    Trimarchi, H.
    Hosp Britanico, Div Nephrol, Buenos Aires, DF, Argentina.
    Evaluating a New International Risk-Prediction Tool in IgA Nephropathy2019Ingår i: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 179, nr 7, s. 942-952Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Importance  Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation.

    Objective  To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide.

    Design, Setting, and Participants  We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan.

    Main Outcomes and Measures  Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots.

    Results  The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration.

    Conclusions and Relevance  In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

  • 41.
    Beckmann, Kerri
    et al.
    Univ South Australia, Australian Ctr Precis Hlth, Adelaide, SA, Australia;Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Uppsala Univ Hosp, Reg Canc Ctr Uppsala, Uppsala, Sweden.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Bosco, Cecilia
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, nr 4, s. 676-683Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.

    Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.

    Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).

    Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.

    Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).

    Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.

    Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

  • 42. Bekema, Hendrika J.
    et al.
    MacLennan, Steven
    Imamura, Mari
    Lam, Thomas B. L.
    Stewart, Fiona
    Scott, Neil
    MacLennan, Graeme
    McClinton, Sam
    Griffiths, T. R. Leyshon
    Skolarikos, Andreas
    MacLennan, Sara J.
    Sylvester, Richard
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    N'Dow, James
    Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma2013Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 64, nr 5, s. 799-810Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Context: Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. Objective: To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND.

    Evidence acquisition: Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

    Evidence synthesis: A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes.

    Conclusions: There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.

  • 43.
    Bergengren, Oskar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    Bratt, Ola
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study2018Ingår i: European Urology Oncology, Vol. 1, nr 1, s. 37-45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract

    Background

    Information about how men with prostate cancer (PC) experience their medical care and factors associated with their overall satisfaction with care (OSC) is limited.

    Objective

    To investigate OSC and factors associated with OSC among men with low-risk PC.

    Design, setting, and participants

    Men registered in the National Prostate Cancer Register of Sweden as diagnosed in 2008 with low-risk PC at the age of ≤70 yr who had undergone radical prostatectomy (RP), radiotherapy (RT), or started on active surveillance (AS) were invited in 2015 to participate in this nationwide population-based survey (n = 1720).

    Outcome measurements and statistical analysis

    OSC data were analysed using ordinal logistic regression. Odds ratios (ORs) were calculated for comparisons between the highest and lowest possible response categories.

    Results and limitations

    A total of 1288 men (74.9%) responded. High OSC was reported by 958 (74.4%). Factors associated with high OSC were high participation in decision-making (OR 4.18, 95% confidence interval [CI] 2.61–6.69), receiving more information (OR 11.1, 95% CI 7.97–15.6), high-quality information (OR 7.85, 95% CI 5.46–11.3), access to a nurse navigator (OR 1.80, 95% CI 1.44–2.26), and better functional outcomes (defined as 25 points higher on the EPIC-26 questionnaire; OR 1.34, 95% CI 1.21–1.48). OSC was not affected by whether a doctor or specialist nurse conducted follow-up (OR 0.84, 95% CI 0.66–1.07). These findings were similar across treatment groups. Men who had undergone RP or RT reported high OSC more often than men on AS (78.2% vs 84.0% vs 72.6%), high participation in decision-making (70.5% vs 64.5% vs 49.2%), and having received more information (40.5% vs 45.8% vs 28.6%), and were less likely to believe they would die from PC (3.8% vs 3.9% vs 8.0%). Limitations include the nonrandomised retrospective design and potential recall bias.

    Conclusions

    Information and participation in decision-making, as well as access to a nurse navigator, are key factors for OSC, regardless of treatment. Men on AS need more information about their treatment and need to participate more in decision-making. OSC was as high among men who had nurse-led follow-up as among men who had doctor-led follow-up.

    Patient summary

    Information about how men with low-risk prostate cancer experience their medical care is limited. In this nationwide population-based study we found that information and participation in decision-making as well as access to a nurse navigator are key factors for satisfaction regardless of treatment. Men who are being closely watched for prostate cancer without immediate curative treatment need more information than they now receive and need to participate more in decision-making than they currently do.

  • 44. Bergerot, Cristiane Decat
    et al.
    Battle, Dena
    Bergerot, Paulo Gustavo
    Dizman, Nazli
    Jonasch, Eric
    Hammers, Hans J.
    George, Daniel J.
    Bex, Axel
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Pal, Sumanta Kumar
    Staehler, Michael D.
    Sources of Frustration Among Patients Diagnosed With Renal Cell Carcinoma2019Ingår i: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, artikel-id 11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite numerous therapeutic advances in renal cell carcinoma (RCC), little is known about patients' perspectives on cancer care. An international survey was conducted to identify points of frustration associated with cancer care reported by patients with RCC. Data were obtained from an online survey, conducted from April 1 to June 15, 2017, through social media and patient networking platforms. This survey obtained baseline demographic, clinicopathologic, and treatment-related information. Open-ended questions accessed sources of frustration in cancer-related care and patients' suggestions for amelioration. Responses were categorized and reviewed by independent reviewers. A qualitative analysis was performed and the Kruskal-Wallis test was used to define associations between baseline characteristics and sources of frustration. Among 450 patients surveyed, 71.5% reported sources of frustration, classified as either emotional (48.4%) or practical (23.1%). The most common were fear of recurrence/progression (15.8%), distrust of their cancer care system (12.9%), and lack of appropriate information (9.8%). Female gender and non-clear cell histology were associated with both types of frustration, and older age was linked to practical sources of frustration. Patients suggested solutions included greater compassion among health care practitioners (20.7%), better access to information (15.1%) and research to improve their chances of being cured (14.7%). Sources of frustration related to emotional and practical causes were identified amongst patients with RCC. Certain demographic and clinical characteristics were associated with more sources of frustration. This study provides the first characterization of specific ways to improve the patient experience by addressing common frustrations.

  • 45. Berglund, Anders
    et al.
    Garmo, Hans
    Tishelman, Carol
    Holmberg, Lars
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lambe, Mats
    Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden2011Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, nr 3, s. 833-840Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer.

    Materials and Methods

    A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+).

    Results

    In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41–0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93–2.05; competing cause sHR 2.66, 95% CI 2.56–2.78; prostate cancer specific sHR 0.98, 95% CI 0.93–1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p <0.01).

    Conclusions

    Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.

  • 46.
    Berglund, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Eisemann, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lalos, Othon
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Personality characteristics of-A stress incontinent women: a pilot study1994Ingår i: Journal of Psychosomatic Obstetrics and Gynaecology, ISSN 0167-482X, E-ISSN 1743-8942, Vol. 15, nr 3, s. 165-170Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Personality traits were assessed by means of the Karolinska Scale of Personality (KSP) and the Eysenck Personality Inventory (EPI) in 45 genuine stress incontinent women and compared with a reference group of continent women in order to investigate the possible impact of this chronic condition on the personality. Women with stress incontinence of long duration scored significantly higher than controls on the KSP scales somatic anxiety, psychic anxiety, psychasthenia and suspicion and on the EPI lie-scale. These findings point to the importance of personality factors in chronic conditions such as urinary incontinence.

  • 47.
    Berglund, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Fugl-Meyer, Kerstin S.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Some Sexological Characteristics of Stress Incontinent Women1996Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 30, nr 3, s. 207-212Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Forty-four women with stress urinary incontinence (SUI) were interviewed in order to investigate sexual activities, sexual function and satisfaction one month before and one year after either one of two possible surgical interventions. The findings were related to sexual response cycle, size of urinary leakage, duration of incontinence and depression. There was no significant difference in sexual activity before and after surgery. One or two sexual dysfunctions within the desire, excitement, orgasmic and resolution phases were reported by the majority both before and after intervention independently of surgical method. Neither the magnitude of the leakage nor the duration of SUI influenced the sexual experiences significantly while continence after surgery promoted sexual desire. The discrepances between the prevalence of sexual dysfunctions and the relatively high level of sexual satisfaction as well as the non-influencing parameters indicate the complexity of human sexuality.

  • 48.
    Berglund, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lalos, Othon
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The pre- and postsurgical nursing of women with stress incontinence1996Ingår i: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 23, nr 3, s. 502-511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the present study was to evaluate subjective and objective methods used for the investigation of stress urinary incontinence (SUI) and to compare the outcome of two different surgical techniques regarding cure rate, postoperative nursing, bladder drainage and postoperative pain relief. The study included 45 women with SUI, randomized either to retropubic urethrocystopexy (n = 30) or pubococcygeal repair (n = 15). The assessment included medical history, gynaecological examination, urine analysis and culture, residual urine, pad test, frequency-continence charts, water urethrocystoscopy, continence test, and cystometry with micturition analysis. Moreover, Beck's Depression Inventory and the Eysenck Personality Inventory were used before surgery. One year after surgery no significant difference in subjective cure rate was found between the two surgical methods (73% vs. 80%, respectively). According to pad tests, 67% of the women in the urethrocystopexy group and 47% in the pubococcygeal repair group had ceased to leak urine. The bladder volume increased significantly in both groups. Sixty-three per cent of the women in the urethrocystopexy and 33% in the pubococcygeal repair group experienced severe to very severe postoperative pain. In these groups, significantly more dysphoric women were found as compared with the group of women with less postoperative pain. Furthermore, the women with more severe pain scored higher on the neuroticism scale. These findings indicate the importance of personality factors in the treatment and nursing of women with SUI.

  • 49. Berglund, Linnea Hergot
    et al.
    Prytz, Hanne Sandberg
    Perski, Aleksander
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Svartberg, Johan
    Testosterone levels and psychological health status in men from a general population: the Troms circle divide o study2011Ingår i: The Aging Male, ISSN 1368-5538, E-ISSN 1473-0790, Vol. 14, nr 1, s. 37-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Methods. aEuro integral Total testosterone and sex hormone-binding globulin levels were analysed and free testosterone levels was calculated in 3413 men participating in the fifth Troms circle divide o study in 2001. Self-administered questionnaires including information about education, marital status, smoking habits and the Hopkins Symptom Checklist-10 (SCL-10, a 10-item psychological health questionnaire) were completed. The cross-sectional data were analysed with partial association and analysis of variance and covariance. Results. aEuro integral The complete SCL-10 was not associated with total or free testosterone, but symptoms of anxiety were negatively associated with both total and free testosterone (p < 0.05). Men presumed to be testosterone deficient, with testosterone levels in the lowest 10th percentile, had increased SCL-10 score compared to men with higher testosterone levels (p == 0.021), before and after adjusting for age, waist circumference, marital status, education and smoking. There was an even stronger association between men presumed to be testosterone deficient and symptoms of anxiety (p < 0.001). However, men with more pronounced symptoms indicating mental disorder did not have lower testosterone levels. Conclusions. aEuro integral Men presumed being testosterone deficient had a higher symptom score, in particularly regarding anxiety, but they did not have pathological symptoms. Thus, lower testosterone levels was only associated with subthreshold symptoms of anxiety and depression.

  • 50.
    Bergman, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Studies on patients with ileal conduit diversion with special regard to renal infection1978Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The conditions for retrograde transport of urine and thereby bacteria in the urinary svstem of diverted patients (device and urinary tract) were studied with roentgeno­logical technigue. Back-flow from the urinary collecting device into the conduit occurred in a fifth of those patients who had a flat stoma. A nipple stoma of at least 2 cm height resisted back-flow better than any flat stoma.

    Ureteral reflux occurred to approximately 30 % of the ureters, both in the supine and erect body positions.The intraluminal pressure in the conduit was "low"

    (^12 cm H2O) in approximately 30 % when reflux occurred.

    The autopsy study showed a higher frequency of renal infections in diverted patients than in non-diverted controls. 5 of 11 patients who died more than 2 months after diversion, and without cancer at autopsy, were attributed to death from renal infection.

    There was a relationship between urographical abnormalities, recognized as associated with pyelonephritis, and raised serum antibody titers against E.coli and/or P.mirabilis.

    Most of the ”not normal" renal units deteriorated after the diversion operation.

    The variable "kidney area" was found to be "small" in a higher frequency after a long postoperative period than after a short one.

    Raised -serum antibody titers occurred in 35 % of the patients and were correlated to growth of the corresponding bacteria (E.coli and P.mirabilisrespectively) in the conduit urine. The frequency of raised antibody titers increased with the time after the diversion operation. After treatment with antibiotics of patients with bacteriuria and raised serum antibody titers, the titers were within normal limits («£512), or decreased significantly, in 22 of 25 patients. Serum antibody titer determinations against E.coli and P.mirabilisare suggested as complement to urinary cultures in the follow-up of diverted patients.

    The residual urine volume in the conduit was shown to be of importance for bacteriuria and raised titer against P.mirabilis.

    Some measures, which possibly may reduce bacteriuria and thereby pyelonephritis, are suggested. A nipple stoma of at least 2 cm height ought to be constructed at the operation. To obtain a low residual urine volume the conduit should be short and unobstructed. The urinary collecting device should be emptied often and connected to a uribag during the night.

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