| 1. |
- Huvila, J., et al.
(författare)
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Combined ASRGL1 and p53 immunohistochemistry as an independent predictor of survival in endometrioid endometrial carcinoma
- 2018
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Ingår i: Gynecologic Oncology. - : Academic Press Inc.. - 0090-8258 .- 1095-6859. ; 149:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods: A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results: A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (29.5%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P < 0.001) of dying of EEC compared to the low-risk group. Conclusions: P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities.
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| 2. |
- Thulin, Helena, et al.
(författare)
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Defecation disturbances after cystectomy for urinary bladder cancer
- 2011
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Ingår i: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 108:2, s. 196-203
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Tidskriftsartikel (refereegranskat)abstract
- What’s known on the subject? and What does the study add?Functional gastrointestinal symptoms and problems are common after radical cystectomy with urinary diversion. This study adds new important epidemiological data on this group of symptoms. OBJECTIVE: To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS: During their follow-up we attempted to contact all men and women aged 30–80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS: The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS: Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.
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| 3. |
- Liedberg, Fredrik, et al.
(författare)
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Cumulative incidence of midline incisional hernia and its surgical treatment after radical cystectomy and urinary diversion for bladder cancer: A nation-wide population-based study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective To study the cumulative incidence and surgical treatment of midline incisional hernia (MIH) after cystectomy for bladder cancer. Methods In the nationwide Bladder Cancer Data Base Sweden (BladderBaSe), cystectomy was performed in 5646 individuals. Cumulative incidence MIH and surgery for MIH were investigated in relation to age, gender, comorbidity, previous laparotomy and/or inguinal hernia repair, operative technique, primary/secondary cystectomy, postoperative wound dehiscence, year of surgery, and period-specific mean annual hospital cystectomy volume (PSMAV). Results Three years after cystectomy the cumulative incidence of MIH and surgery for MIH was 8% and 4%, respectively. The cumulative incidence MIH was 12%, 9% and 7% in patients having urinary diversion with continent cutaneous pouch, orthotopic neobladder and ileal conduit. Patients with postoperative wound dehiscence had a higher three-year cumulative incidence MIH (20%) compared to 8% without. The corresponding cumulative incidence surgery for MIH three years after cystectomy was 9%, 6%, and 4% for continent cutaneous, neobladder, and conduit diversion, respectively, and 11% for individuals with postoperative wound dehiscence (vs 4% without). Using multivariable Cox regression, secondary cystectomy (HR 1.3 (1.0-1.7)), continent cutaneous diversion (HR 1.9 (1.1-2.4)), robot-assisted cystectomy (HR 1.8 (1-3.2)), wound dehiscence (HR 3.0 (2.0-4.7)), cystectomy in hospitals with PSMAV 10-25 (HR 1.4 (1.0-1.9)), as well as cystectomy during later years (HRs 2.5-3.1) were all independently associated with increased risk of MIH. Conclusions The cumulative incidence of MIH was 8% three years postoperatively, and increase over time. Avoiding postoperative wound dehiscence after midline closure is important to decrease the risk of MIH.
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| 4. |
- Xu, H., et al.
(författare)
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Excess protein intake relative to fiber and cardiovascular events in elderly men with chronic kidney disease
- 2016
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 26:7, s. 597-602
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The elevated cardiovascular (CVD) risk observed in chronic kidney disease (CKD) may be partially alleviated through diet. While protein intake may link to CVD events in this patient population, dietary fiber has shown cardioprotective associations. Nutrients are not consumed in isolation; we hypothesize that CVD events in CKD may be associated with dietary patterns aligned with an excess of dietary protein relative to fiber. Methods and Results: Prospective cohort study from the Uppsala Longitudinal Study of Adult Men. Included were 390 elderly men aged 70-71 years with CKD and without clinical history of CVD. Protein and fiber intake, as well as its ratio, were calculated from 7-day dietary records. Cardiovascular events were registered prospectively during a median follow-up of 9.1 (inter-quartile range, 4.5-10.7) years. The median dietary intake of protein and fiber was 66.7 (60.7-71.1) and 16.6 (14.5-19.1) g/day respectively and the protein-to-fiber intake ratio was 4.0 (3.5-4.7). Protein-to-fiber intake ratio was directly associated with serum C-reactive protein levels. During follow-up, 164 first-time CVD events occurred (incidence rate 54.5/1000 per year). Protein-fiber intake ratio was an independent risk factor for CVD events [adjusted hazard ratio, HR per standard deviation increase (95% confidence interval, CI) 1.33 (1.08, 1.64)]. Although in opposing directions, dietary protein [1.18 (0.97, 1.44)], dietary fiber alone [0.81 (0.64, 1.02)], were not significantly associated with CVD events. Conclusions: An excess of dietary protein relative to fiber intake was associated with the incidence of cardiovascular events in a homogeneous population of older men with CKD.
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| 5. |
- Xu, H., et al.
(författare)
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Lipophilic index, kidney function, and kidney function decline
- 2016
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 31, s. 177-177
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Methods and results: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended reexamination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction >= 30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m(2) 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m(2), p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). Conclusions: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.
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| 6. |
- Glimelius, Bengt, et al.
(författare)
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Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®) : a placebo-controlled randomised phase II study (PLIANT)
- 2018
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:3, s. 393-402
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC).Patient and methods: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale.Results: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1–8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups.Conclusions: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.
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| 7. |
- Skoog, Bengt, et al.
(författare)
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Short-term prediction of secondary progression in a sliding window: A test of a predicting algorithm in a validation cohort
- 2019
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Ingår i: Multiple Sclerosis Journal - Experimental, Translational and Clinical. - : SAGE Publications. - 2055-2173. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Multiple Sclerosis Prediction Score (MSPS, www.msprediction.com) estimates, for any month during the course of relapsing–remitting multiple sclerosis (MS), the individual risk of transition to secondary progression (SP) during the following year. Objective: Internal verification of the MSPS algorithm in a derivation cohort, the Gothenburg Incidence Cohort (GIC, n = 144) and external verification in the Uppsala MS cohort (UMS, n = 145). Methods: Starting from their second relapse, patients were included and followed for 25 years. A matrix of MSPS values was created. From this matrix, a goodness-of-fit test and suitable diagnostic plots were derived to compare MSPS-calculated and observed outcomes (i.e. transition to SP). Results: The median time to SP was slightly longer in the UMS than in the GIC, 15 vs. 11.5 years (p = 0.19). The MSPS was calibrated with multiplicative factors: 0.599 for the UMS and 0.829 for the GIC; the calibrated MSPS provided a good fit between expected and observed outcomes (chi-square p = 0.61 for the UMS), which indicated the model was not rejected. Conclusion: The results suggest that the MSPS has clinically relevant generalizability in new cohorts, provided that the MSPS was calibrated to the actual overall SP incidence in the cohort.
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| 8. |
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| 9. |
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| 10. |
- Wieloch, Mattias, et al.
(författare)
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Estimated glomerular filtration rate is associated with major bleeding complications but not thromboembolic events, in anticoagulated patients taking warfarin
- 2013
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 131:6, s. 481-486
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Tidskriftsartikel (refereegranskat)abstract
- Background: Decreased glomerular filtration rate is an established risk factor for bleeding but there are limited data on its association with bleeding risk in well-controlled anticoagulated patients taking warfarin. Objectives: The aim was to investigate the relationship between glomerular filtration rate, major bleeding and thromboembolic complications in patients with tight anticoagulation control. Patients/Methods: A cohort study of patients from a Swedish quality register for anticoagulation, including all the registered patients that received anticoagulation during 2008 in the anticoagulation center of Skane University Hospital, Malmo. Key outcome measures were major bleeding and arterial or venous thrombosis during 2008. A total of 3536 patients (2875 treatment years) were included. Results: Total rates of 2.6 (2.0-3.2) bleeding events and 1.8 (1.3-2.3) thrombotic events per 100 treatment years were recorded (75 bleeding and 51 thromboembolic events). Data on estimated glomerular filtration rate were available in 3349 patients. Mean time in therapeutic range (international normalized ratio 2.0-3.0) was 74.5% (n=2894). Major bleeding events were significantly related to age and percentage of time with international normalized ratio >3.0 (P<0.001). Glomerular filtration rate levels <30 ml/min/1.73 m(2) were particularly associated with high risk of bleeding, especially in elderly patients. No correlation between glomerular filtration rate and thromboembolic events was seen. Conclusions: With good anticoagulation control as measured by time in therapeutic range, patients had a relatively low risk for major bleeding if their renal function is normal. Despite good anticoagulation control, severely impaired kidney function is associated with a very high yearly risk of major bleeding events.
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