The role of human glandular kallikrein 2 for prediction of pathologically organ confined prostate cancer

BACKGROUND: In recent studies serum levels of human glandular kallikrein 2 (hK2) demonstrated significant differences in pathologically organ-confined versus non-organ-confined prostate cancer (PCa). In this study we investigated whether hK2 adds independent information when considered together with traditionally used parameters to predict organ confined (pT2a/b) PCa. METHODS: Serum levels of hK2, total and free prostate-specific antigens (PSA) were obtained one day before radical prostatectomy in 245 consecutive men. These were included with clinical stage and biopsy Gleason grade into univariate analysis and multivariate logistic regression models. RESULTS: pT2a/b PCa was found in n = 148 patients. In univariate analysis all preoperative parameters demonstrated significant association with the presence of pT2a/b PCa. Using multivariate logistic regression model hK2 (P = 0.022), clinical stage (P < 0.0001), and Gleason grade (P < 0.0001) were independent predictors of pT2a/b PCa whereas PSA (P = 0.3) was not. In bootstrap corrected logistic regression based nomograms the addition of hK2 density marginally enhanced predictive accuracy when PSA, PSA density, clinical stage, and Gleason grade were considered (AUC = 0.879 without hK2 density and 0.883 with hK2 density). CONCLUSIONS: hK2 and hK2 density could independently predict pT2a/b PCa. However, improvement in predictive accuracy was marginal when nomograms based on traditional variables were complemented with this serum marker.     

Long-term outcome after Bascom's cleft-lift procedure under tumescent local analgesia for pilonidal sinus disease: a cohort study

Aim

Bascom's cleft-lift procedure for pilonidal sinus disease under tumescent local analgesia is feasible and well tolerated with favourable short-term outcomes. We aimed to assess the 10-year treatment success rate after cleft-lift under tumescent local analgesia.

Method

This was a single-centre cohort study based on prospectively registered perioperative data and survey data with additional data from electronic medical records. The cleft-lift procedure was performed under tumescent local analgesia in a day-surgical setting at a tertiary referral hospital between 1 July 2008 and 31 March 2014. The primary outcome was the 10-year risk treatment success defined as complete wound healing within 180 days of surgery or no recurrence assessed with competing risk analyses. Secondary outcomes were time to complete wound healing, persistent pain and cosmetic satisfaction.

Results

Two hundred patients with complex pilonidal sinus disease were included. Indication was incomplete wound healing after pilonidal sinus surgery in 43 (21.5%) patients, recurrence after previous intervention in 78 (39.0%) or moderate to complex sinuses assessed by a consultant surgeon in 79 (39.5%). One hundred and ninety-five patients had complete wound healing within 180 days with a median time of 29 days (interquartile range 16–47). The cumulative risk of 10-year recurrence was 11.3% (95% CI 6.2%–16.4%) with a median follow-up time of 8.5 (1.0–10.7) years. Treatment success was 86.1% (95% CI 80.6%–91.5%). No significant predictors were associated with recurrence, and 90% of patients experienced no persistent pain.

Conclusion

Cleft-lift performed under tumescent local analgesia has an acceptable 10-year treatment failure rate, making the method feasible in a day-surgery setting.     

Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain

The prevalence of “vertebral endplate signal changes” (VESC) and its association with low back pain (LBP) varies greatly between studies. This wide range in reported prevalence rates and associations with LBP could be explained by differences in the definitions of VESC, LBP, or study sample. The objectives of this systematic critical review were to investigate the current literature in relation to the prevalence of VESC (including Modic changes) and the association with non-specific low back pain (LBP). The MEDLINE, EMBASE, and SveMED databases were searched for the period 1984 to November 2007. Included were the articles that reported the prevalence of VESC in non-LBP, general, working, and clinical populations. Included were also articles that investigated the association between VESC and LBP. Articles on specific LBP conditions were excluded. A checklist including items related to the research questions and overall quality of the articles was used for data collection and quality assessment. The reported prevalence rates were studied in relation to mean age, gender, study sample, year of publication, country of study, and quality score. To estimate the association between VESC and LBP, 2 × 2 tables were created to calculate the exact odds ratio (OR) with 95% confidence intervals. Eighty-two study samples from 77 original articles were identified and included in the analysis. The median of the reported prevalence rates for any type of VESC was 43% in patients with non-specific LBP and/or sciatica and 6% in non-clinical populations. The prevalence was positively associated with age and was negatively associated with the overall quality of the studies. A positive association between VESC and non-specific LBP was found in seven of ten studies from the general, working, and clinical populations with ORs from 2.0 to 19.9. This systematic review shows that VESC is a common MRI-finding in patients with non-specific LBP and is associated with pain. However, it should be noted that VESC may be present in individuals without LBP.     

Racial variations in erythropoietic response to epoetin alfa in chronic kidney disease and the impact of smoking.

BACKGROUND: Of the known risk factors for chronic kidney disease (CKD), race represents one that is non-modifiable, while smoking is another that is modifiable. Moreover, smoking tends to increase red blood cell mass, which is frequently diminished in CKD. No studies have examined the interplay of race with smoking on anaemia management in patients with CKD. METHODS: We examined the effects of smoking on anaemia management in CKD and its variation across race in a previously conducted study of CKD patients (n = 1312) initiated on weekly epoetin alfa and followed for 16 weeks. Smoking status was classified as current vs non-smoker. Race was classified as African-American vs non-African-American. Changes in estimated glomerular filtration rate, urinary albumin excretion, and erythropoietic response to weekly epoetin alfa were examined. RESULTS: Overall, African-Americans had lower baseline Hb than non-African-Americans. African-American non-smokers did not mount an erythropoetic response comparable to other non-smokers by final Hb (mean 11.29 g/dl vs 11.64 g/dl, P<0.001) or week 16 Hb (mean 11.61 g/dl vs 11.86 g/dl, P = 0.02). However, African-American smokers had a more significant erythropoietic response than their non-smoking counterparts and were comparable to their smoking non-African-American counterparts. There was no effect of smoking on renal function or urinary protein excretion over the course of the study. CONCLUSION: African-American non-smokers exhibit a diminished response to standard epoetin alfa dosing than non-smokers in other races. However, African-American smokers with CKD exhibit a response to epoetin alfa comparable to patients of other races. These findings may have implications for African-Americans who have CKD-related anaemia.     

Comparative Analysis of Outcomes in Living and Deceased Donor Liver Transplants for Primary Sclerosing Cholangitis

Introduction  Primary sclerosing cholangitits (PSC) is a progressive fibrosing cholangiopathy eventually leading to end-stage liver disease (ESLD). While literature for deceased donor liver transplantation (DDLT) for PSC abounds, only a few reports describe live donor liver transplant (LDLT) in the setting of PSC. We present a single-center experience on survival outcomes and disease recurrence for LDLT and DDLT for ESLD secondary to PSC. Aim  The aim of this study was to analyze survival outcomes and disease recurrence for LDLT and DDLT for ESLD secondary to PSC. Patients and Methods  A retrospective review of 58 primary liver transplants for PSC-associated ESLD, performed between May 1995 and January 2007, was done. Patients were divided into two groups based on donor status. Group 1 (n = 14) patients received grafts from living donors, while group 2 (n = 44) patients received grafts from deceased donors. An analysis of survival outcomes and disease recurrence was performed. Recurrence was confirmed based on radiological and histological criteria. Results  Recurrence of PSC was observed in four patients in LDLT group and seven in DDLT group. Retransplantation was required in one patient in LDLT group and nine patients in DDLT group. One patient (7%) among LDLT and six patients (14%) among DDLT died. The difference in patient and graft survival was not statistically significant between the two groups (patient survival, p = 0.60; graft survival, p = 0.24). Conclusion  This study demonstrates equivalent survival outcomes between LDLT and DDLT for PSC; however, the rate of recurrence may be higher in patients undergoing LDLT.     

Incidence and Characteristics of Atypical Femoral Fractures: Clinical and Geometrical Data

Despite the multitude of studies published on atypical femoral fractures (AFFs), a profile for patients at risk does not exist. This study aimed first at estimating AFF incidence over a 19‐month‐period in Quebec City using the ASBMR Task force criteria to define AFF. The medical records of patients hospitalized for hip or femoral fracture between June 1, 2009, and December 31, 2010, were reviewed. Thirty‐six cases of atypical fractures were identified during the 19‐month period, representing an AFF incidence of 7.0 (range, 4.7 to 9.3) cases per 100,000 person‐years. In the second part of the study, data regarding the characteristics suspected of increasing the risks of AFF were collected from medical and pharmacological records, proximal femur radiographs, and patient interviews. The data regarding each patient with an AFF during years 2008‐2011 were compared to two controls with a hip or femoral fragility fracture or a traumatic fracture, paired for age and sex. Twenty patients with AFF were added to the 36 patients with AFF selected in the first part, thereby 56 patients with AFF were investigated. The association between the occurrence of AFF and bisphosphonates (BPs) use was proven statistically significant in multivariate analysis, odds ratio (OR) = 10.39 (95% CI, 2.22 to 48.58; p = 0.0029). Compared to controls, patients with AFF had excessive femoral offset (43.1 mm versus 38.3 mm, p = 0.0007), proximal femoral neck angle in varus (128.9 degrees versus 134.0 degrees, p < 0.0001), and had greater proximal cortical thickness. This retrospective study confirms the low incidence of AFF, confirms its significant association with exposure to BPs, and reveals the possible contribution of proximal femoral geometry in AFF occurrence. © 2016 American Society for Bone and Mineral Research.     

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10‐year postrandomization follow‐up study

Long‐term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post‐transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients’ survival was 100%, 94.2%, and 95.8% (P = 0.25), and death‐censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m², respectively (P = 0.16). The incidence of biopsy‐proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus‐associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody‐mediated rejection (n = 6). De novo donor‐specific antibodies were detected in 13% of AZA‐, 21% of MMF‐, and 14% of CsA‐treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well‐selected renal transplant recipient ( ClinicalTrials.gov number: 980654).     

Engagement of transferrin receptor by polymeric IgA1: evidence for a positive feedback loop involving increased receptor expression and mesangial cell proliferation in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis in the world, is characterized by IgA immune complex-mediated mesangial cell proliferation. The transferrin receptor (TfR) was identified previously as an IgA1 receptor, and it was found that, in biopsies of patients with IgAN, TfR is overexpressed and co-localizes with IgA1 mesangial deposits. Here, it is shown that purified polymeric IgA1 (pIgA1) is a major inducer of TfR expression (three- to four-fold increase) in quiescent human mesangial cells (HMC). IgA-induced but not cytokine-induced HMC proliferation is dependent on TfR engagement as it is inhibited by both TfR1 and TfR2 ectodomains as well as by the anti-TfR mAb A24. It is dependent on the continued presence of IgA1 rather than on soluble factors released during IgA1-mediated activation. In addition, pIgA1-induced IL-6 and TGF-beta production from HMC was specifically inhibited by mAb A24, confirming that pIgA1 triggers a TfR-dependent HMC activation. Finally, upregulation of TfR expression induced by sera from patients with IgAN but not from healthy individuals was dependent on IgA. It is proposed that deposited pIgA1 or IgA1 immune complexes could initiate a process of auto-amplification involving hyperexpression of TfR, allowing increased IgA1 mesangial deposition. Altogether, these data unveil a functional cooperation between pIgA1 and TfR for IgA1 deposition and HMC proliferation and activation, features that are commonly implicated in the chronicity of mesangial injuries observed in IgAN and that could explain the recurrence of IgA1 deposits in the mesangium after renal transplantation.