A comparison of graft and patient outcomes following kidney transplantation in extended hour and conventional haemodialysis patients

Differences in early graft function between kidney transplant recipients previously managed with either haemodialysis (HD) or peritoneal dialysis are well described. However, only two single-centre studies have compared graft and patient outcomes between extended hour and conventional HD patients, with conflicting results.This study compared the outcomes of all extended hour (≥24 hours/week) and conventional HD patients transplanted in Australia and New Zealand between 2000 and 2014. The primary outcome was delayed graft function (DGF), defined in an ordinal manner as either a spontaneous fall in serum creatinine of less than 10% within 24 hours, or the need for dialysis within 72 hours following transplantation. Secondary outcomes included the requirement for dialysis within 72 hours post-transplant, acute rejection, estimated glomerular filtration rate at 12 months, death-censored graft failure, all-cause and cardiovascular mortality, and a composite of graft failure and mortality.A total of 4,935 HD patients (378 extended hour HD, 4,557 conventional HD) received a kidney transplant during the study period. Extended hour HD was associated with an increased likelihood of DGF compared with conventional HD (adjusted proportional odds ratio 1.33; 95% confidence interval 1.06-1.67). There was no significant difference between extended hour and conventional HD in terms of any of the secondary outcomes.Compared to conventional HD, extended hour HD was associated with DGF, although long-term graft and patient outcomes were not different

Prognosis of sciatica and back-related leg pain in primary care: the ATLAS cohort

BACKGROUND CONTEXT: Evidence is lacking on the prognosis and prognostic factors of back-related leg pain and sciatica in patients seeing their primary care physicians. This evidence could guide timely appropriate treatment and referral decisions. PURPOSE: The present study aims to describe the prognosis and prognostic factors in primary care patients with low back-related leg pain and sciatica. STUDY DESIGN: This is a prospective cohort study. PATIENT SAMPLE: The present study included adults visiting their family doctor with back-related leg pain in the United Kingdom. OUTCOME MEASURES: Information about pain, function, psychological, and clinical variables, was collected. Good outcome was defined as 30% or more reduction in disability (Roland-Morris Disability Questionnaire). METHODS: Participants completed the questionnaires, underwent clinical assessments, received a magnetic resonance imaging scan, and were followed-up 12 months later. Mixed-effects logistic regression evaluated the prognostic value of six a priori defined variable sets (leg pain duration, pain intensity, neuropathic pain, psychological factors, clinical examination, and imaging variables). A combined model, including variables from all models, examined independent effects. The National Institute for Health Research funded the study. There are no conflicts of interest. RESULTS: A total of 609 patients were included. At 12 months, 55% of patients improved in both the total sample and the sciatica group. For the whole cohort, longer leg pain duration (odds ratio [OR] 0.41; confidence interval [CI] 0.19-0.90), higher identity score (OR 0.70; CI 0.53-0.93), and patient's belief that the problem will last a long time (OR 0.27; CI 0.13-0.57) were the strongest independent prognostic factors negatively associated with improvement. These last two factors were similarly negatively associated with improvement in the sciatica subgroup. CONCLUSIONS: The present study provides new evidence on the prognosis and prognostic factors of back-related leg pain and sciatica in primary care. Just over half of patients improved at 12 months. Patient's belief of recovery timescale and number of other symptoms attributed to the pain are independent prognostic factors. These factors can be used to inform and direct decisions about timing and intensity of available therapeutic options

Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity.

Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H(+) leakage, and the fusion might contribute to invasiveness once a cell is transformed. Cell Rep 2015 Jul 14; 12(2):272-285

Presidential Signing Statements and Executive Power

A recent debate about the Bush administration\u27s use of presidential signing statements has raised questions about their function, legality, and value. We argue that presidential signing statements are legal and that they provide a useful way for the president to disclose his views about the meaning and constitutionality of legislation. In addition, basic tenets of positive political theory suggest that signing statements do not undermine the separation of powers or the legislative process and that, under certain circumstances, they can provide relevant evidence of statutory meaning. Although President Bush has raised many more constitutional challenges within his signing statements than prior presidents have, at least on their face these challenges are similar to challenges made by other recent presidents, such as President Clinton. Whether Bush\u27s views of executive power are significantly different from Clinton\u27s, and if so, whether they are inferior, remain open questions, but these issues are independent of whether signing statements are lawful