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Background: Controversy exists regarding the best-performing vascular access type for patients undergoing haemodialysis. We aimed to compare outcomes of starting dialysis on arteriovenous fistulas (AVFs) versus arteriovenous grafts (AVGs) in haemodialysis patients. Methods: We conducted a systematic search of multiple electronic information sources and bibliographic reference lists. The following outcome parameters were evaluated at 1, 2 and 5 years: primary failure, defined as access never used for dialysis; primary patency, defined as intervention-free access survival; primary-assisted patency, defined as uninterrupted access survival with interventions; and secondary patency, defined as cumulative access survival. Results: We identified 15 comparative studies reporting a total of 118,434 patients who initiated haemodialysis with AVF (n = 95,143) or AVG (n = 23,291). Our analysis demonstrated that AVF was associated with significantly higher primary failure rate (OR: 2.05, p =.0005) but significantly higher rate of primary patency at 1 year (OR: 1.91, p <.00001), at 2 years (OR: 2.52, p <.00001) and at 5 years (OR: 2.59, p <.00001); and primary-assisted patency at 1 year (OR: 1.71, p <.00001), at 2 years (OR: 2.13, p <.00001) and 5 years (OR: 2.79, p <.00001). There was no significant difference in secondary patency at 1 year (OR: 1.08, p <.00001) but AVF had better secondary patency at 2 years (OR: 1.26, p <.00001) and 5 years (OR: 1.60, p <.00001) than AVG. Conclusions: The meta-analysis of best available comparative evidence (Level 2) demonstrated that AVFs may be associated with significantly higher primary failure rate but higher primary patency, primary-assisted patency and secondary patency at 1, 2 and 5 years compared to AVGs. However, the available evidence is subject to significant selection bias and confounding by indication. [ABSTRACT FROM AUTHOR]

Introduction Selenium is an essential trace element that is fundamental to human health. Its biological role is mediated principally by cotranslational incorporation of selenocysteine (Sec; the 21st amino acid) into [...], Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence--binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of the latter stages of spermatogenesis, was associated with a lack of testis-enriched selenoproteins. An axial muscular dystrophy was also present, with features similar to myopathies caused by mutations in selenoprotein N (SEPN1). Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and susceptibility to ultraviolet radiation--induced oxidative damage may mediate the observed photosensitivity. Reduced levels of selenoproteins in peripheral blood cells were associated with impaired T lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, and telomere shortening. Paradoxically, raised ROS in affected subjects was associated with enhanced systemic and cellular insulin sensitivity, similar to findings in mice lacking the antioxidant selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is associated with a multisystem disorder with defective biosynthesis of many selenoproteins, highlighting their role in diverse biological processes.

Background: Physical activity interventions are an important adjunct therapy for people with severe to moderate and/or enduring mental health problems. Football is particularly popular for men in this group. Several interventions have emerged over the past decade and there is a need to clearly articulate how they are intended to work, for whom and in what circumstances. Aims: To develop a theory-driven framework for a football intervention for men with severe, moderate and/or enduring mental health problems using a participatory realist approach. Methods: A participatory literature review on playing football as a means of promoting mental health recovery with a realist synthesis. It included the accounts and input of 12 mental health service users and the contributions of other stakeholders including football coaches and occupational therapists. Results: Fourteen papers were included in the review. Analysis revealed that interventional mechanisms were social connectedness, identity security, normalising experiences and positive affectivity. These supported mental health recovery. Outcomes were moderated by social stigma and several interventional factors such as over-competitiveness. Conclusions: The context mechanism outcome configuration framework for these interventions map well onto social models of mental health recovery and provide insight into how they work. This now requires testing. [ABSTRACT FROM AUTHOR]

RituxiCAN-C4 combined an open-labeled randomized controlled trial (RCT) in 7 UK centers to assess whether rituximab could stabilize kidney function in patients with chronic rejection, with an exploratory analysis of how B cell-depletion influenced T cell anti-donor responses relative to outcome. Between January 2007 and March 2015, 59 recruits were enrolled after screening, 23 of whom consented to the embedded RCT. Recruitment was halted when in a pre-specified per protocol interim analysis, the RCT was discovered to be significantly underpowered. This report therefore focuses on the exploratory analysis, in which we confirmed that when B cells promoted CD4+ anti-donor IFNγ production assessed by ELISPOT, this associated with inferior clinical outcome; these patterns were inhibited by optimized immunosuppression but not rituximab. B cell suppression of IFNγ production, which associated with number of transitional B cells and correlated with slower declines in kidney function was abolished by rituximab, which depleted transitional B cells for prolonged periods. We conclude that in this patient population, optimized immunosuppression but not rituximab promotes anti-donor alloresponses associated with favorable outcomes. Clinical Trial Registration: Registered with EudraCT (2006-002330-38) and www.ClinicalTrials.gov, identifier: NCT00476164. [ABSTRACT FROM AUTHOR]

The interest in regulatory B cells (Bregs) began in the 1970s with the evidence that B cells could downregulate the immune system by the production of "inhibitory" antibodies. Subsequently, a series of results from different studies have emphasized that B cells have antibody‐independent immunoregulatory functions. Since then, different subsets of B cells with regulatory functions and their development and mechanisms of action have been identified both in human and in animal models of inflammation, transplantation, and autoimmunity. The present review outlines the suggested pathways by which Bregs develop, describes the different subsets of Bregs with their phenotypes and function as well as their role in transplantation, highlighting the differences between human and animal studies throughout. [ABSTRACT FROM AUTHOR]

Summary: The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2–11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan–Meier analysis, the presence of DGF was associated with lower graft survival (log‐rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617–11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor. [ABSTRACT FROM AUTHOR]

Background Improvement in long-term renal allograft survival is impeded by incomplete or erroneous coding of causes of allograft loss. This study reports 13-year trends in causes of graft failure across the UK. Methods National Health Service Blood and Transplant (NHSBT) and UK Renal Registry data were linked to describe UK kidney patients transplanted in 2000–13. NHSBT graft failure categories were used, with 'other' recoded when free text was available. Adjusted analyses examined the influence of age, ethnicity and donor type on causes of graft failure. Results In 22 730 recipients, 5389 (23.7%) grafts failed within a median follow-up of 5 years. The two most frequent causes were death with a functioning graft (40.8%) and alloimmune pathology (25.0%). Graft survival was higher in recipients who were younger (mean 47.3 versus 50.7 years), received a pre-emptive transplant (20.2% versus 10.4%), spent less time on dialysis (median 1.6 versus 2.4 years) and received a living donor transplant (36.3% versus 22.2%), with no differences by sex, ethnicity or human leucocyte antigen mismatch. Allograft failure within 2 years of transplantation fell from 12.5% (2000–4) to 9.8% (2009–13). Surgical- and alloimmune-related failures decreased over time while death with a functioning graft became more common. Age, ethnicity and donor type were factors in recurrent primary disease and alloimmune pathology. Conclusions Since 2000 there have been reductions in surgical and alloimmune graft failures in the UK. However, graft failure codes need to be revised if they are to remain useful and effective in epidemiological and quality improvement trials. [ABSTRACT FROM AUTHOR]

Aims: Meta-analysis is of critical importance to decision makers to assess the comparative efficacy and safety of interventions and is integral to health technology assessment. A major problem for the meta-analysis of continuous outcomes is that associated variance data are not consistently reported in trial publications. The omission of studies from a meta-analysis due to incomplete reporting may introduce bias. The objectives of this study are to summarise and describe the methods used for handling missing variance data in meta-analyses in populations with type 2 diabetes mellitus (T2DM). Methods: Electronic databases, Embase, MEDLINE, and the Cochrane Library (accessed June 2015), were systematically searched to identify meta-analyses of interventions in patients with T2DM. Eligible studies included those which analysed the change in HbA1c from baseline. Results: Sixty-seven publications reporting on meta-analyses of change in HbA1c from baseline in T2DM were identified. Approaches for dealing with missing variance data were reported in 41% of publications and included algebraic calculation, trial-level imputation, and no imputation. Conclusions: Meta-analysis publications typically fail to report standardised approaches for dealing with missing variance data. While no particular imputation method is favoured, authors are discouraged from using a no-imputation approach. Instead, authors are encouraged to explore different approaches using sensitivity analyses and to improve the quality of reporting by documenting the methods used to deal with missing variance data. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 28-year-old man presented with a history of hyper-IgD and periodic fever syndrome as a symptom for renal parenchymal calcification secondary to systemic amyloidosis.

Dehydrohalogenation of secondary diarylphosphine ruthenium complexes in the presence of benzonitrile yields stable, isolable nitrile adducts of the formula [Ru-(η5-indenyl)-(PAr2)-(NCPh)-(PPh3)], in which the terminal phosphido ligand is pyramidal at P and contains a stereochemically active lone pair. Unlike the analogous carbonyl adducts [Ru-(η5-indenyl)-(PAr2)-(CO)-(PPh3)], these benzonitrile complexes behave as masked sources of the highly reactive planar phosphido complexes [Ru-(η5-indenyl)-(PAr2)-(PPh3)], which contain a RuPAr2 π bond. This is illustrated by the addition (or cycloaddition) reactions of the benzonitrile adducts with dihydrogen, methyl iodide, and 1-hexene, as well as their thermal decomposition via orthometalation of the PPh3 ligand. Enthalpies of CO vs NCPh dissociation from the [Ru-(η5-indenyl)-(PR2)-(PPh3)] fragments (R = alkyl, aryl) have been calculated, as has the trajectory of addition of H2 to the model planar phosphido complex [Ru-(η5-indenyl)-(PMe2)-(PMe3)]. The latter study shows the intermediacy of an η2-H2 adduct, [Ru-(η5-indenyl)-(PAr2)-(η2-H2)-(PPh3)], in the formation of [RuH-(η5-indenyl)-(HPMe2)-(PMe3)], a further indication of the importance of the variable binding modes of the terminal phosphido ligand in this system. [ABSTRACT FROM AUTHOR]

Introduction United Kingdom surgical training consists of a two-year core surgical training (CST) followed by a six-year higher speciality training (ST). There is a significant step up in responsibility and operative skills when transitioning from core to higher training. One-way trainees can bridge this gap is to "act up" to registrar level "CST-R." The CST "steps up" to the role of ST typically in the latter part of their core training and gains exposure at being the "reg of the week," primary assistant in theatre, managing MDTs, and taking speciality referrals. This can be an excellent training opportunity. This study aims to demonstrate a quantitative improvement in trainee operation as a result of stepping up. Methods This study compares the operative experience of one vascular surgery-themed trainee during six months as a CST and six months acting up as a CST-R. The trainee's eLogbook was searched for all operations between August 3, 2022, and January 31, 2023, and between February 1, 2023, and August 1, 2023. The number of cases performed and the role played in each were analyzed. The number of low complexity cases conducted in each block was used as a baseline to ensure the progression seen was because of increasingly complex ST operating rather than the increase in CST level operating expected throughout CST. An abscess incision and drainage were used as the reference low-complexity case. Results The number of cases the trainee performed independently increased from 13% to 25%, while the number where they were simply assisting decreased from 43% to 35%. The number of cases where the trainer remained scrubbed decreased nonsignificantly from 43% to 39%. The number of low-complexity cases performed remained unchanged for each six-month block. Conclusion As a CST-R, the trainee played a more prominent operative role in a greater number of cases. The CST-R does require a supportive department and consultant body. It also enables other STs to gain more surgical exposure because of their reduced frequency of being the "reg of the week." If a trainee can remain in a post for two six-month blocks, then there is much to be gained from a formalised acting-up program, and consideration should be given to formally incorporating this into core surgical programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, McCaughran et al.)