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High-dose haemodiafiltration has been shown, in a randomised clinical trial, to result in a 23% lower risk of mortality for patients with kidney failure when compared with conventional high-flux haemodialysis. Nevertheless, whether treatment effects differ across subgroups, whether a dose–response relationship with convection volume exists, and the effects on cause-specific mortality remain unclear. The aim of this individual patient data meta-analysis was to compare the effects of haemodiafiltration and standard haemodialysis on all-cause and cause-specific mortality.

In the CONVINCE trial, the primary analysis demonstrated a survival benefit for patients receiving high-dose hemodiafiltration (HDF) as compared with high-flux hemodialysis (HD). A secondary objective was to evaluate effects on health-related quality of life (HRQoL); assessed in eight domains (physical function, cognitive function, fatigue, sleep disturbance, anxiety, depression, pain interference, social participation) applying instruments from the Patient-Reported Outcome Measurement Information System (PROMIS) before randomization and every three months thereafter. In total 1360 adults with dialysis-dependent chronic kidney disease, eligible to receive high-flux HDF (23 liters or more), were randomized (1:1); 84% response rate to all questionnaires. Both groups reported a continuous deterioration in all HRQoL domains. Overall, raw score changes from baseline were more favorable in the HDF group, resulting in a significant omnibus test after a median observation period of 30 months. Most relevant single raw score differences were reported for cognitive function. Patients receiving HDF reported a decline of -0.95 units (95% confidence interval - 2.23 to +0.34) whereas HD treated patients declined by -3.90 units (-5.28 to - 2.52). A joint model, adjusted for mortality differences, utilizing all quarterly assessments, identified a significantly slower HRQoL decline in physical function, cognitive function, pain interference, and social participation for the HDF group. Their physical health summary score declined -0.46 units/year slower compared to the HD group. Thus, the CONVINCE trial showed a beneficial effect of high-dose hemodiafiltration for survival as well as a moderate positive effect on patients’ quality of life, most pronounced with respect to their cognitive function.

Western Europe boasts advanced health care systems, robust kidney care guidelines, and a well-established health care workforce. Despite this, significant disparities in kidney replacement therapy incidence, prevalence, and transplant access exist. This paper presents the third International Society of Nephrology Global Kidney Health Atlas’s findings on kidney care availability, accessibility, affordability, and quality in 22 Western European countries, representing 99% of the region’s population. The known chronic kidney disease (CKD) prevalence across Western Europe averages 10.6%, slightly above the global median. Cardiovascular diseases account for a substantial portion of CKD-related deaths. Kidney failure incidence varies. Government health expenditure differs; however, most countries offer government-funded acute kidney injury, dialysis, and kidney transplantation care. Hemodialysis and peritoneal dialysis are universally available, with variations in the number of dialysis centers. Kidney transplantation is available in all countries (except for 3 microstates), with variable transplant center prevalence. Conservative kidney management (CKM) is increasingly accessible. The region’s kidney care workforce is substantial, exceeding global averages; however, workforce shortages are reported. Barriers to optimal kidney care include limited workforce capacity, lack of surveillance mechanisms, and suboptimal integration into national noncommunicable disease (NCD) strategies. Policy recognition of CKD as a health priority varies across countries. Although Western Europe exhibits strong kidney care infrastructure, opportunities for improvement exist, particularly in CKD prevention, surveillance, awareness, and policy implementation. Efforts to improve CKD care should include automated detection, educational support, and enhanced workflows. Based on these findings, health care professionals, stakeholders, and policymakers are called to act to enhance kidney care across the region.

Abstract:This volume of collected essays contains scholarship on the handling of medieval cultural heritage, broadly conceived. Societies around the world look to the Middle Ages for identity and inspiration, defining the past in light of modern concerns about cultural belonging, claims to political legitimacy, and conceptions of community. The essays in this volume explore such questions as: Who has the authority to decide on cultural heritage matters, and what happens when the heritage of one group is preferred to that of another? What happens to local communities when a site becomes a popular tourist destination or a place for memorializing the past in a way that erases the voices of a particular group of people? What are the lived consequences when claims to cultural heritage define communities along racial, ethnic, religious, linguistic, regional, or historical lines? In bringing together a broad range of global and disciplinary perspectives, this volume aims to extend the conversation about the definition and deployment of the medieval past.

Given the association of Epstein-Barr virus (EBV) with subjective perception of fatigue and demyelination in clinical conditions, the question about potential subclinical effects in the adult general population remains open. We investigate the association between individuals’ EBV immune response and perceived fatigue in a community dwelling cohort (n = 864, age 62 ± 10 years old; 49% women) while monitoring brain tissue properties. Fatigue levels are assessed with the established fatigue severity scale, the EBNA-1 and VCA p18 immunoglobulin G (IgG) chronic response – with multiplex serology and the estimates of local brain volume, myelin content, and axonal density - using relaxometry- and multi-shell diffusion-based magnetic resonance imaging (MRI). In our analysis we adjust for the effects of demographic and cardiovascular risk factors, sleep apnea, depression, and polygenic risk score for multiple sclerosis.We demonstrate that EBNA-1 IgG levels are positively associated with perceived levels of fatigue, whilst VCA p18 IgG levels show a positive correlation with myelin content and a negative one with an estimate of axonal g-ratio in male participants. In the context of EBVs immune response, the polygenic risk for multiple sclerosis is not associated with increased fatigue levels, brain myelination or atrophy. Our findings bring empirical evidence about the potential role of EBVs chronic immune response in perceived fatigue and hint towards a protective role of myelination specific for men. They underscore the added value of advanced assessment of brain tissue microstructure in uncovering the mechanisms behind frequent fatigue complaints associated with EBV infection and multiple sclerosis.

BackgroundMetabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression.MethodsWe searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I2value and χ2test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.ResultsFour studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference −0.8 days (95% CI −7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty).ConclusionAcetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required.PROSPERO registration numberCRD42021278757.

Background: Idiopathic membranous nephropathy is a common cause of nephrotic syndrome in adults. The Kidney Disease Improving Global Outcomes guidelines recommend rituximab or cyclophosphamide and steroids, or calcineurin inhibitor-based therapy. However, there have been few or no head-to-head comparisons of the relative efficacy and safety of different immunosuppression regimens. We conducted a network meta-analysis to evaluate the comparative efficacy and safety of available immunosuppression strategies compared to cyclophosphamide in adults with idiopathic membranous nephropathy. Methods: We performed a systematic search of MEDLINE, Embase and CENTRAL for randomized controlled trials in the treatment of adults with idiopathic membranous nephropathy. The primary outcome was complete remission. Secondary outcomes were kidney failure, partial remission, estimated glomerular filtration rate, doubling of serum creatinine, proteinuria, serious adverse events, discontinuation of treatment, serious infection and bone marrow suppression. Results: Cyclophosphamide had uncertain effects on inducing complete remission when compared to rituximab (OR 0.35, CI 0.10–1.24, low certainty evidence), mycophenolate mofetil (OR 1.81, CI 0.69–4.71, low certainty), calcineurin inhibitor (OR 1.26, CI 0.61–2.63, low certainty) or steroid monotherapy (OR 2.31, CI 0.62–8.52, low certainty). Cyclophosphamide had a higher probability of inducing complete remission when compared to calcineurin inhibitor plus rituximab (OR 4.45, CI 1.04–19.10, low certainty). Compared to other immunosuppression strategies, there was limited evidence that cyclophosphamide had different effects on other pre-specified outcomes. Conclusions: The comparative effectiveness and safety of immunosuppression strategies compared to cyclophosphamide is uncertain in adults with idiopathic membranous nephropathy. Graphical abstract:

Cardiovascular disease (CVD) affects more than two-thirds of patients receiving hemodialysis and is the leading cause of death in this population, yet CVD outcomes are infrequently and inconsistently reported in trials in patients receiving hemodialysis. As part of the Standardised Outcomes in Nephrology-Haemodialysis (SONG-HD) initiative, we convened a consensus workshop to discuss the potential use of myocardial infarction and sudden cardiac death as core outcome measures for CVD for use in all trials in people receiving hemodialysis. Eight patients or caregivers and 46 health professionals from 15 countries discussed selection and implementation of the proposed core outcome measures. Five main themes were identified: capturing specific relevance to the hemodialysis population (acknowledging prevalence, risk, severity, unique symptomology, and pathophysiology), the dilemmas in using composite outcomes, addressing challenges in outcome definitions (establishing a common definition and addressing uncertainty in the utility of biomarkers in hemodialysis), selecting a meaningful metric for decision making (to facilitate comparison across trials), and enabling and incentivizing implementation (by ensuring that cardiologists are involved in the development and integration of the outcome measure into registries, trial design, and reporting guidelines). Based on these themes, participants supported the use of myocardial infarction and sudden cardiac death as core outcome measures of CVD to be reported in all hemodialysis trials.

Coronavirus disease 2019 (COVID-19) disproportionately affects people with chronic diseases such as chronic kidney disease (CKD). We assessed the incidence and outcomes of COVID-19 in people with CKD.

Background: Clinical practice guidelines of dietary management are designed to promote a balanced diet and maintain health in patients undergoing haemodialysis but they may not reflect patients’ preferences. We aimed to investigate the consistency between the dietary intake of patients on maintenance haemodialysis and guideline recommendations. Methods: Cross-sectional analysis of the DIET-HD study, which included 6,906 adults undergoing haemodialysis in 10 European countries. Dietary intake was determined using the Global Allergy and Asthma European Network (GA2LEN) Food Frequency Questionnaire (FFQ), and compared with the European Best Practice Guidelines. Consistency with guidelines was defined as achieving the minimum daily recommended intake for energy (≥ 30 kcal/kg) and protein (≥ 1.1 g/kg), and not exceeding the maximum recommended daily intake for phosphate (≤ 1000 mg), potassium (≤ 2730 mg), sodium (≤ 2300 mg) and calcium (≤ 800 mg). Results: Overall, patients’ dietary intakes of phosphate and potassium were infrequently consistent with guidelines (consistent in 25% and 25% of patients, respectively). Almost half of the patients reported that energy (45%) and calcium intake (53%) was consistent with the guidelines, while the recommended intake of sodium and protein was consistent in 85% and 67% of patients, respectively. Results were similar across all participating countries. Intake was consistent with all six guideline recommendations in only 1% of patients. Conclusion: Patients on maintenance haemodialysis usually have a dietary intake which is inconsistent with current recommendations, especially for phosphate and potassium.

•Chronic pain (CP) was associated with cognitive impairment (CI) in cross-sectional studies.•The potential role of CI on CP occurrence remains debated.•The association between CI and CP occurrence was examined prospectively.•Lower cognitive inhibition was associated with a higher risk of developing CP.

Cardiac rehabilitation is a medically supervised program after coronary events that involves exercise and dietary modification. We evaluated the comparative benefits and harms of cardiac rehabilitation strategies via a network meta-analysis.

Background: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. Methods: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. Results: Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63–1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41–2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62–2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02–1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. Conclusions: In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. Trial registration number: NCT01457001 Graphic abstract:

Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the effectiveness of 3 calcimimetic agents using published data.

Few patients affected by gastric cancer peritoneal metastasis (GCPM) are offered locoregional treatment, despite several proof-of-efficacy trials. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged in recent years as a promising tool to control peritoneal carcinomatosis. The combination of PIPAC with systemic chemotherapy may offer a greater clinical benefit than standard treatment alone.

Objectives: Atopic diseases and adverse childhood experiences are associated with neurodevelopmental disorders including developmental stuttering. This study examined the associations between these factors and lifetime prevalence, age of onset, and persistence of developmental stuttering. Methods: Data from 4874 participants (2264 men and 2610 women) from the PsyCoLaus study were used. Prevalence, age of onset, and persistence of stuttering were investigated through univariate, bivariate, and regression analyses. Results: Regression analyses indicated that hay fever, gender, familial aggregation, and fear of punishment by parents were associated with stuttering onset in childhood with odds ratios (OR) of 2–3. Hay fever was associated with an earlier onset of stuttering (difference of 1.5 years, p= .001). Moreover, early onset of stuttering (OR = 0.8, p= .009) and hay fever (OR = 9.2, p= .002) predicted whether stuttering persisted. Conclusions: This study suggests that immunological imbalances related to atopic diseases such as hay fever and adverse childhood experiences are also related to stuttering. The importance of this link is emphasized by the fact that hay fever is also associated with age of onset and persistence of stuttering.

Clinical practice guidelines for dietary intake in hemodialysis focus on individual nutrients. Little is known about associations of dietary patterns with survival. We evaluated the associations of dietary patterns with cardiovascular and all-cause mortality among adults treated by hemodialysis.

L’objectif de cette étude est d’analyser de manière prospective l’association entre les caractéristiques de sommeil subjectives et basées sur la polysomnographie (PSG) et l’incidence de trouble dépressif majeur (TDM).

Herein, we present the case of a 58 y–o Caucasian man with unremarkable cardiovascular history and a strong family history for cancer. He was diagnosed with lung adenocarcinoma IVb (pleura, pleural effusion, lymph nodes), PDL1: 2% TPS and absence of actionable driver mutations on DNA and RNA NGS (only ERBB2 mutation). Started first–line chemotherapy with cisplatin–pemetrexed regimen and immunotherapy with pembrolizumab. He developed common/superficial femoral and popliteal deep vein thrombosis (DVT) and pulmonary embolism (PE). The patient started low–molecular–weight heparin (LMWH) namely enoxaparin 1 mg/kg x 2/d (weight: 65 Kg). After 1 mo, CT showed PE resolution. Due to DVT persistence and patient’s preference for oral administration, LMWH was replaced with direct oral anticoagulant (DOAC) namely edoxaban 60 mg 1 cp/d. After 2 mo, resolution of common femoral and popliteal vein thrombosis with partial recanalization of superficial femoral DVT were detected. However, he developed brain metastases treated with WB radiotherapy. We decided for edoxaban full dose long–term anticoagulant treatment with monthly cardioncological surveillance. After 6 mo since cancer diagnosis, the patient was still adherent to DOAC therapy, although in a maintenance combined regimen pemetrexed–pembrolizumab based, without both drug–drug interactions and brain bleeding.

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In the general population, cognitive impairment is associated with increased mortality, and higher levels of education are associated with lower risks for cognitive impairment and mortality. These associations are not well studied in patients receiving long-term hemodialysis and were the focus of the current investigation.

The journal transferred to Wolters Kluwer effective 1 January 2018 and all Articles in Press will be published by the new publisher as a result. This Article in Press has therefore been withdrawn from this platform. Should you have any queries please contact the Editor-in-Chief, Prof. Abdulmonem Al-Hayani at hayani30@hotmail.com. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

TET methylcytosine dioxygenase 2( TET2) loss-of-function mutations induce a pre-malignant state known as clonal hematopoiesis of indeterminate potential (CHIP). CHIP occurs in approximately 10% of people over 65 years of age and confers a 10-fold greater risk of developing hematological malignancy. Several environmental factors, including radiation, sleep deprivation, atherosclerosis, and diet, have been associated with the expansion of pre-malignant clones in CHIP patients. It has previously been shown that hematopoietic Tet2deficiency in mice triggers a pro-inflammatory state with increased intestinal permeability, gut bacterial translocation, and accelerated clonal expansion. Gut microbes themselves can exert an influence on myeloid leukemia progression through synthesis of compounds including short-chain fatty acids (SCFAs), which promote intestinal barrier integrity. Dietary levels of one-carbon metabolites and cofactors have been found to alter gut microbial composition, affecting SCFA production and intestinal permeability, in disease-free adults. Given the connection between diet, SCFAs and gut permeability, we sought to determine the impact of dietary one-carbon metabolites on gut microbial composition and function in CHIP progression.

BACKGROUND:Guidelines recommend nephrology referral for people with advanced non–dialysis-dependent chronic kidney disease, based mostly on survival benefits seen in retrospective studies of dialysis patients, which may not be generalizable to the broader population with chronic kidney disease. We aimed to examine the association between outpatient nephrology consultation and survival in adults with stage 4 chronic kidney disease.METHODS:We linked population-based laboratory and administrative data from 2002 to 2014 in Alberta, Canada, on adults with stage 4 chronic kidney disease (sustained estimated glomerular filtration rate ≥ 15 to < 30 mL/min/1.73 m2for > 90 d), who had never had kidney failure and had had no outpatient nephrology encounter in the 2 years preceding study entry. Participants who had never had an outpatient nephrology visit before renal replacement treatment were considered “unexposed.” Participants who saw a nephrologist during follow-up were considered “unexposed” before the first outpatient nephrology visit and “exposed” thereafter. The primary outcome was all-cause mortality.RESULTS:Of the 14 382 study participants (median follow-up 2.7 yr), 64% were aged ≥ 80 years, 35% saw a nephrologist and 66% died during follow-up. Nephrology consultation was associated with lower mortality (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82–0.93). The association was strongest in people < 70 years (HR 0.78, 95% CI, 0.65–0.92), progressively weaker with increasing age, and absent in people ≥ 90 years (HR 1.05, 95% CI 0.88–1.25).INTERPRETATION:The survival benefit of nephrology consultation in adults with stage 4 chronic kidney disease may be smaller than expected and appears to attenuate with increasing age. These findings should inform recommendations for nephrology referral considering the advanced age of the patient population meeting current referral criteria.