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Systemic inflammation and uremic toxins (UT) determine the increased cardiovascular mortality observed in chronic hemodialysis (HD) patients. Among UT, the adipokine Chemerin induces vascular dysfunction by targeting both endothelial and vascular smooth muscular cells (EC and VSMC). As Citrate anion modulates oxidative metabolism, systemic inflammation and vascular function, we evaluated whether citrate-buffered dialysis improves HD efficiency, inflammatory parameters and chemerin-mediated microvascular injury. 45 patients were treated in sequence with acetate, citrate and, again, acetate-buffered dialysis solution (3 months per interval). At study admission and after each treatment switch, we evaluated dialysis efficacy and circulating levels of chemerin and different inflammatory biomarkers. In vitro , we stimulated EC and VSMC with patients’ plasma and we investigated the role of chemerin as UT. Citrate dialysis increased HD efficacy and reduced plasma levels of CRP, fibrinogen, IL6 and chemerin. In vitro , patients’ plasma induced EC and VSMC dysfunction. These effects were reduced by citrate-buffered solutions and paralleled by the decrease of chemerin levels. Consistently, chemerin receptor knockdown reduced EC and VSMC dysfunction. In conclusion, Switching from acetate to citrate improved dialysis efficacy and inflammatory parameters; in vitro , chemerin-induced EC and VSMC injury were decreased by using citrate as dialysis buffer.

Background Acute kidney injury (AKI) during hospitalization is associated with increased complications and mortality. Despite efforts to standardize AKI management, its recognition in clinical practice is limited. Methods To assess and characterize different patterns of AKI diagnosis, we collected clinical data, serum creatinine (sCr) levels, comorbidities and outcomes from adult patients using the Hospital Discharge Form (HDF). AKI diagnosis was based on administrative data and according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria by evaluating sCr variations during hospitalization. Additionally, patients were categorized based on the timing of AKI onset. Results Among 56 820 patients, 42 900 (75.5%) had no AKI, 1893 (3.3%) had AKI diagnosed by sCr changes and coded in the HDF (full-AKI), 2529 (4.4%) had AKI reported on the HDF but not meeting sCr-based criteria (HDF-AKI) and 9498 (16.7%) had undetected AKI diagnosed by sCr changes but not coded in the HDF (KDIGO-AKI). Overall, AKI incidence was 24.5%, with a 68% undetection rate. Patients with KDIGO-AKI were younger and had a higher proportion of females, lower comorbidity burden, milder AKI stages, more frequent admissions to surgical wards and lower mortality compared with full-AKI patients. All AKI groups had worse outcomes than those without AKI, and AKI, even if undetected, was independently associated with mortality risk. Patients with AKI at admission had different profiles and better outcomes than those developing AKI later. Conclusions AKI recognition in hospitalized patients is highly heterogeneous, with a significant prevalence of undetection. This variability may be affected by patients' characteristics, AKI-related factors, diagnostic approaches and in-hospital patient management. AKI remains a major risk factor, emphasizing the importance of ensuring proper diagnosis for all patients.

Acute Kidney Injury (AKI) is a common condition with significant impact on morbidity, mortality, and healthcare costs. This study explores the epidemiology of AKI, highlighting key factors and outcomes. In a retrospective study we evaluated patients admitted to hospital from 2016 to 2019, excluding those with pre-existing chronic kidney disease (CKD) stages 4–5. Data were extracted from hospital databases, with AKI defined by changes in serum creatinine (sCr) according to KDIGO criteria. Additionally, AKI was classified as “de novo” or as AKI on CKD in the subgroup of patients with available pre-hospital eGFR. Outcomes included mortality, hospital stay duration (LOS), AKI recovery, and persistent AKI. Of 87,087 patients, 17,946 (20.6%) developed AKI. AKI patients were older, with more comorbidities, and had significantly higher mortality (17.7% vs. 4.3%, p < 0.001). AKI was associated with in-hospital mortality (HR 1.23, 95% CI 1.16–1.30), longer LOS, and ICU admission. Mortality increased with AKI severity. Considering the 34,285 patients (39% of the total cohort) with pre-hospital eGFR, AKI occurred in 17.3% patients without previous CKD and in 31.1% of patients with previous CKD. These patients presented higher incidence of ICU admission and mortality. Additionally, 17.6% of AKI patients had persistent kidney dysfunction at discharge, often requiring extended hospitalization and ICU care. The substantial impact of AKI on both short- and potentially long-term health emphasizes the importance of early detection, personalized management, and structured follow-up to enhance outcomes and reduce CKD progression risk.

Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities. The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury. CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration. The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

Acute kidney injury (AKI) is characterized by an increasing incidence and poor outcomes in both developed and undeveloped countries. AKI is also acquiring importance in the setting of kidney transplantation (KT): besides all the classical forms of AKI that KT patients may undergo, several transplant-specific injuries can also lead to the loss of graft function. The mechanisms of tissue damage in native and grafted kidneys share several common pathogenic elements. Since appropriate therapeutic treatments are still lacking—probably due to the disease complexity—clinicians are forced to provide only supportive care. In this composite scenario, cell therapies represent an evolving frontier for AKI treatment in native and transplanted kidneys: ex-vivo manipulated stem or immune cells are able to counteract renal dysfunction by a wide range of biological mechanisms. In this review, we will discuss the potential applications of cell therapies in AKI and KT by analyzing the available clinical data and the most promising experimental prospects from a “bench to bedside” perspective.

Bi et al. demonstrated that MSC conditioned medium is effective as stem cell infusion in IRI-AKI [22]; exploiting a similar model, it has been demonstrated that MSC release several vasculotrophic factors including vascular endothelial growth factor (VEGF)-alpha and hepatocyte growth factor (HGF) [23]. [...]heat-inactivated MSC (i.e. unable to secrete paracrine factors) still modulated monocyte function and induced regulatory cytokine release similarly to normal MSC; nevertheless inactivated cells were not able to influence the B- and T-lymphocyte fate [25]. [...]immune regulatory cells are a further way to achieve immune tolerance in transplantation, and several protocols are available to induce ex vivo T-, B-, and M-reg cells; the clinical literature is growing in this field with encouraging data coming from different transplant models such as liver, kidney and hematopoietic cells.

Background Ovarian cancer (OC) is characterized by a low response rate and high frequency of resistance development to currently available treatments. The therapeutic potential of histone methyltransferase DOT1L inhibitor in OC cells has been demonstrated, but optimal efficacy and safety of this targeted therapy approach still require improvement. We set forth to evaluate if this problem can be overcome by combinatorial targeting of this epigenetic modifier and menin, one of its functional partners in chromatin. Methods siRNA-mediated gene knock-down and pharmacological inhibition of menin, a key component of the MLL/SET1 complex and a fitness gene in OC cells, coupled to cell proliferation assays on a panel of high grade serous OC cell lines, including chemotherapy-sensitive and -resistant clones, were applied in order to evaluate how depletion or blockade of this enzyme influences growth and viability of OC cells. RNA sequencing was applied to identify menin target genes and pathways, and the effects of combined inhibition of menin and DOT1L on growth and transcriptome of these OC models were evaluated. Results Silencing and pharmacological inhibition of menin exert antiproliferative effects in all OC cells tested and, in PEO1 and PEO4 cells, a profound impact on transcriptome via down-regulation of cell cycle regulatory pathways, aryl hydrocarbon receptor, MYC and KRAS signalling. We demonstrated association of menin and DOT1L in OC cells and identified a subset of genes co-regulated by the two factors. Interestingly, co-treatment with DOT1L and menin pharmacological inhibitors exerts an additive effect on growth inhibition on chemotherapy-sensitive and -refractory OC cells mediated by transcriptome changes controlled by menin and DOT1L activities. Conclusion These results indicate that menin functionally cooperates with DOT1L in OC cells modulating transcription of genes involved in key cellular functions including, among others, cell proliferation and survival, that are strongly affected by combined inhibition of these two epigenetic regulators, suggesting that this may represent a novel therapeutic strategy for chemotherapy-resistant OCs. Trial registration NA; The manuscript does not contain clinical trials.

Abstract OBJECTIVES Catamenial pneumothorax is an underdiagnosed condition, despite accounting for up to 35% of spontaneous pneumothoraces in young women. This study aims to delineate the most appropriate surgical treatment comparing a 15-year experience of five European centres. METHODS A European multicentre retrospective cohort study was conducted. We evaluated all the spontaneous pneumothoraces occurring in women of childbearing age. We included all the cases with evidence of diaphragmatic alterations. Thirty-six patients were included and evaluated. We compared their surgical treatment, in-hospital variables and rate of recurrence. RESULTS The surgical approach was thoracoscopic for 34 patients and open for 2. Thirty patients presented diaphragmatic involvement. According to the diaphragmatic treatment the patients were divided into three groups: prosthetic replacement (19; 15 synthetic grafts and 5 biological); surgical repair (6; 4 direct sutures and 2 stapling); and no treatment (11). All patients received pleurodesis (6 mechanical, 15 chemical and 3 a combination of these). Median follow-up was 54 months, during which 15 recurrences occurred. Despite no statistically significant difference between the treatment groups, the relapse rate slightly favoured the prosthetic group (26.3% vs 56.8%, P = 0.09) and direct diaphragmatic repair had a significantly higher conversion rate compared with prosthetic replacement (21% vs 100%, P = 0.004). Notably, none of the patients with biological mesh relapsed during the follow-up. CONCLUSIONS Our data suggest treating all diaphragmatic defects with thorough attention. Moreover, prosthetic replacement resulted in a safe and effective procedure and biological mesh should be preferred in this setting, showing excellent postoperative and long-term results. CLINICAL REGISTRATION NUMBER Our institutional review board granted approval and waived the requirement for specific informed consent for this retrospective analysis. Catamenial pneumothorax (CP) is an intriguing clinical entity characterized by the recurrent and spontaneous accumulation of air within the pleural space, affecting women of reproductive age. Graphical Abstract