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INTRODUCTION Biologic sex is an important determinant of health and disease. Over the past several decades, research has revealed sex differences in the epidemiology, risk, clinical manifestations, pathophysiology, and progression [...]

Introduction: Acute kidney injury (AKI) is a frequent early complication post hematopoietic stem cell transplant (HSCT), associated with high morbidity and mortality. Cord blood transplant (CBT) recipients are potentially exposed to more nephrotoxic insults, compared to patients undergoing HSCT from other donor sources. We aimed to identify risk factors for AKI in patients undergoing CBT. We also aimed to identify the impact of AKI on chronic kidney disease (CKD) and survival outcomes by one-year post-CBT. Methods: Adults and children who underwent a first CBT at our Institution were retrospectively evaluated. AKI was staged according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Cox regression models were used to estimate the association of demographic factors and post-CBT parameters with the causespecific hazard of AKI. Results: We identified 276 patients. Median age was 32 years, 28% (77/276) were children (<18 years) and 129 (47%)were white. A myeloablative conditioning regimen was administered to 243 patients (88%) and 248 (90%) received cyclosporine for GVHD prophylaxis. One-hundred and eighty-six patients (67%) developed AKI by day 60 post-transplant, with 72 (26%) developing severe AKI (stage 2 and 3). In a multivariable analysis, each increase in bilirubin level of 1 mg/dL was associated with a 23% increase in the risk of severe AKI (adjusted HR 1.23, 95% CI 1.13 - 1.34, p<.0001). Conversely, systemic steroid administration appeared to be protective of severe AKI (unadjusted HR 0.36, 95% CI 0.18 - 0.72, p=.004) in a univariate model. Two-hundred-forty-seven patients were evaluable at the one-year time point. Among those, 100 patients (40%) developed CKD one-year post-CBT. Severe AKI was associated with a higher hazard of non-relapse mortality (adjusted HR=3.26, 95% CI 1.65-6.45, p=.001) and overallmortality (adjusted HR=2.28, 95% CI 1.22-4.27, p=.01). Discussion: AKI is a frequent complication after CBT and is associated with worse outcomes. Questions remain as to the mechanism of the protective role of steroids on kidney function in the setting of CBT. [ABSTRACT FROM AUTHOR]

Background: Repeated binge drinking is associated with reduced microvascular function. However, microvascular responses to pathophysiological stimulus such as high pressure as well as potential mechanisms that underlie binge‐induced microvascular dysfunction are unknown. Therefore, using an ex vivo experimental model, we examined microvascular responses following a brief period of high intraluminal pressure in isolated arterioles from young adults who have a history of repeated binge drinking. In addition, we examined whether the application of the endothelial nitric oxide synthase cofactor, tetrahydrobiopterin, would restore microvascular function in response to flow and high intraluminal pressure in young adult binge drinkers. Methods: Isolated subcutaneous adipose arterioles were obtained from young adult binge drinkers (BD; n = 14), moderate drinkers (MODs; n = 10), and alcohol abstainers (ABs; n = 12; mean age: 23.7 ± 0.5 years; and body mass index: 23.4 ± 0.4 kg/m2). Arteriolar flow‐induced dilation (FID, pressure gradient: ∆10 to 100 cm H2O) was measured before and after acute high intraluminal pressure with and without tetrahydrobiopterin. Results: Before high pressure, FID at Δ60 and Δ100 cm H2O pressure gradient in BDs was 14% lower and 18% lower, respectively, than ABs (p < 0.05), while MODs and ABs had similar FID across all pressure gradients (p ≥ 0.2). After high pressure, FID in BDs was further reduced by 10% (p < 0.0005) and this impairment was ameliorated by the treatment of tetrahydrobiopterin (4 to 26% higher, p < 0.005). In contrast, FID after high pressure did not change in MODs and ABs (p ≥ 0.5). Conclusions: Microvascular dysfunction in young adult binge drinkers may be exacerbated with acute pathophysiological stimulus. These binge‐induced dysfunctions may be reversed by tetrahydrobiopterin, which suggests a role of oxidative stress and/or uncoupled endothelial nitric oxide synthase in binge drinking. [ABSTRACT FROM AUTHOR]

Simple Summary: Leukemia, the most common form of childhood cancer, accounts for about 30 percent of all cancers that affect children and young adults. Although pain is a common and distressing symptom of childhood leukemia, evidence-based guidance regarding assessment and management is lacking. With 6 international multidisciplinary healthcare professionals, we aimed to review current evidence in literature, addressing diagnosis, assessment and pharmacological management of the most common leukemia-related pain syndromes in children, including cancer-related painful neuropathies and osteonecrosis. We also focus on the impact of pain on quality of life of childhood leukemia patients and the most common pain medications used in the pediatric population, with differences in their utilizations across countries. Pain is one of the most common symptoms in children suffering from leukemia, who are often misdiagnosed with other childhood painful diseases such as juvenile idiopathic arthritis. Corticosteroid-induced osteonecrosis (ON) and vincristine-induced peripheral neuropathy (VIPN) are the most common painful manifestations. Additionally, ongoing pain may continue to impact quality of life in survivorship. This narrative review focuses on the pathophysiological mechanisms of pain in childhood leukemia and current available indications for analgesic treatments. Pain management in children is often inadequate because of difficulties in pain assessment, different indications across countries, and the lack of specific pediatric trials. Analgesic drugs are often prescribed off-label to children by extrapolating information from adult guidelines, with possible increased risk of adverse events. Optimal pain management should involve a multidisciplinary team to ensure assessment and interventions tailored to the individual patient. [ABSTRACT FROM AUTHOR]