Hickson, LaTonya J.

AbstractToxic epidermal necrolysis (TEN) is a rare but often lethal drug reaction involving the skin. Treatment is often centered around suppurative care, and the mortality rate remains unacceptably high, although the clinical and epidemiological features of TEN have been well documented for decades. Recent studies have placed an emphasis on certain medications in the pathophysiology of severe TEN, and our colleagues previously reported several cases of clinical improvement in TEN patients following hemodialysis. Here, we discuss the major considerations for initiating dialysis in TEN patients. By doing so, we hope to encourage others to explore this potential avenue for treating TEN, one of the most serious medical emergencies in the field of dermatology.

ABSTRACT Background The optimal duration of antifrailty interventions and how best to deliver them to patients with chronic kidney disease (CKD) is unknown. The aim of this study was to examine the safety, feasibility and preliminary efficacy of a 4-week supervised exercise intervention on frailty in patients with CKD. Methods We conducted a prospective feasibility study involving patients with ≥stage 3 CKD (1 patient with stage 3 CKD, 7 patients with stage 4 CKD and 17 patients with stage 5 CKD) who were either frail or prefrail according to the physical frailty phenotype and/or had a Short Physical Performance Battery (SPPB) score ≤10. The exercise intervention consisted of two supervised outpatient sessions per week for 4 weeks (eight total sessions). Frailty and other study measures were assessed at baseline and after 4 weeks of exercise. Results Of the 34 participants who completed the baseline assessment and were included in the analyses, 25 (73.5%) completed the 4-week assessment. Overall, 64.0% of patients were on dialysis and 64.0% had diabetes mellitus. After 4 weeks of exercise, frailty prevalence, total SPPB scores and energy/fatigue scores improved. No adverse study-related outcomes were reported. Conclusions The 4 weeks of supervised exercise was safe, was associated with an excellent completion rate and improved frailty parameters in CKD patients with CKD. This study provides important preliminary data for a future larger prospective randomized study. Clinical Trial.gov registration: NCT03535584

Renal diseases pose a significant socio‐economic burden on healthcare systems. The development of better diagnostics and prognostics is well‐recognized as a key strategy to resolve these challenges. Central to these developments are MRI biomarkers, due to their potential for monitoring of early pathophysiological changes, renal disease progression or treatment effects. The surge in renal MRI involves major cross‐domain initiatives, large clinical studies, and educational programs. In parallel with these translational efforts, the need for greater (patho)physiological specificity remains, to enable engagement with clinical nephrologists and increase the associated health impact. The ISMRM 2022 Member Initiated Symposium (MIS) on renal MRI spotlighted this issue with the goal of inspiring more solutions from the ISMRM community. This work is a summary of the MIS presentations devoted to: 1) educating imaging scientists and clinicians on renal (patho)physiology and demands from clinical nephrologists, 2) elucidating the connection of MRI parameters with renal physiology, 3) presenting the current state of leading MR surrogates in assessing renal structure and functions as well as their next generation of innovation, and 4) describing the potential of these imaging markers for providing clinically meaningful renal characterization to guide or supplement clinical decision making. We hope to continue momentum of recent years and introduce new entrants to the development process, connecting (patho)physiology with (bio)physics, and conceiving new clinical applications. We envision this process to benefit from cross‐disciplinary collaboration and analogous efforts in other body organs, but also to maximally leverage the unique opportunities of renal physiology.Level of Evidence1Technical Efficacy Stage2

Abstract Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each). ARAS pigs exhibited elevated serum cholesterol, serum creatinine and renal artery stenosis, with a concomitant decrease in renal blood flow (RBF) and increased blood pressure (BP) compared to healthy pigs. Renal artery injection of either autologous Nx or Hx AMSCs improved diastolic BP, reduced kidney tissue fibrosis, and inflammation (CD3+ T-cells) in ARAS pigs. In addition, renal medullary hypoxia significantly lowered with Nx but not Hx AMSC treatment. Mechanistically, levels of epigenetic 5hmC marks (which reflect gene activation) estimated using DNA immunoprecipitation technique were elevated in profibrotic and inflammatory genes in ARAS compared with normal AMSCs. HPC significantly reduced 5hmC levels in cholesterol biosynthesis and oxidative stress response pathways in ARAS AMSCs. Thus, autologous AMSCs improve key renovascular parameters and inflammation in ARAS pigs, with HPC mitigating pathological molecular effects on inflammatory and profibrotic genes which may play a role in augmenting regenerative capacity of AMSCs.

Background During the menopause transition, women are at an increased risk of developing hypertension, which is a key marker of cardiovascular disease (CVD). Although historically hot flashes have been considered a quality‐of‐life issue, emerging data provides a link between hot flashes and risk of CVD. Poor renal function is suggested to be one of the key physiological contributors to increased risk of hypertension and CVD among women with hot flashes. Thus, the aim of this study was to characterize the relationship between hot flashes and renal function in peri‐ and post‐menopausal women using a retrospective chart review. We hypothesized that women with hot flashes would demonstrate reduced renal function compared to women without hot flashes. Methods We performed a chart review using serum creatinine and estimated glomerular filtration rate (eGFR) as proxies to assess renal function. Electronic health records for Mayo Clinic patients across multiple sites were abstracted for female patients who were diagnosed with peri‐ or post‐menopause between 2016 and 2020, between 45 and 55 years of age, and had available creatinine laboratory test results. Data regarding demographics, anthropometrics, systemic blood pressure, menopausal stage, occurrence of hot flashes, and comorbidities were extracted from electronic health records. Differences between women with and without hot flashes were evaluated using two‐tailed, independent samples t‐tests. We completed a univariate analysis of variance testing the main effects of menopausal status (peri‐ or post‐menopausal) and presence of hot flashes (yes or no). Given the potential modifying effects of menopause, analytical models were performed in duplicate with and without models separated by menopausal status (peri‐and post‐menopause). Results Data from 83 medical charts were assessed, including 57 women with hot flashes and 26 women without hot flashes. Without separating by menopausal status, there were no hot flash‐related differences in age (51 ± 3 vs. 51 ± 3 years, P = 0.64) or body mass index (30 ± 7 vs. 33 ± 11, P = 0.19) between women with and without hot flashes. Additionally, there were no hot flash‐related differences in metrics of blood pressure, including systolic (120 ± 13 vs. 125 ± 20, P = 0.19), diastolic (75 ± 11 vs. 77 ± 13, P = 0.54), and mean arterial pressure (90 ± 11 vs. 92 ± 14, P = 0.62). There were also no hot flash‐related differences in indicators of renal function, including creatinine (0.8 ± 0.1 vs. 0.8 ± 0.2, P = 0.65) and eGFR (88 ± 11 vs. 85 ± 16, P = 0.36). The clinical characteristics of the perimenopausal versus postmenopausal women are summarized in Table 1 by hot flash status . There were no main effects of hot flash or menopausal status on creatinine (menopausal stage: p=0.810, hot flash status: p=0.659, interaction effect: p=0.983) or eGFR (menopausal stage: p=0.508, hot flash status: p=0.405, interaction effect: p=0.834). Conclusions In this retrospective chart review of peri‐ and post‐menopausal women, there were no differences in systemic blood pressure or renal function between groups. Future investigations may include longitudinal markers of renal function and metrics describing frequency and severity of hot flashes.