Citations

Background and Objectives: The aim of our study was to categorize very highly sensitized kidney transplant recipients with pre-transplant panel reactive antibody (PRA) ≥ 98% using an unsupervised machine learning approach as clinical outcomes for this population are inferior, despite receiving increased allocation priority. Identifying subgroups with higher risks for inferior outcomes is essential to guide individualized management strategies for these vulnerable recipients. Materials and Methods: To achieve this, we analyzed the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database from 2010 to 2019 and performed consensus cluster analysis based on the recipient-, donor-, and transplant-related characteristics in 7458 kidney transplant patients with pre-transplant PRA ≥ 98%. The key characteristics of each cluster were identified by calculating the standardized mean difference. The post-transplant outcomes were compared between the assigned clusters. Results: We identified two distinct clusters and compared the post-transplant outcomes among the assigned clusters of very highly sensitized kidney transplant patients. Cluster 1 patients were younger (median age 45 years), male predominant, and more likely to have previously undergone a kidney transplant, but had less diabetic kidney disease. Cluster 2 recipients were older (median 54 years), female predominant, and more likely to be undergoing a first-time transplant. While patient survival was comparable between the two clusters, cluster 1 had lower death-censored graft survival and higher acute rejection compared to cluster 2. Conclusions: The unsupervised machine learning approach categorized very highly sensitized kidney transplant patients into two clinically distinct clusters with differing post-transplant outcomes. A better understanding of these clinically distinct subgroups may assist the transplant community in developing individualized care strategies and improving the outcomes for very highly sensitized kidney transplant patients.

Transient global amnesia (TGA) is a neurological condition characterized by temporary memory loss and classically associated with a reversible unilateral punctate focus of restricted diffusion in the cornu ammonis 1 (CA1) region of the hippocampus. Historically, the lesions were considered to be transient in nature with no long-term imaging abnormality. However, more recent studies have challenged the concept that there are no long-term neurological sequelae. In line with this evidence, we explore the role of ultra-high-resolution imaging using 7 Tesla MRI to evaluate for long-term imaging abnormalities in a 63-year-old woman with a typical clinical course and acute TGA imaging findings. The 7 Tesla MRI revealed a residual lesion on susceptibility-weighted imaging (SWI) with evidence of gliosis and volume loss at the site of the acute lesion in CA1 eight months after the acute episode. This case challenges the traditional mantra of TGA as a fully reversible condition with no long-term imaging findings, suggesting the need for further research using ultra-high-field MRI to determine TGA's potential long-term imaging sequelae and any association with neurocognitive sequelae.

Pre-metabolic syndrome (pre-MetS) may represent the best transition phase to start treatments aimed at reducing cardiometabolic risk factors of MetS. In this study, we investigated the effects of the marine microalga Tisochrysis lutea F&M-M36 (T. lutea) on cardiometabolic components of pre-MetS and its underlying mechanisms. Rats were fed a standard (5% fat) or a high-fat diet (20% fat) supplemented or not with 5% of T. lutea or fenofibrate (100 mg/Kg) for 3 months. Like fenofibrate, T. lutea decreased blood triglycerides (p < 0.01) and glucose levels (p < 0.01), increased fecal lipid excretion (p < 0.05) and adiponectin (p < 0.001) without affecting weight gain. Unlike fenofibrate, T. lutea did not increase liver weight and steatosis, reduced renal fat (p < 0.05), diastolic (p < 0.05) and mean arterial pressure (p < 0.05). In visceral adipose tissue (VAT), T. lutea, but not fenofibrate, increased the β3-adrenergic receptor (β3ADR) (p < 0.05) and Uncoupling protein 1 (UCP-1) (p < 0.001) while both induced glucagon-like peptide-1 receptor (GLP1R) protein expression (p < 0.001) and decreased interleukin (IL)-6 and IL-1β gene expression (p < 0.05). Pathway analysis on VAT whole-gene expression profiles showed that T. lutea up-regulated energy-metabolism-related genes and down-regulated inflammatory and autophagy pathways. The multitarget activity of T. lutea suggests that this microalga could be useful in mitigating risk factors of MetS.

Prior to the 1990s, prolonged postoperative intubation and admission to the intensive care unit was considered the standard of care following liver transplantation. Advocates of this practice speculated that this time allowed patients to recover from the stress of major surgery and allowed their clinicians to optimize the recipients’ hemodynamics. As evidence in the cardiac surgical literature on the feasibility of early extubation grew, clinicians began applying these principles to liver transplant recipients. Further, some centers also began challenging the dogma that patients need to be cared for in the intensive care unit following liver transplantation and instead transferred patients to the floor or stepdown units immediately following surgery, a technique known as “fast-track” liver transplantation. This article aims to provide a history of early extubation for liver transplant recipients and offer practical advice on how to select patients that may be able to bypass the intensive care unit and be recovered in a non-traditional manner.

ABSTRACTExtreme‐intensity exercise is described by W′ext (analogous to J′ for isometric exercise) that is smaller than W′ of severe‐intensity exercise (W′sev) in males. Sex differences in exercise tolerance appear to diminish at near‐maximal exercise, however, there is evidence of greater contributions of peripheral fatigue (i.e. potentiated twitch force; Qpot) in males during extreme‐intensity exercise. Therefore, the current study tested the hypotheses that J′ext would not be different between males and females, however, males would exhibit a greater reduction in neuromuscular function (i.e. maximal voluntary contraction, MVC; Qpot) following extreme‐intensity exercise. Seven males and 7 females completed three severe‐ (Tlim: 2–4 min, S3; 5–8 min, S2; 9–15 min, S1) and three extreme‐intensity (70, 80, 90%MVC) knee‐extension bouts. MVC and Qpot relative to baseline were compared at task failure and at 150 s of recovery. J′ext was significantly less than J′sev in males (2.4 ± 1.2kJ vs 3.9 ± 1.3kJ; p = 0.03) and females (1.6 ± 0.8kJ vs 2.9 ± 1.7kJ; p = 0.05); however, there were no sex differences in J′ext or J′sev. MVC (%Baseline) was greater at task failure following extreme‐intensity exercise (76.5 ± 20.0% vs 51.5 ± 11.5% in males, 75.7 ± 19.4% vs 66.7 ± 17.4% in females), but was not different at 150 s of recovery (95.7 ± 11.8% in males, 91.1 ± 14.2% in females). Reduction in Qpot, however, was greater in males (51.9 ± 16.3% vs 60.6 ± 15.5%) and was significantly correlated with J′ext (r2 = 0.90, p < 0.001). Although there were no differences in the magnitude of J′ext, differences in MVC and Qpot are evidence of sex‐specific responses and highlight the importance of appropriately characterizing exercise intensity regarding exercise domains when comparing physiological responses in males and females.Highlights We have previously shown evidence that extreme‐intensity dynamic exercise is described by W′ext in males and smaller than W′sev. We currently tested for potential sex differences in J′ext (isometric analogue to W′) and neuromuscular responses (i.e. maximal voluntary contraction, MVC; potentiated twitch force, Qpot) during extreme‐intensity exercise. J′ext and extreme‐intensity exercise tolerance was not different between males and females. The reduction in MVC was not different across extreme‐intensity exercise across males and females, whereas the reduction in Qpot was greater in males following all extreme‐intensity exercises, although not after exercise at 90%MVC. Together, although extreme‐intensity exercise tolerance is not different, these data highlight differences in the contributing mechanisms of fatigue during severe‐ and extreme‐intensity exercise between males and females.

This commentary is on the original article by Chiron et al on pages 1607–1616 of this issue.

OBJECTIVE There are no commercially available hybrid closed-loop insulin delivery systems customized to achieve pregnancy-specific glucose targets in the U.S. This study aimed to evaluate the feasibility and performance of at-home use of a zone model predictive controller–based closed-loop insulin delivery system customized for pregnancies complicated by type 1 diabetes (CLC-P). RESEARCH DESIGN AND METHODS Pregnant women with type 1 diabetes using insulin pumps were enrolled in the second or early third trimester. After study sensor wear collecting run-in data on personal pump therapy and 2 days of supervised training, participants used CLC-P targeting 80–110 mg/dL during the day and 80–100 mg/dL overnight running on an unlocked smartphone at home. Meals and activities were unrestricted throughout the trial. The primary outcome was the continuous glucose monitoring percentage of time in the target range 63–140 mg/dL versus run-in. RESULTS Ten participants (HbA1c 5.8 ± 0.6%) used the system from mean gestational age of 23.7 ± 3.5 weeks. Mean percentage time in range increased 14.1 percentage points, equivalent to 3.4 h per day, compared with run-in (run-in 64.5 ± 16.3% versus CLC-P 78.6 ± 9.2%; P = 0.002). During CLC-P use, there was significant decrease in both time over 140 mg/dL (P = 0.033) and the hypoglycemic ranges of less than 63 mg/dL and 54 mg/dL (P = 0.037 for both). Nine participants exceeded consensus goals of above 70% time in range during CLC-P use. CONCLUSIONS The results show that the extended use of CLC-P at home until delivery is feasible. Larger, randomized studies are needed to further evaluate system efficacy and pregnancy outcomes.