Comparable kidney transplant outcomes in selected patients with a body mass index ≥ 40: A personalized medicine approach to recipient selection.

INTRODUCTION: Many kidney transplant (KT) centers decline patients with a body mass index (BMI) ≥40 kg/m2 . This study's aim was to evaluate KT outcomes according to recipient BMI. METHODS: We performed a single-center, retrospective review of adult KTs comparing BMI ≥40 patients (n = 84, BMI = 42 ± 2 kg/m2 ) to a matched BMI < 40 cohort (n = 84, BMI = 28 ± 5 kg/m2 ). Patients were matched for age, gender, race, diabetes, and donor type. RESULTS: BMI ≥40 patients were on dialysis longer (5.2 ± 3.2 years vs. 4.1 ± 3.5 years, p = .03) and received lower kidney donor profile index (KDPI) kidneys (40 ± 25% vs. 53 ± 26%, p = .003). There were no significant differences in prevalence of delayed graft function, reoperations, readmissions, wound complications, patient survival, or renal function at 1 year. Long-term graft survival was higher for BMI ≥40 patients, including after adjusting for KDPI (BMI ≥40: aHR = 1.79, 95% CI = 1.09-2.9). BMI ≥40 patients had similar BMI change in the first year post-transplant (delta BMI: BMI ≥ 40 +.9 ± 3.3 vs. BMI < 40 +1.1 ± 3.2, p = .59). CONCLUSIONS: Overall outcomes after KT were comparable in BMI ≥40 patients compared to a matched cohort with lower BMI with improved long-term graft survival in obese patients. BMI-based exclusion criteria for KT should be reexamined in favor of a more individualized approach.

Comparison of Bolus Dosing of Methohexital and Propofol in Elective Direct Current Cardioversion.

Background Methohexital and propofol can both be used as sedation for direct current cardioversion (DCCV). However, there are limited data comparing these medications in this setting. We hypothesized that patients receiving methohexital for elective DCCV would be sedated more quickly, recover from sedation faster, and experience less adverse effects. Methods and Results This was a prospective, blinded randomized controlled trial conducted at a single academic medical center. Eligible participants were randomly assigned to receive either methohexital (0.5 mg/kg) or propofol (0.8 mg/kg) as a bolus for elective DCCV. The times from bolus of the medication to achieving a Ramsay Sedation Scale score of 5 to 6, first shock, eyes opening on command, and when the patient could state their age and name were obtained. The need for additional medication dosing, airway intervention, vital signs, and medication side effects were also recorded. Seventy patients who were randomized to receive methohexital (n=37) or propofol (n=33) were included for analysis. The average doses of methohexital and propofol were 0.51 mg/kg and 0.84 mg/kg, respectively. There were no significant differences between methohexital and propofol in the time from end of injection to loss of conscious (1.4±1.8 versus 1.1±0.5 minutes; P=0.33) or the time to first shock (1.7±1.9 versus 1.4±0.5 minutes; P=0.31). Time intervals were significantly lower for methohexital compared with propofol in the time to eyes opening on command (5.1±2.5 versus 7.8±3.7 minutes; P=0.0005) as well as at the time to the ability to answer simple questions of age and name (6.0±2.6 versus 8.6±4.0 minutes; P=0.001). The methohexital group experienced less hypotension (8.1% versus 42.4%; P<0.001) and less hypoxemia (0.0% versus 15.2%; P=0.005), had lower need for jaw thrust/chin lift (16.2% versus 42.4%; P=0.015), and had less pain on injection compared with propofol using the visual analog scale (7.2±9.7 versus 22.4±28.1; P=0.003). Conclusions In this model of fixed bolus dosing, methohexital was associated with faster recovery, more stable hemodynamics, and less hypoxemia after elective DCCV compared with propofol. It can be considered as a preferred agent for sedation for DCCV. Registration URL: https://www.clinicaltrials.gov/ct; Unique identifier: NCT04187196.

Improving Outcomes after Allograft Nephrectomy through Use of Preoperative Angiographic Kidney Embolization.

BACKGROUND: Allograft nephrectomy (AN) has been associated with considerable perioperative morbidity. We aimed to determine if preoperative angiographic kidney embolization (PAKE) to induce graft thrombosis before AN improves outcomes. STUDY DESIGN: We reviewed adult kidney transplant alone patients who underwent AN at a single center from 2002 to 2020 and compared perioperative outcomes for patients with and without PAKE. RESULTS: Eighty patients underwent AN, including 54 (67.5%) with PAKE before AN and 26 (32.5%) with AN alone. PAKE was associated with significantly reduced blood loss (PAKE: mean 266 ± 292 mL vs AN alone: 495 ± 689 mL; p = 0.04) and reduced transfusion requirements (PAKE: mean 0.5 ± 0.8 packed red blood cell units vs AN alone: 1.6 ± 2.6 units; p = 0.004) despite similar preoperative hemoglobin levels. Mean operating time (PAKE: 142 ± 43 minutes vs AN alone: 202 ± 111 minutes; p = 0.001) and length of hospital stay (PAKE: 4.3 ± 2.0 days vs AN alone: 9.3 ± 9.4 days; p = 0.0003) also favored PAKE, as did the surgical complication rate (PAKE: 6/54 [11%] vs AN alone: 9/26 [35%], p = 0.02). Long-term patient survival after AN was comparable in both groups. CONCLUSIONS: PAKE was associated with lower intraoperative blood loss, fewer transfusions, reduced operating time, shorter length of stay, and fewer surgical complications compared with AN alone at our center.

Simultaneous pancreas-kidney transplantation in Caucasian versus African American patients: Does recipient race influence outcomes?

The influence of African American (AA) recipient race on outcomes following simultaneous pancreas-kidney transplantation (SPKT) is uncertain. METHODS: From 11/01 to 2/19, we retrospectively studied 158 Caucasian (C) and 57 AA patients (pts) undergoing SPKT. RESULTS: The AA group had fewer patients on peritoneal dialysis (30% C vs. 14% AA), more patients with longer dialysis duration (28% C vs. 51% AA), more sensitized (PRA ≥20%) patients (6% C vs. 21% AA), and more patients with pretransplant C-peptide levels ≥2.0 ng/ml (11% C vs. 35% AA, all P < .05). With a mean 9.2 year follow-up, patient survival (65% C vs. 77% AA, P = .098) slightly favored the AA group, whereas kidney (55% C vs. 60% AA) and pancreas (48% C vs. 54% AA) graft survival rates (GSRs) were comparable. Death-censored kidney (71% C vs. 68% AA) and pancreas (both 62%) GSRs demonstrated that death with a functioning graft (DWFG) was more common in C vs. AA patients (23% C vs. 12% AA, P = .10). The incidence of death-censored dual graft loss (usually rejection) was 7% C versus 21% AA (P = .005). CONCLUSIONS: Following SPKT, AA patients are at a greater risk for dual immunological graft loss whereas C patients are at greater risk for DWFG.

Opioid stewardship training during the transition to residency to prepare medical students to recognize and treat opioid use disorder.

Background: With a drastic shortage of addiction medicine specialists-and an ever-growing number of patients with opioid use disorder (OUD)-there is a dire need for more clinicians to feel confident in prevention and management of OUD and obtain a DEA-X waiver to prescribe medications to treat OUD. Here we determine if it is feasible to certify 4th year medical students with DEA-X waiver training as a component of the PROUD (Prevent and Reduce Opioid Use Disorder) curriculum, and if PROUD enhanced preparedness for medical students to manage OUD as interns. Methods: We implemented a sequential mixed-methods IRB approved study to assess feasibility (completing all required components of DEA-X waiver training) and impact of PROUD (measured by knowledge growth, enhancement for residency, and utilization of training during internship). Students completed 11 hours of required OUD training. Quantitative data included pre-/post- knowledge and curriculum satisfaction assessments as well as long-term impact with follow up survey as interns. Qualitative data was collected by survey and semi-structured focus groups. Results: All 120 graduating medical students completed the required components of the curriculum. Knowledge improved on the Provider Clinical Support Services (12.9-17.3, p < 0.0001) and Brief Opioid Overdose Knowledge assessments (10.15-10.81, p < 0.0001). Course satisfaction was high: 90% recommended online modules; 85% recommended training overall. Six qualitative themes emerged: (1) curriculum content was practical, (2) online modules allowed flexibility, (3) in-person seminars ensured authenticity, (4) timing at the transition to residency was optimal, (5) curriculum enhanced awareness and confidence, and (6) training was applicable to future careers. At 3 months, 60% reported using their training during internship; 64% felt more prepared to treat OUD than peers. Conclusions: PROUD trained 4th year medical students in opioid stewardship. As interns, students felt ready to serve as change agents to prevent, diagnose, and treat OUD.

Compromise of cortical proNGF maturation causes selective retrograde atrophy in cholinergic nucleus basalis neurons.

The degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD) contributes to cognitive impairment. Nerve growth factor (NGF) secreted in the cerebral cortex is necessary for the phenotypic maintenance of BFCNs. AD is associated with disturbances in NGF metabolism, leading to reduced mature NGF levels and to an accumulation of its precursor, proNGF. We previously described that, in rats, this neurotrophic imbalance is sufficient to induce a loss of cortical cholinergic synapses. In the present study, we investigated whether this neurotrophic imbalance can produce an AD-like retrograde degeneration of BFCNs. Using a combination of retrograde labeling and quantitative cell imaging, we could demonstrate that inhibiting cortical proNGF maturation results in an atrophy of BFCNs, a downregulation of the NGF receptors p75 neurotrophin receptor and tropomyosin receptor kinase A, and a reduction in choline acetyltransferase protein expression. The transient increase in sortilin levels and the sustained colocalization with p75 neurotrophin receptor suggest a participation of proNGF in this degenerative process. This study demonstrates that impairments in the extracellular maturation of proNGF are sufficient to cause a somatodendritic retrograde degeneration of the BFCNs.

Rescue of Early bace-1 and Global DNA Demethylation by S-Adenosylmethionine Reduces Amyloid Pathology and Improves Cognition in an Alzheimer's Model.

General DNA hypomethylation is associated with Alzheimer's disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities. To assess a possible human significance of findings, we examined the methylation at 12 CpGs sites in the bace-1 promoter, using genome-wide DNA methylation data from 740 postmortem human brains. Thus, we found significant associations of bace-1 promoter methylation with ß-amyloid load among persons with AD dementia, and PHFtau tangle density. Our results support a plausible causal role for the earliest amyloid beta accumulation to provoke DNA hypomethylation, influencing AD pathological outcomes.

Risk Factor Profile in Parkinson's Disease Subtype with REM Sleep Behavior Disorder.

BACKGROUND: Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. OBJECTIVE: To define risk factors for PD in patients with or without associated RBD. METHODS: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. RESULTS: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). CONCLUSION: The RBD-specific subtype of PD may also have a different risk factor profile.