The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed “long COVID” or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, “brain fog”, headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.

With the demand for heart transplantation continuing to outpace the available donor organs, previously underutilized donors are now being reconsidered. We sought to describe the emerging techniques and outcomes of expanded criteria heart transplantation. A comprehensive review of the recent literature concerning expanded donor selection in heart transplantation was performed using the PubMed MEDLINE database. To characterize trends in transplant practice, the United Network for Organ Sharing (UNOS/OPTN) registry was queried for all adult isolated heart transplants since 2010, and data regarding transplant parameters was collected. Donation after cardiac death (DCD), DCD with normothermic regional perfusion, increased ischemic time, hepatitis C positive donor organs, HIV-positive donor organs, and extended criteria donors were identified as promising avenues currently being explored to expand the number of donor organs. The utilization of various expanded criteria for heart transplantation was summarized since 2010 and showed an increasing use of these donor organs, contributing to the overall increasing frequency of heart transplantation. Utilization of expanded criteria for donor selection in heart transplantation has the potential to increase the supply of donor organs with comparable outcomes in selected recipients.

Revisions to the heart allocation criteria in 2018 motivated an increased use of extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation. Studies have demonstrated inferior post-transplant outcomes in patients bridged with ECMO but do not account for underlying diagnosis. Our objective was to elucidate the differential impact of ECMO on outcomes by heart failure (HF) etiology. The United Network of Organ Sharing database was queried for adults who underwent isolated heart transplantation after October 2018. Patients were stratified by ECMO utilization at the time of transplantation and then by HF etiology. After baseline statistical comparisons, survival analysis relied on Kaplan-Meier estimates and Cox proportional models. A total of 13,203 patients were included, of whom 761 (5.8%) were supported with ECMO. ECMO patients were younger (48 vs 54 years, p < 0.001), less likely to have diabetes (24% vs 30%, p < 0.001), smoke cigarettes (31% vs 41%, p < 0.001), or have prior cardiac surgery (29% vs 36%, p < 0.001), more likely to require dialysis (20% vs 5%, p < 0.001), and spent fewer days on the waitlist (59 vs 190, p < 0.001). After adjustment, ECMO was associated with increased mortality (hazard ratio 1.85, p < 0.001) in the full cohort. After incorporating HF etiology, this increased mortality risk persisted in all subgroups except restrictive cardiomyopathy and congenital heart disease (CHD). Our findings illustrate that HF etiology is associated with differing outcomes when bridging with ECMO. ECMO patients with restrictive cardiomyopathy or CHD did not have increased mortality risk. With ECMO utilization increasing, these data are hypothesis-generating and serve as a basis for further studies.

A synthetic route to orthogonally protected, enantiomerically pure 2-substituted piperazines is described. Starting from α-amino acids, within four steps chiral 2-substituted piperazines are obtained. The key transformation involves an aza-Michael addition between an orthogonally bis-protected chiral 1,2-diamine and the in situ generated vinyl diphenyl sulfonium salt derived from 2-bromoethyl-diphenylsulfonium triflate. Further validation using different protecting groups as well as synthesis on multigram scale was performed. The method was also applied to the construction of chiral 1,4-diazepanes and 1,4-diazocanes. Additionally, the method was utilized in a formal synthesis of chiral mirtazapine.

Objectives: The platelet trigger at which to transfuse platelets to prevent bleeding complications in patients supported with extracorporeal membrane oxygenation (ECMO) is unclear. We aimed to elucidate the association between platelet count and bleeding sequelae in this patient population. Methods: We conducted a single-center retrospective study of all adult patients who received ECMO support from 2017 to 2022. Patients were stratified into two groups: “non-thrombocytopenic” (>30 × 10 ³ cells /μL) versus “thrombocytopenic” (≤30 × 10 ³ cells /μL). Multivariable logistic regression was used to determine the association between thrombocytopenia and bleeding complications; covariates were selected a priori. A post-hoc analysis investigating platelet transfusion status and nadir platelet count as an ordinal variable was also performed. Results: Of 291 VV- and VA-ECMO patients, 69 (24%) were categorized as “thrombocytopenic” and 144 (50%) experienced at least one major bleeding event. Compared to “non-thrombocytopenic” patients, “thrombocytopenic” patients were more likely to be male ( p = 0.049), to require veno-arterial central canulation ( p < 0.001), and to have been on dialysis ( p < 0.001). Confounded by a 72% prophylactic transfusion rate, “Thrombocytopenia” was not associated with an increased risk of major bleeding (aOR: 0.59 [95% CI: 0.31–1.10]). However, in patients with a nadir platelet count between 31 and 50 × 10 ³ cells/μL, the 63% with a prophylactic platelet transfusion had a significant reduction in major bleeding complications ( p = 0.003). Conclusions: Our findings suggest that a platelet transfusion trigger of ≤50 × 10 ³ cells/μL is of benefit for prophylaxis against bleeding during ECMO support.