Prioritizing the primary prevention of heart failure: Measuring, modifying and monitoring risk.

With the rising incidence of heart failure (HF) and increasing burden of morbidity, mortality, and healthcare expenditures, primary prevention of HF targeting individuals in at-risk HF (Stage A) and pre-HF (Stage B) Stages has become increasingly important with the goal to decrease progression to symptomatic (Stage C) HF. Identification of risk based on traditional risk factors (e.g., cardiovascular health which can be assessed with the American Heart Association's Life's Essential 8 framework), adverse social determinants of health, inherited risk of cardiomyopathies, and identification of risk-enhancing factors, such as patients with viral disease, exposure to cardiotoxic chemotherapy, and history of adverse pregnancy outcomes should be the first step in evaluation for HF risk. Next, use of guideline-endorsed risk prediction tools such as Pooled Cohort Equations to Prevent Heart Failure provide quantification of absolute risk of HF based in traditional risk factors. Risk reduction through counseling on traditional risk factors is a core focus of implementation of prevention and may include the use of novel therapeutics that target specific pathways to reduce risk of HF, such as mineralocorticoid receptor agonists (e.g., fineronone), angiotensin-receptor/neprolysin inhibitors, and sodium glucose co-transporter-2 inhibitors. These interventions may be limited in at-risk populations who experience adverse social determinants and/or individuals who reside in rural areas. Thus, strategies like telemedicine may improve access to preventive care. Gaps in the current knowledge base for risk-based prevention of HF are highlighted to outline future research that may target approaches for risk assessment and risk-based prevention with the use of artificial intelligence, genomics-enhanced strategies, and pragmatic trials to develop a guideline-directed medical therapy approach to reduce risk among individuals with Stage A and Stage B HF.

Association of Severe Tongue Edema With Prone Positioning in Patients Intubated for COVID-19.

OBJECTIVES/HYPOTHESIS: Prone positioning is frequently used in patients intubated for COVID-19-related lung injury to improve oxygenation. At our institution, we observed severe tongue edema develop in some of these patients. Hence, we sought to determine the incidence of tongue edema in this cohort and whether prone positioning was a risk factor associated with this complication. STUDY DESIGN: Retrospective cohort study. METHODS: A single-system retrospective cohort study of patients intubated for respiratory failure secondary to COVID-19 who subsequently developed clinically notable tongue edema from March 13 to July 5, 2020. RESULTS: 260 patients were intubated for COVID-19-related respiratory failure during the study period. 158 patients (60.8%) underwent at least one episode of proning. Twelve patients in total (4.6%) developed clinically significant tongue edema. Eleven of the twelve patients (91.7%) who developed tongue edema underwent proning prior to the development of edema. Prone positioning was associated with an increased incidence of tongue edema (odds ratio [OR] 7.56, 95% confidence interval [CI] 0.96-59.46, P = .027). In all proned patients who developed edema, this complication was noted during proning or shortly after supination (range, 0-4 days). Tongue edema was primarily managed with conservative measures; one patient required tracheostomy for definitive management. CONCLUSIONS: Tongue edema appears to develop in a subset of patients with COVID-19 who are intubated. It appears to be associated with prone positioning but is likely multifactorial in nature. Further investigation into its incidence and pathophysiology is warranted. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:287-289, 2022.

Long-term outcomes of endoscopic mucosal resection for early-stage esophageal adenocarcinoma.

BACKGROUND: With growing application of endoscopic therapy for early-stage esophageal cancer, we sought to review our experience of endoscopic mucosal resections (EMRs). The aim of our study was to understand the natural course of these patients, especially with positive margins. METHODS: A prospectively maintained database of all patients undergoing endoscopic therapies at Georgetown University Hospital for esophageal cancer was used for the analysis between 2010 and 2020. RESULTS: Of 80 patients in the EMR database, 35 were performed as index cases for esophageal adenocarcinoma. Majority (74.3%) had a pre-treatment ultrasound confirming absence of regional adenopathy. There were no post-EMR bleeding or perforation events requiring re-intervention. Complete R0 resection was achieved in 22/35 (62.9%) after initial EMR. Thirteen patients had positive margins. Of these 13 patients, only 7 patients underwent repeat endoscopic resection, 2 underwent subsequent esophagectomy, 2 received definitive radiation given poor surgical candidacy, and 2 were lost to follow-up. Overall and 5-year survival of all patients undergoing EMR was 67.9 months and 85%, respectively. Subset analysis of the 13 patients with R1 resection demonstrated an overall survival of 49.2 months and 60% 5-year survival vs overall survival of 78.9 months and 93% 5-year survival for R0 resection. At a median follow-up of 60.5 months, cancer recurrence occurred in 3 patients. All of them were successfully managed with repeat EMR. CONCLUSIONS: Endoscopic resections represent a safe and effective treatment for early-stage esophageal cancer. Patients with high-risk features should be counseled to undergo an esophagectomy if they are operable candidates.

Increased body mass index predicts prolonged survival in patients with head and neck squamous cell carcinoma.

BACKGROUND: Higher body mass index (BMI) may have a protective effect on survival in patients with head and neck cancer. The aim of this study was to determine the effect of BMI on overall survival (OS) in veterans with head and neck squamous cell carcinoma (HNSCC). METHODS: A cohort of 702 patients diagnosed with HNSCC between 1995 and 2019 were identified at the Washington DC Veterans Affairs Medical Center, and 342 patients were included for analysis. Records were queried for clinical-demographic data, BMI, and outcomes. RESULTS: HNSCC patients categorized as overweight or obese at time of diagnosis had a lower 3-year risk of death (p = 0.033) and improved OS (p < 0.001) compared to patients who were underweight or normal weight. The majority of locoregional recurrences occurred in patients with low or normal pretreatment BMI. CONCLUSIONS: Higher BMI at diagnosis may have a protective effect on OS in veterans with HNSCC.

Exploring the functional composition of the human microbiome using a hand-curated microbial trait database.

BACKGROUND: Even when microbial communities vary wildly in their taxonomic composition, their functional composition is often surprisingly stable. This suggests that a functional perspective could provide much deeper insight into the principles governing microbiome assembly. Much work to date analyzing the functional composition of microbial communities, however, relies heavily on inference from genomic features. Unfortunately, output from these methods can be hard to interpret and often suffers from relatively high error rates. RESULTS: We built and analyzed a domain-specific microbial trait database from known microbe-trait pairs recorded in the literature to better understand the functional composition of the human microbiome. Using a combination of phylogentically conscious machine learning tools and a network science approach, we were able to link particular traits to areas of the human body, discover traits that determine the range of body areas a microbe can inhabit, and uncover drivers of metabolic breadth. CONCLUSIONS: Domain-specific trait databases are an effective compromise between noisy methods to infer complex traits from genomic data and exhaustive, expensive attempts at database curation from the literature that do not focus on any one subset of taxa. They provide an accurate account of microbial traits and, by limiting the number of taxa considered, are feasible to build within a reasonable time-frame. We present a database specific for the human microbiome, in the hopes that this will prove useful for research into the functional composition of human-associated microbial communities.

An Auxiliary Medical Education: The Evolution of a Medical Student-Founded Organization in Response to the COVID-19 Era Personal Protective Equipment Shortage.

At the outset of the COVID-19 pandemic, many medical students were removed from clinical duties and had their education put on hold. Some found novel ways to join efforts to respond to the pandemic. Georgetown University School of Medicine medical students created Medical Supply Drive (MSD or MedSupplyDrive), a 501(c)(3), on March 17, 2020, in response to the national shortage of personal protective equipment (PPE). This article reviews the formation of a national response to the pandemic, the methods employed to distribute PPE, and the results of MSD's work from March 17, 2020, through June 20, 2020. A focus was placed on equitable distribution, both within local regions and on the national scale, by distinguishing COVID-19 hotspots, including Native American reservations. As of June 20, 2020, over half a million items were donated, with 1,001 deliveries made to 423 hospitals, 182 clinics, 175 long-term care facilities, 25 homeless shelters, 32 public health departments, and 164 other facilities. From 46 states and the District of Columbia, 1,514 individuals volunteered, and 202 signed up as regional coordinators. MSD formed 2 international organizations, MedSupplyDrive UK and MedSupplyDrive Scotland, and established U.S.-based partnerships with 19 different PPE and aid organizations. MSD gained local, national, and international media attention with over 45 interviews conducted about the organization. While the pandemic temporarily disrupted formal medical education, MSD empowered medical students to actively learn about the needs of their communities and organize ways to address them while incorporating these values into their professional identities. The framework that this organization employed also provides a potential model for future disaster relief efforts in times of crisis. MSD hopes to motivate budding physicians to collaborate and play an active role in tackling public health inequities beyond hospitals and within the communities students will one day serve.

Facial Pressure Injuries from Prone Positioning in the COVID-19 Era.

OBJECTIVE/HYPOTHESIS: This study aimed to determine the incidence of facial pressure injuries associated with prone positioning for COVID-19 patients as well as to characterize the location of injuries and treatments provided. METHODS: This was a retrospective chart review of 263 COVID-19 positive patients requiring intubation in the intensive care units at MedStar Georgetown University Hospital and MedStar Washington Hospital Center between March 1st and July 26th, 2020. Information regarding proning status, duration of proning, presence, or absence of facial pressure injuries and interventions were collected. Paired two-tailed t-test was used to evaluate differences between proned patients who developed pressure injuries with those who did not. RESULTS: Overall, 143 COVID-19 positive patients required proning while intubated with the average duration of proning being 5.15 days. Of those proned, 68 (47.6%) developed a facial pressure injury. The most common site involved was the cheek with a total of 57 (84%) followed by ears (50%). The average duration of proning for patients who developed a pressure injury was significantly longer when compared to those who did not develop pressure injuries (6.79 days vs. 3.64 days, P < .001). CONCLUSIONS: Facial pressure injuries occur with high incidence in patients with COVID-19 who undergo prone positioning. Longer duration of proning appears to confer greater risk for developing these pressure injuries. Hence, improved preventative measures and early interventions are needed. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2139-E2142, 2021.

Altered Differentiation Potential of Gaucher's Disease iPSC Neuronal Progenitors due to Wnt/ß-Catenin Downregulation.

Gaucher's disease (GD) is an autosomal recessive disorder caused by mutations in the GBA1 gene, which encodes acid ß-glucocerebrosidase (GCase). Severe GBA1 mutations cause neuropathology that manifests soon after birth, suggesting that GCase deficiency interferes with neuronal development. We found that neuronopathic GD induced pluripotent stem cell (iPSC)-derived neuronal progenitor cells (NPCs) exhibit developmental defects due to downregulation of canonical Wnt/ß-catenin signaling and that GD iPSCs' ability to differentiate to dopaminergic (DA) neurons was strikingly reduced due to early loss of DA progenitors. Incubation of the mutant cells with the Wnt activator CHIR99021 (CHIR) or with recombinant GCase restored Wnt/ß-catenin signaling and rescued DA differentiation. We also found that GD NPCs exhibit lysosomal dysfunction, which may be involved in Wnt downregulation by mutant GCase. We conclude that neuronopathic mutations in GCase lead to neurodevelopmental abnormalities due to a critical requirement of this enzyme for canonical Wnt/ß-catenin signaling at early stages of neurogenesis.