Faculty Bibliography

PURPOSE/OBJECTIVE:Accelerated 3-year programs (A3YPs) at medical schools were developed to address student debt and mitigate workforce shortage issues. This study investigated whether medical school length (3 vs 4 years) was associated with early residency performance. The primary research question was as follows: Are the Accreditation Council for Graduate Medical Education Milestones (MS) attained by A3YP graduates comparable to graduates of traditional 4-year programs (T4YPs) at 6 and 12 months into internship? METHOD/METHODS:The MS data from students entering U.S. medical schools in 2021 and 2022 from the 6 largest specialties were used: emergency medicine, family medicine, internal medicine, general surgery, psychiatry, and pediatrics. Three-year and 4-year graduates were matched for analysis (2,899 matched learners: 182 in A3YPs and 2,717 in T4YPs). The study used a noninferiority study design to examine data trends between the study cohort (A3YP) and control cohort (T4YP). To account for medical school and residency program effects, the authors used cross-classified random-effects regression to account for clustering and estimate group differences. RESULTS:The mean Harmonized MS ratings for the midyear and end-year reporting periods showed no significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = 0.01 [0.02], P = .77). Mean MS ratings across internal medicine MS for the midyear and end-year reporting periods showed no significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = -0.03 [0.03], P = .31). Similarly, for family medicine, there were no statistically significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = 0.01 [0.02], P = .96). CONCLUSIONS:For the specialties studied, there were no significant differences in MS performance between 3-year and 4-year graduates at 6 and 12 months into internship. These results support comparable efficacy of A3YPs in preparing medical students for residency.

INTRODUCTION/BACKGROUND:Endoscopic ultrasound (EUS) allows for characterization and biopsy of pancreatic lesions. Pancreatic cystic neoplasms (PCN) include mucinous (M-PCN) and nonmucinous lesions (NM-PCN). Pancreatic ductal adenocarcinoma (P-DAC) is the commonest pancreatic solid lesion (PSL), followed by pancreatic neuroendocrine tumor (P-NET). Although EUS is preferred for pancreatic lesion evaluation, its diagnostic accuracy is suboptimal. This multicentric study aims to develop a convolutional neural network (CNN) for detecting and distinguishing PCN (namely M-PCN and NM-PCN) and PSL (particularly P-DAC and P-NET). METHODS:A CNN was developed with 378 EUS examinations from 4 international reference centers (Centro Hospitalar Universitário São João, Hospital Universitario Puerta de Hierro Majadahonda, New York University Hospitals, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo). About 126.000 images were obtained-19.528 M-PCN, 8.175 NM-PCN, 64.286 P-DAC, 29.153 P-NET, and 4.858 normal pancreas images. A trinary CNN differentiated normal pancreas tissue from M-PCN and NM-PCN. A binary CNN distinguished P-DAC from P-NET. The total data set was divided into a training and testing data set (used for model's evaluation) in a 90/10% ratio. The model was evaluated through its sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS:The CNN had 99.1% accuracy for identifying normal pancreatic tissue, 99.0% and 99.8% for M-PCN and NM-PCN, respectively. P-DAC and P-NET were distinguished with 94.0% accuracy. DISCUSSION/CONCLUSIONS:Our group developed the first worldwide CNN capable of detecting and differentiating the commonest PCN and PSL in EUS images, using examinations from 4 centers in 2 continents, minimizing the impact of the demographic bias. Larger multicentric studies are needed for technology implementation.

INTRODUCTION/BACKGROUND:Splenic stiffness (SS) measurement (SSM) is an evolving noninvasive assessment to evaluate portal hypertension. Studies with respect to SSM in patients with alcohol use disorder are limited. METHODS:We studied patients seeking treatment for alcohol use disorder in an inpatient treatment protocol at the National Institutes of Health and parsed SSM into 3 groups based on degree of change. RESULTS:The improved SS group had statistically higher initial SSM and a nonstatistically increased liver stiffness measurement compared with others. DISCUSSION/CONCLUSIONS:SS is dynamic in a subset of patients immediately after alcohol cessation, and improved SS is associated with a normalization of platelet count.

Proximal tubule endocytosis is essential to produce protein free urine as well as to regulate system wide metabolic pathways, such as the activation of Vitamin D. We have determined that the proximal tubule expresses an endolysosomal membrane protein, protein spinster homolog1 (Spns1), which engenders a novel iron conductance that is indispensable during embryonic development. Conditional knockout of Spns1 with a novel Cre-LoxP construct specific to megalin-expressing cells led to the arrest of megalin receptor-mediated endocytosis as well as dextran pinocytosis in proximal tubules. The endocytic defect was accompanied by changes in megalin phosphorylation as well as enlargement of lysosomes confirming previous findings in Drosophila and Zebrafish. The endocytic defect was also accompanied by iron overload in proximal tubules. Remarkably, iron levels regulated the Spns1 phenotypes, because feeding an iron deficient diet or mating Spns1 knockout with divalent metal transporter1 (DMT1) knockout rescued the phenotypes. Conversely, iron loading wild type mice reproduced the endocytic defect, These data demonstrate a reversible, negative feedback for apical endocytosis, and raise the possibility that regulation of endocytosis, pinocytosis, megalin activation, and organellar size and function is nutrient-responsive.

Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of >1.4 kg from morning to night, increasing edema, increasing truncal and abdominal girth with bloating when assuming an upright position and nocturia that is unrelated to menses. There is an increase in morbidity but not mortality. Increased capillary membrane leakage appears to be the underlying pathophysiologic abnormality that explains the myriad of clinical presentations. We present 2 cases of life-threatening complications of IE that resulted in seizures related to acute hyponatremia in one and extreme postural dizziness and fainting induced by postural hypotension in the other. The first patient was successfully treated with salt restriction, timely use of furosemide and limitation of water intake; the other was successfully treated by use of support hose. Treatment of these patients required a fundamental understanding of the intricate pathophysiological consequences of a leaky capillary membrane, an understanding of Starling forces and detailing the effectiveness of a low salt diet, use of diuretics and limited water intake in one and why support hose would be beneficial in the other patient. Both patients experienced significant physical and emotional benefits that substantially improved quality of life.

AIMS/OBJECTIVE:Anal cancer, despite its rarity, is a matter of serious concern in the United States, with an uptrend in recent years and marked racial disparities in mortality rates. The aim of this work was to investigate anal cancer mortality trends and sex race disparities in the United States from 1999 to 2020. METHOD/METHODS:This is a retrospective study using data from the CDC WONDER database (1999-2020). We investigated deaths attributed to anal cancer, identified by the ICD-10 code C21.1, and excluded individuals aged 14 years and under. The Mann-Kendall trend test was used to investigate temporal trends and a t-test was used to compare continuous variables. RESULTS:Both male and female age-adjusted mortality attributed to anal cancer increased significantly during the study period across all subgroups, including race (Black and White), US Census region (Northeast, Midwest, South and West) and age (15-64 and ≥65 years) (p < 0.001 for all comparisons). For each subgroup, women demonstrated significantly higher rates of mortality than men, except in the Black population, where Black men had higher rates than Black women (0.40 vs. 0.29, p < 0.001). Additionally, Black men had significantly higher mean mortality rates than White men (0.40 vs. 0.27, p < 0.001). The highest rates of anal cancer mortality were among geriatric individuals, especially women aged ≥65 years, at 1.18 per 100 000. CONCLUSION/CONCLUSIONS:The rise in anal cancer mortality and racial and sex disparities present a significant challenge for healthcare providers and policy makers. Further studies are required to devise evidence-based strategies to effectively tackle this challenge.

BACKGROUND:New anticancer therapies have improved patient outcomes but associated dermatologic adverse events (AEs) may cause morbidity and treatment discontinuation. A comprehensive estimation of associations between cancer drugs and skin AEs is lacking. METHODS:This study utilized the Food and Drug Administartion (FDA)'s Adverse Event Reporting System database (January 2013-September 2022), with 3,399,830 reports involving 3084 drugs and 16,348 AEs. A nearest neighbor matching model was employed to select 10 controls for each case report, utilizing the cosine similarity of demographic and AE severity factors to minimize false positives/negatives. RESULTS:There were 10,698 unique anticancer drugs (n = 212) to skin AE (n = 873) pairs, of which 676 had significant reporting odds ratios (ROR) > 1, comprising 113 drugs and 144 AEs. The minimum ROR was 1.25, and 50% of associations displayed a ROR >10. The most common were rash (51 agents) and dry skin (28 drugs). Methotrexate induced the most distinct AEs (34), then mechlorethamine (33), and vemurafenib (24). Targeted therapies accounted for 49% of pairs, cytotoxic chemotherapies for 35.9%, and immunotherapies for 11%. CONCLUSIONS:A total of 113 anticancer drugs were identified as significantly associated with skin AEs, most frequently rash and dry skin. Data are likely under-reported but enable quick postmarketing identification of skin toxicity signals.

Dementia and Alzheimer's disease are common occurrences in the population, affecting many patients. Recent research and studies have found a link between oral biofilm and the initiation of these conditions or the worsening of their presentation. Periodontal disease and the associated oral biofilm with its bacteria are often not considered by the medical community when treating these or their patients. Coordination of therapy with a dentist can improve the patient's oral health. Decreasing bacteria in the oral biofilm allows the physician and dentist to provide coordinated total healthcare. Emphasis and education of the patient on the importance of maintaining good oral homecare and routine dental recall prophylaxis appointments to improve their systemic health and limit the progression and worsening of mental health conditions. This article discusses the connection between oral biofilm and systemic health, specifically Alzheimer's disease, and how to improve those conditions through oral healthcare.

Increasing healthcare costs, limited healthcare resources, an aging population, and lifestyle-related diseases make wound management a growing clinical, social, and economic burden. This case series investigated the use of a novel, biocompatible, polymer-based transforming powder dressing (TPD) that transforms in situ to a shape-retentive wound matrix upon hydration for treating wounds of various etiologies.In this institutional review board-approved single-center retrospective case series, the researchers evaluated various acute and chronic wounds treated with TPD over a period of 2 years. Wounds were followed from the first TPD application up to 1 month after the last TPD application or until the wound healed or the patient was lost to follow-up, whichever came first. The researchers evaluated wound etiology, location, number of applications, change in wound surface area, and comorbidities.The researchers identified 50 patients who were treated with TPD and had at least one follow-up visit during the retrospective study period. The majority of wounds treated with TPD were venous leg ulcers (n = 27) followed by traumatic wounds (n = 11) and skin tears (n = 7). Normal rates of wound healing (>10% per week) were observed in the majority of patients (36/50, 72%) over their duration of treatment. Complete healing during the study period was observed in 43% of venous leg ulcers, 55% of traumatic wounds, 71% of skin tears, and 80% of other wound types. No adverse effects of TPD administration were observed. Treatment with TPD resulted in significant reductions in wound area of nearly all wounds, regardless of etiology.