Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity.

Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0-13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4+ T cells and functionally active germinal centers, develop during infancy. BALT structures are prevalent around lung airways during the first 3 years of life, and their numbers decline through childhood coincident with the accumulation of memory T cells. Single-cell profiling and repertoire analysis reveals that early life lung B cells undergo differentiation, somatic hypermutation and immunoglobulin class switching and exhibit a more activated profile than lymph node B cells. Moreover, B cells in the lung and lung-associated lymph nodes generate biased antibody responses to multiple respiratory pathogens compared to circulating antibodies, which are mostly specific for vaccine antigens in the early years of life. Together, our findings provide evidence for BALT as an early life adaptation for mobilizing localized immune protection to the diverse respiratory challenges during this formative life stage.

Implementation of Routine In Situ Simulation in Residency Curriculum Targeting Competency in Technical and Decision-Making Skills.

OBJECTIVE: To describe the development and implementation of a comprehensive in situ simulation-based curriculum for anesthesia residents. DESIGN: This is a prospective study. SETTING: This study was conducted at a university hospital. PARTICIPANTS: This single-center prospective study included all 53 anesthesia residents enrolled in the anesthesia residency program. INTERVENTIONS: Introduction of a routine, high-fidelity, in situ simulation program that incorporates short sessions to train residents in the necessary skill sets and decision-making processes required in the operating room. MEASUREMENTS AND MAIN RESULTS: Our team conducted 182 individual 15-minute simulation sessions over 3 months during regular working hours. All 53 residents in our program actively participated in the simulations. Most residents engaged in at least 3 sessions, with an average participation rate of 3.4 per resident (range, 1-6 sessions). Residents completed an online anonymous survey, with a response rate of 71.7% (38 of 53 residents) over the 3-month period. The survey aimed to assess their overall impression and perceived contribution of this project to their training. CONCLUSIONS: Our proposed teaching method can bridge the gap in resident training and enhance their critical reasoning to manage diverse clinical situations they may not experience during their residency.

Pediatric Plastic Surgery in the COVID-19 Era.

ABSTRACT: The COVID-19 pandemic has forced the healthcare system to adopt novel strategies to treat patients. Pediatric plastic surgeons are uniquely exposed to high rates of infections during examinations and surgeries via aerosol-generating procedures, in part because of the predilection of viral particles for the nasal cavities and pharynx. Telemedicine has emerged as a useful virtual medium for encouraging prolonged patient follow-up while maintaining physical distance. It has proven beneficial in mitigating infection risks while decreasing the financial burden on patients, their families, and healthcare teams. New trends driven by the pandemic added multiple elements to the patient-physician relationship and have left a lasting impact on the field of pediatric plastic surgery in clinical guidelines, surgical care, and patient outcomes. Lessons learned help inform pediatric plastic surgeons on how to reduce future viral infection risk and lead a more appropriately efficient surgical team depending on early triage.

Nano-Ghosts: Biomimetic membranal vesicles, technology and characterization.

Currently, nano-carriers for anti-cancer drug delivery are complex systems, which struggle with immunogenicity and enhanced permeability effect (EPR)-related problems that halt the clinical translation of many therapeutics. Consequently, a rapidly growing field of research has been focusing on biomimetic nano-vesicles (BNVs) as an effective delivery alternative. Nevertheless, the translation of many BNVs is limited due to scalability problems, inconsistent production process, and insufficient loading efficiency. Here we discuss the process of our previously published BNVs, termed Nano-Ghosts (NGs), which are produced from the membrane of mesenchymal stem cells. We demonstrate the flexibility of the process, while alternating physical methodologies (sonication or extrusion) to produce the NGs while preserving their desired characteristics. We also show that our NGs can be labeled using multiple methods (fluorescence, radiolabeling, and genetic engineering) for tracking and diagnostic purposes. Lastly, we demonstrate that the loading efficiency can be improved by using electroporation to accommodate a range of therapeutics (small molecules, peptides and DNA) that can be delivered by the NGs. Our results emphasize the robustness of the NGs technology, its versatility and a vast range of applications, differentiating it from other BNVs and leading the way towards clinical translation.

Risk Factors for Mortality in Patients with Ventral Hernia Admitted Emergently: An Analysis of 48,539 Adult Patients.

BACKGROUND: More than 400,000 cases of ventral hernia (VH) are repaired each year in the U.S. This condition is a major problem with significant morbidly and mortality. The aim of this study was to evaluate independent predictors of in-hospital mortality for patients with a primary diagnosis of VH who were admitted emergently. METHODS: Non-elderly adults (age 18-64 years) with ventral hernias that required emergency admission were analyzed using the National Inpatient Sample database, 2005-2014. Demographics, clinical data, and outcomes were collected. The relationships between mortality and predictors were assessed using a multivariable logistic regression model. RESULTS: Overall, 48,539 patients were identified. The mean (SD) age for both males and females was 50 (9.6). Overall mortality was low (316 or 0.7%). Males accounted for 35% of the total sample and 45% of all mortalities (p <0.001). The mean (SD) hospital length of stay (HLOS) was 4.9 (6.3) and 12.3 (20.6) days in surviving and deceased patients (p <0.001), respectively. Approximately 1.1% of surviving and 6% of deceased patients had gangrene (p <0.001). Intestinal obstruction was observed in 70% of surviving and 83% of deceased patients (p <0.001). While a vast majority of the patients (40,602) were operated on, 8,023 patients were not; 0.7% and 0.4% died, respectively. The mean (SD) HLOS was 5.30 (6.99) days in patients who underwent an operation and 2.97 (2.96) days in those who did not (P <0.0001). Time to operation was 0.81 (1.92) days in surviving and 1.34 (2.42) days in deceased patients (p <0.001). In the final multivariable regression model for patients who underwent an operation, age, male sex, presence of gangrene or obstruction, and longer time to operation were the main risk factors for mortality. For patients who did not undergo an operation, only HLOS and presence of obstruction were the main risk factors for mortality. CONCLUSION: Male sex, presence of gangrene or obstruction at the presentation, and delayed operation were shown to be risk factors for mortality in adult patients with ventral hernia admitted emergently.

Delayed Operation as a Major Risk Factor for Mortality Among Elderly Patients with Ventral Hernia Admitted Emergently: An Analysis of 33,700 Elderly Patients.

BACKGROUND: Elderly patients admitted emergently for ventral hernia may have high rates of complications, including morbidity and mortality. The goal of this study was to retrospectively assess risk factors for in-hospital mortality for elderly patients admitted emergently with a primary diagnosis of ventral hernia. METHODS: Elderly patients with ventral hernia that required emergency admission were analyzed using the National Inpatient Sample database, 2005-2014. Demographics, clinical data, and outcomes were collected. The relationship between mortality and the predictors was assessed using a stratified analysis, multivariable logistic regression model, and multivariable generalized additive model. RESULTS: A total of 33,700 elderly patients were analyzed. The mean (SD) age for males and females was 75 (7.25) and 76.25 (7.75) years, respectively (p<0.001). Approximately 70% of the patients were females. The mean (SD) hospital length of stay (HLOS) was 6.3 (6.5) and 11.6 (13.7) days in survived vs. deceased patients (p<0.001), respectively. Gangrene was present in 1.5% of survivors vs. 5.6% of deceased (p<0.001) patients. Intestinal obstruction was observed in 78% of survivors vs. 88% of deceased patients (p<0.001). Of the 8,554 cases managed non-operatively, 2.1% died. In contrast, in the 25,163 patients who were operated upon, the mortality rate was 2.9%. The mean (SD) HLOS was 7.39 (7.41) days in patients who had an operation vs. 3.82 (3.48) days in those who did not (p<0.0001). Time to operation was 1.12 (1.97) days in survivors vs. 1.81 (3.02) days in deceased patients (p<0.001). In the final multivariable logistic regression model for patients who underwent an operation, delayed operation, elderly male, frailty, invasive diagnostic procedures and presence of gangrene or obstruction were the main risk factors for mortality. In the final model for patients who did not have an operation, age, frailty, presence of gangrene or obstruction and HLOS were the main risk factors for mortality. CONCLUSION: A delayed operation in elderly males and frail patients with intestinal obstruction or gangrene admitted emergently due to ventral hernia significantly increases mortality in this setting.

Subcutaneous fat necrosis of the newborn: A systematic review of surgical management and outcomes.

BACKGROUND: Subcutaneous fat necrosis of the newborn (SCFN) is a rare form of panniculitis manifesting as erythematous plaques or nodules at sites of brown fat in neonates. Surgical management may be indicated in severe cases; however, there is a paucity of literature compiling presentations and outcomes of these surgical patients. METHODS: The authors performed a systematic review, in consultation with a licensed librarian, on MEDLINE and Embase for studies including patients with SCFN who were surgically managed. RESULTS: The search strategy generated 705 results, among which 213 (30.2%) were excluded for lack of discussion on surgical management. Twenty-two studies discussed surgical management of SCFN in 26 patients, but in 6 of these studies the patients were not surgically managed. Ultimately, 16 articles with 16 patients who were surgically managed were included in the study. Average age at diagnosis was 11.8 ± 9.8 days; average age at surgery was 39.5 ± 70.4 days. The most common etiologies were "unknown" (6, 37.5%), therapeutic hypothermia (4, 25.0%), and birth complications (4, 25.0%). Patients harbored nodules on the back (14, 87.5%), upper extremities (7, 43.8%), lower extremities (7, 43.8%), buttocks (5, 31.3%), and head or neck (3, 18.8%). Linear regression models revealed the presence of back lesions and predicted concomitant medical complications (ß = 2.71, p = 0.021). CONCLUSIONS: Patients undergoing surgical management for SCFN most commonly harbor lesions on the back and extremities that are secondary to therapeutic hypothermia or of unknown origin. Reporting of additional cases is needed to further elucidate surgical management and outcomes.

Underrepresented in Medicine Applicants are Less Likely to Successfully Match into Plastic Surgery.

IMPORTANCE: The lack of underrepresented in medicine physicians in academic plastic surgery has been a topic of interest for many years, and accordingly outreach has been undertaken to address the pipeline from medical school to residency and beyond. OBJECTIVE: This study aims to assess and identify the characteristics associated with plastic surgery match success for underrepresented in medicine applicants. DESIGN: Residency application data for first time, US allopathic medical school seniors from the 2017-2018 to 2021-2022 applicant cycles were abstracted from Electronic Residency Application Service applications, and match results were determined using the National Residency Matching Program database and online public sources. Data included self-reported race, and multiple application characteristics. Multivariable logistic regression of application characteristics were used to assess the relationship between underrepresented in medicine status and successfully matching. Binary logistic regression was used in subgroup analyses of each application characteristic, and interactions regression was used to evaluate the relative weight of each characteristic on successfully matching. RESULTS: Underrepresented in medicine applicants were 57% less likely to match than non-underrepresented in medicine applicants (OR 0.43, p = 0.001), though they were 60% less likely to match (ORadj 0.4, p = 0.216) when adjusted. Subgroup analysis revealed that odds of matching as an underrepresented in medicine applicant were significantly increased if the applicant had a home program, took a research year, and had an increased number of published research and presentations (ORs 0.43-0.48, all p < 0.05). Odds of matching as an underrepresented in medicine applicant were significantly decreased if the applicant went to a medical school ranked in the highest or lowest third (ORs 0.41-0.42, all p < 0.01); however, on interaction regression the odds of matching from a highly ranked medical school was increased (OR 3.5, 95% CI 0.98-12.55, p = 0.05). CONCLUSIONS: The likelihood of matching as an underrepresented in medicine applicant is lower than the rest of the applicant population, and there are no individual applicant characteristics that can increase these odds to equal that of the general applicant population.

Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment. METHODS: We tested whether TILs could be in vitro stimulated against neoantigens to achieve selective expansion of neoantigen-reactive TILs. Given their prevalence, mutant p53 or RAS were studied as models of human neoantigens. An in vitro stimulation method, termed "NeoExpand", was developed to provide neoantigen-specific stimulation to TILs. 25 consecutive patient TILs from tumors harboring p53 or RAS mutations were subjected to NeoExpand. RESULTS: We show that neoantigenic stimulation achieved selective expansion of neoantigen-reactive TILs and broadened the neoantigen-reactive CD4+ and CD8+ TIL clonal repertoire. This allowed the effective isolation of novel neoantigen-reactive TCRs. Out of the 25 consecutive TIL samples, neoantigenic stimulation enabled the identification of 16 unique reactivities and 42 TCRs, while conventional TIL expansion identified 9 reactivities and 14 TCRs. Single-cell transcriptome analysis revealed that neoantigenic stimulation increased neoantigen-reactive TILs with stem-like memory phenotypes expressing IL-7R, CD62L, and KLF2. Furthermore, neoantigenic stimulation improved the in vivo antitumor efficacy of TILs relative to the conventional OKT3-induced rapid TIL expansion in p53-mutated or KRAS-mutated xenograft mouse models. CONCLUSIONS: Taken together, neoantigenic stimulation of TILs selectively expands neoantigen-reactive TILs by frequencies and by their clonal repertoire. NeoExpand led to improved phenotypes and functions of neoantigen-reactive TILs. Our data warrant its clinical evaluation. TRIAL REGISTRATION NUMBER: NCT00068003, NCT01174121, and NCT03412877.

Mission Disimpaction: Endoscopic Management of Stercoral Colitis in an Adolescent.

Stercoral colitis is a rare entity of inflammatory colitis with high morbidity and mortality attributable to colonic fecaloma impaction, often a result of chronic constipation. Despite demographic imbalance favoring elders, children hold comparative risk factors for chronic constipation. Suspicion for stercoral colitis is warranted in nearly every stage of life. Computerized tomography (CT) is diagnostic for stercoral colitis, where radiological findings correlate to high sensitivity and specificity. Difficulty exists discerning from other acute and chronic intestinal etiologies with overlapping nonspecific symptoms and laboratory markers. Management involves prompt risk assessment for perforation and immediate disimpaction to avoid ischemic injury, with endoscopic directed disimpaction standard of care for nonoperative measures. Our case describes stercoral colitis in an adolescent with contributive risk factors for fecaloma impaction and is one of the first adolescent case reports involving successful endoscopic management.

Vaginal Reconstruction in the Pediatric Population: An Analysis of a National Database.

OBJECTIVE: In the pediatric population, vaginoplasties can be performed in patients with either congenital malformations or acquired conditions. To our knowledge, there has been no study to date investigating the outcomes of vaginoplasty in the pediatric population using a nationwide database. Here, we present a national cohort study of perioperative characteristics and 30-day complications of vaginoplasty in pediatric patients. METHODS: A level II retrospective, prognosis cohort study was performed using the Pediatric National Surgical Quality Improvement Program (NSQIP-P) database from 2012 to 2020. Data from patients age 0 to 18 who underwent vaginoplasty was queried using CPT code 57,335. Descriptive analysis was performed to elucidate patterns in patient demographics, perioperative characteristics, and 30-day postoperative outcomes. RESULTS: A total of 183 patients were identified. Median age was 2.41 years (IQR 0.9 to 12.1). In this population, 58.5% of patients had ASA class 2, and 33.3% ASA class 3. Congenital malformation was present in 75.9%. Average total length of stay was 2.7 days (SD = 3.8) and readmission rate was 7.86%. Complications included urinary tract infection (3.3%), bleeding/transfusions (2.2%), organ/space surgical site infection (1.1%), and superficial incisional surgical site infection (0.6%). The most common procedures performed simultaneously with vaginoplasty included cystourethroscopy (n = 66), clitoroplasty for intersex state (n = 58), and plastic repair of introitus (n = 22). CONCLUSION: Vaginoplasties in the pediatric population were found to have low rates of 30-day readmission and low incidence of 30-day postoperative complications. Further studies focusing on prospective clinical data related to pediatric vaginoplasty can help identify factors to improve long-term outcomes in this population.

Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers.

Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates that most NeoTCRPBL populations target the same neoantigens as TILs. However, NeoTCRPBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCRPBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichment of clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor. Thus, the NeoTCRPBL signature provides an alternative source for identifying antitumor T cells from PBL of cancer patients, enabling immune monitoring and immunotherapies.

Independent Predictors of In-Hospital Mortality in Elderly and Non-elderly Adult Patients Undergoing Emergency Admission for Hemorrhoids.

BACKGROUND: The study explored determinants of mortality of admitted emergently patients with the primary diagnosis of hemorrhoids, during the years 2005-2014. METHODS: Demographics, clinical data, and outcomes were obtained from the National Inpatient Sample, 2005-2014, in elderly (65+ years) and non-elderly adult patients (18-64 years) with hemorrhoids who underwent emergency admission. Multivariable logistic regression model with backward elimination was used to identify predictors of mortality. RESULTS: 25 808 adult and 26 978 elderly patients were included. Female patients consisted of 42.5% and 59.3% in adult and elderly, respectively. 42 (.2%) adults died, of which 50% were female and 125 (.5%) elderly patients died, of which 60% were female. Mean (SD) age of the adult patients was 47.8 (11) years and in elderly patients was 78.7 (8) years. 82.2% and 85.7% had internal hemorrhoids in adult and elderly patients, respectively. 9326 (36.1%) adult and 7282 (27%) elderly patients underwent an operation. In the final multivariable logistic regression model for adult patients with operation, delayed operation and invasive diagnostic procedures increased the odds of mortality, whereas in elderly patients, delayed operation and frailty index were the risk factors of mortality. In both adults and elderly with no operation, increased hospital length of stay (HLOS) significantly increased the odds of mortality, and undergoing an invasive diagnostic procedure significantly decreased the odds of mortality. CONCLUSION: In all operated patients, increased time to operation and undergoing an invasive diagnostic procedure were the risk factors for mortality. On the other hand, in non-operated emergency hemorrhoids patients, increased age and increased HLOS were the risk factors for mortality while undergoing an invasive diagnostic procedure decreased the odds of mortality.

Evaluation of the Virtual Interviews for Resident Recruitment Due to COVID-19 Travel Restrictions: A Nationwide Survey of US Senior Medical Students.

BACKGROUND AND OBJECTIVES: Due to COVID-19, residency programs could not conduct in-person interviews during the 2020-2021 match and were forced to implement a virtual format. We conducted a nationwide survey of US senior medical students to evaluate their perception of the virtual interview process and to solicit their recommendations for future virtual interview best practices. METHODS: This study was administered to US fourth-year medical students currently participating in the residency match using Survey Monkey during March 2021. Students were contacted through their respective student affairs deans. Surveys solicited demographic information, 26 4-point Likert-scale questions, and four free-response questions. RESULTS: A total of 357 surveys were completed. Most respondents stated that they could confidently represent themselves to the program (71.7%) using a virtual platform. However, only 11.6% stated that they could confidently assess a program's facility using a virtual platform. Although most respondents (58.26%) found that virtual meet and greets helped them better assess their fit for the program, less than half (46%) confidently believed they could assess their fit into the program after the conclusion of the virtual interview. Regarding potential disparities introduced by virtual interviews, 40.6% believed that the virtual interviews introduce greater inequalities into the match process. Two-thirds of respondents (239, 66.95%), believed that there should be a limit on the number of interview offers an applicant can accept, with the maximum number of interviews per specialty capped at 25.7 (10-150). Finally, just over two-thirds (69.47%), claimed they could confidently prepare their rank-order list at the conclusion of the interview. CONCLUSIONS: Most respondents found virtual interviews financially beneficial, however difficulty in assessing fit was a challenge. Best practice recommendations from the respondents include shorter interviews, more engaging resident-led social hours without faculty present, and preinterview packages to include video representations of the program facilities.

Adult and Elderly Risk Factors of Mortality in 23,614 Emergently Admitted Patients with Rectal or Rectosigmoid Junction Malignancy.

Background: Colorectal cancer, among which are malignant neoplasms of the rectum and rectosigmoid junction, is the fourth most common cancer cause of death globally. The goal of this study was to evaluate independent predictors of in-hospital mortality in adult and elderly patients undergoing emergency admission for malignant neoplasm of the rectum and rectosigmoid junction. Methods: Demographic and clinical data were obtained from the National Inpatient Sample (NIS), 2005−2014, to evaluate adult (age 18−64 years) and elderly (65+ years) patients with malignant neoplasm of the rectum and rectosigmoid junction who underwent emergency surgery. A multivariable logistic regression model with backward elimination process was used to identify the association of predictors and in-hospital mortality. Results: A total of 10,918 non-elderly adult and 12,696 elderly patients were included in this study. Their mean (standard deviation (SD)) age was 53 (8.5) and 77.5 (8) years, respectively. The odds ratios (95% confidence interval, P-value) of some of the pertinent risk factors for mortality for operated adults were 1.04 for time to operation (95%CI: 1.02−1.07, p < 0.001), 2.83 for respiratory diseases (95%CI: 2.02−3.98), and 1.93 for cardiac disease (95%CI: 1.39−2.70), among others. Hospital length of stay was a significant risk factor as well for elderly patients­OR: 1.02 (95%CI: 1.01−1.03, p = 0.002). Conclusions: In adult patients who underwent an operation, time to operation, respiratory diseases, and cardiac disease were some of the main risk factors of mortality. In patients who did not undergo a surgical procedure, malignant neoplasm of the rectosigmoid junction, respiratory disease, and fluid and electrolyte disorders were risk factors of mortality. In this patient group, hospital length of stay was only significant for elderly patients.

Mortality Risk Factors in Patients Admitted with the Primary Diagnosis of Tracheostomy Complications: An Analysis of 8026 Patients.

Background: Tracheostomy is a procedure commonly conducted in patients undergoing emergency admission and requires prolonged mechanical ventilation. In the present study, the aim was to determine the prevalence and risk factors of mortality among emergently admitted patients with tracheostomy complications, during the years 2005−2014. Methods: This was a retrospective cohort study. Demographics and clinical data were obtained from the National Inpatient Sample, 2005−2014, to evaluate elderly (65+ years) and non-elderly adult patients (18−64 years) with tracheostomy complications (ICD-9 code, 519) who underwent emergency admission. A multivariable logistic regression model with backward elimination was used to identify the association between predictors and in-hospital mortality. Results: A total of 4711 non-elderly and 3315 elderly patients were included. Females included 44.5% of the non-elderly patients and 47.6% of the elderly patients. In total, 181 (3.8%) non-elderly patients died, of which 48.1% were female, and 163 (4.9%) elderly patients died, of which 48.5% were female. The mean (SD) age of the non-elderly patients was 50 years and for elderly patients was 74 years. The mean age at the time of death of non-elderly patients was 53 years and for elderly patients was 75 years. The odds ratio (95% confidence interval, p-value) of some of the pertinent risk factors for mortality showed by the final regression model were older age (OR = 1.007, 95% CI: 1.001−1.013, p < 0.02), longer hospital length of stay (OR = 1.008, 95% CI: 1.001−1.016, p < 0.18), cardiac disease (OR = 3.21, 95% CI: 2.48−4.15, p < 0.001), and liver disease (OR = 2.61, 95% CI: 1.73−3.93, p < 0.001). Conclusion: Age, hospital length of stay, and several comorbidities have been shown to be significant risk factors in in-hospital mortality in patients admitted emergently with the primary diagnosis of tracheostomy complications. Each year of age increased the risk of mortality by 0.7% and each additional day in the hospital increased it by 0.8%.

Evaluation of the Virtual Interview Format for Resident Recruitment as a Result of COVID-19 Restrictions: Residency Program Directors' Perspectives.

PURPOSE: Due to the COVID-19 pandemic, residency programs could not conduct in-person interviews during the 2020-2021 Match cycle and were forced to implement a virtual format. The authors conducted a nationwide survey of residency program directors (PDs) to assess their confidence in using a virtual platform to holistically evaluate applicants during the 2020-2021 Match cycle and their desire to continue virtual recruitment during forthcoming interview seasons. METHOD: This prospective study was conducted by email questionnaire administered through the survey tool Survey Monkey to residency PDs from March 7, 2021-March 27, 2021. The residency PDs surveyed represented these subspecialties: internal medicine, general surgery, obstetrics and gynecology, pediatrics, psychiatry, and other. Email addresses of PDs were collected from a public list developed by the Accreditation Council for Graduate Medical Education. Surveys contained demographic questions, 4-point Likert scale questions evaluating several factors regarding the interview and matching process, and free-response questions. RESULTS: A total of 463 surveys were sent; response rate was 402 /463 (86.8%). Most PDs were less confident assessing an applicant's interpersonal skills (247, 61.4%) and professionalism (239, 59.5%) using a virtual platform. Assessment of an applicant's "fit" into the program was also challenging: 44.3% (178) of those surveyed disagreed with the statement that they could do so confidently. Additionally, 73.9% (297) of PDs found it challenging to gauge an applicant's genuine interest and only 41.3% (166) strongly agreed or agreed that they could accurately represent their own program using a virtual platform. More than half of PDs (220, 54. 7%) found it more difficult to rank interviewees compared with previous in-person Match cycles. CONCLUSIONS: Most residency PDs found virtual interviews convenient. However, difficulties in assessing fit virtually, gauging applicants' interest, and showcasing their respective programs were challenges that may persist should virtual interviews continue post-pandemic.

Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications.

Obesity-mediated metabolic syndrome remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves the heme oxygenase (HO) system, specifically its inducible form, HO-1. This review collects and updates much of the current knowledge relevant to pharmacology and clinical medicine concerning HO-1 in metabolic diseases and its effect on lipid metabolism. HO-1 has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin and leptin sensitivity. Recent reports indicate that HO-1 with its antioxidants via the effect of bilirubin increases formation of biologically active lipid metabolites such as epoxyeicosatrienoic acid (EET), omega-3 and other polyunsaturated fatty acids (PUFAs). Similarly, HO-1and bilirubin are potential therapeutic targets in the treatment of fat-induced liver diseases. HO-1-mediated upregulation of EET is capable not only of reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, a hallmark of the metabolic syndrome. This process involves browning of white fat tissue (i.e. formation of healthy adipocytes) and reduced lipotoxicity, which otherwise will be toxic to the heart. More importantly, this review examines the activity of EET in biological systems and a series of pathways that explain its mechanism of action and discusses how these might be exploited for potential therapeutic use. We also discuss the link between cardiac ectopic fat deposition and cardiac function in humans, which is similar to that described in obese mice and is regulated by HO-1-EET-PGC1α signaling, a potent negative regulator of the inflammatory adipokine NOV.

Divergent outer retinal circuits drive image and non-image visual behaviors.

Image- and non-image-forming vision are essential for animal behavior. Here we use genetically modified mouse lines to examine retinal circuits driving image- and non-image-functions. We describe the outer retinal circuits underlying the pupillary light response (PLR) and circadian photoentrainment, two non-image-forming behaviors. Rods and cones signal light increments and decrements through the ON and OFF pathways, respectively. We find that the OFF pathway drives image-forming vision but cannot drive circadian photoentrainment or the PLR. Cone light responses drive image formation but fail to drive the PLR. At photopic levels, rods use the primary and secondary rod pathways to drive the PLR, whereas at the scotopic and mesopic levels, rods use the primary pathway to drive the PLR, and the secondary pathway is insufficient. Circuit dynamics allow rod ON pathways to drive two non-image-forming behaviors across a wide range of light intensities, whereas the OFF pathway is potentially restricted to image formation.