Impact of COVID-19 pandemic on physician-scientist trainees to faculty one year into the pandemic.

PURPOSE: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on stress levels, research productivity, and optimism for physician-scientists at all levels of training. METHODS: A multi-institutional cross-sectional survey of medical students, graduate students, and residents/fellows/junior faculty (RFJF) was conducted from April to August 2021 to assess the impact of COVID-19 on individual stress, productivity, and optimism. Multivariate regression analyses were performed to identify associated variables and unsupervised variable clustering techniques were employed to identify highly correlated responses. RESULTS: A total 677 respondents completed the survey, representing different stages of physician-scientist training. Respondents report high levels of stress (medical students: 85%, graduate students: 63%, RFJF: 85%) attributed to impaired productivity concerns, concern about health of family and friends, impact on personal health and impairment in training or career development. Many cited impaired productivity (medical students: 65% graduate students: 79%, RFJF: 78%) associated with pandemic impacts on training, labs closures and loss of facility/resource access, and social isolation. Optimism levels were low (medical students: 37%, graduate students: 38% and RFJF: 39%) with females less likely to be optimistic and more likely to report concerns of long-term effects of COVID-19. Optimism about the future was correlated with not worrying about the long-term effects of COVID-19. Since the COVID-19 pandemic, all respondents reported increased prioritization of time with family/friends (67%) and personal health (62%) over career (25%) and research (24%). CONCLUSIONS: This national survey highlights the significant and protracted impact of the COVID-19 pandemic on stress levels, productivity, and optimism among physician-scientists and trainees. These findings underscore the urgent need for tailored support, including mental health, academic, and career development assistance for this biomedical workforce.

Delta-like ligand 4-mediated Notch signaling controls proliferation of second heart field progenitor cells by regulating Fgf8 expression.

The role played by the Notch pathway in cardiac progenitor cell biology remains to be elucidated. Delta-like ligand 4 (Dll4), the arterial-specific Notch ligand, is expressed by second heart field (SHF) progenitors at time-points that are crucial in SHF biology. Dll4-mediated Notch signaling is required for maintaining an adequate pool of SHF progenitors, such that Dll4 knockout results in a reduction in proliferation and an increase in apoptosis. A reduced SHF progenitor pool leads to an underdeveloped right ventricle (RV) and outflow tract (OFT). In its most severe form, there is severe RV hypoplasia and poorly developed OFT resulting in early embryonic lethality. In its milder form, the OFT is foreshortened and misaligned, resulting in a double outlet right ventricle. Dll4-mediated Notch signaling maintains Fgf8 expression by transcriptional regulation at the promoter level. Combined heterozygous knockout of Dll4 and Fgf8 demonstrates genetic synergy in OFT alignment. Exogenous supplemental Fgf8 rescues proliferation in Dll4 mutants in ex-vivo culture. Our results establish a novel role for Dll4-mediated Notch signaling in SHF biology. More broadly, our model provides a platform for understanding oligogenic inheritance that results in clinically relevant OFT malformations.

Delta-like ligand-4 regulates Notch-mediated maturation of second heart field progenitor-derived pharyngeal arterial endothelial cells.

Mesodermal progenitors in the second heart field (SHF) express Delta-like-ligand 4 (Dll4) that regulates Notch-mediated proliferation. As cells of SHF lineage mature to assume endocardial and myocardial cell fates, we have shown that Dll4 expression is lost, and the subsequent expression of another Notch ligand Jagged1 regulates Notch-mediated maturation events in the developing heart. A subset of SHF progenitors also matures to form the pharyngeal arch artery (PAA) endothelium. Dll4 was originally identified as an arterial endothelial-specific Notch ligand that plays an important role in blood vessel maturation, but its role in aortic arch maturation has not been studied to date secondary to the early lethality observed in Dll4 knockout mice. We show that, unlike in SHF-derived endocardium and myocardium, Dll4 expression persists in SHF-derived arterial endothelial cells. Using SHF-specific conditional deletion of Dll4, we demonstrate that as SHF cells transition from their progenitor state to an endothelial fate, Dll4-mediated Notch signalling switches from providing proliferative to maturation cues. Dll4 expression maintains arterial identity in the PAAs and plays a critical role in the maturation and re-organization of the 4th pharyngeal arch artery, in particular. Haploinsufficiency of Dll4 in SHF leads to highly penetrant aortic arch artery abnormalities, similar to those observed in the clinic, primarily resulting from aberrant reorganization of bilateral 4th pharyngeal arch arteries. Hence, we show that cells of SHF lineage that assume an arterial endothelial fate continue to express Dll4 and the resulting Dll4-mediated Notch signalling transitions from an early proliferative to a later maturation role during aortic arch development.

High prevalence of deleterious mutations in concomitant nonsyndromic cleft and outflow tract heart defects.

Our previous work demonstrating enrichment of outflow tract (OFT) congenital heart disease (CHD) in children with cleft lip and/or palate (CL/P) suggests derangements in common underlying developmental pathways. The current pilot study examines the underlying genetics of concomitant nonsyndromic CL/P and OFT CHD phenotype. Of 575 patients who underwent CL/P surgery at Children's Hospital Los Angeles, seven with OFT CHD, negative chromosomal microarray analysis, and no recognizable syndromic association were recruited with their parents (as available). Whole genome sequencing of blood samples paired with whole-blood-based RNA sequencing for probands was performed. A pathogenic or potentially pathogenic variant was identified in 6/7 (85.7%) probands. A total of seven candidate genes were mutated (CHD7, SMARCA4, MED12, APOB, RNF213, SETX, and JAG1). Gene ontology analysis of variants predicted involvement in binding (100%), regulation of transcription (42.9%), and helicase activity (42.9%). Four patients (57.1%) expressed gene variants (CHD7, SMARCA4, MED12, and RNF213) previously involved in the Wnt signaling pathway. Our pilot analysis of a small cohort of patients with combined CL/P and OFT CHD phenotype suggests a potentially significant prevalence of deleterious mutations. In our cohort, an overrepresentation of mutations in molecules associated with Wnt-signaling was found. These variants may represent an expanded phenotypic heterogeneity within known monogenic disease genes or provide novel evidence of shared developmental pathways. The mechanistic implications of these mutations and subsequent developmental derangements resulting in the CL/P and OFT CHD phenotype require further analysis in a larger cohort of patients.

SARS-CoV-2 seroprevalence among firefighters in Los Angeles, California.

OBJECTIVE: We estimate the seroprevalence of SARS-CoV-2 antibodies among a sample of firefighters in the Los Angeles (LA), California fire department in October 2020 and compare demographic and contextual factors for seropositivity. METHODS: We conducted a serological survey of firefighters in LA, California, USA, in October 2020. Individuals were classified as seropositive for SARS-CoV-2 if they tested positive for IgG, IgM or both. We compared demographic and contextual factors for seropositivity. RESULTS: All firefighters in LA, California, USA were invited to participate in our study, but only roughly 21% participated. Of 713 participants with valid serological data, 8.8% tested positive for SARS-CoV-2 antibodies, and among the 686 with complete survey data 8.9% tested positive for antibodies. Seropositivity was not associated with gender, age or race/ethnicity. Seropositivity was highest among firefighters who reported working in the vicinity of LA International Airport, which had a known outbreak in July 2020. CONCLUSIONS: Seroprevalence among firefighters in our sample was 8.8%, however, we lack a full workplace seroprevalence estimate to compare the relative magnitude against general population seroprevalence (15%). Workplace safety protocols, such as access to personal protective equipment and testing, can mitigate increased risk of infection at work, and may have eliminated differences in disease burden by geography and race/ethnicity in our sample.

Gastric electric stimulator versus gastrectomy for the treatment of medically refractory gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) and laparoscopic gastrectomy (LG) are known therapeutic options for medically refractory gastroparesis (MRG) although there are limited data comparing their outcomes. We aim to compare clinical outcomes between patients undergoing GES vs upfront LG for the treatment of MRG while examining factors associated with GES failure and conversion to LG. METHODS: We retrospectively analyzed 181 consecutive patients who underwent GES or LG for MRG at our institution from January 2003 to December 2017. Data collection consisted of chart review and follow-up telephone survey. Statistical analysis utilized Chi-squared, ANOVA, and multivariable logistic regression. RESULTS: Overall, 130 (72%) patients underwent GES and 51 (28%) LG as primary intervention. GES patients were more likely to have diabetic gastroparesis (GES 67% vs LG 39%, p < 0.001), while primary LG patients were more likely to have post-surgical gastroparesis (GES 5% vs LG 43%, p < 0.001). Postoperatively, primary LG patients had higher rates of major in-hospital morbidity events (GES 5% vs LG 18%, p = 0.017) and longer hospital stays (GES 3 vs LG 9 days, p < 0.001). However, over a mean 35-month follow-up period, there were no differences in the rates of major morbidity, readmissions, or mortality. Multivariable regression analysis revealed patients undergoing GES as a primary intervention were less likely to report improvement in symptoms on follow-up compared to primary LG patients OR 0.160 (95% CI 0.048-0.532). Additionally, patients who converted to LG from GES were more likely to have post-surgical gastroparesis as the primary etiology. CONCLUSION: GES as a first-line surgical treatment of MRG was associated with worse outcomes compared to LG. Post-surgical etiology was associated with an increased likelihood of GES failure, and in such patients, upfront gastrectomy may be a superior alternative to GES. Further studies are needed to determine patient selection for operative treatment of MRG.

Effects of smoking on bariatric surgery postoperative weight loss and patient satisfaction.

BACKGROUND: While general population studies have demonstrated a relationship between cigarette smoking and weight loss, this association is not well established among the bariatric patient population. Given that bariatric patients are inherently weight-concerned, understanding the effects of smoking on postoperative weight loss is essential. We examined the association of preoperative smoking, postoperative smoking and changes in smoking status with weight loss after bariatric surgery. In addition, we examined the association of changes in smoking status with subjective indices of patient satisfaction while controlling for weight loss. METHODS: Retrospective chart review of patients who underwent Sleeve Gastrectomy or Roux-en-Y Gastric Bypass for weight loss at a single institution between August 2000 and November 2017. Additional follow up was obtained by telephone survey. Statistical analysis utilized multivariate logistical regressions. RESULTS: Our study included 512 patients. Majority were female (n = 390, 76.2%) and underwent laparoscopic Roux-en-Y gastric bypass (n = 362, 70.7%). Average age was 46.8 years and average follow up was 6.99 years. Preoperative, postoperative and changes in smoking status were not significantly associated with weight loss. Former smokers were significantly more likely to report postoperative satisfaction with self-overall OR 10.62 (p < 0.01), satisfaction with postoperative outcomes OR 4.18 (p = 0.02), and improvement in quality of life OR 4.05 (p = 0.04) compared to continued smokers independent of weight loss. No difference in rates of satisfaction were found between former smokers and never smokers. Smoking cessation and weight loss were independently predictive of positive responses to these satisfaction indices. CONCLUSIONS: We found no association between preoperative smoking, postoperative smoking or changes in smoking status with postoperative weight loss. Smoking cessation was associated with patient satisfaction and improvement in quality of life compared to continued smokers. Smoking cessation and postoperative weight loss were independently predictive of increased patient satisfaction.

Gender disparities among medical students choosing to pursue careers in medical research: a secondary cross-sectional cohort analysis.

BACKGROUND: Though the proportion of women in medical schools has increased, gender disparities among those who pursue research careers still exists. In this study, we seek to better understand the main factors contributing to the existing gender disparities among medical students choosing to pursue careers in medical research. METHODS: A secondary cross-sectional cohort analysis of previously published data was conducted using a 70-item survey that was sent to 16,418 medical students at 32 academic medical centers, and was IRB exempt from the need for ethical approval at the University of Illinois at Chicago and the University of Pennsylvania. Data was collected from September 2012 to December 2014. Survey results were analyzed using chi-square tests and Cramer's V to determine gender differences in demographic characteristics (training stage, race/ethnicity, marital status, parental status, financial support, and parental career background), career sector choice, career content choice, specialty choice, foreseeable career obstacles, and perceptions about medical research careers. RESULTS: Female respondents were more likely to be enrolled in MD-only programs, while male respondents were more likely to be enrolled in MD/PhD programs. More male students selected academia as their first-choice career sector, while more female respondents selected hospitalist as their first-choice career sector. More female respondents identified patient care and opportunities for community service as their top career selection factors, while more male respondents identified research and teaching as their top career selection factors. Student loan burden, future compensation, and work/life balance were the most reported obstacles to pursuing a career in medical research. CONCLUSIONS: There are many factors from a medical student's perspective that may contribute to the existing gender disparities in pursuing a career in medical research. While much progress has been made in attracting nearly equal numbers of men and women to the field of medicine, active efforts to bridge the gap between men and women in medical research careers are needed.

Laparoscopy as a Diagnostic and Therapeutic Modality for Chronic Abdominal Pain of Unknown Etiology: A Literature Review.

BACKGROUND: Investigate the diagnostic and therapeutic utility of laparoscopy in the management of patients with chronic abdominal pain of unknown origin. METHODS: Ovid MEDLINE, PubMed, and SCOPUS databases were queried to identify relevant published studies. Data on the diagnostic and therapeutic utility of laparoscopy were abstracted and summarized. RESULTS: Laparoscopy achieved a diagnosis in 65% to 94% of patients with chronic abdominal pain of unknown origin. Common intraoperative findings included adhesions, chronic appendicitis, hernias, and enlarged mesenteric lymph nodes. These findings corresponded with the therapeutic procedures that were performed, including laparoscopic adhesiolysis, appendectomy, and hernia repair. Therapeutic utility of laparoscopy based on pain relief, patient satisfaction, and quality of life ranged from 63% to 94%. CONCLUSIONS: Based on current available evidence, diagnostic laparoscopy (DL) is a safe and effective method for identifying organic causes of chronic abdominal pain. Laparoscopic treatment also resulted in substantial pain relief for a majority of patients. However, the efficacy of laparoscopic adhesiolysis remains controversial. We would recommend the use of DL as an early diagnostic tool, but more robust studies are needed to establish the breadth of its therapeutic utility in clinical practice.

Molecular Approaches in Single Ventricle Management.

Advances in medical and surgical management have significantly improved early outcomes in single ventricle congenital heart disease over the last 2 decades. Despite these advances, long-term outcomes remain suboptimal and therapeutic options to address systemic ventricular and/or Fontan failure are limited even in the modern era. Intricate molecular biologic techniques have shed light into the mechanisms of development of single ventricle disease. Efforts are underway to leverage this knowledge to improve clinical diagnosis, therapy, and prognostication. Cell-based therapies aimed at inducing cardiomyocyte proliferation and preventing delayed cardiac dysfunction have already entered the clinical realm. Several more novel biological therapies are expected to become available for patients with single ventricle disease in the near future. These scientific advancements provide us hope and reaffirm our faith that molecular medicine will usher in the next generation of therapies for single ventricle management.

Multiphoton Microscopy of Collagen Structure in Ex Vivo Human Skin Following Electrochemical Therapy.

OBJECTIVES: Injury to healthy dermis and the dermoepidermal junction initiates a robust healing process consisting of fibrous tissue overgrowth, collagen deposition, and scar formation. The conventional management of scars and other skin injuries has largely relied upon surgical soft tissue transfer to resurface and/or replace damaged and dysmorphic tissue with new skin. However, these strategies are invasive, expensive, and may further exacerbate integumentary injury. In this study, we examine the creation of in situ redox generated pH changes in fresh human skin. We believe this process of "electrochemical therapy" (ECT) leads to changes in collagen matrix structure. Our objective is to map local tissue pH landscapes and image changes in collagen structure of non-injured skin following ECT. STUDY DESIGN: Ex vivo human study involving ECT of human skin. METHODS: Remnant fresh ex vivo human facial skin from facelift operations was enveloped in saline-soaked gauze for a maximum of 2 hours prior to ECT and imaging. ECT was performed by inserting platinum-plated needle electrodes connected to a DC power supply. Voltage (4, 5, or 6 V) and time (3, 4, or 5 minutes) were varied systematically. High frequency ultrasound (25 MHz) was performed immediately after ECT on each sample. Treated samples were also imaged using multiphoton microscopy (MPM) with second harmonic generation (SHG) to specifically visualize collagen fibers in the dermis. The pH landscapes were mapped using indicator dyes in bisected specimens and the MPM images were compared with histologic findings. RESULTS: Above 4 V and 3 minutes, a profound reduction in dermal collagen SHG signal was observed at the anode. Although there was less blunting of SHG signal seen at the cathode, a decrease in the fluorescence of the dermoepidermal junction was observed. The pH application suggests ECT spatial selectivity and a direct relationship between voltage and application time. Ultrasound demonstrated gas formation between the anode and cathode, which is consistent with ECT's mechanism of action. Importantly, these electrochemical changes occurred without disrupting dermal and epidermal histologic architecture. CONCLUSION: ECT alters tissue pH leading to dermal collagen structural change. These results offer additional insight into the translational potential of ECT to locally remodel the soft-tissue matrix. Future directions aim to expand into a skin injury model to determine if similar collagen effects are observed in vivo. ECT is incredibly inexpensive (~$5) and may be a means to treat soft tissue injuries using simple needle-based devices and DC battery power supplies. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Factors associated with underrepresented minority physician scientist trainee career choices.

BACKGROUND: Recently, there have been concerted efforts to improve racial and ethnic diversity in the physician-scientist workforce. Identifying factors associated with career choices among those underrepresented in medicine and science is a necessary first step to advance this objective. The aim of the present study was to assess the attitudes and factors associated with academic and research career interests among underrepresented predoctoral physician-scientists. METHODS: A cross-sectional 70-question survey was distributed to all predoctoral single degree (MD or DO) and dual degree (MD/PhD or DO/PhD) trainees at 32 medical schools in the United States from 2012 to 2014. Main outcomes included factors important to advancement in academic medicine, intended medical specialty, and future career plans. To test the post-hoc hypothesis of whether trainees from underrepresented groups have differing perceptions of career trajectories and obstacles than their counterparts, we evaluated responses according to self-identified race/ethnic status using Chi-square and Fisher's exact tests. All tests were two-sided and significance level of < 0.05 was used. RESULTS: There were a total of 4433 responses representing all predoctoral training stages. The response rate was 27%. Most respondents were single degree trainees (MD/DO 79% vs MD/DO-PhD 21%). Most respondents self-identified as White (67%), followed by Multi-racial or Other (14.3%), Asian or Pacific Islander (10.4%), Hispanic (6%), and Black or African American (4.1%). Desired career sector, career intention, and clinical specialty interest differed across race/ethnic groups. With respect to career selection factors, anticipated non-work related responsibilities during residency were also significantly different between these groups. By multivariable regression analysis, Black or African American trainees were significantly less likely than White trainees to indicate a career in academia (OR 0.496, 95% CI 0.322-0.764) and basic research (OR 0.314, 95% CI 0.115-0.857), while Multi-racial or Other trainees were also less likely than White trainees to indicate a career in academia (OR 0.763, 95% CI 0.594-0.980). CONCLUSIONS: These data represent the first in-depth survey of career aspirations, perceptions, and interests between demographically underrepresented and non-underrepresented predoctoral physician-scientist trainees. Our results identify key differences between these cohorts, which may guide efforts to improve diversity within the physician-scientist workforce.

Rac1 modulates mammalian lung branching morphogenesis in part through canonical Wnt signaling.

Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity, and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment, and polarization. Furthermore, Rac1 modulates both noncanonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching. Increased cell death and BrdU uptake were notably seen in the mesenchyme, while no direct effect on the epithelium was observed. Moreover, vasculogenesis was impaired following Rac1 inhibition as shown by decreased Vegfa expression and impaired LacZ staining in Flk1-Lacz reporter mice. Rac1 inhibition decreased Fgf10 expression in conjunction with many of its associated factors. Moreover, using the reporter lines TOPGAL and Axin2-LacZ, there was an evident decrease in canonical Wnt signaling in the explants treated with the Rac1 inhibitor. Activation of canonical Wnt pathway using WNT3a or WNT7b only partially rescued the branching inhibition. Moreover, these results were validated on human explants, where Rac1 inhibition resulted in impaired branching and decreased AXIN2 and FGFR2b expression. We therefore conclude that Rac1 regulates lung branching morphogenesis, in part through canonical Wnt signaling. However, the exact mechanisms by which Rac1 interacts with canonical Wnt in human and mouse lung requires further investigation.

Heart Transplantation for Uhl Anomaly in an Adult.

Uhl anomaly is characterized by the morphologic absence of right ventricular myocardium and is an exceedingly rare cause of nonischemic cardiomyopathy. We report the first case of a successful heart transplantation in a 41-year-old patient who presented in cardiogenic shock from Uhl anomaly causing decompensated right ventricular failure.

Morbidity and Mortality in Adult Congenital Heart Surgery: Physiologic Component Augments Risk Prediction.

BACKGROUND: We sought to evaluate whether the anatomic and physiologic stratification system (ACAP score), released as part of the American College of Cardiology/American Heart Association updated guidelines for management of adult congenital heart disease (ACHD) in 2018, better estimated mortality and morbidity after cardiac operations for ACHD. METHODS: The ACAP score was determined for 318 patients (age ≥18 years) with ACHD undergoing heart surgery at our institution between December 2001 and August 2019. The primary end point was perioperative mortality. The secondary aim was to evaluate the performance of the ACAP, The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Congenital Heart Surgery Mortality Categories, and ACHS mortality scores/categories at predicting a composite adverse outcome of perioperative mortality, prolonged ventilation, and renal failure requiring replacement therapy. Logistic regression models were built to estimate mortality and the composite outcome using anatomic and physiologic components independently and together. Receiver operating characteristic curves were created, and area under the curves were compared using the Delong test. RESULTS: The median age was 37 years (interquartile range, 26.3-50.0 years). There were 9 perioperative mortalities (2.8%). With respect to perioperative mortality, the area under the curve using the anatomic component only was 0.74, which improved to 0.81 after including physiologic severity (P = .05). When physiologic severity was added to the model for the composite outcome, the discriminatory abilities of the ACHS mortality score and the STAT categories increased significantly to 0.83 (95% CI, 0.75-0.91; P = .02) and 0.82 (95% CI, 0.73-0.90; P = .04), comparable to the predictive power of ACAP. CONCLUSIONS: Physiologic severity augments ability to predict mortality and morbidity after cardiac surgery for ACHD. There is need for more robust ACHD-specific risk models.

Left ventricular unloading via percutaneous assist device during extracorporeal membrane oxygenation in acute myocardial infarction and cardiac arrest.

INTRODUCTION: A feared complication of an acute myocardial infarction (AMI) is cardiac arrest (CA). Even if return of spontaneous circulation is achieved, cardiogenic shock (CS) is common. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) supports patients with CS and is often used in conjunction with an Impella device (2.5 and CP) to off-load the left ventricle, although limited evidence supports this approach. METHODS: The goal of this study was to determine whether a mortality difference was observed in VA-ECMO alone versus VA-ECMO with Impella (ECPELLA) in patients with CS from AMI and CA. A retrospective chart review of 50 patients with AMI-CS and CA and were supported with VA-ECMO (n = 34) or ECPELLA (n = 16) was performed. The primary outcome was all-cause mortality at 6-months from VA-ECMO or Impella implantation. Secondary outcomes included in-hospital mortality and complication rates between both cohorts and intensive care unit data. RESULTS: Baseline characteristics were similar, except patients with ST-elevation myocardial infarction were more likely to be in the VA-ECMO group (p = 0.044). The ECPELLA cohort had significantly worse survival after VA-ECMO (SAVE) score (p = 0.032). Six-month all-cause mortality was not significantly different between the cohorts, even when adjusting for SAVE score. Secondary outcomes were notable for an increased rate of minor complications without an increased rate of major complications in the ECPELLA group. CONCLUSIONS: Randomized trials are needed to determine if a mortality difference exists between VA-ECMO and ECPELLA platforms in patients with AMI complicated by CA and CS.

Percutaneous Venopulmonary Extracorporeal Membrane Oxygenation as Bridge to Lung Transplantation.

Mechanical circulatory support (MCS) as a bridge to lung transplant is an infrequent but accepted pathway in patients who have refractory end-stage pulmonary failure. The American Association of Thoracic Surgeons Expert Consensus Guidelines, published in 2023, recommends venovenous (VV) extracorporeal membrane oxygenation (ECMO) as the initial configuration for those patients who have failed conventional medical therapy, including mechanical ventilation, while waiting for lung transplantation and needing MCS. Alternatively, venoarterial (VA) ECMO can be used in patients with acute right ventricular failure, hemodynamic instability, or refractory respiratory failure. With the advancement in percutaneous venopulmonary (VP) ECMO cannulation techniques, this option is becoming an attractive configuration as bridge to lung transplantation. This configuration enhances stability of the right ventricle, prevents recirculation with direct introduction of pulmonary artery oxygenation, and promotes hemodynamic stability during mobility, rehabilitation, and sedation-weaning trials before lung transplantation. Here, we present a case series of eight percutaneous VP ECMO as bridge to lung transplant with all patients mobilized, awake, and successfully transplanted with survival to hospital discharge.

A narrative review of lung cancer screening in underserved populations.

Lung cancer screening with low-dose computed tomography (LDCT) is an effective approach for the early detection of lung cancer and the reduction of lung cancer specific mortality in high risk individuals. Despite recommendations for LDCT screening by the National Comprehensive Cancer Network (NCCN) and the United States Preventive Services Task Force, the utilization of LDCT screening in clinical practice has been low. Moreover, significant disparities in the use of LDCT have been described in underserved populations, including African American or black patients, rural patients with limited access to LDCT screening facilities, and other vulnerable patient groups with known risk factors for developing lung cancer. Several patient, provider, and healthcare systems level approaches have been proposed to mitigate lung cancer screening disparities. Such approaches include raising awareness of LDCT screening benefits and the evidence in support of LDCT screening among healthcare providers, educating patients on LDCT screening and optimizing shared decision-making approaches between patients and providers, and expanding patient access to LDCT screening through free and mobile lung cancer screening programs. As lung cancer screening utilization continues to expand in clinical practice, it will be critical to continue investigating the trends, causes, and outcomes of LDCT screening disparities in underserved populations.

Impact of COVID-19 Pandemic on Physician-Scientist Trainees to Faculty One Year into the Pandemic.

Purpose: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on research productivity for physician-scientists at all levels of training. Methods: A survey of medical students, graduate students, and residents/fellows/junior faculty (RFJF) was conducted from April to August 2021 to assess the impact of COVID-19 on individual stress, productivity, and optimism. Multivariate regression analyses were performed to identify associated variables and unsupervised variable clustering techniques were employed to identify highly correlated responses. Results: A total 677 respondents completed the survey, representing different stages of physician-scientist training. Respondents report high levels of stress (medical students: 85%, graduate students: 63%, RFJF: 85%) attributed to impaired productivity concerns, concern about health of family and friends, impact on personal health and impairment in training or career development. Many cited impaired productivity (medical students: 65% graduate students: 79%, RFJF: 78%) associated with pandemic impacts on training, labs closures and loss of facility/resource access, and social isolation. Optimism levels were low (medical students: 37%, graduate students: 38% and RFJF: 39%) with females less likely to be optimistic and more likely to report concerns of long-term effects of COVID-19. Optimism about the future was correlated with not worrying about the long-term effects of COVID-19. Since the COVID-19 pandemic, all respondents reported increased prioritization of time with family/friends (67%) and personal health (62%) over career (25%) and research (24%). Conclusions: This national survey highlights the significant and protracted impact of the COVID-19 pandemic on stress levels, productivity, and optimism among physician-scientists and trainees. These findings underscore the urgent need for tailored support, including mental health, academic, and career development assistance for this biomedical workforce.

Fate of the Right Ventricular Outflow Tract Following Valve-Sparing Repair of Tetralogy of Fallot.

Valve-sparing repair (VSR) of tetralogy of Fallot (TOF) tends to result in higher residual right ventricular outflow tract (RVOT) gradients. We evaluated the progression and clinical implications of RVOT gradients following VSR of TOF. Demographic, clinical, and operative data were retrospectively collected from consecutive TOF patients who underwent VSR at our institution between 01/2010 and 06/2021. RVOT gradient, pulmonary valve annulus (PVA) diameter and Boston Z-scores were recorded from serial echocardiograms. Data are presented as median and interquartile range or number and percentage. A total of 156 children (boys 92, 59%) underwent VSR at 6.5 (4.9-8.4) months of age and 6.6 kg (5.6- 7.7) weight. There was 1 (0.6%) operative mortality. The remaining 155 patients were followed for 69.4 months (4-106.2). RVOT gradient was 2.4m/s (1.7-2.9) at discharge. It transiently increased, then declined and stabilized during follow-up. PVA Z-score was -1.7 (-3.1 to 0.5) at discharge and 'grew' to -0.8 (-1.7 to 0.4) at last follow-up. Freedom from RVOT re-intervention was 97%, 94% and 91% at 1, 5 and 10-year follow-up. Among 67 (43%) patients with PVA Z-score < -2, a similar RVOT gradient pattern was observed and freedom from RVOT re-intervention was 97%, 95% and 95% at 1, 5 and 8-year follow-up. Following VSR of TOF, RVOT gradients transiently increase and then fall as PVA growth catches up, resulting in durable intermediate outcomes. Patients with PVA Z-score < -2 demonstrated a similar pattern of hemodynamics in the RVOT and excellent freedom from reintervention.