Citations

BACKGROUND: The American Board of Anesthesiology administers the APPLIED Examination as a part of initial certification, which as of 2018 includes 2 components—the Standardized Oral Examination (SOE) and the Objective Structured Clinical Examination (OSCE). The goal of this study is to investigate the measurement construct(s) of the APPLIED Examination to assess whether the SOE and the OSCE measure distinct constructs (ie, factors). METHODS: Exploratory item factor analysis of candidates’ performance ratings was used to determine the number of constructs, and confirmatory item factor analysis to estimate factor loadings within each construct and correlation(s) between the constructs. RESULTS: In exploratory item factor analysis, the log-likelihood ratio test and Akaike information criterion index favored the 3-factor model, with factors reflecting the SOE, OSCE Communication and Professionalism, and OSCE Technical Skills. The Bayesian information criterion index favored the 2-factor model, with factors reflecting the SOE and the OSCE. In confirmatory item factor analysis, both models suggest moderate correlation between the SOE factor and the OSCE factor; the correlation was 0.49 (95% confidence interval [CI], 0.42-0.55) for the 3-factor model and 0.61 (95% CI, 0.54-0.64) for the 2-factor model. The factor loadings were lower for Technical Skills stations of the OSCE (ranging from 0.11 to 0.25) compared with those of the SOE and Communication and Professionalism stations of the OSCE (ranging from 0.36 to 0.50). CONCLUSIONS: The analyses provide evidence that the SOE and the OSCE measure distinct constructs, supporting the rationale for administering both components of the APPLIED Examination for initial certification in anesthesiology.

Abstract Background: The coronavirus disease-2019 (COVID-19) has resulted in nationwide lockdowns, cessation of school and work, and social distancing. Reducing the negative impacts, such as weight-gain, has garnered global attention.Methods: In this dual-center retrospective observational study of 12,889 students (aged 18-20), who performed a national student physical fitness battery between December 1, 2019, to January 20, 2020, and completed a follow-up online questionnaire beginning on May 1, 2020, and ending on May 23, 2020, and examined the associations between weight-gain and COVID-19 induced stress, depression and self-reported physical activity, dietary habits and sedentary time. Results: Participants gained an average of 2.6 kg (95% CI: 2.0 to 3.2 kg) for males and 2.1 kg (1.9 to 2.4 kg) for females. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in males and females respectively (P<0.001). Weight change was associated with sedentary time, COVID-19 induced stress, and depression score. Conclusion: These findings suggest that limiting sedentary time during lockdowns and strategies aimed t improve lifestyle habits and psychological health may be warranted to mitigate weight-gain during the pandemic.Registration: Registered with ChiCTR, registration no.: ChiCTR2000033514

Objectives The purpose of this study was to explore the utility of an injectable purified exosome product derived from human apheresis blood to (1) augment surgical closure of vaginal mesh exposures, and (2) serve as a stand-alone therapy for vaginal mesh exposure. Methods Sixteen polypropylene meshes (1×1–3×3 cm) were implanted in the vaginas of 7 Yorkshire-crossed pigs by urogynecologic surgeons (day 0). On day 7, group 1 underwent surgical intervention via vaginal tissue suture reclosure with (n=2 pigs, n=4 meshes) or without (n=2 pigs, n=4 meshes) exosome injection; group 2 underwent medical intervention with an exosome injection (n=3, n=8 meshes). One animal in group 2 was given oral 2′-deoxy-5-ethynyluridine to track cellular regeneration. Euthansia occurred at 5 weeks. Results Mesh exposures treated with surgical closure alone experienced reexposure of the mesh. Exosome treatment with or without surgical closure resulted in partial to full mesh exposure resolution up to 3×3 cm. Exosome-treated tissues had significantly thicker regenerated epithelial tissue (208 μm exosomes-only and 217 μm surgery+exosomes, versus 80 μm for surgery-only; P < 0.05); evaluation of 2′-deoxy-5-ethynyluridine confirmed de novo regeneration throughout the epithelium and underlying tissues. Capillary density was significantly higher in the surgery+exosomes group ( P = 0.03). Surgery-only tissues had a higher inflammatory and fibrosis response as compared with exosome-treated tissues. Conclusions In this pilot study, exosome treatment augmented healing in the setting of vaginal mesh exposure, reducing the incidence of mesh reexposure after suture closure and decreasing the area of mesh exposure through de novo tissue regeneration after exosome injection only. Further study of varied local tissue conditions and mesh configurations is warranted.

BACKGROUND: Anesthesiology residents’ experiences and perspectives about their programs may be helpful in improving training. The goals of this repeated cross-sectional survey study are to determine: (1) the most important factors residents consider in choosing an anesthesiology residency, (2) the aspects of the clinical base year that best prepare residents for anesthesia clinical training, and what could be improved, (3) whether residents are satisfied with their anesthesiology residency and what their primary struggles are, and (4) whether residents believe their residency prepares them for proficiency in the 6 Accreditation Council for Graduate Medical Education (ACGME) Core Competencies and for independent practice. METHODS: Anesthesiologists beginning their US residency training from 2013 to 2016 were invited to participate in anonymous, confidential, and voluntary self-administered online surveys. Resident cohort was defined by clinical anesthesia year 1, such that 9 survey administrations were included in this study—3 surveys for the 2013 and 2014 cohorts (clinical anesthesia years 1–3), 2 surveys for the 2015 cohort (clinical anesthesia years 1–2), and 1 survey for the 2016 cohort (clinical anesthesia year 1). RESULTS: The overall response rate was 36% (4707 responses to 12,929 invitations). On a 5-point Likert scale with 1 as “very unimportant” and 5 as “very important,” quality of clinical experience (4.7–4.8 among the cohorts) and departmental commitment to education (4.3–4.5) were rated as the most important factors in anesthesiologists’ choice of residency. Approximately 70% of first- and second-year residents agreed that their clinical base year prepared them well for anesthesiology residency, particularly clinical training experiences in critical care rotations, anesthesiology rotations, and surgery rotations/perioperative procedure management. Overall, residents were satisfied with their choice of anesthesiology specialty (4.4–4.5 on a 5-point scale among cohort-training levels) and their residency programs (4.0–4.1). The residency training experiences mostly met their expectations (3.8–4.0). Senior residents who reported any struggles highlighted academic more than interpersonal or technical difficulties. Senior residents generally agreed that the residency adequately prepared them for independent practice (4.1–4.4). Of the 6 ACGME Core Competencies, residents had the highest confidence in professionalism (4.7–4.9) and interpersonal and communication skills (4.6–4.8). Areas in residency that could be improved include the provision of an appropriate balance between education and service and allowance for sufficient time off to search and interview for a postresidency position. CONCLUSIONS: Anesthesiology residents in the United States indicated they most value quality of clinical training experiences and are generally satisfied with their choice of specialty and residency program.

BACKGROUND: A temporary decrease in anesthesiology residency graduates that occurred around the turn of the millennium may have workforce implications. The aims of this study are to describe, between 2005 and 2015, (1) demographic changes in the workforce of physicians trained as anesthesiologists; (2) national and state densities of these physicians, as well as temporal changes in the densities; and (3) retention of medical licenses by mid- and later-career anesthesiologists. METHODS: Using records from the American Board of Anesthesiology and state medical and osteopathic boards, the numbers of licensed physicians aged 30–59 years who had completed Accreditation Council for Graduate Medical Education–accredited anesthesiology residency training were calculated cross-sectionally for 2005, 2010, and 2015. Demographic trends were then described. Census data were used to calculate national and state densities of licensed physicians. Individual longitudinal data were used to describe retention of medical licenses among older physicians. RESULTS: The number of licensed physicians trained as anesthesiologists aged 30–59 years increased from 32,644 in 2005 to 36,543 in 2010 and 36,624 in 2015, representing a national density of 1.10, 1.18, and 1.14 per 10,000 population in those years, respectively. The density of anesthesiologists among states ranged from 0.37 to 3.10 per 10,000 population. The age distribution differed across the years. For example, anesthesiologists aged 40–49 years predominated in 2005 (47%), but by 2015, only 31% of anesthesiologists were aged 40–49 years. The proportion of female anesthesiologists grew from 22% in 2005, to 24% in 2010, and to 28% in 2015, particularly among early-career anesthesiologists. For anesthesiologists with licenses in 2005, the number who still had active licenses in 2015 decreased by 9.6% for those aged 45–49 years, by 14.1% for those aged 50–54 years, and by 19.7% for those aged 55–59 years. CONCLUSIONS: The temporary decrease in anesthesiology residency graduates around the turn of the 21st century decreased the proportion of anesthesiologists who were midcareer as of 2015. This may affect the future availability of senior leaders as well as the future overall workforce in the specialty as older anesthesiologists retire. National efforts to plan for workforce needs should recognize the geographical variability in the distribution of anesthesiologists.

Abstract The tumor-suppressor protein RB acts as a transcription repressor via interaction of its pocket domain with an LXCXE motif in histone deacetylase (HDAC) proteins such as HDAC1. Here, we demonstrate that HDAC5 deficient for the LXCXE motif interacts with both RB-N (via an FXXXV motif) and RB-C segments, and such interactions are diminished by phosphorylation of RB serine-249/threonine-252 and threonine-821. HDAC5 was frequently downregulated or deleted in human cancers such as prostate cancer. Loss of HDAC5 increased histone H3 lysine 27 acetylation (H3K27-ac) and circumvented RB-mediated repression of cell-cycle–related pro-oncogenic genes. HDAC5 loss also conferred resistance to CDK4/6 inhibitors such as palbociclib in prostate and breast cancer cells in vitro and prostate tumors in vivo, but this effect was overcome by the BET-CBP/p300 dual inhibitor NEO2734. Our findings reveal an unknown role of HDAC5 in RB-mediated histone deacetylation and gene repression and define a new mechanism modulating CDK4/6 inhibitor therapeutic sensitivity in cancer cells. Significance: This study defines a previously uncharacterized role of HDAC5 in tumor suppression and provides a viable strategy to overcome CDK4/6 inhibitor resistance in HDAC5-deficent cancer.

AbstractPurpose:Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC.Experimental Design:Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded.Results:We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade–based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months; P = 0.03).Conclusions:These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.

AbstractBackground and AimLiraglutide, a long‐acting GLP‐1 analog, is approved for the treatment of obesity with improvements in fasting blood glucose, hemoglobin A1c, and cardiovascular health. Our aim was to measure the impact of liraglutide dose for obesity on hepatic steatosis measured by ultrasound.MethodsA single‐center, randomized, double‐blind, placebo‐controlled pilot trial was undertaken in nondiabetic obese, otherwise healthy patients aged 18–65 years. Participants were randomly assigned to receive subcutaneous liraglutide (3.0 mg) or placebo over 16 weeks with dose escalation following US Food and Drug Administration guidelines. Both groups received standardized nutritional and behavioral counseling during the 16 weeks. Hepatic fat content was measured by ultrasound at baseline, 8 weeks, and 16 weeks as an attenuation coefficient (ACE). Effects of treatment were assessed using t‐test for the entire groups and for patient subgroup with baseline ACE >0.66 (indicating significant steatosis).ResultsAmong 30 patients (93% female) enrolled, 16 were randomized to placebo and 14 to liraglutide. Baseline body mass indices (BMIs) and average age were similar in the two groups. After 16 weeks, the liraglutide group had a significant improvement in steatosis ACE scores (−0.068 ± 0.02 vs −0.0077 ± 0.02 placebo, P = 0.05). Change in steatosis was positively correlated with change in BMI (R2 = 0.402, P = 0.0007). Within the liraglutide group, patients with baseline ACE >0.66 had improvement in ACE (−0.134 ± 0.03) compared to those without significant steatosis (−0.041 ± 0.02, P = 0.05).ConclusionsIn this pilot trial, liraglutide, 3.0 mg over 16 weeks, reduced hepatic steatosis; a reduction in hepatic steatosis is correlated with BMI reduction, and effects are particularly evident in those with a significant degree of steatosis by ultrasound imaging.

Abstract Background: Patient-ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background.Methods: A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥12 hours.Results: A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P<0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P<0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P<0.01).Conclusion: Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.