Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML.

Inherited predisposition to myeloid malignancies is more common than previously appreciated. We analyzed the whole-exome sequencing data of paired leukemia and skin biopsy samples from 391 adult patients from the Beat AML 1.0 consortium. Using the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines for variant interpretation, we curated 1547 unique variants from 228 genes. The pathogenic/likely pathogenic (P/LP) germline variants were identified in 53 acute myeloid leukemia (AML) patients (13.6%) in 34 genes, including 6.39% (25/391) of patients harboring P/LP variants in genes considered clinically actionable (tier 1). 41.5% of the 53 patients with P/LP variants were in genes associated with the DNA damage response. The most frequently mutated genes were CHEK2 (8 patients) and DDX41 (7 patients). Pathogenic germline variants were also found in new candidate genes (DNAH5, DNAH9, DNMT3A, and SUZ12). No strong correlation was found between the germline mutational rate and age of AML onset. Among 49 patients who have a reported history of at least one family member affected with hematological malignancies, 6 patients harbored known P/LP germline variants and the remaining patients had at least one variant of uncertain significance, suggesting a need for further functional validation studies. Using CHEK2 as an example, we show that three-dimensional protein modeling can be one of the effective methodologies to prioritize variants of unknown significance for functional studies. Further, we evaluated an in silico approach that applies ACMG curation in an automated manner using the tool for assessment and (TAPES) prioritization in exome studies, which can minimize manual curation time for variants. Overall, our findings suggest a need to comprehensively understand the predisposition potential of many germline variants in order to enable closer monitoring for disease management and treatment interventions for affected patients and families.

Post-Hospitalization Home Monitoring Programs During the COVID-19 Pandemic: Survey Results from the Hospital Medicine Re-engineering Network (HOMERuN).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, hospitals and healthcare systems launched innovative responses to emerging needs. The creation and use of programs to remotely follow patient clinical status and recovery after COVID-19 hospitalization has not been thoroughly described. OBJECTIVE: To characterize deployment of remote post-hospital discharge monitoring programs during the COVID-19 pandemic METHODS: Electronic surveys were administered to leaders of 83 US academic hospitals in the Hospital Medicine Re-engineering Network (HOMERuN). An initial survey was completed in March 2021 with follow-up survey completed in July 2022. RESULTS: There were 35 responses to the initial survey (42%) and 15 responses to the follow-up survey (43%). Twenty-two (63%) sites reported a post-discharge monitoring program, 16 of which were newly developed for COVID-19. Physiologic monitoring devices such as pulse oximeters were often provided. Communication with medical teams was often via telephone, with moderate use of apps or electronic medical record integration. Programs launched most commonly between January and June 2020. Only three programs were still active at the time of follow-up survey. CONCLUSIONS: Our findings demonstrate rapid, ad hoc development of post-hospital discharge monitoring programs during the COVID-19 pandemic but with little standardization or evaluation. Additional study could identify the benefits of these programs, instruct their potential application to other disease processes, and inform further development as part of emergency preparedness for upcoming crises.

Analysis of Clinical Criteria for Discharge Among Patients Hospitalized for COVID-19: Development and Validation of a Risk Prediction Model.

BACKGROUND: Patients hospitalized with COVID-19 can clinically deteriorate after a period of initial stability, making optimal timing of discharge a clinical and operational challenge. OBJECTIVE: To determine risks for post-discharge readmission and death among patients hospitalized with COVID-19. DESIGN: Multicenter retrospective observational cohort study, 2020-2021, with 30-day follow-up. PARTICIPANTS: Adults admitted for care of COVID-19 respiratory disease between March 2, 2020, and February 11, 2021, to one of 180 US hospitals affiliated with the HCA Healthcare system. MAIN MEASURES: Readmission to or death at an HCA hospital within 30 days of discharge was assessed. The area under the receiver operating characteristic curve (AUC) was calculated using an internal validation set (33% of the HCA cohort), and external validation was performed using similar data from six academic centers associated with a hospital medicine research network (HOMERuN). KEY RESULTS: The final HCA cohort included 62,195 patients (mean age 61.9 years, 51.9% male), of whom 4704 (7.6%) were readmitted or died within 30 days of discharge. Independent risk factors for death or readmission included fever within 72 h of discharge; tachypnea, tachycardia, or lack of improvement in oxygen requirement in the last 24 h; lymphopenia or thrombocytopenia at the time of discharge; being ≤ 7 days since first positive test for SARS-CoV-2; HOSPITAL readmission risk score ≥ 5; and several comorbidities. Inpatient treatment with remdesivir or anticoagulation were associated with lower odds. The model's AUC for the internal validation set was 0.73 (95% CI 0.71-0.74) and 0.66 (95% CI 0.64 to 0.67) for the external validation set. CONCLUSIONS: This large retrospective study identified several factors associated with post-discharge readmission or death in models which performed with good discrimination. Patients 7 or fewer days since test positivity and who demonstrate potentially reversible risk factors may benefit from delaying discharge until those risk factors resolve.

Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age.

BACKGROUND: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. OBJECTIVE: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. STUDY DESIGN: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. RESULTS: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56-11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69-0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06-0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03-0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36-0.91; P=.019). CONCLUSION: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.

Increasing Trainee Engagement in Surgery Societies: The Society of Asian Academic Surgeons Experience.

INTRODUCTION: Surgical societies provide a plethora of resources for trainees; however, these opportunities are often underused due to suboptimal guidance, sponsorship, or mentorship. Here, we present the Society of Asian Academic Surgeons (SAAS) experience in enhancing the trainee experience and engagement in a surgical society focused on professional development. MATERIALS AND METHODS: We conducted an interactive idea-generating session during the 2022 SAAS Conference with all Associate Members (trainees) present in Honolulu, HI. Recurrent themes, concepts, and ideas/suggestions were carefully considered when planning the next SAAS Conference in Baltimore, MD. We employed a more targeted approach to trainee engagement at the 2023 SAAS Conference, with breakout sessions geared toward various levels of trainees, in addition to increased social events and networking opportunities. We obtained feedback from trainees in attendance through an electronic survey and informal conversations with faculty and Associate Members. RESULTS: Opportunities for surgical subspecialty networking was the most well-received portion of our formal Career Development program. The majority of trainees in attendance were medical students or junior residents who valued the exposure to junior faculty and those in leadership positions at academic institutions. The addition of a group text for easy communication among trainees and informal social activities for Associate Member networking among themselves were crucial in improving the overall conference experience. CONCLUSIONS: Opportunities to maximize trainee engagement in surgical societies are heightened during in-person conferences. Targeted session topics, guided networking opportunities, and creating channels for easier communication along with more social events have enhanced the overall experience for aspiring and current surgical trainees.

Prior Bariatric Surgery is Associated with Improved Total Hip Arthroplasty Outcomes in Patients Who Have Obesity: A National Cohort Study with 6 Years of Follow-Up.

BACKGROUND: Obesity is a risk factor for end-stage hip osteoarthritis (OA). While total hip arthroplasty (THA) is commonly performed to reduce pain and improve function associated with OA, obesity has been associated with an increased risk of complications after THA. Although bariatric surgery may also be utilized to reduce weight, the impact of bariatric surgery on THA outcomes remains inadequately understood. METHODS: This retrospective cohort analysis utilized multicenter electronic medical record data ranging from 2003 to 2023. Patients who have obesity who underwent THA were stratified based on prior bariatric surgery. The final bariatric cohort comprised 451 patients after propensity score matching. Complication rates and revision risks were compared between cohorts at six, 24, and 72 months. Additional analysis stratified patients by interval between bariatric surgery and THA. RESULTS: At six-month follow-up, the bariatric cohort had significantly lower risks of surgical site infection (SSI), wound dehiscence, and deep vein thrombosis (DVT). At 24 months, the bariatric cohort had a lower risk of DVT. At 72 month follow-up, the bariatric cohort had reduced rates of revision, mortality, cardiac morbidity, and Clavien-Dindo grade IV complications. CONCLUSION: Obese patients who underwent bariatric surgery prior to THA experienced reduced medical complications at all time points and reduced rates of revision at 72 months relative to a matched cohort who did not undergo bariatric surgery.

Percent Final Height Is a Novel Method That Identifies Differences Between the Rate of Development in American Children of Different Races.

INTRODUCTION: The Greulich & Pyle (G&P) Radiographic Atlas of Skeletal Development uses hand x-rays obtained between 1926 and 1942 on children of Caucasian ancestry. Our study uses modern Caucasian, Black, Hispanic, and Asian children to investigate patterns of development as a function of percent final height (PFH). METHODS: A retrospective review, at a single institution, was conducted using children who received a hand x-ray, a height measurement taken within 60 days of that x-ray, and a final height. BA and CA were compared between races. PFH was calculated by dividing height at the time of the x-ray by their final height. To further evaluate differences between races in CA or BA, PFH was then modeled as a function of CA or BA using a fifth-degree polynomial regression, and mean ages at the 85th PFH were compared. Patients were then divided into Sanders stages 1, 2-4, and 5-8 and the mean PFH, CA, and BA of the Asian, Black, and Hispanic children were compared with the White children using Student t test. P values less than 0.05 were considered significant. RESULTS: We studied 498 patients, including 53 Asian, 83 Black, 190 Hispanic, and 172 White patients. Mean BA was significantly greater than CA in Black males (1.27 y) and females (1.36 y), Hispanic males (1.12 y) and females (1.29 y), and White females (0.74 y). Hispanic and Black patients were significantly more advanced in BA than White patients (P<0.001). At the 85th PFH, White and Hispanic males were older than Black males by at least 7 months (P<0.001), and White females were significantly older than Hispanic females by 6.4 months (P<0.001). At 85th PFH for males, Hispanic and Black males had greater BA than White males by at least 5 months (P<0.001), and Asian females had a greater BA than Black females by at least 5 months (P<0.001). Compared with White children, Hispanic children were significantly younger at Sanders 2-4 than White children, and Black children were skeletally older at Sanders 5-8. CONCLUSIONS: BA was greater than CA by ≥1 year in Black and Hispanic children, and that these children had a significantly greater BA than their White counterparts. Black males and Hispanic females reached their 85th PFH at younger ages, and Hispanic males and Asian females were the most skeletally mature at their 85th PFH. Our results suggest that BA and CA may vary as a function of race, and further studies evaluating growth via the 85th PFH may be necessary. LEVEL OF EVIDENCE: Therapeutic Study - Level IV.

Prevalence and Causes of Diagnostic Errors in Hospitalized Patients Under Investigation for COVID-19.

BACKGROUND: The COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs). OBJECTIVE: To determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19. DESIGN: Retrospective cohort. SETTING: Eight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN). TARGET POPULATION: Adults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020. MEASUREMENTS: We randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs. RESULTS: Two hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p < 0.01). Diagnostic process faults associated with policies and procedures related to COVID-19 were not associated with DE risk. Fourteen patients (35.9% of patients with errors and 5.4% overall) suffered harm or death due to diagnostic error. LIMITATIONS: Results are limited by available documentation and do not capture communication between providers and patients. CONCLUSION: Among PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation.

Self-reported adherence to direct oral anticoagulants versus warfarin therapy in a specialized thrombosis service-a cross-sectional study of patients in a Canadian Health Region.

PURPOSE: Direct oral anticoagulants (DOACs) have a better safety and efficacy profile than warfarin and are currently recommended for stroke prevention in non-valvular atrial fibrillation (AF) and treatment of venous thromboembolism (VTE). Given that DOACs do not require regular laboratory monitoring compared to warfarin, patients' interactions with the health care system is reduced. Adequate adherence to DOACs is important and reported adherence to anticoagulation is unclear in clinical practice. This study aims to assess self-reported adherence to oral anticoagulants in a specialized Adult Outpatient Thrombosis Service (TS).  METHODS: This cross-sectional study included patients aged ≥ 18 years who were prescribed an oral anticoagulant and had attended at least one appointment with an Adult Outpatient Thrombosis Service (TS) between October 10, 2017, and May 31, 2019. Adherence to oral anticoagulant therapy was assessed using the 12-item validated Adherence to Refills and Medications Scale (ARMS) score. Logistic regression analyses were used to evaluate association between patient characteristics and medication adherence. Adherence rates in DOACs and warfarin were compared. RESULTS: Three hundred and ninety-nine patients completed and returned the survey. Of the 399 who completed the survey, 74% were prescribed DOACs and 26% received warfarin. Most of the patients (89.3%) were ≥ 50 years of age and half (57.3%) were male. About two-thirds (67%) had at least post-secondary education. The duration of anticoagulation use differed between patients on DOAC and warfarin; a greater proportion of those who had used anticoagulants for less than 1 year was on DOACs compared to warfarin (20.9% vs 4.9%, p = 0.001). For patients who had been on anticoagulation for > 5 years, the proportion of warfarin patients was greater than DOAC (57.8% vs 20.5%, p = 0.001). Self-reported adherence to oral anticoagulant therapy using the 12-item ARMS scale for warfarin and DOACs were 87.3% and 90.9%, respectively. Among the warfarin users, patient satisfaction with TS was associated with medication adherence (OR = 0.22; 95% CI: 0.05-0.89). CONCLUSIONS: Self-reported medication adherence was similar between warfarin and DOACs. Since suboptimal adherence is associated with poor clinical outcomes and increased costs, various stakeholders should emphasize the importance of medication adherence to oral anticoagulants at each patient encounter.

Half-pin Breakage in Multiplanar External Fixators Used for Pediatric Deformity Correction.

BACKGROUND: Pediatric patients with leg length discrepancies and complex deformities may require multiplanar external fixators for correction. We have encountered 4 cases of half-pin breakage with the Orthex hexapod frame. The purpose of this study is to report factors associated with half-pin breakage and compare various deformity correction characteristics between 2 hexapod frames - Taylor Spatial Frame (TSF) and Orthex. METHODS: Pediatric patients with lower extremity deformities treated with an Orthex or TSF at a single tertiary children's hospital between 2012 and 2022 were included for retrospective review. Variables compared between frame groups include frame configuration, half-pin/wire fixation, length achieved, angular correction, and frame time. RESULTS: There were 23 Orthex frames (23 patients) and 36 TSF (33 patients) included. Four Orthex and zero TSF had proximal half-pin breakage. The Orthex group was younger on average (10 vs. 12 y, P =.04*) at the time of frame placement. The majority (52%) of Orthex frames were used for simultaneous lengthening and angular correction, while the majority (61%) of TSF was used for only angular correction. Orthex had more half-pins used for proximal fixation (median 3 vs. 2, P <0.0001*) and more frames with nonstandard configuration (7 (30%) vs. 1 (3%), P =0.004*). Orthex group had a longer total frame time (median 189 vs. 146 days, P =0.012*) and longer time required for regenerate healing (117 vs. 89 d, P =0.02*). There were no significant differences in length gained, angular correction, or healing index between Orthex and TSF. Nonstandard configuration, increased number of proximal half-pins, younger age at index surgery, and increased lengthening were associated with pin breakage. CONCLUSIONS: This is the first study to report half-pin breakage while using multiplanar frames in pediatric lower extremity deformity correction. The Orthex and TSF groups consisted of significantly different patients and frame configurations, making it difficult to identify any specific cause for pin breakage. This study shows that pin breakage is likely caused by multiple factors and is associated with the increased complexity of deformity correction. LEVEL OF EVIDENCE: Level III-Retrospective Comparison Study.

Placental growth factor as a sensitive biomarker for vascular cognitive impairment.

INTRODUCTION: High-performing biomarkers measuring the vascular contributions to cognitive impairment and dementia are lacking. METHODS: Using a multi-site observational cohort study design, we examined the diagnostic accuracy of plasma placental growth factor (PlGF) within the MarkVCID Consortium (n = 335; CDR 0-1). Subjects underwent clinical evaluation, cognitive testing, MRI, and blood sampling as defined by Consortium protocols. RESULTS: In the prospective population of 335 subjects (72.2 ± 7.8 years of age, 49.3% female), plasma PlGF (pg/mL) shows an ordinal odds ratio (OR) of 1.16 (1.07-1.25; P = .0003) for increasing Fazekas score and ordinal OR of 1.22 (1.14-1.32; P < .0001) for functional cognitive impairment measured by the Clinical Dementia Rating scale. We achieved the primary study outcome of a site-independent association of plasma PlGF (pg/mL) with white matter injury and cognitive impairment in two of three study cohorts. Secondary outcomes using the full MarkVCID cohort demonstrated that plasma PlGF can significantly discriminate individuals with Fazekas ≥ 2 and CDR = 0.5 (area under the curve [AUC] = 0.74) and CDR = 1 (AUC = 0.89) from individuals with CDR = 0. DISCUSSION: Plasma PlGF measured by standardized immunoassay functions as a stable, reliable, diagnostic biomarker for cognitive impairment associated with substantial white matter burden.

Adaptability on Shifting Ground: a Rapid Qualitative Assessment of Multi-institutional Inpatient Surge Planning and Workforce Deployment During the COVID-19 Pandemic.

BACKGROUND: During the initial wave of COVID-19 hospitalizations, care delivery and workforce adaptations were rapidly implemented. In response to subsequent surges of patients, institutions have deployed, modified, and/or discontinued their workforce plans. OBJECTIVE: Using rapid qualitative methods, we sought to explore hospitalists' experiences with workforce deployment, types of clinicians deployed, and challenges encountered with subsequent iterations of surge planning during the COVID-19 pandemic across a collaborative of hospital medicine groups. APPROACH: Using rapid qualitative methods, focus groups were conducted in partnership with the Hospital Medicine Reengineering Network (HOMERuN). We interviewed physicians, advanced practice providers (APP), and physician researchers about (1) ongoing adaptations to the workforce as a result of the COVID-19 pandemic, (2) current struggles with workforce planning, and (3) evolution of workforce planning. KEY RESULTS: We conducted five focus groups with 33 individuals from 24 institutions, representing 52% of HOMERuN sites. A variety of adaptations was described by participants, some common across institutions and others specific to the institution's location and context. Adaptations implemented shifted from the first waves of COVID patients to subsequent waves. Three global themes also emerged: (1) adaptability and comfort with dynamic change, (2) the importance of the unique hospitalist skillset for effective surge planning and redeployment, and (3) the lack of universal solutions. CONCLUSIONS: Hospital workforce adaptations to the COVID pandemic continued to evolve. While few approaches were universally effective in managing surges of patients, and successful adaptations were highly context dependent, the ability to navigate a complex system, adaptability, and comfort in a chaotic, dynamic environment were themes considered most critical to successful surge management. However, resource constraints and sustained high workload levels raised issues of burnout.

Outcomes of prolonged mechanical ventilation and tracheostomy in critically ill elderly patients: a historical cohort study.

PURPOSE: With an aging global population, the increased proportion of elderly patients in the intensive care unit (ICU) raises important questions regarding optimal management. Currently, data on tracheostomy and its outcomes in the elderly are limited. We aimed to determine the in-hospital survival of elderly ICU patients following tracheostomy, and describe impacts on discharge disposition and functional outcomes. METHODS: We conducted a historical cohort study at two academic hospitals in Toronto. All patients aged ≥ 70 yr who received a tracheostomy during their ICU stay between January 2010 and June 2016 were included in a retrospective chart review. Data on patient demographics, frailty, tracheostomy indication, and outcomes were collected. RESULTS: The study included 270 patients with a mean (standard deviation) age of 81 (6) yr. The majority were admitted to ICU for respiratory failure (147/270, 54%) and received a tracheostomy for prolonged mechanical ventilation (202/270, 75%). Intensive care unit and hospital mortality were 26% (68/270) and 46% (125/270), respectively. Twenty-five percent (67/270) of patients were decannulated during hospital admission, a median [interquartile range (IQR)] of 41 [25-68] days after tracheostomy. Intensive care unit and hospital length of stay were 31 [17-53] and 81 [46-121] days, respectively. At hospital discharge, 6% (17/270) of patients were discharged home, all were frail (median Clinical Frailty Score of 7) and most were tube-fed (101/270, 70%), unable to speak (81/270, 56%), and nonambulatory (98/270, 68%). CONCLUSIONS: In patients aged ≥ 70 yr, tracheostomy during ICU stay marked a transition toward prolonged chronic critical illness. Nearly half of the patients died during the admission, and although a quarter were successfully decannulated, the majority of survivors were left with severe frailty and functional impairment.

RéSUMé: OBJECTIF: Avec le vieillissement de la population mondiale, la proportion accrue de patients âgés aux soins intensifs (USI) soulève d'importantes questions concernant leur prise en charge optimale. À l'heure actuelle, les données sur la trachéotomie et ses issues chez les personnes âgées sont limitées. Nous avions pour objectif de déterminer la survie hospitalière des patients âgés en soins intensifs après une trachéotomie et d'examiner les impacts sur la disposition au congé et les devenirs fonctionnels. MéTHODE: Nous avons mené une étude de cohorte historique dans deux hôpitaux universitaires de Toronto. Tous les patients âgés de ≥ 70 ans ayant reçu une trachéotomie pendant leur séjour à l'USI entre janvier 2010 et juin 2016 ont été inclus dans un examen rétrospectif des dossiers. Les données sur la démographie des patients, leur fragilité, l'indication pour la trachéotomie et les devenirs ont été recueillies. RéSULTATS: L'étude a inclus 270 patients avec un âge moyen (écart type) de 81 (6) ans. La majorité d'entre eux ont été admis à l'USI pour insuffisance respiratoire (147/270, 54 %) et ont subi une trachéotomie pour une ventilation mécanique prolongée (202/270, 75 %). La mortalité à l'USI et à l'hôpital était de 26 % (68/270) et 46 % (125/270), respectivement. Vingt-cinq pour cent (67/270) des patients ont été décanulés pendant leur admission à l'hôpital, [écart interquartile (ÉIQ)] 41 [25-68] jours après la trachéotomie en moyenne. La durée du séjour à l'USI et à l'hôpital était de 31 [17-53] et 81 [46-121] jours, respectivement. Lors du congé de l'hôpital, 6 % (17/270) des patients sont rentrés chez eux, tous étaient fragiles (score médian de fragilité clinique de 7) et la plupart étaient nourris par sonde (101/270, 70 %), incapables de parler (81/270, 56 %) et non ambulatoires (98/270, 68 %). CONCLUSIONS: Chez les patients âgés de ≥ 70 ans, la trachéotomie pendant le séjour aux soins intensifs a marqué une transition vers une maladie chronique grave prolongée. Près de la moitié des patients sont décédés pendant leur séjour, et bien qu'un quart aient été décanulés avec succès, la majorité des survivants se sont retrouvés avec une fragilité sévère et une déficience fonctionnelle.

Patient satisfaction with quality of care of a multidisciplinary thrombosis service - a cross sectional survey.

BACKGROUND: In October 2017 we opened a multidisciplinary Adult Outpatient Thrombosis Service (Thrombosis Service) in a regional health authority servicing over 300 000 people. The Thrombosis Service is a comprehensive thrombosis and anticoagulation management program with unique, interrelated clinics providing a broad spectrum of care for this patient group. Evaluation of patient satisfaction with this new model of patient care is an important quality measurement. METHODS: We conducted a cross-sectional survey of patients who attended the Thrombosis Service between October 2017 and May 2019. We measured patient satisfaction with the seven-item Short Assessment of Patient Satisfaction (SAPS) which uses a 5 point scale (0-4) for responses. The continuous score range for SAPS is 0 to 28. Categorical responses for SAPS are defined as 0-10 very dissatisfied, 11-18 dissatisfied, 19-26 satisfied, and 27-28 very satisfied. We used linear regression analysis to examine the associations between patients' characteristics and their satisfaction with the Thrombosis Service. RESULTS: Of the 1058 surveys distributed, 563 were returned. The mean score for the SAPS was 22.1 (SD 4.1, range 8 to 28). For the categorical response, 85% were satisfied or very satisfied with the Thrombosis Service. The multivariate analysis showed patients with post-secondary education were more satisfied with the Thrombosis Service (ß-coefficient 1.6153, p = 0.024), and patients taking warfarin were less likely to be satisfied with the Thrombosis Service (ß-coefficient -1.5832, p = 0.0390). CONCLUSIONS: The majority of survey participants (85%) who attended an appointment in one of the Thrombosis Service clinics were satisfied or very satisfied with the care they received. This information may benefit other centres who are interested in developing a program to manage thrombosis and anticoagulation.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

National trends for axillary lymph node dissection and survival outcomes for clinical T3/T4 node-negative breast cancer patients undergoing mastectomy with positive lymph nodes.

PURPOSE: Previous studies have suggested axillary lymph node dissection (ALND) can be omitted in early breast cancer patients undergoing mastectomy with positive lymph nodes (LNs). We assessed the national utilization of ALND and overall survival (OS) for larger, locally advanced tumors in patients undergoing mastectomy with positive LNs. METHODS: The National Cancer Database from 2006 to 2016 was queried for mastectomy patients with clinical T3/T4, N0 tumors, and 1-2 positive LNs. Trends and outcomes for ALND were compared to sentinel lymph node biopsy (SLNB) alone. RESULTS: Thousand nine hundred and seventeen women were included. The proportion of ALND decreased from 70% pre-Z0011 to 52% post-Z0011. On Kaplan-Meier analysis, ALND had better OS compared to SLNB alone (p < 0.01). On multivariate analysis, age (p < 0.01), chemotherapy (p < 0.01), and hormonal therapy (p < 0.01) were associated with better OS. In patients who received adjuvant radiation therapy (ART) ALND improved OS on multivariate analysis (p < 0.01). CONCLUSION: This is the first large database study to demonstrate a national trend to forego ALND in mastectomy patients with large or locally advanced tumors (T3/T4abc) and 1-2 positive lymph nodes. This study suggests a survival benefit for ALND, particularly in patients receiving ART. Careful consideration and further investigations should be performed prior to omitting ALND this patient population.

Direct comparison of median and ulnar repetitive nerve stimulation in generalized myasthenia gravis.

INTRODUCTION/AIMS: Ulnar nerve repetitive nerve stimulation (RNS) has been traditionally used in the electrophysiological evaluation of myasthenia gravis (MG). However, its low diagnostic sensitivity remains a limitation. Existing data may suggest that median nerve RNS outperforms that of the ulnar nerve, but a direct comparison is currently lacking. The aim of this study was to directly compare the diagnostic yields between median and ulnar nerve RNS in patients with generalized MG. METHODS: We performed a retrospective analysis of patients with MG who underwent median and ulnar nerve RNS at a single tertiary center. RESULTS: RNS studies of median nerve recording from the abductor pollicis brevis and ulnar nerve recording from the adductor digiti minimi were completed in 28 patients with generalized MG. Abnormal RNS was more frequently observed in the median compared with the ulnar nerve (60.7% vs 35.7%, P = .046). The average magnitude of decrement was higher in the median nerve compared with the ulnar nerve (17.3% vs 9.6%, P = .017). Differences between the median and ulnar nerve RNS studies were restricted to patients with mild manifestations (Myasthenia Gravis Foundation of America class II). DISCUSSION: Median nerve RNS has superior diagnostic sensitivity as compared with ulnar nerve RNS in the assessment of mild generalized MG.

Pearls and Pitfalls of the Virtual Interview: Perspectives From Both Sides of the Camera.

As the SARS-COV-2 pandemic created the need for social distancing and the implementation of nonessential travel bans, residency and fellowship programs have moved toward a web-based virtual process for applicant interviews. As part of the Society of Asian Academic Surgeons 5th Annual Meeting, an expert panel was convened to provide guidance for prospective applicants who are new to the process. This article provides perspectives from applicants who have successfully navigated the surgical subspecialty fellowship process, as well as program leadership who have held virtual interviews.

Comitant Ocular Deviation in Myasthenia Gravis.

BACKGROUND: Occurrence of comitant ocular deviation in myasthenia gravis (MG) is not well described. METHODS: A retrospective analysis of patients with ocular or generalized MG evaluated at a neuro-ophthalmology clinic for a 6-year period. Comitant ocular deviation was defined as magnitude of deviations in all planes varying by <20% from the measurement in the primary position. RESULTS: Among the 120 patients included, 89 patients had ocular and 31 patients generalized MG. At the initial strabismus testing, comitant ocular deviation was present in 27 (22.5%) patients. Among the 16 patients who had a follow-up, ocular deviation remained comitant in 6 patients and converted to incomitant or no ocular deviation in 10 patients. An additional 7 patients demonstrated comitant ocular deviation at follow-up. Brain MRI was performed in 18 patients with comitant ocular deviation, and none showed abnormalities in the brainstem or cerebellum. CONCLUSION: Comitant ocular deviation can be an ocular manifestation of MG. Its presence does not necessarily indicate a central etiology in patients with MG neither excluding a MG diagnosis.

Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on feeding and energy balance.

Endocannabinoid signaling regulates feeding and metabolic processes and has been linked to obesity development. Several hormonal signals, such as glucocorticoids and ghrelin, regulate feeding and metabolism by engaging the endocannabinoid system. Similarly, studies have suggested that leptin interacts with the endocannabinoid system, yet the mechanism and functional relevance of this interaction remain elusive. Therefore, we explored the interaction between leptin and endocannabinoid signaling with a focus on fatty acid amide hydrolase (FAAH), the primary degradative enzyme for the endocannabinoid N-arachidonoylethanolamine (anandamide; AEA). Mice deficient in leptin exhibited elevated hypothalamic AEA levels and reductions in FAAH activity while leptin administration to WT mice reduced AEA content and increased FAAH activity. Following high fat diet exposure, mice developed resistance to the effects of leptin administration on hypothalamic AEA content and FAAH activity. At a functional level, pharmacological inhibition of FAAH was sufficient to prevent leptin-mediated effects on body weight and food intake. Using a novel knock-in mouse model recapitulating a common human polymorphism (FAAH C385A; rs324420), which reduces FAAH activity, we investigated whether human genetic variance in FAAH affects leptin sensitivity. While WT (CC) mice were sensitive to leptin-induced reductions in food intake and body weight gain, low-expressing FAAH (AA) mice were unresponsive. These data demonstrate that FAAH activity is required for leptin's hypophagic effects and, at a translational level, suggest that a genetic variant in the FAAH gene contributes to differences in leptin sensitivity in human populations.