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As medical schools move to integrate the Core Entrustable Professional Activities for Entering Residency (EPAs) into curricula and address the transition from student to resident, residency preparatory courses have become more prevalent. The authors developed an experiential learning EPA-based capstone course for assessment to determine impact on learner self-assessed ratings of readiness for residency and acquisition of medical knowledge. All fourth-year students from the classes of 2018-2020 completed a required course in the spring for assessment of multiple EPAs, including managing core complaints, performing basic procedures, obtaining informed consent, and providing patient handoffs. Learners selected between three specialty-based parallel tracks - adult medicine, surgery, or pediatrics. Students completed a retrospective pre-post questionnaire to provide self-assessed ratings of residency preparedness and comfort in performing EPAs. Finally, the authors studied the impact of the course on knowledge acquisition by comparing student performance in the adult medicine track on multiple choice pre- and post-tests. Four hundred and eighty-one students were eligible for the study and 452 (94%) completed the questionnaire. For all three tracks, there was a statistically significant change in learner self-assessed ratings of preparedness for residency from pre- to post-course (moderately or very prepared: adult medicine 61.4% to 88.6% [p-value < 0.001]; surgery 56.8% to 81.1% [p-value < 0.001]; pediatrics 32.6% to 83.7% [p-value 0.02]). A similar change was noted in all tracks in learner self-assessed ratings of comfort from pre- to post-course for all studied EPAs. Of the 203 students who participated in the adult medicine track from 2019-2020, 200 (99%) completed both the pre- and post-test knowledge assessments. The mean performance improved from 65.0% to 77.5% (p-value < 0.001). An experiential capstone course for the assessment of EPAs can be effective to improve learner self-assessed ratings of readiness for residency training and acquisition of medical knowledge.

OBJECTIVE: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD). METHODS: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling. RESULTS: Among 112 participants with follow-up data, 22 (19.6%) met criteria for PPF between 12 and 24 months. An equal proportion of patients randomized to CYC (n = 11 of 56) and mycophenolate mofetil (n = 11 of 56) developed PPF. The baseline severity of ILD was similar for patients who did, compared to those who did not, experience PPF in terms of their baseline forced vital capacity percent predicted, diffusing capacity for carbon monoxide percent predicted, and quantitative radiological extent of ILD. Predictors in the nomogram included sex, baseline CXCL4 level, and baseline gastrointestinal reflux score. The nomogram demonstrated moderate discrimination in estimating the risk of PPF, with a C-index of 0.72 (95% confidence interval 0.60-0.84). CONCLUSION: The SLS II data set provided a unique opportunity to investigate predictors of PPF and develop a nomogram to help clinicians identify patients with SSc-ILD who require closer monitoring while on therapy and potentially an alternative treatment approach. This nomogram warrants external validation in other SSc-ILD cohorts to confirm its predictive power.

BackgroundPediatric heart transplant candidates on the waitlist have the highest mortality rate among all solid organ transplants. A risk score incorporating a candidate's individual risk factors may better predict mortality on the waitlist and optimize organ allocation to the sickest of those awaiting transplant.MethodsUsing the United Network for Organ Sharing (UNOS) database, we evaluated a total of 5542 patients aged 0-18 years old on the waitlist for a single, first time, heart transplant from January 2010 to June 2019. We performed a univariate analysis on two-thirds (N = 3705) of these patients to derive the factors most associated with waitlist mortality or delisting secondary to deterioration within 1 year. Those with a p

INTRODUCTION: Population health interventions to increase colorectal cancer (CRC) screening rates often exclude individuals with a family history of CRC, and interventions to increase screening in this high-risk group are rare. We aimed to determine the screening rate and barriers and facilitators to screening in this population to inform interventions to increase screening participation. METHODS: We performed a retrospective chart review and cross-sectional survey of patients excluded from mailed fecal immunochemical test (FIT) outreach because of a family history of CRC in a large health system. We used χ 2 , Fisher exact, and Student t tests to compare demographic and clinical characteristics of patients overdue and not overdue for screening. We then administered a survey (mailed and telephone) to overdue patients to assess barriers and facilitators to screening. RESULTS: There were 296 patients excluded from mailed FIT outreach, and 233 patients had a confirmed family history of CRC. Screening participation was low (21.9%), and there were no significant demographic or clinical differences between those overdue and not overdue for screening. There were 79 survey participants. Major patient-reported barriers to screening colonoscopy were patient forgetfulness (35.9%), fear of pain during colonoscopy (17.7%), and hesitancy about bowel preparation (29.4%). To facilitate screening colonoscopy, patients recommended reminders (56.3%), education about familial risk (50%), and colonoscopy education (35.9%). DISCUSSION: Patients with a family history of CRC who are excluded from mailed FIT outreach have low screening rates and report multiple mutable barriers to screening. They warrant targeted efforts to increase screening participation.

OBJECTIVE: To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc). METHODS: Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. RESULTS: Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b = -4.74, P = 0.009 and b = -2.68, P = 0.028, respectively) and higher serially obtained MRSS (b = 4.07, P

Persistent pleural effusions (PPEf) represent a known complication of orthotopic liver transplant (OLT). However, their clinical relevance is not well described. We evaluated the clinical, biochemical, and cellular characteristics of post-OLT PPEf and assessed their relationship with longitudinal outcomes. We performed a retrospective cohort study of OLT recipients between 2006 and 2015. Included patients had post-OLT PPEf, defined by effusion persisting >30 days after OLT and available pleural fluid analysis. PPEf were classified as transudates or exudates (ExudLight) by Light's criteria. Exudates were subclassified as those with elevated lactate dehydrogenase (ExudLDH) or elevated protein (ExudProt). Cellular composition was classified as neutrophil- or lymphocyte-predominant. Of 1602 OLT patients, 124 (7.7%) had PPEf, of which 90.2% were ExudLight. Compared to all OLT recipients, PPEf patients had lower two-year survival (HR 1.63; p = 0.002). Among PPEf patients, one-year mortality was associated with pleural fluid RBC count (p = 0.03). While ExudLight and ExudProt showed no association with outcomes, ExudLDH were associated with increased ventilator dependence (p = 0.03) and postoperative length of stay (p = 0.03). Neutrophil-predominant effusions were associated with increased postoperative ventilator dependence (p = 0.03), vasopressor dependence (p = 0.02), and surgical pleural intervention (p = 0.02). In summary, post-OLT PPEf were associated with increased mortality. Ninety percent of these effusions were exudates by Light's criteria. Defining exudates using LDH only and incorporating cellular analysis, including neutrophils and RBCs, was useful in predicting morbidity.

Background: Emergent endotracheal intubations (ETI) in pulmonary hypertension (PH) patients are associated with increased mortality. Post-intubation interventions that could increase survivability in this population have not been explored. We evaluate early clinical characteristics and complications following emergent endotracheal intubation and seek predictors of adverse outcomes during this post-intubation period. Methods: Retrospective cohort analysis of adult patients with groups 1 and 3 PH who underwent emergent intubation between 2005-2021 in medical and liver transplant ICUs at a tertiary medical center. PH patients were compared to non-PH patients, matched by Charlson Comorbidity Index. Primary outcomes were 24-h post-intubation and inpatient mortalities. Various 24-h post-intubation secondary outcomes were compared between PH and control cohorts. Results: We identified 48 PH and 110 non-PH patients. Pulmonary hypertension was not associated with increased 24-h mortality (OR 1.32, 95%CI 0.35-4.94, P = .18), but was associated with inpatient mortality (OR 4.03, 95%CI 1.29-12.5, P = .016) after intubation. Within 24 h post-intubation, PH patients experienced more frequent acute kidney injury (43.5% vs. 19.8%, P = .006) and required higher norepinephrine dosing equivalents (6.90 [0.13-10.6] mcg/kg/min, vs. 0.20 [0.10-2.03] mcg/kg/min, P = .037). Additionally, the median P/F ratio (PaO2/FiO2) was lower in PH patients (96.3 [58.9-201] vs. 233 [146-346] in non-PH, P = .001). Finally, a post-intubation increase in PaCO2 was associated with mortality in the PH cohort (post-intubation change in PaCO2 +5.14 ± 16.1 in non-survivors vs. -18.7 ± 28.0 in survivors, P = .007). Conclusions: Pulmonary hypertension was associated with worse outcomes after emergent endotracheal intubation than similar patients without PH. More importantly, our data suggest that the first 24 hours following intubation in the PH group represent a particularly vulnerable period that may determine long-term outcomes. Early post-intubation interventions may be key to improving survival in this population.

IntroductionBelatacept has shown potential for prevention of rejection after kidney transplantation, given its demonstration of reduced nephrotoxicity in combination with absence of significant incidence of rejection. However, concerns have been raised regarding increased risk of viral infection.MethodsWe set out to explore the impact of the switch to belatacept on alloimmune and antiviral immunity through the study of patients switched from calcineurin inhibitor (CNI) to belatacept within 3 months of kidney transplantation compared with a matched cohort of control patients on a CNI-based regimen.ResultsAfter the switch to belatacept, immune phenotyping demonstrated a decrease in naive and an increase in terminally differentiated effector memory (TMRA) T cells, with no significant difference compared with control patients. Donor-specific immune response, measured by intracellular cytokine staining (ICS), did not change significantly either by single or double cytokine secretion, but it was associated with the appearance of donor-specific antibody (DSA) in the control but not the belatacept cohort (P = 0.039 for naive and P = 0.002 for TMRA subtypes). Increased incidence of de novo DSA development was observed in the control group (P = 0.035). Virus-specific immune response, as measured by ICS in response to cytomegalovirus (CMV) or Epstein-Barr virus (EBV), was similar in both groups and stable over time.ConclusionWe found that belatacept use was associated with an absence of alloreactivity without impact on immune phenotype, while preserving the antiviral immune response, for patients switched from a CNI-based regimen. In parallel, the antiviral immune response against CMV and EBV was preserved after the belatacept switch (clinicaltrials.gov: NCT01953120).

BACKGROUND: Observational studies have shown that men with systemic sclerosis have an increased risk of interstitial lung disease (ILD) and mortality compared with women. However, previous studies have not controlled for treatment effect or evaluated the biological mechanism or mechanisms underlying this sex difference. We aimed to compare ILD progression and long-term morbidity and mortality outcomes in male and female participants of two randomised controlled trials for systemic sclerosis-associated ILD. METHODS: For this post-hoc analysis, data from all participants in the Scleroderma Lung Study (SLS) I and SLS II were analysed. The primary objective was to explore the effect of sex on the course of the percentage predicted forced vital capacity (FVC) during and after active treatment over the 24-month study periods. In SLS I, 158 participants (111 women, 47 men) were randomly assigned to receive oral cyclophosphamide (cyclophosphamide; ≤2 mg/kg daily) or placebo; in SLS II, 142 participants (105 women, 37 men) were randomly assigned to receive oral mycophenolate mofetil (1500 mg twice daily) or oral cyclophosphamide (≤2 mg/kg daily). Sex (ie, male or female) was self-reported in both studies by the participants. Changes in radiographic fibrosis and time to death and respiratory failure were secondary outcomes of the present analysis. Baseline levels of biomarkers implicated in the pathobiology of systemic sclerosis-associated ILD were measured in bronchoalveolar lavage fluid in SLS I. FINDINGS: In the SLS I placebo group, the rate of decline in percentage predicted FVC from 3 months to 12 months was greater in men than in women, but the difference was not significant (estimated effect -0·29 [95% CI -0·67 to 0·10]; p=0·14). In SLS II, the rate of decline in percentage predicted FVC from 3 months to 12 months was significantly worse in men treated with either cyclophosphamide (estimated effect -0·72; [95% CI -1·14 to -0·31]; p=0·00060) or mycophenolate mofetil (estimated effect -0·34 [-0·58 to -0·10]; p=0·0051) than in women. A greater proportion of men had a decline in percentage predicted FVC of 10% or greater compared with women for the pooled active treatment groups from SLS I and SLS II and the placebo group of SLS I. Men had worse radiographic outcomes at 2 years than women in SLS II, even after adjusting for baseline disease severity and treatment arm assignment. Long-term survival was worse in men in SLS I (log-rank test p=0·080) and SLS II (log-rank test p=0·030). In SLS II, male sex was independently associated with increased mortality (hazard ratio 2·42 [95% CI 1·16 to 5·04]; p=0·018). In bronchoalveolar lavage fluid, men had increased concentrations of pro-fibrotic mediators (eg, matrix metalloproteinase-13 and tissue inhibitor of metallopeptidase 1), whereas women had increased pro-inflammatory mediators (eg, interleukin [IL]-12, IL-7, and granulocyte-colony stimulating factor). INTERPRETATION: In two randomised controlled trials, men with systemic sclerosis-associated ILD had a less favourable course of ILD both with and without active treatment, as well as worse long-term survival. Sex differences in pro-fibrotic or inflammatory mediators of disease might account for these differences and warrant future study. FUNDING: US National Institutes of Health; US National Heart, Lung, and Blood Institute; US National Institute of Arthritis and Musculoskeletal and Skin Diseases; Bristol Myers Squibb; and Hoffmann-LaRoche.

ObjectivesTo characterise the peripheral blood cell (PBC) gene expression changes ensuing from mycophenolate mofetil (MMF) or cyclophosphamide (CYC) treatment and to determine the predictive significance of baseline PBC transcript scores for response to immunosuppression in systemic sclerosis (SSc)-related interstitial lung disease (ILD).MethodsPBC RNA samples from baseline and 12-month visits, corresponding to the active treatment period of both arms in Scleroderma Lung Study II, were investigated by global RNA sequencing. Joint models were created to examine the predictive significance of baseline composite modular scores for the course of forced vital capacity (FVC) per cent predicted measurements from 3 to 12 months.Results134 patients with SSc-ILD (CYC=69 and MMF=65) were investigated. CYC led to an upregulation of erythropoiesis, inflammation and myeloid lineage-related modules and a downregulation of lymphoid lineage-related modules. The modular changes resulting from MMF treatment were more modest and included a downregulation of plasmablast module. In the longitudinal analysis, none of the baseline transcript module scores showed predictive significance for FVC% course in the CYC arm. In contrast, in the MMF arm, higher baseline lymphoid lineage modules predicted better subsequent FVC% course, while higher baseline myeloid lineage and inflammation modules predicted worse subsequent FVC% course.ConclusionConsistent with the primary mechanism of action of MMF on lymphocytes, patients with SSc-ILD with higher baseline lymphoid module scores had better FVC% course, while those with higher myeloid cell lineage activation score had poorer FVC% course on MMF.

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many advanced cancers but are recognized to cause treatment-limiting immune-related adverse events (IrAE). ICI-associated thyroiditis is the most common endocrine IrAE and usually resolves to permanent hypothyroidism. Optimal thyroid hormone replacement in these patients remains unclear. We report the levothyroxine (LT4) dose needed to achieve stable euthyroid state in patients with hypothyroidism from ICI-associated thyroiditis, with comparison to patients with Hashimoto's thyroiditis (HT) and athyreotic state. Methods: We conducted a retrospective study of adults with ICI-associated hypothyroidism treated with LT4 at an academic medical center. Patient data were collected from the electronic medical record. Cases had ICI exposure followed first by hyperthyroidism and then subsequent hypothyroidism. Controls were HT (positive thyroid autoantibodies, requiring LT4) and athyreotic (total thyroidectomy or radioiodine ablation, requiring LT4) patients. Patients with central hypothyroidism, thyroid cancer, pregnancy, gastrointestinal stromal tumors, and use of L-triiodothyronine were excluded. Our primary outcome compared LT4 dose needed to achieve euthyroid state (thyrotropin 0.3-4.7 mIU/L over >6 consecutive weeks) for ICI-associated hypothyroidism, HT, and athyreotic patients, considering the impact of age and possible interfering medications by linear regression modeling. Secondary analysis considered the impact of endocrine specialty care on the time to euthyroid state. Results: One hundred three patients with ICI-associated thyroiditis were identified. Sixty-six of the 103 patients achieved euthyroid state; 2 with intrinsic thyroid gland function recovery and 64 on LT4. The mean LT4 dose achieving stable euthyroid state was 1.45 ± standard deviation (SD) 0.47 mcg/[kg·day] in ICI-associated hypothyroidism, 1.25 ± SD 0.49 mcg/[kg·day] in HT, and 1.54 ± SD 0.38 mcg/[kg·day] in athyreotic patients, using actual body weight. The difference in dose between ICI-associated hypothyroidism and HT was statistically significant (p = 0.0093). Dosing differences were not explained by age or use of interfering medications. Conclusions: ICI-associated thyroiditis represents an increasingly recognized cause of hypothyroidism. Our study demonstrates that patients with ICI-associated hypothyroidism have different thyroid hormone dosing requirements than patients with HT. Based on our findings and prior reports, we recommend that in patients with ICI-associated thyroiditis LT4 therapy be started at an initial weight-based dose of 1.45 mcg/[kg·day] once serum free thyroxine levels fall below the reference range.

In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) guideline on the endoscopic management of choledocholithiasis modified the individual predictors of choledocholithiasis proposed in the widely referenced 2010 guideline to improve predictive performance. Nevertheless, the primary literature, especially for the 2019 iteration, is limited. We performed a systematic review with meta-analysis to examine the diagnostic performance of the 2010, and where possible the 2019, predictors. PROSPERO protocol CRD42020194226. A comprehensive literature search from 2001 to 2020 was performed to identify studies on the diagnostic performance of any of the 2010 and 2019 ASGE choledocholithiasis predictors. Identified studies underwent keyword screening, abstract review, and full-text review. The primary outcomes included multivariate odds ratios (ORs) and 95% confidence intervals for each criterion. Secondary outcomes were reported sensitivities, specificities, and positive and negative predictive value. A total of 20 studies met inclusion criteria. Based on reported ORs, of the 2010 guideline "very strong" predictors, ultrasound with stone had the strongest performance. Of the "strong" predictors, CBD > 6 mm demonstrated the strongest performance. "Moderate" predictors had inconsistent and/or weak performance; moreover, all studies reported gallstone pancreatitis as non-predictive of choledocholithiasis. Only one study examined the new predictor (bilirubin > 4 mg/dL and CBD > 6 mm) proposed in the 2019 guideline. Based on this review, aside from CBD stone on ultrasound, there is discordance between the proposed strength of 2010 choledocholithiasis predictors and their published diagnostic performance. The 2019 guideline appears to do away with the weakest 2010 predictors.

IntroductionVibratory asymmetry and neuromuscular compensation are often seen in laryngeal neuromuscular pathology. However, the ramifications of these findings on voice quality are unclear. This study investigated the effects of varying levels of vibratory asymmetry and neuromuscular compensation on cepstral peak prominence (CPP), an analog of voice quality.Study designIn vivo canine phonation model.MethodsVarying degrees of vocal fold vibratory asymmetry were achieved by stimulating one recurrent laryngeal nerve (RLN) over 11 levels from threshold to maximal muscle activation. For each of these levels, phonation was induced at systematically varied combinations of neuromuscular compensation: three levels each of contralateral RLN stimulation (80%, 90%, and 100% of maximal), superior laryngeal nerve (SLN) activation (0%, 50%, and 100% of maximal), and airflow levels (500, 700, and 900 mL/s). Vocal fold symmetry was determined by assessing the opening phase of the vibratory cycle in high-speed video recordings. Voice quality was estimated acoustically by calculating CPP for each voice sample.ResultsEight hundred twenty-two phonatory conditions with varying degrees of vibratory asymmetry were evaluated. CPP was highest at vibratory symmetry. Increasing levels of asymmetry resulted in significant decreases in CPP. CPP increased significantly with increasing contralateral RLN activation. CPP was significantly higher at 50% SLN activation than 0% or 100% SLN activation.ConclusionVoice quality, as approximated by CPP, is best at vibratory symmetry and deteriorates with increasing degrees of asymmetry. Voice quality may be improved with neuromuscular compensation by increased adduction of the contralateral vocal fold or increased vocal fold tension at mid-levels of SLN activation.Level of evidenceNA, Basic Science Laryngoscope, 132:130-134, 2022.

BackgroundFebrile neutropenia is one of the most common oncologic emergencies and is associated with significant, preventable morbidity and mortality. Most patients who experience a febrile neutropenia episode are hospitalized, resulting in significant economic cost.ObjectiveThis exploratory study implemented a remote monitoring system comprising a digital infrared thermometer and a pulse oximeter with the capability to notify providers in real time of abnormalities in vital signs that could suggest early clinical deterioration and thereby improve clinical outcomes.MethodsThe remote monitoring system was implemented and compared to standard-of-care vital signs monitoring in hospitalized patients with underlying hematologic malignancies complicated by a febrile neutropenia episode in order to assess the feasibility and validity of the system. Statistical analysis was performed using the intraclass correlation coefficient (ICC) to assess the consistency between the measurements taken using traditional methods and those taken with the remote monitoring system for each of the vital sign parameters (temperature, heart rate, and oxygen saturation). A linear mixed-effects model with a random subject effect was used to estimate the variance components. Bland-Altman plots were created for the parameters to further delineate the direction of any occurring bias.ResultsA total of 23 patients were enrolled in the study (mean age 56, SD 23-75 years; male patients: n=11, 47.8%). ICC analysis confirmed the high repeatability and accuracy of the heart rate assessment (ICC=0.856), acting as a supplement to remote temperature assessment. While the sensitivity and specificity for capturing tachycardia above a rate of 100 bpm were excellent (88% and 97%, respectively), the sensitivity of the remote monitoring system in capturing temperatures >37.8 °C and oxygen saturation

BackgroundThe impact of telehealth on cardiovascular care during the COVID-19 pandemic on patient satisfaction and factors associated with satisfaction are not well characterized.MethodsWe conducted a nonrandomized, prospective cross-sectional survey study for outpatient telehealth cardiovascular visits over a 169-day period utilizing a validated telehealth usability questionnaire. For each variable, patients were divided into 2 groups-1 with scores above the median, labeled "greater satisfaction," and the other with scores below the median, labeled "less satisfaction."ResultsA total of 13,913 outpatient telehealth encounters were successfully completed during the study period. A total of 7327 unique patients were identified and received a survey invitation; 5993 (81.8%) patients opened the invitation, and 1034 (14.1%) patients consented and completed the survey. Overall mean and median scores were 3.15 (standard deviation 0.74) and 3.37 (interquartile range 2.73-3.68) (maximum score 4.00). Greater satisfaction was noted among younger patients (mean age 63.3 ± 14.0 years, P = .005), female gender (46.3%, P = .007), non-White ethnicity (24.2% P = .006), self-identified early adopters and innovators of new technology (49.8%, P < .001), 1-way travel time greater than 1 hour (22.3%, P < .001), 1-way travel distance greater than 10 miles (49.0%, P < .001), patients needing child care arrangement (16.4%, P < .001), and history of orthotopic heart transplant (OHT) (5.1%, P = .04).ConclusionPatients reported overall satisfaction with telehealth during the COVID-19 pandemic. Factors associated with patient convenience, along with female gender, younger age, and non-White ethnicity, correlated with greater satisfaction. Cardiovascular comorbidities did not correlate with greater satisfaction except for OHT. Further research into the impact of telehealth on patient satisfaction, safety, and clinical outcomes is needed.

The aim of this study was to test the hypothesis that endovascular aspiration thrombectomy of right atrial thrombus (RAT) using the AngioVac device is as safe and effective in patients with cancer as those without cancer.RAT is a uniquely challenging clinical presentation of venous thromboembolism due to its low incidence and historically high-risk of mortality due to thrombus propagation into the pulmonary arteries. There is a lack of consensus regarding management, particularly in high-risk cancer patients. Endovascular aspiration thrombectomy utilizing the AngioVac device is effective in removal of right atrial thrombus and may be a safer option for patients with cancer in whom avoidance of higher-risk intervention is preferred.This was an institutional review board-approved retrospective single-center case control study of patients with RAT who underwent AngioVac aspiration thrombectomy between August 2013 and July 2020. Analysis of patient demographics and clinical characteristics, thrombus-related factors, and operative details was performed. Primary endpoints included survival, safety, and technical success.A total of 44 patients met inclusion criteria, 20 of whom with active malignancy. The oncology group had a significantly higher Charlson comorbidity index (P = 0.01). Comparative outcomes between the oncology and non-oncology group showed no difference in survival (P = 0.8) or technical success (OR 3, 95% CI 0.83-10.9). There were 9 complications, including 6 minor, 1 moderate, 1 severe, and 1 death.AngioVac aspiration thrombectomy of RAT is as safe and effective in patients with cancer as those without cancer.

ObjectiveThis study aimed to assess the minimal clinically important differences (MCIDs) for the modified Rodnan skin score (mRSS) using combined data from the Scleroderma Lung Studies (I and II).MethodsMCID estimates for the mRSS at 12 months were calculated using three anchors: change in scores on the Health Assessment Questionnaire- Disability Index from baseline to 12 months, change in scores on the Patient Global Assessment from baseline to 12 months, and answer at 12 month for the Short Form-36 health transition question "Compared to one year ago, how would you rate your health in general now?" We determined the mRSS MCID estimates for all participants and for those with diffuse cutaneous systemic sclerosis (dcSSc). We then assessed associations between MCID estimates of mRSS improvement and patient-reported outcomes, using Student's t test to compare the mean differences in patient outcomes between those who met the MCID improvement criteria versus those who did not meet the improvement criteria.ResultsThe mean (SD) mRSS at baseline was 14.75 (10.72) for all participants and 20.93 (9.61) for those with dcSSc. The MCID estimate for mRSS improvement at 12 months ranged from 3 to 4 units for the overall group (improvement of 20-27% from baseline) and was 5 units for those with dcSSc (improvement of 24% from baseline). Those who met the mRSS MCID improvement criteria had statistically significant improvements in scores on the Short Form-36 Physical Component Summary, the Transition Dyspnea Index, and joint contractures at 12 months.ConclusionMCID estimates for the mRSS were 3-4 units for all participants and 5 units for those with dcSSc. These findings are consistent with previously reported MCID estimates for systemic sclerosis.

Background Scant data exists to guide the work-up for fever in hospitalized patients, and little is known about what diagnostic tests medicine residents order for such patients. We sought to analyze how cross-covering medicine residents address fever and how sign-out systems affect their response. Methods We conducted a prospective cohort study to evaluate febrile episodes that residents responded to overnight. Primary outcomes included diagnostic tests ordered, if an in-person evaluation occurred, and the effect of sign-out instructions that advised a "full fever work-up" (FFWU). Results Investigators reviewed 253 fevers in 155 patients; sign-out instructions were available for 204 fevers. Residents evaluated the patient in person in 29 (11%) episodes. The most common tests ordered were: blood cultures (48%), urinalysis (UA) with reflex culture (34%), and chest X-ray (30%). If the sign-out advised an FFWU, residents were more likely to order blood cultures [odds ratio (OR) 14.75, 95% confidence interval (CI) 7.52-28.90], UA with reflex culture (OR 12.07, 95% CI 5.56-23.23), chest X-ray (OR 16.55, 95% CI 7.03-39.94), lactate (OR 3.33, 95% CI 1.47-7.55), and complete blood count (CBC) (OR 3.16, 95% CI 1.17-8.51). In a multivariable regression, predictors of the number of tests ordered included hospital location, resident training level, timing of previous blood culture, in-person evaluation, escalation to a higher level of care, and sign-out instructions. Conclusions Sign-out instructions and a few patient factors significantly impacted cross-cover resident diagnostic test ordering for overnight fevers. This practice can be targeted in resident education to improve diagnostic reasoning and stewardship.

Heat is a well-recognized hazard for workers in many outdoor settings, yet fewinvestigations have compared the prevalence of outdoor work at the community level and rates of heat-related mortality and morbidity. This analysis examines whether heat-related health outcomes occur more frequently in communities with higher proportions of residents working in construction,agriculture, and other outdoor industries. Using 2005–2010 data from Los Angeles County, California, we analyze associations between community-level rates of deaths, emergency department (ED) visits, and hospitalizations during summer heat events and the prevalence of outdoor work. We findgenerally higher rates of heat-related ED visits and hospitalizations during summer heat events in communities with more residents working outdoors. Specifically, each percentage increase in residents working in construction resulted in an 8.1 percent increase in heat-related ED visits and a 7.9 percent increase in heat-related hospitalizations, while each percentage increase in residents working in agriculture and related sectors resulted in a 10.9 percent increase in heat-related ED visits.The findings suggest that outdoor work may significantly influence the overall burden of heat-related morbidity at the community level. Public health professionals and healthcare providers should recognize work and employment as significant heat risk factors when preparing for and respondingto extreme heat events.

ObjectivesTo assess the reliability and the minimal clinically important differences (MCID) for FVC% predicted in the Scleroderma Lung Study I and II.MethodsUsing data from SLS I and II (N=300), we evaluated the test-retest reliability for FVC% predicted (FVC%; screening vs. baseline) using intra-class correlation (ICC). MCID estimates at 12 months were calculated in the pooled cohort (SLS-I and II) using 2 anchors: Transition Dyspnea Index (≥change of 1.5 units for improvement and worsening, respectively) and the SF-36 Health Transition question: "Compared to one year ago, how would you rate your health in general now?", where "somewhat better" or "somewhat worse" were defined as the MCID estimates. We next assessed the association of MCID estimates for improvement and worsening of FVC% with patient reported outcomes (PROs) and computer-assisted quantitation of extent of fibrosis (QLF) and of total ILD (QILD) on HRCT.ResultsReliability of FVC%, assessed at a mean of 34 days, was 0.93 for the pooled cohort. The MCID estimates for the pooled cohort at 12 months for FVC% improvement ranged from 3.0 % to 5.3% and for worsening from -3.0% to -3.3%. FVC% improvement by ≥MCID was associated with either statistically significant or numerical improvements in some PROs, QILD, and QLF, while FVC% worsening ≥MCID was associated with statistically significant or numerical worsening of PROs, QILD, and QLF.ConclusionFVC% has acceptable test-retest reliability, and we have provided the MCID estimates for FVC% in SSc-ILD based changes at 12 months from baseline in two clinical trials. Clinical trial registration available at www.clinicaltrials.gov, IDs NCT00004563 and NCT00883129.

ObjectiveTo assess the efficacy of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) on modified Rodnan skin score (MRSS) in participants enrolled in the Scleroderma Lung Study (SLS) I and II.MethodsSLS I participants received daily oral CYC or matching placebo for 1 year, whereas SLS II participants received daily MMF for 2 years or daily oral CYC for 1 year followed by placebo for second year. We assessed the impact of MMF and CYC on the MRSS in SLS II over a 24-month period. We also compared the change in MRSS in patients with diffuse cutaneous systemic sclerosis (dcSSc) assigned to CYC and MMF in SLS II and SLS I versus placebo in SLS I over a 24-month period using a linear mixed model.ResultsIn SLS II, the baseline mean ± SD MRSS was 14.0 ± 10.6 units for CYC and 15.3 ± 10.4 units for MMF; 58.5% were classified as dcSSc. CYC and MMF were associated with statistically significant improvements in MRSS from baseline over the period of 24 months in dcSSc (P < 0.05 at each time point), but there were no differences between the 2 groups. In the dcSSc subgroup, the change in MRSS from baseline to all 6-month visits was similar in SLS II groups (MMF, CYC, pooled cohort [MMF + CYC]) and in the SLS I CYC group and showed statistically significant improvements compared to SLS I placebo at 12, 18, and 24 months (P < 0.05).ConclusionIn SLS II, MMF and CYC treatment resulted in improvements in MRSS in patients with dcSSc over 24 months. In addition, MMF and CYC treatment resulted in statistically significant improvements in MRSS in patients with dcSSc when compared with the SLS I placebo group.

BackgroundAlthough individuals classified as nonresident aliens, including undocumented immigrants, are entitled to receive emergency dialysis in the United States regardless of their ability to pay, most states do not provide them with subsidized care for maintenance dialysis or kidney transplantation. We explored whether nonresident aliens have similar outcomes to US citizens after receiving kidney transplants covered by Medicaid, a joint federal and state health insurance program.Study designRetrospective observational cohort study.Setting & participantsAll adult Medicaid patients in the US Renal Data System who received their first kidney transplant from 1990 to 2011.PredictorCitizenship status, categorized as US citizen, nonresident alien, or permanent resident.OutcomeAll-cause transplant loss.MeasurementsHRs and 95% CIs estimated by applying Cox proportional hazards frailty models with transplantation center as a random effect.ResultsOf 10,495 patients, 8,660 (82%) were US citizens, 1,489 (14%) were permanent residents, and 346 (3%) were nonresident aliens, whom we assumed were undocumented immigrants. Nonresident aliens were younger, healthier, receiving dialysis longer, and more likely to have had a living donor. 71% underwent transplantation in California, and 61% underwent transplantation after 2005. Nonresident aliens had a lower unadjusted risk for transplant loss compared with US citizens (HR, 0.48; 95% CI, 0.35-0.65). Results were attenuated but still significant when adjusted for demographics, comorbid conditions, dialysis, and transplant-related factors (HR, 0.67; 95% CI, 0.46-0.94).LimitationsCitizenship status was self-reported, possible residual confounding.ConclusionsOur study suggests that the select group of insured nonresident aliens who undergo transplantation with Medicaid do just as well as US citizens with Medicaid. Policymakers should consider expanding coverage for kidney transplantation in nonresident aliens, including undocumented immigrants, given the associated high-quality outcomes in these patients.

Background and aimNon-alcoholic fatty liver disease (NAFLD) is common among HIV-infected (HIV+) adults. The Liver Fat Score (LFS) is a non-invasive, rapid, inexpensive diagnostic tool that uses routine clinical data and is validated against biopsy in HIV-uninfected (HIV-) persons. CT liver-to-spleen (L/S) attenuation ratio is another validated method to diagnose NAFLD. We compared NAFLD prevalence using the LFS versus L/S ratio among Multicenter AIDS Cohort Study participants to assess the LFS's performance in HIV+vs. HIV-men.MethodsIn a cross-sectional analysis of men reporting

In an extreme heat event, people can go to air-conditioned public facilities if residential air-conditioning is not available. Residences that heat slowly may also mitigate health effects, particularly in neighborhoods with social vulnerability. We explored the contributions of social vulnerability and these infrastructures to heat mortality in Maricopa County and whether these relationships are sensitive to temperature. Using Poisson regression modeling with heat-related mortality as the outcome, we assessed the interaction of increasing temperature with social vulnerability, access to publicly available air conditioned space, home air conditioning and the thermal properties of residences. As temperatures increase, mortality from heat-related illness increases less in census tracts with more publicly accessible cooled spaces. Mortality from all internal causes of death did not have this association. Building thermal protection was not associated with mortality. Social vulnerability was still associated with mortality after adjusting for the infrastructure variables. To reduce heat-related mortality, the use of public cooled spaces might be expanded to target the most vulnerable.

Data on vitamin D insufficiency as a cause of inflammation and metabolic dysfunction in HIV-infected individuals are conflicting. We examined the relationships between levels of 25-hydroxyvitamin D [25(OH)D] and biomarkers of inflammation and metabolism in stored blood samples from a prospective trial of vitamin D repletion. Blood samples from HIV-infected individuals on antiretroviral therapy (ART) with HIV-1 RNA

Background and objectivesIn an era where obesity remains an important public health concern, food addiction has emerged as a possible contributor to obesity. The DRD2 gene is the most studied polymorphism. The aim of this study was to investigate a relationship between food addiction questionnaires, body composition measurements, and a dopamine- resistant receptor polymorphism (DRD2 A1) among Asian Americans.Methods and study designA total of 84 Asian American college students were recruited. Participants underwent body composition measurement via bioelectrical impedance, answered questionnaires (Food Craving Inventory and Power of Food Scale), and had blood drawn for genotyping (PCR).ResultsThere was no difference in body composition (BMI, percent body fat) between the A1 (A1A1 or A1A2) and A2 (A2A2) groups. There were statistically significant differences in food cravings of carbohydrates and fast food on the Food Craving Inventory between the A1 and A2 groups (p=0.03), but not for sugar or fat. Among Asian college females, there was also a difference on the Power of Food questionnaire (p=0.04), which was not seen among men. 13 out of 55 women also had >30% body fat at a BMI of 21.4 to 28.5 kg/m2.ConclusionGreater carbohydrate and fast food craving was associated with the DRD2 A1 versus A2 allele among Asian Americans. Further studies examining the ability of dopamine agonists to affect food craving and to reduce body fat in Asian American are warranted. More studies in food addiction among obese Asian Americans are needed with careful definition of obesity, specifically for Asian women.

Background.  Vitamin D insufficiency is prevalent in human immunodeficiency virus-positive (HIV+) persons. Human immunodeficiency virus and antiretroviral therapy (ART) may create unique risk factors, and the optimal vitamin D repletion and maintenance regimen in HIV+ persons remains unclear. Methods.  Human immunodeficiency virus-positive adults on suppressive ART underwent routine serum 25-hydroxyvitamin D (25OHD) screening. Persons with vitamin D insufficiency (25OHD

The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P

Transplantation of hematopoietic stem/progenitor cells (HSPC) modified with a lentiviral vector bearing a potent nontoxic short hairpin RNA (sh1005) directed to the HIV coreceptor CCR5 is capable of continuously producing CCR5 downregulated CD4+ T lymphocytes. Here, we characterized HIV-1 resistance of the sh1005-modified CD4+ T lymphocytes in vivo in humanized bone marrow/liver/thymus (hu BLT) mice. The sh1005-modified CD4+ T lymphocytes were positively selected in CCR5-tropic HIV-1-challenged mice. The sh1005-modified memory CD4+ T lymphocytes (the primary target of CCR5-tropic HIV-1) expressing sh1005 were maintained in lymphoid tissues in CCR5-tropic HIV-1-challenged mice. Frequencies of HIV-1 p24 expressing cells were significantly reduced in the sh1005-modified splenocytes by ex vivo cell stimulation confirming that CCR5 downregulated sh1005 modified cells are protected from viral infection. These results demonstrate that stable CCR5 downregulation through genetic modification of human HSPC by lentivirally delivered sh1005 is highly effective in providing HIV-1 resistance. Our results provide in vivo evidence in a relevant small animal model that sh1005 is a potent early-step anti-HIV reagent that has potential as a novel anti-HIV-1 HSPC gene therapeutic reagent for human applications.