Factors associated with immune responses to SARS-CoV-2 vaccination in autoimmune disease individuals.

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 autoimmune subjects, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted multiple sclerosis (MS) subjects were associated with higher CD8 T cell responses. By contrast, subjects taking mycophenolate mofetil exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low IgG anti-spike response included B cell depletion within the last year, fingolimod, and combination treatment with mycophenolate mofetil (MMF) and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine, is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of pre-existing anti-type I interferon antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

'Whatever we have is what we eat': How marginalised urban populations in the Philippines and Thailand experienced their food environments, food security and diets through COVID-19.

This qualitative cross-country comparative study investigated the lived experience of marginalised urban populations (unemployed, daily wage earners/street vendors, and internal/external migrants) in Manila (Philippines) and Bangkok (Thailand) on food environments, food security and diets during COVID-19. Semi-structured interviews were conducted with individuals (n = 59) in April-May 2022. Thematic analysis revealed loss of income and strict mobility restrictions (Philippines) as key drivers of dietary changes and hunger. Common narratives included financial hardship, loss of personal agency, and daily survival. Coping strategies included drawing on social networks, cash and food aid, and 'scheming' around restrictions. Contextualised crisis policy planning should explicitly consider the lived experience of marginalised populations for future shocks.

Ultralow-Dose Dynamic Expiratory CT and Repeated Imaging Enhance Evaluation for Tracheomalacia.

OBJECTIVE: This study aims to determine if a novel imaging protocol (ultralow-dose dynamic expiratory computed tomography [CT] with repeated imaging) identifies tracheomalacia (TM) more reliably than traditional dynamic tracheal CT. METHODS: We performed a retrospective evaluation of 184 consecutive ultralow-dose dynamic CTs for TM during 2017. The protocol obtains images during 1 inspiration and 2 forced expirations. Tracheal narrowing during both expirations (airway narrowing [percentage] during first dynamic expiration CT [DE1], airway narrowing [percentage] during second dynamic expiration CT [DE2]) was reported as a percentage of inspiratory area. We identified maximum narrowing of each patient's sequence (maximum narrowing [percentage] on either dynamic expiration CT [DEmax] = greatest narrowing of DE1 or DE2) and compared DE1, DE2, and DEmax in individual studies and between patients. Outcomes included frequency of TM, tracheal narrowing, and severity. Reliability was assessed by comparing tracheal area narrowing and TM grade. RESULTS: There was significantly more airway narrowing using 2 expiratory image acquisitions. Average DEmax tracheal area was 12% narrower than DE1 alone and 21% worse than DE2 alone (both P < 0.001). Using DEmax, TM was diagnosed 35% more often than DE1 alone and 31% more often than DE2 alone ( P < 0.001). DEmax identified more severe distribution of TM compared with DE1 or DE2 alone ( P < 0.001). Reliability between DE1 and DE2 was good for tracheal narrowing and moderate for TM grade. The mean effective radiation dose was 2.41 millisievert (mSv) for routine inspiration CT and 0.07 mSv for each dynamic expiration CT (total effective radiation, 2.55 mSv). CONCLUSIONS: Dynamic expiration CT with 2 expiratory image acquisitions enhanced evaluation of TM, minimally increased radiation dose, and should be considered as a noninvasive screening option.

Comparing gastrointestinal stromal tumor outcomes between geriatric and non-geriatric patients: A population-based analysis.

BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients. METHODS: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. RESULTS: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001). CONCLUSIONS: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients.

Ensuring fidelity: key elements to consider in disseminating a diabetes telemanagement program for underserved Hispanic/Latinos living with type 2 diabetes.

Background: The Hispanic/Latino population has greater risk (estimated >50%) of developing type 2 diabetes (T2D) and developing it at a younger age. The American Diabetes Association estimates costs of diagnosed diabetes in 2017 was $327 billion; with medical costs 2.3x higher than patients without diabetes. The purpose of this manuscript is to describe the methodology utilized in a randomized controlled trial aimed at evaluating the efficacy of a diabetes telemanagement (DTM) program for Hispanic/Latino patients with T2D. The intent is to provide information for future investigators to ensure that this study can be accurately replicated. Methods: This study was a randomized controlled trial with 240 participants. Eligible patients (Hispanic/Latino, aged 18+, living with T2D) were randomized to Comprehensive Outpatient Management (COM) or DTM. DTM was comprised of usual care, including routine clinic visits every three months, as well as: Biometrics (a tablet, blood glucose meter, blood pressure monitor, and scale); Weekly Video Visits (facilitated in the patient's preferred language); and Educational Videos (including culturally congruent diabetes self-management education and quizzes). COM consisted of usual care including routine clinic visits every three months. For this study, COM patients received a glucometer, glucose test strips, and lancets. Establishing a therapeutic nurse-patient relationship was a fundamental component of our study for both groups. First contact (post-enrollment) centered on ensuring that patients and caregivers understood the program, building trust and rapport, creating a non-judgmental environment, determining language preference, and establishing scheduling availability (including evenings and weekends). DTM were provided with a tablet which allowed for self-paced education through videos and weekly video visits. The research team and Community Advisory Board identified appropriate educational video content, which was incorporated in diabetes educational topics. Video visits allowed us to assess patient involvement, motivation, and nonverbal communication. Communicating in Spanish, and awareness of diverse Hispanic/Latino backgrounds was critical, as using relevant and commonly-used terms can increase adherence and improve outcomes. Shared decision-making was encouraged to make realistic health care choices. Conclusion: Key elements discussed above provide a framework for future dissemination of an evidence-based DTM intervention to meet the needs of underserved Hispanic/Latino people living with T2D.

Regional Analysis of Myocardial Strain to Wall Thickness Ratio in Cardiac Amyloidosis and Hypertrophic Cardiomyopathy.

BACKGROUND: Increased left ventricular wall thickness is a hallmark of cardiac amyloidosis (CA). Several other disease states, including hypertrophic cardiomyopathy (HCM), share this common feature. Myocardial strain has emerged as a diagnostic and prognostic tool to differentiate causes of increased left ventricular wall thickness. We sought to determine if regional strain differences were present in CA when compared with HCM when indexed to wall thickness as well as adjusting for important factors such as ejection fraction (EF), age, sex, and hypertension. METHODS: We performed a multicenter, retrospective analysis of 122 patients in 3 groups: CA (n=40), HCM (n=44), and controls (n=38). Using commercially available software, we determined peak systolic strain measurements in the base, mid, and apical segments in all 3 cardinal directions of radial strain, circumferential strain, and longitudinal strain. The regional strain was indexed to wall thickness to create a strain to wall thickness (STT) ratio. Analysis of Variance was performed to examine the association of each strain parameter with the disease group, adjusting for age, sex, hypertension, and EF. Multinomial logistic regression was performed to determine which combination of variables can potentially be used to best model the disease group. RESULTS: Ratios of STT at all 3 levels were significantly different with respect to the cardinal directions of radial, circumferential, and longitudinal strain in a multivariable analysis adjusting for age, sex, and hypertension. Specifically, with respect to the basal segments, the STT ratio across CA, HCM, and normal were significantly different in radial (1.13±0.34 vs. 3.79±0.22 vs. 4.12±0.38; P<0.0001), circumferential (-0.79±0.10 vs. -1.62±0.07 vs. -2.25±0.11; P<0.0001), and longitudinal directions (-0.41±0.09 vs. -1.03±0.06 vs. -1.41±0.10; P<0.0001). When adjusting for age, sex, hypertension and EF, only the base was significantly different between the CA and HCM groups in the radial (1.49±0.37 vs. 3.53±0.24; P<0.0001), circumferential -1.04±0.10 vs. -1.44±0.06; P<0.005), and longitudinal (-0.55±0.10 vs -0.94±0.06; P=0.007) directions. Using multinomial logistic regression, the use of age, left ventricular EF, global longitudinal strain, and basal radial strain yielded a diagnostic model with an area under the receiver operating characteristic curve (AUC) of 0.98. A model excluding age, despite being likely an independent predictor in our cohort, yielded an overall AUC of 0.90. When excluding age, the overall AUC was 0.91 and specifically when discriminating CA from HCM was 0.95. CONCLUSIONS: Regional myocardial strain indexed to wall thickness with an STT ratio can differentiate between etiologies of increased left ventricular wall thickness. Differences in myocardial deformation may be independent of wall thickness. Differences in basal strain when indexed to wall thickness in all 3 cardinal directions between CA and HCM are independent of EF. Multinomial logistic regression analysis using strain parameters differentiates CA and HCM with excellent diagnostic accuracy.

Risk Factors for Postdischarge Major Thromboembolism and Mortality in Hospitalized Patients with COVID-19 with Cardiovascular Comorbidities: Insights from the CORE-19 Registry.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with venous and arterial thromboembolism (VTE and ATE) and all-cause mortality (ACM) in hospitalized patients. High-quality data are needed on postdischarge outcomes in patients with cardiovascular disease. OBJECTIVES: To analyze outcomes and identify risk factors for ATE, VTE, and ACM in a high-risk subgroup of hospitalized COVID-19 patients with baseline cardiovascular disease. METHODS: We investigated postdischarge rates and associated risk factors of ATE, VTE, and ACM in 608 hospitalized COVID-19 patients with coronary artery disease, carotid artery stenosis (CAS), peripheral arterial disease (PAD), or ischemic stroke. RESULTS: Through 90 days postdischarge, outcome rates were: ATE 27.3% (10.2% myocardial infarction, 10.1% ischemic stroke, 13.2% systemic embolism, 12.7% major adverse limb event); VTE 6.9% (4.1% deep vein thrombosis, 3.6% pulmonary embolism); composite of ATE, VTE, or ACM 35.2% (214/608). Multivariate analysis showed significant association between this composite endpoint and age >75 years (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.22-2.94, p = 0.004), PAD (OR: 3.23, 95% CI: 1.80-5.81, p ≤ 0.0001), CAS (OR: 1.74, 95% CI: 1.11-2.75, p = 0.017), congestive heart failure (CHF) (OR: 1.84, 95% CI: 1.02-3.35, p = 0.044), previous VTE (OR: 3.08, 95% CI: 1.75-5.42, p < 0.0001), and intensive care unit (ICU) admission (OR: 2.93, 95% CI: 1.81-4.75, p < 0.0001). CONCLUSION: COVID-19 inpatients with cardiovascular disease experience high rates of ATE, VTE, or ACM through 90 days postdischarge. Age >75 years, PAD, CAS, CHF, previous VTE, and ICU admission are independent risk factors.

Profiling Immunological Phenotypes in Individuals During the First Year After Traumatic Spinal Cord Injury: A Longitudinal Analysis.

Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

A Retrospective Study of the Effect of Metformin on Patients with Metastatic Prostate Cancer.

Introduction: Previous studies demonstrated that metformin could lead to an inhibition of proliferation of cancer cells through a shift from anabolic to catabolic metabolism. In this study, we seek to investigate the effect of metformin in metastatic prostate cancer. Methods: Patients followed at Northwell Health Zuckerberg Cancer Center during 2014-2018 were included if they were diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC), with ⩾6 months follow-up with and without metformin treatment. The primary outcomes, 6-month prostate-specific antigen (PSA) response, overall survival (OS), and radiographic progression free survival (rPFS), were evaluated. Results: There were 267 patients included in the final analysis; 196 patients had mHSPC (73.2%) and 71 had mCRPC (26.8%). Within the mHSPC subjects, there was a significant difference in OS between metformin vs nonmetformin groups (148.5 vs 85.6 months; P < .046) in a univariate analysis; patients who took metformin had a significantly longer OS than subjects who did not (median OS: 148.5 vs 86 months; P < .046). There was no significant difference between the 2 groups with respect to either PSA response rate at 6 months or rPFS or OS in patients with mHSPC in both univariate and multivariate analysis. Within the mCRPC subjects, there was no significant difference between metformin and nonmetformin groups with respect to OS (43.3 vs 51.5 months; P < 0.160) or PSA response at 6 months (38.5% vs 57.1%; p < 0.24); however, patients on metformin had a significantly shorter rPFS in both the univariate analysis (7.3 vs 17.4; P < .0002) and in the multivariate analysis (HR = 2.52; 95% CI: 1.24m 5.11; P < .0109). Conclusions: Among patients with mHSPC, use of metformin was not significantly associated with improved OS in the multivariate analysis.

Mortality of Mechanically Ventilated COVID-19 Patients in Traditional versus Expanded Intensive Care Units in New York.

Rationale: During the first wave of the coronavirus disease (COVID-19) pandemic in New York City, the number of mechanically ventilated COVID-19 patients rapidly surpassed the capacity of traditional intensive care units (ICUs), resulting in health systems utilizing other areas as expanded ICUs to provide critical care. Objectives: To evaluate the mortality of patients admitted to expanded ICUs compared with those admitted to traditional ICUs. Methods: Multicenter, retrospective, cohort study of mechanically ventilated patients with COVID-19 admitted to the ICUs at 11 Northwell Health hospitals in the greater New York City area between March 1, 2020 and April 30, 2020. Primary outcome was in-hospital mortality up to 28 days after intubation of COVID-19 patients. Results: Among 1,966 mechanically ventilated patients with COVID-19, 1,198 (61%) died within 28 days after intubation, 46 (2%) were transferred to other hospitals outside of the Northwell Health system, 722 (37%) survived in the hospital until 28 days or were discharged after recovery. The risk of mortality of mechanically ventilated patients admitted to expanded ICUs was not different from those admitted to traditional ICUs (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.95-1.20; P = 0.28), while hospital occupancy for critically ill patients itself was associated with increased risk of mortality (HR, 1.28; 95% CI, 1.12-1.45; P < 0.001). Conclusions: Although increased hospital occupancy for critically ill patients itself was associated with increased mortality, the risk of 28-day in-hospital mortality of mechanically ventilated patients with COVID-19 who were admitted to expanded ICUs was not different from those admitted to traditional ICUs.

Pilot Study: Age is Not a Factor in Time to Surgery for Traumatic Cervical Spine Fracture Patients.

STUDY DESIGN: In a pilot study from an American College of Surgeons (ACS)-verified Level One Trauma Center, we performed a retrospective analysis of patients with cervical spine fractures with or without spinal cord injury (SCI). Long-term mortality was determined from the National Death Index as of December 31, 2013. OBJECTIVE: Examine the influence of age and presence of SCI on time-to-surgery and long-term mortality in patients with cervical spine fractures. SUMMARY OF BACKGROUND DATA: Cervical spine fractures with or without SCI disproportionately impact the elderly, who constitute an increasing percentage of the US population. Early surgical intervention is a safe, modifiable factor that enables early mobilization and may reduce complications. Because of increased comorbidities, surgical treatment of elderly patients with cervical spinal fractures is complex, but prolonged time to surgery is increasingly considered as a factor impacting potential recovery after SCI. MATERIALS AND METHODS: Retrospective chart review using hospital medical charts and mortality data from the National Death Index. RESULTS: Data from patients with cervical spine fractures treated surgically were analyzed, with nearly equal numbers under and over age 65. There was no statistically significant difference between the 2 age groups with respect to time-to-surgery or long-term mortality. In addition, there was no statistically significant difference between the 2 groups of patients, with or without SCI, with respect to time-to-surgery or long-term mortality. CONCLUSIONS: There was no statistically significant differences between patients by age or by SCI status with respect to time-to-surgery or long-term mortality.

Challenges and Lessons Learned for Acute Inpatient Rehabilitation of Persons With COVID-19: Clinical Presentation, Assessment, Needs, and Services Utilization.

OBJECTIVE: The aim of the study was to present: (1) physiatric care delivery amid the SARS-CoV-2 pandemic, (2) challenges, (3) data from the first cohort of post-COVID-19 inpatient rehabilitation facility patients, and (4) lessons learned by a research consortium of New York and New Jersey rehabilitation institutions. DESIGN: For this clinical descriptive retrospective study, data were extracted from post-COVID-19 patient records treated at a research consortium of New York and New Jersey rehabilitation inpatient rehabilitation facilities (May 1-June 30, 2020) to characterize admission criteria, physical space, precautions, bed numbers, staffing, employee wellness, leadership, and family communication. For comparison, data from the Uniform Data System and eRehabData databases were analyzed. The research consortium of New York and New Jersey rehabilitation members discussed experiences and lessons learned. RESULTS: The COVID-19 patients (N = 320) were treated during the study period. Most patients were male, average age of 61.9 yrs, and 40.9% were White. The average acute care length of stay before inpatient rehabilitation facility admission was 24.5 days; mean length of stay at inpatient rehabilitation facilities was 15.2 days. The rehabilitation research consortium of New York and New Jersey rehabilitation institutions reported a greater proportion of COVID-19 patients discharged to home compared with prepandemic data. Some institutions reported higher changes in functional scores during rehabilitation admission, compared with prepandemic data. CONCLUSIONS: The COVID-19 pandemic acutely affected patient care and overall institutional operations. The research consortium of New York and New Jersey rehabilitation institutions responded dynamically to bed expansions/contractions, staff deployment, and innovations that facilitated safe and effective patient care.

Intubated COVID-19 predictive (ICOP) score for early mortality after intubation in patients with COVID-19.

Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73-0.78) in the derivation cohort and 0.71 (95% CI 0.67-0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies.

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial.

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results: Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). Conclusions and Relevance: In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04401293.

Impact of Precision Medicine on Clinical Outcomes: A Single-Institution Retrospective Study.

PURPOSE: The strategy of precision medicine has been widely adopted in the practice of oncology, although the efficacy remains unclear. This study assesses clinical outcomes in patients with an actionable alteration found during FoundationOne CDx™ (F1CDx) testing and who received a targeted therapy based on the results. MATERIALS AND METHODS: This is a retrospective cohort study of patients with tumors that underwent F1CDx from September 2012 to July 2018. F1CDx provided actionable alterations for patients to select appropriate therapies. The primary objective was to estimate the objective response rate (ORR) at 3 months from the start of study treatment. The secondary objectives were to estimate progression-free survival (PFS) and overall survival (OS). RESULTS: One thousand patients underwent F1CDx testing. Six hundred fifty-two patients were identified as having actionable mutations. Thirty-eight patients (18 males and 20 females) received targeted therapy and were included in the study. The most common alterations were PD-1/PDL-1, high-TMB, P13K, and HER2/ERBB2. Patients received various treatments including nivolumab, pembrolizumab, trastuzumab, and everolimus. Eight (23.5%) and six (17.7%) patients achieved partial response (PR) and stable disease (SD), respectively; 20 (58.8%) had progression of disease (PD). The disease control rate was 41.2% (95% CI: 24.7% to 59.3%). The median PFS was 2.7 months (95% CI: 2.3 to 5.4 months), and median OS was 9.9 months (95% CI: 4.5 to 33.7 months). CONCLUSION: Our results demonstrate promising data in precision medicine in real community oncology practice. It warrants further large and prospective studies in patients with actionable alterations.

Treatment-Dose LMWH versus Prophylactic/Intermediate Dose Heparins in High-Risk COVID-19 Inpatients: Rationale and Design of the HEP-COVID Trial.

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.

Adding value to imaging services: a survey of patient and referring physician preferences for direct radiologic reporting of results.

PURPOSE: To identify preferences of patients and referring physicians for direct patient communication and notification of radiologic study results. METHODS: An anonymous survey was conducted of patients undergoing outpatient radiologic imaging studies and their referring physicians. The voluntary surveys elicited responses regarding preferences on a 5-point Likert scale (Strongly disagree, disagree, neutral, agree and strongly agree), as well as indicated by responding yes or no to specific questions. RESULTS: 368 patients completed the survey. 81.5% of patient responders preferred all results communicated from the radiologist within the same day. 65.9% of patients preferred same day results if normal vs 65.8% if abnormal. 34.5% preferred to wait and review normal results with the referring physician. 41.5% preferred to wait and review abnormal results with the referring physician. It was found that patients were more likely to strongly agree with waiting to review results with the referring physician if the results were abnormal, as opposed to normal (18.5% vs 11.9%, respectively; P < 0.014). 64% of physicians did not want results reviewed with their patients; 87.6% did not want a report sent to the patient by the radiologist, even after report was sent to their office. 66.4% of patients surveyed indicated that waiting for imaging results gives them anxiety. CONCLUSIONS: 58-82% of patients preferred same day radiologist communication of their results while 55-87.6% of physicians did not prefer same day radiologist communication of results directly with their patients. 66.4% of patients surveyed indicated that waiting for imaging results gives them anxiety.

Component resolved diagnostics in peanut sensitized children with and without a history of clinical reaction.

Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet's approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels <2 kUA/L rather than ≥2 kUA/L (p < 0.0001). When the ARAH threshold was increased to 1 kUA/L and 2 kUA/L, these thresholds were still significantly associated with PN-sIgE levels of <2, <5, and <14 kUA/L. These findings were not significantly different in patients with and without a history of clinical reactivity. Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.

Twin pregnancy and risk of postpartum hemorrhage.

Objective: To identify maternal and peripartum characteristics in twin gestations that are associated with postpartum hemorrhage (PPH) in which one or more units of packed red blood cells (PRBCs) were either administered or recommended but declined (PPH + PRBC).Methods: This retrospective cohort study evaluated all women with twin gestations who delivered at greater than 23 weeks of gestational age at a single, tertiary medical center from 2011 to 2016. Patients were included if they had documentation of estimated blood loss (EBL) at delivery and complete inpatient medical records available for review. Patients with incomplete records or an intrauterine fetal demise of one or both twins were excluded. The primary outcome was PPH + PRBC. Secondary outcomes included PPH with delivery EBL ≥1500 ml, PPH with atony and uterotonic administration, PPH with maternal hemorrhagic morbidity (MHM), and PPH with severe maternal morbidity (SMM). MHM was a composite outcome defined as PPH associated with any of the following: atony requiring uterotonics, any PRBC transfusion (≥1 unit), uterine or hypogastric artery ligation, hysterectomy, compression sutures, intrauterine balloon tamponade, uterine artery embolization, and/or exploratory laparotomy. SMM was a composite outcome defined as PPH associated with any of the following: administration of ≥4 units of PRBC, administration of ≥2 units of PRBC, and ≥2 units of fresh frozen plasma (FFP), return to operating room for any major procedure (excludes dilation and curettage), any peripartum hysterectomy, uterine artery embolization, intrauterine balloon tamponade or compression suture placed and administration of ≥2 units of PRBC, and/or intensive care unit (ICU) admission for invasive monitoring/treatment. A multivariable logistic regression analysis was performed.Results: A total of 1081 women with twin gestations were included. PPH + PRBC occurred in 4.4% (n = 48), delivery EBL ≥1500 ml occurred in 3.9% (n = 42), and atony with uterotonic administration occurred in 12.1% (n = 131) of the study population. The rate of MHM and SMM were 13.9% (n = 150) and 1.9% (n = 20), respectively. Although the rate of cesarean delivery was high overall (83.2%), it was nearly universal in the PPH + PRBC group (97.9%; p < .02). PPH + PRBC occurred at a rate of 0.5% (n = 1/182) among vaginally delivered twins compared to 5.2% (n = 47/899) among those delivered by cesarean (p < .03). The final multivariable logistic regression model to predict PPH + PRBC identified six significant maternal and peripartum factors: nulliparity, either pregestational or gestational diabetes, intrapartum magnesium sulfate, admission hematocrit <30%, admission platelets <100 000/µL and administration of general anesthesia.Conclusions: A number of maternal and peripartum factors are associated with PPH in twin gestations. Optimization of maternal hematologic parameters and chronic medical conditions, and reduction in the rate of cesarean delivery in twin pregnancies may decrease the risk of postpartum hemorrhage.