Evaluation of an ultrasound-guided freeze-core biopsy system for canine and feline brain tumors.

Objective: To determine if a single brain biopsy utilizing a freeze-core needle harvest system Cassi II under ultrasound guidance provides a diagnostic sample; to evaluate the technique's efficacy in procuring diagnostic samples in comparison with "open" surgical biopsies; and to describe intraoperative complications associated with the technique. Study design: Experimental clinical study. Animals: Seventeen dogs and four cats with magnetic resonance imaging (MRI) diagnoses of readily surgically accessible intracranial masses. Methods: Immediately prior to surgical biopsy (SB), freeze-core biopsy (FCB) sample was obtained from each patient under ultrasound guidance. Results: Histopathology results from single FCB samples were found to be in 100% agreement with the SB samples. Freezing artifact was minimal and did not interfere with histopathologic interpretation. There were no intraoperative complications specifically attributable to the use of the FCB system. Conclusion: Based on the results of this small experimental study, the FCB system is expected to safely yield diagnostic quality intracranial masses biopsy specimens. Clinical significance: This system has the potential of obtaining diagnostic biopsies of more deeply seated brain lesions (i.e., intra-axial tumors considered inaccessible or with large risks/difficulties by standard surgical means) which would provide a definitive diagnosis to guide appropriate therapy.

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.

Socioeconomic and clinical factors associated with excessive gestational weight gain.

PURPOSE: Excessive gestational weight gain (EGWG) is associated with adverse maternal and offspring outcomes but efforts to identify women at high risk for EGWG have been limited. The objective of this study is to identify socioeconomic and clinical factors associated with EGWG. METHODS: This retrospective cohort included pregnant patients who delivered live, term, singleton newborns between January 2018 and February 2020 at seven hospitals within a large health system in New York. Patients were stratified by pre-pregnancy body mass index and then classified based on whether they exceeded the Institute of Medicine guidelines for gestational weight gain (GWG) and whether they gained more than 50 pounds in pregnancy. RESULTS: A total of 44,872 subjects were included for analysis: 48% had EGWG and 17% had GWG exceeding 50 pounds. Patients with EGWG were more likely to be Black race, English speakers, overweight or obese pre-pregnancy, and have a mood disorder diagnosis. Patients who were underweight, multiparous, and those with gestational diabetes were less likely to have EGWG. CONCLUSION: Sociodemographic and clinical findings associated with GWG > 50 pounds were similar but only overweight and not obese patients were at increased risk. Patients at risk for EGWG may benefit from early nutrition counseling and education on lifestyle changes.

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.

COVID-19 stressors for Hispanic/Latino patients living with type 2 diabetes: a qualitative study.

Background and aim: During the early stages of the COVID-19 pandemic, nationwide lockdowns caused disruption in the diets, physical activities, and lifestyles of patients with type 2 diabetes. Previous reports on the possible association between race/ethnicity, COVID-19, and mortality have shown that Hispanic/Latino patients with type 2 diabetes who are socioeconomically disadvantaged are disproportionately affected by this novel virus. The aim of this study was to explore stressors associated with changes in diabetes self-management behaviors. Our goal was to highlight the health disparities in these vulnerable racial/ethnic minority communities and underscore the need for effective interventions. Methods and participants: Participants were enrolled in part of a larger randomized controlled trial to compare diabetes telehealth management (DTM) with comprehensive outpatient management (COM) in terms of critical patient-centered outcomes among Hispanic/Latino patients with type 2 diabetes. We conducted a thematic analysis using patient notes collected from two research nurses between March 2020 and March 2021. Two authors read through the transcripts independently to identify overarching themes. Once the themes had been identified, both authors convened to compare themes and ensure that similar themes were identified within the transcripts. Any discrepancies were discussed by the larger study team until a consensus was reached. Results: Six themes emerged, each of which can be categorized as either a source or an outcome of stress. Sources of stress associated with the COVID-19 pandemic were (1) fear of contracting COVID-19, (2) disruptions from lockdowns, and (3) financial stressors (e.g., loss of income). Outcomes of COVID-19 stressors were (1) reduced diabetes management (e.g., reduced diabetes monitoring and physical activity), (2) suboptimal mental health outcomes (e.g., anxiety and depression), and (3) outcomes of financial stressors. Conclusion: The findings indicated that underserved Hispanic/Latino patients with type 2 diabetes encountered a number of stressors that led to the deterioration of diabetes self-management behaviors during the pandemic.

Biopsy and histologic findings of the dura mater at the level of the foramen magnum in 121 CKCS with Chiari-like malformation.

To describe histopathologic features found in dural biopsies of Cavalier King Charles Spaniels (CKCS) with Chiari-like malformation (CM) and identify any associations between age, duration of clinical signs, syrinx location or syringomyelia (SM, and quality of life (QOL). The medical records of 121 consecutive client owned CKCS with CM and SM, confirmed by whole body magnetic resonance imaging (MRI), that underwent foramen magnum decompression (FMD) with cranioplasty and durectomy with biopsy from 2006 to 2016 were retrospectively reviewed. Dural biopsies were submitted to a board-certified veterinary pathologist for histopathologic interpretation. The chi-square test was used to analyze associations between histologic findings and categorical variables. For continuous measures, the Kruskal-Wallis non-parametric test was used to compare distributions across pathology categories. A result was considered statistically significant at the p < 0.05 level of significance. The mean age, duration of pre-surgical clinical signs, and pre-operative QOL (1-5 scale) were 44.27 months, 44.78 weeks, and 2.72, respectively. Syringomyelia was found in the cervical region only in 39 of 121 (32.23%) of dogs, in the cervical and thoracic region only in 17 of 121 (14.05%) of dogs, and in the cervical, thoracic, and lumbar region combined in 65 of 121 (53.72%) of dogs. Sixty-six of one hundred twenty-one (54.55%) dural biopsy specimens had histopathology changes; fifty-five (45.45%) did not. Forty-three of one hundred twenty-one (35.54%) dural biopsy specimens had osseous metaplasia, 16 of 121 (13.22%) had evidence of fibrosis, 4 of 121 (3.31%) had arachnoid hyperplasia, and 3 of 121 (2.48%) had evidence of mineralization. Most dogs with CM were found to have histopathologic changes in the dura at the time of FMD cranioplasty was performed. These dural changes can be observed in dogs experiencing clinical signs for a time period as short as 4 weeks prior to presentation. The histopathologic changes were not associated with age, breed, duration of clinical signs, the location of syringomyelia or QOL. The influence of histopathologic changes on long-term prognosis in dogs without dural decompression is unknown since all dogs in this study had dural resection.

Health care consequences of hospitalization with Clostrioides difficile infection: a propensity score matching study.

BACKGROUND: Clostridiodies difficile infection (CDI) has been characterized by the Center for Disease Control and Prevention (CDC) as an urgent public health threat and a major concern in hospital, outpatient and extended-care facilities worldwide. METHODS: A retrospective cohort study of patients aged ≥ 18 hospitalized with CDI in New York State (NYS) between January 1, 2014-December 31, 2016. Data were extracted from NY Statewide Planning and Research Cooperative (SPARCS) and propensity score matching was performed to achieve comparability of the CDI (exposure) and non-CDI (non-exposure) groups. Of the 3,714,486 hospitalizations, 28,874 incidence CDI cases were successfully matched to 28,874 non-exposures. RESULTS: The matched pairs comparison demonstrated that CDI cases were more likely to be readmitted to the hospital at 30 (28.26% vs. 19.46%), 60 (37.65% vs. 26.02%), 90 (42.93% vs. 30.43) and 120 days (46.47% vs. 33.74), had greater mortality rates at 7 (3.68% vs. 2.0%) and 180 days (20.54% vs. 11.96%), with significant increases in length of stay and total hospital charges (p < .001, respectively). CONCLUSIONS: CDI is associated with a large burden on patients and health care systems, significantly increasing hospital utilization, costs and mortality.

Prospective F-18 FDOPA PET Imaging Study in Human PD.

Purpose: We present the findings of our final prospective study submitted to the U.S. Food and Drug Administration (FDA) for New Drug Application (NDA) approval for the use of 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (F-18 FDOPA) positron emission tomography (PET) imaging for Parkinson's disease (PD). The primary aim was to determine the sensitivity, specificity, and predictive values of F-18 FDOPA PET in parkinsonian patients with respect to clinical standard-of-truth (SOT). Secondary outcomes included the inter-rater reliability, and correlation of quantitative measures for PET with dopaminergic status. Methods: In 68 parkinsonian subjects, F-18 FDOPA PET scan from 80 to 100 min was acquired following a CT scan. Scan images were presented to one expert in F-18 FDOPA image interpretation and two physicians with prior experience in I-123 FPCIT single-photon emission computed tomography image interpretation. Fifty-six subjects completed the study with a follow-up for SOT determination. Image readers were blind to the clinical/quantitative data; SOT clinician was blind to the image data. Results: For 47 of the 56 patients, SOT was in agreement with the PET scan results. For nine patients, SOT suggested dopaminergic deficit, whereas the imaging showed normal uptake. The specificity and positive predictive values are 91% and 92%, respectively, suggesting high probability that those who test positive by the PET scan truly have dopaminergic degeneration. The sensitivity was 73%. Inter-rater agreement was 0.6-0.8 between the different readers. Conclusion: Our prospective study demonstrates high specificity and moderate sensitivity of F-18 FDOPA PET for PD. We received NDA approval in October 2019. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00748-4.

Transfusion in Root Replacement for Aortic Dissection: The STS Adult Cardiac Surgery Database Analysis.

BACKGROUND: Transfusion in acute aortic syndromes has been studied in a limited fashion. We sought to describe contemporary transfusion practice for root replacement in acute (Stanford) type A aortic dissection. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was interrogated to identify patients who underwent primary aortic root replacement for acute (Stanford) type A aortic dissection (July 2014 to June 2017). Patients (n = 1558) were stratified by type of root replacement. Multivariate regression was used to determine those variables associated with transfusion and postoperative morbidity. RESULTS: Transfusion was required in 90.5% of cases (n = 1410). Operative mortality for all patients was 17.3% (261 deaths). Intraoperative red blood cell transfusion portended reduced short-term survival (odds ratio [OR] 2.00, P = .025). Massive postoperative transfusion was associated with prolonged ventilation (OR 13.47, P < .001), sepsis (OR 4.13, P < .001), and new dialysis-dependent renal failure (OR 2.43, P < .001). Women were more likely to require transfusion (OR 3.03, P < .001), as were patients who had coronary artery bypass (OR 1.57, P = .009), and those in shock (OR 2.27, P < .001). Valve-sparing aortic root replacement was associated with reduced transfusion requirements vs composite roots. Institutional case volume was not appreciably correlated with transfusion. CONCLUSIONS: Most patients undergoing root replacement for aortic dissection require blood products. Composite root replacement is associated with a greater likelihood of transfusion than a valve-sparing operation. Transfusion independently foreshadows greater operative mortality.

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.

Context-dependent induction of autoimmunity by TNF signaling deficiency.

TNF inhibitors are widely used to treat inflammatory diseases; however, 30%-50% of treated patients develop new autoantibodies, and 0.5%-1% develop secondary autoimmune diseases, including lupus. TNF is required for formation of germinal centers (GCs), the site where high-affinity autoantibodies are often made. We found that TNF deficiency in Sle1 mice induced TH17 T cells and enhanced the production of germline encoded, T-dependent IgG anti-cardiolipin antibodies but did not induce GC formation or precipitate clinical disease. We then asked whether a second hit could restore GC formation or induce pathogenic autoimmunity in TNF-deficient mice. By using a range of immune stimuli, we found that somatically mutated autoantibodies and clinical disease can arise in the setting of TNF deficiency via extrafollicular pathways or via atypical GC-like pathways. This breach of tolerance may be due to defects in regulatory signals that modulate the negative selection of pathogenic autoreactive B cells.

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.

Cardiotoxicity screening of long-term, breast cancer survivors-The CAROLE (Cardiac-Related Oncologic Late Effects) Study.

BACKGROUND: Long-term breast cancer survivors are at risk for cardiotoxicity after treatment, but there is insufficient evidence to provide long-term (~10 years) cardiovascular disease (CVD) screening recommendations. We sought to evaluate a tri-modality CVD screening approach. METHODS: This single-arm, feasibility study enrolled 201 breast cancer patients treated ≥6 years prior without CVD at diagnosis. Patients were sub-grouped: cardiotoxic (left-sided) radiation (RT), cardiotoxic (anthracycline-based) chemotherapy, both cardiotoxic chemotherapy and RT, and neither cardiotoxic treatment. Patients underwent electrocardiogram (EKG), transthoracic echocardiogram with strain (TTE with GLS), and coronary artery calcium computed tomography (CAC CT). The primary endpoint was preclinical or clinical CVD. RESULTS: Median age was 50 (29-65) at diagnosis and 63 (37-77) at imaging; median interval was 11.5 years (6.7-14.5). Among sub-groups, 44% had no cardiotoxic treatment, 31.5% had cardiotoxic RT, 16% had cardiotoxic chemotherapy, and 8.5% had both. Overall, 77.6% showed preclinical and/or clinical CVD and 51.5% showed clinical CVD. Per modality, rates of any CVD and clinical CVD were, respectively: 27.1%/10.0% on EKG, 50.0%/25.3% on TTE with GLS, and 50.8%/45.8% on CAC CT. No statistical difference was seen among the treatment subgroups (NS, χ2 test, p = 0.58/p = 0.15). CONCLUSION: This study identified a high incidence of CVD in heterogenous long-term breast cancer survivors, most >10 years post-treatment. Over half had clinical CVD findings warranting follow-up and/or intervention. Each imaging test independently contributed to the detection rate. This provides early evidence that long-term cardiac screening may be of value to a wider group of breast cancer survivors than previously recognized.

Sociodemographic predictors and transportation patterns of COVID-19 infection and mortality.

BACKGROUND: The United States Centers for Disease Control and Prevention (CDC)-sanctioned prevention strategies have included frequent handwashing with soap and water, covering the mouth and nose with a mask when around others, cleaning and disinfecting maintaining a distance of at least 6 feet from others, etc. Although many of these recommendations are based upon observation and past infection control practices, it is important to combine and explore public data sets to identify predictors of infection, morbidity and mortality to develop more finely honed interventions, based on sociodemographic factors. METHOD: Cross-sectional study of both states in the US and counties in NY state. RESULTS: Population density was found to be significantly associated with state-level coronavirus infection and mortality rate (b = 0.49, 95% confidence interval (CI): 0.34, 0.64, P < .0001). States that have lower socioeconomic status, lower mean age and denser populations are associated with higher incidence rates. In regard to NY state, counties with a higher percentage of minority residents had higher COVID-19 mortality rates (b = 2.61, 95% CI: 0.36, 4.87, P = 0.023). Larger population cohorts were associated with lower COVID-19 mortality rates after adjusting for other variables in the model (b = -1.39, 95% CI: -2.07, -0.71, P < 0.001). Population density was not significantly associated with COVID-19 mortality rates after adjustment across counties in the NY state. Public ridership was not indicative of cases or mortality across states in the USA; however, it is a significant factor associated with incidence (but not mortality) in NY counties. CONCLUSION: Population density was the only significant predictor of mortality across states in the USA. Lower mean age, lower median household incomes and more densely populated states were at higher risk of COVID-19 infection. Population density was not found to be a significant independent variable compared to minority status and socioeconomic factors in the New York epicenter. Meanwhile, public ridership was found to be a significant factor associated with incidence in New York counties.

Survival models to support shared decision-making about advance care planning for people with advanced stage cystic fibrosis.

BACKGROUND: For people with advanced stage cystic fibrosis (CF), tailored survival estimates could facilitate preparation for decision-making in the event of acutely deteriorating respiratory function. METHODS: We used the US CF Foundation national database (2008-2013) to identify adult people with incident advanced stage CF (forced expiratory volume in 1 s (FEV1) ≤45% predicted). Using the lasso method for variable selection, we divided the dataset into training and validation samples (2:1), and developed two multivariable Cox proportional hazards models to calculate probabilities of survival from baseline (T0 model), and from 1 year after (T12 model). We also performed Kaplan-Meier survival analyses. RESULTS: 4752 people were included. For the T0 model, FEV1; insurance; non-invasive ventilation; supplemental oxygen; Burkholderia colonisation; cirrhosis; depression; dialysis; current smoking; unclassifiable mutation class and cumulative CF exacerbations predicted increased mortality. Baseline transplant evaluation status of 'accepted, on waiting list' predicted decreased mortality. For the T12 model, interim decrease in FEV1 >10%, and pulmonary exacerbations additionally increased predicted mortality. Lung transplantation was associated with lower mortality. Of the 4752, 93.5%, 86.4%, 79.7% and 73.9% survived to 1, 2, 3 and 4 years, respectively, without considering any confounding variables. The models had moderate predictive ability indicated by the area under the time-dependent receiver operating characteristic curve (0.787, 95% CI 0.769 to 0.794 for T0 model; and 0.779, 95% CI 0.767 to 0.797 for T12 model). CONCLUSION: We have developed models predicting survival in people with incident advanced stage CF, which can be reapplied over time to support shared decision-making about end-of-life treatment choices and lung transplantation. These estimates must be updated as data become available regarding long-term outcomes for people treated with CF transmembrane conductance regulator modulators.

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.

Comparative Survival Analysis of Immunomodulatory Therapy for Coronavirus Disease 2019 Cytokine Storm.

BACKGROUND: Cytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. RESEARCH QUESTION: Do immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)? STUDY DESIGN AND METHODS: We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, > 700 ng/mL; C-reactive protein (CRP), > 30 mg/dL; or lactate dehydrogenase (LDH), > 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-IL-6 antibody (tocilizumab), or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. RESULTS: Five thousand seven hundred seventy-six patients met the inclusion criteria. The most common comorbidities were hypertension (44%-59%), diabetes (32%-46%), and cardiovascular disease (5%-14%). Patients most frequently met criteria with high LDH (76.2%) alone or in combination, followed by ferritin (63.2%) and CRP (8.4%). More than 80% of patients showed an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination showed lower mortality compared with patients receiving standard-of-care (SoC) treatment (hazard ratio [HR], 0.44; 95% CI, 0.35-0.55; P < .0001) and with patients treated with corticosteroids alone (HR, 0.66; 95% CI, 0.53-0.83; P = .004) or in combination with anakinra (HR, 0.64; 95% CI, 0.50-0.81; P = .003). Corticosteroids when administered alone (HR, 0.66; 95% CI, 0.57-0.76; P < .0001) or in combination with tocilizumab (HR, 0.43; 95% CI, 0.35-0.55; P < .0001) or anakinra (HR, 0.68; 95% CI, 0.57-0.81; P < .0001) improved hospital survival compared with SoC treatment. INTERPRETATION: The combination of corticosteroids with tocilizumab showed superior survival outcome when compared with SoC treatment as well as treatment with corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with CCS compared with patients receiving SoC treatment.

Adapting a home telemonitoring intervention for underserved Hispanic/Latino patients with type 2 diabetes: an acceptability and feasibility study.

BACKGROUND: Home telemonitoring is a promising approach to optimizing outcomes for patients with Type 2 Diabetes; however, this care strategy has not been adapted for use with understudied and underserved Hispanic/Latinos (H/L) patients with Type 2 Diabetes. METHODS: A formative, Community-Based Participatory Research approach was used to adapt a home telemonitoring intervention to facilitate acceptability and feasibility for vulnerable H/L patients. Utilizing the ADAPT-ITT framework, key stakeholders were engaged over an 8-month iterative process using a combination of strategies, including focus groups and structured interviews. Nine Community Advisory Board, Patient Advisory, and Provider Panel Committee focus group discussions were conducted, in English and Spanish, to garner stakeholder input before intervention implementation. Focus groups and structured interviews were also conducted with 12 patients enrolled in a 1-month pilot study, to obtain feedback from patients in the home to further adapt the intervention. Focus groups and structured interviews were approximately 2 hours and 30 min, respectively. All focus groups and structured interviews were audio-recorded and professionally transcribed. Structural coding was used to mark responses to topical questions in the moderator and interview guides. RESULTS: Two major themes emerged from qualitative analyses of Community Advisory Board/subcommittee focus group data. The first major theme involved intervention components to maximize acceptance/usability. Subthemes included tablet screens (e.g., privacy/identity concerns; enlarging font sizes; lighter tablet to facilitate portability); cultural incongruence (e.g., language translation/literacy, foods, actors "who look like me"); nursing staff (e.g., ensuring accessibility; appointment flexibility); and, educational videos (e.g., the importance of information repetition). A second major theme involved suggested changes to the randomized control trial study structure to maximize participation, including a major restructuring of the consenting process and changes designed to optimize recruitment strategies. Themes from pilot participant focus group/structured interviews were similar to those of the Community Advisory Board such as the need to address and simplify a burdensome consenting process, the importance of assuring privacy, and an accessible, culturally congruent nurse. CONCLUSIONS: These findings identify important adaptation recommendations from the stakeholder and potential user perspective that should be considered when implementing home telemonitoring for underserved patients with Type 2 Diabetes. TRIAL REGISTRATION: NCT03960424; ClinicalTrials.gov (US National Institutes of Health). Registered 23 May 2019. Registered prior to data collection. https://www.clinicaltrials.gov/ct2/show/NCT03960424?term=NCT03960424&draw=2&rank=1.

Transfusion in Elective Aortic Root Replacement: Analysis of the STS Adult Cardiac Surgery Database.

BACKGROUND: Data on blood use in proximal aortic surgery is limited. This study sought to establish quality benchmarks in the pattern of transfusion during elective aortic root replacement. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was queried to identify all patients who underwent primary elective aortic root replacement between July 2014 and June 2017. Multivariable negative binomial regressions were used to determine whether perioperative transfusion was associated with demographic or procedural factors. Multivariable logistic regression analysis was performed for clinical outcomes. RESULTS: Of 5559 patients analyzed, 38.95% (n = 2165) received no blood products. Patients who had a valve-sparing root replacement were less likely to undergo transfusion than those who received composite roots (bioprosthetic or mechanical valves) or homografts. The 30-day mortality for all patients was 2.57% (n = 143). Transfusion was associated with an increased risk of death at 30 days (odds ratio [OR], 1.833; P = .012), more frequent reoperation for bleeding (OR, 1.766; P < .001), prolonged ventilation (OR, 1.935; P < .001), a longer postoperative hospital stay (OR, 1.056; P < .001), and a higher incidence of new dialysis-dependent renal failure (OR, 2.088; P = .003). There was no correlation between institutional case volume and transfusion practice. CONCLUSIONS: Elective aortic root replacement can be performed with acceptable requirements for blood products. Composite root replacement has a greater likelihood of transfusion than does a valve-sparing procedure. Transfusion is independently associated with more complications after elective aortic root surgery, including 30-day mortality.

Is vaginal misoprostol more effective than oral misoprostol for cervical ripening in obese women?

Objective: To determine if vaginal misoprostol is more effective than oral misoprostol for cervical ripening in obese women.Study design: A retrospective cohort study of obese women undergoing induction of labor from Jan 2013 to Dec 2016 with singleton, viable pregnancies beyond 37 completed weeks of gestational age. Women with an initial Bishop score of 7 or less, with a cervical dilatation of less than 2 cm, who received either vaginal or oral misoprostol as a cervical ripening agent, were included. Primary outcome was interval from the start of induction to the attainment of 3 cm cervical dilatation. Secondary outcomes included the interval from the start of induction to delivery and the rate of cesarean delivery (CD).Result: Of women who met the inclusion criteria, 966 (75.5%) women received oral misoprostol and 314 (24.5%) received vaginal misoprostol. The mean time-interval from the start of induction to attainment of 3-cm dilatation was shorter in the vaginal group (10.5 ± 10.4 h) compared to the oral group (17.2 ± 11.5 h), (p < .0001). Significantly shorter times to delivery were also noted in the vaginal group (17.4 h for vaginal vs. 24.8 h for oral, p < .0001). In the subgroup analysis of nulliparous women, shorter time intervals from the start of induction to attainment of 3-cm dilatation, as well as to delivery, were noted in the vaginal misoprostol group (p < .0001 for both). Multiple linear regression model confirmed route of misoprostol administration as an independent variable in predicting the outcomes (time from start of induction to 3 cm as well as to delivery). Significant findings amongst neonatal outcomes included lower umbilical artery pH and higher rates of neonatal jaundice in the oral misoprostol group.Conclusion: In a population of obese women undergoing induction of labor, vaginal administration of misoprostol was associated shorter time intervals from the start of induction to the attainment of 3 cm of dilatation, as well as to delivery, without increasing the rate of cesarean deliveries or the incidence of adverse maternal and neonatal outcomes.