A real-world study of pneumonitis in non-small cell lung cancer patients receiving durvalumab following concurrent chemoradiation

BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) treated with the programmed death-ligand 1 inhibitor durvalumab has been associated with significant rates of pneumonitis, which has led to higher rates of discontinuation of therapy in real-world populations. Thus far there has been no consensus in the literature on the impact of pneumonitis on survival. METHODS: This is a retrospective cohort study of veterans receiving durvalumab between 12/5/2017 and 4/15/2020. Participants were identified using VINCI data services. Patients were followed through 9/14/2021. Development of clinical pneumonitis was assessed through review of documentation and graded using CTCAE 4.0 criteria. Univariate logistic regression analysis evaluated for associations between body mass index (BMI), age, race, co-morbidity index, chemotherapy regimen, chronic obstructive pulmonary disease (COPD) severity, and development of clinical pneumonitis. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier methods. Cox proportional hazards models were utilized to evaluate the association between risk of death at 1 and 2 years and candidate predictor variables. RESULTS: A total of 284 patients were included in this study. Sixty-one patients developed clinically significant pneumonitis, 7 patients developed grade 5 pneumonitis (death from pneumonitis). The median OS in patients that developed pneumonitis was 27.8 CONCLUSIONS: The incidence of clinically significant pneumonitis is higher than noted in the PACIFIC trial in this cohort, however this high rate of pneumonitis does not have an impact on OS or PFS. Obesity was found to be a significant predictor of pneumonitis in this patient population

Predictors of non-variceal hemorrhage in a national cohort of patients with chronic liver disease

BACKGROUND: Non-variceal hemorrhage in patients with chronic liver disease (CLD) increases morbidity, mortality, and healthcare costs. There are limited data on risk factors for non-variceal hemorrhage in the CLD population. The aim of this study was to assess the predictive value of various clinical and laboratory parameters for non-variceal hemorrhage in CLD patients. METHODS: We conducted a retrospective cohort study of US veterans diagnosed with CLD between 2002 and 2018 within the Veterans Health Administration database. We derived candidate variables from existing risk prediction models for hemorrhage, risk calculators for severity of liver disease, Charlson index of prognostic comorbidities, and prior literature. We used a competing risk analysis to study the relationship between putative risk factors and incidence of non-variceal hemorrhage in patients with CLD. RESULTS: Of 15,183 CLD patients with no history of cancer or anticoagulation use, 674 experienced non-variceal hemorrhage within 1 year of CLD diagnosis. In multivariable analysis, 11 of the 26 candidate variables independently predicted non-variceal hemorrhage: race, international normalized ratio (INR) \u3e 1.5, bilirubin ≥ 2 mg/dL, albumin ≤ 3.5 g/dL, anemia, alcohol abuse, antiplatelet therapy, chronic kidney disease, dementia, proton pump inhibitor prescription, and recent infection. CONCLUSIONS: In this study of almost 15,000 veterans, risk factors for non-variceal bleeding within the first year after diagnosis of CLD included non-Caucasian race, laboratory parameters indicating severe liver disease and recent infection in addition to the risk factors for bleeding observed in a general non-CLD population

Venous thromboembolism in multiple myeloma is associated with increased mortality

BACKGROUND: In multiple myeloma, venous thromboembolism (VTE) is common, and treatments for myeloma, such as lenalidomide, increase the risk of thrombosis while improving survival. The association between VTE and survival is not well known. OBJECTIVES: To determine the association between VTE and survival in multiple myeloma (MM) while adjusting for known confounders that affect risk of thrombosis and survival, including patient characteristics and treatment in a retrospective cohort of US veterans. PATIENTS/METHODS: A cohort of patients with newly diagnosed MM treated within Veterans Health Administration between September 1, 1999, and June 30, 2014, was created to assess the association between VTE and mortality using Cox proportional hazards regression modeling while accounting for known prognostic factors and treatments. RESULTS: The cohort comprised 4446 patients with myeloma, including 2837 patients diagnosed after lenalidomide approval in July 2006. VTE occurred in 327 (7.4%) patients within 1 year and occurred at a median of 77 days (interquartile range, 37-153) after starting therapy for MM. In all patients, VTE was associated with increased mortality at 6 months (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.18-2.37). Patients in the post-lenalidomide cohort with VTE had an increased mortality at both 6 months (aHR, 2.31; 95% CI, 1.52-3.51) and 12 months (aHR, 1.66; 95% CI, 1.19-2.33) after treatment initiation. DISCUSSION: This study shows that VTE during the first 6-12 months of therapy is associated with increased mortality in patients with MM. Studies evaluating thromboprophylaxis in patients at high risk of thrombosis are needed

Chronic anti-coagulation therapy reduced mortality in patients with high cardiovascular risk early in COVID-19 pandemic

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviating these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients hospitalized during the early phase of the pandemic in the United States. METHODS: A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous outpatient therapeutic AC for a least 90 days prior to their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). RESULTS: We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. CONCLUSION: AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus

Impact of sarcopenia on treatment tolerance in United States veterans with diffuse large B‐cell lymphoma treated with CHOP‐based chemotherapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134181/1/ajh24465_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134181/2/ajh24465.pd

Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. RESULTS: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p \u3c 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p \u3c 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84-0.96). CONCLUSIONS: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases

Development and validation of a three-dimensional deep learning-based system for assessing bowel preparation on colonoscopy video

BackgroundThe performance of existing image-based training models in evaluating bowel preparation on colonoscopy videos was relatively low, and only a few models used external data to prove their generalization. Therefore, this study attempted to develop a more precise and stable AI system for assessing bowel preparation of colonoscopy video.MethodsWe proposed a system named ViENDO to assess the bowel preparation quality, including two CNNs. First, Information-Net was used to identify and filter out colonoscopy video frames unsuitable for Boston bowel preparation scale (BBPS) scoring. Second, BBPS-Net was trained and tested with 5,566 suitable short video clips through three-dimensional (3D) convolutional neural network (CNN) technology to detect BBPS-based insufficient bowel preparation. Then, ViENDO was applied to complete withdrawal colonoscopy videos from multiple centers to predict BBPS segment scores in clinical settings. We also conducted a human-machine contest to compare its performance with endoscopists.ResultsIn video clips, BBPS-Net for determining inadequate bowel preparation generated an area under the curve of up to 0.98 and accuracy of 95.2%. When applied to full-length withdrawal colonoscopy videos, ViENDO assessed bowel cleanliness with an accuracy of 93.8% in the internal test set and 91.7% in the external dataset. The human-machine contest demonstrated that the accuracy of ViENDO was slightly superior compared to most endoscopists, though no statistical significance was found.ConclusionThe 3D-CNN-based AI model showed good performance in evaluating full-length bowel preparation on colonoscopy video. It has the potential as a substitute for endoscopists to provide BBPS-based assessments during daily clinical practice

Functional Connectivity of the Caudal Anterior Cingulate Cortex Is Decreased in Autism.

The anterior cingulate cortex (ACC) is frequently reported to have functionally distinct sub-regions that play key roles in different intrinsic networks. However, the contribution of the ACC, which is connected to several cortical areas and the limbic system, to autism is not clearly understood, although it may be involved in dysfunctions across several distinct but related functional domains. By comparing resting-state fMRI data from persons with autism and healthy controls, we sought to identify the abnormalities in the functional connectivity (FC) of ACC sub-regions in autism. The analyses found autism-related reductions in FC between the left caudal ACC and the right rolandic operculum, insula, postcentral gyrus, superior temporal gyrus, and the middle temporal gyrus. The FC (z-scores) between the left caudal ACC and the right insula was negatively correlated with the Stereotyped Behaviors and Restricted Interests scores of the autism group. These findings suggest that the caudal ACC is recruited selectively in the pathomechanism of autism