Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels nor blood coagulation.

Administration of high dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anti-coagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, nor increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anti-coagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.

From Acute Infection to Prolonged Health Consequences: Understanding Health Disparities and Economic Implications in Long COVID Worldwide.

The COVID-19 pandemic has resulted in a growing number of patients experiencing persistent symptoms and physiological changes after recovering from acute SARS-CoV-2 infection, known as Long COVID. Long COVID is characterized by recurring symptoms and inflammation across multiple organ systems. Diagnosis can be challenging, influenced by factors like demographics, comorbidities, and immune responses. Long COVID impacts various organ systems and can have neuropsychological effects. Health disparities, particularly related to race, contribute to a higher burden of infection and ongoing symptoms in minority populations. Managing Long COVID entails addressing a spectrum of symptoms that encompass physical, cognitive, and psychological aspects. The recovery period for patients with Long COVID can vary significantly, influenced by factors like the severity of the disease, hospitalization, comorbidities, and age. Currently, there are no universally effective treatments, although certain interventions show promise, necessitating further research. Self-management and rehabilitation programs can provide relief, but more research is needed to establish their effectiveness. Preventive measures such as vaccination and the use of antiviral medications and metformin. It is imperative to conduct further research to develop evidence-based guidelines and gain a better understanding of the long-term implications of COVID-19. Long COVID could have substantial economic impact on the labor market, productivity, healthcare expenditures, and overall economic growth. To address the challenges patients with long-term complications face, there is a focus on strategies like promoting telework and flexible work arrangements to accommodate diverse symptoms, particularly chronic fatigue and other Long COVID effects. In conclusion, this review emphasizes the multifaceted complexity of Long COVID and the ongoing need to address its potential long-term health and economic impacts.

Alpha-1 Antitrypsin Phenotyping: An Unmet Educational Need of Healthcare Providers.

Background: Diagnosing alpha-1 antitrypsin deficiency (A1ATD) involves two-step laboratory testing, determination of serum alpha-1 antitrypsin (A1AT) level and phenotyping if A1AT < 100 mg/dL. Whether these guidelines are effectuated in clinical practice is uncertain. To begin to address this issue, we determined whether A1AT phenotyping is performed in patients with serum A1AT 57 - 99 mg/dL at our institution. Methods: We reviewed the medical records of patients seen at Jesse Brown Veterans Affairs Medical Center from January 2019 to October 2022 with serum A1AT between 57 and 99 mg/dL. In each case, pertinent demographic, clinical, and pulmonary function tests data were extracted. Data were presented as means and standard deviation (SD) where appropriate. The Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant. Results: Thirty patients (90% males; 60 ± 18 years) with serum A1ATD < 100 mg/mL were identified. Fourteen were African Americans, four Hispanics, and 12 non-Hispanic Whites. The majority were current or ex-smokers. Fourteen (47%) patients had lung disease, 14 (47%) liver disease and one had concomitant lung and liver diseases. Mean ± SD forced expiratory volume in 1 s (FEV1) and lung diffusing capacity were 2.57 ± 1.41 L (67±19% predicated) and 18.7 ± 10 mL/min/mm Hg (64±28% predicted), respectively. Only 13 patients (43%) underwent phenotype testing (seven African Americans, five Whites, and one Hispanic). Six patients had MZ phenotype, four MS, and three SZ. One patient died from acute respiratory failure during the study period. Conclusions: Phenotyping of patients with serum A1AT 57 - 99 mg/dL at our institution is inadequate. Accordingly, regular continuous medical educational programs on A1AT phenotyping targeting healthcare providers are warranted.

Home Oxygen After Hospitalization for COVID-19: Results From the Multi-Center OXFORD Study.

BACKGROUND: In the first months of the pandemic, prior to the introduction of proven-effective treatments, 15-37% of patients hospitalized with COVID-19 were discharged on home oxygen. After proven-effective treatments for acute COVID-19 were established by evidence-based guidelines, little remains known about home oxygen requirements following hospitalization for COVID-19. METHODS: This was a retrospective, multi-center cohort study of subjects hospitalized for COVID-19 between October 2020-September 2021 at 3 academic health centers. Information was abstracted from electronic health records at the index hospitalization and for 60 d after discharge. The World Health Organization COVID-19 Clinical Progression Scale score was used to identify patients with severe COVID-19. RESULTS: Of 517 subjects (mean age 58 y, 47% female, 42% Black, 36% Hispanic, 22% with severe COVID-19), 81% were treated with systemic corticosteroids, 61% with remdesivir, and 2.5% with tocilizumab. About one quarter of subjects were discharged on home oxygen (26% [95% CI 22-29]). Older age (adjusted odds ratio [aOR] 1.02 per 5 y [95% CI 1.02-1.02]), higher body mass index (aOR 1.02 per kg/m2 [1.00-1.04]), diabetes (yes vs no, aOR 1.73 [1.46-2.02]), severe COVID-19 (vs moderate, aOR 3.19 [2.19-4.64]), and treatment with systemic corticosteroids (yes vs no, aOR 30.63 [4.51-208.17]) were associated with an increased odds of discharge on home oxygen. Comorbid hypertension (yes vs no, aOR 0.71 [0.66-0.77) was associated with a decreased odds of home oxygen. Within 60 d of hospital discharge, 50% had documentation of pulse oximetry; in this group, home oxygen was discontinued in 46%. CONCLUSIONS: About one in 4 subjects were prescribed home oxygen after hospitalization for COVID-19, even after guidelines established proven-effective treatments for acute illness. Evidence-based strategies to reduce the requirement for home oxygen in patients hospitalized for COVID-19 are needed.

Risk of 30-Day All-Cause Readmission in Interstitial Lung Disease Patients after COVID-19: National-Level Data.

Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.

Presence of variable extrathoracic airflow limitation in patients with a negative methacholine challenge test.

PURPOSE: Determine whether variable extrathoracic airflow limitation (VEAL) is observed in patients with negative methacholine challenge tests (MCT). METHODS: Electronic medical records of patients undergoing MCT at Jesse Brown VA Medical Center between January 2017 and December 2019 were reviewed. Only patients with negative MCT were selected. Pertinent demographic, clinical, and pulmonary function tests (PFT) and MCT data were abstracted from each record. Spirometric flow-volume loops recorded during each test were inspected by one co-author to determine the first inhaled methacholine concentration at which FEF50/FIF50 was either > 1 or further increased if baseline FEF50/FIF50 after nebulized saline (vehicle) already exceeded 1. Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: One hundred and twenty-seven consecutive patients with normal baseline PFT and negative MCT were identified. Thirteen patients (10.2%) had negative MCT and FEF50/FIF50 > 1 after testing. They were predominately obese (BMI, 31.3 ± 6.6), non-smoking (10), White (8) males (9) aged 51.3 ± 14.1 years (mean ± SD) referred for symptoms suggestive of asthma (n = 7) or for chronic cough (n = 6). Five had obstructive sleep apnea, three gastroesophageal reflux disease, and two chronic rhinosinusitis. FEF50/FIF50 increased significantly from 0.72 ± 0.21 after nebulized saline (vehicle) to 1.21 ± 0.13 after inhaled methacholine (p < 0.001). Median inhaled methacholine concentration eliciting these responses was 1.0 mg/mL (range, 0.25-16 mg/mL). CONCLUSIONS: VEAL is observed in a subset of patients with a negative MCT. This phenomenon should be recognized and reported to the referring healthcare providers and its clinical significance addressed as indicated.

Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans: report of an expert meeting.

The present report summarizes the United States Department of Veterans Affairs (VA) field-based meeting titled "Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans." Our Veteran patient population experiences a high incidence of service-related chronic physical and mental health problems, such as infection, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), various forms of hematological and non-hematological malignancies, neurologic conditions, end-stage organ failure, requiring transplantation, and posttraumatic stress disorder (PTSD). We report the views of a group of scientists who focus on the current state of scientific knowledge elucidating the mechanisms underlying the aforementioned disorders, novel therapeutic targets, and development of new approaches for clinical intervention. In conclusion, we dovetailed on four research areas of interest: 1) microbiome interaction with immune cells after hematopoietic cell and/or solid organ transplantation, graft-versus-host disease (GVHD) and graft rejection, 2) intestinal inflammation and its modification in IBD and cancer, 3) microbiome-neuron-immunity interplay in mental and physical health, and 4) microbiome-micronutrient-immune interactions during homeostasis and infectious diseases. At this VA field-based meeting, we proposed to explore a multi-disciplinary, multi-institutional, collaborative strategy to initiate a roadmap, specifically focusing on host microbiome-immune interactions among those with service-related chronic diseases to potentially identify novel and translatable therapeutic targets.

Vaccination in the Era of Immunosuppression.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for severe infections. Vaccine responses and safety profiles may differ between AIIRD patients and the general population. While patients with autoimmune inflammatory rheumatic diseases (AIIRDs) often experience diminished humoral responses and reduced vaccine efficacy, factors such as the type of immunosuppressant medications used and the specific vaccine employed contribute to these outcomes. Notably, individuals undergoing B cell depletion therapy tend to have poor vaccine immunogenicity. However, despite these considerations, vaccine responses are generally considered clinically sufficient. Ideally, immunosuppressed AIIRD patients should receive vaccinations at least two weeks before commencing immunosuppressive treatment. However, it is common for many patients to already be on immunosuppressants during the immunization process. Vaccination rarely triggers flares in AIIRDs; if flares occur, they are typically mild. Despite the heightened infection risk, including COVID-19, among AIIRD patients with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and other diseases on immunosuppressants, the vaccination rates remain suboptimal. The future directions of vaccination in the era of immunosuppression will likely involve customized vaccines with enhanced adjuvants and alternative delivery methods. By addressing the unique challenges faced by immunosuppressed individuals, we may improve vaccine efficacy, reduce the risk of infections, and ultimately enhance the health outcomes. Additionally, clinical trials to evaluate the safety and efficacy of temporarily discontinuing immunosuppressants during vaccination in various AIIRDs are crucial.

Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need.

Background: Cholangiocarcinoma is a highly aggressive cancer of the biliary tract epithelium. This form of cancer is prevalent in Asia, and recent reports show that its incidence is relatively rare but increasing in the United States. Although risk factors for cholangiocarcinoma have yet to be elucidated, a growing body of literature suggests chronic infection of genetically susceptible individuals with the food-borne zoonotic trematodes Clonorchis sinensis (C sinensis) and Opisthorchis viverrini (O viverrini) may play a role. Observations: Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for almost 30 years. During this period, the trematodes' feeding activities and their excretory-secretory products may damage the bile duct epithelium and promote local inflammation. These pathological processes could then provoke epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to the initiation and progression of cholangiocarcinoma in genetically susceptible people. The International Agency for Research on Cancer has determined that there is sufficient evidence in humans for the carcinogenicity of chronic infections with C sinensis and O viverrini. Conclusions: Timely serodiagnosis of indolent C sinensis and O viverrini infections is important as these parasites may be a risk factor for cholangiocarcinoma in veterans who served in Vietnam. About 774,000 living Americans served in Vietnam and there is an urgent need to develop sensitive and specific serologic assays to detect both acute and indolent infections. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival.

Corrigendum: Reproducibility and rigor in rheumatology research.

[This corrects the article DOI: 10.3389/fmed.2022.1073551.].

Promoting lung cancer screening of high-risk patients by primary care providers.

BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) of the chest of eligible patients remains low. Accordingly, augmentation of appropriate LCS referrals by primary care providers (PCPs) was sought. METHODS: The quality improvement (QI) project was performed between April 2021 and June 2022. It incorporated patient education, shared decision-making (SDM) with PCPs, and tracking of initial LDCT completion. In each case, lag time (LT) to LCS and pack-years (PYs) were calculated from initial LCS eligibility. The cohort's scores were compared to national scores. Patient zip codes were used to create a geographic map of our cohort for comparison with public health data. RESULTS: An immediate and sustained increase in weekly LCS referrals from PCPs was recorded. Of 337 initial referrals, 95% were men, consisting of 66.2% Black, 28.4% White, and 5.4% other. Mean PY was less for minorities (45.3 vs. 37.3 years; p = .0002) but mean LT was greater for Whites (7.9 vs. 6.2 years; p = .03). Twenty-five percent of veterans failed to report to their scheduled screening, and two declined referrals. Notably, most no-show patients lived in transit deserts. Furthermore, Lung-RADS scores 4B/4X were more than double the expected prevalence (p = .008). CONCLUSIONS: The PCPs in this study successfully augmented LCS referrals. A substantial proportion of these patients were no-shows, and our data suggest complex racial and socioeconomic factors as contributing variables. In addition, a higher-than-expected number of initial Lung-RADS scores 4B/4X were reported. A large, multisite QI project is warranted to address overcoming potential transportation barriers in high-risk patient populations.

Immune-mediated lung diseases: A narrative review.

The role of immunity in the pathogenesis of various pulmonary diseases, particularly interstitial lung diseases (ILDs), is being increasingly appreciated as mechanistic discoveries advance our knowledge in the field. Immune-mediated lung diseases demonstrate clinical and immunological heterogeneity and can be etiologically categorized into connective tissue disease (CTD)-associated, exposure-related, idiopathic, and other miscellaneous lung diseases including sarcoidosis, and post-lung transplant ILD. The immunopathogenesis of many of these diseases remains poorly defined and possibly involves either immune dysregulation, abnormal healing, chronic inflammation, or a combination of these, often in a background of genetic susceptibility. The heterogeneity and complex immunopathogenesis of ILDs complicate management, and thus a collaborative treatment team should work toward an individualized approach to address the unique needs of each patient. Current management of immune-mediated lung diseases is challenging; the choice of therapy is etiology-driven and includes corticosteroids, immunomodulatory drugs such as methotrexate, cyclophosphamide and mycophenolate mofetil, rituximab, or other measures such as discontinuation or avoidance of the inciting agent in exposure-related ILDs. Antifibrotic therapy is approved for some of the ILDs (e.g., idiopathic pulmonary fibrosis) and is being investigated for many others and has shown promising preliminary results. A dire need for advances in the management of immune-mediated lung disease persists in the absence of standardized management guidelines.

Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality.

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. Low DNA methylation as well as high RNA expression of MYO1E are associated with a shorter median survival time and an increased risk of mortality for LUAD, but not for LUSC. This study suggests that changes in MYO1E methylation and expression in LUAD patients may have an essential role in lung cancer's pathogenesis. It shows the utility of MYO1E DNA methylation and RNA expression in predicting survival for LUAD patients. Also, given the low normal expression of MYO1E in blood cells MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.

Adalimumab in the treatment of cardiac sarcoidosis: Single center case series and narrative literature review.

Background: Tumor necrosis factor (TNF) inhibitors have been used in the treatment of cardiac sarcoidosis, infliximab being the most commonly used. We have previously reported a case of effective treatment of cardiac sarcoidosis using adalimumab. Objective: To describe our experience of using adalimumab in the treatment of cardiac sarcoidosis. Methods: We conducted a retrospective study to evaluate patients with cardiac sarcoidosis who received adalimumab treatment at the University of Illinois Health between 2011 and 2022. The outcome was evaluated by assessing safety, tolerability, and ability to taper systemic corticosteroids therapy following initiation of adalimumab. Results: Seven patients met the inclusion criteria. Clinical responses to adalimumab were universally positive. Corticosteroid therapy was discontinued in five patients and the dose was reduced in two patients. Furthermore, adalimumab was well tolerated, and no adverse events were reported. Conclusion: Adalimumab was safe and well-tolerated in seven patients with cardiac sarcoidosis seen at our medical center and exhibited corticosteroid-sparing effects. Our observation further warrants large prospective studies to evaluate the safety and efficacy of adalimumab in the treatment of cardiac sarcoidosis.

Mycobacterium iranicum pulmonary disease in an elderly patient with extensive usual interstitial pneumonia: Case report.

We report the first case of Mycobacterium iranicum pulmonary disease in an elderly patient with extensive usual interstitial pneumonia and traction bronchiectasis. He was treated with oral doxycycline, ciprofloxacin, and sulfamethoxazole/trimethoprim daily for 9 months. This was associated with eradication of the microorganism in the sputum and steady weight gain.

Surgery for early-stage lung cancer with video-assisted thoracoscopic surgery versus open thoracotomy: A narrative review.

Recommending video-assisted thoracic surgery (VATS) over open thoracotomy to patients with early-stage non-small-cell lung cancer (NSCLC) is controversial. Accordingly, we reviewed randomized comparative studies to determine the risks and benefits of VATS lobectomy. Electronic searches on PubMed with standard search terms revealed 97 comparative studies published between 1990 and 2022. Of those, only 5 were randomized controlled clinical trials (RCT) and 1 is still ongoing although initial data has been published as an abstract form. A total of 918 patients were evaluated in 5 RCT's. All studies included patients with known or suspected primary lung cancer randomized in a 1:1 ratio to VATS or thoracotomy. Between 2 studies, reports of 1-year, 3-year and 5-year overall survival were found to be similar across surgical modalities. Additionally, no differences were found in the rates of locoregional and distant recurrence. Three studies reported no statistical differences in the number of hilar and mediastinal lymph nodes sampled. Two studies found decreased length of stay following VATS (4 days v 5 days, P = 0.027 and P = 0.008), while 2 found no difference. Increased in-hospital complications were seen in 2 studies (P = 0.008 and P = 0.039). VATS was associated with decreased pain scores, better self-reported QOL at 52 weeks (P = 0.014). Few randomized clinical trials comparing VATS lobectomy to open thoracotomy and lobectomy in early stage NSCLC have been reported. These studies suggest that VATS lobectomy offers similar outcomes with decreased in-hospital complications, pain, length of stay, and improved physical functioning when compared to thoracotomy.