Metformin as adjuvant treatment in hepatitis C virus infections and associated complications.

Hepatitis C virus is an important global cause of hepatitis and subsequently cirrhosis and hepatocellular carcinoma. These infections may also cause extrahepatic manifestations, including insulin resistance and type 2 diabetes mellitus. These two complications can potentially reduce sustained virologic responses (SVR) in some drug regimens for this infection. Metformin has important biochemical effects that can limit viral replication in cellular cultures and can improve the response to antiviral drug therapy based on ribavirin and interferon. Clinical studies comparing treatment regimens with interferon, ribavirin, metformin with these regimens without metformin have demonstrated that metformin increases viral clearance, establishes higher rates of SVRs, and increases insulin sensitivity. Metformin also reduces the frequency of hepatocellular carcinoma in patients who have had SVRs. Larger treatment trials are needed to determine metformin's short-term and long-term treatment effects in patients with diabetes using newer antiviral drugs. In particular, if metformin reduces the frequency of cirrhosis and hepatocellular carcinoma, this would significantly reduce the morbidity and mortality associated with this infection.

Cardiac Muscle Injury and Echocardiographic Plus Electrocardiographic Findings in Patients With 2019 Novel Coronavirus (COVID-19): A Retrospective Cohort Study.

Background: Myocardial injury has been described in coronavirus-2019 (COVID-19). Few studies have reported cardiovascular imaging data with transthoracic echocardiography (TTE) and electrocardiography (ECG) findings in COVID-19 patients, and their correlation with mortality. Methods: We conducted a retrospective cohort study that included COVID-19 patients from March 2020 through February 2021 who had TTE and ECG during hospital admission. Myocardial injury was defined by an elevated high-sensitivity troponin T level > 20 ng/L. Bivariate analysis was used to compare patients with myocardial injury and those without. Multivariate logistic regression analysis was performed to identify the variables associated with mortality. Results: A total of 438 patients were included. The mean age was 62.1 ± 14.9 years, and 58.9% were male. A total of 149 patients died, with a mortality rate of 34%. A total of 260 patients (59.4%) had myocardial injury. The average left ventricular ejection fraction was 59.8% ± 11.2%, with 30 patients (6.8%) having an ejection fraction of < 40%. Patients with myocardial injury had higher mortality than those without (P < 0.05, χ2 test). A multiple regression analysis model indicated that age, race and/or ethnicity, the development of acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the variables significantly associated with mortality. Conclusion: COVID-19 patients with myocardial injury had higher mortality than those without. Age, race and/or ethnicity, acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the clinical variables associated with mortality. The TEE and ECG variables studied were not significantly associated with mortality.

Contexte: Des atteintes myocardiques ont été décrites en présence d'une infection par le coronavirus 2019 (COVID-19). Quelques études ont rapporté des données d'imagerie cardiovasculaire obtenues par échocardiographie transthoracique (ETT) et électrocardiographie (ECG) chez des patients atteints de la COVID-19, et leur corrélation avec la mortalité. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant des patients atteints de la COVID-19 entre mars 2020 et février 2021 qui ont été soumis à une ETT ou à une ECG pendant leur hospitalisation. L'atteinte myocardique était définie comme un taux élevé de troponine T de haute sensibilité > 20 ng/L. Une analyse à deux variables a été utilisée pour comparer les patients présentant une atteinte myocardique et ceux qui n'en présentaient pas. Une analyse de régression logistique à multiples variables a été menée pour définir les variables qui étaient associées à la mortalité. Résultats: L'étude comptait un total de 438 patients. L'âge moyen était de 62,1 ± 14,9 ans; 58,9 % étaient des hommes. Un total de 149 patients sont décédés, soit un taux de mortalité de 34 %. Un total de 260 patients (59,4 %) présentaient une atteinte myocardique. La fraction d'éjection ventriculaire gauche moyenne était de 59,8 % ± 11,2 %, alors que 30 patients (6,8 %) affichaient une fraction d'éjection inférieure à 40 %. Le taux de mortalité était plus élevé chez les patients qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas (p < 0,05, test χ2). Selon un modèle d'analyse de régression multiple, l'âge, la race et/ou l'ethnicité, l'apparition du syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables fortement liées à la mortalité. Conclusion: Parmi les patients atteints de la COVID-19, la mortalité était plus élevée chez ceux qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas. L'âge, la race et/ou l'ethnicité, le syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables cliniques liées à la mortalité. Les variables d'ETT et d'ECG étudiées n'avaient pas de lien important avec la mortalité.

An analysis of retracted COVID-19 articles published by one medical publisher with multiple journals.

Background: The retraction of medical articles periodically occurs in most medical journals and can involve multiple article types. These retractions are beneficial if they remove flawed or fraudulent information from the medical literature. However, retractions may also decrease confidence in the medical literature and require significant amounts of time by editors. Methods: One publisher (Hindawi) announced that it will retract over 1200 articles. Given this, the PubMed database was searched to identify retracted publications on or related to COVID-19, and articles retracted by journals sponsored by the publisher Hindawi were then identified. Results: These journals retracted 25 articles and, in most cases, did not provide an exact explanation about the particular problem(s) resulting in the retraction. The time to retraction was 468.7 ± 109.8 days (median = 446 days). These articles had 9.3 ± 9.9 citations. Conclusion: Analysis of the titles and abstracts of the articles suggests that their removal from the medical literature would have limited effects on the near-term management decisions during the COVID-19 pandemic. Nevertheless, retraction of medical articles creates uncertainty in medical care and science and in the public regarding the validity of medical research and related publications and the level of professionalism of the individuals submitting these articles.

Peer Review and Medical Journals.

Journal editors depend on peer reviewers to make decisions about submitted manuscripts. These reviewers help evaluate the methods, the results, the discussion of the results, and the overall organization and presentation of the manuscript. In addition, reviewers can help identify important mistakes and possible misconduct. Editors frequently have difficulty obtaining enough peer reviews which are submitted in a timely manner. This increases the workload of editors and journal managers and potentially delays the publication of clinical and research studies. This commentary discusses of the importance of peer reviews and make suggestions which potentially can increase the participation of academic faculty and researchers in this important activity.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Cardiopulmonary Exercise Testing in Heart Failure.

Cardiopulmonary exercise testing (CPET) provides important information for the assessment and management of patients with heart failure. This testing measures the respiratory and cardiac responses to exercise and allows measurement of the oxygen uptake (V˙O2) max and the relationship between minute ventilation (V˙E) and carbon dioxide excretion (V˙CO2). These two parameters help classify patients into categories that help predict prognosis, and patients with a V˙O2 < 14 mL/kg/min and V˙E/V˙CO2 slope >35 have a poor prognosis. This testing has been used in drug trials to determine complex physiologic responses to medications, such as angiotensin-converting enzyme inhibitors. For example, a study with enalapril demonstrated that the peak V˙O2 was 14.6 ± 1.6 mL/kg/min on placebo and 15.8 ± 2.0 mL/kg/min on enalapril after 15 days of treatment. The V˙E/V˙CO2 slopes were 43 ± 8 on placebo and 39 ± 7 on enalapril. Chronic heart failure and reduced physical activity measured by cardiopulmonary exercise testing are associated with increases in BNP, and several studies have demonstrated that cardiac rehabilitation is associated with reductions in BNP and increases in V˙O2. Therefore, BNP measurements can help determine the benefits of cardiac rehabilitation and provide indirect estimates of changes in V˙O2. In addition, measurement of microRNAs can determine the status of skeletal muscle used during physical activity and the changes associated with rehabilitation. However, CPET requires complicated technology, and simpler methods to measure physical activity could help clinicians to manage their patients. Recent advances in technology have led to the development of portable cardiopulmonary exercise testing equipment, which can be used in various routine physical activities, such as walking upstairs, sweeping the floor, and making the bed, to provide patients and clinicians a better understanding of the patient's current symptoms. Finally, current smart watches can provide important information about the cardiorespiratory system, identify unexpected clinical problems, and help monitor the response to treatment. The organized use of these devices could contribute to the management of certain aspects of these patients' care, such as monitoring the treatment of atrial fibrillation. This review article provides a comprehensive overview of the current use of CPET in heart failure patients and discusses exercise principles, methods, clinical applications, and prognostic implications.

The Association and Utility of Left Ventricular End-Diastolic Pressure in Predicting the Development of and in Managing Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography.

Contrast-induced nephropathy (CIN) is a significant complication in patients undergoing coronary angiography, and its development is associated with increased morbidity and mortality. Left ventricular end-diastolic pressure (LVEDP) provides one index of left heart filling status. An elevated LVEDP can reflect volume overload or abnormal diastolic function and indicates a cardiac disorder. Data on the association between an elevated LVEDP and CIN are limited and have had conflicting results. We systematically searched the databases PubMed, Embase, and Scopus for full-text articles from database inception to May 2022. Studies were included if they evaluated the association between a high LVEDP and the incidence of CIN in patients undergoing coronary angiography. The study was registered in the PROSPERO CRD42022334070. A second search in PubMed identified randomized controlled trials using LVEDP to guide fluid administration during coronary procedures. Four studies were identified that used LVEDP to classify patients into groups to determine the association between the level and the development of CIN. In these studies, 240 patients of 2441 patients (9.8%) developed CIN. One study found no association between LVEDP levels and the development of CIN. Two studies found an increased frequency of CIN in patients with elevated levels using 2 cutoff points for LVEDP, ≥20 mm Hg and >30 mm Hg. One study found that lower LVEDP levels (5-14 mm Hg) were associated with the development of CIN. Three randomized control trials used LVDEP levels to manage fluid administration in patients undergoing coronary procedures; only one study found that the use of these levels to guide fluid administration resulted in better outcomes. In patients undergoing coronary angiography, an elevated LVEDP was not consistently associated with increased risk of CIN, and using LVEDP levels to guide fluid administration during these procedures did not always improve outcomes in comparison to other protocols. The use of LVEDP levels can help classify patients with cardiac disorders but does not necessarily provide an adequate description of the hemodynamic patterns in these patients to predict or prevent CIN in patients undergoing angiography.

Metformin has immunomodulatory effects which support its potential use as adjunctive therapy in tuberculosis.

Metformin is the preferred oral medication for patients with type 2 diabetes mellitus, and this blood glucose-lowering and insulin-sensitizing drug has immunomodulatory effects that could contribute to the management of patients with various other autoimmune and infectious diseases. Tuberculosis is one such infection, and it remains prevalent worldwide, largely due to the successful evasion of the host's immune responses by the infecting pathogen, Mycobacterium tuberculosis. This review focuses on the possible mechanisms relevant to metformin's modulation of innate and adaptive immune responses to Mycobacterium tuberculosis and its potential use as an adjunctive drug in the treatment of tuberculosis. Current data suggest that metformin increases autophagy, phagocytosis, and mitochondrial reactive oxygen species production, while limiting excess inflammation and tissue destruction. This multifaceted drug also augments cell-mediated immune responses by maintaining CD8+ T cell metabolic homeostasis and improving immunological memory. Several murine models have demonstrated that metformin can reduce tuberculosis severity and tissue pathology, and two in vitro human studies confirmed enhanced immune responses in metformin-treated cells. These studies provide convincing evidence supporting the use of metformin to augment immune responses in patients with tuberculosis.

Esophageal Stent in Acute Refractory Variceal Bleeding: A Systematic Review and a Meta-Analysis.

Background: Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal bleeding have refractory bleeding that is not controlled by medical or endoscopic therapy, and this condition can be life-threatening. Balloon tamponade is a long-standing therapy which is only effective temporarily and has several complications, while transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation may not be readily available at some centers. The use of self-expandable metal stents (SEMSs) in refractory esophageal variceal bleeding has been studied for effectiveness and adverse events and has been recommended for use as a bridge to a more definitive treatment. Aim: To investigate the effectiveness and safety of SEMSs in managing refractory variceal bleeding. Methods: A systematic search of the MEDLINE, EMBASE, and Cochrane library databases was performed from inception to October 2022 using the following terms: "esophageal stent", "self-expandable metal stents", "endoscopic hemostasis", "refractory esophageal varices", and "esophageal variceal bleeding". Studies were included in the meta-analysis if they met the following criteria: (1) patients' age older than 18 and (2) a study (or case series) that has at least 10 patients in the study. Exclusion criteria included (1) non-English publications, (2) in case of overlapping cohorts, data from the most recent and/or most appropriate comprehensive report were collected. DerSimonian-Laird random-effects meta-analysis was performed using the meta package in R statistical software(version 4.2.2). Results: Twelve studies involving 225 patients with 228 stents were included in the analyses. The mean age and/or median age ranged from 49.4 to 69 years, with a male-to-female ratio of 4.4 to 1. The median follow-up period was 42 days. The mean SEMS dwell time was 9.4 days. The most common cause of acute refractory variceal bleeding in chronic liver disease patients included alcohol use followed by viral hepatitis. The pooled rate of immediate bleeding control was 91% (95% CI 82-95%, I2 = 0). The pooled rate of rebleeding was 17% (95% CI 8-32%, I2 = 69). The pooled rate of stent ulceration was 7% (95% CI 3-13%, I2 = 0), and the pooled rate of stent migration was 18% (95% CI 9-32%, I2 = 38). The pooled rate of all-cause mortality was 38% (95% CI 30-47%, I2 = 34). Conclusions: SEMSs should be primarily considered as salvage therapy when endoscopic band ligation and sclerotherapy fail and can be used as a bridge to emergent TIPS or definitive therapy, such as liver transplantation.

Periodic generalized edema following COVID-19 infection.

The unprecedented impact and sequelae of COVID-19 infection are not yet fully understood, and better understanding of the pathophysiology of these infections is needed. Endothelial dysfunction might be common sequelae associated with COVID-19, and increased inflammatory responses, oxidative stress, proinflammatory cytokines, and impaired mitochondrial function also contribute to the pathophysiology of post COVID-19 medical disorders. Systemic capillary leak syndrome following COVID-19 infection, both new onset and exacerbation of a prior disorder, has been reported. The pathophysiology of SCLS is uncertain; it likely develops during transient vascular endothelial dysfunction or endotheliopathy and inflammation resulting from circulating humoral factors. Here, we report a case of adult patient with 2 episodes of systemic capillary leak syndrome following prior COVID-19 infection. This patient had a transient response to intravenous IgG.

Prolonged cough and dyspnea following a single episode of intense silica exposure.

Long term exposure to silica at worksites can cause silicosis. This typically has two radiographic forms, simple silicosis and complicated or conglomerate silicosis. Patients with acute silicosis have rapid progression of disease with fulminant respiratory failure over months rather than years. The patient described in this case report had a one-time 4 to 5-h exposure to silica and sand dust at work when his mask malfunctioned. He developed cough and shortness of breath. During his initial clinic visit he had significant cough. His chest examination was clear without crackles or wheezes. His pulmonary function tests were within normal limits. His chest x-ray was clear. Both symptoms, especially the cough, persisted over the next 6+ months even after treatment with oral corticosteroids and inhaled corticosteroids and long-acting beta agonists. Consequently, this patient developed severe cough following a one-time exposure to silica particulates. Laboratory studies have demonstrated that silica exposure can cause reactive oxygen species which potentially could have activated transient receptor potential vanilloid 1 channels in the afferent sensory nerves in his bronchial epithelium. This could cause sustained cough for more than 6 months. His symptoms improved but did not resolve with corticosteroid treatment. Therefore, this case demonstrates that acute silica exposure can cause sustained airway symptoms in healthy workers.

Neutrophil bactericidal activity and host defenses in cystic fibrosis: a narrative review.

Background and Objective: Cystic fibrosis (CF) is a disorder that affects the cystic fibrosis transmembrane conductance regulator (CFTR). Without properly functioning CFTR channels, chloride does not exit respiratory epithelial cells, and consequently the mucus lining the surface of the cells becomes thick. This viscous mucus accumulates and causes abnormal function of the mucociliary apparatus, which can lead to bacterial colonization, infections with Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), and eventually lung damage. Recent studies have shown that the increased susceptibility to respiratory infections in CF patients may also be due to defects in neutrophil function, but the exact mechanism is uncertain. Methods: The PubMed database was searched on February 10, 2023 and again on July 23, 2023 to compile a comprehensive list of clinical and experimental studies to evaluate neutrophil function in CF. The first search included a combination of MeSH terms: "cystic fibrosis" and "neutrophils/physiology". A separate second search included a combination of the MeSH terms: "neutrophils" and "cystic fibrosis transmembrane conductance regulator". Key Content and Findings: Neutrophils from patients with CF have decreased transfer of chloride into phagolysosomes after bacterial ingestion and have dysregulated degranulation. This reduces the production of toxic oxidative radicals, especially hypochlorous acid (HOCl), and reduces bactericidal activity. CFTR potentiators correct the dysregulated degranulation in patients with CF and increased neutrophil killing activity. A reduced concentration of chloride in in vitro assays also reduces neutrophil killing activity; these observations are relevant to the reduced chloride concentrations in respiratory secretions in patients with CF. Conclusions: This literature review summarizes studies that demonstrate that an important defect in CF neutrophils lies in the oxygen-dependent pathway in phagolysosomes and studies with ivacaftor demonstrate that this drug corrects CF neutrophil function. These studies demonstrate the potential utility of using easily available neutrophils to study drug effects in CF patients.

Clinical significance of BPI-ANCA in patients with cystic fibrosis: a single center prospective study.

Recurrent pulmonary exacerbation due to infection and inflammation remain the major cause of mortality and morbidity in patients with cystic fibrosis (CF). Increased levels of BPI-ANCA have been linked to Pseudomonas colonization and pulmonary exacerbations in patients with CF. The majority of these studies were done in Europe, and it is unclear whether similar findings are true in CF patients who lives in United States. In our single center study of 47 patients with CF, the prevalence of BPI-ANCA was 19% at baseline and 15% at annual follow-up visit. Overall, there were no statistical differences noted in FEV1 and frequency of pulmonary exacerbations in CF patients who were positive for BPI-ANCA compared to those who were negative for BPI-ANCA. The role of BPI-ANCA in patients with CF still remains unclear.

The Utility of Fecal Calprotectin in the Diagnosis and Management of Microscopic Colitis.

Background: The incidence of microscopic colitis has increased over time. To date, there is no specific biomarker for microscopic colitis, and the diagnosis relies on histopathological tissue obtained during colonoscopy which is an invasive and costly procedure. Unlike Crohn's disease and ulcerative colitis, the utility of fecal calprotectin in diagnosing or monitoring microscopic colitis has not been established, and studies on the role of fecal calprotectin in microscopic colitis are limited. In this retrospective study, we analyzed the utility of this biomarker in the diagnosis of microscopic colitis. Methods: The medical records of patients who have been diagnosed with collagenous colitis and lymphocytic colitis aged 18-89 years old were retrospectively reviewed. Patient characteristics were recorded in those who had fecal calprotectin measured. Results: There were 198 patients who were diagnosed with collagenous colitis and lymphocytic between October 1, 2015, and July 31, 2022. Twenty-three patients had fecal calprotectin levels measured and were included in this study. The mean age was 51.7 ± 7.8 years in all groups. Thirteen patients were female. Six patients (26.1%) were diagnosed with collagenous colitis, and 17 patients (73.9%) were diagnosed with lymphocytic colitis. The fecal calprotectin cut-off in this lab is 50 µg/g stool. Median fecal calprotectin levels were 30.1 µg/g (15.6, 122.5), 19.5 µg/g (16.5, 64.6), and 33.2 µg/g (15.6, 134.9) in all groups, collagenous colitis, and lymphocytic colitis, respectively. Conclusion: The utility of fecal calprotectin in diagnosing microscopic colitis is limited. Our study suggests the diagnosis should be based on histopathology tissue obtained during colonoscopy.

Severe Acute Respiratory Distress Syndrome Secondary to Concomitant Influenza A and Rhinovirus Infection Complicated by Methicillin-resistant Staphylococcus aureus Pneumonia in an Early Pregnancy Patient With Vaping-induced Lung Injury.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury characterized by rapid onset of widespread inflammation in the lungs. Multiple risk factors, including pneumonia, non-pulmonary sepsis, aspiration of gastric contents or inhalation injury, have been reported, to cause ARDS. We present a case of a healthy young woman in her first trimester with vaping-induced lung injury who presented with spontaneous pneumothorax and acute respiratory distress syndrome with concomitant influenza A and rhinovirus infection followed by methicillin-resistant Staphylococcus aureus pneumonia.

Eosinophilia with Lung Involvement in an Elderly Patient with a History of Chronic Obstructive Pulmonary Disease.

Eosinophilia with pulmonary involvement is characterized by the presence of peripheral blood eosinophilia, typically >500 cells/mm3, nonspecific pulmonary symptoms, and radiographic evidence of pulmonary disease. Clinical, laboratory, and radiologic features can be overlapping in these diseases, thus, it is wise to approach eosinophilia with pulmonary involvement systematically to determine the diagnosis and provide definitive treatment for a better outcome. The authors present a case of idiopathic chronic eosinophilic pneumonia in a patient with a long history of chronic obstructive pulmonary disease (COPD) which was resolved by corticosteroid.