Drug-Induced Liver Injury in Hospitalized Patients during SARS-CoV-2 Infection.

In the last few years, the world has had to face the SARS-CoV-2 infection and its multiple effects. Even though COVID-19 was first considered to be a respiratory disease, it has an extended clinical spectrum with symptoms occurring in many tissues, and it is now identified as a systematic disease. Therefore, various drugs are used during the therapy of hospitalized COVID-19 patients. Studies have shown that many of these drugs could have adverse side-effects, including drug-induced liver injury-also known as DILI-which is the focus of our review. Despite the consistent findings, the pathophysiological mechanism behind DILI in COVID-19 disease is still complex, and there are a few risk factors related to it. However, when it comes to the diagnosis, there are specific algorithms (including the RUCAM algorithm) and biomarkers that can assist in identifying DILI and which we will analyze in our review. As indicated by the title, a variety of drugs are associated with this COVID-19-related complication, including systemic corticosteroids, drugs used for the therapy of uncontrolled cytokine storm, as well as antiviral, anti-inflammatory, and anticoagulant drugs. Bearing in mind that hepatotoxicity is very likely to occur during COVID-19, especially in patients treated with multiple medications, we will also refer to the use of other drugs used for DILI therapy in an effort to control and prevent a severe and long-term outcome.

Coagulation Profile of COVID-19 Patients.

Coronavirus disease is a viral infection that can affect multiple systems and be expressed with many-or no-symptoms. The viral infection begins when the virus binds to the host's receptor and from that point on, it is transmitted to the rest of the body, where it causes inflammatory reactions. Among other tissues and systems, SARS-CoV-2 impacts the coagulation system, where it triggers the immunothrombotic response. Its effects are rather intense and can lead to many complications. COVID-19-associated coagulopathy is frequently observed in hospitalized patients, especially ICU patients, and can be proven detrimental. It is usually accompanied by other complications, such as sepsis-induced coagulopathy, disseminated intravascular coagulation and venous thromboembolism. Since all these conditions lead to poor prognosis for severely ill patients, thromboprophylaxis and coagulopathy prognosis are just as important as the therapeutic handling of these patients. Since the beginning of the pandemic, many biomarkers have been considered useful when trying to assess the thrombotic risk of hospitalized patients or evaluate the severity of their situation. At the same time, many drugs have already been tested-while others are still being trialed-in order to find the optimal therapy for each urgent situation.

Hepatic Fibrosis Is a Risk Factor for Greater Severity and Worse Outcome of Acute Ischemic Stroke.

Background: Nonalcoholic fatty liver disease, particularly in the presence of hepatic fibrosis, is associated with an increased risk of cardiovascular events, including ischemic stroke. However, it is unclear whether hepatic fibrosis is associated with the severity and outcome of acute ischemic stroke. Aim: To evaluate the relationship between hepatic fibrosis and the severity at admission and in-hospital outcome of acute ischemic stroke. Patients and methods: We prospectively studied all patients who were admitted to our department with acute ischemic stroke between September 2010 and February 2018 (n = 1107; 42.1% males, age 79.8 ± 7.2 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS ≥ 21. The presence of hepatic fibrosis was evaluated with the Fibrosis-4 index (FIB-4). The outcome was assessed with dependency at discharge (modified Rankin Scale between 2 and 5) and with in-hospital mortality. Results: Patients with severe stroke had a higher FIB-4 index than patients with non-severe stroke (2.7 ± 1.7 and 2.3 ± 1.4, respectively; p < 0.05). Independent risk factors for severe IS were age (relative risk (RR) 1.064, 95% confidence interval (CI) 1.030−1.100, p < 0.001), female sex (RR 1.723, 95% CI 1.100−2.698, p = 0.012), atrial fibrillation (RR 1.869, 95% CI 1.234−2.831, p = 0.002), diastolic blood pressure (DBP) (RR 1.019, 95% CI 1.006−1.033, p = 0.001), and the FIB-4 index (RR 1.130, 95% CI 1.007−1.268, p = 0.022). At discharge, 64.2% of patients were dependent. The FIB-4 index did not differ between patients who were dependent and those who were independent at the time of discharge (2.3 ± 1.5 and 2.1 ± 1.2, respectively; p = 0.061). During hospitalization, 9.8% of patients died. Patients who died during hospitalization had a higher FIB-4 index than those who were discharged (2.9 ± 1.8 and 2.3 ± 1.4, respectively; p < 0.005). Independent risk factors for in-hospital mortality were DBP (RR 1.022, 95% CI 1.010−1.034, p < 0.001), serum glucose levels (RR 1.004, 95% CI 1.001−1.007, p = 0.007), serum triglyceride levels (RR 0.993, 95% CI 0.987−0.999, p = 0.023), NIHSS (RR 1.120, 95% CI 1.092−1.149, p < 0.001), and the FIB-4 index (RR 1.169, 95% CI 1.060−1.289, p = 0.002). Conclusions: Hepatic fibrosis, evaluated with the FIB-4 index, appears to be associated with more severe ischemic stroke and might also represent an independent risk factor for in-hospital mortality in patients admitted with acute ischemic stroke.

Diabetic Patient Adherence to Yearly Influenza Vaccination in Northern Greece.

Background Influenza virus infection is associated with increased morbidity and mortality in patients with diabetes mellitus. Public health authorities recommend yearly vaccination of diabetic patients against seasonal influenza. Methods We surveyed to define the adherence to influenza vaccination and associated factors among diabetic patients in Thessaloniki, Greece. Predictors of adherence to yearly influenza vaccination were assessed with logistic regression models. Results A total of 206 patients were enrolled, with 47.1% reporting yearly vaccination against influenza (95% confidence interval, CI:40.3% to 53.9%). In univariate models, the absence of additional indications for vaccination was associated with a decreased likelihood of vaccination uptake (OR:0.29, 95% CI:0.11 to 0.68, p=0.007); older diabetic patients were more likely to receive influenza vaccination (34% increase per 10 years of age). These associations were attenuated in multivariable analysis. Conclusion Our study demonstrates a significant gap in influenza vaccination coverage rate in diabetic patients. Our data could be extrapolated to enhance the uptake of vaccines against SARS-CoV-2: emphasis should be placed on patient education.

Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience.

Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has driven the largely expanding field of monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), a long-acting antibody combination that inhibits the attachment of the SARS-CoV-2 spike protein to the surface of cells, has proved promising in reducing the incidence of symptomatic COVID-19 or death in high-risk individuals without major adverse events when given as prophylaxis, as well as early treatment. Real-world data confirm the antibody combination's prophylaxis efficacy in lowering the incidence, hospitalization, and mortality associated with COVID-19 in solid organ transplant recipients, patients with immune-mediated inflammatory diseases and hematological malignancies, and patients in B-cell-depleting therapies. Data suggest a difference in neutralization efficiency between the SARS-CoV-2 subtypes in favor of the BA.2 over the BA.1. In treating COVID-19, AZD7442 showed a significant reduction in severe COVID-19 cases and mortality when given early in the course of disease, and within 5 days of symptom onset, without being associated with severe adverse events, even when it is used in addition to standard care. The possibility of the development of spike-protein mutations that resist monoclonal antibodies has been reported; therefore, increased vigilance is required in view of the evolving variants. AZD7442 may be a powerful ally in preventing COVID-19 and the mortality associated with it in high-risk individuals. Further research is required to include more high-risk groups and assess the concerns limiting its use, along the SARS-CoV-2 evolutionary trajectory.

Nonalcoholic fatty liver disease in lean subjects: Prognosis, outcomes and management.

Nonalcoholic fatty liver disease (NAFLD) accounts for most cases of chronic liver disease worldwide, with an estimated global prevalence of approximately 25% and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. NAFLD is strongly connected to metabolic syndrome, and for many years, fatty liver was considered to be an exclusive feature of obese patients. However, recent studies have highlighted the presence of NAFLD in non-obese subjects, with or without increased visceral fat or even in lean subjects without increased waist circumference. "Lean NAFLD" is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology, prognosis and management compared with NAFLD in overweight/obese patients. In the present editorial, we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries. Moreover, we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population. Finally, we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and non-lean cohorts.

Systemic lupus erythematosus in a patient with multiple system atrophy: A case report.

RATIONALE: Multiple system atrophy is a late-onset rare neurodegenerative movement disorder which results in debilitating disease. Fever frequently ensues in the context of infections which can be associated with significant morbidity and mortality, but among alternative diagnostic possibilities neoplasms and autoimmune disorders should be considered. PATIENT CONCERNS: We describe a case of a prolonged febrile syndrome in a 55-year-old female patient with onset of multiple system atrophy two years before presentation. Patient history and symptoms were not contributive to guide the diagnostic work-up. DIAGNOSIS: Initial evaluation provided no specific findings. Repeat testing of auto-antibodies revealed positive antinuclear and anti-ds DNA antibodies coupled with low complement which in conjunction with renal biopsy substantiated the diagnosis of systemic lupus erythematosus flare. INTERVENTION: Pending the biopsy result, treatment with hydroxychloroquine and corticosteroids was initiated. Due to failure to achieve remission, azathioprine was added, but symptoms persisted. Following the diagnosis of lupus nephritis, azathioprine was discontinued and induction treatment with cyclophosphamide in accordance with the Euro-Lupus regimen was initiated and upon completion followed by maintenance therapy with mycophenolate mofetil. OUTCOMES: The patient achieved remission after cyclophosphamide was added to treatment with corticosteroids and has not experienced new flares during the next two years. The neurological syndrome has remained stable during this period. LESSONS: To our knowledge, we report the first case of concurrent systemic lupus erythematosus and multiple system atrophy. Prolonged fever presents unique challenges in patients with rare diseases.

Factors associated with delayed presentation at the emergency department in patients with acute ischemic stroke.

Background and aims: Pre-hospital delay is a crucial factor that determines the eligibility for intravenous thrombolysis in patients with acute ischemic stroke. We aimed to evaluate the time to presentation at the emergency department (ED) and the factors that affect this time. Patients and methods: We prospectively studied 682 patients who were admitted with acute ischemic stroke (43.3% men, age 79.9 ± 6.6 years). Results: The median time to presentation at the ED was 2.1 h (range 0.15 to 168 h); 68.8% of the patients arrived within 4.5 h and 56.5% arrived within 3 h from the onset of symptoms. Independent predictors of presentation within 4.5 h were the use of emergency medical services (EMS) for transportation to the hospital (OR 2.61, 95% CI 1.38-4.94, p = .003), family history of cardiovascular disease (CVD)(OR 4.0 0,95%CI 1.61-12.23, p = .006) and the absence of history of smoking (OR 2.49, 95% CI 1.13-5.42, p = .021). Independent predictors of presentation within 3 h were the use of EMS for transportation to the hospital (OR 6.24, 95% CI 2.52-16.63, p = .0001), family history of CVD (OR 3.07, 95% CI 1.14-9.43, p = .03), and a moderately severe stroke at admission (OR vs. minor stroke 0.38, 95% CI 0.16-0.87, p = .02). Conclusions: A considerable proportion of patients with acute ischemic stroke arrives at the ED after the 4.5-h threshold for performing intravenous thrombolysis. Non-smokers, patients with a family history of CVD, with moderately severe stroke and those who use the EMS are more likely to arrive on time.