Addition of Dulaglutide or Empagliflozin to Standard-of-Care Treatment: Effect on Liver Steatosis in Patients With Type 2 Diabetes Mellitus.

Background Patients with liver steatosis and diabetes mellitus can benefit from medications like glucagon-like peptide 1 receptor agonists or sodium-glucose co-transporter 2 inhibitors, as far as both hyperglycemia and fatty liver are concerned. Studies comparing members of both these families have not yet been published. We aimed to compare the effects of Empagliflozin and Dulaglutide, focusing primarily on liver steatosis. Methodology This prospective, observational, controlled study enrolled 78 patients from two centers in Athens, Greece. Adults with type 2 diabetes mellitus (DM2) and nonalcoholic fatty liver disease were assigned to one of three groups and received either Empagliflozin or Dulaglutide or any other medical treatment deemed appropriate by their physician. The primary endpoint was the reduction in liver fat fraction, assessed using magnetic resonance imaging-proton density fat fraction. Additionally, we evaluated the proportion of patients achieving a relative reduction above 30% of their initial liver fat concentration. Results The Empagliflozin group exhibited a reduction in liver fat fraction. Furthermore, the percentage of patients with a relative reduction of liver steatosis, >30%, was significantly larger in this group, compared to the Dulaglutide and Control groups. Significant body weight reduction was observed in all three groups, but no improvement in fibrosis assessing scores was noted. Conclusions Empagliflozin is effective in improving liver steatosis, while Dulaglutide does not exhibit a similar effect. Larger studies, comparing these or related agents, are necessary, to further assess benefits in patients with DM2 and nonalcoholic fatty liver.

Long-Term Effect on Health-Related Quality of Life in Patients With COVID-19 Requiring Hospitalization Compared to Non-hospitalized COVID-19 Patients and Healthy Controls.

Background In this study, we aimed to evaluate the health-related quality of life (HRQL) in patients with severe coronavirus disease 2019 (COVID-19) six months after their hospitalization and compare it to that of non-hospitalized patients with mild COVID-19 and healthy controls. Methodology Participants were enrolled between September 2021 and April 2022 and included hospitalized COVID-19 patients at General Hospital of Athens "Hippocration" who had been discharged at least six months prior to enrollment, non-hospitalized patients with COVID-19, and healthy controls. Collected data included demographics, disease severity, medication history, and comorbidities. Participants completed a EuroQol 5 Dimensions 5Levels (EQ5D5L), a Short Form 36 version 2 (SF36v2), a Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and a Post-COVID-19 Functional Status Scale (PCFSS) regarding HRQL before and six months after infection with severe acute respiratory syndrome coronavirus 2. In the case of healthy controls, two sets of questionnaires were completed at least six months apart. Statistical analysis was performed using the SPSS version 25 software (IBM Corp., Armonk, NY, USA). Results A total of 151 participants were enrolled. Hospitalized patients with COVID-19 demonstrated a statistically significant deterioration in most parameters of SF36v2 as well as both parameters of the EQ5D5L and FACIT-F questionnaires. Hospitalized patients exhibited worse results in SF36v2 and EQ5D5L when compared to both healthy controls as well as those with mild COVID-19 (p < 0.05). Hospitalized women, in particular, were shown to fare worse than other women in parameters associated with both mental/psychological and physical health (p < 0.05). Hospitalized patients between 41 and 60 years old demonstrated a statistically significant drop in the scores of all three main questionnaires compared to their previous health status (p < 0.05). Hospitalized patients between 61 and 80 years old exhibited a similar trend, but statistical significance was achieved in fewer parameters. HRQL decline was greater in both age groups compared to that of healthy and milder disease counterparts. There was a significant correlation between the results from the three main questionnaires. Similarly, PCFS scale values were shown to correlate with disease severity (hospitalization or not) and age. Conclusions HRQL remained noticeably impacted six months after hospitalization due to COVID-19. The physical and mental/psychological stress of severe COVID-19 translated into lasting health deterioration, especially for women and those aged 41-60 years old. The use of questionnaires, such as those implemented in this study, might help in the early detection of patients who could benefit from rehabilitation programs. Psychological, as well as physical and social, support is crucial to alleviate the burden of post-COVID-19 symptomatology and expedite the recovery of this group of patients.

Pharmacotherapy for Non-alcoholic Fatty Liver Disease Associated with Diabetes Mellitus Type 2.

Non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus type 2 commonly coexist as a manifestation of metabolic syndrome. The presence of diabetes promotes the progression of simple fatty liver to non-alcoholic steatohepatitis (NASH) and cirrhosis, and the presence of NAFLD increases the risk of diabetic complications. This coexistence affects a large part of the population, imposing a great burden on health care systems worldwide. Apart from diet modification and exercise, recent advances in the pharmacotherapy of diabetes offer new prospects regarding liver steatosis and steatohepatitis improvement, enriching the existing algorithm and supporting a multifaceted approach to diabetic patients with fatty liver disease. These agents mainly include members of the families of glucagon-like peptide-1 analogues and the sodium-glucose co-transporter-2 inhibitors. In addition, agents acting on more than one receptor simultaneously are presently under study, in an attempt to further enhance our available options.

Do the Kinetics of Antibody Responses Predict Clinical Outcome in Hospitalized Patients With Moderate-to-Severe COVID-19?

BACKGROUND/AIM: The relationship between the kinetics of antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the severity of Coronavirus Disease 2019 (COVID-19) is poorly understood. The aim of the present study was to investigate whether serum SARS-CoV-2 antibody kinetics serve as an early predictor of clinical deterioration or recovery in hospitalized patients with COVID-19. PATIENTS AND METHODS: In this prospective observational study, 102 consecutive patients (median age: 60 years, 58% males) with symptomatic COVID-19 infection diagnosed by real-time polymerase chain reaction assay, hospitalized in two tertiary hospitals, were included. Rapid test for qualitative detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) SARS-CoV-2 antibodies was performed at pre-defined time intervals during hospitalization (days: 0, 3, 7, 10, 14, 21 and 28). RESULTS: During a 3-month follow-up period after COVID-19 disease onset, a total of 87 patients were discharged, 12 patients were intubated and entered the Intensive Care Unit, and three patients died. The median time for seroconversion was 10 days for IgM and 12 days for IgG post onset of symptoms. Univariate logistic regression analysis found no associations between IgM or IgG positivity and clinical outcomes or complications during hospitalization for COVID-19 infection. Diabetes and dyslipidemia were the only clinical risk factors predictive of COVID-19-related complications during hospitalization. CONCLUSION: SARS-CoV-2 antibody responses do not predict clinical outcome in hospitalized patients with moderate-to-severe COVID-19 infection.

A case of adenoviral covid-19 vector vaccine possibly linked to severe but reversible interstitial lung injury post-vaccination.

BACKGROUND: Several safe and effective vaccines against nCoV-19 have been developed to contain the pandemic with very few severe adverse-reactions reported. Vaccine-induced interstitial lung disease (ILD) is a very rare and difficult to recognise and diagnose adverse-reaction and is mostly associated with Influenza vaccines. METHODS: We report a 55-yr old male who presented with severe respiratory failure that required for several days oxygen supplementation with high flow nasal cannula, and myocardial infarction. Symptoms onset was eighteen days after the first shot of adenoviral AZD1222 vector vaccine. Possible SARS-CoV-2 natural infection post-vaccination was excluded with rigorous laboratory work-up including multiple nasopharengeal rt-qPCR tests for SARS-CoV-2 detection and close monitoring of his serum SARS-CoV-2 antibodies. Other potential infectious agents and alternate diagnoses were thoroughly investigated. RESULTS: Patient responded impressively to high dose steroids. A repeat chest CT nine days after the first one showed a remarkable resolution of the bilateral ground glass opacities. Except for his cardiology medication, no supplemental oxygen neither steroids were prescribed upon his discharge. On one month follow-up, no residual pulmonary dysfunction was noticed with patient preserving a SatO2 of 97-98% on ambient air. CONCLUSION: Vaccine-induced ILD might constitute a rare nCoV-19 post-vaccination adverse-event. According to current restricted data, when post-vaccination ILD is early suspected and recognised, then prompt implementation of steroid treatment reverses significantly the lung lesions without progression to fibrosis.

Liver Ultrasound Attenuation: An Ultrasound Attenuation Index for Liver Steatosis Assessment.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disease type in the Western countries. Ultrasound (US) is used for NAFLD and hepatic steatosis (HS) grading. The most popular US method for NAFLD assessment is the hepatorenal index (HRI), but because of its limitations, other noninvasive methods have been developed. The Resona 7 US system has recently incorporated an US attenuation-related quantitative feature, liver ultrasound attenuation (LiSA), for HS estimation. The purpose of this study is to compare LiSA's and HRI's performance on NAFLD assessment. METHODS: A total of 159 NAFLD patients having a magnetic resonance imaging-proton density fat fraction (MRI-PDFF) examination were examined by 2 radiologists, who performed LiSA and HRI measurements in the liver. Correlation of LiSA's and HRI's measurements with MRI-PDFF values was calculated through Pearson correlation coefficient (PCC). To further investigate the performance of LiSA and HRI, optimum cutoffs, provided by the literature, were used to correspond HS grades to MRI-PDFF results. Moreover, a receiver operating characteristic (ROC) analysis on LiSA measurements and steatosis grades was performed. RESULTS: Magnetic resonance imaging-PDFF was better correlated with LiSA (PCC = 0.80) than HRI (PCC = 0.67). Receiver operating characteristic analysis showed better performance range for LiSA (77.8%-91.8%) than for HRI (72.8%-85.4%) on all HS grades for all studies used for corresponding MRI-PDFF values to HS grades. CONCLUSIONS: The results indicate that LiSA is more accurate than HRI in HS differentiation and can lead to more accurate grading of HS on NAFLD patients.

Real-Life Effectiveness and Safety of Baricitinib as Adjunctive to Standard-of-Care Treatment in Hospitalized Patients With Severe Coronavirus Disease 2019.

BACKGROUND: Therapeutic options for hospitalized patients with severe coronavirus disease 2019 (sCOVID-19) are limited. Preliminary data have shown promising results with baricitinib, but real-life experience is lacking. We assessed the safety and effectiveness of add-on baricitinib to standard-of-care (SOC) including dexamethasone in hospitalized patients with sCOVID-19. METHODS: This study is a 2-center, observational, retrospective cohort study of patients with sCOVID-19, comparing outcomes and serious events between patients treated with SOC versus those treated with SOC and baricitinib combination. RESULTS: We included 369 patients with sCOVID-19 (males 66.1%; mean age 65.2 years; median symptom duration 6 days). The SOC was administered in 47.7% and combination in 52.3%. Patients treated with the combination reached the composite outcome (intensive care unit [ICU] admission or death) less frequently compared with SOC (22.3% vs 36.9%, P = .002). Mortality rate was lower with the combination in the total cohort (14.7% vs 26.6%, P = .005), and ICU admission was lower in patients with severe acute respiratory distress syndrome (29.7% vs 44.8%, P = .03). By multivariable analysis, age (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.36-2.44, per 10-year increase), partial pressure of oxygen/fraction of inspired oxygen ratio (OR = 0.60, 95% CI = .52-0.68, per 10 units increase), and use of high-flow nasal cannula (OR = 0.34; 95% CI, .16-0.74) were associated with the composite outcome, whereas baricitinib use was marginally not associated with the composite outcome (OR = 0.52; 95% CI, .26-1.03). However, baricitinib use was found to be significant after inverse-probability weighted regression (OR = 0.93; 95% CI, .87-0.99). No difference in serious events was noted between treatment groups. CONCLUSIONS: In real-life settings, addition of baricitinib to SOC in patients hospitalized with sCOVID-19 is associated with decreased mortality without concerning safety signals.

Fatty liver index and hypertension-mediated organ damage in never-treated hypertensive patients without diabetes mellitus.

BACKGROUND: We investigated whether fatty liver index (FLI), a surrogate marker of nonalcoholic fatty liver disease (NAFLD), is associated with hypertension-mediated organ damage (HMOD) in never-treated hypertensive patients without diabetes mellitus. METHODS: We performed both clinic and ambulatory blood pressure (BP) measurements, and calculated the FLI for all participants. A FLI of no less than 60 indicates a high-risk of underlying NAFLD, whereas a FLI of less than 60 indicates lower risk. We evaluated left ventricular mass (LVM) by echocardiography, arterial stiffness by carotid--femoral pulse wave velocity (PWV), capillary rarefaction by nailfold capillaroscopy, as well as urinary albumin-to-creatinine ratio (ACR). HMOD was defined according to the categorical thresholds for each domain, except for capillary rarefaction in which case the categorization of patients was made by the median. RESULTS: We included 146 hypertensive patients (men, 43.8%; mean age, 56.6 ±â€Š10.8 years; BMI, 30.3 ±â€Š4.9 kg/m2; FLI, 57.2 ±â€Š27.7; office, systolic/diastolic, and 24-h BP, 153.5 ±â€Š15.8/94.7 ±â€Š9.8 mmHg, and 140.5 ±â€Š9.9/83.8 ±â€Š9 mmHg, respectively). Patients with FLI at least 60 (n = 76) were younger, with higher BMI and 24-h SBP, compared with patients with FLI less than 60 (n = 70). FLI was associated with HMOD after adjustment (LVM indexed to height, P = 0.004; PWV, P = 0.047; reduced capillary density, P = 0.001; and logACR, P = 0.003). High-risk FLI phenotype and FLI z scores increased the likelihood of any HMOD by 3.8 (95% confidence interval, 1.6-7.1) and 5.4 (95% confidence interval, 2.3-15.0) times, respectively. However, the increased number of HMOD domains has progressively stopped being determined by the FLI z scores (P = 0.65). CONCLUSION: High-risk FLI pattern was associated with various HMOD, and may re-classify never-treated hypertensive patients without diabetes mellitus into a higher cardiovascular risk level.

Wilson disease: 30-year data on epidemiology, clinical presentation, treatment modalities and disease outcomes from two tertiary Greek centers.

OBJECTIVE: Wilson disease is a rare genetic disorder of copper metabolism with a wide range of clinical presentations. The aim of this study is to describe the 30-year clinical experience in the management of Wilson disease patients followed at two Greek referral centers. METHODS: A retrospective chart review was performed to identify past and present Wilson disease patients diagnosed during the last 30 years. RESULTS: Sixty-three patients were included. The median age of diagnosis was 19 (3-59) years, while nine (14%) patients were older than 40 years old. Clinical presentation included asymptomatic liver disease (57.1%), neurological disease (20.6%), overt liver disease (12.7%), acute liver failure (6.3%) and other (3.2%). Kayser-Fleischer rings were detected in 27/62 with a higher frequency in neurologic patients (P < 0.001). Ceruloplasmin values were low in 55/63 with significantly lower values in patients with neurological disease (P = 0.048) and in cirrhotic patients (P = 0.017). Increased 24-hour urine copper was measured in 59/63 patients. D-penicillamine was administered in 56/63 patients (88.8%), followed by trientine (6/63, 9.5%), while one patient needed liver transplantation at baseline. At least one treatment switch was performed in 18 patients. By the end of follow-up, all non-cirrhotic patients (25/25) were stable, 3/23 (13%) cirrhotic developed decompensated liver disease, two developed HCC, three received a liver transplant and two died. Five out of 13 neurologic patients had persisting symptoms despite treatment. CONCLUSION: Wilson disease presents with a wide spectrum of clinical manifestations and should be investigated even in older patients, as early diagnosis, close follow-up and treatment monitoring usually provide favorable outcomes.