Steatotic Liver Disease and Sepsis Outcomes-A Prospective Cohort Study (SepsisFAT).

Background: While it has been shown that steatotic liver disease (SLD) is associated with systemic changes in immune response, the impact of SLD on sepsis outcomes has not yet been established. The aim of this study was to investigate the association between SLD and sepsis severity and outcomes. Methods: A prospective observational study included consecutively hospitalized adult patients with community-acquired sepsis during a 16-month period. Results: Of the 378 included patients (49.5% male, median age of 69, IQR 57-78 years), 174 (46%) were diagnosed with SLD. Patients with SLD were older and more frequently fulfilled the criteria for metabolic syndrome. There were no differences in the source and etiology of sepsis between the groups. Patients with SLD exhibited a higher incidence of acute kidney injury (29.3% vs. 17.6%), the need for renal replacement therapy (16.1% vs. 8.8%), and more frequent use of invasive mechanical ventilation (29.3% vs. 18.1%). In-hospital mortality was significantly higher in the SLD group (18.39% vs. 9.8%). The multivariable analysis indicated that SLD was associated with mortality (HR 2.82, 95% CI 1.40-5.71) irrespective of the other elements within metabolic syndrome. Conclusions: SLD might be associated with higher sepsis in-hospital mortality, and more frequent development of acute kidney and respiratory insufficiency requiring more critical care support.

Incidence, risk factors, and clinical findings of syphilis among men living with HIV in Croatia during the COVID-19 pandemic.

We conducted a nationwide longitudinal observational study to estimate the incidence of syphilis in a cohort of male persons living with HIV (MLWH) in Croatia in the pre-COVID-19 and COVID-19 years. Data were reviewed and extracted from the clinical database. We analyzed 1187 MLWH (≥ 18 years) in care in Croatia from 2018 to 2021 and used Poisson regression to calculate rates. We observed a 91.4% increase in incidence between 2019 and 2020; the overall rate was 6.0/100 person-years, and the annual rate ranged from 3.3/100 person-years in 2018 to 9.3/100 person-years in 2021. We found higher rates in men who have sex with men, MLWH with a baseline history of syphilis, MLWH with a more recent HIV diagnosis, and a lower rate in those who had clinical AIDS. The rate of syphilis serological testing was 3.5% lower in 2020 compared to 2019. Recurrent syphilis was more likely asymptomatic compared to the first episodes. In conclusion, during the COVID-19 epidemic years, there was a huge increase in syphilis. Results highlight the need for enhanced and novel prevention interventions.

TGF Beta as a Prognostic Biomarker of COVID-19 Severity in Patients with NAFLD-A Prospective Case-Control Study.

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in Western countries, has been identified as a possible risk factor for COVID-19 severity. However, the immunological mechanisms by which NAFLD exacerbates COVID-19 remain unknown. Transforming growth factor-beta 1 (TGF-ß1) has an important immunomodulatory and pro-fibrotic role, which has already been described in NAFLD. However, the role of TGF-ß1 in COVID-19 remains unclear, and could also be the pathophysiology link between these two conditions. The aim of this case-control study was to analyze the expression of TGF-ß1 in COVID-19 patients depending on the presence of NAFLD and COVID-19 severity. Serum TGF-ß1 concentrations were measured in 60 hospitalized COVID-19 patients (30 with NAFLD). NAFLD was associated with higher serum TGF-ß1 concentrations that increased with disease severity. Admission TGF-ß1 concentrations showed good discriminative accuracy in predicting the development of critical disease and COVID-19 complications (need for advanced respiratory support, ICU admission, time to recovery, development of nosocomial infections and mortality). In conclusion, TGF-ß1 could be an efficient biomarker for predicting COVID-19 severity and adverse outcomes in patients with NAFLD.

Distinct Cytokine Profiles in Severe COVID-19 and Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles in patients with severe COVID-19 and NAFLD. A total of 94 patients with severe COVID-19 were included. Upon admission, clinical and laboratory data were collected, a liver ultrasound was performed to determine the presence of steatosis, and subsequently, 51 were diagnosed with NAFLD according to the current guidelines. There were no differences in age, sex, comorbidities, and baseline disease severity between the groups. Serum cytokine concentrations were analyzed using a multiplex bead-based assay by flow cytometry. Upon admission, the NAFLD group had higher C-reactive protein, procalcitonin, alanine aminotransferase, lactate dehydrogenase, and fibrinogen. Interleukins-6, -8, and -10 and CXCL10 were significantly higher, while IFN-γ was lower in NAFLD patients. Patients with NAFLD who progressed to critical illness had higher concentrations of IL-6, -8, -10, and IFN-ß, and IL-8 and IL-10 appear to be effective prognostic biomarkers associated with time to recovery. In conclusion, NAFLD is associated with distinct cytokine profiles in COVID-19, possibly associated with disease severity and adverse outcomes.

Association of Nonalcoholic Fatty Liver Disease With COVID-19 Severity and Pulmonary Thrombosis: CovidFAT, a Prospective, Observational Cohort Study.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease associated with systemic changes in immune response, which might be associated with coronavirus disease 2019 (COVID-19) severity. The aim of this study was to investigate the impact of NAFLD on COVID-19 severity and outcomes. Methods: A prospective observational study included consecutively hospitalized adult patients, hospitalized between March and June 2021, with severe COVID-19. Patients were screened for fatty liver by ultrasound and subsequently diagnosed with NAFLD. Patients were daily followed until discharge, and demographic, clinical, and laboratory data were collected and correlated to clinical outcomes. Results: Of the 216 patients included, 120 (55.5%) had NAFLD. The NAFLD group had higher C-reactive protein (interquartile range [IQR]) (84.7 [38.6-129.8] mg/L vs 66.9 [32.2-97.3] mg/L; P = .0340), interleukin-6 (49.19 [22.66-92.04] ng/L vs 13.22 [5.29-39.75] ng/L; P < .0001), aspartate aminotransferase (58 [40-81] IU/L vs 46 [29-82] IU/L; P = .0123), alanine aminotransferase (51 [32-73] IU/L vs 40 [23-69] IU/L; P = .0345), and lactate dehydrogenase (391 [285-483] IU/L vs 324 [247-411] IU/L; P = .0027). The patients with NAFLD had higher disease severity assessed by 7-category ordinal scale, more frequently required high-flow nasal cannula or noninvasive ventilation (26, 21.66%, vs 10, 10.42%; P = .0289), had longer duration of hospitalization (IQR) (10 [8-15] days vs 9 [6-12] days; P = .0018), and more frequently had pulmonary thromboembolism (26.66% vs 13.54%; P = .0191). On multivariable analyses, NAFLD was negatively associated with time to recovery (hazard ratio, 0.64; 95% CI, 0.48 to 0.86) and was identified as a risk factor for pulmonary thrombosis (odds ratio, 2.15; 95% CI, 1.04 to 4.46). Conclusions: NAFLD is associated with higher COVID-19 severity, more adverse outcomes, and more frequent pulmonary thrombosis.

Structural changes in the rat placenta during the last third of gestation discovered by stereology.

Structural changes in the rat placenta during the last third of gestation were for the first time assessed by stereology. Fischer female rats were euthanized on the day 16 or day 19 of gestation, and 35 placentas were collected. Three randomly selected placentas from each group were stereologically analyzed for the absolute volume. The proportion of the glycogenic cells and the trophoblast giant cells (TGC) in the basal part of the placenta was calculated using volume density. The absolute volume of the rat placenta on the day 16 of gestation was determined as 0.0638 cm3. The labyrinth comprised 0.0274 cm3, the basal plate 0.0271 cm3 and the decidua 0.0093 cm3. On the day 19 of gestation, the absolute volume of the placenta was 0.1627 cm3, the labyrinth occupied 0.0922 cm3, the basal plate 0.0596 cm3 and the decidua 0.0109 cm3. The volume density of trophoblast giant cells was 0.174 cm0 on the day 16 and 0.107 cm0 on the day 19 of gestation. The glycogenic cells comprised 0.379 percentage of the basal plate on the day 16 and 0.236 on the day 19 of gestation. We conclude that the absolute volume of the whole placenta and the labyrinth has increased from day 16 to the day 19 of gestation. In contrast, the volume density of glycogenic cells and trophoblast giant cells was higher on the day 16 than on the day 19 of gestation, probably due to the intensive trophoblast invasion during that time.

Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain.

The nucleolar protein 2 gene encodes a protein specific for the nucleolus. It is assumed that it plays a role in the synthesis of ribosomes and regulation of the cell cycle. Due to its link to cell proliferation, higher expression of Nop2 indicates a worse tumor prognosis. In this work we used Nop2(gt1gaj) gene trap mouse strain. While lethality of homozygous animals suggested a vital role of this gene, heterozygous animals allowed the detection of expression of Nop2 in various tissues, including mouse brain. Histochemistry, immunohistochemistry and immunoelectron microscopy techniques, applied to a mature mouse brain, human brain and on mouse neural stem cells revealed expression of Nop2 in differentiating cells, including astrocytes, as well as in mature neurons. Nop2 was detected in various regions of mouse and human brain, mostly in large pyramidal neurons. In the human, Nop2 was strongly expressed in supragranular and infragranular layers of the somatosensory cortex and in layer III of the cingulate cortex. Also, Nop2 was detected in CA1 and the subiculum of the hippocampus. Subcellular analyses revealed predominant location of Nop2 within the dense fibrillar component of the nucleolus. To test if Nop2 expression correlates to cell proliferation occurring during tissue regeneration, we induced strokes in mice by middle cerebral artery occlusion. Two weeks after stroke, the number of Nop2/nestin double positive cells in the region affected by ischemia and the periventricular zone substantially increased. Our findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue.