Human Alveolar Echinococcosis, Croatia.

Alveolar echinococcosis is a parasitic disease caused by the tapeworm larval stage of Echinococcus multilocularis. This zoonotic disease has not been known to occur in Croatia. We report a confirmed case of human alveolar echinococcosis in a patient in Croatia who had never visited a known E. multilocularis-endemic area.

Nonalcoholic fatty liver disease as a risk factor for Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea while nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. The aim of this study was to determine whether NAFLD increases susceptibility to CDI. A retrospective cohort study included patients ≥ 65 years, treated with antimicrobial therapy ≥ 24 h, and hospitalized ≥ 72 h in a 36-month period. Three-hundred fourteen patients were included; 83 with NAFLD and 231 controls. Except for diabetes mellitus (37.35% vs. 25.11%, p = 0.0462) and obesity (18.07% vs. 8.23%, p = 0.0218) that were more frequent in NAFLD group, there were no differences in other comorbidities, hospital admissions, antibiotic therapy within 3 months, prescription, and duration of antibiotic therapy. Fourteen (16.9%) patients with NAFLD and 17 (7.4%) in control group developed in-hospital CDI (p = 0.0156). The Charlson Age-Comorbidity Index > 6 (OR 4.34, 95%CI 1.39-13.57), hospital admission within 3 months (OR 7.14, 95%CI 2.33-21.83), serum albumins < 28 g/L (OR 3.15, 95%CI 1.04-9.53), NAFLD (OR 3.27, 95%CI 1.04-10.35), eGFR < 40 (OR 4.89, 95%CI 1.61-14.88), treatment with piperacillin/tazobactam (OR 4.86, 95%CI 1.59-14.83), and carbapenems (OR 3.99, 95%CI 1.28-12.40) were independently associated with CDI. Our study identified NAFLD as an independent predictor of CDI.

IL-1ß production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease. Liver inflammation underlies infection-induced fibrosis, cirrhosis and liver cancer but the processes that promote hepatic inflammation by HCV are not defined. We provide a systems biology analysis with multiple lines of evidence to indicate that interleukin-1ß (IL-1ß) production by intrahepatic macrophages confers liver inflammation through HCV-induced inflammasome signaling. Chronic hepatitis C patients exhibited elevated levels of serum IL-1ß compared to healthy controls. Immunohistochemical analysis of healthy control and chronic hepatitis C liver sections revealed that Kupffer cells, resident hepatic macrophages, are the primary cellular source of hepatic IL-1ß during HCV infection. Accordingly, we found that both blood monocyte-derived primary human macrophages, and Kupffer cells recovered from normal donor liver, produce IL-1ß after HCV exposure. Using the THP-1 macrophage cell-culture model, we found that HCV drives a rapid but transient caspase-1 activation to stimulate IL-1ß secretion. HCV can enter macrophages through non-CD81 mediated phagocytic uptake that is independent of productive infection. Viral RNA triggers MyD88-mediated TLR7 signaling to induce IL-1ß mRNA expression. HCV uptake concomitantly induces a potassium efflux that activates the NLRP3 inflammasome for IL-1ß processing and secretion. RNA sequencing analysis comparing THP1 cells and chronic hepatitis C patient liver demonstrates that viral engagement of the NLRP3 inflammasome stimulates IL-1ß production to drive proinflammatory cytokine, chemokine, and immune-regulatory gene expression networks linked with HCV disease severity. These studies identify intrahepatic IL-1ß production as a central feature of liver inflammation during HCV infection. Thus, strategies to suppress NLRP3 or IL-1ß activity could offer therapeutic actions to reduce hepatic inflammation and mitigate disease.

Risk factors for coronary artery abnormalities in children with Kawasaki disease: a 10-year experience.

Kawasaki disease (KD) is an acute systemic vasculitis of childhood. Due to development of coronary artery aneurysms (CAA) it is considered the most common cause of acquired heart disease in children. The clinical and laboratory features of patients with complete and incomplete KD were compared in order to identify the possible predictors of CAA development. A cross-sectional study of children with KD treated at the University Hospital for Infectious Diseases, Zagreb, between January 2003 and December 2012 was conducted. A total of 111 KD patients were included; 70.3% patients had complete KD. Patients with complete KD had more frequently rash, changes on extremities and mucous membranes, as well as higher serum bilirubin, aminotransferases, gamma-glutamyl transferase and lactate dehydrogenase levels. Patients with incomplete KD had longer duration of fever before the diagnosis (8 vs. 7 days) and delayed IVIG treatment (day 8 vs. 7). CAA was detected in seven children (6.3%). Disease duration before hospitalization >6 days (OR 7.16, 95% CI 1.51-100.35), age <6 months (OR 25.86, 95% CI 1.68-398.35) and platelet count >771 after the 7th day of disease (OR 13.33, 95% CI 2.19-80.87) were independently associated with CAA development. The diagnosis and treatment in incomplete KD can be delayed due to the absence of major criteria. Age, duration of symptoms prior hospitalization and platelet count were identified as independent predictors of CAA development.

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.

Influenza and hepatitis B vaccination coverage among healthcare workers in Croatian hospitals: a series of cross-sectional surveys, 2006-2011.

BACKGROUND: Healthcare workers (HCWs) are at an increased risk of exposure to and transmission of infectious diseases. Vaccination lowers morbidity and mortality of HCWs and their patients. To assess vaccination coverage for influenza and hepatitis B virus (HBV) among HCWs in Croatian hospitals, we conducted yearly nationwide surveys. METHODS: From 2006 to 2011, all 66 Croatian public hospitals, representing 43-60% of all the HCWs in Croatia, were included. Statistical analysis was performed using the Kruskal-Wallis analysis of variance, Dunn's multiple comparison analysis and the chi-square test, as appropriate. RESULTS: The median seasonal influenza vaccination coverage rates in pre-pandemic (2006-2008) seasons were 36%, 25% and 29%, respectively. By occupation, influenza vaccination rates among physicians were 33 ± 21%, 33 ± 22% among graduate nurses, 30 ± 34% among other HCWs, 26 ± 21% among housekeeping and the lowest, 23 ± 17%, among practical nurses (p < 0.01). In 2009-2010 season, seasonal influenza vaccination coverage was 30%, while overall vaccination coverage against pandemic influenza was fewer than 5%. Median vaccination coverage in the post-pandemic seasons of 2010-2011 and 2011-2012 decreased to 15% and 14%, respectively (reduction of 24% and 35%, respectively, p < 0.0001). Meanwhile, the median mandatory HBV vaccination coverage was 98%, albeit with considerable differences according to work setting (range 19-100%) and occupation (range 4-100%). CONCLUSIONS: We found substantial year-on-year variations in seasonal influenza vaccination rates, with reduction in post pandemic influenza seasons. HBV vaccination is satisfactory compared to seasonal influenza vaccination coverage, although substantial variations by occupation and work setting were observed. These findings highlight the need for national strategies that optimize vaccination coverage among HCWs in Croatian hospitals. Further studies are needed to establish the potential role of mandatory vaccination for seasonal influenza.

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.

Case Report: Amphotericin B and Mefloquine as a Salvage Treatment of Alveolar Echinococcosis.

Alveolar echinococcosis is an emerging zoonotic disease caused by the parasite Echinococcus multilocularis. Most patients are diagnosed at a late stage, when lifelong treatment with benzimidazoles is required to stop disease progression. However, for patients who do not tolerate benzimidazole therapy, there are no alternatives. Here, we present a patient with advanced alveolar echinococcosis who was successfully treated with amphotericin B deoxycholate and mefloquine as a rescue therapy after he developed albendazole intolerance.

Association of Immune Semaphorins with COVID-19 Severity and Outcomes.

Semaphorins have recently been recognized as crucial modulators of immune responses. In the pathogenesis of COVID-19, the activation of immune responses is the key factor in the development of severe disease. This study aimed to determine the association of serum semaphorin concentrations with COVID-19 severity and outcomes. Serum semaphorin concentrations (SEMA3A, -3C, -3F, -4D, -7A) were measured in 80 hospitalized adult patients with COVID-19 (moderate (n = 24), severe (n = 32), critical, (n = 24)) and 40 healthy controls. While SEMA3C, SEMA3F and SEMA7A serum concentrations were significantly higher in patients with COVID-19, SEMA3A was significantly lower. Furthermore, SEMA3A and SEMA3C decreased with COVID-19 severity, while SEMA3F and SEMA7A increased. SEMA4D showed no correlation with disease severity. Serum semaphorin levels show better predictive values than CRP, IL-6 and LDH for differentiating critical from moderate/severe COVID-19. SEMA3F and SEMA7A serum concentrations were associated with the time to recovery, requirement of invasive mechanical ventilation, development of pulmonary thrombosis and nosocomial infections, as well as with in-hospital mortality. In conclusion, we provide the first evidence that SEMA3A, SEMA3C, SEMA3F and SEMA7A can be considered as new biomarkers of COVID-19 severity.

Extracorporeal membrane oxygenation in COVID-19: Results of the Croatian Extracorporeal Membrane Oxygenation Referral Center.

At the beginning of the COVID-19 pandemic, the role of extracorporeal membrane oxygenation (ECMO) was uncertain and the outcomes of ECMO-treated patients were unfavorable. During the pandemic, medical community realized that carefully selected patients may benefit from ECMO support. The goal of the study was to present the outcomes of ECMO-treated patients with severe COVID-19 ARDS referred to the respiratory ECMO hub in Croatia and to determine variables that influenced the outcome. Our study included all adult patients with confirmed COVID-19 ARDS that required ECMO treatment, in the period between February 2020 and April 2022. All ECMO circuits were veno-venous with femoro-jugular configuration, with drainage at the femoral site. A total of 112 adult patients with COVID-19 induced ARDS were included in the study. All patients had veno-venous ECMO treatment and 34 survived. Surviving patients were discharged home either from the hospital or from a designated rehabilitation facility. The mortality was associated with the incidence of nosocomial bacteremia, occurrence of heparin induced thrombocytopenia and acute renal failure. In order to reduce the mortality in COVID-19 ECMO patients, the treatment should be started as soon as criteria for ECMO are met. Furthermore, complications of the procedure should be detected as soon as possible. However, despite even the optimal approach, the mortality in COVID-19 ECMO patients will surpass that of non-COVID-19 ARDS ECMO patients, mostly due to poor resolving and long lasting ARDS with longer ECMO runs and ensuing infectious complications.

Emergence of Echinococcus multilocularis in Central Continental Croatia: A Human Case Series and Update on Prevalence in Foxes.

Human alveolar echinococcosis (HAE), caused by the metacestode stage of Echinococcus multilocularis, has emerged in many European countries over the last two decades. Here, we report the first data on the new HAE focus with increasing incidence in central Croatia, describe its clinical presentation and outcomes in diagnosed patients, and provide an update on the prevalence and geographic distribution of Echinococcus multilocuaris in red foxes. After the initial case in 2017 from the eastern state border, from 2019 to 2022, five new autochthonous HAE cases were diagnosed, all concentrated in the Bjelovar-Bilogora County (the county incidence in 2019 and 2021: 0.98/105, in 2022: 2.94/105/year; prevalence for 2019-2022: 4.91/105). The age range among four female and two male patients was 37-67 years. The patients' liver lesions varied in size from 3.1 to 15.5 cm (classification range: P2N0M0-P4N1M0), and one patient had dissemination to the lungs. While there were no fatalities, postoperative complications in one patient resulted in liver transplantation. In 2018, the overall prevalence of red foxes was 11.24% (28/249). A new focus on HAE has emerged in central continental Croatia, with the highest regional incidence in Europe. Screening projects among residents and the implementation of veterinary preventive measures following the One Health approach are warranted.

The Impact of Nonalcoholic Fatty Liver Disease on Severe Community-Acquired Pneumonia Outcomes.

Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality, while nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD is associated with systemic changes in immune response, possibly linked to CAP severity. However, the impact of NAFLD on CAP outcomes has not been determined. The aim of this study was to evaluate clinical course, complications and outcomes of severe CAP requiring ICU treatment in patients with NAFLD in the pre-COVID-19 era. A retrospective cohort study included 138 consecutively hospitalized adult patients with severe CAP admitted to the ICU during a 4-year period: 80 patients with NAFLD and 58 controls. Patients with NAFLD more frequently presented with ARDS (68.7% vs. 43.1%), and required invasive mechanical ventilation (86.2% vs. 63.8%), respiratory ECMO (50% vs. 24.1%), and continuous renal replacement therapy (62.5% vs. 29.3%). Mortality was significantly higher in the NAFLD group (50% vs. 20.7%), and the time from hospital admission to death was significantly shorter. In survival analysis, NAFLD (HR 2.21, 95%CI 1.03-5.06) was associated with mortality independently of other components of metabolic syndrome. In conclusion, our study identified NAFLD as an independent predictor of mortality in patients with severe CAP.

Etiology and Outcomes of Healthcare-Associated Meningitis and Ventriculitis-A Single Center Cohort Study.

Healthcare associated meningitis and ventriculitis (HCAMV) are serious complications of neurosurgical procedures. We conducted a retrospective cohort study of patients with HCAMV treated at the University Hospital for Infectious Diseases Zagreb during the 2013-2019 period. A total of 144 patients with 151 episodes of HCAMV were included. The most common indications for neurosurgical procedures were brain tumor, hemorrhage and hydrocephalus. Etiology was identified in 90 (59.6%) episodes (either positive CSF culture or positive PCR), and in other 61 (40.39%) the diagnosis of HCAMV was made based on clinical and CSF parameters, without microbiologic confirmation. Carbapenem-resistant Acinetobacter baumannii was the most common pathogen (15.89%), followed by Staphylococcus aureus (13.91%), Pseudomonas aeruginosa (13.25%) and Coagulase negative staphylococci (7.95%). Overall, 24 (16.3%) patients died, and the majority had adverse outcomes, persistent vegetative state (8, 5.56%) and severe disability (31, 21.53%). The worst clinical outcomes were observed in A. baumannii infections. High rate of complications, the need for external ventricular drainage (re)placement often complicated with nosocomial infections and prolonged stay in intensive care units were observed. Clinicians should be aware of local microbial epidemiology on guiding proper empirical antimicrobial treatment in patients with HCAMV.

Extracorporeal membrane oxygenation for the treatment of ARDS in Covid-19 and influenza patients: Does etiology matter?

At the beginning of the COVID 19 pandemic, the outcome of patients treated with ECMO was discouraging. Subsequently, it became clear that a certain group of patients may benefit from ECMO treatment. The primary objective of this study was to compare the outcome of ECMO treatment in COVID-19 and influenza patients referred to a tertiary care center. A total of 119 adult patients required ECMO treatment following ARDS secondary to H1N1 (49) and SARS-CoV-2 (70) in the referral ECMO Center based in Zagreb between October 2009 and October 2021. Our study revealed a significantly higher mortality in COVID-19 patients compared to H1N1 influenza when the onset of ARDS was severe enough to require ECMO support. Based on these results and current knowledge, we argue that ECMO treatment for ARDS in COVID-19 patients is more challenging compared to H1N1 influenza patients. Therefore, referral to the most experienced ECMO centers should be considered. Additionally, patient selection and timing for ECMO treatment play a key role in relation to outcome. Mortality rate in COVID-19 patients requiring ECMO treatment may be used as a reference frame for ECMO centers to ensure best possible care and outcome.

Mid trimester amniotic fluid soluble receptor tunica interna endothelial cell kinase-2 levels and risk for preeclampsia.

OBJECTIVES: The purpose of this study was to determine if elevated concentration of soluble receptor tunica interna endothelial cell kinase-2 (Tie-2) in the amniotic fluid represent a risk factor for the subsequent development of preeclampsia (PE). STUDY DESIGN: Amniotic fluid samples were collected as a part of routine clinical diagnostics from women referred to clinical care due to genetic indications. A total of 12 women with preeclampsia and 26 normotensive pregnant women were included in the study. Mean gestational age at amniocentesis was 17.92 weeks of pregnancy in preeclampsia and 17.88 in control group, respectively. Concentrations of sTie-2 in the amniotic fluid were determined by a standardized enzyme immunoassay. RESULTS: Median concentration of Tie-2 in the amniotic fluid of PE patients was lower (median 1.109 ng/ml) compared with normotensive pregnant women (median 1.433 ng/Ml) but the difference was not statistically significant (p = 0.2973). Concentration of sTie-2 in the amniotic fluid did not significantly correlate with maternal age, gestational age at amniocentesis or delivery, as well as weight or length at birth. A difference in the gestational age at delivery in PE patients (mean 37.7 weeks) and normotensive pregnant controls (mean 39.8 weeks) was statistically significant (p = 0.0003). Birth weight and length of children delivered by PE women (mean 2863.3 g and 48.3 cm) were significantly lower compared with normal pregnancies (mean 3591.2 g and 51.4 cm, p = 0.0002 and p = 0.006, respectively). CONCLUSION: Our results suggest that amniotic fluid concentrations of sTie-2 do not predict development of PE and that further studies on biomarkers as predictors of PE should include other angiogenic biological response modifiers.

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.

COVID-19 and Pulmonary Thrombosis-An Unresolved Clinical Puzzle: A Single-Center Cohort Study.

Pulmonary thrombosis (PT) is a frequent complication of COVID-19. However, the risk factors, predictive scores, and precise diagnostic guidelines on indications for CT pulmonary angiography (CTPA) are still lacking. This study aimed to analyze the clinical and laboratory characteristics associated with PT in patients with COVID-19. We conducted a cohort study of consecutively hospitalized adult patients with COVID-19 who underwent CTPA at the University Hospital for Infectious Diseases in Zagreb, Croatia between 1 April and 31 December 2021. Of 2078 hospitalized patients, 575 (27.6%) underwent CTPA. PT was diagnosed in 178 (30.9%) patients (69.6% males, median age of 61, IQR 50-69 years). The PT group had a higher CRP, LDH, D-dimer, platelets, and CHOD score. PT was more frequent in patients requiring ≥15 L O2/min (25.0% vs. 39.7%). In multivariable analysis, only D-dimer ≥ 1.0 mg/L (OR 1.78, 95%CI 1.12-2.75) and O2 ≥ 15 L (OR 1.89, 95%CI 1.26-2.84) were associated with PT. PT was not associated with in-hospital mortality. In conclusion, our data confirmed a high incidence of PT in hospitalized patients with COVID-19, however, no correlation with traditional risk factors and mortality was found. CTPA should be performed in patients requiring high-flow supplemental oxygen or those with increased D-dimer levels.

Do Semaphorins Play a Role in Development of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease?

Nonalcoholic fatty liver disease (NAFLD) is associated with systemic changes in immune response linked with chronic low-grade inflammation and disease progression. Semaphorins, a large family of biological response modifiers, were recently recognized as one of the key regulators of immune responses, possibly also associated with chronic liver diseases. The aim of this study was to identify semaphorins associated with NAFLD and their relationship with steatosis and fibrosis stages. In this prospective, case-control study, serum semaphorin concentrations (SEMA3A, -3C, -4A, -4D, -5A and -7A) were measured in 95 NAFLD patients and 35 healthy controls. Significantly higher concentrations of SEMA3A, -3C and -4D and lower concentrations of SEAMA5A and -7A were found in NAFLD. While there was no difference according to steatosis grades, SEMA3C and SEMA4D significantly increased and SEMA3A significantly decreased with fibrosis stages and had better accuracy in predicting fibrosis compared to the FIB-4 score. Immunohistochemistry confirmed higher expression of SEMA4D in hepatocytes, endothelial cells and lymphocytes in NAFLD livers. The SEMA5A rs1319222 TT genotype was more frequent in the NAFLD group and was associated with higher liver stiffness measurements. In conclusion, we provide the first evidence of the association of semaphorins with fibrosis 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.

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes.

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013-2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33-84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5-73), and the median hospital LOS was 34 days (range 7-97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3-5, 6 (26.0%) had slight disability/mRS 2-1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6-69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3-5, one (4.3%) had slight disability/mRS 2-1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.