Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies

Incidence, risk factors and impact on clinical outcomes of bloodstream infections in patients hospitalised with covid-19: A prospective cohort study

With the aim of describing the burden and epidemiology of community-acquired/healthcare-associated and hospital-acquired bloodstream infections (CA/HCA-BSIs and HA-BSIs) in patients hospitalised with COVID-19, and evaluating the risk factors for BSIs and their relative impact on mortality, an observational cohort study was performed on patients hospitalised with COVID-19 at San Paolo Hospital in Milan, Italy from 24 February to 30 November 2020. Among 1351 consecutive patients hospitalised with COVID-19, 18 (1.3%) had CA/HCA-BSI and 51 (3.8%) HA-BSI for a total of 82 episodes of BSI. The overall incidence of HA-BSI was 3.3/1000 patient-days (95% CI 2.4–4.2). Patients with HA-BSI had a longer hospital stay compared to CA/HCA-BSI and no-BSI groups (27 (IQR 21–35) vs. 12 (7–29) vs. 9 (5–17) median-days, p < 0.001) but a similar in-hospital mortality (31% vs. 33% vs. 25%, p = 0.421). BSI was not associated with an increased risk of mortality (CA/HCA-BSI vs. non-BSI aOR 1.27 95%CI 0.41–3.90, p = 0.681; HA-BSI vs. non-BSI aOR 1.29 95%CI 0.65–2.54, p = 0.463). Upon multivariate analysis, NIMV/CPAP (aOR 2.09, 95% CI 1.06– 4.12, p = 0.034), IMV (aOR 5.13, 95% CI 2.08–12.65, p < 0.001) and corticosteroid treatment (aOR 2.11, 95% CI 1.06–4.19, p = 0.032) were confirmed as independent factors associated with HA-BSI. Development of HA-BSI did not significantly affect mortality. Patients treated with corticosteroid therapy had double the risk of developing BSI

A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection

The opportunistic pathogen Pseudomonas aeruginosa (Pa) causes severe nosocomial infections, especially in immunocompromised individuals and the elderly. Increasing drug resistance, the absence of a licensed vaccine and increased hospitalizations due to SARS-CoV-2 have made Pa a major healthcare risk. To address this, we formulated a candidate subunit vaccine against Pa (L-PaF), by fusing the type III secretion system tip and translocator proteins with LTA1 in an oil-in-water emulsion (ME). This was mixed with the TLR4 agonist (BECC438b). Lung mRNA sequencing showed that the formulation activates genes from multiple immunological pathways eliciting a protective Th1-Th17 response following IN immunization. Following infection, however, the immunized mice showed an adaptive response while the PBS-vaccinated mice experienced rapid onset of an inflammatory response. The latter displayed a hypoxic lung environment with high bacterial burden. Finally, the importance of IL-17 and immunoglobulins were demonstrated using knockout mice. These findings suggest a need for a balanced humoral and cellular response to prevent the onset of Pa infection and that our formulation could elicit such a response

Immunogenicity and protective efficacy of nanoparticle formulations of L-SseB against Salmonella infection

Salmonella enterica, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, S. enterica causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the Salmonella pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic E. coli to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined via challenging the mice with S. enterica serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from S. enterica challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against S. enterica

Interessamento entesitico in bambini e adolescenti con malattia infiammatoria cronica intestinale: uno studio ecografico

Background: joint involvement is the most common extraintestinal manifestation in paediatric IBD patients. Several studies in adult population have shown that enthesis ultrasound (US) has a high sensitivity in the diagnosis of enthesitis. Objectives: The objective is to evaluate, using a high frequency ultrasound probe, the prevalence of subclinical entheseal involvement in paediatric IBD patients. Methods: 27 paediatric IBD patients [12 Crohn's disease, 13 ulcerative colitis and 2 IBD type unclassified; 15 females and 12 males, mean age of 13,7 years (ranging 7,2-21,0 years)] without clinical signs or symptoms of musculo-skeletal involvement were consecutively investigated with US (ESAOTE MyLAB 70 6-18 MHz linear array transducer) and compared with 24 healthy controls matched for age and sex. Twelve enthesis were scored according to the Madrid Sonographic Enthesis Index (MASEI) in both groups. Results: no patients reached the MASEI score value suggestive for an early spondyloarthritis involvement but the average MASEI score was significantly higher in IBD patients compared to controls (3.15\ub12.84 vs 0.96\ub11.12, p=0.0006).There was also a significantly higher percentage of patients with at least one enthesis with power Doppler (PD) score 652 (37% vs 16%; p= 0.037) and at least one enthesis with dishomogeneous echostructure (59% vs 0%; p= 0.000). No differences were found in terms of erosions, calcifications and structural thickness. In IBD patients, no correlation was found between MASEI total score and sex, age, disease duration and clinical activity scores. Conclusions: US detectable enthesopathy is frequent even in paediatric IBD patients

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project

Background: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. Methods: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. Discussion: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. Trial registration: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380

Seasonal and spatial variability in condition of age-0+ Argentine hake Merluccius hubbsi Marini, 1933, in the San Jorge Gulf (Argentina): A bottom-up perspective

In the north Patagonian region of the Argentinean Continental Shelf, the San Jorge Gulf (SJG; 45°‐47°S, 65°30ʹ‐67°30ʹW) is the main nursery ground of age‐0+ Argentine hake Merluccius hubbsi Marini, 1933, one of the most important fishery resources in Argentina. The gulf exhibits strong seasonal and spatial fluctuations in environmental features, which might affect survival of age‐0+ individuals and recruitment to the adult population. Our main goal was to evaluate the seasonal and spatial dynamics of their nutritional status within the SJG in winter 2016, spring 2016 and summer 2017. Condition indices (relative condition factor Kn, hepatosomatic index HSI and liver lipid content %L) and diet information (feeding incidence and relative importance of prey) were combined with physical (temperature and salinity) and biological (satellite chlorophyll‐a concentration; chl‐a) data. Age‐0+ condition indices and prey intake showed significant seasonal variations, with minimum values in winter, intermediate in summer and maximum in spring, strongly coupled to the mean chl‐a concentration in each season. Herbivorous euphausiids Euphausia spp. were the preferred prey along the study period. A bottom‐up effect on condition of age‐0+ hake is suggested, manifested as lower condition values in winter, the less productive season. Spatially, better conditioned individuals matched sectors of the gulf where chl‐a concentrations were higher, coupled to the presence of frontal systems. Monitoring age‐0+ hake nutritional status is relevant in the current global change scenario, which might modify phytoplankton biomass and composition and, consequently, the herbivorous zooplankton abundances.Fil: Temperoni, Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Massa, Agueda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Martos, Patricia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Marinas; ArgentinaFil: Marrari, Marina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Identification of the Clinical Features Distinguishing Psoriatic Arthritis and Fibromyalgia

To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM)

Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non -vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non -vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson's Chi-square and Mann -Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non -vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039-0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582-1.703, p = 0.987). Conclusions: This study provides real -world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first -booster uptake rates. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)