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Background Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. Methods We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS ( n  = 6), CER20 (single dose of CER-001 20 mg/kg; n  = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n  = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n  = 5), Group B (CER-001 5 mg/kg BID, n  = 5), Group C (CER-001 10 mg/kg BID, n  = 5), and Group D (CER-001 20 mg/kg BID, n  = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. Results CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. Conclusions CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. Trial registration The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020–004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

Background: Coronavirus disease is a pandemic that has disrupted many human lives, threatening people’s physical and mental health. Each pandemic wave struck in different ways, infectiveness-wise and mortality-wise. This investigation focuses on critically ill patients affected by the last two variants, Delta and Omicron, and aims to analyse if any difference exists between the two groups. Methods: intensive care unit (ICU) COVID-19 consecutive admissions between 1 October 2021 and 31 March 2022 were recorded daily, and data concerning the patients’ demographics, variants, main comorbidities, ICU parameters on admission, and the outcome were analysed by a univariate procedure and by a multivariate analysis. Results: 65 patients were enrolled, 31 (47.69%) belonging to the Omicron versus 34 (52.31%) to the Delta group. The mortality rate was 52.94% for the Omicron group versus 41.9% for the Delta group. A univariate analysis showed that the Omicron variant was associated with total comorbidities number, Charlson Comorbidity Index (CCI), pre-existing pulmonary disease, vaccination status, and acute kidney injury (AKI). In stepwise multivariate analysis, the total number of comorbidities was positively associated with the Omicron group, while pulmonary embolism was negatively correlated with the Omicron group. Conclusion: Omicron appears to have lost some of the hallmarks of the Delta variant, such as endothelialitis and more limited cellular tropism when it comes to the patients in the ICU. Further studies are encouraged to explore different therapeutic approaches to treat critical patients with COVID-19.

Background Ventilator-associated pneumonia (VAP) remains a significant complication among critically ill patients, with associated mortality approaching 50%. Despite the implementation of established preventive strategies, additional interventions are urgently needed to further reduce the incidence of VAP. Probiotic therapy has emerged as a promising adjunctive approach; the benefits of probiotic therapy may be more pronounced in critically ill patients without pre-existing infections. The PROACT study will evaluate the prophylactic role of probiotics in a critically ill population with acute brain injury to reduce the VAP incidence, while also exploring microbiological endpoints and mortality to refine patient selection criteria. Methods The PROACT study is a prospective, randomized, double-blind, placebo-controlled, multicenter trial designed to evaluate the efficacy of probiotic prophylaxis in adult critically ill patients requiring invasive mechanical ventilation following acute brain injury (e.g., head trauma, ischemic or hemorrhagic stroke). Patients with suspected pulmonary aspiration or pre-existing pulmonary infections at enrollment are excluded to reduce confounding. Participants are randomized in a 1:1 ratio to receive either a placebo (glucose polymer) or a probiotic formulation containing Lactobacillus acidophilus LA-5, Lactobacillus plantarum , Bifidobacterium lactis BB12, and Saccharomyces boulardii . The assigned intervention is administered twice daily via nasogastric tube and oropharyngeal application for up to 30 days or until intensive care unit (ICU) discharge. The primary endpoint is the incidence of VAP, as defined by current international guidelines, in the intention-to-treat (ITT) population. Secondary endpoints include the incidence of VAP in the modified intention-to-treat (mITT) population, catheter-related bloodstream infections, occurrence of sepsis and septic shock, 30-day all-cause mortality, ICU length of stay, and duration of mechanical ventilation. The study is powered at 80% ( α  = 0.05) to detect a clinically meaningful difference based on effect size estimates based on the PROVAP study, requiring a total sample size of 208 patients. All participating centers implement standard VAP prevention bundles as part of routine care. Discussion By evaluating the efficacy of probiotic therapy in preventing VAP and the impact on mortality among critically ill brain-injured patients, this trial has the potential to generate high-quality evidence supporting the incorporation of probiotics into standard VAP prevention protocols. The findings may have significant implications for clinical practice guidelines and public health policy related to infection control and microbiome-targeted interventions in the intensive care setting. Trial registration Registered at ClinicalTrials.gov (identifier: [NCT06092554]). Registered on 2023-10-15.

Odontogenic infections represent a frequent condition that in some cases, if not treated promptly, can spread quickly to the rest of the body and turn into life-threatening infections. In this work, the case is reported of a 59-year-old woman, diabetic and overweight, who presented to the Odontostomatology and Otolaryngology Section of the Policlinic of Bari with mandibular tooth infection that had developed into a deep neck space infection leading to the involvement of cavernous sinuses and near mediastinum. The diagnosis, the surgical drainage of the phlegmon and removal of infection foci, appropriate control of the airways, and a correct antibiotic therapy made it possible to avoid a potentially fatal condition. Prompt management and early diagnosis of deep space neck infections, such as phlegmon and/or necrotizing fasciitis, with the auxilium of CT scans and tools such as LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis), NLR (Neutrophil-to-Lymphocyte Ratio), and LRINECxNLR scores (Laboratory Risk Indicator for Necrotizing Fasciitis and Neutrophil to Lymphocyte Ratio), are advised to evade delays and complications that could potentially worsen the patient’s outcome.

Background: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines’ immunization findings. Methods: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. Results: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. Conclusions: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.