Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project.

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.

Relationship between oral lesions and severe SARS-CoV-2 infection in intensive care unit patients.

OBJECTIVE: Oral lesions received increased attention as likely new signs or secondary manifestations of COVID-19. Therefore, we clinically examined oral cavity of patients with COVID-19 and investigated oral lesions and patient comorbidities as possible risk factors of COVID-19 disease outcome. METHODS: From January to March 2022, a prospective study was conducted by recruiting all COVID-19 patients admitted to the Intensive Care Unit and Respiratory Intensive Care Unit of Maxi-Emergencies Hospital in Bari, Italy. RESULTS: From the enrolled 103 COVID-19 patients, 46.6% were females and 53.4% were males. Findings show that risk of presenting with severe COVID-19 disease was higher in patients who developed oral lesions related to COVID-19 than those with no oral lesions (RR = 7.998, p = .002). Next, patients with concomitant autoimmune diseases were at higher risk of a negative COVID-19 disease outcome than those without comorbidities (OR = 8.838, p = .026). CONCLUSIONS: COVID-19-related lesions of oral mucosa should not be ignored as they can be early and easily detectable signs of severe COVID-19 disease condition, thus, serving as a prevention measure for any potential unfortunate event. Findings of this study, without implying causation, offer a direction for future investigations that aim to confirm the presence of specific oral lesions in COVID-19 patients as signs of severe disease progression.

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast.

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.

COVID-19 Variants in Critically Ill Patients: A Comparison of the Delta and Omicron Variant Profiles.

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.

Cavernous Sinus Involvement and Near Miss Mediastinitis following Mandibular Tooth Infection Treated during the COVID-19 Pandemic: Clinical Diagnosis and Treatment.

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.

A comparison between fenoldopam and low-dose dopamine in early renal dysfunction of critically ill patients.

OBJECTIVE: Fenoldopam mesylate is a selective dopamine-1 agonist, with no effect on dopamine-2 and alpha1 receptors, producing a selective renal vasodilation. This may favor the kidney oxygen supply/demand ratio and prevent acute renal failure. The aim of the study was to investigate if fenoldopam can provide greater benefit than low-dose dopamine in early renal dysfunction of critically ill patients. DESIGN: Prospective, multiple-center, randomized, controlled trial. SETTING: University and city hospital intensive care units. PATIENTS: One hundred adult critically ill patients with early renal dysfunction (intensive care unit stay<1 wk, hemodynamic stability, and urine outputor=1.5 mg/dL and10% of the baseline value at the end of infusion, compared with only 46% in dopamine group (chi-square=4.06, p=.04). Total urinary output during drug infusion was not significantly different between groups. After 1 day, urinary output was lower in group F compared with group D (p<.05). CONCLUSIONS: In critically ill patients, a continuous infusion of fenoldopam at 0.1 microg/kg/min does not cause any clinically significant hemodynamic impairment and improves renal function compared with renal dose dopamine. In the setting of acute early renal dysfunction, before severe renal failure has occurred, the attempt to reverse renal hypoperfusion with fenoldopam is more effective than with low-dose dopamine.