Adjunctive use of oral MAF is associated with no disease progression or mortality in hospitalized patients with COVID-19 pneumonia: The single-arm COral-MAF1 prospective trial.

Based on a growing body of evidence that a dysregulated innate immune response mediated by monocytes/macrophages plays a key role in the pathogenesis of COVID-19, a clinical trial was conducted to investigate the therapeutic potential and safety of oral macrophage activating factor (MAF) plus standard of care (SoC) in the treatment of hospitalized patients with COVID-19 pneumonia. Ninety-seven hospitalized patients with confirmed COVID-19 pneumonia were treated with oral MAF and a vitamin D3 supplement, in combination with SoC, in a single-arm, open label, multicentre, phase II clinical trial. The primary outcome measure was a reduction in an intensive care unit transfer rate below 13% after MAF administration. At the end of the study, an additional propensity score matching (PSM) analysis was performed to compare the MAF group with a control group treated with SoC alone. Out of 97 patients treated with MAF, none needed care in the ICU and/or intubation with mechanical ventilation or died during hospitalization. Oxygen therapy was discontinued after a median of nine days of MAF treatment. The median length of viral shedding and hospital stay was 14 days and 18 days, respectively. After PSM, statistically significant differences were found in all of the in-hospital outcomes between the two groups. No mild to serious adverse events were recorded during the study. Notwithstanding the limitations of a single-arm study, which prevented definitive conclusions, a 21-day course of MAF treatment plus SoC was found to be safe and promising in the treatment of hospitalized adult patients with COVID-19 pneumonia. Further research will be needed to confirm these preliminary findings.

Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion.

Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence.

Diagnostic issues faced by a rare disease healthcare network during Covid-19 outbreak: data from the Campania Rare Disease Registry.

BACKGROUND: The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. METHODS: To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. RESULTS: Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P < 0.001 and 37 versus 349, P < 0.001, respectively) and 2018 (117 versus 389, P < 0.001 and 37 versus 282, P < 0.001, respectively). Eighty-two among 98 rare disease experts completed the questionnaire. Diagnostic success (95%), access to diagnosis (80%) and follow-up (72%), lack of Personal Protective Equipment (60%), lack of Covid-19 guidelines (50%) and the need for home therapy (78%) were the most important issues raised during Covid-19 outbreak. CONCLUSIONS: This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.

Internal Modifications to Optimize Pollution and Emissions of Internal Combustion Engines through Multiple-Criteria Decision-Making and Artificial Neural Networks.

The present work proposes several modifications to optimize both emissions and consumption in a commercial marine diesel engine. A numerical model was carried out to characterize the emissions and consumption of the engine under several performance parameters. Particularly, five internal modifications were analyzed: water addition; exhaust gas recirculation; and modification of the intake valve closing, overlap timing, and cooling water temperature. It was found that the result on the emissions and consumption presents conflicting criteria, and thus, a multiple-criteria decision-making model was carried out to characterize the most appropriate parameters. In order to analyze a high number of possibilities in a reasonable time, an artificial neural network was developed.

Dalbavancin for infective endocarditis: a single centre experience.

Infective endocarditis (IE) is a life-threatening disease, mostly caused by gram-positive cocci, needing a 4-6 weeks antibiotic course. Dalbavancin is a lipoglycopeptide active on gram-positive microorganisms, with a unique pharmacokinetic profile. We describe our experience with dalbavancin to complete the intravenous antibiotic regimen for difficult-to-treat IE cases due to gram-positive bacteria. We treated 10 severely ill patients, each presenting several comorbidities. Seven patients were microbiologically cured from IE, but two patients experienced IE relapse due to the same microrganism. Short-term mortality after dalbavancin was nil, but late mortality (within 1 year of hospital discharge) was 60%. No death was related to dalbavancin therapy. Treatment was generally well tolerated. Dalbavancin may be an option to complete IE treatment in selected cases, once blood culture clearance and improvement of clinical conditions under standard therapy is reached, allowing shortening of hospitalization.

Psychological distress and resilience of mothers and fathers with respect to the neurobehavioral performance of small-for-gestational-age newborns.

BACKGROUND: The existence of psychological distress (PD) during pregnancy is well established. Nevertheless, few studies have analyzed the PD and resilience of mothers and fathers during high-risk pregnancy. This study analyzes the differences between parents' PD and resilience and the relation between them and the neurobehavioral performance of their SGA newborns. METHODS: This prospective study compares two groups of parents and newborns: case group (52 parents and 26 SGA fetuses) and comparison group (68 parents and 34 appropriate-for-gestational-age, AGA, fetuses). In each group, the parents were evaluated during the last trimester of pregnancy, to obtain standardized measures of depression, stress, anxiety, and resilience. At 40 ± 1 weeks corrected gestational age, psychologists evaluated the state of neonatal neuromaturity achieved. RESULTS: Multivariate analysis of variance showed, in gender comparisons, that mothers obtained higher scores than fathers for psychological distress but lower ones for resilience. Similar differences were obtained in the comparison of parents' distress to intrauterine growth by SGA vs. AGA newborns. Mothers of SGA newborns were more distressed than the other groups. However, there were no differences between the fathers of SGA vs. AGA newborns. Regarding neurobehavioral performance, the profiles of SGA newborns reflected a lower degree of maturity than those of AGA newborns. Hierarchical regression analyses showed that high stress and low resilience among mothers partially predict low neurobehavioral performance in SGA newborns. CONCLUSIONS: These findings indicate that mothers of SGA newborns may need psychological support to relieve stress and improve their resilience. Furthermore, attention should be paid to the neurobehavioral performance of their babies in case early attention is needed.