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Medical errors and complications pose a major threat to the safety of healthcare systems worldwide. This article was hence aimed at determining the current burden of complications of medical and surgical care in the US. We searched the latest version of the US Centers for Disease Control and Prevention (CDC) WONDER online database (years 2018–2022) using ICD-10 codes Y40-Y84 (complications of medical and surgical care). The age-adjusted death rate for complications of medical and surgical care increased from 1.17 × 100,000 in 2018 to 1.49 × 100,000 in 2021, but then declined to 0.85 × 100,000 in 2022. The gender-specific analysis showed a similar trend, with the age-adjusted death rate values always being higher in men than in women. A clear age-dependent relationship was also found in the crude mortality rate for complications of medical and surgical care, as higher death rates were observed in older patients. This analysis reveals that the burden of complications of medical and surgical care has increased over time, especially during the COVID-19 pandemic, but has then considerably declined in 2022. However, root cause analysis and actions are still needed for preventing the still noticeable consequences of medical complications. [ABSTRACT FROM AUTHOR]

This study is aimed at developing a simple epidemiologic model that could help predict the impaired neutralization of new SARS-CoV-2 variants. We explored the potential association between neutralization of recent and more prevalent SARS-CoV-2 sublineages belonging to the Omicron family (i.e., BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1 and XBB.1) expressed as FFRNT50 (>50% suppression of fluorescent foci fluorescent focus reduction neutralization test) in recipients of four doses of monovalent mRNA-based coronavirus disease 2019 (COVID-19) vaccines, with epidemiologic variables like emergence date and number of spike protein mutations of these sublineages, cumulative worldwide COVID-19 cases and cumulative number of COVID-19 vaccine doses administered worldwide at the time of SARS-CoV-2 Omicron sublineage emergence. In the univariate analysis, the FFRNT50 value for the different SARS-CoV-2 Omicron sublineages was significantly associated with all such variables except with the number of spike protein mutations. Such associations were confirmed in the multivariate analysis, which enabled the construction of the equation: “−0.3917 × [Emergence (date)] + 1.403 × [COVID-19 cases (million)] − 121.8 × [COVID-19 Vaccine doses (billion)] + 18,250”, predicting the FFRNT50 value of the five SARS-CoV-2 Omicron sublineages with 0.996 accuracy (p = 0.013). We have shown in this work that a simple mathematical approach, encompassing a limited number of widely available epidemiologic variables, such as emergence date of new variants and number of COVID-19 cases and vaccinations, could help identifying the emergence and surge of future lineages with major propensity to impair humoral immunity.

BackgroundProcalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics.MethodsSerum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions undergoing a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease.ResultsMedian bproCt levels were higher in MTC than in non-MTC. A positive correlation was found for bproCt with bCt (P0.07 ng/ml (sensitivity: 85.7%, specificity: 98.9%, positive predictive value [PPV]: 98.2%, negative predictive value [NPV]: 90.6%, P0.07 ng/ml in 38/39 (97.4%) patients with MTC >10 mm, it was above said cut-off only in 15/23 (65.2%) patients with tumors ≤10 mm. A sproCt >0.19 ng/ml was able to identify MTC [sensitivity: 90.0%, specificity:100.0%, PPV: 100.0%, NPV: 86.7% (P

In anticipation of an interseasonal respiratory syncytial virus (RSV) epidemic, a clinician-led reporting system was rapidly established to capture RSV infections in Swiss hospitals, starting in January 2021. Here, we present details of the reporting system and first results to June 2021. An unusual epidemiology was observed with an interseasonal surge of RSV infections associated with COVID-19-related non-pharmacological interventions. These data allowed real-time adjustment of RSV prophylaxis guidelines and consequently underscore the need for and continuation of systematic nationwide RSV surveillance.

Neutrophilic inflammation is a key determinant of cystic fibrosis (CF) lung disease. Neutrophil-derived free DNA, released in the form of extracellular traps (NETs), significantly correlates with impaired lung function in patients with CF, underlying their pathogenetic role in CF lung disease. Thus, specific approaches to control NETosis of neutrophils migrated into the lungs may be clinically relevant in CF. We investigated the efficacy of phosphodiesterase (PDE) type-4 inhibitors, in vitro, on NET release by neutrophils from healthy volunteers and individuals with CF, and in vivo, on NET accumulation and lung inflammation in mice infected with Pseudomonas aeruginosa. PDE4 blockade curbed endotoxin-induced NET production and preserved cellular integrity and apoptosis in neutrophils, from healthy subjects and patients with CF, challenged with endotoxin, in vitro. The pharmacological effects of PDE4 inhibitors were significantly more evident on CF neutrophils. In a mouse model of Pseudomonas aeruginosa chronic infection, aerosol treatment with roflumilast, a selective PDE4 inhibitor, gave a significant reduction in free DNA in the BALF. This was accompanied by reduced citrullination of histone H3 in neutrophils migrated into the airways. Roflumilast-treated mice showed a significant improvement in weight recovery. Our study provides the first evidence that PDE4 blockade controls NETosis in vitro and in vivo, in CF-relevant models. Since selective PDE4 inhibitors have been recently approved for the treatment of COPD and psoriasis, our present results encourage clinical trials to test the efficacy of this class of drugs in CF.

BackgroundThe immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population.MethodsOf 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1–3.7) and 6.1 (5.3–7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR).ResultsOverall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes.ConclusionsAdults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.