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Background Noonan syndrome (NS) is a clinically and genetically heterogeneous disorder. Since its clinical phenotype is often mild and difficult to differentiate from other syndromes, its diagnosis can be challenging and its prevalence in the pediatric population is most certainly underestimated. The difficulty in identifying Noonan syndrome is also increased by the fact that genetic tests are currently not able to detect an underlying mutation in around 10% of the cases. Methods This is a retrospective, observational study conducted at the Institute for Maternal and Child “Burlo Garofolo” in Trieste, Italy. We recruited all the patients with clinical and/or genetic diagnosis of NS who were evaluated at the Department of Pediatrics between October 2015 and October 2020. Statistical analyses were performed with IBM SPSS Statistics software. The association between discrete variables has been evaluated through chi-squared test, indicating statistically significant p with Pearson test or Fischer test for variables less than 5. Results We recruited a total of 35 patients affected by Noonan syndrome. In 24 patients (75%) we identified an underlying genetic substrate: 17 patients had a mutation on PTPN11 (61%), 2 in SOS1, KRAS and SHOC2 (7% each) and only 1 in RAF1 (4%). 25% of the subjects did not receive a genetic confirm. As for the phenotype of the syndrome, our study identified the presence of some clinical features which were previously unrelated or poorly related to NS. For example, renal and central nervous system abnormalities were found at a higher rate compared to the current literature. On the contrary, some features that are considered very suggestive of NS (such as lymphatic abnormalities and the classical facial features) were not frequently found in our population. Conclusions In our analysis, we focused on the main phenotypic features of NS, identifying various clinical manifestation that were not associated with this genetic condition before. This could be helpful in raising the knowledge of NS’s clinical spectrum, facilitating its diagnosis.

Background. Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with rapidly progressive evolution and an unfavorable outcome. Nintedanib (NTD) is an antifibrotic drug that has been shown to be effective in slowing down the progression of the disease. The aim of our study was to examine the efficacy, especially in terms of the functional decline, and the safety profile of NTD in patients treated with the recommended dose and subjects who reduced or suspended the therapy due to the occurrence of adverse reactions. Methods. We conducted a real-life retrospective study based on the experience of NTD use in two centers between 2015 and 2022. Clinical data were evaluated at baseline, at 6 and 12 months after the NTD introduction in the whole population and in subgroups of patients who continued the full-dose treatment, at a reduced dosage, and at the discontinuation of treatment. The following data were recorded: the demographic features, IPF clinical features, NTD therapeutic dosage, tolerability and adverse events, pulmonary function tests (PFTs), the duration of treatment upon discontinuation, and the causes of interruption. Results. There were 54 IPF patients who were included (29.6% females, with a median (IQR) age at baseline of 75 (69.0–79.0) years). Twelve months after the introduction of the NTD therapy, 20 (37%) patients were still taking the full dose, 11 (20.4%) had reduced it to 200 mg daily, and 15 (27.8%) had stopped treatment. Gastrointestinal intolerance predominantly led to the dose reduction (13.0%) and treatment cessation (20.4%). There were two deaths within the initial 6 months (3.7%) and seven (13.0%) within 12 months. Compared to the baseline, the results of the PFTs remained stable at 6 and 12 months for the entire NTD-treated population, except for a significant decline in the DLCO (% predicted value) at both 6 (38.0 ± 17.8 vs. 43.0 ± 26.0; p = 0.041) and 12 months (41.5 ± 15.3 vs. 44.0 ± 26.8; p = 0.048). The patients who continued treatment at the full dose or a reduced dosage showed no significant differences in the FVC and the DLCO at 12 months. Conversely, those discontinuing the NTD exhibited a statistically significant decline in the FVC (% predicted value) at 12 months compared to the baseline (55.0 ± 13.5 vs. 70.0 ± 23.0; p = 0.035). Conclusions. This study highlights the functional decline of the FVC at 12 months after the NTD initiation among patients discontinuing therapy but not among those reducing their dosage.

Background prolonged, low-dose glucocorticoid treatment reduces systemic inflammation and mortality in patients with SARS-CoV-2-related pneumonia requiring respiratory support. Previous studies reported a significant C-reactive protein (CRP) reduction in the early days of treatment compared to placebo. While CRP is an independent predictor of severity in community-acquired pneumonia, there is no evidence on the correlation between CRP changes and mortality within a glucocorticoid-treated population. Methods data from the MEDEAS randomized controlled trial were re-analyzed as a single cohort of patients with SARS-CoV-2-related pneumonia undergoing either dexamethasone 6 mg/day for 10 days or methylprednisolone 80 mg/day for ≥ 8 days from hospitalization. CRP relative decrease between treatment initiation and day 3 was calculated and tested to predict 28-day mortality. Additionally, clinically relevant CRP percentage changes by day 3 were calculated and tested to predict survival. A stratification was performed for baseline PaO 2 :FiO 2 , and a multivariable analysis was conducted to adjust for confounders. Results 597 patients were included in the analysis. In multivariable logistic regression analysis, the relative decrease in CRP by day 3 was significantly associated with 28-day survival (OR 0.77; 95%CI 0.64–0.99; p  = 0.011). Furthermore, a ≥ 5% CRP reduction was associated with a lower mortality compared to either < 5% reduction or any increase in CRP levels by day 3 (8.2% versus 18.5%; OR 0.40; 95%CI 0.23–0.69; p  = 0.001) in the whole cohort. When stratifying for baseline PaO 2 :FiO 2 , a ≥ 5% CRP reduction resulted in a lower mortality (10.9% versus 28.3%; OR 0.31; 95%CI 0.16–0.61; p = < 0.001) in the more severe subgroup of patients presenting with a PaO 2 :FiO 2 ≤200, while a ≥ 20% reduction was required to significantly impact on mortality among those presenting with a PaO 2 :FiO 2  > 200 (3.7% versus 10.0%; OR 0.35; 95%CI 0.13–0.97; p  = 0.043). Conclusions in patients with COVID-19-related severe pneumonia receiving low-dose glucocorticoid treatment, even early reductions in CRP levels, together with other meaningful clinical traits, predict survival, representing a possible biomarker to guide personalized interventions. Trial registration The MEDEAS randomized controlled trial was registered on ClinicalTrials.gov on 18 November 2020 (NCT04636671).

Since the first description of COVID-19 infection, among clinical manifestations of the disease, including fever, dyspnea, cough, and fatigue, it was observed a high incidence of thromboembolic events potentially evolving towards acute respiratory distress syndrome (ARDS) and COVID-19-associated-coagulopathy (CAC). The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status of COVID-19 can be explained by the increase in coagulation levels of D-dimer, lymphocytes, fibrinogen, interleukin 6 (IL-6), and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction, and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

Importance Protein recombinant vaccine NVX-CoV2373 (Novavax) against COVID-19 was authorized for its use in adults in late 2021, but evidence on its estimated effectiveness in a general population is lacking. Objective To estimate vaccine effectiveness of a primary cycle with NVX-CoV2373 against SARS-CoV-2 infection and symptomatic COVID-19. Design, Setting, and Participants Retrospective cohort study linking data from the national vaccination registry and the COVID-19 surveillance system in Italy during a period of Omicron predominance. All adults starting a primary vaccination with NVX-CoV2373 between February 28 and September 4, 2022, were included, with follow-up ending on September 25, 2022. Data were analyzed in February 2023. Exposures Partial (1 dose only) vaccination and full vaccination (2 doses) with NVX-CoV-2373. Main Outcomes and Measures Notified SARS-CoV-2 infection and symptomatic COVID-19. Poisson regression models were used to estimate effectiveness against both outcomes. Adjusted estimated vaccine effectiveness was calculated as (1 − incidence rate ratio) × 100. Results The study included 20 903 individuals who started the primary cycle during the study period. Median (IQR) age of participants was 52 (39-61) years, 10 794 (51.6%) were female, and 20 592 participants (98.5%) had no factors associated with risk for severe COVID-19. Adjusted estimated vaccine effectiveness against notified SARS-CoV-2 infection in those partially vaccinated with NVX-CoV2373 was 23% (95% CI, 13%-33%) and was 31% (95% CI, 22%-39%) in those fully vaccinated. Estimated vaccine effectiveness against symptomatic COVID-19 was 31% (95% CI, 16%-44%) in those partially vaccinated and 50% (95% CI, 40%-58%) in those fully vaccinated. Estimated effectiveness during the first 4 months after completion of the primary cycle decreased against SARS-CoV-2 infection but remained stable against symptomatic COVID-19. Conclusions and Relevance This cohort study found that, in an Omicron-dominant period, protein recombinant vaccine NVX-CoV2373 was associated with protection against SARS-CoV-2 infection and symptomatic COVID-19. The use of this vaccine could remain an important element in reducing the impact of the SARS-CoV-2 pandemic.

ObjectivesTo assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT).DesignData from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP-DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics.ResultsWe analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At the per-patient level, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At the per-endoscopist level, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90).ConclusionThe low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes.

There are significant associations between possession of certain HLA class I alleles and rate of progression to AIDS. Immunological data provide an explanatory mechanism for this relationship. Patients with HLA types associated with rapid disease progression recognize a significantly smaller fraction of their known repertoire of viral epitopes than do patients with HLA types associated with slow progression. Population frequency of HLA types (or super-types) and their capacity to elicit cytotoxic T lymphocyte responses are also negatively correlated. These data provide an immunological mechanism to explain HLA-related risk of progression to AIDS and emphasize the central role of viral evolution in the pathogenesis of HIV.

The healthcare sector has always been compliant with the dynamics associated with social and economic sustainability. However, healthcare represents an industry with a significant environmental impact, given its characteristics (a large number of employees, buildings, and structures, complex managerial practices, and high use of consumable and investment goods). Environmental sustainability is becoming a goal and guiding principle in all sectors, including healthcare. The United Kingdom, through its National Health System - NHS and its Royal Colleges of Surgeons and Physicians, has recently taken the lead in analyzing the environmental impact on healthcare, providing healthcare managers and staff with a series of documents, including guidelines and operational checklists. According to the British analysis, in addition to more sustainable buildings and management practices devoted to saving resources, the principles of environmental sustainability should also be incorporated into medical practices. Starting from the recent literature, a multidisciplinary group of scholars designed a Delphi questionnaire. Twenty-seven Italian healthcare executives enrolled in the EMMLOS Executive Master of the University of Pavia, Italy, participated in the pilot study. The results underline the relevance of a topic gradually gaining traction in the Italian healthcare sector. However, the effective inclusion of environmentally sustainable practices in hospitals and especially within the clinical community still appears in its early infancy. Policymakers, healthcare managers, academics, and clinical scientific societies should therefore support clinical staff and users (patients, families, and citizens) in the organizational change toward more environmentally sustainable practices, leading the definition of new rules and processes, including the measurement, evaluation, and reporting of the results achieved and the dissemination and sharing of knowledge and best practices.

La morte cardiaca improvvisa costituisce una delle principali cause di morte nei paesi industrializzati. In Italia l’incidenza di questo fenomeno è stimata intorno a 0.7/1000 abitanti/anno. La morte cardiaca improvvisa è la principale causa di morte improvvisa in bambini, adolescenti e giovani adulti. Si verifica spesso in soggetti apparentemente sani e può rappresentare la prima manifestazione di una patologia cardiaca sottostante. Questa problematica è divenuta di particolare interesse da quando è stato dimostrato che i defibrillatori impiantabili sono in grado di prevenire la morte improvvisa in popolazioni selezionate ad alto rischio. L’indagine autoptica eseguita sulla vittima documenta, in un’elevata percentuale dei casi (40% circa), la presenza di una malattia cardiaca ereditaria con o senza evidente substrato morfologico (morte improvvisa non spiegata). In questo contesto, lo screening cardiologico dei familiari dei soggetti deceduti improvvisamente, oltre a poter consentire l’identificazione della malattia nei casi senza substrato morfologico, è utile per predisporre strategie di prevenzione della morte improvvisa in altri membri della stessa famiglia. In questa rassegna viene esaminata la letteratura a riguardo e vengono analizzati gli algoritmi diagnostici per lo screening delle famiglie con storia di morte improvvisa. Viene riportata inoltre l’esperienza in questo campo maturata nella Regione Lazio nel periodo compreso tra il 2001 e il 2008.