Genetics and clinical phenotype of Erdheim–Chester disease: A case report of constrictive pericarditis and a systematic review of the literature

Background: Erdheim–Chester disease (ECD) is a rare form of histiocytosis. An increasing number of genetic mutations have been associated with this syndrome, confirming its possible neoplastic origin. Recently, a connection between the BRAF mutational status and a specific phenotype was described; however, no studies have yet evaluated the correlations between other mutations and the clinical features of the disease. Objectives: This study aims to clarify the association between the clinical phenotype and genetic mutations identified in the neoplastic cell lines of ECD. Methods: We describe a case of ECD characterized by pericardial involvement and a KRAS mutation shared with chronic myelomonocytic leukemia. Hence, through a meta-analysis of individual participant data of all genetically and clinically described cases of ECD in the literature, we aimed to elucidate the association between its clinical phenotype and baseline genetic mutations. Results: Of the 760 studies screened, our review included 133 articles published from 2012 to April 2021. We identified 311 ECD patients whose genotype and phenotype were described. We found five main genes (BRAF, KRAS, NRAS, PIK3CA, and MAP2K1) whose mutation was reported at least three times. Mutation of BRAF led to a neurological disease (183 of 273 patients, 67%; p < 0.001); KRAS- and NRAS-mutated patients mainly showed cutaneous (five of six patients, 83.3%, p < 0.004) and pleural (four of nine patients, 44%, p = 0.002) involvement, respectively; PIK3CA was not associated with specific organ involvement; and MAP2K1 mutations caused the disease to primarily involve the peritoneum and retroperitoneum (4 of 11, 36.4%, p = 0.01). Conclusion: This work implies a possible influence of baseline mutation over the natural history of ECD, underscoring the importance of a thorough genetic analysis in all cases with the ultimate goal of identifying a possible targeted therapy for each patient

Off-label use of covid-19 vaccines from ethical issues to medico-legal aspects: An italian perspective

During the COVID-19 outbreak, the lack of official recommendations on the treatment has led healthcare workers to use multiple drugs not specifically tested and approved for the new insidious disease. After the availability of the first COVID-19 vaccines (Comirnaty Pfizer-BioNTech and Moderna COVID19 vaccine), an authorization was issued by national and international Drug Regulatory Agencies in order to speed up their introduction on the market and their administration on a large scale. Despite the authorization, the off-label use of these vaccines may still be possible especially to answer specific concerns as the lack of vaccine doses, the delay in the delivery of planned doses or the pressure from public opinion and political influence also in relation to the evolution of the pandemic. This paper aims to assess the possible off-label use of COVID-19 vaccines and the ethical and medico-legal implications of this eventuality. The scope of this paper is to point out the possible consequences of off-label use of COVID-19 vaccines and possible mitigation and preventive measures to be taken by healthcare workers involved in vaccination procedures

The Black Sea Physics Analysis and Forecasting System within the Framework of the Copernicus Marine Service

This work describes the design, implementation and validation of the Black Sea physics analysis and forecasting system, developed by the Black Sea Physics production unit within the Black Sea Monitoring and Forecasting Center as part of the Copernicus Marine Environment and Monitoring Service. The system provides analyses and forecasts of the temperature, salinity, sea surface height, mixed layer depth and currents for the whole Black Sea basin, excluding the Azov Sea, and has been operational since 2016. The system is composed of the NEMO (v 3.4) numerical model and an OceanVar scheme, which brings together real time observations (in-situ temperature and salinity profiles, sea level anomaly and sea surface temperature satellite data). An operational quality assessment framework is used to evaluate the accuracy of the products which set the basic standards for the future upgrades, highlighting the strengths and weaknesses of the model and the observing system in the Black Sea

Lymphatic Function of the Lower Limb after Groin Dissection for Vulvar Cancer and Reconstruction with Lymphatic SCIP Flap

Inguinofemoral lymphadenectomy, frequently performed for vulvar cancer, is burdened with substantial immediate and long-term morbidity. One of the most disabling treatment-related sequelae is lower limb lymphedema (LLL). The present study aims to describe the wound complications and the severity of LLL in patients who have undergone groin dissection for vulvar cancer and immediate inguinal reconstruction with the Lymphatic Superficial Circumflex Iliac Perforator flap (L-SCIP). We retrospectively reviewed the data of patients who underwent bilateral groin dissection and unilateral inguinal reconstruction with the L-SCIP. The presence and severity of postoperative LLL during the follow-up period were assessed by lymphoscintigraphy and limbs’ volume mea-surement. In addition, immediate complications at the level of the inguinal area were registered. The changes between preoperative and postoperative limb volumes were analyzed by Student’s t test. p values < 0.05 were considered significant. Thirty-one patients were included. The mean variation of volume was 479 ± 330 cc3 in the side where groin reconstruction had been performed, and 683 ± 425 cc3 in the contralateral side, showing smaller variation in the treated side (p = 0.022). Lymphoscintigraphy confirmed the clinical findings. Based on our results, inguinal reconstruction with L-SCIP performed at the same time of groin dissection in patients treated for vulvar cancer can provide a significant protective effect on LLL

A Possible Outbreak by Serratia Marcescens: Genetic Relatedness between Clinical and Environmental Strains

Serratia marcescens (SM) is a Gram-negative bacterium that is frequently found in the environment. Since 1913, when its pathogenicity was first demonstrated, the number of infections caused by SM has increased. There is ample evidence that SM causes nosocomial infections in immunocompromised or critically ill patients admitted to the intensive care units (ICUs), but also in newborns admitted to neonatal ICUs (NICUs). In this study, we evaluated the possible genetic correlation by PFGE between clinical and environmental SM strains from NICU and ICU and compared the genetic profile of clinical strains with strains isolated from patients admitted to other wards of the same hospital. We found distinct clonally related groups of SM strains circulating among different wards of a large university hospital. In particular, the clonal relationship between clinical and environmental strains in NICU and ICU 1 was highlighted. The identification of clonal relationships between clinical and environmental strains in the wards allowed identification of the epidemic and rapid implementation of adequate measures to stop the spread of SM

Black sea observing system

The ultimate goal of modern operational oceanography are end user oriented products with high scientific quality. Beneficiaries are the governmental services, coast and offshore based enterprises and research institutions that make use of the products generated by operational oceanography. Direct users are coastal managers, shipping, search and rescue, oil spill combat, offshore industry, ports, fishing, tourism, and recreation industry. Indirect beneficiaries, through climate forecasting based on ocean observations, are food, energy, water and medical suppliers. Availability of updated information on the actual state as well as forecast of marine environment is essential for the success and safety of maritime operations in the offshore industry. Various systems for the collection and presentation of marine data for the needs of different users have been developed and put in operation in the Black Sea. The systems are located both along the coast and in the open sea and the information they provide is used by both the maritime industry and the widest range of users. The Black Sea Monitoring and Forecasting Center in the frame of the Copernicus Marine Service is providing regular and systematic information about the physical state of the ocean, marine ecosystem and wave conditions in the Black Sea area, assimilating observations, keeping efficient operations, advanced technology and high quality modeling products. Combining and optimizing in situ, remote sensing, modeling and forecasting into a Black Sea observing system is a task that has to be solved, and that will allow to get a more complete and comprehensive picture of the state of the marine environment as well as to forecast future changes of physical and biogeochemical state of the Black Sea and the Black Sea ecosystem

Potential use of untreated wastewater for assessing COVID-19 trends in southern Italy

As a complement to clinical disease surveillance, the monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in wastewater can be used as an early warning system for impending epidemics. This study investigated the dynamics of SARS-CoV-2 in untreated wastew-ater with respect to the trend of coronavirus disease 2019 (COVID-19) prevalence in Southern Italy. A total of 210 wastewater samples were collected between May and November 2020 from 15 Apulian wastewater treatment plants (WWTP). The samples were concentrated in accordance with the stan-dard of World Health Organization (WHO, Geneva, Switzerland) procedure for Poliovirus sewage surveillance, and molecular analysis was undertaken with real-time reverse-transcription quantitative PCR (RT-(q) PCR). Viral ribonucleic acid (RNA) was found in 12.4% (26/210) of the samples. The virus concentration in the positive samples ranged from 8.8 × 102 to 6.5 × 104 genome copies/L. The receiver operating characteristic (ROC) curve modeling showed that at least 11 cases/100,000 inhabitants would occur after a wastewater sample was found to be positive for SARS-CoV-2 (sensi-tivity = 80%, specificity = 80.9%). To our knowledge, this is the first study in Italy that has applied wastewater-based epidemiology to predict COVID-19 prevalence. Further studies regarding methods that include all variables (meteorological phenomena, characteristics of the WWTP, etc.) affecting this type of wastewater surveillance data would be useful to improve data interpretation

Performance of Prognostic Scoring Systems in MINOCA: A Comparison among GRACE, TIMI, HEART, and ACEF Scores

Background: the prognosis of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is not benign; thus, prompting the need to validate prognostic scoring systems for this population. Aim: to evaluate and compare the prognostic performance of GRACE, TIMI, HEART, and ACEF scores in MINOCA patients. Methods: A total of 250 MINOCA patients from January 2017 to September 2021 were included. For each patient, the four scores at admission were retrospectively calculated. The primary outcome was a composite of all-cause death and acute myocardial infarction (AMI) at 1-year follow-up. The ability to predict 1-year all-cause death was also tested. Results: Overall, the tested scores presented a sub-optimal performance in predicting the composite major adverse event in MINOCA patients, showing an AUC ranging between 0.7 and 0.8. Among them, the GRACE score appeared to be the best in predicting all-cause death, reaching high specificity with low sensitivity. The best cut-off identified for the GRACE score was 171, higher compared to the cut-off of 140 generally applied to identify high-risk patients with obstructive AMI. When the scores were tested for prediction of 1-year all-cause death, the GRACE and the ACEF score showed very good accuracy (AUC = 0.932 and 0.828, respectively). Conclusion: the prognostic scoring tools, validated in AMI cohorts, could be useful even in MINOCA patients, although their performance appeared sub-optimal, prompting the need for risk assessment tools specific to MINOCA patients

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

Background: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. Methods: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). Results: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). Conclusion: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated

Measurement of isotopic separation of argon with the prototype of the cryogenic distillation plant Aria for dark matter searches

The Aria cryogenic distillation plant, located in Sardinia, Italy, is a key component of the DarkSide-20k experimental program for WIMP dark matter searches at the INFN Laboratori Nazionali del Gran Sasso, Italy. Aria is designed to purify the argon, extracted from underground wells in Colorado, USA, and used as the DarkSide-20k target material, to detector-grade quality. In this paper, we report the first measurement of argon isotopic separation by distillation with the 26 m tall Aria prototype. We discuss the measurement of the operating parameters of the column and the observation of the simultaneous separation of the three stable argon isotopes: 36Ar , 38Ar , and 40Ar . We also provide a detailed comparison of the experimental results with commercial process simulation software. This measurement of isotopic separation of argon is a significant achievement for the project, building on the success of the initial demonstration of isotopic separation of nitrogen using the same equipment in 2019