The impact of pipeline changes and temperature increase in a hospital historically colonised with Legionella

Healthcare-related Legionnaires' disease has a devastating impact on high risk patients, with a case fatality rate of 30-50%. Legionella prevention and control in hospitals is therefore crucial. To control Legionella water colonisation in a hospital setting we evaluated the effect of pipeline improvements and temperature increase, analysing 237 samples over a 2-year period (first year: 129, second year: 108). In the first year, 25.58% of samples were positive for Legionella and 16.67% for amoeba. Assessing the distance of the points analysed from the hot water tank, the most distal points presented higher proportion of Legionella colonisation and lower temperatures (nearest points: 6.4% colonised, and temperature 61.4 °C; most distal points: 50% and temperature 59.1 °C). After the first year, the hot water system was repaired and the temperature stabilised. This led to a dramatic reduction in Legionella colonisation, which was negative in all the samples analysed; however, amoeba colonisation remained stable. This study shows the importance of keeping the temperature stable throughout the circuit, at around 60 °C. Special attention should be paid to the most distal points of the circuit; a fall in temperature at these weak points would favour the colonisation and spread of Legionella, because amoeba (the main Legionella reservoir) are not affected by temperature

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis

Background: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team. Methods: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up. Results: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE. Conclusions: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team

Daratumumab in combination with urelumab to potentiate anti-myeloma activity in lymphocytedeficient mice reconstituted with human NK cells

Daratumumab is an anti-CD38 fully human IgG1 mAb approved for multiple myeloma treatment. One of the proposed mechanisms of action is the induction of antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells. NK cells acquire surface CD137 expression in the presence of solid-phase-attached daratumumab and when encountering a daratumumab-coated CD38+ tumor cell line. In this setting, addition of the agonist anti-CD137 mAb urelumab enhances NK-cell activation increasing CD25 expression and IFNɣ production. However, in vitro ADCC is not increased by the addition of urelumab both in 4h or 24h lasting experiments. To study urelumab-increased daratumumab-mediated ADCC activity in vivo, we set up a mouse model based on the intravenous administration of a luciferase-transfected multiple myeloma cell line of human origin, human NK cells and daratumumab to immuno-deficient NSG mice. In this model, intravenous administration of urelumab 24h after daratumumab delayed tumor growth and prolonged mice survival

Guia per a la prevenció i el control de la legionel·losi

Malaltia dels legionaris; Pneumònia; EpidemiologiaLegionnaires disease; EpidemiologyEnfermedad de los legionariosLa Guia per a la prevenció i el control de la legionel·losi actualitza la informació sobre la malaltia, integra la normativa vigent sobre el control de les instal·lacions relacionades amb la legionel·losi i aposta pel futur amb capítols relacionats amb la prevenció primària als hospitals o els mètodes de desinfecci

The Siblings With Ischemic Stroke Study (SWISS) Protocol

BACKGROUND: Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. METHODS: Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. DISCUSSION: Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members

Long-term exposure to PM10 above WHO guidelines exacerbates COVID-19 severity and mortality

Background: age, sex, race and comorbidities are insufficient to explain why some individuals remain asymptomatic after SARS-CoV-2 infection, while others die. In this sense, the increased risk caused by the long-term exposure to air pollution is being investigated to understand the high heterogeneity of the COVID-19 infection course. Objectives: we aimed to assess the underlying effect of long-term exposure to NO2 and PM10 on the severity and mortality of COVID-19. Methods: a retrospective observational study was conducted with 2112 patients suffering COVID-19 infection. We built two sets of multivariate predictive models to assess the relationship between the long-term exposure to NO2 and PM10 and COVID-19 outcome. First, the probability of either death or severe COVID-19 outcome was predicted as a function of all the clinical variables together with the pollutants exposure by means of two regularized logistic regressions. Subsequently, two regularized linear regressions were constructed to predict the percentage of dead or severe patients. Finally, odds ratios and effects estimates were calculated. Results: we found that the long-term exposure to PM10 is a more important variable than some already stated comorbidities (i.e.: COPD/Asthma, diabetes, obesity) in the prediction of COVID-19 severity and mortality. PM10 showed the highest effects estimates (1.65, 95% CI 1.32-2.06) on COVID-19 severity. For mortality, the highest effect estimates corresponded to age (3.59, 95% CI 2.94-4.40), followed by PM10 (2.37, 95% CI 1.71-3.32). Finally, an increase of 1 µg/m3 in PM10 concentration causes an increase of 3.06% (95% CI 1.11%-4.25%) of patients suffering COVID-19 as a severe disease and an increase of 2.68% (95% CI 0.53%-5.58%) of deaths. Discussion: these results demonstrate that long-term PM10 burdens above WHO guidelines exacerbate COVID-19 health outcomes. Hence, WHO guidelines, the air quality standard established by the Directive 2008/50/EU, and that of the US-EPA should be updated accordingly to protect human health