Introducción: datos de varios países del mundo sugieren que los niños con COVID-19 podrían presentar síntomas diferentes y menos graves que los adultos. Sin embargo, los patrones epidemiológicos y ...clínicos en este grupo poblacional son poco claros. Métodos: el presente es un estudio observacional, con una caracterización inicial transversal-analítica, y con un componente longitudinal o de seguimiento a un grupo de menores con sospecha y/o diagnóstico confirmado de COVID-19, que presentaron desenlaces como mejoría, traslado a un nivel superior de atención o defunción por sintomatología respiratoria. Los niños recibieron atención médica en el Hospital General Regional con Medicina Familiar N.o 1 (HGR C/MF N.o 1), y se les realizó prueba de reacción en cadena de la polimerasa en tiempo real (RT-PCR). Resultados: se estudiaron 98 niños como casos sospechosos para COVID-19, a quienes se les realizó RT-PCR. Del total, 24 resultaron positivos y 74 fueron negativos. La mediana de edad de los participantes fue 64,4 meses (0 a 203 meses), 55 menores eran de sexo masculino, 59 niños tuvieron manejo ambulatorio, y de estos 14 presentaron resultado positivo. Entre los que requirieron manejo hospitalario (39), 10 niños dieron positivo para SARS-CoV-2, y, de estos, 84,7% alcanzaron mejoría y fueron dados de alta; 4 fueron trasladados a hospitales de nivel superior de atención. De los 98 niños en estudio, 11 fallecieron, 7 con resultado negativo y 4 con resultado positivo para SARS-CoV-2.
Background
Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes.
Objective
The aim of this study was to evaluate the ...effectiveness, safety and economic cost of nivolumab in real-world clinical practice.
Setting
Fifteen regional and academic hospitals from Spain participated in this study.
Methods
This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system.
Main outcome measures
Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable.
Results
A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0–1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8–8.1). The median PFS was 5.3 months (95% CI 3.2–7.3), and OS was 9.7 months (95% CI 7.6–11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0–1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00–€231,171.00).
Conclusions
This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0–1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.
Numerous socio‐economic activities depend on the seasonal rainfall and groundwater recharge cycle across the Central American Isthmus. Population growth and unregulated land use changes resulted in ...extensive surface water pollution and a large dependency on groundwater resources. This work combines stable isotope variations in rainfall, surface water, and groundwater of Costa Rica, Nicaragua, El Salvador, and Honduras to develop a regionalized rainfall isoscape, isotopic lapse rates, spatial–temporal isotopic variations, and air mass back trajectories determining potential mean recharge elevations, moisture circulation patterns, and surface water–groundwater interactions. Intra‐seasonal rainfall modes resulted in two isotopically depleted incursions (W‐shaped isotopic pattern) during the wet season and two enriched pulses during the mid‐summer drought and the months of the strongest trade winds. Notable isotopic sub‐cloud fractionation and near‐surface secondary evaporation were identified as common denominators within the Central American Dry Corridor. Groundwater and surface water isotope ratios depicted the strong orographic separation into the Caribbean and Pacific domains, mainly induced by the governing moisture transport from the Caribbean Sea, complex rainfall producing systems across the N‐S mountain range, and the subsequent mixing with local evapotranspiration, and, to a lesser degree, the eastern Pacific Ocean fluxes. Groundwater recharge was characterized by (a) depleted recharge in highland areas (72.3%), (b) rapid recharge via preferential flow paths (13.1%), and enriched recharge due to near‐surface secondary fractionation (14.6%). Median recharge elevation ranged from 1,104 to 1,979 m a.s.l. These results are intended to enhance forest conservation practices, inform water protection regulations, and facilitate water security and sustainability planning in the Central American Isthmus.
Groundwater and surface water isotope ratios depicted the strong orographic separation into the Caribbean and Pacific domains.
Groundwater recharge was characterized by (a) depleted recharge in highland areas (72.3%), (b) rapid recharge via preferential flow paths (13.1%), and enriched recharge due to near‐surface secondary fractionation (14.6%).
Median recharge elevation ranged from 1,104 to 1,979 m a.s.l.
Monkeypox is the most prevalent Orthopoxvirus zoonosis infection since the eradication of smallpox. The current multi-country outbreak involves five WHO regions affecting mainly Europe. Accurate ...clinical and virological aspects of the disease outside endemic areas are needed.
We performed an observational study of cases diagnosed in Madrid (Spain) (May/June 2022). Confirmation from vesicular lesions swabs, Orthopoxvirus real-time PCR, sequencing, phylogenetic analysis, and direct detection by Electron microscopy was performed. In addition, a structured epidemiological questionnaire was completed systematically to gather sociodemographic, clinical, and behavioral data from all confirmed cases.
We extracted data from 48 patients, all cisgender men. The median age was 35 years (IQR 29 - 44), and 87.5% were MSM. The most prevalent symptoms were the presence of vesicular-umbilicated and pseudo-pustular skin lesions (93.8%), asthenia (66.6%), and fever (52.1%). In addition, the location of the lesions in the genital or perianal area was related to the role in sexual intercourse (p<0.001). Sequencing analysis indicated the virus circulating in Spain belongs to the western African clade. Like the other European cases in the outbreak, the Spanish isolates are a direct descendant of viruses previously detected in Nigeria, the UK, Singapore, and Israel in 2017-2018.
Monkeypox is an emerging infectious disease in Europe where community transmission is reported, mainly in MSM. The first symptom was skin lesions instead of classical fever and rash. The disease follows a self-limited course, and there have been no cases with a serious presentation or severe complications.
Aim
Severe functional tricuspid regurgitation (FTR) is associated with high risk of cardiovascular events, particularly heart failure (HF) and mortality. MicroRNAs (miRNAs) have been recently ...identified as novel biomarkers in different cardiovascular conditions, but no studies have focused on FTR. We sought to (1) to identify and validate circulating miRNAs as regulators of FTR and (2) to test association of miRNA with heart failure and mortality in FTR.
Methods and results
Consecutive patients with isolated severe FTR (n = 100) evaluated in the outpatient Heart Valve Clinic and age‐ and gender‐matched subjects with no TR (controls, n = 50) were prospectively recruited. The experimental design included (1) a screening phase to identify candidate miRNA differentially expressed in FTR (n = 8) compared with controls (n = 8) through miRNA array profiling of 192 miRNAs using quantitative reverse transcription PCR arrays qRT‐PCR) and (2) a validation phase in which candidate miRNAs identified in the initial screening were selected for further validation by qRT‐PCR in a prospectively recruited cohort of FTR (n = 92) and controls (n = 42). Bioinformatics analysis was used to predict their potential target genes and functional pathways elicited. A combined endpoint of hospital admission due to heart failure (HF) and all‐cause mortality was defined. Initial screening identified 16 differentially expressed miRNAs in FTR compared with controls, subsequently confirmed in the validation phase (n = 16 were excluded due to significant haemolysis). miR‐186‐5p, miR‐30e‐5p, and miR‐152‐3p identified FTR with high predictive value AUC of 0.93 (0.88–0.97), 0.83 (0.75–0.91) and 0.84 (0.76–0.92), respectively. During a median follow‐up of 20.4 months (IQR 8–35 months), 32% of FTR patients reached the combined endpoint. Patients with low relative expression of miR‐15a‐5p, miR‐92a‐3p, miR101‐3p, and miR‐363‐3p, miR‐324‐3p, and miR‐22‐3p showed significantly higher rates of events (log‐rank test for all P < 0.01). Both miR‐15a‐5p hazard ratio: 0.21 (0.06–0.649, P = 0.007) and miR‐92a‐3p (0.27 (0.09–0.76), P = 0.01 were associated with outcomes after adjusting for age, gender, and New York Heart Association functional class.
Conclusions
Circulating miRNAs are novel diagnostic and prognostic biomarkers in severe FTR. The quantification of miR‐186‐5p, miR‐30e‐5p, and miR‐152‐3p held strong diagnostic value, and the quantification of miR‐15a‐5p and miR‐92a‐3p are independently associated with outcomes. The recognition of specific miRNAs offers a novel perspective for TR evaluation.
Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to ...study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention.
Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011.
Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NFκB, IκBα, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors.
Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.
Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes ...have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase.
Background
Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction ...with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors.
Study Design
405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis‐Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS‐SZ) and interactions between these.
Results
Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case–control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS‐SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe.
Conclusions
We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.
We reported that a Mediterranean Diet (MedDiet), supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence and several other adverse outcomes. In order to assess its ...translational effects in the real world we evaluated the effect of MedDiet from 1st gestational visit in GDM rate compared with control (CG) and intervention (IG) groups from the previously referred trial. As secondary objective we also compared adverse perinatal outcomes between normoglycemic and diabetic women. This trial is a prospective, clinic-based, interventional study with a single group. 1066 eligible normoglycaemic women before 12 gestational weeks were assessed. 932 women (32.4 ± 5.2 years old, pre-gestational BMI 22.5 ± 3.5 kg/m
) received a motivational lifestyle interview with emphasis on daily consumption of EVOO and nuts, were followed-up and analysed. Binary regression analyses were used to examine the risk for each pregnancy outcome, pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), caesarean-section, perineal trauma, preterm delivery, small (SGA) and large for gestational age (LGA), and Neonatal Intensive Care Unit admissions. GDM was diagnosed in 13.9%. This rate was significantly lower than the CG: RR 0.81 (0.73-0.93),
< 0.001 and no different from the IG: RR 0.96 (0.85-1.07),
= 0.468. GWG was lower in diabetic women (10.88 ± 6.46 vs. 12.30 ± 5.42 Kg;
= 0.013). Excessive weight gain (EWG) was also lower in GDM RR 0.91 (0.86-0.96);
< 0.001 without a significant increase of insufficient weight gain. LGA were also lower (1 (0.8%) vs. 31 (3.9%);
< 0.05)), and SGA were similar (5 (3.8%) vs. 30 (3.7%)). LGA were associated to EWG (RR 1.61 (1.35-1.91),
< 0.001). Differences in other maternal-foetal outcomes were not found. In conclusions an early MedDiet nutritional intervention reduces GDM incidence and maternal-foetal adverse outcomes and should be universally applied as 1st line therapy. GDM might not be consider as a high risk pregnancy any longer.
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