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    Neonatal Infection Due to SARS-CoV-2: An Epidemiological Study in Spain

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    Objective: Coronavirus disease 2019 (COVID-19) cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to increase worldwide. Although some data from pediatric series are available, more evidence is required, especially in neonates, a group with specific characteristics that deserve special attention. This study aimed to describe general and clinical characteristics, management, and treatment of postnatal-acquired (community and nosocomial/hospital-acquired) COVID-19 neonatal cases in Spain. Methods: This was a national prospective epidemiological study that included cases from a National Registry supported by the Spanish Society of Neonatology. Neonates with postnatal SARS-CoV-2 infection were included in this study. General data and infection-related information (mode and source of transmission, age at diagnosis, clinical manifestations, need for hospitalization, admission unit, treatment administered, and complementary studies performed, hospital stay associated with the infection) were collected. Results: A total of 40 cases, 26 community-acquired and 14 nosocomial were registered. Ten were preterm newborns (2 community-acquired and 8 nosocomial COVID-19 cases). Mothers (in both groups) and healthcare workers (in nosocomial cases) were the main source of infection. Hospital admission was required in 22 community-acquired cases [18 admitted to the neonatal intermediate care unit (NIMCU) and 4 to the neonatal intensive care unit (NICU)]. Among nosocomial COVID-19 cases (n = 14), previously admitted for other reasons, 4 were admitted to the NIMCU and 10 to the NICU. Ten asymptomatic patients were registered (5 in each group). In the remaining cases, clinical manifestations were generally mild in both groups, including upper respiratory airways infection, febrile syndrome or acute gastroenteritis with good overall health. In both groups, most severe cases occurred in preterm neonates or neonates with concomitant pathologies. Most of the cases did not require respiratory support. Hydroxychloroquine was administered to 4 patients in the community-acquired group and to 2 patients in the nosocomial group. Follow-up after hospital discharge was performed in most patients. Conclusions: This is the largest series of COVID-19 neonatal cases in Spain published to date. Although clinical manifestations were generally mild, prevention, treatment, and management in this group are essential

    Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

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    OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies

    Familial Recurrent Myocarditis Triggered by Exercise in Patients With a Truncating Variant of the Desmoplakin Gene

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    Background Variants of the desmosomal protein desmoplakin are associated with arrhythmogenic cardiomyopathy, an important cause of ventricular arrhythmias in children and young adults. Disease penetrance of desmoplakin variants is incomplete and variant carriers may display noncardiac, dermatologic phenotypes. We describe a novel cardiac phenotype associated with a truncating desmoplakin variant, likely causing mechanical instability of myocardial desmosomes. Methods and Results In 2 young brothers with recurrent myocarditis triggered by physical exercise, screening of 218 cardiomyopathy-related genes identified the heterozygous truncating variant p.Arg1458Ter in desmoplakin. Screening for infections yielded no evidence of viral or nonviral infections. Myosin and troponin I autoantibodies were detected at high titers. Immunohistology failed to detect any residual DSP protein in endomyocardial biopsies, and none of the histologic criteria of arrhythmogenic cardiomyopathy were fulfilled. Cardiac magnetic resonance imaging revealed no features associated with right ventricular arrhythmogenic cardiomyopathy, but multifocal subepicardial late gadolinium enhancement was present in the left ventricles of both brothers. Screening of adult cardiomyopathy cohorts for truncating variants identified the rare genetic variants p.Gln307Ter, p.Tyr1391Ter, and p.Tyr1512Ter, suggesting that over subsequent decades critical genetic/exogenous modifiers drive pathogenesis from desmoplakin truncations toward different end points. Conclusions The described novel phenotype of familial recurrent myocarditis associated with a desmoplakin truncation in adolescents likely represents a serendipitously revealed subtype of arrhythmogenic cardiomyopathy. It may be caused by a distinctive adverse effect of the variant desmoplakin upon the mechanical stability of myocardial desmosomes. Variant screening is advisable to allow early detection of patients with similar phenotypes

    PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis

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    The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC

    Play as a Method to Reduce Overweight and Obesity in Children: An RCT.

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    BACKGROUND: Overweight and obesity are the result of a complex interaction between genetic and environmental factors, which begins prenatally. AIM: To analyse an intervention based on play as a means of improving the body composition of children who are overweight or obese. METHODS: The Kids-Play study is a randomized clinical trial (RCT) consisting of 49 children aged 8-12 years on a nine-month intervention programme based on physical activity, play and nutritional advice. Controls had another 49 children, who received only nutritional advice. RESULTS: The play-based intervention achieved a moderate-vigorous level of physical activity in the study group of 81.18 min per day, while the corresponding level for the control group was only 37.34 min. At the start of the intervention, the children in the study group had an average body fat content of 41.66%, a level that decreased to 38.85% by the end of the programme. Among the control group, body fat increased from 38.83% to 41.4% during the same period. CONCLUSIONS: The intervention programme considered, based on both play and nutritional recommendations, produced a decrease in body fat among children aged 8-12 years. However, the control group, which received only nutritional recommendations, experienced an increase in body weight

    Ascertaining breast cancer patient experiences through a journey map: A qualitative study protocol.

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    BACKGROUND: The current cancer care system must be improved if we are to have in-depth knowledge about breast cancer patients' experiences throughout all the stages of their disease. AIM: This study seeks to describe breast cancer patients' experience over the course of the various stages of illness by means of a journey model. METHODS: This is a qualitative descriptive study. Individual, semi-structured interviews will be administered to women with breast cancer and breast cancer survivors. Patients will be recruited from nine large hospitals in Spain and intentional sampling will be used. Data will be collected by means of a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data will be processed adopting a thematic analysis approach. DISCUSSION: The outcomes of this study will afford new insights into breast cancer patients' experiences, providing guidance to improve the care given to these individuals. This protocol aims to describe the journey of patients with breast cancer through the healthcare system to establish baseline data that will serve as the basis for the development and implementation of a patient-centered, evidence-based clinical pathway

    Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus

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    AIM: To stablish a consensus on the treatment strategy for advanced non-small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. METHODS: After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1-9 range scale (1-3 = disagree, 7-9 = agree). Consensus was reached if 2/3 of the participants are in the median range. RESULTS: In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. CONCLUSIONS: A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations

    Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome

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    RNA-binding motif protein 3 is a molecular marker of hypothermia that has proved neuroprotective in neurodegenerative disease models. However, its relationship to the well-recognized therapeutic effect of hypothermia in ischaemic stroke had not been studied. In this work, the expression of RNA-binding motif protein 3 was investigated in ischaemic animal models subjected to systemic and focal brain hypothermia, specifically the effects of RNA-binding motif protein 3 silencing and overexpression on ischaemic lesions. Moreover, the association of RNA-binding motif protein 3 levels with body temperature and clinical outcome was evaluated in two independent cohorts of acute ischaemic stroke patients (n = 215); these levels were also determined in a third cohort of 31 patients derived from the phase III EuroHYP-1 trial of therapeutic cooling in ischaemic stroke. The preclinical data confirmed the increase of brain RNA-binding motif protein 3 levels in ischaemic animals subjected to systemic and focal hypothermia; this increase was selectively higher in the cooled hemisphere of animals undergoing focal brain hypothermia, thus confirming the direct effect of hypothermia on RNA-binding motif protein 3 expression, while RNA-binding motif protein 3 up-regulation in ischaemic brain regions led to functional recovery. Clinically, patients with body temperature <37.5 degrees C in the first two cohorts had higher RNA-binding motif protein 3 values at 24 h and good outcome at 3 months post-ischaemic stroke, while RNA-binding motif protein 3 levels in the cooled third cohort tended to exceed those in placebo-treated patients. These results make RNA-binding motif protein 3 a molecular marker associated with the effect of hypothermia in ischaemic stroke and suggest its potential application as a promising protective target

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