👤 Neus Amer Salas

Real-world evidence on nirsevimab impact beyond the first season when given under universal immunisation programmes is emerging. We aimed to assess the medium-term impact of universal infant respiratory syncytial virus (RSV) prophylaxis with nirsevimab across inpatient and outpatient settings during two consecutive RSV seasons. NIRSE-GAL is an ongoing, population-based, prospective, longitudinal study in Galicia, Spain. For this study, we included all infants eligible for nirsevimab in the 2023-24 RSV campaign in Galicia, followed up from their first RSV season (2023-24) until the end of their second RSV season (2024-25). The primary endpoint was RSV-related lower respiratory tract infection (LRTI) hospitalisation. Secondary endpoints were LRTI hospitalisation, acute bronchitis or bronchiolitis hospitalisation, pneumonia admissions, all-cause hospitalisations, and primary health-care outcomes (acute bronchitis or bronchiolitis, wheezing or asthma, LRTI, respiratory infections, acute otitis media, and all otitis diagnoses). The first recurrences of these endpoints were also assessed as secondary endpoints. Impact was estimated by Poisson regression models using weekly incidence rates of historical non-pandemic seasons (2017-18 to 2022-23) as comparators, adjusted for RSV seasonality, and evaluated across three follow-up periods: the first RSV season, the second RSV season, and up to 18 months. This study is registered with ClinicalTrials.gov, NCT06180993. Of 12 492 eligible infants, 11 796 received nirsevimab (94·4% coverage). Compared with historical cohorts, RSV-related LRTI hospitalisations decreased by 85·9% (95% CI 80·2-90·0) in the first season and 55·3% (22·5-74·3) in the second, with an estimated 123 infants needing to be immunised to prevent a second-season admission. First LRTI hospitalisations decreased by 59·8% (46·5-69·8) in the first season and 48·1% (33·1-59·7) up to 18 months. Acute bronchitis or bronchiolitis admissions decreased by 59·0% (37·9-72·9) in the first season and 58·7% (40·6-71·3) up to 18 months. All-cause hospitalisation declined by 20·3% (3·1-34·4) in the first season, with no significant reduction thereafter. First recurrent admissions in the second season decreased by 78·2% (25·6-93·6) for RSV-related LRTI, 62·4% (30·9-79·6) for LRTI, and 76·9% (5·3-94·4) for acute bronchitis or bronchiolitis. First outpatient visits declined during the first season by 30·8% (17·5-41·9) for bronchitis or bronchiolitis, 33·4% (21·6-43·4) for LRTI, and 27·7% (14·9-38·5) for wheezing or asthma. First recurrent outpatient visits also declined, by 52·5% (39·7-62·6) for acute bronchitis or bronchiolitis, 28·2% (17·8-37·3) for wheezing or asthma, and 47·3% (35·3-57·2) for LRTI. Universal infant nirsevimab prophylaxis markedly reduced RSV-related hospitalisations and outpatient morbidity, with sustained reductions in RSV-related LRTI hospitalisations into the second season and no signal of adverse shift in RSV morbidity. These findings provide robust population-level evidence that could be valuable for infant immunisation policies and cost-effectiveness models. Sanofi and AstraZeneca. For the Spanish translation of the abstract see Supplementary Materials section. Show less

Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805-0.880), Show less

Hypertrophic cardiomyopathy (HCM) is characterized by a heterogeneous presentation and clinical course. A minority of HCM patients develop end-stage HCM and require cardiac transplantation. The genetic basis of end-stage HCM is unknown but small series, isolated case reports and animal models have related the most aggressive heart failure course with the presence of multiple mutations. Twenty-six patients (age 40.4 ± 14.5 years; 46% male) transplanted for end-stage HCM underwent genetic screening of 10 HCM-related genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, TNNC1, MYL3, MYL2, ACTC, LDB3). Additional genetic screening of LAMP2/PRKAG2 and mitochondrial DNA (mtDNA) was performed in four and three cases, respectively. Findings were correlated with clinical and histological features. Pathogenic mutations were identified in 15 patients (58%). Thirteen patients (50%) had mutations in sarcomeric genes (six in MYH7, three in MYBPC3, two in MYL2, one in TNNI3, and one in MYL3) and two patients had mutations in LAMP2. Only three patients (13%) had double mutations and all in homozygosis. Except for a more frequent family history of HCM, patients with mutations in sarcomeric genes did not show any clinical feature that distinguished them from patients without mutations in these genes. Evaluation of 44 relatives from 12 families identified 13 mutation carriers, 9 of whom had an overt HCM phenotype. Heart transplanted HCM has a heterogeneous genetic background where multiple mutations are uncommon. The clinical course of HCM is not primarily dependent on the presence of multiple sarcomeric mutations. Clinical and genetic evaluation of relatives does not support differential clinical management in HCM based on genetics. Show less

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% saturated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (< 10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrate, 38% fat (22% monounsaturated, < 10% saturated)]. At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT). Apo C-III genotype significantly affected basal glucose concentrations (P < 0.045) and insulin concentrations after the OGTT (P < 0.012). APOC3*S1/APOC3*S2 subjects (n = 13) had higher insulin concentrations after the OGTT than APOC3*S1/APOC3*S1 subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regression analysis showed that this polymorphism predicted the insulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest that the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sensitivity to insulin, especially when persons consume diets rich in saturated fat. Show less

The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. The SstI polymorphism, arising from a cytosine to guanosine substitution in the 3' untranslated region of the APOC3 gene distinguishes between two alleles--S1 and S2. The S2 allele has been associated with elevated plasma triacylglycerol, cholesterol, and apolipoprotein (apo) C-III concentrations. In 90 young men we examined the effect of the same mutation on the response of low-density-lipoprotein (LDL) cholesterol to dietary monounsaturated fat. The frequency for the S2 allele was 0.14. Subjects were fed a low-fat diet for 25 d, followed by a diet rich in monounsaturated fatty acid (22% MUFA, 38% total fat) for 28 d; lipoproteins were measured at the end of each diet. There were no significant differences in initial total cholesterol between subjects with the APOC3*S1/APOC3*S1 (S1/S1) and APOC3*S1/APOC3*S2 (S1/S2) genotypes. After consumption of the diet high in MUFA, significant increases in LDL cholesterol (0.13 mmol/L, P < 0.027) were noted in the S1/S1 subjects whereas a significant decrease was observed in the S1/S2 subjects (-0.18 mmol/L, P < 0.046). Significant genotypic effects were seen for diet-induced changes in LDL cholesterol (P < 0.00034), total cholesterol (P < 0.009), and apo B (P < 0.0014). A study of the effect of the interaction between this mutation with that present in position -76 of the APOA1 gene promoter region (G/A) revealed that both mutations had an additive effect on changes in total cholesterol, LDL cholesterol, and apo B induced by diets. Plasma LDL-cholesterol responsiveness to the diet may be explained, at least in part, by variation at the APOC3 gene locus. Show less