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digital. 2024-03-28T02:59:01ZAmbient temperature and seasonal variation in inpatient mortality from respiratory diseases: a retrospective observational study
http://hdl.handle.net/10230/59602
Ambient temperature and seasonal variation in inpatient mortality from respiratory diseases: a retrospective observational study
Achebak, Hicham; García Aymerich, Judith; Rey, Grégoire; Chen, Zhaoyue; Méndez Turrubiates, Raúl Fernando; Ballester, Joan
Background: The seasonal fluctuation in mortality and hospital admissions from respiratory diseases, with a winter peak and a summer trough, is widely recognized in extratropical countries. However, little is known about the seasonality of inpatient mortality and the role of ambient temperature remains uncertain. We aimed to analyse the association between ambient temperature and in-hospital mortality from respiratory diseases in the provinces of Madrid and Barcelona, Spain. Methods: We used data on daily hospitalisations, weather (ie, temperature and relative humidity) and air pollutants (ie, PM2.5, PM10, NO2 and O3) for the Spanish provinces of Madrid and Barcelona during 2006-2019. We applied a daily time-series quasi-Poisson regression in combination with distributed lag non-linear models (DLNM) to assess, on the one hand, the seasonal variation in fatal hospitalisations and the contribution of ambient temperature, and on the other hand, the day-to-day association between temperature and fatal hospital admissions. The analyses were stratified by sex, age and primary diagnostic of hospitalisation. Findings: The study analysed 1 710 012 emergency hospital admissions for respiratory diseases (mean [SD] age, 60.4 [31.0] years; 44.2% women), from which 103 845 resulted in in-hospital death (81.4 [12.3] years; 45.1%). We found a strong seasonal fluctuation in in-hospital mortality from respiratory diseases. While hospital admissions were higher during the cold season, the maximum incidence of inpatient mortality was during the summer and was strongly related to high temperatures. When analysing the day-to-day association between temperature and in-hospital mortality, we only found an effect for high temperatures. The relative risk (RR) of fatal hospitalisation at the 99th percentile of the distribution of daily temperatures vs the minimum mortality temperature (MMT) was 1.395 (95% eCI: 1.211-1.606) in Madrid and 1.612 (1.379-1.885) in Barcelona. In terms of attributable burden, summer temperatures (June-September) were responsible for 16.2% (8.8-23.3) and 22.3% (15.4-29.2) of overall fatal hospitalisations from respiratory diseases in Madrid and Barcelona, respectively. Women were more vulnerable to heat than men, whereas the results by diagnostic of admission showed heat effects for acute bronchitis and bronchiolitis, pneumonia and respiratory failure. Interpretation: Unless effective adaptation measures are taken in hospital facilities, climate warming could exacerbate the burden of inpatient mortality from respiratory diseases during the warm season. Funding: European Research Council Consolidator Grant EARLY-ADAPT, European Research Council Proof-of-Concept Grants HHS-EWS and FORECAST-AIR.
2023-01-01T00:00:00ZManagement of paraesophageal hiatus hernia: recommendations following a European expert Delphi consensus
http://hdl.handle.net/10230/59601
Management of paraesophageal hiatus hernia: recommendations following a European expert Delphi consensus
Gerdes, Stephan; Schoppmann, Sebastian F.; Bonavina, Luigi; Boyle, Nicholas; Müller-Stich, Beat P.; Gutschow, Christian A.; Hiatus Hernia Delphi Collaborative Group
Aims: There is considerable controversy regarding optimal management of patients with paraesophageal hiatus hernia (pHH). This survey aims at identifying recommended strategies for work-up, surgical therapy, and postoperative follow-up using Delphi methodology. Methods: We conducted a 2-round, 33-question, web-based Delphi survey on perioperative management (preoperative work-up, surgical procedure and follow-up) of non-revisional, elective pHH among European surgeons with expertise in upper-GI. Responses were graded on a 5-point Likert scale and analyzed using descriptive statistics. Items from the questionnaire were defined as "recommended" or "discouraged" if positive or negative concordance among participants was > 75%. Items with lower concordance levels were labelled "acceptable" (neither recommended nor discouraged). Results: Seventy-two surgeons with a median (IQR) experience of 23 (14-30) years from 17 European countries participated (response rate 60%). The annual median (IQR) individual and institutional caseload was 25 (15-36) and 40 (28-60) pHH-surgeries, respectively. After Delphi round 2, "recommended" strategies were defined for preoperative work-up (endoscopy), indication for surgery (typical symptoms and/or chronic anemia), surgical dissection (hernia sac dissection and resection, preservation of the vagal nerves, crural fascia and pleura, resection of retrocardial lipoma) and reconstruction (posterior crurorrhaphy with single stitches, lower esophageal sphincter augmentation (Nissen or Toupet), and postoperative follow-up (contrast radiography). In addition, we identified "discouraged" strategies for preoperative work-up (endosonography), and surgical reconstruction (crurorrhaphy with running sutures, tension-free hiatus repair with mesh only). In contrast, many items from the questionnaire including most details of mesh augmentation (indication, material, shape, placement, and fixation technique) were "acceptable". Conclusions: This multinational European Delphi survey represents the first expert-led process to identify recommended strategies for the management of pHH. Our work may be useful in clinical practice to guide the diagnostic process, increase procedural consistency and standardization, and to foster collaborative research.
2023-01-01T00:00:00ZThe impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer
http://hdl.handle.net/10230/59600
The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer
Boll, Lilian Marie; Perera Bel, Júlia; Rodriguez-Vida, Alejo; Arpí Llucià, Oriol; Rovira, Ana; Juanpere, Nuria; Vázquez Montes de Oca, Sergio; Hernández Llodrà, Silvia; Lloreta Trull, Josep, 1958-; Albà Soler, Mar; Bellmunt Molins, Joaquim, 1959-
Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment and can result in complete remissions even at advanced stages of the disease. However, only a small fraction of patients respond to the treatment. To better understand which factors drive clinical benefit, we have generated whole exome and RNA sequencing data from 27 advanced urothelial carcinoma patients treated with anti-PD-(L)1 monoclonal antibodies. We assessed the influence on the response of non-synonymous mutations (tumor mutational burden or TMB), clonal and subclonal mutations, neoantigen load and various gene expression markers. We found that although TMB is significantly associated with response, this effect can be mostly explained by clonal mutations, present in all cancer cells. This trend was validated in an additional cohort. Additionally, we found that responders with few clonal mutations had abnormally high levels of T and B cell immune markers, suggesting that a high immune cell infiltration signature could be a better predictive biomarker for this subset of patients. Our results support the idea that highly clonal cancers are more likely to respond to ICI and suggest that non-additive effects of different signatures should be considered for predictive models.
2023-01-01T00:00:00ZExploring adaptive phenotypes for the human calcium-sensing receptor polymorphism R990G
http://hdl.handle.net/10230/59599
Exploring adaptive phenotypes for the human calcium-sensing receptor polymorphism R990G
Sinigaglia, Barbara; Escudero, Jorge; Biagini, Simone Andrea, 1983-; García Calleja, Jorge; Moreno, Josep; Dobón Berenguer, Begoña, 1987-; Acosta, Sandra; Mondal, Mayukh, 1989-; Walsh Capdevila, Sandra, 1991-; Aguileta, Gabriela; Vallès, Mònica; Forrow, Stephen; Martín Caballero, Juan; Migliano, Andrea Bamberg; Bertranpetit, Jaume, 1952-; Muñoz López, Francisco José, 1964-; Bosch Fusté, Elena
Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.
2024-01-01T00:00:00Z