Radiation Genes: a database devoted to microarrays screenings revealing transcriptome alterations induced by ionizing radiation in mammalian cells

The analysis of the great extent of data generated by using DNA microarrays technologies has shown that the transcriptional response to radiation can be considerably different depending on the quality, the dose range and dose rate of radiation, as well as the timing selected for the analysis. At present, it is very difficult to integrate data obtained under several experimental conditions in different biological systems to reach overall conclusions or build regulatory models which may be tested and validated. In fact, most available data is buried in different websites, public or private, in general or local repositories or in files included in published papers; it is often in various formats, which makes a wide comparison even more difficult. The Radiation Genes Database (http://www.caspur.it/RadiationGenes) collects microarrays data from various local and public repositories or from published papers and supplementary materials. The database classifies it in terms of significant variables, such as radiation quality, dose, dose rate and sampling timing, as to provide user-friendly tools to facilitate data integration and comparison

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Links between chromatin structure and regulation of alternative pre-mRNA splicing in mammalian cells

Intron removal is a necessary step for expression of most genes in higher eukaryotes, and alternative splice selection is a highly regulated mechanism that endows a single gene with the possibility to codify for multiple transcripts. Pre-mRNA splicing occurs largely co-transcriptionally, and its outcome is influenced by transcription elongation and chromatin structure. In this thesis we have used two different approaches to study novel links between chromatin structure and alternative splicing regulation. In the first approach, we identified genome-wide progesterone-regulated cassette exons and compared them with nucleosome density profiles, with the aim of finding correlations between changes in nucleosome positioning and changes in alternative splicing. We find that, even if all exons harbor a well-positioned exonic nucleosome, four different classes of nucleosome density profiles can be identified around alternative exons, which strongly correlate with the DNA sequence GC content. Transitions between these profiles occur upon hormone stimulation and can be correlated with alternative splicing changes, although changes in nucleosome profiles are also observed in non-regulated exons. In particular hormone-induced exon inclusion is more frequently linked to changes in nucleosome density than hormone-induced skipped exons, which tend to have low nucleosome density profiles even before hormone treatment. Peaks of nucleosome density before alternative exons tend to correlate with exon inclusion. In the second approach, we took advantage of ENCODE data of chromatin epigenetic signatures and RNA-Seq in multiple cell lines to evaluate functional enrichment of histone modifications over alternative exons. We find that three histone modifications (H3K4me3, H3K27ac and H3K9ac) co-occur in a subset of exons when they are highly included. These features are sufficient to predict differential inclusion levels in other cell lines. Moreover, they are enriched in exons characterized by the presence of DNase hypersensitive sites, promoter signatures and RNA Pol II accumulation. These observations suggest a functional role for 3-dimensional genome structure in the regulation of alternative splicing.La eliminación de intrones es un paso necesario para expresar la mayoría de los genes en eucariotas superiores. La selección alternativa del corte y empalme (pre-mRNA splicing) es un mecanismo altamente regulado que dota a un solo gen con la posibilidad de codificar para múltiples transcritos. El splicing del pre-mRNA se produce en gran parte de manera cotranscripcional y por esto resultado está influenciado por la elongación de la transcripción y la estructura de la cromatina. En esta tesis se han utilizado dos enfoques diferentes para estudiar nuevos vínculos entre la estructura de la cromatina y la regulación del splicing alternativo. En el primer enfoque hemos identificado, a nivel de todo el genoma, exons internos regulados por progesterona y los hemos comparados con los perfiles de densidad de nucleosomas, con el objetivo de encontrar correlaciones entre los cambios en el posicionamiento de nucleosomas y en el splicing alternativo. Hemos encontrado que, aunque todos los exones albergan un nucleosoma bien posicionado, se pueden identificar cuatro clases diferentes de perfiles de densidad de nucleosomas alrededor de exones alternativos, que se correlacionan fuertemente con el contenido G+C en la secuencia del ADN. Las transiciones entre estos perfiles se producen tras la estimulación con la hormona y se pueden correlacionar con los cambios en splicing alternativo, aunque se observan también cambios en los perfiles de nucleosomas en exones no regulados. La inclusión de exones inducida por la hormona está relacionada más a menudo con cambios en la densidad de nucleosomas que la exclusión. Estos exones excluidos tienden a tener perfiles de baja densidad nucleosomal incluso antes del tratamiento hormonal. Los picos de densidad de nucleosomas antes de exones alternativos tienden a correlacionarse con la exclusión de exones. En el segundo enfoque nos aprovechamos de los datos de ENCODE de marcas epigenéticas de la cromatina y de RNA-Seq en múltiples líneas celulares, para evaluar el enriquecimiento funcional de las modificaciones de histonas en exones alternativos. Encontramos que tres modificaciones de las histonas (H3K4me3, H3K27ac y H3K9ac) co-ocurren en un subconjunto de exones mas incluidos. Estas características son suficientes para predecir los niveles de inclusión diferenciales de estos exones entre líneas celulares. Además, estos exones se caracterizan también por la presencia de sitios hipersensibles a la DNasa, de marcas de promotores y la acumulación de ARN Pol II . Estas observaciones sugieren un papel funcional para la estructura en 3 dimensiones del genoma en la regulación del splicing alternativo

Erratum to: Promoter-like epigenetic signatures in exons displaying cell type-specific splicing

Es tracta d'un erratum de l'article publicat a Promoter-like epigenetic signatures in exons displaying cell type-specific splicing-Genome Biology, 2015, 16, 236. DOI: 10.1186/s13059-015-0797-8After the publication of this work [1] an error was noticed in Fig. 7. The panel‘h’ is missing from Fig. 7. Please see the corrected figure below. The publisher apologises for this error