Long-term patient-reported outcome measures after injury: National trauma research action plan (NTRAP) scoping review protocol

Background: A significant proportion of patients who survive traumatic injury continue to suffer impaired functional status and increased mortality long after discharge. However, despite the need to improve long-term outcomes, trauma registries in the USA do not collect data on outcomes or care processes after discharge. One of the main barriers is the lack of consensus regarding the optimal outcome metrics.Objectives: To describe the methodology of a scoping review evaluating current evidence on the available measures for tracking functional and patient-reported outcomes after injury. The aim of the review was to identify and summarize measures that are being used to track long-term functional recovery and patient-reported outcomes among adults after injury.Methods: A systematic search of PubMed and Embase will be performed using the search terms for the population (adult trauma patients), type of outcomes (long-term physical, mental, cognitive, and quality of life), and measures available to track them. Studies identified will be reviewed and assessed for relevance by at least two reviewers. Data will be extracted and summarized using descriptive statistics and a narrative synthesis of the results. This protocol is being reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines.Dissemination: This scoping review will provide information regarding the currently available metrics for tracking functional and patient-reported outcomes after injury. The review will be presented to a multi-disciplinary stakeholder group that will evaluate these outcome metrics using an online Delphi approach to achieve consensus as part of the development of the National Trauma Research Action Plan (NTRAP). The results of this review will be presented at relevant national surgical conferences and published in peer-reviewed scientific journals

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

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

Emergency general surgery procedures in hematopoietic stem cell transplant recipients

Background: Outcomes of emergency general surgery (EGS) procedures on hematopoietic stem cell transplant (HST) recipients have not been defined in a large, national database. Whether EGS during HST engraftment admission, or in HST patients with graft versus host disease (GVHD) results in worse outcomes is unknown.Methods: The National Inpatient Sample (NIS) was examined for patients with a history of BMT between 2001 and 2014.Results: There were 520,000 HST admissions meeting inclusion criteria, of which, 14,143 (2.7%) required EGS. Of those requiring EGS, 378 (2.7%) were during engraftment admission and 13,765 (97.3%) on subsequent admission. For those requiring EGS during subsequent admission, 9,920 (72.1%) had a history of GVHD and 3,845 (27.9%) did not. On multivariate analysis, requirement of EGS was associated with mortality (OR: 1.71, 95%CI: 1.47-1.99, p \u3c 0.001). For patients requiring EGS, engraftment admission or GVHD was not associated with mortality.Conclusions: While EGS results in worse survival for the HST population, patients in their engraftment admission do not appear to be at increased mortality risk. In addition, GVHD does not worsen survival

Qualitative analysis of a cultural dexterity program for surgeons: Feasible, impactful, and necessary

Objectives: Ineffective cross-cultural communication contributes to adverse outcomes for minority patients. To address this, the authors developed a novel curriculum for surgical residents built on the principle of cultural dexterity, emphasizing adaptability to clinical and sociocultural circumstances to tailor care to the needs of the individual patient. This study\u27s objective was to evaluate the feasibility, acceptability, and perception of this program upon conclusion of its first year.Design, setting, and participants: The curriculum was implemented at 3 general surgery programs. The flipped classroom model combined independent study via e-learning modules with interactive role-playing sessions. Sessions took place over 1 academic year. Four focus groups were held, each with 6 to 9 participants, to gain feedback on the curriculum. Focus groups were recorded and transcribed, and the data were analyzed using a grounded theory approach.Results: Five major themes emerged: (1) Role modeling from senior colleagues is integral in developing communication/interpersonal skills and attitudes toward cultural dexterity. (2) Cultural dexterity is relevant to the provision of high-quality surgical care. (3) Barriers to providing culturally dexterous care exist at the system level. (4) Buy-in at all levels of the institution is necessary to implement the principles of cultural dexterity. (5) The shared experience of discussing the challenges and triumphs of caring for a diverse population was engaging and impactful.Conclusion: Early implementation of the curriculum revealed that the tension between surgical residents\u27 desire to improve their cultural dexterity and systemic/practical obstacles can be resolved. Combining surgically relevant didactic materials with experiential learning activities can change the paradigm of cross-cultural training

GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments

PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6.

To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease

PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6

Objectives To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Methods Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Results Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. Conclusions These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants