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

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

ChatGPT-4 generates orthopedic discharge documents faster than humans maintaining comparable quality : a pilot study of 6 cases

Background and purpose - Large language models like ChatGPT-4 have emerged. They hold the potential to reduce the administrative burden by generating everyday clinical documents, thus allowing the physician to spend more time with the patient. We aimed to assess both the quality and efficiency of discharge documents generated by ChatGPT-4 in comparison with those produced by physicians. Patients and methods - To emulate real -world situations, the health records of 6 fictional orthopedic cases were created. Discharge documents for each case were generated by a junior attending orthopedic surgeon and an advanced orthopedic resident. ChatGPT-4 was then prompted to generate the discharge documents using the same health record information. The quality assessment was performed by an expert panel (n = 15) blinded to the source of the documents. As secondary outcome, the time required to generate the documents was compared, logging the duration of the creation of the discharge documents by the physician and by ChatGPT-4. Results - Overall, both ChatGPT-4 and physiciangenerated notes were comparable in quality. Notably, ChatGPT-4 generated discharge documents 10 times faster than the traditional method. 4 events of hallucinations were found in the ChatGPT-4-generated content, compared with 6 events in the human/physician produced notes. Conclusion - ChatGPT-4 creates orthopedic discharge notes faster than physicians, with comparable quality. This shows it has great potential for making these documents more efficient in orthopedic care. ChatGPT-4 has the potential to significantly reduce the administrative burden on healthcare professionals

ARTIFICIAL INTELLIGENCE ACCURATELY DETECTS TRAUMATIC THORACOLUMBAR FRACTURES ON SAGITTAL RADIOGRAPHS

AbstractBackground contextTraumatic thoracolumbar (TL) fractures are frequently encountered in emergency rooms. Sagittal and anteroposterior radiographs are the first step in the trauma routine imaging. Up to 30% of TL fractures are missed in this imaging modality, thus requiring a CT and/or MRI to confirm the diagnosis. A delay in treatment leads to increased morbidity, mortality, exposure to ionizing radiation and financial burden. Fracture detection with Machine Learning models has achieved expert level performance in previous studies. Reliably detecting vertebral fractures in simple radiographic projections would have a significant clinical and financial impact.PurposeTo develop a deep learning model that detects traumatic fractures on sagittal radiographs of the TL spine.Study design/settingRetrospective Cohort study.MethodsWe collected sagittal radiographs, CT and MRI scans of the TL spine of 362 patients exhibiting traumatic vertebral fractures. Cases were excluded when CT and/or MRI where not available. The reference standard was set by an expert group of three spine surgeons who conjointly annotated the sagittal radiographs of 171 cases. CT and/or MRI were reviewed to confirm the presence and type of the fracture in all cases. 302 cropped vertebral images were labelled ‘fracture’ and 328 ‘no fracture’. After augmentation, this dataset was then used to train, validate, and test deep learning classifiers based on ResNet18 and VGG16 architectures. To ensure that the model’s prediction was based on the correct identification of the fracture zone, an Activation Map analysis was conducted.ResultsVertebras T12 to L2 were the most frequently involved, accounting for 48% of the fractures. A4, A3 and A1 were the most frequent AO Spine fracture types. Accuracies of 88% and 84% were obtained with ResNet18 and VGG16 respectively. The sensitivity was 89% with both architectures but ResNet18 showed a higher specificity (88%) compared to VGG16 (79%). The fracture zone was precisely identified in 81% of the heatmaps.ConclusionsOur AI model can accurately identify anomalies suggestive of vertebral fractures in sagittal radiographs by precisely identifying the fracture zone within the vertebral body.Clinical significanceClinical implementation of a diagnosis aid tool specifically trained for TL fracture identification is anticipated to reduce the rate of missed vertebral fractures in emergency rooms.</jats:sec

Demographics and clinical features of humeral shaft fractures: the Latin American multicentre prospective study (HSF-LAMPS)

To present transversal data (demographic and clinical) on isolated humeral shaft fractures (HSFs) in Latin American countries. Methods: Patients were enrolled between December 2015 and April 2017 at 11 medical institutions from six Latin America countries. Inclusion criteria: Age >= 18 years and a closed, isolated 12A, 12B, or 12C fracture (Arbeitsgemeinschaft fur Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) classification). The patients' demographic, comorbidity, and other baseline data were recorded. The outcome measures included the basal results of the research and the associations among the demographic factors, fracture features, and type of treatment applied. Results: A total of 123 patients were included. There was a preponderance of men (61.8%), whose mean age was significantly lower than that of the women (31.48 vs. 60.55). Overweight or obesity was present in 61.0% of women; 56.1% of patients were sedentary, 75.6% were nonsmokers, and 74.0% had no chronic disease. The type or treatment (operative/nonoperative) was not significantly associated with the patient's or fracture's characteristics. Falls and traffic accidents were the main causes of HSFs. Intramedullary nailing treatment was performed significantly more often in women, elderly patients, patients who did not participate in sports, and patients participating in only home activities. Minimally invasive plate osteosynthesis was performed significantly more frequently in men and in those who were self-employed. Open reduction internal fixation was performed significantly more often when the cause of the fracture was a traffic accident and when radial nerve palsy was present. Conclusion: The demographics and etiological differences observed in comparison to the current literature show the importance of regional studies for both preventive measures and educational guidance2731

Surgical site infection after gastrointestinal surgery in children : an international, multicentre, prospective cohort study

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.Peer reviewe