Perioperative mortality in bariatric surgery: meta-analysis.

BACKGROUND: Bariatric surgery is an established treatment for severe obesity; however, fewer than 1 per cent of eligible patients undergo surgery. The perceived risk of surgery may contribute to the low uptake. The aim of this study was to determine perioperative mortality associated with bariatric surgery, comparing different operation types and data sources. METHODS: A literature search of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was conducted to identify studies published between 1 January 2014 and 31 July 2020. Inclusion criteria were studies of at least 1000 patients reporting short-term mortality after bariatric surgery. Data were collected on RCTs. Meta-analysis was performed to establish overall mortality rates across different study types. The primary outcome measure was perioperative mortality. Different operation types were compared, along with study type, in subgroup analyses. The study was registered at PROSPERO (2019: CRD 42019131632). RESULTS: Some 4356 articles were identified and 58 met the inclusion criteria. Data were available on over 3.6 million patients. There were 4707 deaths. Pooled analysis showed an overall mortality rate of 0.08 (95 per cent c.i. 0.06 to 0.10; 95 per cent prediction interval 0 to 0.21) per cent. In subgroup analysis, there was no statistically significant difference between overall, 30-day, 90-day or in-hospital mortality (P = 0.29). There was no significant difference in reported mortality for RCTs, large studies, national databases or registries (P = 0.60). The pooled mortality rates by procedure type in ascending order were: 0.03 per cent for gastric band, 0.05 per cent for sleeve gastrectomy, 0.09 per cent for one-anastomosis gastric bypass, 0.09 per cent for Roux-en-Y gastric bypass, and 0.41 per cent for duodenal switch (P < 0.001 between operations). CONCLUSION: Bariatric surgery is safe, with low reported perioperative mortality rates.

Weight loss surgery helps patients with severe obesity. This study looked at the risk of dying after weight loss surgery in over 3.6 million patients. The risk was less than 1 in 1000 (0.08 per cent). The risk was lowest for gastric band and sleeve gastrectomy, then for gastric bypasses and highest for the duodenal switch operation. This shows that weight loss surgery is safe, with a low risk of dying similar to that of other common operations.

A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function.

INTRODUCTION: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. METHODS: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. RESULTS: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ-induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. CONCLUSION: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. TRIAL REGISTRATION: NCT02723786.

Transparency in surgical randomized clinical trials: cross-sectional observational study.

BACKGROUND: RCTs provide the scientific basis upon which treatment decisions are made. To facilitate critical review, it is important that methods and results are reported transparently. The aim of this study was to explore transparency in surgical RCTs with respect to trial registration, disclosure of funding sources, declarations of investigator conflicts and data-sharing. METHODS: This was a cross-sectional review of published surgical RCTs. Ten high-impact journals were searched systematically for RCTs published in years 2009, 2012, 2015 and 2018. Four domains of transparency were explored: trial registration, disclosure of funding, disclosure of investigator conflicts, and a statement relating to data-sharing. RESULTS: Of 611 RCTs, 475 were eligible for analysis. Some 397 RCTs (83.6 per cent) were registered on a trial database, of which 190 (47·9 per cent) had been registered prospectively. Prospective registration increased over time (26 per cent in 2009, 33·0 per cent in 2012, 54 per cent in 2015, and 72·7 per cent in 2018). Funding disclosure was present in 55·0, 65·0, 69·4 and 75·4 per cent of manuscripts respectively. Conflict of interest disclosure was present in 49·5, 89·1, 94·6 and 98·3 per cent of manuscripts across the same time periods. Data-sharing statements were present in only 15 RCTs (3·2 per cent), 11 of which were published in 2018. CONCLUSION: Trial registration, disclosure of funding and disclosure of investigator conflicts in surgical RCTs have improved markedly over the past 10 years. Disclosure of data-sharing plans is exceptionally low. This may contribute to research waste and represents a target for improvement.

ANTECEDENTES: Los ensayos clínicos aleatorizados y controlados (randomized controlled trials, RCT) proporcionan la base científica para la toma de decisiones terapéuticas. Es importante que los métodos y los resultados se presenten de forma transparente para facilitar la revisión crítica. El objetivo de este estudio fue investigar la transparencia en los RCTs del ámbito quirúrgico según su registro, declaraciones de las fuentes de financiación del estudio y conflicto de interés de los investigadores, así como información referente a compartir los datos. MÉTODOS: Revisión transversal de RCTs quirúrgicos publicados. Se realizó una búsqueda sistemática de los RCTs publicados en 10 revistas de alto impacto en los años 2009, 2012, 2015 y 2018. Se exploraron cuatro dominios de transparencia: el registro de los ensayos, la declaración de los fondos utilizados, la declaración de los conflictos de los investigadores y la información referente a la forma de compartir los datos. RESULTADOS: De 611 RCTs, se incluyeron en el análisis 475. Un total de 397 (83,6%) estudios se registraron en una base de datos de ensayos clínicos, de forma prospectiva en 190 (47,9%). El registro prospectivo aumentó a lo largo del tiempo (26,0% en 2009, 33,0% en 2012, 53,5% en 2015 y 72,7% en 2018). Se mencionaban las fuentes de financiación en el 55%, 65%, 69,4% y 75,4% de los manuscritos, respectivamente. La declaración de conflictos de interés estuvo presente en el 49,5%, 89,1%, 94,6% y 98,3% de los manuscritos en esos mismos períodos de tiempo. Las declaraciones relativas a compartir los datos de la investigación constaban en solo 15 (3,2%) RCTs, 11 de los cuales fueron publicados en el 2018. CONCLUSIÓN: En los últimos 10 años ha mejorado de forma notable el registro de los ensayos y las declaraciones de las fuentes de financiación y conflicto de interés en los RCTs quirúrgicos. La declaración referente a compartir los datos es excepcionalmente baja, lo que puede contribuir al desperdicio de la investigación y constituye un objetivo de mejora.

Variation in global uptake of the Surgical Safety Checklist.

BACKGROUND: The Surgical Safety Checklist (SSC) is a patient safety tool shown to reduce mortality and to improve teamwork and adherence with perioperative safety practices. The results of the original pilot work were published 10 years ago. This study aimed to determine the contemporary prevalence and predictors of SSC use globally. METHODS: Pooled data from the GlobalSurg and Surgical Outcomes studies were analysed to describe SSC use in 2014-2016. The primary exposure was the Human Development Index (HDI) of the reporting country, and the primary outcome was reported SSC use. A generalized estimating equation, clustering by facility, was used to determine differences in SSC use by patient, facility and national characteristics. RESULTS: A total of 85 957 patients from 1464 facilities in 94 countries were included. On average, facilities used the SSC in 75·4 per cent of operations. Compared with very high HDI, SSC use was less in low HDI countries (odds ratio (OR) 0·08, 95 per cent c.i. 0·05 to 0·12). The SSC was used less in urgent compared with elective operations in low HDI countries (OR 0·68, 0·53 to 0·86), but used equally for urgent and elective operations in very high HDI countries (OR 0·96, 0·87 to 1·06). SSC use was lower for obstetrics and gynaecology versus abdominal surgery (OR 0·91, 0·85 to 0·98) and where the common or official language was not one of the WHO official languages (OR 0·30, 0·23 to 0·39). CONCLUSION: Worldwide, SSC use is generally high, but significant variability exists. Implementation and dissemination strategies must be developed to address this variability.

ANTECEDENTES: Se ha demostrado que la utilización de la lista de verificación de seguridad quirúrgica (Surgical Safety Checklist, SSC) reduce la mortalidad y mejora el trabajo en equipo, así como el cumplimiento de las prácticas de seguridad perioperatorias. Los resultados de un trabajo piloto original se publicaron hace 10 años. El objetivo de este estudio fue determinar la prevalencia actual y los predictores de uso de la SSC a nivel mundial. MÉTODOS: Se analizaron los datos agrupados de los estudios GlobalSurg y Surgical Outcomes para describir la utilización de la SSC entre 2014-2016. La principal variable de exposición fue el índice de desarrollo humano (Human Development Index, HDI) del país informante y la principal variable de resultado, la tasa de utilización de la SCC. Para determinar las diferencias en la utilización de la SSC por paciente, centro y características nacionales se utilizó una ecuación de estimación generalizada con conglomerados por centros. RESULTADOS: Se incluyeron 85.957 pacientes de 1.464 centros en 94 países. La tasa media de utilización de la SSC fue del 75,4% de las operaciones. Al compararlos con países de HDI muy alto, la utilización de la SCC fue menor en los países con HDI bajo (razón de oportunidades, odds ratio, OR 0,08, i.c. del 95% 0,05-0,12). En países con HDI bajo, la SSC se utilizó menos en operaciones urgentes en comparación con operaciones electivas (OR 0,68, i.c. del 95% 0,53- 0,86) a diferencia de los países con HDI elevado, en los que se utilizó por igual en ambas situaciones (OR 0,96, i.c. del 95% 0,87-1,06). La utilización de la SSC fue menor en operaciones de obstetricia y ginecología que en cirugía abdominal (OR 0,91, i.c. del 95% 0,85 a 0,98) y en aquellos países en los que el idioma habitual u oficial era diferente a los idiomas oficiales de la OMS (OR 0,30, i.c. del 95% 0,23 a 0,39). CONCLUSIÓN: A nivel mundial, el uso de SSC en general es alto, pero existe una variabilidad significativa. Se deben desarrollar estrategias de implementación y difusión para resolver esta variabilidad.

Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.

Staphylococcus pseudoxylosus sp. nov., isolated from bovine mastitis.

Strain S04009T, a Gram-stain-positive, coagulase-negative staphylococcus, was isolated from bovine mastitis in France. 16S rRNA gene analysis revealed it to be closely related to the coagulase-negative species Staphylococcusxylosus, Staphylococcussaprophyticus, Staphylococcuscaeli and Staphylococcus edaphicus. At the whole-genome level, strain S04009T had an average nucleotide identity value <95 % and an inferred DNA-DNA hybridization value <70 % when compared to these species. Furthermore, phenotypic characteristics distinguished S04009T from those species. From these related species only strain S04009T and S. xylosus are able to ferment xylose and these two can be distinguished by the inability of strain S04009T to express urease activity. Based on the genotypic and phenotypic results, it is proposed that this isolate is a novel species, with the name Staphylococcus pseudoxylosus sp. nov. The type strain is S04009T (=DSM 107950T=CCUG 72763T=NCTC 14184T).

Multicentre study of multidisciplinary team assessment of pancreatic cancer resectability and treatment allocation.

BACKGROUND: Multidisciplinary team (MDT) meetings have been adopted widely to ensure optimal treatment for patients with cancer. Agreements in tumour staging, resectability assessments and treatment allocation between different MDTs were assessed. METHODS: Of all patients referred to one hospital, 19 patients considered to have non-metastatic pancreatic cancer for evaluation were selected randomly for a multicentre study of MDT decisions in seven units across Northern Europe. Anonymized clinical information and radiological images were disseminated to the MDTs. All patients were reviewed by the MDTs for radiological T, N and M category, resectability assessment and treatment allocation. Each MDT was blinded to the decisions of other teams. Agreements were expressed as raw percentages and Krippendorff's α values, both with 95 per cent confidence intervals. RESULTS: A total of 132 evaluations in 19 patients were carried out by the seven MDTs (1 evaluation was excluded owing to technical problems). The level of agreement for T, N and M categories ranged from moderate to near perfect (46·8, 61·1 and 82·8 per cent respectively), but there was substantial variation in assessment of resectability; seven patients were considered to be resectable by one MDT but unresectable by another. The MDTs all agreed on either a curative or palliative strategy in less than half of the patients (9 of 19). Only fair agreement in treatment allocation was observed (Krippendorff's α 0·31, 95 per cent c.i. 0·16 to 0·45). There was a high level of agreement in treatment allocation where resectability assessments were concordant. CONCLUSION: Considerable disparities in MDT evaluations of patients with pancreatic cancer exist, including substantial variation in resectability assessments.

Systematic review of the use of big data to improve surgery in low- and middle-income countries.

BACKGROUND: Technological advances have led to the generation of large amounts of data, both in surgical research and practice. Despite this, it is unclear how much originates in low- and middle-income countries (LMICs) and what barriers exist to the use of such data in improving surgical care. The aim of this review was to capture the extent and impact of programmes that use large volumes of patient data on surgical care in LMICs. METHODS: A PRISMA-compliant systematic literature review of PubMed, Embase and Google Scholar was performed in August 2018. Prospective studies collecting large volumes of patient-level data within LMIC settings were included and evaluated qualitatively. RESULTS: A total of 68 studies were included from 71 LMICs, involving 708 032 patients. The number of patients in included studies varied widely (from 335 to 428 346), with 25 reporting data on 3000 or more LMIC patients. Patient inclusion in large-data studies in LMICs has increased dramatically since 2015. Studies predominantly involved Brazil, China, India and Thailand, with low patient numbers from Africa and Latin America. Outcomes after surgery were commonly the focus (33 studies); very few large studies looked at access to surgical care or patient expenditure. The use of large data sets specifically to improve surgical outcomes in LMICs is currently limited. CONCLUSION: Large volumes of data are becoming more common and provide a strong foundation for continuing investigation. Future studies should address questions more specific to surgery.

Systematic review of management of incidental gallbladder cancer after cholecystectomy.

BACKGROUND: Gallbladder cancer is rare, but cancers detected incidentally after cholecystectomy are increasing. The aim of this study was to review the available data for current best practice for optimal management of incidental gallbladder cancer. METHODS: A systematic PubMed search of the English literature to May 2018 was conducted. RESULTS: The search identified 12 systematic reviews and meta-analyses, in addition to several consensus reports, multi-institutional series and national audits. Some 0·25-0·89 per cent of all cholecystectomy specimens had incidental gallbladder cancer on pathological examination. Most patients were staged with pT2 (about half) or pT1 (about one-third) cancers. Patients with cancers confined to the mucosa (T1a or less) had 5-year survival rates of up to 100 per cent after cholecystectomy alone. For cancers invading the muscle layer of the gallbladder wall (T1b or above), reresection is recommended. The type, extent and timing of reresection remain controversial. Observation time may be used for new cross-sectional imaging with CT and MRI. Perforation at initial surgery had a higher risk of disease dissemination. Gallbladder cancers are PET-avid, and PET may detect residual disease and thus prevent unnecessary surgery. Routine laparoscopic staging before reresection is not warranted for all stages. Risk of peritoneal carcinomatosis increases with each T category. The incidence of port-site metastases is about 10 per cent. Routine resection of port sites has no effect on survival. Adjuvant chemotherapy is poorly documented and probably underused. CONCLUSION: Management of incidental gallbladder cancer continues to evolve, with more refined suggestions for subgroups at risk and a selective approach to reresection.

Staphylococcus caeli sp. nov., isolated from air sampling in an industrial rabbit holding.

Strain 82T, a Gram-stain-positive, coagulase-negative staphylococcus was isolated from an air sample obtained from an industrial rabbit holding in Italy. It is phylogenetically closely related to the coagulase-negative species Staphylococcus saprophyticus, Staphylococcus xylosus and Staphylococcus edaphicus. However, it could be distinguished from these species by sequence differences between the 16S rRNA, hsp60, rpoB, dnaJ and gap genes. At the whole genome level, the isolate had an average nucleotide identity of <95 % and an inferred DNA-DNA hybridization of <70 % when compared to these species. Based on the genotypic results, it is proposed that this isolate is a novel species, with the name Staphylococcus caeli sp. nov. The type strain is 82BT (=NCTC 14063T=CCUG 71912T).

A mecC allotype, mecC3, in the CoNS Staphylococcus caeli, encoded within a variant SCCmecC.

BACKGROUND: Methicillin resistance in staphylococci is conferred by an alternative PBP (PBP2a/2') with low affinity for most ß-lactam antibiotics. PBP2a is encoded by mecA, which is carried on a mobile genetic element known as SCCmec. A variant of mecA, mecC, was described in 2011 and has been found in Staphylococcus aureus from humans and a wide range of animal species as well as a small number of other staphylococcal species from animals. OBJECTIVES: We characterized a novel mecC allotype, mecC3, encoded by an environmental isolate of Staphylococcus caeli cultured from air sampling of a commercial rabbit holding. METHODS: The S. caeli isolate 82BT was collected in Italy in 2013 and genome sequenced using MiSeq technology. This allowed the assembly and comparative genomic study of the novel SCCmec region encoding mecC3. RESULTS: The study isolate encodes a novel mecA allotype, mecC3, with 92% nucleotide identity to mecC. mecC3 is encoded within a novel SCCmec element distinct from those previously associated with mecC, including a ccrAB pairing (ccrA5B3) not previously linked to mecC. CONCLUSIONS: This is the first description of the novel mecC allotype mecC3, the first isolation of a mecC-positive Staphylococcus in Italy and the first report of mecC in S. caeli. Furthermore, the SCCmec element described here is highly dissimilar to the archetypal SCCmec XI encoding mecC in S. aureus and to elements encoding mecC in other staphylococci. Our report highlights the diversity of mecC allotypes and the diverse staphylococcal species, ecological settings and genomic context in which mecC may be found.

Evaluating the collection, comparability and findings of six global surgery indicators.

BACKGROUND: In 2015, six indicators were proposed to evaluate global progress towards access to safe, affordable and timely surgical and anaesthesia care. Although some have been adopted as core global health indicators, none has been evaluated systematically. The aims of this study were to assess the availability, comparability and utility of the indicators, and to present available data and updated estimates. METHODS: Nationally representative data were compiled for all World Health Organization (WHO) member states from 2010 to 2016 through contacts with official bodies and review of the published and grey literature, and available databases. Availability, comparability and utility were assessed for each indicator: access to timely essential surgery, specialist surgical workforce density, surgical volume, perioperative mortality, and protection against impoverishing and catastrophic expenditure. Where feasible, imputation models were developed to generate global estimates. RESULTS: Of all WHO member states, 19 had data on the proportion of the population within 2h of a surgical facility, 154 had data on workforce density, 72 reported number of procedures, and nine had perioperative mortality data, but none could report data on catastrophic or impoverishing expenditure. Comparability and utility were variable, and largely dependent on different definitions used. There were sufficient data to estimate that worldwide, in 2015, there were 2 038 947 (i.q.r. 1 884 916-2 281 776) surgeons, obstetricians and anaesthetists, and 266·1 (95 per cent c.i. 220·1 to 344·4) million operations performed. CONCLUSION: Surgical and anaesthesia indicators are increasingly being adopted by the global health community, but data availability remains low. Comparability and utility for all indicators require further resolution.

No Evidence that Knops Blood Group Polymorphisms Affect Complement Receptor 1 Clustering on Erythrocytes.

Clustering of Complement Receptor 1 (CR1) in the erythrocyte membrane is important for immune-complex transfer and clearance. CR1 contains the Knops blood group antigens, including the antithetical pairs Swain-Langley 1 and 2 (Sl1 and Sl2) and McCoy a and b (McCa and McCb), whose functional effects are unknown. We tested the hypothesis that the Sl and McC polymorphisms might influence CR1 clustering on erythrocyte membranes. Blood samples from 125 healthy Kenyan children were analysed by immunofluorescence and confocal microscopy to determine CR1 cluster number and volume. In agreement with previous reports, CR1 cluster number and volume were positively associated with CR1 copy number (mean number of CR1 molecules per erythrocyte). Individuals with the McC b /McC b genotype had more clusters per cell than McC a /McC a individuals. However, this association was lost when the strong effect of CR1 copy number was included in the model. No association was observed between Sl genotype, sickle cell genotype, α+thalassaemia genotype, gender or age and CR1 cluster number or volume. Therefore, after correction for CR1 copy number, the Sl and McCoy polymorphisms did not influence erythrocyte CR1 clustering, and the effects of the Knops polymorphisms on CR1 function remains unknown.

Frequency of surgical treatment and related hospital procedures in the UK: a national ecological study using hospital episode statistics.

BACKGROUND: Despite evidence of high activity, the number of surgical procedures performed in UK hospitals, their cost and subsequent mortality remain unclear. METHODS: Time-trend ecological study using hospital episode data from England, Scotland, Wales and Northern Ireland. The primary outcome was the number of in-hospital procedures, grouped using three increasingly specific categories of surgery. Secondary outcomes were all-cause mortality, length of hospital stay and healthcare costs according to standard National Health Service tariffs. RESULTS: Between April 1, 2009 and March 31, 2014, 39 631 801 surgical patient episodes were recorded. There was an annual average of 7 926 360 procedures (inclusive category), 5 104 165 procedures (intermediate category) and 1 526 421 procedures (restrictive category). This equates to 12 537, 8073 and 2414 procedures per 100 000 population per year, respectively. On average there were 85 181 deaths (1.1%) within 30 days of a procedure each year, rising to 178 040 deaths (2.3%) after 90 days. Approximately 62.8% of all procedures were day cases. Median length of stay for in-patient procedures was 1.7 (1.3-2.0) days. The total cost of surgery over the 5 yr period was £54.6 billion ($104.4 billion), representing an average annual cost of £10.9 billion (inclusive), £9.5 billion (intermediate) and £5.6 billion (restrictive). For each category, the number of procedures increased each year, while mortality decreased. One-third of all mortalities in national death registers occurred within 90 days of a procedure (inclusive category). CONCLUSIONS: The number of surgical procedures in the UK varies widely according to definition. The number of procedures is slowly increasing whilst the number of deaths is decreasing.