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.

Unmet Surgical Need among Adults in A Mixed Urban-Rural Community in Nigeria: A Survey of 1,993 Adults Using the Sosas Survey Tool.

INTRODUCTION: Community-based prevalence studies are known to be more accurate than hospital-based records. However, such community-based prevalence studies are uncommon in low- and middle-income countries including Nigeria. Allocation of resources and prioritization of health care needs by policy makers require data from such community-based studies to be meaningful and sustainable. This study aims to assess the prevalence of common surgical conditions amongst adults in Nigeria. METHODS: A descriptive cross-sectional community-based study to determine the prevalence of congenital and acquired surgical conditions in adults in a mixed rural-urban area of Lagos was conducted. The study population comprised resident members in the Ikorodu Local Government Area (LGA) of Lagos State. Data was collected using a modified version of the interviewer-administered questionnaire, the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey tool. Data was analysed using the REDCap analytic tool. RESULTS: Eight hundred and fifty-six households were surveyed with a yield of 1,992 adults. There were 95 adults who complained of surgical conditions giving a prevalence rate of 5%. Vast majority of reported conditions were acquired deformities (n=94) while only 1 congenital deformity was reported. Others included breast lumps, anterior neck swelling, and groin swellings. CONCLUSION: The most common surgical complaints in our setting among adults were acquired conditions of the extremities and open wounds/sores. With an estimated population of 90 million adults and approximately 1,200 orthopaedic and general surgeons respectively, the surgeon-to-affected population ratio is 1:10,000. There is a large gap to be filled in terms of surgical manpower development.

INTRODUCTION: Les études de prévalence communautaires sont connues pour être plus précises que les dossiers hospitaliers. Cependant, de telles études de prévalence communautaires sont rares dans les pays à revenu faible et intermédiaire, y compris le Nigeria. L'allocation des ressources et la priorisation des besoins de santé par les décideurs nécessitent des données issues de telles études communautaires pour être significatives et durables. Cette étude vise à évaluer la prévalence des affections chirurgicales courantes chez les adultes au Nigeria. MÉTHODES: Une étude descriptive transversale basée sur la communauté pour déterminer la prévalence des conditions chirurgicales congénitales et acquises chez les adultes dans une zone rurale-urbaine mixte de Lagos a été menée. La population étudiée comprenait des membres résidents de la zone de gouvernement local (LGA) d'Ikorodu, dans l'État de Lagos. Les données ont été collectées à l'aide d'une version modifiée du questionnaire administré par un enquêteur, l'outil d'enquête Surgeons OverSeas Assessment of Surgical Need (SOSAS). Les données ont été analysées à l'aide de l'outil analytique REDCap. RÉSULTATS: Huit cent cinquante-six ménages ont été enquêtés, ce qui a donné 1 992 adultes. Quatre-vingt-quinze adultes se sont plaints de conditions chirurgicales, donnant un taux de prévalence de 5 %. La grande majorité des conditions rapportées étaient des déformations acquises (n=94) tandis qu'une seule déformation congénitale a été signalée. Les autres incluaient des nodules mammaires, des gonflements antérieurs du cou et des gonflements inguinaux. CONCLUSION: Les plaintes chirurgicales les plus courantes dans notre cadre parmi les adultes étaient des conditions acquises des extrémités et des plaies ouvertes/ulcères. Avec une population estimée à 90 millions d'adultes et environ 1 200 chirurgiens orthopédiques et généralistes respectivement, le ratio chirurgien-population affectée est de 1:10,000. Il y a un grand écart à combler en termes de développement de la main-d'œuvre chirurgicale. MOTS CLÉS: Prévalence, Charge de morbidité, Chirurgie, Plaies.

HDAC Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling.

BACKGROUND: Diastolic dysfunction (DD) is associated with the development of heart failure and contributes to the pathogenesis of other cardiac maladies, including atrial fibrillation. Inhibition of histone deacetylases (HDACs) has been shown to prevent DD by enhancing myofibril relaxation. We addressed the therapeutic potential of HDAC inhibition in a model of established DD with preserved ejection fraction. METHODS: Four weeks after uninephrectomy and implantation with deoxycorticosterone acetate pellets, when DD was clearly evident, 1 cohort of mice was administered the clinical-stage HDAC inhibitor ITF2357/Givinostat. Echocardiography, blood pressure measurements, and end point invasive hemodynamic analyses were performed. Myofibril mechanics and intact cardiomyocyte relaxation were assessed ex vivo. Cardiac fibrosis was evaluated by picrosirius red staining and second harmonic generation microscopy of left ventricle (LV) sections, RNA sequencing of LV mRNA, mass spectrometry-based evaluation of decellularized LV biopsies, and atomic force microscopy determination of LV stiffness. Mechanistic studies were performed with primary rat and human cardiac fibroblasts. RESULTS: HDAC inhibition normalized DD without lowering blood pressure in this model of systemic hypertension. In contrast to previous models, myofibril relaxation was unimpaired in uninephrectomy/deoxycorticosterone acetate mice. Furthermore, cardiac fibrosis was not evident in any mouse cohort on the basis of picrosirius red staining or second harmonic generation microscopy. However, mass spectrometry revealed induction in the expression of >100 extracellular matrix proteins in LVs of uninephrectomy/deoxycorticosterone acetate mice, which correlated with profound tissue stiffening based on atomic force microscopy. ITF2357/Givinostat treatment blocked extracellular matrix expansion and LV stiffening. The HDAC inhibitor was subsequently shown to suppress cardiac fibroblast activation, at least in part, by blunting recruitment of the profibrotic chromatin reader protein BRD4 (bromodomain-containing protein 4) to key gene regulatory elements. CONCLUSIONS: These findings demonstrate the potential of HDAC inhibition as a therapeutic intervention to reverse existing DD and establish blockade of extracellular matrix remodeling as a second mechanism by which HDAC inhibitors improve ventricular filling. Our data reveal the existence of pathophysiologically relevant covert or hidden cardiac fibrosis that is below the limit of detection of histochemical stains such as picrosirius red, highlighting the need to evaluate fibrosis of the heart using diverse methodologies.

Is General Anesthesia for Endovascular Thrombectomy Helpful or Harmful?

Endovascular thrombectomy (EVT) has significantly improved outcomes for patients with acute ischemic stroke due to large vessel occlusion. However, despite advances, more than half of patients remain functionally dependent 3 months after their initial stroke. Anesthetic strategy may influence both the technical success of the procedure and overall outcomes. Conventionally, general anesthesia (GA) has been widely used for neuroendovascular procedures, particularly for the distal intracranial circulation, because the complete absence of movement has been considered imperative for procedural success and to minimize complications. In contrast, in patients with acute stroke undergoing EVT, the optimal anesthetic strategy is controversial. Nonrandomized studies suggest GA negatively affects outcomes while the more recent anesthesia-specific RCTs report improved or unchanged outcomes in patients managed with versus without GA, although these findings cannot be generalized to other EVT capable centers due to a number of limitations. Potential explanations for these contrasting results will be addressed in this review including the effect of different anesthetic strategies on cerebral and systemic hemodynamics, revascularization times, and periprocedural complications.

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.

Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation.

RATIONALE: Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in preclinical models of heart failure (HF). However, since the inhibitors target BRD4 ubiquitously, it is unclear whether this chromatin reader protein functions in cell type-specific manner to control pathological myocardial fibrosis. Furthermore, the molecular mechanisms by which BRD4 stimulates the transcriptional program for cardiac fibrosis remain unknown. OBJECTIVE: We sought to test the hypothesis that BRD4 functions in a cell-autonomous and signal-responsive manner to control activation of cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart. METHODS AND RESULTS: RNA-sequencing, mass spectrometry, and cell-based assays employing primary adult rat ventricular fibroblasts demonstrated that BRD4 functions as an effector of TGF-ß (transforming growth factor-ß) signaling to stimulate conversion of quiescent cardiac fibroblasts into Periostin (Postn)-positive cells that express high levels of extracellular matrix. These findings were confirmed in vivo through whole-transcriptome analysis of cardiac fibroblasts from mice subjected to transverse aortic constriction and treated with the small molecule BRD4 inhibitor, JQ1. Chromatin immunoprecipitation-sequencing revealed that BRD4 undergoes stimulus-dependent, genome-wide redistribution in cardiac fibroblasts, becoming enriched on a subset of enhancers and super-enhancers, and leading to RNA polymerase II activation and expression of downstream target genes. Employing the Sertad4 (SERTA domain-containing protein 4) locus as a prototype, we demonstrate that dynamic chromatin targeting of BRD4 is controlled, in part, by p38 MAPK (mitogen-activated protein kinase) and provide evidence of a critical function for Sertad4 in TGF-ß-mediated cardiac fibroblast activation. CONCLUSIONS: These findings define BRD4 as a central regulator of the pro-fibrotic cardiac fibroblast phenotype, establish a p38-dependent signaling circuit for epigenetic reprogramming in heart failure, and uncover a novel role for Sertad4. The work provides a mechanistic foundation for the development of BRD4 inhibitors as targeted anti-fibrotic therapies for the heart.

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

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.

Wound Healing and Wound Care in Neonates: Current Therapies and Novel Options.

GENERAL PURPOSE: To provide wound care information that considers the specific physiology of neonates. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Differentiate the use of hydrocolloids, hydrogels, foam dressings, and barrier creams in the neonatal population.2. Identify issues related to the use of solvents, alginates, collagen dressings, and negative-pressure wound therapy in neonates. ABSTRACT: OBJECTIVETo discuss what is known about the wound milieu in premature and full-term neonates, including the unique challenges pediatric clinicians face, the therapies that have proven effective, and the therapies contraindicated for use in neonatal wound healing to guide treatment that accounts for the specific physiological characteristics of this often overlooked population. DATA SOURCES: Data were collected on neonatal wound healing from a wide variety of sources, including PubMed, Google Scholar, journals, and textbooks. STUDY SELECTION: Selection criteria included publications focused on the differences and nuances of wound healing in neonates in comparison with all other age groups. DATA EXTRACTION: Data were extracted based on articles covering wound healing therapies with proven effectiveness in neonates. Terms for neonatal wound care were compiled, and then a comprehensive literature search was performed by the authors. DATA SYNTHESIS: Although many therapies are safe for treatment of older children and adolescents, most have not been explicitly tested for neonatal use. This article reviews therapies with proven effectiveness and/or specific concerns in the neonatal population. CONCLUSION: This review sheds light on the advantages and disadvantages of current standards of care regarding wound healing for neonates to direct researchers and clinicians toward developing treatments specifically for this delicate population.

To discuss what is known about the wound milieu in premature and full-term neonates, including the unique challenges pediatric clinicians face, the therapies that have proven effective, and the therapies contraindicated for use in neonatal wound healing to guide treatment that accounts for the specific physiological characteristics of this often overlooked population. Data were collected on neonatal wound healing from a wide variety of sources, including PubMed, Google Scholar, journals, and textbooks. Selection criteria included publications focused on the differences and nuances of wound healing in neonates in comparison with all other age groups. Data were extracted based on articles covering wound healing therapies with proven effectiveness in neonates. Terms for neonatal wound care were compiled, and then a comprehensive literature search was performed by the authors. Although many therapies are safe for treatment of older children and adolescents, most have not been explicitly tested for neonatal use. This article reviews therapies with proven effectiveness and/or specific concerns in the neonatal population. This review sheds light on the advantages and disadvantages of current standards of care regarding wound healing for neonates to direct researchers and clinicians toward developing treatments specifically for this delicate population.

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.

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.

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.

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.

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).

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).

Does functional outcome depend on the quality of the fracture fixation? Mid to long term outcomes of ankle fractures at two university teaching hospitals.

BACKGROUND: The aim of our study was to assess the adequacy of reduction and internal fixation of ankle fractures and the long-term functional outcomes of patients treated in two university teaching hospitals by general orthopaedic surgeons. METHOD: We performed a retrospective study involving two large trauma units in the UK, reviewing all operatively treated unstable ankle fractures performed in one centre between 1st October 2006 and 31st December 2007 and another centre between 1st January 2009 and 31st December 2009. All patients were contacted by postal follow up at a minimum of 6-years using the Olerud-Molander Ankle Score (OMAS). RESULTS: 261 patients underwent operative treatment for ankle fractures during the study period at the two hospitals. 107 patients responded to the questionnaire. Analysis of patients' functional outcome by fracture type reveals that the outcome scores decrease as the complexity of the ankle fracture increases. A significant finding within subgroup analysis found that trimalleolar fractures (B3) have worse outcomes than bimalleolar fractures (B2 and C); which in turn have worse outcomes than isolated lateral malleolar fractures (B1). Analyzing the outcome of patients based on the severity of malreduction revealed that Pettrone's value was inversely proportional to the OMAS. CONCLUSION: We have found a significant reduction in patient reported function in patients whose fractures were malreduced at time of surgery.

The views of children and young people on the use of silk garments for the treatment of eczema: a nested qualitative study within the CLOTHing for the relief of Eczema Symptoms (CLOTHES) randomized controlled trial.

BACKGROUND: Many children suffer with skin diseases but to date most dermatological research has been done 'on' rather than 'with' children; in this study we actively sought the experiences of children and young people. Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition that affects around 20% of children and can impact on the health and wellbeing of children and their families. The role of specialist clothing in the management of AE is poorly understood. OBJECTIVES: The aim of this study, which was nested in a randomized controlled trial, was to qualitatively examine child participants' experiences of using silk garments for the treatment of AE. METHODS: Eighteen children aged 5-15 years, who took part in the CLOTHing for the relief of Eczema Symptoms (CLOTHES) trial, participated in age-appropriate individual interviews or focus groups. RESULTS: Thematic analysis generated four themes directly related to the silk garments: (i) expectations of the garments; (ii) wearing the garments; (iii) asking if the garments helped; and (iv) thoughts about the garments. The conclusions from this nested qualitative study are that there was some limited improvement in eczema for some children but that the hoped-for 'miracle cure' did not transpire. A mixed picture of knowledge, beliefs and experiences of using the silk garments emerged. CONCLUSIONS: Engaging children in the evaluation of the garments provided first-hand nuanced insights that enhanced understanding of the CLOTHES study as a whole. This nested study demonstrates that children can and indeed want to be engaged in dermatological research in meaningful ways that add to our understanding of treatment options.

The spillover effect of midwife attrition from the Nigerian midwives service scheme.

BACKGROUND: The Nigerian Midwives Service Scheme (MSS) increased use of antenatal services at rural public sector clinics. However, it is unclear if women who would not have otherwise sought care, or those who would have sought care in rural private sector clinics caused this change. Additionally, it is also unclear if the reported midwife attrition was associated with a spillover of the scheme's effect on urban areas. We sought to answer these two questions using data from two nationally representative surveys. METHODS: We used an interrupted time series model to assess trends in the use of obstetric (i.e. antenatal and delivery) services among rural and urban respondents in the 2008 and 2013 Nigerian demographic and health surveys. RESULTS: We found that the MSS led to a 5-percentage point increase in the use of antenatal services at rural public sector clinics, corroborating findings from a previous study. This change was driven by women who would not have sought care otherwise. We also found that there was a 4-percentage point increase in the use of delivery services at urban public sector clinics, and a concurrent 4-percentage point decrease in urban home deliveries. These changes are most likely explained by midwives' attrition and exemplify a spillover of the scheme's effect. CONCLUSION: Midwife attrition from the Nigerian MSS was associated with a spillover of the scheme's effect on the use of delivery services, on urban areas.

Effect of day of the week on short- and long-term mortality after emergency general surgery.

BACKGROUND: The effect of day of the week on outcome after surgery is the subject of debate. The aim was to determine whether day of the week of emergency general surgery alters short- and long-term mortality. METHODS: This was an observational study of all patients undergoing emergency general surgery in Scotland between 1 January 2005 and 31 December 2007, followed to 2012. Multilevel logistic and Cox proportional hazards regression were used to assess the effect of day of the week of surgery on outcome after adjustment for case mix and risk factors. The primary outcome was perioperative mortality; the secondary outcome was overall survival. RESULTS: A total of 50 844 patients were identified, of whom 31 499 had an emergency procedure on Monday to Thursday and 19 345 on Friday to Sunday. Patients undergoing surgery at the weekend were younger (mean 45·9 versus 47·5 years; P < 0·001) and had fewer co-morbidities, but underwent riskier and/or more complex procedures (P < 0·001). Patients who had surgery at the weekend were more likely to have been operated on sooner than those who had weekday surgery (mean time from admission to operation 1·2 versus 1·6 days; P < 0·001). No difference in perioperative mortality (odds ratio 1·00, 95 per cent c.i. 0·89 to 1·13; P = 0·989) or overall survival (hazard ratio 1·01, 0·97 to 1·06; P = 0·583) was observed when surgery was performed at the weekend. There was no difference in overall survival after surgery undertaken on any particular day compared with Wednesday; a borderline reduction in perioperative mortality was seen on Tuesday. CONCLUSION: There was no difference in short- or long-term mortality following emergency general surgery at the weekend, compared with mid-week.