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

Granulomatous cheilitis associated with exacerbations of Crohn's disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Crohn's disease is a disease involving the whole gastrointestinal tract from the mouth to the anus. Oral lesions are considered to be an important extraintestinal manifestation. Granulomatous cheilitis has been recognized as an early manifestation of Crohn's disease. It may follow, coincide with or precede the onset of Crohn's disease. The aim of this presentation is to describe a rare case of a patient with Crohn's disease in whom significant swelling of the lower lip not only preceded the diagnosis of Crohn's disease for two years, but it manifested as an early clinical index of the recurrence of the intestinal disease as well.</p> <p>Case presentation</p> <p>A man aged 25 was admitted in our department on August 1999 with chronic diarrhea and loss of weight. His bowel symptoms started in 1998 at the age of 24. However, two years previously (June 1996) he noticed a swelling of the lower lip, which contrasted significantly with the previously normal appearance of his mouth. A lip biopsy performed at that time was compatible with granulomatous cheilitis. Crohn's disease involving the terminal ileum and large bowel was diagnosed in 1998 and confirmed on the basis of colonoscopy, enteroclysis and histology findings of the small and large bowel. Conservative treatment resulted in clinical and laboratory improvement of the bowel symptoms and lip swelling. During the following years the disease was active with exacerbations and remissions of mild to moderate severity. The swelling of the lower lip occurred in parallel with the exacerbations of the bowel disease, returning to normal during periods of remission.</p> <p>Conclusion</p> <p>Significant swelling of the lower lip due to granulomatous cheilitis could be the first manifestation of Crohn's disease, preceding intestinal symptoms. Exacerbation of the lip lesion could be an early clinical sign of a relapse of the underlying intestinal disease.</p

CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a ‘pro-/anti-tumour' approach to tumour host interaction in colorectal cancer

BACKGROUND: The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour budding', is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a 'pro-/anti-tumour' approach defined by an established 'pro-tumour' (tumour budding) and host-related 'anti-tumour' factor of the adaptive immunological microenvironment (CD8+ lymphocytes). METHODS: Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field. RESULTS: In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (P>0.001), vascular invasion (P=0.009), worse survival in univariate (P>0.001) and multivariable (P>0.001) analysis, and furthermore in lymph node-negative patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (P>0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P>0.001). CONCLUSION: The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease

Saccharin disrupts bacterial cell envelope stability and interferes with DNA replication dynamics

......RRMC and EM are supported by the NC3Rs PhD Studentship NC/V001582/1. RRMC and RD are supported by a Biotechnology and Biological Sciences Research Council New Investigator Award BB/V007823/1 and an MRC Award MR/Y001354/1. RRMC and CP are supported by the Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award (SBF006\1040). RD received a Research Mobility Award from the Young European Research University Network to collaborate with CSL and visit UiT. The work was supported by joint Research Grants BB/T007168/1 and BB/T006625-1 from the Biotechnology and Biological Sciences Research Council to CJR and ELB, as well as BBSRC research grant BB/W000393/1 to CJR. The work was further supported by a grant by the North Norwegian Health Trust (HelseNord, HN 1688-23) to CSL. MMH and ALW would like to thank the Tromsø Research Foundation and UiT Centre for New Antibacterial Strategies (CANS) for a start-up grant (TFS project ID: 18_CANS)

Role of tumor size in the pre-operative management of rectal cancer patients

Clinical management of rectal cancer patients relies on pre-operative staging. Studies however continue to report moderate degrees of over/understaging as well as inter-observer variability. The aim of this study was to determine the sensitivity, specificity and accuracy of tumor size for predicting T and N stages in pre-operatively untreated rectal cancers

Regional variability in peatland burning at mid-to high-latitudes during the Holocene

[eng] Northern peatlands store globally-important amounts of carbon in the form of partly decomposed plant detritus. Drying associated with climate and land-use change may lead to increased fire frequency and severity in peatlands and the rapid loss of carbon to the atmosphere. However, our understanding of the patterns and drivers of peatland burning on an appropriate decadal to millennial timescale relies heavily on individual site-based reconstructions. For the first time, we synthesise peatland macrocharcoal records from across North America, Europe, and Patagonia to reveal regional variation in peatland burning during the Holocene. We used an existing database of proximal sedimentary charcoal to represent regional burning trends in the wider landscape for each region. Long-term trends in peatland burning appear to be largely climate driven, with human activities likely having an increasing influence in the late Holocene. Warmer conditions during the Holocene Thermal Maximum (∼9–6 cal. ka BP) were associated with greater peatland burning in North America's Atlantic coast, southern Scandinavia and the Baltics, and Patagonia. Since the Little Ice Age, peatland burning has declined across North America and in some areas of Europe. This decline is mirrored by a decrease in wider landscape burning in some, but not all sub-regions, linked to fire-suppression policies, and landscape fragmentation caused by agricultural expansion. Peatlands demonstrate lower susceptibility to burning than the wider landscape in several instances, probably because of autogenic processes that maintain high levels of near-surface wetness even during drought. Nonetheless, widespread drying and degradation of peatlands, particularly in Europe, has likely increased their vulnerability to burning in recent centuries. Consequently, peatland restoration efforts are important to mitigate the risk of peatland fire under a changing climate. Finally, we make recommendations for future research to improve our understanding of the controls on peatland fires

Regional variability in peatland burning at mid- to high-latitudes during the Holocene

Acknowledgements This work developed from the PAGES (Past Global Changes) C-PEAT (Carbon in Peat on EArth through Time) working group. PAGES has been supported by the US National Science Foundation, Swiss National Science Foundation, Swiss Academy of Sciences and Chinese Academy of Sciences. We acknowledge the following financial support: UK Natural Environment Research Council Training Grants NE/L002574/1 (T.G.S.) and NE/S007458/1 (R.E.F.); Dutch Foundation for the Conservation of Irish Bogs, Quaternary Research Association and Leverhulme Trust RPG-2021-354 (G.T.S); the Academy of Finland (M.V); PAI/SIA 80002 and FONDECYT Iniciación 11220705 - ANID, Chile (C.A.M.); R20F0002 (PATSER) ANID Chile (R.D.M.); Swedish Strategic Research Area (SRA) MERGE (ModElling the Regional and Global Earth system) (M.J.G.); Polish National Science Centre Grant number NCN 2018/29/B/ST10/00120 (K.A.); Russian Science Foundation Grant No. 19-14-00102 (Y.A.M.); University of Latvia Grant No. AAp2016/B041/Zd2016/AZ03 and the Estonian Science Council grant PRG323 (TrackLag) (N.S. and A.M.); U.S. Geological Survey Land Change Science/Climate Research & Development Program (M.J., L.A., and D.W.); German Research Foundation (DFG), grant MA 8083/2-1 (P.M.) and grant BL 563/19-1 (K.H.K.); German Academic Exchange Service (DAAD), grant no. 57044554, Faculty of Geosciences, University of Münster, and Bavarian University Centre for Latin America (BAYLAT) (K.H.K). Records from the Global Charcoal Database supplemented this work and therefore we would like to thank the contributors and managers of this open-source resource. We also thank Annica Greisman, Jennifer Shiller, Fredrik Olsson and Simon van Bellen for contributing charcoal data to our analyses. Any use of trade, firm, or product name is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewedPostprin

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts