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Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from Abbvie and Teva. Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer. Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs. Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of Journal of Headache Pain, and associate editor of Brain. Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an associate editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the editorial board for Journal of Headache Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society. Eric Liebler declares consulting fees from ElecroCore, Inc. Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health. Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant. Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler. Esme Ekizoğlu declares honoraria from Allergan-AbbVie. David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer. Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain. Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva. Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita Pharm. Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma. Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, International Headache Society (IHS), National Institute for Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB. Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris. Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis. Mi Ji Lee declares consulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu. Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan. Daniele Martinelli declares honoraria from AbbVie and Lundbeck. Teshamae S. Monteith has the following disclosures over the past three years: clinical trial site principal investigator for studies sponsored by Abbvie, Eli Lilly, Ipsen and Rehaler, participation in advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. Dr Monteith has provided unpaid service on the board of directors for the International Headache Society (2021-2023) and currently on the executive board for the Florida Society of Neurology. Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva. Aynur Özge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan. Mario Peres accepted honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. MP is president of ABRACES. Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva. Todd J. Schwedt declares grants/contracts with American Heart Association, Amgen, Henry Jackson Foundation, National Headache Foundation, National Institutes of Health, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, United States Department f Defense, American Migraine Foundation and Mayo Clinic. Consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix. He declares royalties from UpToDate and stock options from Aural. Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly. Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma. Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea. Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent. Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen. Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from AbbVie, Eli Lilly, Dompé, Ipsen, Lundbeck, Pfizer, Medscape, Teva. All remaining authors report no disclosures or conflicts of interest

Background: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications., Methods: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group., Results: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained., Conclusion: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Francesca Puledda declares speaker and consultancy fees from TEVA.Simona Sacco declares grants/contracts, consulting fees or honoraria from Novartis, Uriach, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, NovoNordisk, Abbott, AstraZeneca, Pfizer.Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology and Drugs.Messoud Ashina is a consultant, speaker, or scientific advisor for AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva; a primary investigator for ongoing AbbVie and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711) and received institutional research grant from Lundbeck and Novartis. MA serves as associate editor of the Journal of Headache and Pain, and associate editor of Brain.Sait Ashina has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva, Theranica. SA is an Associate Editor for Neurology Reviews, BMC Neurology, and Frontiers in Neurology, and serves on the Editorial Board for the Journal of Headache and Pain. SA serves as a Trustee on the Board of the International Headache Society and is a member of the Education Committee of the International Headache Society.Eric Liebler declares consulting fees from ElecroCore, Inc.Andrea Cipriani is supported by the National Institute for Health Research (NIHR) Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration and by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.Min Kyung Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. He received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. He received grants from Yonsei University College of Medicine (6-2021-0229), the Korea Health Industry Development Institute (KHIDI) (Grant No.: HV22C0106), and a National Research Foundation of Korea (NRF) grant.Alexandra Cocores declares grants/contracts from AbbVie, Eli Lilly, Rehaler.Esme Ekizoğlu declares honoraria from Allergan‐AbbVie.David Garcia-Azorin declares grants/contracts from Carlos II Research and Castilla and Leon Regional Health, consulting fees from Eli-Lilly, WHO, Lundbeck or honoraria from AbbVie, Teva, Novartis, Pfizer.Carl Göbel declares honoraria from Fielmann AG and German Society for the Study of Pain.Maria Teresa Goicochea, personal fees as speaker or advisory board and/or non-financial support from Pfizer, AbbVie and Teva.Amr Hassan declares consulting fees or honoraria from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, Elixir pharma, Allergan, Merck, Biologix, Roche, Bayer, Chemipharm, Al Andalus, and Clavita pharm.Koichi Hirata declares consulting fees from Otsuka Pharma, and honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo, Eisai, Eli Lilly Japan KK, MSD, Otsuka Pharma, Pfizer Japan, and Sawai Pharma.Jan Hoffmann declares grants/contracts from Bristol Myers Squibb, IHS, National Institute of Health and Care Research (NIHR), Medical Research Council (MRC) and Migraine Trust, consulting fees or honoraria from AbbVie, Cannovex, Eli Lilly, Novartis, Teva, Allergan, Chordate Medical AB, Lundbeck, Sanofi, MD Horizonte, Pfizer, Sage, NEJM Journal Watch Neurology, Oxford University Press, Quintessence Publishing, Springer Healthcare. He holds stock options from Chordate Medical AB.Bronwyn Jenkins declares honoraria from Allergan/AbbVie, Eli-Lilly, Novartis, Pfizer, Teva, Viatris.Katharina Kamm declares grants/contracts from the German Headache and Migraine Society, Novartis, consulting fees from Hormosan, and honoraria from Lundbeck, TEVA, derCampus, Novartis.Mi Ji Lee declares onsulting fees or honoraria from Eli-Lilly, Lundbeck, Pfizer, NuEyne Co, Teva AbbVie, SK Chemical, CKD Pharma, and YuYu.Marco Lisicki declares honoraria from Teva, AbbVie, Novartis, Pfizer and Allergan.Daniele Martinelli declares honoraria from AbbVie and Lundbeck.Teshamae S. Monteith has the following disclosures over the past 3 years: clinical trial site principal investigator for studies sponsored by Eli Lilly and AbbVie (all paid to the institution), participation in an advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Novartis, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. TSM has provided unpaid service on the board of directors for the International Headache Society (2021–2023) and currently on the executive board for the Florida Society of Neurology.Raffaele Ornello declares grants/contracts from Novartis, consulting fees/honoraria from Eli Lilly, AbbVie, Pfizer, and Teva.Aynur Ozge declares consulting fees or honoraria from AbbVie Lilly, Teva, Abdi Ibrahim, İlko and Drogsan.Mario Peres accepted honoraria for lectures, presentations, speakers bureaus, manuscript writing and educational events from Pfizer, Teva, AbbVie-Allergan, Lundbeck. Accepted travel support from Teva. Participated in advisory boards, AbbVie-Allergan, Eli Lilly, Pfizer, Kenvue, Eurofarma, Sanofi-Aventis. Mario Peres is president of ABRACES.Patricia Pozo-Rosich declares grants/contracts from ERANet Neuron, Instituto Salud Carlos III, Novartis, Teva and AbbVie and consulting fees or honoraria from AbbVie, Almirall, Eli Lilly, Lundbeck Medscape, Novartis, Pfizer, Teva.Todd J. Schwedt declares grants/contracts with AHA, Amgen, Henry Jackson Foundation, NIH, Patient Centered Outcomes Research Institute, Pfizer, Spark Neuro, US Dept. of Defense, AMF, NHF and Mayo Clinic with consulting fees from AbbVie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Click Therapeutics, Collegium, Eli Lilly, Equinox, Ipsen, Unpharma, Lundbeck, Novartis, Satsuma, Scilex, Theranica, and Tonix.Marcio Nattan P. Souza declares consulting fees or honoraria from Teva, Libbs, Pfizer, Sandoz, Lundbeck, Allergan/AbbVie, Lilly.Tsubasa Takizawa declares grants/research funds from Eli Lilly, Pfizer and Tsumura and advisory/consulting fees and/or honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Teijin, Pfizer, Kyowa Kirin, Elsai, Kowa, UCB Japan, Takeda, and Santen Pharma.Gisela M. Terwindt declares grants/contracts from European Community, Dutch Heart Foundation, IRRF, Dioraphte and Dutch Brain Council with consulting fees or honoraria from Novartis, Lilly, Teva, AbbVie/Allergan, Lundbeck, Pfizer, Spring Media, Ashfield MedComms, Remedica Cygnea.Nicolas Vandenbussche declares consulting fees or honoraria Pfizer, AbbVie, Novartis, Teva, Babinski VZW, ACREHAB UGent.Shuu-Jiun Wang declares honoraria from AbbVie, Pfizer and Biogen.Cristina Tassorelli declares grants/contracts from AbbVie with consulting fees or honoraria from Eli Lilly, Dompé, Teva, Lundbeck, Pfizer, Medscape.All remaining authors report no disclosures or conflicts of interest.

Objective: In acute pancreatitis (AP), bacterial translocation and subsequent infection of pancreatic necrosis are the main risk factors for severe disease and late death. Understanding how immunological host defence mechanisms fail to protect the intestinal barrier is of great importance in reducing the mortality risk of the disease. Here, we studied the role of the T reg /Th17 balance for maintaining the intestinal barrier function in a mouse model of severe AP., Design: AP was induced by partial duct ligation in C57Bl/6 or DEREG mice, in which regulatory T-cells (T reg ) were depleted by intraperitoneal injection of diphtheria toxin. By flow cytometry, functional suppression assays and transcriptional profiling we analysed T reg activation and characterised T-cells of the lamina propria as well as intraepithelial lymphocytes (IELs) regarding their activation and differentiation. Microbiota composition was examined in intestinal samples as well as in murine and human pancreatic necrosis by 16S rRNA gene sequencing., Results: The prophylactic T reg- depletion enhanced the proinflammatory response in an experimental mouse model of AP but stabilised the intestinal immunological barrier function of Th17 cells and CD8 + /γδTCR + IELs. T reg depleted animals developed less bacterial translocation to the pancreas. Duodenal overgrowth of the facultative pathogenic taxa Escherichia/Shigella which associates with severe disease and infected necrosis was diminished in T reg depleted animals., Conclusion: T regs play a crucial role in the counterbalance against systemic inflammatory response syndrome. In AP, T reg -activation disturbs the duodenal barrier function and permits translocation of commensal bacteria into pancreatic necrosis. Targeting T regs in AP may help to ameliorate the disease course., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflict of interest LK received previous speaker fees and/or travel expenses from Recordati Rare Diseases and Roche Diagnostics GmbH. FK has no financial interests to declare. KH received previous speaker fees from Recordati Rare Diseases. BS received previous speaker fees and travel expenses from Novartis Pharma GmbH and Topcon Corporation. SP received previous speaker fees and/or travel expenses from Novartis Pharma GmbH, Oertli AG, Bayer AG, Alcon Pharma GmbH and Pharm-Allergan GmbH. NL received income from honoraria as a lecturer from Alcon Laboratories, NIDEK Co., and CenterVue SpA. CP received previous speaker fees from Novartis Pharma GmbH and travel expenses from Recordati Rare Diseases Inc.

Biological drugs are vital but often high-cost components of cancer treatment. Several biosimilar versions of these drugs have been approved in Europe and/or the USA, with many more in development. However, there is some disconnect between the biosimilars that are approved for use and those accessible in clinical practice, with availability impacted by factors including patent litigation and complex healthcare insurance policies, particularly in the USA. Provided the barriers to widespread uptake can be overcome, biosimilars offer potential benefits including cost savings and improved patient access versus the reference product (RP). This article provides an up-to-date and focused perspective on the development and use of biosimilars in the haemato-oncology setting. European and US regulatory pathways governing biosimilar licensing demand that there are no clinically meaningful differences between a biosimilar and its RP. Pathways are rigorously enforced and involve comprehensive non-clinical evaluations and clinical trials in selected indications to establish the equivalence or non-inferiority of efficacy, and the comparability of safety, of the biosimilar versus its RP. 'Indication extrapolation' is only permitted if scientifically justifiable considering mechanism(s) of action, pharmacokinetics, immunogenicity and safety in relevant patient populations. Switching treatment from RP to biosimilar is supported by most available data, predominantly from indications other than cancer, and post-marketing pharmacovigilance programmes are warranted. Notably, the potential benefits of biosimilar cancer treatment may extend beyond direct cost savings: for example, the availability of biosimilars of common regimen components may help incentivise the evaluation and/or clinical use of new treatment approaches and novel drugs.

Objectives: To analyse treatment outcomes and share clinical data from a large, single-centre, well-curated database (8174 eyes/6664 patients with 120 756 single entries) of patients with neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (VEGF). By making our depersonalised raw data openly available, we aim to stimulate further research in AMD, as well as set a precedent for future work in this area., Setting: Retrospective, comparative, non-randomised electronic medical record (EMR) database cohort study of the UK Moorfields AMD database with data extracted between 2008 and 2018., Participants: Including one eye per patient, 3357 eyes/patients (61% female). Extraction criteria were ≥1 ranibizumab or aflibercept injection, entry of 'AMD' in the diagnosis field of the EMR and a minimum of 1 year of follow-up. Exclusion criteria were unknown date of first injection and treatment outside of routine clinical care at Moorfields before the first recorded injection in the database., Main Outcome Measures: Primary outcome measure was change in VA at 1 and 2 years from baseline as measured in Early Treatment Diabetic Retinopathy Study letters. Secondary outcomes were the number of injections and predictive factors for VA gain., Results: Mean VA gain at 1 year and 2 years were +5.5 (95% CI 5.0 to 6.0) and +4.9 (95% CI 4.2 to 5.6) letters, respectively. Fifty-four per cent of eyes gained ≥5 letters at 2 years, 63% had stable VA (±≤14 letters), 44% of eyes maintained good VA (≥70 letters). Patients received a mean of 7.7 (95% CI 7.6 to 7.8) injections during year 1 and 13.0 (95% CI 12.8 to 13.2) injections over 2 years. Younger age, lower baseline VA and more injections were associated with higher VA gain at 2 years., Conclusion: This study benchmarks high quality EMR study results of real life AMD treatment and promotes open science in clinical AMD research by making the underlying data publicly available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the association between effort-reward imbalance (ERI) and health indicators among Bolivian school teachers., Design: School-based cross-sectional study., Setting: Sixty randomly selected schools from rural (33) and urban (27) schools in Chuquisaca, Bolivia., Participants: A total of 1062 school teachers were invited to participate, of which 597 answered the questionnaire (response 56.2%)., Exposure Measure: Psychosocial factors at work were explored through the short version of the Effort-Reward Questionnaire., Primary and Secondary Outcome Measures: Health outcomes included self-rated overall health, mental distress (12-item General Health Questionnaire ≥5) and the 7-day prevalence of low back pain (LBP) as well as neck or shoulder pain (Nordic Questionnaire). Crude and adjusted ORs and their 95% CIs for each health outcome were calculated using logistic regression models., Results: The median value for the effort-reward ratio was 0.91 (range: 0.3-2.3) with higher values for teachers from rural versus urban schools. Overall, about 43% of the teachers reported their overall health as fair or poor; 45% suffered mental distress, 17% reported LBP and 29% neck or shoulder pain. Prevalences were higher for teachers employed at rural schools compared with those at urban schools. After adjusting for potential confounders and school location, ERI was statistically significantly associated with fair/poor self-rated health (adjusted OR 1.7, 95% CI 1.0 to 2.9); mental distress (1.9; 95% CI 1.2 to 3.1) and LBP (2.3; 95% CI 1.3 to 4.1)., Conclusion: Our results indicate the urgent need to improve psychosocial working conditions among Bolivian school teachers, in order to promote their health and well-being., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study is to determine whether any correlation between CT findings and functional parameters exists to predict subclinical glucocorticoid secretion., Materials and Methods: This is a retrospective database study of 55 patients with incidentally discovered adenomas, investigated through CT with an adrenal protocol, assessing diameters and attenuation values on the unenhanced and contrast-enhanced phases. Patients underwent blood cortisol and corticotropin evaluation and overnight dexamethasone suppression test (DST), in accordance with clinical recommendations. Cortisol levels higher than 50 nmol/L after DST identified subclinical cortisol secretion. We identified 28 subjects with lipid-rich nonsecreting adenomas, nine with lipid-rich secreting adenomas, 11 with lipid-poor nonsecreting adenomas, and seven with lipid-poor secreting adenoma., Results: Cortisol levels after DST were significantly and positively related to mass diameters. At univariate analysis, maximum and minimum diameters and attenuation in the delayed phase were significantly related to the presence of secreting or nonsecreting adenoma; at multivariate analysis, only the minimum diameter and the attenuation in the venous phase entered the stepwise logistic regression. Similarly, minimum diameter and attenuation in the venous phase emerged also at the multivariate stepwise regression between radiologic parameters and cortisol levels after DST. The formula of the radiologic score computed by using the coefficients of the multivariate regression was as follows: (0.1914 × minimum diameter) + (0.0308 × enhanced attenuation). The diagnostic accuracy of this discriminatory score in differentiating secreting from nonsecreting adenomas was 84.9%, the sensitivity was 81.3%, and the specificity was 87.2%. Adenomas with scores greater than 7.59 were considered as secreting adenomas, and adenomas with scores less than 7.36 were considered as nonsecreting adenomas., Conclusion: This study shows that imaging parameters can predict subclinical cortisol hypersecretion in patients with adrenal adenomas.

Background: The C-terminal agrin fragment (CAF), a circulating byproduct of neuromuscular junction disassembly, has been proposed as a possible biomarker for sarcopenia. However, its validity in "real-world", multimorbid older persons is currently unknown. The present study was undertaken to verify if serum CAF levels were associated with sarcopenia in a population of old and very old persons living in the community., Methods: Data were from the ilSIRENTE Aging and Longevity Study, a prospective cohort study conducted in all persons aged 80years and older residing in the Sirente geographic area (Italy; n=332). The identification of sarcopenia was based on the criteria elaborated by the European Working Group on Sarcopenia in Older People (EWGSOP). Serum levels of CAF were determined using a commercial ELISA kit., Results: Sarcopenia was identified in 101 participants (30.8%). Serum levels of CAF were significantly higher in older adults with sarcopenia compared with non-sarcopenic participants (96.99±5.40pmol/L vs. 76.54±2.15pmol/L; p<0.001). The association remained significant in both genders after adjustment for several possible confounding factors, including age, cognition, disability status, body mass index, congestive heart failure, lung diseases, diabetes, renal failure, and plasma levels of C-reactive protein and interleukin 6., Conclusions: Our results obtained from a fairly large sample of old and very old, multimorbid community-dwellers show that elevated serum CAF levels are associated with sarcopenia, independent of age, gender and several clinical, functional, anthropometric, and biochemical variables. The determination of serum CAF concentration may therefore be proposed as a simple screening test for sarcopenia in the community., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: To analyze diagnostic accuracy of prompt post mortem Computed Tomography (pmCT) in determining causes of death in patients who died during trauma room management and to compare the results to gold standard autopsy during office hours., Methods: Multiple injured patients who died during trauma room care were enrolled. PmCT was performed immediately followed by autopsy during office hours. PmCT and autopsy were analyzed primarily regarding pmCT ability to find causes of death and secondarily to define exact causes of death including accurate anatomic localizations. For the secondary analysis data was divided in group-I with equal results of pmCT and autopsy, group-II with autopsy providing superior results and group-III with pmCT providing superior information contributing to but not majorly causing death., Results: Seventeen multiple trauma patients were enrolled. Since multiple trauma patients were enrolled more injuries than patients are provided. Eight patients sustained deadly head injuries (47.1%), 11 chest (64.7%), 4 skeletal system (23.5%) injuries and one patient drowned (5.8%). Primary analysis revealed in 16/17 patients (94.1%) causes of death in accordance with autopsy. Secondary analysis revealed in 9/17 cases (group-I) good agreement of autopsy and pmCT. In seven cases autopsy provided superior results (group-II) whereas in 1 case pmCT found more information (group-III)., Discussion: The presented work studied the diagnostic value of pmCT in defining causes of death in comparison to standard autopsy. Primary analysis revealed that in 94.1% of cases pmCT was able to define causes of death even if only indirect signs were present. Secondary analysis showed that pmCT and autopsy showed equal results regarding causes of death in 52.9%., Conclusions: PmCT is useful in traumatic death allowing for an immediate identification of causes of death and providing detailed information on bony lesions, brain injuries and gas formations. It is advisable to conduct pmCT especially in cases without consent to autopsy to gain information about possible causes of death and to rule out possible clinical errors.

Purpose of this study is to evaluate radiographic therapy response, clinical outcome and adverse effects of CyberKnife radiosurgery in patients suffering from orbital metastases. Sixteen orbital metastases originating from different solid cancers in fourteen patients were treated by single fraction CyberKnife radiosurgery. Radiographic response and clinical outcome were evaluated. The treated tumor volume ranged from 0.2 to 35 cm3 (median 2.3 cm3, mean 7.0 cm3, SD 6 10.4 cm3, CI 0.9-9.4 cm3). The prescription dose ranged from 16.5-21 Gy (median 18 Gy, mean 18.2 Gy, SD 6 1.2 Gy, CI 17.0-18.4 Gy). A no change situation was observed in nine lesions, partial remission in four as well as complete remission in one metastasis. Tumor growth was stabilized or regressive following CyberKnife therapy in 87% of the cases. Recurrence was observed in two cases (13%). Before therapy, three patients suffered from visual disturbance and five patients reported diplopia. Six patients had no initial symptoms. After therapy, one patient indicated improvement of the present visual deficit and two patients no change. Out of the two patients with persistent diplopia, two reported improvement after therapy and three no change. No progression of symptoms was noted in any of the cases. Fourteen out of sixteen treated lesions were stable or regressive following CyberKnife radiosurgery (87%). As no serious adverse effects were reported in this series, CyberKnife therapy was shown to be of great value for local management of orbital metastases.

As other cytokine families, chemokines have multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage. Chemokines play important roles in leukocyte trafficking and leukocyte activation, hence, blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicate that additional roles of chemokines in the regulation of innate and adaptive immune responses may adversely affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential and possible adverse effects of anti-chemokine strategies in renal inflammation.

Background: The microenvironment in the bone marrow - including lymphocytes - is part of the pathophysiology of multiple myeloma (MM). High dose chemotherapy followed by autologous stem cell transplantation is standard of care for younger patients., Aim: To determine the influence of reinfused lymphocyte subsets on event free survival (EFS) and overall survival (OS)., Methods: In peripheral blood (PB) and aphaeresis products (AP) of 41 MM patients lymphocyte subsets were determined by flow cytometry and were correlated with clinical outcome., Results: PB lymphocyte subsets did not influence EFS or OS. Residual plasma cells in the AP were not correlated with poor outcome, whereas a high percentage of B cells (CD19+) showed a trend towards reduced EFS (P = 0.051). A high amount of CD4 cells and an increased CD4/CD8 ratio were significantly associated with prolonged EFS. In contrast, high percentage of HLA-DR positive lymphocytes showed negative impact on EFS and OS (P = 0.03 and 0.02, respectively)., Conclusion: Obtained data suggest the non-activated (HLA-DR negative) helper CD4+ T cells in the AP to be tumour protective.

Lupus nephritis is a common solid organ manifestation of systemic lupus erythematosus (SLE). The disease is tightly linked to the production of autoantibodies and circulating immune complexes, i.e. immune complex glomerulonephritis. In this process chemokines mediate multiple biological effects, e.g. orchestrating proinflammatory microenvironments, the recruitment of immune cell subsets into the kidney, as well as the local activation of such immune effector cells. Autoimmune mice with targeted deletions of certain single chemokines or chemokine receptors are protected from renal autoimmune tissue injury. Interventional studies with specific antagonists against certain chemokines and chemokine receptors further support these findings. In this review we summarise the available experimental and human data on the expression and functional role of chemokines and chemokine receptors in lupus nephritis.

Cancer research with sole focus on the cancer cell and possibly growth factors cannot faithfully reproduce the environmental interaction, such as adhesion of tumor cells to e.g. stromal cells, which may determine the response of these tumors to therapy. Methodologically cell adhesion studies are often difficult since complete but careful detachment is the prerequisite for most signal transduction assays. We describe for the first time an alternative method for the co-incubation of multiple myeloma cells on long term primary bone marrow stromal cultures using the bone marrow stromal cell line HS-5. The methods are precisely described, advantages and disadvantages are discussed, and troubleshooting advises are given.

Apoptotic markers and tumor-associated antigens might be suitable to indicate the response to radiochemotherapy early. We analyzed the courses of nucleosomes, CEA, CA 19-9 and CYFRA 21-1 in 25 colorectal cancer patients during radiochemotherapy (4 postoperative, 13 preoperative, 8 local relapse therapy). Blood was taken before therapy, daily during the first week, once weekly during the following weeks, and at the end of the radiochemotherapy. After a temporary decline 6 h after the first irradiation, nucleosomes rose in most patients rapidly reaching a maximum during the first days which was followed by a subsequent decrease. In patients receiving postoperative therapy after complete resection of tumor, nucleosome levels generally were lower than in patients with preoperative or relapse therapy. Correspondingly, CEA, CA 19-9 and CYFRA 21-1 levels of postoperatively treated patients were the lowest whereas those with tumor relapse had the highest ones. During preoperative therapy, lower nucleosome concentrations were found in patients with response to therapy resulting in a smaller area under the curve of days 1-3 (AUC) than in those with progressive disease (p = 0.028). The other parameters did not indicate the response to therapy at the initial treatment phase. In conclusion, the course of nucleosomes (AUC) might be valuable for the early prediction of therapy response in preoperatively treated colorectal cancer patients., (Copyright (c) 2006 S. Karger AG, Basel.)

Nucleosomes appear spontaneously in elevated concentrations in the serum of patients with malignant diseases as well as during chemo- and radiotherapy. We analyzed whether their kinetics show typical characteristics during radiochemotherapy and enable an early estimation of therapy efficacy. We used the Cell Death Detection Elisa plus (Roche Diagnostics) and investigated the course of nucleosomes in the serum of 32 patients with a local stage of pancreatic cancer who were treated with radiochemotherapy for several weeks. Ten of them received postsurgical therapy, 21 received primary therapy and 1 received therapy for local relapse. Blood was taken before the beginning of therapy, daily during the first week, once weekly during the following weeks and at the end of radiochemotherapy. The response to therapy was defined according to the kinetics of CA 19-9: a decrease of CA 19-9 > or =50% after radiochemotherapy was considered as 'remission'; an increase of > or =100% (which was confirmed by two following values) was defined as 'progression'. Patients with 'stable disease' ranged intermediately. Most of the examined patients showed a decrease of the concentration of nucleosomes within 6 h after the first dose of radiation. Afterwards, nucleosome levels increased rapidly, reaching their maximum during the following days. Patients receiving postsurgery, primary or relapse therapies did not show significant differences in nucleosome values during the time of treatment. Single nucleosome values, measured at 6, 24 and 48 h after the application of therapy, could not discriminate significantly between patients with no progression and those with progression of disease. However, the area under the curve of the first 3 days, which integrated all variables of the initial therapeutic phase, showed a significant correlation with the progression-free interval (p=0.008). Our results indicate that the area under the curve of nucleosomes during the initial phase of radiochemotherapy could be valuable for the early prediction of the progression-free interval.

There is still controversy as to which surgical method is the most suitable for repair of abdominal aortic aneurysm with concomitant horseshoe kidney (AAA-HSK). We report three cases of AAA-HSK treated with endovascular aneurysm repair. In one of these patients we sacrificed the accessory renal artery by applying coils before the operation. Renal infarction, hypertension, or elevated serum creatinine level was not observed in any of our patients. If the blood supply to the kidneys is taken into consideration, endovascular aneurysm repair is our preferred surgical method for repair of AAA-HSK when anatomic conditions are suitable for stent-graft application and kidney function is normal.

Objective: To compare S-100B and interleukin-8 serum values on scene/at admission and 12 hrs later with respect to neurologic long-term outcome 12 months after cardiac arrest and return of spontaneous circulation, as well as after severe traumatic brain injury., Design: Prospective comparative cohort study., Setting: On scene; intensive care units of a university hospital., Patients: Twenty patients with out-of-hospital cardiac arrest. Twenty patients with severe traumatic brain injury., Interventions: Therapy was adjusted to the standards of modern prehospital and intensive care management by physicians who were not involved in the study., Measurements and Main Results: First median S-100B values of the cardiac arrest group (4.42 ng/mL) mounted as high as those of the traumatic brain injury group (4.11 ng/mL). Within 12 hrs, S-100B levels significantly decreased to 0.75 ng/mL in cardiac arrest patients and to 0.68 ng/mL in traumatic brain injury patients but remained significantly elevated compared with the controls (0.04 ng/mL). Interleukin-8 levels of the cardiac arrest patients on scene (30.33 pg/mL) were clearly elevated above normal (12.60 pg/mL) and increased significantly to 101.40 pg/mL after 12 hrs. They showed no significant difference compared with those of the traumatic brain injury patients (78.75 pg/mL and 96.00 pg/mL, respectively). Multivariate Cox regression analysis in cardiac arrest patients identified only the S-100B level measured 12 hrs after study entry as an independent predictor for unfavorable neurologic outcome according to the Glasgow Outcome Scale score. In contrast, S-100B as well as interleukin-8 levels quantified 12 hrs after admission significantly predicted an unfavorable neurologic course in the traumatic brain injury group., Conclusions: Significantly elevated S-100B and interleukin-8 serum levels 12 hrs after cardiac arrest suggest that primary brain damage and systemic inflammatory response are comparably serious with that of traumatic brain injury. In both collectives, increased S-100B values measured 12 hrs after insult correlated well with an unfavorable neurologic outcome after 12 months.