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Guidance for the design and reporting of studies evaluating the clinical performance of tests for present or past SARS-CoV-2 infection.
No full textThe complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts.
No full textArthritis typically involves recurrence and progressive worsening at specific predilection sites, but the checkpoints between remission and persistence remain unknown. Here, we defined the molecular and cellular mechanisms of this inflammation-mediated tissue priming. Re-exposure to inflammatory stimuli caused aggravated arthritis in rodent models. Tissue priming developed locally and independently of adaptive immunity. Repeatedly stimulated primed synovial fibroblasts (SFs) exhibited enhanced metabolic activity inducing functional changes with intensified migration, invasiveness and osteoclastogenesis. Meanwhile, human SF from patients with established arthritis displayed a similar primed phenotype. Transcriptomic and epigenomic analyses as well as genetic and pharmacological targeting demonstrated that inflammatory tissue priming relies on intracellular complement C3- and C3a receptor-activation and downstream mammalian target of rapamycin- and hypoxia-inducible factor 1α-mediated metabolic SF invigoration that prevents activation-induced senescence, enhances NLRP3 inflammasome activity, and in consequence sensitizes tissue for inflammation. Our study suggests possibilities for therapeutic intervention abrogating tissue priming without immunosuppression
Leukotrienes Are Dispensable for Vaginal Neutrophil Recruitment as Part of the Immunopathological Response During Experimental Vulvovaginal Candidiasis.
No full textRecruitment of polymorphonuclear neutrophils (PMNs) into the vaginal lumen is the hallmark of an acute immunopathologic inflammatory response during vulvovaginal candidiasis (VVC) caused by Recurrent VVC (RVVC) remains a chronic health burden in affected women worldwide despite the use of antifungal therapy. Based on the role leukotrienes (LTs) play in promoting inflammation, leukotriene receptor antagonists (LTRAs) targeted for LTB (etalocib) or LTC, LTD and LTE (zafirlukast or montelukast) have been shown to reduce inflammation of epithelial tissues. An open-label pilot study using long-term regimens of zafirlukast in women with RVVC indicated the potential for some relief from recurrent episodes. To investigate this clinical observation further, we evaluated the effects of LT antagonistic agents and LT deficiency on the immunopathogenic response in a mouse model of VVC. Results showed that mice given daily intraperitoneal injections of individual LTRAs, starting 2days prior to vaginal inoculation with and continuing through 14days post-inoculation, had no measurable reduction in PMN migration. The LTRAs were also ineffective in reducing levels of the hallmark vaginal inflammatory markers (S100A8, IL-1β) and tissue damage (LDH) associated with the immunopathogenic response. Finally, LT-deficient 5-lipoxygenase knockout mice showed comparable levels of vaginal fungal burden and PMN infiltration to wild-type mice following inoculation with a vaginal (ATCC 96113) or laboratory (SC5314) isolate. These results indicate that despite some clinical evidence suggestive of off-target efficacy of LTRAs in RVVC, LTs and associated signaling pathways appear to be dispensable in the immunopathogenesis of VVC
Atrial disease and heart failure: the common soil hypothesis proposed by the Heart Failure Association of the European Society of Cardiology.
No full textQUADAS-C: A Tool for Assessing Risk of Bias in Comparative Diagnostic Accuracy Studies.
No full textComparative diagnostic test accuracy studies assess and compare the accuracy of 2 or more tests in the same study. Although these studies have the potential to yield reliable evidence regarding comparative accuracy, shortcomings in the design, conduct, and analysis may bias their results. The currently recommended quality assessment tool for diagnostic test accuracy studies, QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2), is not designed for the assessment of test comparisons. The QUADAS-C (Quality Assessment of Diagnostic Accuracy Studies-Comparative) tool was developed as an extension of QUADAS-2 to assess the risk of bias in comparative diagnostic test accuracy studies. Through a 4-round Delphi study involving 24 international experts in test evaluation and a face-to-face consensus meeting, an initial version of the tool was developed that was revised and finalized following a pilot study among potential users. The QUADAS-C tool retains the same 4-domain structure of QUADAS-2 (Patient Selection, Index Test, Reference Standard, and Flow and Timing) and comprises additional questions to each QUADAS-2 domain. A risk-of-bias judgment for comparative accuracy requires a risk-of-bias judgment for the accuracy of each test (resulting from QUADAS-2) and additional criteria specific to test comparisons. Examples of such additional criteria include whether participants either received all index tests or were randomly assigned to index tests, and whether index tests were interpreted with blinding to the results of other index tests. The QUADAS-C tool will be useful for systematic reviews of diagnostic test accuracy addressing comparative questions. Furthermore, researchers may use this tool to identify and avoid risk of bias when designing a comparative diagnostic test accuracy study
Concepts and prospects of minimally invasive colorectal cancer surgery.
No full textIt is important that clinical radiologists understand and appreciate the minimally invasive surgery (MIS) options available to surgeons. Operative technologies are constantly evolving, and accurate, informed interpretation of clinical imaging is essential for optimum surgical management. Concurrent advancements in both MIS and radiological staging have certainly improved treatment decisions and outcomes. This article outlines the history, current concepts, evolving techniques, and future prospects of MIS as it pertains to colorectal cancer surgery
Case series of 100 supraorbital mini-craniotomies in patients with good grade aneurysmal subarachnoid haemorrhage at a single neurosurgical Centre.
No full textBACKGROUND
Endovascular techniques are becoming more common for cerebral aneurysms, but not all patients are suitable and open surgery is necessary for some. The traditional pterional approach requires a large craniotomy and this carries some morbidity in itself. With the growing expectation for minimally invasive surgery, we present our experience in supraorbital mini-craniotomy for good grade aneurysmal subarachnoid haemorrhage.
METHODS
Data on good-grade subarachnoid haemorrhage patients having aneurysms clipped via this approach were collected prospectively. Aneurysms at all anterior circulation sites were included, with the exception of the pericallosal artery, which was not within reach. A long-term follow-up questionnaire was sent to patients who had a supraorbital approach to clip the aneurysm at more than 1 year from hospital discharge.
RESULTS
Our results demonstrate mortality of 1% and severe residual disability in 10% of patients. Approach-related complications were low and it was considered that the operating space was not restricted in any of our cases. Return to work was achieved in 70% of patients who were working at the time of their haemorrhage.
CONCLUSIONS
Supraorbital micro-craniotomy is a safe approach for patients with proximal anterior circulation aneurysms, with low mortality and morbidity
Introduction of Systematized Nomenclature of Medicine-Clinical Terms Coding Into an Electronic Health Record and Evaluation of its Impact: Qualitative and Quantitative Study.
No full textBACKGROUND
This study describes the conversion within an existing electronic health record (EHR) from the International Classification of Diseases, Tenth Revision coding system to the SNOMED-CT (Systematized Nomenclature of Medicine-Clinical Terms) for the collection of patient histories and diagnoses. The setting is a large acute hospital that is designing and building its own EHR. Well-designed EHRs create opportunities for continuous data collection, which can be used in clinical decision support rules to drive patient safety. Collected data can be exchanged across health care systems to support patients in all health care settings. Data can be used for research to prevent diseases and protect future populations.
OBJECTIVE
The aim of this study was to migrate a current EHR, with all relevant patient data, to the SNOMED-CT coding system to optimize clinical use and clinical decision support, facilitate data sharing across organizational boundaries for national programs, and enable remodeling of medical pathways.
METHODS
The study used qualitative and quantitative data to understand the successes and gaps in the project, clinician attitudes toward the new tool, and the future use of the tool.
RESULTS
The new coding system (tool) was well received and immediately widely used in all specialties. This resulted in increased, accurate, and clinically relevant data collection. Clinicians appreciated the increased depth and detail of the new coding, welcomed the potential for both data sharing and research, and provided extensive feedback for further development.
CONCLUSIONS
Successful implementation of the new system aligned the University Hospitals Birmingham NHS Foundation Trust with national strategy and can be used as a blueprint for similar projects in other health care settings
Joint replacement surgery for elbow tumours: a systematic review of outcomes.
No full textBackground
Tumour resection followed by joint reconstruction is a surgical option in the appropriate patient. The evidence for such reconstructive surgery of the elbow joint is limited. The aim of this study is to review the literature to evaluate the outcomes of joint replacement surgery in tumours of the elbow.
Methods
A systematic review of PUBMED and EMBASE databases was conducted. Case series and comparative studies reporting results after total elbow arthroplasty, modular endo-prosthetic replacement and custom prosthesis were eligible for inclusion.
Results
Eleven eligible studies were identified (n = 134). At mean follow-up of 44 months, the overall revision rate was 14% and complication rate was 28%. The mean Mayo Elbow Performance Score was 75, with 56% of patients reporting good or excellent outcomes. The mean post-operative range of motion was 97°.
Discussion
Elbow prosthesis reconstruction after tumour resection can provide good functional outcomes at mid-term follow-up. The complication and revision rates are comparable to other indications for elbow replacement surgery. Further prospective studies are required to compare outcomes between different elbow arthroplasty options after tumour resection
Impact of home parenteral nutrition on family members: A national multi-centre cross-sectional study.
No full textBACKGROUND & AIMS
Home parenteral nutrition (HPN) is a necessary treatment for patients with chronic, type 3, intestinal failure (IF). HPN often requires lifestyle adaptations, which are likely to affect quality of life (QoL) in both patients and family members. The aim of this study was to identify the level of burden on family members who are involved with HPN care and to understand specific factors that contribute to any burden.
METHODS
Patients over the age of 18 and receiving HPN were identified in IF clinics from multiple centres across the U.K. Eligible patients were asked to complete the parenteral nutrition impact questionnaire (PNIQ) to assess their QoL, while family members were asked to complete the burden scale for family caregivers (BSFC). Logistical regression was undertaken giving adjusted odds ratios (aOR).
RESULTS
678 participants completed the survey representing 339 patients with their appointed family member. Mean PNIQ score was 11.53 (S.D. 5.5), representing a moderate impact of HPN on patients' QoL. On the BSFC scale, 23% of family members reported a moderate to very severe subjective burden indicating an increased risk of psychosomatic symptoms. After adjusting for age and gender, predictors of BSFC included: family members self-reported health status using the EuroQol visual analogue scale (aOR 19.91, 95% CI 1.69, 233.99, p = 0.017) and support received by health services (aOR = 5.83, 95% CI = 1.93, 17.56, p = 0.002). Employment status, disease type, number of nights on HPN and length of time on HPN were not associated with BSFC.
CONCLUSIONS
Family members with a poor health status or lack of support by health service were more likely to have a moderate to very severe subjective burden. Tailored support from the multi-professional IF team may reduce the burden experienced by family members of people dependent on HPN