Introduction: In the UK, general surgeons must demonstrate competency in emergency general surgery before obtaining a certificate of completion of training. Subsequently, many consultants develop focused elective specialist interests which may not mirror the breadth of procedures encountered during emergency practice. Recent National Emergency Laparotomy Audit analysis found that declared surgeon special interest impacted emergency laparotomy outcomes, which has implications for emergency general surgery service configuration. We sought to establish whether local declared surgeon special interest impacts emergency laparotomy outcomes. Methods: Adult patients having emergency laparotomy were identified from our prospective National Emergency Laparotomy Audit database from May 2016 to May 2019 and categorised as colorectal or oesophagogastric according to operative procedure. Outcomes included 30-day mortality, return to theatre and length of stay. Binomial logistic regression was used to identify any association between declared consultant specialist interest and outcomes. Results: Of 600 laparotomies, 358 (58.6%) were classifiable as specialist procedures: 287 (80%) colorectal and 71 (20%) oesophagogastric. Discordance between declared specialty and operation undertaken occurred in 25% of procedures. For colorectal emergency laparotomy, there was an increased risk of 30-day mortality when performed by a non-colorectal consultant (unadjusted odds ratio 2.34; 95% confidence interval 1.10-5.00; p = 0.003); however, when adjusted for confounders within multivariate analysis declared surgeon specialty had no impact on mortality, return to theatre or length of stay. Conclusion: Surgeon-declared specialty does not impact emergency laparotomy outcomes in this cohort of undifferentiated emergency laparotomies. This may reflect the on-call structure at Birmingham Heartlands Hospital, where a colorectal and oesophagogastric consultant are paired on call and provide cross-cover when needed.

Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000 STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Each clinical state was characterized by different frequencies of nine discrete phenotypic clusters within four distinct STM subpopulations with diverse homeostatic, regulatory and inflammatory functions. This cellular atlas, combined with deep-phenotypic, spatial and functional analyses of synovial biopsy fluorescent activated cell sorted STMs, revealed two STM subpopulations (MerTKposTREM2high and MerTKposLYVE1pos) with unique remission transcriptomic signatures enriched in negative regulators of inflammation. These STMs were potent producers of inflammation-resolving lipid mediators and induced the repair response of synovial fibroblasts in vitro. A low proportion of MerTKpos STMs in remission was associated with increased risk of disease flare after treatment cessation. Therapeutic modulation of MerTKpos STM subpopulations could therefore be a potential treatment strategy for RA.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest chronic idiopathic dysimmune neuropathy. Pathophysiologic processes involve both cellular and humoral immunity. There are various known forms of CIDP, likely caused by varying mechanisms. CIDP in its different forms is a treatable disorder in the majority of patients. The diagnosis of CIDP is clinical, supported routinely by electrophysiology. Cerebrospinal fluid analysis may be helpful. Routine immunology currently rarely adds to the diagnostic process but may contribute to the identification of an associated monoclonal gammopathy with or without hematologic malignancy and the consideration of alternative diagnoses, such as POEMS syndrome, anti-myelin associated glycoprotein (MAG) neuropathy or chronic ataxic neuropathy, with ophthalmoplegia, M-protein, cold aglutinins and disialosyl antibodies (CANOMAD). The search for antibodies specific to CIDP has been unsuccessful for many years. Recently, antibodies to paranodal proteins have been identified in a minority of patients with severe CIDP phenotypes, often unresponsive to first-line therapies. In conjunction with reports of high rates of antibody responses to neural structures in CIDP, this entertains the hope that more discoveries are to come. Although still arguably for only a small minority of patients, in view of current knowledge, such progress will enable earlier accurate diagnosis with direct management implications but only if the important, unfortunately and infrequently discussed issues of immunologic technique, test reliability and reproducibility are adequately tackled.

Background: Multi-component lifestyle interventions are the first line treatment for obesity. Dietitians are ideally placed healthcare professionals to deliver such interventions. However, only a small proportion of patients with obesity are referred by general practice to dietitians, and the reasons for this are not clear. The present study aimed to explore general practice healthcare professionals' (GPHCPs) experiences and perceptions of dietitians in the context of obesity management. Methods: A convenience sample of GPHCPs practicing in the UK was recruited via a targeted social media strategy, using virtual snowball sampling. Data were collected using semi-structured interviews and analysed using framework analysis. Results: In total, 20 participants were interviewed (11 general practice nurses and nine general practitioners). Experiences of referring patients with obesity for dietetic intervention resulted in two main themes: (i) access barriers and (ii) the dietetic consult experience. Three themes emerged from participants' perceptions of a role for general practice dietitians: (i) utilising dietetic expertise; (ii) access to dietitian; and (iii) time. Participants experienced barriers to accessing dietitians for obesity management and felt that having a dietitian working within their general practice team would help address this. Having a dietitian embedded within their general practice team was perceived to have the potential to alleviate GPHCPs' clinical time pressures, offer opportunities for upskilling, and may improve patient engagement with obesity management. Conclusions: GPHCPs perceived that embedding a dietitian within their general practice team would be valuable and beneficial for obesity management. Our findings provide support for the funding of general practice dietitian roles in the UK.

No abstract available

Background: Whether or not clinically implementable exercise interventions in haemodialysis patients improve quality of life remains unknown. Objectives: The PEDAL (PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease) trial evaluated the clinical effectiveness and cost-effectiveness of a 6-month intradialytic exercise programme on quality of life compared with usual care for haemodialysis patients. Design: We conducted a prospective, multicentre randomised controlled trial of haemodialysis patients from five haemodialysis centres in the UK and randomly assigned them (1 : 1) using a web-based system to (1) intradialytic exercise training plus usual-care maintenance haemodialysis or (2) usual-care maintenance haemodialysis. Setting: The setting was five dialysis units across the UK from 2015 to 2019. Participants: The participants were adult patients with end-stage kidney disease who had been receiving haemodialysis therapy for > 1 year. Interventions: Participants were randomised to receive usual-care maintenance haemodialysis or usual-care maintenance haemodialysis plus intradialytic exercise training. Main outcome measures: The primary outcome of the study was change in Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score (from baseline to 6 months). Cost-effectiveness was determined using health economic analysis and the EuroQol-5 Dimensions, five-level version. Additional secondary outcomes included quality of life (Kidney Disease Quality of Life Short Form, version 1.3, generic multi-item and burden of kidney disease scales), functional capacity (sit-to-stand 60 and 10-metre Timed Up and Go tests), physiological measures (peak oxygen uptake and arterial stiffness), habitual physical activity levels (measured by the International Physical Activity Questionnaire and Duke Activity Status Index), fear of falling (measured by the Tinetti Falls Efficacy Scale), anthropometric measures (body mass index and waist circumference), clinical measures (including medication use, resting blood pressure, routine biochemistry, hospitalisations) and harms associated with intervention. A nested qualitative study was conducted. Results: We randomised 379 participants; 335 patients completed baseline assessments and 243 patients (intervention, n = 127; control, n = 116) completed 6-month assessments. The mean difference in change in physical component summary score from baseline to 6 months between the intervention group and control group was 2.4 arbitrary units (95% confidence interval -0.1 to 4.8 arbitrary units; p = 0.055). Participants in the intervention group had poor compliance (49%) and very poor adherence (18%) to the exercise prescription. The cost of delivering the intervention ranged from £463 to £848 per participant per year. The number of participants with harms was similar in the intervention (n = 69) and control (n = 56) groups. Limitations: Participants could not be blinded to the intervention; however, outcome assessors were blinded to group allocation. Conclusions: On trial completion the primary outcome (Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score) was not statistically improved compared with usual care. The findings suggest that implementation of an intradialytic cycling programme is not an effective intervention to enhance health-related quality of life, as delivered to this cohort of deconditioned patients receiving haemodialysis. Future work: The benefits of longer interventions, including progressive resistance training, should be confirmed even if extradialytic delivery is required. Future studies also need to evaluate whether or not there are subgroups of patients who may benefit from this type of intervention, and whether or not there is scope to optimise the exercise intervention to improve compliance and clinical effectiveness. Trial registration: Current Controlled Trials ISRCTN83508514.

Eosinophilic granulomatosis with polyangiitis (eGPA) is a rare vasculitis of small-medium sized vessels that can cause both anterior and posterior ischaemic optic neuropathies. Herein, the authors present a rare case of eGPA presenting initially as an acute unilateral anterior ischaemic optic neuropathy from short posterior ciliary artery vasculitis. The diagnosis presented a challenge as clinical and histopathological evidence suggested allergic rhinosinusitis, and no invasive fungal sinusitis was found. The high serum eosinophilia, asthma, optic neuropathy and paranasal sinus abnormalities fulfilled the criteria for a diagnosis of eGPA. Furthermore serum was positive for myeloperoxidase antibodies. Subsequently the case was successfully treated with oral glucocorticoids and intravenous rituximab.

Objective: To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved. Background: Disability in IIH is predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need. Methods: A prospective, open-label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4-weekly (assessments were 3-monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30-day pretreatment period) compared to 12 months. Results: Fifty-five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) [95% CI] 10.8 (4.0) [9.5, 11.9], p < 0.001 and MHD reduced by 13.0 (9.5) [10.2, 15.7], p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) [9.6, 15.3], p < 0.001, headache severity (scale 0-10) fell by 1.3 (1.7) [0.9, 1.9], p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) [1.6, 6.9], p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test-6 score and quality of life Short Form-36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients). Conclusions: This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene-related peptide is likely a modulator driving headache and a useful therapeutic target.

No abstract available.

Background & aims: We evaluated the efficacy and safety of upadacitinib, an oral selective inhibitor of Janus kinase 1, as induction therapy for ulcerative colitis (UC). Methods: We performed a multicenter, double-blind, phase 2b study of 250 adults with moderately to severely active UC and an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressive agents, and/or biologic therapies. Patients were randomly assigned to groups that received placebo or induction therapy with upadacitinib (7.5 mg, 15 mg, 30 mg, or 45 mg, extended release), once daily for 8 weeks. The primary endpoint was the proportion of participants who achieve clinical remission according to the adapted Mayo score at week 8. No multiplicity adjustments were applied. Results: At week 8, 8.5%, 14.3%, 13.5%, and 19.6% of patients receiving 7.5 mg, 15 mg, 30 mg, or 45 mg upadacitinib, respectively, achieved clinical remission compared with none of the patients receiving placebo (P = .052, P = .013, P = .011, and P = .002 compared with placebo, respectively). Endoscopic improvement at week 8, defined as endoscopic subscore of ≤ 1, was achieved in 14.9%, 30.6%, 26.9%, and 35.7% of patients receiving upadacitinib 7.5 mg, 15 mg, 30 mg, or 45 mg, respectively, compared with 2.2% receiving placebo (P = .033, P < .001, P < .001, and P < .001 compared with placebo, respectively). One event of herpes zoster and 1 participant with pulmonary embolism and deep venous thrombosis (diagnosed 26 days after treatment discontinuation) were reported in the group that received upadacitinib 45 mg once daily. Increases in serum lipid levels and creatine phosphokinase with upadacitinib were observed. Conclusion: In a phase 2b trial, 8 weeks of treatment with upadacitinib was more effective than placebo for inducing remission in patients with moderately to severely active UC. (ClinicalTrials.gov, Number: NCT02819635).