Lincoln County Hospital

Abstract Background Unlike some advanced therapies for Ulcerative Colitis (UC), upadacitinib (upa), a selective JAK1 inhibitor, is effective in biologic-exposed patients.1 IL-22 is a key pathogenic cytokine that signals via JAK1. High IL-22 activity, characterised by increased neutrophil chemotaxis and extracellular matrix (ECM) dysfunction, is associated with ustekinumab and anti-TNF resistance.2 Its receptor is expressed mainly on epithelial cells in the gut. We used an epithelial colonic organoid model to explore the effect of upa on these resistance mechanisms. Methods Left-sided colon biopsies were sampled from inactive UC and healthy control patients (HC) undergoing diagnostic endoscopy. Crypts were isolated using published protocols, suspended in Matrigel (Corning, US) and incubated at 37ºC.3 Before experimentation, the resulting organoids were differentiated for 72 hours in Wnt-free media. They were exposed for 24 hours to: 0.001% DMSO vehicle control, DMSO + IL-22 10 ng/ml, IL-22 10 ng/ml + 5 μM or 1 μM or 0.1 μM upa. RNA was extracted with Qiagen MiniKit and profiled with Next Generation Sequencing. Differentially expressed genes (DEGs) and pathways were determined. Proteins in the supernatant were quantified using Luminex multiplex panels for immune and fibrosis markers. Analyses were performed in R 4.3.2. Results Following IL-22 stimulation of HC organoids (n = 10), there were 2102 DEGs, with 1035 upregulated. These related to pathways involved in protein translation and interferon alpha/beta signalling. IL-22 induced a more pronounced transcriptional response in UC organoids (n = 7), including 4900 DEGs, of which 2400 were upregulated. These related to interferon alpha/beta signalling, IL-10 and IL-1 signalling, innate immune processes like complement cascade, and ECM mechanisms like keratinisation. There were 969 and 971 shared up-/downregulated genes, respectively. UC organoid genes were perturbed to a higher degree, up to 8 log fold change and -4 log fold change, respectively, compared to HC. In a dose-dependent manner, upa strongly inhibited the expression of key proinflammatory and treatment resistance transcripts, such as metalloproteinases, that were induced by IL-22 in our model. Similar findings were seen at proteomic level, where upa suppressed key IL-22-inducible proteins, such as the chemokines CXCL1 and CXCL10. Conclusion Upa inhibits IL-22-induced resistance mechanisms originating in colonic epithelial cells in UC, potentially contributing to its relative effectiveness in biologic-refractory patients. The breadth and degree of transcriptomic changes is more marked in UC compared to HC organoids after cytokine stimulation, suggesting they should be used in organoid research for UC as they more closely mimic in vivo conditions.

Background Periprosthetic femoral fractures (PFFs) are a growing indication for revision total hip arthroplasty (THA), particularly in elderly patients with complex comorbidities. Surgical management is challenging, with significant morbidity and mortality. This study evaluates outcomes following revision arthroplasty for PFFs at a tertiary trauma centre in the United Kingdom . Methods A retrospective review was conducted of 24 patients who underwent revision arthroplasty for PFFs between February 2021 and January 2022. Data collected included patient demographics, fracture classification, implant history, surgical details, and complications. Follow-up data were extracted from electronic health records up to February 2025. The primary outcome was the need for further revision; secondary outcomes included mortality and postoperative complications. Results The cohort had a mean age of 78.3 years (IQR: 16), with most injuries resulting from low-energy trauma. Vancouver B-type fractures were the most common, and three patients sustained interprosthetic fractures. Surgical strategies included modular fluted stems (n=13), femoral replacement prostheses (n=7), and cemented stems (n=4). Complications included one infection managed with suppressive antibiotics, two recurrent dislocations, and two cases of leg length discrepancy. One patient required further revision for instability. Twelve patients died during follow-up: two within 30 days, three within one year, and seven after one year. Thirteen patients were followed remotely due to frailty or relocation. Conclusion Revision arthroplasty for PFFs involves technically demanding procedures with significant risks. Despite the complexity, outcomes were in line with published data. Multidisciplinary care, timely surgical intervention, and individualised implant selection remain critical to optimise outcomes in this high-risk population.

Asthma is a heterogeneous disease characterized by overlapping clinical and inflammatory features. This study aimed to provide insight into the systemic inflammatory profile in asthma, greater understanding of asthma endotypes and the contribution of genetic risk factors to both. 4205 patients with asthma aged 16-60 were recruited from UK centers; serum cytokines were quantified from 708, including cytokines associated with Type 1, 2 and 17 inflammation. 3037 patients were genotyped for 25 single nucleotide polymorphisms associated with moderate-severe asthma. Serum cytokines associated with Th2 inflammation showed high coordinated expression for example, IL-4/IL-5 (R2 = 0.513). The upper quartile of the serum cytokine data identified 43.7% of patients had high levels for multiple Th2 cytokines. However, the groups defined by serum cytokine profile were not clinically different. Childhood-onset asthma was characterized by elevated total IgE, allergic rhinitis and dermatitis. Exacerbation prone patients had a higher BMI, smoking pack-years, asthma control questionnaire score and reduced lung function. Patients with blood eosinophils of > 300 cells/µL had elevated total IgE and lower smoking pack-years. None of these groups had a differential serum cytokine profile. Asthma risk alleles for; rs61816764 (FLG) and rs9303277 (IKFZ3) were associated with childhood onset disease (p = 2.67 × 10- 4 and 2.20 × 10- 7; retrospectively). No genetic variant was associated with cytokine levels. Systemic inflammation in asthma is complex. Patients had multiple overlapping inflammatory profiles suggesting several disease mechanisms. Genetic risk factors for moderate-severe asthma confirmed previous associations with childhood onset of asthma.

BACKGROUND: Patients with giant cell arteritis (GCA) often present with a range of symptoms including blurred vision, headache, myalgia, and lethargy. The diagnosis of GCA is guided by the American College of Rheumatology (ACR) criteria established in 1990. Despite being considered the gold standard for diagnosing GCA, temporal artery biopsy (TAB) is a procedure that carries potential complications, and its sensitivity can be variable. The aim of this study was to compare the positive TAB rates for GCA at our institution with the rates published in the medical literature.METHODS: A retrospective review was performed for all patients who underwent TAB at our institution between 2015 and 2016.RESULTS: A total of 108 consecutive patients who underwent temporal artery biopsy (TAB) were included. The demographic data revealed that GCA is more prevalent in females (69.4%) compared to males (30.6%), aligning with existing literature. The total positivity rate for TAB at our institution was 32%, which is notably lower than the published reference range of 60-66%.CONCLUSIONS: The lower-than-expected positivity rate and the significant number of false negatives emphasize the need for a multidisciplinary approach and the incorporation of newer imaging modalities.

BackgroundThe term "cardiomyopathy" encompasses a wide range of diseases with various underlying causes. Dilated cardiomyopathy (DCM) is characterized by ventricular dilation and impaired cardiac function in the absence of congenital, valvular, hypertensive, or ischemic heart disease (IHD). This study was motivated by the high prevalence of underlying DCM and chronic heart failure, coupled with a lack of comprehensive information on DCM. The primary objective of this study was to identify the clinical characteristics and contributing factors associated with individuals diagnosed with DCM.MethodsA total of 120 patients with DCM were enrolled in a two-year, hospital-based observational cross-sectional study conducted within the Medicine Department of a tertiary care center. The study assessed risk factors, including IHD, diabetes mellitus, alcohol consumption, and smoking.ResultsDCM was observed across all age groups, though it was notably more prevalent among middle-aged individuals (n = 50, or 41.7%) and the elderly (n = 35, or 37.5%). The condition was more commonly seen in men. IHD emerged as the predominant risk factor, affecting 75% of patients (n = 90), followed by diabetes mellitus (n = 85, or 70.8%), alcohol use (n = 75, or 62.5%), and smoking (n = 50, or 41.7%). Common symptoms included pedal edema, palpitations, easy fatigability, and exertional dyspnea.ConclusionIn conclusion, DCM is a critical condition that necessitates vigilant monitoring. Consistent observation of symptoms, recognition of potential triggers, and prompt identification of adverse drug reactions, electrolyte disturbances, and echocardiographic changes are essential. This awareness and early detection were responsible for the lower mortality and early symptom improvement observed in the present study group.

Conservation translocations may be a useful tool for the restoration of declining freshwater invertebrates, but they are poorly represented in the literature. We conducted a before‐after/control‐impact (BACI) experiment to test the efficacy of conservation translocation for re‐establishing abundant populations of the amphipod Gammarus lacustris, a declining species and wildlife food resource in depressional wetlands in the upper Midwest of the United States of America. Each study site (n = 19) contained at least one treatment wetland receiving translocated G. lacustris from a local donor and one control wetland. We selected study wetlands based on a suite of wetland characteristics and randomly assigned recipient versus control treatment. Gammarus lacustris was detected post‐translocation at only 2 of 22 recipient wetlands (1 of 19 sites). Overall, there was a statistical increase in G. lacustris density in recipient wetlands compared to controls; however, the results were of minimal biological significance due to being driven by a single site with low G. lacustris densities. Accordingly, our results suggest that future conservation translocations of amphipods might be successful if limited to recently restored wetlands or informed by a more complex habitat suitability model to differentiate dispersal limitations from habitat limitations. To develop such a model would involve identifying the fewest, most influential physical and biological factors (e.g. wetland size/structure, fish, aquatic vegetation, and water chemistry) from the numerous inter‐related factors that correlate with the abundance of naturally occurring G. lacustris; candidate wetlands to receive amphipods would be those for which the model predicts abundant G. lacustris but in which they do not presently occur.

Background: Governance of coronavirus disease 2019 (COVID-19) responses has been challenging for all countries. Syria has been particularly challenged, due to protracted multi-party conflict and debilitated health systems fragmented across several governance areas. To improve response governance, we need a better understanding of frontline response policy implementation across the country. This study explored perspectives of COVID-19 response governance among frontline healthcare providers over time and across all areas of Syria. Methods: We used a qualitative longitudinal study design, conducting five rounds of remote semi-structured key informant interviews in Arabic (i.e., approximately 8 interviews each in March 2020, July 2020, September 2020, December 2020, and September 2021) with 14 purposively sampled public and private healthcare providers in the three main areas-of-control [i.e., opposition-controlled area (OCA), autonomous administration-controlled area (AACA), al-Assad government-controlled area (GCA)]. We conducted integrative thematic analysis in Arabic, within and across geography and time, as described by Neale [2021]. Results: Almost all participants across all areas and rounds expressed distrust of local health authorities and dissatisfaction with COVID-19 response governance. This was most apparent in initial rounds and in GCA. Response planning was identified as insufficient, non-participatory, and non-transparent, with limited infrastructure and resources as the main challenges across time. Anticipated rapid virus spread and health systems collapse did not occur. Community adherence to prevention measures varied, starting weakly due to public skepticism, increasing immediately after first cases were confirmed and then fluctuating with case numbers and challenges of insecurity and misinformation. Perceptions of COVID-19 vaccination were positive, while low uptake and hesitancy were attributed to misinformation, disinformation, and disinterest. Participant optimism increased over time. Suggested improvements to COVID-19 response governance focused on strengthening current health systems’ capacity and improving coordination. Conclusions: Addressing transparency and misinformation should be a first step to improving public engagement and trust and thus response governance for COVID-19 and future health emergencies.

Dermatologic conditions which are related to diabetes include acanthosis nigricans, characterized by a hyper-pigmented, velvety, cutaneous thickening that appears predominantly in the neck, axilla, and groin areas; necrobiosis lipoidica (NL), a chronic, necrotizing, granulomatous skin disease; granuloma annulare; diabetic bullae and diabetic dermopathy; and infections. As these conditions can be present in the lower extremity, they should be sought and easily recognized by the health care providers who manage the diabetic lower extremity.

Aims and ObjectivesThe novel ED triage tool was developed after the authors found that 3 current triage tools for older adults injured by low level falls had very low specificity, resulting in significant over-triage. A Delphi study with experienced EM clinicians was subsequently carried out to create the novel tool. The triage tool utilised their responses.The aim was to determine whether these criteria could be used to identify patients with serious injuries at the point of ED triage, and hopefully improve their care.Method and DesignA retrospective review of 250 consecutive patients attending an East Midlands Trauma Unit after a fall or collapse from a height of less than two metres was carried out. The notes were examined to assess whether the patient met triage criteria in the new triage tool. The primary aim of the triage tool was to identify those with an Injury Severity Score of 9 or more. The sensitivity and specificity of the novel triage tool was calculated. The performance of individual triage criteria was assessed to determine whether any were particularly discriminatory.Results and ConclusionThe triage tool did not reach the ideal levels of sensitivity and specificity. Of the 55 criteria identified by clinicians as requiring immediate assessment, a significant proportion were not met by any patient. Patients who fell with acute illnesses were more likely to have abnormal observations than those with serious injuries, making criteria reliant on abnormal observations less useful.A combination of criteria such as pain in 2 body regions and reduced GCS was more predictive of serious injuries than a single criterion.The criteria generated by the Delphi study may be able to identify over 65s at risk of serious injuries after low-level falls, but further refinement of the tool and a larger sample size will be required for retrospective validation.

Aims and ObjectivesPrevious work carried out by the authors revealed that current triage tools for older trauma patients identified those with serious injuries, but specificity ranged from 11% - 31%, potentially resulting in significant levels of over-triage. The ideal triage tool should have an over-triage rate of under 35% with an under-triage rate of 5%.Our aim was to develop a triage tool better able to discriminate between those seriously injured after low level falls and the minimally injured patient. Method and DesignAn electronic three round Delphi study was designed to utilise the experience of triage nurses, and associate specialists and consultants in Emergency Medicine. Participants initially listed criteria they use to determine whether a patient aged 65 and over who had fallen less than two metres required immediate assessment, assessment within 30 minutes or routine assessment. In subsequent rounds participants rated their agreement or disagreement with each criterion and if consensus was reached that criterion was accepted. If pre-determined consensus was not reached the criterion was discarded.Results and ConclusionTwenty-nine clinicians completed three rounds of the study. A wide range of potential triage criteria were identified for this patient group. A total of 55 criteria reached consensus for immediate assessment, 16 for assessment at 30 minutes and 8 for routine assessment. The Delphi study revealed that senior clinicians use multiple criteria to decide which older patients who have fallen are at risk of serious injuries. Such a large number of criteria mean the Delphi study has failed to immediately generate a triage tool for the older, low-energy trauma patient. Owing to the study design we were unable to reduce the number of criteria further.Future work will focus on refining the criteria to aid development of a useable triage tool, especially as many immediate triage criteria are unlikely to be present in this patient group.