Bronglais General Hospital

Abstract Aim Premature failure of arthroplasty implants, primarily caused by aseptic loosening, remains a significant challenge in orthopaedic care. This process is driven by wear-debris-induced inflammatory factors (WDIF), which activate osteoclast precursors, including monocytes, initiating osteolysis. This study aimed to elucidate the mechanisms behind CD14+ monocyte migration in response to WDIF-derived stimuli, exploring their potential as diagnostic tools for aseptic loosening. Method Human monocytes were isolated from healthy donors and labelled with PKH26 fluorescent dye. Revision tissue from aseptic loosening patients and healthy synovium from trauma patients (control) were xenografted into NOD-SCID mice (N=6). Labelled monocytes were injected intravenously, and their migration was tracked non-invasively using in vivo fluorescence imaging over 72 hours. Post-euthanasia, fluorescence intensity in transplanted tissues and major organs (liver, kidney, lung, spleen, heart) was quantified. Statistical significance was determined using a T-test (p<0.05). Results PKH26-labeled monocytes, predominantly the classical CD14++CD16- subset, exhibited significant migration toward revision tissue stimuli compared to controls (p=0.0021). Fluorescence microscopy showed peak signal intensity at the 72-hour mark, confirming targeted migration. Ex vivo imaging validated these findings, with minimal fluorescence in other organs. Conclusions This study highlights WDIF as key mediators in the recruitment of circulatory CD14+ monocytes to periprosthetic tissues, advancing our understanding of aseptic loosening. The findings suggest CD14+ monocytes as potential biomarkers for early detection of aseptic loosening, offering a promising pathway to improve diagnostics and extend the longevity of arthroplasty implants.

Central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children, with prognosis remaining dismal for some of these malignancies. Though the past two decades have seen advancements in surgery, radiation, and targeted therapy, major unresolved hurdles continue to undermine the therapeutic efficacy. These include challenges in suboptimal drug delivery through the blood-brain barrier (BBB), marked intra-tumoral molecular heterogeneity, and the elusive tumor microenvironment. Drug repurposing or re-tasking FDA-approved drugs with evidence of penetration into the CNS, using newer methods of intracranial drug delivery facilitating optimal drug exposure, has been an area of intense research. This could be a valuable tool, as most of these agents have already gone through the lengthy process of drug development and the evaluation of safety risks and the optimal pharmacokinetic profile. They can now be used and tested in clinics with an accelerated and different approach. Conclusions: The next-generation therapeutic strategy should prioritize repurposing oncologic and non-oncologic drugs that have been used for other indication, and have demonstrated robust preclinical activity against pediatric brain tumors. In combination with novel drug delivery techniques, these drugs could hold significant therapeutic promise in pediatric neurooncology.

Background: In the United States, over 38 million people have diabetes mellitus (DM) and more than 6 million have heart failure (HF). DM and HF often coexist, and each condition independently increases the likelihood of developing the other. Approximately 40% of individuals with HF also have DM, and this prevalence is even higher among older adults and hospitalized patients. While there has been concern regarding the increasing burden of disease for both conditions individually over the last decade, a comprehensive examination of mortality trends associated with their coexistence has not been thoroughly explored. Methods: This study analyzed death certificates from the CDC WONDER database, specifically focusing on mortality caused by the simultaneous presence of HF and DM among individuals aged 75 years and older. The data covers the period from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, and race/ethnicity. Results: Between 1999 and 2020, a total of 663,016 deaths were reported in patients with coexisting HF and DM. Overall, AAMR increased from 154.1 to 186.1 per 100,000 population between 1999 and 2020, with an initial increase from 1999 to 2005 (APC: 0.80; 95% CI: -0.17 to 2.94), a significant decline from 2005 to 2011 (APC: -2.82; 95% confidence interval (CI): -5.47 to – 1.71), a subsequent increase from 2011 to 2018 (APC: 0.61; 95% CI: -0.59 to 2.18), and finally a steep increase from 2018 to 2020 (APC: 11.30; 95% CI: 6.98 to 14.11). Gender-based analysis revealed that older men had consistently higher AAMRs than older women (Men: 185; 95% CI: 184.3 to 185.6; vs Women: 135.4; 95% CI: 135 to 135.8). Furthermore, we found that AAMRs were the highest among non-Hispanic American Indian or Alaska natives (214.4; 95% CI: 207.5 to 221.4) followed by non-Hispanic African Americans (179.9; 95% CI: 178.5 to 181.4), Hispanics (159.5; 95% CI: 158 to 161.1), non-Hispanic White (152.9; 95% CI: 152.5 to 153.3), and non-Hispanic Asian or Pacific Islander populations (104.1; 95% CI 102.4 to 105.8) (Figure 1). Conclusion: The mortality rate due to coexisting HF and DM has increased in the elderly population over the past decade. Males and non-Hispanic American Indians or Alaskan Natives had the highest AAMRs in our study.

To assess whether prodromal symptoms of RA, as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between 1 January 2004 and 1 May 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. In total, 70 115 cases were eligible for inclusion, of which 66.4% were female. Twenty-one symptoms were coded in >0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (1.71, 99.76 % confidence interval 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82). There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.

Abstract Aims This annual audit was carried out to assess the quality of emergency appendicectomy service in our hospital between January 2013 and September 2022. We audited 5 main qualities; time to surgery, operative techniques (laparoscopic, open), length of stay (LOS), 30 days post-operative re-admission rate, and the rate of “negative” appendicectomy. These parameters were compared against the available national audit outcome. Methods A retrospective analysis was conducted. Patients were identified from the hospital database. Data including demographics, above qualities and histology were collected from the hospital clinical information system “Myrddin” and Welsh Clinical Portal. Results Table shows the outcome of emergency appendicectomy between January 2013 and September 2022. Conclusions The increase of rate of laparoscopic appendicectomy over 10 years time reaching 98% was associated with decrease in the 30 days re-admission rate. Rate of “Negative Appendecectomy” is comparable to national outcome and has decreased significantly during COVID time.

Investigation of head and neck cancers places a significant burden on the National Health Service and effective resource allocation is of perpetual importance. Existing risk calculators are designed to stratify the likelihood of underlying malignancy according to symptoms, but are less relevant in secondary care as they do not integrate clinical examination findings (e.g. naso-endoscopy). We looked to evaluate the utility of magnetic resonance imaging (MRI) in investigating patients with unilateral odynophagia and a normal clinical examination. A retrospective analysis was conducted over a 54-month period; 484 consecutively-recruited adult patients who underwent MRI of the neck for suspected malignancy were included. Imaging reports, case notes, and histopathology results were reviewed. Patients with previously diagnosed/treated malignancy, undergoing surveillance, or those with pathology of the salivary glands, oral cavity or thyroid gland, were excluded. A multivariate binary logistical regression model was performed to calculate the odds ratios and probabilities of malignancy for each presenting symptom, with and without negative nasoendoscopy findings. The overall incidence of malignancy within the cohort was 173/484 patients (35.7%; 95% CI 31.5%-40.2%) with no cases of malignancy in patients presenting with odynophagia and a normal nasoendoscopy (0/39). The presence of a neck lump was significantly associated with malignancy, (odds ratio [OR] 2.03, p = .001; 95% CI 1.59-2.58), as was dysphagia (OR 1.52, p = .009; 95% CI 1.11-2.11). Conversely, globus was found to have an inverse association (OR 0.41, p < .001; 95% CI 0.24-0.70). New patients presenting with odynophagia alone and normal endoscopy or globus have a low likelihood of underlying malignancy, justifying reassurance and follow-up in the event of persistent symptoms. Contrariwise, patients with a neck lump, dysphagia, odynophagia and multiple concurrent aerodigestive tract symptoms, or an abnormal endoscopy have a high likelihood of underlying malignancy and should be investigated accordingly.

The aim of this study was to investigate nurse and allied health professional experiences and attitudes toward critical care research in Wales. Data were collected related to demographic characteristics, involvement in and understanding of research, perceived influences and attitudes towards research. We calculated means (ranges) for continuous variable and frequencies (proportions) for discrete variables and performed an exploratory factor analysis. Response rate was 55% (n = 575). Most respondents (84%) had participated in research less than five times in the previous 12 months, yet 91% believed research led to improved care patients. Only 32% respondents felt they were encouraged by managers to participate in research. Only 25% respondents had undertaken research training. Few respondents (29%) reported receiving adequate information regarding study progress or results (25%). Linear regression models indicate that a higher level of formal education was associated with a more positive view of research across all attitude factors. Promotion of research by colleagues and recognition/ opportunities for involvement in critical care research, were positively associated with the acceptability and experience of research. A number of factors have been identified that could be targeted to improve recruitment to critical care research, including identification of staff to promote research, improved communication of study progress and findings and management encouragement to attend research training. Staff attitudes were positive towards the benefit of research on patient care in Wales.

A 61-year-old Caucasian man (previously fit and well) presented to the emergency department with 2 days of non-traumatic, non-radiating lower back pain. He was admitted to our department having been provisionally diagnosed with discitis. Later that night, while being reassessed, a skin lesion on his thigh appeared and gas could be palpated. The patient was then taken immediately to theatre and a radical surgical debridement was performed. The organism that grew from tissue samples was Clostridium septicum, which when identified is an indication to exclude colonic neoplasms. The patient managed to preserve his limb on this occasion, however, he underwent a right hemicolectomy for what proved to be a colonic tumour at a later date.