University Hospitals of Morecambe Bay NHS Foundation Trust

Combination chemotherapy provides significant survival advantage in patients with advanced gastro-oesophageal adenocarcinoma compared with best supportive care. Peri-operative chemotherapy is standard of care for patients with operable disease. We hypothesised that biomarkers of genomic instability and inflammation may have clinical utility in these patients. We initiated open-label, non-randomised biomarker studies in patients with advanced disease due to receive Epirubicin, Cisplatin and Capecitabine (ECX)/Epirubicin, Cisplatin and Fluorouracil (ECF) or Epirubicin, Oxaliplatin and Capecitabine (EOX)/Epirubicin, Oxaliplatin and Fluorouracil (EOF) regimens (advanced study, n = 375), and in patients planned to receive perioperative chemotherapy with the same regimen (peri-operative study, n = 306). Relative telomere length (RTL) in peripheral blood mononuclear cells (PBMCs) and plasma levels of 10 inflammatory cytokines were analysed to determine association with progression-free and overall survival, and response. Blood samples were collected prior to treatment and on each treatment cycle. Both studies comprised biomarker discovery and validation cohorts. Here we report analysis of the discovery cohorts. In advanced disease, high pre-treatment levels of IL8 and IL10 associated with poor Progression Free Survival (PFS) and Overall Survival (OS) in univariate analysis, and IL6 with poor OS. In multivariate analysis, IL6 and IL8 remained associated with OS, and IL8 with PFS. In the perioperative study, cytokine levels were significantly lower and no relationships were observed. There was no association between RTL and any endpoint in either study. Pre-treatment RTL was not prognostic, although IL6/IL8 were negative prognostic factors in advanced disease. Levels of these were lower in patients with localised disease, suggesting an association with disease progression. Further analysis of systemic inflammatory status in gastro-oesophageal adenocarcinoma may be promising for development of future predictive biomarker signatures.

<h3>Background</h3> Acute exacerbations of interstitial lung disease (AEILD) are devastating events with high mortality. A definite AEILD is defined by &lt;30-day deterioration in respiratory symptoms, not due to cardiac, thrombotic or pneumothorax causes, with new bilateral ground-glass changes on a background of ILD.¹ High-resolution CT imaging is central to this definition, yet its use during AEILD admissions is variable and understudied. We evaluated whether CT imaging during AEILD admission was associated with survival and differences in care. <h3>Methods</h3> We conducted a multicentre retrospective observational study of ICD-10-coded primary ILD admissions in patients ≥18 years, across 11 NHS hospitals in North West England between 01.01.2017 and 31.12.2019. AEILD events were identified using clinical criteria via manual review. Events were grouped by whether thoracic CT imaging was performed. Primary outcome was time to death from admission commencement. <h3>Results</h3> 511 AEILD admissions were identified; 192 (37.6%) had CT imaging. Median survival was significantly longer in the CT group (144 vs. 100 days; p=0.027); mean survival was also higher (493.8 vs. 394.7 days). Respiratory team involvement was more frequent in the CT group (79.2% vs. 62.1%; p&lt;0.001), as was high-dose intravenous methylprednisolone use (11.5% vs. 3.8%; p=0.002). Mean length of stay was longer in the CT group (11.5 vs. 6.6 days; p&lt;0.001), while palliative care input was more common in the non-CT group (20.1% vs. 14.6%). Baseline demographics, lung function and comorbidity scores were similar. <h3>Discussion</h3> CT imaging during AEILD admissions was associated with improved survival, more respiratory specialist input and greater use of high-dose steroid treatment. This may reflect diagnostic certainty influencing care escalation, or that in the non-CT group some patients were too unstable to undergo imaging and further management. <h3>Conclusion</h3> Hospitalised AEILD patients face high mortality. Our findings suggest variation in CT use may influence care and outcomes. Further prospective studies are needed to determine whether CT imaging contributes directly to improved survival or is a proxy for more intensive management. <h3>Reference</h3> Collard HR, <i>et al. Am J Respir Crit Care Med</i>. 2016;<b>194</b>(3):265–75.

<bold>Background:</bold> High flow nasal oxygen (HFNO) is an intervention used in severe hypoxaemia for critically unwell patients. While evidence of use in intensive care is increasingly established, evidence is limited in the ward-based setting. We sought to determine outcomes from HFNO use on the respiratory ward. <bold>Methods:</bold> We undertook a retrospective review of ward HFNO use between 01.01.2023 and 31.12.2023 across 2 Lancashire hospitals. Primary outcome was time from HFNO initiation to death. Patient demographics and clinical diagnosis were taken from medical records. <bold>Results:</bold> 102 admissions were identified. 57.8% (59/102) had no underlying respiratory disease. 62.7% (64/102) were diagnosed with pneumonia. Mean duration of HFNO was 4.67 days. Mean and median survival were 111 days and 9.5 days respectively, with a 66.7% all-cause inpatient mortality rate. There was no statistical difference in survival between those with and without respiratory disease (p=0.699). With a significance value of p=0.1, clinical frailty score (HR 1.15, p=0.097) and starting HFNO >72 hours after admission began (HR 2.471, p=0.004) were associated with mortality. <bold>Conclusion:</bold> Our real-world data demonstrates high inpatient mortality with HFNO use in the ward setting. More studies with inclusion of ward-based HFNO are needed, alongside national guidelines to help identify the optimal patient group to receive this treatment. <fig><object-id>erj;66/suppl_69/PA2431/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

Sciatic hernias are the rarest form of pelvic floor hernia and pose significant diagnostic challenge due to their variable presentations. We present a case of an elderly female with progressive right-sided hip pain and an inability to weight-bear, ultimately diagnosed via MRI as a sciatic hernia containing small bowel. A successful laparoscopic transabdominal preperitoneal (TAPP) repair was performed with the mesh fixated and peritoneum closed using the novel device, LiquiBandFIX8. No complications were experienced intraoperatively, and there was full symptom resolution and no recurrence at follow-up. This case highlights the atypical presentation of sciatic hernias and further adds to the existing literature on the management of this condition. Laparoscopic TAPP repair combined with anchoring using LiquiBandFIX8 is a safe and effective treatment option, providing minimal invasiveness and favourable postoperative outcomes. Its use may represent an important advancement in repair of sciatic hernia.

Background: Uterine rupture is a severe obstetric complication traditionally associated with a past history of caesarean section or other factors causing uterine scarring. However, instances of atypical uterine rupture in patients have been reported. This case report present an atypical instance of uterine rupture in a patient with no known risk factors, emphasising the need for high suspicion for uterine rupture even in absence of risk factors. Case Presentation: The case discusses a gravida 3, para 2 female with no significant history, except for treatment for cervical intraepithelial neoplasia. No history of caesarean section or uterine scarring. Presented with light vaginal bleeding and later diagnosed with a miscarriage at 20+1 weeks of gestation. Managed with misoprostol per trust guidelines, the patient developed severe pain, signs of sepsis, and shock. An ultrasound revealed a heterogeneous mass in the lower uterine segment and free fluid in the pelvis. ACT scan confirmed a ruptured uterus with the foetus and placenta lying anteriorly and hemoperitoneum present. Alaparotomy was performed under general anaesthesia and the uterus was repaired. Postoperatively, the patient developed ileus and a pulmonary embolism, which were treated, leading to gradual recovery. Conclusion: This atypical case of uterine rupture highlights the need to maintain a high level of suspicion for uterine rupture, even in the absence of traditional risk factors. It also underscores the importance of careful patient management during labour induction with misoprostol, especially when complications arise. This case serves as a reminder to clinicians to consider all possible diagnoses when a patient's condition deteriorates, even in the absence of conventional risk factors. More research is needed on the use of labour-inducing drugs, particularly misoprostol, in the management of intrauterine foetal death.

Background Plantar foot pressure is a significant risk factor for ulceration in diabetic feet. However, foot pressure-based ulceration risk prediction has remained confined to the contribution of compressive pressure measured under controlled laboratory conditions for more than 30 years. This ignores the strong evidence that two important shear pressures are critical for tissue damage and ulceration genesis. It also prevents the cumulative effect of free-living behaviors on compressive and shear pressures from being integrated into predictive models of ulceration risk, and therefore risk prediction in real time. To address these fundamental limitations, the primary objective of this study was to assess the functionality of a novel LOMIS insole device that measures both shear and compressive pressure during daily activities over extended periods. The secondary objectives include assessing safety, validity, suitability, and feasibility as a clinical intervention. Methods Eighty patients with diabetes (aged 18–85 years, with feet classified as low, moderate, or high risk of ulceration) recruited from three clinical sites. Phase one includes a controlled walking assessment in the laboratory; Phase 2 pilots the device during participants’ free-living activities over five days, and phase three extends this to a three-month longitudinal study of compressive and shear pressure under real-life conditions. Discussion This is the first multi-center pilot study of a novel in-shoe pressure and shear measurement system that aimed to continuously measure the risk of foot ulceration. Through iterative testing to establish safety and functionality evidence, this study supports the development of digital healthcare technology and predictive foot ulceration risk models based on free-living data. Testing the feasibility and functionality of the LOMIS device in free-living circumstances will inform subsequent efficacy study designs and the pathway toward implementation in healthcare services. Trial registration ISRCTN87061146, Registered on 06/10/2022 https://www.isrctn.com/ISRCTN87061146 Protocol version 9, 12/02/2024

Background: Cerebrovascular disease is a leading cause of morbidity and mortality in the US, mainly affecting older adults. Aging significantly influences its manifestations and pathophysiology, impacting late-life quality. However, mortality trends in cerebrovascular disease among older adults of different gender, race, and geographic areas have not been thoroughly examined. Understanding these correlations and current death patterns is crucial for improving medical treatment and strategies. Research Aim: To investigate the impact of gender, race, and geographic disparities on cerebrovascular disease-related mortality rates among older adults in the United States, utilizing CDC-WONDER data from 1999 to 2020. Methodology: Cerebrovascular disease-related data from the CDC-WONDER database (1999-2020) using ICD-10 codes I60-I69 were analyzed. Annual Percent Change (APC), and Age-adjusted mortality rates (AAMR) per 100,000 persons were calculated and stratified by gender, race, place of death, state, census regions, and urban/rural classification. Joinpoint regression was utilized to assess trend changes and APC. Results: Between 1999 and 2020, 3,813,729 elderly individuals died from cerebrovascular disease. Overall, AAMR decreased from 1264.3 to 812.5, yet a rise was noted from 2018 to 2020, particularly in males (APC 6.069* vs. 4.668* in females). Non-Hispanic (NH) Blacks showed the highest APC (8.026*) from 2018 to 2020, while NH American Indians or Alaska Natives declined from 2013 to 2020 (-0.926). Non-metropolitan areas consistently had higher AAMRs, sharply increasing since 2018 (APC 4.818* vs. 5.135*). The Midwest had the highest APC (7.253*) from 2018 to 2020, while the South had the lowest APC (4.598*). Tennessee had the highest overall AAMR (1076.3) from 1999 to 2020, and New York had the lowest AAMR (609.7). (Figure 1) Conclusion: Despite declining overall mortality, persistent disparities exist in cerebrovascular disease-related mortality, with NH black males and rural residents facing the highest rates. Urgent public health action is needed, given the alarming rise in mortality from 2018 to 2020.

Dysphagia places a substantial burden on the critically ill, affecting 12%-84% of this cohort, and is independently associated with worse outcomes. Pharyngeal electrical stimulation (PES-treatment) is a novel dysphagia therapy with an emerging evidence base. This retrospective observational study describes our dysphagia service and reports the use of PES-treatment as a standard of care in recovering critically ill patients at a single-site tertiary UK hospital. Patients admitted to Acute or Cardio-Thoracic adult intensive care units between 1st July 2017 and 30th June 2022 were routinely referred to Speech and Language Therapy (SLT) following tracheostomy, or suspected dysphonia/dysphagia. Clinical assessments and direct laryngeal visualisation using Fibreoptic Evaluation of Swallowing (FEES) were performed. Severe dysphagia was defined as Penetration-Aspiration Score of ⩾6 and patients were offered PES-treatment when staffing allowed. Of 289 patients with severe dysphagia, 19 underwent a course of PES-treatment with the remaining patients receiving standard care. PES-treatment patients were significantly less likely to remain nil-by-mouth (11.1% vs 62.5%, Chi2 p < 0.001) or to have an enteral feeding tube in situ at discharge from critical care (27.8% vs 62.5%, p = 0.006) than those receiving standard dysphagia care. Both groups demonstrated an improvement in Penetration-Aspiration Score at repeat FEES: PES-treatment mean difference -2.0 (p = 0.003); non-PES-treatment -1.68 (p < 0.001); (61% PES-treatment improved vs 40% non-PES-treatment, p = 0.09). Our observations suggest that PES may be effective in the general critical care population. PES may offer new treatment options for patients and healthcare staff managing severe dysphagia and its significant consequences.