Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus

Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10-15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. Here we show that response to axitinib in this setting is characterised by a distinct and predictable set of features. We conduct a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders have higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predict response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features include plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario.CC BY 4.0 (Creative Commons Attribution

Informant accuracy of IQCODE, AD8 and GPCOGi for diagnosis of dementia: does your friend know best?

BACKGROUND: Increasing numbers of people require evaluation for possible dementia. However, research on the accuracy of informant questionnaires in primary care remains limited. METHODS: This study assessed the diagnostic accuracy of IQCODE, AD8, and GPCOGi based on the informant's relationship to the patient. We recruited 240 participants from 21 general practices in South West England. The reference standard for a diagnosis of dementia was made by a specialist clinician using ICD-10 criteria. A threshold of greater than 3.3 on IQCODE, greater or equal to 2 on AD8 and less than 5 on the informant component of GPCOG was used to indicate an abnormal test. RESULTS: Of 238 participants with informant data, 131 had dementia, 60 had CIND, and 47 had normal cognition. Median informant age was 70 years (IQR 60 years to 78 years). 71% of informants were female and 56% were spouses. On all three questionnaires, compared to spouses, adult descendants tended to score participants more cognitively impaired, whereas friends scored participants less cognitively impaired. However, there was little evidence of difference by informant type once fully adjusted. Sensitivity by informant type ranged from 91 to 100% for IQCODE, 94-100% for AD8 and 99% to100% for GPCOGi. There was no significant difference in sensitivity by informant type. Specificity by informant type ranged from 25 to 79% for IQCODE, 13-75% for AD8 and 17-38% for GPCOGi. Adult descendants tended to have the lowest specificity at 25% (95% CI 10-47%) for IQCODE, 13% (95% CI 3-32%) for AD8 and 17% (95% CI 5-37%) for GPCOGi. Friends tended to have the highest specificity at 79% (95% CI 49-95%) for IQCODE, 75% (95% CI 48-93%) for AD8 and 38% (95% CI 15-64%) for GPCOGi. CONCLUSIONS: An informant of any relationship type, using IQCODE, AD8 or GPCOGi may be useful for ruling out dementia but not for ruling it in. We found no evidence of difference between spouse or adult descendants but friends performed significantly better overall on IQCODE and AD8.CC BY 4.0 (Creative Commons Attribution

British Thyroid Association Survey of Graves' Disease Management in the UK

BACKGROUND: Recent years have seen changes and uncertainties in evidence and guideline recommendations in Graves' disease treatment. To understand the impact of these developments on current practice, we undertook a survey of Graves' disease management in the United Kingdom and compared this to other national and international surveys. METHOD: Members of the British Thyroid Association, the UK Society for Endocrinology and regional endocrinology networks, were invited by e-mail to complete a 15-min online survey (October 2022 to March 2023). RESULTS: Out of 158 eligible respondents, 99% were endocrinologists. For a 40-year-old female with a first presentation of Graves' hyperthyroidism, TSH-receptor antibodies (TRAb) were requested at diagnosis and at follow-up by 95% and 76%, respectively. Isotope scans and ultrasound were rarely requested (< 5%). Majority (95%) would treat with antithyroid drugs (ATD), predominantly Carbimazole (CMZ), while radioactive iodine (RAI) was preferred for recurrent disease (81%). Common reasons for avoiding RAI were thyroid eye disease, pregnancy intention, or contact with young children whereas biochemical severity, goitre, or male sex did not influence decision to use RAI. Propylthiouracil (PTU) was preferred in preconception and early pregnancy, but after the first-trimester, 50% would continue PTU while 50% switch back to CMZ. CONCLUSIONS: The survey confirms a growing application of TRAbs, both for diagnostic and prognostic purposes. ATDs remain the preferred first-line therapy for Graves' disease, which is consistent with global trends but contrary to National Institute of Health and Care Excellence (NICE) guidance. Further studies are required to explore the clinical and pragmatic determinants of current treatment approaches.CC BY 4.0 Internationa

Assessing the environmental impact of propofol use in anaesthesia: a call for surveillance monitoring

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Management of post-operative anaemia in patients undergoing surgery for colorectal cancer: a qualitative focus group-based study

BACKGROUND: Optimal management of anaemia following surgery for colorectal cancer remains unclear. Peri-operative anaemia is common in patients undergoing resectional surgery for colorectal cancer. A significant amount of research has been conducted into the management of pre-operative anaemia; however, little work has investigated post-operative anaemia. We intended to investigate the facilitators of and barriers against the standardised correction of post-operative anaemia. These can aid in identifying optimum treatment for patients following surgery for colorectal cancer. METHODS: Four focus groups were held with 29 participants from a multidisciplinary panel of healthcare professionals from two different NHS hospital sites in the UK. The discussions were audio recorded and underwent professional transcription. Transcripts were checked against recordings before undergoing thematic analysis using a realist approach. RESULTS: Four themes were identified. The key barriers to standardised post-operative anaemia correction were a lack of protocoled guidelines or a defined pathway, insufficient education and training, and systemic barriers, such as financial drivers and drug availability. The key facilitator identified was collaboration and communication. DISCUSSION: This study has identified several key barriers and thresholds which can be used in future studies to improve the standardised management of post-operative anaemia.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

AI versus the spinal surgeons in the management of controversial spinal surgery scenarios

AIMS: The use of artificial intelligence (AI) in spinal surgery is expanding, yet its ability to match the diagnostic and treatment planning accuracy of human surgeons remains unclear. This study aims to compare the performance of AI models-ChatGPT-3.5, ChatGPT-4, and Google Bard-with that of experienced spinal surgeons in controversial spinal scenarios. METHODS: A questionnaire comprising 54 questions was presented to ten spinal surgeons on two occasions, four weeks apart, to assess consistency. The same questionnaire was also presented to ChatGPT-3.5, ChatGPT-4, and Google Bard, each generating five responses per question. Responses were analyzed for consistency and agreement with human surgeons using Kappa values. Thematic analysis of AI responses identified common themes and evaluated the depth and accuracy of AI recommendations. RESULTS: Test-retest reliability among surgeons showed Kappa values from 0.535 to 1.00, indicating moderate to perfect reliability. Inter-rater agreement between surgeons and AI models was generally low, with nonsignificant p-values. Fair agreements were observed between surgeons' second occasion responses and ChatGPT-3.5 (Kappa = 0.24) and ChatGPT-4 (Kappa = 0.27). AI responses were detailed and structured, while surgeons provided more concise answers. CONCLUSIONS: AI large language models are not yet suitable for complex spinal surgery decisions but hold potential for preliminary information gathering and emergency triage. Legal, ethical, and accuracy issues must be addressed before AI can be reliably integrated into clinical practice.All rights reserve

Intravascular Shockwave Lithotripsy for the Treatment of Severe Peripheral Arterial Disease: A Single-Centre Experience

Background Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral arterial disease. Various revascularization techniques are employed to treat peripheral arterial disease. Intravascular shockwave lithotripsy (IVL) is a relatively new procedure for the treatment of calcific lower limb peripheral arterial diseases (PAD). Objectives To assess the effectiveness and safety of shockwave lithotripsy in patients with severe PAD through an evaluation of limb salvage rate and patient survival. Methods A retrospective study of all patients treated with shockwave lithotripsy between November 2019 and June 2024 was performed. The primary outcome was amputation-free survival and secondary outcomes were potential complications of IVL (thrombo-embolization, perforation, and restenosis). Patients were followed up in the clinic and assessed both clinically and with a duplex scan at three months. Results A total of 38 patients were included in the study. The median age was 71 years; 28 were males. Among the patients, 28 (73.68%) were diabetic, 4 patients (10.53%) were current smokers, 10 patients (26.32%) were ex-smokers, and 24 patients (63.16%) were non-smokers. According to the Rutherford classification of PAD, 33 of the 38 patients were in stages 4-6. Only five patients were stage 3. Total number of treated arteries was 47. Treated lesions were 49% in the superficial femoral artery (SFA), 36% in the popliteal artery, 8% in the common femoral artery (CFA), 4% received treatment of the iliac arteries, and 2% of the posterior tibial artery. All treated arteries showed improved angiographic results. Four patients (10.53%) developed distal embolization. No perforation was recorded, and no significant flow-limiting dissection was recorded to require treatment. At the three-month follow-up, imaging revealed improvement in 58% of patients while 5% showed no improvement. Notably, follow-up imaging was not conducted in 37% of patients due to evident clinical improvement such as ulcer healing, palpable pulses, and the presence of Doppler signals. Seven patients required reintervention within three months after the initial IVL operation and 4 patients got revascularized after this period resulting in 11 patients requiring revascularisation after the initial operation. Amputation-free survival was 79% (30 patients). Conclusion Shockwave lithotripsy is associated with a high limb salvage rate and low complication rate. Further research is needed into long-term effectiveness and the role of shockwave treatment as an adjuvant to traditional revascularization techniques of patients with CLTI and short-distance claudicants.This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

Safety and efficacy of a novel 'One-Visit, Both-Cataracts' high-volume see-and-treat immediate sequential bilateral cataract surgery service in a public healthcare setting

PURPOSE: To evaluate the safety and efficacy of a novel cataract surgery pathway that combines a See-and-Treat (S&T) model with Immediate Sequential Bilateral Cataract Surgery (ISBCS) at the Nightingale Hospital, Exeter, UK. METHODS: A retrospective observational study was conducted on 102 consecutive patients (204 eyes) who underwent S&T ISBCS between July 2023 and July 2024. Patients were triaged based on referral information and underwent preoperative telephone consultations. On the day of surgery, clinical assessment and bilateral cataract surgery were completed in a single visit. Data collected included patient demographics, intraoperative and postoperative outcomes, and complications. RESULTS: Of the 127 patients listed, 102 (84.3%) completed S&T ISBCS. No intraoperative complications were recorded. Fourteen patients (13.7%) required unplanned postoperative consultations, with most cases being non-sight-threatening and self-resolving. Cystoid macular oedema (CMO) was reported in 2.9% of eyes, with no cases of visual loss or endophthalmitis. CONCLUSION: The S&T ISBCS model demonstrated safety and efficiency in delivering cataract care, with a high one-visit completion rate and low complication rates. This model offers significant time and resource savings whilst maintaining patient safety. It holds potential for broader implementation in healthcare settings facing increased demand for cataract services. Further studies are recommended to assess long-term outcomes and optimise this approach.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

Longitudinal Study on Clinical Predictors for Allergic Bronchopulmonary Aspergillosis in Children and Young People with Cystic Fibrosis Highlights the Impact of Infection with Aspergillus and Pseudomonas and Ivacaftor Treatment

Allergic bronchopulmonary aspergillosis (ABPA) is a well-known complication in children and young people with cystic fibrosis (CF) and without treatment causes structural lung damage. We performed a longitudinal observational study to identify clinical risk factors for ABPA in a cohort of children and young people with CF aged 8 to 17 years at baseline. Anonymised annual review UK CF Registry data from 2009 to 2019 for patients aged 8-17 years in 2009 were collected, with lung transplant recipients excluded. Baseline characteristics are presented for the whole group and cross-sectional comparisons made according to the presence of ABPA or not in 2009. Longitudinal analysis from 2009 to 2019 was completed on the group without ABPA in 2009 to identify predictors for the subsequent development of ABPA using a complementary log-log regression model. In 2009, there were 1612 patients, of which 1420 were ABPA-negative and 192 ABPA-positive. Aspergillus colonisation (p = 0.01) and IV antibiotic use (p < 0.0001) were associated with having ABPA in 2009. Longitudinal analysis of the group without ABPA in 2009 identified male gender, younger age, lower lung function, Pseudomonas aeruginosa infection, and Aspergillus colonisation to be significantly associated with the development of ABPA (p < 0.0001). Ivacaftor was significantly associated with reduced ABPA (OR 0.46, p = 0.01) but not lumacaftor/ivacaftor (OR 0.64, p = 0.28). Chronic oral macrolide use was significantly associated with increased risk of development of ABPA (OR 1.30, p < 0.0001). This study shows that lower lung function, Aspergillus colonisation, and Pseudomonas aeruginosa infection in children with CF were associated with the development of ABPA, highlighting the need for enhanced surveillance in these patients. This is the first study to show a protective association of ivacaftor and ABPA.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

Management of severe and fulminant Clostridioides difficile infection in adults

Clostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.CC BY 4.0 (Creative Commons Attribution