Oxford University Hospitals NHS Trust

Abstract Aims Free tissue transfer is a common plastic surgical procedure with a wide array of applications. There is limited consensus on how free flap ischaemia time impacts flap survival. This systematic review aims to evaluate the association between free flap ischaemia time and acute flap failure rate. Methods A systematic review and meta-analysis in compliance with PRISMA statement standards was conducted following registration on the PROSPERO Register (CRD420251052841). A search strategy was developed and the search conducted in September 2024. Studies eligible for inclusion reported length of ischaemia time for free flap surgery and acute flap failure rate. 78 articles were eligible for inclusion and were published between 1997 and 2024. Study populations ranged from 7 to 3926 patients, with a pooled total of 26 374 free flaps in 23 615 patients. The meta-analysis showed overall risk of flap failure was 3.5% (95% c.i. 3%–4.1%). Meta-regression using ischaemia time as a continuous variable showed an increasing risk of acute flap failure from 3% (2.3%–3.9%) at 30 min ischaemia time to 7.5% (4.4%–12.5%) at 240 min. The variables study type, flap type, indication and risk of bias did not account for between study heterogeneity which was substantial. Conclusions This study has systematically assessed existing literature to show a significant association between prolonged ischaemia time and acute free flap loss. This association can guide microsurgical training as carrying out microsurgery in a time efficient manner has a positive impact on free flap survival.

Abstract Background Surgical site infection (SSI) is a common complication following major thoracic and abdominal surgery, associated with increased morbidity, prolonged hospitalisation, and is costly. Negative pressure wound therapy (NPWT) has been proposed as a prophylactic strategy to reduce wound complications, but trial evidence has been inconsistent. Methods This meta-analysis was carried out using the Preferred Reporting Items in Systematic Reviews and Meta-Analysis (PRISMA). A literature search was carried out March 2025, and titles/abstracts screened against our pre-defined inclusion criteria. Summary statistics for outcomes of interest underwent meta-analyses to a confidence interval (c.i.) of 95% and are presented as Forest Plots for Odds Ratio (OR) or mean difference (MD). Results 12 157 patients across 42 randomised trials in abdominal and thoracic surgery were included for analysis. NPWT significantly reduced SSI compared with standard dressings (OR = 0.54; 95% c.i.:0.43–0.69). The effect was consistent across commercial devices (PICO™and Prevena™). NPWT was associated with shorter length of hospital stay (MD = –1.21 days; 95% c.i., –1.61 to –0.80) but not with reduced risk of organ/space infection, wound dehiscence, or reoperation. Publication bias was detected; trim-and-fill analysis attenuated but did not eliminate the benefit (adjusted OR = 0.73; 95% c.i.:0.54–0.98). Discussion NPWT was associated with a nearly 50% reduction in SSI and shorter hospital stay after open abdominal surgery, with consistent benefit across device types. However, evidence of publication bias and limited long-term and patient-reported outcome data suggest that effect size may be overestimated. Selective use in high-risk patients and further investigator-led pragmatic trials are warranted.

Opioid-induced neurotoxicity (OIN) is a significant complication in palliative care, presenting with symptoms of hypersomnolence, hallucinations, cognitive dysfunction (including delirium), myoclonus and hyperalgesia. Due to limited research studies, a consensus on recognising these clinical manifestations is yet to be reached, complicating both early diagnosis and management. This rapid review aims to synthesise current evidence on the prevalence, clinical manifestations, risk factors and management strategies of OIN in the palliative care setting to enhance clinical practice. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search of Medline, Embase and the Cochrane Central Database, complemented by supplementary searches in ten palliative care journals. Studies with five or more palliative care patients were included, excluding those involving minors, animal models or substance misuse. Data were extracted, cross-checked and synthesised narratively. A total of 21 studies met the inclusion criteria. Prevalence of OIN varied widely from 6.4% to 38%, with common symptoms including delirium, myoclonus and hyperalgesia. Identified risk factors included age, renal and liver dysfunction, high opioid doses and concurrent use of specific medications. Opioid rotation and dose reduction emerged as potential management strategies, though patient responses varied significantly. OIN is under-diagnosed due to symptom overlap with other conditions. While opioid rotation and dose reduction show promise in managing OIN, further research is needed to establish standardised diagnostic criteria and effective treatment protocols. Enhanced clinical awareness and an individualised approach to opioid prescribing are crucial for improving patient outcomes in palliative care. CRD42024543988.

545 Background: The LITESPARK-013 study (NCT04489771) showed similar efficacy and safety between 200 mg and 120 mg (approved dose) doses of the HIF-2α inhibitor bel in pts with pretreated advanced ccRCC. We report exploratory biomarker analyses (including HIF-2α IHC, RNAseq, and WES) from this study. Methods: Pts with advanced ccRCC whose disease progressed after 1-3 prior systemic therapies (including an anti–PD-[L]1 therapy) were randomly assigned 1:1 to bel 200 mg or 120 mg QD. Treatment arms were pooled for biomarker analyses. Association of HIF-2α tumor proportion score (TPS; IHC D6T8V) and H-score (sum of each percentage multiplied by its corresponding intensity [0, 1+, 2+, 3+]) with clinical outcomes (ORR, PFS, OS) were tested at prespecified multiplicity-adjusted α = 0.05. Associations of RNAseq-based HIF-2α co-expression and HIF-2α cancer cell scores, glycolysis, angiogenesis, and other HIF-2α–related genes and signatures were tested at prespecified multiplicity-adjusted α = 0.10. Associations for molecular subtypes (Motzer et al. Cancer Cell . 2020;38:803) were tested at nominal α = 0.05. DNA mutations were evaluated by WES. Results: Of 154 pts, HIF-2α IHC was evaluable in 136, RNAseq in 109, and WES in 113 pts. HIF-2α TPS and H-score were positively associated with PFS ( P = 0.016 and 0.012, respectively), but not ORR or OS. HIF-2α cancer cell score was positively associated with ORR ( P = 0.085), but not PFS or OS. No associations with clinical outcome were observed for HIF-2α co-expression score. Glycolysis and angiogenesis were positively associated with ORR ( P = 0.036) and PFS ( P = 0.070), respectively, but these were no longer significant after adjustment of other signatures. ORR was consistent across molecular subtypes and by DNA mutation status (Table), with notably higher ORR in the BAP1 mutant vs wild-type group. Conclusions: In this first RNA and WES biomarker analysis of bel, HIF-2α TPS and H-score were potentially associated with PFS, and BAP1 mutation was potentially predictive of improved ORR in pts with RCC. Molecular subtypes, other RCC-related signatures, and VHL mutation showed no associations or trends with ORR, PFS, or OS. Prospective biomarker evaluations are needed to confirm these findings. Clinical trial information: NCT02853344 . n ORR, % (95% CI) All RNAseq evaluable 109 26.6 (18.6-35.9) Molecular subtypes Angiogenic 12 33.3 (9.9-65.1) Angiogenic/stromal 24 25.0 (9.8, 46.7) Immune/proliferative 22 27.3 (10.7-50.2) Stromal/proliferative 17 23.5 (6.8-49.9) Proliferative 17 23.5 (6.8-49.9) Other (unassignable to a subtype) 17 29.4 (10.3-56.0) VHL Mut 80 25.0 (16.0-35.9) WT 33 24.2 (11.1-42.3) PBRM1 Mut 59 23.7 (13.6-36.3) WT 54 25.9 (15.0-39.7) SETD2 Mut <jats:td colspan="1" rowspan=