St. Mark's Hospital

Achieving efficient and stable hydrogen evolution reaction (HER) with earth-abundant electrocatalysts is pivotal for boosting the efficiency of alkaline water electrolysis. Here, we report an oxygen vacancy (O v )-rich Cu₂O/NiO heterostructure, which triggers a peculiar interfacial charge transfer from NiO to Cu₂O, creating catalytically active Ni³⁺–Cu 0/+ dual sites to synergistically promote water dissociation and hydrogen adsorption. The Cu₂O/NiO heterostructure exhibits a low overpotential of 19.7 mV at 10 mA cm⁻² with Tafel slope of 36 mV dec⁻¹, outperforming most of the reported catalysts. The anion exchange membrane (AEM) electrolyzer equipped Cu₂O/NiO electrode enables 1.78 V to reach 1 A cm⁻² for more than 200 hours of continuous operation. A thorough characterization study involving HRTEM/XPS/EPR/XANES and DFT calculation exemplifies the interfacial charge transfer dynamics in Cu₂O/NiO heterostructure and its HER catalytic mechanism, offering a new paradigm for rational design of noble metal-free HER electrocatalysts for practical AEM water electrolysis. • Interfacial charge transfer from NiO to Cu₂O in oxygen vacancy-rich Cu₂O/NiO • Catalytically active Ni³⁺–Cu 0/+ dual sites promote HER • 19.7 mV overpotential at 10 mA cm⁻² with 36 mVdec⁻¹ Tafel slopes were obtained • HRTEM/XPS/EPR/XANES and DFT exemplified interfacial charge transfer in Cu₂O/NiO

ABSTRACT Stoma formation diverts the flow of faeces to an opening on the skin, away from a section of bowel. Stomas are used to reduce the risks of bowel surgery and their effects are thought to be temporary and benign. However, negative effects [e.g. diversion colitis (inflammation in the excluded segment), poor quality of life, and an unclear effect on homeostasis] occur. We investigated these changes and whether distal feeding (DF) – the introduction of nutrition directly into the defunctioned bowel prior to stoma reversal – could mitigate these effects. A series of clinical, qualitative, immunological, metabolomic and microbiomic experiments conducted across 133 patients identified consistent changes in immune and microbiome response which differed according to stoma formation and underlying disease process [colorectal cancer (CRC) with or without chemotherapy, intestinal failure (IF)], including a unique immune signature in circulating memory T-cell homing in stoma patients. DF induced the proliferation and altered homing of memory T cells, particularly in patients who had received chemotherapy. DF led to changes in serum metabolites, increased circulating markers of gut health (citrulline, serotonin), and modified the faecal microbiota. DF also promoted a faster return of bowel function and earlier hospital discharge in patients with CRC, while in IF it accelerated intestinal autonomy from parenteral nutrition. This in-depth analysis of sequential experiments characterises gut homeostasis and post-operative systemic immunity after stoma formation in CRC and IF patients, and quantifies and explains the benefit of DF in these groups. This research program has wide-ranging implications for patients worldwide with stomas. Given its simplicity, affordability and wide applicability, DF has the potential to become a transformative adjunct in surgical recovery and improved long-term gut health in patients with stomas.

Abstract Background It is uncertain if sessile serrated lesions (SSLs) in patients with inflammatory bowel disease (IBD) represent coincidental sporadic lesions or a distinct biological entity. Molecular studies suggest SSLs in IBD are more frequently KRAS mutated, contrasting with the BRAF driven pathway typical of sporadic SSLs.¹,² More recent data supports a distinct clinicopathologic and molecular profile,3 the understanding of which is critical for optimising surveillance strategies. Methods Colonic serrated lesions from St. Mark’s Hospital pathology database (2014–2022) were reviewed and classified as SSL or dysplastic SSL (SSL-D) and stratified by disease background: IBD, serrated polyposis syndrome (SPS) or sporadic. Cases with overlapping conditions or indeterminate features were excluded. Lesion size, location, patient demographics and IBD subtype and extent were compared. Ethical approval was obtained for this study. Results IBD group: 224 SSLs were identified (200 SSL, 24 SSL-D; dysplasia rate 10.7%). 132 out of 157 patients had ulcerative colitis. No significant differences were seen in lesion location, size or IBD related factors between SSL and SSL-D (Table 1). Median cumulative inflammatory burden for SSL-D was 3.58. SSL-Ds did not show a significant right-sided predominance. SSL-Ds were more frequent in older patients (median 69 vs 60 yrs, p = 0.006). Sporadic group: 5304 SSLs (5030 SSL, 274 SSL-D; dysplasia rate 5.2%) were identified. SSL-Ds were predominantly right-sided and more frequent in older patients (median 68 vs 61 yrs; p < 0.001). SPS group: 4554 SSLs (3662 SSL, 82 SSL-D; dysplasia rate 2.2%) were identified. SSL-Ds were also mainly right-sided and more frequent in older patients (median 64 vs 41 yrs; p < 0.001). The proportion of low to high grade dysplasia was similar across groups (p = 0.32), but dysplasia rates were significantly higher in IBD (p < 0.000001). SSL-Ds occured throughout the IBD colon, lacking the right-sided predominance seen in sporadic or SPS cases (IBD p = 0.3; Sporadic p = <0.001; SPS p = 0.007). Demographically, groups were similar with no significant age difference (p = 0.058). Conclusion SSLs in IBD show a significantly higher dysplasia rate than those in SPS or sporadic cases, despite similar demographic and morphologic features. SSL-Ds in IBD were more likely to be found throughout the colon compared with the typical right sided dominance seen in SPS and sporadic cases. Traditional risk factors for advanced neoplasia, including disease duration and extent, did not distinguish dysplastic from non-dysplastic SSLs in IBD, although small numbers of SSL-D may underestimate significant findings. Further clinical and molecular investigation is needed to clarify the unexpectedly high dysplasia rate in IBD associated SSLs.

Abstract Background Perianal Crohn’s disease (pCD) is a morbid condition with a prevalence of approximately 20% in patients within 10 years of diagnosis of Crohn’s disease (CD) (1). The changing global epidemiology of inflammatory bowel disease (IBD) suggests that the rising incidence of CD, particularly in areas with currently low prevalence, may translate into an increased future burden of pCD (2). Given the significant impact this condition has on patient quality of life, a Priority Setting Partnership (PSP) was established to define the top 10 priorities for future research into pCD, with an aim to develop a coordinated and inclusive research agenda, and anticipate future global needs. Methods The PSP was conducted in collaboration with the James Lind Alliance (JLA) using standardised JLA methodology. An initial survey was circulated to gather unanswered research questions from key stakeholders globally. From this, a longlist of 51 summary questions was formed. A second survey asked stakeholders to prioritise the 51 summary questions, and the highest ranking 19 questions were taken into the final workshop. During the final workshop, a panel of people with lived or professional experience of pCD ranked the top 10 research priorities, in a process facilitated by JLA advisors using Nominal Group Technique. Results 1200 individual research uncertainties were submitted by over 464 respondents, representing 30 countries. The majority of responses were from the United Kingdom (19%), the Netherlands (14%), Portugal (13%), the United States (US) (11%) and Brazil (9%). Patients provided 58% of responses, with 20% of responses coming from lower and middle-income countries according to the World Bank Criteria. From the 51 summary questions that were developed from these responses, the Top 10 research priorities were established in the final workshop (Figure 1). Themes that were identified in the Top 10 included elucidating the underlying causes of pCD, improving strategies for early diagnosis, determining predictors of quality of life, and advancing therapeutic approaches and quality of life across the full spectrum of disease. Conclusion This Global pCD PSP marks an importance advance towards stakeholder-driven, focused research in pCD, providing a roadmap for researchers, clinicians and funders to align future research with patient and clinician priorities.

Abstract Background Perianal Crohn’s disease (pCD) is a challenging form of Crohn’s disease, which includes both fistulising and non-fistulising features, such as anorectal stricture, skin tags and erosive disease (1). Whilst non-fistulising pCD (nfpCD) can result in a significant disease burden for patients, these features are under-recognised in clinical practice, current guidelines and clinical research relating to pCD (2,3). Informed by a review of existing classification systems, this study aimed to develop a novel classification system to guide identification and management of non-fistulising pCD. Methods Following a systematic review to identify existing classification systems, a modified nominal group technique expert consensus process was used to develop a novel classification system for non-fistulising pCD. This process involved several phases including ideas generation, clarification of ideas, several rounds of voting and patient and public involvement (PPI). Results Twenty-two existing classification systems for non-fistulising pCD were identified, the majority (18/22, 88%) of which focused on categorising non-fistulising pCD. Participating panellists included multidisciplinary experts from the TOpClass consortium, with representation from 10 countries. The initial round of voting established a need for a novel classification system (n = 18 89% [A+], 11% [A]), and passed a number of statements relating to the content of the classification. The final classification structure was passed with 100% consensus (n = 27, 93%,[A+], 7% [A]) (Figure 1). The final statements to accompany the classification were passed with a mean 98% consensus (n = 28, 80% [A+], 18% [A]) (Table 1). The novel structure classifies nfpCD according to the presence of stricturing disease, erosive disease and skin tags with severity ranging from minimal symptoms (Class 1) to severe symptoms requiring defunctioning ostomy (Class 2c), proctectomy (Class 3) or perineal symptoms after proctectomy (Class 4). The structure complements the existing TOpClass classification for fistulising pCD, to enable classification of patients with both fistulising and non-fistulising features of pCD. The classification system incorporates patient goals and symptom burden, and introduces a number of novel concepts, such as velocity and destruction to provide a clinically useful framework. Conclusion This expert consensus has developed a dynamic, comprehensive and patient-focused system for optimising the classification of patients with non-fistulising pCD for clinical and research use. Further validation in prospective cohorts is planned to ensure clinical applicability.

Abstract Background The combination of the increasing use of social media by young people, and their nature as a means of communication that allows for unrestricted self-expression, renders them a key forum for information exchange, including health-related topics. Inflammatory bowel disease (IBD), particularly since it is affecting younger cohorts, has previously been central to studies on social media usage. This systematic review aims to summarise previously employed methodologies in social media studies and synthesize available information on social media usage patterns by IBD patients. Methods This systematic review was registered on PROSPERO (CRD420251006915) and reported according to PRISMA guidelines. Studies were included if they were reporting on the usage of social media by IBD patients or if they were examining social media content created by IBD patients, and written in English. Results Initial search returned 941 studies, and after title, abstract and full-text screening, 32 studies were included for data extraction. Studies were grouped according to their methodological design, into content-based analyses (21) and survey-based studies reporting on usage trends (11). Three subtypes of content analysis were encountered: thematic analysis, quality analysis and sentiment analysis. Within platform-specific studies, Youtube was the most frequently examined, with a recent increase in TikTok-focused studies. The most commonly reported reasons to use social media were information seeking and connecting with the wider community, for peer-to-peer support. Main domains of interest in information seeking included details of daily living with IBD (expressed through sharing of lived experiences), information on medical and surgical treatment options, and diet. Conclusion This systematic review summarises the available evidence on both methodologies and key trends in social media–based research within IBD populations. It highlights the growing interest in this area, reflecting a wider recognition that social media represents an important channel of communication and support for people living with IBD. Healthcare professionals should remain attuned to contemporary modes of communication and aware of the insights such platforms can offer into patients’ experiences and needs. Conflict of interest: Mr. Argyriou, Orestis: No conflict of interest Petmeza, Christina Anna: No conflict of interest Goyal, Chirag: No conflict of interest Ghersin, Itai: No conflict of interest Worley, Guy: No conflict of interest Tozer, Philip: Personal Fees: Takeda - speakers fees, member of Inspire, and advisory boards Ferring - speakers fees Falk - speakers fees Tillott’s - speakers fees J & J - speakers fees Abbvie - speakers fees Hart, Ailsa: Grant: Takeda Personal Fees: Abbvie, Amgen, Arena, AZ, Falk, Celltrion, Eli Lilly, Ferring, Genentech/ Roche, GSK, Pfizer, Takeda, Napp, Pharmacosmos, Janssen (J & J), Bristol-Myers Squibb, Gilead, Galapagos, Alfasigma Sahnan, Kapil: Speaker fees from Takeda, JnJ, Intuitive Ad Board with Medtronic

Single-shot pulsed-field ablation (PFA) catheters show promising safety and efficacy for achieving pulmonary vein isolation (PVI) in atrial fibrillation (AF). However, additional PFA applications are sometimes required after standard PFA delivery to achieve PVI. This study aimed to evaluate the real-world frequency and location of acute residual pulmonary vein (PV) connections using 3-dimensional electroanatomic mapping (3D-EAM) during index PFA. Patients undergoing index PVI with a single-shot PFA catheter and receiving postablation 3D-EAM were prospectively studied. First-pass isolation (FPI) rates and distribution of residual PV connections were assessed. A total of 535 patients from 48 international centers (89 operators) were included (paroxysmal AF 375; persistent AF 160). Mean procedure time was 75.9 ± 31.9 minutes, and mapping time was 8.4 ± 5.2 minutes. Ablation was performed with a pentaspline, variable conformation PFA catheter in 72.7% of cases and a fixed-loop PFA catheter in 27.3%. Bilateral FPI was achieved in 75.1% of patients (paroxysmal AF 77.1% vs persistent AF 70.6%; P = .126). The individual PV FPI rate was 92.7% (1834 of 1978 PVs). Excluding common PVs, residual PV connections were more frequent in superior PVs (superior 8.9% vs inferior 3.8%; P < .001), specifically in the left superior PV (10.1%). Predictors of FPI included standard 4-vein anatomy (odds ratio, 1.83; 95% confidence interval, 1.09-3.07; P = .021) and the pentaspline catheter (odds ratio, 3.53; 95% confidence interval, 1.81-6.87; P < .001). Using 3D-EAM, an acute residual connection of at least 1 PV was observed in a quarter of patients after standard PFA delivery and was most common in the left superior PV. Potential mechanisms include reversible electroporation, highlighting the potential need for additional lesions and the value of a mandatory post-PFA "waiting period."

BackgroundAPC c.3920T>A; p.Ile1307Lys (I1307K), prevalent in individuals of Ashkenazi Jewish (AJ) origin, has been associated with a modestly increased colorectal cancer (CRC) risk. Clinical recommendations for I1307K heterozygotes vary across countries and expert groups, reflecting differences in population frequencies, modest risk estimates and limited data in non-AJ individuals.MethodsWe analysed UK Biobank data comprising 466 315 individuals (8944 with CRC), using genomic analysis to classify AJ and non-AJ ancestries.ResultsI1307K was identified in 7.1% of AJ and 0.08% of non-AJ white participants. No significant association with CRC was observed in AJ (OR: 0.71; 95% CI: 0.17 to 2.95) or non-AJ white individuals (OR: 1.05; 95% CI: 0.50 to 2.22). The previously established OR of 1.7–1.8 for AJ individuals lies within our 95% CI, indicating underpowered results due to limited CRC cases. No significant associations were detected for other cancers. Unbiased, adequately powered CRC case–control studies in non-AJ populations would require cohorts far larger than current resources for feasible analysis.ConclusionClinical actionability of I1307K should prioritise risk stratification based on overall CRC risk and ancestry-dependent variant detection rates. However, management strategies need not differ by ancestry once a carrier is identified, as the biological impact of I1307K should be consistent across populations.

Faecal calprotectin (FC) is a marker of gastrointestinal (GI) inflammation that is widely used in primary care to identify patients who need to be referred for endoscopic assessment. Most guidelines advise against its use in older adults because of higher rates of colorectal cancer (CRC) in this group, and many studies include only younger adults, even though FC is still used in older adults. To evaluate FC performance in identifying inflammatory bowel disease (IBD) and significant organic pathology in adults aged ≥50 years, to help inform its use and interpretation in primary care. Where available, faecal immunochemical test (FIT) data were also analysed. A retrospective observational study of patients who were referred from primary care to secondary care for colonoscopy at Imperial College Healthcare NHS Trust. Patients who had undergone FC testing, followed by a colonoscopy, were recruited and grouped into younger adults (aged 18-49 years) and older adults (aged ≥50 years). Data were then collected using electronic health records to allow for analysis of FC diagnostic performance. In total, 669 patients were included: 423 aged 18-49 years and 246 aged ≥50 years. There were no significant differences in FC levels between the groups (median FC level: 71 µg/g versus 85.5 µg/g respectively, P = 0.29). An FC level of >50 µg/g showed a high sensitivity for inflammatory bowel disease (IBD) in both groups (94.1% in those aged 18-49 years and 93.8% in those aged ≥50 years), but the positive predictive value was low - particularly in those aged ≥50 years (12.8%) versus the younger cohort (20.9%). An FC level of >50 µg/g outperformed FIT (threshold 10 µg/g) for the diagnosis of IBD and organic pathology in both groups. However, in patients aged ≥50 years, FIT outperformed FC at 150 µg/g for the diagnosis of organic pathology, including CRC. These data show that FC remains a sensitive test in older adults. FC may have a role as a 'rule-out' test in adults aged ≥50 years who have lower GI symptoms and a negative FIT, when CRC is not suspected.