Cranford Hospice is Hawke's Bay's leading palliative care provider. Our dedicated team is available 24 hours a day, seven days a week.
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The Apollonion Private Hospital is an ultra-modern Hospital purposely built to offer the best medical care to its patients.
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Al Zahra Hospital Sharjah is the first and the largest private general hospital in the UAE with both inpatient and outpatient treatment at an international standard,
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UT Health East Texas is passionate about delivering the highest quality care with unmatched compassion, outstanding service and innovative technology.
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<p>The role of the human microbiome in GI disease is an area of significant clinical and academic interest. The microbiome may well influence a number of GI diseases ranging from cancer,<cross-ref type="bib" refid="R1">1 2</cross-ref><cross-ref type="bib" refid="R2"></cross-ref> to IBD,<cross-ref type="bib" refid="R3">3 4</cross-ref><cross-ref type="bib" refid="R4"></cross-ref> to liver disease.<cross-ref type="bib" refid="R5">5 6</cross-ref><cross-ref type="bib" refid="R6"></cross-ref></p> <p>One of the current challenges faced by microbiome researchers is the variance in terminology, methodological approaches and lack of consistency regarding outcomes. This is an issue that is not unique to this area and reflects rapid evolution of a particular research field. While attempts have been made to standardise the reporting of human microbiome research, for example, using the STORMS (Strengthening The Organization and Reporting of Microbiome Studies) checklist,<cross-ref type="bib" refid="R7">7</cross-ref> such tools are yet to be widely adopted, leading to inconsistencies that affect the reproducibility of results.</p> <p>By using examples related to colorectal neoplasia, we seek to...
<p>Cholangiocarcinoma (CCA) is a highly aggressive adenocarcinoma of the biliary tract system with unsatisfactory therapeutic options.<cross-ref type="bib" refid="R1">1</cross-ref> Standard frontline treatment for unresectable or metastatic CCA consisting of cisplatin and gemcitabine combined with checkpoint inhibitors targeting programmed cell death ligand 1 or programmed cell death 1 offers objective response rates of less than 30% and a median survival of approximately a year.<cross-ref type="bib" refid="R1">1</cross-ref> Targeted therapies against <I>FGFR2</I> fusions and <I>IDH1</I> mutations have gained regulatory approval in CCA, but these are applicable only in a minority of patients.<cross-ref type="bib" refid="R1">1</cross-ref> Disease-agnostic approvals of therapies targeting HER2 overexpression, <I>NTRK</I> fusions, <I>RET</I> fusions and microsatellite-unstable tumours also benefit patients with CCA, but again, only a small minority. Therefore, novel strategies to treat CCA are urgently needed.</p> <p>Molecular heterogeneity stands as a major barrier to improving outcomes in CCA. Genetic alterations in DNA only explain a part of this heterogeneity. A rising...
<sec id="s1"><st>Message</st> <p>Computer-aided detection (CADe) has increased adenoma detection in randomised trials. However, unlike other detection adjuncts, CADe is lesion specific, that is, it is trained on a specific set of lesions. If the training does not include sufficient examples of precancerous lesion subsets, CADe may not perform adequately for lesions in that subset. In a prospective assessment of a second-generation CADe programme in 165 colonoscopies, we identified 26 flat lesions ≥10 mm in 17 patients. The endoscopist identified 22 of 26 lesions before the CADe programme. In 13 lesions, the CADe either generated no detection signal or only a signal over part of the lesion after colonoscope position or luminal inflation adjustment. Thus, the second-generation CADe algorithm, like the first generation, frequently fails to effectively detect large flat colorectal lesions, which are likely very important lesions that a CADe programme should identify.</p> </sec> <sec id="s2"><st>Details</st> <p>The first CADe...
<sec id="s1"><st>Case presentation</st> <p>A 71-year-old man presented with a 2-months history of arrhythmia of undetermined cause, dysphagia, vomiting and 10 kg weight loss. The patient’s history was unremarkable except for multinodular goitre and hypertension. Laboratory exams did not demonstrate significant alterations, white cell count was 7.8<FONT FACE="arial,helvetica">x</FONT>10<sup>9</sup>/L (ref range: 4.0–10.0), haemoglobin 16.2 g/L (ref range: 12.0–15.0), platelet 281<FONT FACE="arial,helvetica">x</FONT>10<sup>9</sup>/L (ref range: 150–450), C reactive protein <0.05 mg/L (ref range: <5). Tumour markers were within normal range. An echocardiogram (<cross-ref type="fig" refid="F1">figure 1</cross-ref>) and gastroscopy (<cross-ref type="fig" refid="F2">figure 2</cross-ref>) were performed.</p> </sec> <sec id="s2"><st>Question</st> <p>What is the clinical problem?</p> </sec> <sec id="s3"><st>Answer</st> <p>A CT revealed a paraoesophageal hiatal hernia (POH) that has determined compressive effect on adjacent structures (<cross-ref type="fig" refid="F3">figure 3</cross-ref>). As shown in the echocardiogram, there was an ab-extrinsic atrial compression that resulted in arrhythmia. The endoscopy confirmed the presence of a huge hernia and grade D oesophagitis according to Los Angeles...
<sec><st>Background and objective</st>
<p>Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis.</p>
</sec>
<sec><st>Designs</st>
<p>Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves.</p>
</sec>
<sec><st>Results</st>
<p>RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score (cd-score), derived from the expression levels of four long ncRNAs (RP11.443C10.1, CTD-2339L15.3, LINC00567 and DiGeorge syndrome critical region gene (DGCR9)), was found to surpass commonly used biomarkers, such as carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and CA72-4, in distinguishing GC patients from healthy donors across training, testing and external validation cohorts, with AUC values of 0.959, 0.942 and 0.949, respectively. Additionally, the cd-score could effectively identify GC patients with negative gastrointestinal tumour biomarkers and those in early-stage. Furthermore, molecular biological assays revealed that knockdown of DGCR9 inhibited GC tumour growth.</p>
</sec>
<sec><st>Conclusions</st>
<p>Our proposed serum exosome ncRNA feature provides a promising liquid biopsy approach for enhancing the early diagnosis of GC.</p>
</sec>
<sec><st>Background</st>
<p>Treatment strategies for Crohn’s disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous haematopoietic stem cell transplantation (SCT) is an emerging therapy for medically refractory CD though the mechanisms through which it circumvents refractory pathophysiology are unknown.</p>
</sec>
<sec><st>Objective</st>
<p>The objective of this study is to understand how the immune system reconstitutes post-SCT and whether SCT may function as a cellular therapy restoring appropriately responsive immune cell populations from haematopoietic stem cells (HSCs).</p>
</sec>
<sec><st>Design</st>
<p>Adults with CD with active clinical and endoscopic disease who failed available medical therapies were enrolled in a phase II study of SCT for refractory CD (n=19). Blood and intestinal samples were collected longitudinally and analysed using CyTOF and scRNA-seq. Stem cell autografts were functionally assayed in mouse xenograft models.</p>
</sec>
<sec><st>Results</st>
<p>scRNA-seq and CyTOF analyses reveal that SCT predominantly affected the intestinal myeloid lineage with loss of inflammatory populations and return of macrophages capable of supporting mucosal healing. Xenograft models using patient HSCs suggested that HSCs support the early reconstitution of the myeloid lineage and reveal an impairment of short and long-term HSC engraftment that may determine SCT outcomes.</p>
</sec>
<sec><st>Conclusions</st>
<p>This study suggests SCT functions as a myeloid-directed cellular therapy reinforcing the critical role of macrophages in refractory CD pathophysiology and as a target for cellular therapies. Furthermore, we report an unrecognised functional heterogeneity among HSC subpopulations in CD that may be relevant to our understanding of CD treatment and pathophysiology.</p>
</sec>
<sec><st>Background</st>
<p>Oat ingestion in coeliac disease (CD) is generally regarded as safe but can trigger enteropathy and T cells specific for oat avenin in the gut and blood of some individuals.</p>
</sec>
<sec><st>Objective</st>
<p>To correlate immune and clinical outcomes to oats, purified avenin and oat feeding studies were performed to examine symptoms, T-cell immunity and intestinal histology in CD.</p>
</sec>
<sec><st>Design</st>
<p>33 treated HLA-DQ2.5+ adult CD patients underwent single-bolus or 6-week oat avenin or 3-month whole oats ingestion. T cell activation after avenin ingestion was measured using serum interleukin 2 (IL-2), a sensitive and specific biomarker of gluten-induced T cell activation and symptoms in CD. Symptom measures, intestinal histology, and immune studies on blood and duodenum were undertaken.</p>
</sec>
<sec><st>Results</st>
<p>Among 29 CD participants, avenin induced dose-dependent T-cell activation in 11 (38%) and acute symptoms in 17 (59%). Higher IL-2 levels correlated with more severe symptoms. A single highly symptomatic patient vomited in response to avenin (1/29; 3%) and exhibited a striking pro-inflammatory cytokine profile similar to wheat-induced responses. Avenin increased the frequency of CD38-expressing tetramer+integrin β7+ T effector memory CD4+ T cells in the blood, however symptoms, IL-2 release and tetramer frequency fell following 6-week avenin intake and no enteropathy was observed.</p>
</sec>
<sec><st>Conclusion</st>
<p>Gluten-contamination-free oats can trigger acute dose-dependent immune and symptom responses but usually at a level insufficient to cause sustained symptoms or enteropathy. In 1 of 29 (3%) participants, oat avenin triggered a pro-inflammatory wheat-like response, highlighting that a minority of CD patients may need to exclude oats. Informed choice regarding oats ingestion in CD is important.</p>
</sec>
<sec><st>Background</st>
<p>A large proportion of individuals with coeliac disease (CeD) remain undiagnosed.</p>
</sec>
<sec><st>Objective</st>
<p>The aim of this study was to assess serological screening for CeD in the adult general population.</p>
</sec>
<sec><st>Design</st>
<p>The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017–2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found.</p>
</sec>
<sec><st>Results</st>
<p>Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10<FONT FACE="arial,helvetica">x</FONT> ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals.</p>
</sec>
<sec><st>Conclusion</st>
<p>The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD.</p>
</sec>
<sec><st>Background</st>
<p>Given the imperative to combat climate change, reducing the healthcare sector’s implications on the environment is crucial.</p>
</sec>
<sec><st>Objective</st>
<p>This study aims to offer a comprehensive assessment of the environmental impact of gastrointestinal endoscopy (GIE) procedures, specifically focusing on greenhouse gas (GHG) emissions and waste generation.</p>
</sec>
<sec><st>Design</st>
<p>A prospective study was conducted at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India, from 29 May to 10 June 2023, including all consecutive GIE procedures. Carbon emissions for various variables involved were calculated with specific emission factors using ‘The GHG Protocol’.</p>
</sec>
<sec><st>Results</st>
<p>Based on data from 3244 consecutive patients undergoing 3873 procedures, the study revealed a total carbon footprint of 148 947.32 kg CO<SUB>2</SUB>e or 38.45 kg CO<SUB>2</SUB>e per procedure. Excluding patient travel, the emissions were 6.50 kg CO<SUB>2</SUB>e per procedure. The total waste generated was 1952.50 kg, averaging 0.504 kg per procedure, far less than 2–3 kg per procedure in the West. The waste disposal breakdown was 9.5% direct landfilling, 64.8% incineration, then landfilling and 25.7% recycling, which saved 380 kg CO<SUB>2</SUB>e. India effectively recycles 25.7% of hospital-related waste, which undergoes landfilling in the West. The primary contributors to GHG emissions were patient travel (83.09%), electricity consumption (10.42%), medical gas transport and usage (3.63%) and water consumption (1.86%). Diagnostic procedures generate less waste and lower carbon footprint than therapeutic procedures.</p>
</sec>
<sec><st>Conclusion</st>
<p>This study highlights the significant environmental footprint of GIE procedures, emphasising the importance of optimising practices to reduce patient travel and repeat procedures, alongside improving electricity and water management for sustainable healthcare.</p>
</sec>
<sec><st>Background</st>
<p>Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.</p>
</sec>
<sec><st>Objective</st>
<p>We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8<sup>+</sup> T cells.</p>
</sec>
<sec><st>Design</st>
<p>4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model.</p>
</sec>
<sec><st>Results</st>
<p>Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. <I>Pseudomonas</I> and <I>Veillonella</I> species were enriched while certain oral bacteria, including <I>Corynebacterium</I> and <I>Staphylococcus</I> species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8<sup>+</sup> T cells, thereby promoting HNSCC tumourigenesis.</p>
</sec>
<sec><st>Conclusion</st>
<p>CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8<sup>+</sup> T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.</p>
</sec>
<sec><st>Background</st>
<p>GI cancers pose an increasing global health burden, with their impact on the working-age population (WAP) aged 15–64 years remaining largely unexplored despite the crucial role of this group in societal and economic well-being.</p>
</sec>
<sec><st>Objective</st>
<p>To assess trends and cross-country inequality in the global burden of six GI cancers from 1990 to 2021 among individuals in the WAP.</p>
</sec>
<sec><st>Design</st>
<p>The 2021 Global Burden of Disease study dataset was used to obtain estimates of GI cancer incidence and 95% uncertainty intervals, including the number of cases, crude incidence rate and age-standardised incidence rate (ASIR). WAP GI cancer epidemiology was assessed at the national, regional and global levels, evaluating trends from 1990 to 2021 from overall, local and Sociodemographic Index (SDI) perspectives and using standard health equity methods to quantify cross-country inequality.</p>
</sec>
<sec><st>Results</st>
<p>Colorectal cancer exhibited the greatest burden of GI cancer among the WAP in 2021. From 1990 to 2021, the number of GI cancer cases rose by 51.9%, although the ASIR declined by 23.4%. These rates exhibit geographic variation, with the most cases and the highest ASIR in China and Mongolia, respectively. Incidence was disproportionately concentrated in higher SDI countries, and worsening inequality was evident over time.</p>
</sec>
<sec><st>Conclusions</st>
<p>While the ASIR of GI cancer is trending downwards among the WAP, high incidence rates, regional variability and an unequal burden of disease emphasise the need for flexible, targeted medical interventions to support policymaking and medical resource allocation.</p>
</sec>
<sec><st>Background</st>
<p>Early detection of colorectal cancer (CRC) is crucial for improving the survival rates of patients.</p>
</sec>
<sec><st>Objective</st>
<p>We aimed to develop a novel strategy for early CRC detection using the fragmentomic features of circulating cell-free mitochondrial DNA (ccf-mtDNA).</p>
</sec>
<sec><st>Design</st>
<p>Here, a total of 1147 participants, including 478 healthy controls (HCs), 112 patients with advanced adenomas (AAs) and 557 patients with CRC, were enrolled from five hospitals and plasma samples were collected for capture-based ccf-mtDNA sequencing.</p>
</sec>
<sec><st>Results</st>
<p>Our data analysis revealed significantly aberrant ccf-mtDNA fragmentomic features in patients with CRC and AA when compared with HCs. Then, a CRC detection (CD) model was constructed based on the fragmentomic features of ccf-mtDNA from 246 patients with CRC and 168 HC in the training cohort, showing area under the curve of 0.9863, sensitivity of 92.68% and specificity of 93.45%. Both internal and two external validation cohorts demonstrated the excellent capacity of CD model in distinguishing patients with early-stage CRC from HCs, greatly surpassing the performance of serum biomarkers. Furthermore, our CD model can also detect patients with AA with a sensitivity of 79.35% in AA cohort 1 and 85.00% in AA cohort 2.</p>
</sec>
<sec><st>Conclusion</st>
<p>In conclusion, based on aberrant ccf-mtDNA fragmentomic features, a novel and non-invasive approach was established for the detection of patients with early-stage CRC or AA, with high performance.</p>
</sec>
<sec><st>Background</st>
<p>Cyst size, its growth rate, and diameter of the main pancreatic duct (MPD) are all associated with pancreatic carcinoma prevalence in intraductal papillary mucinous neoplasms (IPMNs).</p>
</sec>
<sec><st>Objective</st>
<p>To examine the above factors in relation to future risk of incident pancreatic carcinoma in individuals with IPMNs harbouring no high-risk stigmata.</p>
</sec>
<sec><st>Design</st>
<p>In a prospective longitudinal cohort, we analysed 2549 patients with IPMNs. A multivariable cause-specific Cox proportional hazards regression model was built to estimate HRs for incident pancreatic carcinoma.</p>
</sec>
<sec><st>Results</st>
<p>IPMN size at baseline and its annual growth rate over 2 years of follow-up were associated with incident pancreatic carcinoma (p<SUB>trend</SUB><0.001). The multivariable cause-specific HR per 10 mm increase in IPMN size was 1.28 (95% CI 1.10 to 1.50). The annual growth rates of 1.5–2.4 mm/year and ≥2.5 mm/year over 2 years were associated with multivariable cause-specific HRs of 1.91 (95% CI 0.78 to 4.67) and 4.52 (95% CI 2.28 to 8.98), respectively (vs <1.5 mm/year). Neither IPMN size at 5 years nor its maximum growth rate during 5 years was associated with incident pancreatic carcinoma (p<SUB>trend</SUB>>0.07). MPD diameter at 5 years was associated with incident pancreatic carcinoma (multivariable cause-specific HR per 2 mm increase, 2.12; 95% CI 1.72 to 2.63). A predictive nomogram was generated for calculating the risk of incident pancreatic carcinoma.</p>
</sec>
<sec><st>Conclusion</st>
<p>IPMN size and its growth rate predict future pancreatic carcinoma risk only during first 5 years of follow-up. MPD diameter at 5 years may identify patients who still harbour a high risk for pancreatic carcinoma.</p>
</sec>
<sec><st>Background</st>
<p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The combination of tremelimumab and durvalumab is now a standard treatment option for advanced HCC.</p>
</sec>
<sec><st>Objective</st>
<p>To study immune responses in HCC patients treated with tremelimumab and durvalumab.</p>
</sec>
<sec><st>Design</st>
<p>We treated 28 HCC patients with durvalumab, tremelimumab and locoregional therapies. We performed a high-dimensional multiomics analysis including whole exome sequencing, single-cell RNA seq, CO-Detection by indEXing, flow cytometry and multiplex cytokine/chemokine analysis of patients’ blood and tumour samples and integrated this data to elucidate immune correlatives and response mechanisms. Mice with syngeneic HCC were treated with anti-PD-L1 plus anti-CTLA4 for hepatic lymphocytes, tumour-infiltrating lymphocytes and peripheral blood mononuclear cell analysis.</p>
</sec>
<sec><st>Results</st>
<p>The median overall survival was 19.2 months. Tumour tissue analysis revealed enhanced interferon responses, with stronger effects in responders. Gene set variation analysis indicated enhanced antigen presentation in responders. Spatial analysis revealed that non-responder tumours had higher numbers of Tregs located in neighbourhoods enriched with immune cells and expressed higher levels of ICOS and PD-1. Conversely, non-responder PD1+CD8+T in these Treg-enriched neighbourhoods expressed lower ICOS. Cell-communication analysis demonstrated that Treg-CD8+T interaction was enhanced in non-responder tissue. Peripheral blood analysis showed increased classical monocytes in responders and Tregs in non-responders. Treg-CD8+T interaction was confirmed in preclinical models. Finally, single-patient computational analysis from the all-across analysis was performed on 860 features, which led to the identification of multiomics feature sets including Treg features.</p>
</sec>
<sec><st>Conclusion</st>
<p>Our study provides a blueprint for in-depth analysis of immune correlates in immunotherapy studies and demonstrates the importance of Treg distribution in HCC.</p>
</sec>
<sec><st>Trial registration numbers</st>
<p> <A HREF="NCT02821754">NCT02821754</A> and the EudraCT identifier: 2019-002767-98.</p>
</sec>
<p>Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated condition characterised by eosinophilic infiltration of the oesophagus, leading to significant morbidity due to oesophageal dysfunction. The pathogenic course of EoE begins with tissue injury, marked by the intricate interplay of oesophageal barrier dysfunction and T helper 2-mediated inflammation. In response to tissue damage, a subsequent phase of tissue remodelling features a complex interaction between epithelial cells and stromal cells, aimed at tissue repair. The persistence of inflammation drives these mechanisms towards oesophageal fibrostenosis, mainly through the transforming growth factor-dependent, myofibroblast-driven accumulation of the extracellular matrix. Currently, treatment options for EoE are limited, with dietary intervention, proton pump inhibitors and oral steroids serving as first-line therapies. Dupilumab, an antiinterleukin (IL) 4/IL-13 agent, is the only biologic that has been approved by European and American regulatory authorities. However, emerging OMIC technologies significantly advance our understanding of EoE pathogenesis, revealing novel cellular and molecular mechanisms driving the disease. This progress has accelerated the identification of new therapeutic targets and agents, some already under clinical investigation, potentially expanding our therapeutic arsenal and paving the way for more personalised approaches. In this evolving landscape, artificial intelligence (AI) has shown great potential to further elaborate on the complexities of EoE heterogeneity, offering standardised tools for diagnosis, disease phenotyping, and prediction of treatment response. Though still in their early stages, integrating OMICs and AI marks a pivotal step towards precision medicine in EoE.</p>
<p>Chronic liver disease is a cluster of disorders associated with complex haemodynamic alterations, which is characterised by structural and functional disruptions of the intrahepatic and extrahepatic vasculature. ‘Vasomics’ is an emerging omics discipline that comprehensively analyses and models the vascular system by integrating pathophysiology of disease, biomechanics, medical imaging, computational science and artificial intelligence. Vasomics is further typified by its multidimensional, multiscale and high-throughput nature, which depends on the rapid and robust extraction of well-defined vascular phenotypes with clear clinical and/or biological interpretability. By leveraging multimodality medical imaging techniques, vascular functional assessments, pathological image evaluation, and related computational methods, integrated vasomics provides a deeper understanding of the associations between the vascular system and disease. This in turn reveals the crucial role of the vascular system in disease occurrence, progression and treatment responses, thereby supporting precision medicine approaches. Pathological vascular features have already demonstrated their key role in different clinical scenarios. Despite this, vasomics is yet to be widely recognised. Therefore, we furnished a comprehensive definition of vasomics providing a classification of existing hepatic vascular phenotypes into the following categories: anatomical, biomechanical, biochemical, pathophysiological and composite.</p>
<sec id="s1"><st>Basic science</st><sec id="s1-1"><st>An encyclopaedia of models for precision medicine in hepatocellular cancer</st> <p>Müller M, May S, Hall H, <I>et al</I>. Human-correlated genetic models identify precision therapy for liver cancer. <I>Nature</I> 2025; 639: 754–764. doi: 10.1038/s41586-025-08585-z</p> <p>Some patients with hepatocellular carcinoma (HCC) have excellent responses to current systemic chemotherapy, but the overwhelming majority do not. HCC is a highly heterogeneous disease, and the advance to precision medicine has been hampered by a lack of human-relevant preclinical models that recapitulate this disease heterogeneity accurately. To tackle this, this international team created a large number of genetically engineered mouse models (GEMMs), driven by combinations of the mutations causing HCC. These GEMMs, resulting from inducing these genetic changes in up to 11 genetic loci at a time in single hepatocytes, allowed the tracking of premalignant clones through to late-stage and even metastatic disease, recapitulating key biological features of HCC not seen before...
<p>We read with interest the recently published randomised controlled trial (RCT) ‘SPHINX’,<cross-ref type="bib" refid="R1">1</cross-ref> addressing the role of endoscopic sphincterotomy (ES) with fully covered s metal stent (FCSEMS) placement in preventing post-ERCP pancreatitis (PEP). Although this is the largest RCT on the topic, several concerns warrant discussion.</p> <p>Published data report variable rates of PEP after SEMS ranging from 0% to 26.8%,<cross-ref type="bib" refid="R2">2–4</cross-ref><cross-ref type="bib" refid="R3"></cross-ref><cross-ref type="bib" refid="R4"></cross-ref> with lot of heterogeneity regarding the PEP preventive measures. Nevertheless severe pancreatitis remains rare. To assess the impact of ES a larger sample size will be required.</p> <p>The SPHINX trial sample estimation was based on two studies by Tol <I>et al,</I><cross-ref type="bib" refid="R5">5</cross-ref> which reported 18% PEP with FCSEMS placement in the preoperative biliary drainage setting, and Zhou <I>et al,</I><cross-ref type="bib" refid="R6">6</cross-ref> 31.7% PEP in the non-ES group, which is way higher than the presumed 16% in the SPHINX trial. Furthermore, it...
<p>We recently read with great interest the article by Devin Abrahami <I>et al</I>.<cross-ref type="bib" refid="R1">1</cross-ref> We would like to raise some concerns that warrant further discussion. The association between proton pump inhibitors (PPIs) and the risk of inflammatory bowel disease (IBD) remains a debate, the authors mostly focus on the protopathic bias introduced by study design. However, in this study, the authors used histamine-2 receptor antagonists (H2RAs) as an active comparator. While this partially balanced the bias introduced by indications, it may have masked the potential impact of PPIs on the incidence of IBD.</p> <p>In the general population, the age-standardised and sex-standardised incidence of IBD is 10.9 per 100 000 person-years.<cross-ref type="bib" refid="R2">2</cross-ref> Bin Xia <I>et al</I> through the NHS and UK Biobank cohorts, investigated the association between PPIs and the risk of IBD, reporting incidence rates of 12.8 and 34.6 per 100 000 person-years for non-regular PPI users, respectively.<cross-ref type="bib"...
<p>We read with great interest the recent article by Antonelli <I>et al</I><cross-ref type="bib" refid="R1">1</cross-ref> on the quality assessment for artificial intelligence in digestive endoscopy (QUAIDE) framework, which enhances the quality and reproducibility of artificial intelligence (AI)-based gastrointestinal endoscopy research. While QUAIDE provides a solid foundation for pre-clinical research design, we see opportunities for further improvement in several key areas.</p> <p>First, preclinical endoscopy AI research often involves sensitive patient data, requiring strict adherence to data privacy and ethical standards.<cross-ref type="bib" refid="R2">2</cross-ref> Currently, the QUAIDE framework does not adequately address data privacy protection, particularly in terms of anonymisation, de-identification, data-sharing agreements and informed consent. Including these standards is crucial for ensuring patient data safety, especially in multicentre collaborations, where varying anonymisation practices across centres increase the risk of data breaches.<cross-ref type="bib" refid="R3">3</cross-ref> Establishing unified data management protocols would ensure consistency across centres, reduce legal and ethical risks and safeguard data confidentiality...
<p>I read with interest the recent article of Wilkinson-Smith and colleagues on the assessment of colonic motility by means of MRI and high-resolution colonic manometry (HRCM),<cross-ref type="bib" refid="R1">1</cross-ref> showing that patients with constipation and irritable bowel syndrome (IBS) may display some abnormalities when such investigated. I would like to make some observations on this study.</p> <p>Since HRCM probes were positioned 35 cm from the anal verge, I would be very cautious in claiming that those were ‘colonic’ studies, since (by considering the physiological bending of the large bowel) at the very best only a very limited colonic area was studied. Indeed, the authors in the methods reported that only the sigmoid colon was actually investigated in a systematic manner. Both MRI and HRCM were carried out as short-timed studies (respectively, 2 and 4 hours duration) conducted in a viscus that fully displays its motor activity over a 24-hour time span.<cross-ref type="bib"...
<p>We thank Ramchandani <I>et al</I> for their letter on the SPHINX trial and appreciate the opportunity to address their points.<sup><cross-ref type="bib" refid="R1">1 2</cross-ref><cross-ref type="bib" refid="R2"></cross-ref></sup></p> <sec id="s1"><st>Sample size</st> <p>The SPHINX trial aimed to assess whether endoscopic sphincterotomy (ES) could reduce post-ERCP pancreatitis (PEP). However, quantifying this effect proved difficult due to conflicting results from previous, heterogeneous randomised controlled trials (RCTs), which differed in sample size, patient populations and stent types.<cross-ref type="bib" refid="R3">3–5</cross-ref><cross-ref type="bib" refid="R4"></cross-ref><cross-ref type="bib" refid="R5"></cross-ref> The trial by Zhou <I>et al</I> (2012) reported a 69% relative risk reduction in PEP after ES, which served as reference for our sample size calculation.<cross-ref type="bib" refid="R3">3</cross-ref> However, since the other trials did not show this benefit, we considered this effect overestimated.<cross-ref type="bib" refid="R4">4 5</cross-ref><cross-ref type="bib" refid="R5"></cross-ref> The SPHINX trial was designed to detect a 50% relative risk reduction in PEP in patients with suspected distal malignant biliary obstruction (MBO). Based on...
<p>We read with great interest the recent publication by Lou <I>et al</I>,<cross-ref type="bib" refid="R1">1</cross-ref> which addressed the challenge of false positives in next-generation sequencing (NGS) due to highly homologous <I>PRSS1</I> paralogs.<cross-ref type="bib" refid="R2">2 3</cross-ref><cross-ref type="bib" refid="R3"></cross-ref> <I>PRSS1</I> was the first gene linked to chronic pancreatitis,<cross-ref type="bib" refid="R4">4</cross-ref> with p.Arg122His (c.365G>A) and p.Asn29Ile (c.86A>T) being the most common mutations associated with the Mendelian form of the disease. Accurate identification of <I>PRSS1</I> variants is crucial for genetic diagnosis and counselling, guiding both patient management and familial risk assessment.</p> <p>Although <I>PRSS1</I> pathogenic variants are typically inherited in an autosomal dominant manner, they have also been reported in idiopathic pancreatitis, defined by the absence of precipitating factors and a negative family history prior to genetic analysis.<cross-ref type="bib" refid="R5">5–8</cross-ref><cross-ref type="bib" refid="R6"></cross-ref><cross-ref type="bib" refid="R7"></cross-ref><cross-ref type="bib" refid="R8"></cross-ref> However, large-scale data on the frequency of de novo PRSS1 variants in idiopathic pancreatitis remain limited. To address this...
<p>We read with great interest the study by Danpanichkul <I>et al</I>,<cross-ref type="bib" refid="R1">1</cross-ref> which assessed the global burden of gastrointestinal cancers, including oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers, from 2000 to 2021. The study revealed that the burden of all types of cancers varies across geographical and socioeconomic levels. The incidence rates of some types of gastrointestinal cancer in higher sociodemographic index (SDI) countries tend to decrease or increase at a slower rate compared with the more significant rise observed in lower SDI countries. Another study on global gastrointestinal cancer also noted that the incidence tends to be concentrated in countries with higher SDI.<cross-ref type="bib" refid="R2">2</cross-ref> In this global context, quantifying the inequalities in the burden of gastrointestinal cancers across countries is crucial for informing targeted strategies and optimising future efforts to reduce the global disparities in cancer burden.</p> <p>We use the SDI to represent the...
<p>We read with great interest the article by Coté <I>et al</I> titled ‘Sphincterotomy for biliary sphincter of Oddi disorder and idiopathic acute recurrent pancreatitis: the RESPOnD longitudinal cohort’ published in Gut.<cross-ref type="bib" refid="R1">1</cross-ref> The study aimed to measure the benefit of sphincterotomy for suspected sphincter of Oddi disorder (SOD) and provided valuable insights into the management of this contentious condition. While the study offers significant contributions to the field, we would like to raise some concerns and discuss potential areas for further investigation.</p> <p><l type="ord"><li><p>Placebo effect: the observed improvement rate of 57% using the predefined primary outcome and as high as 73% when using the PGIC alone raises questions about the contribution of a placebo response. Given the high expectations of patients and the significant intervention involved in ERCP, a substantial placebo effect is plausible.<cross-ref type="bib" refid="R2">2</cross-ref> A placebo-controlled randomised trial would be necessary to differentiate the true effect...
<p>Thanks to Dr Zeng for his insightful comments<cross-ref type="bib" refid="R1">1</cross-ref> about our recent publication on 12-month outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for sphincterotomy for sphincter of Oddi disorders (SOD).<cross-ref type="bib" refid="R2">2</cross-ref> Many of the comments were addressed in the discussion of the paper, especially the significance of the unmeasured placebo response and greater importance of patient characteristics such as somatisation and opioid exposure compared with physician-defined factors like a dilated duct.</p> <p>We disagree that RESPOnD’s heterogeneous patient population reduces the study’s generalisability. RESPOnD subjects represent the full spectrum of SOD subtypes and thus have lower selection bias compared with more stringent enrolment criteria. For example, restricting subjects to those with a dilated bile duct would have precluded our observation that duct size correlated poorly with response to sphincterotomy.</p> <p>As noted by Dr Zeng, sphincterotomy does not seem to be a promising intervention for idiopathic acute recurrent pancreatitis because...
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