Effect of sarcopenia on liver cirrhosis with complicating oesophageal and gastric varices after endoscopic therapy.

Several investigators have reported that sarcopenia is common in patients with liver cirrhosis. However, few studies have probed the association between sarcopenia and liver cirrhosis complicated with oesophageal and gastric variceal bleeding (LC-EGVB). We aimed to investigate the impact of sarcopenia on rebleeding after endoscopic therapy in patients with LC-EGVB. Computed tomography (CT) radiographs from the third lumbar vertebra were selected to analyse body composition, including skeletal muscle tissue, visceral and subcutaneous adipose tissue using SliceOmatic software. Sarcopenia was defined using validated cutoff values for patients with liver cirrhosis: 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. A total of 187 patients with LC-EGVB and 309 controls were included in this study. The rate of sarcopenia in controls (17.4 %) was significantly lower than that in patients with LC-EGVB (41.2 %). Patients with LC-EGVB exhibiting sarcopenia showed a high prevalence of portal vein thrombosis and rebleeding rate at 1 year. The rate of sarcopenia in the rebleeding group was significantly higher than that in the non-rebleeding group. Univariate and multivariate analyses showed that sarcopenia was an independent risk factor for rebleeding within 1 year in patients with LC-EGVB. Patients with LC-EGVB displayed a high prevalence of sarcopenia. Sarcopenia was observed to be an independent risk factor for rebleeding within 1 year.

Shortened radiofrequency delivery time to optimize efficiency and safety of pulmonary vein isolation with the radiofrequency balloon: insights from the COLLABORATE registry.

AIMS: Previous clinical studies on pulmonary vein isolation (PVI) with a radiofrequency balloon (RFB) reported safe and effective procedures using conventional ablation settings with 20/60 s RF delivery via posterior/anterior (PST/ANT) electrodes. The latest evidence suggests that reducing the application time to 15 s (s) on the posterior wall when facing the oesophageal region is as effective as applying 20 s. To prospectively assess whether reducing RF time on PST/ANT segments to 15/45 s can ensure sufficient quality of lesion metrics and compare the new shortened ablation settings with the conventional one in terms of safety, and effectiveness at 1-year. METHODS AND RESULTS: A total of 641 patients from seven European centres were enrolled in a collaborative registry, with 374 in the conventional RF delivery group and 267 in the shortened RF delivery group. Procedural outcomes, lesion metrics, and safety profiles were assessed and compared between the groups. Freedom of any atrial tachycarrythmias at one year was 85.4% and 88.2% in the SHRT and CONV groups, respectively. The shortened RF delivery strategy was associated with significantly shorter procedure times (median 63.5 vs. 96.5 min, P < 0.001) and shortened fluoroscopy exposure (median 10.0 vs. 14.0 min, P < 0.001) compared to conventional delivery. Efficacy metrics, including first-pass isolation rates and time to isolation, were comparable between groups. Shortened RF delivery was associated with a lower incidence of procedural complications (1.4% vs. 5.3%, P = 0.04) and optimized thermal characteristics. CONCLUSION: Analyses from the COLLABORATE registry demonstrate that shortening RF energy delivery times to 15/45 s (PST/ANT) during PVI with the RFB resulted in comparable freedom from recurrent atrial tachyarrhythmia compared to conventional delivery times with comparable efficiency and safety.

Evaluating the effectiveness of citation count as a measure of methodological quality in esophagogastric surgery research: a comparative analysis with the MINORS score and levels of evidence.

Aim: The primary objective was to assess the relationship between the citation number and the quality of the articles, as compared with the level of evidence and the MINORS score. This study's secondary objective was to characterize the 50 most cited articles in the field of oesophagectomy research. Background: There has been an increased need for an evaluation tool to indicate research quality. Available quality assessment tools include the Level of Evidence, the MINORS score, the Cochrane Risk of Bias 2.0 Tool, the Newcastle Ottawa Scale, CASP Appraisal Checklists, and Legend Evidence Evaluation tools. Methods: The Web of Science allowed evaluating and comparing articles on oesophagectomy research. The quality of the 50 most cited articles was assessed using the Oxford Centre level of evidence classification and the methodological index for non-randomized studies (MINORS). Results: Level of evidence II studies were cited more than level IV (P=0.008). There was a significant positive correlation between citation number and MINORS score (P=0.002). The median MINORS score was highest amongst level II studies, followed by levels III, IV, and I. The median MINORS score for level II evidence was significantly higher than for level IV (P=0.001). The study sample size is associated with higher levels of evidence but does not correlate with the citation number. Female authors contributed to 4 out of 50 articles. Recently published articles tended to be cited more frequently. More authors equated to more citations. Prospective studies are more likely to be cited. Conclusion: Citation analysis can be used as an indicator of quality when assessing articles. It should, however, be used with caution as highly cited work, famous authors, and journals are all more likely to be cited. Citation analysis should be used alongside other well-established tools.

The experiences of patients with oesophageal cancer receiving chemoradiotherapy treatment: a qualitative study embedded in the SCOPE2 trial.

OBJECTIVES: This qualitative study explored patients' experiences and perceptions of the SCOPE2 trial. SCOPE2 examined radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemoradiotherapy (dCRT). SETTING: Recruitment at five clinical sites in England and Wales, UK. PARTICIPANTS: SCOPE2 trial participants were invited to take part in interviews from across five clinical sites. Participants self-selected to take part in up to three interviews across four different time points: baseline (before treatment) and at 2-3 months, 3-6 months or 6 months+ after baseline. There were five female and five male interview participants. INTERVENTIONS: Participants were randomised to standard dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine, or an escalated dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine. METHODS: This qualitative study used semistructured longitudinal interviews to explore the impact of treatment on patient outlook and quality of life and the impact of the COVID-19 pandemic. Interview data were thematically analysed. RESULTS: 10 patients participated in 16 longitudinal interviews. Three participants were accompanied by companions. Participants experienced side-effects from radiotherapy and chemotherapy including nausea, throat pain, difficulties eating and regaining appetite, thrombosis and fatigue, although most of these symptoms gradually improved. Participants required more ongoing information and support regarding treatment side-effects and cancer status in order to improve their overall quality of life. Best practice examples involved key contacts providing practical advice and signposting support. CONCLUSION: Participants of the SCOPE2 trial reported short and longer-term side-effects from chemoradiotherapy, but these usually lessened over time. Participants attempted to be positive about their survival prospects by readjusting their expectations, priorities and lifestyles. Providing patients with ongoing opportunities to discuss detailed and timely information regarding treatment side-effects, aftercare and cancer status could improve the overall health and well-being of patients during oesophageal cancer trials and pathways. TRIAL REGISTRATION NUMBER: NCT02741856; ISRCTN: 97125464.

Splenic Stiffness Measurement Combined With Liver Stiffness Measurement Compared With Baveno VII Criteria in Predicting the Presence of Oesophageal and Gastric Varices in Patients With Compensated Advanced Liver Cell Disease (cALCD).

INTRODUCTION: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) is being increasingly used as a screening tool to predict varices. Our aim was to test the utility of Baveno VII criteria and other combinations of LSM, platelet count (PC), and splenic stiffness measurement (SSM) to predict the presence of varices in a cohort of Sri Lankan patients with compensated advanced liver cell disease (cALCD). METHODS: Consecutive patients with newly diagnosed Child-Pugh class A cALCD (non-viral, BMI<30) were recruited prospectively. They underwent gastroscopy. LSM and SSM were taken using vibration-controlled transient elastography (VCTE) (Echosens FibroScan 502 Touch; Echosens SA, Paris, France) by a single operator who was unaware of endoscopy findings. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of different Baveno VII criteria to predict the varices and different combinations of LSM, SSM, and PC were also explored. RESULTS: One hundred and seventy-four individuals were recruited. The mean age was 61.4 ((95% CI: 59.7-62.8) years. A total of 110 individuals were males, and 106 had varices. Our results indicated that the three Baveno VII criteria had sensitivities of 61%, 63%, and 42%, and specificities of 79%, 77%, and 87% to predict varices. SSM>30kPa alone and in combination with LSM>15kPa had sensitivities of 81 and 75%, specificities of 72 and 83%, PPVs of 82 and 87%, NPVs of 71% and 67%, and accuracies of 78 and 78%, respectively, to predict varices. CONCLUSION: Baveno VII criteria had a low sensitivity but high specificity in predicting the presence of varices. However, SSM>30kPa alone or in combination with LSM>15kPa had better sensitivity, specificity, PPV, NPV, and accuracy in predicting varices.

Cerium oxide mimetic enzyme based colorimetric detection of potential oesophageal cancer biomarkers.

Oesophageal cancer (OC) is a prevalent malignant tumor that poses a significant threat to individuals. Current mainstream detection method is endoscopy, which requires professional operators and expensive instruments. Therefore, it is crucial to develop a rapid, easy-to-operate, and low-cost detection method. In this study, an RNA colorimetric biosensor was successfully constructed using cerium oxide mimetic enzyme. The sensor is constructed on 96-well plates, which are immobilized with DNA-RNA-DNA complexes in microtiter wells when target RNA is present. This immobilization is based on the principle of base complementary pairing. The CeO2 immobilized has the unique advantage of catalyzing the bluing of 3,3',5,5'-tetramethylbenzidine (TMB) directly without the need any additional oxidant in microtiter wells. This property allows for the detection of RNA and enables the visualization of multiple sample assays. Furthermore, the RNA colorimetric sensor demonstrates good selectivity, immunity to interference, and high stability. Under optimal conditions, the sensor exhibited linearity in the range of 10-13 to 10-9 M with a detection limit of 33.26 fM. Therefore, this study presents a new detection method for oesophageal cancer screening.

Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial.

Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P < 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P < 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P = 0.036). Interpretation: The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. Funding: National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

Comparing methods for detection of gastro-oesophageal reflux in anaesthetized dogs.

OBJECTIVE: To compare the sensitivity and specificity of pH with multichannel intraluminal impedance (pH-MII), pH-metry (pH) alone and MII alone to direct observation of GOR by endoscopy in anaesthetized dogs. STUDY DESIGN: A prospective comparative trial in a live canine model. ANIMALS: A group of 35 (22 females, 13 males) dogs of various breeds. The mean (range) body weight and age were 31.9 (14-40) kg and 5.6 (0.75-12) years, respectively. METHODS: All dogs were premedicated with medetomidine and morphine, anaesthesia was induced with propofol and maintained on isoflurane in oxygen. A monitoring assembly consisting of an endoscopy camera, endotracheal tube and a disposable flexible pH-MII catheter was used to measure oesophageal pH, MII and directly visualize reflux. Visual reflux score was (0-3) and pH was recorded on a data capture sheet. Reflux was considered to have occurred whenever oesophageal pH was < 4.0 or > 7.5, device software analysing MII data detected fluid or a visual reflux score of 2 or 3 were assigned. Receiver operator curves (ROC) analysis was used to determine sensitivity and specificity for each monitoring method to detect GOR. RESULTS: Endoscopy identified GOR in 20 dogs (57%), pH-MII in 19 dogs (54%), pH alone in 13 dogs (37%) and MII alone in 12 dogs (24%). ROC analysis showed fair accuracy for pH-MII and pH alone, whereas MII demonstrated low accuracy. CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, pH-MII is a reliable method for detecting GOR and emerges as a promising tool for future research. Endoscopy is reliable and provides the ability to subjectively quantify the volume of reflux; however, it lacks the ability to discern the pH of refluxate. pH alone misses reflux events with intermediate pH (4.1-7.4). Incorporation of impedance addresses some of the limitations associated with pH alone and enhances diagnostic accuracy.

Performance of spleen stiffness measurement by 100-Hz vibration-controlled transient elastography, liver stiffness, APRI score and their combination for predicting oesophageal varices in liver cirrhosis.

BACKGROUND: Oesophageal varices (EV) rupture remains one of the most severe complications of cirrhosis. As the gold standard to predict this accident, esophagogastroduodenoscopy (EGD) itself also has a weakness. Not all patients are convenient with this modality in clinical practice apart from the risk and cost burden. Hence, the search for other non-invasive modalities with high accuracy is still noteworthy. Among them, spleen stiffness measurement (SSM) with 100 Hz probe, liver stiffness measurement (LSM), and the aspartate amino transferase to platelet ratio index (APRI) score became popular and intensively studied with good accuracy, but the results remain conflicting. This study aims to investigate the performance of SSM, LSM, APRI score, and their combination especially as a screening tool for predicting EV in liver cirrhosis patients. METHODS: In this cross-sectional study, we included 141 patients with liver cirrhosis who had undergone endoscopy, SSM, LSM, and APRI score calculation between January and March 2023 were enrolled. Diagnostic accuracy was assessed by the area under the receiver-operator curve (AUC). Transient elastography (TE) measurement was performed using a spleen-dedicated FibroScan with a 100-Hz probe. RESULTS: Of the 141 patients, the most common aetiology was hepatitis B in 71 patients (50.4 %). EV were found in 116 patients. Using the AUC, SSM at a cutoff of 40 kPa had the best performance with an AUC of 0.892 (CI 95 %: 0.814-0.969, p <0.0001), with sensitivity 88.79 % and specificity 80 %). Meanwhile, LSM and APRI score had an AUC of 0.832 (CI 95 %: 0.742-0.922, p <0.0001) and 0.780 (CI 95 %: 0.660-0.900, p <0.0001), respectively. The combination of all measurement tools did not show better performance than SSM alone with an AUC of 0.892 (CI 95 %: 0.802-0.982, P <0.0001) CONCLUSION: SSM provides better performance than LSM and APRI scores for predicting EV. Performance of SSM alone is non-inferior compare to multiple diagnostic tools combined.

More than chest pain: A case of oesophageal foreign body ingestion.

BACKGROUND:  Physicians often focus on possible cardiac causes in patients presenting with chest pain. However, this case highlights a patient who presented with chest pain caused by ingestion of a foreign body after an uneventful meal eaten an hour prior to presentation. The fishbone was discovered after imaging. The article aims to raise awareness regarding the potential origins of chest pain, highlighting that it may stem from non-cardiac conditions. METHODS:  The methodology employed in this study involved conducting a case study that meticulously examined the repercussions and management strategies associated with foreign body ingestion. RESULTS:  The case report delineates the scenario of a 27-year-old male patient who inadvertently ingested a fishbone during a routine meal. It details the swift decline in clinical status, the meticulous diagnostic procedures employed, the subsequent management strategies implemented and the ultimate discharge of the patient in a stable condition. CONCLUSION:  This case highlights the importance of comprehensive history taking and considering a wide range of causes of chest pain when evaluating a patient. The foreign body ingested with the resulting cardiac complications could have been fatal if not promptly diagnosed.Contribution: This study contributed to advancing awareness surrounding foreign body ingestion, shedding light on potential complications and offering valuable insights into effective management strategies.

High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma.

OBJECTIVE: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy. DESIGN: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed. RESULTS: A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity. CONCLUSION: Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.

Thromboprophylaxis in oesophageal cancer patients-a study protocol for a randomised, controlled trial (TOP-RCT).

BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment. METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery. DISCUSSION: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population. TRIALS REGISTRATION: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.

Casual effects of type 1 diabetes mellitus on site-specific digestive cancers: a Mendelian randomisation analysis.

Objective: Despite several observational studies attempting to investigate the potential association between type 1 diabetes mellitus (T1DM) and the risk of digestive cancers, the results remain controversial. The purpose of this study is to examine whether there is a causal relationship between T1DM and the risk of digestive cancers. Methods: We conducted a Mendelian randomisation (MR) study to systematically investigate the effect of T1DM on six most prevalent types of digestive cancers (oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, pancreatic cancer, and colorectal cancer). A total of 1,588,872 individuals were enrolled in this analysis, with 372,756 being the highest number for oesophageal cancer and 3,835 being the lowest for pancreatic cancer. Multiple MR methods were performed to evaluate the causal association of T1DM with the risk of six site-specific cancers using genome-wide association study summary data. Sensitivity analyses were also conducted to assess the robustness of the observed associations. Results: We selected 35 single nucleotide polymorphisms associated with T1DM as instrumental variables. Our findings indicate no significant effect of T1DM on the overall risk of oesophageal cancer (OR= 0.99992, 95% CI: 0.99979-1.00006, P= 0.2866), stomach cancer (OR=0.9298,95% CI: 0.92065-1.09466, P= 0.9298), hepatocellular carcinoma (OR= 0.99994,95% CI: 0.99987-1.00001, P= 0.1125), biliary tract cancer (OR=0.97348,95% CI: 0.8079-1.1729, P= 0.7775)), or pancreatic cancer (OR =1.01258, 95% CI: 0.96243-1.06533, P= 0.6294). However, we observed a causal association between T1DM and colorectal cancer (OR=1.000, 95% CI: 1.00045-1.0012, P<0.001), indicating that T1DM increases the risk of colorectal cancer. We also performed sensitivity analyses, which showed no heterogeneity or horizontal pleiotropy. For the reverse MR from T1DM to six digestive cancers, no significant causal relationships were identified. Conclusions: In this MR study with a large number of digestive cancer cases, we found no evidence to support the causal role of T1DM in the risk of oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, or pancreatic cancer. However, we found a causal positive association between T1DM and colorectal cancer. Further large-scale prospective studies are necessary to replicate our findings.

Outcomes of patients with Barrett's oesophagus with low-grade dysplasia undergoing endoscopic surveillance in a tertiary centre: a retrospective cohort study.

BACKGROUND AND AIM: Barrett's oesophagus predisposes individuals to oesophageal adenocarcinoma (OAC), with the risk of progression to malignancy increasing with the degree of dysplasia, categorized as either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). The reported incidence of progression to OAC in LGD ranges from 0.02% to 11.43% per annum. In patients with LGD, Australian guidelines recommend 6-monthly endoscopic surveillance. We aimed to describe the surveillance practices within a tertiary centre, and to determine the predictive value of surveillance as well as other risk factors for progression. METHODS: Endoscopy and pathology databases were searched over a 10-year period to collate all cases of Barrett's oesophagus with LGD. Medical records were reviewed to document patient factors and endoscopic and histologic details. Because follow-up times varied greatly, survival analysis techniques were employed. RESULTS: Fifty-nine patients were found to have LGD. Thirteen patients (22.0%) progressed to either HGD or OAC (10 (16.9%) and three (5.1%) respectively); the annual incidence rates of progression to HGD/OAC and OAC were 5.5% and 1.1% respectively. All patients who developed OAC had non-guideline-adherent surveillance. A Cox model found only two predictors of progression: (i) guideline-adherent surveillance, performed in 16 (27.1%), detected progression to HGD/OAC four times earlier than non-guideline-adherent surveillance (95% confidence interval (CI) = 1.3-12.3; P = 0.016). (ii) The detection of visible lesions at exit endoscopy independently predicted progression (hazard ratio = 6.5; 95% CI = 1.9-22.8; P = 0.003). CONCLUSION: Barrett's oesophagus with LGD poses a significant risk of progression to HGD/OAC. Guideline-recommended surveillance is effective, but is difficult to adhere to. Clinical predictors for those who are more likely to progress are yet to be defined.

NEDD4L affects KLF5 stability through ubiquitination to control ferroptosis and radiotherapy resistance in oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC) contributes to high mortality. Modulating ferroptosis may reverse resistance to radiotherapy. This article was to explore the ubiquitination modification of KLF5 and its effect on ferroptosis in ESCC. KLF5 was under-expressed by shRNA plasmids in the cells and ROS levels were analysed by flow cytometry, ferroptotic gene expression was detected by qRT-PCR, MDA and GSH levels were determined by ELISA, cell morphology was observed by transmission electron microscopy, and Fe ion levels were analysed by immunofluorescence. Cells were treated with Ferrostatin-1 and NAC and analysed for cell proliferation by colony formation assay, cell migration and invasion by Transwell assays, and apoptosis by flow cytometry. DNA damage in cells was also analysed using comet assay, EdU doping assay, γH2AX fluorescence, DNA-PKcs and PCR. NEDD4L and KLF5 binding was analysed by immunoprecipitation. Changes in ferroptosis, DNA damage and resistance were analysed in cells with both silencing NEDD4L and KLF5. Changes in tumour resistance to radiation were analysed in mice underexpressing NEDD4L and KLF5. Low expression of KLF5 significantly promotes cellular lipid peroxidation levels, with decreased expression of SOD and GPX4, and increased expression of ACSL4. Concurrently, MDA levels deplete GSH, and cells exhibit typical ferroptotic morphology with increased Fe2+ content. KLF5 inhibition results in enhanced cellular clonogenicity, migration and invasion activities, reduced apoptosis, increased tail DNA, nuclear EdU incorporation, nuclear γH2AX foci and elevated expression of DNA-PKcs, LIG4, RAD9B and BMI1. Ferrostatin-1 and NAC reverse these effects. NEDD4L ubiquitination modifies and degrades KLF5, with NEDD4L/KLF5 inhibition mitigating cellular ferroptosis and DNA damage, thereby promoting radiosensitivity both in vitro and in vivo. NEDD4L increases radiosensitivity by accelerating cellular ferroptosis via ubiquitination modification of KLF5.

The biogeographic patterns of the olive fly and its primary symbiont Candidatus Erwinia dacicola across the distribution area of the olive tree.

The olive fly, Bactrocera oleae (Rossi, 1790), is the major insect pest of olives attacking both cultivated and wild olive. Bactrocera oleae carries a primary and vertically transmitted symbiont, the bacterium Candidatus Erwinia dacicola. As any primary symbiont, it plays an important role in the reproduction and lifespan of the fly. The genetic 16S rRNA diversity of the primary symbiont and the mitochondrial haplotype variation of the insect host were simultaneously examined in 54 olive fly populations. The aim was to unravel the biogeographic patterns of this economically relevant host-bacteria interaction across a wide distribution area. Three symbiont haplotypes were identified. The primary symbiont showed a lower haplotype diversity than that of its host, a characteristic indicative of a long-term interaction. A significant genetic and geographic association between host and primary symbiont was observed, with an East-West genetic differentiation pattern in the Mediterranean basin, coinciding with the historical genetic distribution of the olive tree. The study shows promise, informing and aiding the development of future tools for the control of the olive fly.