|
1
|
-
"The important value of this study lies in its clear finding that lean MASLD patients show no statistically significant differences from non-lean MASLD patients in terms of MASH, cardiovascular disease, and mortality risk, while their risks of cirrhosis, hypertension, and liver fibrosis are actually lower. The core clinical implication of this finding is that normal BMI should not be a reason to relax screening and risk assessment for MASLD and its complications. Of course, the study also has limitations: the definition of 'lean' varies across studies, which may introduce classification bias; and some outcomes (e.g., mortality, MASH, fibrosis) show high heterogeneity (I² > 90%), requiring cautious interpretation. Nevertheless, this is a study with direct practical guidance for clinical practice, particularly suitable for readers in hepatology, cardiology, endocrinology, and general medicine, as it helps shift MASLD screening strategies from an obesity-centered approach to multidimensional metabolic risk assessment."
-
Mapouka M, Pabingui E, Tazinkeng NN, Gurmessa M, Vickos U, Ndemazie NB, Camengo Police SM. Outcomes of liver and cardiovascular metabolic diseases among lean vs non-lean individuals with metabolic dysfunction-associated steatotic liver disease. World J Gastroenterol 2026; 32(13): 114657 [DOI: 10.3748/wjg.v32.i13.114657]
|
|
2
|
-
"The authors integrated multiple GEO datasets, combined bioinformatics methods such as WGCNA and LASSO, and identified four exercise-responsive skeletal muscle genes (LAMA4, PECAM1, PXDN, THBS4), which were subsequently validated in an animal model. The study is clear in its approach and logically coherent. Its value lies in moving beyond the general attribution of exercise-induced improvement in MASLD to simply weight loss or metabolic improvement, instead attempting to pinpoint specific molecular mediators from the perspective of muscle–liver crosstalk. In particular, the detectability of PECAM1 and THBS4 in serum suggests their potential as liquid biopsy biomarkers or myokine-like candidates, offering reference value for the future development of exercise-mimetic drugs or precision intervention strategies."
-
Zhang JH, Chen K, Zhu XM, Zhou H, Jiang JM, Zou YQ, Liu KR, Zhang L, Li Y. Exercise-responsive skeletal muscle genes mechanistically linked to metabolic dysfunction-associated steatotic liver disease. World J Gastroenterol 2026; 32(13): 113985 [DOI: 10.3748/wjg.v32.i13.113985]
|
|
3
|
-
"This is a well-organized and potentially meaningful study investigating exercise-responsive skeletal muscle biomarkers in MASLD. The integration of multiple GEO datasets, combined with WGCNA, LASSO modeling, validation cohort analysis, and animal experiments, represents a comprehensive approach. The identification of candidate genes involved in muscle-liver communication is of interest and may contribute to a better understanding of the mechanisms underlying the beneficial effects of exercise in MASLD. Nevertheless, one issue should be clarified. In the “Identification of DEGs” section and in Figure 1, the authors indicate that GSE161749, GSE48278, GSE156247, and GSE53598 were included. However, in Figure 2A/2B, the PCA legend appears to include GSE72462 instead of GSE156247. Please clarify which dataset was actually used and correct the figure or text accordingly."
-
Zhang JH, Chen K, Zhu XM, Zhou H, Jiang JM, Zou YQ, Liu KR, Zhang L, Li Y. Exercise-responsive skeletal muscle genes mechanistically linked to metabolic dysfunction-associated steatotic liver disease. World J Gastroenterol 2026; 32(13): 113985 [DOI: 10.3748/wjg.v32.i13.113985]
|
|
4
|
-
"The gut–muscle axis shares its conceptual underpinnings with the gut–lung axis, encompassing bidirectional crosstalk driven by gut dysbiosis, microbial translocation, immune dysregulation, and epigenetic modification. Short-chain fatty acids (SCFAs) — most notably butyrate — serve as the principal metabolic intermediary, promoting skeletal muscle protein synthesis and mitochondrial integrity through FFAR2/FFAR3 receptor signaling, AMPK–PGC-1α pathway activation, and PI3K/Akt/mTOR-mediated anabolism, while simultaneously exerting epigenetic regulation via histone deacetylase (HDAC) inhibition.
A mechanistically distinctive feature of the gut–muscle axis is robust retrograde signaling from muscle to gut. Exercise-derived lactate directly fuels SCFA-producing bacteria, and muscle-secreted myokines actively modulate microbial diversity — thereby constituting an actionable, bidirectional feedback loop with no clear counterpart in the gut–lung axis. Furthermore, gut microbiota-derived secondary bile acids activate farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) in skeletal muscle, representing a pathway of particular relevance to gut–muscle biology.
Clinically, dysbiosis-driven SCFA depletion accelerates sarcopenia in aging populations, whereas patients with inflammatory bowel disease (IBD) face compounded muscle wasting attributable to chronic inflammation and nutrient malabsorption. Therapeutic strategies — encompassing probiotics, fecal microbiota transplantation (FMT), and butyrate supplementation — mirror those proposed for the gut–lung axis, with multi-omics integration and AI-driven analytics defining the shared frontier of precision medicine.
In summary, the gut–muscle axis both extends and substantively complements the gut–lung axis paradigm. Crucially, physical activity emerges as a uniquely potent bidirectional therapeutic modality, making it particularly suited for addressing muscle wasting in IBD and aging populations.
"
-
Huang HJ, Liu PP, Dong DF. Research progress on comorbidity between gastrointestinal and pulmonary diseases from the perspective of the gut-lung axis. World J Gastroenterol 2026; 32(11): 115846 [DOI: 10.3748/wjg.v32.i11.115846]
|
|
5
|
-
"I thank Khan et al for conducting this meta-analysis and finding out that hypoalbuminemia is a risk factor for mortality in cholangitis. I have a few comments that have to be taken into account while interpreting this study. First, this meta-analysis includes only retrospective studies. Second, there is no subgroup analysis by benign versus malignant aetiology of acute cholangitis. The outcomes of cholangitis depend on aetiology, which is not studied. This indicates whether hypoalbuminemia is due to cholangitis as an acute-phase reactant, or whether any underlying aetiology needs to be identified. Whether any intervention in acute cholangitis with hypoalbuminemia has any role in the outcome has not been studied. However, this meta-analysis provides meaningful research questions for future prospective studies."
-
Khan RTY, Ahsam S, Kumar SK, Khan K, Kakar MT, Hyder A, Malik W, Mubarak M, Luck NH. Hypoalbuminemia as a predictor of mortality in patients with acute cholangitis: A systematic review and meta-analysis. World J Gastrointest Pathophysiol 2026; 17(1): 113373 [PMID: 41884201 DOI: 10.4291/wjgp.v17.i1.113373]
|
|
6
|
-
"Sheriefet al. [1]demonstrated dual parametric evaluation to assess diagnostic performance for Hepatocellular carcinoma (HCC), discriminating from Hepatitis C-related liver Cirrhosis and Healthy control cohorts via plasma in a single centred Egyptian population.This study [1] revealed two leading biomarkers with exceptional accuracy (AUC >0.99); hsa-miR-21-5p (Sensitivity and Specificity of 98.6% and 96.7%, respectively) and Leukocyte-associated immunoglobulin-like receptor-1(LAIR-1) mean fluorescence intensity (MFI) (Sensitivity and Specificity of 100 % and 98.3%, respectively).
Sherief et al. [1]aims to address one of the clinically challenging issues i.e. lack of sensitive, specific circulatory biomarker/s for early diagnosis of Hepatocellular Carcinoma (HCC).Commentary noted several strengths of the study by Sherief et al. [1],such as; looks technicallymoderatein study design, methodology and innovation level i.e. prospective study, minimally invasive sample collection, exploration of dual parameters: tumour derived circulatory micro-RNA and immune related marker. Additionally, study employed rigorous statistical analysis for diagnostic performance assessment including ROC curve analysis, comparative Sensitivity/Specificity,revealed promising findings that may pave for future research towards biomarkers validation and discovery.
However,present commentary observed several concerns for the study by Sherief et al. [1]; (i) Lack of mechanistic cascade exploration including causal pathway/s.(ii) Median age of HCC cohort is significantly higher than Hepatitis C-related liver Cirrhosis and Healthy control, may be a biasing factor in expression pattern. (iii) Since study did not include follow up subjects that limits for probing of prognostic markers. (iv) Paucity of multi-centric involvement for diversified population, may limit the findings for generalized conception. (v) Validation of findings through blinded samples may demonstrate a better decision regarding applicability. (vi) Authors used word ‘noninvasive’, for plasma-based markers investigation(vii) Global Cancer statistics 2022,wasalready published in 2024[2], still authors used GLOBOCON 2020 [3] reference in epidemiological outline in the manuscript [1], latest reference can provide contemporary status.
The article by Sherief et al. [1], demonstrated balanced and structured scientific contents along with logical explanations. However, addition of graphical abstract to present the study in nutshell may improve the visibility for readers.
A large sample sized, multi-centered,longitudinal study, involving diversified geographical and ethnic population of HCC, Hepatitis C-related liver Cirrhosis, Healthy control cohorts, and mechanistically relevant subgroups, using common protocol, validation through blinded samples, may provide potential edge for HCCdiagnosticsto achieve common consensus and identification of prognostic biomarkers. Integrated nomogram ofhsa-miR-21-5p with LAIR-1 MFI, may be explored for possible better diagnosticsetup. Application of Artificial Intelligence (AI) may be explored for diagnostic performance as well as high throughput outcomes.
References:
1. Sherief DE, Shehata HH, Nosair N, Othman AAA, Sadaka E, Elgamal R. Dual-parameter liquid biopsy using plasma miR-21-5p and T cell LAIR-1 mean fluorescence intensity for hepatocellular carcinoma diagnosis in a high-risk Egyptian cohort. World J Gastrointest Oncol 2026 March 15a; 18(3): 116567.
2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for36 cancers in185 countries. CA Cancer J Clin. 2024; 74:229–263
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71: 209-249
"
-
Sherief DE, Shehata HH, Nosair N, Othman AAA, Sadaka E, Elgamal R. Dual-parameter liquid biopsy using plasma miR-21-5p and T cell LAIR-1 mean fluorescence intensity for hepatocellular carcinoma diagnosis in a high-risk Egyptian cohort. World J Gastrointest Oncol 2026; 18(3): 116567 [DOI: 10.4251/wjgo.v18.i3.116567]
|
|
7
|
-
"I read with ken interest about the following article. As a reader I have few comments/ suggestions also.
Alok Bharadwaj, Manas Taneja, Sneha Dubey, Aditya Saxena. Very low-density lipoprotein and the human health. World J Exp Med 2026;16(1): 117024 [DOI: 10.5493/wjem.v16.i1.117024]
Abstract
Apo B100, TGL and cholesterol are present in LDL in addition to VLDL. But the ratio of TGL: cholesterol may vary.
PATHOLOGICAL ROLE OF VLDL:
Metabolism-associated fatty liver disease and liver disease:
Distinction between NAFLD, MAFLD and MASLD may be provided
Following the classification of metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction-associated steatotic liver disease (MASLD). Both MASLD and MALFD were linked to higher all-cause mortality risk, but MASLD identified a greater number of individuals compared to MAFLD. (Song R, Li Z, Zhang Y, Tan J, Chen Z. Comparison of NAFLD, MAFLD and MASLD characteristics and mortality outcomes in United States adults. Liver Int. 2024;44:1051-1060. doi:10.1111/liv.15856)
Metabolic-associated fatty liver disease (MAFLD) exhibits a raised VLDL secretion rate attributed to increased intrahepatic TGs hydrolysis. They apparent the absence of immediate VLDL secretion reduction yet maintained a consistent apo B100 secretion rate, as informed by previous studies/
I would like to reframe this sentence: in the presence of elevated counter-regulatory hormones, lipolysis takes place in the adipose tissue releasing free fatty acids into circulation. Majority of these fatty acids are take up liver and converted into triglycerides. If VLDL secretion from liver is not proportionate to the level of fatty acid entry into liver, fatty acids may get accumulated in the liver causing different forms of fatty liver.
In individuals with insulin resistance and higher body weight, there is an elevation in apo C-III levels within VLDL.
Apo CIII is an inhibitor of lipoprotein lipase, thus inhibiting lipolysis of TGL in VLDL, thus increasing VLDL concentration in blood.
Insulin resistance and MetS
Insulin-hampered VLDL production, along with insulin resistance, leads to increased and decreased production of VLDL, often associated with hypertriglyceridemia
Does VLDL increase or decrease with insulin resistance
Hepatic VLDL production is decreased by glucagon
Mechanism behind this
Alterations of VLDL in various disorders have been explained well.
All the mechanistic pathways have been adequately addressed
"
-
Bharadwaj A, Taneja M, Dubey S, Saxena A. Very low-density lipoprotein and the human health. World J Exp Med 2026; 16(1): 117024 [PMID: 41883448 DOI: 10.5493/wjem.v16.i1.117024]
|
|
8
|
-
"This letter to the Editor notes the potential significance of clinical situation in patients who suffer from emphysematous pyelonephritis. This is very important. Clinical findings and symptoms must be the cornestone in these conditions in order to avoid the worse outcomes of patients.
In addition, the Modified National Early Warning Score 2 based on physiological situation of patient shoud be very helpfull, as well as computed tomography findings."
-
Sevik C, Erbin A, Canat HL. Integrating Modified National Early Warning Score 2, computed tomography staging, and laboratory markers for enhanced prognostic stratification in emphysematous pyelonephritis. World J Nephrol 2026; 15(1): 113952 [PMID: 41884236 DOI: 10.5527/wjn.v15.i1.113952]
|
|
9
|
-
"This manuscript defined as Editorial is generally good, but it mildly offers new lights in concept of diabetic nephropathy complications and its progression in death.
Pathophysiology paragragh is better than the other parts of manuscript. Addiotionally, inequalities and differences between racial and ethic groups were noted, which is not usual in other published manuscripts."
-
Gembillo G, Ricca MF, Santoro D. Diabetes-related renal complications: Insights on the impact of diabetic kidney disease on mortality. World J Nephrol 2026; 15(1): 108432 [PMID: 41884250 DOI: 10.5527/wjn.v15.i1.108432]
|
|
10
|
-
"Reader’s code: 00106360
Commentary on the Article
Impact of metabolic dysfunction-associated steatotic liver disease on liver metastasis and survival in pancreatic cancer
The study by Chon HY et al. examines the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on liver metastasis and survival in patients with Pancreatic Ductal Adenocarcinoma. Using a large retrospective cohort of 2123 patients, the authors assessed hepatic steatosis primarily through the hepatic steatosis index (HSI) and additionally validated findings using CT-based measurements of liver fat. The study found no significant association between MASLD and the presence of liver metastasis at diagnosis or during follow-up, suggesting that hepatic steatosis may not be a key determinant of metastatic spread in pancreatic cancer (Chon et al., 2026).
The findings contrast with previous research in other malignancies, such as colorectal and breast cancers, where hepatic steatosis has been reported to influence liver metastasis risk or metastasis-free survival (van Saane et al., 2019; Wu et al., 2020). In the present study, tumor size and elevated CA19-9 levels were the main predictors of liver metastasis, while diabetes mellitus was associated with improved survival outcomes, possibly reflecting earlier detection among diabetic patients (Chon et al., 2026).
Critical Appraisal of the Study
The study by Chon HY and colleagues evaluates the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and liver metastasis in patients with Pancreatic Ductal Adenocarcinoma. Using a large retrospective cohort of 2123 patients, the authors investigated whether hepatic steatosis, measured by the hepatic steatosis index (HSI), influences the development of liver metastasis and overall survival.
Strengths
One of the major strengths of this study is its large sample size and long study period (2006–2021), which enhances the statistical power and reliability of the findings. The authors used robust statistical methods, including logistic regression and Cox proportional hazards models, to analyze risk factors for both baseline and newly developed liver metastases. Another notable strength is the additional CT-based validation in a subgroup of patients, which helps corroborate the HSI-based assessment of hepatic steatosis. The study also carefully adjusted for multiple potential confounders such as age, BMI, diabetes, lipid profile, tumor size, and CA19-9 levels.
Limitations
Despite these strengths, several limitations should be considered. First, the retrospective design limits the ability to establish causal relationships. Second, the primary assessment of hepatic steatosis relied on the HSI, an indirect surrogate marker derived from BMI and liver enzyme ratios, which may be influenced by cancer-related factors such as cachexia, inflammation, or biliary obstruction. Third, important pathological variables (e.g., lymph node status, lymphovascular invasion, and perineural invasion) were not consistently available and therefore could not be included in the multivariate models. Additionally, the CT-based validation was limited to a subset of patients, which may introduce selection bias.
Clinical Implications
Clinically, the findings suggest that MASLD may not be a significant determinant of liver metastasis in pancreatic cancer, contrasting with observations in other malignancies. Instead, established markers such as tumor size and elevated CA19-9 levels appear to remain more reliable predictors of metastatic risk and mortality. These results highlight the aggressive biological behavior of pancreatic cancer, where tumor-driven mechanisms may outweigh the influence of underlying hepatic metabolic conditions. Future prospective studies incorporating advanced imaging, histologic confirmation, and molecular analysis of the tumor–liver microenvironment are needed to further clarify the role of MASLD in pancreatic cancer progression.
Despite its strengths, including a large sample size and robust statistical modeling, the retrospective design and reliance on HSI rather than histologic confirmation limit the ability to establish causality. Nevertheless, this study contributes important evidence suggesting that the relationship between MASLD and metastasis may be cancer-specific and biologically complex.
Reference
Chon HY, Rhee H, Kim J, et al. Impact of metabolic dysfunction-associated steatotic liver disease on liver metastasis and survival in pancreatic cancer. World Journal of Gastroenterology. 2026;32(11):115488.
van Saane AM, et al. Non-alcoholic fatty liver disease and colorectal liver metastasis risk. Liver International. 2019.
Wu W, et al. Hepatic steatosis and liver metastasis-free survival in breast cancer. Cancer Medicine. 2020.
"
-
Chon HY, Rhee H, Kim J, Leem G, Jo JH, Chung MJ, Park JY, Bang S, Park SW, Kim SU, Lee HS. Impact of metabolic dysfunction-associated steatotic liver disease on liver metastasis and survival in pancreatic cancer. World J Gastroenterol 2026; 32(11): 115488 [DOI: 10.3748/wjg.v32.i11.115488]
|
|
11
|
-
"Esophageal variceal bleeding is one of the most severe complications of cirrhotic portal hypertension, associated with high rates of rebleeding and mortality. Although endoscopic variceal band ligation (EVBL) is currently the standard treatment, its reliance on repeated endoscopic follow-up presents challenges, including invasiveness, high resource consumption, and poor patient tolerance.
This study focuses on the potential application of multiparametric ultrasound (MP-US) in predicting outcomes following EVBL, proposing a novel follow-up strategy that is noninvasive, individualized, and reproducible, with significant promise for clinical translation.
The article begins with the clinical burden of EVB, progressively introduces the limitations of current diagnostic and therapeutic approaches, and naturally transitions to the technical advantages and research evidence supporting MP-US, culminating in future research directions. The structure is well-organized, and the logic is rigorous. The critical analysis of existing technologies is insightful. The article objectively highlights the limitations of HVPG and repeated endoscopy, particularly their inaccessibility in resource-limited settings. It also provides a reasonable evaluation of the shortcomings of noninvasive tools such as the Baveno criteria and elastography in predicting postprocedural outcomes, reflecting the authors' deep understanding of clinical realities. The analysis of MP-US's clinical application is thorough. By integrating measurements of liver stiffness, spleen stiffness, and perfusion imaging, MP-US enables a comprehensive assessment of portal hypertension from both structural and hemodynamic perspectives, overcoming the limitations of traditional single-parameter prediction models. Citing data from Ainora et al, the study demonstrates the potential of MP-US in predicting variceal eradication and guiding individualized follow-up. The outlook on future research directions is instructive. The article notes that current studies are mostly small-sample, single-center designs lacking standardized operating and interpretation protocols, and calls for multicenter, prospective studies to validate the clinical value of MP-US—a recommendation with practical significance. Figure 1 is highly informative, clearly illustrating the evolutionary pathway from invasive to noninvasive diagnostic tools, facilitating readers' understanding of technological advancements.
Areas for improvement and suggestions: The issue of MP-US technical standardization requires further clarification. Although the article mentions that MP-US is influenced by factors such as operator experience and equipment variability, it does not delve deeply into how to achieve standardized operation and interpretation; future research should focus on this aspect. A cost-effectiveness analysis is lacking. While MP-US has the potential to reduce the frequency of endoscopic examinations, its high equipment costs and reliance on contrast agents may limit its widespread adoption in certain regions. Future studies should incorporate health economic evaluations. The integration of AI with MP-US warrants further exploration. The article mentions the application of AI in endoscopic measurement but does not explore the possibility of combining AI with MP-US. Future research could investigate AI-based automated analysis of MP-US images and risk prediction models.
This study, with its clear logic, solid literature support, and forward-looking perspective, systematically elaborates on the potential application of MP-US in post-EVBL follow-up. It not only provides clinicians with new diagnostic and therapeutic insights but also points future researchers toward promising directions. If further advancements are made in MP-US standardization, multicenter validation, and AI integration, it holds the potential to achieve truly noninvasive, precise, and individualized management of portal hypertension in patients with cirrhosis."
-
Martínez-Díaz FM, Jiménez-Cuevas EA, Morales-Galicia AE, Ramírez-Mejía MM, Qi XS, Poo JL, Méndez-Sánchez N. Toward noninvasive prediction of treatment outcomes in patients with variceal bleeding. World J Gastroenterol 2026; 32(11): 115723 [DOI: 10.3748/wjg.v32.i11.115723]
|
|
12
|
-
"This systematic review of 8 randomized trials (1758 participants) rigorously evaluates adjunctive pharmacotherapies for diuretic resistance in acute decompensated heart failure (ADHF), adhering to PRISMA guidelines and using Cochrane’s RoB 2.0 for bias assessment. Key findings show proximal nephron-targeted agents (acetazolamide, SGLT2 inhibitors) and distal thiazide diuretics effectively boost decongestion: acetazolamide raises successful decongestion rates (42.2% vs 30.5%), SGLT2 inhibitors enhance urine output and reduce worsening HF, while thiazides prompt greater weight loss but increase renal dysfunction risk. Notably, older agents (high-dose spironolactone, low-dose dopamine/nesiritide) yield no meaningful clinical benefits. The review’s strength lies in its exclusive focus on randomized trials, but heterogeneity in endpoints and short follow-up limit generalizability. It provides a mechanistically guided, stepwise clinical framework for ADHF management, emphasizing personalized adjunct selection, and identifies the need for large head-to-head trials and long-term outcome research to address existing evidence gaps."
-
Patel V, Zameer R, Kumar B, Das M. Adjunctive pharmacologic therapies for diuretic resistance in acute decompensated heart failure: Systematic review of randomized trials. World J Meta-Anal 2026; 14(1): 118496 [DOI: 10.13105/wjma.v14.i1.118496]
|
|
13
|
-
"The article raises critical issues regarding healthcare expenditure and the anesthesiologist’s responsibility in cost containment. While the narrative is informative, a more quantitative economic comparison and inclusion of updated guidelines or contemporary practice data would strengthen the conclusions. Additionally, deeper exploration of medico-legal concerns and institutional resistance could enhance its practical impact. Nevertheless, the review addresses a clinically meaningful topic."
-
Karim HMR. Healthcare delivery cost and anesthesiologists: Time to have a greater role and responsibility. World J Anesthesiol 2019; 8(3): 19-24 [DOI: 10.5313/wja.v8.i3.19]
|
|
14
|
-
"
I read with great interest the study by Khalifa et al. published in the World Journal of Orthopedics, evaluating the impact of surgeon handedness on radiological and functional outcomes following primary total knee arthroplasty (TKA). The authors should be commended for addressing an underexplored yet clinically relevant surgeon-related variable in arthroplasty practice.
The finding that overall limb alignment and functional outcomes were not significantly influenced by operating on the dominant versus non-dominant side is reassuring. However, the increased incidence of tibial component malalignment (MPTA outliers) on the non-dominant side highlights an important technical nuance that may have implications for implant longevity, particularly in mechanically aligned TKA performed with conventional instrumentation.
The subgroup analysis comparing intramedullary and extramedullary tibial guides is particularly interesting, suggesting that technique selection may interact with laterality. These findings underscore the potential value of ergonomic optimization and heightened intraoperative vigilance when operating on the non-dominant side.
Future prospective studies incorporating sagittal and rotational alignment parameters, inclusion of left-handed surgeons, and long-term survivorship data would further clarify the clinical significance of these observations. Additionally, evaluating whether navigation or robotic assistance mitigates the subtle asymmetries associated with surgeon handedness could provide valuable insights.
Overall, this study contributes meaningfully to the ongoing discussion regarding modifiable surgeon-related factors influencing TKA precision and outcomes."
-
Khalifa AA, Abdelaal AM, Moustafa MM. Does surgeon handedness affect the outcomes after primary total knee arthroplasty? A retrospective cohort study. World J Orthop 2026; 17(2): 113696 [PMID: 41695728 DOI: 10.5312/wjo.v17.i2.113696]
|
|
15
|
-
"I would like to congratulate the authors on this clinically relevant study. The authors provided a conclusion that differs from previously published results. ETV is generally considered renal-neutral and is commonly used in DCLD due to its renal safety. The statement that ETV is associated with a greater decrease in GFR than TMV is overfitting, as it is a retrospective study. The Difference in decline of approximately 4 mL/min/1.73 m² is very small and may not be clinically meaningful in patients with normal GFR, even though it is statistically significant. The conclusion should be interpreted with caution and requires additional long-term prospective studies to substantiate this claim. Furthermore, the authors did not report any additional adverse events during the study period. "
-
Ma SP, Wang L, Zhang YL, Wan X, Liu Q, Tang YL, Malhi LR, Ge SF. Effects of tenofovir amibufenamide and entecavir on estimated glomerular filtration rate in treatment-naïve patients with chronic hepatitis B. World J Hepatol 2026; 18(2): 114346 [PMID: 41809484 DOI: 10.4254/wjh.v18.i2.114346]
|
|
16
|
-
"I congratulate the authors on this relevant study on this study. As the authors pointed out, Klebsiella is the leading cause of liver abscesses in Asia and is increasingly prevalent in India. It is important to have culture reports at various time points, as they will help us in deciding empirical antibiotics. The authors have shown that the isolated organisms are highly resistant to ampicillin and have low resistance to cephalosporins and carbapenems. With this large amount of data, the authors would have identified the poor prognostic predictors of PLA and treatment outcome. The authors did not present the data on complications of these abscess such as biliary fistula "
-
Mai-Phan TA, Thai KP, Le KL, Pham TN, Tran MQ, Pham PC, Duong NNQ, Trinh MT, Le NK. Klebsiella pneumoniae as leading cause of pyogenic liver abscess: Three years study in Southern Vietnam. World J Hepatol 2026; 18(2): 113695 [PMID: 41809471 DOI: 10.4254/wjh.v18.i2.113695]
|
|
17
|
-
"Wang and Pan present an editorial that meaningfully extends the discussion of ERAS in elderly gastric cancer patients beyond feasibility toward biologically grounded recovery. Building on prior evidence by Li et al. demonstrating the safety and protocol adherence of ERAS in older adults. The authors appropriately emphasize physiological heterogeneity, frailty, and resilience as key determinants of postoperative outcomes rather than chronological age alone.
The proposed multidomain framework integrating nutritional inflammatory balance, circadian regulation, psychological resilience, and digital monitoring, offers an important conceptual advance. However, many of these strategies rely on resource intensive multidisciplinary teams, biomarker surveillance, and wearable technologies, which may limit generalizability outside high-volume or well-resourced centers.
Future efforts may benefit from parallel development of simplified, scalable ERAS adaptations for elderly patients. Overall, this editorial provides a valuable roadmap for evolving ERAS from protocol compliance toward patient-centered, biologically informed recovery in an aging surgical population."
-
Wang G, Pan SJ. From feasibility to biological recovery: Reframing enhanced recovery pathways after surgery in elderly gastric cancer patients. World J Gastroenterol 2026; 32(7): 116264 [PMID: 41694491 DOI: 10.3748/wjg.v32.i7.116264]
|
|
18
|
-
"This Editorial thoroughly explores the field of AI use in diagnostic radiology.
It provides a complete overview of the potential and the current applications of AI in the field with great potential, strong diagnostic performance but in my opinion it does spotlight with the due consideration the potential drawbacks coming from the extensive use of AI in the clinical field.
The enthusiasm generated from the high precision and performance and the consequent advantages in terms of resource and time save for operators outpaced evaluation of broader consequences. Concerns include trainee deskilling, automation bias, unclear medicolegal accountability, and inequitable access due to infrastructure demands. The authors emphasize that technical accuracy alone is insufficient and call for longitudinal studies, training models that preserve independent reasoning, and deployment strategies that address equity. Without systematic assessment of professional, clinical, and societal impacts, AI adoption risks being driven by non-evidence-based factors."
-
He ZX, Wang J, Yang JS. Expanding the applications of artificial intelligence in emergency radiology: Advancing precision medicine and resource efficiency. World J Radiol 2026; 18(1): 117814 [PMID: 41640709 DOI: 10.4329/wjr.v18.i1.117814]
|
|
19
|
-
"This study demonstrates that presenilin-1 (PS-1) is significantly associated with β-catenin activation, PTEN phosphorylation, advanced tumor stage, and poor survival in gastric cancer. The combination of clinical data and functional assays strengthens the evidence for the PS-1/β-catenin/p-PTEN axis in promoting invasion and metastasis. These findings highlight a potential therapeutic target for gastric cancer treatment."
-
Lin X, Lin GF, Gu FT, Li YL. Increasing expression of presenilin 1, β-catenin, and p-PTEN and its regulatory roles on cell invasion in gastric cancer. World J Gastrointest Oncol 2026; 18(2): 115689 [PMID: 41695939 DOI: 10.4251/wjgo.v18.i2.115689]
|
|
20
|
-
"In this paper, the tumor indicators of patients with gastric cancer after operation were detected and analyzed. It was found that CEA and AFP were closely related to the recurrence of gastric cancer, which provided a good basis for judging the health level of patients with gastric cancer after operation. But it also needs the support of large-scale clinical data. At the same time, patients with gastric cancer need more tumor indicators to explore a better combination for judging the prognosis of patients with gastric cancer."
-
Duan XX, Yu X, Zhou L. Timeliness of postoperative serum carcinoembryonic antigen monitoring for predicting recurrence after gastric cancer surgery. World J Gastrointest Surg 2026; 18(1): 114309 [PMID: 41695866 DOI: 10.4240/wjgs.v18.i1.114309]
|
|
21
|
-
"Dear Editor,
I am writing in response to your invitation to comment on the prospective study by Güneş et al., entitled “Diagnostic value of interleukin-8 in colon cancer,” published in your esteemed journal. The authors provide valuable data reinforcing the role of interleukin-8 (IL-8) as an independent diagnostic biomarker in colon adenocarcinoma. Their work rightly concludes that IL-8 holds promise, particularly as part of a multi-marker panel.
I would like to extend this discussion by contextualizing IL-8 within the current, rapidly evolving biomarker landscape of colorectal cancer (CRC), as recently elaborated in an editorial on this topic. The future of CRC management lies in a dynamic, multi-layered biomarker strategy that integrates three key pillars: 1) Mismatch repair (MMR) status to dictate therapeutic class (chemotherapy vs. immunotherapy); 2) Perioperative carcinoembryonic antigen (CEA) for immediate risk stratification, especially within microsatellite stable (MSS) disease; and 3) Postoperative circulating tumor DNA (ctDNA) as a dynamic tool to guide treatment intensity and de-escalation, as definitively demonstrated by the recent AGITG DYNAMIC-III trial.
In this framework, the findings on IL-8 by Güneş et al. present a compelling opportunity. While its standalone diagnostic accuracy (AUC=0.68) is moderate, its independent predictive value suggests a distinct biological role, likely rooted in its pro-inflammatory and angiogenic functions. This positions IL-8 not as a replacement for the aforementioned pillars, but as a potential complementary element, particularly within the MSS cohort.
Specifically, IL-8 could enhance the second pillar (risk stratification) by providing additional biological granularity. For instance, in MSS patients with normal or borderline CEA levels, an elevated IL-8 might signal a more aggressive tumor biology driven by inflammation, potentially identifying a subset that would benefit from closer surveillance or adjuvant therapy. Furthermore, given its link to angiogenesis and immune modulation, IL-8 merits investigation as a predictive biomarker for responses to anti-angiogenic therapies (e.g., bevacizumab) and possibly immunotherapy, even in MSS/pMMR tumors.
Therefore, I propose that the next logical step for research, as inspired by both this study and the broader editorial perspective, is to evaluate IL-8 within integrated multi-marker panels. Combining IL-8 with CEA, ctDNA, and potentially other inflammatory markers (e.g., CRP) in algorithm-driven models could significantly improve diagnostic sensitivity, prognostic stratification, and predictive accuracy. This approach aligns perfectly with the paradigm of dynamic precision oncology, where multiple data streams are synthesized to guide personalized therapeutic navigation.
I congratulate the authors on their contribution and thank you for the opportunity to share these perspectives, hoping they may stimulate further research into the integrative potential of IL-8 within the modern CRC biomarker ecosystem.
Sincerely,
Pr Nabil Ismaili
Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Hrealth (FM6SS), Casablanca, Morocco, nismaili@um6ss.ma, 0000-0001-5786-5134"
-
Güneş G, Fırat Oğuz E, Kayılıoğlu I, Dinç T. Diagnostic value of interleukin-8 in colon cancer: Prospective, case-control study. World J Gastrointest Surg 2026; 18(1): 115444 [PMID: 41695859 DOI: 10.4240/wjgs.v18.i1.115444]
|
|
22
|
-
"Systemic antifungal therapy is the backbone of treatment for invasive fungal infections, but it carries an under-recognized burden of endocrine and physiological toxicity. The review by Thakkar et al. (2026) provides an important framework for understanding how these agents affect human cytochrome P450 enzymes and renal function, leading to adrenal insufficiency, mineralocorticoid excess, and electrolyte abnormalities. This review deserves recognition, and adding a global perspective to it could provide new recommendations. If possible, I would like to submit a letter addressing this perspective."
-
Thakkar S, Kantroo V, Nagendra L, Dutta D, Kamrul-Hasan ABM, Kalra S, Bhattacharya S. Endocrine consequences of antifungal therapy: A missed entity. World J Clin Cases 2026; 14(2): 117140 [PMID: 41608146 DOI: 10.12998/wjcc.v14.i2.117140]
|
|
23
|
-
"I read with interest the study comparing the ASGE lexicon and the AGREE classification for adverse events in gastrointestinal endoscopy. The authors are to be commended for their rigorous analysis of a large institutional registry and for highlighting the conceptual differences between two widely used adverse event frameworks.
The high concordance observed between ASGE and AGREE confirms that both systems are robust for capturing clinically significant complications. However, the discordance noted for transient cardiorespiratory and sedation-related events raises an important interpretive issue. The ASGE lexicon intentionally captures such occurrences as “incidents,” supporting quality improvement and preventive strategies, whereas AGREE excludes many of these events by design, prioritising clinical consequence and post-procedural intervention. While this approach improves specificity, it may inadvertently narrow the safety signal.
From a patient-centred perspective, events such as inadequate sedation, procedural discomfort, or transient hypoxia—although self-limiting—can significantly influence patient-reported experience, satisfaction, and trust in endoscopic services. These experiential harms may not require escalation of care yet remain meaningful to patients and may affect willingness for repeat procedures. Their exclusion from adverse event datasets risks underestimating quality concerns that are increasingly relevant in value-based care.
The study also underscores that adverse event classification represents only one dimension of endoscopy quality. Domains such as procedural appropriateness, missed or delayed diagnoses, bowel preparation adequacy, photodocumentation quality, scheduling delays, and patient-initiated procedure termination are not captured by adverse event frameworks but are integral to comprehensive quality assessment.
In summary, while standardised adverse event classification remains essential for benchmarking and safety governance, it should be complemented by patient-reported experience measures and broader quality indicators. A multidimensional framework integrating safety, experience, and appropriateness may better align endoscopy quality metrics with contemporary patient-centred practice."
-
Corsi O, Martinez R, Aguirre J, Friedrich I, Galeno V, Jimenez V, Briones P, Díaz LA, Espino A, Vargas JI. Application of a novel adverse event classification scale in a Latin American gastrointestinal endoscopy unit. World J Gastrointest Endosc 2026; 18(1): 111384 [PMID: 41607391 DOI: 10.4253/wjge.v18.i1.111384]
|
|
24
|
-
"This minireview provides a timely and balanced synthesis of the evolving role of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) in the management of pancreatic neuroendocrine tumors (pNETs). The authors appropriately frame EUS-RFA as a promising yet still selective therapeutic option, and the “lights and shadows” construct is effective in highlighting both its clinical potential and its current limitations
A major strength of the article lies in its comprehensive collation of published clinical experience across functioning and non-functioning pNETs. The tabulated summaries are particularly valuable for readers seeking an overview of technical success, clinical response, and adverse event profiles. Importantly, the authors avoid overstating efficacy and consistently acknowledge the predominance of retrospective series, limited follow-up durations, and heterogeneity in response definitions—an intellectua rigour that strengthens the manuscript.
From a conceptual standpoint, the review highlights a key paradigm shift: EUS-RFA is no longer merely a salvage or palliative modality, but a potential intermediate option within the “grey zone” of small, low-grade pNETs, especially in patients unfit for surgery or those prioritizing minimally invasive approaches. This raises an important clinical question not fully resolved in current guidelines—whether EUS-RFA should eventually be positioned as a disease-modifying therapy rather than an alternative to surveillance.
The discussion on radiological response assessment underscores a critical unmet need in the field. The lack of standardized imaging endpoints, timing of follow-up, and correlation with long-term oncologic outcomes limits meaningful comparison across studies. Future consensus on response metrics—possibly integrating contrast-enhanced harmonic EUS, cross-sectional imaging, and biochemical markers—would significantly enhance interpretability and clinical adoption.
Finally, the article appropriately calls attention to procedural standardization and risk mitigation, particularly regarding pancreatitis prevention and proximity to the main pancreatic duct. These considerations will be central if EUS-RFA is to move beyond expert centers into broader clinical practice.
Overall, this review serves as a valuable reference for gastroenterologists, endosonographers, and multidisciplinary teams managing pNETs. It also clearly delineates the research priorities required before EUS-RFA can be fully integrated into evidence-based treatment algorithms."
-
Tringali A, Caiazzo A. Role of endoscopic ultrasound in the treatment of pancreatic neuroendocrine tumors: Lights and shadows of endoscopic ultrasound-guided radiofrequency ablation. World J Gastrointest Endosc 2026; 18(1): 113617 [PMID: 41607387 DOI: 10.4253/wjge.v18.i1.113617]
|
|
25
|
-
"Commentary: Clinical Considerations in Immunocompromised Patients With Edwardsiella tarda–Associated Spontaneous Bacterial Peritonitis
The case report by Usuda et al., recently published in the World Journal of Clinical Cases, represents a notable contribution to clinical microbiology by documenting, to the best of current knowledge, the first reported case of spontaneous bacterial peritonitis (SBP) caused by Edwardsiella tarda in an immunocompromised patient undergoing dialysis [1].This report substantially expands the recognized infectious spectrum in patients with end-stage renal disease (ESRD) and underscores the need for heightened clinical awareness of atypical and opportunistic pathogens in this vulnerable population.
One particularly commendable aspect of this report is the authors’ detailed discussion of the virulence mechanisms of E. tarda. The organism’s capacity to survive and replicate within macrophages plays a pivotal role in its pathogenicity, especially in hosts with compromised cellular immunity [2,3]. In the present case, the coexistence of diabetic nephropathy and long-term dialysis likely created a permissive immunological milieu that facilitated this opportunistic infection. Such intracellular persistence provides a plausible explanation for the severe and insidious clinical course observed, even in the absence of classical epidemiological exposures such as raw seafood consumption or contact with freshwater environments.
Equally noteworthy is the authors’ adherence to principles of antimicrobial stewardship. The stepwise transition from empirical broad-spectrum therapy with cefmetazole to targeted, de-escalated treatment using cefalexin—guided by comprehensive antimicrobial susceptibility testing (Table 3)—offers a valuable therapeutic reference for clinicians managing similarly rare infections.
Nevertheless, building on the authors’ insightful acknowledgment of the limitations surrounding “ascites culture conversion,” I would like to propose a more structured and rigorous framework for defining treatment endpoints in such high-risk cases. While clinical and symptomatic improvement remains an essential marker of response, it may be insufficient when dealing with pathogens such as E. tarda, which possess the ability to persist intracellularly [4,5]. Accordingly, I suggest an integrated “imaging-to-microbiology” strategy prior to antibiotic discontinuation.
First, advanced imaging modalities—such as abdominal computed tomography or high-resolution ultrasonography—should be systematically incorporated to objectively assess the resolution of ascites. Complete radiological absorption of ascitic fluid would substantially strengthen the clinical justification for treatment cessation. Conversely, if residual ascites is detected, even in minimal or loculated forms, reliance on systemic inflammatory markers such as C-reactive protein or leukocyte counts alone may be misleading. Given the organism’s persistence potential [3], repeat diagnostic paracentesis should be strongly considered to confirm microbiological eradication. This dual confirmation—radiological and microbiological—would provide a more robust and evidence-based rationale for terminating antimicrobial therapy [6], thereby reducing the risk of relapse in immunocompromised patients.
In conclusion, while this case report fills an important gap in the current literature, it also highlights the need to refine discharge and treatment-completion criteria for rare causes of SBP. Adoption of an imaging-guided microbiological confirmation strategy may enhance the precision of clinical decision-making and ultimately improve long-term outcomes in patients with complex comorbidities.
参考文献
[1]Usuda D , Furukawa D, Imaizumi R et al. Spontaneous bacterial peritonitis due to Edwardsiella tarda in an immuno-compromised dialysis patient: A case report and review of literature. World J Clin Cases 2026,6; 14(1): 115102.
[2][2]Qin L, Li F, Wang X, Sun Y, Bi K, Gao Y. Proteomic analysis of macrophage in response to Edwardsiella tarda-infection. Microb Pathog, 2017; 111: 86-93 [RCA] [PMID: 28826764 DOI: 10.1016/j.micpath.2017.08.028]
[3]Zhang L, Ni C, Xu W, Dai T, Yang D, Wang Q, Zhang Y, Liu Q. Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda. J Bacteriol 2016; 198: 1534-1542 [RCA] [PMID: 26953340 DOI: 10.1128/JB.00978-15]
[4]An L, Chan JL, Nguyen M, Yang S, Deville JG. Case Report: Disseminated Edwardsiella tarda infection in an immunocompromised patient. Front Cell Infect Microbiol 2023; 13: 1292768 [RCA] [PMID: 38053529 DOI: 10.3389/fcimb.2023.1292768]
[5]Matsukawa H, Usuda D, Takami H, Nomura T, Sugita M. A Case of Edwardsiella tarda Infection With Iliopsoas Abscess Following Acute Pyelonephritis. Cureus 2024; 16: e58868 [RCA] [PMID: 38800258 DOI: 10.7759/cureus.58868]
[6]A Rimola , G García-Tsao, M Navasa, L J Piddock, R Planas, B Bernard, J M Inadomi. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club. J Hepatol, 2000; 32(1):142-53[RCA][PMID: 10673079 DOI: 10.1016/s0168-8278(00)80201-9]"
-
Usuda D, Furukawa D, Imaizumi R, Ono R, Kaneoka Y, Nakajima E, Kato M, Sugawara Y, Shimizu R, Inami T, Kawai K, Matsubara S, Tanaka R, Suzuki M, Shimozawa S, Hotchi Y, Osugi I, Katou R, Ito S, Mishima K, Kondo A, Mizuno K, Takami H, Komatsu T, Nomura T, Sugita M. Spontaneous bacterial peritonitis due to Edwardsiella tarda in an immuno-compromised dialysis patient: A case report and review of literature. World J Clin Cases 2026; 14(1): 115102 [PMID: 41551684 DOI: 10.12998/wjcc.v14.i1.115102]
|
|
26
|
-
" This paper presents a systematic retrospective analysis of the incidence and clinical significance of gallstones and gallbladder wall thickening in patients with liver cirrhosis, offering valuable clinical observations for practitioners. The study clearly indicates that the prevalence of gallbladder abnormalities—including gallstones and asymptomatic wall thickening—is significantly higher in patients with cirrhosis, especially in the decompensated stage, compared to the general population. This finding aligns with previous research and further supports the pivotal role of portal hypertension and hepatic dysfunction in the development of gallbladder pathology.
Notably, the authors emphasize that these imaging findings are often related to cirrhosis itself rather than being indicators of acute cholecystitis. This distinction is clinically important, as it can help prevent unnecessary interventions—such as misdiagnosis and surgery for presumed acute cholecystitis—particularly in asymptomatic individuals. Moreover, the study suggests that gallbladder abnormalities correlate more strongly with the decompensated state of cirrhosis than with its etiology, providing a fresh perspective on the mechanisms underlying gallbladder changes in these patients.
However, several limitations should be acknowledged. First, the retrospective design and single-center sample may limit the generalizability of the results. Second, the study lacks in-depth analysis of subgroups based on the etiology of cirrhosis, leaving it unclear whether findings differ notably in non-alcoholic liver disease patients. Finally, potential influencing factors such as gallbladder motility and medication use were not systematically evaluated, even though they may contribute to wall thickening and stone formation.
Overall, this paper offers practical clinical insights into the imaging assessment of the gallbladder in cirrhotic patients. Future prospective, multicenter studies incorporating more pathophysiological parameters—such as gallbladder motility and bile composition—could help further elucidate the complex relationship between cirrhosis and gallbladder disorders and contribute to optimized clinical decision-making."
-
Tsankof A, Protopapas AA, Kyritsi V, Gogou C, Kyziroglou M, Papathanasiou E, Chatzikosma C, Michalopoulos A, Savopoulos C, Protopapas AN. Gallstones and gallbladder wall thickening in patients with cirrhosis: Prevalence and clinical impact. World J Clin Cases 2026; 14(1): 114043 [PMID: 41551687 DOI: 10.12998/wjcc.v14.i1.114043]
|
|
27
|
-
"This meta-analysis systematically retrieved and synthesized evidence from 30 randomized controlled trials (RCTs) involving nearly 17,000 patients, providing the most comprehensive assessment to date on the efficacy of indomethacin for preventing post-ERCP pancreatitis (PEP). It offers valuable, up-to-date evidence-based references for clinical practice, and the authors' efforts are highly commendable. Nevertheless, while acknowledging its contributions, two critical methodological limitations must be highlighted, which may compromise the interpretation and generalizability of its findings.
The present commentary aims to identify two key methodological flaws in this meta-analysis that seriously undermine the statistical validity and clinical interpretability of its results. First, the authors inappropriately disaggregated seven multi-arm randomized controlled trials into multiple independent pairwise comparisons for inclusion in the analysis. This practice directly violates the core assumption of data independence in meta-analyses: different comparison groups derived from the same trial are correlated due to the shared control arm. Treating these as independent samples artificially inflates the total sample size, misestimates the weight of each study, and leads to an inappropriate narrowing of confidence intervals, thereby increasing the risk of Type I or Type II errors. Second, the definition of the "control group" in the study encompasses interventions with extremely high clinical heterogeneity, including placebo, normal saline, other active medications (e.g., diclofenac, somatostatin), and invasive procedures (e.g., pancreatic duct stenting). Pooling these controls with vastly different mechanisms of action and therapeutic efficacies renders the reported pooled relative risk (RR = 0.85) clinically meaningless. Furthermore, the high heterogeneity observed (I² = 79%) is most likely attributable to this flawed methodological design. In summary, the aforementioned issues cast doubt on the statistical credibility of the primary conclusion—that "indomethacin does not significantly reduce the incidence of PEP"—and also make it difficult to provide a reasonable clinical interpretation for practice.
Given that this review incorporates multiple interrelated interventions for comparison, network meta-analysis would represent a more appropriate methodological framework. It can rigorously integrate data from multi-arm trials and simultaneously evaluate the relative efficacy of all relevant preventive strategies."
-
Tian F, Huang ZC, Khizar H, Qiu K. Efficacy of indomethacin for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: A comprehensive meta-analysis of randomized controlled trials. World J Gastroenterol 2026; 32(1): 113232 [PMID: 41551526 DOI: 10.3748/wjg.v32.i1.113232]
|
|
28
|
-
"This meta-analysis systematically retrieved and synthesized evidence from 30 randomized controlled trials (RCTs) involving nearly 17,000 patients, providing the most comprehensive assessment to date on the efficacy of indomethacin for preventing post-ERCP pancreatitis (PEP). It offers valuable, up-to-date evidence-based references for clinical practice, and the authors' efforts are highly commendable. Nevertheless, while acknowledging its contributions, two critical methodological limitations must be highlighted, which may compromise the interpretation and generalizability of its findings.
The present commentary aims to identify two key methodological flaws in this meta-analysis that seriously undermine the statistical validity and clinical interpretability of its results. First, the authors inappropriately disaggregated seven multi-arm randomized controlled trials into multiple independent pairwise comparisons for inclusion in the analysis. This practice directly violates the core assumption of data independence in meta-analyses: different comparison groups derived from the same trial are correlated due to the shared control arm. Treating these as independent samples artificially inflates the total sample size, misestimates the weight of each study, and leads to an inappropriate narrowing of confidence intervals, thereby increasing the risk of Type I or Type II errors. Second, the definition of the "control group" in the study encompasses interventions with extremely high clinical heterogeneity, including placebo, normal saline, other active medications (e.g., diclofenac, somatostatin), and invasive procedures (e.g., pancreatic duct stenting). Pooling these controls with vastly different mechanisms of action and therapeutic efficacies renders the reported pooled relative risk (RR = 0.85) clinically meaningless. Furthermore, the high heterogeneity observed (I² = 79%) is most likely attributable to this flawed methodological design. In summary, the aforementioned issues cast doubt on the statistical credibility of the primary conclusion—that "indomethacin does not significantly reduce the incidence of PEP"—and also make it difficult to provide a reasonable clinical interpretation for practice.
Given that this review incorporates multiple interrelated interventions for comparison, network meta-analysis would represent a more appropriate methodological framework. It can rigorously integrate data from multi-arm trials and simultaneously evaluate the relative efficacy of all relevant preventive strategies."
-
Ding Y, Wang CY, Pan YT, Wang YJ, Zhao AG, Wen HZ. Scutellaria baicalensis Georgi as a potential therapeutic drug intervention in ulcerative colitis: Mechanisms of action and clinical trials. World J Gastroenterol 2026; 32(1): 114558 [PMID: 41551522 DOI: 10.3748/wjg.v32.i1.114558]
|
|
29
|
-
"I read the excellent paper by Rajak et al.
The review is organized and precisely addresses the role of microplastics in inducing metabolic-associated steatotic liver disease and its progression.
The review raises a growing emergency: the relationship between air pollution and human health.
This can be a stimulus for policymakers and international organizations to take concrete action.
However, it should be remembered that a proper lifestyle can mitigate the negative impact of microplastics on the liver and human health in general.
While waiting for long-term measures, this is information that can yield short-term results.
On this issue, it will be my concern to send a letter to the editor.
Sincerely, Gianni Testino"
-
Rajak S, Shahi A, Yadav A, Medhe P, Sinha RA. Microplastics in metabolic dysfunction-associated steatotic liver disease: An emerging threat to liver health. World J Hepatol 2025; 17(12): 111198 [PMID: 41479513 DOI: 10.4254/wjh.v17.i12.111198]
|
|
30
|
-
"1.The article does not cover the temporal and spatial dynamic changes of inflammatory cytokines during the development of NSCLC, as well as how these changes affect the occurrence and development of drug resistance. For instance, are there any differences in the expression levels of inflammatory cytokines in the early stage, progression stage, and resistance stage of the tumor? Are their distributions different in various parts of the tumor (such as the primary lesion and metastatic lesion)?
It is suggested to utilize techniques such as in situ hybridization and immunohistochemistry, combined with single-cell sequencing and spatial transcriptomics, to study the temporal and spatial dynamic changes of inflammatory cytokines in different development stages and different locations of NSCLC. By analyzing longitudinal samples of patients (such as before treatment, during treatment, and after resistance), the dynamic change patterns of inflammatory cytokines during the process of drug resistance can be revealed.
2. Although IL-6R blockade shows the effect of reversing drug resistance, single-target therapy may have limitations in efficacy or the risk of drug resistance escape. It is suggested to explore IL-6/IL-8 dual-target inhibition in preclinical models, or to combine it with downstream pathway inhibitors (such as JAK/STAT, PI3K/AKT, NF-κB inhibitors) or immune checkpoint inhibitors to evaluate its synergistic anti-tumor effect and its remodeling effect on the tumor microenvironment, in order to provide theoretical basis for future clinical trials of combination therapy."
-
Calibasi-Kocal G. Inflammatory cytokine-associated cisplatin resistance in non-small cell lung cancer and re-sensitization through interleukin-6 receptor blockade. World J Clin Oncol 2025; 16(12): 114275 [PMID: 41480163 DOI: 10.5306/wjco.v16.i12.114275]
|
|
31
|
-
"Author:
Priya Hazrah
Professor, Department of Surgery, Lady Hardinge Medical College, New Delhi.
Email: priyahazrah@gmail.com, ORCID ID 0009-0008-1915-3978
Deborshi Sharma
Director Professor Department of Surgey ABVIMS, New Delhi.
Email: drdeborshi@gmail.com, ORCID ID 0000-0001-8251-8484
Sonali Mittal
Assistant professor, Lady Hardinge Medical College, New Delhi
Email: sonali.prachi@gmail.com, ORCID 0000-0002-6289-7656
Corresponding Author:
Priya Hazrah
Professor Department of Surgery, Lady Hardinge Medical College, New Delhi.
Email: priyahazrah@gmail.com
We read with tremendous interest your article entitled “Mastering the third space: Innovations in intramural endoscopic surgery for gastrointestinal disorders.” It was a very apt and concise review of commonly performed third space endoscopy (TSE) procedures, namely the C, Z, E, and G POEM (per oral endoscopic myotomy). Here, we would like to highlight other evolving procedures related to third space endoscopy and also the emerging concept of “fourth space endoscopy.”
POETRE, peroral esophageal tunnelling for restoration of the esophagus, based on the principle of TSE, is an innovative technique of submucosal tunnelling proposed to be a useful therapeutic option in long-segment complete esophageal luminal obstruction in a few case series [1, 2]. PREM/PAEM (per rectal/per anal myotomy) is another novel use of TSE with limited exploration in patients with Hirschsprung’s disease [3]. STER (submucosal tunnelling endoscopic resection) and POET (peroral endoscopic excision of tumor) have been reported to be safe procedures for resection of extramucosal tumors in the upper gastrointestinal tract with acceptable complication rates vouched for in recent meta-analyses [4-7]. Further, TSE can be used to gain peritoneal access, as seen in POEM+F (POEM with fundoplication).
Building upon the model of third space endoscopy is a forthcoming concept of fourth space endoscopy based on the technique of sub-serosal dissection for excision of extramucosal tumors in the upper gastrointestinal tract, like gastrointestinal stromal tumors, leiomyoma, hamartoma, etc., published in a limited case series [8]. The feasibility of using the principle of the fourth-space endoscopy procedure for vagotomy is investigational and has been reported currently in an anecdotal non-human study [9]. The fourth space is also utilized at times in POEM to enable a full-thickness myotomy [10].
References
1. Wagh MS, Draganov PV. Per-oral endoscopic tunneling for restoration of the esophagus: a novel endoscopic submucosal dissection technique for therapy of complete esophageal obstruction. Gastrointest Endosc. 2017 Apr;85(4):722-727. doi: 10.1016/j.gie.2016.08.035. Epub 2016 Sep 7. PMID: 27612924.
2. Félix C, Barreiro P, Rodrigues Azevedo J, Maia L, Küttner-Magalhães R, Pedroto I, Chagas C. Per-oral endoscopic tunneling for restoration of the esophagus (POETRE) in the management of a complete esophageal obstruction. Endosc Int Open. 2021 Jul;9(7):E1084-E1085. doi: 10.1055/a-1463-3059. Epub 2021 Jun 17. PMID: 34222634; PMCID: PMC8211479.
3. Bapaye A, Dashatwar P, Biradar V, Biradar S, Pujari R. Initial experience with per-rectal endoscopic myotomy for Hirschsprung's disease: medium and long term outcomes of the first case series of a novel third-space endoscopy procedure. Endoscopy. 2021 Dec;53(12):1256-1260. doi: 10.1055/a-1332-6902. Epub 2021 Mar 2. PMID: 33291158.
4. Onimaru M, Inoue H, Bechara R, Tanabe M, Abad MRA, Ueno A, Shimamura Y, Sumi K, Ikeda H, Ito H. Clinical outcomes of per-oral endoscopic tumor resection for submucosal tumors in the esophagus and gastric cardia. Dig Endosc. 2020 Mar;32(3):328-336. doi: 10.1111/den.13471. Epub 2019 Jul 22. PMID: 31234231.
5. Peng W, Tan S, Huang S, Ren Y, Li H, Peng Y, Fu X, Tang X. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors with more than 1-year' follow-up: a systematic review and meta-analysis. Scand J Gastroenterol. 2019 Apr;54(4):397-406. doi: 10.1080/00365521.2019.1591500. Epub 2019 Mar 29. PMID: 30925071.
6. Song S, Wang X, Zhang S, Li Y, Zhang X, Chu X. Efficacy and complications of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors and exploration for influencing factors. Z Gastroenterol. 2018 Apr;56(4):365-373. English. doi: 10.1055/s-0043-123765. Epub 2018 Jan 18. PMID: 29346827.
7. Cao B, Lu J, Tan Y, Liu D. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan;113(1):52-59. doi: 10.17235/reed.2020.6989/2020. PMID: 33222480.
8. Liu F, Zhang S, Ren W, Yang T, Lv Y, Ling T, Zou X, Wang L. The fourth space surgery: endoscopic subserosal dissection for upper gastrointestinal subepithelial tumors originating from the muscularis propria layer. Surg Endosc. 2018 May;32(5):2575-2582. doi: 10.1007/s00464-017-5985-z. Epub 2017 Dec 20. PMID: 29264757.
9. Kadkhodayan K, Irani S. Endoscopic truncal vagotomy. Exploring the fourth space. A technical feasibility study in a porcine model. VideoGIE. 2025 Mar 4;10(7):340-344. doi: 10.1016/j.vgie.2025.02.012. PMID: 40642399; PMCID: PMC12237756.
10. Jiang T, Yang Y, Luo W. Application of the fourth space in peroral endoscopic myotomy (POEM) surgery for achalasia. Rev Esp Enferm Dig. 2025 Jun 27. doi: 10.17235/reed.2025.11331/2025. Epub ahead of print. PMID: 40575899.
"
-
Restrepo-Rodas G, Rodriguez J. Mastering the third space: Innovations in intramural endoscopic surgery for gastrointestinal disorders. World J Gastrointest Endosc 2025; 17(12): 111206 [PMID: 41479932 DOI: 10.4253/wjge.v17.i12.111206]
|
|
32
|
-
"This article addresses an important and timely topic: differentiation-based strategies for colorectal cancer (CRC) therapy using natural products. The authors present a comprehensive in vitro study suggesting that Ferula assafoetida (FA) induces differentiation and apoptosis in Caco-2 colon cancer cells, potentially via activation of the JNK/MAPK pathway. As a reader, the work is interesting, methodologically broad, and conceptually aligned with current interests in natural compound–based cancer therapeutics, although certain conceptual and interpretative gaps limit its translational impact.
As a reader, I would regard this article as a useful exploratory study that justifies further mechanistic, protein-level, and in vivo investigations, rather than a conclusive demonstration of FA as a differentiation therapy for CRC."
-
Abdelsalam HM, Abdelghany AM, Ahmed WA, Diab AA, Abdellateif MS. Ferula assafoetida induced colon cancer cells differentiation through JNK/MAPK signalling pathway activation. World J Exp Med 2025; 15(4): 110757 [PMID: 41497690 DOI: 10.5493/wjem.v15.i4.110757]
|
|
33
|
-
"his retrospective study by Cooper et al. provides a valuable comparison of endoscopic band ligation (EBL) and endoscopic thermal therapy (ETT) as initial treatments for nodular gastric antral vascular ectasia (GAVE), a rare and challenging subtype. The analysis of 37 patients demonstrates that EBL outperforms ETT, with significantly higher clinical remission rates (90% vs. 69%, P=0.041), shorter treatment intervals (172 vs. 928 days, P=0.013), and fewer required endoscopic sessions (1.95 vs. 5.56, P=0.009), supported by improved hemoglobin levels and reduced transfusions. The findings robustly advocate for EBL as a first-line approach due to its efficiency and lower treatment burden. However, limitations include the small sample size, single-center design, and retrospective nature, which may affect generalizability. Despite this, the study fills a critical gap in nodular GAVE management and underscores the need for prospective multicenter trials to validate EBL's superiority and optimize clinical protocols."
-
Cooper JA, Statham E, Holyfield A, Shoreibah MG, Peter S. Initial treatment approaches for nodular gastric antral vascular ectasia: A comparison of endoscopic band ligation and thermal therapies. World J Gastrointest Endosc 2025; 17(12): 111872 [PMID: 41479935 DOI: 10.4253/wjge.v17.i12.111872]
|
|
34
|
-
"The minireview by El Dada et al. offers a timely synthesis of endoscopic ultrasound (EUS)-guided coil embolization for gastric varices (GVs), highlighting its potential as a safer, precise alternative to traditional therapies like cyanoacrylate injection. Strengths include systematic comparisons with meta-analytic data (e.g., 96.7% obliteration rate for EUS-coil/cyanoacrylate vs. 70.6% for cyanoacrylate alone), practical technical details (coil selection, Doppler confirmation), real-world case illustrations, and cost-effectiveness analysis (1,831vs.11,000 hospitalization). However, limitations persist: reliance on retrospective/single-center data, absence of randomized controlled trials (RCTs) against TIPS/BRTO, and lack of long-term (>5 years) rebleeding/complication data (e.g., coil migration). The authors appropriately call for multicenter RCTs to standardize protocols, explore material combinations, and integrate predictive biomarkers. Despite gaps, the review compellingly argues for EUS-coil’s inclusion in GV guidelines, serving as a valuable reference for advancing therapeutic endoscopy with balanced analysis of efficacy, safety, and accessibility."
-
El Dada A, El Khoury M, Stephan P, Nehme F. Endoscopic ultrasound-guided coil embolization for gastric varices: A promising alternative to traditional therapies. World J Gastrointest Endosc 2025; 17(12): 110168 [PMID: 41479939 DOI: 10.4253/wjge.v17.i12.110168]
|
|
35
|
-
"Name of Journal: World Journal of Gastroenterology
Manuscript Type: LETTER TO THE EDITOR
Dialister-Associated Succinate Dysregulation in Crohn’s Disease: Clinical and Therapeutic Implications
1Fotios S. Fousekis, 1Konstantinos H. Katsanos, 2Konstantinos Vlachos, 2Georgios D. Lianos
1Department of Gastroenterology, University Hospital of Ioannina, University of Ioannina Ioannina, Greece
2Department of Surgery, University Hospital of Ioannina, University of Ioannina, Greece
Corresponding author: Fotios S. Fousekis, MD, PhD, Department of Gastroenterology, University Hospital of Ioannina, University of Ioannina Ioannina, Greece, email: fotisfous@gmail.com
Abstract
Growing evidence suggests that altered gut microbiota–derived succinate metabolism plays an important role in Crohn’s disease activity and postoperative recurrence. Particular emphasis is placed on Dialister, a gut bacterial genus that consumes succinate inefficiently, potentially leading to its accumulation and increased intestinal inflammation. Elevated succinate may impair immune regulation and enhance inflammatory signaling through SUCNR1 activation and hypoxia-inducible factor-1α stabilization. Recent findings identifying specific Dialister strains associated with postoperative recurrence provide new insight into disease monitoring and risk stratification. Although the study offers an integrative view linking microbial composition, metabolism, and inflammation, further validation using direct metabolomic and shotgun metagenomic approaches is needed. Overall, succinate appears to be a promising biomarker and therapeutic target, supporting future microbiota- and metabolism-based strategies for the management of inflammatory bowel disease.
Key words: Crohn’s disease; Inflammatory bowel disease; Gut microbiota; Succinate; Dialister; Postoperative recurrence
Core tip
Accumulation of the microbial metabolite succinate is increasingly recognized as a key driver of inflammation in Crohn’s disease. Recent evidence links Dialister enrichment to impaired succinate clearance, disease activity, and postoperative recurrence, highlighting succinate as a promising biomarker and therapeutic target in inflammatory bowel disease.
To the editor
Dialister, an anaerobic Gram-negative genus of the human gut microbiome, has gained clinical interest due to its role in succinate metabolism. While capable of utilizing succinate as a substrate for propionate production, Dialister exhibits relatively slow consumption rates compared with efficient succinate consumers such as Phascolarctobacterium. This inefficiency may result in elevated luminal succinate levels, particularly in the context of inflammatory bowel disease (IBD) (1). Succinate accumulation may disrupt regulatory T cell (Treg) function by promoting FOXP3 degradation, thereby reducing immune tolerance and further amplifying inflammation (2). Furthermore, elevated succinate stabilizes hypoxia-inducible factor-1α (HIF-1α) by inhibiting prolyl hydroxylase activity, which prevents HIF-1α degradation and leads to enhanced inflammatory gene expression and perpetuation of tissue injury, particularly in IBD (3).
We read with great interest the recently published article by Boronat-Toscano and colleagues on Dialister-driven succinate accumulation and its association with disease activity and postoperative recurrence in Crohn’s disease (4). This study offers valuable insights into a rapidly growing field of research that links gut microbiota, host metabolism, and inflammation. It positions succinate not just as a metabolic by-product but also as a functional biomarker and potential therapeutic target. One of the major strengths of this work is its integrative, multi-level approach, which combines clinical and biochemical measures of disease activity, such as the Harvey–Bradshaw Index, C-reactive protein, and fecal calprotectin, with gut microbiome profiling using 16S rRNA sequencing and host molecular markers related to succinate signaling, specifically the expression of the succinate receptor SUCNR1 (4). Notably, this study highlights specific Dialister operational taxonomic units (OTUs) in the intestinal mucosa that correlate with the risk and severity of postoperative recurrence. This goes beyond existing knowledge by identifying strain-level microbial signatures with potential predictive value, suggesting that variability within Dialister is vital for patient stratification and disease progression after surgery. The authors also propose a mechanism for succinate accumulation in Crohn's disease, involving the downregulation of NADH dehydrogenase and the upregulation of fumarate reductase and succinate transporters. This metabolic shift enhances succinate production and export by the gut microbiota (4).
Despite these strengths, we would like to highlight several issues that merit further discussion. The functional analysis of the gut microbiome is based on predictive approaches (PICRUSt2) rather than on direct measurements of metabolic fluxes or shotgun metagenomic sequencing. Validation of these predictions is essential for robust conclusions. Targeted metabolomic analyses, using mass spectrometry or nuclear magnetic resonance, allow for direct quantification of metabolites as succinate and can confirm the functional activity of predicted pathways (5). In addition shotgun metagenomic sequencing may provide a more comprehensive and direct assessment of the genetic potential for metabolic pathways, including those involved in succinate production and consumption, by sequencing all microbial DNA present in a sample (6).
These findings also open important avenues for future research and therapeutic development in inflammatory bowel disease. Given the central role of succinate in promoting intestinal inflammation through SUCNR1 activation and HIF-1α stabilization, strategies aimed at reducing succinate accumulation or blocking its downstream signaling pathways warrant further investigation. Microbiota-targeted interventions, including dietary fiber enrichment, prebiotics, and probiotics designed to enhance the abundance of efficient succinate-consuming bacteria such as Phascolarctobacterium, represent a particularly promising approach, as preclinical studies have demonstrated their ability to lower succinate levels, attenuate inflammatory signaling, and restore epithelial barrier integrity (7). Avoiding supplementation of the diet with refined inulin may be considered, as evidence from mouse models suggests that it can induce abnormal succinate accumulation in the intestinal lumen, thereby contributing to colonic inflammation (8). In parallel, pharmacological inhibition of SUCNR1 using small-molecule antagonists, as well as interventions targeting HIF-1α stabilization, may offer complementary strategies to suppress succinate-driven inflammation (9, 10). Huo et al. demonstrated that the SUCNR1 inhibitor NF-56-EJ40 may suppress glycolysis in intestinal epithelial cells and attenuates Th17-mediated inflammation in a dextran sodium sulfate–induced mouse model of ulcerative colitis. Treatment reduced pro-inflammatory cytokine production, improved epithelial barrier integrity, and alleviated colonic injury, supporting SUCNR1 antagonism as a therapeutic strategy targeting both metabolic and immune pathways (7). Consistently, genetic deletion of SUCNR1 in mice protected against both acute colitis and intestinal fibrosis, while in human fibroblasts derived from Crohn’s disease patients, succinate increased SUCNR1 expression and promoted inflammatory and fibrotic markers that were effectively reversed by SUCNR1 blockade (11). While these approaches are supported by growing mechanistic and translational evidence, well-designed clinical trials will be essential to determine their efficacy and safety in patients with IBD.
Conclusion
The study conducted by Boronat-Toscano et al. enhances the understanding of how microbiota-driven metabolic dysregulation relates to Crohn’s disease by identifing succinate and Dialister-associated microbial signatures associated as important factors that influence disease activity and the likelihood of postoperative recurrence. These findings support the use of succinate-related biomarkers in future risk assessment and postoperative monitoring strategies. Additionally, they provide a strong biological basis for therapeutic interventions that target succinate metabolism or SUCNR1-mediated signaling. Overall, this study marks a crucial step towards developing metabolically informed, microbiome-based precision medicine for IBD.
Author contributions: Fousekis FS wrote the original draft; Lianos GD contributed to conceptualization, writing, reviewing and editing; Katsanos KH and Vlachos K participated in drafting the manuscript; and all authors have read and approved the final version of the
manuscript.
References
1. Anthamatten L, von Bieberstein PR, Menzi C, Zund JN, Lacroix C, de Wouters T, Leventhal GE. Stratification of human gut microbiomes by succinotype is associated with inflammatory bowel disease status. Microbiome. 2024;12(1):186. PMID: 39350289 PMCID: PMC11441152 DOI: 10.1186/s40168-024-01897-8
2. Wang H, Hu D, Cheng Y, Gao Q, Liu K, Mani NL, Tang AY, Iyer R, Gao B, Zhou Q, Yu Q, Weinberg SE, Zhang X, Cong Y, Dulai PS, Zhang Y, Liu Z, Fang D. Succinate drives gut inflammation by promoting FOXP3 degradation through a molecular switch. Nat Immunol. 2025;26(6):866-80. PMID: 40457062 PMCID: PMC12399925 DOI: 10.1038/s41590-025-02166-y
3. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ, O'Neill LAJ. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature. 2013;496(7444):238-42. PMID: 23535595 PMCID: PMC4031686 DOI: 10.1038/nature11986
4. Boronat-Toscano A, Queipo-Ortuño MI, Monfort-Ferré D, Suau R, Vañó-Segarra I, Valldosera G, Cepero C, Astiarraga B, Clua-Ferré L, Plaza-Andrade I, Aranega-Martín L, Cabrinety L, Abadia de Barbarà C, Castellano-Castillo D, Moliné A, Caro A, Domènech E, Sánchez-Herrero JF, Benaiges-Fernandez R, Fernández-Veledo S, Vendrell J, Ginés I, Sumoy L, Manyé J, Menacho M, Serena C. Dialister-driven succinate accumulation is associated with disease activity and postoperative recurrence in Crohn's disease. World J Gastroenterol. 2025;31(45):112618. PMID: 41378335 PMCID: PMC12687013 DOI: 10.3748/wjg.v31.i45.112618
5. Han S, Van Treuren W, Fischer CR, Merrill BD, DeFelice BC, Sanchez JM, Higginbottom SK, Guthrie L, Fall LA, Dodd D, Fischbach MA, Sonnenburg JL. A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature. 2021;595(7867):415-20. PMID: 34262212 PMCID: PMC8939302 DOI: 10.1038/s41586-021-03707-9
6. Mitra S, Forster-Fromme K, Damms-Machado A, Scheurenbrand T, Biskup S, Huson DH, Bischoff SC. Analysis of the intestinal microbiota using SOLiD 16S rRNA gene sequencing and SOLiD shotgun sequencing. BMC Genomics. 2013;14 Suppl 5(Suppl 5):S16. PMID: 24564472 PMCID: PMC3852202 DOI: 10.1186/1471-2164-14-S5-S16
7. Huo L, Chen Q, Jia S, Zhang Y, Wang L, Li X, Li Z, Sun B, Shan J, Lin J, Yang L, Sui H. Gut microbiome promotes succinate-induced ulcerative colitis by enhancing glycolysis through SUCNR1/NF-kappaB signaling pathway. Am J Physiol Cell Physiol. 2025;329(2):C440-C54. PMID: 40549551 DOI: 10.1152/ajpcell.00411.2025
8. Tian S, Paudel D, Hao F, Neupane R, Castro R, Patterson AD, Tiwari AK, Prabhu KS, Singh V. Refined fiber inulin promotes inflammation-associated colon tumorigenesis by modulating microbial succinate production. Cancer Rep (Hoboken). 2023;6(11):e1863. PMID: 37489647 PMCID: PMC10644334 DOI: 10.1002/cnr2.1863
9. Haffke M, Fehlmann D, Rummel G, Boivineau J, Duckely M, Gommermann N, Cotesta S, Sirockin F, Freuler F, Littlewood-Evans A, Kaupmann K, Jaakola VP. Structural basis of species-selective antagonist binding to the succinate receptor. Nature. 2019;574(7779):581-5. PMID: 31645725 DOI: 10.1038/s41586-019-1663-8
10. Kim YI, Yi EJ, Kim YD, Lee AR, Chung J, Ha HC, Cho JM, Kim SR, Ko HJ, Cheon JH, Hong YR, Chang SY. Local Stabilization of Hypoxia-Inducible Factor-1alpha Controls Intestinal Inflammation via Enhanced Gut Barrier Function and Immune Regulation. Front Immunol. 2020;11:609689. PMID: 33519819 PMCID: PMC7840603 DOI: 10.3389/fimmu.2020.609689
11. Macias-Ceja DC, Ortiz-Masia D, Salvador P, Gisbert-Ferrandiz L, Hernandez C, Hausmann M, Rogler G, Esplugues JV, Hinojosa J, Alós R; Navarro F, Cosin-Roger J, Calatayud S, Barrachina MD. Succinate receptor mediates intestinal inflammation and fibrosis. Mucosal Immunol. 2019;12(1):178-87. PMID: 30279517 DOI: 10.1038/s41385-018-0087-3
"
-
Boronat-Toscano A, Queipo-Ortuño MI, Monfort-Ferré D, Suau R, Vañó-Segarra I, Valldosera G, Cepero C, Astiarraga B, Clua-Ferré L, Plaza-Andrade I, Aranega-Martín L, Cabrinety L, Abadia de Barbarà C, Castellano-Castillo D, Moliné A, Caro A, Domènech E, Sánchez-Herrero JF, Benaiges-Fernandez R, Fernández-Veledo S, Vendrell J, Ginés I, Sumoy L, Manyé J, Menacho M, Serena C. Dialister-driven succinate accumulation is associated with disease activity and postoperative recurrence in Crohn’s disease. World J Gastroenterol 2025; 31(45): 112618 [PMID: 41378335 DOI: 10.3748/wjg.v31.i45.112618]
|
|
36
|
-
"This minireview systematically synthesizes the intricate interplay between depression and gastric cancer (GC), incorporating neuroendocrine, immunological, and psychosocial mechanisms. The authors effectively underscore the bidirectional causality supported by 52 referenced studies, in alignment with the biopsychosocial model. Nonetheless, there are opportunities to enhance methodological rigor and visual communication. Although Figure 1 delineates key components of the bidirectional relationship, its informational density is suboptimal. The figure lacks a hierarchical structuring of pathways (e.g., neuroendocrine versus immune mechanisms) and does not quantify effect sizes (e.g., hazard ratios from cited meta-analyses). It is recommended to incorporate a summary table for comparison."
-
Chen Z, Gong TJ, Zhao L. Bidirectional relationship between depression and the risk and prognosis of gastric cancer. World J Gastrointest Oncol 2025; 17(12): 113272 [PMID: 41480211 DOI: 10.4251/wjgo.v17.i12.113272]
|
|
37
|
-
"I want to congratulate the authors, Zhang et al, for conducting a study and identifying the predictors of refractory GERD. They have identified the disease duration and anxiety as significant risk factors and at least 90 minutes of moderate-intensity physical activity per week as a protective factor for refractory GERD. One of the important findings in this study is the association of significant Overlap DGBI symptoms (such as dyspepsia, constipation, and diarrhoea) in at least 50% of GERD patients. Since most patients had a duration of illness of more than 4 years, complications of GERD and their comparison between the groups were not noted in this study (a limitation). Although hydrogen impedance is used for diagnosis, the comparison of impedance parameters is not provided. H pylori infection is a protective factor for GERD/Barrett's, which is also a limitation. This study has provided a meaningful conclusion regarding the association between long-term symptoms and refractoriness.
"
-
Zhang N, Wang Y, Fang SS, Han M, Zheng QW, Zhu YY, Zhang MY, Li JJ, Cui LX, Tian JL, Deng YH, Zhu SL, Ni HM, Zhou L, Zuo GL, Huang TS, Liao Q, Li XQ, Shang YY, Wang YJ, Tian Y, Ge LY, Han HQ, Hu WM, Jiang Y, Li YJ, Mao X, Yang LH, Yao JM, Zheng X, Wang HW, Fang SQ. Clinical characteristics and risk factors of refractory gastroesophageal reflux disease: A multicenter cross-sectional study. World J Gastroenterol 2025; 31(45): 113060 [PMID: 41378325 DOI: 10.3748/wjg.v31.i45.113060]
|
|
38
|
-
"The present Letter provides a concise academic response to the article identified by Reader’s code 05354032. The comments focus on several important aspects of the study, including its methodological design, data interpretation, and clinical applicability. The aim is to offer constructive perspectives that may help clarify key issues and support future improvements in related research."
-
Ardila CM, Ángel-Estrada S, González-Arroyave D. Robot-assisted vs conventional lumbar interbody fusion: A systematic review and meta-analysis of perioperative, radiographic, and clinical outcomes. World J Orthop 2025; 16(11): 110276 [PMID: 41355831 DOI: 10.5312/wjo.v16.i11.110276]
|
|
39
|
-
"The study title "Comparison of the efficacy of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma: A retrospective study" by Lei et al. aims to compare the long-term survival and perioperative outcomes of Laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC). This retrospective study included 254 patients with small HCC who were collected from Hospital of Chongqing Medical University between December 2022 and March 2025. The results showed that LH was associated with longer operative time, greater blood loss, prolonged recovery, higher costs, and increased complication rates. Consequently, LH, though associated with increased perioperative morbidity, provides superior long-term survival outcomes compared with RFA in patients with small HCC. This study had many limitations such as potential for selection bias and confounding factors that were not controlled for is inherent. The decision to undergo either LH or RFA was made based on clinical judgment and patient-specific factors, which could introduce bias. The sample size was still be insufficient to detect subtle differences in outcomes between the two modalities, especially for subgroups with specific tumor characteristics or comorbidities. Moreover, LH and RFA techniques have evolved over time, and variations in operator experience and institutional protocols could influence outcomes."
-
Lei ZL, Tan ZL, Luo YH, Yang M, Wang JL, Qin Z, Liu YY. Comparison of the efficacy of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma: A retrospective study. World J Gastroenterol 2025; 31(45): 111540 [PMID: 41378322 DOI: 10.3748/wjg.v31.i45.111540]
|
|
40
|
-
"We are delighted to read the high-quality review by Zheng et al[1], published in the World Journal of Gastroenterology, which offers insightful perspectives on the neuroimmune mechanisms contributing to the pathogenesis of inflammatory bowel disease (IBD). The intricate interplay between the autonomic nervous system (ANS) and the immune response, particularly involving vagus nerve stimulation (VNS) and its effects on macrophages, provides a promising avenue for future therapeutic interventions in IBD.
The review underscores the emerging concept of neuroimmune interactions, particularly the cholinergic anti-inflammatory pathway (CAIP), which regulates inflammation through the vagus nerve and its interaction with intestinal macrophages. This is an exciting area of research, especially in the context of IBD, where inflammation is at the heart of the disease's pathology. Macrophages, as highlighted in the review, play a crucial role in maintaining intestinal homeostasis, but when overactivated, they contribute to the excessive production of proinflammatory cytokines, exacerbating the condition. This review draws attention to how the cholinergic system can modulate macrophage activity, reducing the inflammatory burden through the activation of the α7 nicotinic acetylcholine receptor (α7nAChR).
The role of VNS as an approach to activate the cholinergic pathway and regulate inflammation in IBD is a breakthrough concept. Studies showing the beneficial effects of VNS in reducing inflammation and enhancing immune tolerance are promising, offering a potential alternative to conventional treatments, especially in patients with refractory IBD. Furthermore, the use of VNS to modulate the autonomic nervous system offers a unique therapeutic strategy for restoring balance between sympathetic and parasympathetic tones in patients, whose autonomic dysfunction may contribute to disease exacerbation.
While the current data on VNS in IBD are promising, the review rightly calls for further research to better establish the clinical applicability of VNS, especially through non-invasive techniques such as transauricular and transcervical VNS. These methods, as highlighted, may offer a safer and more accessible alternative to invasive VNS, which has shown positive effects in treating other inflammatory conditions. The ongoing exploration of VNS in clinical trials, coupled with advancements in understanding the mechanisms of cholinergic signaling in immune cells, opens new avenues for therapeutic interventions in chronic inflammatory diseases.
However, as the review mentions, there are still challenges that need to be addressed. The precise mechanisms through which VNS modulates immune responses, particularly in macrophages, are still under investigation. Additionally, while VNS has shown potential in preclinical models, there is a need for larger, well-designed clinical studies to confirm the safety, efficacy, and long-term benefits of VNS in IBD patients. The heterogeneity of IBD, along with differences in patient responses to treatment, further complicates the development of standardized protocols for VNS treatment.
In conclusion, the review provides an excellent overview of the current state of research on neuroimmune interactions in IBD, with a special focus on the potential of VNS as a novel therapeutic strategy. The integration of neuroimmune regulation, particularly through the cholinergic pathway, into the treatment of IBD represents an innovative approach that could offer significant improvements in patient outcomes. As we move forward, I hope that the continued research in this field will provide more concrete evidence to support the use of VNS in clinical practice, potentially offering a transformative treatment for IBD patients who have not responded to traditional therapies.
LIMITATIONS OF THE REVIEW
While the review provides a comprehensive overview of the potential therapeutic role of vagus nerve stimulation (VNS) in inflammatory bowel disease (IBD), there are some limitations that should be addressed in future research. First, while the article highlights the promising effects of VNS, particularly through the cholinergic anti-inflammatory pathway (CAIP), there is a lack of in-depth discussion regarding the specific cellular mechanisms involved. The exact signaling pathways through which VNS modulates macrophage activity and alters immune responses remain unclear, and more detailed mechanistic studies are needed to provide a clearer understanding.
Additionally, the review does not fully address the challenges associated with the translation of VNS into clinical practice. For instance, the variability in patient response to VNS, the optimal stimulation parameters (e.g., frequency, duration, and intensity), and the potential side effects of VNS, particularly in IBD patients with coexisting conditions, are aspects that require more attention.
Lastly, the review focuses primarily on the autonomic nervous system's role in IBD, but it overlooks other possible neuroimmune interactions that could also influence disease progression. A broader exploration of how other neural pathways or neuropeptides contribute to IBD would provide a more comprehensive view of the neuroimmune mechanisms at play.
CONCLUSION
The review provides an insightful exploration of the neuroimmune mechanisms involved in inflammatory bowel disease (IBD), particularly focusing on the role of intestinal macrophages and the cholinergic anti-inflammatory pathway. Vagus nerve stimulation (VNS) represents a promising non-invasive therapeutic approach for modulating the immune system and controlling inflammation in IBD. However, further research is needed to fully understand the mechanisms behind VNS and to establish its efficacy in clinical settings for treating chronic inflammatory diseases such as IBD. With the development of non-invasive VNS technologies, future therapies may offer safer and more effective treatments for patients suffering from IBD."
-
Zheng L, Duan SL. Neuroimmune interactions in inflammatory bowel disease: Role of intestinal macrophages and the cholinergic pathway. World J Gastroenterol 2025; 31(44): 109440 [PMID: 41356522 DOI: 10.3748/wjg.v31.i44.109440]
|
|
41
|
-
"This editorial provides a comprehensive and insightful overview of self-expandable metal stents (SEMS) in acute colonic obstruction, standing out for its clinical relevance and systematic organization. The authors adeptly synthesize cutting-edge techniques (e.g., fluoroscopy-free stenting, two-person colonoscopy) and critical considerations like stent design selection, backed by high-quality recent evidence, which offers valuable guidance for clinical practice. The discussion of complications and mitigation strategies is pragmatic, while the exploration of future directions (e.g., zero-border stents, multidisciplinary collaboration) reflects a forward-thinking perspective.
The academic expression is precise and fluent, with consistent use of professional terminology and clear logical progression. A minor suggestion is to include brief comparative data on cost-effectiveness among different stenting techniques or stent types, which would further assist healthcare institutions in decision-making. Overall, this is a high-quality, clinically impactful piece that serves as an excellent reference for gastroenterologists and surgeons specializing in colorectal disorders."
-
Sun HY, Li ZC, Wang HL. Current mechanisms and techniques for placement of self-expandable metal stents in acute colonic obstruction. World J Gastrointest Surg 2025; 17(11): 110512 [PMID: 41357659 DOI: 10.4240/wjgs.v17.i11.110512]
|
|
42
|
-
"The editorial authored by Watanabe presents a timely and clinically pertinent overview of lisocabtagene maraleucel (liso-cel) CAR-T therapy, specifically addressing nodal and gastrointestinal follicular lymphoma (GI-FL). The author skillfully amalgamates essential findings from the TRANSCEND FL trial, emphasizing the extraordinary 97% overall response rate and a 94% complete response rate, alongside a notably reduced toxicity profile where grade ≥3 cytokine release syndrome (CRS) was absent, and grade ≥3 neurotoxicity was observed in merely 3% of patients. This concentrated analysis on the unique advantages of liso-cel—particularly its defined CD4+/CD8+ composition and the feasibility of outpatient treatment—addresses a significant void in the existing literature, especially in light of the historical exclusion of GI-FL from crucial CAR-T trials. The comparative framework juxtaposing lisocabtagene maraleucel with axicabtagene ciloleucel and tisagenlecleucel provides invaluable insights for clinical decision-making.
Nevertheless, the editorial's otherwise robust examination fails to explore subtleties regarding the durability of response in high-risk subpopulations. Although the reported 12-month progression-free survival rate exceeding 85% is promising, emerging data indicate that follicular lymphoma patients with specific genomic alterations (e.g., TP53 mutations or 1p36 deletions) display varied responsiveness to CAR-T therapy. This omission is particularly salient for GI-FL, where the biological characteristics of the disease may diverge from those of nodal FL due to influences from the microenvironment.
Furthermore, the editorial rightly recognizes cost as a barrier but insufficiently emphasizes how the manufacturing logistics of Liso-Cel disproportionately hinder accessibility in advanced GI-FL cases. Unlike nodal FL, where treatment delays may be manageable, GI-FL frequently presents urgent complications necessitating swift intervention. The three-week manufacturing timeline for liso-cel—despite improvements over previous platforms—remains a challenge for these patients, a difficulty exacerbated by the absence of validated bridging strategies tailored to gastrointestinal involvement.
Looking ahead, the integration of endoscopic and molecular staging systems (e.g., Paris classification) with CAR-T therapy response biomarkers emerges as a critical research priority. Real-world studies should specifically investigate GI-FL cohorts to ascertain whether mucosal disease localization influences CAR-T trafficking or persistence. Additionally, the formulation of risk-adapted conditioning regimens could optimize the therapeutic index in patients with gastrointestinal involvement, where organ-specific toxicities remain inadequately characterized. Watanabe's appeal for multicenter collaboration should explicitly encompass these mechanistic and health-services research inquiries to propel personalized CAR-T applications across follicular lymphoma subtypes."
-
Watanabe T. Emerging role of lisocabtagene maraleucel chimeric antigen receptor-T cell in nodal and gastrointestinal follicular lymphoma. World J Gastroenterol 2025; 31(45): 112336 [PMID: 41378337 DOI: 10.3748/wjg.v31.i45.112336]
|
|
43
|
-
"This review elevates our understanding of acetaminophen (APAP)-induced acute liver injury from a “single toxic metabolite acting on hepatocytes” model to a dynamic network involving multiple hepatic cell populations. Second, it clearly maps out current and potential therapeutic targets, essentially providing a “cell-type–oriented treatment roadmap” for future translational work. The discussion of CYP2E1/CYP3A4, species differences, and risk factors (such as alcohol use, malnutrition, underlying liver disease, and concomitant enzyme-inducing drugs) helps clinicians better identify high-risk populations and appreciate the limitations of extrapolating from animal models, thereby supporting more individualized risk assessment and dosing. In the treatment section, the authors extend beyond the classical “N-acetylcysteine golden window” and cover emerging strategies such as inhibition of NAPQI formation (e.g. fomepizole), mitochondria-targeted antioxidants (Mito-Tempo, MitoQ), modulation of ferroptosis/ferritinophagy, NLRP3–STING inflammasome pathways, as well as cell-based and hepatocyte transplantation therapies. This allows clinical readers to quickly grasp potential combination or alternative approaches that are entering or approaching clinical trials, while signaling to basic scientists multiple promising cellular pathways and targets for deeper exploration. Overall, the article reads as an up-to-date progress review on the multicellular mechanisms and therapeutic targets of APAP-induced acute liver injury, offering both mechanistic clarity and topic inspiration for those working on drug-induced liver injury, emergency/critical care, and liver transplantation—while also realistically emphasizing that most of the evidence remains at the experimental or early translational stage and is not yet ready to change clinical guidelines."
-
Yang D, Kim B, Kim JW. Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury. World J Gastroenterol 2025; 31(45): 112720 [PMID: 41378327 DOI: 10.3748/wjg.v31.i45.112720]
|
|
44
|
-
"this review provides a clear and systematic overview of the interactions among intestinal macrophages, the enteric nervous system, and the cholinergic anti-inflammatory pathway in inflammatory bowel disease (IBD). By closely linking basic mechanistic insights with the potential clinical application of vagus nerve stimulation (VNS)—especially low-frequency, non-invasive VNS—the paper offers a fresh “neuroregulation–immune modulation” angle on IBD treatment, which is currently dominated by immunosuppressants and biologics. In terms of clinical practicality, the authors emphasize the promise of non-invasive VNS as a safer and more tolerable approach, while frankly acknowledging that current evidence still largely comes from animal models and a few pilot clinical studies, with a lack of large-scale randomized controlled trials. This “promising yet cautious” tone is valuable for clinical readers. On the one hand, the paper helps gastroenterologists and basic scientists understand why heart rate variability (HRV), emotional status, and autonomic imbalance may be linked to IBD course and relapse; on the other hand, it reminds readers that VNS and α7nAChR-targeted agents are still at the stages of proof-of-concept and early translation. In the short term, their main value lies in inspiring new research designs (for example, clinical trials stratified by HRV, combined with intestinal macrophage phenotype analysis), rather than immediately changing standard treatment pathways. Overall, this work reads like a forward-looking “blueprint” for neuro-immune therapies in IBD and is particularly thought-provoking for readers interested in IBD mechanisms and novel therapeutic strategies."
-
Zheng L, Duan SL. Neuroimmune interactions in inflammatory bowel disease: Role of intestinal macrophages and the cholinergic pathway. World J Gastroenterol 2025; 31(44): 109440 [PMID: 41356522 DOI: 10.3748/wjg.v31.i44.109440]
|
|
45
|
-
"Commentary on "Large Language Models and Large Concept Models in Radiology: Present Challenges, Future Directions, and Critical Perspectives"
The transition from LLMs to LCMs, aiming for enhanced semantic reasoning, is fundamentally challenged by the necessity of building these sophisticated models upon historical data streams polluted by human cognitive biases [1]. Diagnostic interpretation errors are often not perceptual misses but interpretive errors driven by faulty reasoning [2,3]. These biases include Anchoring Bias, where a radiologist becomes fixated on an initial impression despite contradictory evidence, often coupled with Confirmation Bias, the inclination to seek information only to affirm that initial theory [2,4,5]. Similarly, Availability Bias, or availability heuristics, predisposes the interpreter to recall recently seen or memorable diagnoses regardless of the actual prevalence [3,4,6]. When AI learns its "concepts" or "relationships" from millions of reports generated under the influence of these specific biases, it may normalize or amplify flawed reasoning patterns, potentially leading to widespread, systemic diagnostic vulnerabilities that mirror rather than correct human limitations [3]. For instance, an AI trained primarily on reports that exhibit Zebra Retreat—the avoidance of accurate but rare diagnoses due to lack of confidence—will systematically underreport uncommon but critical findings, reducing the diagnostic sensitivity for edge cases [2,6].
The core strength of future AI systems must therefore lie not just in conceptual depth but in active debiasing, mitigating the human errors that underpin the training corpus [4,5]. If AI recommendations are opaque, clinicians may fall prey to Blind Obedience or Premature Closure by accepting the machine's initial diagnosis without critical Type 2 analysis [2,6]. To counter this, AI must incorporate the same cognitive forcing strategies used by human interpreters, demanding metacognition ("thinking about thinking") to identify susceptibility to bias [3,4]. Furthermore, AI must specifically address the Hindsight Bias that plagues retrospective quality review [2,6], by ensuring its decision pathways are fully auditable and transparent, allowing for objective assessment of whether an error resulted from inherent data contamination or algorithmic failure. As AI integrates deeper into clinical workflows, its ability to enhance safety hinges on proactively resisting the transfer and propagation of predictable human cognitive limitations [6].
References
1. Merchant SA, Merchant N, Varghese SL, Shaikh MJS. Large language models and large concept models in radiology: Present challenges, future directions, and critical perspectives. World J Radiol. 2025;17(11):114754. [DOI: 10.4329/wjr.v17.i11.114754]
2. Onder O, Yarasir Y, Azizova A, Durhan G, Onur MR, Ariyurek OM. Errors, discrepancies and underlying bias in radiology with case examples: a pictorial review. Insights Imaging. 2021;12:51. [PMID: 33877458. DOI: 10.1186/s13244-021-00986-8]
3. Chen J, Gandomkar Z, Reed WM. Investigating the impact of cognitive biases in radiologists' image interpretation: A scoping review. Eur J Radiol. 2023;166:111013. [PMID: 37541180. DOI: 10.1016/j.ejrad.2023.111013]
4. Busby LP, Courtier JL, Glastonbury CM. Bias in Radiology: The How and Why of Misses and Misinterpretations. Radiographics. 2018;38:236–247. [PMID: 29194009. DOI: 10.1148/rg.2018170107]
5. Gunderman RB. Biases in radiologic reasoning. AJR Am J Roentgenol. 2009;192:561–564. [PMID: 19234247. DOI: 10.2214/AJR.08.1220]
6. Yoon SY, Lee KS, Bezuidenhout AF, Kruskal JB. Spectrum of Cognitive Biases in Diagnostic Radiology. Radiographics. 2024;44:e230059. [PMID: 38843094. DOI: 10.1148/rg.230059]
"
-
Merchant SA, Merchant N, Varghese SL, Shaikh MJS. Large language models and large concept models in radiology: Present challenges, future directions, and critical perspectives. World J Radiol 2025; 17(11): 114754 [PMID: 41356761 DOI: 10.4329/wjr.v17.i11.114754]
|
|
46
|
-
"The authors present a clinically important case highlighting the coexistence of mixed connective tissue disease (MCTD) and tuberculosis (TB), a scenario that poses substantial diagnostic challenges in TB-endemic regions. The manuscript is well structured and clearly describes the sequence of clinical events, laboratory workup, and therapeutic decisions. The discussion appropriately emphasizes the overlap between autoimmune manifestations and infectious etiologies, particularly when both present with pulmonary involvement.
From an academic standpoint, the case is relevant and contributes meaningfully to the limited global literature examining MCTD–TB coexistence. The authors successfully integrate immunological findings with epidemiological considerations, underscoring the need for high clinical suspicion and comprehensive autoimmune evaluation in complex presentations. The reference list is current and well selected, drawing from both rheumatology and infectious disease literature.
The language is generally clear and understandable, although a few sections may benefit from stylistic tightening to improve flow, particularly in the discussion where multiple concepts are presented in close succession. Minor grammatical refinements could enhance readability. The inclusion of comprehensive tables and immunological profiles strengthens the diagnostic clarity of the case.
For future research and case documentation, the authors may consider:
1. Providing a more detailed longitudinal follow-up, especially regarding TB status, autoimmune markers, and treatment tapering, as long-term outcomes for MCTD-TB coexistence are not well described in the literature.
2. Elaborating on radiologic findings, given the central role of imaging in differentiating pulmonary TB from autoimmune lung involvement.
3. Discussing possible immunopathological links between chronic infections and autoimmune flare, which could enrich the mechanistic understanding of such overlap syndromes.
4. Addressing medication safety monitoring, particularly concerning hepatotoxicity in the context of ATT combined with corticosteroids and hydroxychloroquine.
Overall, this is a valuable clinical contribution that highlights key diagnostic considerations in resource-limited, TB-endemic settings. The manuscript is academically sound, clinically relevant, and will be informative for physicians managing complex autoimmune presentations.
"
-
Sial F, Basit A, Ghafoor N, Sial W, Basil AM. Mixed connective tissue disease and tuberculosis coexistence as a diagnostic dilemma: A case report. World J Clin Cases 2025; 13(33): 109866 [PMID: 41356082 DOI: 10.12998/wjcc.v13.i33.109866]
|
|
47
|
-
"The review by Nian et al. offers a thorough and thoughtfully articulated overview of current insights into Osteopontin (OPN)–mediated PI3K/AKT signaling and its pivotal influence on gastrointestinal cancer progression, metastatic behavior, and therapeutic resistance. The authors skillfully synthesize mechanistic and translational findings, underscoring how OPN-driven activation of the PI3K/AKT pathway promotes epithelial–mesenchymal transition, metabolic adaptation, immune escape, and chemoresistance. Their discussion of OPN splice variants, tumor microenvironment interactions, and biomarker-informed therapeutic strategies provides meaningful guidance for advancing precision oncology.
A major strength of the review is its emphasis on the inherent complexity and compensatory nature of OPN–PI3K/AKT signaling, which helps explain the challenges associated with single-agent therapeutic approaches. The recommendation to pursue combination strategies—such as pairing PI3K/AKT inhibitors with immune checkpoint blockade or OPN-targeted antibodies—is timely and supported by accumulating preclinical data. Furthermore, the manuscript’s focus on PIK3CA mutation subsets and OPN expression as potential predictive biomarkers may enable more refined patient stratification in future clinical trials.
Despite these promising avenues, clinical translation remains constrained. Current trials evaluating PI3K/AKT inhibitors in gastrointestinal malignancies have yielded limited efficacy and notable toxicity, highlighting the need for more rigorous biomarker-driven study designs. Although the review acknowledges these issues, a deeper appraisal of the reasons underlying clinical shortcomings—and the specific contribution of OPN signaling to these obstacles—would further strengthen its clinical impact.
In sum, this review provides a valuable contribution by elucidating the diverse oncogenic roles of OPN and outlining strategic paths toward overcoming therapeutic resistance. Continued research into isoform-specific activity, tumor microenvironmental dynamics, and rational combinatorial regimens will be crucial for realizing the therapeutic potential of targeting the OPN–PI3K/AKT axis in gastrointestinal cancers."
-
Nian H, Bai Y, Wang HY, Yu H, Zhang ZL, Shi RH, Zhang S, Wu YB, Zhou DH, Du QC. Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors. World J Gastrointest Oncol 2025; 17(11): 109923 [PMID: 41281471 DOI: 10.4251/wjgo.v17.i11.109923]
|
|
48
|
-
"This article presents an interesting retrospective study involving a substantial cohort of patients, highlighting the role of total neoadjuvant therapy (TNT), specifically the RAPIDO protocol, compared to conventional long-course chemoradiotherapy (LCCRT) in the management of locally advanced rectal cancer (LARC). The study focuses on early surgical outcomes, a topic of significant clinical relevance.
The cornerstone of LARC treatment remains optimal surgical resection via total mesorectal excision (TME). To reduce locoregional failure, preoperative concurrent chemoradiotherapy has long been the standard of care. However, as noted in the article and supported by prior evidence (e.g., Fokas et al.), the efficacy of this approach is primarily confined to local control, while distant metastases continue to be a major cause of treatment failure and compromised survival.
The intensification of neoadjuvant therapy through TNT addresses this limitation by achieving early systemic control, significant tumor downstaging, and higher rates of pathological complete response, all without compromising early surgical outcomes compared to LCCRT, as demonstrated in this study. Moreover, the authors report that TNT is associated with a shorter total stoma duration and a lower permanent stoma rate, which are meaningful benefits for patients' quality of life.
Recent landmark trials, such as RAPIDO and PRODIGE 23, have provided robust evidence supporting the use of TNT, showing improved pathological complete response, better treatment compliance, and reduced distant metastases compared to LCCRT. This study adds valuable real-world data to the growing body of literature affirming the safety and feasibility of TNT from a surgical perspective.
We commend the authors for their contribution and agree that further prospective studies with longer follow-up are warranted to evaluate long-term oncological outcomes.
(By Prof Sanaa El Majjaoui and Pr Nabil Ismaili)"
-
Jabbar SAA, Choo ALE, Wong NW, Ngu JCY, Teo NZ. Comparing early surgical outcomes between total neoadjuvant therapy and standard long course chemoradiotherapy for rectal cancer. World J Gastrointest Oncol 2025; 17(11): 111250 [PMID: 41281487 DOI: 10.4251/wjgo.v17.i11.111250]
|
|
49
|
-
"This minireview describes the important role of 0steopontin (OPN)-regulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in gastrointestinal tumor proliferation, metastasis, chemoresistance, and immune evasion.
Targeting osteopontin-regulated PI3K/AKT signaling pathway with PI3K/AKT inhibitors or OPN neutralizing antibodies may reverse drug resistance and suppress metastasis. Further research should be needed to find combination therapies which have the potential to provide more effective anti-tumor activity towards refractory cancers."
-
Nian H, Bai Y, Wang HY, Yu H, Zhang ZL, Shi RH, Zhang S, Wu YB, Zhou DH, Du QC. Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors. World J Gastrointest Oncol 2025; 17(11): 109923 [PMID: 41281471 DOI: 10.4251/wjgo.v17.i11.109923]
|
|
50
|
-
"I want to congratulate the authors for conducting this excellent study on the impact of PAD in PEP. This study has demonstrated that PAD, particularly Type B, has a Significant risk of PEP. This subgroup analysis of PAD is important for advancing efforts to prevent PEP. This study included predominantly older patients, where the prevalence of PAD is higher. Whether the presence of only PAD increases the risk of pancreatitis is still difficult to interpret. As PAD increases the difficulty of CBD cannulation, requiring advanced cannulation techniques which itself may increase the risk of PEP, furthermore indication of ERCP is also analysed in both groups "
-
Shu J, Liao YS, Zhang YJ, Zhou WL, Zhang H. Impact of periampullary diverticulum on the incidence of post-endoscopic retrograde cholangiography pancreatitis. World J Gastrointest Endosc 2025; 17(11): 111243 [PMID: 41256294 DOI: 10.4253/wjge.v17.i11.111243]
|
