Catharanthus roseus intoxication mimicking acute cholangitis.

BACKGROUND: Catharanthus roseus, a Madagascar native flowering plant, is known for its glossy leaves and vibrant flowers, and its medicinal significance due to its alkaloid compounds. As a source of vinblastine and vincristine used in chemotherapy, Catharanthus roseus is also employed in traditional medicine with its flower and stalks in dried form. Its toxicity can lead to various adverse effects. We report a case of Catharanthus roseus juice toxicity presenting as acute cholangitis, emphasizing the importance of healthcare providers obtaining detailed herbal supplement histories. CASE PRESENTATION: A 65-year-old woman presented with abdominal pain, fever, anorexia, and lower limb numbness. Initial diagnosis of acute cholangitis was considered, but imaging excluded common bile duct stones. Further investigation revealed a history of ingesting Catharanthus roseus juice for neck pain. Laboratory findings showed leukocytosis, elevated liver enzymes, and hyperbilirubinemia. The patient developed gastric ulcers, possibly due to alkaloids in Catharanthus roseus. No bacterial growth was noted in blood cultures. The patient recovered after discontinuing the herbal extract. CONCLUSIONS: Catharanthus roseus toxicity can manifest as fever, hepatotoxicity with cholestatic jaundice, and gastric ulcers, mimicking acute cholangitis. Awareness of herbal supplement use and potential toxicities is crucial for healthcare providers to ensure prompt diagnosis and appropriate management. This case emphasizes the need for public awareness regarding the possible toxicity of therapeutic herbs and the importance of comprehensive patient histories in healthcare settings.

The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease.

OBJECTIVE: A definitive diagnosis of gastroesophageal reflux disease (GERD) depends on endoscopic and/or pH-study criteria. However, high resolution manometry (HRM) can identify factors predicting GERD, such as ineffective esophageal motility (IEM), esophago-gastric junction contractile integral (EGJ-CI), evaluating esophagogastric junction (EGJ) type and straight leg raise (SLR) maneuver response. We aimed to build and externally validate a manometric score (Milan Score) to stratify the risk and severity of the disease in patients undergoing HRM for suspected GERD. METHODS: A population of 295 consecutive patients undergoing HRM and pH-study for persistent typical or atypical GERD symptoms was prospectively enrolled to build a model and a nomogram that provides a risk score for AET > 6%. Collected HRM data included IEM, EGJ-CI, EGJ type and SLR. A supplemental cohort of patients undergoing HRM and pH-study was also prospectively enrolled in 13 high-volume esophageal function laboratories across the world in order to validate the model. Discrimination and calibration were used to assess model's accuracy. Gastroesophageal reflux disease was defined as acid exposure time >6%. RESULTS: Out of the analyzed variables, SLR response and EGJ subtype 3 had the highest impact on the score (odd ratio 18.20 and 3.87, respectively). The external validation cohort consisted of 233 patients. In the validation model, the corrected Harrel c-index was 0.90. The model-fitting optimism adjusted calibration slope was 0.93 and the integrated calibration index was 0.07, indicating good calibration. CONCLUSIONS: A novel HRM score for GERD diagnosis has been created and validated. The MS might be a useful screening tool to stratify the risk and the severity of GERD, allowing a more comprehensive pathophysiologic assessment of the anti-reflux barrier. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT05851482).

Machine learning improves the prediction of significant fibrosis in Asian patients with metabolic dysfunction-associated steatotic liver disease - The Gut and Obesity in Asia (GO-ASIA) Study.

BACKGROUND: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non-alcoholic fatty liver disease (NAFLD/MASLD). AIMS: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients. METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria). RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p < 0.001, each). ML models showed 7%-12% better discrimination than FIB-4 to detect SF. Optimised random forest (RF) yielded best NPV/F1 in overall set (0.947/0.754), test set (0.798/0.588) and validation set (0.852/0.559), as compared to FIB4 in overall set (0.744/0.499), test set (0.722/0.456), and validation set (0.806/0.507). Compared to FIB-4, RF could pick 10 times more patients with SF, reduce unnecessary referrals by 28%, and prevent missed referrals by 78%. Age, AST, ALT fasting plasma glucose, and platelet count were top features determining the SF. Sequential use of SAFE < 140 and FIB4 < 1.2 (when SAFE > 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set). CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.

Malaysian joint societies' consensus recommendations on diagnosis and management of disorders of esophagogastric junction outflow.

Disorders of esophagogastric junction (EGJ) outflow, including achalasia and EGJ outflow obstruction, are motility disorders characterized by inadequate relaxation of lower esophageal sphincter with or without impaired esophageal peristalsis. Current guidelines are technical and less practical in the Asia-Pacific region, and there are still massive challenges in timely diagnosis and managing these disorders effectively. Therefore, a Malaysian joint societies' task force has developed a consensus on disorders of EGJ outflow based on the latest evidence, while taking into consideration the practical relevance of local and regional context and resources. Twenty-one statements were established after a series of meetings and extensive review of literatures. The Delphi method was used in the consensus voting process. This consensus focuses on the definition, diagnostic investigations, the aims of treatment outcome, non-surgical or surgical treatment options, management of treatment failure or relapse, and the management of complications. This consensus advocates the use of high-resolution esophageal manometry for diagnosis of disorders of EGJ outflow. Myotomy, via either endoscopy or laparoscopy, is the preferred treatment option, while pneumatic dilatation can serve as a secondary option. Evaluation and management of complications including post-procedural reflux and cancer surveillance are recommended.

Efficacy and safety of nab-paclitaxel in metastatic gastric cancer: a meta-analysis.

Background: Nab-paclitaxel is formulated to address several limitations of paclitaxel. Methods: A systematic review was done of several databases and a meta-analysis with a random-effects model was conducted to assess the efficacy and safety of nab-paclitaxel in metastatic gastric cancer (MGC). Results: Included studies revealed that nab-paclitaxel provides a 30.4% overall response rate and 65.7% disease control rate in MGC patients. The overall survival was 9.65 months and progression-free survival was 4.48 months, associated with the treatment line and regimen. The highest incidence of grade 3 and higher treatment-related adverse events was for neutropenia (29.9%). Conclusion: Nab-paclitaxel provides better disease response and longer survival with manageable side effects in MGC compared with paclitaxel.

Levels of PIVKA-II and alpha-fetoprotein in unresectable hepatocellular carcinoma compared to healthy controls and predictive values of both markers with radiological responses after loco-regional interventions.

Background: The significance of the current study was to determine normative levels of PIVKA-II and AFP in patients with unresectable HCC and healthy participants. The second goal was to assess the roles of PIVKA-II and AFP in predicting radiological response after loco-regional therapy. Methods: This prospective cohort study enrolled consecutive samples of HCC patients and healthy controls. Venous blood samples were obtained at baseline and after interventions to determine serum levels of PIVKA-II and AFP using the chemiluminescent microparticle immunoassay method. Radiologic responses were determined based on the WHO criteria. Results: Fifty-four HCC patients (mean age 58.9 years, 49 males) and 40 healthy controls (mean age 33.5 years, 26 males) were recruited. The median serum levels of PIVKA-II and AFP in HCC vs. healthy controls were 988.4 vs. 24.2 mAU/ml and 13.6 vs. 1.7 ng/ml, respectively (both p < 0.001). With ROC curve analysis, the area under the curve (AUC) for PIVKA-II was 0.95 95% CI [0.90-0.99], and for AFP it was 0.98, 95% CI [0.95-1.0]). The cut-off value for PIVKA-II was 41.4 mAU/ml, and AFP was 4.8 ng/ml. PIVKA-II levels correlated significantly with radiological responses (r = 0.64, p = 0.02) but not AFP (r = 0.09, p = 0.2). Conclusion: PIVKA-II and AFP levels are distinctive between unresectable HCC and healthy controls. However, PIVKA-II, not AFP, can predict the radiological response after loco-regional therapy.

Climate Change and the Esophagus: Speculations on Changing Disease Patterns as the World Warms.

PURPOSE OF REVIEW: Esophageal disorders, including gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), and esophageal cancer, may be affected by climate change. Our review describes the impact of climate change on risk factors associated with esophageal diseases and speculates how these climate-related factors impacted esophageal disorders and their management. RECENT FINDINGS: Climate change is responsible for extreme weather conditions (shifts in rainfall, floods, droughts, and forest fires) and global warming. These consequences affect basic human needs of water and food, causing changes in population dynamics and pose significant threats to digestive health, including common esophageal disorders like GERD, EoE, and esophageal cancers. The changing patterns of esophageal diseases with climate change are likely mediated through risk factors, including nutrition, pollutants, microplastics, and the microbiota-gut-brain axis. The healthcare process itself, including GI endoscopy practices commonly employed in diagnosing and therapeutics of esophageal diseases, may, in turn, contribute to climate change through plastic wastage and greenhouse gas emissions, thus creating the climate change lifecycle. Breaking the cycle would involve changes at the individual level, community level, and national policy level. Prevention is key, with individuals identifying and remediating risk factors and reducing carbon footprints. The ABC (Advocacy, Broadcast, and Collaborate) activities would help enhance awareness at the community level. Higher-level programs such as the Bracing Resilience Against Climate Effects (BRACE) would lead to broader and larger-scale adoption of public health adaptation strategies at the national level. The impact of climate change on esophageal disorders is likely real, mediated by several risk factors, and creates a climate change lifecycle that may only break if changes are made at individual, community, and national levels.

Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal Cancer Progression.

BACKGROUND: Accumulation of cancer-associated fibroblasts (CAFs) in the tumor stroma is linked to poor prognosis in colorectal cancer (CRC). CAF-cancer cell interplay, facilitated by secretomes including transforming growth factor-beta 1 (TGF-ß1), supports fibroblast activation, drives colorectal carcinogenesis, and contributes to CRC aggressive phenotypes. Although widely used, traditional CAF biomarkers are found to have heterogeneous and non-specific expression. Amine oxidase copper containing 3 (AOC3) and leucine-rich repeat-containing 17 (LRRC17) have been reported to be emerging markers of myofibroblasts. AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression. METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control.  Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-ß1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium. RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-ß1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-ß1 (p-value<0.01). CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.

Real-world practice of Helicobacter pylori management: A survey among physicians in Southeast Asia.

BACKGROUND: Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management. MATERIALS AND METHODS: Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide. RESULTS: There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p < 0.001). CONCLUSIONS: Choosing inappropriate regimens containing antibiotics with high resistance rates is not uncommon in Southeast Asia, especially among non-GI physicians. In countries with high clarithromycin resistance, the PBMT regimen is underutilized.

The Brain-Gut Clinic in Hospital Universiti Sains Malaysia: Pioneering New Service to Advance Neuro-Gastroenterology and Motility in Malaysia.

Neurogastroenterology and motility is a new but advanced subspecialty within gasteroenterology that cater to difficult, persistent and refractory gut-brain symptoms. Hospital USM has the country's first and new state-of-the art motility lab that was recently launched on the 25 May 2023, and is covered in nationwide media. Another first is the Brain-Gut Clinic, established on the 16 November 2022. The clinic is a new concept that builds on unique multiple disciplines in relation to the gut-brain axis. It is hoped that there will be more awareness on the existence of neurogastroenterology and motility among doctors and community, and that more research can be forthcoming to reduce the disease burden.

Hepatoprotective effects of silymarin in management of liver injury caused by tuberculosis treatment.

Tuberculosis (TB) is a chronic infection of global-health concern because of its high incidence, costly medical treatment, drug resistance and risk of co-infections. Anti-TB treatment involves a combination of drugs with high degree of liver toxicity, leading to drug-induced liver injury in 2-28% of patients who receive anti-TB treatment. In this case report, a patient with TB experienced drug-induced liver injury, and the initiation of treatment with silymarin 140 mg three-times daily resulted in a significant hepatoprotective effects as shown by the decreased liver enzyme activity. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

A prospective comparison of UK and Malaysian patients with irritable bowel syndrome in secondary care.

BACKGROUND: The prevalence of irritable bowel syndrome (IBS) is now known to be similar in various geographical regions, but there has been no study directly comparing characteristics of patients with IBS between populations. AIMS: To evaluate clinical and psychological differences between adults with IBS seen in secondary care in the United Kingdom (UK) and Malaysia. METHODS: Age- and sex-matched patients with IBS from a single centre in the UK (Leeds) and two centres in Malaysia (Kuala Lumpur and Kota Bharu), who fulfilled Rome III criteria, were recruited prospectively. Demographic characteristics and gastrointestinal and psychological symptoms were compared between both groups. RESULTS: A total of 266 (133 UK and 133 Malaysian) age- and sex-matched patients with Rome III IBS were recruited (mean age: 45.1 years Malaysia, vs. 46.5 years UK; 57.9% female). UK patients were more likely to consume alcohol than Malaysian patients (54.1% vs. 10.5%, p < 0.001). Compared with Malaysian patients, UK patients had more frequent abdominal pain, abdominal bloating, meal-related symptoms (p < 0.001 for all), higher symptom scores (mean 268.0 vs 166.0; p < 0.001), greater limitation of activities due to IBS (p = 0.007) and were more likely to report abnormal anxiety scores (p < 0.001). Higher perceived stress (mean 21.3 vs. 19.1, p = 0.014) and gastrointestinal symptom-specific anxiety scores (mean 50.8 vs. 43.0, p < 0.001) were also observed in UK patients. Finally, UK patients had higher somatoform symptom-reporting scores (mean 8.9 vs. 6.9, p < 0.001). CONCLUSIONS: IBS is more severe and is associated with a higher level of psychological symptoms in the UK compared with Malaysian patients in secondary care.

Role of silymarin in the management of deranged liver function in non-alcoholic steatohepatitis: a case report.

Non-alcoholic fatty liver disease is one of the main causes of elevated liver enzymes and chronic liver disease worldwide. It ranges from steatosis to steatohepatitis, leading to cirrhosis and related liver dysfunction. Silymarin is a herbal medicine, mostly used for liver disorders owing to its supposed hepatoprotective action. This report recommends silymarin in a patient with diabetes and grade II non-alcoholic steatohepatitis, confirming significant hepatoprotective effects as shown by the reduction of liver enzyme activities. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

A Malaysian consensus report on the diagnosis and treatment of Helicobacter pylori infection.

Helicobacter pylori is one of the most common chronic bacterial infections in humans and responsible for 90% of duodenal ulcers and 70-90% of gastric ulcers. Despite this, many misconceptions regarding the appropriate diagnostic method and treatment strategies still exist in the Malaysian clinical practice. Under the initiative of the steering committee, an expert panel consisting of nine key opinion leaders in the field of gastroenterology convened to develop a set of consensus statements that are relevant to the Malaysian healthcare practice. The panel members reviewed the current evidence on the management of H. pylori infection, focusing on the best practices that are relevant to the Malaysian population based on clinical experience and published clinical evidence. Using the modified Delphi method, the panel achieved consensus in three areas of H. pylori infection management: indications for testing, diagnosis, and treatment. The panel proposed a set of 19 consensus statements, which were synthesized via two rounds of blinded voting and group discussions. The recommendations provided are relevant to the Malaysian population and can be used as a guide by physicians across various healthcare settings to facilitate appropriate diagnostic testing and treatment of H. pylori infection.

Management of non-alcoholic fatty liver disease incidentally detected during other medical assessments.

Elevated liver enzyme levels are a frequent incidental finding in primary care, and non-alcoholic fatty liver disease is the main cause of incidental elevation of liver enzymes worldwide. The features of the disease vary from simple steatosis, characterized by a benign prognosis, to non-alcoholic steatohepatitis and cirrhosis, increasing morbidity and mortality. In this case report, abnormal liver activity was incidentally detected during other medical assessments. The patient was treated with silymarin 140 mg three times daily, resulting in decreased serum liver enzyme levels over treatment with a good safety profile. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.