Safety of Tepotinib Challenge after Capmatinib-Induced Pneumonitis in a Patient with Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation: A Case Report.

The targeted agents capmatinib and tepotinib provide a new treatment for patients with non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutation (METex14). However, drug-induced pneumonitis is an uncommon but threatening adverse effect found in patients treated with both capmatinib and tepotinib. The safety of treating a patient with a MET inhibitor after drug-induced pneumonitis by another MET inhibitor remains unclear. Here, we present a case of a patient with NSCLC harboring a METex14 who was treated with a standard dose of tepotinib after advanced capmatinib-induced pneumonitis and did not present pneumonitis relapse. Tepotinib may be a safe option when medical professionals consider switching MET inhibitors after patients experience pneumonitis.

Comparison between transpancreatic sphincterotomy and needle-knife fistulotomy in difficulty biliary access, a retrospective study in Taiwan.

BACKGROUND: Selective deep biliary cannulation is the first and the most important step before further biliary therapy. Transpancreatic sphincterotomy (TPS), and needle knife fistulotomy (NKF) were commonly used in patients with difficult cannulation, but few studies compare the outcome between TPS and NKF. METHODS: A total of 78 patients who met the criteria of difficult cannulation in the National Taiwan University hospital from October 2015 to October 2017 were retrospectively reviewed. Their baseline demographics, success rate of biliary cannulation, and the rate of adverse events were assessed. RESULTS: 31 patients and 47 patients underwent TPS and NKF for difficult biliary access, respectively. The characteristics of the 2 groups were similar, but patients in TPS group had more frequent pancreatic duct cannulation. Bile duct cannulation was successful in 23 patients (74.2%) in the TPS group and 39 (83.0%) in the NKF group (P = 0.34). There was no difference between the TPS and NKF in the rate of adverse events, including post-ERCP pancreatitis (PEP) (16.1% vs. 6.4%, p = 0.17), and hemorrhage (3.2% vs. 8.5%, p = 0.35). No perforation occurred. CONCLUSIONS: Both TPS and NKF have good biliary access rate in patient with difficult cannulation. TPS has acceptable successful rate and similar complication rate, compared with NKF.

Can Chinese herbal medicine offer feasible solutions for newly diagnosed esophageal cancer patients with malnutrition? a multi-institutional real-world study.

Background: Esophageal cancer (EC) is a major cause of cancer-related mortality in Taiwan and globally. Patients with EC are highly prone to malnutrition, which adversely affects their prognosis. While Chinese herbal medicine (CHM) is commonly used alongside conventional anti-cancer treatments, its long-term impact on EC patients with malnutrition remains unclear. Methods: This study utilized a multi-center cohort from the Chang Gung Research Database, focusing on the long-term outcomes of CHM in EC patients with malnutrition between 1 January 2001, and 31 December 2018. Patients were monitored for up to 5 years or until death. Overall survival (OS) rates were calculated using the Kaplan-Meier method. Overlap weighting and landmark analysis were employed to address confounding and immortal time biases. Additionally, the study analyzed prescription data using a CHM network to identify key CHMs for EC with malnutrition, and potential molecular pathways were investigated using the Reactome database. Results: EC patients with malnutrition who used CHM had a higher 5-year OS compared with nonusers (22.5% vs. 9% without overlap weighting; 24.3% vs. 13.3% with overlap weighting; log-rank test: p = 0.006 and 0.016, respectively). The median OS of CHM users was significantly longer than that of nonusers (19.8 vs. 12.9 months, respectively). Hazard ratio (HR) analysis showed a 31% reduction in all-cause mortality risk for CHM users compared with nonusers (HR: 0.69, 95% confidence interval: 0.50-0.94, p = 0.019). We also examined 665 prescriptions involving 306 CHM, with Hedyotis diffusa Willd. exhibiting the highest frequency of use. A CHM network was created to determine the primary CHMs and their combinations. The identified CHMs were associated with the regulation of immune and metabolic pathways, particularly in areas related to immune modulation, anti-cancer cachexia, promotion of digestion, and anti-tumor activity. Conclusion: The results of this study suggest a correlation between CHM use and improved clinical outcomes in EC patients with malnutrition. The analysis identified core CHMs and combinations of formulations that play a crucial role in immunomodulation and metabolic regulation. These findings lay the groundwork for more extensive research on the use of CHM for the management of malnutrition in patients with EC.

Investigation of the Correlation between Enterovirus Infection and the Climate Factor Complex Including the Ping-Year Factor and El Niño-Southern Oscillation in Taiwan.

Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) and El Niño-Southern Oscillation (ENSO) are possible CFCs. This study aimed to determine the relationship between these two CFCs and the incidence of enterovirus infection. Children aged 15 years and younger with enterovirus infection and/or EVSC were enrolled between 2007 and 2022. Each year was categorized into a ping-year or non-ping-year according to the PYF. Poisson regression was used to evaluate the associations between the PYF, ENSO, and the incidence of enterovirus infection. Compared to the ping-year group, the incidence rate of enterovirus infection, the incidence rate of EVSC, and the ratio of EVSC in the non-ping-year group were 1.24, 3.38, and 2.73 times higher, respectively (p < 0.001). For every one-unit increase in La Niña, the incidence rate of enterovirus infection decreased to 0.96 times (p < 0.001). Our study indicated that CFCs could be potential predictors for enterovirus infection, and the PYF was more suitable than ENSO. Further research is needed to improve the predictive model.

Seven-day vonoprazan-based triple therapy as first-lineHelicobacter pylori treatment in comparison with extended sequential therapy.

Background and Aim: Vonoprazan as a new acid blocker has more potency and longer lasting acid suppression than proton pump inhibitors. Whether the efficacy of vonoprazan-based triple therapy is comparable with or even better than that of currently recommended first-line therapies is still unknown. Our study aims to compare the eradication rate and major adverse effects between 7-day vonoprazan-based triple therapy with high-dose amoxicillin and 14-day extended sequential therapy. Methods: We performed a retrospective analysis from the database of 13C-urea breath test at Fu Jen Catholic University Hospital. All patients with a definite diagnosis of Helicobacter pylori infection by rapid urease test, urea breath test, stool antigen test, or pathology report were recruited. Patients receiving first-line regimens with vonoprazan-based triple therapy or extended sequential therapy were included. The respective eradication rate determined by 13C-urea breath test and major adverse effects were demonstrated. Results: Totally, 106 patients were recruited in the vonoprazan-based triple therapy group and 357 in the extended sequential therapy group. There was no significant difference in eradication rate between vonoprazan-based triple therapy with high-dose amoxicillin and extended sequential therapy (83.0 vs 88.8%, P = 0.12). Major adverse effects occurred in 13 of the extended sequential therapy group but none in the other group (0% vs 3.6%, P = 0.046). Conclusions: Seven-day vonoprazan-based triple therapy with high-dose amoxicillin is a potential first-line anti-Helicobacter pylori regimen alternative to current standard treatment, with the advantages of simplicity, short treatment duration, low pill burden, and fewer major adverse effects.

The Potential Complementary Role of Using Chinese Herbal Medicine with Western Medicine in Treating COVID-19 Patients: Pharmacology Network Analysis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic in 2019-coronavirus disease (COVID-19). More and more Western medicine (WM) and Chinese herbal medicine (CHM) treatments have been used to treat COVID-19 patients, especially among Asian populations. However, the interactions between WM and CHM have not been studied. This study aims at using the network pharmacology approach to explore the potential complementary effects among commonly used CHM and WM in a clinical setting from a biomolecular perspective. Three well-published and widely used CHM formulas (National Research Institute of Chinese Medicine 101 (NRICM101), Qing-Fei-Pai-Du-Tang (QFPDT), Hua-Shi-Bai-Du-Formula (HSBDF)) and six categories of WM (Dexamethasone, Janus kinase inhibitors (JAKi), Anti-Interleukin-6 (Anti-IL6), anticoagulants, non-vitamin K antagonist oral anticoagulants (NOAC), and Aspirin) were included in the network pharmacology analysis. The target proteins on which these CHM and WM had direct effects were acquired from the STITCH database, and the potential molecular pathways were found in the REACTOME database. The COVID-19-related target proteins were obtained from the TTD database. For the three CHM formulas, QFPDT covered the most proteins (714), and 27 of them were COVID-19-related, while HSBDF and NRICM101 covered 624 (24 COVID-19-related) and 568 (25 COVID-19-related) proteins, respectively. On the other hand, WM covered COVID-19-related proteins more precisely and seemed different from CHM. The network pharmacology showed CHM formulas affected several inflammation-related proteins for COVID-19, including IL-10, TNF-α, IL-6, TLR3, and IL-8, in which Dexamethasone and Aspirin covered only IL-10 and TNF-α. JAK and IL-6 receptors were only inhibited by WM. The molecular pathways covered by CHM and WM also seemed mutually exclusive. WM had advantages in cytokine signaling, while CHM had an add-on effect on innate and adaptive immunity, including neutrophil regulation. WM and CHM could be used together to strengthen the anti-inflammation effects for COVID-19 from different pathways, and the combination of WM and CHM may achieve more promising results. These findings warrant further clinical studies about CHM and WM use for COVID-19 and other diseases.

Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease.

Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.