Real-world analysis of afatinib as a first-line treatment for patients with advanced stage non-small-cell lung cancer with uncommon EGFR mutations: a multicenter study in Vietnam.

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X-S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

Role of indocyanine green fluorescence imaging for evaluating blood supply in the gastric conduit via the substernal route after McKeown minimally invasive esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a determining factor of morbidity and mortality after esophagectomy. Adequate perfusion of the gastric conduit is crucial for AL prevention. This study aimed to determine whether intraoperative angiography using indocyanine green (ICG) fluorescence improves the incidence of AL after McKeown minimally invasive esophagectomy (MIE) with gastric conduit via the substernal route (SR). METHODS: This retrospective cohort study included 120 patients who underwent MIE with gastric conduit via SR for esophageal cancer between February 2019 and April 2023. Of 120 patients, 88 experienced intraoperative angiography using ICG (ICG group), and 32 patients experienced intraoperative angiography without ICG (no-ICG group). Baseline characteristics and operative outcomes, including AL as the main concern, were compared between the 2 groups. In addition, the outcomes among patients in the ICG group with different levels of fluorescence intensity were compared. RESULTS: The ICG and no-ICG groups were comparable in baseline characteristics and operative outcomes. There was no significant difference between the 2 groups regarding the rate of AL (31.0% vs 37.5%; P = .505), median dates of AL (9 vs 9 days; P = .810), and severity of AL (88.9%, 11.11%, and 0.0% vs 66.7%, 16.7%, and 16.7% for grades I, II, and III, respectively; P = .074). Patients in the ICG group with lower intensity of ICG had higher rates of leakage (24.6%, 39.3%, and 100% in levels I, II, and III of ICG intensity, respectively; P = .04). CONCLUSION: The use of ICG did not seem to reduce the rate of AL. However, abnormal intensity of ICG fluorescence was associated with a higher rate of AL, which implies a predictive potential.

Sex Differences in Clustering Unhealthy Lifestyles Among Survivors of COVID-19: Latent Class Analysis.

BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group. CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.

Prevalence and determinants of constipation in children in Asia: a systematic review and meta-analysis.

Background: Constipation is prevalent worldwide, significantly increasing healthcare costs and diminishing the quality of life in children affected. Current studies have yielded mixed results regarding the factors associated with constipation, and mainly focusing on patients outside of Asia. Moreover, most of these studies lack focus on the paediatric population. This study aimed to identify the prevalence and associated factors of constipation among children in Asia. Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and Cochrane for cohort and cross-sectional studies published from database inception up to October 12, 2022, and continued with manual searching until September 2, 2023. Eligible studies were those that included children in Asia aged 0-18 years old suffering from idiopathic constipation, with prevalence value provided in the English abstract. The analysis included clinical and general population. Children with organic constipation, who had undergone gastrointestinal surgery, or with congenital defects were excluded, as these factors affect the incidence of constipation. Data included in the analysis were extracted from published reports only. The extracted data were pooled using random-effects model to analyse the prevalence of constipation in children in Asia. This study is registered with PROSPERO, CRD42022367122. Findings: Out of 4410 systematically searched studies and 36 manually searched ones, a total of 50 studies were included in the final analysis, encompassing data from 311,660 children residing in Asia. The pooled prevalence of constipation was 12.0% (95% CI 9.3-14.6%, I2 = 99.8%). There was no significant difference in constipation prevalence observed by sex and geographical location. Nonetheless, adolescents and children aged 1-9 years exhibited a significantly higher prevalence constipation compared to infants (p < 0.0001) Additionally, significant differences in constipation rates were observed across various diagnostic methods, population sources, and mental health conditions. Interpretation: Despite the high heterogeneity resulting from varying diagnostic tools or definitions used among studies, our review adds to the literature on constipation among children in Asia. It reveals a notably high prevalence of constipation in this demographic. Diagnostic methods, age, and compromised mental health emerged as significant influencers of constipation among children in Asia, highlighting potential strategies to mitigate constipation prevalence in children in Asia. Funding: The National Science and Technology Council, Taiwan.

Barriers and enablers to people-centred viral hepatitis care in Vietnam and the Philippines: Results of a patient journey mapping study.

In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi-structured interviews were conducted with a purposive, quota-based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre-awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre-awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people-centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites.

Mimosa pudica L. extract ameliorates pulmonary fibrosis via modulation of MAPK signaling pathways and FOXO3 stabilization.

ETHNOPHARMACOLOGICAL RELEVANCE: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing pulmonary disorder that has a poor prognosis and high mortality. Although there has been extensive effort to introduce several new anti-fibrotic agents in the past decade, IPF remains an incurable disease. Mimosa pudica L., an indigenous Vietnamese plant, has been empirically used to treat respiratory disorders. Nevertheless, the therapeutic effects of M. pudica (MP) on lung fibrosis and the mechanisms underlying those effects remain unclear. AIM OF THE STUDY: This study investigated the protective effect of a crude ethanol extract of the above-ground parts of MP against pulmonary fibrogenesis. MATERIALS AND METHODS: Inflammatory responses triggered by TNFα in structural lung cells were examined in normal human lung fibroblasts and A549 alveolar epithelial cells using Western blot analysis, reverse transcription-quantitative polymerase chain reaction assays, and immunocytochemistry. The epithelial-to-mesenchymal transition (EMT) was examined via cell morphology observations, F-actin fluorescent staining, gene and protein expression measurements, and a wound-healing assay. Anti-fibrotic assays including collagen release, differentiation, and measurements of fibrosis-related gene and protein expression levels were performed on TGFß-stimulated human lung fibroblasts and lung fibroblasts derived from mice with fibrotic lungs. Finally, in vitro anti-fibrotic activities were validated using a mouse model of bleomycin-induced pulmonary fibrosis. RESULTS: MP alleviated the inflammatory responses of A549 alveolar epithelial cells and lung fibroblasts, as revealed by inhibition of TNFα-induced chemotactic cytokine and chemokine expression, along with inactivation of the MAPK and NFκB signalling pathways. MP also partially reversed the TGFß-promoted EMT via downregulation of mesenchymal markers in A549 cells. Importantly, MP decreased the expression levels of fibrosis-related genes/proteins including collagen I, fibronectin, and αSMA; moreover, it suppressed collagen secretion and prevented myofibroblast differentiation in lung fibroblasts. These effects were mediated by FOXO3 stabilization through suppression of TGFß-induced ERK1/2 phosphorylation. MP consistently protected mice from the onset and progression of bleomycin-induced pulmonary fibrosis. CONCLUSION: This study explored the multifaceted roles of MP in counteracting the pathobiological processes of lung fibrosis. The results suggest that further evaluation of MP could yield candidate therapies for IPF.

Partitioning recombinant chitinase from Nicotiana benthamiana by an aqueous two-phase system based on polyethylene glycol and phosphate salts.

The objectives of this study were to purify 42 kDa chitinase derived from Trichoderma asperellum SH16 produced in Nicotiana benthamiana by a polyethylene glycol (PEG)/salt aqueous two-phase system (ATPS). The specific activities of the crude chitinase and the partially purified chitinase from N. benthamiana were about 251 unit/mg and 386 unit/mg, respectively. The study found the 300 g/L PEG 6000 + 200 g/L potassium phosphate (PP) and 300 g/L PEG 6000 + 150 g/L sodium phosphate (SP) systems had the highest partitioning efficiency for each salt in primary extraction. However, among the two types of salt, PP displayed higher efficiency than SP, with a partitioning coefficient K of 4.85 vs. 3.89, a volume ratio V of 2.94 vs. 2.68, and a partitioning yield Y of approximately 95 % vs. 83 %. After back extraction, the enzymatic activity of purified chitinase was up to 834 unit/mg (PP) and 492 unit/mg (SP). The purification factors reached 3.32 (PP) and 1.96 (SP), with recovery yields of about 59 % and 61 %, respectively. SDS-PAGE and zymogram analysis showed that the recombinant chitinase was significantly purified by using ATPS. The purified enzyme exhibited high chitinolytic activity, with the hydrolysis zone's diameter being around 2.5 cm-3 cm. It also dramatically reduced the growth of Sclerotium rolfsii; the colony diameter after treatment with 60 unit of enzyme for 104 spores was only about 1 cm, compared to 3.5 cm in the control. The antifungal effect of chitinase suggests that this enzyme has great potential for applications in agricultural production as well as postharvest fruit and vegetable preservation.

Operative Experience of Esophageal Surgery among General Surgery Residents in the United States: An Analysis of ACGME Operative Case Logs.

INTRODUCTION: Esophageal surgery is an essential component of general surgery training and encompasses several types of cases that are logged by general surgery residents. There is a scarcity of data on the quality and volume of esophageal surgery experience during surgical residency in the United States. We analyzed trends for 9 different esophageal procedure categories logged by residents in the United States, with the aim to identify areas for improvement in training. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from programs accredited by the ACGME over a fourteen-year period from 2009 to 2023. Data on mean esophageal cases reported by graduates, including mean in each procedure subcategory were retrieved. Cases were categorized as either surgeon chief or surgeon junior for each procedure category. Mann-Kendall trend test was used to obtain tau statistics and p-value for trends in mean operative surgical volume for the total number of cases in each operative category over the study period. Trends in surgeon chief and surgeon junior cases were also investigated for each operative category. RESULTS: The mean number of all esophageal procedures performed per resident during their training increased significantly from 10.5 in 2009 to 16 in 2022 (τ = 0.833, p < 0.001). This trend observed among all esophageal procedures during this 14-year study can be largely attributed to the steady increase in the number and proportion of laparoscopic esophageal antireflux procedures performed (τ = 0.950, p < 0.001). Additionally, esophagectomy procedures had a statistically significant, but modest, increase during the study period (τ = 0.505, p = 0.023), from a mean of 1 case during training in 2009 to a peak of 1.3 in 2020. Although the general trend of esophagus procedures increased during the study period, most categories (7 out of 9) either decreased or did not significantly change. Esophagogastrectomy volume decreased significantly by 30%, from 1 per resident during their training in 2009 to 0.7 in 2022 (τ = -0.510, p = 0.018), esophageal diverticulectomy procedures decreased by 50% from 0.2 to 0.1 (τ = -0.609, p = 0.009), and operations for esophageal stenosis decreased by 75% from 0.4 to 0.1 (τ = -0.734, p = 0.001). Mean number of esophageal bypasses (τ = -0.128, p = 0.584), repair of perforated esophageal disease (τ = -0.333, p = 0.156), and other major esophagus procedures (τ = 0.416, p = 0.063) did not significantly change. CONCLUSION: The operative volume of esophageal surgery that general surgery residents in the United States are exposed to has significantly risen over the past 14 years, largely driven by the increase in laparoscopic antireflux procedures. However, given the recent advances and the resultant heterogeneity in both esophageal surgery, the increase in resident operative volume is still inadequate to ensure the training of safe and adept esophageal surgeons, necessitating postresidency specialized training for trainees interested in esophageal surgery.

Billroth-II modified with hinged anti-peristaltic afferent loop versus Roux-en-Y reconstruction after distal gastrectomy for gastric cancer: A propensity-score match analysis.

BACKGROUND: This study aimed to evaluate the effectiveness of modified Billroth-II with a hinged anti-peristaltic afferent loop by comparing it with the Roux-en-Y method. METHODS: We retrospectively analyzed 344 patients with gastric cancer who underwent distal gastrectomy between 2016 and 2021. Propensity score matching was conducted to balance baseline characteristics. RESULTS: After propensity score matching, there were 117 patients in each group. The Billroth-II group was significantly better regarding operating time (184.7 vs 225.3 minutes), postoperative hospital stays (7.9 vs 9.2 days), and time to semi-solid diet tolerance (2.8 vs 3.8 days). The Billroth-II group demonstrated comparable results with the Roux-en-Y group in weight loss, hemoglobin changes, reflux esophagitis, food residue, and gastritis severity. Presentation of bile in gastric remnant was significantly higher in the Billroth-II group (42.9% vs 10.3%). CONCLUSION: There were no significant differences in functional outcomes between Billroth-II and Roux-en-Y reconstructions. The Billroth-II was superior to Roux-en-Y in operating time, hospital stays, and time to semi-solid diet tolerance. The Billroth-II could be considered an acceptable alternative reconstruction after distal gastrectomy.

Trends in gastric surgery operative experience among general surgery residents in the United States: A nationwide retrospective analysis.

BACKGROUND: Gastric surgery is a crucial component of general surgery training. However, there is a paucity of high-quality data on operative volume and the diversity of surgical procedures that general surgery residents are exposed to. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from the American College of Graduate Medical Education-accredited program from 2009 to 2022. Data on the mean number of gastric procedures, including the mean in each subcategory, were retrieved. A Mann-Kendall trend test was used to investigate trends in operative volume. RESULTS: Between 2009 and 2022, the mean overall logged gastric procedures rose significantly (τ = 0.722, P < .001) from 36.2 in 2009 to 49.2 in 2022 (35.9% increase). The most substantial growth was seen in laparoscopic gastric reduction for morbid obesity (mean 1.9 in 2017 to 19 in 2022; τ = 0.670, P = .009). A statistically significant increase was also seen in laparoscopic partial gastric resections, repair of gastric perforation, and "other major stomach procedures" (P < .05 for all comparisons). Open gastrostomy, open partial gastric resections, and open vagotomy all significantly decreased (P < .05 for all comparisons). There was no significant change in the volume of laparoscopic gastrectomy, total gastric resections, and non-laparoscopic gastric reductions for morbid obesity (P > .05 for all comparisons). CONCLUSION: There has been a substantial increase in the volume of gastric surgery during residency over the past 14 years, driven mainly by an increase in laparoscopic gastric reduction. However, there may still be a need for further gastric surgical training to ensure well-rounded general surgeons.

A robust and flexible baculovirus-insect cell system for AAV vector production with improved yield, capsid ratios and potency.

Manufacturing of adeno-associated viruses (AAV) for gene and cell therapy applications has increased significantly and spurred development of improved mammalian and insect cell-based production systems. We developed a baculovirus-based insect cell production system-the SGMO Helper-with a novel gene architecture and greater flexibility to modulate the expression level and content of individual Rep and Cap proteins. In addition, we incorporated modifications to the AAV6 capsid sequence that improves yield, capsid integrity, and potency. Production of recombinant AAV 6 (rAAV6) using the SGMO Helper had improved yields compared to the Bac-RepCap helper from the Kotin lab. SGMO Helper-derived rAAV6 is resistant to a previously described proteolytic cleavage unique to baculovirus-insect cell production systems and has improved capsid ratios and potency, in vitro and in vivo, compared with rAAV6 produced using Bac-RepCap. Next-generation sequencing sequence analysis demonstrated that the SGMO Helper is stable over six serial passages and rAAV6 capsids contain comparable amounts of non-vector genome DNA as rAAV6 produced using Bac-RepCap. AAV production using the SGMO Helper is scalable using bioreactors and has improved yield, capsid ratio, and in vitro potency. Our studies demonstrate that the SGMO Helper is an improved platform for AAV manufacturing to enable delivery of cutting-edge gene and cell therapies.

Identifying Community Safety and Policy-Based Injury Prevention Opportunities to Reduce Golf Cart Injuries.

BACKGROUND: In small US communities, golf cart utilization has become increasingly more common. In the past 3 years, the incidence and severity of pediatric golf cart-related trauma evaluated at our trauma center has noticeably increased. Thus, the aim of this study was to analyze trends, identify risk and protective factors, and provide community-level recommendations to improve golf cart safety for children in a coastal community. METHODS: A retrospective cross-sectional study of our institutional trauma registry was performed. The registry was queried for golf cart injuries between 2012 -2022. Demographics, accident details, hospital course and outcomes were reviewed. Data analysis involved quantitative statistics. Incident locations were mapped, including additional data from the County emergency medical service. Additionally, customer education at four prominent golf rental shops was observed. RESULTS: Annual golf cart-related traumas doubled starting in 2020. Of 235 total patients, 105 (46%) were children. Median age was 11.5 years (range 2-17). 55% were female and 67% were non-Hispanic White. 80% were out-of-county residents. The most common injury location was extremity (56%). Median ISS was 4, and 3% died. Only 10% of children were restrained. 41% were ejected and most (84%) were front-facing passengers. Ejection was associated with more severe injury (OR 4.13, p = 0.01). Most injuries occurred during 5-10 pm (47%), weekends and summertime. Nighttime injuries were more severe than daytime (p = 0.04). A hotspot of crashes was identified in a zone where golf carts were restricted. Rental stores provided education on seat belt use, car seat use for infants, and off-limit zones. However, rules were not enforced. CONCLUSION: Our results inform the following golf cart injury prevention opportunities: raising awareness of injury risks to children in high-tourist areas, partnering with rental stores to enforce rules, improving signage, adding protected lanes, and adopting a no nighttime operation policy. LEVEL OF EVIDENCE: IV.

Targeting Dendritic Cell Dysfunction to Circumvent Anti-PD1 Resistance in Head and Neck Cancer.

PURPOSE: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed. EXPERIMENTAL DESIGN: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model. RESULTS: An aPD1-resistant mouse model showed poor priming in the tumor DLN due to type 1 conventional dendritic cell (cDC1) dysfunction, which correlated with exhausted and poorly responsive antigen-specific T cells. Tumor microenvironment analysis also showed decreased cDC1 in aPD1-resistant tumors compared with sensitive tumors. Following neoadjuvant aPD1 therapy, pathologic responses in patients also positively correlated with baseline transcriptomic cDC1 signatures. In an aPD1-resistant model, intratumoral cDC1 vaccine was sufficient to restore aPD1 response by enhancing T-cell infiltration and increasing antigen-specific responses with improved tumor control. Mechanistically, CCL5 expression significantly correlated with neoadjuvant aPD1 response and enforced expression of CCL5 in an aPD1-resistant model, enhanced cDC1 tumor infiltration, restored antigen-specific responses, and recovered sensitivity to aPD1 treatment. CONCLUSIONS: These data highlight the contribution of tumor-infiltrating cDC1 in HNSCC aPD1 response and approaches to enhance cDC1 infiltration and function that may circumvent aPD1 resistance in patients with HNSCC.

A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

General Versus Nongeneral Anesthesia for Middle Meningeal Artery Embolization for Chronic Subdural Hematomas: Multicenter Propensity Score Matched Study.

BACKGROUND AND OBJECTIVES: The choice of anesthesia type (general anesthesia [GA] vs nongeneral anesthesia [non-GA]) in middle meningeal artery embolization (MMAE) procedures for chronic subdural hematomas (cSDH) differs between institutions and left to care team discretion given lack of standard guidelines. We compare the outcomes of GA vs non-GA in MMAE. METHODS: Consecutive patients receiving MMAE for cSDH at 14 North American centers (2018-2023) were included. Clinical, cSDH characteristics, and technical/clinical outcomes were compared between the GA/non-GA groups. Using propensity score matching (PSM), patients were matched controlling for age, baseline modified Rankin Scale, concurrent/prior surgery, hematoma thickness/midline shift, and baseline antiplatelet/anticoagulation. The primary end points included surgical rescue and radiographic success rates (≥50% reduction in maximum hematoma thickness with minimum 2 weeks of imaging). Secondary end points included technical feasibility, procedural complications, and functional outcomes. RESULTS: Seven hundred seventy-eight patients (median age 73 years, 73.2% male patients) underwent 956 MMAE procedures, 667 (70.4%) were non-GA and 280 were GA (29.6%). After running 1:3 PSM algorithm, this resulted in 153 and 296 in the GA and non-GA groups, respectively. There were no baseline/procedural differences between the groups except radial access more significantly used in the non-GA group (P = .001). There was no difference between the groups in procedural technical feasibility, complications rate, length of stay, surgical rescue rates, or favorable functional outcome at the last follow-up. Subsequent 1:1 sensitivity PSM retained the same results. Bilateral MMAE procedures were more performed under non-GA group (75.8% vs 67.2%; P = .01); no differences were noted in clinical/radiographic outcomes between bilateral vs unilateral MMAE, except for longer procedure duration in the bilateral group (median 73 minutes [IQR 48.3-100] vs 54 minutes [39-75]; P < .0001). Another PSM analysis comparing GA vs non-GA in patients undergoing stand-alone MMAE retained similar associations. CONCLUSION: We found no significant differences in radiological improvement/clinical outcomes between GA and non-GA for MMAE.

Concomitant Surgical Ablation for Treatment of Atrial Fibrillation in Patients Undergoing Minimally Invasive Mitral Valve Surgery: A Single-Center Experience in Vietnam.

BACKGROUND: This study presents the early and midterm outcomes of combining atrial fibrillation (AF) treatment with minimally invasive mitral valve surgery (MIMVS) at our center. METHODS: From January 2017 to June 2022, our center treated a total of 86 patients with both MIMVS and surgical AF ablation. The patient cohort included 62 women (72.1%) and 24 men (27.9%). The average EuroScore II was 2.64 ± 1.49%, and the patients were followed up for an average period of 46.31 ± 9.84 months. RESULTS: Postoperatively, 95.3% of patients experienced a change in sinus rhythm, and 86.2% were discharged in sinus rhythm. The hospital's mortality rate was 2.3%, with a late mortality rate of 3.5%. Survival analysis revealed an atrial fibrillation-free 5-year follow-up rate of 59.1 ± 9.1%. The 5-year survival rate was 92.7 ± 3.3%. CONCLUSION: Our 5-year experience demonstrates that the combination of MIMVS and surgical AF ablation can be routinely performed with favorable peri- and postoperative outcomes. This reflects our hospital's culture and guidance on patient selection, particularly when adopting minimally invasive approaches for multiple procedures.

Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection.

Background: Biomarker testing has gradually become standard of care in precision oncology to help physicians select optimal treatment for patients. Compared to single-gene or small gene panel testing, comprehensive genomic profiling (CGP) has emerged as a more time- and tissue-efficient method. This study demonstrated in-depth analytical validation of K-4CARE, a CGP assay that integrates circulating tumor DNA (ctDNA) tracking for residual cancer surveillance. Methods: The assay utilized a panel of 473 cancer-relevant genes with a total length of 1.7 Mb. Reference standards were used to evaluate limit of detection (LOD), concordance, sensitivity, specificity and precision of the assay to detect single nucleotide variants (SNVs), small insertion/deletions (Indels), gene amplification and fusion, microsatellite instability (MSI) and tumor mutational burden (TMB). The assay was then benchmarked against orthogonal methods using 155 clinical samples from 10 cancer types. In selected cancers, top tumor-derived somatic mutations, as ranked by our proprietary algorithm, were used to detect ctDNA in the plasma. Results: For detection of somatic SNVs and Indels, gene fusion and amplification, the assay had sensitivity of >99%, 94% and >99% respectively, and specificity of >99%. Detection of germline variants also achieved sensitivity and specificity of >99%. For TMB measurement, the correlation coefficient between whole-exome sequencing and our targeted panel was 97%. MSI analysis when benchmarked against polymerase chain reaction method showed sensitivity of 94% and specificity of >99%. The concordance between our assay and the TruSight Oncology 500 assay for detection of somatic variants, TMB and MSI measurement was 100%, 89%, and 98% respectively. When CGP-informed mutations were used to personalize ctDNA tracking, the detection rate of ctDNA in liquid biopsy was 79%, and clinical utility in cancer surveillance was demonstrated in 2 case studies. Conclusion: K-4CARE™ assay provides comprehensive and reliable genomic information that fulfills all guideline-based biomarker testing for both targeted therapy and immunotherapy. Integration of ctDNA tracking helps clinicians to further monitor treatment response and ultimately provide well-rounded care to cancer patients.

Pacemaker implantation after concomitant tricuspid valve repair in patients undergoing minimally invasive mitral valve surgery: Results from the Mini-Mitral International Registry.

Objective: Randomized evidence suggests a high risk of pacemaker implantation for patients undergoing mitral valve (MV) surgery with concomitant tricuspid valve repair (cTVR). We investigated the impact of cTVR on outcomes in the Mini-Mitral International Registry. Methods: From 2015 to 2021, 7513 patients underwent minimally invasive MV with or without cTVR in 17 international centers (MV: n = 5609, cTVR: n = 1113). Propensity matching generated 1110 well-balanced pairs. Multivariable analysis was applied. Results: Patients with cTVR were older and had more comorbidities. Propensity matching eliminated most differences except for more TR in patients who underwent cTVR (77.2% vs 22.1% MV, P < .001). Mean matched age was 71 years, and 45% were male. European System for Cardiac Operative Risk Evaluation II was still 2.68% (interquartile range [IQR], 0.80-2.63) vs 1.9% (IQR, 1.12-3.9) in matched MV (P < .001). MV replacement (30%) and atrial fibrillation surgery (32%) were similar in both groups. Cardiopulmonary bypass (161 minutes [IQR, 133-203] vs MV: 130 minutes [IQR, 103-166]; P < .001) and crossclamp times (93 minutes [IQR, 66-123] vs MV: 83 minutes [IQR, 64-107]; P < .001) were longer with cTVR. Although in-hospital mortality was similar (cTVR: 3.3% vs MV: 2.2%; P = .5), postoperative pacemaker implantations (9% vs MV: 5.8%; P = .02), low cardiac output syndrome (7.7% vs MV: 4.4%; P = .02), and acute kidney injury (13.8% vs MV: 10%; P = .01) were more frequent with cTVR. cTVR eliminated relevant TR in most patients (greater-than-moderate TR: 6.8%). Multivariable analysis identified MV replacement, atrial fibrillation, and cTVR as risk factors of postoperative pacemaker implantation. Conclusions: cTVR in minimally invasive MV surgery is an independent risk factor for pacemaker implantation in this international registry. It is also associated with more bleeding, low output syndrome, and acute kidney injury. It remains unclear whether technical or patient factors (or both) explain these differences.

Laparoscopic-cholangioscopic cooperative modified tunnel technique for hepatolithiasis combined with dilated common bile duct: A case report and literature review.

INTRODUCTION: Intrahepatic and extrahepatic lithiasis, a condition characterized by the presence of stones in the liver and bile ducts, is a common disease in Asia, particularly in East and Southeast Asia. We report a case with laparoscopic exploration of the common bile duct using a flexible cholangioscope and modified trans-common bile duct tunnel for hepatolithiasis combined with the dilated common bile duct. PRESENTATION OF CASE: A 35-year-old male patient has had chronic epigastric and right upper quadrant pain. The common bile duct was 11 mm dilated, and hepatolithiasis was also present, according to an upper abdomen MRI. The largest stone measured between 14 and 21 mm. A modified trans-common bile duct tunnel from the abdominal wall into the common bile duct was used in a laparoscopic procedure to examine the common bile duct. Complications during the procedure or following it were not present. The procedure took 120 min, and the blood loss was about 50 ml. The patient was discharged on the sixth postoperative day, and a follow-up visit one month later revealed that single-session stone clearance had been accomplished. DISCUSSION: Laparoscopic exploration of the common bile duct using a cholangioscope and modified trans-choledochal tube is applicable in selected patients and can be effectively and safely used to treat hepatolithiasis combined with the dilated common bile duct. CONCLUSION: In this case, we present an innovative approach for hepatolithiasis when combined with dilated common bile duct.

Prevalence of coeliac disease in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: There is some evidence of a higher prevalence of coeliac disease (CD) among patients with SLE than in the general population. However, the prevalence estimates vary substantially. OBJECTIVE: To investigate the prevalence of CD among patients with SLE through systematic review and meta-analysis. METHODS: We performed searches in the databases of Medline, Embase, Cochrane and Web of Science Core Collection between 1 January 1990 and 9 July 2023. A total of 2053 publications were rendered in the searches, of which 68 were reviewed in full text and 14 included in the analyses. Primary analysis estimated the pooled prevalence of biopsy-verified CD in patients with SLE. In the secondary analysis, the prevalence of serological markers indicative of CD was investigated. The quality of studies was appraised using the Joanna Briggs Institute Critical Appraisal Tool. We conducted meta-regression analyses to investigate associations between the prevalence of CD in individuals with SLE and publication year, study population size, CD prevalence in the general population, proportion of females and quality assessment score. RESULTS: A total of 14 studies met the inclusion criteria, of which 11 were included in the primary analysis of biopsy-verified CD. Among 1238 patients with SLE, 14 had CD. The weighted pooled prevalence of CD was 0.7% (95% CI 0.0 to 1.8). The weighted pooled prevalence of CD serological markers in 1063 patients with SLE was 3.7% (95% CI 1.4 to 6.7). In meta-regression analyses, no associations between CD prevalence and study characteristics, demographics and quality assessment scores were found. CONCLUSIONS: In this meta-analysis, we found a weighted pooled prevalence of biopsy-verified CD in patients with SLE comparable with the prevalence in the general population. Our findings do not support routine screening for CD in patients with SLE. However, individual screening could be considered in cases of clinical suspicion and additional risk factors for CD. PROSPERO REGISTRATION NUMBER: CRD42022339594.