Background: EGFR exon 20 insertions account for 1% to 10% of EGFR mutations in nonsmall-cell lung cancer (NSCLC) and are known to confer resistance to traditional tyrosine kinase inhibitors. However, the prognostic significance of these mutations in early-stage resected NSCLC remains unclear. This study assesses outcomes in patients with resected NSCLC harboring EGFR exon 20 insertions, comparing them to patients with common EGFR mutations and those with wild-type EGFR. Methods: We retrospectively reviewed 3,235 patients who underwent resection for NSCLC at Tri-Service Hospital between 2008 and 2021. After excluding cases lacking EGFR testing, incomplete data, or advanced-stage disease, 44 patients with exon 20 insertions were matched to 602 patients with common EGFR mutations and 729 with wild-type EGFR. Clinical characteristics, disease-free survival (DFS), and overall survival (OS) were analyzed using the Kaplan-Meier method, with statistical comparisons performed using the log-rank test. Cox proportional hazards models were used to identify independent prognostic factors. Results: Patients with exon 20 insertions were younger and more frequently presented with stage IA disease. The 5-year DFS was 79% in the exon 20 insertion group, compared to 81% in the common mutation group and 83.9% in the wild-type group. The 5-year OS was 78.5% for exon 20, 91.9% for common mutations, and 91% for wild-type. While no significant differences in DFS or OS were observed between groups, the exon 20 insertion group had a higher incidence of secondary cancers. Multivariable analysis indicated that exon 20 insertion was independently associated with worse OS, but not with DFS. Conclusion EGFR exon 20 insertions do not significantly shorten DFS, but are associated with inferior OS in early-stage resected NSCLC. Given the limited treatment options, the role of adjuvant therapy warrants further investigation.

Purpose: Senior nursing and medical interns’ lack of familiarity and confidence with respect to practicing universal precaution for the prevention of occupational needlestick or sharp injuries may harm themselves. Trainees’ self-reported needlestick or sharp injury rate was known to be especially high during the first 2 months of internship in Taiwan. This prospective cohort study aimed to assess the effect of newly developed virtual reality (VR) game, which uses Gagne’s learning model to improve universal precaution for needlestick or sharp injury prevention and decrease the rates of needle stick or sharp injuries in new-coming medical and nursing interns in Taiwan. Methods: From 2017 to 2019, the VR system was developed and applied in training of 59 new-coming nursing and 50 medical interns. Occupational needlestick or sharp injury prevention was sought to be achieved through a game of right and wrong choices for safe or unsafe universal precaution behaviors. Results: In comparison with medical interns, a higher proportion of nursing interns had past experiences of deep occupational needlestick or sharp injury. Before VR training, the familiarity and confidence for needlestick or sharp injury prevention were higher among nursing interns than medical interns. Trainees with past experiences of deep needlestick or sharp injury exhibited better performance on the accuracy rate and time needed to complete 20 decisions than those without past experiences in VR practice. All trainees showed an improved performance after VR training. A high proportion of trainees reported that the VR-based training significantly decreased their anxiety about needlestick or sharp injury prevention. Conclusion This self-developed VR game system using Gagne’s flow improved universal precaution for needlestick or sharp injury prevention and reduced the needlestick or sharp injury rates in the first 2 months of nursing and medical internship.

Purpose: In contrast to the core part of the clinical interviewing and physical examination (PE) skills course, corresponding to the basic, head-to-toe, and thoracic systems, learners need structured feedback in the cluster part of the course, which includes the abdominal, neuromuscular, and musculoskeletal systems. This study evaluated the effects of using Dreyfus scale-based feedback, which has elements of continuous professional development, instead of Likert scale-based feedback in the cluster part of training in Taiwan. Methods: Instructors and final-year medical students in the 2015–2016 classes of National Yang-Ming University, Taiwan comprised the regular cohort, whereas those in the 2017–2018 classes formed the intervention cohort. In the intervention cohort, Dreyfus scale-based feedback, rather than Likert scale-based feedback, was used in the cluster part of the course. Results: In the cluster part of the course in the regular cohort, pre-trained standardized patients rated the class climate as poor, and students expressed low satisfaction with the instructors and course and low self-assessed readiness. In comparison with the regular cohort, improved end-of-course group objective structured clinical examination scores after the cluster part were noted in the intervention cohort. In other words, the implementation of Dreyfus scale-based feedback in the intervention cohort for the cluster part improved the deficit in this section of the course. Conclusion The implementation of Dreyfus scale-based feedback helped instructors to create a good class climate in the cluster part of the clinical interviewing and PE skills course. Simultaneously, this new intervention achieved the goal of promoting medical students’ readiness for interviewing, PE, and self-directed learning.

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1