CAN008 prolongs overall survival in patients with newly diagnosed GBM characterized by high tumor mutational burden.

BACKGROUND: A previous phase 1 dose-escalation study in Taiwan indicated CAN008 (asunercept) with standard concurrent chemoradiotherapy (CCRT) improved progression-free survival (PFS) in newly diagnosed glioblastoma (GBM) patients. This study evaluates the efficacy of CAN008 in promoting overall survival (OS) and identifies genetic alterations associated with treatment responses. METHODS: We compared OS of 5-year follow-ups from 9 evaluable CAN008 cohort patients (6 received high-dose and 3 received low-dose) to a historical Taiwanese GBM cohort with 164 newly diagnosed patients. CAN008 treatment response-associated genetic alterations were identified by whole-exome sequencing and comparing variant differences between response groups. Associations among patient survival, tumor mutational burden (TMB), and genetic alterations were analyzed using CAN008 cohort and TCGA-GBM dataset. RESULTS: OS for high-dose CAN008 patients at 2 and 5 years was 83% and 67%, respectively, and 40.1% and 8.8% for the historical GBM cohort, respectively. Better OS was observed in the high-dose CAN008 cohort (without reaching the median survival) than the historical GBM cohort (median OS: 20 months; p=0.0103). Five high-dose CAN008 patients were divided into good and poor response groups based on their PFS. A higher variant count and TMB were observed in good response patients, whereas no significant association was observed between TMB and patient survival in the newly diagnosed TCGA-GBM dataset, suggesting TMB may modulate patient CAN008 response. CONCLUSION: CAN008 combined with standard CCRT treatment prolonged the PFS and OS of newly diagnosed GBM patients compared to standard therapy alone. Higher treatment efficacy was associated with higher TMB.

[Improving the Pap Smear Screening Rate for Cervical Cancer in a Health Management Center: A Quality Improvement Program].

BACKGROUND & PROBLEMS: Early detection tests are highly effective in helping adult women prevent the onset of cervical cancer. However, the cervical Pap smear screening rate in a health management center was only 54.3% in 2020. PURPOSE: This project was developed to improve the Pap smear screening rate for cervical cancer in a health management center. RESOLUTION: The strategies developed included revising the health examination lists, developing an online appointment booking system, designing a patient decision aid, creating a standardized simulation moulage for education, and rechecking patient's National Health Insurance cards. RESULTS: After implementation of these strategies, the Pap smear screening rate for cervical cancer rose from 54.3% to 81.2%. The screening rate at the health management center in 2022 reached 96.6%. CONCLUSIONS: Shared decision-making can elucidate the comprehensive options available to clients and support them in considering their options and achieving informed choices regarding Pap smear preferences.

Prognostic value of an APOBEC3 deletion polymorphism for glioma patients in Taiwan.

OBJECTIVE: The molecular pathogenesis of malignant gliomas, characterized by diverse tumor histology with differential prognosis, remains largely unelucidated. An APOBEC3 deletion polymorphism, with a deletion in APOBEC3B, has been correlated to risk and prognosis in several cancers, but its role in glioma is unclear. The authors aimed to examine the clinical relevance of the APOBEC3 deletion polymorphism to glioma risk and survival in a glioma patient cohort in Taiwan. METHODS: The authors detected deletion genotypes in 403 glioma patients and 1365 healthy individuals in Taiwan and correlated the genotypes with glioma risk, clinicopathological factors, patient survival, and patient sex. APOBEC3 gene family expression was measured and correlated to the germline deletion. A nomogram model was constructed to predict patient survival in glioma. RESULTS: The proportion of APOBEC3B-/- and APOBEC3B+/- genotypes was higher in glioblastoma (GBM) patients than healthy individuals and correlated with higher GBM risk in males. A higher percentage of cases with APOBEC3B- was observed in male than female glioma patients. The presence of APOBEC3B-/- was correlated with better overall survival (OS) in male astrocytic glioma patients. No significant correlation of the genotypes to glioma risk and survival was observed in the female patient cohort. Lower APOBEC3B expression was observed in astrocytic glioma patients with APOBEC3B-/- and was positively correlated with better OS. A 5-factor nomogram model was constructed based on male patients with astrocytic gliomas in the study cohort and worked efficiently for predicting patient OS. CONCLUSIONS: The germline APOBEC3 deletion was associated with increased GBM risk and better OS in astrocytic glioma patients in the Taiwan male population. The APOBEC3B deletion homozygote was a potential independent prognostic factor predicting better survival in male astrocytic glioma patients.

[Project to Improve Satisfaction in the Conscription Physical Examinations Service].

BACKGROUND & PROBLEMS: In response to a decrease in satisfaction to 69.3%, we resolved to optimize the process of conducting conscription physical examinations. After an investigatory panel conducted an analysis, the following problems were identified. Firstly, the poorly designed route lead to dense queues between exam stations. Secondly, the procedures for changing the dates of conscription physical examinations were cumbersome. Lastly, unexpected contacts between examinees and the patients in the hospital occurred from time to time, which increases the risk of cross infection. PURPOSE: This project was developed to improve the level of satisfaction in conscription physical examinations and increase the quality of medical services provided. RESOLUTION: After brainstorming and reviewing the related literature, we identified several actions to address and resolve the problems. We adopted non-crossing lines, divided the servicemen's cabins for inspection, simplified the information system process, relocated the physical examination venue, and planned education and training. RESULTS: Satisfaction with the examination process increased from 69.3% to 90.3%. CONCLUSIONS: A survey-based review of the conscription physical examination process should be conducted annually to ensure the procedures are as smooth as possible and to improve the quality of medical services provided.

[Reducing Abnormal Culture Rates of Digestive Endoscopy in a Health Management Center].

BACKGROUND: Endoscopic evaluation plays an indispensable role in medical treatments designed to prevent, diagnose, and cure gastrointestinal disease. Surveillance culture monitoring may be useful in monitoring the outcome of reprocessing. PURPOSE: In this project, microbiologic surveillance cultures were employed to improve the quality of flexible endoscope disinfection. RESOLUTION: This project, implemented from February 1st, 2018 to February 28th, 2019, used several approaches to improve the positive culture rate. We redesigned and implemented the standard operating procedures for endoscope reprocessing, established an in-service training course, provided education materials on reprocessing, and installed a storage cabinet that custom-built to accommodate the endoscope. RESULTS: The positive culture rate was reduced from 5.8% to 0%. CONCLUSIONS: Endoscopy culturing is a useful method to assess the effectiveness of standard reprocessing procedures. The development of guidelines and skill practices should follow current, evidence-based practice and infection prevention principles, and related documents should be organized. We suggest regularly deploying quality-improvement techniques to improve performance and service delivery.

Colonization With Multidrug-Resistant Organisms Among Healthy Adults in the Community Setting: Prevalence, Risk Factors, and Composition of Gut Microbiome.

BACKGROUND: The prevalence of colonization with multidrug-resistant organisms (MDROs) among healthy adults in the community is largely unknown. This study investigated the colonization rate of multidrug-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in the community in Taiwan, and compared the gut microbiota between MDRO carriers and non-carriers. METHODS: This prospective cohort study was conducted from March 2017 to February 2018 at the Hsin-Chu and Jin-Shan branches of National Taiwan University Hospital. Nasal swabs and stool samples were obtained from healthy adults attending a health examination to screen for MDROs. Bacteria isolates of MDROs were tested for antibiotic susceptibility and resistant genes. Relevant data were collected using a standardized questionnaire to evaluate the risk factors for MDROs carriage, and 16S rRNA metagenomics sequencing was performed to analyze gut microbiota. RESULTS: Among 187 participants, 4.6% (8/174) carried MRSA and 41.4% (77/186) carried third-generation cephalosporin-resistant (3GC-R) Escherichia coli or Klebsiella pneumoniae. The carriage rate of AmpC beta-lactamases and ESBL-producing strains were 16.1 and 27.4%, respectively. No carbapenem-resistant Enterobacteriaceae (CRE) or VRE were detected. The dominant resistant gene of E. coli isolates was CTX-M-type (73%), while that of K. pneumoniae was AmpC beta-lactamases (80%). In the multivariate analysis, the significant risk factors for carrying 3GC-R E. coli or K. pneumoniae were being an employee of technology company A [adjusted odds ratio (aOR) 4.127; 95% confidence interval (CI) 1.824-9.336; p = 0.001], and traveling to Southeast Asia in the past year (aOR 6.545; 95% CI 1.071-40.001; p = 0.042). The gut microbiota analysis showed that the phylum Proteobacteria and the family Enterobacteriaceae were significantly more abundant in 3GC-R E. coli and K. pneumoniae carriers. CONCLUSION: A high rate of Taiwanese adults in the community carried 3GC-R Enterobacteriaceae, while no CRE or VRE colonization was noted. Compared with non-carriers, an expansion of Enterobacteriaceae in gut microbiota was found among 3GC-R Enterobacteriaceae carriers.

Functional Change of Effector Tumor-Infiltrating CCR5+CD38+HLA-DR+CD8+ T Cells in Glioma Microenvironment.

Human glioma facilitates an impaired anti-tumor immunity response, including defects in circulation of T lymphocytes. The level of CD8+ T-cell activation acts as an immune regulator associated with disease progression. However, little is known about the characteristics of peripheral and tumor-infiltrating CD8+ T cells in patients with glioma. In this study, we examined the level of CD8+ T-cell activation in a group of 143 patients with glioma and determined that peripheral CD3+ T cells decreased in accordance with disease severity. The patients' peripheral CD8+ T-cell populations were similar to that of healthy donors, and a small amount of CD8+ tumor-infiltrating lymphocytes was identified in glioma tissues. An increase in activated CD8+ T cells, characterized as CD38+HLA-DR+, and their association with disease progression were identified in the patients' peripheral blood and glioma, and shown to display enriched CCR5+ and TNFR2+ expression levels. Ex vivo examination of CD38+HLA-DR+CD8+ T cells indicated that this subset of cells displayed stronger secretion of IFN-γ and IL-2 before and after a 6-h stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin (ION) relative to healthy CD38+HLA-DR+CD8+ T cells, indicating the functional feasibility of CD38+HLA-DR+CD8+ T cells. Higher CCL5 protein and mRNA levels were identified in glioma tissues, which was consistent with the immunohistochemistry results revealing both CCL5 and CD38+HLA-DR+CD8+ T cell expression. Patients' CCR5+CD38+HLA-DR+CD8+ T cells were further validated and shown to display increases in CD45RA+CCR7- and T-bet+ accompanied by substantial CD107-a, IFN-γ, and Granzyme B levels in response to glioma cells.

The impact of door-to-electrocardiogram time on door-to-balloon time after achieving the guideline-recommended target rate.

BACKGROUND: Little is known about the components and contributing factors of door-to-balloon time after implementation of Door-to-Balloon Alliance quality-improving (QI) strategies, including the impact of door-to-ECG time on door-to-balloon time. OBJECTIVE: We investigated whether modification of emergency department (ED) triage processes could improve door-to-ECG and door-to-balloon times after implementation of QI strategies. METHODS: This was a retrospective before-and-after study of a prospectively collected database. From June 2014 to October 2014, interventions were implemented in our ED, including a protocol-driven ECG initiation and moving an ECG station and technician to the triage area. The primary outcome was the percentage of patients with ST-elevation myocardial infarction (STEMI) who received ECG within 10 min of arrival; the secondary outcome was the percentage of patients with door-to-balloon times of <90 min from arrival. Patients from the year pre- and post-QI initiative were defined as the control and intervention groups, respectively. RESULTS: Enrollment comprised 214 patients with STEMI: 109 before the intervention and 105 after the intervention. We analyzed the components of the door-to-balloon process and found the door-to-ECG process was the most critical interval of delay (20.8%). Unrecognized symptoms were the most common cause of delay in the door-to-ECG process resulting in a significant impact on the door-to-balloon time. The intervention group had a higher percentage of patients with door-to-ECG times <10 min than did the control group (93.3% vs. 79.8%, p = 0.005), with a corresponding improvement in door-to-balloon times <90 min (91.1% vs. 76.2%, p = 0.007). In subgroup analysis, the intervention benefits occurred only in non-transferred or walk-in patients. After adjustment for possible co-variates, the QI interventions remained a significant contributing factor for achieving the door-to-ECG and door-to-balloon targets. CONCLUSIONS: The modification of ED triage processes through implementation of QI strategies are effective in achieving better door-to-ECG times and thus, achieving door-to-balloon times <90 min. In patients presenting with ambiguous symptoms, improved door-to ECG target achievement rates, through a protocol-driven and multidisciplinary approach allows for earlier identification of STEMI.

Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.

Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.