Kaohsiung Chang Gung Memorial Hospital Research Articles

Prognostic factors and treatment responses among patients with gross residual disease in differentiated thyroid cancer

Background: Various postoperative staging systems were developed to assess the outcome of differentiated thyroid cancer (DTC) from initial risk after surgery to dynamic changing prognosis during follow-up. The objective of our retrospective cohort study was to identify risk factors contributing to macroscopic positive surgical margin (R2 resection) and parameters in discriminating the treatment responses and prognosis among R2 patients. Methods: In total, 242 DTC patients with extrathyroidal extension who underwent a thyroidectomy at Kaohsiung Chang Gung Memorial Hospital between January 2013 and July 2018, were included. The patients were grouped according to the presence or absence of gross residual disease (R2). The R2 patients were further classified into two categories according to their treatment response into excellent and non-excellent groups. The parameters and treatment outcomes were compared between these groups. Results: The mean follow-up time was 45.3 months. 207 (85.5%) patients had either surgery-free or microscopic margins (R0/R1), while 35 (14.5%) had R2 resection. In the R2 group (n = 35), 15 (42.9%) patients achieved an excellent response, while 20 (57.1%) achieved a non-excellent response. Statistically significant differences were observed in the extent of neck dissection, TSH-Tg level, post-RAI Tg level, nodal status, and recurrence between the two groups. The Kaplan–Meier curves for 5-year local and distant recurrence-free survival (LRFS and DRFS) of R0/R1 vs. R2 patients were 90.0% vs. 66.3%, and 98.4% vs.90.7% respectively, (p <0.001). Among the R2 patients, the excellent responders had a higher LRFS than non-excellent responders (93.3% vs. 45.1%, p=0.008). Conclusion: There are significant disparities in RFS among R2 patients with different treatment responses. The nodal status of PTC and thyroglobulin level after thyroidectomy and RAI were factors contributing to difference in their treatment responses.

Immune control in Kawasaki disease knowledge mapping: a bibliometric analysis.

Kawasaki disease is a systemic vascular disease with an unclear pathophysiology that primarily affects children under the age of five. Research on immune control in Kawasaki disease has been gaining attention. This study aims to apply a bibliometric analysis to examine the present and future directions of immune control in Kawasaki disease. By utilizing the themes "Kawasaki disease," "Kawasaki syndrome," and "immune control," the Web of Science Core Collection database was searched for publications on immune control in Kawasaki disease. This bibliometric analysis was carried out using VOSviewers, CiteSpace, and the R package "bibliometrix." In total, 294 studies on immune control in Kawasaki disease were published in Web of Science Core Collection. The three most significant institutions were Chang Gung University, the University of California San Diego, and Kaohsiung Chang Gung Memorial Hospital. China, the United States, and Japan were the three most important countries. In this research field, Clinical and Experimental Immunology was the top-referred journal, while the New England Journal of Medicine was the most co-cited journal. The Web of Science Core Collection document by McCrindle BW et al. published in 2017 was the most cited reference. Additionally, the author keywords concentrated on "COVID-19," "SARS-CoV-2," and "multisystem inflammatory syndrome in children" in recent years. The research trends and advancements in immune control in Kawasaki disease are thoroughly summarised in this bibliometric analysis, which is the first to do so. The data indicate recent research frontiers and hot directions, making it easier for researchers to study the immune control of Kawasaki disease.

Abstract 5533: The difference of immune microenvironment betweende novometastatic and non-metastatic microsatellite instability-high colorectal cancer

Abstract Introduction: Microsatellite instability-high (MSI-H) colorectal cancer (CRC) consists of 15% of all CRC but only 2-4% of metastatic CRC. The favorable prognosis of non-metastatic (early-stage) MSI-H CRC may be related to vigorous immune reaction in tumor microenvironment. However, the mechanisms of immune evasion in metastatic (late stage) MSI-H CRC are largely unknown. Materials and Methods: We retrospectively collected patients with MSI-H CRC from National Taiwan University Hospital and Kaohsiung Chang Gung Memorial Hospital. The archival tumor specimens were used for immune cells analysis by Nanostring PanCancer Immune Panel, and spatial immune characterization by multiplex immunofluorescence stains. Only surgical resected primary tumors and metastatic tumors were included. Gene expression and immune cells composition were compared between non-metastatic and de novo metastatic tumors. Results: We enrolled 59 and 27 patients with early-stage and late-stage MSI-H CRC, respectively. Twelve metastatic site tumors were also collected. The clinicopathologic characteristics between patients who have early- and late-stage MSI-H CRC were not significantly different. There are heterogeneous immune cell compositions in these 98 MSI-H tumors. Compared to early-stage MSI-H tumors, there are significantly fewer cytotoxic (difference -0.497, p = 0.001) and dendritic cells (difference -0.528, p = 0.021) in late-stage MSI-H tumors. Gene set enrichment analysis disclosed significantly decrease in the expression of JAK-STAT-IFN-γ- and antigen processing-related pathways in late-stage MSI-H tumors. The top 5 genes with significantly differential expression between late-stage and early-stage tumors are C7, TNFRSF12A, MFGE8(up-regulated) and CXCL5, IFNL1, GZMH, HMGB1 and CXCR1 (down-regulated). Conclusions: There are significantly fewer cytotoxic and dendritic cells in late-stage MSI-H CRC, compared to early-stage MSI-H CRC, which is associated with decrease expression in JAK-STAT-IFN-γ- and antigen processing-related pathways. Citation Format: Kuo-Hsing Chen, Chia-Lang u Hs, Yu-Li Su, Chang-Tsu Yuan, Jia-Huei Tsai, Yi-Hsin Liang, Ann-Lii Cheng, Kun-Huei Yeh. The difference of immune microenvironment betweende novometastatic and non-metastatic microsatellite instability-high colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5533.

Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma: The Effectiveness of Different Particle Sizes in Downstaging and Bridging in Living Donor Liver Transplantation

To compare the effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) with different particle sizes in bridging and downstaging in pretransplant hepatocellular carcinoma patients. Assess the recurrent and survival rates after living donor liver transplantation (LDLT). Retrospective review of 580 patients who underwent TACE using DEB from August 2012 to June 2020 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and post-TACE computed tomography scan images of the liver were reviewed, and treatment responses were assessed using modified Response Evaluation Criteria in Solid Tumors criteria. Patients were divided by who met the criteria (n = 342) or beyond (n = 238) the University of California San Francisco criteria for successful bridging and downstaging rate evaluation. Each group was divided into subgroups according to DEB particle sizes (group A: <100μm, group B: 100-300 μm, group C: 300-500 μm, and group D: 500-700 μm) to compare objective response rate and post-LDLT survival rate. Overall successful bridging and downstaging rate is 97.1% and 58.4%, respectively, in the group of patients who meet the criteria (n = 332) and are beyond (n = 139) the University of California San Francisco criteria. Group B (100-300 μm) had a higher successful bridging rate (99.5%, P = .003) and downstaging rate (63.8%, P = .443). This subgroup also demonstrated a higher objective response rate in single (93.2%, P = .038) tumors, multiple (83.3%, P = .001) tumors, and tumors with size less than 5 cm (93.9%, P = .005). There are no significant differences in post-LDLT overall survival rate between different particle sizes. TACE with 100 to 300 μm DEB particles is associated with a better chance of bridging and downstaging hepatocellular carcinoma patients to LDLT.

A comprehensive study of pre-eclampsia in IVF and natural conceptions: clinical phenotypes, perinatal outcomes and neonatal echocardiography

Research question: What differences exist in the preeclampsia phenotypes, perinatal outcomes, and neonatal echocardiography between pregnancies conceived naturally and through in vitro fertilization? DesignFrom January 2002 to December 2022, a total of 610 women diagnosed with preeclampsia were included. This research was conducted within the IVF and Maternal-Fetal Medicine Department of Kaohsiung Chang Gung Memorial Hospital. Participants were divided into two groups, one achieved pregnancy through IVF and another, spontaneously. This study reviewed preeclampsia phenotypes, perinatal outcomes, and screening of newborn echocardiography. Results: After conducting propensity score matching, the natural conception group had a higher prevalence of early-onset preeclampsia (53.9% vs. 37.7%, p = 0.04) and exhibited more severe features (89.1% vs. 69.8%, p = 0.01), when compared to the IVF group. Regarding perinatal outcomes, neonates in the IVF group had higher placental weights than those in the natural conception group (580 vs. 480 g, p = 0.031). There were no differences in the prevalence of abnormal newborn echocardiography. Multivariate analysis showed that greater gestational age at delivery reduced the likelihood of abnormal cardiac echo (RR 0.950, p=0.001), while pregestational diabetes increased it (RR 1.451, p=0.044). Septal defects were the most common, occurring in 15.5% of infants. Conclusion: Our study revealed that the impact of IVF conception on the preeclampsia severity is not as expected. Through neonatal echocardiography, a higher occurrence of abnormalities was observed compared to the general population. Furthermore, these issues were not linked to conception method, suggesting undisclosed factors that could influence the clinical features and perinatal outcomes of preeclampsia.

Factors associated with prolonged progression-free survival of patients treated with first-line afatinib for advanced epidermal growth factor receptor-mutated non-small cell lung cancer.

This study aimed to investigate the factors associated with prolonged progression-free survival (PFS) (>36 months) of advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first-line afatinib. We performed a retrospective analysis of data of patients with advanced EGFR-mutated NSCLC receiving first-line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022. The data of 546 treatment-naïve EGFR-mutated advanced NSCLC patients were analyzed. Median PFS and overall survival were 14.5 months and 27.2 months, respectively. The PFS of 462 patients (84.6%) was less than 36 months and of 84 patients (15.4%) was more than 36 months. The PFS > 36 months group had a significantly higher percentage of patients with uncommon mutations (p = 0.002). The PFS ≤36 months group had significantly higher incidences of bone, liver, and adrenal metastases (all p < 0.05) and a higher rate of multiple distant metastases. Multivariate logistic regression analysis showed that liver metastasis was negatively and independently associated with prolonged PFS (adjusted odds ratio = 0.246 [95% CI: 0.067-0.908], p = 0.035). The median overall survival of the PFS >36 months group was 46.0 months and that of the PFS ≤36 months group was 22.9 months (log-rank test, p < 0.001). We found that EGFR-mutated NSCLC patients receiving first-line afatinib were prone to shorter PFS if they had distant organ metastasis, especially liver metastasis.

Peri-operative extracorporeal membrane oxygenation in adult and pediatric living donor liver transplantation: a single-center experience.

Extracorporeal membrane oxygenation (ECMO) is a potential rescue therapy for patients with acute cardiopulmonary dysfunction refractory to conventional treatment. In this study, we described the clinical profiles and outcomes of adult and pediatric living donor liver transplantation (LDLT) patients who received ECMO support during the peri-operative period. From June 1994 to December 2020, eleven out of the 1,812 LDLTs performed at Kaohsiung Chang Gung Memorial Hospital required ECMO support: six for respiratory failure, three for cardiogenic shock, and two for refractory septic shock. Comparison between the survivor and non-survivor groups was made. The survival rate for liver transplantation (LT) patients on ECMO support is 36.4%-40% in adults and 33.3% in pediatrics, while the survival rate per indication is as follows: acute respiratory distress syndrome (ARDS) (50%), cardiogenic shock (33.3%), and sepsis (0%). Shorter durations of LT-to-ECMO and pre-ECMO mechanical ventilation were observed in the survivor group. On the other hand, we observed persistently elevated total bilirubin levels in non-survivors, while none of the survivors had aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels >1,000 U/L. A higher proportion of non-survivors were on concurrent continuous renal replacement therapy (CRRT). Our experience has proven ECMO's utility during the peri-operative period for both adult and pediatric LDLT patients, more specifically for indications other than septic shock. Further studies are needed to better understand the factors leading to poor outcomes in order to identify patients who will more likely benefit from ECMO.

A Prospective Study of Clinical Features of Anterior Uveitis in Taiwan.

In this study, we reported the patterns, epidemiology, and clinical features of anterior uveitis (AU) in Taiwan, an area of Eastern Asia. This prospective, cross-sectional case series study was performed to identify patients with AU at two tertiary medical centers (Kaohsiung Chang Gung Memorial Hospital and Kaohsiung Veterans General Hospital) located at the southern Taiwan between December 1, 2018, and March 31, 2020. The clinical diagnoses, ocular presentations, and laboratory data, including the results of the aqueous polymerase chain reaction tests, were investigated in these patients. A total of 112 patients, with a mean age of 48.9 years, were included. Most patients (87.5%) presented with unilateral eye disease, with 30 cases of ocular hypertension at the first presentation (27%). The most common clinical diagnoses were idiopathic AU (37.5%), human leukocyte antigen (HLA)-B27-associated acute AU (25.0%), and herpetic AU (18.8%). Among patients with herpetic AU, cytomegalovirus (CMV) was the most common pathogen (17/21, 81%). Compared to HLA-B27-associated acute AU, CMV-related AU was mostly observed in patients that were older in age, exhibited higher intraocular pressure, more keratic precipitates, greater iris atrophy, and more pseudophakia, but was least reported in those with posterior synechiae. This prospective study identified the pattern and clinical features of AU in southern Taiwan.

Real-world efficacy and safety of low-dose pembrolizumab in patients with advanced and refractory gynecologic cancers

The approved standard dose of pembrolizumab (200mg administrated every 3 weeks) for cancer treatment imposes a significant financial burden on patients. However, no study has analyzed the clinical outcomes of low-dose pembrolizumab among individuals diagnosed with gynecologic cancer. The primary objective of this study was to assess the effectiveness and safety of a low-dose pembrolizumab regimen in real-world clinical practice. We retrospectively assessed the efficacy and safety data of patients with gynecologic malignancies who received pembrolizumab between 2017 and 2022at Kaohsiung Chang Gung Memorial Hospital. Furthermore, we conducted a comparative analysis of the objective response rate (ORR) and progression-free survival (PFS) between patients with deficient mismatch repair (dMMR) and proficient MMR (pMMR). A total of thirty-nine patients were included and received pembrolizumab at fixed dosages of 50mg (5.1%), 100mg (84.6%) and 200mg (10.3%) per cycle. Compared to the pMMR group, the dMMR group exhibited a tendency toward improved ORR (45.5% vs. 13.0%, p=0.074), and notably, the median duration of response remained unreached. There was no significant difference in PFS between the dMMR and pMMR groups; however, the patients with dMMR in tumor tissue had a trend of better survival (p=0.079). Incidence of immune-related adverse events (irAEs) of any grade was observed in 13 patients (33.3%), with 3 individuals (7.7%) experiencing grade 3 or 4 events. Low-dose pembrolizumab may be a cost-effective and safe treatment option without compromising clinical outcomes in patients with refractory gynecologic cancers.

Impact of Genomic Alterations on the Clinical Outcome of Patients With Hepatitis B-related Hepatocellular Carcinoma Receiving Curative Surgery: A Retrospective Cohort Study.

The aim of the current study was to obtain comprehensive genomic information on viral hepatitis B (HBV)-related hepatocellular carcinoma (HCC) and identify potential biomarkers of early recurrence in patients receiving curative surgery. A total of 104 patients with HBV-related HCC receiving curative surgery at Kaohsiung Chang Gung Memorial Hospital between January 2017 and December 2020 were identified, including 52 patients each with and without recurrence. Next-generation sequencing was performed to investigate genomic alterations caused by surgical resection of specimens. The Kaplan-Meier method was used to estimate disease-free survival and overall survival. The landscape of gene mutations in HCC patients of our cohort showed a median number of single nucleotide variants of 250, a median number of insertions and deletions of 22, and a median number of protein-coding mutations of 185. The 10 most frequently mutated genes were TP53 (43%), TTN (39%), MUC16 (28%), PCLO (25%), OBSCN (22%), ADGRV1 (19%), ALB (18%), SYNE1 (18%), DNAH17 (17%), and RYR1 (17%). The tumour mutation burden was 4.8 mutations per megabase, and high microsatellite instability was reported in only three patients. In addition, the mutational signatures showed that aristolochic acid exposure was highly implicated in our HCC cohort. Five mutant genes, TBC1D4, ITGA4, RPS6KA3, VWA8, and FMN2, were more frequent in the recurrence group than that in the non-recurrence group. Our results present an in-depth genomic analysis of HBV-related HCC. The study findings provide an improved understanding of the related molecular mechanisms and identify potential biomarkers associated with early tumour recurrence after curative resection.

Design and Validation of a Deep Learning Model for Renal Stone Detection and Segmentation on Kidney-Ureter-Bladder Images.

Kidney-ureter-bladder (KUB) imaging is used as a frontline investigation for patients with suspected renal stones. In this study, we designed a computer-aided diagnostic system for KUB imaging to assist clinicians in accurately diagnosing urinary tract stones. The image dataset used for training and testing the model comprised 485 images provided by Kaohsiung Chang Gung Memorial Hospital. The proposed system was divided into two subsystems, 1 and 2. Subsystem 1 used Inception-ResNetV2 to train a deep learning model on preprocessed KUB images to verify the improvement in diagnostic accuracy with image preprocessing. Subsystem 2 trained an image segmentation model using the ResNet hybrid, U-net, to accurately identify the contours of renal stones. The performance was evaluated using a confusion matrix for the classification model. We conclude that the model can assist clinicians in accurately diagnosing renal stones via KUB imaging. Therefore, the proposed system can assist doctors in diagnosis, reduce patients' waiting time for CT scans, and minimize the radiation dose absorbed by the body.

Impact of Sirolimus versus Mycophenolate Mofetil on Kidney Function after Calcineurin Inhibitor Dose Reduction in Liver Transplant Recipients.

Impaired kidney function is associated with increased morbidity and mortality in patients undergoing liver transplantation. Although immunosuppressants are essential in these patients, they impair kidney function. This study aimed to compare adverse kidney outcomes between patients treated with a reduced dose of tacrolimus (calcineurin inhibitor) plus sirolimus or mycophenolate mofetil (MMF) in the liver transplant center at Kaohsiung Chang Gung Memorial Hospital between April 2011 and December 2017. Propensity score matching was used to identify 232 patients. The risk of adverse kidney outcomes was estimated using Cox proportional hazards regression, and changes in kidney function over time were analyzed using linear mixed modeling. Acute kidney disease risks in this study cohort were not significantly different for the two immunosuppressants (aHR 1.04; 95% CI: 0.70-1.55, p = 0.8328). However, sirolimus use was significantly associated with a higher risk of estimated glomerular filtration rate decline > 30% than MMF (aHR, 2.09; 95% CI: 1.33-3.28; p = 0.0014). Our results demonstrate that sirolimus use may have worsened long-term kidney outcomes compared to MMF. Close monitoring of kidney function, dose adjustment, and timely transition to MMF is necessary for LT patients receiving sirolimus.

Bibliometric and visual analysis of Kawasaki disease in children from 2012 to 2022.

In recent years, the incidence of Kawasaki disease among the pediatric population has experienced a significant increase. With complications mainly affecting the cardiovascular system, Kawasaki disease has received widespread attention from scholars worldwide. Numerous articles on Kawasaki disease in children have been published far. However, there is a lack of studies that use visualization methods to perform a bibliometric analysis of the relevant literature. This study aims to obtain overall information on the output characteristics of publications on childhood Kawasaki disease between 2012 and 2022 through bibliometric analysis, identify research hotspots and frontiers, and provide new ideas and references for future clinical and scientific research. Literature meeting the inclusion criteria was screened from the Web of Science Core Collection, PubMed, and Scopus databases. Visual analysis of the literature by country, institution, journal, author, keywords, and references was performed using Citespace (6.1.R6), VOSviewer (1.6.18), and the online bibliometric website (https://bibliometric.com/). A total of 4,867 eligible publications were included. The number of annual publications is generally rising, rapidly increasing since 2019. Among countries and institutions, China and KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL have the highest output of articles. With 104 publications, Ho-Chang Kuo has a high impact in the field of KD. The most cited author is Jane W. Newburger. The most prolific journal is FRONTIERS IN PEDIATRICS. CIRCULATION is the most frequently co-cited journal. The most popular keyword in frequency and centrality is "immunoglobulin". The reference with the highest burst intensity was Verdoni L, LANCET, 2020. Kawasaki disease in children remains a hot topic among pediatricians worldwide and is receiving increasing attention. We innovated the "national-institutional-journal" model, which promotes further international cooperation in this field. The hot topics in the field of pediatric KD are "KD pathogenesis", "immunoglobulin resistance and complementary therapy", and "cardiovascular complications". Frontiers include disease-related ("multisystem inflammatory syndrome", "coronavirus disease 2019", "hypotension"), treatment-related ("procalcitonin", " anakinra"), and pathogenesis ("polymerase chain reaction").

#6546 RENAL TUBULAR TOXICITY OF ORGANOPHOSPHATE FLAME RETARDANTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Organophosphate flame retardants (OPFRs) are widely utilized flame retardants and considered less harmful than legacy brominated flame retardants. However, owing to their widespread utilization, OPFRs have led to extensive and persistent human exposure, with potentially hazardous effects on human health such as nephrotoxicity. Experimental and clinical studies have revealed that OPFR exposure is associated with renal tubular toxicity and renal impairment. However, the nephrotoxic mechanisms of OPFRs have not yet been clarified, and their impact on renal tubular injury has less been evaluated in patients with chronic kidney disease (CKD). In this cross-sectional observational study, we assessed the urinary OPFR concentrations in CKD patients to evaluate the associations between OPFR exposure and renal tubular injury in this population. Method Adult CKD patients in Taiwan (≥ 20 years of age and with non-dialysis-dependent CKD stage 3–5) were recruited from the Kaohsiung Chang Gung Memorial Hospital between January 2020 and May 2021. The first-void urine samples in the morning were collected to measure the concentrations of 10 common OPFR compounds using an ultra-performance liquid chromatography-tandem mass spectrometry (Waters, Milford, MA, USA). The urinary novel renal biomarkers were also measured using enzyme-linked immunosorbent assays (kidney injury molecule-1 [KIM1] and 8-hydroxy-2-deoxyguanosine [8-OHdG]; Abcam, Trumpington, Cambridge, UK). OPFRs with concentrations below a limit of quantitation (LOQ) were considered undetectable, and LOQ/√2 was assigned to the non-detected samples for analysis. The associations between urinary renal biomarkers and ΣOPFR concentrations (i.e., the sum of 10 OPFR compounds) were assessed via Spearman's correlation analysis. Simple linear regression analyses were conducted to evaluate the correlations between urinary renal biomarkers, ΣOPFR concentrations, and baseline patient characteristics. The effects of OPFR exposure on the urinary concentrations of KIM-1 and 8-OHdG in the enrolled CKD patients were examined in multiple linear regression analyses, adjusting for age, sex, body mass index, diabetes, hypertension, renal function, proteinuria, and covariates with a p-value &amp;lt; 0.1 in univariate analyses via the enter method. Results In this study, 163 CKD patients were enrolled for analysis (stage 3: n = 79 [49.47%]; stage 4: n = 48 [29.45%]; stage 5: n = 36 [22.08%]). The overall detection frequency of urinary OPFRs was 98.77% in the study cohort, with a median ΣOPFR of 2.04 μg/g Cr (interquartile range [IQR], 0.84–4.27). The median urinary KIM-1 and 8-OHdG concentrations were 185.89 ng/g Cr (IQR, 83.05–441.60) and 71.23 μg/g Cr (IQR, 37.87–149.73), respectively. In our analysis, urinary ΣOPFR concentrations were positively correlated with urinary KIM-1 and 8-OHdG concentrations (rs = 0.267 for KIM-1, p = 0.001; rs = 0.281 for 8-OHdG, p &amp;lt; 0.001) (Figure 1). In the multiple linear regression analyses, urinary ΣOPFR concentration was identified as an independent predictor positively associated with urinary renal biomarkers in the enrolled patients, with a 0.260 log ng/g Cr (95% confidence interval [CI], 0.140–0.380, p &amp;lt; 0.001) increase in urinary KIM1 and a 0.227 log μg/g Cr elevation (95% CI, 0.124–0.330, p &amp;lt; 0.001) in urinary 8-OHdG by per log μg/g Cr ΣOPFR (Figure 2). Conclusion OPFR exposure is common and associated with renal tubular injury as well as increased oxidative stress in CKD patients, which highlights its nephrotoxic potential in this vulnerable population.

Global trends in research on extracorporeal shock wave therapy (ESWT) from 2000 to 2021

BackgroundThis study intended to analyze the application of extracorporeal shock wave therapy in medicine and to evaluate the quality of related literature.MethodsAll publications were extracted from 2000 to 2021 from the Web of Science Core Collection (WoSCC). The literature characteristics were depicted by VOSviewer (version 1.6.15) and the online bibliometric website (http://bibliometric.com/). The future trends and hotspots were conducted by Bibliographic Item Co-occurrence Matrix Builder (version 2.0) and gCLUTO software.ResultsWe analyzed 1774 articles corresponding to the criteria for ESWT publications from 2000 to 2021. Most studies were conducted within the United States and China which besides have the most cooperation. The most published research institutions are Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, and Kaohsiung Medical University. Six research hotspots were identified by keyword clustering analysis: Cluster0: The effects of ESWT on muscle spasticity; Cluster1: The application of ESWT in osteoarthritis (OA); Cluster2: Therapeutic effect of ESWT on tendon diseases; Cluster3: Early application of ESWT/ESWL in urolithiasis; Cluster4: The Role of angiogenesis in ESWT and the efficiency of ESWT for penile disease; Cluster5: The Special value of radial extracorporeal shock wave therapy (rESWT).ConclusionsA comprehensive and systematic bibliometric analysis of ESWT was conducted in our study. We identified six ESWT-related research hotspots and predicted future research trends. With the gradual increase of research on ESWT, we find that ESWT is used more and more extensively, such in musculoskeletal disease, bone delay union, neurological injury, andrology disorders, lymphedema, and so on. In addition, the mechanism is not destructive damage, as initially thought, but a restorative treatment. Furthermore, delayed union, cellulite, burn, and diabetic foot ulcers may be the future direction of scientific study.

Abstract 954: PIK3CA mutation induces immunogenicity and increases the immune checkpoint inhibitor response in urothelial carcinoma

Abstract Background: Immune checkpoint inhibitor (ICI) has been widely used for advanced urothelial carcinoma (mUC) globally. However, little is known about the potential predictive factors of the ICI response. The study aims to identify a potential biomarker to predict ICI response in UC. Material and methods: We performed targeted next generation sequencing (NGS) of pre-treatment tumor Formalin-fixed paraffin-embedded (FFPE) samples by using ACTOnco® comprehensive genomic panel (ACT Genomics, Co. Ltd., Taiwan) to target all coding exons of 440 cancer-associated genes. We retrospective analyzed a total of 70 patients with mUC underwent at least one cycle of ICI with or without chemotherapy at Kaohsiung Chang Gung Memorial Hospital between April 2016 and November 2019. Patients were defined as responders (CR/PR) and non-responders (SD/PD) according to the RECIST evaluation. TMB was estimated by calculating all coding exons variants, including somatic non-synonymous, frameshift and splice site variants. Results: A total of 55 UC tumor samples passed QC process were analyzed. The median age was 67, and 74% of all patients were in ICI monotherapy cohort. The most common genetic alterations were TP53 (66%), KMT2D (42%) and MUC16 (32%). In ICI monotherapy group, responders had a higher TMB than non-responders (median 19.5 vs 6.5 mt/Mb; p = 0.004). Patients with high TMB on ICI monotherapy had a significantly longer PFS (14.6 vs 2.9 months; p = 0.003) and OS (NR vs 11.0 months; p = 0.01) than TMB low patients. We found that PIK3CA (32% vs 3%), UBR5 (23% vs 0%), PRKDC (32% vs 10%) were the top 3 enriched mutations between responders and non-responders. All PIK3CA mutation were hot-spot mutation, and tumor harbored PIK3CA mutation had a median high TMB than PIK3CA wild type in UC, NSCLC, breast and colorectal cancer. By analyzing tumor and immune microenvironment by TISIDB platform, UC with PIK3CA mutation was highly associated with increasing MHC molecules expression (HLA-A, HLA-B, HLA-C, B2M) in UC and gastric cancer. In vitro study, we confirmed anti-PDL1 with PBMC had a synergistic cytotoxicity in PIK3CA mutated cell lines (BFTC-909, AGS and DLD-1), but not in PIK3CA wild type cell lines (T24, RT4, UMUC-14, N87 and SW837). Knocking-down PIK3CA expression diminished the cytotoxic activity of anti-PDL1 with PBMC in BFTC-909 and AGS cells. PIK3CA down-regulation inhibits antigen presentation machinery process. We confirmed that knockout PIK3CA gene function by CRISPR/Cas9 decreased MHC1 and B2M molecules expression, and showing modest resistance to ICI than mice with preserved PIK3CA function. Conclusion: UC with PIK3CA missense mutation exhibits a higher immunogenicity through enhancing MHC class I and B2M expression. PIK3CA missense mutation is a potential predictive marker for ICI response in UC. Citation Format: Harvey Yu-Li Su, Ling-Yi Xiao, Shih-Yu Huang, Li-Chung Chang, Yi-Hua Chen, Hao-Lun Luo, Chia-Ling Wu. PIK3CA mutation induces immunogenicity and increases the immune checkpoint inhibitor response in urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 954.

Safety of cold snare polypectomy vs conventional hot polypectomy for 4 to 10 mm gastric polyps: A single‐center retrospective study

AbstractEndoscopic polypectomy has become standard in the management of most polyps in the gastrointestinal tract, but bleeding is the most common adverse event. Polypectomy with a cold snare (CSP) has been increasingly utilized in recent years, but further evidence is required to establish its safety of gastric polypectomy. The aim of this study was to compare intraprocedure and postprocedure adverse events in patients who underwent CSP vs conventional hot snare polypectomy (HSP) of gastric polyps. Electronic medical records and endoscopy reports of all patients who underwent gastric polypectomy at the Kaohsiung Chang Gung Memorial Hospital between January 2019 and June 2021 were retrospectively reviewed. Data on patient demographics, polyp characteristics, method of polypectomy, and adverse events were collected. A total of 193 gastric polyps removed from 111 patients were reviewed. The mean age was 58.1 years, and 74.8% were female. Of these, 142 polyps were removed from 78 patients by HSP, compared to 51 polyps removed from 33 patients by CSP. The mean polyp size was 7.9 mm in the HSP group and 7.5 mm in the CSP group (P = .306). Nine patients (11.5%) from HSP group and 5 (15.2%) from CSP group presented with immediate bleeding that were managed by endoscopic treatment (P = .755). There was no serious adverse event, such as delayed bleeding or perforation, occurred in this study. In multivariate logistic regression, only the number of polyps resected &gt;1 was identified as independent risk factor of immediate post‐polypectomy bleeding. Therefore, the safety of CSP was non‐inferior to HSP and could be an additional option for removal of gastric polyps ≤10 mm.

Safety Analysis of Bevacizumab in Ovarian Cancer Patients

Bevacizumab (BEV) is beneficial for ovarian cancer patients, but the real world's patient settings differ from those in clinical trials. This study tries to illustrate adverse events in the Taiwanese population. Patients with epithelial ovarian cancer treated with BEV at Kaohsiung Chang Gung Memorial Hospital between 2009 and 2019 were retrospectively reviewed. The receiver operating characteristic curve was adopted to identify the cutoff dose and the presence of BEV-related toxicities. A total of 79 patients receiving BEV in neoadjuvant, frontline, or salvage settings were enrolled. The median follow-up time was 36.2 months. Twenty patients (25.3%) had "De novo" hypertension or the worsening of a preexisting one. Twelve patients (15.2%) had "De novo" proteinuria. Five patients (6.3%) had thromboembolic events/hemorrhage. Four patients (5.1%) had gastrointestinal perforation (GIP), and one patient (1.3%) had wound-healing complications. Patients with BEV-related GIP had at least two risk factors for developing GIP, most of which were conservatively managed. This study revealed a compatible but distinct safety profile from those reported in clinical trials. The presence of BEV-related changes in blood pressure showed a dose-dependent trend. Most of the BEV-related toxicities were managed individually. Patients with potential risks for developing BEV-related GIP should use BEV with caution.

Center for Quality Management, Kaohsiung Chang Gung Memorial Hospital, Recipient of the 2022 National Healthcare Quality Award - Excellent Center Award Accountability in Quality Management: A Team with Innovation and Excellence of Quality Management

&lt;p&gt;高雄長庚紀念醫院品質管理中心以「創新品質與病人安全管理專業」運用「資訊智能資源整合」發展「卓越醫療品質特色」等成果，榮獲2022年第23屆國家醫療品質獎―卓越中心之殊榮。中心核心團隊發展專業特色如：「智能指標管理，做為高層決策之依據」、「建立病安通報系統，確保病人安全」、「研發醫病共享決策(Shared Decision Making, SDM)輔助工具，創立國際中文版翻譯」、「開發急性腎損傷(acute kidney injury, AKI)智能照護系統」、「營造優質病安文化」、「積極人才培育專業證照」等，引領全院進行跨領域專業多元合作，提供最高品質的醫療服務。榮獲「卓越中心」象徵本院為實現正向醫品病安文化價值，全方位提升醫療品質及病人安全成效之肯定，期望藉此經驗分享，引領同儕，追求更卓越的醫療品質。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;The center of quality management, Kaohsiung Chang Gung Memorial Hospital has utilized its innovation and professionalism in quality and patient safety management to facilitate smart information and resource integration, achieving outstanding healthcare quality. In 2022, these achievements enabled the center to win the 23rd National Healthcare Quality Award in the Excellent Center category. The core management team of the center has developed the following professional features: smart index management for providing referential data to hospital executives when making decisions; establishing a patient safety report system to ensure the safety of all patients; developing the patient decision aids (PDAs) for shared decision making (SDM) and translating the international PDAs into Mandarin Chinese version; developing an acute kidney injury care system; fostering adequate patient safety culture; and promoting talent cultivation and professional certification. The center guides the entire hospital staff to participate in interdisciplinary collaboration to provide healthcare services of the highest quality. Winning the Excellent Center Award signifies approval of the efforts made by the hospital to promote positive healthcare culture and values through enhancing every aspect of healthcare quality and patient safety. By sharing its experience, the center hopes to play a leading role in the healthcare industry and help other institutions strive for excellent healthcare quality.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Kaohsiung Chang Gung Memorial Hospital, Recipient of the 2022 National Healthcare Quality Award - Distinguish Institution Award Pursuing Innovation and Excellence in Healthcare Quality: Emphasis on Quality Management and Error Free in Patient Safety

&lt;p&gt;高雄長庚紀念醫院創立於1986年，深耕南臺灣37年，從專業走向卓越，重視醫療品質；以王創辦人「要做就做最好的」為共同目標，自2003年開始參與財團法人醫院評鑑暨醫療品質策進會（以下簡稱醫策會）主辦「NHQA國家醫療品質獎」，19年期間屢獲佳績，2016年榮獲醫策會國家醫療品質獎頒發智慧醫療（Smart Hospital）全機構標章，近年連續獲得「醫品標竿獎」、「熱心分享獎」、「防疫貢獻獎」、「實證醫學類持續參與特別獎」、「主題類深耕品質獎」，更獲得3項「卓越中心」獎項，於2022年榮獲「特優機構」獎項。&lt;/p&gt; &lt;p&gt;本院在院長、副院長、執行長等領導下，全員投入持續改善，整合教學、研究、辯論與知識轉譯等多元面向的發展，體現實證醫學於提升醫療品質之價值；透過高擬真情境訓練增強臨床知識、專業精神、決策能力和信心，確保病人的品質和安全；超前部署精進創新，打造屬於高雄長庚之專業品牌形象。追求品質永無止盡，需要實事求是、追根究柢，以展現卓越之價值與提供卓越的醫療服務。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Founded in 1986, the Kaohsiung Chang Gung Memorial Hospital has rooted its operation in Taiwan to pursue professionalism and excellence while focusing on healthcare quality over the past 37 years. The common goal set by Yung-Ching Wang, the founder of the Hospital, for all staff members is to complete every task to the best of their ability. The Hospital began participating in the National Healthcare Quality Award launched by the Joint Commission of Taiwan (JCT) in 2003 and has received multiple awards. Notably, the Hospital received the Smart Hospital Award - Whole Institution from JCT in 2016. It proceeded to win the Healthcare Benchmark Award, Experience Sharing Award, Pandemic Prevention Contribution Award, Special Award for Continual Participation in Evidencebased Medicine, and Special Theme Quality Awards consecutively in recent years, in addition to receiving three Excellent Center awards. In 2022, the Hospital won the Distinguish Institution Award. Under the leadership of the superintendent, deputy superintendent, and chief executive officer, all members of the Hospital continue to improve every aspect of its operation and ensure multifaceted development in the areas of medical education, research, debates, and knowledge translation, thereby highlighting the value of evidence-based medicine in improving healthcare quality. Hospital staff also participate in high-fidelity simulation to ensure patient care quality and safety by enhancing their clinical knowledge, professionalism, decision-making ability, and confidence. Relevant strategies have been deployed in advance to create a professional brand image for the Hospital, which continues to pursue outstanding healthcare quality, seek truth from facts, foster adequate values, and provide excellent healthcare services.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;