Glaucoma Diagnostic Performance of Macular Ganglion Cell Complex Thickness Using Regular and Long Axial Length Normative Databases

The risks of misdiagnosing a healthy individual as glaucomatous or vice versa may be high in a population with a large majority of highly myopic individuals, due to considerable morphologic variability in high myopic fundus. This study aims to compare the diagnostic ability of the regular and long axial length databases in the RS-3000 Advance SD-OCT (Nidek) device to correctly diagnose glaucoma with high myopia. Patients with high myopia (axial length ≥ 26.0 mm) in Chang Gung Memorial Hospital, Taiwan between 2015 and 2020 were included. Glaucoma was diagnosed based on glaucomatous discs, visual field defects and corresponding retinal nerve fiber layer defects. The sensitivity, specificity, diagnostic accuracy and likelihood ratios of diagnosing glaucoma via mGCC thickness in both superior/inferior and GChart mapping using the regular and long axial length normative databases. The specificity and diagnostic accuracy of mGCC thickness for distinguishing glaucomatous eyes from nonglaucomatous eyes among highly myopic eyes were significantly improved using the long axial length database (p=0.046). There were also significant proportion changes in S/I mapping as well as GChart mapping (37.3% and 48.0%, respectively; p<0.01) from abnormal to normal in the myopic normal eye group when using the long axial length normative database. The study revealed that clinicians could utilize a long axial length database to effectively decrease the number of false-positive diagnoses or to correctly identify highly myopic normal eyes misdiagnosed as glaucomatous eyes.

Data Homogeneity Effect in Deep Learning-Based Prediction of Type 1 Diabetic Retinopathy

This study is aimed at evaluating a deep transfer learning-based model for identifying diabetic retinopathy (DR) that was trained using a dataset with high variability and predominant type 2 diabetes (T2D) and comparing model performance with that in patients with type 1 diabetes (T1D). The Kaggle dataset, which is a publicly available dataset, was divided into training and testing Kaggle datasets. In the comparison dataset, we collected retinal fundus images of T1D patients at Chang Gung Memorial Hospital in Taiwan from 2013 to 2020, and the images were divided into training and testing T1D datasets. The model was developed using 4 different convolutional neural networks (Inception-V3, DenseNet-121, VGG1, and Xception). The model performance in predicting DR was evaluated using testing images from each dataset, and area under the curve (AUC), sensitivity, and specificity were calculated. The model trained using the Kaggle dataset had an average (range) AUC of 0.74 (0.03) and 0.87 (0.01) in the testing Kaggle and T1D datasets, respectively. The model trained using the T1D dataset had an AUC of 0.88 (0.03), which decreased to 0.57 (0.02) in the testing Kaggle dataset. Heatmaps showed that the model focused on retinal hemorrhage, vessels, and exudation to predict DR. In wrong prediction images, artifacts and low-image quality affected model performance. The model developed with the high variability and T2D predominant dataset could be applied to T1D patients. Dataset homogeneity could affect the performance, trainability, and generalization of the model.

Inappropriate manipulation and drainage exacerbate post-operative pain and prolong the hospital stay after laparoscopic appendectomy for pediatric complicated appendicitis

Background This study examined whether drain placement or not is associated with the postoperative outcomes of pediatric patients following trans-umbilical single-port laparoscopic appendectomy (TUSPLA) for complicated appendicitis. Methods The medical records of pediatric patients undergoing TUSPLA for acute complicated appendicitis from January 2012 to September 2018 in Kaohsiung Chang Gung Memorial Hospital were reviewed retrospectively. They were classified according to whether they received passive drainage with a Penrose drain (Penrose group) (19), active drainage with a Jackson-Pratt drain with a vacuum bulb (JP group) (16), or no drain (non-drain group) (86). The postoperative outcomes of the three groups were compared. Results Postoperative visual analog scale pain score was significantly higher in the non-drain group than in either the JP group or Penrose group. Patients in the Penrose group had a significantly longer postoperative hospital stay than those in the non-drain group and a higher rate of intra-abdominal abscess, while patients in the JP group had a significantly shorter postoperative hospital stay; moreover, no patient in JP group developed a postoperative intra-abdominal abscess. Conclusions Compared to passive drainage with a Penrose drain or no drain, active drainage with a JP drain shorter the postoperative hospital stay and decreased the risk of postoperative intra-abdominal abscess.

Clinical Features and Molecular Characteristics of Methicillin-Susceptible Staphylococcus aureus Ocular Infection in Taiwan

This study analyzed the clinical features and molecular characteristics of methicillin-susceptible Staphylococcus aureus (MSSA) ocular infections in Taiwan and compared them between community-associated (CA) and health-care-associated (HA) infections. We collected S. aureus ocular isolates from patients at Chang Gung Memorial Hospital between 2010 and 2017. The infections were classified as CA or HA using epidemiological criteria, and the isolates were molecularly characterized using pulsed-field gel electrophoresis, multilocus sequence typing, and Panton-Valentine leukocidin (PVL) gene detection. Antibiotic susceptibility was evaluated using disk diffusion and an E test. A total of 104 MSSA ocular isolates were identified; 46 (44.2%) were CA-MSSA and 58 (55.8%) were HA-MSSA. Compared with HA-MSSA strains, CA-MSSA strains caused a significantly higher rate of keratitis, but a lower rate of conjunctivitis. We identified 14 pulsotypes. ST 7/pulsotype BA was frequently identified in both CA-MSSA (28.3%) and HA-MSSA (37.9%) cases. PVL genes were identified in seven isolates (6.7%). Both CA-MSSA and HA-MSSA isolates were highly susceptible to vancomycin, teicoplanin, tigecycline, sulfamethoxazole–trimethoprim, and fluoroquinolones. The most common ocular manifestations were keratitis and conjunctivitis for CA-MSSA and HA-MSSA, respectively. The MSSA ocular isolates had diverse molecular characteristics; no specific genotype differentiated CA-MSSA from HA-MSSA. Both strains exhibited similar antibiotic susceptibility.

Comparing the Expressions of Vitamin D Receptor, Cell Proliferation, and Apoptosis in Gastric Mucosa With Gastritis, Intestinal Metaplasia, or Adenocarcinoma Change

Background: This study aimed to compare the expression of vitamin D receptor (VDR), cell proliferation, and apoptosis in the gastric mucosa of patients with gastritis, intestinal metaplasia (IM), and adenocarcinoma using artificial intelligence.Material and Methods: This study retrospectively enrolled patients at the Keelung Chang Gung Memorial Hospital from November of 2016 to June, 2017, who were diagnosed with gastric adenocarcinoma. The inclusion criteria were patients' pathologic reports that revealed all compartments of Helicobacter pylori infection, gastritis, IM, and adenocarcinoma simultaneously in the same gastric sample. Tissue slides after immunohistochemical (IHC) staining were transformed into digital images using a scanner and counted using computer software (QuPath and ImageJ). IHC staining included PA1-711 antibody for VDR, Ki67 antigen for proliferation, and M30 antibody CK18 for apoptosis.Results: Twenty-nine patients were included in the IHC staining quantitative analysis. The mean age was 69.1 ± 11.3 y/o. Most (25/29, 86.2%) patients had poorly differentiated adenocarcinoma. The mean expression of Ki67 and CK18 increased progressively from gastritis and IM to adenocarcinoma, with statistical significance (P &lt; 0.05). VDR expression did not correlate with Ki67 or CK18 expression. Survival time was only correlated with tumor stage (correlation coefficient = −0.423, P value &lt; 0.05), but was not correlated with the expression of VDR, Ki67, and CK18.Conclusion: Ki67 expression and CK18 expression progressively increased in the areas of gastritis, IM, and adenocarcinoma. No correlation between VDR expression and Ki67 or CK18 expression was found in this study.

Multi-Institutional Validation of a Mammography-Based Breast Cancer Risk Model

PURPOSE Accurate risk assessment is essential for the success of population screening programs in breast cancer. Models with high sensitivity and specificity would enable programs to target more elaborate screening efforts to high-risk populations, while minimizing overtreatment for the rest. Artificial intelligence (AI)-based risk models have demonstrated a significant advance over risk models used today in clinical practice. However, the responsible deployment of novel AI requires careful validation across diverse populations. To this end, we validate our AI-based model, Mirai, across globally diverse screening populations. METHODS We collected screening mammograms and pathology-confirmed breast cancer outcomes from Massachusetts General Hospital, USA; Novant, USA; Emory, USA; Maccabi-Assuta, Israel; Karolinska, Sweden; Chang Gung Memorial Hospital, Taiwan; and Barretos, Brazil. We evaluated Uno's concordance-index for Mirai in predicting risk of breast cancer at one to five years from the mammogram. RESULTS A total of 128,793 mammograms from 62,185 patients were collected across the seven sites, of which 3,815 were followed by a cancer diagnosis within 5 years. Mirai obtained concordance indices of 0.75 (95% CI, 0.72 to 0.78), 0.75 (95% CI, 0.70 to 0.80), 0.77 (95% CI, 0.75 to 0.79), 0.77 (95% CI, 0.73 to 0.81), 0.81 (95% CI, 0.79 to 0.82), 0.79 (95% CI, 0.76 to 0.83), and 0.84 (95% CI, 0.81 to 0.88) at Massachusetts General Hospital, Novant, Emory, Maccabi-Assuta, Karolinska, Chang Gung Memorial Hospital, and Barretos, respectively. CONCLUSION Mirai, a mammography-based risk model, maintained its accuracy across globally diverse test sets from seven hospitals across five countries. This is the broadest validation to date of an AI-based breast cancer model and suggests that the technology can offer broad and equitable improvements in care.

592 ATR-mediated CD47 and PD-L1 upregulation restricts radiotherapy-induced immune priming and abscopal responses in colorectal cancer

BackgroundBackground: Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically; however, incidences of abscopal tumor remission are extremely rare. We sought to unravel the post-irradiation immune escape mechanisms in CRC.MethodsMethodsFlow cytometry, gene knockdown, RNA and T cell receptor sequencing, and multiple murine syngeneic CRC models were used to interrogate mechanisms of CRC immune evasion following radiotherapy. Comparison of immunohistochemistry staining between pretreatment biopsy and post-irradiation surgical specimens was performed in rectal patients who underwent neoadjuvant radiotherapy with 5 Gy for 5 fractions.ResultsResultsWe find that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells (APCs) to phagocytose them thereby preventing TAA cross-presentation. This post-irradiation CD47 and PD-L1 upregulation can be observed in CRC cells treated with either photon or proton radiotherapy and across a wide variety of human solid tumor cells. Concordantly, rectal cancer patients who responded poorly (tumor regression grade 4–5, n = 10) to neoadjuvant radiotherapy exhibited significantly elevated post-irradiation CD47 levels (P = 0.005). In murine CRC models, the combination of radiotherapy, αSIRPα, and αPD-1 (RSP) profoundly enhances TAA uptake, activation of innate immune sensors, and TAA cross-priming across various antigen-presenting myeloid populations in the irradiated tumor microenvironment and facilitates TAA-presenting APC migration to secondary lymphoid organs. Furthermore, we observed robust production of TAA-specific CD8 T cells, functional activation of effector T cells, and increased tumor-infiltrating T cell clonality and clonal diversity in mice treated with RSP. Importantly, radiotherapy coupled with phagocytosis checkpoint blockade significantly improves complete response rates in both irradiated and abscopal tumors and prolongs survival in three distinct murine CRC models, including a cecal orthotopic model. In addition, αSIRPα exerts superior tumoricidal efficacy than αCD47 in combination with RT and αPD-1. We find RSP efficacy to be STING dependent as knockout animals lose most benefit of phagocytosis checkpoint blockade.ConclusionATR-mediated CD47 and PD-L1 upregulation restrains radiation-induced immune priming in CRC. Blockade of the phagocytosis checkpoints SIRPα and PD-1 during radiotherapy promotes vigorous anti-CRC immune priming leading to systemic tumor regression.AcknowledgementsThis study is supported in part by NIH grant P30 CA16672, the MD Anderson Andrew Sabin Family Fellowship, and Chang Gung Memorial Hospital grant CMRPG3K1751. RCH was supported by the CPRIT Research Training Grant (RP170067) and Ralph B. Arlinghaus Ph.D. Scholarship. The authors are grateful to the members of the Advanced Cytometry & Sorting Facility at South Campus, Tissue Bank of Chang Gung Memorial Hospital at Linkou, and MHC Tetramer Core Facility at Baylor College of Medicine for their invaluable help.Ethics ApprovalThis study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan; approval number: 202001191B0C601.

Does catheter material affect functional performance of intravenous ports via the superior vena cava?

Introduction The catheter is the only intravascular portion of an implanted port and plays a crucial role in catheter related complications. Both polyurethane and silicone are biocompatible materials which are utilized for catheter manufacturing, but their correlation to complications remains controversial. The aim of this study was to try to analyze the relationship between catheter materials and complications. Materials and methods A total of 3144 patients who underwent intravenous port implantation between March 2012 and December 2018 at Chang Gung Memorial Hospital, Linkou, Taiwan were recruited. Of these, 1226 patients received silicone catheter port implantation and 1679 received polyurethane catheter ports. Case matching was done prior to analysis and catheter related complications and cumulative complication incidence for each group were compared. Results Intergroup differences were identified in entry vessel (p = 0.0441), operation year (p < 0.0001), operation method (p = 0.0095), functional period (p < 0.0001), patient follow up status (p < 0.0001), operating time for vessel cutdown (p < 0.0001) and wire assisted approach (p = 0.0008). Stratified by specific entry vessel, no statistical difference was found in complication rate or incidence between the silicone and polyurethane groups. We further compared the cumulative complication incidence of the silicone and polyurethane groups, and also found no statistical difference (p = 0.4451). Conclusion As long as external stress forces generated by surrounding structures and focused on potential weak points are avoided, both silicone and polyurethane materials provide sufficient structural stability to serve as reliable vascular access for patients.

Bone Marrow Hypocellularity in Patients with End-Stage Kidney Disease

Background. Anemia and pancytopenia are not uncommon in patients with chronic kidney disease (CKD). Nevertheless, there is insufficient literature analyzing bone marrow pathology in patients with CKD or end-stage kidney disease (ESKD) receiving dialysis. Methods. This observational cohort study included 22 patients with ESKD and 23 patients with CKD that received bone marrow biopsy and aspiration at Chang Gung Memorial Hospital. Demographic, hematological, and biochemical data were collected at the time of bone marrow study for analysis. Results. Bone marrow aspiration demonstrated that patients with ESKD had a lower percentage of blasts than patients with CKD (0.52 ± 0.84 versus 1.06 ± 0.78 %, p = 0.033). Bone marrow biopsy revealed that the overall incidence of hypocellular bone marrow was 55.6%. Furthermore, patients with ESKD had higher proportion of hypocellular bone marrow than patients with CKD (72.7% versus 39.1%, p = 0.023). In a multivariate logistic regression model, it was revealed that ESKD status (odds ratio 9.43, 95% confidence interval 1.66–53.63, p = 0.011) and megakaryocyte count within bone marrow (odds ratio 0.48, 95% confidence interval 0.29–0.79, p = 0.004) were significant predictors for bone marrow hypocellularity. Conclusion. Bone marrow hypocellularity is common in patients with kidney dysfunction. Hypocellular marrow occurs more frequently in patients with ESKD than patients with CKD.

Does Neutrophil to Lymphocyte Ratio Have a Role in Identifying Cytokeratin 19-Expressing Hepatocellular Carcinoma?

Background: Cytokeratin 19-positive (CK19(+)) hepatocellular carcinomas (HCC) are generally associated with poor prognosis after hepatectomy. It is typically detected from postoperative immunochemistry. We have analyzed several clinically available biomarkers, in particular, neutrophil to lymphocyte ratio (NLR) and aim to develop a panel of biomarkers in identifying CK19 expression in (HCC) preoperatively. Methods: We retrospectively reviewed 36 HCC patients who underwent liver resections during January 2017 to March 2018 in Chang Gung Memorial Hospital. Patients were grouped based on the status of CK19 expression and their baseline characteristics, perioperative and oncologic outcomes were compared. Novel biomarkers including NLR, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and uric acid were analyzed and correlated with CK19 expression. Results: NLR is highly associated with CK19 expression. NLR alone gave an AUROC of 0.728 (p-value = 0.043), higher than AFP, CEA or tumor size alone. NLR when combined with AFP, CEA and uric acid, gave an AUROC as high as 0.933 (p-value = 0.004). Conclusion: The current study demonstrated the predictive capability of NLR in combination with AFP, CEA and uric acid for CK19 expression in HCC patients preoperatively. Further prospective, large-scale studies are warranted to validate our findings.