China Medical University Hospital Research Articles

Increased intraoperative vein ligation in microsurgical varicocelectomy is associated with pain improvement.

Varicocele is a major cause of male infertility. However, few studies have discussed the potential associations between the pain caused by varicocele and preoperative and intraoperative factors. The aim of this study was to evaluate factors potentially associated with changes in pain score after microsurgical varicocelectomy. This retrospective study was conducted between August 2020 and August 2022 at China Medical University Hospital in Taichung, Taiwan. Patient characteristics including age, body mass index, semen analysis, testicular volume, and the number of veins ligated were collected. Preoperative and intraoperative factors were analyzed to determine if they were correlated with changes in numeric rating scale (NRS) after microsurgical varicocelectomy. A total of 44 patients with clinical varicocele underwent subinguinal microsurgical varicocelectomy and were analyzed. The overall pain resolution rate was 91%, and the average satisfaction score after surgery was 9.2 according to their subjective feelings. Multivariate analysis revealed that severe varicocele grade (odds ratio [OR] 16.5, 95% confidence interval [CI] 3.01-90.47; P = .018) and the number of veins ligated (OR 6, 95% CI 1.6-22.48; P = .013), were significantly associated with changes in NRS after surgery. In addition, the area under the receiver operating characteristic curve for changes in NRS and the total number of veins ligated was 0.869. Microsurgical varicocelectomy had a high success rate for scrotal pain and satisfaction. Severe varicocele grade and the number of veins ligated in microsurgical varicocelectomy were associated with postoperative pain improvement.

Correlation between impulse oscillometry parameters and test for respiratory and asthma control in kids (TRACK) in asthma control of preschoolers with asthma

Little research has been conducted to evaluate the correlation between impulse oscillometry (IOS), Childhood Asthma Control Test (C-ACT), and Test for Respiratory and Asthma Control in Kids (TRACK). This study was conducted at China Medical University Hospital between September 1, 2019, and March 31, 2021. Children aged 2-6 years who had been diagnosed with asthma with acute exacerbation were enrolled and followed-up until the end of the study. Correlations between the parameters of IOS, C-ACT and TRACK were assessed. The validity and reliability of TRACK were verified. A total of 114 children with asthma and acute exacerbations were recruited. Their mean age was 4.1±1.1 years, and 60.5% were males. After a year of treatment, the change of R5-R20 from baseline 0.64±0.38kPa/L/s to 12th month 0.48±0.2kPa/L/s (p=0.022). TRACK and C-ACT scores were significantly correlated during the observation period. R5-R20 in IOS at baseline and at the 12th month of follow-up as well as the change in IOS parameters were significantly associated with C-ACT (p=0.003, 0.015, and 0.001, respectively). R5% and R5-R20 changes in IOS were associated with TRACK (p=0.04 and 0.025, respectively). Sensitivity and specificity of TRACK were 80.8% (67.5-90.4) and 100% (94.1-100), respectively, with cut-off points >95 and AUC 93.8%. TRACK score appears to have a stronger association with the IOS parameter than C-ACT score. Our findings indicate that TRACK is a valid tool for assessing asthma control in preschool children.

A Combination of FPU-Net and Feature Clustering Methods for Accurate Segmentation of Femoral Neck in Radiographic Diagnosis.

In this study, we develop an innovative method that assists computer-aided diagnosis in the determination process of the exact location of the femoral neck junction in plain radiographs. Our algorithm consists of two phases, i.e., coarse prediction and fine matching, which are implemented by supervised deep learning method and unsupervised clustering, respectively. In coarse prediction, standard masks are first produced by a specialist and trained in our proposed feature propagation network (FPU-Net) with supervised learning on the femoral neck dataset. In fine matching, the standard masks are first classified into different categories using our proposed three parameters with unsupervised learning. The predicted mask from FPU-Net is matched with each category of standard masks by calculating the values of intersection of union (IOU), and finally the predicted mask is substituted by the standard mask with the largest IOU value. A total of 4320 femoral neck parts in anterior-posterior (AP) pelvis radiographs collected from China Medical University Hospital database were used to test our method. Simulation results show that, on the one hand, compared with other segmentation methods, the method proposed in this paper has a larger IOU value and better suppression of noise outside the region of interest; on the other hand, the introduction of unsupervised learning for fine matching can help in the accurate localization segmentation of femoral neck images. Accurate femoral neck segmentation can assist surgeons to diagnose and reduce the misdiagnosis rate and burden.

Machine learning of cell population data, complete blood count, and differential count parameters for early prediction of bacteremia among adult patients with suspected bacterial infections and blood culture sampling in emergency departments.

Bacteremia is a life-threatening complication of infectious diseases. Bacteremia can be predicted using machine learning (ML) models, but these models have not utilized cell population data (CPD). The derivation cohort from emergency department (ED) of China Medical University Hospital (CMUH) was used to develop the model and was prospectively validated in the same hospital. External validation was performed using cohorts from ED of Wei-Gong Memorial Hospital (WMH) and Tainan Municipal An-Nan Hospital (ANH). Adult patients who underwent complete blood count (CBC), differential count (DC), and blood culture tests were enrolled in the present study. The ML model was developed using CBC, DC, and CPD to predict bacteremia from positive blood cultures obtained within 4h before or after the acquisition of CBC/DC blood samples. This study included 20,636 patients from CMUH, 664 from WMH, and 1622 patients from ANH. Another 3143 patients were included in the prospective validation cohort of CMUH. The CatBoost model achieved an area under the receiver operating characteristic curve of 0.844 in the derivation cross-validation, 0.812 in the prospective validation, 0.844 in the WMH external validation, and 0.847 in the ANH external validation. The most valuable predictors of bacteremia in the CatBoost model were the mean conductivity of lymphocytes, nucleated red blood cell count, mean conductivity of monocytes, and neutrophil-to-lymphocyte ratio. ML model that incorporated CBC, DC, and CPD showed excellent performance in predicting bacteremia among adult patients with suspected bacterial infections and blood culture sampling in emergency departments.

Effects of Human Leukocyte Antigen DRB1 Genetic Polymorphism on Anti-Cyclic Citrullinated Peptide (ANTI-CCP) and Rheumatoid Factor (RF) Expression in Rheumatoid Arthritis (RA) Patients.

Rheumatoid arthritis (RA) is a systemic disease characterized by non-infectious inflammation of the joints and surrounding tissues, which can cause severe health problems, affect the patient's daily life, and even cause death. RA can be clinically diagnosed by the occurrence of blood serological markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). However, about 20% of RA patients exhibit negative results for both markers, which makes RA diagnosis difficult and, therefore, may delay the effective treatment. Previous studies found some evidence that human leukocyte antigen (HLA)-related genes might be the susceptibility genes for RA and their polymorphisms might contribute to varieties of susceptibility and disease severity. This study aimed for the genetic polymorphisms of the RA patient genome and their effects on the RA patient's serological makers, RF and anti-CCP. A total of 4580 patients' electronic medical records from 1992 to 2020 were retrieved from the China Medical University Hospital database. The most representative single-nucleotide polymorphisms (SNPs) were identified through a genome-wide association study (GWAS) followed by enzyme-linked immunosorbent assay (ELISA) validation using the blood from 30 additional RA patients. The results showed significant changes at the position of chromosome 6 with rs9270481 being the most significant locus, which indicated the location of the HLA-DRB1 gene. Further, patients with the CC genotype at this locus were more likely to exhibit negative results for RF and anti-CCP than those with the TT genotype. The C allele was also more likely to be associated with negative results for RF and anti-CCP. The results demonstrated that a genetic polymorphism at rs9270481 affected the expression of RF and anti-CCP in RA patients, which might indicate the necessity to develop a personalized treatment plan for each individual patient based on the genetic profile.

Aspirin Use and the Risk of Hepatocellular Carcinoma: A Meta-analysis.

*College of Medicine, Tzu Chi University, Hualien, Taiwan †Division of Hepatogastroenterology, Department of Internal Medicine, Taichung Tzu Chi Hospital, Taichung, Taiwan ‡Department of Public Health, College of Public Health §Department of Medicine, College of Medicine, China Medical University, Taichung, Taiwan ∥Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan The authors declare that they have nothing to disclose. Address correspondence to: Shih-Wei Lai, MD, Department of Family Medicine, China Medical University Hospital, No 2, Yu-De Road, Taichung City 404, Taiwan (e-mail: [email protected]).

Efficacy of Warfarin Therapy Guided by Pharmacogenetics: A Real-world Investigation Among Han Taiwanese

The anticoagulation activity of warfarin in populations with CYP2C9, VKORC1, and CYP4F2 variants differs between individuals and is correlated with poor international normalized ratio (INR) control. Pharmacogenetics-guided warfarin dosing has been successfully developed for patients with genetic variations in recent years. However, few real-world data have been used to investigate the INR and warfarin dosage and the time to target INR. This study examined the largest collection of genetic and clinical real-world data related to warfarin to provide further evidence supporting the benefits of pharmacogenetics in clinical outcomes. We retrieved a total of 69,610 INR-warfarin records after the index date from 2,613 patients in the China Medical University Hospital database between January 2003 and December 2019. Each INR reading was obtained from the latest laboratory data after the hospital visit date. Patients with a history of malignant neoplasms or pregnancy before the index date were excluded, as were patients without data on INR measurements after the fifth day of prescription, genetic information, or gender variables. The primary outcomes were the INR and warfarin dosage during days 7, 14, 28, 56, and 84 after prescription. The secondary outcome was the time required to reach the INR ranges of 1.5 to 3.0 and >4.0. A total of 59,643 INR-warfarin records from 2188 patients were retrieved. The average INR was higher for homozygous carriers of the minor allele at CYP2C9 and VKORC1 during the first 7 days (1.83 [1.03] [CYP2C9*1] and 2.46 [1.44] [CYP2C9*3], P < 0.001; 1.39 [0.36] [rs9923231 G/G], 1.55 [0.79] [rs9923231 G/A], and 1.96 [1.13] [rs9923231 A/A], P < 0.001) than for the wild-type allele. These patients with variants required lower warfarin doses than those with the wild-type allele during the first 28 days. CYP4F2 variant patients seemed to require higher doses of warfarin than those in the wild-type group; however, no significant difference in the average INR was observed (1.95 [1.14] [homozygous V433 carriers], 1.78 [0.98] [heterozygous V433M carriers], and 1.66 [0.91] [homozygous M433 carriers], P=0.016). Our study indicates that genetic variants in the Han population may enhance warfarin responsiveness, which holds clinical relevance. An increased warfarin dosage was not linked to a shorter time to therapeutic INR between CYP4F2 variant patients and those with a wild-type allele. Assessing CYP2C9 and VKORC1 genetic polymorphisms before initiating warfarin treatment in real-world practice is essential for potentially vulnerable patients and is likely to optimize therapeutic dosing.

Prescription system to calculate precise doses of Chinese herbal medicine to avoid toxic effects

Background and objectivesTraditional Chinese Medicine (TCM) is a therapeutic system which has been practiced for thousands of years. Although for much of its history the decoction of medicinal herbs was the most common method of consuming the herbal treatments, TCM prescriptions are now primarily prepared using concentrated Chinese herbal extracts (CCHE) in powder or granular form. However, determining the precise dose of each single Chinese herbal constituent within a prescription creates a challenge in clinical practice due to the potential risk of toxicity. To alleviate this, we invented the Chinese Intelligence Prescription System (CIPS) to calculate the exact dose of each single herb within an individual prescription. MethodsIn this study, we applied CIPS in a real-world setting to analyze clinical prescriptions collected and prepared at the TCM Pharmacy of China Medical University Hospital (CMUH). ResultsOur investigation revealed that 3% of all prescriptions filled in a 1-month period contained inexact dosages, suggesting that more than 170,000 prescriptions filled in Taiwan in a given month may contain potentially toxic components. We further analyzed the data to determine the excess dosages and outline the possible associated side effects. ConclusionsIn conclusion, CIPS offers TCM practitioners the ability to prepare exact Chinese herbal medicine (CHM) prescriptions in order to avoid toxic effects, thereby ensuring patient safety.

New classification for bone type at dental implant sites: a dental computed tomography study

ObjectiveThis study proposed a new classification method of bone quantity and quality at the dental implant site using cone-beam computed tomography (CBCT) image analysis, classifying cortical and cancellous bones separately and using CBCT for quantitative analysis.MethodsPreoperative CBCT images were obtained from 128 implant patients (315 sites). First, measure the crestal cortical bone thickness (in mm) and the cancellous bone density [in grayscale values (GV) and bone mineral density (g/cm3)] at the implant sites. The new classification for bone quality at the implant site proposed in this study is a “nine-square division” bone classification system, where the cortical bone thickness is classified into A: > 1.1 mm, B:0.7–1.1 mm, and C: < 0.7 mm, and the cancellous bone density is classified into 1: > 600 GV (= 420 g/cm3), 2:300–600 GV (= 160 g/cm3–420 g/cm3), and 3: < 300 GV (= 160 g/cm3).ResultsThe results of the nine bone type proportions based on the new jawbone classification were as follows: A1 (8.57%,27/315), A2 (13.02%), A3 (4.13%), B1 (17.78%), B2 (20.63%), B3 (8.57%) C1 (4.44%), C2 (14.29%), and C3 (8.57%).ConclusionsThe proposed classification can complement the parts overlooked in previous bone classification methods (bone types A3 and C1).Trial registrationThe retrospective registration of this study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH 108-REC2-181.

Feature-enhanced adversarial semi-supervised semantic segmentation network for pulmonary embolism annotation

This study established a feature-enhanced adversarial semi-supervised semantic segmentation model to automatically annotate pulmonary embolism (PE) lesion areas in computed tomography pulmonary angiogram (CTPA) images. In the current study, all of the PE CTPA image segmentation methods were trained by supervised learning. However, when CTPA images come from different hospitals, the supervised learning models need to be retrained and the images need to be relabeled. Therefore, this study proposed a semi-supervised learning method to make the model applicable to different datasets by the addition of a small number of unlabeled images. By training the model with both labeled and unlabeled images, the accuracy of unlabeled images was improved and the labeling cost was reduced. Our proposed semi-supervised segmentation model included a segmentation network and a discriminator network. We added feature information generated from the encoder of the segmentation network to the discriminator so that it could learn the similarities between the prediction label and ground truth label. The HRNet-based architecture was modified and used as the segmentation network. This HRNet-based architecture could maintain a higher resolution for convolutional operations to improve the prediction of small PE lesion areas. We used a labeled open-source dataset and an unlabeled National Cheng Kung University Hospital (NCKUH) (IRB number: B-ER-108-380) dataset to train the semi-supervised learning model, and the resulting mean intersection over union (mIOU), dice score, and sensitivity reached 0.3510, 0.4854, and 0.4253, respectively, on the NCKUH dataset. Then we fine-tuned and tested the model with a small number of unlabeled PE CTPA images in a dataset from China Medical University Hospital (CMUH) (IRB number: CMUH110-REC3-173). Comparing the results of our semi-supervised model with those of the supervised model, the mIOU, dice score, and sensitivity improved from 0.2344, 0.3325, and 0.3151 to 0.3721, 0.5113, and 0.4967, respectively. In conclusion, our semi-supervised model can improve the accuracy on other datasets and reduce the labor cost of labeling with the use of only a small number of unlabeled images for fine-tuning.

Immunometabolic modulation by targeting UCP2 and IL-17A boost anti-tumor immunity against pancreatic cancer

Abstract Metabolic reprograming of cytotoxic effectors by tumor microenvironment (TME) is one of the key mechanisms by which TME impairs the success of cancer immunotherapy. Therapeutic strategies that mitigate the immunosuppressive TME and selectively enhance bioenergetic fitness of cytotoxic effectors may enhance benefits of immunotherapy, particularly in TME-abundant pancreatic cancer. IL-17 is a key TME cytokine engaged in a feed-forward loop promoting the immunosuppressive milieu that facilitates cancer progression. Mitochondrial uncoupling protein 2 (UCP2) acts as an inhibitor of T cell metabolic fitness and directly promotes tumorigenesis. Therefore, we hypothesized that targeting IL-17 and UCP2 could act additionally to enhance antitumor immune response and directly inhibit pancreatic cancer growth. UCP2 deficiency regulated bioenergetic metabolism and mTOR signaling in cytotoxic T cells to enhance IFN-γ production and anti-tumor immune responses. UCP2 inhibition increased anti-tumor immunity in PBMCs and tumors of patients with PDAC. The dual inhibition of IL-17 and UCP2 boosted antitumor immunity and suppressed tumorigenesis in tumor-bearing mice. Combination of UCP2 and IL-17 blockade may offer additional complimentary and cooperative mechanisms of antitumor immunity against pancreatic cancer. 1. Ministry of Science and Technology (MOST 108-2320-B-039-024-MY3) 2. China Medical University Hospital (DMR-110-186) 3. Chinese Medicine Research Center, China Medical University from the Featured Areas Research 4. Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (CMRC-CHM-2)

Universal screening for Lynch syndrome in operated colorectal cancer by immunohistochemistry: a cohort of patients in Liaoning province, China.

Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome worldwide. Due to the decreasing family size in Liaoning province. The Bethesda and Amsterdam II criteria have lower sensitivity and specificity and are not suitable for the local population. Immunohistochemistry screening for mutations in DNA mismatch repair (MMR) in newly diagnosed colorectal cancer can improve the detection rate of LS. All newly diagnosed colorectal cancer patients who underwent surgery between January 2018 and June 2020 at Cancer Hospital of China Medical University and Shengjing Hospital of China Medical University from Liaoning China were included retrospectively, and the ratio of universal LS screening by immunohistochemistry, MMR protein deficiency (dMMR) ratio, MLH1 loss, MSH2 loss, MSH6 loss, and PMS2 loss was analyzed. The clinicopathological characteristics of patients with pMMR and dMMR were analyzed. A total of 7019 colorectal cancer patients underwent surgery and 4802 (68.41%) patients were screened by immunohistochemistry for MMR, 258 (5.37%) cases were reported to have a loss of MMR expression. In the dMMR group, a higher number of patients were under 50 years old, more tumors were located at the right colon, less patients have lymph node metastasis, more tumors were stage II, and histological types of mucinous carcinoma or signet ring carcinoma were more common, compared with the pMMR group. Only 2.71% dMMR patients meet Amsterdam criteria II, 2.71% of patients meet Revised Bethesda guidelines, and 17.83% meet Chinese LS criteria. Twenty-five dMMR patients were confirmed by next-generation sequencing and five families were confirmed as Lynch family. These data imply that universal screening for LS by immunohistochemistry may be effective in Liaoning province.

P152 The prevalence of Thiopurine-methyltransferase and NUTD15 in patient with ulcerative colitis: a hospital-based study in central Taiwan

Abstract Background Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme involved in the metabolism of these thiopurine drugs. Methylation of thiopurine drugs by TPMT competes with the formation of their active 6-thioguanine nucleotide metabolite, thereby potentially modulating the therapeutic and toxic effects of these drugs. Polymorphisms in TPMT and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine-induced leukopenia in the Western and East Asian countries, but the frequency of the risk alleles is lower in Asians. Recently, a variant in the NUDT15 was reported to be associated with early severe leukopenia in Asians. The exact role of these polymorphisms in patients with ulcerative colitis (UC) in Taiwan is uncertain. The aim of this study was to investigate the prevalence of TPMT and NUDT 15 variants and other characteristics in patients with UC in central Taiwan. Methods From January 1980 to November 2022, a total of 172 consecutive patients with UC at the China Medical University Hospital, a tertiary referral center in central Taiwan, were enrolled in this study. Clinical characteristics of patients with UC, including gender, age at diagnosis, disease phenotype and behavior, were collected. We used polymerase chain reaction-restriction fragment length polymorphism method to determine the allelic frequencies of TPMT and NUD15 variants in our UC patients. Results A total of 172 patients with UC was enrolled into our current study. The mean diagnostic age of these enrolled patients was 46.1 years (ranging from 21 years to 75 years old). Male accounted for the majority of all patients in our present study (64.5%). Among these 172 patients with UC, TPMT variants were tested in 138 patients, which showed the allelic frequencies of TPMT*1 were 98.5% (136/138) for patients with UC. The allelic frequencies of TPMT*3C were 1.5% (2/138) for patients with UC. No TPMT*2, 3A, 3B, 3D and 4-8 were found in these populations. In addition, NUD15 was tested in 123 patients with UC, which showed normal metabolizer in 109 patients (88.6%, 109/123), intermediate metabolizer in 14 patients (11.4%, 14/123), and poor metabolizer in 0 patient (0%, 0/123). Conclusion NUDT15 mutation rate was significantly higher than TPMT polymorphism and reached 11.4%. NUDT15 mutation was associated with thiopurine-induced leukopenia. The measurement of NUDT15 polymorphism can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of UC. Phenotypic TPMT and NUDT15 analysis could be useful to better manage UC therapy with thiopurine.

Chinese Herbal Medicine Improved Survival in Stage IV Breast Cancer Patients: Data Mining of the Incorporated Taiwan Cancer Registry Database and Hospital Database.

According to recent research, breast cancer has become the most commonly diagnosed non-skin cancer type among the entire population. Meanwhile, Chinese herbal medicine (CHM) has become an important therapy to improve the survival rate and quality of life in metastatic cancer patients, as part of a wider trend toward more personalized medicine. However, there is a lack of research in terms of the association between stage IV breast cancer and CHM. Therefore, this study aimed to investigate the association between CHM and the survival rate in breast cancer patients at different cancer stages, with a particular focus on patients diagnosed with stage IV. Patients with an initial diagnosis of breast cancer identified from the Taiwan Cancer Registry Database (TCRD) and China Medical University Hospital (CMUH) database were included in this study. Demographic characteristics including gender, age, and comorbidities were evaluated. Between-group differences for continuous and categorical variables were evaluated by the Student's t-test and Chi-square test, respectively. Patients diagnosed with breast cancer were recruited and divided into cohorts of CHM users and non-users with a 1:1 propensity score matching. The survival of breast cancer patients was assessed by the Cox proportional hazard model. The cumulative incidence of survival was assessed by Kaplan-Meier analysis. The adjuvant CHM treatment was associated with a higher survival rate in stage IV breast cancer patients (HR: 0.45, 95% CI: 0.2853-0.7044]. Additionally, the use of CHM had a positive impact on survival in stage IV breast cancer patients who had received surgery (P: .0273, HR: 0.3406, 95% CI: 0.1309-0.8865), chemotherapy (P: .0004, HR: 0.3893, 95% CI: 0.231-0.656), and hormone therapy (P: .0013, HR: 0.3491, 95% CI: 0.1836-0.6636). In terms of the specific CHM associated with survival, Zhi-Gan-Cao-Tang (ZGCT), Phellodendron chinense Schneid. (huang-bai), and Paeonia lactiflora Pall. (chi-shao) were the 3 most commonly prescribed herbal medicines correlated with a higher survival rate among stage IV breast cancer patients. CHM associated with conventional management achieved significant survival benefits in patients with stage IV breast cancer. Additional randomized controlled trials for prospective study are recommended for further validation.

Periostin promotes ovarian cancer metastasis by enhancing M2 macrophages and cancer-associated fibroblasts via integrin-mediated NF-κB and TGF-β2 signaling

BackgroundOvarian cancer has the highest mortality among gynecological cancers due to late diagnosis and lack of effective targeted therapy. Although the study of interplay between cancer cells with their microenvironment is emerging, how ovarian cancer triggers signaling that coordinates with immune cells to promote metastasis is still elusive.MethodsMicroarray and bioinformatics analysis of low and highly invasive ovarian cancer cell lines were used to reveal periostin (POSTN), a matrix protein with multifunctions in cancer, with elevated expression in the highly invasive cells. Anchorage independent assay, Western blot, RNA interference, confocal analysis and neutralizing antibody treatment were performed to analyze the effects of POSTN on tumor promotion and to explore the underlying mechanism. Chemotaxis, flow cytometry and cytokine array analyses were undertaken to analyze the involvement of POSTN in cancer-associated fibroblast (CAF) and macrophage modulation. Correlations between POSTN expression levels and clinical characteristics were analyzed using the Oncomine, commercial ovarian cancer cDNA and China Medical University Hospital patient cohort. In vivo effect of POSTN on metastasis was studied using a mouse xenograft model.ResultsExpression of POSTN was found to be elevated in highly invasive ovarian cancer cells. We observed that POSTN was co-localized with integrin β3 and integrin β5, which was important for POSTN-mediated activation of ERK and NF-κB. Ectopic expression of POSTN enhanced whereas knockdown of POSTN decreased cancer cell migration and invasion in vitro, as well as tumor growth and metastasis in vivo. POSTN enhanced integrin/ERK/NF-κB signaling through an autocrine effect on cancer cells to produce macrophage attracting and mobilizing cytokines including MIP-1β, MCP-1, TNFα and RANTES resulting in increased chemotaxis of THP-1 monocytes and their polarization to M2 macrophages in vitro. In agreement, tumors derived from POSTN-overexpressing SKOV3 harbored more tumor-associated macrophages than the control tumors. POSTN induced TGF-β2 expression from ovarian cancer cells to promote activation of adipose-derived stromal cells to become CAF-like cells expressing alpha smooth muscle actin and fibroblast activation protein alpha. Consistently, increased CAFs were observed in POSTN overexpressing SKOV3 cells-derived metastatic tumors. In clinical relevance, we found that expression of POSTN was positively correlated with advanced-stage diseases and poor overall survival of patients.ConclusionsOur study revealed a POSTN-integrin-NF-κB-mediated signaling and its involvement in enhancing M2 macrophages and CAFs, which could potentially participate in promoting tumor growth. Our results suggest that POSTN could be a useful prognosis marker and potential therapeutic target.

Reconstruction of nasal airway in patients of class IIId maxillary defect with vastus lateralis muscle-chimeric double skin paddle ALT flap

A reconstructive challenge in patients with class IIId maxillary defect is how to obliterate the defect and restore a patent nasal airway. The current strategy using the single anterolateral thigh (ALT) fasciocutaneous flap for reconstruction may result in permanent mouth breathing. As the ALT flap was a common option in reconstruction processes, this study aimed to evaluate the benefits of vastus lateralis (VL) muscle-chimeric double skin paddle ALT flap in simultaneous defect and nasal airway reconstruction. This study included 21 patients with class IIId maxillary defect who underwent free ALT flap reconstruction (n = 11, single ALT flap group; n = 10, VL muscle-chimeric double skin paddle ALT flap (chimeric ALT flap) group) at the China Medical University Hospital from August 2015 to September 2019. Associated parameters collected for analysis included gender, age, body mass index (BMI), operative time, hospitalization, clinical stage, preoperative treatment, flap/defect size, comorbidities, postoperative RT, mouth breathing and short/long term complications. No significant differences were observed in age, BMI, hospitalization, clinical stage, preoperative treatment, defect size, comorbidities, and postoperative RT between the two groups; however, the chimeric ALT flap group as dominated by male patients (p = 0.009), and had longer operative times (12.1h vs. 10.1h, p = 0.002) and larger flap sizes (180 cm2 vs. 96.7 cm2, p = 0.013). Compared with the chimeric ALT flap group, the single ALT flap group suffered from permanent mouth breathing. Nasal airway reconstruction should be considered in patients with class IIId maxillary defect. Compared to the single ALT flap, the chimeric ALT flap is a superior reconstructive option for patients with class IIId maxillary defect, although a longer surgical duration and larger flap size are required.

Code-Switching Automatic Speech Recognition for Nursing Record Documentation: System Development and Evaluation.

Taiwan has insufficient nursing resources due to the high turnover rate of health care providers. Therefore, reducing the heavy workload of these employees is essential. Herein, speech transcription, which has various potential clinical applications, was employed for the documentation of nursing records. The requirement of including only one speaker per transcription facilitated data collection and system development. Moreover, authorization from patients was unnecessary. The aim of this study was to construct a speech recognition system for nursing records such that health care providers can complete nursing records without typing or with only a few edits. Nursing records in Taiwan are mainly written in Mandarin, with technical terms and abbreviations presented in both Mandarin and English. Therefore, the training set consisted of English code-switching information. Next, transfer learning (TL) and meta-TL (MTL) methods, which perform favorably in code-switching scenarios, were applied. As of September 2021, the China Medical University Hospital Artificial Intelligence Speech (CMaiSpeech) data set was established by manually annotating approximately 100 hours of recordings from 525 speakers. The word error rate (WER) of the benchmark model of syllable-based TL was 29.54% in code-switching. The WER of the proposed model of syllable-based MTL was 22.20% in code-switching. The test set comprised 17,247 words. Moreover, in a clinical case, the proposed model of syllable-based MTL yielded a WER of 31.06% in code-switching. The clinical test set contained 1159 words. This paper has two main contributions. First, the CMaiSpeech data set-a Mandarin-English corpus-has been established. Health care providers in Taiwan are often compelled to use a mixture of Mandarin and English in nursing records. Second, an automatic speech recognition system for nursing record document conversion was proposed. The proposed system can shorten the work handover time and further reduce the workload of health care providers.

Definite therapy of mixed infection alleviates refractory dilemma of adult chronic suppurative otitis media.

The characteristics, risk factors, microbial distributions and effective treatment regimens for Chronic suppurative otitis media (CSOM) patients intractable to empirical therapy were analyzed. Adult CSOM patients of China Medical University Hospital from 2018 to 2020 were included. Subjects of refractory and non-refractory groups were investigated for characteristics of age, sex, nation, comorbidities, otomycosis, and associated complications. Risk factors, microbiology distributions, and treatment regimens were analyzed. Twenty-six refractory patients (55.0±17.7 years) and 66 non-refractory patients (54.1±13.7 years) were studied. A significantly higher rate of otomycosis and CSOM complications was observed in refractory group than in non-refractory one (73.1% vs. 36.4%; p=0.002; 57.7% vs. 10.6%, p<0.001, respectively). Multivariate analysis revealed atopic diathesis (p=0.048), otomycosis (p=0.003) and CSOM complications (p<0.001) were risk factors of refractory CSOM. Coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA) were the prevailing pathogens. Patients of refractory group tented to have higher rates of mixed infection (42.9%% vs. 23.7%) and significantly more included fungal pathogen (19.0% vs. 2.6%; p=0.049) than those of non-refractory cohort. Topical treatment of fungus significantly improved outcome of refractory CSOM. Atopic diathesis, otomycosis, and CSOM-associated complications were risk factors of refractory CSOM. Systemic and local treatment to possible drug-resistant pathogens, likely CoNS and fungus, possible improves recalcitrant CSOM. Correspondingly, early identification of CSOM complications, routine culture and susceptibility testing and treatment of resistant bacteria and fungus are key elements to the successful management of adult CSOM.

High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a form of cancer that is characterized by infiltration of the bone marrow, blood, and other tissues by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells of the hematopoietic system. Patients with acute myeloid leukemia (AML) receiving azacitidine (AZA) alone or in combination with venetoclax (VEN-AZA) are at increased risk for invasive fungal infections (IFIs). We compared the incidence and risk of IFI during these treatment regimens in a single Taiwan hospital. A total of 61 patients with AML received at least one course of AZA in the hematology ward of China Medical University Hospital (Taichung, Taiwan) between September 2012 and June 2020. Thirty-eight patients (62.3%) received AZA monotherapy; 23 (37.7%) received VEN-AZA. Incidence rates of probable and proven IFI were 18% and 1.6%, respectively, during AZA treatment. One proven case of Fusarium spp. infection was isolated by skin and soft tissue culture. Most (75%) IFI cases occurred during the first cycle of AZA therapy. Half of all IFI cases occurred in patients with prolonged neutropenia. The risk of IFI was significantly higher for the European LeukemiaNet (ELN) nonfavorable-risk group (intermediate- and adverse-risk group) versus the ELN favorable-risk group and for patients with prolonged neutropenia versus those without (P<0.05 for both comparisons). In this study, median OS did not differ significantly between patients with and without IFIs during AZA-containing regimens (14.6 months vs 13.7 months; P=0.59). The incidence of IFI was high in this AML cohort treated with AZA-containing regiments in Taiwan. The majority of IFI cases occurred during the early cycles of AZA (cycles 1-2). Prospective studies are needed to determine the optimal choice of antifungal prophylaxis agent during VEN-AZA therapy for AML.

Using Whole Exome Sequencing to Identify the Pathogenic Variant of F7 C.681+1 G>t As a Potential Cause of Severe Bleeding Clinic Presentation in a Newborn Baby

Ching-Tien Peng1, 2, 3 Chien-Yu Lin4 Yin-Ting Chen1 1.Division of Pediatric Hematology & Oncology, China Medical University Children's Hospital, Taichung, 40447, Taiwan 2.Department of Biotechnology, Asia University, Taichung, 40447, Taiwan 3.Divisions of Pediatrics, China Medical University Hsinchu Hospital, Zhubei City, Hsinchu County, 30272, Taiwan. 4.Divisions of Laboratory Medicine, China Medical University Hsinchu Hospital, Zhubei City, Hsinchu County, 30272, Taiwan. Objective: The clinical manifestations of Factor VII deficiency vary, most cases remain asymptomatic or mild, and cases with severe clinical presentation are rarely reported. It is a rare hereditary hemorrhagic disorder passed on through autosomal recessive inheritance. We present a 2-day-old male infant with large cephalohematoma and intracranial hemorrhage, who was diagnosed using whole exome sequencing with Factor VII deficiency. Materials and Methods: Whole exome sequencing and Sanger sequencing were used to verify related variants. Other routine blood coagulation and factor activity tests were conducted by Divisions of Laboratory Medicine, China Medical University Hospital, Taiwan. Results: A 2-day-old male newborn was identified to develop left intracranial hemorrhage with unknown causes. The laboratory coagulation factor test results indicated a prolonged prothrombin time and normal activated partial thromboplastin time. The test results for Fibrinogen (279.9 mg/dL) and Factor activity analysis, included Factor VIII (85.6%), Factor V (49.3%), Factor VII (<1.0%), Factor IX (81.3%), and Factor X (42.7%). The results for VWF activity and antigen are normal. Subsequently, whole exome sequencing was used to conduct genetic tests, which revealed the homozygote mutation at F7 c.681+1 G>T (NM_000131). Further variant tests on the family members suggested that the father, mother, and older sister had heterozygote mutation at the same site. Conclusions: We used next-generation sequencing, which uses array-based sequencing to process reactions in parallel and enables the simultaneous investigation of multiple genes at a manageable cost, to identify the variants. While there is still little research on whether there is a relationship between different gene mutations and clinical presentations. The sequencing results revealed homozygote mutation at F7 c.681+1 G>T (NM_000131). The pathogenicity level was indicated to be "Highly pathogenic" in the ClinVar archive. Studies have reported the association of such mutation with severe hemorrhage disorders. Therefore, the present study offers critical empirical insights in that it applies to clinical practice in a clinical setting and identifies a pathogenic variant. We will present the hypothesis mechanism at the ASH meetings.