Taipei Veterans General Hospital Research Articles

Deep convolutional neural network with fusion strategy for skin cancer recognition: model development and validation

We aimed to develop an accurate and efficient skin cancer classification system using deep-learning technology with a relatively small dataset of clinical images. We proposed a novel skin cancer classification method, SkinFLNet, which utilizes model fusion and lifelong learning technologies. The SkinFLNet's deep convolutional neural networks were trained using a dataset of 1215 clinical images of skin tumors diagnosed at Taichung and Taipei Veterans General Hospital between 2015 and 2020. The dataset comprised five categories: benign nevus, seborrheic keratosis, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. The SkinFLNet's performance was evaluated using 463 clinical images between January and December 2021. SkinFLNet achieved an overall classification accuracy of 85%, precision of 85%, recall of 82%, F-score of 82%, sensitivity of 82%, and specificity of 93%, outperforming other deep convolutional neural network models. We also compared SkinFLNet's performance with that of three board-certified dermatologists, and the average overall performance of SkinFLNet was comparable to, or even better than, the dermatologists. Our study presents an efficient skin cancer classification system utilizing model fusion and lifelong learning technologies that can be trained on a relatively small dataset. This system can potentially improve skin cancer screening accuracy in clinical practice.

FRI481 Clinical Characteristics Of Neutropenic Patients Under Anti-thyroid Drug: A Retrospective Cohort Study In Taiwan

Abstract Disclosure: C. Tseng: None. C. Tseng: None. H. Chen: None. P. Chen: None. C. Huang: None. Background: Thionamide-induced agranulocytosis (TiA), is a rare adverse event with a reported incidence of around 0.1-1.75%. To reduce mortality, prompt recognition is critical but the differential diagnosis of TiA cases from non-TiA neutropenia can be challenging as other causes of neutropenia, such as concomitant chemotherapy, liver dysfunction or infection, may simultaneously exist. The present study aimed at investigating the possible factors associated with the development of TiA. Method: This is a retrospective cohort study of patients treated with anti-thyroid drugs (ATDs) in Taipei Veterans General Hospital from 2006-2018. Patients who developed a neutropenic event under treatment of ATDs were identified from the medical records. TiA was defined as (1) development of neutropenia under treatment or within 7 days of previous exposure to the same ATDs; (2) total recovery of neutropenia within one month after discontinuation of the culprit drug with absolute neutrophil count > 1500/μL; (3) exclusion of other causes for neutropenia. The incidence and risk factors for developing TiA were analyzed and compared to those with non-TiA neutropenia. Results: Among 6644 patients treated with ATDs, 66 (mean age, 53±15 years; 16.2% men) developed a neutropenic event and 20 were diagnosed with TiA (incidence: 0.3%). In univariate analysis, TiA was associated with shorter treatment duration, lesser cumulative ATD dosage, higher ATDs dosage, higher absolute neutrophil count and higher free T4 level at the time of the neutropenic event, compared to non-TiA neutropenia. After accounting for age, gender and time to neutropenia, ATDs dosage at the time of neutropenic event [odds ratio (OR) and 95% confident intervals (CIs): 635.47, 1.88-214562.36], free T4 level (OR and 95% CIs: 17.23, 1.02-290.58), and absolute neutrophil count (OR and 95% CIs: 1.00, 1.00-1.01) were still independently associated with TiA in multivariable logistic regression. Conclusions: TiA patients were more likely to have higher free T4 level, higher absolute neutrophil count at the time of neutropenic event and had received higher dosage of ATDs, compared to non-TiA cases. Presentation: Friday, June 16, 2023

FRI484 Assessment Of Early-trimester Maternal Thyroid Function And Iodine Nutritional Status Of Pregnant Women In Northern Taiwan

Abstract Disclosure: G. Su: None. C. Yeh: None. C. Yang: None. C. Hwu: None. H. Chen: None. F. Wang: None. C. Huang: None. Background: The American Thyroid Association (ATA) has proposed to lower the early-trimester upper limit of the TSH reference interval to become 0.5 mIU/L less than the non-pregnant value. The local-regional reference intervals in Taiwan is unknown. The aim of the study is to evaluate the early-trimester thyroid function and iodine nutritional status of pregnant women in Taiwan. Methods: Women aged ≥20 years-old and in gestation 8 to 15 weeks were recruited in Taipei Veterans General Hospital from March 2019 to July 2022. Thyroid function and antibodies, including TSH, free T4, free T3, total T4, total T3, anti-thyroglobulin antibody (aTG) and anti-thyroidperoxidase antibody (aTPO), TSH receptor antibody, were measured. The gestation-specific thyroid function reference range was derived from the 2.5th and 97.5th percentiles of the studied women. Random spot urine sample was collected and urinary iodine concentration was checked by inductively coupled plasma mass spectrometry. A simple food frequency questionnaire was also completed. Results: A total of 211 women were enrolled and the derived early-trimester upper limit of serum TSH (median: 0.92 [0.007-3.08] uIU/mL) was lower than the value provided by the manufacturer (0.27-4.2 uIU/mL), while the upper limit of free T4 (median: 1.28 [0.93-2.15] ng/dL) and free T3 (3.00 [2.30-5.10]ng/dL) were both higher than the non-pregnant value (0.93-1.7 ng/dL and 2.0-4.4 ng/dL, respectively). The range of total T4 (median: 9.90 [6.39-15.36] ng/dL) and total T3 (median: 136 [89.50-223.20] ng/dL) in the studied women were similar to the non-pregnant range (5.1-14.1 ng/dL and 80-200 ng/dL, respectively). The positivity rate of aTG & aTPO were 8.6%. Two patients with mild Graves’ disease and three patients with subclinical hypothyroidism were incidentally detected and treated. The positive predictive value for detecting thyroid dysfunction using the non-pregnant reference interval was only 15.9% because subclinical hyperthyroidism (18.2%, n=37) would be over-diagnosed and subclinical hypothyroidism (1.0%, n=2) would be under-diagnosed. The overall median UIC was 160.9 μg/L, indicating a sufficient iodine status. Dairy products were the most commonly consumed iodine-containing food type with 71.8% of the pregnant women ingesting dairy products ≥3 days/week. The median intake frequency for seaweed, fish, and seafood were one day per week. Approximately 34.0% of the women took multivitamin every day, but 58.4% of the women never took multivitamin. Conclusion: Our results indicate that the iodine nutritional status in the early trimester of pregnancy is adequate and that the upper limit of serum TSH was approximately 1.12 uIU/mL lower than the upper limit provided by the manufacturer. Gestation-specific thyroid function reference intervals are needed for correct diagnosis of thyroid dysfunction in pregnancy. Presentation: Friday, June 16, 2023

Iodine Concentration in the Breast Milk and Urine as Biomarkers of Iodine Nutritional Status of Lactating Women and Breastfed Infants in Taiwan.

Breast milk iodine concentration (BMIC) can be different when median urinary iodine concentration (UIC) is similar. The BMIC, UIC/creatinine (Cr), estimated 24-h urinary iodine excretion (24-h UIE) of lactating women in Taiwan is unknown. This study enrolled lactating women from Taipei Veterans General Hospital (August 2021-February 2023). Each participant provided a random spot urine sample, two breast milk samples, a blood sample, and completed a food frequency questionnaire on the same day. Iodine measurement was performed by inductively coupled plasma mass spectrometry. The median UIC of the enrolled 71 women was 91.1 μg/L, indicating insufficient iodine status; however, the median BMIC was 166.6 μg/L and this suggested that the amount of iodine delivered through breast milk was adequate for the breastfed infants. BMIC was correlated with UIC/Cr and 24-h UIE (both rs = 0.49) but not with UIC (rs = 0.18) or thyroid stimulating hormone (rs = 0.07). Women who did not consume dairy products (adjusted odds ratio: 24.41, 95% confidence interval: 1.26-471.2) and multivitamins (adjusted odds ratio: 8.26, 95% confidence interval: 1.76-38.79) were at increased odds for having lower BMIC. The results suggest that measuring maternal UIC alone may not be sufficient, as BMIC, UIC/Cr, and 24-h UIE are all important biomarkers. Ingestion of dairy products and multivitamins were independently associated with BMIC.

Serum brain-derived neurotrophic factor levels as a predictor for Alzheimer disease progression.

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of Alzheimer's disease (AD), and decreased peripheral levels of this protein are associated with an increased risk of developing the disease. This study focuses on whether serum BDNF levels could be used as a predictor of AD progression. In this longitudinal observational study, we recruited cognition normal participants (N=98) and AD (N=442) from the Clinic at the Taipei Veterans General Hospital. We conducted a mini-mental status exam, a 12-item memory test, a categorical verbal fluency test, and a modified 15-item Boston naming test. A Serum BDNF level and Apolipoprotein E (APOE) allele status were measured. The AD patients were followed prospectively. Based on the difference of MMSE scores, these patients were divided into fast decliners (decline ≧ 3/year) and slow decliners (MMSE decline < 3/year). Logistic regression was conducted to examine the impact of serum BDNF levels and other factor on the likelihood of AD patients being slow decliners. Pearson's correlation was used to estimate the relationship between serum BDNF levels and the score of neuropsychological tests. In a logistic regression model containing serum BDNF levels, age, sex, APOE4 carrier status, education levels, and baseline MMSE score, higher serum BDNF levels were associated with a slower rate of cognitive decline in the AD group. Serum BDNF levels positively correlated with the results of multiple neuropsychological tests. BDNF is a protective factor against AD progression and likely plays a role in establishing a link between AD pathology and clinical manifestations.

Effects of cancer on stroke recurrence and mortality: A single-center retrospective cohort study.

Whether patients with stroke and cancer have specific characteristics remains controversial. In addition, research regarding the effects of individual cancer types on stroke outcomes remains scarce. This study investigated the mortality and stroke recurrence rates in patients with stroke and concomitant cancer and evaluated outcome predictors. This study retrospectively enrolled 2610 patients in the Taipei Veterans General Hospital Stroke Registry registered from January 2019 to December 2020. A total of 1868 patients were included after excluding those without acute ischemic stroke or hospitalization. The patients were then categorized into the following diagnostic groups: cancer-associated stroke (CAS), stroke and inactive cancer, and stroke without cancer. The discharge mortality rate, 1-year mortality rate, and 1-year stroke recurrence rate were compared. Multiple clinical characteristics and comorbidities-age, sex, stroke severity, coagulopathy, common vascular risk factors, and acute stroke treatment-were also assessed. A total of 302 (16.2%) patients had concomitant cancer; 39 (2.1%) patients were classified as having CAS and 263 (14.1%) as having stroke with inactive cancer. The baseline characteristics, stroke severity, and type of acute reperfusion therapy were similar among the three groups. However, the stroke recurrence and mortality rates were much higher in the patients with CAS in both short-term and long-term follow-up. The 30-day and 1-year mortality rates for the CAS, inactive cancer, and no cancer groups were 17.9%, 12.5%, and 4.7%, (p<0.001) and 51.3%, 33.8%, and 12.4%, (p<0.001) respectively. Patients with stroke and active cancer had similar stroke severity. However, the 1-year mortality and stroke recurrence rates were higher in these patients than in patients with inactive cancer or the control group.

Reduction in the Incidence Density of Pressure Injuries in Intensive Care Units after Advance Preventive Protocols.

(1) Background: Patients who are critically ill or undergo major surgery are admitted to intensive care units (ICUs). Prolonged immobilization is the most likely cause of pressure injuries (PrIs) in the ICU. Previous studies of Western populations found that effective protocols could reduce the incidence of PrIs, and the efficacy of systemic targeted intervention protocols in preventing PrIs in the Chinese population needs to be surveyed. (2) Methods: We reviewed cases of PrIs in the ICUs of Taipei Veterans General Hospital from 2014 to 2019. The ICU nurses at the hospital began to implement targeted interventions in January 2017. The incidence density of PrIs was calculated by dividing the number of PrIs by person days of hospitalizations in the pre-bundle (2014-2016) and post-bundle (2017-2019) stages. Poisson regression was performed to compare the trend of incidence densities. (3) Results: The incidence density of PrIs was 9.37/1000 person days during the pre-bundle stage and 1.85/1000 person days during the post-bundle stage (p < 0.001). The relative risk (RR) was 0.197 (95% confidence interval: 0.149-0.26). The incidence densities of iatrogenic PrIs and non-iatrogenic PrIs decreased as the RRs decreased. (4) Conclusions: Targeted interventions could significantly reduce the incidence of PrIs. Healthcare providers must follow the bundle care protocol for PrI prevention to improve the quality of healthcare and promote patient health.

Clinical characteristics of neutropenic patients under antithyroid drug: Twelve-year experience in a medical center.

Thionamide-induced agranulocytosis (TiA) is a rare adverse event with a reported incidence of approximately 0.1% to 1.75%. Prompt recognition of TiA is critical to reduce the mortality rate. However, the differential diagnosis between cases of TiA and non-TiA neutropenia can be challenging due to the potential simultaneous involvement of other causes of neutropenia, such as concomitant chemotherapy, liver dysfunction, or infection. The aim of the present study was to investigate the possible factors associated with the development of TiA. This was a retrospective cohort study of patients treated with antithyroid drugs (ATDs) in Taipei Veterans General Hospital, Taipei, Taiwan, from 2006 to 2018. Patients who developed a neutropenic event during treatment with ATDs were identified from their medical records. The diagnosis of TiA was based on the following: (1) development of neutropenia during treatment or within 7 days after previous exposure to the same ATDs; (2) complete resolution of neutropenia within 1 month after discontinuation of the culprit drug with an absolute neutrophil count (ANC) >1500/μL; and (3) exclusion of other causes of neutropenia. The incidence and risk factors of TiA were analyzed and compared with those of non-TiA neutropenia. Among 6644 patients treated with ATDs, 66 (mean age: 53 ± 15 years; 16.2% men) developed a neutropenic event and 20 were diagnosed with TiA (incidence: 0.3%). In the univariate analysis, compared with non-TiA neutropenia, TiA was associated with a lower Charlson Comorbidity Index, shorter treatment duration, lower cumulative ATD dosage, higher ATD dosage, higher ANC, and higher levels of free T4 at the time of the neutropenic event. In the multivariate logistic regression analysis, after adjusting for age, gender and the time to neutropenia, the cumulative ATD dose to neutropenia and ATD dosage at the time of the neutropenic event, Charlson Comorbidity Index, free T4 levels (odds ratio [OR], 4.44; 95% CI, 1.48-13.25), and ANC (OR, 1.00; 95% CI, 1.00-1.01) remained independently associated with TiA. Patients with TiA were more likely to have higher levels of free T4 and ANC at the time of the neutropenic event vs those with non-TiA neutropenia.

Diet and exercise are a fundamental part of comprehensive care for type 2 diabetes.

Diet and exercise are a fundamental part of comprehensive care for type 2 diabetes.

Incidence and contributing factors of non-root canal treated teeth with chronic fatigue root fracture: A cross-sectional study

Chronic fatigue root fracture describes a root fracture in a non-root canal treated (non-RCT) tooth. This study aimed to report the incidence and contributing factors of non-RCT teeth with chronic fatigue root fracture in a Taiwanese population. This cross-sectional study included teeth extracted at Taipei Veterans General Hospital in Taiwan between 2018 and 2019. The reasons for extractions were recorded and included vertical and horizontal root fractures (VRF and HRF). Comparisons of clinical factors between teeth with fatigue VRF and teeth with fatigue HRF were performed by chi-square or Fisher exact test, where appropriate. Of the 4207 extracted teeth examined, 263 (6.25%) had tooth fracture. Thirty-two non-RCT teeth had chronic fatigue root fracture, including 16 with VRF and 16 with HRF. The incidence was 0.76% (32/4207). The occurrence of chronic fatigue root fracture was higher in males (83.9%). The mean age of the 31 patients with chronic fatigue root fracture was 71.7±13.1 years. More than half of these teeth had intact crowns with severe attrition. The fatigue VRF occurred more frequently in molars (P=0.003), in roots with a long oval cross-section (P=0.037), and in terminal teeth (P=0.013) than the fatigue HRF. The incidence of chronic fatigue root fracture is 0.76%. Both VRF and HRF occur mainly in aged males, in posterior teeth with attrition, and in teeth without restoration. Tooth position, cross-section root morphology, and terminal tooth are contributing factors related to chronic fatigue root fracture.

#3736 SACUBITRIL/VALSARTAN IMPROVES THE VASCULAR ACCESS FLOW OF HEMODIALYSIS PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION

Abstract Background and Aims Sacubitril/valsartan improved left ventricular systolic and diastolic function in patients with heart failure with reduced ejection fraction&amp;lt;40% (HFrEF) and end-stage kidney disease. However, there was no report concerning the effect of sacubitril/valsartan on access flow (Qa) of vascular access in maintenance hemodialysis (HD) patients with HFrEF. We aimed to investigate the effect of sacubitril/valsartan on Qa of vascular access in HD patients with HFrEF. Method We retrospectively screened the HD patients who received echocardiogram and Qa measurement in Taipei Veterans General Hospital and Cheng Hsin General Hospital from Jan. 2019 to Dec. 2021. Patients with HFrEF received twice of both echocardiography and Qa at 1 year apart were enrolled and divided into two groups, including those with or without the treatment of sacubitril/valsartan. The difference of Qa at baseline and 1 year later was compared by Wilcoxon signed-rank test, with a statistical significance of P&amp;lt;0.05. Results A total of 33 HD patients with HFrEF were analyzed with a mean HD vintage of 4.7 years. Sixteen patients received sacubitril/valsartan and the other 17 patients received conventional treatment. The mean Qa increased significantly from 633.8 to 948.8 mL/min (P&amp;lt;0.001) and the Qa change correlated with LVEF change [Fig. 1. correlation coefficient (r) =0.70, P=0.006] after 1-year treatment of sacubitril/valsartan; however, there was neither significant change of Qa (from 637.7 to 621.8 mL/min, P=0.44) nor correlation with LVEF change (Fig. 2, r=0.41, P=0.13) for controls after one year. Conclusion Sacubitril/Valsartan improves Qa in HD patients with HFrEF possibly related to the increase of LVEF.

Pelvic organ prolapse: Minimally invasive approach.

aDepartment of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan, ROC; bDepartment of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC cInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC dFemale Cancer Foundation, Taipei, Taiwan, ROC Received date: June 4, 2023 Accepted date: June 7, 2023. Conflicts of interest: Dr. Peng-Hui Wang, an editorial board member at the Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare no conflicts of interest related to the subject matter or materials discussed in this article. *Address Correspondence. Dr. Peng-Hui Wang, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei 112, Taiwan, ROC. Tel: 886 2 28757566; Fax: 886 2 55702788; E-mail addresses: [email protected]; [email protected] (P.-H. Wang) This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Improved Survival Analyses Based on Characterized Time-Dependent Covariates to Predict Individual Chronic Kidney Disease Progression.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 497 patients with stage 3-5 chronic kidney disease (CKD) who were treated at the ward of Taipei Veterans General Hospital from January 2006 to 2019 in Taiwan. The patients underwent 3-year-long follow-up sessions for clinical measurements, which occurred every 3 months. Three time-dependent survival models, namely the Cox proportional hazard model (Cox PHM), random survival forest (RSF), and an artificial neural network (ANN), were used to process patient demographics and laboratory data for predicting progression to renal failure, and important features for optimal prediction were evaluated. The individual prediction of CKD progression was validated using the Kaplan-Meier estimation method, based on patients' true outcomes during and beyond the study period. The results showed that the average concordance indexes for the cross-validation of the Cox PHM, ANN, and RSF models were 0.71, 0.72, and 0.89, respectively. RSF had the best predictive performances for CKD patients within the 3 years of follow-up sessions, with a sensitivity of 0.79 and specificity of 0.88. Creatinine, age, estimated glomerular filtration rate, and urine protein to creatinine ratio were useful factors for predicting the progression of CKD patients in the RSF model. These results may be helpful for instantaneous risk prediction at each follow-up session for CKD patients.

Prognostic values of circulating TREM2+ and ARG1+ Mreg cells in adults with treatment‐naïve diffuse large B‐cell lymphoma

Introduction: Novel Trem2+ (triggering receptor expressed on myeloid cells 2) and Arg1+ (arginase 1) regulatory myeloid cells (Mreg) that lead to the dysfunction of CD8+ T cells and facilitate tumor growth were recently discovered in a murine cancer model by Yonatan Katzenelenbogen et al. However, as the roles of Mreg cells have never been examined in human cancer patients, we aim to elucidate the clinical impact of circulating Mreg cells on patients with treatment-naive B-cell NHL, especially focusing on DLBCL. Methods: This prospective, observational study enrolled 102 adults with newly diagnosed and treatment-naïve B-cell NHL, including 62 DLBCL, 25 FL (4 grade 3B), 4 MCL, 4 MZL, 2 LPL, 2 BL, and 3 mature B-cell neoplasms, from December 2020 to November 2022. We obtained human circulating TREM2+ and ARG1+ Mreg cells from freshly isolated peripheral blood and calculated their percentages among CD45+ and CD15- cells by flow-cytometry analysis. Non-stain (NS) and fluorescence minus one (FMO) controls were used for gating positive levels of surface TREM2 and intracellular ARG1, respectively. Results: Among 102 patients with B-cell NHL, those with high-risk IPI had significantly higher percentages of circulating Mreg cells than patients with intermediate or low-risk IPI (5.46% vs. 1.71% vs. 0.63%, P H vs. L < 0.001, P H vs. I = 0.032, P I vs. L = 0.005); patients with aggressive subtypes (including grade-3B FL) had significantly higher percentages of circulating Mreg cells than patients with indolent subtypes (1.89% vs. 0.93%, P = 0.023). For 62 DLBCL patients, those with high IPI risk (9.18% vs. 1.25%, P < 0.001), bulky mass ≥ 7.5 cm (5.08% vs. 1.18%, P = 0.057), or DEL (5.13% vs. 1.21%, P = 0.036) had significantly higher percentages of circulating Mreg cells (Figures A–F). More importantly, DLBCL patients with circulating Mreg cells ≥4.5% had significantly worse PFS and OS than those with Mreg cells <4.5% after a median follow-up of 14 months (Figures G and H); when utilizing multivariate Cox regression analysis, “circulating Mreg cells ≥4.5%” remained an independent prognostic factor for both PFS and OS after adjusting for confounding factors, including age, sex, high-risk IPI, bulky mass ≥7.5 cm, BM involvement, non-GCB type, and DEL. The research was funded by: The research was funded by grants from: (1) the Taiwan Ministry of Science and Technology (MOST 111-2314-B-075-037), (2) Taipei Veterans General Hospital (V110B-012), (3) the Chong Hin Loon Memorial Cancer and Biotherapy Research Center, (4) the Melissa Lee Cancer Foundation, and (5) the Taiwan Clinical Oncology Research Foundation. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers No conflicts of interests pertinent to the abstract.

The Endophenotypic Effect of the SORL1 Variant rs2298813 on Regional Brain Volume in Patients with Alzheimer’s Disease

AbstractBackgroundTwo common variants of sortilin‐related receptor 1 gene (SORL1), rs2298813 and rs1784933, have been associated with late‐onset Alzheimer’s disease (AD) in the Han Chinese population in Taiwan. However, neuroimaging correlates of these two SORL1 variants remain unknown. We aimed to determine whether the two SORL1 polymorphisms were associated with any volumetric differences in brain regions in AD patients.MethodsWe recruited 200 patients with late‐onset AD from Taipei Veterans General Hospital. All patients received a structural magnetic resonance imaging brain scan and completed a battery of neurocognitive tests at enrollment. We followed up to assess changes in Mini‐Mental State Examination (MMSE) scores in 155 patients (77.5%) at an interval of 2 years. Volumetric measures and cortical thickness of various brain regions were performed using FreeSurfer. Regression analysis controlled for apolipoprotein E status. Multiple comparisons were corrected for using the false discovery rate.ResultThe rs2298813 and rs1783933 genotypes were not associated with cognitive test performance or clinical progression. The homozygous major allele of rs2298813 was associated with larger volumes in the right putamen (p = 0.0442) and right pallidum (p = 0.0346). There was no link of the rs1784933 genotypes with any of the imaging measures. In the rs2298813 homozygous major allele carriers, the right putaminal volume was associated with verbal fluency (p = 0.008) and clinical progression (p = 0.020). In the minor allele carriers, the right putaminal and right pallidal volumes were not significantly related to cognitive test scores or clinical progression.ConclusionThe major and minor alleles of rs2298813 had differential effects on the right lentiform nucleus volume and distinctively modulated the association between the regional volume and cognitive function.

Pre-cluster symptoms and treatment response in cluster headache: A large cohort in Taiwanese patients (S41.005)

<h3>Objective:</h3> This study aimed to analyze the prevalence, symptomatology, and predictivity of upcoming bouts of pre-cluster symptoms (PCS). Also, we investigated the associations between different PCS and treatment responses for CH. <h3>Background:</h3> PCS are symptoms preceding the upcoming bouts. Some patients could predict the CH bout based on these symptoms and might have roles in pre-emptive treatment. This study analyzed the characteristic of PCS in a large Asian cohort. Moreover, we explored the linkage between PCS and the treatment outcome of CH. <h3>Design/Methods:</h3> We prospectively collected consecutive data from patients with CH. Each patient completed semi-structured interviews during CH bouts, which included 50 questions about CH symptomatology, severity, and PCS. After CH bout, we recorded responses to acute and preventive treatments. The thirty-five PCS were divided into six categories: localized (head &amp; neck) pain, general pain, fatigue &amp; mood changes, sleep problems, constitutional symptoms, and cranial autonomic symptoms. <h3>Results:</h3> A total of 131 CH patients (M: F= 98: 33) were recruited during the study period. The prevalence of PCS was 64.9%, with a mean (± SD) duration of 2.2 (± 3.9) days before CH bouts. Up to 64.1 % of CH patients were able to predict upcoming bouts. Among six categories of PCS, head and neck pain symptoms were most common (82.4%), and were more able to predict upcoming bouts (presence: absence= 68.5% vs. 43.5%, p=0.023, OR=2.8 [95% CI 1.1–7.1]). Moreover, PCS associated with response to CH preventive treatments: sleep alternation and restlessness before upcoming bouts are more likely responsive to verapamil (OR=2.1 [95% CI 1.0–4.3] and 2.3 [95% CI 1.1–4.6], respectively). <h3>Conclusions:</h3> About two-thirds of CH patients had PCS. Head and neck pain symptoms were the most common PCS with the highest predictivity of the upcoming bout. Certain PCS linked to better response to verapamil, which provides insights into future treatment strategies. <b>Disclosure:</b> The institution of ShuTing Chen has received research support from Ministry of Science and Technology (Taiwan). The institution of ShuTing Chen has received research support from Taipei Veterans General Hospital . Ms. Lin has nothing to disclose. Miss TSENG has nothing to disclose. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen-Idec. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for International Headache Society (IHS). The institution of Dr. Wu has received research support from Ministry of Science and Technology of Taiwan. The institution of an immediate family member of Dr. Wu has received research support from Ministry of Science and Technology of Taiwan.

One risk factor predicts another risk factor.

aDepartment of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan, ROC; bDepartment of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC cDepartment of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan, ROC dFemale Cancer Foundation, Taipei, Taiwan, ROC Received date: March 11, 2023 Accepted date: March 13, 2023 Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. *Address correspondence. Miss Wen-Hsun Chang, Department of Nursing, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei 112, Taiwan, ROC. Tel: 886 2 28757566; Fax: 886 2 55702788 E-mail addresses: [email protected] (W.-H. Chang) This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effect of co-medications and potential risk factors of high-dose methotrexate-mediated acute hepatotoxicity in patients with osteosarcoma.

Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of HD-MTX-mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited. This cohort study included patients with newly diagnosed OGS who were treated with HD-MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD-MTX-mediated acute hepatotoxicity, co-medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD-MTX-mediated acute hepatotoxicity. Almost all patients with OGS treated with HD-MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3-4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high-risk subgroups for HD-MTX-mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD-MTX. However, the concurrent use of PPIs, TMP-SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy. Co-administration of PPIs, TMP-SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well-monitored and adequately pre-medicated patients with OGS undergoing chemotherapy with HD-MTX. Clinicians should pay particular attention to ALT levels when prescribing HD-MTX to children and women.

Deep learning in detecting tumor spread through air spaces

Lung cancer is a leading cause of death on a global scale. Professor I-Fang Chung leads a team of researchers at the Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taiwan, investigating how machine learning can help predict the risk of tumour recurrence following lung cancer surgery. The standard treatment for early-stage lung cancer patients is complete surgical resection of the tumour but disease recurrence within the first five years following surgery is common. The route of this recurrence is usually tumour spread through the air spaces (STAS) and the presence of STAS has recently been identified as a risk factor for recurrence of tumours. The researchers are exploring the importance of STAS and how targeting this phenomenon and using machine learning methods to aid in the analysis of medical imaging of diseased tissues can help in predicting the recurrence risk of post-surgery lung cancer patients. Dr Yi-Chen Yeh, a pathologist from the Taipei Veterans General Hospital, is working with Chung to employ a variety of deep-learning object detection methodologies to detect STAS in pathology images. Regions of interest (ROI) images extracted from pathology whole slide images (WSI) are marked and annotated, which provides location information for STAS. Deep learning object detection methods are used to train a model which can find STAS, then additional techniques including using pre-trained model parameters, augmenting random image data and modifying loss function are used to improve the detection rates for the model. Their model helps pathologists identify STAS and accurately predicts patient outcomes.

Risk Factors for Treatment Failure in Skin and Soft Tissue Infections Caused by Nontuberculous Mycobacteria

This study investigated the characteristics of patients with skin and soft tissue infections (SSTIs) caused by nontuberculous mycobacteria (NTM) and identified the risk factors for treatment failure in these patients. Data of patients with NTM SSTIs who received treatment between January 2014 and December 2019 at Taipei Veterans General Hospital were collected retrospectively. Possible risk factors were determined using univariate and multivariate analysis with logistic regression models. A total of 47 patients (24 male, 23 female; age, 57.1 ± 15.2 years) were enrolled. Type 2 diabetes mellitus was the most common comorbidity. The most common mycobacterial species was the Mycobacterium abscessus complex, and the most commonly affected site was the axial trunk. Treatment was successful in 38 patients (81%). Six patients had recurrent infections (13%) after the treatment course was completed, and 3 patients (6.4%) died of NTM-related infection. Delayed treatment for more than 2 months and antibiotic-alone treatment were 2 independent risk factors for treatment failure of NTM SSTIs. Delayed treatment for more than 2 months and antibiotic-alone treatment were associated with a higher failure rate in patients with NTM SSTIs. Therefore, the differential diagnosis of NTM infection should always be considered when the treatment course is prolonged but not effective. Early identification of causative NTM species and appropriate antibiotic treatment may lower the risk of treatment failure. Prompt surgical treatment is suggested if available.