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Objective: Tele-health care service of alternative practice for chronic pain disease is worthwhile of developing, especially in the period of COVID- 19 pandemic. Targeting on myofascial trigger points, this study was performed to assess the possible short-term pain relief and functional improvement in patients by applying the device of BIOCERAMIC material enhanced by frequencies of tempo sound and visible light spectrum (BioS & L). Methods: Fourteen patients who participated in the procedure for the selection of trigger points for the BioS &L treatment, assessment of pain levels using a visual analog scale (VAS) analysis, and detection of abnormal resonance of 12 harmonic frequencies using a quantum resonance spectrometer (QRS). Results: Comparing the pre- and post-treatment of BioS &L on pain score of 12 HFs (V1-V12) as measured by VAS estimated by mixed model showed 91.7% (11/12) improvement with statistically significant results. The distribution of differences in the QRS score estimated by the mixed model among participants with pre-test QRS level ≥ 2 showed 83.3% (15/16) of HFs with statistically significant results. Conclusion: Treatment of BioS &L at trigger points providing pain relief is explained by the hypothesis of microvascular physiology and physics of wave propagation. This study provides a workshop with a concept of digitalization of complementarity and traditional medical service and tele-health care, which fulfills distant data connection and remote practice. In the period of epidemic spread, it helps to decrease close contact on both health care providers and patients.

Background: Previous epidemiological investigations examining the association between Kawasaki disease (KD) and cerebrovascular disease have had conflicting results. We analyzed the association between KD and cerebrovascular disease by conducting a population-based retrospective cohort study designed to investigate the hypothesis that KD could be a risk factor for subsequent cerebrovascular disease. Methods: From the National Health Insurance Research Database of Taiwan, the data of children (aged 0–18 years old) with KD (n=8467) were collected. Starting with the first year of study observation (referred to as the baseline year), data was collected for each child with KD, and 4 non-KD patients matched for sex, urbanization level of residence, and parental occupation were randomly selected to form the non-KD cohort (n=33 868) for our analysis. For the period from January 1, 2000, to December 31, 2012, we calculated the follow-up person-years for each patient, which is the time from the index date to the diagnosis of cerebrovascular disease, death, or the end of 2012. Furthermore, we compared the incidence, the incidence rate ratio, and the 95% CI of cerebrovascular disease between the KD and non-KD cohorts. Results: The overall cerebrovascular disease incidence rate was found to be 3.19-fold higher, which is significantly higher, in the KD cohort than in the non-KD cohort (14.73 versus 4.62 per 100 000 person-years), and the overall risk of cerebrovascular disease remained higher in the KD cohort (adjusted hazard ratio, 3.16 [95% CI, 1.46–6.85]). Furthermore, children aged Conclusions: This nationwide retrospective cohort study shows that KD may increase the risk of subsequent cerebrovascular disease, especially in those with KD aged

Purpose: To report the surgical outcomes of antegrade balloon dacryocystoplasty combined with pushed-type monocanalicular intubation as a primary surgical treatment in patients with congenital nasolacrimal duct obstruction. Methods: A retrospective cohort study was conducted at National Cheng Kung University Hospital. The medical records of all patients with congenital nasolacrimal duct obstruction who underwent antegrade balloon dacryocystoplasty followed by pushed-type monocanalicular intubation as the primary surgical treatment from January 2018 to July 2020 were included. The monocanalicular tube was removed 1 to 2 weeks after intubation. Surgical success was defined as resolved epiphora 1 month after the tube was removed. Results: A total of 62 eyes of 48 patients were involved in this study. The mean age of the total population was 24.1 months (range: 12 to 66 months). The mean duration of the tube indwelling in the nasolacrimal duct was 9.5 days (range: 4 to 15 days). A total of 60 of the 62 eyes (96.77%) reported surgical success. Early tube loss occurred in 2 eyes (3.23%); however, epiphora was not reported afterward. No complications other than tube loss were recorded. There were no recurrences in patients who had undergone successful surgery observed up to July 2020. Conclusions: Antegrade balloon dacryocystoplasty with short-term pushed-type monocanalicular intubation as a primary surgical treatment for congenital nasolacrimal duct obstruction may have high potential with a high success rate and a low complication rate. [ J Pediatr Ophthalmol Strabismus . 2021;58(6):365–369.]

BACKGROUND Acute appendicitis is one of the most common acute abdominal emergencies around the world, which is always associated with infection. Infection with Salmonella typhi, an enteric pathogen, is a rare cause of acute appendicitis. We here report a patient with acute appendicitis associated with Samonella typhi infection, accompanied with spleen and kidney infarction, providing a rare example for a common surgical emergency. CASE SUMMARY A 25-year-old Pakistani man presented to the hospital with a 3-d history of fevers, vomiting, and abdominal pain. Computed tomography (CT) revealed a thickened intestinal wall of the ileocecal junction with multiple enlarged lymph nodes nearby. He was diagnosed with acute appendicitis and received laparoscopic appendectomy, which showed mild inflammation of the appendix. After the surgery, the patient presented again with a high fever (> 39 °C) and diarrhea. A CT angiography scan indicated spleen and kidney infarction. According to the blood culture, the diagnosis was finally clear to be Samonella typhi infection. The pyrexia and enteric symptoms were relieved after the application of intravenous levofloxacin. CONCLUSION This case, characterized by the combination of Salmonella typhi infection, acute appendicitis, and renal and splenic infraction, serves as a rare example for a common surgical emergency.

Background Microelectrode recording (MER)-guided deep brain stimulation (DBS) remains the standard electrophysiological procedure to place the DBS lead at the optimal target. When single-track MER or test stimulation yields suboptimal results, trajectory adjustments are needed. Intraoperative computed tomography (iCT) can be useful to visualize the microelectrode and verify possible adjustments. The aim of this study was to evaluate the effect of iCT in MER during frameless stereotactic DBS for Parkinson disease (PD). Methods We retrospectively collected 28 PD patients, of whom 19 received iCT and 9 did not, and measured intracranial volume, cerebral volume, cerebrospinal fluid volume, and pneumocephalus volume. Euclidean distance was assessed according to merged preoperative brain CT and magnetic resonance imaging and postoperative brain CT. Results Fifty-six hemispheres in the 28 patients were analyzed for MER tracks. The patients who received iCT had a significantly lower mean number of MER tracks (1.6 vs. 2.6, P = 0.013) and lower mean Euclidean distance (2.2 mm vs. 2.7 mm, P = 0.033) compared with those who did not receive iCT. Although there was a trend of a decrease in pneumocephalus using intraoperative imaging, there was no significant difference in surgical time. Conclusions iCT can reduce the number of MER tracks and increase surgical accuracy. Further studies are warranted to investigate whether iCT can reduce surgical complications and improve surgical outcomes.

Many studies have revealed that statin therapy reduced mortality in cancer patients, especially in breast cancer, but the effect for second cancer was unclear. We, therefore, performed a comparable cohort study to determine the risk of second cancer in breast cancer patients with statin therapy. Using claims data from Taiwan’s National Health Insurance Program, this study enrolled newly diagnosed breast cancer patients from 2000 to 2007 with and without statin therapy as the statin (n = 1222) and nonstatin (n = 4888) cohorts, respectively. The nonstatin cohort was propensity score matched by cohort entry year, age, and randomly selected comorbidities. These two cohorts were followed up until the diagnosis of second cancer, death, or the end of 2011. Cox proportional hazard models were used to estimate the hazard ratios. The statin cohort had a lower incidence rate than the nonstatin cohort for second cancer (7.37 vs. 8.36 per 1000 person-years), although the difference was not significant (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.65–1.26). Compared with the nonstatin cohort, the second cancer risk was significantly higher for patients taking pravastatin (aHR 2.71, 95% CI 1.19–6.19) but lower for those receiving multiple statin treatment (aHR 0.45, 95% CI 0.25–0.81) and combined lipophilic and hydrophilic type of statin (aHR 0.42, 95% CI 0.20–0.89). The risk was lower for patients receiving a cumulative defined daily dose (cDDD) of > 430 (aHR 0.41, 95% CI 0.19–0.86). This study showed that there is little association between statin use and second cancer risk in breast cancer patients.

Background and Purpose: No data exists on whether proportional recovery (PR) is associated with health-related quality of life (HRQOL) domains. We evaluated whether PR was associated with domain-specific HRQOL scores at 3 months after ischemic stroke. Methods: This prospective cohort study enrolled patients with ischemic stroke between January 2017 and June 2018. Impaired strength was assessed using the Fugl-Meyer Upper Extremity (range, 0–66 points) and Motricity Index (range, 0–100 points) during index hospitalization and 3 months. Both measures are well-validated and reliable in patients with stroke to assesses motor functioning. PR (defined as 70% of difference between initial score and maximum possible recovery) was calculated from the initial measurements. HRQOL was measured using Neuro-QOL domains: upper extremity, depression, and cognition domains. PR was evaluated with HRQOL domains using binomial logistic regression. Results: Final analysis included 84 patients (mean age 67.8±16.4 years; 44% male; 51.2% White). For both Fugl-Meyer Upper Extremity and Motricity Index, the PR threshold was met for 48.8% of patients. Failure to meet Motricity Index PR was only associated with increased odds of HRQOL depression impairment (adjusted odds ratio, 11.8 [95% CI, 1.23–112.7]). Failure to meet Fugl-Meyer Upper Extremity PR threshold was not associated with HRQOL impairment after adjustment. Conclusions: Our findings suggest that reaching the PR threshold provides poor discrimination of HRQOL. Despite not meeting expected PR thresholds, patients can still maintain un-impaired HRQOL, suggesting other factors play a role in preserved HRQOL.

By enhancing vagal activity, auricle transcutaneous electric nerve stimulation (TENS) is developed as a non-invasive therapy for heart failure. Nevertheless, though shoulder TENS used for treating adhesive capsulitis could affect vagal tone, its potential impact on heart functions remains unclear. In this study, electrocardiogram (ECG) and heart rate (HR) of subjects in response to sham, right-sided, or left-sided shoulder TENS (TENS-S, TENS-R, and TENS-L, respectively; 5 min) were recorded and analyzed. During the stimulation period, TENS-R constantly and TENS-L transiently decreased the HR of subjects; both TENS-R and TENS-L increased powers of the low- and high-frequency spectra. While TENS-R exhibiting no effect, TENS-L increased the ratio of low/high-frequency power spectrum indicating TENS-R decreased the HR through potentiating cardiac vagal tone. Collectively, these results suggest TENS could be an early and non-invasive therapy for heart failure patients before considering implant devices or devices are not feasible; moreover, therapists/physicians need to carefully monitor the potential adverse events during treatment for patient safety.Trial registration: The study protocol was registered in ClinicalTrials.gov (NCT03982472; 11/06/2019).

Objective Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming. Methods A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn–Tolosa–Marín tremor rating score compared to the preoperative baseline. Results Among the six patients, tremor rating scores differed significantly among the three experimental conditions ( P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R2=0.24; P=0.04). No significant adverse events were encountered. Conclusions Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.

Background/purpose To investigate nerve excitability changes in patients with fibromyalgia and the correlation with clinical severity. Methods We enrolled 20 subjects with fibromyalgia and 22 sex and age-matched healthy subjects to receive nerve excitability test and nerve conduction study to evaluate the peripheral axonal function. Results In the fibromyalgia cohort, the sensory axonal excitability test revealed increased superexcitability (%) (P = 0.029) compared to healthy control. Correlational study showed a negative correlation between increased subexcitability (%) (r = −0.534, P = 0.022) with fibromyalgia impact questionnaire (FIQ) score. Computer modeling confirmed that the sensory axon excitability pattern we observed in fibromyalgia cohort was best explained by increased Barrett–Barrett conductance, which was thought to be attributed to paranodal fast K+ channel dysfunction. Conclusion The present study revealed that paranodal sensory K+ conductance was altered in patients with fibromyalgia. The altered conductance indicated dysfunction of paranodal fast K+ channels, which is known to be associated with the generation of pain.

Background Retrospective studies have suggested that patients with dementia have higher prevalence of atopic dermatitis (AD) than those without dementia. However, the temporal association of AD with subsequent dementia remains unknown. Objective To assess the temporal association of AD with subsequent dementia. Methods We included data of patients with AD aged 45 years and older (n = 1059) and 1:10 age, sex, residence, income, and dementia-related comorbidity–matched controls (n = 10,590) from the Taiwan National Health Insurance Research Database and reviewed their subsequent dementia development from the enrollment date to the end of 2013. Results After adjustments for dementia-related comorbidities, patients with AD were found to be more likely to develop any dementia (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.24-3.29), particularly Alzheimer's disease (HR, 3.74; 95% CI, 1.17-11.97), during the follow-up period than those in the control group. Moderate-to-severe AD was associated with a high subsequent dementia risk (HR, 4.64; 95% CI, 2.58-8.33). Sensitivity analyses with the exclusion of the first 3 (HR, 2.20; 95% CI, 1.28-3.80) or 5 (HR, 2.05; 95% CI, 1.08-3.89) years of observation revealed consistent findings. Conclusion AD may be an independent risk factor for new-onset dementia. Clinicians may monitor the trajectory of neurocognitive function among elderly patients with AD. Additional studies elucidating the pathomechanisms between AD and subsequent dementia are warranted.

Background and Purpose: Patients with obsessive-compulsive disorder (OCD) tend to be comorbid with stroke-related risk factors, including obesity, hypertension, and diabetes. However, the temporal association between OCD and subsequent stroke risk is unclear. Methods: Using data collected between 2001 and 2010 by Taiwan’s National Health Insurance Research Database, 28 064 adult patients with OCD (International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD-9-CM ] code: 300.3) and 28 064 age-, sex-, and comorbidity-matched controls were included in this study. Patients who developed ischemic ( ICD-9-CM codes: 433, 434, and 435) and hemorrhagic ( ICD-9-CM codes: 430, 431, and 432) stroke during follow-up (from enrollment to end of 2011) were identified. Moreover, medications used for treating OCD were assessed. Results: Patients with OCD (hazard ratio [HR], 3.02 [95% CI, 1.91–4.77]), especially middle-aged (HR, 2.66 [95% CI, 1.34–5.29]) and elderly adults (HR, 3.46 [95% CI, 1.70–7.05]), had an elevated risk of developing ischemic stroke during the follow-up period compared with non-OCD controls. The cumulative HR of hemorrhagic stroke did not differ (HR, 0.87 [95% CI, 0.42–1.80]) between the OCD and non-OCD groups. In patients with OCD, both short- (HR, 1.69 [95% CI, 0.74–3.88]; HR, 0.31 [95% CI, 0.05–1.95]) and long-term use (HR, 1.37 [95% CI, 0.60–3.16]; HR, 0.90 [95% CI, 0.22–3.76]) of OCD medications were not correlated with ischemic and hemorrhagic stroke compared with nonuse. Conclusions: Clinicians should closely monitor cerebrovascular disease and related risks in patients with OCD. The pathomechanism of OCD with an increased risk of ischemic stroke warrants further investigation.

Purpose Exploration of the effect of chronic recurrent seizures in focal epilepsy on brain volumes has produced many conflicting reports. To determine differences in brain structure in temporal lobe epilepsy (TLE) and extratemporal epilepsy (using frontal lobe epilepsy (FLE) a surrogate) further, we performed a retrospective analysis of a large cohort of patients with seizure-onset zone proven by intracranial monitoring. Methods A total of 120 TLE patients, 86 FLE patients, and 54 healthy controls were enrolled in this study. An analysis of variance of voxel-based morphometry (VBM) was used to seek morphometric brain differences among TLE patients, FLE patients, and healthy controls. Additionally, a vertex-based surface analysis was utilized to analyze the hippocampus and thalamus. Significant side-specific differences in hippocampal gray matter volume were present between the left TLE (LTLE), right TLE RTLE (RTLE), and control groups ( pResults Vertex analyses revealed significant volume reduction in inferior parts of the left hippocampus in the LTLE group and lateral parts of the right hippocampus in the RTLE group compared to controls ( pConclusion Our results highlight the variation in morphometric lateralized changes in the brain between different epilepsy onset zones, providing critical insight into the natural history of people with drug-resistant focal epilepsies.

BACKGROUND Follicular lymphoma (FL) is more common in lymph nodes, while primary extranodal lymphomas are rare. Urinary tract lymphoid neoplasms are extremely rare, accounting for less than 5% of all extranodal lymphomas. Only one case of FL from the renal pelvis has previously been reported. CASE SUMMARY A 70-year-old male patient with a history of esophageal cancer visited our hospital for follow-up examination. Abdominal computed tomography revealed a malignant mass in the right renal pelvis. The whole-body positron emission tomography/computed tomography showed a significant increase in fluorodeoxyglucose uptake of this soft tissue mass and no abnormal fluorodeoxyglucose uptake in the esophageal wall. The patient underwent radical resection of a malignant tumor in the right kidney, which was confirmed by postoperative pathology to be FL. The patient received no radiation or chemotherapy after surgery, and no recurrence of lymphoma or other malignant tumors was found at the 1-year follow-up. CONCLUSION Extranodal FL is more common in the skin and gastrointestinal tract but rarely occurs in the urinary tract. This is the second report of primary renal FL. Localized extranodal FL is expected to have a favorable prognosis and can be cured by local resection.

Objective: In stroke patients, extensive interventions for incidental thyroid nodules can be burdensome and costly. It appears that the risk of malignancy has not been reported in angiographically detected nodules and outcomes have not yet been described in patients, receiving acute stroke work-up. Materials and Methods: Incidental thyroid nodules were found on neck computerized tomography angiography or magnetic resonance angiography performed during inpatient stroke workup (January 2017 to September 2019). These patient cases were reviewed based on sonography reports, diagnosis, and follow-up care. Results: Of the 13 563 patients, 192 had incidental thyroid nodules (prevalence 1.4%). Twenty-six died from comorbidities and 22 received thyroid sonography. Twelve nodules from 10 patients had sonographic characteristics for biopsy: 10 benign, 1 indeterminate, and 1 papillary thyroid cancer (risk of malignancy: 8%). The cancer patient underwent hemithyroidectomy and is disease-free. Follow-up of the remaining patients showed no worsening or suspicious nodules. The American College of Radiology (ACR) guidelines would have prevented 8 unnecessary sonograms and 1 biopsy without missing malignancy. Conclusion: Although a small risk of malignancy was noted, 95% of patients undergoing additional diagnostic thyroid testing had clinically insignificant results. The ACR guidelines can prevent unnecessary interventions. Given the 14% mortality rate in the study cohort, it is proposed that a clinical evaluation of patients is important before undergoing further diagnostics, as comorbidities may be worse than a thyroid cancer.

Background Polycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD. Methods A nationwide population-based cohort study was performed using Taiwan’s National Health Insurance Research Database. We used patients’ hospitalization files for the entire analysis during 2000–2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection. Results A total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51–2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46–4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29–2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69–4.30). Conclusions Taken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.

Evidence suggests that levels of treatment refractoriness and brain-derived neurotrophic factor (BDNF) rs6265 polymorphism are related to the antidepressant effects of conventional antidepressants and repetitive transcranial magnetic stimulation. However, whether these factors are associated with the antidepressant effects of low-dose ketamine remains unclear. In total, 71 patients with treatment-resistant depression (TRD) were randomized to 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline control infusion groups. They were further divided into three treatment refractoriness groups according to the Maudsley staging method and were genotyped for Val66Met BDNF polymorphism. Participants’ Hamilton Depression Rating Scale (HDRS) scores were assessed preinfusion, at 40, 80, 120, and 240 min postinfusion, and sequentially on days 2–7 and 14 after infusion. Patients with any Val allele exhibited an antidepressant response (p = 0.029) to 0.5 mg/kg ketamine vs. 0.2 mg/kg ketamine vs. saline control infusions. However, the trajectory of HDRS scores did not differ (p = 0.236) between the treatment groups among Met/Met carriers. In the low treatment refractoriness group, the 0.2 mg/kg ketamine infusion exhibited the optimal antidepressant effect (p = 0.002); in the moderate treatment refractoriness group, the 0.5 mg/kg ketamine infusion achieved the strongest antidepressant effect (p = 0.006); however, in the high treatment refractoriness group, the trajectory of depressive symptoms did not differ between treatments (p = 0.325). In future clinical practice, ketamine dose may be adjusted according to the level of treatment refractoriness and BDNF rs6265 polymorphism to achieve the optimal antidepressant effect for patients with TRD.

Objectives This study aimed to assess the comparative efficacy of 4 ablation strategies on the incidence rates of freedom from atrial fibrillation (AF) or atrial tachycardia (AT) through a 3-year follow-up in patients with persistent AF. Background The optimal substrate modification strategies using catheter ablation for patients with persistent AF remain unclear. Methods Patients with persistent AF were enrolled consecutively to undergo each of 4 ablation strategies: (a) Group 1 (Gp 1, n=69), pulmonary vein isolation (PVI) plus rotor ablation assisted by similarity index and phase mapping; (b) Gp 2 (n=75), PVI plus linear ablations at the left atrium; (c) Gp 3 (n=42), PVI plus elimination of complex fractionated atrial electrograms; (d) Gp 4 (n=67), PVI only. Potential confounders were adjusted via a multivariate survival parametric model. Results Baseline characteristics were similar across the 4 groups. At a follow-up period of 34.9±38.6 months, patients in Gp 1 showed the highest rate of freedom from AF compared with the other 3 groups (p=0.002), while patients in Gp 3 and 4 showed lower rates of freedom from AT than those of the other two groups (p=0.006). Independent predictors of recurrence of AF were the ablation strategy (p=0.002) and left atrial diameter (LAD) (p=0.01). Conclusion In patients with persistent AF, a substrate modification strategy using rotor ablation assisted by similarity index and phase mapping provided a benefit for maintaining sinus rhythm compared to the other strategies. Both ablation strategy and baseline LAD predicted the 3-year outcomes of freedom from AT/AF This article is protected by copyright. All rights reserved.

Purpose Management of peptic ulcer bleeding is clinically challenging. Accurate characterization of the bleeding during endoscopy is key for endoscopic therapy. This study aimed to assess whether a deep learning model can aid in the classification of bleeding peptic ulcer disease. Methods Endoscopic still images of patients (n = 1694) with peptic ulcer bleeding for the last 5 years were retrieved and reviewed. Overall, 2289 images were collected for deep learning model training, and 449 images were validated for the performance test. Two expert endoscopists classified the images into different classes based on their appearance. Four deep learning models, including Mobile Net V2, VGG16, Inception V4, and ResNet50, were proposed and pre-trained by ImageNet with the established convolutional neural network algorithm. A comparison of the endoscopists and trained deep learning model was performed to evaluate the model’s performance on a dataset of 449 testing images. Results The results first presented the performance comparisons of four deep learning models. The Mobile Net V2 presented the optimal performance of the proposal models. The Mobile Net V2 was chosen for further comparing the performance with the diagnostic results obtained by one senior and one novice endoscopists. The sensitivity and specificity were acceptable for the prediction of “normal” lesions in both 3-class and 4-class classifications. For the 3-class category, the sensitivity and specificity were 94.83% and 92.36%, respectively. For the 4-class category, the sensitivity and specificity were 95.40% and 92.70%, respectively. The interobserver agreement of the testing dataset of the model was moderate to substantial with the senior endoscopist. The accuracy of the determination of endoscopic therapy required and high-risk endoscopic therapy of the deep learning model was higher than that of the novice endoscopist. Conclusions In this study, the deep learning model performed better than inexperienced endoscopists. Further improvement of the model may aid in clinical decision-making during clinical practice, especially for trainee endoscopist.

OBJECTIVE: This study aimed to evaluate the effect of adiposity and fat distribution on the odds of elevated cardiovascular risk factors among adults with type 2 diabetes mellitus. METHODS: The present cross-sectional study included 2,427 adults with type 2 diabetes mellitus. Body fat was assessed by dual-energy x-ray absorptiometry. Multivariate-adjusted logistic regression was used to estimate effects of adiposity parameters on elevated hemoglobin A(1c) (HbA(1c), ≥7.0%), hypertension (blood pressure ≥140/90 mmHg), and elevated low-density lipoprotein (LDL) cholesterol (≥2.6 mmol/L). RESULTS: The multivariable-adjusted odds ratio (OR) for elevated HbA(1c) was 0.82 (95% CI: 0.70–0.96) for each SD increase in leg fat mass. The multivariable-adjusted OR for hypertension was 1.15 (95% CI: 1.00–1.32) for each SD increase in android fat mass. Multivariable-adjusted ORs for elevated LDL cholesterol ranged from 1.16 (95% CI: 1.00–1.35) to 1.27 (95% CI: 1.06–1.51) for each SD increase in arm and android fat mass and percentage of total, truncal, arm, and android fat. Each SD increase in BMI, truncal-to-leg fat ratio, and android-to-gynoid fat ratio was significantly associated with increased risks of elevated HbA(1c), hypertension, and elevated LDL cholesterol. CONCLUSIONS: Subcutaneous fat in the lower body was associated with a more favorable glycemic profile, but not blood pressure or lipid profile, whereas central adiposity was associated with poor control of cardiovascular risk factors among patients with type 2 diabetes mellitus.

Objective No relapse risk prediction tool is currently available to guide treatment selection for multiple sclerosis (MS). Leveraging electronic health record (EHR) data readily available at the point of care, we developed a clinical tool for predicting MS relapse risk. Methods Using data from a clinic‐based research registry and linked EHR system between 2006 and 2016, we developed models predicting relapse events from the registry in a training set (n = 1435) and tested the model performance in an independent validation set of MS patients (n = 186). This iterative process identified prior 1‐year relapse history as a key predictor of future relapse but ascertaining relapse history through the labor‐intensive chart review is impractical. We pursued two‐stage algorithm development: (1) L1‐regularized logistic regression (LASSO) to phenotype past 1‐year relapse status from contemporaneous EHR data, (2) LASSO to predict future 1‐year relapse risk using imputed prior 1‐year relapse status and other algorithm‐selected features. Results The final model, comprising age, disease duration, and imputed prior 1‐year relapse history, achieved a predictive AUC and F score of 0.707 and 0.307, respectively. The performance was significantly better than the baseline model (age, sex, race/ethnicity, and disease duration) and noninferior to a model containing actual prior 1‐year relapse history. The predicted risk probability declined with disease duration and age. Conclusion Our novel machine‐learning algorithm predicts 1‐year MS relapse with accuracy comparable to other clinical prediction tools and has applicability at the point of care. This EHR‐based two‐stage approach of outcome prediction may have application to neurological disease beyond MS.

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce mortality in patients with cancer, especially breast cancer, but their influence on second cancer risk is uncertain. This study aimed to examine whether NSAID use is associated with second cancer risk in patients with breast cancer. This population-based propensity score-matched cohort study using Taiwan’s National Health Insurance Research Database enrolled patients with newly diagnosed breast cancer (n = 7356) with and without (n = 1839) NSAID therapy from 2000 to 2009. They were followed up until the diagnosis of second cancer, death, or end of 2011. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). The NSAID cohort had a lower incidence rate of second cancer than the non-NSAID cohort (5.57 vs. 9.19 per 1,000 person-years), with an aHR of 0.63 (95% confidence interval (CI) 0.46–0.87). When compared with the non-NSAID cohort, the second cancer incidence was lower in patients taking non-cyclooxygenase 2 inhibitors (aHR 0.67, 95% CI 0.47–0.94) and in those receiving multiple NSAIDs during follow-up (aHR 0.55, 95% CI 0.37–0.84). A dose–response relationship existed in NSAID cumulative days. The findings demonstrate that NSAID use reduces second cancer risk in a dose-dependent manner in patients with primary breast cancer.

BACKGROUND Aortic dissection is a rare but severe complication of percutaneous transluminal angioplasty and stenting (PTAS) for stenosis of the subclavian artery (SA). This retrospective study was designed to evaluate the risk factors and outcomes of patients with severe stenosis of the SA who underwent PTAS complicated by aortic dissection. METHODS Between 1999 and 2018, 169 cases of severe symptomatic stenosis of the SA underwent PTAS at our institute. Of them, six cases complicated by aortic dissection were included in this study. We evaluated the demographic features, technical factors of PTAS, and clinical outcomes in these six patients. RESULTS Aortic dissection occurred in 5.3% (6/113) of all left SA stenting cases but in none of the right SA stenting cases. All patients had hypertension and a high severity of SA stenosis (85.0 ± 13.0%, 60%-95%). Five of the six patients received balloon-expandable stents (83.3%). All patients had spontaneous resolution of the aortic dissection with conservative treatment. In a 63.33 ± 33.07 (7-118) month follow-up, five of the six patients (83.3%) had long-term symptom relief and stent patency. CONCLUSION Aortic dissection occurred in patients who underwent PTAS for severe stenosis of the left SA, mainly with balloon-expandable stents. We suggest using self-expandable stents and angioplasty with an undersized balloon during PTAS for severe stenosis of the left proximal SA to prevent aortic dissection.

Background: Evidence suggests that clinical markers, such as comorbid anxiety, body weight, and others can assist in predicting response to low-dose ketamine infusion in treatment resistant depression patients. However, whether a composite of clinical markers may improve the predicted probability of response is uncertain. Methods: The current study investigated the results of our previous randomized placebo-controlled and open-label trials in which 73 patients with treatment-resistant depression (TRD) received a single ketamine infusion of 0.5 mg/kg. Clinical characteristics at baseline, including depression severity, duration of the current episode, obesity, comorbidity of anxiety disorder, and current suicide risk, were assessed as potential predictors in a classification and regression tree model for treatment response to ketamine infusion. Results: The predicted probability of a composite of age at disease onset, depression severity, duration of current episode, and obesity/overweight was significantly greater (area under curve = .736, p = .001) than that of any one marker (all p > .05). The most powerful predictors of treatment response to ketamine infusion were younger age at disease onset and obesity/overweight. The strongest predictors of treatment nonresponse were longer duration of the current episode and greater depression severity at baseline. Discussion: Depression severity, duration of the current episode, obesity, and age at disease onset may predict treatment response versus nonresponse to low-dose ketamine infusion. However, whether our predicted probability for a single infusion may be applied to repeated infusions would require further investigation. Clinical trial registration: UMIN Clinical Trials Registry (UMIN000023581 and UMIN000016985).

Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear. Seventy-one patients with treatment-resistant depression were randomized to 3 treatment groups: a single 0.5 or 0.2 mg/kg ketamine or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale before infusions and at postinfusion period (at 40 min and up to 2 weeks). Low (mild) versus medium versus high (severe) interest-activity symptom domain groups were classified on the basis of the cutoff point of ± 0.4 standard deviation. The effect of baseline interest-activity symptoms on outcomes was tested using generalized estimating equation models. The interest-activity symptom domain as a continuous variable (β = 8.413, p = .016) was related to the trajectory of depressive symptoms. Stratified by levels of the interest-activity symptom domain, in the low interest-activity, 0.2 mg/kg ketamine infusion (β = 0.013) demonstrated the greatest antidepressant effect (p

BackgroundPrimary hyperparathyroidism (PHPT) is a common endocrinopathy that may increase fracture risk and decrease bone mineral density (BMD). Some patients develop distal renal tubular acidification dysfunction under conditions of hyperchloraemia or hyperchloraemic acidosis. To examine whether this dysfunction influences the clinical outcome, we explored the distal renal tubular acidification function in patients with PHPT and its effects on the clinical manifestations of the disease.MethodsWe retrospectively analysed 75 PHPT patients with regard to renal tubular acidification and blood gas analysis. The patients were divided into two groups, the renal tubular acidification dysfunction group and normal function group.ResultsSerum phosphate level and total hip bone density were significantly decreased and 25OHD level was significantly increased in the renal tubular acidification dysfunction group in comparison to the normal function group. Female patients in the renal tubular acidification dysfunction group showed significantly decreased femoral neck and total hip BMD and increased susceptibility to fracture. However, there were no such differences in male patients between the two groups.ConclusionsAbout 54.6 % of PHPT patients in our study population had abnormal distal renal tubular acidification. PHPT patients with abnormal distal renal tubular acidification may have lower hip bone density. Female PHPT patients with abnormal distal renal tubular acidification showed increased susceptibility to fractures and the development of osteoporosis.

Background Rheumatoid arthritis (RA) is an inflammatory disease that causes the destruction of soft tissues and cartilage around joints. Owing to the widespread use of potent disease-modifying antirheumatic drugs, the need for total knee and hip arthroplasties (TKA and THA) has been reduced in patients with RA. However, the current association between RA and either THA or TKA has not been demonstrated in large-scale epidemiological studies. Methods We conducted a large-scale retrospective cohort study of patients diagnosed with RA during a 12-year period (2000-2012) in Taiwan. We recruited 32,949 patients with RA and 32,949 individually propensity score-matched non-RA controls. Results After adjusting for confounding factors, we found that the risk of THA or TKA was 4.02 times higher in patients with RA than in those without RA (95% confidence interval [CI], 3.77-4.52). The risk of THA or TKA was highest in patients with RA younger than 40 years (adjusted hazard ratio, 43.18; 95% CI, 16.01-116.47). Compared with non-RA patients, patients with RA were 4.82 times more likely to undergo THA (95% CI, 3.84-6.04), 3.85 times more likely to undergo TKA (95% CI, 3.48-4.25), and 19.06 times more likely to undergo both THA and TKA (95% CI, 8.90-40.80). Conclusion These findings document a 4.02-fold greater long-term risk of undergoing THA or TKA in RA patients relative to non-RA patients in Taiwan.

Background: Atrial fibrillation (AF) is related to a higher risk of thromboembolic events and mortality. Some studies have demonstrated that the inflammatory biomarker interleukin-6 (IL-6) is associated with a higher risk of higher thrombosis in AF patients, but the real effect of IL-6 remains a controversy. Methods: We conducted a systematic review and meta-analysis to investigate the association between IL-6 and thromboembolic events, as well as bleeding events, acute coronary syndrome (ACS) events and all-cause mortality in AF. Results: A total of five studies involving 22 928 patients met our inclusion criteria for the systematic review. The higher level of IL-6 in AF patients is related to long-term thromboembolic events including stroke (RR 1.44, CI 95% 1.09-1.90, p=0.01). IL-6 meant a higher risk of long-term bleeding risk (RR 1.36, CI 95% 1.06-1.74, p=0.02), ACS risk (RR 1.81, CI 95% 1.43-2.30, p

Praeruptorin A (PA) is one of the active ingredients found in the dried root of Peucedanum praeruptorum Dunn, has been reported to possess anticancer effects against various types of cancer. However, the effect of PA on human hepatocellular carcinoma (HCC) remains uncleared. In this study, our results indicated that PA did not induce cytotoxicity or alter cell cycle distribution in human HCC cells (Huh-7, SK-Hep-1, and PLC/PRF/5 cells). Instead, PA inhibited the migration and invasion of human HCC cells while downregulating the expression of matrix metalloproteinase-1 (MMP1) and activating the extracellular signal-regulated kinase (ERK) signaling pathways. Furthermore, blocking the ERK signaling pathway through siERK restored the expression of MMP1 and the invasive ability of PA-treated HCC cells. In conclusion, our results demonstrate the antimetastatic activity of PA against human HCC cells, supporting its potential as a therapeutic agent of HCC treatments.

The research is to explore the association between nontyphoidal salmonellosis (NTS) and subsequent gastric cancer. We conducted a retrospective study by analyzing hospitalization dataset from the National Health Insurance Research Database in Taiwan. Patients aged 20 years and older with NTS (n = 9 097) admitted between January 1, 2000, and December 31, 2012, were enrolled and followed up until December 31, 2013. The primary outcome was the incidence of gastric cancer. Cox proportional hazards regression was used to estimate the risk of malignancy, accounting for the competing risk of death. In addition, we conducted a sensitivity analysis by propensity score matching and exclusion of malignancy within 1 year observation to minimize measurable confounding and protopathic bias. Negative controls were applied to examine the presence of possible unmeasured confounders in the study. The study included 18 194 patients (9097 in each NTS and non-NTS group). The median follow-up time was 7 years. The incidence density rate of gastric cancer was 0.72 per 1000 person-years for the NTS group and 0.40 per 1000 person-years for the non-NTS group. The NTS group had a modestly higher risk of gastric cancer (aHR, 2.02; 95% CI 1.18–3.45) than the non-NTS group. The sensitivity analyses revealed consistent results. Patients with NTS are associated with increased risk of subsequent gastric cancer compared with non-NTS patients. Future research is needed to examine whether NTS is parallel, reactive or causative to gastric cancer.

Yi-Fen Lei,1,2 Hsiu-Chen Lin,3,4 Hsiu-Li Lin,5 Yow-Sheng Uang,2 Hui-Wen Cheng,2 Li-Hsuan Wang2,6 1Department of Pharmacy, Mackay Memorial Hospital, Taipei 10449, Taiwan; 2School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan; 3Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; 4Department of Clinical Pathology, Taipei Medical University Hospital, Taipei 11031, Taiwan; 5Department of Neurology, General Cathay Hospital, New Taipei City 22174, Taiwan; 6Department of Pharmacy, Taipei Medical University Hospital, Taipei 11031, TaiwanCorrespondence: Li-Hsuan WangSchool of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 11031, TaiwanEmail shiuan@tmu.edu.twObjective: The effect of statins and fibrates on the risk of chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the effects of statins and fibrates on the risk of COPD in patients with hyperlipidemia.Patients and Methods: This study involved a retrospective cohort with a follow-up period of 6 years. We identified patients who were diagnosed as having hyperlipidemia between 2000 and 2016 from Taiwan’s National Health Insurance Research Database. A Cox proportional hazard model was used to estimate the risk of COPD among different groups. The dose-related effects of statins and fibrates on the risk of COPD were evaluated according to the defined daily dose (DDD).Results: Patients with hyperlipidemia not using statins and fibrates (group II) had a significantly higher risk of COPD compared with their comparison group, with an adjusted hazard ratio (HR) of 1.091 [95% confidence interval (CI): 1.034– 1.152, p < 0.01]. Dose-dependent reduction in the risk of COPD was observed in patients with hyperlipidemia using statins or fibrates compared with patients not using them. Moreover, with an increase in cumulative exposure, a reduced risk of COPD was observed in patients using more than 361 DDDs, with an adjusted HR of 0.474 (95% CI: 0.401– 0.559, p < 0.001). Patients on fibrate monotherapy using more than 541 DDDs were observed to have an adjusted HR of 0.454 (95% CI: 0.226– 0.910, p < 0.05) and those on statin monotherapy with over 361 DDDs were noted to have an adjusted HR of 0.583 (95% CI: 0.459– 0.740, p < 0.001).Conclusion: This study demonstrated that an increase in the cumulative exposure of statins and fibrates significantly reduced the risk of COPD in patients with hyperlipidemia, and the risk reduction appeared to be significantly dose dependent.Keywords: hyperlipidemia, statin, fibrates, chronic obstructive pulmonary disease, cohort study

Background/Purpose Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) disorder that causes relapsing inflammation and severe mucosal damage in the intestine. Crohn’s disease (CD)-related stricturing complications are a major cause of surgery, disability, and reduced quality of life. Endoscopic balloon dilation (EBD) has been shown to reliably delay or prevent surgery in patients with stricturing CD. However, cases of EBD performed for stricture in CD in Taiwan are rare. In this study, we want to evaluate the experiences regarding EBD for stricturing CD in Taiwan. Methods We conducted a retrospective analysis of 9 medical centers in Taiwan. Patients with CD-related strictures who were treated with EBD were included and analyzed. Results In nine medical centers, a total of 26 CD patients (19 male, 7 female, mean disease duration 75.4 ± 65.2 months) underwent 42 EBD procedures during the study period. Among the subjects, an 83.3% (35/42) EBD success rate was seen, but 26.9% (7/26) patients underwent surgery after ineffective EBD. In the surgery group, the the small bowel strictures was high compared with the non-surgery group (p = 0.01). There were no significant differences in disease phenotype, disease duration or history of fistulizing disease. In the surgery group, immunosuppressant use was high, and 5-aminosalicylic acid (5-ASA) use was low compared with the non-surgery group. After EBD, the physicians tended to change the drugs, especially increasing the use of biologic agents. Conclusion EBD is a safe and effective procedure for CD-related stricture, with a 83.3% success rate in Taiwan.

Objective Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression. Design Prospective, longitudinal study. Participants A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals. Methods OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at ∼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria. Main Outcome Measures Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression. Results More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%–33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%–20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%–8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%–92.4%), 94.9% (95% CI: 90.6%–99.2%), and 96.9% (95% CI: 93.5%–100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2–5.0) or likely (HR: 4.6, 95% CI: 1.5–14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning. Conclusions Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients.

Background: Worsening glycemic control indicates elevated risk of pancreatic ductal adenocarcinoma (PDAC). We developed prediction models for PDAC among those with worsening glycemic control after diabetes diagnosis. Methods: In 2000–2016 records within the Veterans Affairs Health System (VA), we identified three cohorts with progression of diabetes: (i) insulin initiation (n = 449,685), (ii) initiation of combination oral hypoglycemic medication (n = 414,460), and (iii) hemoglobin A1c (HbA1c) ≥8% with ≥Δ1% within 15 months (n = 593,401). We computed 12-, 36-, and 60-month incidence of PDAC and developed prediction models separately for males and females, with consideration of >30 demographic, behavioral, clinical, and laboratory variables. Models were selected to optimize Akaike's Information Criterion, and performance for predicting 12-, 36-, and 60-month incident PDAC was evaluated by bootstrap. Results: Incidence of PDAC was highest for insulin initiators and greater in males than in females. Optimism-corrected c-indices of the models for predicting 36-month incidence of PDAC in the male population were: (i) 0.72, (ii) 0.70, and (iii) 0.71, respectively. Models performed better for predicting 12-month incident PDAC [c-index (i) 0.78, (ii) 0.73, (iii) 0.76 for males], and worse for predicting 60-month incident PDAC [c-index (i) 0.69, (ii) 0.67, (iii) 0.68 for males]. Model performance was lower among females. For subjects whose model-predicted 36-month PDAC risks were ≥1%, the observed incidences were (i) 1.9%, (ii) 2.2%, and (iii) 1.8%. Conclusions: Sex-specific models for PDAC can estimate risk of PDAC at the time of progression of diabetes. Impact: Our models can identify diabetes patients who would benefit from PDAC screening.

Background GEMINI trials and real-world studies in Western population have demonstrated the effectiveness and safety of vedolizumab (VDZ) for IBD. However, long-term real-world evidence of VDZ in Asian populations remains limited. This study aimed to investigate the effectiveness and safety of VDZ in Taiwan CD and UC patients, and the IBD relapse after VDZ discontinuation. Methods Data were prospectively collected (January 2018-May 2020) from the Taiwan Society of IBD (TSIBD) registry, one of the largest real-world Asian IBD cohorts. Patients (>18 years old) receiving ≥1 dose of VDZ with up to a 1-year follow-up period were analyzed. Effectiveness at 6 month and 1 year including clinical response (CRS), clinical remission (CRM), steroid-free remission (SRM) and mucosal healing (MH);and safety outcome were analyzed descriptively. IBD relapse after VDZ treatment discontinuation was assessed since the reimbursement period in Taiwan is limited due to drug holiday required by government. Results A total of 274 patients (CD:127, UC:147) were included. At VDZ initiation, average [SD] age (year): 33.4 [14.6] in CD and 42.4 [14.3] in UC; median disease duration (years): 3.1 in CD and 3.9 in UC; 50.4% of CD and 70.7% of UC patients were biologics (bio)-naïve. Treatment effectiveness was analyzed (Figure 1-4). At 6 months, effectiveness in the CD bio-naïve group was significantly higher than the bio-exposed patients in CRS (67.4% vs 43.9%, p=0.047), CRM (62.8% vs 39.0%, p=0.025), and SRM (43.3% vs 4.3%, p=0.001), respectively. At 1 year, the CD bio-naïve group had higher CRS (82.1% vs 60.7%, p=0.026) than the bio-exposed group. There was no difference in effectiveness between bio-naïve and bio-exposed groups in UC at both 6 months and 1 year. Three patients (1.1%) reported serious infections (respiratory infection, intractable infection with underlying myelodysplastic syndrome and intestinal perforation due to endoscopy) and two (0.7%) had infusion-related reactions. No malignancies or hepatic injuries were reported. After limited treatment up to one year due to reimbursement, 58% (54/93) of patients had IBD relapse (CD: 27 [62.8%], UC: 27 [54%]). After cessation of VDZ, the mean [SD] time to IBD relapse was 5.5 [4.0] months in CD, and 5.8 [5.7] months for UC. Conclusion This study has shown the effectiveness and safety of VDZ therapy for Taiwan IBD patients. Better outcomes were observed in bio-naïve CD patients, whereas bio-naïve and bio-exposed UC patients have comparable outcomes. After a limited VDZ treatment duration, over one-half of patients had IBD relapse, with the majority occurring within 5 months of VDZ discontinuation. These data suggest that continued VDZ therapy would benefit the majority of IBD patients in Taiwan.

BACKGROUND There remains an unmet need in objective tests for diagnosing asthma in children. The objective of this study was to investigate the potential of metabolomic profiles of exhaled breath condensate (EBC) to discriminate stable asthma in Asian children in the community. METHODS One hundred and sixty-five Asian children (92 stable asthma and 73 non-asthmatic controls) participating in a population-based cohort were enrolled and divided into training and validation sets. Nuclear magnetic resonance-based metabolomic profiles of EBC samples were analyzed by using orthogonal partial least squares discriminant analysis. RESULTS EBC metabolomic signature (lactate, formate, butyrate, and isobutyrate) had an area under the receiver operator characteristic curve (AUC) of 0.826 in discriminating children with and without asthma in the training set, which significantly outperformed FeNO (AUC = 0.574; P

AIM Acute diverticulitis (AD) is commonly diagnosed in outpatient and emergency departments and is associated with severe complications such as perforation and fistula. Symptoms of irritable bowel syndrome (IBS), such as abdominal pain, constipation and diarrhoea, are also common with AD. This study aimed to evaluate the strength of a possible association between IBS and AD. METHOD This retrospective study analysed records from Taiwan's National Health Insurance Research Database and involved a total of 25 810 patients, including 12 905 IBS patients diagnosed between 2000 and 2012. The IBS and non-IBS cohorts were matched by propensity score for age, gender, comorbidities and medication, then compared for confounding variables by the chi-square test or Student's t-test. The association between AD and IBS was determined using Cox proportional hazards models. Kaplan-Meier curves assessed the cumulative incidence of AD in IBS patients. RESULTS The overall incidence of AD was 3.95-fold higher in the IBS cohort than in the non-IBS cohort (63.34 vs 16.02 per 100 000 person-years, respectively) and IBS was an independent risk factor for subsequent diagnosis of AD in multivariate Cox proportional hazards regression model adjusted hazards ratio (aHR = 3.84, 95% CI = 2.29-6.44, P

OBJECTIVES: To investigate the association between erectile dysfunction and fibromyalgia, and to clarify related comorbidities and treatment modalities. METHODS: This retrospective cohort study was carried out using 1 million records in the National Health Insurance Research Database. From 2001 to 2012, a total of 53 678 male patients newly diagnosed with fibromyalgia were recruited as the fibromyalgia cohort, and the same number of the non-fibromyalgia cohort was enrolled and matched with propensity score with age, income, comorbidities, and prescribed medications. All records were followed up until the end of 2013. The Cox proportional hazards model was carried out to assess the risk of erectile dysfunction among fibromyalgia patients. RESULTS: The incidence rates of erectile dysfunction were 36.86 and 21.15 (per 10 000 person-years) in the fibromyalgia and non-fibromyalgia cohorts, respectively, and a significantly increased risk of erectile dysfunction in fibromyalgia patients was noted (adjusted hazard ratio 1.69, 95% confidence interval 1.55-1.85, P

Purpose: Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors, we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01, and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815). Patients and Methods: Personalized neoantigen vaccines were designed and manufactured according to our bioinformatics analysis results from the whole-exome sequencing of tumor and peripheral blood cell DNAs. Patients were scheduled to be vaccinated subcutaneously with adjuvant on days 1, 4, 8, 15, and 22 (prime phase), and days 78 and 162 (boost phase). Additional immunizations were administrated every 2–3 months as per patient's potential benefit. The safety and efficacy were assessed through adverse events (AE), progression-free survival (PFS), overall survival (OS), and other parameters. Results: Of the 22 patients enrolled with advanced malignancies, 20 had no or mild AEs, while 2 had grade 3 or 4 acute allergic reactions only after their sixth boost vaccination. The disease control rate was 71.4%. The median PFS was 4.6 months, whereas the median OS was not reached (12-month OS = 55.1%). Around 80% of individual peptides or peptide pools elicited measurable specific immune response. In addition, our findings revealed several potential biomarkers for the prediction of better response. Conclusions: iNeo-Vac-P01 as monotherapy is feasible and safe for patients with advanced solid tumors. It could elicit T-cell–mediated immune response targeting tumor neoantigens, and might have promising antitumor efficacy. See related commentary by Filderman and Storkus, p. 4429

Summary Objectives: To explore the association between nontyphoidal salmonellosis (NTS) and the risk of acute ischemic stroke (IS) by using a nationwide, population-based study. Methods A retrospective cohort study using claim data from Taiwan's National Health Insurance Research Database (NHIRD), patients aged 18 years and older with histories of NTS (N = 1618) were included from January 1, 2000-December 31, 2012, and the non-NTS group (N = 6472) without NTS were matched by propensity score. The follow-up period was defined as the time from the initial diagnosis of NTS to the date of development of IS, death or 31 December, 2013. Patients previously diagnosed with stroke were excluded. The Cox proportional hazard model with robust sandwich estimator was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of IS after adjusting for demographic and clinical covariates. Results: The adjusted hazard ratio (aHR) for the NTS group compared with the non-NTS group was 1.34 (95% confidence interval [CI], 1.10–1.65) for overall stroke. Furthermore, the NTS cohort had an increased risk of IS compared to the non-NTS groups (aHR, 1.42; 95% CI, 1.14–1.78). Stratified analysis showed that compared with propensity score matched non-NTS group, subjects aged ≥65 years, female, those with hypertension, hyperlipidemia, COPD, cancer and heart failure had higher risk of developing stroke. A 1.93-fold significant increase risk for stroke was observed during the first 3–12 months of follow-up (95% CI, 1.07–3.48). Conclusions: Patients with NTS is associated with increased risk of developing ischemic stroke compared with non-NTS patients. Timely and mindful treatment plan about NTS may be a milestone to stroke prevention especially in some subpopulation.

The association between systemic inflammation, executive dysfunction, and gray matter (GM) volume difference in first-episode affective disorders, including bipolar and major depressive disorders, is unclear.Twenty-two patients with first-episode bipolar disorder, 22 age- and sex-matched patients with first-episode major depressive disorder, and 22 matched controls were enrolled in our study; all patients underwent comprehensive assessments, including clinical assessment, executive function examination (Wisconsin card sorting test [WCST]), proinflammatory cytokine receptors (soluble interleukin-6 receptor and tumor necrosis factor-α receptor 1 [TNFR1]), and brain magnetic resonance imaging. Voxel-based morphometry was performed to analyze the GM volume difference between bipolar and major depressive disorders.Patients with bipolar disorder were more likely to exhibit higher levels of TNFR1 (P = .038), more number of deficits in WCST (P.05), and smaller GM volume in the middle frontal cortex (uncorrected voxel level P.001) compared with those with major depressive disorder and healthy controls. Positive associations were observed between the middle frontal cortex volume, executive function, and the TNFR1 level.GM volume reduction in the middle frontal cortex, a greater level of systemic inflammation, and executive dysfunction were observed in first-episode affective disorders, especially bipolar disorder. A positive correlation between middle frontal cortex volume, executive function, and the TNFR1 level may indicate a divergent effect of brain and systemic inflammation functioning in the early phase (first episode) of affective disorder.

Gastric carcinoma (GC) disproportionately affects Asian Americans. We examined whether history of upper gastrointestinal (GI) endoscopy was associated with lower stage at GC diagnosis among Asian Americans and whether origin of providers influenced referral for endoscopy. We employed Surveillance Epidemiology and End Results–Medicare data on Asian Americans diagnosed with GC in 2004–2013 (n = 1,554). Stage distribution, GI conditions at diagnosis, and history of endoscopy were compared between Asian ethnic groups. Multivariate logistic regression adjusting for age, sex, poverty level, tumor location, and histology was used to examine the association of ethnicity and endoscopic history with stage I disease at diagnosis of GC. Koreans were more likely to be diagnosed with stage I, T1a GC and have prior history of endoscopy, compared with other Asian ethnicities (24% vs. 8% for stage I, T1a; 40% vs. 15% for endoscopy). Patients with primary care providers of concordant ethnic origin were more likely to have history of endoscopy. Asian American patients with GC with history of endoscopy were more likely to be diagnosed with GC at stage I disease (adjusted OR, 3.07; 95% confidence interval, 2.34–4.02). Compared with other Asian Americans, Koreans were diagnosed with GC at earlier stages owing to common history of endoscopy, which was more often undergone by patients with primary care providers of concordant ethnic origin. Overall, upper GI endoscopy was associated with early detection of GC in Asian Americans. Novelty and Impact. It is well-established that Asian Americans in the United States are disproportionately affected by gastric cancer. In our study we found that Asian American patients treated by physicians of similar ethnic background are more likely to undergo upper GI endoscopy in the United States, leading to early detection of gastric cancer and longer survival. Given this, targeted endoscopic screening in Asian Americans should be considered for early detection of GC.

While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade. We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed. Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p

Summary Objective This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. Design We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and Results Among patients with eGFR levels of Conclusions tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

Background Frontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown. Methods In total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls. Results Compared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion. Conclusion Reduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.

Studies have demonstrated that conduct disorder is related to risky sexual behaviors, the dominant risk factor for contracting a sexually transmitted infection (STI). However, the association between conduct disorder and STIs remains unclear. Using the Taiwan National Health Insurance Research Database, 5733 adolescents with conduct disorder and 22,932 age- and sex-matched controls without conduct disorder were enrolled from 2001 to 2009 and were subject to follow-up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was performed to examine the likelihood of subsequently contracting an STI for patients and controls. Patients with conduct disorder were more likely than controls to develop any STI (HR 3.95, 95% CI 2.97–5.26) after adjusting for demographic data, psychiatric comorbidities, and use of medications. Long-term use of second-generation antipsychotics (SGAs) was related to a reduced risk (HR 0.36, 95% CI 0.14–0.91) of developing an STI among patients with conduct disorder. Adolescents with conduct disorder had an increased risk of developing any STI later in life compared with those without conduct disorder. Long-term use of SGAs was associated with a lower risk of subsequent STI.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case‐control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53‐2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04‐1.85) (heterogeneity‐P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2‐deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Dia1, which belongs to the diaphanous-related formin family, influences a variety of cellular processes through straight actin elongation activity. Recently, novel DIA1 mutants such as p.R1213X (p.R1204X) and p.A265S, have been reported to cause an autosomal dominant sensorineural hearing loss (DFNA1). Additionally, active DIA1 mutants induce progressive hearing loss in a gain-of-function manner. However, the subcellular localization and pathological function of DIA1(R1213X/R1204X) remains unknown. In the present study, we demonstrated the localization of endogenous Dia1 and the constitutively active DIA1 mutant in the cochlea, using transgenic mice expressing FLAG-tagged DIA1(R1204X) (DIA1-TG). Endogenous Dia1 and the DIA1 mutant were regionally expressed at the organ of Corti and the spiral ganglion from early life; alongside cochlear maturation, they became localized at the apical junctional complexes (AJCs) between hair cells (HCs) and supporting cells (SCs). To investigate HC vulnerability in the DIA1-TG mice, we exposed 4-week-old mice to moderate noise, which induced temporary threshold shifts with cochlear synaptopathy and ultrastructural changes in stereocilia 4 weeks post noise exposure. Furthermore, we established a knock-in (KI) mouse line expressing AcGFP-tagged DIA1(R1213X) (DIA1-KI) and confirmed mutant localization at AJCs and the tips of stereocilia in HCs. In MDCKAcGFP-DIA1(R1213X) cells with stable expression of AcGFP-DIA1(R1213X), AcGFP-DIA1(R1213X) revealed marked localization at microvilli on the apical surface of cells and decreased localization at cell-cell junctions. The DIA1-TG mice demonstrated hazy and ruffled circumferential actin belts at AJCs and abnormal stereocilia accompanied with HC loss at 5 months of age. In conclusion, Dia1 plays a pivotal role in the development and maintenance of AJCs and stereocilia, ensuring cochlear and HC integrity. Subclinical/latent vulnerability of HCs may be the cause of progressive hearing loss in DFNA1 patients, thus suggesting new therapeutic targets for preventing HC degeneration and progressive hearing loss associated with DFNA1.

Background Hypokalemia is a common clinical problem. The association between urinary tract infection (UTI) and hypokalemia is not clear. Hypokalemia is common in patients with UTI in clinical observation. The aim of the study is to determine if UTI is associated with hypokalemia. Methods Patients hospitalized with UTI and the control group were retrieved from the Longitudinal Health Insurance Database 2005. The control group was patients hospitalized with other reasons and were matched for the confoundings of UTI and hypokalemia. We analyze the risk of hypokalemia using logistic regression and calculate the odds ratio (OR) and 95% confidence interval (CI) of OR. Results We analyzed 43,719 UTI patients and control patients. Hypokalemia was found in 4540 (10.4%) patients with UTI and 1842 (4.2%) control patients. The percentage of patients with hypokalemia was higher in UTI patients (chi-square, p p Conclusions Urinary tract infection is associated with hypokalemia among inpatients. The association is independent of patients’ comorbidities and medications. Recurrent UTI is associated with increased hypokalemia in UTI patients.