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Overdrainage of cerebrospinal fluid is one of the most notorious complications after ventriculoperitoneal shunt implantation. Siphon effect plays a major role in the development of overdrainage. Various overdrainage-preventing devices have been invented to counteract the siphon effect. Though some of the devices are designed to reduce the flow instead of providing antisiphoning effect, they are generally called antisiphon devices (ASDs). The basics of siphoning, the mechanisms and physical properties of currently available devices are described in this article. The clinical efficacy, shunt survival, and considerations on patient factors are also discussed. There are three kinds of ASD design, diaphragm, gravitational, and flow reducing devices. Flow reducing ASD is always open and the flow it controls is relatively stable. On the other hand, it may not provide sufficient flow in nocturnal intracranial pressure elevations. Diaphragm and gravitational devices are sensitive to the position of the patients. Diaphragm device is sensitive to the external pressure and the relative position of the device to the mastoid process. The gravitational device is sensitive to the angle between the axis of the device and the head. Many studies showed encouraging results with gravitational devices. Studies regarding diaphragm devices either showed better or similar outcomes comparing to differential pressure valves. Clinical studies regarding flow-reducing devices and head-to-head comparison between different mechanisms are warranted. This review aims to provide a useful reference for clinical practice of hydrocephalus.

AIM To determine the bidirectional link between periodontitis and fibromyalgia. MATERIALS AND METHODS In this cohort study, 196,428 periodontitis patients and 196,428 propensity score-matched non-periodontitis controls were enrolled. A Cox proportional hazard model was utilized to estimate the risk of fibromyalgia and survival analysis was adopted to assess the time-dependent effect of periodontitis on fibromyalgia. Subgroup analyses stratified by age, sex, and tracking period were conducted to identify susceptible populations. A parallel and symmetrical cohort that recruited 141,439 fibromyalgia patients and 141,439 propensity score-matched non-fibromyalgia controls ascertained the inverse effect of fibromyalgia on incident periodontitis. RESULTS Patients with periodontitis were more likely to develop fibromyalgia than non-periodontitis controls (HR = 1.42, 95% CI = 1.39-1.44, P < 0.001), which persisted in the survival analysis (log-rank test P < 0.0001). This effect was significant in both sexes and all age subgroups, and was particularly evident in males (HR = 1.52, 95% CI = 1.48-1.56, P < 0.001) and younger periodontitis patients (HR = 1.55, 95% CI = 1.50-1.60, P < 0.001). Fibromyalgia patients who never had periodontitis presented with greater risk for periodontitis over time (HR = 1.43, 95% CI = 1.40 - 1.45, P < 0.001; log-rank test P < 0.0001). CONCLUSIONS Patients of both sexes and all age subgroups with periodontitis presented with a greater risk of fibromyalgia. Subgroups that were the most susceptible to periodontitis-associated fibromyalgia were periodontitis patients that were males and below 30 years old. Risks of periodontitis were also greater in fibromyalgia patients who never had periodontitis. This article is protected by copyright. All rights reserved.

Gastrointestinal dysfunction is one of the complications after stroke. If it is not treated in time, it will affect the rehabilitation process after stroke and reduce the quality of life of patients. In this study, we conducted a systematic review and meta-analysis of the reports on the treatment of gastrointestinal dysfunction after stroke with traditional Chinese medicine (TCM) in recent years to provide evidence for clinical diagnosis and treatment.The clinical randomized controlled trials (RCTs) published in Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases from January 2010 to August 2021 were searched. After screening the qualified literatures, literature quality evaluation was performed. The software Stata 16.0 was used to analyze and compare the outcome indicators of TCM and conventional western medicine treatment, and the utility of TCM in the treatment of gastrointestinal disorders after stroke was comprehensively evaluated.A total of 16 studies were finally selected including a total of 1,589. Meta-analysis showed that TCM treatment of gastrointestinal disorders after stroke was more effective than conventional western medicine treatment [odds ratio (OR) =3.94; 95% confidence interval (CI): 2.63 to 5.89; P=0.000]. It was also shown that TCM can reduce the recovery time of bowel sounds and is superior to conventional western medicine [standard mean difference (SMD) =-1.92; 95% CI: -2.51 to -1.34; P=0.000]; reduce defecation and flatulence recovery time (SMD =-2.51; 95% CI: -3.41 to -1.61; P=0.000); increase gastrin level (SMD =0.80; 95% CI: 0.35 to 1.25; P=0.001); increase motilin level (SMD =2.27; 95% CI: 1.55 to 3.00; P=0.000); increase serum albumin level (SMD =0.72; 95% CI: 0.54 to 0.90; P=0.000); increase transferrin levels (SMD =1.11; 95% CI: 0.86 to 1.36; P=0.000); and it can increase serum prealbumin levels (SMD =1.50; 95% CI: 0.78 to 2.22; P=0.000).The use of TCM in the treatment of gastrointestinal dysfunction after stroke can effectively reduce symptoms, shorten the recovery time of bowel sounds, the first defecation and flatulence time, promote gastric motility and gastrointestinal hormone secretion, and improve the nutritional status of patients.

Summary Background and purpose Stroke is a rare complication of snakebites, but may lead to serious sequelae. We aimed to explore the relationship between venomous snakebite and the risk for acute stroke, in a nationwide population-based cohort study. Methods This retrospective cohort study used claims data between 1 January 2000 and 31 December 2012, from the Taiwan National Health Insurance Research Database. The study included data of patients aged 18 years or older with venomous snakebite (n = 535), matched for propensity score with controls without venomous snakebite (n = 2140). The follow-up period was the duration from the initial diagnosis of venomous snakebite and administration of antivenom to the date of an acute stroke, or until 31 December 2013. The competing risk model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of stroke, ischemic stroke and hemorrhagic stroke, after adjusting for demographic and other possible stroke risk factors. Results The adjusted HR for the venomous snakebite group compared with the control group was 2.68 for hemorrhagic stroke (95% CI = 1.35-5.33). Stratified analysis showed that the older age group (>65 years old) had a higher risk of hemorrhagic stroke. A 2.72-fold significant increase in the risk for hemorrhagic stroke was observed following venomous snakebite with antivenom usage (95% CI = 1.41–5.26). Conclusion Venomous snakebite is associated with an increased risk of hemorrhagic stroke after the use of antivenom. Further study of the underlying mechanism is warranted.

Influenza infection could trigger acute myocardial infarction. Obstructive sleep apnea (OSA) increases risk for myocardial infarction. Evidence evaluating the risk of influenza in patients with OSA is limited. We aimed to investigate the association between OSA and influenza using a nationwide population-based data set.A total of 5483 individuals with OSA were enrolled from January, 2000, to December, 2012, and compared with a control group of 21,932 individuals who had never been diagnosed with OSA (at a 1:4 ratio propensity score matched by age, sex, index years, and comorbidities) in the context of subsequent influenza infection. Cox proportional hazard regression analysis was conducted to analyze the association between OSA and influenza incidence. We conducted sensitivity analyses to examine our finding.During the 1.81 (±2.12) years of the follow-up period, the incidence rate of influenza infection was higher in the OSA group compared with the non-OSA group (36.40 and 30.09 per 100 person-years). After adjusting for age, sex, comorbidities, outpatients visits, the risk of influenza infection among patients with OSA was significantly higher (hazard ratio = 1.18; 95% confidence interval = 1.14-1.23; P 0.001). Sensitivity analyses showed consistent positive association. Males with OSA had increased risk of influenza infection compared with males without OSA (adjusted HR, 1.21; 95% CI, 1.16-1.27; P value for interaction = 0.03).This study found a significantly higher risk of influenza infection in patients with OSA, and sex acted as an effect modifier between OSA and risk of influenza infection.

BackgroundDecompressive craniectomy is employed as treatment for traumatic brain swelling in selected patients. We discussed the effect of temporal muscle resection in patients with intractable intracranial hypertension and temporal muscle swelling after craniectomy.MethodsRecords of 280 craniectomies performed on 258 patients who were admitted with severe head injury were retrospectively reviewed. Eight patients developed intractable increased intracranial pressure with temporal muscle swelling within 24 h after craniectomy and were treated by muscle resection.ResultsThe initial Glasgow Coma Scale score was 7 ± 1. The mean intracranial pressure was 41.7 ± 8.59 mmHg before muscle resection and 14.81 ± 8.07 mmHg immediately after surgery. Five patients had skull fracture and epidural hematoma at the craniectomy site. The mean intensive care unit stay was 11.25 ± 5.99 days. Glasgow Outcome Scale-Extended scoring performed during the 12-month follow-up visit showed that 6 patients (75%) had a favorable outcome.ConclusionsOur study findings indicate that a direct impact on the temporal region during trauma may lead to subsequent temporal muscle swelling. Under certain circumstances, muscle resection can effectively control intracranial pressure.

Urinary Tract Infections (UTIs) due to ureteral catheters has been frequently seen. The risk factors of this include both timing and those of the female gender. However, the association of Acute Pyelonephritis (APN) with use of ureteral DJ stents has rarely been investigated.The results indicate that the percentage of those with regards gender, age, duration of implantation, ureteral stent type, hypertension, T2DM, presence of urinary tract infection, benign prostate hyperplasia and pregnancy status were significantly statistically higher in APN patients than non-APN patients. APN did not associate with the use of antibiotics, urolithiasis, chronic kidney disease, malignancy, or uric acid stone in patients with a ureteral catheter.

Nasopharyngeal carcinoma (NPC), the most common head and neck cancer, is characterized by distinct geographic distribution and familial aggregation. Multiple risk factors, including host genetics, environmental factor and EBV infection, have been linked to the development of NPC, particularly in the familial clustering cases. However, the cause of NPC endemicity remains enigmatic due possibly to the complicated interplay between these risk factors. Recently, positive Epstein-Barr virus (EBV) DNA loads at nasopharyngeal (NP) cavity has been found to reflect NPC development and applied in NPC screening. To examine whether the increased NP EBV loads could aggregate in the families and be affected by host genetics and environmental factor, EBV loads were obtained by 510 NP brushing samples from eligible unaffected individuals, who have 2 or more relatives affected with NPC, in 116 high-risk NPC families. The correlation of relative pairs was estimated using S.A.G.E. (version 6.4, 2016), and host heritability of NP EBV loads was calculated with variance component models using SOLAR (version 8.4.2, 2019). In result, significant correlations of EBV loads were observed between parent-offspring pairs and sibling-sibling pairs (P

The traditional Chinese medicine of Qingxin Kaiqiao Recipe (QKR) is effective in the treatment of Alzheimer’s disease (AD). This study aims to investigate whether QKR improves the cognitive ability and takes neuroprotective effect on APP/PS1 double transgenic mice via the PI3K/Akt pathway. APP/PS1 double transgenic mice were randomly divided into a model, donepezil-treated, or QKR-treated group (L-QKR: 4.75 mg/kg/d, M-QKR: 9.5 mg/kg/d, and H-QKR: 19 mg/kg/d, respectively). Wild-type C57/BL6J mice were used as the control group. Morris water maze (MWM) was used to test the ability of spatial navigation and memorization; terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay was applied to test the apoptosis; amyloid protein granule deposition was detected via Methenamine silver staining; Western blot (WB) analysis, immunohistochemistry, and RT-PCR were applied to measure the expression of Aβ and corresponding indicators of the PI3K/Akt pathway. Compared with the model group, QKR significantly relieved the cognitive impairment, reduced the deposition of senile plaques, decreased the expression of GSK-3α and Aβ, and increased the expression of p-PI3K, p-Akt, and IDE. In addition, the number of TUNEL-positive cells decreased after treatment using QKR. The current study proved that QKR, especially at the high dose tested, exerted a protective effect on improving learning and memory, inhibiting apoptosis, and reducing the process of pathological degeneration in the hippocampus of AD mice.

Four new indole-diterpenoids, named penerpenes K-N (1–4), along with twelve known ones (5–16), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus Penicillium sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound 4 represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds (4, 9, and 15) were cytotoxic to cancer cell lines, of which compound 9 was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC50 value of 5.3 μM. Moreover, six compounds (5, 7, 10, 12, 14, and 15) showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633.

IntroductionInfections play a role in autoimmune diseases (AD). Leptospirosis has been linked to the trigger of systemic lupus erythematosus.ObjectiveTo investigate subsequent risk of major AD in hospitalized Taiwanese for Leptospirosis.MethodsRetrospective observational cohort study was employed. The enrolled period was from 2000 to 2012. In the main model, we extracted 4026 inpatients with leptospirosis from the Taiwan National Health Insurance Research Database (NHIRD) and 16,104 participants without leptospirosis at a 1:4 ratio propensity-score matched (PSM) by age, gender, index year, and comorbidities. The follow-up period was defined as the time from the initial diagnosis of leptospirosis to major AD occurrence or 2013. This study was re-analyzed by frequency-matching as a sensitivity analysis for cross-validation. Univariable and multivariable Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsThe adjusted HR (95% CI) of major ADs for the leptospirosis group was 4.45 (3.25–6.79) (p < 0.001) compared to the controls after full adjustment. The risk of major ADs was 5.52-fold (95% CI, 3.82–7.99) higher in leptospirosis patients hospitalized for seven days and above than the controls, while 2.80-fold (95% CI, 1.68–5.61) in those hospitalized less than seven days. The sensitivity analysis yields consistent findings. Stratified analysis revealed that the association between leptospirosis and major ADs was generalized in both genders, and all age groups.ConclusionsSymptomatic leptospirosis is associated with increased rate of subsequent major ADs, and the risk seems to be higher in severe cases.

Objective Chronic obstructive pulmonary disease (COPD) is associated with atherosclerosis. Previous studies including limited sample sizes have shown the prevalence of peripheral arterial occlusive disease (PAOD) among COPD patients. We sought to investigate the incidence of PAOD among COPD patients in Taiwan using a national database. Methods COPD patients were collected from the National Health Insurance Research Database of Taiwan from 1996 to 2010. The COPD cohort was propensity score matched according to age, sex, and comorbidities of atrial fibrillation, hypertension, diabetes, hyperlipidemia, cerebrovascular accidents, and chronic liver disease to patients without COPD (the control cohort). We evaluated the incidence of PAOD in COPD patients and the risk of PAOD associated with atrial fibrillation, hypertension, diabetes, hyperlipidemia, cerebrovascular accidents, and chronic liver disease. Results The study included 51,869 COPD patients and 51,869 control patients without COPD. The incidence of PAOD was 1.23-fold higher (95% confidence interval [CI] =1.17-1.29) in the COPD group than in the non-COPD group. Moreover, COPD and atrial fibrillation alone (adjusted hazard ratio (aHR) 2.99; P=0.001), hypertension alone (aHR, 2.05; P

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

Background We redesigned decompressive craniectomy and cranioplasty procedures to decrease the inherent risk of complications. This novel technique, called decompressive cranioplasty, not only may decrease the complication rate but also may improve the cosmetic result, obviate the need for artificial skull implant, and increase the decompressive volume compared with traditional craniectomy. Methods In decompressive cranioplasty, the Agnes Fast craniotomy was adopted without cutting the temporalis muscle from the underlying bone flap. After opening the dura with or without removal of intracranial hematomas, duraplasty was performed with an intracranial pressure monitor inserted. Four miniplates were bent into a “Z” shape, and the vascularized bone flap was elevated approximately 1.2–1.5 cm above the outer cortex of the skull and fixed with the miniplates. Subsequent cranioplasty was done with a mini-incision on the miniplate sites and reshaping of the miniplate to align the outer cortex of the bone flap. Results We successfully performed decompressive cranioplasty in 3 emergent cases—2 traumatic subdural hematomas and 1 malignant middle cerebral artery infarction. Postoperative brain computed tomography demonstrated adequate decompression in all cases. Cosmetic outcome was excellent, and there was no temporal hallowing. Mastication function was not affected. At 6-month follow-up, there was no bone flap shrinkage and no hydrocephalus. Conclusions Decompressive cranioplasty is a safe and effective method in the management of patients with brain edema and intracranial hypertension. It is simple to perform and may reduce the morbidity associated with traditional decompressive craniectomy and subsequent cranioplasty.

Increased serum levels of pro-inflammatory biomarkers are consistently associated with cognitive decline. The omega-3 unsaturated fatty acids (n-3 PUFAs) had been linked to slowing cognitive decline due to their potential anti-inflammatory effects. To our knowledge, the different regiments of pure DHA, pure EPA, and their combination on various associated symptoms of dementia, including a mild form of cognitive impairment (MCI) and Alzheimer's disease (AD), have never been studied.This multisite, randomized, double-blind, placebo-controlled trial was conducted at two veteran's retirement centers and one medical center in central Taiwan between 2013 and 2015. 163 MCI or AD patients were randomly assigned to placebo (n = 40), docosahexaenoic acid (DHA, 0.7 g/day, n = 41), eicosapentaenoic acid (EPA, 1.6 g/day, n = 40), or EPA (0.8 g/day) + DHA (0.35 g/day) (n = 42) group for 24 months. The results were measured as the cognitive and functional abilities, biochemical, and inflammatory cytokines profiles. Chi-square tests, two-sample t-test, ANOVA, and linear mixedeffects models were conducted with p 0.05.131 (80%) participants had completed the trial with all cognitive, functional, and mood status assessments. The statistically significant difference between the placebo and treatment groups was not determined, concerning the changes in cognitive, functional, and mood status scores, the biochemical profiles, and inflammatory cytokines levels. However, EPA was found to reduce the C-C motif ligands 4 (CCL4) level (p 0.001). Additionally, EPA could reduce the constructional praxis (p 0.05) and spoken language ability scores (p 0.01), and DHA also reduced the spoken language ability score (p 0.05).Overall, n-3 PUFAs supplements did not reduce cognitive, functional, and depressive symptom outcomes, but spoken language ability and constructional praxis subitems of ADAS-cog. These findings show that attention to clinical heterogeneity in dementia is crucial when studying nutrients interventions, such as n-3 PUFAs. In addition, with small effect size CCL4 is a better indicator than other inflammatory cytokines for EPA treatment response.

OBJECTIVES Studies on the association of estimated glomerular filtration rate (eGFR) levels with hospital discharge disposition after stroke are limited with inconsistent results. This study investigated the odds of home discharge with eGFR levels at admission for patients with stroke using the Taiwan Stroke Registry (TSR) data. METHODS From the TSR database, a total of 51,338 stroke patients from 2006 to 2015 were categorized into five groups based on eGFR levels at admission. The proportion of home discharge by the eGFR levels was calculated and logistic regression analysis was used to estimate the related odds ratio (OR) and 95% confidence interval. RESULTS Near 85% of stroke patients were discharged to home. The proportion of home discharges decreased as the eGFR level declined. Compared to patients with eGFR ≥90 mL/min/1.73 m2, the adjusted ORs of home discharge were 0.91, 0.85, 0.63, 0.56 for patients with eGFR 60-89, eGFR 30-59, eGFR 15-29, and eGFR < 15 mL/min/1.73 m2 or on dialysis, respectively, in a graded relationship. The trends were consistent in the ischemic stroke and hemorrhagic stroke patients. The areas under the receiver operating characteristic curve for all stroke patients, ischemic stroke patients, and hemorrhagic stroke patients were 0.801, 0799, 0.815, respectively. CONCLUSION The odds of home discharge for stroke patients decreased with a significant independent graded association with declining eGFR levels. Renal function could predict home discharge after stroke.

Introduction Intracerebral hemorrhage (ICH) is associated with high mortality and morbidity rates. However, both the rhythmic variation and prognostic value of brain temperature after ICH remain unknown. In this study, we investigated brain temperature rhythm and its prognostic value for post-operative mortality and long-term functional outcomes in patients with ICH. Methods Post-operative diurnal brain temperature patterns at the basal ganglion are described. Following surgery for ICH, 78 patients were enrolled, and intracranial pressure and brain temperature were monitored using a fiber optic device. Brain temperature mesor, amplitude, and acrophase were estimated from the recorded temperature measurements, using cosinor analysis, and the association between these patterns and clinical parameters, mortality, and functional outcomes at the 12-month follow-up were examined. Results According to cosinor analysis, brain temperature in 55.1% of patients showed a circadian rhythm within 72 h post-surgery. The rhythm-adjusted mesor of brain temperature (± standard deviation) was 37.6 (± 0.7) °C, with a diminished mean amplitude. A temperature acrophase shift was also observed. Multivariate logistic regression analysis revealed that initial age and circadian rhythm of brain temperature appeared to be predictive and prognostic of functional outcomes. Further, patients with higher brain temperature mesor were more likely to survive than those with a lower mesor. Conclusion For patients with ICH, brain temperature rhythm analysis is an improved prognostic tool for mortality and functional outcome predictions.

ObjectiveThe aim of this study was to investigate the relationship between non-typhoidalSalmonella(NTS) infection and the risk of Kawasaki disease (KD) by using a nationwide population-based data set in Taiwan.MethodsIn this retrospective cohort study, we enrolled 69,116 patients under 18 years of age, with NTS from January 1st, 2000, to December 31st, 2013, using the population-based National Health Insurance Research Database of Taiwan. A comparison group without NTS was matched (at a 1:4 ratio) by propensity score. The two cohorts were followed from the initial diagnosis of NTS until the date of KD development or December 31st, 2013. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for covariates. Also, we conducted sensitivity analyses to examine our findings.ResultsAfter adjusting for covariates, the risk of KD for the children with NTS was significantly higher than that of the comparison group (hazard ratio = 1.31; 95% confidence interval = 1.03-1.66; p < 0.01). Stratified analysis showed that the associated risk of the investigated outcome was significant in children aged ≤2 years (aHR= 1.31, 95% C.I. 1.02-1.69), in female patients (aHR= 1.46, 95% C.I. 1.03-2.08), and in those without allergic diseases.ConclusionsNTS is associated with an increased risk of KD in Taiwanese children.

Hypothermia has been used in postoperative management of traumatic brain injury (TBI), however, the rhythmic variation and prognostic value of brain temperature after TBI have never been studied. This study describes diurnal brain temperature patterns in comatose patients with TBI. Mesors of brain temperature, amplitude, and acrophase were estimated from recorded temperature measurements using cosinor analysis. The association of these patterns with clinical parameters, mortality, and functional outcomes in a 12-month follow-up was examined. According to the cosinor analysis, 59.3% of patients presented with circadian rhythms of brain temperature in the first 72 h postoperatively. The rhythm-adjusted mesor of brain temperature was 37.39 ± 1.21 °C, with a diminished mean amplitude of 0.28 (±0.25) °C, a shift of temperature acrophase was also observed. Multivariate logistic regression analysis revealed that initial Glasgow coma scale score, age, elevated blood glucose level, and circadian rhythm of brain temperature seemed to be predictive and prognostic factors of patients’ functional outcomes. For the prediction of survival status, younger patients or those patients with mesor within the middle 50% of brain temperature were more likely to survive. The analysis of brain temperature rhythms in patients with moderate and severe TBI provided additional predictive information related to mortality and functional outcomes.

Background Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood. Methods Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE. Results Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed. Conclusion Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.

Objective This study aimed to investigate the risk of Alzheimer’s disease among patients with age-related macular degeneration and its association with confounding comorbidities. Method This was a population-based, retrospective cohort study. By accessing data from the National Health Insurance Research Database of Taiwan, we identified 10,578 patients aged 50–100 years who were newly diagnosed with age-related macular degeneration between 2000 and 2012 and 10,578 non- age-related macular degeneration individuals. The comorbidities assessed were osteoporosis, diabetes, cirrhosis, cerebrovascular disease, chronic kidney disease, hypertension, hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease. Results Patients with age-related macular degeneration had a 1.23-fold increased risk of their condition advancing to Alzheimer’s disease (aHR = 1.23, 95% CI = 1.04–1.46). The younger patients were diagnosed with age-related macular degeneration, the more likely patients got Alzheimer’s disease (50–64 age group: aHR = 1.97, 95% CI = 1.04–3.73; 65–79 age group: aHR = 1.27, 95% CI = 1.02–1.58; 80–100 age group: aHR = 1.06, 95% CI = 0.78–1.45). In addition, there were significantly higher risks of Alzheimer’s disease for patients with cirrhosis (aHR = 1.50, 95% CI = 1.09–2.06) in the age-related macular degeneration cohort than in the non-age-related macular degeneration cohort. Conclusion Patients with age-related macular degeneration may exhibit a higher risk of Alzheimer’s disease than people without age-related macular degeneration.

Background Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV) associated cancer, exhibits an extremely high incidence in southern Chinese. Given that human leukocyte antigen (HLA) plays critical roles in antigen presentation and relates to NPC susceptibility, it is speculated that certain HLA variants may affect EBV reactivation, which is a key pathogenic factor of NPC. Therefore, we attempted to identify HLA alleles associated with the indicator of EBV reactivation, Zta‐IgA, in healthy males from NPC endemic area. Methods HLA alleles of 1078 healthy males in southern China from the 21‐RCCP study were imputed using genome‐wide single nucleotide polymorphism data. EBV Zta‐IgA in blood samples were measured using an enzyme‐linked immunosorbent assay. Multiple logistic regression analysis was used to evaluate the effect of HLA allele on Zta‐IgA serological status and its potential joint association with smoking. The binding affinity for Zta‐peptide was predicted using NetMHCIIpan 4.0. Results HLA‐DRB1*09:01 was found to be associated with a higher risk of Zta‐IgA seropositivity (odds ratio = 1.80, 95% confidence interval = 1.32–2.45; p = 1.82 × 10−4). Compared with non‐smokers without HLA‐DRB1*09:01, the effect size increased to 2.19‐ and 3.70‐fold for the light and heavy smokers carrying HLA‐DRB1*09:01, respectively. Furthermore, HLA‐DRB1*09:01 showed a stronger binding affinity to Zta peptide than other HLA‐DRB1 alleles. Conclusions Our study highlighted the pivotal role of genetic HLA variants in EBV reactivation and the etiology of NPC. Smokers with HLA‐DRB1*09:01 have a significantly higher risk of being Zta‐IgA seropositive, which indicates the necessity of smoking cessation in certain high‐risk populations and also provide clues for further research on the etiology of NPC., We conducted an association study for human leukocyte antigen (HLA) alleles and Epstein–Barr virus Zta‐IgA serological status in healthy males from a nasopharyngeal carcinoma endemic area. We found that HLA‐DRB1*09:01 was associated with a high risk of Zta‐IgA seropositivity and the effect increased when combined with smoking. In silico prediction indicated that HLA‐DRB1*09:01 had a distinctive binding motif pattern and a stronger binding affinity to Zta peptide in comparison with other HLA‐DRB1 alleles.

Background Whether a sex difference exists in long-term cardiovascular (CV) outcomes after acute myocardial infarction (AMI) is worth exploration. This study is sought to investigate the relationships among sex, age and the long-term prognosis after AMI. Methods This population-based retrospective cohort study used Taiwan's National Health Insurance Research Database (NHIRD) to investigate the sex differences in in-hospital and long-term CV outcomes in patients with AMI. We enrolled patients who were first diagnosed with AMI from January 1, 2000 to December 31, 2013. The outcomes of interest included all-cause mortality, CV death, nonfatal stroke, nonfatal heart failure, and AMI recurrence during hospitalization and 5-year follow up. The CV outcomes were also analyzed by age stratification. Results Overall, 201,921 patients with AMI were analyzed; 68.72% were men and 31.28% were women, with mean ages of 65.34 ± 14.12 and 73.05 ± 12.22 years, respectively. Major adverse cardiac events (MACE) during hospitalization and up to 5 years were consistently greater in women than in men. Multivariable regression analysis revealed no sex difference existed in long-term all-cause and CV mortality. Men of all age groups consistently showed higher risk of both short- and long-term recurrence of AMI. Nonetheless, the female sex still independently predicted increased risk of nonfatal stroke and heart failure from hospitalization until 3-year follow up. Conclusion Women with AMI had poorer short-term and long-term outcomes. The sex differences in long-term all-cause and CV death disappear after multivariate analysis. Nonetheless, female AMI patients independently predicted higher risk of stroke and heart failure from hospitalization until a 3-year follow-up. To better understand the pathophysiology of female patients with AMI and develop more effective management, more studies in this field are necessary in the future.

Thalamic hemorrhage bears the worst outcome among supratentorial intracerebral hemorrhage (ICH). Minimally invasive endoscopic-aided surgery (MIS) has been proved to be safe and effective in evacuating ICH. However, the ideal timing of MIS is still a controversy. In this study, we present our experience in the treatment of patients with thalamic hemorrhage by ultrarapid MIS evacuation. This retrospective analysis enrolled seven patients treated with ultrarapid MIS evacuation of thalamic hemorrhage. Seven patients treated with EVD with similar ICH score were included as match control. Primary endpoints included rebleeding, morbidity, and mortality. Hematoma evacuation rate was evaluated by comparing the pre- and postoperative computed tomography (CT) scans. Glasgow Outcome Scale Extended (GOSE) and modified Rankin Score (mRS) were noted at the 6-month and 1-year postoperative follow-up. Among the seven patients, six were accompanied with intraventricular hemorrhage. All patients received surgery within 6 hours after the onset of stroke. The mean hematoma volume was 35 mL, and the mean operative time was 116.4 minutes. The median hematoma evacuation rate was 74.9%. There was no rebleeding or death reported after the surgery. The median GOSE and mRS were 3 and 5, respectively, at 6 months postoperatively. Further, 1-year postoperative median GOSE and mRS were 3 and 5, respectively. The data suggest that the ultrarapid MIS technique is a safe and effective way in the management of selected cases with thalamic hemorrhage, with favorable long-term functional outcomes. However, a large, prospective, randomized-controlled trial is needed to confirm these findings.

The study was conducted to evaluate the effect of water temperatures and intraperitoneal administration of microcystins (MCs) on the pharmacokinetics characteristics of epigallocatechin gallate (EGCG) in snakehead fish (Ophiocephalus argus Cantor) by RP-HPLC method. The results showed that EGCG was absorbed and eliminated more faster at 20ºC than at 10ºC. Then the detected results also showed that EGCG was significantly absorbed fast in MCs-treated group than in control group. However, EGCG elimination became very lowly in MCs-treated group. Therefore, the pharmacokinetic characteristics of EGCG were significantly affected by water temperature and MCs toxin.

OBJECTIVE This study aimed to determine the effect of radiotherapy (RT) on the risk of herpes zoster (HZ) in patients with gynecological cancers via a nationwide population-based study. METHODS Based on patient data obtained from the National Health Insurance Research Database, 1928 gynecological cancer patients were identified with 1:1 matching for RT and non-RT cohorts by age, index date, and cancer type. Another cohort consisting of 964 non-cancer individuals matched was used as normal control. The incidence of HZ was compared between cancer patients with and without RT. Age, comorbidities, cancer-related surgery and chemotherapy (CT), and cancer type were adjusted as confounders. RESULTS The risk of HZ in cancer patients was higher than that of non-cancer individuals (14.23 versus 8.34 per 1,000 person-years [PY], the adjusted hazard ratio [aHR]=1.38, p=0.044). In the cancer population, the incidence of HZ for the RT and non-RT cohorts was 20.55 versus 10.23 per 1,000 PY, respectively (aHR=1.68, p=0.009). Age >50 years was an independent factor for developing HZ. The 5-year actuarial incidence for patients receiving neither RT nor CT, RT alone, CT alone, and combined modalities was 5.4%, 6.9%, 3.7%, and 9.9%, respectively (p

Objective Patients with endometriosis may seek traditional Chinese medicine (TCM) to help them conceive. The present study aims to evaluate the effects of TCM on reproductive and pregnancy outcomes in patients with endometriosis. Materials and methods The patients with endometriosis taken from the National Health Insurance (NHI) research database between 2000 and 2012 were divided into two cohorts based on the use of TCM treatment. The two cohorts were matched by age and comorbidities and followed up until a new diagnosis of infertility, ectopic pregnancy, or miscarriage. Multivariable Cox proportional hazards models were used to evaluate the hazard ratio (HR) of reproductive and pregnancy outcomes. Results A total of 5244 patients with endometriosis were analyzed, including 1748 TCM users and 3496 matched control subjects. The proportion of infertility was higher in TCM users than in non-TCM users (adjusted hazard ratio [HR]: 1.34, 95% confidence interval [CI]: 1.13–1.60). However, there was no significant difference in the proportion of ectopic pregnancies between TCM users and non-TCM users (adjusted HR: 0.82, 95% CI: 0.60–1.13). There was no significant difference in the proportion of miscarriages between TCM users and non-TCM users (adjusted HR: 1.23, 95% CI: 0.95–1.61). Conclusion TCM treatment showed insignificant efficacy in decreasing the risk of ectopic pregnancy and miscarriage in patients with endometriosis.

Objective: A number of publications have assessed the prevalence of hypertension in polycystic ovary syndrome (PCOS) patients with inconclusive results. Since in general populations the occurrence of hypertension is related to age and comorbidities, we investigated the incidence rate and hazard ratios (HRs) of hypertension between healthy subjects and young women with PCOS as well as comorbidities. Methods: We conducted a population-based retrospective cohort study by using the National Health Insurance Research Database in Taiwan. The cohort included women with the diagnosis of PCOS between 2000 and 2012. Those without PCOS were selected as the control group at a ratio of 4:1 by an age-matched systematic random-sampling method. Cox proportional hazard regression analysis was used to determine the effects of PCOS on the risks of developing hypertension. Stratification analysis was performed to elucidate the interaction among PCOS and the comorbidities, which affect the incidence of hypertension. Results: The PCOS cohort consisted of 20,652 patients with PCOS and the comparison cohort consisted of 82,608 matched patients without PCOS. There was no difference in the distribution of age between the PCOS cohort and the comparison cohort (29.1 ± 6.8 vs. 29.0 ± 6.5, p = 0.32). The incidence rates of hypertension were 7.85 and 4.23 per 1,000 person-years in the PCOS and comparison groups, respectively. A statistically significant higher risk of hypertension was found in the PCOS cohort (adjusted HR = 1.62, 95% confidence interval = 1.48–1.76) than in the comparison cohort. After a joint analysis of comorbidities, the adjusted HR of hypertension was 9.44 (95% confidence interval = 7.27–12.24) for PCOS patients with comorbidities of diabetes mellitus (DM) and hyperlipidemia compared with women with neither PCOS nor DM and hyperlipidemia. Conclusion: The risk of developing hypertension in young women with PCOS was higher than in controls in this cohort study. The comorbidities of DM and hyperlipidemia could interact with PCOS patients and further increase the risk of hypertension. An earlier screening for hypertension and comorbidities in patients with PCOS may be warranted, even in young women.

Background Coronary artery disease is common in patients with end-stage renal disease (ESRD). Patients with ESRD are a high-risk group for cardiac surgery and have increased morbidity and mortality. Most studies comparing ESRD patients receiving coronary artery bypass grafting (CABG) or percutaneous coronary intervention have found that the long-term survival is good in ESRD patients after CABG. The aim of our study was to compare ESRD patients who underwent CABG with the general population who underwent CABG, in terms of prognosis and hospital costs. Methods This study analyzed data from the National Health Insurance Research Database in Taiwan for patients who were diagnosed with ESRD and received CABG (ICD-9-CM codes 585 or 586) between January 1, 2004, and December 31, 2009. The ESRD patients included in this study all received catastrophic illness cards with the major illness listed as ESRD from the Ministry of Health and Welfare in Taiwan. The control subjects were randomly selected patients without ESRD after propensity score matching with ESRD patients according to age, gender, and comorbidities at a 2:1 ratio from the same dataset. Results A total of 48 ESRD patients received CABG, and their mean age was 62.04 ± 10.04 years. Of these patients, 29.2% were aged ≥70 years, and 66.7% were male. ESRD patients had marginally higher intensive care unit (ICU) stays (11.06 vs 7.24 days) and significantly higher ICU costs (28,750 vs 17,990 New Taiwan Dollars (NTD)) than non-ESRD patients. Similarly, ESRD patients had significantly higher surgical costs (565,200 vs. 421,890 NTD), a higher perioperative mortality proportion (10.4% vs 2.1%) and a higher postoperative mortality proportion (33.3% vs 11.5%) than non-ESRD patients. Conclusions After CABG, ESRD patients had a higher risk of mortality than non-ESRD patients, and ICU and surgery costs were also higher among the ESRD patients than among patients without ESRD.

Developing rapid and sensitive diagnostic methods for dengue virus (DENV) infection is of prime priority because DENV infection is the most prevalent mosquito-borne viral disease. This work proposes an electrochemical impedance spectroscopy (EIS)-based genosensor for the label-free and nucleic acid amplification-free detection of extracted DENV RNA intended for a sensitive diagnosis of DENV infection. A concentration ratio of 0.04 mM 6-mercaptohexanoic acid (MHA) to 1 mM 6-mercapto-1-hexanol (MCH) was selected to modify thin-film gold electrodes as a link to control the coverage of self-designed probe DNA (pDNA) at a density of 4.5 &plusmn, 0.4 &times, 1011 pDNA/cm2. The pDNA/MHA/MCH-modified genosensors are proven to improve the hybridization efficiency of a synthetic 160-mer target DNA (160mtDNA) with a 140-mer electrode side overhang as compared to other MHA/MCH ratio-modified genosensors. The MHA(0.04 mM)/MCH(1 mM)-modified genosensors also present good hybridization efficiency with the extracted DENV serotype 1 (DENV1) RNA samples, having the same electrode side overhangs with the 160mtDNA, showing a low detection limit of 20 plaque forming units (PFU)/mL, a linear range of 102&ndash, 105 PFU/mL and good selectivity for DENV1. The pDNA density-controlled method has great promise to construct sensitive genosensors based on the hybridization of extracted DENV nucleic acids.

Traditional Chinese medicine (TCM) is commonly used for urinary symptoms in Eastern countries. Since there are few effective treatments available for patients with interstitial cystitis/bladder pain syndrome (IC/BPS), the psychological burden leads to increased healthcare-seeking behavior. Some patients may therefore seek TCM treatment for related urinary symptoms. Due to limited clinical research evaluating the effects of TCM on IC/BPS, we conducted a nationwide population-based cohort study to investigate the relationship between TCM and mental disorders among these patients. The IC/BPS cohort and its matched non-IC/BPS comparison cohort were recruited from the National Health Insurance (NHI) Research Database between 2000 and 2011. Patients with the use of Chinese herbal medicine (CHM) granules or acupuncture over 90 days per year were enrolled as the TCM users. Multivariable Cox proportional hazards models were used to evaluate the hazard ratio (HR) of mental disorders related to interstitial cystitis. The incidence of mental disorders in the 2 cohorts was assessed with Kaplan–Meier curves. A total of 1123 patients with IC/BPS and 4492 matched non-IC/BPS subjects were included in this study. The IC/BPS cohort demonstrated higher incidence rate of mental disorders than the cohort without IC/BPS (adjusted HR: 2.21, 95% confidence interval [CI]: 1.73–2.81). There was no statistically significant difference in the risk of mental disorders between IC/BPS patients with and without CHM granules or acupuncture treatment (adjusted HR: 0.99, 95% CI: 0.58–1.68). Our results indicated that CHM and acupuncture showed insignificant efficacy in the prevention of mental disorders in IC/BPS patients.

Background Insulin is highly recommended for diabetes management in persons with liver cirrhosis. However, few studies have evaluated its long-term effects in these persons. We conducted this study to compare the risks of mortality, liver-related complications, and cardiovascular events in persons with type 2 diabetes mellitus (T2DM) and compensated liver cirrhosis. Methods From January 1, 2000, to December 31, 2012, we selected 2047 insulin users and 4094 propensity score-matched nonusers from Taiwan’s National Health Insurance Research Database. Cox proportional hazard models were used to assess the risks of outcomes. Results The mean follow-up time was 5.84 years. The death rate during the follow-up period was 5.28 and 4.07 per 100 person-years for insulin users and nonusers, respectively. In insulin users, the hazard ratios and 95% confidence intervals (CIs) of all-cause mortality, hepatocellular carcinoma, decompensated cirrhosis, hepatic failure, major cardiovascular events, and hypoglycemia were 1.31 (1.18–1.45), 1.18 (1.05–1.34), 1.53 (1.35–1.72), 1.26 (1.42–1.86), 1.41 (1.23–1.62), and 3.33 (2.45–4.53), respectively. Conclusions This retrospective cohort study indicated that among persons with T2DM and compensated liver cirrhosis, insulin users were associated with higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared with insulin nonusers.

Background& aims Type 2 diabetes mellitus (T2DM) management in patients with cirrhosis is complicated. No clinical trials have investigated appropriate antidiabetic drug use in these patients. This study compared the risks of all-cause mortality, major adverse cardiovascular events (MACE) and hepatic outcomes between patients with T2DM and cirrhosis using and not using thiazolidinedione (TZD). Methods We selected 1,705 propensity score-matched TZD users and nonusers from a Taiwan National Health Insurance Research Database cohort of T2DM patients with compensated cirrhosis between January 1, 2000, and December 31, 2012 and followed them until December 31, 2013. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risks of investigated outcomes for TZD users. Results MACE incidence rates during follow-up were 2.14 and 1.30 per 100 patient-years for TZD users and nonusers, respectively (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI], 1.32-2.19). On the basis of TZD use, the aHRs (95% CIs) for stroke, ischemic heart disease and heart failure were 1.81 (1.28-2.55), 1.59 (1.03-2.44) and 2.09 (1.22-3.60) respectively. Compared with TZD nonusers, rosiglitazone users had significantly higher aHR [1.67 (1.26-2.20)] and pioglitazone users had no significant difference of aHR [1.12 (0.90-1.64)]. All-cause mortality, hepatocellular carcinoma, decompensated cirrhosis and hepatic failure risks did not differ significantly between TZD users and nonusers. Conclusions Compared with nonuser, TZD users demonstrated significantly higher MACE risks. Therefore, the risks of cardiovascular complications should be considered when prescribing TZDs to patients with T2DM and cirrhosis.

Objective Overweight and hyperlipidemia, the two established risk factors for acute ischemic stroke, are paradoxically associated with favorable outcomes. The paradox may be resolved by the concept of protein energy wasting (PEW), in which total cholesterol level and body mass index are used as nutritional indexes for predicting outcomes of chronic kidney disease. Methods Among 12 271 people with acute ischemic stroke and chronic kidney disease, 2086 were defined as being at risk of PEW—with a body mass index Results Based on the propensity score, 2081 PEW participants were matched to the same number of non-PEW control participants. PEW was associated with a higher mortality risk at 3 mo (adjusted hazard ratio, 1.19; 95% confidence interval [CI], 1.02–1.42) and 1 y (adjusted hazard ratio, 1.33; 95% CI1.13–1.52). PEW was also associated with poor functional outcomes (modified Rankin Scale score >2) at 1 mo (adjusted odds ratio, 1.32; 95% CI, 1.08–1.61) and 3 mo (adjusted odds ratio, 1.27; 95% CI, 1.03–1.56). Conclusions According to the PEW-based assessment system, a modest decrease in body mass index and total cholesterol levels suggests malnutrition and is associated with adverse outcomes of acute ischemic stroke.

Background/Purpose Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. Methods The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. Results Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. Conclusion This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings.

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis. The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87; 95% CI: 1.37-2.57; P=0.000), but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63; 95% CI:-0.45-1.72; P=0.26] and overall survival (OS) (MD=-0.67; 95% CI:-2.54-1.20; P=0.49). In the sub analysis, better ORR was obtained with the addition of EGFR (OR=1.75; 95% CI: 1.20-2.56; P=0.004) and VEGFR (OR=2.5; 95% CI: 1.28-4.87; P=0.007) targeted therapy. Furthermore, the sub analysis of EGFR target showed an significant improvement on PFS (MD=1.36; 95% CI: 0.29-2.43; P=0.01). No significant differences were observed in the incidences of neutropenia (OR=1.37; 95% CI: 0.89-2.12), thrombocytopenia (OR=1.40; 95% CI: 0.83-2.39), anemia (OR=1.21; 95% CI: 0.62-2.38), peripheral neuropathy (OR=1.52; 95% CI: 0.81-2.88), increased AST/ALT (OR=1.40; 95% CI: 0.82-2.39) as well as fatigue (OR=1.65; 95% CI: 0.96-2.84) in either of the treatment groups. In conclusion, better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present meta-analysis without the cost of increased unacceptable toxicities, but regretfully not for the OS. The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS. Otherwise, there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone. Given the paucity of favorable data, we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

This study aimed to investigate the long-term outcomes of sulfonylurea (SU) use in patients with T2DM and compensated liver cirrhosis. From January 1, 2000, to December 31, 2012, we selected the data of 3781 propensity-score-matched SU users and nonusers from Taiwan’s National Health Insurance Research Database. The mean follow-up time for this study was 5.74 years. Cox proportional hazards models with robust sandwich standard error estimates were used to compare the risks of main outcomes between SU users and nonusers. The incidence of mortality during follow-up was 3.24 and 4.09 per 100 person-years for SU users and nonusers, respectively. The adjusted hazard ratios and 95% confidence intervals for all-cause mortality, major cardiovascular events, and decompensated cirrhosis in SU users relative to SU nonusers were 0.79 (0.71–0.88), 0.69 (0.61–0.80), and 0.82 (0.66–1.03), respectively. The SU-associated lower risks of death and cardiovascular events seemed to have a dose–response trend. This population-based cohort study demonstrated that SU use was associated with lower risks of death and major cardiovascular events compared with SU non-use in patients with T2DM and compensated liver cirrhosis. SUs may be useful for glycemic management for patients with liver cirrhosis.