Search

Metabolic-associated fatty liver disease (MAFLD) is a growing global problem associated with increasing obesity prevalence. Lifestyle modifications are currently recommended, including weight reduction, exercise, and diet control. This study evaluated the short-term effect of lifestyle modifications on transient elastography (TE) values in an obese population with MAFLD. Thirty-two MAFLD patients were recruited for this prospective study and all subjects participated in a 3-month program of lifestyle modification. Sequential demographic parameters and biochemical tests were compared before and after program completion. Liver fat and fibrosis changes were measured using TE with controlled attenuated parameter (CAP) and liver stiffness measurements (LSM). The mean age was 38.7 years old (10 males). The body weight (88.09 kg vs. 80.35 kg), body mass index (32.24 kg/m

Background/purpose Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking. Methods Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis. Results Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55 mg/dL) and lower albumin levels (≤2.54 mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC = 0.762, sensitivity 75.0%, and specificity 66.7%). Conclusion Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality.

Drug-coated balloon (DCB) has emerged as an alternative therapeutic choice for in-stent restenosis (ISR) lesions. Cutting balloon angioplasty (CBA) is also a strategy utilized to treat tight stenotic lesions or ISR lesions. Few studies have focused on whether CBA plus DCB could achieve a better result in lowering the incidence of recurrent ISR. This study aimed to evaluate the efficacy of CBA plus DCB for ISR lesions.Between August 2011 and December 2017, 681 patients (937 lesions) were diagnosed with ISR and treated with DCBs in our hospital. The CBA plus DCB group comprised 90 patients who underwent PCI with further CBA plus DCB, and the DCB alone group comprised 591 patients who underwent percutaneous coronary intervention (PCI) with DCB alone.Baseline characteristics, the types of previous stents, lesion type, prevalence of ostial lesion and left main lesion, and pre-PCI and post-PCI stenotic percentage showed no significant difference between the two groups. Only post-PCI reference luminal diameter and size of DCB were larger in the CBA plus DCB group. During the one-year follow-up period, late loss and clinical outcomes did not differ between the two groups before and after propensity score matching. The incidence of subtotal/total occlusion with delay flow was lower in the CBA plus DCB group after propensity score matching (4.1% versus 10.9%; P = 0.030).In these patients with ISR lesions, the clinical outcomes and the incidence of repeat target lesion revascularization were similar after treatment with CBA plus DCB versus DCB alone. Further study is warranted, including prospective, randomized comparisons.

T cell based immunotherapies can be applicable to acute myeloid leukemia (AML). Therefore, the selection of optimal T cells, cell manufacturing, and therapeutic T cell engineering are essential for the development of effective adoptive T cell therapies for AML. Autologous tumor-infiltrating lymphocytes (TILs) have been in clinical trials to treat solid malignancies. Herein, we assessed whether TILs can be isolated from the bone marrow (BM) of AML patients, expanded ex vivo and utilized as a novel therapeutic strategy for AML. To this end, firstly we analyzed the immunophenotypes of a series of primary BM samples from AML patients (N = 10) by flow cytometry. We observed a variable amount of CD3+ TILs (range ∼2.3–∼32.6% of mononuclear cells) among BM samples. We then developed a novel protocol that produced a three-log ex vivo expansion of TILs isolated from AML patient BM (N = 10) and peripheral blood (PB) (N = 10), including from patients with a low number of CD3+ T cells, within 3, 4 weeks. Further, we identified previously described naïve T cells (CCR7+CD95-/or CD62L+CD45RA+) in AML BM and PB samples, which seemed to be required for a successful TILs ex vivo expansion. Finally, we showed that the expanded TILs could: (1) cause cytotoxicity to autologous AML blasts ex vivo (90.6% in control without T cell treatment vs. 1.89% in experimental groups with PB derived T cells and 1.77% in experimental groups with BM derived TILs, p

Background: Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Methods: We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. Results: After multivariable adjustment, HGF (Q4v1OR:3.74;p-trend=0.0001), SLAMF1 (Q4v1OR:4.07;p-trend=0.0001), CSF1 (Q4v1OR:3.00;p-trend=0.002), uPA (Q4v1OR:3.36;p-trend=0.002), IL-8 (Q4v1OR:2.83;p-trend=0.004), and OPG (Q4v1OR:2.44;p-trend=0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. Conclusion: This is the first prospective study to assess immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis.

To determine whether liver stiffness (LS) and fibrosis-4 (Fib-4) index were useful in assessing the occurrence of liver-related complications (LRC) in chronic hepatitis C (CHC) patients after direct-acting antivirals (DAAs) had been administered. This retrospective study enrolled CHC patients achieving sustained virological response (SVR) after DAA. A total of 697 (male/female: 294/403, mean age: 63.8 year) patients with measured LS and complete lab data at SVR were enrolled, followed, and analyzed. In a median follow-up of 21.4 months after SVR, 39 patients developed LRC including 28 with hepatocellular carcinoma (HCC), with the 30-month cumulative incidence of LRC and HCC being 7.7% and 5.1%, respectively. Predictions of occurrence of LRC and HCC were 0.820 and 0.774 for LS, and 0.775 and 0.737 for Fib-4, with optimal cutoffs of LS and Fib-4 being 14.5 kPa and 2.9 for LRC prediction. In multivariate analysis, LS was associated with the occurrence of LRC (hazard ratio: 3.97, 95% confidence interval [1.866, 8.446], p

ObjectivesDuring the COVID-19 outbreak, medical educators’ main concern has been how to prepare new physicians and medical students to meet their obligations as healthcare providers under novel circumstances. This study aims at exploring how trainees perceive their commitments as physicians under the threat of a pandemic.DesignA qualitative method was employed. Researchers interviewed medical students under clerkship training (fifth and sixth-year medical students) and new physicians undergoing postgraduate year (PGY) and specialty training.SettingA university hospital in Taipei, Taiwan.ParticipantsThe team conducted three focus groups for participants in three separate training stages: clerks, PGY students (PGYs), and residents. Researchers collected data from 31 March to 2 April 2020 and analysed the thematic analysis results.ResultsSeventeen medical students and new physicians took part in the focus groups, five of whom (31.25%) were female. Participants consisted of four residents, six PGYs, and seven medical students. Through their responses, the authors determined four major dimensions with corresponding subdimensions that significantly affected their sense of medical professionalism, including medical knowledge and clinical skills, sense of duty towards public health, teamwork and protection of patient rights.ConclusionsWe therefore concluded that participants grew to accept their roles after acquiring the knowledge and skills needed to care for patients with COVID-19. Alternative teaching arrangements and their impact on trainees’ clinical performance require further discussion.

Purpose Improved long-term survival after low anterior resection (LAR) for rectal cancer highlights the importance of functional outcome. Urogenital and anorectal dysfunction is frequently reported after conventional LAR. Advanced minimally invasive techniques such as robotic (RoTME) and transanal total mesorectal excision (TaTME) might improve functional results by precisely dissecting and preserving autonomic nerves. We compared functional outcomes after RoTME or TaTME in a multicenter study. Methods One hundred twenty patients (55 RoTME/65 TaTME) were prospectively included in four participating centers. Anorectal (Wexner and low anterior resection syndrome (LARS) Score), urinary (International Consultation on Incontinence—Male/Female Lower Urinary Tract Symptoms Score (ICIQ-MLUTS/ICIQ-FLUTS) and International Prostate Symptom Scale (IPSS)), and sexual (International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI)) outcomes at 12 months after surgery were compared to preoperative scores. The response rate to the 1-year postoperative functional assessment by questionnaire was 79.5%. Results RoTME enabled better anorectal function compared to TaTME (LARS score 4.3 ± 2.2 vs. 9.8 ± 1.5, p = 0.038, respectively). TaTME proved superior at preserving male urinary function, while female urinary function was comparable in both groups, with only mild postoperative impairment (RoTME vs. TaTME, respectively: ICIQ-MLUTS 13.8 ± 4.9 vs. 1.8 ± 5.8, p = 0.038; ICIQ-FLUTS Incontinence Score − 0.3 ± 1.0 vs. − 0.2 ± 0.9, p = 0.844). Both techniques demonstrated comparable male (RoTME − 13.4 ± 2.7 vs. TaTME − 11.7 ± 3.4, p = 0.615) and female (RoTME 5.2 ± 4.6 vs. TaTME 10.5 ± 6.4, p = 0.254) sexual function. Conclusion After adjustment for risk factors, RoTME provided better anorectal functional results, whereas TaTME was better at preserving male urinary function. Overall, both techniques demonstrated only mild postoperative functional impairment.

Background and aim Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their impact on distension-induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults. Methods Eighteen healthy volunteers (13 men, mean age 27.5 years, aged 20-43 years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid-esophagus. Secondary peristalsis was performed with 10 and 20 mL rapid air injections. Two different sessions including acute administration of codeine (60 mg) or the placebo were randomly performed. Results Codeine significantly increased 4-second integrated relaxation pressure (IRP-4s) (P = 0.003) and shortens distal latency (DL) (P = 0.003) of primary peristalsis. The IRP-4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10 mL (P = 0.048) and 20 mL (P = 0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10 mL than the placebo (P = 0.007), but not for air injection with 20 mL (P = 0.305). Conclusions In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.

BACKGROUND AND AIMS Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH AND RESULTS Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P

The estrogen-related receptor (ERR) family of orphan nuclear receptors are transcriptional activators for genes involved in mitochondrial bioenergetics and metabolism. The goal of this study was to explore the role of ERRα in lipid metabolism and the potential effect of inhibiting ERRα on the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In the current study, three experimental mouse models: high-fat diet, high-carbohydrate diet, and a genetic model of hepatic insulin resistance where the liver hyperinsulinemia signal is mimicked via hepatic deletion of Pten (phosphatase and tensin homolog deleted on chromosome 10), the negative regulator of the insulin/phosphatidylinositol 3-kinase signaling pathway, were used. A recently developed small-molecule inhibitor for ERRα was used to demonstrate that inhibiting ERRα blocked NAFLD development induced by either high-carbohydrate diet or high-fat diet feeding. ERRα inhibition also diminished lipid accumulation and attenuated NASH development in the Pten null mice. Glycerolipid synthesis was discovered as an additional mechanism for ERRα-regulated NAFLD/NASH development and glycerophosphate acyltransferase 4 was identified as a novel transcriptional target of ERRα. In summary, these results establish ERRα as a major transcriptional regulator of lipid biosynthesis in addition to its characterized primary function as a regulator for mitochondrial function. This study recognizes ERRα as a potential target for NAFLD/NASH treatment and elucidates novel signaling pathways regulated by ERRα.

BACKGROUND Recent studies have demonstrated that inhibition of CD26 potentiates stromal cell-derived factor-1α (SDF-1α), promotes tissue regeneration, and suppresses the rejection of organ transplants. This study investigated whether the combination of a CD26 inhibitor (CD26i) with granulocyte colony-stimulating factor (G-CSF) and short-term immunosuppressants modulates vascularized composite tissue allotransplant survival in a rodent orthotopic hindlimb allotransplant model. METHODS The hindlimb allotransplantation from Brown-Norway to Lewis rats was divided into 4 groups. Group 1 (controls) did not receive any treatment. Group 2 was treated with short-term antilymphocyte serum (ALS) and cyclosporine-A (CsA). Group 3 was administrated CD26i and G-CSF. Group 4 received a combination of CD26i/G-CSF/ALS/CsA. Each subgroup comprised 10 rats. Peripheral blood and sampling of transplanted tissues were collected for immunological and histological analysis. RESULTS The results revealed that allotransplant survival was found to be significantly prolonged in group 4 with CD26i/G-CSF/ALS/CsA treatment compared with those in the other groups. The interleukin-10 and transforming growth factor-βl levels, the percentage of CD4+/CD25+/FoxP3+ T cells, as well as the levels of SDF-1α expressions were significantly increased in group 4 compared with those in the other groups. Group 4 revealed a statistical increase in the percentage of donor cells (RT1n) expression in the recipient peripheral blood, and the mixed lymphocyte reaction showed hyporesponsiveness of the T cells to donor alloantigens. CONCLUSION The combination of CD26i/G-CSF and short-term immunosuppressants prolongs allotransplant survival by inducing immunoregulatory effects and enhancing the percentage of SDF-1α expression. This immunomodulatory approach has great potential as a strategy to increase vascularized composite allotransplantation survival.

Early recognition of adult-onset immunodeficiency associated with neutralizing anti-interferon gamma autoantibodies (anti-IFNγ Abs) remains difficult, and misdiagnoses have been reported. Although febrile lymphadenopathy is among the most common initial manifestations of this disorder, no comprehensive clinicopathologic analysis of lymphadenopathy in patients with anti-IFNγ Abs has been reported. Here, we describe 26 lymph node biopsy specimens from 16 patients. All patients exhibited concurrent disseminated nontuberculous mycobacterial infections, and 31% received a tentative diagnosis of lymphoma at initial presentation. We found 3 distinct histomorphologic patterns: well-formed granuloma (46%), suppurative inflammation or loose histiocytic aggregates (31%), and lymphoproliferative disorder (LPD, 23%). The latter shared some of the features of malignant T-cell lymphoma, IgG4-related disease, and multicentric Castleman disease. Half of the specimens with LPD had monoclonal T cells, and 33.3% were indistinguishable from angioimmunoblastic T-cell lymphoma as per current diagnostic criteria. All lymphadenopathy with LPD features regressed with antibiotics without administration of cytotoxic chemotherapy or immunotherapy. The median follow-up time was 4.3 years. Our study highlights the substantial challenge of distinguishing between lymphoma and other benign lymphadenopathy in the setting of neutralizing anti-IFNγ Abs. Increased vigilance and multidisciplinary discussion among clinicians and pathologists are required to achieve the most appropriate diagnosis and management.

Background: Exposure to traffic-related pollution is positively associated with cardiovascular diseases (CVD), but little is known about how different sources of traffic pollution (eg, gasoline-powered cars, diesel-engine vehicles) contribute to CVD. Therefore, we evaluated the association between exposure to different types of engine exhaust and CVD mortality. Methods: We recruited 12,098 participants from REVEAL-HBV cohort in Taiwan. The CVD mortality in 2000–2014 was ascertained by the Taiwan Death Certificates. Traffic pollution sources (2005–2013) were based on information provided by the Directorate General of Highway in 2005. Exposure to PM2.5 was based on a land-use regression model. We applied Cox proportional hazard models to assess the association of traffic vehicle exposure and CVD mortality. A causal mediation analysis was applied to evaluate the mediation effect of PM2.5 on the relationship between traffic and CVD mortality. Results: A total of 382 CVD mortalities were identified from 2000 to 2014. We found participants exposed to higher volumes of small car and truck exhausts had an increased CVD mortality. The adjusted hazard ratio (HR) was 1.10 for small cars (95% confidence interval [CI], 0.94–1.27; P-value = 0.23) and 1.24 for truck (95% CI, 1.03–1.51; P-value = 0.03) per one unit increment of the logarithm scale. The findings were still robust with further adjustment for different types of vehicles. A causal mediation analysis revealed PM2.5 had an over 60% mediation effect on traffic-CVD association. Conclusions: Exposure to exhaust from trucks or gasoline-powered cars is positively associated with CVD mortality, and air pollution may play a role in this association.

Graphical abstract, Introduction A population-specific genomic reference is important for research and clinical practice, yet it remains unavailable for Han Chinese (HC) in Taiwan. Objectives We report the first whole genome sequencing (WGS) database of HC (1000 Taiwanese genome (1KTW-WGS)) and demonstrate several applications to cardiovascular medicine. Methods Whole genomes of 997 HC were sequenced to at least 30X depth. A total of 20,117 relatively healthy HC individuals were genotyped using a customized Axiom GWAS array. We performed a genome-wide genotype imputation technique using IMPUTE2. Results We identified 26.7 million single-nucleotide variants (SNVs) and 4.2 million insertions-deletions. Of the SNVs, 16.1% were novel relative to dbSNP (build 152), and 34.2% were novel relative to gnomAD. A total of 18,450 healthy HC individuals were genotyped using a customized Genome-Wide Association Study (GWAS) array. We identified hypertension-associated variants and developed a hypertension prediction model based on the correlation between the WGS data and GWAS data (combined clinical and genetic models, AUC 0.887), and also identified 3 novel hyperlipidemia-associated variants. Each individual carried an average of 16.42 (SD = 3.72) disease-causing variants. Additionally, we established an online SCN5A (an important cardiac gene) database that can be used to explore racial differences. Finally, pharmacogenetics studies identified HC population-specific SNVs in genes (CYP2C9 and VKORC1) involved in drug metabolism and blood clotting. Conclusion This research demonstrates the benefits of constructing a population-specific genomic reference database for precision medicine.

The underlying causes of heartburn, characteristic symptom of gastroesophageal reflux disease (GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease (NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1 (TRPV1), transient receptor potential melastatin 8 (TRPM8), and acid-sensing ion channel 3 (ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterized TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of patients with GERD. We studied 10 patients with NERD, 10 with erosive reflux disease (ERD), 7 with functional heartburn (FH), and 8 with Barrett's esophagus (BE). Biopsies obtained from the distal esophageal mucosa were costained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of

International guidelines do not recommend surgery for the first episode of primary spontaneous pneumothorax (PSP), except in cases of persistent air leak, hemopneumothorax, bilateral pneumothorax, or occupations at risk. However, these recommendations have been challenged because of a significant reduction in the recurrence rate in emerging studies. We evaluated the rationale of recommendations by systematically reviewing RCTs and observational studies by using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. We searched articles in PubMed, EMBASE, and Cochrane databases up to August 15, 2020. The primary outcomes were the recurrence rate and complication rate. The secondary outcomes were hospital stay and drainage duration. Nine eligible studies with 1121 patients were retrieved and analyzed. The recurrence rate was lower in the VATS than in conservative treatment with moderate evidence (OR 0.13, 95% CI 0.09 to 0.19, P 2 = 0%). We did not find significant differences in complication rate (Peto OR 1.17, 95% CI 0.33 to 4.12, P = 0.80), hospital stay duration (MD − 0.48 days, 95% CI − 2.84 to 1.87, P = 0.69, very low evidence), and in drainage duration (MD − 3.99 days, 95% CI − 9.06 to 1.08, P = 0.12, very low evidence) between the two groups. Our results would suggest VATS treatment as a weak recommendation for patients with the first episode of PSP, based on our systematic review of the current evidence by using the GRADE system, indicating that different treatments will be appropriate for different patients and that patients’ values and preferences should be incorporated through shared decision making.Trial REGISTRY: PROSPERO; No.: CRD42020162267.

Background Liberal oxygen therapy might increase the mortality rate of patients. Non-rebreathing masks (NRM) are a high-flow, non-invasive oxygen device that can provide oxygen concentration up to 95%. This study aimed to determine the impact of using NRM in patients with respiratory failure. Methods This retrospective cohort study was conducted in four medical institutions in Taiwan from January 2010 to December 2016. The association between mortality and NRM use before receiving ventilator support in patients with respiratory failure in the emergency department was analyzed. Patients were divided into the NRM treatment and no NRM treatment groups. A 1:4 propensity score matching was conducted. Regarding the duration of NRM use, treatments were grouped as 0 h, 0–1 h, 1–2 h, and >2 h. Results A total of 18,749 patients were included, with 1074 using NRM. After propensity score matching, 1028 patients using NRM (0–1 h: 508, 1–2 h: 193, and >2 h: 327) and 4112 patients not using NRM were analyzed. The 30-day mortality rates were 29.1%, 28.5%, 27.5%, and 35.5% in the 0 h, 0–1 h, 1–2 h, and >2 h treatment groups, respectively. Patients with respiratory failure due to pulmonary disease using NRM over 2 h had a higher mortality rate than patients not using NRM (hazard ratio: 1.3, 95% CI: 1.01–1.66). Conclusions Prolonged use of NRM in patients with respiratory failure due to pulmonary disease possibly increases mortality.

Cajanus cajan (L.) Millsp., known as pigeon pea, is one of the major grain legume crops of the tropical world. It recognizes as an ethnomedicine to possess various functions, such as helping in healing wound and cancer therapy. We investigated whether 95% ethanol extracts from C. cajan root (EECR) protect against methylglyoxal (MGO)-induced insulin resistance (IR) and hyperlipidemia in male Wistar rats and explored its possible mechanisms. The hypoglycemic potential of EECR was evaluated using α-amylase, α-glucosidase activities, and advanced glycation end products (AGEs) formation. For in vivo study, the rats were divided into six groups and orally supplemented with MGO except for Group 1 (controls). Group 2 was supplemented with MGO only, Group 3: MGO + metformin, Group 4: MGO + Low dose-EECR (L-EECR; 10 mg/kg bw), Group 5: MGO + Middle dose-EECR (M-EECR; 50 mg/kg bw), and Group 6: MGO + High dose-EECR (H-EECR; 100 mg/kg bw). EECR possessed good inhibition of α-glucosidase, α-amylase activities, and AGEs formation (IC

Background The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. Methods We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. Results During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). Conclusions This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12–16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

Laparoscopic surgery for rectal cancer is technically challenging. Robotic and transanal TME (TaTME) are both novel approaches developed to provide better visualization and dissection. We aim to combine both approaches in a hybrid procedure and evaluate the feasibility as well as patient and oncological outcomes in this study. A review of a prospectively maintained database of patients who underwent a hybrid abdominal robotic approach with TaTME for rectal cancer between January 2016 and October 2018 was undertaken. Patient demographics, tumor characteristics and surgical outcomes were recorded and analyzed. A total of 69 patients (43 males, 26 females) received this hybrid approach. Their median age was 58 years (range 35–87) with a mean BMI of 24.3 kg/m2 (range 16.4–44.2). Median distance from anal verge was 5 cm (range 2–9). The patients had a median hospital length of stay of 7 days (range 5–28). Complication rate was 17.4% (12 patients) with 3 patients (4.3%) requiring a reoperation. TME quality was optimal with all of them either complete (81.2%) or almost complete (18.8%). 65 patients (94.2%) had an R0 resection with 4 patients (5.8%) with involved circumferential resection margins (≤ 1 mm). The median number of lymph nodes harvested was 20 (range 6–37). After a median follow-up of 27.7 months (range 7–42), local recurrence was identified in 2 patients (4%). Three patients (5.2%) had distant recurrence at the 3-year mark. Hybrid robotic abdominal dissection with transanal TME for rectal cancer appears to be feasible with comparable surgical outcomes to other traditional approaches.

To evaluate the safety of outpatient percutaneous endovascular abdominal aortic repair (PEVAR) versus inpatient PEVAR without or with adjunct procedures.Between January 2012 and June 2019, a cohort of 359 patients comprising 168 (46.8%) outpatients and 191 (53.2%) inpatients who had undergone PEVAR were enrolled. All the patients were asymptomatic but had indications for endovascular aortic repair, ie, fit for intravenous anesthesia and anatomically feasible with standard devices. Patient sex, age, comorbidities, smoking status, type of anesthesia, adjunct procedures, type of graft device, operative times, mortality, complications, and readmissions were analyzed.Median follow-up period was 16.5 months (interquartile range, 9-31 months). Except for a higher percentage of tobacco use (42.6% vs 28.8%; P = .04), dyslipidemia (39.7% vs 19.2%; P.01), and use of local anesthesia (99.4% vs 82.2%; P.01) in the outpatients, there was no significant difference in the type of graft and adjunct procedures used. No outpatient mortality occurred. There was no difference in the number, severity, and onset of complications (all P.05). Outpatient unexpected same-day admission, 30-day readmission, and emergency department visit rates were 4.8%, 2.4% (P = .13), and 10% (P.01), respectively. Operative times for outpatient PEVAR without adjunct procedures were shorter (P.01).Outpatient PEVAR can be performed with a safety profile similar to that of inpatient PEVAR. The unexpected same-day admission, 30-day readmission, and emergency department visit rates were low. The outpatient PEVARs without adjunct procedures took less time.

Human leukocyte antigen (HLA) gene variation is associated with risk of cancers, particularly those with infectious etiology or hematopoietic origin, given its role in immune presentation. Previous studies focused primarily on HLA allele/haplotype-specific associations. To answer whether associations are driven by HLA class I (essential for T-cell cytotoxicity) or class II (important for T-cell helper responses) genes, we analyzed GWAS from 24 case–control studies and consortia comprising 27 cancers (totaling >71,000 individuals). Associations for most cancers with infectious etiology or of hematopoietic origin were driven by multiple HLA regions, suggesting that both cytotoxic and helper T-cell responses are important. Notable exceptions were observed for nasopharyngeal carcinoma, an EBV-associated cancer, and CLL/SLL forms of non-Hodgkin lymphomas; these cancers were associated with HLA class I region only and HLA class II region only, implying the importance of cytotoxic T-cell responses for the former and CD4+ T-cell helper responses for the latter. Our findings suggest that increased understanding of the pattern of HLA associations for individual cancers could lead to better insights into specific mechanisms involved in cancer pathogenesis. Significance: GWAS of >71,000 individuals across 27 cancer types suggest that patterns of HLA Class I and Class II associations may provide etiologic insights for cancer.

Aim Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function. Methods We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke. Results Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3-5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m2. Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60-89 mL/min/1.73 m2. Statin therapy in patients with an eGFR of 60-89 mL/min/1.73 m2 may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57). Conclusions In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.

Secondary post-traumatic orbital reconstructions are challenging. Portable computed tomography (CT) provides the option to acquire real-time, intraoperative images that help to detect the insufficient reconstruction of the orbit immediately. We retrospectively analyzed patients who received intraoperative CT imaging and analyzed the effect of intraoperative CT scans on revision rates and orbital volume changes before, during, and after surgery.From August 2014 to September 2016, eleven patients received intraoperative cone-beam CT scans to evaluate the results of secondary orbit reconstruction using Medpor + titanium implants. Patient demographics, surgical details, CT scanning protocol, and follow-up results were analyzed. 3D CT volumetry was used to analyze the orbital volume based on OsiriX MD software.Based on intraoperative CT findings, seven cases required intraoperative revision to further augment the orbital cavity or adjust implants. The mean preoperative measured enophthalmos was 3.41±1.4 mm (range: 2-6 mm), which decreased to 0.73±0.4 mm (range: 0-1 mm) at postop assessment (p0.0001). On the fracture side, there was a significant difference between preoperative vs. intraoperative and preoperative vs. postoperative volume measurements (p0.01 for both subsets), but no significant difference between intraoperative vs. postoperative measurements.Intraoperative CT is a valuable tool in secondary orbital reconstruction cases based on clinical enophthalmos evaluation and 3D CT volumetry. For these patients, the avoidance of another revision surgery may outweigh the disadvantage of increased operation time and additional radiation exposure.

Background Transanal total mesorectal excision is a promising surgical procedure for mid to low rectal cancer. Objective This study aimed to determine the short-term outcomes of Chinese patients treated with transanal total mesorectal excision. Design This was an observational study using data from an online registry system. Setting Study participants were recruited from 40 different centers across 15 provinces in China. Patients Patients with either benign or malignant rectal disease who underwent transanal total mesorectal excision procedure and were registered in the Chinese Transanal Total Mesorectal Excision Registry Collaborative from May 2010 to November 2019 were included. Intervention Patients underwent transanal total mesorectal excision. Main outcome measures The primary outcomes measured were the postoperative complications and pathological outcomes. Results In total, 1283 patients, comprising 888 men (69.2%) and 395 women (39.8%) with a median age of 61 (22-92) years and a median BMI of 23.6 (14.5-46.3) kg/m2, were analyzed. Among 40 participating centers, the average number of registered cases was 32.1±34.7, and 12 centers (30%) registered >40 cases in the registry. Among 849 patients with rectal cancer who underwent laparoscopic-assisted transanal total mesorectal excision, the conversion rate was 0.5% in the abdominal phase and 1.9% in the perineal phase. Three patients reported urethral injury (0.5%). The postoperative complication rate and the anastomotic leakage incidence were 18.4% and 5.8%. The quality of the total mesorectum excision specimens was found to be complete in 81.9% of patients. In addition, the positive circumferential resection margin rate was 2.8%. Limitations The primary limitation of this registry study was the high percentage of missing data (10.8% overall), and, for some of the analyzed variables, up to 35% of the data was missing. Postoperative complications were not monitored after discharge, resulting in a lower morbidity rate than the 30-day morbidity rate reported in other studies. Conclusions The short-term outcomes of patients who underwent transanal total mesorectal excision procedures in China were acceptable. See Video Abstract at http://links.lww.com/DCR/B414. Excisin total del mesorrecto por va transanal resultados a corto plazo de casos de un registro nacional en china ANTECEDENTES:La excision total del mesorrecto por via transanal es un procedimiento quirurgico prometedor para el cancer de recto medio y bajo.OBJETIVO:Determinar los resultados a corto plazo de los pacientes chinos tratados con escision mesorrectal total transanal.DISENO:Estudio observacional con datos de un sistema de registro en linea.AJUSTE:Los participantes del estudio fueron reclutados en 40 centros diferentes en 15 provincias de China.PACIENTES:Se incluyeron pacientes con enfermedad rectal benigna o maligna que se sometieron a una cirugia de excision total del mesorrecto por via transanal y que se registraron en el Registro Colaborativo de Excision Total del Mesorrecto por via Transanal en China desde mayo de 2010 hasta noviembre de 2019.INTERVENCION:Excision total delmesorrecto por via transanal.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones postoperatorias y resultados patologicos.RESULTADOS:Fueron analizados un total de 1.283 pacientes, que comprendian 888 hombres (69,2%) y 395 mujeres (39,8%) con una mediana de edad de 61 (22-92) anos y una mediana de indice de masa corporal de 23,6 (14,5-46,3) kg / m2. Entre los 40 centros participantes, el promedio de casos registrados fue de 32,1 ± 34,7, y 12 centros (30%) inscribieron > 40 casos en el registro. Entre 849 pacientes con cancer de recto que se sometieron a excision total del mesorrecto peeor via transanal asistida por laparoscopia, la tasa de conversion fue del 0,5% en la fase abdominal y del 1,9% en la fase perineal. Tres pacientes refirieron una lesion uretral (0,5%). La tasa de complicaciones posoperatorias y la incidencia de fuga anastomotica fueron del 18,4% y el 5,8%, respectivamente. La calidad de las muestras de excision total del mesorrecto se evaluo como completa en el 81,9% de los pacientes. Ademas, la tasa de margen de reseccion circunferencial positiva fue del 2,8%.LIMITACIONES:La principal limitacion del presente estudio de registros fue el alto porcentaje de datos faltantes (10,8% en general), y para algunas de las variables analizadas, faltaba hasta el 35% de los datos. Las complicaciones postoperatorias no fueron verificadas despues del alta, lo que resulto en una tasa de morbilidad mas baja que la tasa de morbilidad a 30 dias informada en otros estudios.CONCLUSIONES:Los resultados a corto plazo de los pacientes que se sometieron al procedimiento de excision total del mesorrecto por via transanal en China fueron aceptables. Consulte Video Resumen en http://links.lww.com/DCR/B414. (Traduccion-Dr. Xavier Delgadillo).

Background Because more than one neoadjuvant treatment is available for advanced rectal cancer, the aim of this study was to compare the differential clinical and pathologic effects of different combinations of chemoradiation regimens, treatment sequencing, and timing to surgery on patient outcomes. Patients and Methods Between January 2015 and October 2018, 126 newly diagnosed patients with rectal cancer with magnetic resonance imaging-based cT3-4 or N+ rectal disease for curative-intent treatment received 1 of 4 neoadjuvant regimens, followed by immediate surgery or delayed surgery. Whole post-neoadjuvant surgical specimens were assessed by 3-dimensional digital whole-tumor microarray imaging and immunostaining in pathology to analyze the global tumor pathologic regression grades, residual tumor distribution patterns, the extent of lymphovascular permeation, lymph node positivity, and the overall density of lymphocyte infiltration in the tumor microenvironment. These factors were further examined to identify possible correlations with clinical outcomes. Results Among the 4 neoadjuvant treatment groups, including 2 conventional regimens, we found a significant increase of stromal CD3+ and CD8+ immune infiltrates in the postneoadjuvant tumor microenvironment in the 3 groups with delayed surgery after different chemoradiation regimens compared with the group with immediate surgery after a short course of RT alone. Independent of neoadjuvant chemoradiation regimens, the post-induction high-intermediate-low stromal-infiltrating CD8+ T-cell densities corresponded to tumor regression grades, distant metastasis rates, and disease-free survival and were prognostic factors for the further stratification of patients with American Joint Committee on Cancer stage III rectal cancer into different risk groups after surgery. Conclusion The effectiveness of induction strategies on tumor remission and disease recurrence in advanced rectal cancer was significantly correlated with an enhanced cytotoxic immune response in the tumor microenvironment.

Aims USP6 rearrangement underpins self-limiting fibroblastic/myofibroblastic neoplasms, including nodular fasciitis (NF), myositis ossificans (MO), aneurysmal bone cyst (ABC), and related variants. The aim of this study was to characterise UPS6 and fusion partners in order to delineate the clinicopathological, genetic and bone-forming features in such lesions of soft tissue (ST). Methods and results Break-apart fluorescence in-situ hybridisation (FISH) validated USP6 rearrangement in 31 of 35 NF [comprising three of three fasciitis ossificans (FO) cases, seven of eight cellular variant of fibroma of tendon sheath (C-FTS), four of six MO, three of three ST-ABC, and two of two fibro-osseous pseudotumours of digits (FOPD)]. As determined with FISH and reverse transcription polymerase chain reaction, MYH9-USP6 was the commonest fusion in four C-FTS and 20 NF, including one intravascular case and two infantile (one retroperitoneal) cases. The presence of MYH9-USP6 confirmed the diagnosis of two NFs> 50 mm with prominent ischaemic necrosis. COL1A1-USP6 was predominant in ossifying lesions, including all FO, MO, ST-ABC and FOPD with identified partner genes, and was also present in non-ossifying head and neck NF (HN-NF) and C-FTS in two cases each. A cervical NF of a 14-month-old girl harboured the novel COL1A2-USP6. Ossifying lesions showed considerable genetic and morphological overlaps. Sharing COL1A1-USP6, FO and FOPD showed similar central or haphazard bone matrix deposition. Besides zonation of outward bone maturation, four COL1A1-USP6-positive MO had incipient to sieve-like pseudocysts reminiscent of ST-ABC. Conclusion MYH9-USP6 is present in some C-FTS and most NF, including rare variants, but is unrelated to bone formation. All bone-forming USP6-rearranged lesions adopt COL1A1 as the 5' partner, indicating close genetic kinships. However, COL1A1/COL1A2 also contributes to the pathogenesis of minor subsets of non-ossifying USP6-rearranged HN-NF and C-FTS.

Objectives: To investigate the effect of cholecystectomy on the subsequent risk of acute myocardial infarction (AMI) in patients with gallbladder stones (GBS). Methods: We used the Taiwan National ...

Anatomical barriers (e.g., pedicles, narrow foramina) can hinder direct access to, and removal of, disc fragments that have migrated far downward. Using transforaminal full-endoscopic lumbar discectomy (FELD), we devised a modified technique, the suprapedicular retrocorporeal approach, for herniations in which the disc has migrated to the axilla of the traversing nerve roots. In the present report, we have described our preliminary results.Soft, highly downward-migrated disc herniation was treated with transforaminal FELD through the suprapedicular retrocorporeal approach in 22 patients from June 2017 to May 2019. The clinical outcomes were evaluated, including the preoperative and postoperative visual analog scale scores for the back and leg, Oswestry disability index, and MacNab criteria for surgical success.The affected discs were at L4-L5 in 14 patients, L3-L4 in 6 patients, and L5-S1 in 2 patients. In each case, the affected disc was successfully removed using the suprapedicular retrocorporeal approach. The mean follow-up was 18.1 ± 5.7 months. The mean visual analog scale scores for back and leg pain improved significantly (P0.05 for both). The mean Oswestry disability index had decreased from 62.5 ± 14.2 preoperatively to 10.5 ± 5.9 postoperatively (P0.05). Using the MacNab criteria, 13 patients reported excellent outcomes and 9, good outcomes. No complications or recurrence developed during follow-up.The suprapedicular retrocorporeal technique is a feasible and effective surgical option in transforaminal FELD for the treatment of herniation in which the disc has migrated to the axilla of the traversing nerve roots.

Background Low-acuity outpatients constitute the majority of emergency department (ED) patients, and these patients often experience an unpredictable length of stay (LOS). Effective LOS prediction might improve the quality of ED care and reduce ED crowding. Objective The objective of this study was to explore the potential of natural language processing (NLP) of the first ED physicians' clinical notes and to evaluate NLP-based short-term prediction models based on mixed-type clinical data. Methods A retrospective study was conducted at an ED of a tertiary teaching hospital in Taiwan from January 2017 to June 2017. In total, 12,962 low-acuity outpatients were enrolled. Using structured data (e.g., demographic variables and vital signs) and different sections of the first SOAP notes as predictors, we developed six NLP-based prediction models (i.e., term frequency-inverse document frequency (TF-IDF) and truncated singular value decomposition (SVD)) to predict LOS. The metric for model evaluation is the mean squared error (MSE). Results Of the six NLP-based models, the model using structured data and all the sections of the first SOAP notes processed by the TF-IDF and truncated SVD method performed the best, with an MSE of 3.00 [95% CI: 2.94–3.06]. In addition, ten important topics extracted by the TF-IDF and truncated SVD method had significant effects on the LOS (p Conclusion NLP-based models can be used as an early short-term prediction of LOS and have the potential for mixed-type clinical data analysis. The proposed models would likely aid ED physicians' decision-making processes and improve ED quality of care.

Caustic substance ingestion is frequently life-threatening, and its pathological mechanisms of tissue damage are well documented. However, few studies have assessed the combined effects of pH and the ingested dose on patient outcomes. Additionally, the miscellaneous chemical properties are not immediately available for providing predictive insights to physicians. This study aimed to provide a new perspective of the risk assessment of caustic substance ingestion based on the pH and dose.The retrospective study analyzed adults treated for caustic substance ingestion at Chang Gung Memorial Hospital between January 1999 and December 2018. Uniformly strict inclusion/exclusion criteria and a double-checked process during chart review were adopted. All patients underwent urgent esophagogastroduodenoscopy (EGD) within 24 h. Caustic mucosal damage was graded using Zargar's modified endoscopic classification. The pH and ingested dose of caustic substances were clearly recorded. Statistical analyses were conducted using IBM SPSS, version 22.Based on the 468 enrolled cases, the pH and dose were valuable predictors of the extent of gastrointestinal tract injury, commonly encountered complications, and long-term overall survival outcomes. Risks of mortality and perforation were dose-dependent for acids and pH-dependent for alkalis. The severe EGD findings (grade ≥ 2b) in this study were pH-dependent for both substances and additionally dose-dependent for acids.Combining pH and dose, we proposed a new perspective for the risk assessment of caustic substance ingestion. Such findings may provide predictive insights for resolving clinical uncertainty before the availability of examination results. "Large doses of acids" and "high pH of alkalis" deserve special attention. This new perspective with a retrospective nature requires further validation.

Background Neoadjuvant chemoradiotherapy followed by an esophagectomy is the standard treatment for locally advanced esophageal cancer, but remains a great challenge for elderly patients. Therefore, we aim to evaluate the efficacy of definitive chemoradiotherapy in elderly patients with esophageal cancer. Methods From December 2007 to October 2017, forty esophageal cancer patients aged ≥ 70 years receiving definitive chemoradiotherapy were retrospectively analyzed. All patients received cisplatin-based chemotherapy. Ten patients received standard doses of cisplatin 20 mg/m2 and 5-FU 800 mg/m2 for 1-4 days, during the first and fifth weeks of radiotherapy. Eighteen patients received modified doses of cisplatin 16-18 mg/m2 and 5-FU 600-800 mg/m2. Twelve patients received lower doses of cisplatin 10-12 mg/m2 and 5-FU 400-600 mg/m2. The endpoints were overall survival (OS), tumor response rate and treatment compliance. Results The 3-year OS rate was 28.8% The 3-year OS rates for patients receiving standard, modified and lower doses were 12.5%, 53.8% and 0.0%, respectively (p=0.05). There were 87.5% of patients completing the scheduled radiotherapy dose, along with 2 cycles of concurrent chemotherapy. The response rate (clinical complete response and partial response rate) was 70.0%. Multivariate analysis revealed that no statistical difference was found in the overall survival among these 3 groups of chemotherapy dosage. The treatment response was the only independent prognostic factor regarding overall survival (p Conclusion Definitive chemoradiotherapy with dose modification is a feasible, safe and reasonable treatment for elderly esophageal cancer patients. Achieving a better compliance to chemoradiotherapy through an optimal dose modification of chemotherapy may provide better clinical outcomes and would be the treatment goal for elderly esophageal cancer patients.

BACKGROUND The Barcelona Clinic Liver Cancer (BCLC) guidelines were updated in 2012, and a single large hepatocellular carcinoma (HCC) more than 5 cm was regarded as BCLC stage A rather than B in the updated version. In this study, we sought to re-evaluate the outcomes of patients with HCC who underwent liver resection (LR) within (stage 0 and A) and beyond (stage B and C) the BCLC guideline recommendations of the updated BCLC staging system. METHODS This retrospective study enrolled 774 consecutive patients with naive HCC who underwent LR from 2011 to 2018 at our institution. The overall survival (OS) and recurrence-free survival (RFS) of these patients were examined. RESULTS Of the patients, 606 had BCLC stage 0 or A HCC, and 168 had BCLC stage B or C HCC. The 5-year OS and RFS among the patients within the BCLC criteria for LR were 75.2% and 56.1%, respectively, vs 54.9% and 34.0%, respectively, among the patients beyond the BCLC criteria (P

Esophageal atresia with/without tracheoesophageal fistula (EA/TEF) is a congenital digestive tract anomaly that represents a major therapeutic challenge. Postoperative digestive morbidities such as gastroesophageal reflux disease (GERD) and esophageal stricture are common. The aim of this study was to identify the incidence of and potential risk factors for digestive morbidities after EA/TEF repair. We retrospectively reviewed all EA/TEF patients who underwent repair at a single institution between January 1999 and December 2018, excluding patients who died prior to discharge. Patient demographics, perioperative management, and postoperative GERD and esophageal stricture rates were collected. We performed univariate and multivariate analyses to examine risk factors associated with postoperative GERD and esophageal stricture. The study enrolled 58 infants (58.6% male, 17.2% with type A EA/TEF, 62.1% with associated anomalies). Postoperative GERD occurred in 67.2% of patients and was the most common digestive morbidity. Esophageal stricture occurred in 37.9% of patients after EA/TEF repair. Multivariate analysis showed that long-gap EA/TEF and postoperative GERD were independent risk factors for esophageal stricture after repair surgery.Conclusion: The incidence of postoperative GERD and esophageal stricture was 67.2% and 37.9%, respectively. The risk factors for postoperative esophageal stricture were long-gap EA/TEF and postoperative GERD. What is Known: • EA/TEF is a congenital digestive tract anomaly with a high postoperative survival rate but can be complicated by many long-term morbidities. What is New: • Long-gap EA/TEF and postoperative GERD are risk factors of anastomotic stricture after repair. • Surgeons and pediatricians should be highly experienced in managing anastomotic tension and the GERD.

PURPOSE: The study compared the incidence and predictors of hepatocellular carcinoma (HCC) within and beyond year 5 of entecavir (ETV) therapy.The study enrolled 1397 CHB patients who were naïve to nucleos(t)ide analogue (NA) treatment and had received ETV monotherapy for more than 12 months.The cumulative incidences of HCC at 3, 5, and 10 years of ETV treatment were 4%, 9.1%, and 15.8%, respectively. In the entire cohort, the annual incidence rates of HCC were 2.28% within the first 5 years and 1.34% within 5-10 years of therapy. The incidences of HCC did not differ significantly within and beyond 5 years of ETV therapy (p = 0.53), including patients with cirrhosis (p = 0.85) and without cirrhosis (p = 0.47). At year 5 of treatment, the multivariate analysis showed that the fibrosis-4 (FIB-4) index and alpha-fetoprotein (AFP) levels were independent risk factors for HCC development beyond year 5. The 10-year cumulative incidences of HCC beyond year 5 in the high-risk group (FIB-4 2.20 and AFP 3.21 ng/mL) and low-risk group (FIB-4 ≤ 2.20 and AFP ≤ 3.21 ng/mL) were 48.7% and 0%, respectively. APA-B score at 12 months and year 5 had a higher C-index for the prediction of HCC beyond year 5 than the PAGE-B at baseline and year 5 (p = 0.003 and p = 0.039, respectively) CONCLUSIONS: The HCC incidence tended to decrease but did not change significantly within and beyond 5 years of ETV therapy. The FIB-4 index and AFP levels at year 5 were predictive of HCC development beyond year 5 of ETV therapy.

The albumin-bilirubin (ALBI) grade has been validated as a significant predictor for hepatocellular carcinoma (HCC). However, there is little information about the impact of postoperative ALBI grade in patients with HCC who are undergoing liver resection. We enrolled 525 HCC patients who received primary resection from April 2001 to March 2017. The impact of the pre- and post-operative ALBI grades on overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. During the follow-up period (mean, 65 months), 253 (48.1%) patients experienced recurrence, and 85 (16.2%) patients died. Multivariate analysis revealed that diabetes mellitus (DM) (p = 0.011), alpha-fetoprotein levels (AFP) (p p = 0.008), liver cirrhosis (p p p = 0.006), DM (p = 0.002), AFP (p = 0.027), and ALBI grade at the first year after resection (p

(1) Background: The association of sugar-sweetened beverages (SSBs) with cardiovascular disease (CVD) mortality in younger adults (age 20–39) is rarely mentioned in the literature. Younger adults are less vulnerable to CVDs, but they tend to consume more SSBs. This prospective study aimed to assess the association between CVD mortality and SSBs in younger adults between 1994 and 2017. (2) Methods: The cohort enrolled 288,747 participants consisting of 139,413 men and 148,355 women, with a mean age 30.6 ± 4.8 years, from a health surveillance program. SSBs referred to any drink with real sugar added, such as fructose corn syrup or sucrose. One serving of SSB contains about 150 Kcal of sugar in 12 oz of drink. Cox models were used to estimate the mortality risk. (3) Results: There were 391 deaths from CVDs in the younger adults, and the positive association with CVD mortality started when SSB intake was ≥2 servings/day (HR: 1.59, 95% CI: 1.16–2.17). With mortalities from diabetes and kidney disease added to CVDs, the so-called expanded CVD mortality risk was 1.49 (95% CI: 1.11–2.01). By excluding CVD risk factors (hypertension, diabetes, and smoking), the CVD mortality risk increased to 2.48 (95% CI: 1.33–4.62). The dose–response relationship persisted (p < 0.05 for trend) in every model above. (4) Conclusions: Higher intake of SSBs (≥2 servings/day) was associated with increased CVD mortality in younger adults. The younger adults (age 20–39) with SSB intake ≥2 servings/day had a 50% increase in CVD mortality in our study, and the mortality risk increased up to 2.5 times for those without CVD risk factors. The dose–response relationship between the quantity of SSB intake and the mortality risk of CVD in younger adults discourages SSB intake for the prevention of CVD mortality.

Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear.This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis.The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76).ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.

Myocardial perfusion imaging (MPI) is the method most commonly used to assess patients with suspected coronary artery disease for the presence of myocardial ischemia and risk of subsequent adverse cardiac events. Studies are limited on the incidence of major adverse cardiac event (MACE) in patients with normal MPI results.The aim of this study was to investigate the incidence and risk factors of MACE in patients with normal or near-normal MPI results.In this single-center retrospective chart review study, patients who had received MPI tests at a nuclear medicine department of a medical center in 2017 were consecutively enrolled. All of the participants in this study were patients with normal or near-normal MPI results, and were followed for two years to assess the incidence of MACE (death, hospitalized for percutaneous coronary intervention; CABG, heart failure and stroke). Participants with or without MACE were compared to determine whether demographic, comorbidity, and MPI data were significant risk factors.Of the 1,629 participants (age = 70.4 ± 11.3 years, 49.4% male) enrolled, 387 (23.8%) were classified into the normal MPI group and 1,242 (76.2%) were classified into the near-normal MPI group. Notably, 61 participants (15.8%) in the normal MPI group and 206 (16.6%) in the near-normal MPI group experienced MACE events during the two-year follow-up. The risk factors of MACE identified in this study included being older in age, being male, and having poor myocardial perfusion parameters (i.e., ejection fraction) during MPI.Over the two-year study period, 15.8% of the participants with normal MPI results and 16.6% of those with near-normal MPI results experienced major adverse cardiac events. Thus, it is critical to inform patients regarding the potential risk of MACE risk and to educate them on how to mitigate this risk by actively managing their hyperlipidemia level and left ventricular ejection fraction.正常與近似正常心肌血流灌注掃描之醫療資料分析—兩年內重大心臟血管不良事件風險.心肌血流灌注掃描（myocardial perfusion imaging, MPI）廣泛應用在檢查心肌缺血及冠狀動脈疾病，目前對於MPI檢查正常與日後發生重大心臟血管不良事件（major adverse cardiac event, MACE）的現況尚不清楚。.針對接受藥物性MPI檢查之病人（≥ 20歲），且MPI結果為正常或接近正常者，分析其2年內MACE的發生率及危險因子。.此為回顧性病歷觀察研究，資料收集期間為2017年1月至2017年12月止，利用核醫報告系統取得病人資料，其接受加藥式MPI檢查結果為正常或接近正常者，並與醫療資料庫進行串接；採描述性統計及羅吉斯迴歸分析等進行資料分析。.研究納入1,629人，平均年齡為70.4歲，男女比例相當。MPI正常組有387人，兩年內發生MACE有61人（15.8%）；MPI接近正常組有1,242人，兩年內發生MACE有206人（16.6 %）；此外，年齡較高、男性、MPI檢查較差的壓力態左心室射出分率是MACE的危險因子。.本研究發現MPI正常並非零風險，2年內發生MACE機率有15.8%，MPI接近正常則16.6%，對於此類病人，清楚的衛教MACE風險及危險因子控管是照護的重點。.

Background This retrospective study analyzed the clinical characteristics and outcomes of patients with anaerobic spondylodiscitis. Methods From a total of 382 patients with infectious spondylodiscitis, nine patients (2.4%; two male and seven female with an average age of 67 years) with anaerobic spondylodiscitis between March 2003 and March 2017 were analyzed. Results Most of the patients (77.8%) initially presented with afebrile back pain. Hematogenous spread occurred in seven patients and postoperative infection in two patients. Bacteroid fragilis was the most common pathogen isolated from three patients. Atypical radiographic characteristics, including a vertebral fracture with the preservation of disk height or coexisting spondylolytic spondylolisthesis, occurred in four patients with hematogenous anaerobic spondylodiscitis. The eradication rate of anaerobic infection was significantly higher in the patients with hematogenous infection than in those with postoperative infection (100% vs. 0%, p = 0.0476). Anaerobic spondylodiscitis accounted for 2.4% of cases of infectious spondylodiscitis and predominantly affected the female patients. Conclusions Diagnostic delay may occur because of atypical spinal radiographs if the patient reports only back pain but no fever. Anaerobic infection following elective spinal instrumentation has a higher recurrence rate.

BackgroundTenofovir disoproxil fumarate (TDF) is effectively used as the first-line antiviral for chronic hepatitis B virus (HBV) infection in adults and children older than 12 years. To date, no confirmed case of virologic breakthrough (VBT) in a pediatric case has been reported.Case presentationHere we describe a case of a 5-year old, asymptomatically infected with HBV infection two months after chemotherapy for precursor B acute lymphoblastic leukemia (ALL). Although the 5-year old male is South African, his family originated from Guinea. At the end of the one-year follow-up, the infection progressed to chronic HBV infection, with a high viral load. At 36 weeks (8 months) post-treatment with lamivudine (LAM), there was a partial virologic response (PVR) and after 61 weeks (14 months), he was switched to TDF rescue monotherapy. Even with TDF treatment, he still experienced VBT and subsequent PVR. The full-length genome of HBV isolated 78 weeks after the switch to rescue TDF monotherapy was sequenced and belonged to genotype E. In addition to the LAM mutations (rtS256G and rtM267L), missense mutations in B-cell, T-cell, HLA class I and II-restricted epitopes emerged, which were to evade and escape host surveillance, leading to delayed viral clearance, persistence and disease progression. Two further events of VBT occurred between weeks 113 and 141 of TDF rescue-therapy. Viral loads and liver enzymes are normalizing progressively with long-term therapy.ConclusionAlthough the host immune reconstitution may be delayed, prolonged TDF treatment was effective in treating this pediatric case of HBV infection with VBT and PVR.

Background Glucose-6-phosphate dehydrogenase deficiency is a rarely recognized predisposing factor for rhabdomyolysis. Rhabdomyolysis with coronavirus disease 2019 has been increasingly seen during the pandemic. We report the uncommon occurrence of coronavirus disease 2019 pneumonia, severe rhabdomyolysis, and acute renal failure in the setting of glucose-6-phosphate dehydrogenase deficiency. Case presentation A 19-year-old African American male presented with myalgias, diaphoresis, and dark urine. Testing for severe acute respiratory syndrome coronavirus 2 was positive. He had severe rhabdomyolysis with creatine kinase levels up to 346,695 U/L. He was oliguric and eventually required hemodialysis. Progressive hypoxemia, methemoglobinemia, and hemolytic anemia occurred following one dose of rasburicase for hyperuricemia. Glucose-6-phosphate dehydrogenase deficiency was diagnosed. Full recovery followed a single volume exchange transfusion and simple packed red blood cell transfusions. Conclusions Glucose-6-phosphate dehydrogenase deficiency may predispose individuals to rhabdomyolysis due to severe acute respiratory syndrome coronavirus 2, presumably due to altered host responses to viral oxidative stress. Early screening for glucose-6-phosphate dehydrogenase deficiency can be useful for management of patients with rhabdomyolysis.

Basketball is a popular sport worldwide with a high injury risk. In this study, we conducted survey composed of clinical symptom reporting scale, physical examination and meticulous portable musculoskeletal ultrasound to 19 elite male high school basketball players and 15 regular male high school students. Our study showed the incidence of ultrasonographic findings of any lesion, suprapatellar effusion and proximal patellar tendinopathy is significantly higher in player group, and the incidence of asymptomatic ultrasonographic lesion is also higher in player group. Screening for asymptomatic lesions bares clinical relevance and plays a role in prevention of symptom development. With the concise and easy-to-perform ultrasonography protocol we performed and being interpreted by sports team physician, the protocol can offer precise diagnosis of common injury and screening for asymptomatic lesion potentially progressive.

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can be fatal. However, very few studies have provided comprehensive analyses and specified the differences in symptoms observed in different parts of the GI tract. This study aimed to comprehensively analyze clinical manifestations and management of GI CMV disease. This retrospective cohort study enrolled the patients who had CMV diseases of the GI tract proved by CMV immunohistochemistry stain from the pathology database in a 4000-bed tertiary medical center between January 2000 and May 2021. The patient characteristics, clinical manifestations, endoscopic features, treatments, outcomes, and prognostic factors were analyzed. A total of 356 patients were enrolled, including 46 infected in the esophagus, 76 in the stomach, 30 in the small intestine, and 204 in the colon. In total, 49.4% patients were immunocompromised. The overall in-hospital mortality rate was 20.8%: CMV enteritis had the highest rate (23.3%). Sixty percent of patients received antiviral treatment and 16% were administered both intravenous and oral anti-viral drugs (Combo therapy, minimal and mean treatment duration were 14 and 39.9 ± 25 days). Prognostic factors of in-hospital mortality included age, immune status, albumin level, platelet count, GI bleeding, time-to-diagnosis, and Combo therapy. In the survival analysis, immunocompetent patients receiving Combo therapy had the best survival curve, and immunocompromised patients receiving non-Combo therapy had the worst survival curve. Combo therapy ≥14 days resulted in a better outcome for both immunocompromised and immunocompetent patients. In conclusion, CMV GI diseases affect both immunocompromised and immunocompetent hosts, and a complete treatment course should be considered for patients with poor prognostic factors.

Background: The results of long-term renal evolution in HCV-infected patients using sofosbuvir and velpatasvir (SOF/VEL), with or without ribavirin (RBV), are lacking. Aims: We evaluated the renal safety for HCV-infected patients receiving SOF/VEL. Methods: Between 1 June 2019 and 6 July 2020, we included 594 HCV-infected patients receiving SOF/VEL +/− RBV for 12 weeks in Taiwan. Viral eradication rate (defined by sustained virological response at week 12 post-treatment; SVR12) and changes to renal function were considered. Results: SVR12 was achieved in 99.3% (590/594) upon per-protocol analysis. Patients saw improved hepatobiliary function and fibrosis after the start of SOF/VEL therapy. For renal function, those with baseline estimated glomerular filtration rate (eGFR) ≥ 60 (mL/min/1.73 m2) experienced transient on-treatment reduction in renal function that improved upon ending treatment, but recurrent eGFR degradation during one-year follow-up. The use of RBV (OR = 5.200, 95% CI: 1.983–13.634, p = 0.001) was a significant risk factor at SVR24, while diabetes mellitus (OR = 2.765, 95% CI: 1.104–6.922, p = 0.030) and the use of RBV (OR = 3.143, 95% CI: 1.047–9.435, p = 0.041) were identified as significant risk factors of worsening renal function at SVR48. SOF/VEL did not worsen renal function among those with stage 4–5 chronic kidney disease (CKD) who were not receiving dialysis. Conclusions: A trend of decline in eGFR at 1 year after SOF/VEL treatment was observed among diabetic patients with baseline eGFR ≥ 60 (mL/min/1.73 m2) and concomitant use of RBV. The close monitoring of renal function is warranted. Further study should be conducted in order to weigh the risks and benefit of RBV.

Virtual reality (VR) has become a common tool and is often considered for sport-specific purposes. Despite the increased usage, the transfer of VR-adapted skills into the real-world (RW) has not yet been sufficiently studied, and it is still unknown how much of the own body must be visible to complete motoric tasks within VR. In addition, it should be clarified whether older adults also need to perceive their body within VR scenarios to the same extent as younger people extending the usability. Therefore, younger (18–30 years old) and elderly adults (55 years and older) were tested (n = 42) performing a balance-, grasping- and throwing task in VR (HMD based) accompanied with different body visualization types in VR and in the RW having the regular visual input of body’s components. Comparing the performances between the age groups, the time for completion, the number of steps (balance task), the subjective estimation of difficulty, the number of errors, and a rating system revealing movements’ quality were considered as examined parameters. A one-way ANOVA/Friedmann with repeated measurements with factor [body visualization] was conducted to test the influence of varying body visualizations during task completion. Comparisons between the conditions [RW, VR] were performed using the t-Tests/Wilcoxon tests, and to compare both age groups [young, old], t-Tests for independent samples/Mann-Whitney-U-Test were used. The analyses of the effect of body visualization on performances showed a significant loss in movement’s quality when no body part was visualized (p < .05). This did not occur for the elderly adults, for which no influence of the body visualization on their performance could be proven. Comparing both age groups, the elderly adults performed significantly worse than the young age group in both conditions (p < .05). In VR, both groups showed longer times for completion, a higher rating of tasks’ difficulty in the balance and throwing task, and less performance quality in the grasping task. Overall, the results suggest using VR for the elderly with caution to the task demands, and the visualization of the body seemed less crucial for generating task completion. In summary, the actual task demands in VR could be successfully performed by elderly adults, even once one has to reckon with losses within movement’s quality. Although more different movements should be tested, basic elements are also realizable for elderly adults expanding possible areas of VR applications.

Objective. Cervical osseous foraminal stenosis (COFS) results from the uncinate process and facet hyperostosis. Currently, the optimal surgical technique for the treatment of COFS remains controversial. Materials and Methods. Patients with COFS presenting radiculopathy underwent posterior endoscopic cervical foraminotomy by the circumferential decompression technique. The neck disability index (NDI), the visual analogue scale (VAS), and the modified MacNab criteria were used to evaluate the outcomes. In addition, the range of motion (ROM) and the slippage distance between the operated vertebrae in flexion-extension position were measured to evaluate the stability of the cervical spine. Results. There were 24 consecutive patients in the study. The mean follow-up period was 16.2 months (range: 12-26 months). The NDI and VAS scores for arm/neck pain improved significantly from preoperatively to the last follow-up. The satisfaction rate by modified MacNab criteria was 91.7% on the third postoperative day and 100% on the day of final follow-up. There were no significant differences in intervertebral ROM or slippage distance between the last follow-up and preoperatively ( P = 0.968 , P = 0.394 ). Arm pain occurred in one patient, and sustained fingers numbness in two patients, but these symptoms resolved at the last follow-up. Conclusions. Posterior endoscopic cervical foraminotomy by the circumferential decompression technique is a safe and effective treatment for COFS. Moreover, it preserves the stability and physiological mobility of the cervical spine.

Prostate cancer is featured by its heterogeneous nature, which indicates a different prognosis. Castration-resistant prostate cancer (CRPC) is a hallmark of the treatment-refractory stage, and the median survival of patients is only within two years. Neuroendocrine prostate cancer (NEPC) is an aggressive variant that arises from de novo presentation of small cell carcinoma or treatment-related transformation with a median survival of 1–2 years from the time of diagnosis. The epigenetic regulators, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been proven involved in multiple pathologic mechanisms of CRPC and NEPC. LncRNAs can act as competing endogenous RNAs to sponge miRNAs that would inhibit the expression of their targets. After that, miRNAs interact with the 3’ untranslated region (UTR) of target mRNAs to repress the step of translation. These interactions may modulate gene expression and influence cancer development and progression. Otherwise, epigenetic regulators and genetic mutation also promote neuroendocrine differentiation and cancer stem-like cell formation. This step may induce neuroendocrine prostate cancer development. This review aims to provide an integrated, synthesized overview under current evidence to elucidate the crosstalk of lncRNAs with miRNAs and their influence on castration resistance or neuroendocrine differentiation of prostate cancer. Notably, we also discuss the mechanisms of lncRNA–miRNA interaction in androgen receptor-independent prostate cancer, such as growth factors, oncogenic signaling pathways, cell cycle dysregulation, and cytokines or other transmembrane proteins. Conclusively, we underscore the potential of these communications as potential therapeutic targets in the future.

Trichomonas vaginalis infection is one of the most widespread sexually transmitted infections in the world. There are approximately 276 million cases worldwide. Most men remain undiagnosed and untreated because they are asymptomatic. The chronic inflammation induced by persistent infection may increase the risk of developing genitourinary cancers. In this study, we aimed to investigate the association between trichomoniasis and benign prostate hyperplasia (BPH), prostate cancer (PCa), and bladder cancer (BC) in Taiwan. We designed a case–control study by using the database of the National Health Insurance program in Taiwan. We used the International Classification of Diseases, 9th Revision classifications to classify all the medical conditions in the case and control groups. All odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed using multivariable logistic regression to adjust for all comorbidities and variables. From 2000 to 2015, we enrolled a total of 62,544 individuals as the case group and 187,632 as the control group. Trichomoniasis exposure had a significant association with BPH and PCa (adjusted OR: BPH = 2.685, 95% CI = 1.233–4.286, P = 0.013; PCa = 5.801, 95% CI = 1.296–26.035, P = 0.016). The relative risk was much higher if patients had both trichomoniasis and depression (adjusted OR = 7.682, 95% CI = 5.730–9.451, P