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Background: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. Aims: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. Methods: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. Results: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. Conclusion: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan–Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Combination therapy with antiseizure medications (ASMs) is a rational strategy if monotherapy cannot effectively control seizures, thereby aiming to improve tolerance and treatment persistence. Objectives: To compare the efficacy of different ASM combinations among patients. Design: Patients with epilepsy on monotherapy who had a second ASM added as concomitant two-drug therapy from January 2009 to May 2019 in the Chang Gung Research Database, Taiwan, were included in the analysis. Methods: ASM combinations were compared based on their primary mechanism of action (MoA) which are as follows: gamma-aminobutyric acid receptor (G), sodium channel blocker (SC), synaptic vesicle protein 2A (SV2), calcium channel blocker (C), and multiple mechanisms (M). Treatment persistence was compared, and the predictors of persistence were analyzed. Results: In total, 3033 patients were enrolled in this study. Combined ASMs with different MoAs had significantly longer treatment persistence than ASMs with similar MoAs, specifically SC and M combinations. Patients receiving combined ASMs with different MoAs were less likely to discontinue treatment [adjusted hazards ratio: 0.83 (95% CI: 0.75–0.93), p < 0.001]. Among all combinations, the SC + SV2 combination had the longest treatment persistence (mean ± SD: 912.7 ± 841.6 days). Meanwhile, patients receiving the G combination had a higher risk of treatment discontinuation than those receiving the SC + SV2 combination. Underlying malignancies were associated with an increased risk of treatment discontinuation across all MoA categories. Male patients receiving the SC, SV2, and M combinations were more likely to discontinue treatment than female patients. Moreover, patients with renal disease were more likely to discontinue treatment with the SV2 combinations. Conclusion: ASM combinations with different MoAs had superior efficacy and tolerability to ASM combinations with similar MoAs, particularly SC and M combinations. In our cohort, factors associated with treatment discontinuation included underlying malignancy, male sex, and renal disease. These findings may provide valuable insights into the use of ASM combinations if monotherapy cannot adequately control seizures. [ABSTRACT FROM AUTHOR]

Patients with juvenile myoclonic epilepsy (JME) may not achieve seizure freedom despite optimal treatment with antiseizure medications (ASMs). The aim of this study was to investigate the clinical and social features of patients with JME, and to determine the factors associated with outcomes. We retrospectively identified 49 patients with JME (25 females, mean age 27.6 ± 8.9 years) who were assessed at the Epilepsy Centre of Linkou Chang Gung Memorial Hospital in Taiwan. The patients were divided into two groups, those who were seizure-free and those with ongoing seizures according to their seizure outcome at the last follow-up for one year. Clinical features and social status were compared between these two groups. Twenty-four (49%) of the JME patients were seizure-free for at least one year, while 51% continued to experience seizures despite being treated with multiple ASMs. The presence of epileptiform discharges in the last electroencephalogram and seizures during sleep were significantly associated with worse seizure outcomes (p < 0.05). The patients who were seizure-free had a higher employment rate compared to those who continued to experience seizures (75% vs. 32%, p = 0.004). Despite receiving ASM treatment, a considerable proportion of the patients with JME continued to have seizures. Moreover, poor seizure control was associated with a lower employment rate, which may lead to negative socioeconomic consequences related to JME. [ABSTRACT FROM AUTHOR]

Background and Objectives: Endoscopic variceal ligation (EVL) is the primary and secondary treatment for acute esophageal variceal bleeding. Post-banding ulcer bleeding (PBUB) may lead to bleeding episodes following EVL, increasing mortality. The aim of this study was to evaluate the risk factors for PBUB and predict the 6-week mortality risk after PBUB. Materials and Methods: We retrospectively analyzed the data collected from cirrhotic patients with EVL from 2015 to 2017. The incidence of PBUB and the 6-week mortality rate were evaluated. Risk factors for PBUB and predictive factors for mortality after PBUB were analyzed. Results: A total of 713 patients were enrolled in this study. Among the studied subjects, the incidence of PBUB was 5.8% (N = 41). The 6-week mortality rate was 63.4% (26/41). In multivariate analysis, MELD score ≥20 (OR: 3.77, 95% CI: 1.94–7.33, p < 0.001), ALBI score of 3 (OR: 2.67, 95% CI: 1.34–5.3, p = 0.005) and the presence of gastric varices (OR: 2.1, 95% CI: 1.06–4.16, p = 0.03) were associated with the development of PBUB. Patients with ALBI grade 3 (OR: 4.8, 95% CI: 1.18–19.6, p = 0.029) and Child-Pugh scores B and C (OR: 16.67, 95% CI: 1.75–158.1, p = 0.014) were associated with 6-week mortality after PBUB. Conclusions: PBUB is a complication with low incidence but increased mortality following EVL. The ALBI grade is a useful score to predict not only the development of PBUB but also the 6-week mortality after PBUB. [ABSTRACT FROM AUTHOR]

Background: Low-dose aspirin and clopidogrel have demonstrated potential chemoprevention for colorectal cancer (CRC). Proton-pump inhibitors (PPI) are commonly prescribed with anticoagulation drugs, but the relationship between PPI and CRC is unclear. Moreover, evidence of CRC risk under direct oral anticoagulant (DOAC) is limited. This study aimed to investigate the effects of anticoagulation drugs combined with or without PPI on the risks of CRC in Taiwan.Methods: A retrospective case-control study of 1,024,227 cases based on the Chang Gung Research Database from 2010 to 2017 was performed. Clinical characteristics, indications, duration of anticoagulation and PPI use, and CRC occurrence data were collected. Logistic regression was employed to adjust for known confounders of CRC risk.Results: Monotherapy of clopidogrel decreased the risk of CRC (AOR 0.70; 95% CI 0.60-0.83), while no protective effect was observed in aspirin alone or aspirin plus clopidogrel. DOAC did not affect CRC significantly. The risk of CRC increased in patients with PPI (AOR 1.38; 95% CI 1.28-1.49) and PPI plus DOAC (OR 3.91; 95% CI 1.49-10.27), while PPI plus aspirin decreased the risk of CRC (OR 0.48; 95% CI 0.32-0.73). PPI plus clopidogrel showed no significant effect on the CRC.Conclusion: This study suggests clopidogrel alone and PPI plus aspirin offer a preventative benefit against CRC in the Taiwanese population studied. The same effect was not observed in DOAC. Moreover, a significant increase in CRC was observed in patients on PPI monotherapy and PPI plus DOAC, suggesting a possible risk. [ABSTRACT FROM AUTHOR]

Juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy which is closely related to the sleep-wake cycle. This study aimed to investigate whether sleep disturbance is more common among patients with JME and the impact this may have on their quality of life (QOL). Thirty-four patients with JME and age- and gender-matched controls were recruited into this case control study, and assessed using validated sleep questionnaires including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Stanford Sleepiness Scale (SSS). QOL was assessed using the Quality of Life in Epilepsy Inventory (QOLIE-31). The patients had a significantly higher PSQI score and higher proportion of abnormal PSQI scores than the controls. They also had higher ESS and SSS scores, but without statistical significance. The patients with poor sleep quality had significantly lower overall QOL, emotional well-being, and energy/fatigue subscale scores. The use of a higher number of antiseizure medications, dosage of levetiracetam, and usage of antiseizure medication polytherapy were associated with sleep disorders. Our results showed that sleep disturbance is common in patients with JME, and also that it has an impact on their QOL. [ABSTRACT FROM AUTHOR]

Background: The effective dose of perampanel in status epilepticus (SE), refractory SE (RSE), and super-refractory SE (SRSE) in humans is unknown, and the potential of perampanel in treating SE has not been evaluated in a large cohort. Methods: Data of intensive care patients with RSE and SRSE treated with perampanel were retrospectively reviewed and analyzed. Results: Eighty-one patients received perampanel, including 39 females with median age 64 [17–91] years, perampanel responders (n = 27), and non-responders (n = 54). The initial perampanel dose was positively associated with treatment response in patients with RSE or SRSE (OR = 1.27, 95% CI 1.03–1.57, p = 0.025), while the maximum dose was negatively associated with treatment response (OR = 0.74, 95% CI 0.58–0.96, p = 0.022). Hypoxia caused seizures in six patients; five died in hospital and one had severe disability. A statistically non-significant tendency toward better response was found in patients with unique SE type and cause, particularly in nonconvulsive status epilepticus (NCSE) without coma (NCSE without coma vs. generalized tonic–clonic seizure: OR = 4.14, 95% CI 0.98–17.47, p = 0.053). In the high-dose (≥ 16 mg/day) groups, although distributions of modified Rankin Scale (mRS) scores were similar between perampanel responders and non-responders at discharge, a greater proportion of perampanel responders had less change in mRS scores from baseline than did perampanel non-responders (median mRS: 0 vs 4, p = 0.064). No cardiorespiratory adverse events or laboratory abnormalities were noted with perampanel treatment. Conclusions: Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE. [ABSTRACT FROM AUTHOR]

Background: Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study.Methods: We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining.Results: IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893-0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: [Formula: see text] CONCLUSIONS: The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year. [ABSTRACT FROM AUTHOR]

Background: There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin.Methods: After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion.Results: A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure.Conclusions: Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori. [ABSTRACT FROM AUTHOR]

Aberrant metabolisms have been hypothesized to precede the occurrence of hepatocellular carcinoma (HCC), therefore, we investigated biomarkers associated with subsequent HCC in peripheral bloods using metabolomic technologies. A cohort of 475 HCC-naïve liver cirrhotic patients were recruited and prospectively followed. A total of 39 patients developed HCC in the follow-up period. Baseline plasma metabolites were explored using untargeted nuclear magnetic resonance. Candidates were then quantified by ultra-performance liquid chromatography. A series of univairiate and multivariate analysis showed that Phenylalanine (Phe) and Glutamine (Gln) levels are associated with time to HCC, independent of viological etiologies and age. A HCC risk score R was then constructed using the polynomial combination of age, Phe and Gln in the units of micromolar (μM): R = Age ∗ 0.0694 + Phe ∗ 0.3399 + Phe 2 ∗ - 0.00188154 + Gln ∗ - 0.0133 + Gln 2 ∗ 0.00002244 R correlates with the time to HCC significantly (Hazard ratio [HR] = 2.368, 95% confidence interval [CI] 1.760–3.187, P < 0.001). An additional cross-sectional analysis showed that Phe and Gln concentrations both correlates with HCC occurrence in the next 3 years (area under the receiver operating characteristic curve [AUC] = 0.607 and 0.629, P = 0.033 and 0.010 respectively). In conclusion, phenylalanine and glutamine concentrations in the peripheral blood correlate with subsequent HCC. [ABSTRACT FROM AUTHOR]

We examined the seroprevalence change of anti‐hepatitis D virus (HDV) antibodies in Taiwan from 2006 to 2019. A total of 1147 patients who had chronic hepatitis B virus (HBV) infection were assessed. Of them, 51 (4.4%) were positive for anti‐HDV antibodies. Comparison between anti‐HDV‐positive and negative groups was performed to examine clinical and virological factors related to anti‐HDV positivity. It was found that the median HBV‐DNA concentration was 1.6 × 105 IU/mL (range, <20‐4.5 × 1010 IU/mL) and <20 IU/mL (range, <20‐2.0 × 109 IU/mL) for patients with negative and positive anti‐HDV antibodies, respectively (P < .001). In addition, a progressive year‐to‐year decrease of anti‐HDV seroprevalence was unveiled. For patients who had HBV‐DNA >15 000 IU/mL, the year‐to‐year (calculated every 2 years) seropositive rates of anti‐HDV were 10.0%, 7.9%, 0.7%, 0.3%, 0%, 0%, and 0% (P < .001). For patients who had HBV‐DNA <15 000 IU/mL, the year‐to‐year seropositive rates were 18.6%, 12.8%, 7.8%, 5.0%, 7.3%, 8.0%, and 3.7% (P < .001). In conclusion, seropositive of anti‐HDV was inversely associated with HBV‐DNA levels. A progressive decrease of anti‐HDV seroprevalence was found with no anti‐HDV‐positive cases detected in high HBV‐DNA patient group after 2014. Highlight: Seroprevalence of anti‐HDV is decreasing in Taiwan.From 2006‐2019, 4.4% of chronic hepatitis B patients were anti‐HDV positive.Seroprevalence of anti‐HDV is inversely correlated with HBV‐DNA levels.No anti‐HDV‐positive cases were found after 2014 in high HBV DNA patients. [ABSTRACT FROM AUTHOR]

While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury. [Display omitted] • Oral fecal gavage (OFG) or pasteurized fecal gavage (OPG) mitigates AILI in mice • OFG and OPG enrich gut Lachnospiraceae and butyrate by UGI tract • Butyrate suppresses ferroptosis via activating AMPK-P62-Nrf2 signaling and mitophagy • Combined N-acetylcysteine and butyrate therapy significantly reduces AILI mortality Yang et al. show that oral fecal gavage (OFG) reshapes gut microbiota, protecting mice from acetaminophen-induced liver injury (AILI). OFG enriches gut Lachnospiraceae and butyrate. Butyrate counteracts AILI-related ferroptosis through Nrf2 antioxidant signaling and mitophagy, highlighting upper gastrointestinal tract microbial selection and potential for microbial metabolites in AILI treatment. [ABSTRACT FROM AUTHOR]

Background: The incidence of cefepime-induced neurotoxicity (CIN) has been previously underestimated, and there have only been sporadic reports from critical neurological settings. The present study aimed to investigate the potential factors associated with disease development, electroencephalography (EEG) sub-classification, and outcome measures.Methods: The 10-year medical records of patients who underwent EEG between 2007 and 2016 at a tertiary medical center in Taiwan, and developed encephalopathy after cefepime therapy were retrospectively reviewed. Age- and sex-matched controls were included for further analysis. Demographic data, the occurrence of clinical seizures, non-convulsive status epilepticus (NCSE), use of antiepileptic drugs (AEDs), receiving maintenance or urgent hemodialysis, EEG findings, and functional outcomes were analyzed. The Chi-square test and a logistic regression model were applied to survey significant prognostic factors relating to mortality.Results: A total of 42 CIN patients were identified, including 25 patients from wards and 17 from intensive care units; their mean age was 75.8 ± 11.8 years. Twenty-one patients (50%) had chronic kidney disease, and 18 (43%) had acute kidney injury. Among these patients, 32 (76%) received appropriate cefepime dose adjustment. Three patients had a normal renal function at the time of CIN onset. The logistic regression model suggested that maintenance hemodialysis and longer duration of cefepime use were independently associated with the development of CIN, with odds ratios of 3.8 and 1.2, respectively. NCSE was frequently noted in the CIN patients (64%). Generalized periodic discharge with or without triphasic morphology was the most common EEG pattern (38%), followed by generalized rhythmic delta activity and generalized spike-and-waves. AEDs were administered to 86% of the patients. A total of 17 patients (40%) did not survive to hospital discharge. Adequate cefepime dose adjustment and early cefepime discontinuation led to a better prognosis.Conclusions: CIN was associated with high mortality and morbidity rates. Neurotoxic symptoms could still occur when the cefepime dose was adjusted, or in patients with normal renal function. Patients with maintenance hemodialysis or a longer duration of cefepime therapy tended to develop CIN. Early recognition of abnormal EEG findings allowed for the withdrawal of the offending agent, resulting in clinical improvements and a better prognosis at discharge. [ABSTRACT FROM AUTHOR]

The polyp detection rate (PDR) is an important quality indicator for colonoscopy. Several factors have been shown to be associated with PDR. However, whether the moderate sedation is a factor for polyp detection remains controversial. This study aims to assess factors associated with polyp detection including the moderate sedation factor during colonoscopy. Patients who underwent colonoscopy from June 1, 2014 to May 31, 2015 were enrolled into this retrospective study. Patients with poor colon preparation and failure to reach the cecum were excluded. The clinical factors, including patient's sex, age, midazolam/fentanyl sedation, indications, endoscopist colonoscopy volume, and use of antispasmodic agent were evaluated by multivariate analysis. A total of 3373 patients were included in this study. The mean age was 55.8 years, and 1980 patients (58.7%) were male. Among the 3373 patients, 2513 (74.5%) underwent midazolam/fentanyl‐based sedated colonoscopy. The multivariate analysis showed that male sex, age over 50 years old, midazolam/fentanyl sedation and indications of screening and surveillance were significantly associated with polyp detection. Moreover, when stratified by sex and age, the midazolam/fentanyl sedation was associated with polyp detection in male patients and patients over 50 years old. This study has highlighted the role of midazolam/fentanyl sedation administered by colonoscopists as a modifiable factor that may increase polyp detection during colonoscopy. [ABSTRACT FROM AUTHOR]

Background: Seroclearance of hepatitis B surface antigen (HBsAg) has been rarely achieved in the treatment of chronic hepatitis B (CHB) patients. We administered HBsAg-based recombinant vaccine in patients with low HBsAg concentrations.Methods: Twenty hepatitis B e antigen-negative patients, with HBsAg < 1000 IU/ml, were enrolled. Vaccines were administered every 8 weeks for 48 weeks (seven doses). HBsAg levels and anti-HBs were assayed longitudinally until 48 weeks post-vaccination. HLA genotyping and cDNA microarray were performed to search for response predictors.Results: Nineteen patients completed the study. At the end of vaccination, HBsAg declined significantly (Δ = − 0.27 ± 0.49 log IU/ml, p = 0.0005). The annual decline rate was significantly greater than that of an age-, gender-, and baseline HBsAg-matched control group (Δ = − 0.18 ± 0.46 versus + 0.11 ± 0.42 log IU/ml/year; p = 0.0229). Two patients achieved HBsAg seroclearance. Fourteen had significant HBsAg decline (Δ = − 0.64 ± 0.88 log IU/ml). No significant adverse events occurred during the trial. cDNA microarray identified the top up- and down-regulated genes in responders as HLA-DQ and HLA-DMB, respectively. HLA genotyping identified HLA-DQB1*04, HLA-DRB1*04, and HLA-B*40 as predictors for non-response (p = 0.0499, 0.0152, and 0.0314, respectively).Conclusions: In low-level HBsAg CHB patients, serial HBsAg-based vaccinations were safe, resulting in significant HBsAg decline. HLA gene expression and genotypes played a role in vaccine responsiveness (ClinicalTrials.gov Identifier: NCT01817725). [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Commonly used non‐invasive fibrosis scores usually included serum transaminase levels in the equations, including Aspartate transaminase to Platelet Ratio Index (APRI) and fibrosis‐4 (FIB‐4). Transaminases fluctuated significantly in chronic hepatitis B patients with exacerbations, leading to unsteady score values. As such, here, we aim to develop a transaminase‐free score suitable for pretherapeutic evaluation of fibrosis stages. Methods: Firstly, 1082 treatment‐naïve chronic hepatitis B patients were enrolled and divided into modeling (n = 541) and verification (n = 541) cohorts. Secondly, 265 patients having received liver biopsy, with known Ishak fibrosis stages, were included for independent correlation. Results: Cross‐sectional analysis of 1082 patients revealed age‐dependent variation of association between virological factors and cirrhosis. A fibrosis score including Anti‐hepatitis B e antibody, Basal core promoter (BCP) A1762T mutation, and Platelet count Index (named ABPI) was derived from the modeling cohort. ABPI performed better than APRI and FIB‐4 in the verification cohort for identifying cirrhotic patients (comparison of area under the receiver operating characteristic curves: ABPI vs APRI and FIB‐4 = 0.785 vs 0.563 [P < 0.001] and 0.700 [P = 0.026], respectively). The performance of ABPI was even better in young (< 40 years old) hepatitis B patients (area under the receiver operating characteristic curves: 0.856 vs 0.402 [P < 0.001] and 0.599 [P = 0.009], respectively). Finally, in the independent cohort of 265 patients with known Ishak fibrosis stages, it was found that ABPI effectively distinguished between Ishak fibrosis stages 3 and > 3 and between 4 and > 4 (P < 0.001 for each). Conclusions: We developed a transaminase‐free fibrosis score (ABPI) utilizing basal core promoter A1762T data, which outperformed APRI and FIB‐4. [ABSTRACT FROM AUTHOR]

Abstract: Aim: A genome‐wide association study (GWAS) had identified a single nucleotide polymorphism (SNP), GALNT14‐rs9679162, capable of predicting chemotherapy responses in advanced hepatocellular carcinoma (HCC). Here, we revisited the GWAS database to search for necessary SNPs that could improve our outcome prediction. Methods: A cohort of 116 HCC patients receiving split‐dose chemotherapy composed of 5‐fluorouracil, mitoxantrone and cisplatin was enrolled. The GALNT14‐rs9679162 together with four other leading candidate SNPs (rs6025211, rs715171, LOC105369482‐rs1955024 and WWOX‐rs13338697) was genotyped and correlated with time‐to‐tumor progression (TTP) and overall survival (OS). Results: GALNT14‐rs9679162‐TT genotype remained an effective predictor for favorable TTP and OS (P = 0.012 and 0.002). Additionally, it was found that WWOX‐rs13338697‐CT genotype was associated with unfavorable TTP (P = 0.031), independent of GALNT14‐rs9679162 genotype (adjusted P = 0.045), and rs6025211‐CT genotype was associated with unfavorable OS (P = 0.014), independent of GALNT14‐rs9679162 genotype (adjusted P = 0.025). Combinations of these SNPs stratified patients into three groups with differential treatment outcomes. Patients with GALNT14‐rs9679162‐TT/WWOX‐rs13338697‐non‐CT genotypes achieved the most favorable treatment outcomes (n = 19; median TTP, median OS and response rate were 3.9 months, 6.8 months and 4/19 [21.1%], respectively); whereas patients with GALNT14‐rs9679162‐non‐TT/rs6025211‐CT genotypes associated with the most unfavorable treatment outcomes (n = 40; median TTP, median OS and response rate were 1.9 months, 3.5 months and 1/40 [2.5%], respectively). The remaining patients constituted a third subgroup with intermediate clinical outcomes. Conclusions: Three genetic variants, GALNT14‐rs9679162, WWOX‐rs13338697 and rs6025211, stratified advanced HCC patients into three groups with differential treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) colitis is considered rare in immunocompetent patients.Objective: The predictors of mortality and the differences between immunocompetent and immunocompromised patients with this disease remain unknown. Thus, the aim of this retrospective cohort study was to clarify these issues.Patients and methods: We enrolled all patients who were histologically diagnosed with CMV colitis between April 2002 and December 2016 in the Linkou Chang Gung Memorial Hospital. Patients were divided into two groups: immunocompetent and immunocompromised, and the differences between them were analyzed to develop in-hospital mortality predictors.Results: A total of 69 patients (42, immunocompetent; 27, immunocompromised) were enrolled. The most common symptoms were melena in the immunocompetent group and diarrhea in the immunocompromised group. The in-hospital mortality rate showed no statistically significant difference between the two groups (26.2% vs 25.9%, P=0.981). Early diagnosis was the only significant independent predictor of in-hospital mortality (odds ratio [OR] 1.075, 95% CI 1.005-1.149, P=0.035). The cutoff of diagnostic timing was 9 days from admission, derived from the receiver operating characteristic curve using the Youden index.Conclusion: CMV colitis in immunocompetent patients is markedly more common and fatal than has generally been acknowledged. Being alert to different ways in which this disease can present itself will enable early diagnosis and significantly reduce mortality. [ABSTRACT FROM AUTHOR]

This study aimed to identify predictors of success rate of mesenchymal stem cell (MSC) isolation from human deciduous teeth pulp. A total of 161 deciduous teeth were extracted at the dental clinic of Chang Gung Memorial Hospital. The MSCs were isolated from dental pulps using a standard protocol. In total, 128 colonies of MSCs were obtained and the success rate was 79.5%. Compared to teeth not yielding MSCs successfully, those successfully yielding MSCs were found to have less severe dental caries (no/mild-to-moderate/severe: 63.3/24.2/12.5% versus 12.5/42.4/42.4%, P<0.001) and less frequent pulpitis (no/yes: 95.3/4.7% versus 51.5/48.5%, P<0.001). In a multivariate regression model, it was confirmed that the absence of dental caries (OR = 4.741, 95% CI = 1.564–14.371, P=0.006) and pulpitis (OR = 9.111, 95% CI = 2.921–28.420, P<0.001) was significant determinants of the successful procurement of MSCs. MSCs derived from pulps with pulpitis expressed longer colony doubling time than pulps without pulpitis. Furthermore, there were higher expressions of proinflammatory cytokines, interleukin- (IL-) 6 and monocyte chemoattractant protein- (MCP-) 1, P<0.01, and innate immune response [toll-like receptor 1 (TLR1) and TLR8, P<0.05; TLR2, TLR3, and TLR6, P<0.01] in the inflamed than noninflamed pulps. Therefore, a carious deciduous tooth or tooth with pulpitis was relatively unsuitable for MSC processing and isolation. [ABSTRACT FROM AUTHOR]

Extensive bile ductular reactions (DRs) accompany many cholestatic liver diseases such as primary biliary cholangitis and primary sclerosing cholangitis (PSC) as well as parenchymal liver cell diseases such as alcoholic liver disease, non‐alcoholic steatohepatitis and HCV and HBV infections. DRs originate from bile ducts or hepatocytes after damage and can be identified by expression of markers associated with cholangiocytes, often being associated with disease progression and fibrosis. In a recent issue of The Journal of Pathology, Govaere et al employed high‐throughput RNA sequencing to compare the transcriptomic profiles of DR cells from liver diseases of different aetiology; HCV infection affecting hepatocytes and PSC initially affecting biliary epithelial cells. Both DR transcriptomes were markedly different from that of their neighbouring hepatocytes and 330 genes were significantly differently expressed between the DRs of the HCV and PSC liver diseases. Exploring such gene expression profiles could enable therapeutic targeting of DRs, on the one hand to inhibit liver fibrosis and inflammation and conversely to promote hepatocyte and cholangiocyte regeneration. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Linked Article: Govaere et al. J Pathol 2019; DOI: https://doi.org/10.1002/path.5228 [ABSTRACT FROM AUTHOR]

The liver's ability to regenerate is indisputable; for example, after a two-thirds partial hepatectomy in rats all residual hepatocytes can divide, questioning the need for a specific stem cell population. On the other hand, there is a potential stem cell compartment in the canals of Hering, giving rise to ductular reactions composed of hepatic progenitor cells ( HPCs) when the liver's ability to regenerate is hindered by replicative senescence, but the functional relevance of this response has been questioned. Several papers have now clarified regenerative mechanisms operative in the mouse liver, suggesting that the liver is possibly unrivalled in its versatility to replace lost tissue. Under homeostatic conditions a perivenous population of clonogenic hepatocytes operates, whereas during chronic damage a minor population of periportal clonogenic hepatocytes come to the fore, while the ability of HPCs to completely replace the liver parenchyma has now been shown. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Many cases of carbon monoxide poisoning in Taiwan are due to burning charcoal. Nevertheless, few reports have analyzed the mortality rate of these patients who survive to reach a hospital and die despite intensive treatment. Therefore, this study examined the clinical features, physiological markers, and outcomes after carbon monoxide poisoning and the associations between these findings. Methods: We analyzed the records of 261 patients who were referred for management of carbon monoxide intoxication between 2000 and 2010. Patients were grouped according to status at discharge as alive (survivor, n = 242) or dead (non-survivor, n = 19). Demographic, clinical, laboratory, and mortality data were obtained for analysis. Results: Approximately half of the cases (49.4%) attempted suicide by burning charcoal. Most of the patients were middle-aged adults (33±19 years), and were referred to our hospital in a relatively short period of time (6±10 hours). Carbon monoxide produced many serious complications after exposure: fever (26.1%), hypothermia (9.6%), respiratory failure (34.1%), shock (8.4%), myocardial infarction (8.0%), gastrointestinal upset (34.9%), hepatitis (18.4%), renal failure (25.3%), coma (18.0%) and rhabdomyolysis (21.8%). Furthermore, the non-survivors suffered greater incidences of hypothermia (P<0.001), respiratory failure (P<0.001), shock (P<0.001), hepatitis ((P=0.016), renal failure (P=0.003), coma (P<0.001) than survivors. All patients were treated with high concentration of oxygen therapy using non-rebreather mask. However, hyperbaric oxygen therapy was only used in 18.8% of the patients. In a multivariate-Cox-regression model, it was revealed that shock status was a significant predictor for mortality after carbon monoxide poisoning (OR 8.696, 95% CI 2.053-37.370, P=0.003). Finally, Kaplan-Meier analysis confirmed that patients with shock suffered greater cumulative mortality than without shock (Log-rank test, Chi-square 147.404, P<0.001). Conclusion: The mortality rate for medically treated carbon monoxide-poisoned patients at our center was 7.3%. Furthermore, the analysis indicates that shock was most strongly associated with higher risk of mortality. [ABSTRACT FROM AUTHOR]

We examined the characteristic changes of hepatitis B virus (HBV) in antiviral drug treatment-naive patients referred for pretreatment evaluation in Taiwan during 2008-2012. Over time, we observed substantial decreases in the prevalence of HBV e antigen (HBeAg) and increasing prevalence of the precore G1899A mutation and HBV-DNA levels in HBeAg-positive patients. [ABSTRACT FROM AUTHOR]

Background: Chronic pancreatitis (CP) is a necroinflammatory process resulting in extensive pancreatic fibrosis. Granulocyte colony-stimulating factor (G-CSF), a hematopoietic stem cell mobilizer, has been shown to exert an anti-fibrotic effect partly through the enrichment of bone marrow (BM) cells in fibrotic organ. We aimed to test the effect of G-CSF on fibrosis in a mouse model of CP. Methods: CP was induced in C57Bl/6J mice by consecutive cerulein injection (50 µg/kg/day, 2 days a week) for 6 weeks. Mice were then treated with G-CSF (200 µg/kg/day, 5 day a week) or normal saline for 1 week, and sacrificed at week 7 or week 9 after first cerulein injection. Pancreatic histology, pancreatic matrix metallopeptidase 9 (MMP-9), MMP-13 and collagen expression were examined. Pancreatic myofibroblasts were isolated and cultured with G-CSF. Collagen, MMP-9 and MMP-13 expression by myofibroblasts was examined. The BM-mismatched mice model was used to examine the change of BM-derived myofibroblasts and non-myofibroblastic BM cells by G-CSF in the pancreas. Results: The pancreatic collagen expression were significantly decreased in the G-CSF-treated group sacrificed at week 9. While collagen produced from myofibroblasts was not affected by G-CSF, the increase of MMP13 expression was observed in vitro. There were no effect of G-CSF in the number of myofibroblasts and BM-derived myofibroblasts. However, the number of non-myofibroblastic BM cells and macrophages were significantly increased in the pancreata of cerulein- and G-CSF-treated mice, suggesting a potential anti-fibrotic role of non-myofibroblastic BM cells and macrophages stimulated by G-CSF. Conclusions: Our data indicated that G-CSF contributed to the regression of pancreatic fibrosis. The anti-fibrotic effects were possibly through the stimulation of MMP-13 from myofibroblasts, and the enhanced accumulation of non-myofibroblastic BM cells and macrophages in the pancreas. [ABSTRACT FROM AUTHOR]

Background: The hepatitis C virus (HCV) genotype-specific impacts on the host metabolic alterations remained inconclusive. Methods: A prospective study including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) ≥2.5). Paired t-tests were used to compare the pre- and post-treatment variables. Results: Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR) but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001) and apolipoprotein A1 (p = 0.012) were only found in G2, whereas increased triglyceride/HDL (p = 0.01) ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019) and apolipoprotein A1 (p = 0.012) but a decrease in HOMA-IR (p = 0.04), C-peptide (p = 0.019) and hemoglobin A1c (p = 0.047) were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002) was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01) but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041) and triglyceride (p = 0.044) levels than G2 patients. Conclusions: G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR. [ABSTRACT FROM AUTHOR]

Introduction This retrospective observational study examined the clinical features, the degrees of toxic hepatitis, physiological markers and clinical outcomes after intentional paraquat poisoning and sought to determine what association, if any, might exist between these findings. Methods A total of 187 patients were referred for management of intentional paraquat ingestion between 2000 and 2010. Patients were categorized into two groups according to their hepatic complication, i.e. with ( N = 87) or without ( N = 100) toxic hepatitis. Demographic, clinical and laboratory data were obtained for analysis. Mortality rates were also analysed. Results It was found that patients with toxic hepatitis were younger (39.7 ± 13.7 vs 44.2 ± 16.6 year old, P = 0.046), and suffered from greater incidences of acute respiratory failure (63.2 vs 48.0%, P = 0.037) and acute renal failure (75.9 vs 56.0%, P = 0.004) than patients without hepatitis. The hospitalization period was longer in patients with hepatitis than without hepatitis (16.2 ± 14.6 vs 11.2 ± 12.1 days, P = 0.012), even though there was no difference in mortality rate between both groups (56.3 vs 53.0%, P = 0.649). Notably, the symptoms of toxic hepatitis developed within 6.7 ± 6.3 days of exposure to paraquat with aspartate aminotransferase (AST) 138 ± 156 U/L, alanine aminotransferase (ALT) 127 ± 114 U/L and total bilirubin 2.7 ± 2.6 mg/dL. The hepatitis peaked at 9.5 ± 8.8 days with AST 125 ± 139 U/L, ALT 183 ± 181 U/L and total bilirubin 3.2 ± 3.6 mg/dL. Nevertheless, the symptoms resolved within 17.3 ± 9.8 days of paraquat exposure, and none of the patients died of hepatic complication. Conclusions A substantial proportion of paraquat patients suffered from hepatic complication (46.52%), but the spectrum of hepatitis in these patients seemed mild and transient. [ABSTRACT FROM AUTHOR]

Summary Bone marrow (BM) cells may transdifferentiate into circulating fibrocytes and myofibroblasts in organ fibrosis. In this study, we investigated the contribution and functional roles of BM-derived cells in murine cerulein-induced pancreatic fibrosis. C57/BL6 female mice wild-type (WT) or Col 1α1r/r male BM transplant, received supraphysiological doses of cerulein to induce pancreatic fibrosis. The CD45+Col 1+ fibrocytes isolated from peripheral blood (PB) and pancreatic tissue were examined by in situ hybridization for Y chromosome detection. The number of BM-derived myofibroblasts, the degree of Sirius red staining and the levels of Col 1α1 mRNA were quantified. The Y chromosome was detected in the nuclei of PB CD45+Col 1+ fibrocytes, confirming that circulating fibrocytes can be derived from BM. Co-expression of α-smooth muscle actin illustrated that fibrocytes can differentiate into myofibroblasts. The number of BM-derived myofibroblasts, degree of collagen deposition and pro-collagen I mRNA expression were higher in the mice that received Col 1α1r/r BM, (cells that produce mutated, collagenase-resistant collagen) compared to WT BM, indicating that the genotype of BM cells can alter the degree of pancreatic fibrosis. Our data indicate that CD45+Col 1+ fibrocytes in the PB can be BM-derived, functionally contributing to cerulein-induced pancreatic fibrosis in mice by differentiating into myofibroblasts. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) has been identified as a significant genetic biomarker in disease, cancer and evolution. Mitochondria function as modulators for regulating cellular metabolism. In the clinic, mtDNA variations (mutations/single nucleotide polymorphisms) and dysregulation of mitochondria-encoded genes are associated with survival outcomes among cancer patients. On the other hand, nuclear-encoded genes have been found to regulate mitochondria-encoded gene expression, in turn regulating mitochondrial homeostasis. These observations suggest that the crosstalk between the nuclear genome and mitochondrial genome is important for cellular function. Therefore, this review summarizes the significant mechanisms and functional roles of mtDNA variations (DNA level) and mtDNA-encoded genes (RNA and protein levels) in cancers and discusses new mechanisms of crosstalk between mtDNA and the nuclear genome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oxidative phosphorylation (OXPHOS) consists of four enzyme complexes and ATP synthase, and is crucial for maintaining physiological tissue and cell growth by supporting the main bioenergy pool. Cytochrome c oxidase (COX) has been implicated as a primary regulatory site of OXPHOS. Recently, COX subunit 5B (COX5B) emerged as a potential biomarker associated with unfavorable prognosis by modulating cell behaviors in specific cancer types. However, its molecular mechanism remains unclear, particularly in colorectal cancers (CRCs). To understand the role of COX5B in CRCs, the expression and postoperative outcome associations using independent in-house patient cohorts were evaluated. A higher COX5B tumor/nontumor expression ratio was associated with unfavorable clinical outcomes (p = 0.001 and 0.011 for overall and disease-free survival, respectively. In cell-based experiments, the silencing of COX5B repressed cell growth and enhanced the susceptibility of CRCs cells to anticancer drugs. Finally, downstream effectors identified by RNA sequencing followed by RT-qPCR and functional compensation experiments revealed that the tight junction protein Claudin-2 (CLDN2) acts downstream of COX5B-mediated bioenergetic alterations in controlling cell growth and the sensitivity to anticancer drugs in CRCs cells. In conclusion, it was found that COX5B promoted cell growth and attenuated anticancer drugs susceptibility in CRCs cells by orchestrating CLDN2 expression, which may contribute to unfavorable postoperative outcomes of patients with CRCs. [ABSTRACT FROM AUTHOR]

Complex biomolecules absorb in the mid-infrared (λ = 2-20 μm), giving vibrational spectra associated with structure and function. We used Fourier transform infrared (FTIR) microspectroscopy to "fingerprint" locations along the length of human small and large intestinal crypts. Paraffin-embedded slices of normal human gut were sectioned (10 μm thick) and mounted to facilitate infrared (IR) spectral analyses. IR spectra were collected using globar (15 μm × 15 μm aperture) FTIR microspectroscopy in reflection mode, synchrotron (⩽10 μm × 10 μm aperture) FTIR microspectroscopy in transmission mode or near-field photothermal microspectroscopy. Dependent on the location of crypt interrogation, clear differences in spectral characteristics were noted. Epithelial-cell IR spectra were subjected to principal component analysis to determine whether wavenumber- absorbance relationships expressed as single points in "hyperspace" might on the basis of multivariate distance reveal biophysical differences along the length of gut crypts. Following spectroscopic analysis, plotted clusters and their loadings plots pointed toward symmetric (vs)PO2- (1,080 cm-1) vibrations as a discriminating factor for the putative stem cell region; this proved to be a more robust marker than other phenotypic markers, such as β-catenin or CD133. This pattern was subsequently confirmed by image mapping and points to a novel approach of nondestructively identifying a tissue's stem cell location. vsPO2-, probably associated with DNA conformational alterations, might facilitate a means of identifying stem cells, which may have utility in other tissues where the location of stem cells is unclear. [ABSTRACT FROM AUTHOR]

Salmonella enteritidis infection occurs primarily in animals and often results in self-limited gastroenteritis in accidental cross contamination in human. However, the acute renal failure could be a rare but serious complication of the S. enteritidis infection. We report one case of acute renal failure from severe dehydration caused by S. enteritidis food poisoning. The acute renal failure completely recovered after hydration and antibiotic treatment. [ABSTRACT FROM AUTHOR]

Unexpected high risk of synchronous/metachronous hepatocellular carcinoma (HCC) and transitional cell carcinoma (TCC) co-occurrence has been discovered previously. Here, we searched for genetic variation contributing to the co-occurrence of this double primary cancer (DPC). Using targeted exome sequencing, a panel of variants associated with concurrent DPC was identified. However, only a nonsynonymous variant within the Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1) gene was associated with DPC occurrence (p = 0.002), compared with that in the healthy population. Further independent cohort verification analysis revealed that the SYNE1-rs9479297-TT genotype (versus TC + CC genotypes) was enriched in patients with DPC, compared with that in those with TCC alone (p = 0.039), those with HCC alone (p = 0.006), those with non-HCC/non-TCC (p < 0.001), and healthy population (p < 0.001). SYNE1 mRNA expression reduced in both patients with HCC and TCC, and its lower expression in HCC was associated with shorter recurrence-free (p = 0.0314) and metastasis-free (p = 0.0479) survival. SYNE1-rs9479297 genotypes were correlated with tissue SYNE1 levels and clinical outcomes in HCC patients. Finally, SYNE1 silencing enhanced the cell proliferation and migration of HCC/TCC cells. In conclusion, SYNE1-rs9479297 genotypes were associated with HCC/TCC DPC co-occurrence and correlated with SYNE1 expression, which in turn contributed to HCC/TCC cell proliferation and migration, thereby affecting clinical outcomes. [ABSTRACT FROM AUTHOR]

Long-term use of gastric-acid-suppressive drugs is known to be associated with several adverse effects. However, the association between enteric infection and acid suppression therapy is still uncertain. This study aimed to evaluate the association between gastric acid suppression and the risk of enteric infection. Materials and Methods: We conducted a population-based case-control study using the data from Chang Gung Research Database (CGRD) in Taiwan. Between January 2008 and December 2017, a total of 154,590 adult inpatients (age > 18) were identified. A pool of potential eligible controls according to four propensity scores matching by sex, age, and index year were extracted (n = 89,925). Subjects with missing data or who received less than 7 days of proton pump inhibitors (PPIs) and/or H2-receptor antagonists (H2RAs) were excluded. Finally, 17,186 cases and 69,708 corresponding controls were selected for analysis. The use of PPIs and H2RAs, the result of microbiological samples, and co-morbidity conditions have been analyzed. Confounders were controlled by conditional logistic regression. Results: 32.84% of patients in the case group used PPIs, compared with 7.48% in the control group. Of patients in the case group, 9.9% used H2RAs, compared with 6.9% in the control group. Of patients in the case group, 8.3% used a combination of PPIs and H2RAs, compared with 2.7% in the control group. The most common etiological pathogens were Enterococcus (44.8%), Clostridioides difficile (34.5%), and Salmonella spp. (10.2%). The adjusted odds ratio (OR) for PPI use with enteric infection was 5.526 (95% confidence interval [CI], 5.274–5.791). For H2RAs, the adjusted odds ratio was 1.339 (95% confidence interval [CI], 1.261–1.424). Compared to the control group, persons with enteric infection had more frequent acid-suppressive agent usage. Conclusions: This study demonstrates that gastric-acid-suppressive drug use is associated with an increased risk of enteric infection after adjusting for potential biases and confounders. [ABSTRACT FROM AUTHOR]

Simple Summary: Boron neutron capture therapy (BNCT) is becoming one of the most promising radiotherapies for aggressive cancers, but the detailed cellular mechanisms of BNCT remain largely underexplored. Solid tumors are composed of heterogeneous cell populations, which create a 3-dimensional complicated microenvironment for tumor progression. To recapture the influences of the microenvironment on BNCT efficacy, we applied a self-assembly 3D cell culture system with two different types of pancreatic cancer cells. In contrast to previous findings with γ-ray exposure, we found that the 3D architecture of pancreatic tumor can facilitate the susceptibility of cancer cells to BNCT, as compared to 2D tissue structure; a computer simulation model was established to further confirm this unexpected finding. These outcomes can contribute to better understanding of the radiobiology of BNCT, and the developed models may facilitate the recent development in personalized radiotherapy. Pancreatic cancer is a leading cause of cancer death, and boron neutron capture therapy (BNCT) is one of the promising radiotherapy techniques for patients with pancreatic cancer. In this study, we evaluated the biological effectiveness of BNCT at multicellular levels using in vitro and in silico models. To recapture the phenotypic characteristic of pancreatic tumors, we developed a cell self-assembly approach with human pancreatic cancer cells Panc-1 and BxPC-3 cocultured with MRC-5 fibroblasts. On substrate with physiological stiffness, tumor cells self-assembled into 3D spheroids, and the cocultured fibroblasts further facilitated the assembly process, which recapture the influence of tumor stroma. Interestingly, after 1.2 MW neutron irradiation, lower survival rates and higher apoptosis (increasing by 4-fold for Panc-1 and 1.5-fold for BxPC-3) were observed in 3D spheroids, instead of in 2D monolayers. The unexpected low tolerance of 3D spheroids to BNCT highlights the unique characteristics of BNCT over conventional radiotherapy. The uptake of boron-containing compound boronophenylalanine (BPA) and the alteration of E-cadherin can partially contribute to the observed susceptibility. In addition to biological effects, the probability of induced α-particle exposure correlated to the multicellular organization was speculated to affect the cellular responses to BNCT. A Monte Carlo (MC) simulation was also established to further interpret the observed survival. Intracellular boron distribution in the multicellular structure and related treatment resistance were reconstructed in silico. Simulation results demonstrated that the physical architecture is one of the essential factors for biological effectiveness in BNCT, which supports our in vitro findings. In summary, we developed in vitro and in silico self-assembly 3D models to evaluate the effectiveness of BNCT on pancreatic tumors. Considering the easy-access of this 3D cell-assembly platform, this study may not only contribute to the current understanding of BNCT but is also expected to be applied to evaluate the BNCT efficacy for individualized treatment plans in the future. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) mutations are highly associated with cancer progression. The poor prognosis of hepatocellular carcinoma (HCC) is largely due to high rates of tumor metastasis. This emphasizes the urgency of identifying these patients in advance and developing new therapeutic targets for successful intervention. However, the issue of whether mtDNA influences tumor metastasis in hepatoma remains unclear. In the current study, multiple mutations in mtDNA were identified by sequencing HCC samples. Among these mutations, mitochondrially encoded 12S rRNA (MT-RNR1) G709A was identified as a novel potential candidate. The MT-RNR1 G709A polymorphism was an independent risk factor for overall survival and distant metastasis-free survival. Subgroup analysis showed that in patients with cirrhosis, HBV-related HCC, α-fetoprotein ≥ 400 ng/mL, aspartate transaminase ≥ 31 IU/L, tumor number > 1, tumor size ≥ 5 cm, and histology grade 3-4, MT-RNR1 G709A was associated with both shorter overall survival and distant metastasis-free survival. Mechanistically, MT-RNR1 G709A was clearly associated with hexokinase 2 (HK2) expression and unfavorable prognosis in HCC patients. Our data collectively highlight that novel associations among MT-RNR1 G709A and HK2 are an important risk factor in HCC patients. [ABSTRACT FROM AUTHOR]

Background: Delayed post-polypectomy bleeding (PPB) is a major complication of polypectomy. The effect of prophylactic hemoclipping on delayed PPB is uncertain. The aim of this study was to evaluate the effectiveness of prophylactic hemoclipping and identify the risk factors of delayed PPB.Methods: Patients with polyps sized 6 to 20 mm underwent snare polypectomy from 2015 to 2017 were retrospectively reviewed. The patients with prophylactic hemoclipping for delayed PPB prevention were included in the clipping group, and those without prophylactic hemoclipping were included in the non-clipping group. The incidence of delayed PPB and time to bleeding were compared between the groups. Multivariate analysis was used to identify the risk factors of delayed PPB. Propensity score matching was used to minimize potential bias.Results: After propensity score matching, 612 patients with 806 polyps were in the clipping group, and 576 patients with 806 polyps were in the non-clipping group. There were no significant differences in the incidence of delayed PPB and days to bleeding between two groups (0.8% vs 1.3%, p = 0.4; 3.4 ± 1.94 days vs 4.13 ± 3.39 days, p = 0.94). In the multivariate analysis, the polyp size [Odds ratio (OR):1.16, 95% confidence interval (CI):1.01-1.16, p = 0.03), multiple polypectomies (OR: 4.64, 95% CI:1.24-17.44, p = 0.02) and a history of anticoagulant use (OR:37.52, 95% CI:6.49-216.8, p < 0.001) were associated with delayed PPB.Conclusions: In polyps sized 6 to 20 mm, prophylactic hemoclip placement did not decrease the risk of delayed PPB. Patients without risk factors including multiple polypectomies and anticoagulant use are no need to performing prophylactic hemoclipping. [ABSTRACT FROM AUTHOR]