Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.

Acidosis ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Bilirubin ; Blood Glucose ; Blood Urea Nitrogen ; Carbon Dioxide ; Creatinine ; Electrolytes ; Enzyme-Linked Immunosorbent Assay ; Hematocrit ; Hemodynamics ; Humans ; Hydrogen-Ion Concentration ; Liver ; Magnesium ; Male ; Oxygen ; Potassium ; Rats ; Resuscitation ; Shock, Hemorrhagic ; Sodium

PURPOSE: Neurogenesis in neonatal period after birth occurs consequently through a series of neuronal stem/progenitor cell proliferation and differentiation. This stage is critical for determining of normal development and maturation of the brain throughout the life. Therefore, exposure to a certain physical or chemical factor(s) during pregnancy can result in serious damage in the developing brain. Bisphenol A (BPA), a plasticizer, is generally known as an endocrine disruptor exhibiting adverse effects when exposed to animals under experimental conditions. The purpose of this study was to investigate the changes in neuronal stem cell proliferation and differentiation during neonatal brain development in BPA-exposed pregnant rats. METHODS: After exposure of BPA to pregnant rats, infant brains were excised at days 3, 7, and 14 after birth, and tissues were processed for histological and biochemical analyses. RESULTS: Proliferating cell nuclear antigen (PCNA) immunostaining showed that whereas cells in the hippocampus at days 3 and 7 after birth were highly proliferating, the cells at day 14 divided less often. Immunohistochemical staining for nestin in the control group revealed that nestin-positive cells were only observed at day 3 after birth, but the immunoreactivity was not observed at day 14. In addition, glial fibrillary acidic protein (GFAP) immunoreactive cells were observed from days 7 to 14 in control tissues. However, in the BPA-exposed groups, 1) the number of PCNA-positive cells in the BPA-exposed groups at days 3 and 7 were higher than those of the control, 2) nestin-positive cells were observed at day 3 which is earlier than that of control, and 3) GFAP-positive cells were detected in the hippocampus tissue from day 3. Furthermore, western blotting showed that exposure to BPA in pregnant rats resulted in earlier expression of nestin in the neuronal rat brain compared to the controls. CONCLUSION: Taken together, it is assumed that precocious neurogenesis in the infant rat hippocampus might be due to BPA exposure during the gestational period. Further studies on adult brain perinatally exposed to BPA are needed to evaluate the pathological status of the hippocampus.
Adult ; Animals ; Benzhydryl Compounds ; Blotting, Western ; Brain ; Cell Proliferation ; Glial Fibrillary Acidic Protein ; Hippocampus ; Humans ; Infant ; Infant, Newborn ; Intermediate Filament Proteins ; Nerve Tissue Proteins ; Neurogenesis ; Neurons ; Parturition ; Phenols ; Plastics ; Pregnancy ; Proliferating Cell Nuclear Antigen ; Rats ; Stem Cells

Background:From April to July in 2009 and 2010,unexplained severe hemorrhagic fever-like illnesses occurred in farmers from the Huaiyangshan mountains range.Methods:Clinical specimens (blood,urine,feces,and throat swabs) from suspected patients were obtained and stored.Mosquitoes and ticks in affected regions were collected.Virus was isolated from 2 patients and characterized by whole genome sequencing.Virus detection in additional patients and arthropods was done by virus-specific reverse transcription (RT) PCR.Clinical and epidemiological data of RT-PCR confirmed patients were analyzed.Results:An unknown virus was isolated from blood of two patients and from Haemaphysalis ticks collected from dogs.Whole genome sequence analysis identified the virus as a novel member of the family Bunyaviridae,most closely related to the viruses of the genus Phlebovirus within which it forms a separate lineage.Subsequently,infection was confirmed by RT-PCR in 33 of 58 suspected patients.The illness in these patients was characterized by fever,severe malaise,nausea,vomiting,and diarrhea.Prominent laboratory findings included low white cell- and platelet counts,coagulation disturbances,and elevation of liver enzymes.Hemorrhagic complications were observed in 3 cases,5 (15%) patients died.Conclusions:A novel tick-borne Bunyavirus causing life-threatening hemorrhagic fever in humans has emerged in the Huaiyangshan mountain areas of China.Further studies are needed to determine the epidemiology,geographic distribution and vertebrate animal ecology of this virus.

OBJECTIVE: We wanted to evaluate the impact of two reconstruction algorithms (halfscan and multisector) on the image quality and the accuracy of measuring the severity of coronary stenoses by using a pulsating cardiac phantom with different heart rates (HRs). MATERIALS AND METHODS: Simulated coronary arteries with different stenotic severities (25, 50, 75%) and different luminal diameters (3, 4, 5 mm) were scanned with a fixed pitch of 0.16 and a 0.35 second gantry rotation time on a 64-slice multidetector CT. Both reconstruction algorithms (halfscan and multisector) were applied to HRs of 40-120 beats per minute (bpm) at 10 bpm intervals. Three experienced radiologists visually assessed the image quality and they manually measured the stenotic severity. RESULTS: Fewer measurement errors occurred with multisector reconstruction (p = 0.05), a slower HR (p < 0.001) and a larger luminal diameter (p = 0.014); measurement errors were not related with the observers or the stenotic severity. There was no significant difference in measurements as for the reconstruction algorithms below an HR of 70 bpm. More nonassessable segments were visualized with halfscan reconstruction (p = 0.004) and higher HRs (p < 0.001). Halfscan reconstruction had better quality scores when the HR was below 60 bpm, while multisector reconstruction had better quality scores when the HR was above 90 bpm. For the HRs between 60 and 90 bpm, both reconstruction modes had similar quality scores. With excluding the nonassessable segments, both reconstruction algorithms achieved a similar mean measured stenotic severity and similar standard deviations. CONCLUSION: At a higher HR (above 90 bpm), multisector reconstruction had better temporal resolution, fewer nonassessable segments, better quality scores and better accuracy of measuring the stenotic severity in this phantom study.
*Algorithms ; Artifacts ; Computer Simulation ; Coronary Angiography/*methods ; Coronary Stenosis/*radiography ; Electrocardiography ; *Heart Rate ; Image Processing, Computer-Assisted/*methods ; Models, Cardiovascular ; Observer Variation ; Phantoms, Imaging ; Reproducibility of Results ; Severity of Illness Index ; Tomography, Spiral Computed/*methods

PURPOSE: To evaluate mortality and morbidity of very low birth weight infants(VLBW infants) born in the Busan area from 1996 to 2005. METHODS: A total of eight neonatal intensive care units (4 university hospitals and 4 general hospitals) in Busan participated in this study. A total of 1,414 VLBW infants were divided into three groups: period I, 1996 to 2000; period II, 1999 to 2002; period III, 2003 to 2005, based on date of birth. We performed a retrospective review of medical records of VLBWinfants and compared the survival rate, morbidity and mortality over the three periods. RESULT: The number of VLBW infants admitted to 8 NICUs in 1996-2005 was a total of 1,414 (1.3% incidence, mean gestational age 29.1+/-2.7 wk, mean birth weight 1158+/-235 g), including 361 (24.7%) extremely low birth weight infants (ELVW infants) who were less than 1,000 g at birth weight. Overall survival rate of VLBW infants was 66.1%. The survival rate of VLBW infants increased significantly over the three periods (period I:57.6%, period II:67.8%, period III:75.7%, P<0.01). Overall survival rate of ELBW infants was 33.8%, and increased from 26.4% in period I to 44.2% in period III (P<0.01). The incidence of respiratory distress syndrome was 45.1%; patent ductus arteriosus, 16.4%; bronchopulmonary dysplasia, 13.1%; blood culture positive sepsis, 12.7%; necrotizing enterocolitis, 6.6%; severe intracranial hemorrhage, 6.5%; and severe retinopathy of prematurity, 5.9%. The main causes of death were respiratory distress syndrome and sepsis. CONCLUSION: Overall survival rate of very low birth weight infant in Busan area during the last 10 years was 66.1%, and increased significantly over the three periods.
Birth Weight ; Bronchopulmonary Dysplasia ; Busan* ; Cause of Death ; Ductus Arteriosus, Patent ; Enterocolitis, Necrotizing ; Gestational Age ; Hospitals, University ; Humans ; Incidence ; Infant* ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Very Low Birth Weight* ; Intensive Care Units, Neonatal ; Intracranial Hemorrhages ; Medical Records ; Mortality ; Parturition ; Retinopathy of Prematurity ; Retrospective Studies ; Sepsis ; Survival Rate

Objective To investigate the efficacy and safety of photoselective vaporization treatment on benign prostatic hyperplasia(BPH)in the elderly over 70 years old.Methods From August 2004 to December 2005,a total of 126 patients with lower urinary tract symptoms secondary to BPH underwent photoselective vaporization of the prostate(PVP)with an 80 W quasicontinuous KTP laser.The patients aged between 70 and 96 years,(median 78.0),with 46 cases above 80 years. Prostatic volume was 24～86 ml,in an average of 47.0 ml,with 46 cases above 60 ml.Results The mean operative time was 46.8 min(range from 30 to 100 min).After operation,the catheter was pulled out in 69 cases within 24 hours and the patients generally urinated well.At three-months follow-up,the mean I-PSS decreased significantly from(25.0?3.7)to(16.3?2.0)(P＜0.01), while the Qmax increased from(5.8?2.7)ml/s to(16.3?4.8)ml/s(P＜0.01).Complications consisted of 4 cases of hematuria,6 urinary infection and 1 acute epididymitis.Conclusions The study indicates that PVP,a minimal invasive surgical procedure,is a safe and effective procedure for the treatment of BPH in the elderly.