Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

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. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Minimally invasive endoscopic evacuation with the novel, portable Axonpen neuroendoscopic system for spontaneous intracerebral hemorrhage.

Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.

Long-term outcomes of coils embolization for superior hypophyseal artery aneurysms.

Objective: Superior hypophyseal artery (SHA) aneurysms are intradural, and their rupture can result in subarachnoid hemorrhage. Considering the related surgical difficulty and anatomical restrictions, endovascular treatment (EVT) is considered the most favorable modality for SHA aneurysms; however, the long-term outcomes of EVT have rarely been reported. The study assessed the incidence of and risk factors for recurrence of SHA aneurysms after EVT as well as the correlation factors for SHA aneurysm rupture. Methods: We included 112 patients with SHA aneurysms treated with EVT at our facility between 2009 and 2020. Here, EVT included non-stent-assisted (simple or balloon-assisted) or stent-assisted coiling. Flow diverter was not included because it was barely used due to its high cost under our national insurance's limitation, and a high proportion of ruptured aneurysms in our series. Univariate and multivariate logistic regression was performed to evaluate the correlation factors for SHA aneurysm rupture, along with the incidence of and risk factors for post-EVT SHA aneurysm recurrence and re-treatment. Results: In our patients, the mean angiographic follow-up period was 3.12 years. The presence of type IA or IB cavernous internal carotid artery (cICA) was strongly correlated with SHA aneurysm rupture. Recurrence occurred in 17 (13.4%) patients, of which only 1 (1.4%) patient had received stent-assisted coiling. All cases of recurrence were observed within 2 years after EVT. The multivariate logistic regression results showed that ruptured aneurysm and non-stent-assisted coiling were independent risk factors for aneurysm recurrence. Of the 17 cases of aneurysm recurrence, 9 (52.9%) received re-treatment. Moreover, aneurysm rupture was the only factor significantly correlated with re-treatment in multivariate logistic regression. No re-recurrence was observed when a recurrent aneurysm was treated with stent-assisted coiling. Conclusion: Type I cICA was common factor for aneurysm rupture. Although flow-diverter treatment serves as another suitable technique that was not compared with, coils embolization was effective treatment modality for SHA aneurysms, leading to low recurrence and complication rates, especially with stent use. All cases of recurrence occurred within 2 years after EVT; they were strongly associated with prior aneurysm rupture. Further stent-assisted coiling was noticed to prevent re-recurrence.

Middle cerebral artery infarction, A rare complication of intracranial cryptococcoma in an immunocompetent patient: A case report and literature review.

Background: This report presents the first case of intracranial cryptococcoma arising from the right frontal lobe causing right middle cerebral artery infarction. Intracranial cryptococcomas usually occur in the cerebral parenchyma, basal ganglia, cerebellum, pons, thalamus, and choroid plexus; they may mimic intracranial tumors, but seldom cause infarction. Of the 15 cases of pathology-confirmed intracranial cryptococcomas in the literature, no case has been complicated by middle cerebral artery (MCA) infarction. Here, we discuss a case of intracranial cryptococcoma with an ipsilateral middle cerebral artery infarction. Case Description: A 40-year-old man was referred to our emergency room due to progressive headaches and acute left hemiplegia. The patient was a construction worker with no history of avian contact, recent travel, or human immunodeficiency virus (HIV) infection. Brain computed tomography (CT) showed an intra-axial mass, and subsequent magnetic resonance imaging (MRI) delineated a large mass of 53 mm in the right middle frontal lobe and a small lesion of 18 mm in the right caudate head, with marginal enhancement and central necrosis. A neurosurgeon was consulted in view of the intracranial lesion, and the patient underwent en-bloc excision of the solid mass. The pathology report later identified a Cryptococcus infection rather than malignancy. The patient underwent 4 weeks of postoperative treatment with amphotericin B plus flucytosine; he then received subsequent oral antifungal treatment for 6 months, and had neurologic sequelae that manifested as left side hemiplegia. Conclusion: Diagnosis of fungal infections in the CNS remains challenging. This is especially true of Cryptococcus CNS infections that present as a space-occupying lesion in an immunocompetent patient. A Cryptococcus infection should be considered in the differential diagnoses in patients with brain mass lesions, as this infection can be misdiagnosed as a brain tumor.

Effectiveness and safety of 8-week glecaprevir/pibrentasvir in HCV treatment-naïve patients with compensated cirrhosis: real-world experience from Taiwan nationwide HCV registry.

BACKGROUND: Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce. METHODS: The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated. RESULTS: Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related. CONCLUSIONS: In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.

The Prognostic Impacts of Body Mass Index and Distance to the Peritoneal Bottom on Laparoscopic Ventriculoperitoneal Shunt Placement.

OBJECTIVE: Laparoscopic ventriculoperitoneal shunt surgery has been reported to have several advantages in selected patients. However, the prognostic factors have been understudied specifically for this surgery. We sought to investigate the factors influencing the complications after the laparoscopic ventriculoperitoneal shunt placement. METHODS: All surgeries in this prospective study were performed by the same team of neurosurgeons and general surgeons. Clinical parameters as well as potential risk factors for postoperative complications were analyzed. The endpoint was overall complications requiring surgical revision within the follow-up period after surgery. RESULTS: Ninety-nine patients (51 male and 48 female) scheduled for laparoscopic-assisted ventriculoperitoneal shunt surgery between 2019 and 2021 were included. Overall shunt complication rate was 9% (9 of 99 cases), and there was 1 patient (1%) who had distal dysfunction among them. Body mass index ≥27 kg/m2 (hazard ratio 4.87; 95% confidence interval 1.05-22.57; P = 0.043), and nonprogrammable shunts (hazard ratio 7.91; 95% confidence interval 1.51-41.50; P = 0.014) were significantly associated with an increased risk of complications. Among 75 patients who received programmable shunts, the vertical distance from the distal tip to the presumed bottom of peritoneal cavity was significant positively associated with the number of pressure adjustments (R2 0.511, adjusted R2 0.504, and P < 0.001). CONCLUSIONS: Ventriculoperitoneal shunt surgery provided benefits with little complication rate, whereas patients treated with nonprogrammable shunts and obese patients had less favorable outcome. A positive correlation between the vertical distance from the distal tip to the bottom of peritoneal cavity and pressure adjustments inferred to the advantage of the laparoscopic method.

Delayed Progressive Mass Effect After Secured Ruptured Middle Cerebral Artery Aneurysm: Risk Factors and Outcomes.

Objective: Delayed progressive mass effect (DPME) after securing an aneurysm is uncommon following microsurgical or endovascular repair and leads to a poor clinical outcome. Patients with ruptured middle cerebral artery (MCA) aneurysms have a high risk of postoperative oedema and mass effect, which may require decompressive treatment. Because few studies have discussed the risk and predictive factors, we focused on ruptured MCA aneurysms and evaluated the outcomes of these patients and the necessity of salvage surgery when DPME presented. Methods: Data on 891 patients with aneurysmal subarachnoid haemorrhage (aSAH) treated between January 2011 and February 2020 were extracted from the medical database of a tertiary referral centre. A total of 113 patients with aSAH resulting from at least one MCA aneurysm were identified. After excluding patients with several clinical confounders, we enrolled 80 patients with surgically treated aSAH. We examined the characteristics of aneurysms and hematomas, perioperative contrast pooling patterns, presence of distal hematomas, perisylvian low density, occlusive treatment modality, management strategies, the need for salvage surgical decompression, and postoperative 90-day outcomes to identify possible risk factors. Results: DPME was observed in 27 of the 80 patients (33.7%). The DPME and non-DPME group differed significantly in some respects. The DPME group had a higher risk of salvage surgery (p < 0.001) and poorer outcomes (mRS at day 90; p = 0.0018). The univariate analysis indicated that the presence of hematoma, CTA spot signs, perisylvian low density, and distal hematoma were independent risk factors for DPME. We also noted that DPME remained an independent predictor of a poorer 90-day functional outcome (mRS ≤ 2). Conclusion: DPME can lead to salvage decompression surgery and directly relates to poor outcomes for patients with a ruptured MCA aneurysm. Distal hematoma, perisylvian low density, and CTA spot signs on preoperative images can predict DPME.

The Role of Intraventricular Hemorrhage in Traumatic Brain Injury: A Novel Scoring System.

Traumatic intraventricular hemorrhage (tIVH) is associated with increased mortality and disability in traumatic brain injury (TBI). However, the significance of tIVH itself remains unclear. Our goal is to assess whether tIVH affects in-hospital mortality and short-term functional outcomes. We retrospectively reviewed the records of 5048 patients with TBI during a 5-year period, and 149 tIVH patients were analyzed. Confounding was reduced using the inverse probability of treatment weighting (IPTW) based on propensity score. The association between IVH and outcomes was investigated using logistic regression in the IPTW-adjusted cohort. In our study, after adjustment for analysis, the in-hospital mortality rate (11.4% vs. 9.2%) and the poor functional outcome rate (37.9% vs.10.6%) were significantly higher in the tIVH group than in the non-tIVH group. Factors independently associated with outcomes were age ≥ 65 years, Glasgow Coma Scale (GCS) severity score, and the Graeb score. The Traumatic Graeb Score, a novel scoring system for predicting functional outcomes associated with tIVH, comprised the sum of the following components: GCS scores of 3 to 4 (=2 points), 5 to 12 (=1 point), 13 to 15 (=0 points); age ≥ 65 years, yes (=1 point), no (=0 points); Graeb score (0-12 points). A Traumatic Graeb Score ≥ 4 is an optimal cutoff value for poor short-term functional outcomes.

Low-Level Fluvalinate Treatment in the Larval Stage Induces Impaired Olfactory Associative Behavior of Honey Bee Workers in the Field.

Fluvalinate is a widely used insecticide for varroa mite control in apiculture. While most beekeepers have ignored the effects of low levels of fluvalinate on bees, this study aims to demonstrate its effects at very low concentrations. We first used fluvalinate doses ranging from 0.4 to 400 ng/larva to monitor the capping, pupation, and emergence rates of larval bees. Second, we used the honey bees' proboscis extension reflex reaction to test the learning ability of adult bees that were exposed to fluvalinate doses from 0.004 to 4 ng/larva in the larval stage. The brood-capped rate of larvae decreased dramatically when the dose was increased to 40 ng/larva. Although no significant effect was observed on brood-capping, pupation, and eclosion rates with a dose of 4 ng/larva, we found that the olfactory associative behavior of adult bees was impaired when they were treated with sublethal doses from 0.004 to 4 ng/larva in the larval stage. These findings suggest that a sublethal dose of fluvalinate given to larvae affects the subsequent associative ability of adult honey bee workers. Thus, a very low dose may affect the survival conditions of the entire colony.

Ledipasvir/sofosbuvir for HCV genotype 1, 2, 4-6 infection: Real-world evidence from a nationwide registry in Taiwan.

BACKGROUND/PURPOSE: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. METHODS: Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common. CONCLUSION: LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.

Factors Associated with Significant Platelet Count Improvement in Thrombocytopenic Chronic Hepatitis C Patients Receiving Direct-Acting Antivirals.

To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of <150 × 103/µL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/µL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99-1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06-1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58-0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98-0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71-0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.

Outreach onsite treatment with a simplified pangenotypic direct-acting anti-viral regimen for hepatitis C virus micro-elimination in a prison.

BACKGROUND: Prisoners are at risk of hepatitis C virus (HCV) infection, especially among the people who inject drugs (PWID). We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals (DAA) regimen, 12 wk of sofosbuvir/velpatasvir, in a PWID-dominant prison in Taiwan. AIM: To implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in Taiwan. METHODS: HCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen, 12 wk of sofosbuvir/ velpatasvir, from two cohorts in Penghu Prison, either identified by mass screen or in outpatient clinics, in September 2019. Another group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control group. The primary endpoint was sustained virological response (SVR12, defined as undetectable HCV ribonucleic acid (RNA) 12 wk after end-of-treatment). RESULTS: A total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign; 91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/ pibrentasvir before mass screening were enrolled as a control. The HCV micro-elimination group had significantly lower proportion of diabetes, hypertension, hyperlipidemia, advanced fibrosis and chronic kidney diseases, but higher levels of HCV RNA. The SVR12 rate was comparable between the HCV micro-elimination and control groups, 95.8% (203/212) vs 94.5% (86/91), respectively, in intent-to-treat analysis, and 100% (203/203) vs 98.9% (86/87), respectively, in per-protocol analysis. There was no virological failure, treatment discontinuation, and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination group. CONCLUSION: Outreach mass screening followed by immediate onsite treatment with a simplified pangenotypic DAA regimen, sofosbuvir/velpatasvir, provides successful strategies toward HCV micro-elimination among prisoners.

Sofosbuvir/Velpatasvir for Hepatitis C Virus Infection: Real-World Effectiveness and Safety from a Nationwide Registry in Taiwan.

INTRODUCTION: Pangenotypic direct-acting antivirals are expected to cure hepatitis C virus (HCV) in more than 95% of treated patients. However, data on the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) in Taiwan are limited. This study aims to characterize the patient population in the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry and evaluate treatment outcome in Taiwanese patients receiving SOF/VEL. METHODS: This study was a retrospective-prospective, observational, multicenter, real-world analysis. Adults with chronic hepatitis C were treated with SOF/VEL 400/100 mg ± ribavirin for 12 weeks. The primary outcome was sustained virologic response 12 weeks after end of therapy (SVR12). Factors associated with not achieving SVR12 were evaluated using logistic regression and covariate analysis. Safety was also assessed. RESULTS: In total, 3480 patients were included: 86.8% genotype 1/2, 2.8% genotype 3, 0.1% genotype 4/5, 9.6% genotype 6; unclassified, 0.8%; 12.2% compensated cirrhosis; 3.3% decompensated cirrhosis; and 15.8% chronic kidney disease. Overall SVR12 rate was 99.4% (genotype 1, 99.5%; genotype 2, 99.4%; genotype 3, 96.9%; genotype 4, 100%; genotype 6, 99.7%). SVR12 rates among patients with compensated cirrhosis, decompensated cirrhosis, and chronic kidney disease stages 4-5 were 99.5%, 100%, and 100%, respectively. There were 21 patients (0.6%) who did not achieve SVR12. Factors associated with failure were treatment adherence below 60%, high viral load, and genotype 3 (p < 0.001, p = 0.028, and p = 0.001, respectively). Adverse events occurred in 10% of patients; 0.6% were serious and one was related to treatment. Treatment discontinuation occurred in 0.3% of patients; none were treatment related. The estimated glomerular filtration rate remained stable throughout treatment and follow-up, regardless of baseline values and cirrhosis status. CONCLUSION: SOF/VEL was highly effective and well tolerated in Taiwanese patients, irrespective of viral genotype, liver disease severity, and comorbidities.

Rescue embolization with direct coil delivery from dual-lumen balloon microcatheter.

BACKGROUND: Balloon microcatheters are widely used for endovascular treatment. However, no reports on direct coil embolization from dual-lumen balloon microcatheters are available in the literature. This report is the first description of direct coil embolization using this type of balloon microcatheter for looming bleeding emergencies. METHODS: This retrospective review demonstrates the indications and advantages of coil embolization from an inflated balloon catheter to reduce blood loss and simultaneously occlude bleeding. RESULTS: Five patients who underwent emergency endovascular treatment using coil embolization directly delivered from a dual-lumen balloon were identified. Etiologies included vertebro-vertebral arteriovenous fistula, ruptured vertebral artery dissecting aneurysm, vertebral artery injury during cervical spinal operation, and failed stent retrieval procedures for acute infarction. Complete hemostasis was achieved with all procedures. CONCLUSION: Our experience demonstrates the feasibility of direct coil embolization by using a dual-lumen balloon to rapidly halt bleeding in some rare emergency situations, which may save lives.

Ticagrelor versus clopidogrel in stent-assisted coil embolization of unruptured intracranial aneurysms.

BACKGROUND: Dual antiplatelet therapy is widely used for stent-assisted coil embolization (SACE) for unruptured intracranial aneurysms (UIAs) to prevent thromboembolic events (TEs). Compared to clopidogrel associated with aspirin, knowledge of the safety and efficacy of ticagrelor is lacking in large studies to date. METHODS: A retrospective cohort study was conducted from January 2016 to December 2018 with at least one year of follow-up in a single institution and systemic review. RESULTS: Altogether, 153 patients with UIA receiving SACE were separated into two groups: 113 patients receiving clopidogrel plus aspirin and 40 patients receiving ticagrelor plus aspirin. Acute in-stent thrombotic events were noted in two patients in the clopidogrel group (1.77%) and none in the ticagrelor group (0%). Additionally, one patient (0.88%) in the clopidogrel group had an early ischemic stroke (<3 months). Delayed ischemic stroke was noted in 6 patients (5.31%) in the clopidogrel group and 3 patients (7.50%) in the ticagrelor group. There were no major hemorrhagic events in either group. The two groups showed no significant differences with regard to ischemic stroke or hemorrhagic stroke. CONCLUSION: Compared to the clopidogrel based regimen, ticagrelor can also reduce TEs without increasing bleeding tendency for SACE of UIAs. Ticagrelor combined with low-dose aspirin is a safe and effective alternative option for SACE.

Impact of Sofosbuvir-Based Direct-Acting Antivirals on Renal Function in Chronic Hepatitis C Patients With Impaired Renal Function: A Large Cohort Study From the Nationwide HCV Registry Program (TACR).

BACKGROUND & AIMS: Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS: The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). RESULTS: The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS: Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

Structural basis of an epitope tagging system derived from Haloarcula marismortui bacteriorhodopsin I D94N and its monoclonal antibody GD-26.

Specific antibody interactions with short peptides have made epitope tagging systems a vital tool employed in virtually all fields of biological research. Here, we present a novel epitope tagging system comprised of a monoclonal antibody named GD-26, which recognises the TD peptide (GTGATPADD) derived from Haloarcula marismortui bacteriorhodopsin I (HmBRI) D94N mutant. The crystal structure of the antigen-binding fragment (Fab) of GD-26 complexed with the TD peptide was determined to a resolution of 1.45 Å. The TD peptide was found to adopt a 310 helix conformation within the binding cleft, providing a characteristic peptide structure for recognition by GD-26 Fab. Based on the structure information, polar and nonpolar forces collectively contribute to the strong binding. Attempts to engineer the TD peptide show that the proline residue is crucial for the formation of the 310 helix in order to fit into the binding cleft. Isothermal calorimetry (ITC) reported a dissociation constant KD of 12 ± 2.8 nm, indicating a strong interaction between the TD peptide and GD-26 Fab. High specificity of GD-26 IgG to the TD peptide was demonstrated by western blotting, ELISA and immunofluorescence as only TD-tagged proteins were detected, suggesting the effectiveness of the GD-26/TD peptide tagging system. In addition to already-existing epitope tags such as the FLAG tag and the ALFA tag adopting either extended or α-helix conformations, the unique 310 helix conformation of the TD peptide together with the corresponding monoclonal antibody GD-26 offers a novel tagging option for research.

Predictive Value of Swab Cultures for Cryopreserved Flaps During Delayed Cranioplasties.

OBJECTIVE: To assess the predictive value of swab cultures of cryopreserved skull flaps during cranioplasties for surgical site infections (SSIs). METHODS: A retrospective review was conducted of consecutive patients who underwent delayed cranioplasties with cryopreserved autografts between 2009 and 2017. The results of cultures obtained from swabs and infected surgical sites were assessed. The accuracy, sensitivity, and specificity of swab cultures for SSIs were evaluated. RESULTS: The study included 422 patients categorized into two groups, swab and nonswab, depending on whether swab cultures were implemented during cranioplasties. The overall infection rate was 7.58%. No difference was seen in infection rates between groups. There were 18 false-positive and no true-positive swab culture results. All bacteria between swab cultures and SSI cultures were discordant. Meanwhile, there were 19 false-negative swab cultures. The results showed high specificity but low sensitivity for swab cultures to predict SSI occurrence and the pathogens. CONCLUSIONS: Owing to low accuracy and sensitivity, swab cultures of cryopreserved autografts should not be routinely performed during delayed cranioplasties.

Nationwide registry of glecaprevir plus pibrentasvir in the treatment of HCV in Taiwan.

The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.