Orchestrating vesicle transport, ESCRTs and kinase surveillance during abscission.

During the final stage of cell division, the future daughter cells are physically separated through abscission. This process requires coordination of many molecular machines, including endocytic and secretory vesicle trafficking proteins as well as ESCRT (endosomal sorting complex required for transport) proteins, that mediate a complex series of events to culminate in the final separation of daughter cells. Abscission is coordinated with other cellular processes (for example, nuclear pore reassembly) through mitotic kinases such as Aurora B and Polo-like kinase 1, which act as master regulators to ensure proper progression of abscission.

A last-minute rescue of trapped chromatin.

Chromosome segregation and cytokinesis must be tightly coordinated to ensure that chromosomes are accurately partitioned between dividing cells. In this issue, Steigemann et al. (2009) report that Aurora B kinase promotes proper chromosome segregation by delaying abscission when chromatin is trapped between dividing cells.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

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.

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 treatment failure of direct-acting antivirals for chronic hepatitis C: A real-world nationwide hepatitis C virus registry programme in Taiwan.

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)-infected patients. The real-world treatment outcome in Taiwanese patients on a nationwide basis is elusive. METHODS: The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end-of-treatment). RESULTS: A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype-1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment-naïve noncirrhotic, treatment-naïve cirrhotic, treatment-experienced noncirrhotic and treatment-experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment-experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment-naïve noncirrhotic patients (94.8%) and treatment-experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence < 60% ( adjusted odds ratio [aOR]/95% confidence interval [CI]: 117.1/52.4-261.3, P < .001), followed by GT3/GT2 (aOR/CI: 5.78/2.25-14.9, P = .0003 and aOR/CI: 1.55/1.05-2.29, P = .03, compared with GT1), active hepatocellular carcinoma (aOR/CI: 4.29/2.57-7.16, P < .001), the use of sofosbuvir/ribavirin (aOR/CI: 2.51/1.67-3.77, P < .001) and daclatasvir/asunaprevir (aOR/CI: 3.29/1.94-5.58, P < .001), decompensated liver cirrhosis (aOR/CI: 2.50/1.20-5.22, P = .02) and high HCV viral loads (aOR/CI: 2.16/1.57-2.97, P < .001). CONCLUSIONS: DAAs are highly effective in treating Taiwanese HCV patients in the real-world setting. Maintaining DAA adherence and selecting highly efficacious regimens are keys to ensure treatment success.

Early strategy of scepter XC balloon angioplasty and simultaneous Nimodipine infusion for vasospasm following ruptured aneurysm.

BACKGROUND: Cerebral vasospasm still results in high morbidity and mortality rates in patients after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to establish a protocol for the management of vasospasm and demonstrate our experience of angioplasty using the Scepter XC balloon catheter. METHODS: In this retrospective study, a computed tomography angiography and perfusion image was arranged if early symptoms occurred or on the 7th day following aneurysmal SAH. In patients with clear consciousness, balloon angioplasties were performed for symptomatic vasospasms, which were not improved within 6-12 h after maximal medical treatments. In unconscious patients, balloon angioplasties were performed for all patients with angiographic vasospasms. RESULTS: Fifty patients underwent Scepter XC balloon angioplasty among 396 consecutive patients who accepted endovascular or surgical treatments for ruptured aneurysms. All angioplasty procedures were successful without complications. 100% angiographic improvement and 94% clinical improvement were reached immediately after the angioplasties. A favorable functional outcome (modified Rankin Score of ≤2) could be achieved in 82% of patients. Even in patients with poor clinical grading (Hunt-Hess grade 4-5), a clinical improvement rate of 87.5% and favorable outcome rate was 70.8% could be achieved. CONCLUSION: Balloon angioplasty with Scepter XC balloon catheter is safe and effective for post-SAH vasospasm. This device's extra-compliant characteristics could considerably improve the quality of angioplasty procedures. For all patients, even those with poor neurological status, early treatment with combined protocol of nimodipine and angioplasty can have good clinical outcomes.

Sleep Disturbances Following Traumatic Brain Injury in Older Adults: A Comparison Study.

OBJECTIVES: To compare the prevalence of sleep disturbances in older adults with traumatic brain injury (TBI) with that of age- and gender-matched controls and to determine the risk factors for post-TBI sleep disturbances and the effects of post-TBI disturbances on quality of life (QOL). DESIGN: Cross-sectional case-comparison study. PARTICIPANTS: Eighty older adults (aged ≥65 years) with first-time TBI more than 3 months since injury and 80 older adults controls without TBI who completed sleep and health-related QOL questionnaires. RESULTS: Older adults with TBI showed a higher prevalence of obstructive sleep apnea (OSA), insomnia, and daytime sleepiness than older adult controls. Being male, having higher levels of depression and pain, and the presence of insomnia were significantly correlated with the risks of OSA, insomnia, and daytime sleepiness following TBI, respectively. Both OSA and insomnia were significantly correlated with low QOL in older adults with TBI. CONCLUSIONS: Sleep disturbances are highly prevalent in older adults with TBI. Gender differences, depression severity, and pain level are correlated with the occurrence of post-TBI sleep disturbances. Both OSA and insomnia are regarded as major contributors to low QOL in older people with TBI. Interventions targeted at post-TBI sleep disturbances may improve QOL of older adults.

Crystal Structure of PigA: A Prolyl Thioester-Oxidizing Enzyme in Prodigiosin Biosynthesis.

Prodigiosin is an intensely red pigment comprising three pyrroles. The biosynthetic pathway includes a two-step proline oxidation catalyzed by phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PigA), with flavin adenine dinucleotide (FAD) as its cofactor. The enzyme is crystallized in the apo form and in complex with FAD and proline. As an acyl coenzyme A dehydrogenase (ACAD) family member, the protein folds into a ß-sheet flanked by two α-helical domains. PigA forms a tetramer, which is consistent with analytical ultracentrifugation results. FAD binds to PigA in a similar way to that in the other enzymes of the ACAD family. The variable conformations of loop ß4-ß5 and helix αG correlate well with the structural flexibility required for substrate entrance to the Re side of FAD. Modeling with PigG, the acyl carrier protein, suggests a reasonable mode of interaction with PigA. The structure helps to explain the proline oxidation mechanism, in which Glu244 plays a central role by abstracting the substrate protons. It also reveals a plausible pocket for oxygen binding to the Si side of FAD.

Early Initiation of Post-Pyloric Feeding in Patients with Major Burns: Experience in Taiwan Formosa Water Park Dust Explosion Disaster.

Early initiation of enteral nutrition improves clinical outcomes in critical patients with serious burns. Post-pyloric tube feeding is a valuable therapeutic option for severely burned patients with poor gastric emptying. How early post-pyloric feeding can be initiated to provide more benefits to patients has not yet been examined. A fire erupted at a recreational water park in New Taipei City, Taiwan, on June 27, 2015. The results of early initiation versus delayed post-pyloric feeding in severely burned patients in this mass-casualty incident were compared. Door-to-post-pyloric feeding time ≤ 24 h was considered as early post-pyloric feeding (EPF) and that > 24 h was considered as delayed post-pyloric feeding (DPF). Thirteen patients with severe burn injuries (> 40% of the total body surface area) were assigned to undergo either EPF (five patients) or DPF (eight patients). This study is a "fortuitously controlled" study, and the authors were able to formulate and test whether EPF is better than DPF by comparing the two groups. In patients in the EPF, the intake of calories increased rapidly and was maintained throughout the study period. In addition, rapid restoration of plasma magnesium concentrations as well as pronounced recovery of platelet count in the EPF group was observed. In conclusion, our findings indicate that the time from injury to the onset of post-pyloric feeding is crucial, and EPF allows for the administration of calculated caloric needs. Therefore, EPF can be successfully initiated with beneficial outcomes of nutritional reconstruction in severely burned patients.

Distributed Newton Methods for Deep Neural Networks.

Deep learning involves a difficult nonconvex optimization problem with a large number of weights between any two adjacent layers of a deep structure. To handle large data sets or complicated networks, distributed training is needed, but the calculation of function, gradient, and Hessian is expensive. In particular, the communication and the synchronization cost may become a bottleneck. In this letter, we focus on situations where the model is distributedly stored and propose a novel distributed Newton method for training deep neural networks. By variable and feature-wise data partitions and some careful designs, we are able to explicitly use the Jacobian matrix for matrix-vector products in the Newton method. Some techniques are incorporated to reduce the running time as well as memory consumption. First, to reduce the communication cost, we propose a diagonalization method such that an approximate Newton direction can be obtained without communication between machines. Second, we consider subsampled Gauss-Newton matrices for reducing the running time as well as the communication cost. Third, to reduce the synchronization cost, we terminate the process of finding an approximate Newton direction even though some nodes have not finished their tasks. Details of some implementation issues in distributed environments are thoroughly investigated. Experiments demonstrate that the proposed method is effective for the distributed training of deep neural networks. Compared with stochastic gradient methods, it is more robust and may give better test accuracy.

Symptomatic cord compression by paraspinal musculature following cervical laminectomy: rare complication.

PURPOSE: Cervical laminectomy is an effective treatment for multilevel cervical compressive myelopathy. Symptomatic spinal cord compression (SSCC) by paraspinal musculature (PSM) following cervical laminectomy is rarely reported. The aim of this study was to evaluate the frequency and pathogenesis of this complication after cervical laminectomy. METHODS: Between 2007 and 2016, the medical records of 1309 cervical laminectomy patients were reviewed. From these 1309 records, seven patients (five men and two women; average age, 64.12 years; range 48-78 years) with SSCC by PSM following cervical laminectomy were identified. The incidence and possible risk factors of this rare condition were evaluated. RESULTS: The frequency of SSCC by PSM following cervical laminectomy was 0.53%. Presenting symptoms included paralyses and paresthesias, depending on the level and severity of cervical spinal cord compression. The initial onset of neurologic deterioration varied from 12 h to 21 days after operation. Most patients recovered well after surgical management with an average Barthel index of 74.3 at 6 months after surgery. In comparison with 63 controls, this rare complication was associated with preoperative cervical kyphosis, prior antiplatelet therapy, and posterior decompression with prone position. CONCLUSIONS: SSCC by PSM is a rare but devastating complication following cervical laminectomy, especially in those patients with preoperative kyphosis, prior antiplatelet treatment, and decompression with prone position. MRI is an ideal tool to identify this complication. Rapid cervical cord decompression and avoidance of recurrent compressive events can achieve a good clinical outcome. These slides can be retrieved under Electronic Supplementary Material.

Correlations between clinical hormone change and pathological features of pituicytoma.

PURPOSE: Pituicytoma is a rare low-grade glioma arising from the pituicytes of the posterior pituitary. To date, the clinical and pathological correlates of pituicytoma have not been investigated. This study was thus designed to examine the correlation between pituicytoma and the normal pituitary gland. METHODS: The records of patients who underwent pituitary surgery at Chang Gung Memorial Hospital in Linkou, Taiwan between 2000 and 2016 were reviewed. Patients who received a pathological diagnosis of pituicytoma were included; however, those with inadequate specimens for pathological study were excluded. Clinical information, including patients' presenting symptoms, serum hormone levels, neuroimages, and specimens, were collected. Hematoxylin and eosin stains and immunohistochemical (IHC) stains were performed for differential diagnosis. RESULTS: Among the 1532 patients who underwent pituitary surgery, nine (0.59%) received a pathological diagnosis of pituicytoma. Two patients were excluded due to inadequate specimens. Among the seven remaining patients, six presented with hormone changes. The IHC stains revealed that pituicytoma has no secretory function; however, the resected pituitary glands showed positive results for hormone change. Coexisting pituicytoma and adrenocorticotropic hormone adenoma were identified in one patient with a diagnosis of Cushing disease. CONCLUSIONS: Pituicytoma revealed a negative endocrine secretory function through IHC staining. Additionally, pituicytoma is associated with hypersecretion of the pituitary gland both clinically and pathologically. Diagnosing pituicytoma before pathological confirmation is difficult because the tumour may present with hormone dysfunction. Therefore, IHC staining of specimens is useful to exclude the possibility of coexisting pituicytoma and pituitary adenoma.

Neurenteric cysts: risk factors and management of recurrence.

BACKGROUND: Neurenteric cysts are rare central nervous system lesions with excellent outcome after total excision. The authors report their experience in the management of these lesions, especially if recurrence occurs. Risk factors of recurrence were analyzed, which have never been reported according to the literature review. METHODS: Twelve patients underwent surgical treatment for neurenteric cysts from April 1998 to July 2015. We retrospectively reviewed the clinical, radiological, operative, and pathological findings for these patients. Correlations between clinical characteristics and recurrence were analyzed. RESULTS: This series included six intracranial and six intraspinal cases. Total resection was achieved in 4 of the 12 cases and partial resection in 8. Six of the patients that underwent partial resection suffered from recurrence, and an additional operation was needed in five. Three of the recurrent intracranial lesions had refractory symptoms and were finally controlled through cyst-peritoneal or ventricle-peritoneal shunts. Risk factors of recurrence were revealed as age ≦30 years old (p = 0.02), subtotal resection in the first operation (p = 0.01), and size of supratentorial NECs >30 ml (p = 0.04). Two-thirds of recurrences occurred in the first 2 years after treatment. CONCLUSIONS: NECs express high recurrence rates when total excision cannot be achieved. The preoperative diagnosis error plays a major role leading to an incorrect surgical strategy and recurrence. MRI with FLAIR and DWI is recommended to improve the preoperative diagnosis. Although timely reoperation is indicated for symptomatic recurrence, adhesion may cause reoperation to become more challenging. C-P or V-P shunts are suggested as the second-line treatment, resulting in excellent prognosis. Patients with mucin-secreting cells noted histologically are susceptible to recurrence.

Rutin, a flavonoid and principal component of saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model.

This study investigated the antifatigue effects of rutin, a flavonoid extracted from the ethyl acetate extract of S. involucrata. Mice were subjected to a weight-loaded forced swim test (WFST) on alternate days for 3 wk. Rutin was administered orally to the mice for 7 days in dosages of 15, 30, and 60 mg/kg body weight, and several biomarkers of physical fatigue were evaluated: swimming time, change in body weight, lipid peroxidation, lactic acid (LA), glycogen, and the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). On Day 7, the rutin-treated mice had a 3-fold longer exhaustive swimming time than the control mice, as well as significantly reduced blood LA concentrations. The 15, 30, and 60 mg/kg body weight rutin-supplemented groups displayed 11.2%, 22.5%, and 37.7% reduced malondialdehyde (MDA) concentrations, respectively, in brain and muscle tissues compared with the control exercised group. Our results indicated that the administration of rutin protected the mice against the depletion of SOD and GPx activities significantly. Following 7 days of rutin treatment, we sacrificed the mice and analyzed their soleus muscle and brain for peroxisome proliferator-activated receptor-α coactivator (PGC-1α) and sirtuin 1 (SIRT1) mRNA expression. We observed that rutin treatment increased PGC-1α and SIRT1 mRNA and protein expression. The changes in these markers of mitochondrial biogenesis were associated with increased maximal endurance capacity. The application of 2D gel electrophoresis to analyze the rutin-responsive protein profiles in the WFST mouse brain further revealed the upregulation of the CB1 cannabinoid receptor-interacting protein 1, myelin basic protein, Rho GDP dissociation inhibitor (GDI) alpha, and TPI, indicating that rutin might inhibit anxiety through the upregulation of the expression of anxiety-associated proteins. Western blot analysis of MAPK expression further confirmed the antianxiety effects of rutin. Our study results thus indicate that rutin treatment ameliorates the various impairments associated with physical fatigue.

Expression of LEF1 is an independent prognostic factor for patients with oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Lymphoid-enhancing factor 1 (LEF1) is a transcription factor mediating Wnt/ß-catenin signaling. In this study, we analyzed the clinicopathologic significance of LEF1 expression in oral squamous cell carcinoma (OSCC). METHODS: Expression levels of LEF1 in 135 cases of OSCC were determined by immunohistochemistry. The results were correlated with clinicopathologic parameters and patient outcome. RESULTS: LEF1 was only occasionally detected in basal and parabasal cells of nontumorous squamous epithelium. Overexpression of LEF1 was observed in 33 of 135 OSCCs (24%). LEF1 was more frequently expressed in moderately to poorly differentiated cancer (p = 0.0035) and was associated with lymphovascular invasion (p = 0.0252). Overexpression of LEF1 was significantly associated with poor prognosis (p = 0.0176, hazard ratio = 1.96, 95% CI = 1.02-3.75). Multivariate analysis revealed LEF1expression and margin status to be the significant independent predictors for overall survival. CONCLUSION: Our study suggests LEF1 expression in OSCC may play an important role in tumor progression and can be served as a predictor of poor prognosis for patients with OSCC.

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.

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.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

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.