Effects of direct-acting antiviral therapy for patients with advanced hepatocellular carcinoma and concomitant hepatitis C-A population-based cohort study.

OBJECTIVE: We analyzed real-world data to elucidate the effects of anti-Hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy on survival in patients with advanced hepatocellular carcinoma (HCC) and concomitant HCV infection treated with sorafenib. MATERIALS AND METHODS: This population-based retrospective cohort study used the Taiwan National Health Insurance Research Database and the Registration System for Patients Treated with Oral Hepatitis C Antivirals to identify patients with advanced HCC and concomitant HCV infection who received initial targeted therapy (sorafenib) in 2018-2019. The overall survival (OS) of the DAA and non-DAA groups were compared using the Kaplan-Meier survival analysis. Propensity score matching was performed using a ratio of 1:4 to reduce confounding between the DAA and non-DAA groups. RESULTS: The study included 1,684 patients (122 DAA and 1,562 non-DAA users) with HCC and concomitant HCV infection who used sorafenib for the first time in 2018-2019. The Kaplan-Meier survival analysis indicated that advanced HCC patients who used DAAs had longer OS compared to non-DAA patients. The mean survival times were 20.7 months for DAA and 12.5 months for non-DAA. Results obtained after propensity matching indicated a significant difference in OS between the DAA and non-DAA groups. CONCLUSIONS: The analysis of big data from the Taiwan National Health Insurance Research Database revealed that advanced HCC patients on sorafenib benefited from DAAs as a treatment for HCV infection. Patients whose HCV infection was cured had better OS.

Real-world results of immune checkpoint inhibitors from the Taiwan National Health Insurance Registration System.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are a major advance in cancer treatment, but their payment benefits are unclear, resulting in financial risk. In Taiwan, the National Health Insurance Administration (NHIA) has adapted risk-sharing mechanisms to cover ICIs by collecting and assessing real-world evidence, such as case registration data, to adjust benefit packages for each medication, increase payment benefits of ICIs, and enable national health insurance sustainability. PATIENTS AND METHODS: This nationwide, multicenter, retrospective cohort study assessed the real-world use, effectiveness, and safety of ICIs reimbursed by the NHIA for treating multiple advanced cancers in Taiwan. We obtained data mainly from the NHIA Immune Checkpoint Inhibitor Registry Database. RESULTS: Between April 1, 2019, and March 31, 2020, 1644 patients received at least one dose of ICIs. The overall response rate (RR) was 29.1%. The metastatic urothelial carcinoma of patients ineligible for chemotherapy showed the highest RR. The estimated median progression-free survival (PFS) was 2.8 months (95% confidence interval [CI]=2.7-3 months), and renal cell carcinoma showed the longest PFS. The median PFS was reached in patients with most cancers except classic Hodgkin's lymphoma, which had a small sample size. The estimated survival probability was 50%. CONCLUSIONS: Under the national registration tracking system, Taiwan's high-cost drug policy has enabled access to new medicines and maximized patient benefits.

Anti-malarial and anti-inflammatory effects of Gleichenia truncata mediated through inhibition of GSK3ß.

Gleichenia truncata is a highland fern from the Gleicheniaceae family known for its traditional use among indigenous communities in Asia to treat fever. The scientific basis of its effect has yet to be documented. A yeast-based kinase assay conducted in our laboratory revealed that crude methanolic extract (CME) of G. truncata exhibited glycogen synthase kinase-3 (GSK3)-inhibitory activity. GSK3ß is now recognized to have a pivotal role in the regulation of inflammatory response during bacterial infections. We have also previously shown that lithium chloride (LiCl), a GSK3 inhibitor suppressed development of Plasmodium berghei in a murine model of malarial infection. The present study is aimed at evaluating G. truncata for its anti-malarial and anti-inflammatory effects using in vivo malarial and melioidosis infection models respectively. In a four-day suppressive test, intraperitoneal injections of up to 250 mg/kg body weight (bw) G. truncata CME into P.berghei-infected mice suppressed parasitaemia development by >60%. Intraperitoneal administration of 150 mg/kg bw G. truncata CME into Burkholderia pseudomallei-infected mice improved survivability by 44%. G. truncata CME lowered levels of pro-inflammatory cytokines (TNF-α, IFN-γ) in serum and organs of B. pseudomallei-infected mice. In both infections, increased phosphorylations (Ser9) of GSK3ß were detected in organ samples of animals administered with G. truncata CME compared to controls. Taken together, results from this study strongly suggest that the anti-malarial and anti-inflammatory effects elicited by G. truncata in part were mediated through inhibition of GSK3ß. The findings provide scientific basis for the ethnomedicinal use of this fern to treat inflammation-associated symptoms.

Biological conversion of wood hydrolysate to succinic acid by Anaerobiospirillum succiniciproducens.

Anaerobiospirillum succiniciproducens grew on a minimal salts medium containing wood hydrolysate (equivalent to 27 g glucose l(-1)) and, when supplemented with 10 g corn steep liquor l(-1) as a complex nitrogen source, succinic acid at 24 g l(-1) was obtained (yield = 88% w/w glucose). This may therefore be an economical method to produce succinic acid.

Clinical and electrophysiological characteristics in children with atrioventricular nodal reentrant tachycardia.

Atrioventricular (AV) nodal reentrant tachycardia is one of the most common supraventricular tachycardias in childhood. However, information about AV nodal reentrant tachycardia in childhood is limited, especially about the variant and multiple forms. The purpose of this retrospective study was to investigate the clinical and electrophysiological characteristics in pediatric patients with AV nodal reentrant tachycardia. Forty-eight pediatric patients with AV nodal reentrant tachycardia were included (ages 11-18 years; 25 males and 23 females). The age of onset and duration of symptoms were significantly younger and shorter in pediatric patients, respectively. A higher incidence of antegrade dual AV nodal pathways was found in adult patients than pediatric patients (72.9 vs 52.1% p = 0.003). Both antegrade and retrograde slow pathway functions were better in pediatric than adult patients. There was no significant difference between children and adults in the occurrence of variant and multiple forms of AV nodal reentrant tachycardia. This study demonstrated that pediatric patients have different electrophysiologic characteristics from those of adult patients.

Small intestinal mucosal hyperplasia caused by an enterokinase inhibitor from red kidney bean in rats.

A specific enterokinase inhibitor (EKI) was purified from red kidney bean (RKB). Male weanling rats fed a diet containing this purified EKI (0.06%) for 6 d showed increases in mucosal weights, protein, DNA and lactic dehydrogenase contents in their small intestines compared to age-matched control rats fed a standard diet. Total mucosal EK and disaccharidase activities were, however, decreased in EKI-fed rats. Thus, oral consumption of EKI from RKB led to small intestinal mucosal hyperplasia in rats. The mucosal hyperplasia observed in EKI-fed rats is not likely due to decreased turnover of mucosal proteins as a result of reduced luminal proteases since luminal contents of trypsin, chymotrypsin and elastase in EKI-fed rats were similar to those of control rats. Enterokinase inhibitor may have a direct hyperplastic effect on the small intestine of rats.

Fine-needle aspiration biopsy in diagnosis of soft tissue infections.

This study explores the efficacy of fine-needle tissue aspiration biopsy in the diagnosis of soft tissue infections that cannot be sampled satisfactorily by regular microbiological techniques. Aspiration biopsy was performed on 50 patients with presumptive soft tissue infections. The conditions investigated were decubitus, diabetic, ischemic, venous, and traumatic ulcers (2, 6, 1, 2, and 7 patients, respectively), cellulitis (23 patients), chronic osteomyelitis (5 patients), and infected surgical wounds (4 patients). Where possible, comparison with superficial cultures was made. All of the cultures obtained from aspirate samples taken from ulcers, chronic osteomyelitis, and infected surgical wounds were positive. In cellulitis, cultures from aspirates were positive in 30 and 81% of the cases, respectively, depending on the presence or absence of concomitant antimicrobial therapy. These results suggest that fine-needle deep tissue aspiration biopsy is reliable and clinically applicable for deep tissue sample collection. The procedure is simple, brief, and does not cause significant discomfort to the patient. It also plays an important role in providing a guideline for antimicrobial therapy.

Pancreatic and intestinal digestive enzymes in post-weanling rats with hypothalamic obesity.

Male Sprague-Dawley rats received bilateral electrolytic lesions in the ventromedial hypothalamic nuclei (VMNL rats) at the age of 31 days; sham-lesioned rats served as controls. For 28 post-operative days all animals self-selected from three synthetic diets, each high in carbohydrate, fat and protein, respectively. Following this, half of the VMNL rats and half of the controls were switched to lab chow for 14 days. Body weights were comparable among the groups, but linear growth was greatly reduced and body fat (Lee Index) was elevated in VMNL rats, irrespective of diet. In the sham-lesioned controls, the synthetic diets reduced most parameters of exocrine pancreatic activity. In VMNL rats, in contrast, pancreatic parameters were unaffected by the synthetic diet. The data suggest that VMN lesions disinhibit the exocrine pancreas. In contrast, most parameters of intestinal activity were not influenced by VMN lesions.

Pancreatic growth and enzyme profiles in weanling rats with normophagic hypothalamic obesity.

Weanling male rats with ventromedial hypothalamic lesions (VMNL rats) and sham-operated controls were killed 1, 2, 4, and 5 weeks postoperatively. The VMNL rats developed normophagic hypothalamic obesity in the presence of normal body weight and reduced linear growth. In both VMNL and control rats, pancreatic weight and protein content increased with time but were lower in the lesioned animals. Pancreatic DNA content was arrested in VMNL rats and remained so during the remainder of the experiment. The only significant enzyme changes (trypsinogen, amylase, and lipase) were evident in higher trypsinogen concentration in VMNL rats during 2 and 4 weeks after lesion production. In view of previous data on both hypophysectomized and VMNL rats and the known role of the ventromedial hypothalamic nucleus in neuroendocrine and neuroautonomic function, it is speculated that the changes observed here are in part due to disruption of neuroendocrine and in part due to disturbance of neuroautonomic control systems.

Effect of glucose and insulin on small intestinal brush border enzymes in fasted rats.

Fasting reduced small intestinal length. It also decreased mucosal weight, DNA and protein content, and concentrations of enterokinase, maltase, and sucrase in both duodenal and jejunal segments. In contrast, the concentrations of lactase and leucine aminopeptidase were not affected. Concomitantly, serum insulin levels dropped to one-fifth of the control levels while serum glucose concentrations showed a lesser degree of reduction. Glucose supplementation alone raised the serum insulin level, prevented the decrease in DNA content, and showed a protective effect on mucosal protein, mucosal weight, mucosal thickness, and villus height. Glucose also protected the sucrase and maltase concentrations; more significantly for maltase in the jejunal segment. Insulin alone, although it increased the serum insulin level to that found with glucose supplementation alone, had no protective effect on the loss in protein, DNA, and most enzymes except for maltase concentration in the jejunal segment. Addition of insulin to glucose did not modify the glucose effect on the contents of DNA, protein, and concentrations of sucrase and maltase. These results suggest that the glucose effect on the mucosa is not mediated by insulin. In addition, the retention of both maltase and sucrase activities through only glucose supplementation suggests the loss of maltase and sucrase in fasting is due to nutrient rather than specific substrate restriction.