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Cassidy Driscoll posted an update 1 day, 3 hours ago
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients.
Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939.
Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout.
Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%).
Idebenone’s potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.
Idebenone’s potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.Antibiotics are widely used to treat various inflammatory bowel diseases caused by enterotoxigenic Escherichia coli (ETEC). However, continuous use of antibiotics may lead to drug resistance. In this study, we investigated the role of human β-defensin 118 (DEFB118) in regulating the ETEC-induced inflammation and intestinal injury. ETEC-challenged or non-challenged mice were treated by different concentrations of DEFB118. We show that ETEC infection significantly increased fecal score (P less then 0.05) and serum concentrations of interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Moreover, the concentrations of D-lactic acid, C-reactive protein (CRP), creatinine (CREA), and urea (P less then 0.05) were both increased in the ETEC-challenged mice. However, DEFB118 significantly decreased their concentrations in the serum (P less then 0.05). DEFB118 not only alleviated tissue damage in spleen upon ETEC challenge, but also increased the villus height in duodenum and ileum (P less then 0.05). Moreover, DEFB118 improved the localization and abundance of tight junction protein ZO-1 in jejunal epithelium. Interestingly, DEFB118 decreased the expression levels of critical genes involving in mucosal inflammatory responses (NF-κB, TLR4, IL-1β, and TNF-α) and the apoptosis (caspase3) upon ETEC challenge (P less then 0.05), whereas DEFB118 significantly upregulated the expression of mucosa functional genes such as the mucin1 (MUC1) and sodium-glucose transporter-1 (SGLT-1) in the ETEC-challenged mice (P less then 0.05). These results indicated a novel function of the DEFB118. The anti-inflammatory effect of DEFB118 should make it an attractive candidate to prevent various bacteria-induced inflammatory bowel diseases.In inflammatory rheumatic disorders, the immune system attacks and damages the connective tissues and invariably internal organs. During the past decade, remarkable advances having been made towards our understanding on the cellular and molecular mechanisms involved in rheumatic diseases. The discovery of IL-23/IL-17 axis and the delineation of its important role in the inflammation led to the introduction of many needed new therapeutic tools. We will present an overview of the rationale for targeting therapeutically the IL-23/IL-17 axis in rheumatic diseases and the clinical benefit which has been realized so far. Finally, we will discuss the complex interrelationship between IL-23 and IL-17 and the possible uncoupling in certain disease settings.
Hyperbaric oxygen therapy (HBOT) improves short-term outcomes for ulcerative colitis (UC) patients hospitalized for acute flares. Longer-term impacts and cost-effectiveness are unknown.
We compared disease outcomes and cost-effectiveness of HBOT in addition to standard ofcare versus standard of care alonefor UC patients hospitalized for acute flares using a microsimulation model. Published literature was used for transition probabilities, costs, and quality-adjusted life year (QALY) estimates. We modeled 100,000 individuals in each group over a 5-year horizon and compared rates of re-hospitalization, rescue medical therapy, colectomy, death, and cost-effectiveness at a willingness-to-pay of $100,000/QALY. Probabilistic sensitivity analyses were performed with 500 samples and 250 trials, in addition to multiple microsimulation sensitivity analyses.
The use of HBOT at the time of index hospitalization for an acute UC flare is projected to reduce the risk of re-hospitalization, inpatient rescue medical therapy, and inpatient emergent colectomy by over 60% (p < 0.001) and mortality by over 30% (p <0.001), during a 5-year horizon. The HBOT strategy costs more ($5600 incremental cost) but also yielded higher QALYs (0.13 incremental yield), resulting in this strategy being cost-effective ($43,000/QALY). selleck kinase inhibitor Results were sensitive to HBOT costs and rates of endoscopic improvement with HBOT. Probabilistic sensitivity analyses observed HBOT to be more cost-effective than standard of care in 95% of iterations.
The use of HBOT to optimize response to steroids during the index hospitalization for an acute UC flare is cost-effective and is projected to result in significant reductions in disease-related complications in the long term.
The use of HBOT to optimize response to steroids during the index hospitalization for an acute UC flare is cost-effective and is projected to result in significant reductions in disease-related complications in the long term.