Gradyschou3402

Protein receptors located on cellular membrane play a role in maintaining intercellular connections as well as corneal hydration. Discussion/ Conclusion These studies prompt development of novel therapeutic strategies such as tear drops or ointments that target certain proteins to maintain corneal homeostasis. However, more in vitro and in vivo studies are required to prove the effectiveness of exogenous administration of molecules in improving healing outcome. Hence, more future investigation of the molecular pathways highlighted in this review will reveal novel therapeutic tools such as gene or cell therapy to treat corneal diseases.Introduction Anti-inflammatory, topical therapy of severe keratitis in Dry Eye Disease (DED) and ocular Graft-versus-Host Disease (oGvHD) includes steroids, cyclosporine (Cs) and others. In Germany a commercial product containing 0.1 % Cs in a cationic formulation is available since 2015. Objective The aim of this study was to present real-life data using cationic 0.1 % Cs in oGvHD patients. Methods Retrospective study of n=26 oGvHD and n=41 DED patients with corneal staining of at least Oxford grade III. GSK-3 activity Parameters analyzed were OSDI, corneal staining, IOP, TFBUT, Schirmer and visual acuity. In addition it was evaluated, how different Cs formulations were tolerated. Results Corneal staining improved significantly in one eye in DED but not in oGvHD. In DED cationic 0.1 % Cs was not tolerated by 32 % of the patients, in contrast to 0.05 % Cs in castor oil not tolerated by 47 % and liposomal 0.05 % Cs by 63 %. In oGvHD patients cationic 0.1 % Cs was not tolerated by 62 %, 0.05 % Cs in castor oil by 33 % and liposomal 0.05 % Cs by 39 % of the patients. Conclusions This study demonstrates differences between the tolerance of different Cs formulations depending on the underlying cause of severe keratitis. Cationic 0.1 % Cs is considerably less tolerated in oGvHD. As oGvHD patients were excluded from clinical trials leading to approval of the commercial product, its use should be considered with care.Background FOLFIRI plus bevacizumab have been widely used as first-line treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab versus FOLFIRI plus bevacizumab. Methods The subjects comprised 120 chemotherapy-naïve patients with mCRC. The study group received a 24-h infusion of irinotecan at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1-14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a dose of 150 mg/m2, 5-fluorouracil given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2,400 mg/m2 as a 46-h infusion, and 200 mg/m2 leucovorin on days 1 and 15. Bevacizumab was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results From December 2013 through January 2018, 120 patients were randomly assigned, 61 patients to the 24h-SIRI/B and 59 patients to the FOLFIRI/B. The median follow-up period was 22.8 months. The 1-year PFS rate was 43.14% in the 24h-SIRI/B arm and 19.15% in the FOLFIRI/B arm (HR = 0.312 [95%CI 0.13-0.78], p = 0.01). The median PFS was 10.2 months (95%CI 8.8-14.3) and 10.0 months (95%CI 7.4-11.0), and the median OS was 29.7 months (95%CI 22.9-43.9) and 28.8 months (95%CI 18.4-ND), respectively (p = 0.3758, p = 0.8234). The overall RR was 86.3 and 61.7%, respectively (p = 0.0053). AEs were similar. Conclusions Our results show that the 24h-SIRI/B regimen is an effective and reasonably well-tolerated regimen for the first-line treatment of mCRC.Introduction Spinal cord injury (SCI) causes most severe motor and sensory dysfunctions. In Chinese traditional medicine, the agonist of a purinergic receptor is believed to have a positive effect on SCIs, and 2-Methylthio-adenosine-5'-diphosphate (2-MesADP) is a selective agonist of the P2Y purinergic receptor. Methods To investigate its therapeutic function and molecular mechanism in SCI, transcriptome analysis associated with weighted gene co-expression network analysis (WGCNA) was carried out at various time points after T9 crush injury. Results 2-MesADP demonstrated recovery of limb motor function at the 6 weeks after injury, accompanied by neuronal regeneration and axon remyelination at 2 and 6 weeks. Furthermore, gene profiling revealed alternated gene expression with the treatment of 2-MesADP. These genes were assigned to a total of 38 modules, followed by gene ontology analysis; of these, 18 represented neuronal apoptosis and regeneration, immune response, synaptic transmission, cell cycle, and angiogenesis. In the neuronal apoptosis and regeneration module, Nefh, NeuroD6, and Dcx in the 2-MesADP group were noticed due to their interesting expression pattern. The gene expression patterns of Mag, Mog, and Cnp, which played key roles in myelination, were significantly changed with the treatment of 2-MesADP. Wnt signal pathway was the most important pathway in 2-MesADP treatment for acute SCI. Conclusion 2-MesADP enhanced locomotor recovery in mouse SCI by altering the expression of neuronal apoptosis and remyelination-related genes and Wnt signaling pathways.Objectives To assess the validity of the subtotal petrosectomy (STP) technique in problematic cases of cochlear implant (CI) surgery, and review indications, outcomes, and related controversies. Study design This is a retrospective review of data from a private quaternary referral center of otology and skull base surgery. Patients and methods A review of patients who underwent CI with STP (STP-CI) as the leading approach was performed. Demographics, indications, surgical details, and main outcomes were evaluated. The surgeries performed were usually single-stage procedures encompassing a comprehensive mastoidectomy, blind sac closure of the external auditory canal (EAC), and mastoid obliteration with autologous fat. Results A total of 107 cases were included. Mean follow-up was 7.1 years (range 1-13 years). The most frequent indication for STP-CI was chronic otitis media with/without cholesteatoma (32.7%), followed by open mastoid cavity (26.1%), and cochlear ossification (17.7%). Other difficult conditions where STP facilitates successful implantation include inner-ear malformations, temporal-bone trauma, unfavorable anatomic conditions, and revision surgery.