Treatment of symptomatic oral mucositis with sodium hyaluronate and synthetic amino acid precursors of collagen in patients undergoing haematopoietic stem cell transplantation.

The purpose of the study is to evaluate the clinical effects of Mucosamin® (a spray preparation containing sodium hyaluronate combined with a pool of amino acids of precursor collagen, including L-Proline, L-Leucine, L-Lysine and glycine) on wound healing and pain management of oral mucositis after hematopoietic stem cell transplantation. The importance of professional dental hygiene by dental hygienist in reducing the severity of oral mucositis as unique therapy or in addition to therapy with Mucosamin® was also evaluated. One hundred thirty-seven patients undergoing hematopoietic stem cell transplantation were recruited in a case-control study and divided into 4 groups: Group A: professional oral hygiene + Mucosamin®; Group B: professional oral hygiene + standard treatment with chlorhexidine 0.20%;; Group C: only Mucosamin®; Group D: only standard treatment with chlorhexidine 0.20%. The following evaluations were made: WHO mucositis scale, OMAS mucositis scale, VAS, periodontal recording, days of mucositis. Comparing the groups at the onset of OM on WHO scale, it was observed that Group A grade 1 occurrence was more statistically significant than Group B (p= 0.03*); comparison between Group A and D showed a statistically significant difference in favour of Group A (p= 0.0002*). Also OMAS scale showed a statistically significant difference between groups who assumed Mucosamin, who developed lower OM grade (p = 0.001*). There was a statistically significant difference between group A compared with group B over the overall duration of OM (p = 0.02*), as well as between group A and group D (p=0.03*). According to the present study the combination of a careful debridement, correct oral hygiene during hospitalization and the use of Mucosamin® exponentially reduces the severity and duration of mucositis and consequently the discomfort of the patient. Moreover, it can be stated that the use of Mucosamin® also results in a reduction in the extent of chemotherapy lesions. Hyaluronic acid and amino acid-based sprays can be a valuable therapeutic aid in the treatment of mucositis.

HCV NS3 naturally occurring variants in HIV/HCV coinfected DAA-naïve patients: consideration for HCV genotyping resistance testing.

PURPOSE: Data on the frequency of HCV naturally occurring drug-resistant variants (RAVs) at baseline in HIV/HCV coinfected patients are scarce. METHODS: NS3-HCV RAVs were studied by full-population direct sequencing from plasma specimens of 345 DAA-naïve patients with HCV chronic hepatitis (159 of them with HIV/HCV-coinfection). RESULTS: NS3 RAVs were identified in 31.5 % of patients, with a significant proportion of HIV/HCV coinfected DAA-naïve patients compared to those with HCV monoinfection (38 vs. 25 % p = 0.0104, OR 1.84; 95 % CI 1.162-2.916). CONCLUSIONS: HCV resistance genotyping test before treatment may be worth in special populations such as HIV/HCV coinfection to optimize patient treatment.

Use of sodium hyaluronate and synthetic amino acid precursors of collagen for the symptomatic treatment of mucositis in patients undergoing haematopoietic stem cell transplants.

Oral mucositis (OM) may occur in up to 100% of patients undergoing condition regimen to hematopoietic stem cell transplant (HSCT). From the patient’s perspective, OM is one of the most debilitating side effects of transplantation. It is commonly thought that oral hygiene can modify the incidence and severity of oral mucositis, therefore professional oral health care (POHC) is recommended prior to conditioning regimen for HSCT. A new strategy for the treatment of OM is sodium hyaluronate (SH) combined with amino acid precursors of collagen (Aas) (Mucosamin®). SH is a mucoaderent polymer acting as a mechanical barrier and pain reliever. Furthermore, it allows prolonged contact of the product with the mucous membrane. In this study, a total of 68 adult patients due to undergo HSCT for allogenic and autologous transplant were enrolled at the Stem Cell Transplant Unit. The patients were divided into two groups. One group was treated with POHC before HSCT and applications of Mucosamin® during the recovery after transplantation. The second group served as controls, with the usual treatment of Clorexidine 0.20% adopted by the department. After HSCT the same clinician, an expert in oral medicine trained for the clinical trial, evaluated symptoms of the patients’ mucositis of both groups every day. The treated patients developed less severe OM, therefore Mucosamin® seems to have a protective role against the more severe phases of mucositis. The maximum OM pain, measured with the VAS scale, was higher in patients who did not use Mucosamin®. In the treated group OM resolved sooner than in the control group.

Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life.

OBJECTIVES: First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following three different strategies: A) with 'GRT-guided' regimens (N=18); B) with 'AASLD/EASL recommended, not GRT-guided' regimens (N=72); C) with 'not recommended, not GRT-guided' regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with 'GRT-guided' regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving 'AASLD/EASL recommended, not GRT-guided' regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a 'not recommended, not GRT-guided regimen' (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT. CONCLUSION: Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation.

Relationship between the early boceprevir-S isomer plasma concentrations and the onset of breakthrough during HCV genotype 1 triple therapy.

In a prospective cohort of 18 patients treated with boceprevir, we examined the role of boceprevir plasma concentration at the onset of breakthrough during the treatment. Nine patients experienced breakthrough during therapy. The resistance patterns were as follows: S122S/R, I132V, T54A/I132V, V156S/I170A, V36M/T54S/R155K, V36M/R155K and T54/R155K. Boceprevir-S isomer (SCH 534128) median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43-58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL. Low boceprevir plasma concentration can lead to virologic resistance; therapeutic drug monitoring should be used to prevent the onset of viral breakthrough during triple-regimen therapy with boceprevir.