Topical paromomycin with or without gentamicin for cutaneous leishmaniasis.

BACKGROUND: There is a need for a simple and efficacious treatment for cutaneous leishmaniasis with an acceptable side-effect profile. METHODS: We conducted a randomized, vehicle-controlled phase 3 trial of topical treatments containing 15% paromomycin, with and without 0.5% gentamicin, for cutaneous leishmaniasis caused by Leishmania major in Tunisia. We randomly assigned 375 patients with one to five ulcerative lesions from cutaneous leishmaniasis to receive a cream containing 15% paromomycin-0.5% gentamicin (called WR 279,396), 15% paromomycin alone, or vehicle control (with the same base as the other two creams but containing neither paromomycin nor gentamicin). Each lesion was treated once daily for 20 days. The primary end point was the cure of the index lesion. Cure was defined as at least 50% reduction in the size of the index lesion by 42 days, complete reepithelialization by 98 days, and absence of relapse by the end of the trial (168 days). Any withdrawal from the trial was considered a treatment failure. RESULTS: The rate of cure of the index lesion was 81% (95% confidence interval [CI], 73 to 87) for paromomycin-gentamicin, 82% (95% CI, 74 to 87) for paromomycin alone, and 58% (95% CI, 50 to 67) for vehicle control (P<0.001 for each treatment group vs. the vehicle-control group). Cure of the index lesion was accompanied by cure of all other lesions except in five patients, one in each of the paromomycin groups and three in the vehicle-control group. Mild-to-moderate application-site reactions were more frequent in the paromomycin groups than in the vehicle-control group. CONCLUSIONS: This trial provides evidence of the efficacy of paromomycin-gentamicin and paromomycin alone for ulcerative L. major disease. (Funded by the Department of the Army; ClinicalTrials.gov number, NCT00606580.).

Use of Polyurethane-Covered Stents for Exclusion of Pulmonary Arteriovenous Malformations.

PURPOSE: To evaluate the safety, technical success and short-term effectiveness of polyurethane-covered stent (PK Papyrus, BioTronik, Berlin) in the treatment of pulmonary arteriovenous malformations (PAVMs) that are not amenable to embolotherapy. MATERIALS AND METHODS: In this IRB-approved, retrospective study, data from patients who received polyurethane-covered stents for exclusion of PAVMs were analyzed. The study included 5 patients (all women) with a median age of 40 years (range 25-60). Patients presented with hypoxemia, TIAs, and/or epistaxis; 4 were confirmed to have HHT. All had multiple PAVMs diagnosed on chest CT and underwent embolization with other devices in addition to the polyurethane-covered stent. The indication for stent placement in all cases was a short and/or tortuous feeding artery. Safety was assessed by immediate or short-term complications, e.g., migration, stent thrombosis, and fracture. Technical success was defined as the ability to accurately place the stent at the intended location. Effectiveness was defined as successful exclusion of PAVM with no perfusion across the AVM. RESULTS: Technical success of stent placement was 100%. AVM exclusion rate was 80% after single stent deployment; in the case of incomplete exclusion, success was achieved using an overlapping stent to completely cover a second feeding artery. During the median follow-up period of 5 months (range 2-10), all stents remained patent, and AVMs were excluded without other complications. CONCLUSION: Exclusion of PAVMs with polyurethane-covered stents is technically feasible, safe, and shows short-term effectiveness for PAVMs with a short/tortuous feeding artery when traditional embolization techniques are not possible.

Improvement of pulmonary sarcoidosis following sleeve gastrectomy.

Pulmonary sarcoidosis is unlikely to resolve if it persists for greater than five years. A growing body of literature supports the involvement of the microbiome in sarcoidosis and a role for sex hormones in pulmonary fibrosis. Additionally, obesity is a risk factor for the development of sarcoidosis. Bariatric surgery is an effective treatment for obesity and can lead to microbial and endocrine changes. Here, we report the clinical improvement of longstanding pulmonary sarcoidosis following sleeve gastrectomy.

Topical paromomycin for New World cutaneous leishmaniasis.

BACKGROUND: Paromomycin-based topical treatments were shown to be effective in curing cutaneous leishmaniasis (CL) lesions caused by Leishmania major in Tunisia. Cure rates of an index lesion were approximately 80%. As a follow on, we conducted a similar Phase 3 trial in Panama to demonstrate the efficacy of these treatments against New World species. The primary objective was to determine if a combination topical cream (paromomycin-gentamicin) resulted in statistically superior final clinical cure rates of an index lesion compared to a paromomycin alone topical cream for the treatment of CL, primarily caused by Leishmania panamensis. METHODS: We conducted a randomized, double blind, Phase 3 trial of topical creams for the treatment of CL caused by Leishmania spp. Three hundred ninety nine patients with one to ten CL lesions were treated by topical application once daily for 20 days. The primary efficacy endpoint was percentage of subjects with clinical cure of an index lesion confirmed to contain Leishmania with no relapse. RESULTS: The clinical cure of the index lesion for paromomycin-gentamicin was 79% (95% CI; 72 to 84) and for paromomycin alone was 78% (95% CI; 74 to 87) (p = 0.84). The most common adverse events considered related to study cream application were mild to moderate dermatitis, pain, and pruritus. CONCLUSIONS: Superiority of paromomycin-gentamicin was not demonstrated. However, the approximately 80% cure rates for both topical creams were similar to those demonstrated in Tunisia and previously reported with parenteral antimonials.

PEG-based hydrogels with tunable degradation characteristics to control delivery of marrow stromal cells for tendon overuse injuries.

Marrow stromal cells (MSCs) have been suggested as a means to improve healing in tendon overuse injuries (tendinopathy), but optimal delivery methods for these cells have yet to be determined. In this study novel degradable hydrogels based on oligo(poly(ethylene glycol) fumarate) (OPF) and acrylated poly(ethylene glycol)-dithiothreitol (Ac PEG-DTT) with tunable degradation times ranging from a few days to >1 month were synthesized as MSC carriers for tendon overuse injuries. The addition of higher amounts of OPF or higher dithiothreitol (DTT) concentrations resulted in enhanced fold swelling and degradation. Three formulations, including non-degrading, slower degrading (degraded in ∼10 days) and faster degrading (degraded in ∼5 days) hydrogels were selected for studies with MSCs in tendon tissue explants that had been treated with collagenase as a reproducible model of tendinopathy. Quantitative analysis of the resulting histology images indicated that cell delivery from the hydrogels was dependent on the degradation rate, with cells present in the tissue only after hydrogel dissolution. In addition, significantly more cells were found in the tendon after 14 days with the fast degrading (53±19) vs. slow degrading (20±6) hydrogels. Based on these results, OPF/Ac PEG-DTT hydrogels provide a versatile biomaterial platform to control cell delivery and thus better identify dosing regimens required for MSC-based therapies for tendinopathy.