Case Report: Local Treatment of a Leishmania tropica Infection in a Syrian Child with a Novel Filmogenic Preparation of Pharmaceutical Sodium Chlorite (LeiProtect®)

Cutaneous leishmaniasis (CL) frequently entails chronic skin lesions that heal only slowly. Until now, the available therapeutic options are very limited. Here, we present a case of a 5½-year-old Syrian refugee with two progressive lower-leg skin ulcers caused by Leishmania tropica. The patient received topical treatment with LeiProtect®, a newly developed, hydroxypropylcellulose-based, filmogenic gel containing nontoxic concentrations of pharmaceutical sodium chlorite. The skin lesions completely healed within 8 weeks and did not relapse during 1 year of follow-up, underlining the efficacy of this novel local therapy of CL.

Injectable “nano-micron” combined gene-hydrogel microspheres for local treatment of osteoarthritis

Sustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA) through the delivery of therapeutic microRNAs (miRNAs) to targeted cells. However, direct injection of crude miRNAs for local gene therapy is limited due to its inadequate transfection efficiency, easy inactivation, and short half-life. Here, a multifunctional gene vector, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP), was employed to form G5-AHP/miR-140 nanoparticles by forming a complex with microRNA-140 (miR-140). Then, the nanoparticles were entrapped in hydrogel microspheres (MSs) to construct a “nano-micron” combined gene hydrogel to alleviate the degradation of articular cartilage. Monodisperse gelatin methacryloyl hydrogel MSs were produced under ultraviolet light using one-step innovative microfluidic technology. Evenly dispersed MSs showed better injectability in sustainable and matrix metalloproteinases (MMPs)-responsive degradation methods for local gene delivery. The G5-AHP/miR-140 nanoparticles released from the MSs exhibited high gene transfection efficacy and long-term bioactivity, facilitated endocytosis, and thus maintained the metabolic balance of cartilage matrix by promoting the expression of type II collagen and inhibiting the expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and MMP13 in chondrocytes. After injection of the “nano-micron” combined gene hydrogel into the articular cavity of the OA model, the gene hydrogel increased G5-AHP/miR-140 nanoparticle retention, prevented articular cartilage degeneration, and reduced osteophyte formation in a surgically induced mouse model of OA. The present study provides a novel cell-free approach to alleviate the progression of OA that shows potential for locally injected gene delivery systems.

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Glioblastoma is an unmet clinical need. Local treatment strategies offer advantages, such as the possibility to bypass the blood–brain barrier, achieving high drug concentrations at the glioblastoma site, and consequently reducing systemic toxicity. In this study, we evaluated the feasibility of using hyaluronic acid (HA) for the local treatment of glioblastoma. HA was conjugated to doxorubicin (DOX) with distinct bio-responsive linkers (direct amide conjugation HA-NH-DOX), direct hydrazone conjugation (HA-Hz-DOX), and adipic hydrazone (HA-AdpHz-DOX). All HA-DOX conjugates displayed a small size (less than 30 nm), suitable for brain diffusion. HA-Hz-DOX showed the best performance in killing GBM cells in both 2D and 3D in vitro models and displayed superior activity in a subcutaneous GL261 tumor model in vivo compared to free DOX and other HA-DOX conjugates. Altogether, these results demonstrate the feasibility of HA as a polymeric platform for the local treatment of glioblastoma and the importance of rationally designing conjugates.

Aggressive local treatment for recurrent intrahepatic cholangiocarcinoma—Stereotactic radiofrequency ablation as a valuable addition to hepatic resection

Background To evaluate the efficacy, safety and overall clinical outcome of local treatment for recurrent intrahepatic cholangiocellular carcinoma after hepatic resection. Methods Between 2007 and 2019 72 consecutive patients underwent hepatic resection for primary intrahepatic cholangiocellular carcinoma. If amenable, recurrent tumors were aggressively treated by HR or stereotactic radiofrequency ablation with local curative intent. Endpoints consisted of morbidity and mortality, locoregional and de novo recurrence, disease free survival, and overall survival. Results After a median follow-up of 28 months, recurrence of intrahepatic cholangiocellular carcinoma was observed in 43 of 72 patients undergoing hepatic resection (60.3%). 16 patients were subsequently treated by hepatic resection (n = 5) and stereotactic radiofrequency ablation (n = 11) with local curative intention. The remaining 27 patients underwent palliative treatment for first recurrence. Overall survival of patients who underwent repeated aggressive liver-directed therapy was comparable to patients without recurrence (p = 0.938) and was better as compared to patients receiving palliative treatment (p = 0.018). The 5-year overall survival rates for patients without recurrence, the repeated liver-directed treatment group and the palliative treatment group were 54.3%, 47.7% and 12.3%, respectively. By adding stereotactic radiofrequency ablation as an alternative treatment option, the rate of curative re-treatment increased from 11.9% to 37.2%. Conclusion Repeated hepatic resection is often precluded due to patient morbidity or anatomical and functional limitations. Due to the application of stereotactic radiofrequency ablation in case of recurrent intrahepatic cholangiocellular carcinoma, the number of patients treated with curative intent can be increased. This leads to favorable clinical outcome as compared to palliative treatment of intrahepatic cholangiocellular carcinoma recurrence.

Effect of Topical PTH 1-34 Functionalized to Biogran® in the Process of Alveolar Repair in Rats Submitted to Orchiectomy

(1) Background: There are many therapies for osteoporosis control and bone maintenance; anabolic drugs such as teriparatide and bone grafts help in the repair process and stimulate bone formation. Thus, the aim of the present study was to evaluate the behavior of repaired bone in the presence of PTH (teriparatide) associated with Biogran® (biomaterial) through a sonochemical procedure after extraction in rats. (2) Methods: The insertion of Biogran® with PTH in the alveolus was performed 30 days after incisor extraction. Euthanasia occurred after 60 days. (3) Results: The use of local treatment of PTH loaded with Biogran® in healthy rats promoted good results for micro-CT, with an increase in percentage and bone volume, number and trabecular separation and less total porosity. Greater immunostaining for Wnt, β-Catenin and osteocalcin proteins and lower expression for Thrombospondin-Related Adhesive Protein (TRAP), which shows an increase in the number of osteoblasts and inhibition of osteoclast action. However, the treated orchiectomized groups did not obtain such expressive results. (4) Conclusion: The use of Biogran® with PTH improved alveolar repair in rats. However, new researches with more efficient doses must be studied to collaborate effectively with the formation of a quality bone after the orchiectomy.

Hypericum perforatum and Azadirachta indica (Neem) oil in the management of chronic leg ulcers: An uncontrolled retrospective observational case review

Chronic nonhealing leg ulcers are debilitating with high morbidity in a vulnerable patient population and pose a frequent clinical and socioeconomic problem. Numerous local treatment options exist, but clinical trials are rare and wound management still represents a big challenge. Recently a wound dressing based on the natural remedies Hypericum perforatum and Neem oil has been proposed for chronic wound management, but trials on nonhealing leg ulcers are missing. Uncontrolled retrospective observational case review on all patients under our supervision with chronic leg ulcers who underwent treatment with a plant-derived wound dressing based on Hypericum perforatum and Azadirachta indica (Neem) oil. It could be retrieved in a total 16 cases (11 female) with a median age of 71 years. All ulcers (7 ulcers on the leg and 9 ulcers on the feed) showed a complete healing after a median healing time of 82 days (Mean 85, range 14-180 days). No side effects occurred, medication was painless or even reduced pain. Wound dressings based on Hypericum perforatum and Neem oil are well tolerated and could be a potential additional simple treatment option in the management of non-healing leg ulcers. Prospective controlled trials are needed to confirm these observations.

Effectiveness of Perioperative Local Use of Anesthetics and Antiseptics in Patients with Purulent-necrotic Lesions of Lower Extremities in Diabetes Mellitus

Background: Every second patient with the diabetes mellitus (DM) needs surgery due to purulent-necrotic changes in the feet. The aim of the study was comparative morphological examination of the course of the wound process in purulent-necrotic lesions of the lower extremities of patients with DM with different approaches to local treatment in the perioperative period. Materials and Methods: We investigated changes in the histological structure and the nature of the reactions of skin tissues, muscles and fascia during the healing of an ulcer in patients with the diabetes mellitus after various types of local treatment. Then the specimens were photographed and analyzed using the OLIMPUS BX 41 light microscope. Results: In the first comparison group, which used standard anesthesia techniques and locally antiseptic povidon-iodine - granulation tissue was characterized by the complete absence of fibrous structures and the presence of a small number of small-sized neoplastic vessels with swollen endothelium. And in patients of the II observation group who received locally decamethoxin and infiltration anesthesia with a 2% solution of lidocaine after surgery during the study of histological preparations of the affected tissues, a significant decrease in signs of pathological vascular reaction was established compared with the comparison group. Conclusions: In group 1 (control) healing of wounds on the third-seventh day is characterized by somewhat slow regeneration. Wound healing was most favorable in patients of the second group, where infiltration anesthesia was used by local anesthetic and antiseptic decamethoxin.