Toxicity and response to ipilimumab and nivolumab in older patients with metastatic melanoma: A multicentre retrospective analysis.

Combination immunotherapy with nivolumab and ipilimumab is an effective therapy in the treatment of metastatic melanoma, however, its benefit in older patients is unclear. A multicentre retrospective study was performed to compare the efficacy and toxicity of combination immunotherapy in metastatic melanoma in patients ≥65 years versus <65 years, and complications of steroids used to manage toxicity. One hundred and thirty-nine patients were included with 52 patients ≥65 years (median age: 70; range: 65-83) and 87 patients <65 years (median age: 52; range: 22-64). Median overall survival was similar in patients ≥65 years versus <65 years (14.9 vs. 17.3 months p = .58). Median progression-free survival was also similar in both groups (7.1 vs. 6.9 months p = .79), as was overall response rate (48.1% vs. 44.8% p = .73). Age was not associated with a difference in overall survival on multivariate analysis. There was similar rates of Grade 3 or higher adverse events in patients ≥65 years versus <65 years (50% vs. 49% p = 1.0) and discontinuation rates secondary to toxicity (55.8% vs. 56% p = 1.0). Median duration of steroids used to treat adverse events was similar (11 vs. 12 weeks p = .46). Complications of steroids requiring inpatient admission was numerically higher in the older patients (41.3% vs. 20.4% p = .07). Patients ≥65 years received similar benefit from combination immunotherapy in comparison to their younger counterparts with similar toxicity.

Reconstruction of Drug-induced Cleft Palate Using Bone Marrow Mesenchymal Stem Cell in Rodents.

BACKGROUND: Triamcinolone acetonide (TAC) (Kenacort*) is a commonly used synthetic glucocorticoid in today's medical practice. The drug is also a potential agent in inducing cleft palates in rats. This drug has been used to induce cleft palate in the fetus of the pregnant rats to bring out a suitable animal model for human cleft lip and palate. The drug was given intraperitoneally to induce congenital cleft palate in pregnant mother rats. AIM: The aim of this study is to induce congenital cleft palate in pregnant Wister albino rats and reconstruct the defect with bone marrow mesenchymal stem cells (BMSCs) isolated from the same species along with PLGA (poly lactic co glycolic acid) scaffold. METHODS: Twenty female animals were divided into two groups. Each group contains 10 animals. The animals were allowed to mate with male rat during the esterase period and the day, in hich vaginal plug was noticed was taken to be day 0. The pregnant rats were given triamcinolone acetonide (Kenacort* 10 mg/1 ml intramuscularly/intravenous [IM/IV] injections) injection intraperitoneally at two different dosages as the existing literature. The injection was given on the 10, 12, and 14th day of gestation. The clinical changes observed were recorded, and the change in the body weight was noted carefully. Group 1 which received 0.5 mg/kg body weight of TAC had many drug toxic effects. Group 2 which received 0.05 mg/kg body weight produced cleft palate in rat pups. The pups were divided into three groups. Group A control group without cell transplant, the cleft was allowed to close by itself. Group B containing palate reconstructed with plain PLGA scaffold (Bioscaffold, Singapore) without BMSC, Group C containing BMSC and PLGA scaffold (Bioscaffold, Singapore), Group C operated for the cleft palate reconstruction using BMSCs and PLGA scaffold. There was faster and efficient reconstruction of bone in the cleft defect in Group C while there was no defect closure in Group A and B. RESULTS: There was complete reconstruction of the cleft palate in the group of rat pups which received BMSCs along with PLGA scaffold. Bone growth in the cleft defect was faster; complete fusion of the defect was achieved. CONCLUSION: The dosage of drug used for inducing cleft palate was standardized in rodents for a definitive congenital cleft palate model. The cleft palate induced was reconstructed using BMSCs and PLGA scaffold. This was compared with a control group and the other group with plain PLGA used for reconstruction of the palate. This study will invite future research in the effect of the drug on human beings, especially on pregnant mothers.

Invivo comparative evaluation of tertiary dentin deposit to three different luting cements a histopathological study.

The aim of the study is to evaluate histopathologically the amount of tertiary dentin deposit stimulated by three different luting cements. With the informed consent for fifteen patients crown preparation was done for maxillary and mandibular premolar teeth which were scheduled for orthodontic extraction. Copings were cemented with three different luting cements zinc oxide eugenol, glass ionomer and zinc polycarboxylate which were classified as Groups A, B and C respectively. The teeth were later extracted and histopathologically analysed for pulpodentinal reactions using a control study group. Statistically Tukey-HSD procedure was used to identify the significant group and one way ANNOVA was used to analyse the thickness of tertiary dentin among the study group. Tertiary dentin was seen in most of the specimens. When the three groups were compared zinc oxide eugenol helps in stimulation of tertiary dentin formation.