Efficacy and tolerability of concomitant use of bedaquiline and delamanid for multidrug- and extensively drug-resistant tuberculosis: a systematic review and meta-analysis

alexandrossfakianakis shared this article with you from Inoreader Efficacy and tolerability of concomitant use of bedaquiline and delamanid for multidrug- and extensively drug-resistant tuberculosis: a systematic review and meta-analysis via Clinical Infectious Diseases Advance Access Abstract The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of WHO-defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95%CI: 64.3-81.8). Sputum culture conversion at six months ranged from 61-95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95%CI: 4.1-11.6) and few cardiac events were reported (0.8%, n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity. View on Web

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Efficacy and safety of rituximab biosimilars or reference product as first‐line treatment in patients with low‐tumour‐burden follicular lymphoma: A systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Efficacy and safety of rituximab biosimilars or reference product as first‐line treatment in patients with low‐tumour‐burden follicular lymphoma: A systematic review and meta‐analysis via Journal of Clinical Pharmacy and Therapeutics Follicular lymphoma is a subtype of B-cell Non-Hodgkin lymphoma and is the second most common lymphoma diagnosed in the United States and Western Europe. The role of rituximab in the first-line treatment of low-tumour-burden follicular lymphoma has been supported by a large number of data. However, whether rituximab biosimilars have the same efficacy and safety as the reference drug (MabThera) is still controversial. Electronic databases and the ClinicalTrail.gov website were extensively searched using relevant search criteria. Studies were screened according to inclusion and exclusion criteria. Then the risk of bias of the included studies was assessed using the RoB 2 assessment scale, and the RevMan 5.4 statistical software was used for meta-analysis. Finally, four clinical randomized controlled trials involving 1223 patients were included. There were no statistically significant differences in efficacy and safety between biosimilars and MabThera groups. Our study concluded that the efficacy and safety of rituximab biosimilars in the treatment of low-tumour-burden follicular lymphoma are highly similar to those of the original drug. Abstract What is Known and Objective The role of rituximab in the first-line treatment of low-tumour-burden follicular lymphoma (LTB-FL) has been supported by a large number of data. However, whether rituximab biosimilars have the same efficacy and safety as the reference drug (MabThera) is still controversial. Methods Electronic databases and the ClinicalTrail.gov website were extensively searched using relevant search criteria. The risk of bias of the included studies was assessed using the RoB 2 assessment scale, and the RevMan 5.4 statistical software was used for meta-analysis. Results and Discussion A total of 1223 patients were included in four clinical randomized controlled trials. There was no statistical difference in efficacy between biosimilars and MabThera groups (the objective response rate: RR = 1.00, 95% CI: 0.93–1.08, p = 0.92; the progression-free survival: RR = 1.04, 95% CI: 0.96–1.12, p = 0.30; the overall survival: RR = 1.00, 95% CI: 0.98–1.03, p = 0.76; the serious adverse events: RR = 1.15, 95% CI: 0.69–1.89, p = 0.59; the infusion-related reaction: RR = 0.91, 95% CI: 0.77–1.09, p = 0.32). In terms of safety, there was also no significant difference between two groups. What is New and Conclusion Our study concluded that the efficacy and safety of rituximab biosimilars in the treatment of LTB-FL are highly similar to those of the original drug. View on Web

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Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy

alexandrossfakianakis shared this article with you from Inoreader Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy via Neuro-Oncology Advance Access Abstract Background Ultra-high dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising anti-tumor efficacy compared to conventional dose rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes. Methods Cohorts of three-week-old male and female C57Bl/6 mice exposed to hypofractionated (2×10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months post-treatment. Animals were sacrificed 6 months post-irradiation and tissues analyzed for neurological and cerebrovascular decrements. Results The neurological impact of FLASH-RT was analyzed over a 6-month follow-up. FLASH-RT ameliorated neuroco gnitive decrements induced by CONV-RT and preserved synaptic plasticity and integrity at the electrophysiological (long-term potentiation), molecular (synaptophysin) and structural (Bassoon/Homer-1 bouton) levels in multiple brain regions. The benefits of FLASH-RT were also linked to reduced neuroinflammation (activated microglia) and a preservation of cerebrovascular structure, by maintaining aquaporin-4 levels and minimizing microglia colocalized to vessels. Conclusions Hypofractionated FLASH-RT affords significant and long-term normal tissue protection in the radiosensitive juvenile mouse brain when compared to CONV-RT. The capability of FLASH-RT to preserve critical cognitive outcomes and electrophysiological properties over 6-months is noteworthy and highlight its potential for resolving long-standing complications faced by pediatric brain tumor survivors. While care must be exercised before clinical translation is realized, present findings document the marked benefit s of FLASH-RT that extend from synapse to cognition and the microvasculature. View on Web

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