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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Evaluation of the transdentinal capability of the intrinsic antibacterial cetylpyridinium chloride/cholesterol sterosomes in vitro and in vivo

alexandrossfakianakis shared this article with you from Inoreader Evaluation of the transdentinal capability of the intrinsic antibacterial cetylpyridinium chloride/cholesterol sterosomes in vitro and in vivo via International Endodontic Journal Abstract Abstract Aim Dentinal tubules serve as disease-causing channels for infiltration and penetration of bacteria and their by-products; which are regarded as the major driver of pathogenesis in pulpal inflammation and infection. In this study, we aimed to evaluate the transdentinal potential of nanoscale cetylpyridinium chloride/cholesterol (CPC/Chol) sterosomes, which are a recently developed type of cationic non-phospholipid liposomal nanocarrier; as well as their intrinsic and universal antibacterial activity. Methodology CPC/Chol sterosomes were formulated, with a hydrodynamic diameter of 134 ± 4 nm, a low polydisperse index of 0.161 ± 0.007, and a positive zeta potential of 41 ± 3 mV at pH 7.4. Transdentinal diffusion ability of sterosomes was evaluated using human dentine blocks in vitro, and Wistar rat molar teeth in vivo. The intrinsic antibacterial activities of CPC/Chol sterosomes against E. faecalis, S. mutans, F. nucleatum, and P. gingivalis were further examined. Results CPC/Chol sterosomes successfully penetrated through the dentinal tubules, and diffused into the pulp, which could be internalized by dental pulp cells with a high efficiency. Additionally, they exhibited substantial levels of intrinsic antibacterial activity against these Gram-positive and Gram-negative endodontic bacteria and their biofilms. Conclusions Given its high penetration and diffusion ability through the dentine and pulp, great potential for multi-drug delivery, and distinct intrinsic antibacterial activity; sterosome-based nanocarriers might serve as a promising therapeutic strategy aimed at targeting various specific pathways associated with pulpal diseases. This will help determine and characterize the most appropriate prophylactic and therapeutic targets for early intervention in our future dentistry practice. View on Web

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Polygenic risk scores for prediction of breast cancer

alexandrossfakianakis shared this article with you from Inoreader Polygenic risk scores for prediction of breast cancer in Korean women via International Journal of Epidemiology - Advance Access Abstract Background Polygenic risk scores (PRSs) for breast cancer, developed using European and Asian genome-wide association studies (GWAS), have been shown to have good discrimination in Asian women. However, prospective calibration of absolute risk prediction models, based on a PRS or PRS combined with lifestyle, clinical and environmental factors, in Asian women is limited. Methods We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS. Results< /div>All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women <50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS. Conclusions Absolute risk models incorporating PRS trained in European and Asian GWAS and population-appropriate average age-specific incidences may be useful for risk-stratified interventions in Korean women. View on Web

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COVID‐19‐associated coagulopathy in children: A multicenter observational cohort study

alexandrossfakianakis shared this article with you from Inoreader COVID‐19‐associated coagulopathy in children: A multicenter observational cohort study via Pediatric Blood & Cancer Abstract SARS-CoV-2 infection (coronavirus disease 2019 [COVID-19]) induces a stark procoagulant state, with many hospitalized adults developing thrombosis despite prophylactic anticoagulation. This study aimed to characterize hemostatic parameters and associated clinical outcomes of COVID-19, such as thrombosis and bleeding, in children and to assess thromboprophylaxis use. This multicenter observational cohort study included 79 patients aged up to 18 years admitted to all pediatric hospitals in Québec, Canada, with SARS-CoV-2 infection during a 5-month period. D-dimers were elevated in 18/19 patients (94.7%) and fibrinogen in 15/26 patients (60%). Eleven patients (13.9%) received anticoagulant thromboprophylaxis. One thrombotic event and one major bleed were observed. View on Web

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Soft tissue dimensional change following guided bone regeneration on peri‐implant defects using soft‐type block or particulate bone substitutes: 1‐year outcomes of a randomized controlled clinical trial

alexandrossfakianakis shared this article with you from Inoreader Soft tissue dimensional change following guided bone regeneration on peri‐implant defects using soft‐type block or particulate bone substitutes: 1‐year outcomes of a randomized controlled clinical trial via Journal of Clinical Periodontology Abstract Objective To compare the peri-implant soft-tissue dimensional changes following guided bone regeneration between particulate (particle group) and collagenated soft-block-type (block group) biphasic calcium phosphate (BCP). Materials and Methods This study investigated 35 subjects: 18 particle-group and 17 block-group patients. Cone-beam computed tomography obtained at 6 months post-surgery and optical impressions taken periodically (presurgery, 6 months post-surgery and 1 year post-surgery) were superimposed. The ridge contour changes over time and the peri-implant mucosal thicknesses were measured diagonally and horizontally, and analysed statistically. Results The increases in diagonal (1.12±0.78 mm) and horizontal (2.79±1.90 mm) ridge contour of the block group were significantly higher than the particle group during the first 6 months (p < 0.05), however, the contour hardly changed thereafter (diagonal: 0.07±0.75 mm; horizontal: -0.34±1.26 mm), resulting in the 1-year contour changes similar between the two groups. Regardless of the type of BCP, the ridge contour increased significantly over 1 year when the dehiscence defect had a contained configuration (p < 0.05). Conclusion The soft-tissue dimensional increases for 1 year were similar between the two groups. The mucosal contour increase was larger when the surgery was conducted in a more-contained defect, and this was not influenced by the type of BCP. This article is protected by copyright. All rights reserved. View on Web

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