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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Impact of AJCC 8 pT staging in cutaneous head and neck squamous cell carcinoma in a nonselected real‐world patient sample

alexandrossfakianakis shared this article with you from Inoreader Impact of AJCC 8 pT staging in cutaneous head and neck squamous cell carcinoma in a nonselected real‐world patient sample via Head & Neck Abstract Objective Our aim was to evaluate characteristics associated with worse survival and the effectiveness of AJCC 8 in a real-world cohort of HNCSCC from South Brazil. Methods A 10-year retrospective cohort study (2011–2020) at a tertiary care center comprising 647 HNCSCC excised from 435 patients. Results At multivariable analysis, ear/nose/zygomatic or periorbital site, compromised or exiguous margins, and advanced pT stage were independent factors associated to DFS, while age, pN, and loco-regional recurrence were independent factors associated to DSS. Cox-regression multivariable models showed that the pT stage was statistically significant for the DFS, but not DSS. A significant distinction was only observed between T1 and T2. Conclusion It was only in the lower categories of AJCC 8 (T1 and T2) that we were able to demonstrate the ability to stratify tumors with a significant risk of poor disease-related outcomes. View on Web

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A novel stapler‐assisted technique for closure of persistent tracheoesophageal puncture fistula

alexandrossfakianakis shared this article with you from Inoreader A novel stapler‐assisted technique for closure of persistent tracheoesophageal puncture fistula via Head & Neck Abstract Tracheoesophageal puncture (TEP) is a reliable method to restore voice and is an important part of voice rehabilitation following laryngectomy. However, complications following this procedure, including peri-prosthetic leakage and resulting aspiration pneumonia, may necessitate surgical closure. In this study, we present an effective and reliable method for TEP closure using a stapler-assisted technique. Case series study for patients who underwent stapler-assisted TEP closure reviewed from 2017 to 2021. All five patients had successful closure of their TEP tract without further leakage. No postoperative bleeding, wound infection, or esophageal stenosis occurred. One patient had postoperative stomal stenosis. The stapler-assisted technique for TEP closure is easy, quick, and effective. The reliability and quick return to oral intake post-operatively make it a preferable option over previous techniques. View on Web

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Dosage optimization of voriconazole in children with haematological malignancies based on population pharmacokinetics

alexandrossfakianakis shared this article with you from Inoreader Dosage optimization of voriconazole in children with haematological malignancies based on population pharmacokinetics via Journal of Clinical Pharmacy and Therapeutics This is a population pharmacokinetic study of voriconazole in Chinese children with haematological malignancies. A population pharmacokinetic model was developed and evaluated. Based on the final model, appropriate administration regimens were recommended, which could enhance the rational use of voriconazole in children with haematological malignancies. Abstract What is Known and Objectives Voriconazole has a complex pharmacokinetic profile and exhibits different pharmacokinetic characteristics in adults and children. Nevertheless, few studies have been conducted on the population pharmacokinetics (PPK) of voriconazole in children with haematological malignancies. This study aims to build a PPK model and propose a suitable voriconazole treatment scheme for children with haematological malignancies. Methods We retrospectively collected 146 samples from 67 children aged from 1.08 to 17.92 years. The PPK model was established using nonlinear mixed effects modelling (NONMEM). Dosage simulations were conducted on the basis of the final model's covariates. Results and Discussion Data were fully characterized by a one-compartment model with first-order absorption and elimination. The weight (WT), CYP2C19 phenotype, and Albumin (ALB) were notable covariates for clearance (CL). The typical values of CL, the volume of distribution (V), and oral bioavailability (F) were 2.29 L/h, 76 L, and 0.902, respectively. The proposed doses for different CYP2C19 genotypes were presented in this ranking: EM (extensive metabolizer) > IM (intermediate metabolizer) > PM (poor metabolizer). Furthermore, higher dosages for light WT patients were recommended while lower ALB levels required lower doses. The probability of achieving the target (PTA) for the recommended doses ranged from 72.2% to 99%. What is New and Conclusion We successfully built a voriconazole PPK model for children with hematologic malignancies. Dosing regimens were developed for different patients based on the final model, which could enhance the rational use of voriconazole in children with haematological malignancies. 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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A Breakthrough Improvement Collaborative Significantly Reduces Hospital Stay After Elective Colectomy for Cancer Across a Healthcare System

alexandrossfakianakis shared this article with you from Inoreader A Breakthrough Improvement Collaborative Significantly Reduces Hospital Stay After Elective Colectomy for Cancer Across a Healthcare System via Annals of Surgery - Most Popular Articles Objective: This multicenter study aimed to assess (1) the effect of an improvement collaborative on enhanced recovery after surgery (ERAS) protocol adherence after elective colectomy and (2) the association between adherence and patient outcomes. Background: ERAS pathways provide a framework to standardize care processes and improve postoperative outcomes in patients after colon surgery. Despite growing evidence of its effectiveness, adherence to these guidelines remains a challenge. Methods: This prospective, multicenter collaborative was initiated throughout 11 hospitals in Flanders, Belgium. A structured audit tool was used to study patient outcomes and adherence to 12 ERAS components, defined by the collaborative. Three retrospective audits (based on patient record analysis) were conducted in 2017, 2019, and 2021, respectively. Results: Overall, 740 patients were included (45.4% female; mean±SD age, 71±12 years). The overall adherence increased from 42.8% in 2017 to 58.4% in 2019 and 69.2% in 2021. Compared with low adherence, length of stay was increasingly reduced by 1.3 days for medium [95% confidence interval (95% CI): −2.5; 0.0], 3.6 days for high (95% CI: −4.9; −2.2), and up to 4.4 days for very high adherence (95% CI: −6.1; −2.7). Corresponding odds ratios for postoperative complications were 0.62 (95% CI: 0.33; 1.17), 0.19 (95% CI: 0.09; 0.43), and 0.14 (95% CI: 0.05; 0.39), respectively. No increase in 30-day readmissions was observed. Conclusions: A peer-constructed improvement collaborative effectively increases adherence to an ERAS protocol in individual hospitals. Across time, length of stay and postoperative complications decreased significantly, and a dose-response relationship was observed. 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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