Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

alexandrossfakianakis shared this article with you from Inoreader Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol via Pediatric Blood & Cancer Abstract The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulativ e incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades

alexandrossfakianakis shared this article with you from Inoreader Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades via Journal of Medical Virology Abstract COVID-19 pandemic has revealed how vulnerable and inexperienced we are when dealing with an unprecedented global infectious threat. Looking back on the last few decades, there has been a surge in zoonotic-derived viruses globally. Notably, these outbreaks emerged as harmless zoonotic diseases within a favorable environment, then spilled over to humans and widely spread to become outbreaks. Most of these are respiratory viruses (particularly Orthomyxoviridae Orthomyxoviridae or Coronaviridae Coronaviridae family), with high transmissibility and can be easily spread. Low- and middle-income countries, particularly those with tropical climates, provide ideal environments for the growth and evolution of these zoonotic viruses. Nevertheless, a lot of our advanced centers for infectious diseases are located in high-income countries (HIC) and focus on human pathogens only (e.g., influenza, RSV, adenovirus). We should critically think about reallocating health resources in th e near-term. It is an urge for a few surveillance centers aim to detect surges in cases of respiratory pathogens or any spikes in cases, and suppress the transmission chain from an early stage. In this article, we digest lessons learned from the previous spillover pandemics and suggest actionable tactics to deal with future pandemics properly. This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The incidence and characterization of weight gain associated with MEK inhibitors in pediatric patients

alexandrossfakianakis shared this article with you from Inoreader The incidence and characterization of weight gain associated with MEK inhibitors in pediatric patients via Pediatric Blood & Cancer Abstract Background Mitogen-activated protein kinase enzyme (MEK) inhibitors are used in the treatment of pediatric patients with neurofibromatosis, low grade glioma, and astrocytoma, and may demonstrate a unique side effect profile in this population. Inhibition of MEK has been shown to decrease interleukin (IL)-6 production, a proinflammatory cytokine. The inhibition of IL-6 and other proinflammatory cytokines is thought to decrease muscle wasting and may contribute to weight gain. However, there is limited information on the association of MEK inhibition and weight gain in children and adolescents. This study aimed to characterize and define the incidence of significant weight gain associated with MEK inhibitors in pediatric patients. Methods This was a retrospective chart review conducted at a tertiary pediatric hospital. Children 1–18.99 years old were included if they started a MEK inhibitor from July 1, 2013–October 31, 2021, and continued therapy for at least 6 months. Significant weight gain was defined as ≥5% increase in patient's weight-for-age percentile. Results Sixty-seven patients were included in the analysis. Sixty-two received trametinib and 5 received selumetinib. An increase in weight-for-age percentile ≥5% was seen in 60% of patients receiving selumetinib and 56% on trametinib. The Dunnett's multiple comparisons test revealed a difference in weight-for-age percentile from baseline to end of data collection (p = .0173). Patients who were obese at baseline were more likely to lose weight during treatment, while underweight patients increased in weight-for-age percentiles. Conclusions Weight gain may be a notable side effect associated with the use of MEK inhibitors in pediatric patients. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Automated Creak Differentiates Adductor Laryngeal Dystonia and Muscle Tension Dysphonia

alexandrossfakianakis shared this article with you from Inoreader Automated Creak Differentiates Adductor Laryngeal Dystonia and Muscle Tension Dysphonia via The Laryngoscope Objective The purpose of this study was to determine whether automated estimates of vocal creak would differentiate speakers with adductor laryngeal dystonia (AdLD) from speakers with muscle tension dysphonia (MTD) and speakers without voice disorders. Methods Sixteen speakers with AdLD, sixteen speakers with MTD, and sixteen speakers without voice disorders were recorded in a quiet environment reading aloud a standard paragraph. An open-source creak detector was used to calculate the percentage of creak (% creak) in each of the speaker's six recorded sentences. Results A Kruskal-Wallis one-way analysis of variance revealed a statistically significant effect of group on the % creak with a large effect size. Pairwise Wilcoxon tests revealed a statistically significant difference in % creak between speakers with AdLD and controls as well as between speakers with AdLD and MTD. Receiver operating characteristic curve analyses indicated that % creak differentiated AdLD from both controls and speakers with MTD with high sensitivity and specificity (area under the curve statistics of 0.94 and 0.86, respectively). Conclusion Percentage of creak as calculated by an automated creak detector may be useful as a quantitative indicator of AdLD, demonstrating the potential for use as a screening tool or to aid in a differential diagnosis. Level of Evidence 3 Laryngoscope, 2023 View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.