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

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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

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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

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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

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Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups

alexandrossfakianakis shared this article with you from Inoreader Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups via Neuro-Oncology Advance Access Abstract Background The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse. Methods Hundred-forty-four patients with DMB (n=99) or MBEN (n=45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients, were evaluated. Results Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs 93% [MBEN]). Patients' age >3 years was associated with more unfavorable 5y-PFS (47% [>3 years] vs 85% [<1 year] vs 84% [1-3 years]). DNA methylation profiles available (n=78) were reclassified according to the 2021 WHO classification into SHH-1 (n=39), SHH-2 (n=38), and SHH-3 (n=1). Hierarchical clustering de lineated two subgroups among SHH-2: SHH-2a (n=19) and SHH-2b (n=19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs 83% [SHH-1] vs 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using two independent cohorts (total n=188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations. Conclusion These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with higher risk of r elapse. View on Web

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Photo‐/ mechanical and physical implant surface decontamination approaches in conjunction with surgical peri‐implantitis treatment: A systematic review

alexandrossfakianakis shared this article with you from Inoreader Photo‐/ mechanical and physical implant surface decontamination approaches in conjunction with surgical peri‐implantitis treatment: A systematic review via Journal of Clinical Periodontology Abstract Aim To evaluate the efficacy of adjunctive/alternative photo-/mechanical and physical implant-surface decontamination approaches compared to a standard instrumentation in conjunction with surgical peri-implantitis treatment. Materials and Methods Randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) investigating the efficacy of adjunctive or alternative photo-/mechanical/physical measures for implant surface decontamination in conjunction with surgical peri-implantitis treatment without (PICOS 1) or with (PICOS 2) additional decontamination methods performed in test and control groups with changing inflammation parameters. Changes in bleeding scores (i.e., bleeding index (BI), or bleeding on probing (BOP)), suppuration (SUP) and PD values were considered as primary outcomes. Results Six articles describing five original RCTs were eligible for analysis. Based on two RCTs, the adjunctive/alternative use of an air polishing with glycine or erythritol powders did not improve BOP reduction compared to a standard instrumentation (PICOS 1). Based on one RCT, alternative use of titanium brushes resulted in significantly higher BOP reduction compared to either air polishing or a standard instrumentation (PICOS 1). During reconstructive therapy and as an adjunct to implantoplasty, use of a titanium brush did not have a benefit on the BOP and mean PD reductions compared to the control group (i.e., implantoplasty + mechanical and chemical implant surface decontamination; 1 RCT; PICOS 2). An Er:YAG laser resulted in significantly higher PD reduction after 6 months (1 RCT), whereas no difference between the test and respective controls could be detected after 1 and 2 years (1 RCT). Additionally, the use of the Er:YAG laser was not associated with improved BOP reductions over respective controls (2 RCTs; PICOS 2). Conclusions Due to the limited available data, clinical efficacy of photo-/mechanical and physical implant surface decontamination in conjunction with surgical peri-implantitis therapy is inconclusive. However, titanium brushes may be beneficial in reducing signs of inflammation. View on Web

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A Novel Sampling Device for the Quantification of Primary Aromatic Amines on Surfaces

alexandrossfakianakis shared this article with you from Inoreader A Novel Sampling Device for the Quantification of Primary Aromatic Amines on Surfaces via Annals of Work Exposures and Health Advance Access Abstract Primary aromatic amines (PAAs) are a class of hazardous substances where many compounds are classified as carcinogen, mutagen, and reproduction toxin (CMR). PAAs can be taken up by dermal exposure. In the polyurethane industry, a valid and trustworthy method for the quantification of PAAs in the presence of isocyanates that could interfere is of great interest, especially on workplaces where a regular contact to PAAs cannot be excluded. The aim of this work is the development, validation, and verification of a novel sampling device to quantify selectively the PAA load on work surfaces. We describe the synthesis of Cell-ßALA-PEMSA analytical papers and their characterization by infrared spectroscopy and thermogravimetric analysis. The recovery of TDA and MDA spiked on these filters is satisfactory. An excellent selectivity of Cell-ßALA-PEMSA papers towards PAAs in the presence of isocyanates of almost 100% was found by wipe tests of amine/isocya nate contaminated surfaces. First positive field tests were achieved at certain areas in a Polyurethane Technical Application Department where surface contamination with PAAs was expected, and the Cell-ßALA-PEMSA analytical papers were superior to an established method of surface sampling. However, recovery of these amines from surfaces shows a large variability, and more work is required to address influencing surface properties. View on Web

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Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study via Clinical Infectious Diseases Advance Access ABSTRACT Background Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron). Methods This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic chara cteristics, baseline health, and vaccine status. Results The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status. Conclusions Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms. View on Web

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Role of non‐coding RNAs with emphasis on long non‐coding RNAs as cervical cancer biomarkers

alexandrossfakianakis shared this article with you from Inoreader Role of non‐coding RNAs with emphasis on long non‐coding RNAs as cervical cancer biomarkers via Journal of Medical Virology Abstract Cervical cancer is a significant public health problem in developing countries, as most cases present at an advanced stage. This review aimed to analyze the role of non-coding RNAs as diagnostic and prognostic biomarkers in cervical cancers. Published studies on specific microRNA signatures in body fluids and cervical cancer tissues are highly heterogeneous, and there are no validated assays. The precision of the various immune-associated lncRNA signatures should be assessed in clinical samples. Even though lncRNAs are tissue and cancer-specific, safe and appropriate methods for delivery to tumor tissues, toxicities and side effects are to be explored. Few studies have evaluated deregulated lncRNA expression levels with clinicopathological factors in a limited number of clinical samples. Prospective studies assessing the diagnostic and prognostic roles of circulating lncRNAs and P-Element-induced wimpy testis interacting PIWI RNAs (Piwil RNAs) in cervical ca ncer cases are essential. For the clinical application of lnc-RNA-based biomarkers, comprehensive research is needed as the impact of non-coding transcripts on molecular pathways is complex. The standardization and validation of deregulated ncRNAs in non-invasive samples of cervical cancer cases are needed. This article is protected by copyright. All rights reserved. View on Web

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Immunological efficacy of pneumococcal vaccination including the 13-valent pneumococcal vaccine in adult patients with sickle-cell disease: results of the randomized DREVAC controlled trial

alexandrossfakianakis shared this article with you from Inoreader Immunological efficacy of pneumococcal vaccination including the 13-valent pneumococcal vaccine in adult patients with sickle-cell disease: results of the randomized DREVAC controlled trial via Clinical Infectious Diseases Advance Access Abstract Background Patients with sickle-cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD. Methods This was a randomized open-labelled phase 2 study of the immunogenicity of PCV13 at week (W)0, followed by PPSV23 at W4, compared to PPSV23 alone at W4 in adult patients with SCD. The proportion of responders (four-fold increase of serotype-specific IgG antibodies) to at least 10-shared serotypes was assessed at W8. Secondary endpoints were: i) geometrical mean titers (GMTs), ii) responders to 0-1, 2-5, 6-9, and 10-12 serotypes, iii) pneumococcal opsonophagocytic (OPA) activity, and iv) response durability at W24 and W96. Results In total, 128 patients were randomized in the PCV13/PPSV23 (n=63) or PPSV23-alone groups (n=65). At W8, 24.5 6% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary endpoint (p=0.016). These numbers were 36.2% and 8.7% for OPA responders (p=0.002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, and 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At W96, GMTs were significantly higher in the PCV13/PPSV23 than in the PPSV23 alone group for five serotypes (4, 14, 19A, 19F, 23F). Conclusions A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical Trial Registration: NCT02274415 View on Web

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