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Hematology, Transfusion and Cell Therapy May 2024Improvements in clinical assessment have occurred since the last published recommendations on the diagnosis and treatment of acute promyelocytic leukemia in 2013. Here,...
Diagnosis and management of acute promyelocytic leukemia: Brazilian consensus guidelines 2024 on behalf of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy.
Improvements in clinical assessment have occurred since the last published recommendations on the diagnosis and treatment of acute promyelocytic leukemia in 2013. Here, a committee of specialists of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy presents a comprehensive review on the current knowledge, focusing on the advances in diagnosis, risk assessment, and frontline and salvage therapy. The concept of urgent diagnosis is explored as well as the management of critical situations such as coagulopathy and differentiation syndrome. Recent adjustments in risk stratification based on white blood cell counts only are presented together with the incorporation of chemo-free regimens for non-high-risk patients. Special conditions such as acute promyelocytic leukemia in children, the elderly and pregnant women are discussed. Finally, acute promyelocytic leukemia is presented as a highly curable disease because of the real possibility of targeted therapy towards differentiation, and, paradoxically, as a serious and urgent condition that deserves prompt recognition and management to avoid early mortality.
PubMed: 38890097
DOI: 10.1016/j.htct.2024.05.002 -
The Journal of Clinical Endocrinology... Jun 2024Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder with reproductive and metabolic dysregulation. PCOS has been associated with inflammation and...
CONTEXT
Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder with reproductive and metabolic dysregulation. PCOS has been associated with inflammation and Metabolic Syndrome (MetS); however, the moderating effects of inflammation as measured by C-reactive protein (CRP) and menopause on the PCOS-MetS association have not been studied in Hispanic/Latinas with PCOS who have a higher metabolic burden.
OBJECTIVE
We studied the cross-sectional association between PCOS and (i) MetS in 7316 females of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), (ii) subcomponents of MetS including impaired fasting glucose (IFG) and elevated triglycerides (TGL), and (iii) effect modification by menopausal status and CRP.
DESIGN
HCHS/SOL is a multicenter, longitudinal, and observational study of US Hispanic/Latinos. Our study sample included females from Visit 2 with self-reported PCOS and MetS (ages 23-82 years).
RESULTS
PCOS (prevalence=18.8%) was significantly associated with MetS prevalence (OR=1.41[95% confidence interval: 1.13-1.76]), IFG and TGL (OR=1.42[1.18-1.72], OR=1.48[1.20-1.83] respectively). We observed effect modification by menopausal status (ORpre=1.46, pint=0.02; ORpost=1.34, pint=0.06) and CRP (ORelevated=1.41, pint=0.04; ORnormal=1.26, pint=0.16) on the PCOS-MetS association. We also observed a super-additive interaction between CRP and PCOS, adjusting for which resulted in an attenuated effect of PCOS on MetS (OR=1.29[0.93-1.78]).
CONCLUSIONS
Hispanic/Latino females with PCOS had higher odds of MetS, IFG, and elevated TGL, than their peers without PCOS. Interaction analyses revealed that the odds of MetS are higher among PCOS females who have pre-menopausal status or high inflammation. Interventions in Hispanic/Latinas should target these outcomes for effective management of the disease.
PubMed: 38888178
DOI: 10.1210/clinem/dgae426 -
Journal of Clinical Oncology : Official... Jun 2024JCO We report 4-year results of the phase II randomized AtezoTRIBE study. Eligible patients with metastatic colorectal cancer (mCRC) received first-line fluorouracil,...
Upfront Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Bevacizumab With or Without Atezolizumab for Patients With Metastatic Colorectal Cancer: Updated and Overall Survival Results of the ATEZOTRIBE Study.
JCO We report 4-year results of the phase II randomized AtezoTRIBE study. Eligible patients with metastatic colorectal cancer (mCRC) received first-line fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (control group, n = 73) or FOLFOXIRI/bevacizumab plus atezolizumab (experimental group, n = 145). We present overall survival (OS) and updated outcomes according to tumor immune-related biomarkers, both in the intention-to-treat (ITT) population and the cohort of patients with proficient mismatch repair (pMMR) tumors. Median follow-up was 45.2 months (IQR, 42.6-49.2). In the ITT population, median OS was 33.0 and 27.2 months for experimental and control groups, respectively (hazard ratio [HR], 0.78 [80% CI, 0.61 to 0.98]; = .084). An interaction effect between Immunoscore Immune-Checkpoint (IC) and treatment arm was observed (, .089), with higher benefit from atezolizumab in the Immunoscore IC-high group. In the pMMR cohort (N = 202), median OS was 30.8 and 29.2 months for experimental and control groups, respectively (HR, 0.80 [80% CI, 0.63 to 1.02]; = .117). Interactions between treatment group and tumor mutational burden (TMB) and Immunoscore IC were reported (, .043 and .092, respectively), with patients bearing TMB-high and Immunoscore IC-high tumors deriving higher benefit from the addition of atezolizumab. First-line FOLFOXIRI/bevacizumab plus atezolizumab improves OS in patients with mCRC. In the pMMR group, patients with Immunoscore IC-high and/or TMB-high tumors are identified as a subgroup of interest to further develop this treatment.
PubMed: 38865678
DOI: 10.1200/JCO.23.02728 -
European Journal of Applied Physiology Jun 2024Imbalances of muscle strength and tendon stiffness can increase the operating strain of tendons and risk of injury. Here, we used a new approach to identify...
PURPOSE
Imbalances of muscle strength and tendon stiffness can increase the operating strain of tendons and risk of injury. Here, we used a new approach to identify muscle-tendon imbalances and personalize exercise prescription based on tendon strain during maximum voluntary contractions (ε) to mitigate musculotendinous imbalances in male adult volleyball athletes.
METHODS
Four times over a season, we measured knee extensor strength and patellar tendon mechanical properties using dynamometry and ultrasonography. Tendon micromorphology was evaluated through an ultrasound peak spatial frequency (PSF) analysis. While a control group (n = 12) continued their regular training, an intervention group (n = 10) performed exercises (3 × /week) with personalized loads to elicit tendon strains that promote tendon adaptation (i.e., 4.5-6.5%).
RESULTS
Based on a linear mixed model, ε increased significantly in the control group over the 9 months of observation (p = 0.010), while there was no systematic change in the intervention group (p = 0.575). The model residuals of ε, as a measure of imbalances in muscle-tendon adaptation, demonstrated a significant reduction over time exclusively in the intervention group (p = 0.007). While knee extensor muscle strength increased in both groups by ~ 8% (p < 0.001, p = 0.064), only the intervention group showed a trend toward increased normalized tendon stiffness (p = 0.824, p = 0.051). PSF values did not change significantly in either group (p > 0.05).
CONCLUSION
These results suggest that personalized exercise prescription can reduce muscle-tendon imbalances in athletes and could provide new opportunities for tendon injury prevention.
PubMed: 38842575
DOI: 10.1007/s00421-024-05525-z -
Catheterization and Cardiovascular... Jun 2024
PubMed: 38838185
DOI: 10.1002/ccd.31118 -
Environmental Epidemiology... Jun 2024Toxicological studies indicate that neonicotinoids may be associated with disruptions in liver function due to an increase in oxidative stress. There are scant...
BACKGROUND
Toxicological studies indicate that neonicotinoids may be associated with disruptions in liver function due to an increase in oxidative stress. There are scant epidemiological studies investigating the chronic hepatotoxic effects of neonicotinoids.
OBJECTIVE
To examine the association between detectable concentrations of parent neonicotinoids and neonicotinoid metabolites with liver function markers among US adults, and whether sex modifies this association.
METHODS
National Health and Nutrition Examination Survey 2015-2016 data were used to estimate associations between detectable neonicotinoids and serum alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transaminase (GGT), albumin, total bilirubin, total protein, and Hepatic Steatosis Index (HSI) using multiple linear regression.
RESULTS
Detectable levels of -desmethyl-acetamiprid were associated with a decrease in GGT (β = -3.54 unit/l; 95% confidence interval [CI] = -6.48, -0.61) and detectable levels of 5-hydroxy-imidacloprid were associated with a decrease in HSI (β = -1.11; 95% CI = -2.14, -0.07). Sex modified the association between any parent neonicotinoid and ALP ( = 0.064) and the association between clothianidin and ALP ( = 0.019), with a pattern of positive associations in males and inverse associations in females, though stratified associations did not reach statistical significance. Sex also modified the association between 5-hydroxy-imidacloprid and total protein ( = 0.062), with a significant positive association in females (β = 0.14 g/dl; 95% CI = 0.03, 0.25) and a null association in males.
CONCLUSION
Detectable concentrations of neonicotinoid metabolites were inversely associated with GGT and HSI in US adults. Evidence suggests neonicotinoids may influence liver function differently depending on sex. Future research is recommended to replicate the findings as the study was limited in its cross-sectional nature and inability to examine continuous neonicotinoid concentrations with liver function.
PubMed: 38799264
DOI: 10.1097/EE9.0000000000000310 -
Cardiovascular Diagnosis and Therapy Apr 2024Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ....
BACKGROUND
Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes.
METHODS
In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems.
RESULTS
Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in (n=60, 11.2%) and (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the (n=7, 1.3%) and (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including and variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively.
CONCLUSIONS
The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA ( variants) and FD ( variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.
PubMed: 38716318
DOI: 10.21037/cdt-23-191 -
ACS Applied Materials & Interfaces May 2024In this study, we demonstrate that elastic strain applied to a current collector can influence the overall thermodynamic and kinetic picture of sodium metal...
In this study, we demonstrate that elastic strain applied to a current collector can influence the overall thermodynamic and kinetic picture of sodium metal electrodeposition and hence the performance of a sodium metal battery. To controllably study the role of strain in electrochemical performance, we utilize NiTi foil as a stable current collector, nucleation interface, and superelastic material. Our findings demonstrate that a locked-in elastic tensile strain near 8% results in 40 mV lower onset potential for sodium electrodeposition, 19% decrease in charge transfer resistance, and 20% lower cumulative sodium loss, among other effects. These performance improvements are correlated primarily to the control of the irreversible behavior in the first few minutes of electroplating. Given the prevalence of strain buildup in commercial battery cell configurations, our work highlights that strained current collector interfaces can result in significant long-term chemo-mechanical performance outcomes broadly relevant to sodium and other metal battery design considerations.
PubMed: 38693062
DOI: 10.1021/acsami.4c02809 -
Gene Jul 2024Cells sense, respond, and adapt to environmental conditions that cause stress. In a previous study using HeLa cells, we isolated reporter cells responding to the...
Cells sense, respond, and adapt to environmental conditions that cause stress. In a previous study using HeLa cells, we isolated reporter cells responding to the endoplasmic reticulum (ER) stress inducers, thapsigargin and tunicamycin, using a highly sensitive promoter trap vector system. Splinkerette PCR and 5' rapid amplification of cDNA ends (5' RACE) identified a novel transcript that is upregulated by ER stress. Its endogenous expression increased approximately 10-fold in response to thapsigargin and tunicamycin within 1 h, but was down-regulated after 4 h. Because the transcript starts from an intron of a long noncoding RNA known as LINC-PINT, we designated the newly identified transcript TISPL (transcript induced by stressors from LINC-PINTlocus). TISPL was also expressed under several other stress conditions. It was particularly increased > 10-fold upon glucose starvation and 7-fold by arsenite exposure. Furthermore, in silico analyses, including a ChIP-atlas search, revealed that there is an ATF4-binding region with a c/ebp-Atf response element (CARE) downstream of the transcription start site of TISPL. Based on these results, we hypothesized that TISPL may be induced by the phospho-eIF2α and ATF4- axis of the integrated stress response pathway, which is known to be activated by the stress conditions listed above. As expected, knockout of ATF4 abolished the stress-induced upregulation of TISPL. Our results indicate that TISPL may be a useful biomarker for detecting stress conditions that activate ATF4. Our highly sensitive trap vector system proved beneficial in discovering new biomarkers.
Topics: Activating Transcription Factor 4; Humans; HeLa Cells; Up-Regulation; Endoplasmic Reticulum Stress; RNA, Long Noncoding; Thapsigargin; Tunicamycin; Arsenites
PubMed: 38615981
DOI: 10.1016/j.gene.2024.148464 -
Bone Reports Jun 2024Tumor-induced osteomalacia is caused by excessive fibroblast growth factor 23 production mainly from phosphaturic mesenchymal tumors. Surgical excision or tumor ablation...
Healing of tumor-induced osteomalacia as assessed by high-resolution peripheral quantitative computed tomography is not similar across the skeleton in the first years following complete tumor excision.
Tumor-induced osteomalacia is caused by excessive fibroblast growth factor 23 production mainly from phosphaturic mesenchymal tumors. Surgical excision or tumor ablation are the preferred treatment. Information on bone microarchitecture parameters assessed by high-resolution peripheral quantitative computed tomography is limited. We report a woman with hypophosphatemic osteomalacia with generalized pain, weakness and recurrent fractures, and a large thoracic vertebral mass extending to the posterior mediastinum. Detailed radiologic and histopathologic evaluation revealed a phosphaturic mesenchymal tumor. Two surgeries were necessary for complete removal of the mass. Clinical symptoms improved after attaining normophosphatemia. Four-year post-surgical HR-pQCT parameters, compared to baseline, showed in the left distal radius, stable trabecular and cortical volumetric bone mineral density although below reference range. There was stability of trabecular number and thickness. Both stiffness and failure load decreased. A shift in cortical parameters was noted in year 2. In the left distal tibia, trabecular volumetric bone mineral density decreased whereas cortical volumetric bone mineral density markedly increased, as did cortical area. There was stability in the trabecular number and thickness. Both stiffness and failure load improved. Findings from HR-pQCT measurements in this patient disclosed that the healing of osteomalacia is not similar across the peripheral skeletal sites in the first years following tumor removal. Results contrasted low but stable volumetric bone mineral density in the distal radius with increase in the distal tibia at the expense of cortical bone. Our report helps further delineate the pattern of bone healing after treatment of this rare bone disorder.
PubMed: 38584681
DOI: 10.1016/j.bonr.2024.101758