Diagnostic yield of bone marrow aspiration in paediatric primary immune thrombocytopenia: impact of evolution and adherence to medical guidelines over the last 25 years.

The aim of this study is to analyse the diagnostic value of bone marrow aspiration (BMA) in a retrospective cohort of patients with suspected immune thrombocytopaenia (ITP). We further measure changes in the percentage of patients who underwent this study and whether testing or not was in accordance with current guidelines at the time of diagnosis. We conducted a chart review of 243 patients with ITP who underwent follow-up in our institution between 1995 and 2022. The patients were divided into historical cohorts based on the practice guidelines of the Spanish Society of Pediatric Hematology and Oncology (SEHOP) and the American Society of Hematology (ASH) in place at the time of follow-up. For each case, time of disease presentation or initial diagnosis was defined as that which occurred in the first 72 h following disease onset. Based on data from the historical cohorts studied, we observed a lower total number of BMAs at diagnosis over time (p < 0.005). A gradual reduction was seen in the number of BMAs with the introduction of guidelines, including a progressively lower number of BMAs performed without indication (p < 0.05). Subsequent to the initial diagnosis, the procedure played a decisive role in only 2 patients (0.58%), allowing for a diagnosis of acquired aplastic anaemia in both cases. In both of them on diagnosis, BMA did not appear to be indicated, although subsequent analysis after 72 h raised suspicion of bone marrow failure. CONCLUSION: BMA at presentation did not significantly alter the diagnosis in our cohort of patients with an initial suspicion of ITP, although the procedure was decisive in diagnosing 2 cases of acquired aplastic anaemia during the subsequent course of the disease. Regarding the number of aspirations performed, our findings show that increased physician compliance with current guidelines reduced the rate of unnecessary BMAs. WHAT IS KNOWN: • BMA is a supplementary test for the diagnosis of ITP. • The usefulness of this invasive diagnostic procedure is not clearly stated in current guidelines. WHAT IS NEW: • Adjustments to scientific guidelines have led to a reduction in the number of BMAs performed on our patients with suspected ITP in the last 27 years. • While the risks and benefits of BMA at the time of diagnosis are unclear in patients with suspected ITP, the procedure does not contribute significant information to support the diagnosis.

A Comprehensive Review of Continuous Glucose Monitoring Accuracy during Exercise Periods.

Continuous Glucose Monitoring (CGM) has been a springboard of new diabetes management technologies such as integrated sensor-pump systems, the artificial pancreas, and more recently, smart pens. It also allows patients to make better informed decisions compared to a few measurements per day from a glucometer. However, CGM accuracy is reportedly affected during exercise periods, which can impact the effectiveness of CGM-based treatments. In this review, several studies that used CGM during exercise periods are scrutinized. An extensive literature review of clinical trials including exercise and CGM in type 1 diabetes was conducted. The gathered data were critically analysed, especially the Mean Absolute Relative Difference (MARD), as the main metric of glucose accuracy. Most papers did not provide accuracy metrics that differentiated between exercise and rest (non-exercise) periods, which hindered comparative data analysis. Nevertheless, the statistic results confirmed that CGM during exercise periods is less accurate.

Range of Motion and Injury Occurrence in Elite Spanish Soccer Academies. Not Only a Hamstring Shortening-Related Problem.

Sanz, A, Pablos, C, Ballester, R, Sanchez-Alarcos, JV, and Huertas, F. Range of motion and injury occurrence in elite Spanish soccer academies. Not only a hamstring shortening-related problem. J Strength Cond Res 34(7): 1924-1932, 2020-Age-related development of range of motion (ROM) during an active hip flexion (active straight leg raise) and its relationship with hamstring injury occurrence were examined in 1657 young male soccer players (9-18 years of age). Age-related differences in ROM showed a significant decrease from U9 to U11 (p = 0.001), from U11 to U13 (p < 0.005), and from U9 to U13 (p < 0.001), whereas ROM increased from U13 to U15 and from U13 to U18 (both p's < 0.001). Interestingly, younger and older players reached similar ROM values (U9-U18, p = 0.87). Higher ROM was found in dominant than nondominant leg in all age groups (all ps < 0.001). No differences related to playing position were found on ROM (all ps > 0.478). During the follow-up period (11 months) 97 hamstring injuries were reported showing higher rates in the older age groups (p < 0.001) and outfield players (p < 0.001). Remarkably, no differences in ROM average were found between injured players and noninjured players (p = 0.152). Our results suggest that ROM during hip flexion does not only depend on the hamstrings shortening but also on the variables related to joint stability, motor control, and hip flexor muscle weakness. Sport scientists in youth sport soccer academies should develop age-specific screening and action plans to develop strength, motor control, and flexibility to optimize ROM and reduce injuries from the grassroots stages.

Experimental Evidence for a State-Point-Dependent Density-Scaling Exponent of Liquid Dynamics.

A large class of liquids obey density scaling characterized by an exponent, which quantifies the relative roles of temperature and density for the dynamics. We present experimental evidence that the density-scaling exponent γ is state-point dependent for the glass formers tetramethyl-tetraphenyl-trisiloxane (DC704) and 5-polyphenyl ether (5PPE). A method is proposed that from dynamic and thermodynamic properties at equilibrium estimates the value of γ. The method applies at any state point of the pressure-temperature plane, both in the supercooled and the normal liquid regimes. We find that γ is generally state-point dependent, which is confirmed by reanalyzing data for 20 metallic liquids and two model liquids.

Imaging and bone marrow assessments improve minimal residual disease prediction in multiple myeloma.

The value of minimal residual disease (MRD) status by bone marrow and imaging analysis as independent prognostic factors has been well established in multiple myeloma (MM). Nevertheless data about their potential complementarity for a more accurate assessment are limited. With this aim, we retrospectively analyzed the prediction of outcome with the combination of PET-CT and MRD, assessed by multiparameter flow cytometry (MFC) in 103 patients with newly diagnosed MM. We confirmed the benefit in terms of progression-free survival (PFS), linked to the achievement of negativity by MFC (hazard ratio [HR] 0.53; 95% confidence interval [CI]: 0.28-0.98), and PET-CT (HR 0.18; 95% CI: 0.09-0.36) individually. By combining both techniques, patients who became MRD-/PET-, with a median of PFS 92 months, had significant prolonged median PFS (P < .001). This is compared with MRD+/PET- and PET+ patients (median PFS of 45 and 28 months, respectively). We observed a significant difference (P = .003) in overall survival (OS) outcomes between MRD-/PET- and MRD+/PET- patients (4-year OS 94.2% and 100%, respectively), vs PET+ patients (4-year OS 73.8%). All survival results were confirmed in a conditional landmark analysis. These findings support the potential complementarity between PET-CT and MFC, and highlight their better predictive capability when improving sensitivity.

Enhanced Accuracy of Continuous Glucose Monitoring during Exercise through Physical Activity Tracking Integration.

Current Continuous Glucose Monitors (CGM) exhibit increased estimation error during periods of aerobic physical activity. The use of readily-available exercise monitoring devices opens new possibilities for accuracy enhancement during these periods. The viability of an array of physical activity signals provided by three different wearable devices was considered. Linear regression models were used in this work to evaluate the correction capabilities of each of the wearable signals and propose a model for CGM correction during exercise. A simple two-input model can reduce CGM error during physical activity (17.46% vs. 13.8%, p < 0.005) to the magnitude of the baseline error level (13.61%). The CGM error is not worsened in periods without physical activity. The signals identified as optimal inputs for the model are "Mets" (Metabolic Equivalent of Tasks) from the Fitbit Charge HR device, which is a normalized measurement of energy expenditure, and the skin temperature reading provided by the Microsoft Band 2 device. A simpler one-input model using only "Mets" is also viable for a more immediate implementation of this correction into market devices.

Isochronal superposition and density scaling of the α-relaxation from pico- to millisecond.

The relaxation dynamics in two van der Waals bonded liquids and one hydrogen-bonding molecular liquid are studied as a function of pressure and temperature by incoherent neutron scattering using simultaneous dielectric spectroscopy. The dynamics are studied in a range of alpha relaxation times from pico- to milliseconds, primarily in the equilibrium liquid state. In this range, we find that isochronal superposition and density scaling work not only for the two van der Waals liquids but also for the hydrogen-bonding liquid, though the density scaling exponent is much smaller for the latter. Density scaling and isochronal superposition are seen to break down for intra-molecular dynamics when it is separated in time from the alpha relaxation, in close agreement with previous observations from molecular dynamics simulations.

Liquid dynamics in partially crystalline glycerol.

We present a dielectric study on the dynamics of supercooled glycerol during crystallization. We explore the transformation into a solid phase in real time by monitoring the temporal evolution of the amplitude of the dielectric signal. Neither the initial nucleation nor the crystal growth influences the liquid dynamics visibly. For one of the samples studied, a tiny fraction of glycerol remained in the disordered state after the end of the transition. We examined the nature of the α relaxation in this frustrated crystal and find that it is virtually identical to the bulk dynamics. In addition, we have found no evidence that supercooled glycerol transforms into a peculiar phase in which either a new solid amorphous state or nano-crystals dispersed in a liquid matrix are formed.

Relaxation processes in a lower disorder order transition diblock copolymer.

The dynamics of lower disorder-order temperature diblock copolymer leading to phase separation has been observed by X ray photon correlation spectroscopy. Two different modes have been characterized. A non-diffusive mode appears at temperatures below the disorder to order transition, which can be associated to compositional fluctuations, that becomes slower as the interaction parameter increases, in a similar way to the one observed for diblock copolymers exhibiting phase separation upon cooling. At temperatures above the disorder to order transition TODT, the dynamics becomes diffusive, indicating that after phase separation in Lower Disorder-Order Transition (LDOT) diblock copolymers, the diffusion of chain segments across the interface is the governing dynamics. As the segregation is stronger, the diffusive process becomes slower. Both observed modes have been predicted by the theory describing upper order-disorder transition systems, assuming incompressibility. However, the present results indicate that the existence of these two modes is more universal as they are present also in compressible diblock copolymers exhibiting a lower disorder-order transition. No such a theory describing the dynamics in LDOT block copolymers is available, and these experimental results may offer some hints to understanding the dynamics in these systems. The dynamics has also been studied in the ordered state, and for the present system, the non-diffusive mode disappears and only a diffusive mode is observed. This mode is related to the transport of segment in the interphase, due to the weak segregation on this system.

Changes in mobility of plastic crystal ethanol during its transformation into the monoclinic crystal state.

Transformation of deuterated ethanol from the plastic crystal phase into the monoclinic one is investigated by means of a singular setup combining simultaneously dielectric spectroscopy with neutron diffraction. We postulate that a dynamic transition from plastic crystal to supercooled liquid-like configuration through a deep reorganization of the hydrogen-bonding network must take place as a previous step of the crystallization process. Once these precursor regions are formed, subsequent crystalline nucleation and growth develop with time.

Accuracy of Two Continuous Glucose Monitoring Devices During Aerobic and High-Intensity Interval Training in Individuals with Type 1 Diabetes.

Background: This study aimed to evaluate the accuracy of Dexcom G6 (DG6) and FreeStyle Libre-2 (FSL2) during aerobic training and high-intensity interval training (HIIT) in individuals with type 1 diabetes. Methods: Twenty-six males (mean age 29.3 ± 6.3 years and mean duration of diabetes 14.9 ± 6.1 years) participated in this study. Interstitial glucose levels were measured using DG6 and FSL2, while plasma glucose levels were measured every 10 min using YSI 2500 as the reference for glucose measurements in this study. The measurements began 20 min before the start of exercise and continued for 20 min after exercise. Seven measurements were taken for each subject and exercise. Results: Both DG6 and FSL2 devices showed significant differences compared to YSI glucose data for both aerobic and HIIT exercises. Continuous glucose monitoring (CGM) devices exhibited superior performance during HIIT than aerobic training, with DG6 showing a mean absolute relative difference of 14.03% versus 31.98%, respectively. In the comparison between the two devices, FSL2 demonstrated significantly higher effectiveness in aerobic training, yet its performance was inferior to DG6 during HIIT. According to the 40/40 criteria, both sensors performed similarly, with marks over 93% for all ranges and both exercises, and above 99% for HIIT and in the >180 mg/dL range, which is in accordance with FDA guidelines. Conclusions: The findings suggest that the accuracy of DG6 and FSL2 deteriorates during and immediately after exercise but remains acceptable for both devices during HIIT. However, accuracy is compromised with DG6 during aerobic exercise. This study is the first to compare the accuracy of two CGMs, DG6, and FSL2, during two exercise modalities, using plasma glucose YSI measurements as the gold standard for comparisons. It was registered at clinicaltrials.gov (NCT06080542).

Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure.

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.

Prevention of Barrett esophagus and esophageal adenocarcinoma by smoothened inhibitor in a rat model of gastroesophageal reflux disease.

BACKGROUND: Activated hedgehog (Hh) pathway is associated with development of both Barrett esophagus (BE) and esophageal adenocarcinoma (EAC). We hypothesize that blockade of the Hh pathway with smoothened (Smo) inhibitor can prevent the development of BE/EAC in the Levrat model, in which induced gastroduodenoesophageal reflux (GDER) leads to esophageal carcinogenesis. METHODS: GDER was induced in 6- to 8-week-old male Sprague-Dawley rats. The Smo inhibitor (10 mg/kg/d) was given orally on postoperative weeks 10 to 16, 18 to 22, and 24 to 28, and rats were killed on week 28. The primary outcome measure was the incidence of BE and EAC. To examine potential therapeutic effects of Smo inhibition on tumor tissue, semiquantitative immunohistochemistry for Ki-67 and caspase 3 was performed. In treated animals that developed cancer, gene expression was analyzed. RESULTS: Thirty-eight of 48 controls and 32 of 46 treated animals survived to 28 weeks. messenger ribonucleic acid (mRNA) expression of Indian Hh, a ligand of transmembrane receptor patched 1, was 184× higher in BE and 99× higher in EAC compared with normal esophageal tissue (P = 0.0239 and P = 0.0004, respectively). Compared with controls, the incidence of BE and EAC was decreased in treated animals by 35.7% (relative risk reduction, 36%; P = 0.0015) and 36% (relative risk reduction, 62%; P = 0.0033), respectively. Compared with untreated EAC, Ki-67 was downregulated (P = 0.04) and cleaved caspase 3 was no different in treated EAC (P = 0.398). Of the 84 well-known genes involved in cancer drug resistance, 50 were dysregulated in treated EAC (P < 0.05 for each gene). CONCLUSIONS: Smo inhibitor prevents the development of BE and EAC in an in vivo model of GDER.

Localized translational motions in semicrystalline poly(ethylene terephthalate) studied by incoherent quasielastic neutron scattering.

One of the simplest ways to confine polymeric materials is by self-assembling during the crystallization process. The remaining amorphous phase is then constrained by the lamellar crystals. In this manuscript, we aim to shed additional light in the understanding of the amorphous chains dynamics of semicrystalline polymers above the Tg by using incoherent quasielastic neutron scattering QENS in a nanoscopic time scale (10(-9)-10(-10)s) on poly(ethylene terephthalate). The observed dynamics is satisfactorily described by a theoretical model that considers that the proton mobility follows a random jump-diffusion in a restricted environment. We demonstrate that the combination of macroscopic with nanoscopic dynamic tools allows a complete description of the confined dynamics on a paradigmatic semicrystalline polymer like poly(ethylene terephthalate).

Feasibility, safety, acceptability, and yield of office-based, screening transnasal esophagoscopy (with video).

BACKGROUND: Endoscopic screening for esophageal neoplasia can identify patients eligible for early intervention for precancerous lesions. Unsedated transnasal esophagoscopy may provide an efficient and accurate endoscopic assessment with fewer risks and less cost, compared with conventional upper endoscopy. OBJECTIVE: To assess the feasibility, safety, acceptability, and yield of unsedated transnasal esophagoscopy in a primary care population. DESIGN: Multicenter, prospective, cross-sectional study. SETTING: Two outpatient tertiary-care centers. PATIENTS: This study involved a general medical clinic population aged between 40 and 85 years. INTERVENTION: Unsedated, office-based transnasal esophagoscopy. MAIN OUTCOME MEASUREMENTS: Procedure yield; completeness of examination; procedure length; adverse events and complications; choking, gagging, pain, or anxiety during the examination; and overall tolerability. RESULTS: A total of 426 participants (mean [± standard deviation] age 55.8 ± 9.5 years; 43% male) enrolled in the study, and 422 (99%) completed the examination. Mean (± standard deviation) examination time was 3.7 ± 1.8 minutes. There were no serious adverse events, and 12 participants (2.8%) reported minor complications. Participants reported minimal choking, gagging, pain, or anxiety. The examination was well-tolerated by most participants. Overall, 38% of participants had an esophageal finding that changed management (34% erosive esophagitis, 4% Barrett's esophagus). LIMITATIONS: Nonrandomized study, tertiary-care centers only, self-selected population with a large proportion reporting esophageal symptoms. CONCLUSION: Unsedated transnasal esophagoscopy is a feasible, safe, and well-tolerated method to screen for esophageal disease in a primary care population. Endoscopic findings are common in this patient population.

Relaxation Dynamics of Biomass-Derived Copolymers With Promising Gas-Barrier Properties.

This article presents an experimental study on the relaxation dynamics of a series of random copolymers based on bio-friendly comonomers with interesting gas barrier properties. We analyze the relaxation response in the glassy and ultraviscous regime of poly (trimethylene furanoate/sebacate) random copolymers via dielectric spectroscopy. We report lower values of dynamic fragility [a dimensionless index introduced in 1985 (Angell, Relaxations in Complex Systems, 1985)] in comparison to popular polyesters widely used in industry, such as poly (ethylene terephthalate), suggesting that the amorphous phase of these furanoate-based polyesters adopt an efficient chain packing. This is consistent with their low permeability to gases. We also discuss on different equations (phenomenological and theory-based approaches) for fitting the temperature-evolution of the alpha relaxation time.

No Evidence that CD33 rs12459419 Polymorphism Predicts Gemtuzumab Ozogamicin Response in Consolidation Treatment of Acute Myeloid Leukemia Patients: Experience of the PETHEMA Group.

Gemtuzumab ozogamicin (GO) is a conjugate of a monoclonal antibody and calicheamicin, which has been reapproved for the treatment of acute myeloid leukemia (AML). AML patients with the CD33 rs12459419 CC genotype might benefit from the addition of GO to intensive treatment in contrast to patients with CT/TT genotypes. Nevertheless, contradictory results have been reported. We sought to shed light on the prediction of GO response in AML patients with rs12459419 polymorphism who were treated with GO in the consolidation (n = 70) or reinduction (n = 20) phase. The frequency distribution of the rs12459419 polymorphism in the complete cohort of patients was 44.4% (n = 40), 50% (n = 45), and 5.6% (n = 5) for CC, CT, and TT genotypes, respectively. Regarding the patients treated with GO for consolidation, we performed a Kaplan-Meier analysis of overall survival and relapse-free survival according to the rs12459419 polymorphism (CC vs. CT/TT patients) and genetic risk using the European Leukemia Net (ELN) 2010 risk score. We also carried out a Cox regression analysis for the prediction of overall survival, with age and ELN 2010 as covariates. We found no statistical significance in the univariate or multivariate analysis. Additionally, we performed a global Kaplan-Meier analysis for the patients treated with GO for reinduction and did not find significant differences; however, our cohort was too small to draw any conclusion from this analysis. The use of GO in consolidation treatment is included in the approval of the compound; however, evidence regarding its efficacy in this setting is lacking. Rs12459419 polymorphism could help in the selection of patients who might benefit from GO. Regrettably, in our cohort, the rs12459419 polymorphism does not seem to be an adequate tool for the selection of patients who might benefit from the addition of GO in consolidation cycles.

Detection of early stage precursor during formation of plastic crystal ethanol from the supercooled liquid state: a simultaneous dielectric spectroscopy with neutron diffraction study.

Transformation of deuterated ethanol from supercooled liquid into a plastic crystal or rotator phase is investigated by means of a particular experimental setup combining simultaneously dielectric spectroscopy with neutron diffraction techniques. We demonstrate that, previous to the growth of the bcc lattice of the plastic crystal phase, the formation of a precursor or intermediate phase through a liquid-liquid phase separation takes place. Once this precursor phase is formed, subsequent (plastic) crystalline nucleation and growth is expected to develop.