Chronic myeloproliferative neoplasm in adulthood in CBL syndrome harboring a splice-site CBL variant alongside a novel constitutional CSF3R variant.

Casitas B-cell lineage (CBL) syndrome is a rare RASopathy known to predispose to CBL-mutated juvenile myelomonocytic leukemia (JMML) in childhood. Adulthood acute myeloid leukemia arising out of a genetic aberrancies consistent with prior CBL-mutated JMML has been twice previously described, but chronic myeloproliferative neoplasia has not. We present a case of progressive myeloproliferative neoplasm in adulthood in the context of CBL syndrome alongside a novel CSF3R variant. We also review pathogenic splice-site mutations in CBL-mutated JMML.

Arsenic-induced neurotoxicity in patients with acute promyelocytic leukaemia.

Arsenic trioxide is an essential component of therapy for acute promyelocytic leukaemia (APL) and is currently dosed on actual body weight with no upper limit. Arsenic-induced neurotoxicity is a well-recognised complication; however, there is uncertainty about its relationship to arsenic dose and obesity. We conducted a large multicentre retrospective study of 487 patients with APL treated with arsenic-based therapy across 23 sites in Australia from 2008 to 2023. The primary outcome was incidence of neurotoxicity, and secondary outcomes included relationship of neurotoxicity to obesity and cumulative arsenic dose. Any-grade neurotoxicity occurred in 113 (23%) patients, predominantly peripheral neuropathy (91%). Most events were grade 1-2 severity (85%), with grade 3 events in 12% and grade 4-5 in 3%. The incidence of neurotoxicity increased with BMI (non-obese: 16%, obesity class I: 25%, obesity class II-III: 41%; p < 0.001). On univariable analysis, obesity class I (OR 1.81, p = 0.036), obesity class II-III (OR 3.93, p < 0.001), weight >100 kg (OR 2.72, p < 0.001), daily arsenic trioxide dose >15 mg (OR 5.05, p < 0.001) and cumulative induction dose >500 mg (OR 3.95, p < 0.001) were all significantly associated with neurotoxicity. Obesity class II-III and induction dose >500 mg remained significant on multivariable analysis. Our study highlights the strong association between BMI, arsenic trioxide dose and neurotoxicity. Pre-emptive dose reductions should be considered for obese patients receiving high doses of arsenic.

The Current Role of Platelet Function Testing in Clinical Practice.

Platelet dysfunction, whether hereditary or acquired, may increase an individual's risk of spontaneous, posttraumatic, or postoperative bleeding. Conversely, increased platelet reactivity on antiplatelet agents following vascular (in particular, coronary vascular) intervention may increase the risk of thrombosis and adverse vascular events. The aim of platelet function testing is to identify and characterize platelet dysfunction in these settings to inform bleeding/ thrombosis risk and guide perioperative prophylactic management strategies. A vast array of screening and diagnostic tests is available for this purpose. The successful clinical application of platelet function tests depends on the knowledge of their analytical strengths and limitations and the correct extrapolation of derived results to a particular clinical scenario. This review critically appraises traditional and contemporary platelet function testing focusing on their role in clinical practice.

Addition of sodium alginate and pectin to a carbohydrate-electrolyte solution does not influence substrate oxidation, gastrointestinal comfort, or cycling performance.

Eight well-trained cyclists ingested 68 g·h-1 of a carbohydrate-electrolyte solution with sodium alginate and pectin (CHO-ALG) or a taste and carbohydrate type-matched carbohydrate-electrolyte solution (CHO) during 120 min of cycling at 55% maximal power followed by an ∼20 min time trial. Oxygen uptake, carbon dioxide production, blood glucose concentration, substrate oxidation, gastrointestinal symptoms, and time trial performance (CHO-ALG: 1219 ± 84 s, CHO: 1267 ± 102 s; P = 0.185) were not different between trials. Novelty Inclusion of sodium alginate and pectin in a carbohydrate drink does not influence blood glucose, substrate oxidation, gastrointestinal comfort, or performance in cyclists.

Thermal signature characteristics of vehicle/terrain interaction disturbances: implications for battlefield vehicle classification.

Thermal emissivity spectra (8-14 microm) of track impressions/background were determined in conjunction with operation of six military vehicle types, T-72 and M1 Tanks, an M2 Bradley Fighting Vehicle, a 5-ton truck, a D7 tractor, and a High Mobility Multipurpose Wheeled Vehicle (HMMWV), over diverse soil surfaces to determine if vehicle type could be related to track thermal signatures. Results suggest soil compaction and fragmentation/pulverization are primary parameters affecting track signatures and that soil and vehicle/terrain-contact type determine which parameter dominates. Steel-tracked vehicles exert relatively low ground-contact pressure but tend to fragment/pulverize soil more so than do rubber-tired vehicles, which tend mainly to compact. In quartz-rich, lean clay soil tracked vehicles produced impressions with spectral contrast of the quartz reststrahlen features decreased from that of the background. At the same time, 5-ton truck tracks exhibited increased contrast on the same surface, suggesting that steel tracks fragmented soil while rubber tires mainly produced compaction. The structure of materials such as sand and moist clay-rich river sediment makes them less subject to further fragmentation/pulverization; thus, compaction was the main factor affecting signatures in these media, and both tracked and wheeled vehicles created impressions with increased spectral contrast on these surfaces. These results suggest that remotely sensed thermal signatures could differentiate tracked and wheeled vehicles on terrain in many areas of the world of strategic interest. Significant applications include distinguishing visually/spectrally identical lightweight decoys from actual threat vehicles.