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A randomized phase 2 study combining midostaurin, low-dose cytarabine and venetoclax in newly diagnosed AML ≥60 years.

In randomized studies, addition of FLT3 inhibitors failed to improve survival in older patients with FLT3-ITD AML unfit for intensive chemotherapy. Although hypomethylating agents or low-dose cytarabine combined with venetoclax is standard, FLT3-ITD is an important mechanism of resistance and a barrier to improved survival. Recent studies show promise for the addition of gilteritinib or quizartinib to less intensive venetoclax-based therapy, however resulting marrow toxicity requires substantial reductions to administered treatment. The INTERVENE study (Investigating Novel Triplets to Extend R…

The Impact of Intraoperative Fluid Management on Postoperative Complications Following Thoracic Surgery: An Evaluation From the German Thoracic Registry.

OBJECTIVES: This study assessed the impact of perioperative crystalloid volume on postoperative complications after lung surgery. Postoperat … and application of exclusion criteria, a matching process was carried out. Two hundred four matched triplets (n = 612) were formed. INTERVENTIONS: Differences were analyzed only in patients receiving crystalloid administration. Data on biometrics, perioperative management, and postoperative complications were analyzed, including subgroup analyses (wedge v …

A simple and broadly applicable nanobody-based approach to generate potent TNFR agonists.

The receptors of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF) are of overwhelming scientific and clinical relevance and sta … TRAILR2/DR5, GITR, OX40, TNFR1 and TNFR2, we show here that genetic fusion of single-chain encoded triplets of these nanobodies with oligomerizing protein scaffolds regularly results in potent hexa-, nona- and dodecavalent agonists inducing TNFR signaling with EC50-values in the sub-nanomolar range. The oligovalent nanobody formats described exhibit super …

Validation of the new IMS/IMWG consensus genomic staging (CGS) of high-risk multiple myeloma (HRMM) in a contemporary cohort of 1209 patients.

Due to its high clinical and biological complexity, multiple myeloma (MM) is a malignancy of heterogeneous prognoses and outcomes. The International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) formulated a consensus genomic staging (CGS) of high-risk MM (HRMM), aiming to refine and homogenize the classification of high-risk disease. We evaluated the new HRMM criteria in a cohort of 1209 consecutive newly diagnosed MM patients with complete CGS data (except TP53 mutations), treated in a single center with contemporary regimens, including triplets and quadruplets, between 20…

Прогресс в нескольких миеломах: ключевые обновления из ASH 2025 Встреча.

С расширением иммунных стратегий происходит стремительная трансформация терапевтического ландшафта с множественными миеломами (ММ). В этой редакционной статье резюмируются ключевые выдержки из ММ, представленные Американскому обществу гематологии (АШ) 2025 :: встреча на высшем уровне, в ходе которой особое внимание было уделено вопросу о том, каким образом подходы к адаптации к минимально остаточным заболеваниям (МВД) и иммунные платформы следующего поколения изменяют методы лечения на всех этапах заболевания ММ. В недавно диагностированном MM (NDMM) минимальное остаточное заболевание (MRD)-ад

Совпадение в аннотации оригинала
The therapeutic landscape of multiple myeloma (MM) is undergoing rapid transformation with the expansion of immune-based strategies. This ed … nd overall survival (OS) benefits with BsAb teclistamab plus daratumumab compared to other standard triplets, with response rates approaching those historically observed with chimeric antigen receptor (CAR) T cell therapy. A novel rational BsAb combination of BsAb elranatamab anda cereblon E3 ligase modulatory drug (CELMoD) iberdomide in MagnetisMM-30 show …

Advancing biomedical data analytics using explainable neural network-based learning model for progressive neurodegenerative disorder diagnosis.

Huntington's disease (HD) is an inherited neurological disease caused by variations in the huntingtin (HTT) gene, which leads to neuronal degeneration. Conventionally, HD is affiliated with the gathering and misfolding of mutant HTT arising from an increased number of CAG triplets. Artificial Intelligence has emerged as an important tool in healthcare, supporting the monitoring, detection, and management of HD. Machine learning and deep learning methods are widely used for automated HD identification using neuroimaging, genetic, and clinical data. However, most DL models behave like a black bo…

Outcomes of Newly Diagnosed Multiple Myeloma Patients Requiring Dialysis.

INTRODUCTION: Renal impairment (RI) is a common complication in newly diagnosed multiple myeloma (NDMM), with 1-5% of patients presenting wi … high-risk cytogenetics. All patients received bortezomib-based induction therapy (19% doublets, 71% triplets, 10% quadruplets; 12% anti-CD38 antibodies). Median follow-up was 37.2 months. Dialysis independence was achieved by 31 patients (42.5%) after a median of 52 days (range 3-247). Dialysis independence was associated with improved survival (median 36 …

Influence of genetic and environmental factors on transverse growth.

OBJECTIVES: The aim of the study was to determine the genetic and environmental effects on transverse growth of craniofacial structures, within and between identical and fraternal twins. METHODS: The sample consisted of 142 children in total, divided into 29 pairs of monozygotic twins, 42 pairs of dizygotic twins, and 1 set of dizygotic triplets. Postero-anterior cephalometric radiographs were taken at the ages of 9, 12, and 15 years. Intercanine width, maxillary width, mandibular width, nasal width, and facial width variables were measured. The genetic and environmental components of varianc…

TP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates.

TP53 mutations are found in 5%-10% of de novo myelodysplastic syndrome (MDS) and AML cases. By contrast, in therapy related MDS and AML, mut … AML has been APR-246 (eprenetapopt) a p53 reactivator, in combination with azacitidine, but also in triplets with venetoclax. Despite positive results in phase II trials, a phase III trial did not confirm superior response or improved survival. Other agents, like magrolimab (anti-CD47 antibody), failed to demonstrate improved activity in TP53-mutant MDS an …

Presentation and Prognosis of Excessive Asymptomatic Atrial Ectopy in Children and Adolescents With Structurally and Functionally Normal Hearts.

Excessive premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are presumed to be benign and self-resolv … stimulant medications were the chief predictors for a reduction of PAC burden on follow-up. Atrial triplets at presentation were associated with a 5.4% increase. In conclusion, this study confirms that excessive asymptomatic childhood PACs with structurally normal hearts are rare and short-term to medium-term prognosis is benign.

Comparison of the diagnostic value of a small, single channel, electrocardiogram monitoring patch with a standard 3-lead Holter system over 24 hours in dogs.

INTRODUCTION/OBJECTIVES: The aim of this study was to compare a novel small event recorder device, the Carnation Ambulatory Monitor (CAM), w … 087), number of ventricular ectopic complexes (P=0.55), ventricular couplets (P=0.186), ventricular triplets (P=0.203), ventricular tachycardia (P=0.05), Lown grade (P=0.233), presence or absence of ventricular bigeminy, trigeminy, supraventricular tachycardia, and atrial fibrillation (P=0.98) did not differ. The CAM missed some relevant events, like compl …

Remote self-report and speech-in-noise measures predict clinical audiometric thresholds.

Developments in smartphone technology and the COVID-19 pandemic have highlighted the feasibility and need for remote, but reliable hearing t … hearing loss (HL, N=18), were measured using English-language digits (0-9), binaurally presented as triplets in one of four speech-shaped noise maskers (broadband, low-pass filtered at 2, 4, 8 kHz) and two digit phases (diotic, antiphasic). High, significant intraclass correlation coefficients indicated strong internal consistency of remote-DIN SRTs, which …

Outcome of Monochorionic Pregnancies after Selective Feticide with Bipolar Cord Coagulation: A German Single Center Experience.

OBJECTIVES: To review the outcome of complicated monochorionic pregnancies after fetoscopic selective feticide with bipolar cord coagulation … gnosed 56 monochorionic pregnancies, including 43 diamniotic and 8 monoamniotic twins, as well as 5 triplets, complicated by discordant fetal anomalies (n = 10), selective intrauterine growth restriction (n = 29), twin-to-twin transfusion syndrome (n = 13), twin reversed arterial perfusion sequence (n = 3), or severe early twin anemia polycythemia sequence …

Effective Head Impact Kinematics to Preserve Brain Strain.

Conventional kinematics-based brain injury metrics often approximate peak maximum principal strain (MPS) of the whole brain but ignore the a … enue to reduce an arbitrary head impact into an idealized but actual "impact mode" characterized by triplets of basic kinematic variables. They retain specific physical interpretations of head impact and may be an advancement over state-of-the-art kinematics-based scalar metrics for more effective impact comparison in the future.

Frequent premature ventricular contractions. Association of burden and complexity with prognosis according to the presence of structural heart disease.

INTRODUCTION: Premature ventricular contractions (PVC) have been associated with mortality and heart failure (HF) regardless the presence of … on burden was 2.7 (IQR: 1.6-6.7). SHD patients had more polymorphic PVCs, 77% versus 65%, p = .022, triplets and episodes of non-sustained ventricular tachycardia (NSVT): 44% versus 27%, p = .002; 30% versus 12%, p < .0001. In idiopathic patients, a PVC% in the third quartile was independently associated with all-cause mortality hazard ratio (HR) 2.288 (1. …

Relationship Between Ventricular Arrhythmias, Conduction Disorders, and Myocardial Fibrosis in Patients With Systemic Sclerosis.

BACKGROUND: Delayed-enhancement magnetic resonance imaging (DE-MRI) is a noninvasive diagnostic tool able to identify myocardial fibrosis. I … ions [PVCs]/24 hours) (48 ± 304 vs. 69 ± 236, P = 0.97), ventricular arrhythmia severity (couplets, triplets, runs) on Holter ECG, or in the presence of conduction disorders (36% vs. 40%, P = 0.86) between patients with and without myocardial fibrosis. In univariate analysis, diffuse fibrosis was weakly associated with the number of PVCs/24 hours (R = 0.15 …

Evidence of cardiac electrical remodeling in patients with Huntington disease.

OBJECTIVE: Although Huntington's disease (HD) is a disease of the central nervous system, HD mortality surveys indicate heart disease as a m … onounced. Further, both variables correlated with the product of the cytosine-adenine-guanine (CAG) triplets' repeat length and the subjects' age (CAP), the former R = 0.423 (p = 0.018) and the latter R = 0.499 (p = 0.004). There was no correlation between the CAP score and any of variables representing autonomic nervous system activity. CONCLUSIONS: Both …

Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus.

BACKGROUND: Phenol-soluble modulins (PSM) are amphipathic proteins produced by Staphylococcus aureus that promote virulence, inflammatory re … ts with SSTI, HAP, and IE were matched 1:1:1 based on geographic origin of the infection to form 54 triplets (North America n = 27, Europe n = 25, Australia n = 2). All isolates underwent spa typing and were classified using eGenomics. In vitro PSM production was quantified by high-performance liquid chromatography/mass spectrometry. Fischer's Exact Test a …

Ambulatory Monitoring and Arrhythmic Outcomes in Pediatric and Adolescent Patients With Duchenne Muscular Dystrophy.

BACKGROUND: Patients with Duchenne Muscular Dystrophy (DMD) develop cardiac fibrosis and dilated cardiomyopathy. We described the frequency … ined atrial tachycardia (P=0.01), frequent premature ventricular contractions, ventricular couplets/triplets, and nonsustained ventricular tachycardia (P<0.001) compared to the other groups. LVEF <35% (P<0.001) was the only predictor of clinically significant Holter finding. Four patients (40%) had change in medication in the LVEF <35% group compared to 9 …

Toxicity of concurrent radiochemotherapy for locally advanced non--small-cell lung cancer: a systematic review of the literature.

Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two met … ute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets.