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Prognostic Significance of Monocytic-like Phenotype in AML patients treated with Venetoclax and Azacytidine

Blood Adv. 2025 Apr 18:bloodadvances.2024015734. doi: 10.1182/bloodadvances.2024015734. Online ahead of print.

ABSTRACT

The prognostic impact of monocytic differentiation in AML patients receiving Venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed AML patients treated with Ven-Aza, we used multiparametric flow cytometry (MFC) to define mono-blasts as AML blasts co-expressing ≥2 monocytic markers (CD4, CD36, CD64) per ELN guidelines. Patients with higher mono-blasts/CD45+ proportions had lower complete response rates (OR=0.24, p=0.005) and significantly shorter overall survival (OS, 4.0 versus 14.9 months, p=0.003). A ≥10% mono-blasts/CD45+ threshold, identified via maximally selected rank statistics, stratified patients into mono-blasthigh (≥10%) and mono-blastlow (<10%) groups. MFC reclassified 20% of FAB non-M4/5 and 15% of FAB M4/5 cases into mono-blasthigh and mono-blastlow groups, respectively. Multivariable analysis confirmed mono-blasthigh status as an independent adverse prognostic factor for OS (HR=1.95, p=0.023), with a particularly strong impact in ELN 2024 favorable-risk patients (HR=2.81, p=0.024). Our findings highlight monocytic differentiation, assessed via MFC, as a key predictor of Ven-Aza resistance and poor survival, independent of genetic classification. Given its availability in routine diagnostics, MFC-based monocytic assessment could improve AML risk stratification and treatment decisions in patients eligible for less intensive therapies.

PMID:40249917 | DOI:10.1182/bloodadvances.2024015734

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Mepolizumab in severe uncontrolled CRSwNP: a real-life multicentre study in Northeast Italy

Rhinology. 2025 Apr 18. doi: 10.4193/Rhin24.420. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the efficacy of mepolizumab as add-on therapy to intranasal corticosteroids for the treatment of severe, uncontrolled Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in a real-life setting in the Triveneto region of northeast Italy.

METHODS: Patients with severe CRSwNP receiving mepolizumab were followed up at 1, 3, 6, 9 and 12 months from the first administration. At baseline and at each follow-up, patients underwent nasal endoscopy, completed the Sinonasal Outcome Test 22, Visual Analogue Scales for smell, nasal obstruction, rhinorrhoea and facial pain, the Nasal Congestion Score and the Asthma Control Test. Peak nasal inspiratory flow, Sniffin’ Sticks Identification Test and blood eosinophil count were also evaluated.

RESULTS: Ninety patients from twelve different rhinological units were enrolled in the study. Both patient- and physician- derived outcome measures significantly improved within the first month after biological treatment initiation, maintaining the benefit at subsequent follow-ups. Nine percent of patients discontinued the treatment due to lack of benefit within the first year. No major adverse events were reported.

CONCLUSIONS: Mepolizumab is effective in improving nasal obstruction and the sense of smell in patients with severe uncontrolled CRSwNP, based on both patient- and physician derived outcome measures.

PMID:40249916 | DOI:10.4193/Rhin24.420

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Without Fail: Muscular Adaptations in Single Set Resistance Training Performed to Failure or with Repetitions-in-Reserve

Med Sci Sports Exerc. 2025 Apr 18. doi: 10.1249/MSS.0000000000003728. Online ahead of print.

ABSTRACT

METHODS: Forty-two young, resistance-trained men and women were randomly assigned to 1 of 2 parallel groups: A group that trained to failure on all exercises (FAIL) or a submaximal effort group (2-RIR) that trained with two repetitions in reserve for the same exercises. Participants performed a single set of 9 exercises targeting all major muscle groups per session, twice weekly for 8 weeks. We assessed pre-post study changes in muscle thickness for the biceps brachii, triceps brachii, and quadriceps femoris, along with measures of muscular strength, power, endurance, and ability to estimate RIR in the bench press and squat.

RESULTS: Results indicated that both FAIL and 2-RIR elicited appreciable gains in most of the assessed outcomes. Several measures of hypertrophy tended to favor FAIL, although absolute differences between conditions were generally modest. Increases in countermovement jump height favored FAIL, but with no clear statistical support for either the null or alternative hypothesis. Increases in strength and local muscular endurance were similar between conditions. Participants demonstrated greater accuracy in estimating RIR for the bench press compared to the squat and improved their accuracy over the intervention, particularly for the bench press.

CONCLUSIONS: These findings suggest that single-set routines can be a time-efficient strategy for promoting muscular adaptations in resistance-trained individuals, even when transitioning from higher-volume programs. Training to failure in single-set routines may modestly enhance some measures of muscle hypertrophy and power, but not strength or local muscle endurance.

PMID:40249908 | DOI:10.1249/MSS.0000000000003728

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Rest Activity Rhythms and their Association with Cardiorespiratory Fitness and Walking Energetics in Older Adults: Study of Muscle, Mobility and Aging

Med Sci Sports Exerc. 2025 Apr 18. doi: 10.1249/MSS.0000000000003730. Online ahead of print.

ABSTRACT

PURPOSE: It is recognized that disruptions in circadian behavior, such as with shift work or jet lag, are associated with diminished health. This known relationship implies that people with stronger indices of circadian behavior will exhibit improved physiology. To address the association between rhythmic activity behavior and physiology we proposed that metrics indicative of ‘more rhythmic’ rest-activity patterns would be associated with better cardiorespiratory fitness and walking energetics in a cohort of older adults.

METHODS: Using baseline data from the Study of Muscle, Mobility and Aging (N = 799, Age: 76 ± 5 yrs, 58% female), we quantified metrics describing rhythmic aspects of rest-activity behavior (amplitude, robustness, time of peak activity, others) from continuous wrist-worn accelerometry. We used linear models to examine cross-sectional associations between rhythmic metrics with VO2peak and walking energetics (cost-capacity ratio at slow and preferred walking speeds) adjusted for age, sex, race, height, health conditions, and other factors.

RESULTS: Metrics that reflect more rhythmic behavior were associated with VO2peak (higher amplitude: Q1: 18.4 vs. Q4: 22.0 mL·kg-1·min-1; p-trend <0.001, higher pseudo F-statistic/robustness Q1: 19.2 vs. Q4: 21.3 mL·kg-1·min-1; p-trend <0.001, and earlier time of peak activity (Q1 (earliest): 20.9 vs. Q4 (latest): 19.2 mL·kg-1·min-1; p-trend <0.001). Similar trends were observed with lower cost-capacity ratio at preferred and slow walking speeds (amplitude, pseudo F-statistic, acrophase: p-trend <0.001 for all).

CONCLUSIONS: More rhythmic activity behavior and earlier time of peak activity were associated with better cardiorespiratory fitness and walking energetics. These findings support the framework that rhythmic activity supports healthy physiology. Further investigations are warranted to determine if declines in rhythmicity of human behavior are predictive of disease.

PMID:40249906 | DOI:10.1249/MSS.0000000000003730

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Dietary Carbohydrates Influence the Performance Outcomes of Short-Term Heat Acclimation

Med Sci Sports Exerc. 2025 Apr 18. doi: 10.1249/MSS.0000000000003726. Online ahead of print.

ABSTRACT

PURPOSE: Studies on heat acclimation (HA) involving high-intensity exercise report impairments in time trial (TT) performance in the heat immediately after HA. This study aimed to determine whether a high-carbohydrate (HC) diet can enhance 3.22 km run TT performance in the heat following exercise-intensive short-term HA.

METHODS: Fourteen healthy military-age males were assigned to either a HC diet (70 %kcal carbohydrate (CHO), n = 7) or lower CHO comparison (COMP, 35 %kcal CHO, n = 7) to be consumed during and for one week after a 6-day HA protocol.

RESULTS: Baseline descriptive statistics, heat tolerance, and run performance were similar between groups (p > 0.05). Both groups acclimated, showing reduced heart rate, rectal and skin temperature, and increased sweat rate (each p ≤ 0.03) during heat stress testing one day and five days after HA. The HC group demonstrated a faster TT (959 ± 103 sec vs. 1067 ± 172, p = 0.02, g = 0.71) than COMP one day post-HA. HC showed improved TT performance from baseline at one day (p = 0.01, g = 0.59) and five days post-HA (p = 0.04, g = 0.59). The HC group showed greater TT improvement at one day (-7.0 ± 4.9 % vs. -0.7 ± 4.7 %, p = 0.03, g = 1.23) and five days post-HA (-8.4 ± 4.9 % vs. -2.8 ± 3.9 %, p = 0.01, g = 1.18), with no group differences in HA outcomes or relative strain during TT.

CONCLUSIONS: Insufficient CHO intake during heavy daily exertion in unacclimated heat stress, such as in short-term HA, may affect post-HA performance outcomes unless addressed with additional CHO consumption.

PMID:40249903 | DOI:10.1249/MSS.0000000000003726

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Evaluation of error detection and treatment recommendations in nucleic acid test reports using ChatGPT models

Clin Chem Lab Med. 2025 Apr 21. doi: 10.1515/cclm-2025-0089. Online ahead of print.

ABSTRACT

OBJECTIVES: Accurate medical laboratory reports are essential for delivering high-quality healthcare. Recently, advanced artificial intelligence models, such as those in the ChatGPT series, have shown considerable promise in this domain. This study assessed the performance of specific GPT models-namely, 4o, o1, and o1 mini-in identifying errors within medical laboratory reports and in providing treatment recommendations.

METHODS: In this retrospective study, 86 medical laboratory reports of Nucleic acid test report for the seven upper respiratory tract pathogens were compiled. There were 285 errors from four common error categories intentionally and randomly introduced into reports and generated 86 incorrected reports. GPT models were tasked with detecting these errors, using three senior medical laboratory scientists (SMLS) and three medical laboratory interns (MLI) as control groups. Additionally, GPT models were tasked with generating accurate and reliable treatment recommendations following positive test outcomes based on 86 corrected reports. χ2 tests, Kruskal-Wallis tests, and Wilcoxon tests were used for statistical analysis where appropriate.

RESULTS: In comparison with SMLS or MLI, GPT models accurately detected three error types, and the average detection rates of the three GPT models were 88.9 %(omission), 91.6 % (time sequence), and 91.7 % (the same individual acted both as the inspector and the reviewer). However, the average detection rate for errors in the result input format by the three GPT models was only 51.9 %, indicating a relatively poor performance in this aspect. GPT models exhibited substantial to almost perfect agreement with SMLS in detecting total errors (kappa [min, max]: 0.778, 0.837). However, the agreement between GPT models and MLI was moderately lower (kappa [min, max]: 0.632, 0.696). When it comes to reading all 86 reports, GPT models showed obviously reduced reading time compared with SMLS or MLI (all p<0.001). Notably, our study also found the GPT-o1 mini model had better consistency of error identification than the GPT-o1 model, which was better than that of the GPT-4o model. The pairwise comparisons of the same GPT model’s outputs across three repeated runs showed almost perfect agreement (kappa [min, max]: 0.912, 0.996). GPT-o1 mini showed obviously reduced reading time compared with GPT-4o or GPT-o1(all p<0.001). Additionally, GPT-o1 significantly outperformed GPT-4o or o1 mini in providing accurate and reliable treatment recommendations (all p<0.0001).

CONCLUSIONS: The detection capability of some of medical laboratory report errors and the accuracy and reliability of treatment recommendations of GPT models was competent, especially, potentially reducing work hours and enhancing clinical decision-making.

PMID:40249886 | DOI:10.1515/cclm-2025-0089

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Decoding Recurrence in Early-Stage and Locoregionally Advanced Non-Small Cell Lung Cancer: Insights From Electronic Health Records and Natural Language Processing

JCO Clin Cancer Inform. 2025 Apr;9:e2400227. doi: 10.1200/CCI-24-00227. Epub 2025 Apr 18.

ABSTRACT

PURPOSE: Recurrences after curative resection in early-stage and locoregionally advanced non-small cell lung cancer (NSCLC) are common, necessitating a nuanced understanding of associated risk factors. This study aimed to establish a natural language processing (NLP) system to efficiently curate recurrence data in NSCLC and analyze risk factors longitudinally.

PATIENTS AND METHODS: Electronic health records of 6,351 patients with NSCLC with >700,000 notes were obtained from Mount Sinai’s data sets. A deep learning-based customized NLP system was developed to identify cohorts experiencing recurrence. Recurrence types and rates over time were stratified by various clinical features. Cohort description analysis, Kaplan-Meier analysis for overall recurrence-free survival (RFS) and distant metastasis-free survival (DMFS), and Cox proportional hazards analysis were performed.

RESULTS: Of 1,295 patients with stage I-IIIA NSCLC with surgical resections, 336 patients (25.9%) experienced recurrence, as identified through NLP. The NLP system achieved a precision of 94.3%, a recall of 93%, and an F1 score of 93.5. Among 336 patients, 52.4% had local/regional recurrences, 44% distant metastases, and 3.6% unknown recurrence. RFS rates at years 1-5 were 93%, 81%, 73%, 67%, and 61%, respectively (96%, 89%, 84%, 80%, and 75% for distant metastasis). Stage-specific RFS rates at year 5 were 73% (IA), 62% (IB), 47% (IIA), 46% (IIB), and 20% (IIIA). Stage IB patients had a significantly higher likelihood of recurrence versus stage IA (adjusted hazard ratio [aHR], 1.63; P = .02). The RFS was lower in patients with clinically significant TP53 alteration (v TP53-negative or unknown significance), affecting overall RFS (aHR, 1.89; P = .007) and DMFS (aHR, 2.47; P = .009) among stage IA/IB patients.

CONCLUSION: Our scalable NLP system enabled us to generate real-world insights into NSCLC recurrences, paving the way for predictive models for preventing, diagnosing, and treating NSCLC recurrence.

PMID:40249880 | DOI:10.1200/CCI-24-00227

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Photodynamic Therapy With Liquid Crystal Loaded Methylene Blue in the Treatment of Verruca

Photodermatol Photoimmunol Photomed. 2025 May;41(3):e70023. doi: 10.1111/phpp.70023.

ABSTRACT

BACKGROUND: Verrucae (warts) are caused by human papilloma viruses. Photodynamic therapy (PDT) is a widely recommended option to treat warts.

OBJECTIVES: To assess the role of liquid crystal loaded methylene blue (MB) combined with intense pulsed light (IPL) in the treatment of verrucae.

PATIENTS AND METHODS: A total of 42 clinically and dermoscopically confirmed patients complaining of at least four cutaneous warts of various types were recruited in this clinical study. The lesions for the same patient were divided into 4 groups: Group (1) received topical 10% liquid crystal loaded MB, then was subjected to two passes of IPL with a 650 nm cutoff filter; Group (2) was subjected to two passes of IPL; and Group (3) received topical 10% liquid crystal loaded MB gel. They underwent four sessions at 2-week intervals. Group (4) was left with no treatment (control).

RESULTS: Complete disappearance of warts was observed in 52.4%, 19%, and 4.8% in Group 1, 2, and 3, respectively, with no recurrence throughout the following 3 months. Regarding PDT-treated group, verruca plantaris showed the best result, followed by verruca plana, then verruca vulgaris. Comparing all groups, there was a statistically significant difference in which the PDT group showed the best result.

CONCLUSION: PDT using 10% liquid crystal loaded MB combined with IPL is an effective option in wart treatment with the best results in V. plantaris, followed by V. plana and V. vulgaris.

PMID:40249838 | DOI:10.1111/phpp.70023

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Risk Factors for Poor Outcomes in Pediatric Bacterial Meningitis With Cerebrospinal Fluid Shunts: A Nationwide Surveillance in Japan

Pediatr Infect Dis J. 2025 Apr 17. doi: 10.1097/INF.0000000000004834. Online ahead of print.

ABSTRACT

BACKGROUND: Bacterial meningitis remains a life-threatening condition in pediatric patients with cerebrospinal fluid (CSF) shunts. While infection prevention has been extensively studied, risk factors for severe outcomes such as death and neurological sequelae remain poorly understood. We examined the clinical characteristics of pediatric bacterial meningitis with CSF shunts, focusing on the risk factors associated with poor outcomes.

METHODS: This study is part of a nationwide surveillance of pediatric bacterial meningitis in Japan from 2009 to 2021. We extracted pediatric meningitis cases with CSF shunts from the database. Clinical characteristics, risk factors for poor outcomes, defined as death or severe neurological sequelae and causative organisms were assessed. Logistic regression models were used to identify significant risk factors.

RESULTS: In this study, 167 pediatric cases of bacterial meningitis with CSF shunts were included. In multivariable analysis, male sex [odds ratio (OR): 2.82, 95% confidence interval (CI): 1.00-7.96, P = 0.04] and younger age (OR: 0.98, 95% CI: 0.97-1.00, P = 0.002) were significant risk factors for poor outcomes. The most common causative organism was Staphylococcus spp. (65.9%), predominantly coagulase-negative Staphylococci (45.3%). While the reduction in Streptococcus pneumoniae and Haemophilus influenzae cases following vaccine introduction was not statistically significant, a decreasing trend was observed.

CONCLUSION: Younger age and male sex were significant risk factors for poor outcomes. In addition, vaccination may have contributed to a decline in Streptococcus pneumoniae and Haemophilus influenzae infections.

PMID:40249832 | DOI:10.1097/INF.0000000000004834

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Statistical analysis of fluorescence intensity transients with Bayesian methods

Sci Adv. 2025 Apr 18;11(16):eads4609. doi: 10.1126/sciadv.ads4609. Epub 2025 Apr 18.

ABSTRACT

Molecular movement and interactions at the single-molecule level, particularly in live cells, are often studied using fluorescence correlation spectroscopy (FCS). While powerful, FCS has notable drawbacks: It requires high laser intensities and long acquisition times, increasing phototoxicity, and often relies on problematic statistical assumptions in data fitting. We introduce fluorescence intensity trace statistical analysis (FITSA), a Bayesian method that directly analyzes fluorescence intensity traces. FITSA offers faster, more stable convergence than previous approaches and provides robust parameter estimation from far shorter measurements than conventional FCS. Our results demonstrate that FITSA achieves comparable precision to FCS while requiring substantially fewer photons. This advantage becomes even more pronounced when accounting for statistical dependencies in FCS analysis, which are often overlooked but necessary for accurate error estimation. By reducing laser exposure, FITSA minimizes phototoxicity effects, representing a major advancement in the quantitative analysis of molecular processes across fields.

PMID:40249821 | DOI:10.1126/sciadv.ads4609