Tag: pubmed

EClinicalMedicine. 2024 May 17;72:102630. doi: 10.1016/j.eclinm.2024.102630. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: Diarrhoeal disease poses a significant global health challenge, especially in children under three years old. Despite the effectiveness of oral rehydration therapy (ORT), its adoption remains low. Glucose-based ORS (GORS) is the standard, but novel formulations like glucose-free amino acid-based VS002A have emerged as potential alternatives. This study aimed to compare the safety and efficacy of VS002A against the standard WHO-ORS in treating non-cholera acute watery diarrhoea in children.

METHODS: A triple-blind, randomized trial enrolled 310 male infants and children aged 6-36 months, who were assigned to receive WHO-ORS or VS002A over a 16-month period, from June 2021 to September 2022. Both groups received standard of care, including zinc supplementation. The Primary study outcome measured was the duration of diarrhoea. Secondary outcomes included stool output, treatment failure and adverse events. Exploratory endpoints included urinary output, body weight changes, blood biochemistry, stool microbiology and gut health biomarkers.

FINDINGS: Both VS002A and WHO-ORS were well-tolerated with a low adverse event rate. While not different statistically (p = 0.10), duration of diarrhoea was shorter in children treated with VS002A vs. WHO-ORS (65.4 h vs. 72.6 h). Similarly, stool output was also lower vs. WHO-ORS in children treated with VS002A, though not statistically different (p = 0.40). Serum citrulline levels, an indicator of gut health, were higher in the VS002A group at 24 h suggesting a potential protective effect (p = 0.06).

INTERPRETATION: The findings of this study support the non-inferiority of VS002A, a glucose-free amino acid-based ORS compared to the WHO-ORS standard of care. VS002A was shown to be safe and effective in treating non-cholera acute watery diarrhoea in young children. VS002A may offer advantages in pathogen-driven diarrhoea, supported by trends toward a lower duration of diarrhoea and stool output within the per protocol group. Furthermore, individuals with prolonged diarrhoea, severe malnutrition, environmental enteric dysfunction or have issues with obesity or insulin resistance, could benefit from a glucose-free ORS. This research contributes to addressing the persistent challenge of childhood diarrhoea by presenting an alternative glucose-free ORS formulation with potential advantages in select scenarios, offering a promising avenue for improving paediatric diarrhoea management worldwide.

FUNDING: The study was funded by Entrinsic Bioscience, LLC., Norwood, MA, USA.

PMID:38800804 | PMC:PMC11127191 | DOI:10.1016/j.eclinm.2024.102630

Addict Biol. 2024 May;29(5):e13402. doi: 10.1111/adb.13402.

ABSTRACT

Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.

PMID:38797559 | DOI:10.1111/adb.13402

Clin Gastroenterol Hepatol. 2024 Jun;22(6):1151-1156. doi: 10.1016/j.cgh.2024.02.030.

NO ABSTRACT

PMID:38797533 | DOI:10.1016/j.cgh.2024.02.030

Br J Haematol. 2024 May 26. doi: 10.1111/bjh.19559. Online ahead of print.

ABSTRACT

Methotrexate (MTX), although an indispensable part of contemporary treatment protocols for childhood acute lymphoblastic leukaemia (ALL)/lymphomas (LBL) in improving outcomes, can lead to serious neurotoxicity with long-term consequences. The aetiopathogenesis, predisposing factors and treatment for MTX-induced neurotoxicity are not yet well defined. The aim of our study was to detect the incidence, risk factors and to assess the overall outcomes of MTX-induced neurotoxicity among large cohort of paediatric ALL/LBL patients treated on a uniform protocol. We conducted retrospective audit of medical records of 622 consecutive children (≤14 years) diagnosed with ALL and LBL between January 2018 and December 2022 and treated on modified BFM-95 protocol at the Department of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram. Risk factors predisposing to MTX-induced neurotoxicity were identified using binary logistic regression analysis. Forty-three children were diagnosed with MTX-induced neurotoxicity with an incidence rate of 6.9%. More than two-thirds of them had high-grade MTX-induced neurotoxicity CTCAE v5.0 with a median age of 9 years (range: 9 months to 14 years). Almost half of them developed MTX neurotoxicity during Protocol M followed by Phase-Ib consolidation (15%). Majority of these patients (84%, 36/43) were challenged again with MTX, with 11% (4/36) developing recurrence. Fifteen per cent had persistent neurological deficits at last follow-up. Univariate analysis found older age (age > 5 years) (p < 0.001), T-cell phenotype (p = 0.040), tumour lysis syndrome during induction (p < 0.001), baseline renal problems prior to MTX exposure (p < 0.001) and CNS leukaemic involvement (p < 0.003) to be significantly associated with MTX neurotoxicity. On multivariate analysis, older age (>5 years), tumour lysis during induction and CNS leukaemia retained statistical significance (p < 0.05). Methotrexate-induced neurotoxicity during paediatric acute lymphoblastic leukaemia/lymphoma therapy is a transient phenomenon in majority and re-challenge with MTX is generally safe. Older age children who develop tumour lysis during induction and CNS leukaemic involvement are at increased risk for MTX-induced neurotoxicity during ALL/LBL treatment.

PMID:38797523 | DOI:10.1111/bjh.19559

Water Environ Res. 2024 May;96(5):e11041. doi: 10.1002/wer.11041.

ABSTRACT

The aim of the study is to investigate the leaching of fluorescent dissolved organic matter (fDOM) from microplastics. In addition, this study identifies the connection between fDOM and microplastics in the aquatic environment. Three-dimensional excitation-emission matrix identified five fluorophores, that is, peak A, M, T, T_uv, and W_uv, and the parallel factor analysis modeling identified five components, that is, tryptophan-like, p-hydroxy acetophenone, humic acid (C-like), detergent-like, and fulvic acid (M-like) in the urban surface water. Mimic experiments using commonly used synthetic plastic (like microplastics) in Mili-Q water under solar radiation and dark environments demonstrate the release of fDOM from plastic. Two fluorophore peaks were observed at Ex/Em = 250/302 nm and Ex/Em = 260/333 nm for the expanded polystyrene plastic polymer and one fluorophore peak at Ex/Em = 260/333 nm for the low-density polyethylene. Fluorophore and component intensity exhibited notable associations with microplastics in the aquatic environment. These findings indicated that the characteristics and dynamics of fDOM in urban surface water are influenced by microplastics. PRACTITIONER POINTS: Fluorescent dissolved organic matters were identified in urban surface waters. Expanded polystyrene (EPS) had shown two fluorophores at Em/Ex = 250/302 and Em/Ex = 260/333. Low-density polyethylene (LDPE) had one fluorophore at Em/Ex = 260/333. Fluorophore and component intensity in the aquatic settings exhibited associations with microplastics.

PMID:38797514 | DOI:10.1002/wer.11041

J Oral Maxillofac Surg. 2024 May 7:S0278-2391(24)00282-9. doi: 10.1016/j.joms.2024.05.001. Online ahead of print.

ABSTRACT

BACKGROUND: Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis.

PURPOSE: The study’s purpose is to measure the association between PNI and survival outcomes in patients with HNOS.

STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated.

PREDICTOR VARIABLE: The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive.

MAIN OUTCOME VARIABLE(S): The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT).

COVARIATES: Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy).

ANALYSES: Analytic statistical methods were used for the data analysis. Pearson χ² or Fisher’s exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance.

RESULTS: The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P ＜ .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients.

CONCLUSION AND RELEVANCE: Positive PNI status was associated with decreased DFS and increased risk of MT.

PMID:38797510 | DOI:10.1016/j.joms.2024.05.001

Curr Probl Cardiol. 2024 May 24:102632. doi: 10.1016/j.cpcardiol.2024.102632. Online ahead of print.

ABSTRACT

BACKGROUND: Post-traumatic stress disorder (PTSD) is increasingly recognized for its effects beyond mental health, with emerging evidence suggesting a significant association with cardiovascular diseases (CVD). This systematic review and meta-analysis aimed to synthesize available evidence on the association between PTSD and various cardiovascular outcomes.

METHODS: We conducted a comprehensive literature search in databases until March 15, 2024. Studies were included if they were observational in design and assessed the association between PTSD and cardiovascular outcomes. Data were extracted on study characteristics, participant demographics, PTSD assessment, cardiovascular outcomes, and effect estimates. Meta-analyses were performed using random-effects models, and heterogeneity was assessed using the I² statistic. All statistical analyses were conducted using R software version 4.3.

RESULTS: Twenty studies met the inclusion criteria, encompassing a total of over 335,000 participants. The pooled analyses demonstrated a statistically significant increased risk of any CVD (HR = 1.417, 95% CI: 1.313-1.522), MI (HR = 1.415, 95% CI: 1.331-1.500), and stroke (HR = 2.074, 95% CI: 1.165-2.982) associated with PTSD. Substantial heterogeneity was observed across the studies for stroke and MACE, and evidence of publication bias was noted.

CONCLUSION: This meta-analysis confirms a significant association between PTSD and an increased risk of several cardiovascular outcomes, indicating the importance of integrating cardiovascular risk management with psychiatric care for PTSD patients to mitigate the heightened risk of CVDs. Future research should focus on exploring the underlying mechanisms and potential interventions to manage both PTSD and its associated cardiovascular risks effectively.

PMID:38797508 | DOI:10.1016/j.cpcardiol.2024.102632

Int J Radiat Oncol Biol Phys. 2024 May 24:S0360-3016(24)00668-0. doi: 10.1016/j.ijrobp.2024.05.018. Online ahead of print.

ABSTRACT

PURPOSE: Radiation-induced lymphopenia (RIL) is common among patients undergoing radiotherapy (RT), and severe RIL has been linked with adverse outcomes. The severity and risk of RIL can be predicted from baseline clinical characteristics and dosimetric parameters. However, dose-volume (DV) indices are highly correlated with one another and are only weakly associated with RIL. Here we introduce the novel concept of “composite dosimetric score” (CDS) as the index that condenses the dose distribution in immune tissues of interest to study the dosimetric dependence of RIL. We derived an improved multivariate classification scheme for risk of grade 4 (G4) RIL, based on this novel RT dosimetric feature, for patients receiving chemoRT for esophageal cancer.

METHODS AND MATERIALS: DV indices were extracted for 734 patients who received chemoRT for biopsy-proven esophageal cancer. Non-negative matrix factorization was used to project the DV indices of lung, heart, and spleen into a single CDS; XGBoost was employed to explore significant interactions among predictors; and logistic regression was applied to combine the resultant CDS along with baseline clinical factors and interaction terms to facilitate individualized prediction of immunotoxicity. Five-fold cross-validation was applied to evaluate the model performance.

RESULTS: The CDS for selected immune organs at risk (OARs, i.e., heart, lung, and spleen) (1.791, 95 CI [1.350,2.377]) was a statistically significant risk determinant for G4RIL. Pearson correlation coefficients for CDS vs. G4RIL risk for individual immune OARs were greater than any single DV indices. Personalized prediction of G4RIL based on CDS and 4 clinical risk factors yielded an area under the curve value of 0.78. Interaction between age and CDS revealed that G4RIL risk increased more sharply with increasing CDS for patients ≥65.

CONCLUSIONS: Risk of immunotoxicity for patients undergoing chemoRT for esophageal cancer can be predicted by CDS. The CDS concept can be extended to immunotoxicity in other cancer types and in dose-response models currently based on DV indices. Personalized treatment planning should leverage CDS methods rather than using individual or subsets of DV indices.

PMID:38797500 | DOI:10.1016/j.ijrobp.2024.05.018

Int J Radiat Oncol Biol Phys. 2024 May 24:S0360-3016(24)00671-0. doi: 10.1016/j.ijrobp.2024.05.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Cardiac substructure dose metrics are more strongly linked to late cardiac morbidities than whole-heart metrics. MR-guided radiation therapy (MRgRT) enables substructure visualization during daily localization, allowing potential for enhanced cardiac sparing. We extend a publicly available state-of-the-art deep learning (DL) framework, nnU-Net, to incorporate self-distillation (nnU-Net.wSD) for substructure segmentation for MRgRT.

METHODS: Eighteen (Institute A) patients who underwent thoracic or abdominal radiation therapy on a 0.35 T MR-guided linac were retrospectively evaluated. On each image, one of two radiation oncologists delineated reference contours of 12 cardiac substructures (chambers, great vessels, and coronary arteries) used to train (n=10), validate (n=3), and test (n=5) nnU-Net.wSD leveraging a teacher-student network and comparing to standard 3D U-Net. The impact of using simulation data or including 3-4 daily images for augmentation during training was evaluated for nnU-Net.wSD. Geometric metrics (Dice similarity coefficient (DSC), mean distance to agreement (MDA), and 95% Hausdorff distance (HD95)), visual inspection, and clinical dose volume histograms (DVHs) were evaluated. To determine generalizability, Institute A’s model was tested on an unlabeled dataset from Institute B (n=22) and evaluated via consensus scoring and volume comparisons.

RESULTS: nnU-Net.wSD yielded a DSC (reported mean ± standard deviation) of 0.65±0.25 across the 12 substructures (Chambers: 0.85±0.05, Great Vessels: 0.67±0.19, and Coronary Arteries 0.33±0.16, mean MDA <3 mm, and mean HD95 <9 mm) while outperforming the 3D U-Net (0.583±0.28, p<0.01). Leveraging fractionated data for augmentation improved over a single MR-SIM timepoint (0.579±0.29, p<0.01). Predicted contours yielded DVHs that closely matched the clinical treatment plans where mean and D_0.03cc doses deviated by 0.32±0.5 Gy and 1.42±2.6 Gy respectively. No statistically significant differences between Institute A and B volumes (p>0.05) for 11 of 12 substructures with larger volumes requiring minor changes and coronary arteries exhibiting more variability.

CONCLUSIONS: This work is a critical step to rapid and reliable cardiac substructure segmentation to improve cardiac sparing in low-field MRgRT.

PMID:38797498 | DOI:10.1016/j.ijrobp.2024.05.013

Radiother Oncol. 2024 May 24:110340. doi: 10.1016/j.radonc.2024.110340. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to reveal the association of fatigue with weekly changes in the body composition in patients with nasopharyngeal carcinoma (NPC) and identified the independent strength.

METHODS: Four body composition indexes and fatigue were assessed before treatment (T0, baseline) and once a week throughout radiotherapy (T1-T7). Generalized additive mixed models (GAMMs) were used to explore the trajectories and longitudinal relationships of fatigue and weekly changes in body composition. The marginal structural model (MSM) was used to control the effect of depression and anxiety.

RESULTS: The trajectories of fatigue in 105 participants reached a peak in the fifth week, and changes in body composition started appearing from the second week. Four body composition indexes, weight, body mass index (BMI), body fat rate, and lean body weight loss weekly were positively associated with fatigue. High magnitude of effects was revealed when anxiety and depression were controlled as time-dependent confounders. The positive associations with fatigue were manifested in patients aged >53 years, those with senior high and above education, no drinking, >5000 Y/month of family inflow, ≥ stage III, or those receiving a dose of ≥70 Gy, ≥3 cycles of induced chemotherapy, and ≤1 cycle of concurrent chemotherapy (CCRT).

CONCLUSIONS: Loss of weight, BMI, body fat rate, and lean body weight could be used to independently evaluate the development of fatigue in patients with NPC during radiotherapy. Positive associations between fatigue and weekly body composition loss were found in patients with certain characteristics.

PMID:38797492 | DOI:10.1016/j.radonc.2024.110340