Salinity stress severely restricts the culture and geographical expansion of Macrobrachium rosenbergii. Artificial selective breeding has generated a salt-tolerant (NY) strain that can survive and grow normally under 10‰ salinity, while the commercial Suhu No.1 (SH) strain and commercial population (PT) exhibit weaker salt adaptability. In the present study, we performed whole-genome resequencing, transcriptome and untargeted metabolomic analyses to systematically reveal the molecular basis of salinity tolerance in the NY strain. Population genetic analyses including ADMIXTURE, PCA and phylogenetic tree demonstrated obvious genetic differentiation among NY, SH and PT populations, and genome-wide Fst scanning screened candidate genes mainly enriched in ion transport, osmotic regulation and energy metabolism pathways. Transcriptomic analysis identified 156 differentially expressed genes (DEGs) between NY and SH strains, with principal component analysis showing clear inter-group separation. Functional enrichment indicated that DEGs were predominantly involved in starch and sucrose metabolism, glycolysis/gluconeogenesis, autophagy and cellular homeostasis. qRT-PCR validation confirmed the reliability of transcriptome expression patterns of key salt-tolerance genes such as NKA, NHX, TPS and HSP70. Untargeted metabolomics identified a total of 1079 metabolites and 69 differentially accumulated metabolites (DAMs). DAMs were significantly enriched in starch and sucrose metabolism, phosphotransferase system (PTS) and ABC transporters under both positive and negative ion modes. Integrated transcriptomic and metabolomic analysis revealed 9 shared KEGG pathways in positive ion mode and 14 in negative ion mode, and key genes and metabolites displayed coordinated variation in carbohydrate metabolism, transmembrane transport and osmotic adjustment. Collectively, the NY strain achieves strong salinity tolerance by integrating genetic variation, transcriptional reprogramming and metabolic remodeling, synergistically maintaining ion homeostasis, osmotic balance and energy supply. This study provides important genetic resources and a theoretical framework for molecular breeding and salinity adaptation mechanism research of M. rosenbergii.
Historically, traumatic cardiac arrest studies have described poor survival rates and argued that resuscitation is futile. However, recent reports have demonstrated that survival rates may be higher than previously appreciated. Our objectives were to determine survival rates in traumatic cardiac arrest patients and assess for factors associated with survival to hospital discharge. We conducted a registry review study of adult traumatic cardiac arrest patients (≥ 17 years old) in Nova Scotia over a 16-year period (2007-2023). Data were collected from the paramedic electronic Patient Care Record and the Nova Scotia Trauma Registry. The primary outcome was survival to hospital discharge. We compared characteristics between survivors and non-survivors and assessed for predictors of survival. Descriptive statistics, t-tests, chi-square analysis, and multivariable logistic regression models were used. A total of 1042 patients were included in the analysis. Ages ranged from 17 to 96 years (mean 50.03 ± 19.2), and 80.7% were male. Most injuries were blunt trauma (71.7%, 747/1042). The overall survival rate was 1.9% (20/1042). Compared to non-survivors, patients who survived to hospital discharge had lower mean Injury Severity Score (17.8 ± 11.1 vs. 34.4 ± 21.3, p < 0.001). On multivariate analysis, survival to discharge was associated with critical care transport (OR 27.16, 95%CI 7.32-103.86) and direct transport to final facility (OR 4.10, 95%CI 1.37-11.80), while increasing Injury Severity Score (OR 0.93, 95%CI 0.88-0.97) was associated with mortality. Survival to hospital discharge was observed in 1.9% of traumatic cardiac arrest patients. Critical care transport and direct transport to the final facility were associated with patient survival. The identified predictors of survival may help inform prehospital triage and resuscitation strategies for patients experiencing traumatic cardiac arrest. RéSUMé: OBJECTIFS: Historiquement, les études sur l’arrêt cardiaque traumatique ont décrit de faibles taux de survie et soutenu que la réanimation est futile. Cependant, des rapports récents ont démontré que les taux de survie pourraient être plus élevés que ce qui avait été précédemment estimé. Nos objectifs étaient de déterminer les taux de survie chez les patients ayant subi un arrêt cardiaque traumatique et d’évaluer les facteurs associés à la survie jusqu’à la sortie de l’hôpital. MéTHODES: Nous avons mené une étude de révision du registre auprès de patients adultes ayant subi un arrêt cardiaque traumatique (≥ 17 ans) en Nouvelle-Écosse sur une période de 16 ans (2007–2023). Les données ont été recueillies à partir du dossier électronique des soins paramédicaux et du registre de traumatologie de la Nouvelle-Écosse. Le critère principal était la survie jusqu’à la sortie de l’hôpital. Nous avons comparé les caractéristiques entre les survivants et les non-survivants et évalué les prédicteurs de la survie. Des statistiques descriptives, des tests t, une analyse du chi carré et des modèles de régression logistique multivariable ont été utilisés. RéSULTATS: Un total de 1042 patients ont été inclus dans l’analyse. L’âge variait de 17 à 96 ans (moyenne 50.03 ± 19.2), et 80.7% étaient des hommes. La plupart des blessures étaient des traumatismes contondants (71.7%, 747/1042). Le taux de survie globale était de 1.9% (20/1042). Comparés aux non-survivants, les patients ayant survécu à une sortie de l’hôpital présentaient un score moyen de gravité des blessures plus faible (17.8 ± 11.1 vs. 34.4 ± 21.3 p < 0.001). Dans l’analyse multivariée, la survie jusqu’à la sortie était associée au transport en soins critiques (OR 27.16; 95%CI 7.32–103.86) et au transport direct vers l’installation finale (OR 4.10; 95%CI 1.37-11.80), tandis qu’une augmentation du score de gravité des blessures (OR 0.93; 95%CI 0.88–0.97) était associée à la mortalité. CONCLUSIONS: La survie jusqu’à la sortie de l’hôpital a été observée chez 1.9% des patients ayant subi un arrêt cardiaque traumatique. Le transport en soins intensifs et le transport direct vers l’installation finale ont été associés à la survie des patients. Les prédicteurs identifiés de la survie peuvent aider à orienter les stratégies de triage et de réanimation préhospitalières pour les patients subissant un arrêt cardiaque traumatique.
Symptom presentation at diagnosis is considered a surrogate marker of disease stage in pancreatic ductal adenocarcinoma (PDAC). However, its prognostic impact across resectability stages remains unclear. We evaluated whether symptoms serve as biological risk indicators using stratified analyses of surgical and non-surgical cohorts. This retrospective single-center study included 729 patients with PDAC: non-resected (n = 519) and resected (n = 210), including 179 with anatomically resectable disease. Patients were classified as asymptomatic or symptomatic at the time of diagnosis. Overall survival (OS) was compared, and preoperative variables were assessed as independent predictors of OS. Symptomatic patients had a significantly worse overall survival (OS) across cohorts. In the non-resected cohort, the 3-year OS was 1.8% in symptomatic patients vs. 10.3% in asymptomatic patients (p < 0.001). In the resected cohort, the 5-year OS was 27.6% vs. 38.7% (p = 0.024). In the resectable cohort, the 5-year OS was 22.5% vs. 38.3% (p < 0.001). Symptom presentation independently predicted a poorer OS in multivariable analyses of resected patients (hazard ratio, 1.58; p = 0.024) and those with anatomically resectable disease (hazard ratio, 1.83; p = 0.015). Symptoms at diagnosis were associated with a poorer OS in PDAC, regardless of resectability, suggesting a simple, broadly available marker that may complement anatomical stratification.
The optimal strategy for laryngeal preservation in locally advanced hypopharyngeal carcinoma (LAHPC) remains undefined. This prospective observational study compared long-term outcomes between two primary treatment approaches: induction chemotherapy followed by concurrent chemoradiotherapy (IC-CCRT) and neoadjuvant chemotherapy followed by surgery and adjuvant (chemo)radiotherapy (NAC-Sur-RT). From December 2018 to December 2023, 199 patients with LAHPC were prospectively enrolled and treated with either IC-CCRT (n = 124) or NAC-Sur-RT (n = 75). The primary endpoints were survival with functional larynx (SFL), overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS). Prognostic factors were identified using multivariable Cox regression. In the matched cohort (median follow-up 49 months), NAC-Sur-RT was associated with significantly superior 5-year OS (58.3% vs 46.2%; adjusted HR = 0.60; 95% CI 0.38-0.95; P = 0.031) and DMFS (56.2% vs 41.6%; adjusted HR = 0.59; 95% CI 0.38-0.92; P = 0.023), and PFS (52.2% vs 37.2%; adjusted HR = 0.64; 95% CI 0.42-0.98; P = 0.040). Conversely, NAC-Sur-RT was associated with a significantly higher risk of SFL failure (27.0% vs 43.1%; adjusted HR = 2.18; 95% CI 1.45-3.27; P < 0.001). No significant differences were found in LFFS or LRFFS. Failure pattern analysis indicated more isolated local recurrences with IC-CCRT (15.3% vs 5.3%) but higher regional recurrence with NAC-Sur-RT (1.6% vs 6.7%). Multivariable analysis confirmed NAC-Sur-RT as an independent predictor of improved OS (HR = 0.60; P = 0.031), PFS (HR = 0.64; P = 0.040), and DMFS (HR = 0.59; P = 0.023), but also of worse SFL (HR = 2.18; P < 0.001). AJCC stage IVB disease independently predicted inferior OS (HR = 9.05; 95% CI 1.52-53.81; P = 0.015) and DMFS (HR = 8.49; 95% CI 1.53-47.23; P = 0.015). Additionally, NAC-Sur-RT was associated with significantly higher rates of severe (grade 3-4) toxicities, including laryngeal/esophageal, mucosal, hematologic, and functional adverse events. In this non-randomized prospective comparison, the NAC-Sur-RT strategy was associated with superior survival outcomes (OS, PFS, DMFS) but at the cost of increased severe toxicity and a significantly lower rate of functional larynx preservation. IC-CCRT offers a higher probability of survival with a functional larynx despite a higher risk of local recurrence. Treatment selection should be individualized, balancing survival benefits, functional outcomes, and toxicity profiles. The study was approved by the ethics board of the Chinese PLA General Hospital and registered in the Chinese Clinical Trial Registry (registered number: ChiCTR2000039813).
Colonic interposition is the preferred option for alimentary tract reconstruction when a gastric conduit pull-up is not feasible. Aim of this study was to evaluate perioperative outcomes of patients undergoing colonic interposition for various indications in our tertiary-care center over a 15-year period. Following institutional board approval, all consecutive patients who underwent colonic interposition for esophageal replacement were identified from a prospectively maintained database. Comprehensive chart review and descriptive statistical analyses were performed. Ninety-three patients (62 men, 31 women, median age 65 years, IQR 55.5-72) underwent colonic interposition between January 2009 and December 2023. Benign disease was present in 17.2%, whereas malignancy accounted for 82.8%. A hand-sewn cervical anastomosis was performed in 96.8% of patients. The colonic graft, predominantly based on the left colic artery (89.2%) was routed through the posterior mediastinum in 51.6% and via the retrosternal route in 47.3%. Median operative time was 303 min (IQR 247.5-364). Major complications included anastomotic leakage (28%), anastomotic stenosis (30.1%), pleural empyema (11.8%), and postoperative bleeding (10.8%). The reoperation rate was 38.7%, with a median hospital stay of 29 days (IQR 20-63). In-hospital mortality was 18.3%. Colonic interposition after esophagectomy is associated with substantial morbidity and mortality, particularly in the salvage and secondary reconstruction setting, and should be confined to experienced, high-volume centers. FMS_D_007.23-I-1.
The CXCR3-B receptor plays a crucial role in inducing apoptosis upon binding with its ligands. Here, we aimed to rationally design an ultra-short (5-base) DNA aptamer targeting the N-terminal domain of CXCR3-B and evaluate its therapeutic potential in Acute Lymphoblastic Leukemia (ALL). An in-silico library of 32 pentanucleotide aptamers (comprising adenine and guanine) was constructed. The three-dimensional structure of the CXCR3-B N-terminus was modeled and docked with the aptamers, followed by targeted molecular docking and binding stability scoring to evaluate complex interactions. In vitro, Nalm-6 cells were treated with the lead aptamer (GAGGA), a scrambled control, and proteinase K. Cell viability, metabolic activity, and apoptosis were assessed via trypan blue, MTT, and Annexin V/PI flow cytometry. The expression of BAX, P53, and CDKN1A (p21) was quantified using qPCR. The GAGGA aptamer exhibited the highest binding affinity and complex stability in silico. In vitro, GAGGA at 600 µM significantly reduced metabolic activity and viability after 24 h compared with untreated and scrambled aptamer controls. The apoptotic cell ratio increased significantly (13.65% vs. 2.98% in control), accompanied by the significant upregulation of BAX, P53, and CDKN1A. Pre-treatment with proteinase K abolished these effects, confirming receptor-specific binding. Our findings demonstrate that the ultra-short GAGGA aptamer specifically targets CXCR3-B and triggers apoptotic pathways in ALL cells. While the effective concentration is high, likely due to the lack of nuclease resistance in unmodified ultra-short oligonucleotides, this study provides a novel molecular scaffold for future aptamer-based ALL therapies following appropriate chemical modifications.
Pembrolizumab monotherapy improves survival in advanced non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 50%. However, survival in randomised trials may not fully reflect outcomes in routine practice, with implications for economic evaluation. To evaluate the cost-effectiveness of pembrolizumab monotherapy compared with platinum-based chemotherapy from an Australian health-payer perspective, integrating both randomised controlled trial (RCT) and real-world evidence (RWE). A semi-Markov model with three health states (progression-free, progressed disease, death) was developed over a 3-year horizon. Clinical inputs were derived from KEYNOTE-024 for the RCT scenario and from nationwide Australian real-world data for the RWE scenario, with chemotherapy outcomes retained from the pivotal trials in both scenarios. Direct medical costs (2024 AU$) and quality-adjusted life years (QALYs) were estimated. Incremental cost-effectiveness ratios (ICERs) were calculated, probabilistic and deterministic sensitivity analyses conducted. Compared with chemotherapy, pembrolizumab monotherapy was associated with incremental costs of AU$87,399 (RCT-based) and AU$75,935 (RWE-based), and incremental QALY gains of 0.23 and 0.11, respectively. Corresponding ICERs were AU$385,561/QALY (RCT) and AU$705,729/QALY (RWE). At a AU$75,000/QALY willingness-to-pay (WTP) threshold, the probability of cost-effectiveness was < 1% in both scenarios. Differences in overall survival between trial and real-world cohorts likely contributed to the variation in ICERs. At current pricing and Australian WTP thresholds, pembrolizumab monotherapy is unlikely to be cost-effective, with RWE-informed scenarios yielding less favourable cost-effectiveness estimates than from trial data. These findings highlight that cost-effectiveness estimates may be sensitive to differences between trial-based and real-world effectiveness inputs.
Previously, traumatic amputations particularly those caused by blunt trauma were treated with proper subsequent amputations. However, this led to postoperative pain, disturbances in multiple functions of the extremities including sensory capability and fine motor dexterity. We presented five cases of traumatic fingertip amputation treated with spare part composite graft. In spare part composite grafting, both the amputated finger and the distal end (stump) of injured finger was fixated directly after skeletonization of the amputated finger. The blood supply initially depends on diffusion, and later with neovascularization. The regional flap for the soft tissue defect closure was then applied to the composite graft. At the final follow-up of minimum a month, complete graft survival with favorable functional and aesthetic outcomes with minimal complications were observed. Four of the cases had preserved, normal sensory. The spare part composite graft and the use of regional flap for defect closure is an alternative option in selected fingertip amputation with satisfactory results.
This report presents final 2024 infant mortality statistics by age at death, maternal race and Hispanic origin, maternal age, gestational age, leading causes of death, and maternal state of residence. Trends in infant mortality are also examined. Descriptive tabulations of data are presented and interpreted for infant deaths and infant mortality rates using the 2024 period linked birth/infant death file. The linked birth/infant death file is based on birth and death certificates registered in all 50 states and the District of Columbia. A total of 20,048 infant deaths were reported in the United States in 2024, which was not significantly different from 2023 (20,162). The U.S. infant mortality rate was 5.52 infant deaths per 1,000 live births, which was not significantly different from the rate in 2023 (5.61). The change in the neonatal mortality rate from 3.65 in 2023 to 3.66 in 2024 was not significant. The postneonatal mortality rate declined 4.6% from 1.96 in 2023 to 1.87 in 2024. Changes in mortality rates for infants by maternal race and Hispanic origin and among Hispanic-origin subgroups were not significant. Infants of Black non-Hispanic women had the highest mortality rate (10.98) in 2024, followed by infants of American Indian and Alaska Native non-Hispanic (9.20) and Native Hawaiian or Other Pacific Islander non-Hispanic (7.90), Hispanic (4.88), White non-Hispanic (4.41), and Asian non-Hispanic (3.72) women. The mortality rate decreased from 2023 to 2024 for infants born at 39-40 weeks of gestation (1.64 to 1.55), but the rate change was not significantly different for other gestational age categories. Among the five leading causes of infant death in 2024, mortality rates for sudden infant death syndrome declined compared with 2023. Infant mortality rates by state for 2024 ranged from a low of 2.97 in New Hampshire to a high of 9.65 in Mississippi.
Advanced cardiovascular life support (ACLS) provides a structured approach to the management of cardiac arrest and life-threatening arrhythmias, building on early recognition, high-quality cardiopulmonary resuscitation (CPR), and timely defibrillation. The 2026 Singapore ACLS guidelines present updated, evidence-based recommendations informed by the latest guidance from the American Heart Association and the European Resuscitation Council. Key updates include optimisation of CPR quality, integration of point-of-care ultrasonography, and refined use of pharmacological and electrical therapies during resuscitation. The role of extracorporeal CPR as a rescue strategy in selected patients and the importance of organised post-resuscitation care in improving neurological outcomes are emphasised. Management of tachyarrhythmias and bradyarrhythmias is also addressed. Special circumstances, including pulmonary embolism, drowning and cardiac arrest during pregnancy, are discussed. These guidelines aim to standardise practice and improve survival and functional outcomes following cardiac arrest in Singapore.
Candida albicans biofilms pose significant challenges in clinical settings due to their resistance to conventional antifungal treatments and their association with increased morbidity. This study aimed to evaluate the antifungal efficacy of hypocrellin B (HB)-mediated antimicrobial photodynamic therapy (aPDT) against biofilms formed by various strains of C. albicans, including standard, azole-sensitive, and azole-resistant strains. The effects of HB-aPDT on the viability, metabolic activity, and biomass of C. albicans biofilms were assessed using colony-forming unit (CFU) assays, XTT reduction assays, and crystal violet (CV) staining. Confocal laser scanning microscopy (CLSM) was used to observe changes in cell membrane integrity. The generation of reactive oxygen species (ROS) was analyzed using flow cytometry, and the impact on gene expression was examined using quantitative real-time PCR (qRT-PCR). HB-aPDT significantly reduced the survival of C. albicans biofilms in a dose- and light-dependent manner. CLSM revealed photodamage to cell membranes post-treatment, and an increased presence of ROS was observed in the treated biofilms. Gene expression analysis showed downregulation of virulence-related and ergosterol biosynthesis genes, indicating a potential disruption of key pathways in fungal pathogenesis. HB-mediated aPDT effectively reduced the viability and disrupted the structural integrity of C. albicans biofilms, including those resistant to conventional antifungals. This study highlights the potential of HB-aPDT as an innovative approach for managing drug-resistant Candida infections and offers a promising alternative to traditional antifungal therapies.
Acute heart failure (AHF) carries high morbidity and mortality and is traditionally managed with diuretics, vasodilators, and inotropes. Although guidelines recommend SGLT-2 inhibitors for chronic heart failure to reduce morbidity and mortality, their efficacy and safety when initiated during AHF hospitalization remain incompletely defined. To address this gap, we performed the largest, most contemporary meta-analysis focused exclusively on in-hospital initiation, including the first comprehensive pooled evaluation of decongestion outcomes. We systematically searched PubMed, Scopus, Cochrane CENTRAL, and Google Scholar from inception to February 7, 2026, following PRISMA 2020 guidelines and a pre-registered PROSPERO protocol. Eligible studies were randomized controlled trials enrolling adults hospitalized with AHF receiving in-hospital SGLT-2 inhibitors versus placebo/standard care. Random-effects models (REML) pooled clinical, decongestion, and safety outcomes. Eighteen RCTs (n = 15,560) were included. In-hospital SGLT-2 initiation significantly reduced heart failure worsening or hospitalization (RR 0.77, 95% CI 0.67-0.88; NNT = 48) and improved quality of life (KCCQ-12 MD + 2.88 points, p = 0.01). Decongestion outcomes favored SGLT-2 inhibitors, with improved diuretic efficiency (SMD 0.52, p = 0.001), greater weight loss (MD - 0.94 kg, p < 0.001), and lower NT-proBNP (MD - 313.6 pg/mL, p = 0.04). All-cause mortality showed a modest reduction (RR 0.74, p = 0.035) but demonstrated potential publication bias and was attenuated in trim-and-fill analysis. Cardiovascular and non-cardiovascular death, and hospitalization length, were not significantly different. Critically, no increase was detected in AKI, hypotension, hypoglycemia, ketoacidosis, genitourinary infections, or other serious adverse events. In-hospital SGLT-2 inhibitor initiation appears safe and is associated with reduced clinical events and modest improvements in decongestion markers. These findings support early in-hospital initiation as a feasible and safe strategy, although the current evidence, while promising, highlights the need for further long-term confirmatory data and provides a basis for potential updates to acute heart failure guidelines. CRD420261297253.
To evaluate the efficacy and safety of early aspirin discontinuation followed by P2Y12 inhibitor monotherapy versus standard dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This systematic review and meta-analysis followed PRISMA 2020 guidelines and a prespecified protocol registered in PROSPERO (CRD420261293472). MEDLINE, Embase, Scopus, and CENTRAL were searched through December 2025 for randomized controlled trials comparing early aspirin discontinuation (≤ 3 months) with standard DAPT in ACS patients undergoing PCI with drug-eluting stents. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment (Cochrane RoB 2.0). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Seven trials including 20,501 patients (10,246 early discontinuation; 10,255 standard DAPT) were analyzed. Early aspirin discontinuation significantly reduced bleeding (RR, 0.46; 95% CI, 0.36-0.60; p < 0.001; I²=21.9%). There was no significant difference in major adverse cardiovascular events (RR, 0.98; 95% CI, 0.77-1.26) or in myocardial infarction, stroke, repeat revascularization, or all-cause mortality. However, early aspirin discontinuation was associated with an increased risk of stent thrombosis (RR, 1.72; 95% CI, 1.07-2.78). In trials with aspirin discontinuation within 1 month, bleeding reduction remained substantial, with numerically higher but nonsignificant ischemic outcomes. In ACS patients undergoing PCI, early aspirin discontinuation reduces bleeding without a statistically significant increase in overall ischemic events; however, a significant increase in stent thrombosis was observed. These results support individualized decision-making, particularly favoring patients at high bleeding risk and low thrombotic risk treated with potent P2Y12 inhibitors. Further adequately powered studies focused on rare ischemic outcomes, including stent thrombosis, are warranted.
暂无摘要（点击查看详情）
We studied immunogenic properties of biofilm and agar cultures of Francisella tularensis strains. Analysis of the interaction of F. tularensis biofilm cultures with macrophages from experimental animals showed that the bacteria adapt to adverse conditions by forming biofilms, thereby increasing their virulence and subsequently suppressing the functional activity of immune cells. Biofilm formation in 7-day-old cultures of F. tularensis strains was associated with an increase in the virulent potential, which led to a decrease in the mean survival time and the overall survival rate of the experimental animals.
暂无摘要（点击查看详情）
Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory condition characterized by high morbidity and mortality, with limited effective pharmacological therapies currently available. The search for novel compounds with anti-inflammatory and antioxidant properties remains essential to improve clinical outcomes. In this context, Pentyl (2E)-3-(3-methoxyphenyl)prop-2-enoate (MAP), a phenolic cinnamic acid derivative, emerges as a promising candidate due to its potential biological activities. This study aimed to investigate the anti-inflammatory effects of MAP using an integrative approach combining in silico and in vivo analyses. Initially, pharmacokinetic and toxicological predictions indicated favorable oral bioavailability, adequate distribution, low predicted toxicity, and compliance with Lipinski's rules. Molecular docking studies demonstrated significant interactions with key inflammation-related targets, while density functional theory (DFT) calculations revealed electronic stability and favorable orbital distribution. Additionally, molecular dynamics simulations confirmed the stability of ligand-protein complexes, with low root mean square deviation (RMSD) values over time. Subsequently, the in vivo effects of MAP were evaluated in a rat model of intestinal ischemia-reperfusion (iI/R)-induced ARDS. Oral administration of MAP (20, 40, or 60 mg/kg) significantly reduced leukocyte infiltration, oxidative stress markers, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) while attenuating histopathological lung damage. Furthermore, MAP enhanced antioxidant defenses by increasing glutathione levels and catalase activity, alongside reducing nitric oxide production. Importantly, no evidence of acute genotoxicity was observed at the tested doses. In summary, MAP demonstrated consistent anti-inflammatory and antioxidant effects across computational and experimental models, effectively mitigating key pathological features of ARDS. These findings suggest that MAP is a promising adjuvant therapeutic candidate for acute respiratory inflammatory conditions, although further studies are necessary to elucidate its mechanisms of action and support its potential clinical application.
Protein-energy malnutrition (PEM) is common in gastrointestinal (GI) cancers and may worsen inpatient outcomes. Contemporary national data describing the impact of PEM among young adults with GI malignancies are limited. We conducted a retrospective cohort study using HCUP NIS data from 2018 to 2021. We identified hospitalizations of adults aged 18 to 39 years with GI cancers using ICD 10 CM codes C15 to C26. We defined PEM using ICD-10-CM diagnosis codes recorded during the index hospitalization; therefore, PEM reflects clinically documented/coded malnutrition rather than the full burden of nutritional risk or clinically undiagnosed malnutrition. Primary outcomes were in hospital mortality and discharge disposition. Secondary outcomes were LOS and total hospital charges. We used survey weighted multivariable logistic and linear regression to estimate adjusted associations, accounting for age, sex, race or ethnicity, payer, income quartile, admission type, calendar year, and age adjusted CCI. Among 58,910 weighted hospitalizations of young adults with gastrointestinal cancers, 11,915 (20.2%) had protein-energy malnutrition (PEM). Compared with those without PEM, hospitalizations with PEM had a higher burden of advanced disease and acute illness, including a greater prevalence of metastatic disease (71.8% vs. 53.1%), and experienced worse unadjusted outcomes, including higher in-hospital mortality (8.4% vs. 3.2%), longer length of stay (10.43 vs. 5.63 days), and higher total hospital charges ($133,790 vs. $83,702). In adjusted analyses, PEM was independently associated with increased odds of in-hospital mortality (aOR 2.13, 95% CI 1.72-2.56; p < 0.001) and higher odds of non-home discharge (aOR 1.67, 95% CI 1.47-1.89; p < 0.001). PEM was also associated with substantially greater resource utilization, including an adjusted increase of 4.49 hospital days (β + 4.492; SE 0.248; p < 0.001) and $53,513 higher total hospital charges (β +$53,512.6; SE $5,527.6; p < 0.001). PEM affected one in five hospitalizations among young adults with GI cancers and was independently associated with increased mortality, non-home discharge, LOS, and hospital charges. These findings support routine inpatient nutritional assessment and early intervention in this high risk population.
Small-for-gestational-age (SGA) infants face elevated risk of undernutrition and developmental delays. Multidomain interventions may be needed to promote growth and neurodevelopment. To evaluate the effect of an integrated intervention package on growth and neurodevelopment in term SGA infants. Individually randomized clinical trial conducted in low-resource neighborhoods of South Delhi, India. Term SGA infants were enrolled within 14 days of birth; 1300 infants were randomized and followed up to 12 months of age. Recruitment occurred from January 14, 2023, until July 31, 2024, with follow-up completed on August 6, 2025. Outcome assessors were blinded to participant allocation. Infants were randomized in a 1:1 ratio to receive either an integrated intervention package including health, nutrition, early child stimulation, and psychosocial support (n = 647) or usual care through government programs (n = 653). The primary outcomes were weight and weight-for-age z score at 12 months. Secondary outcomes included linear growth, neurodevelopment (assessed using the Bayley Scales of Infant and Toddler Development, Third Edition), anemia, and mortality. At 12 months, 1261 infants (97%) (mean age, 6 days; 48.1% male) had completed follow-up. The mean weight was 8.0 kg (SD, 0.9 kg) in the intervention group vs 7.8 kg (SD, 0.9 kg) in the usual care group (mean difference, 0.22 kg [95% CI, 0.11-0.32 kg]). The mean weight-for-age z score was -1.3 (SD, 0.9) vs -1.6 (SD, 1.0), respectively (mean difference, 0.24 [95% CI, 0.14-0.35]). The intervention group had a lower prevalence of underweight (23.9% vs 32.6%; risk difference, -8.75 [95% CI, -13.70 to -3.80] percentage points), stunting (20.1% vs 27.2%; risk difference, -7.17 [95% CI, -11.85 to -2.49] percentage points), wasting (13.9% vs 19.4%; risk difference, -5.52 [95% CI, -9.63 to -1.41] percentage points), and anemia (34.0% vs 72.5%; risk difference, -38.49 [95% CI, -44.36 to -32.61] percentage points) and higher cognitive scores (mean difference, 1.73 [95% CI, 0.32-3.14]), language scores (mean difference, 2.74 [95% CI, 1.51-3.98]), and motor composite scores (mean difference, 2.32 [95% CI, 1.25-3.38]). Nine children in the usual care group and 5 in the intervention group died. Among term SGA infants, an integrated intervention improved weight and weight-for-age z scores at 12 months. Clinical Trials Registry-India Identifier: CTRI/2021/11/037881.
Major advances in drug development and supportive care have led to a paradigm shift in the management of many of the aspects of clinical care for older adults with acute myeloid leukemia. The development of validated geriatric assessments now enable clinicians to personalize treatment recommendations based on function, frailty, and fitness. The emergence of novel theory-driven methods to capture patient preferences has further enabled clinical teams to personalize therapy recommendations to what matters most to patients. Despite increasing excitement in the field created by the introduction of these new therapies and supportive care interventions, outcomes for older adults with acute myeloid leukemia remain very poor. Even with the best available therapies, median survival for most older adults is tragically short at around 15 months. Five-year survival for adults over the age of 75 years is profoundly low, below 10%. For many patients, current therapies fail to dramatically extend life or improve the quality of life. These stark realities must inform clinical decision making and fuel further research. This review critically examines current treatment options including recently approved targeted agents in the upfront and relapsed setting including FLT3 inhibitors, isocitrate dehydrogenase 1/2 inhibitors, and the newly approved menin inhibitors. We review the use of geriatric assessments and validated screening tools to characterize patient fitness and frailty beyond clinician-graded measures. We also introduce theory-driven preference assessments that are increasingly being used to capture patient treatment outcome priorities.