Tag: nevin manimala

Curr Mol Med. 2025 Jun 3. doi: 10.2174/0115665240361878250601074746. Online ahead of print.

ABSTRACT

BACKGROUND: Leukemia is marked by clonal hematopoietic stem cell expansion and metabolic reprogramming. The BNT162b2 mRNA COVID-19 vaccine has been proven effective, though questions remain about its broader physiological effects. This study investigates metabolomic alterations in leukemic bone marrow potentially associated with BNT162b2 vaccination.

OBJECTIVE: To compare the bone marrow metabolomic profiles of leukemia patients with and without BNT162b2 vaccination, and healthy unvaccinated controls, to explore potential metabolic differences.

METHODS: Bone marrow samples were obtained from three groups: vaccinated leukemia patients (n=7), unvaccinated leukemia patients without COVID-19 history (n=2), and unvaccinated healthy controls (n=7). Untargeted metabolomics was performed using LC-QTOF-MS. Data were analyzed using XCMS and MetaboAnalyst 5.0 to identify statistically significant metabolite differences and affected pathways. Fold change >1.5 and p<0.05 were considered significant.

RESULTS: Distinct metabolic profiles were observed between the leukemia and control groups. Increased glycolysis, pentose phosphate pathway activity, and altered tryptophan, lipid, and heme metabolism were noted in leukemia samples. Metabolic changes in vaccinated patients (ASL) were more similar to unvaccinated leukemia patients (LO) than to healthy controls, with minor vaccine-associated variations. Notable metabolites included 5-methoxyindoleacetate, phosphorylcholine, and tetrahydrofolic acid.

CONCLUSION: This preliminary study identified altered metabolic pathways in leukemia bone marrow and suggests metabolomic differences associated with BNT162b2 vaccination. While the findings do not support a causal link between mRNA vaccination and leukemia development, they highlight the need for further studies to understand vaccine-induced metabolic modulation in hematological contexts.

PMID:40464175 | DOI:10.2174/0115665240361878250601074746

Curr Med Imaging. 2025 Jun 3. doi: 10.2174/0115734056343395250526140343. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) complicated with interstitial lung abnormalities (ILAs) is often overlooked and can progress to severe diabetesinduced pulmonary fibrosis (DiPF). Therefore, early diagnosis of T2DM complicated with ILAs is crucial. Chest computed tomography (CT) is an important method for diagnosing T2DM complicated with ILAs. Quantitative computed tomography (QCT) is more objective and accurate than visual assessment on CT. However, there are currently limited studies on T2DM complicated with ILAs based on quantitative CT.

OBJECTIVE: This study aimed to explore the utility of quantitative computed tomography for early detection of lung injury in individuals with T2DM by examining CT-derived metrics in T2DM complicated with ILAs.

METHODS: We collected data from 135 T2DM complicated with ILAs on chest CT scans retrospectively, alongside 135 non-diabetic controls with normal CT findings. Employing digital lung software, chest CT images were processed to extract quantitative parameters: total lung volume (TLV), emphysema index (LAA-950%, the percentage of lung area with attenuation < -950 Hu to total lung volume), pulmonary fibrosis index (LAA-700~-200%, the percentage of lung area with attenuation from -700Hu to -200 Hu to the total lung volume), and pulmonary peripheral vascular index (ratio TAV/TNV, the number of blood vessels TNV, the cross-sectional area of blood vessels TAV). Statistical comparisons between groups utilized Mann-Whitney U or t-tests. Correlations between Hemoglobin A1c (HbA1c) levels and CT parameters were assessed via Pearson or Spearman correlations. Parameters showing statistical significance were further examined through receiver operating characteristic (ROC) analysis.

RESULTS: The T2DM-ILAs cohort displayed a significantly higher LAA-700~-200% compared to controls (Z = -7.639, P< 0.001), indicative of increased fibrotic changes. Conversely, TLV (Z =-3.120, P=0.002), TAV/TNV (Z = -9.564, P< 0.001), and LAA-950% (Z = -4.926, P < 0.001) were reduced in T2DM-ILAs patients. The correlation between HbA1c and various CT quantitative indicators was not significant, HbA1c and TLV (r=-0.043, P=0.618), HbA1c and TAV (r=0.143, P=0.099), HbA1c and TNV (r=0.064, P=0.461), HbA1c and LAA-700~-200% (r=0.102, P=0.239), HbA1c and LAA-950% (r=-0.170, P=0.049), HbA1c and TAV/TNV (r=0.175, P=0.043). The peripheral vascular marker, TAV/TNV, excelled in distinguishing T2DM-related lung changes (AUC=0.84, P<0.001), outperforming LAA-700~-200% (AUC=0.77,P<0.001). A composite index incorporating multiple quantitative parameters achieved the highest diagnostic accuracy (AUC = 0.91, P< 0.001).

CONCLUSION: Quantitative CT parameters distinguish T2DM complicated with ILAs from non-diabetic individuals, suggesting a distinct pattern of lung injury. Our findings imply a particular susceptibility of small pulmonary blood vessels to injury in T2DM.

PMID:40464171 | DOI:10.2174/0115734056343395250526140343

J Cachexia Sarcopenia Muscle. 2025 Jun;16(3):e13843. doi: 10.1002/jcsm.13843.

ABSTRACT

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance, accompanied by alterations in the peripheral skeletal muscle (SKM). We have recently shown that titin, a giant sarcomere protein, is hyperphosphorylated in HFpEF. MuRF1 is a muscle-specific ubiquitin E3-ligase that interacts with titin. Blocking this interaction via small molecules (MyoMed205) can improve muscle function and mitochondrial activity in HFpEF. This study aimed to investigate the impact of MyoMed205 on titin phosphorylation and its association with changes in muscle structure and function.

METHODS: Obese ZSF1 rats with established HFpEF received rat chow with (n = 15) or without (n = 15) MyoMed205 and were compared with lean littermates (n = 15), serving as controls. After 12 weeks, in vitro SKM force, atrophy and titin-as well as contractile protein expression-were evaluated (soleus and extensor digitorum longus [EDL]). Statistical analysis was performed via multiple unpaired t-test or one-way ANOVA.

RESULTS: In HFpEF, titin hyperphosphorylation by 13% in the EDL (p = 0.09) and 14% (p = 0.03) in the soleus muscle was evident. This hyperphosphorylation was driven in part by an increase in S11878 phosphorylation (EDL: +68%, p = 0.004; Sol: +23.8%, p = 0.03), which was linked to myofiber atrophy (r = -0.68, p = 0.006) and a decline in maximal specific muscle force (r = -0.54, p = 0.008). In the EDL, significant changes in protein expression related to atrophy (MuRF1 [+24.9%, p = 0.02], GDF8 [+20.6%, p = 0.09]) and calcium handling (slow troponin C [-46%, p = 0.02], fast troponin I [+35.8%, p = 0.02]) were found in HFpEF. All of the above-mentioned effects in HFpEF were almost completely abolished by MyoMed205 treatment, and significantly elevated titin expression was visible (+19.7%, p_con = 0.04, p_HFpEF = 0.01).

CONCLUSIONS: Titin hyperphosphorylation may negatively impact skeletal muscle integrity and function in HFpEF. MyoMed205 reduced titin hyperphosphorylation and was associated with preserved skeletal muscle function and mass. Further studies are necessary to confirm the direct role of titin hyperphosphorylation on muscle function and to evaluate the therapeutic potential of MyoMed205 in HFpEF.

PMID:40464169 | DOI:10.1002/jcsm.13843

J Diabetes. 2025 Jun;17(6):e70108. doi: 10.1111/1753-0407.70108.

ABSTRACT

AIMS: In patients with new onset type 2 diabetes, this study aimed to analyze glucose-lowering medication use patterns between 2014 and 2022.

MATERIALS AND METHODS: This retrospective study included adults with incident type 2 diabetes in the University of California Health System between 2014 and 2022. We determined medications used within 1 year of diagnosis and evaluated statistical evidence of use pattern changes via Mann-Kendall trend tests. Four categories of high-risk patients requiring cardio-kidney-metabolic protection were also evaluated in stratified analyses based on 2024 ADA guidelines.

RESULTS: Of 40 150 patients with incident type 2 diabetes, 38.5% initiated glucose-lowering medication within 1 year. Metformin remained the most used medication from 2014 to 2022. From 2014 to 2022, usage of GLP-1 receptor agonists and SGLT-2 inhibitors increased exponentially. GLP-1 receptor agonist use increased from below 2.5%-21%. While SGLT-2 inhibitor use increased from less than 2.5%-14%. This growth coincided with a decline in sulfonylurea usage. Among high-risk, insulin was most prevalent in those with heart failure or chronic kidney disease. However, usage of insulin declined overall in all groups. Utilization of SGLT-2 inhibitors was particularly high in patients with prior heart failure.

CONCLUSIONS: In adults with new onset type 2 diabetes, GLP-1 receptor agonist and SGLT-2 inhibitor utilization has markedly increased, coordinating with evolving guidelines that emphasize cardiovascular and chronic kidney disease management. However, overall adoption rates of these medications remain low based on indicated populations. Sulfonylurea use declined while metformin remains the most frequently initiated treatment.

PMID:40464139 | DOI:10.1111/1753-0407.70108

Emerg Med Australas. 2025 Jun;37(3):e70081. doi: 10.1111/1742-6723.70081.

ABSTRACT

INTRODUCTION: Emergency departments (ED) in Australia have experienced an increase in patient presentations. To address this demand, we introduced phlebotomists at ED triage seeking to reduce ED waiting and disposition times. We report the impact of this intervention.

METHOD: Using a quantitative retrospective comparative study design guided by the STROBE checklist, we investigated the impact on ED performance before and after the introduction of phlebotomists (the intervention). Data from two periods-T1 (January-June 2021) and T2 (January-June 2023) were obtained and analysed for all ED presentations.

RESULTS: A total of 90,020 patients were included (T1: 46,639; T2: 43,381). Post-intervention improvements included an increase in short stay unit-admissions from triage (3.1% vs. 5.9%, p < 0.001) and a decrease in the proportion of patients transferred to a cubicle from the waiting room (T1: 78.8%; T2: 76.4%). However, patients who left the ED before treatment was completed (known as ‘Did not Wait’) rose significantly (9.8% vs. 11.5%) as did waiting room times (80.02 vs. 112.91 min). Overall, ED length of stay (EDLOS) increased significantly (mean T1: 305.1 to T2: 319.4 min; p < 0.001). There were significant increases in blood tests (T1: 52.0% vs. T2: 59.9%) and ECGs (16.5% vs. 19.1%) performed.

CONCLUSION: The introduction of phlebotomists at triage failed to reduce waiting, treatment and disposition times and increased the number of investigations performed with an overall increase in EDLOS. We observed an increase in the number of patients directed from the waiting room to the short stay unit and fewer patients transferred from the waiting room to an ED cubicle.

PMID:40464127 | DOI:10.1111/1742-6723.70081

Am J Med Genet A. 2025 Jun 4:e64143. doi: 10.1002/ajmg.a.64143. Online ahead of print.

ABSTRACT

The main objective of this study is to establish normative craniocervical junction parameters in pediatric patients with achondroplasia and evaluate differences between patients with and without symptoms of foramen magnum stenosis (FMS) using static and dynamic MRI. A retrospective chart review identified 80 pediatric patients with achondroplasia evaluated at a single institution between 2007 and 2023. Patients were categorized into two groups based on clinical presentation: those with symptoms suggestive of FMS (FMSS group) and those who underwent imaging for unrelated indications (Non-FMSS group). Craniocervical MRI parameters, including minimal canal and cord diameters, atlanto-dental interval (ADI), clival-axial angle (CXA), and space available for the cord (SAC), were measured in neutral, flexion, and extension positions. Statistical comparisons were performed using t-tests, with p-values < 0.05 considered significant. A total of 80 neutral and 69 flexion-extension MRIs were analyzed. Patients in the FMSS group displayed significantly smaller minimal cord and canal diameters across all positions compared to the Non-FMSS group (p < 0.001). SAC measurements were also significantly smaller in the FMSS group. Changes in ADI between flexion and extension were modest and not clinically significant. Interobserver reliability was high across all measured parameters. This study provides preliminary normative data for craniocervical junction parameters in pediatric patients with achondroplasia, highlighting key differences between those with and without symptoms of foramen magnum stenosis. The findings suggest that SAC, minimal cord, and canal diameters may serve as valuable measurements for evaluating cervical stenosis in this population. Further research with larger cohorts and standardized protocols is necessary to validate these parameters.

PMID:40464123 | DOI:10.1002/ajmg.a.64143

J Cosmet Dermatol. 2025 Jun;24(6):e70231. doi: 10.1111/jocd.70231.

ABSTRACT

BACKGROUND: Single-wavelength lasers (755 or 810 nm) are widely used to remove unwanted hair. Recently, combined-wavelength diode lasers have been introduced to improve the safety of darker skin types, owing to their varying absorption spectra and penetration depths. However, their application beyond hair removal remains unclear.

AIMS: This study aimed to evaluate the efficacy of a high-power triple-wavelength diode laser (810, 940, and 1060 nm) in treating hirsutism, inflammatory follicular disorders, and aesthetic concerns such as hairline enhancement in darker skin types.

PATIENTS/METHODS: This retrospective study was conducted at the Escallent Institute of Lasers & Aesthetic Medicine (EILAM), Gurugam, India, using a Primelase device with a triple-wavelength diode laser. The study involved adults with skin type IV who presented with facial hirsutism and follicular disorders, including trichostasis spinulosa, pilonidal sinus disease, and hidradenitis suppurativa. Efficacy was assessed using hair counting and the Global Aesthetic Improvement Scale (GAIS), whereas safety was evaluated based on reported adverse effects, such as pain, erythema, and edema.

RESULTS: The GAIS scores indicated a mean improvement of 3.4 ± 0.4 out of 4, representing a 50%-75% improvement. Hair counting revealed a statistically significant hair reduction of 82.9% ± 15.4%, with reductions ranging from 56% to 100%. No adverse events were observed.

CONCLUSION: The high-power triple-wavelength diode laser demonstrated both efficacy and safety in treating facial hirsutism and other follicular disorders as well as aesthetic concerns such as hairline enhancement, particularly in darker skin tones.

PMID:40464115 | DOI:10.1111/jocd.70231

Clin Endocrinol (Oxf). 2025 Jun 4. doi: 10.1111/cen.15289. Online ahead of print.

ABSTRACT

BACKGROUND: Calcium homeostasis is critical for numerous physiological functions, and while total calcium is commonly measured in clinical practice, albumin-adjusted calcium is widely used to account for protein binding, despite concerns about its accuracy and lack of standardized reference intervals. This study aims to establish a reliable reference range for albumin-adjusted calcium using real-world data from a high-volume tertiary care laboratory.

METHODS: This study analyzed data from 33,159 individuals aged 18-80 years, selected from an initial population of 106,920 patients based on specific biochemical and clinical exclusion criteria. Statistical analysis involved outlier detection, partitioning, and calculation of age-specific reference intervals using the 2.5th and 97.5th percentiles.

RESULTS: The study established age-stratified reference intervals for albumin-adjusted calcium (18-49 years: 2.17-2.55 mmol/L; 50-79 years: 2.20-2.61 mmol/L) and total calcium (18-49 years: 2.17-2.56 mmol/L; 50-79 years: 2.17-2.62 mmol/L).

CONCLUSIONS: Our study reveals that albumin-adjusted calcium reference intervals are age-dependent, with slightly higher upper limits (≈0.05 mmol/L) than traditionally used total calcium ranges, potentially reducing overdiagnosis of hypercalcemia. Further studies are needed to validate these reference intervals across different automated analyzers and diverse patient populations to ensure broader clinical applicability.

PMID:40464109 | DOI:10.1111/cen.15289

Pharmacoepidemiol Drug Saf. 2025 Jun;34(6):e70167. doi: 10.1002/pds.70167.

NO ABSTRACT

PMID:40464089 | DOI:10.1002/pds.70167

Stroke. 2025 Jun 4. doi: 10.1161/STROKEAHA.125.051088. Online ahead of print.

ABSTRACT

BACKGROUND: Oral anticoagulants are superior to antiplatelet agents for preventing cardioembolic stroke but concerns about increased risk of intracranial hemorrhage limit their use. Although rivaroxaban demonstrably increases intracranial bleeding risk compared with aspirin, the comparative risk of intracranial hemorrhage with apixaban versus aspirin remains uncertain. We aimed to clarify this risk through a meta-analysis of randomized controlled trials.

METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for randomized controlled trials comparing apixaban with aspirin for ischemic stroke prevention. Studies were excluded if no intracranial hemorrhage events were reported in either arm. In the primary analysis, we used the Mantel-Haenszel method to meta-analyze the relative risk of intracranial hemorrhage with apixaban versus aspirin therapy. We conducted sensitivity analyses to examine the strength of these findings and to examine the secondary outcome of hemorrhagic stroke (which excludes epidural and subdural hematomas).

RESULTS: Three randomized controlled trials met our inclusion criteria, comprising a total of 10 626 patients and 74 incident intracranial hemorrhage events. In the pooled analysis, the relative risk of intracranial hemorrhage with apixaban versus aspirin therapy was 0.67 ([95% CI, 0.43-1.08]; P=0.10). These findings were consistent in sensitivity analyses utilizing alternative statistical estimators, in analyses limited to primary prevention trials, and in analyses utilizing the outcome of hemorrhagic stroke (relative risk, 0.72 [95% CI, 0.39-1.31]; P=0.28).

CONCLUSIONS: In randomized controlled trials evaluating ischemic stroke prevention, apixaban demonstrated a safety profile comparable-and potentially superior-to aspirin with respect to intracranial hemorrhage risk. These findings warrant a reconsideration of clinical practices that favor aspirin over apixaban, because of the concerns about intracranial hemorrhage risk.

PMID:40464082 | DOI:10.1161/STROKEAHA.125.051088