Category: Nevin Manimala

Cardiol Ther. 2025 Jan 18. doi: 10.1007/s40119-024-00393-2. Online ahead of print.

ABSTRACT

INTRODUCTION: This prospective, single-arm pharmacodynamic study assessed the effect of colchicine (COLC) [Strides Pharma UK Ltd, Watford, Hertfordshire, England] 0.5 mg administered orally once daily for 14 days on platelet reactivity with respect to aspirin reaction units (ARUs) and P2Y₁₂ reaction units (PRUs).

METHODS: Twenty-two patients with stable coronary artery disease (CAD) on dual antiplatelet therapy (DAPT) with daily maintenance aspirin and clopidogrel were recruited. Baseline platelet function was evaluated with the VerifyNow™ ARU and PRU assays (Werfen, Bedford, MA, USA) and assessed post-completion of COLC 0.5 mg once daily for 14 days.

RESULTS: In this study, the median ARU baseline score was 463, and post-COLC it was 436, which was not statistically significant (p = 0.485). The mean difference in scores was -18.31 (95% confidence interval [CI] -74.34 to 37.71, p = 0.504). At baseline, 27.3% of the patients had “aspirin resistance” or were non-responders, compared to 13.6% post-COLC (p = 0.423). The median baseline PRU score was 210, and post-COLC it was 199, which was also not statistically significant (p = 0.581). The mean difference in scores was -7.31 (95% CI -31.1 to 16.5, p = 0.530). At baseline, 50% of the patients had “clopidogrel resistance” or were non-responders, compared to 45.5% post-COLC (p = 0.999). Two patients experienced mild gastrointestinal upset during the trial without interruption of COLC, and there were no serious adverse events or treatment-emergent adverse events.

CONCLUSIONS: There were no significant differences in ARUs and PRUs post-COLC trial in patients with stable CAD. This pilot pharmacodynamic study could be clinically informative in patients on DAPT. Further studies are required to confirm these exploratory findings.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06567678, prospectively registered 20/8/2024.

PMID:39826082 | DOI:10.1007/s40119-024-00393-2

J Mol Model. 2025 Jan 18;31(2):53. doi: 10.1007/s00894-024-06254-y.

ABSTRACT

CONTEXT: Ionization and adsorption in gas discharge are similar to electrophilic and nucleophilic reactions. The molecular descriptors characterizing reactions such as electrostatic potential descriptors are useful in predicting the electrical strength of environmentally friendly gases. In this study, descriptors of 73 molecules are employed for correlation analysis with electrical strength. These molecular descriptors are categorized into two types: area-related descriptors and reactivity-related descriptors. Furthermore, the predictive performance between statistical models and machine learning models is compared. The statistical models include multiple linear regression, and polynomial regression, while machine learning models consist of K-nearest neighbors, random forest, and gradient boosting decision trees. The results indicate that machine learning models are generally better than statistical models in terms of predictive accuracy and stability, with gradient boosting decision trees demonstrating the best performance. Specifically, the coefficient of determination and mean squared error on the testing set after 1000 training iterations are 0.864 and 0.105, respectively. Therefore, the application of molecular reactivity descriptors and machine learning methods can effectively predict the electrical strength of gaseous medium.

METHODS: The Gaussian 16 software is employed to optimize the molecular structure with the M06-2X functional and def2 series basis sets in this study. Then, the Multiwfn is utilized for wavefunction analysis to obtain molecular surface descriptors.

PMID:39826053 | DOI:10.1007/s00894-024-06254-y

Updates Surg. 2025 Jan 18. doi: 10.1007/s13304-025-02071-x. Online ahead of print.

ABSTRACT

The surgical risk is higher for obese patients undergoing laparoscopic left hemicolectomy. To enhance the surgical safety and efficacy for obese patients, we have innovatively integrated the advantages of various surgical approaches to modify a pancreas-guided C-shaped surgical procedure. The safety and quality were assessed through a retrospective analysis. Colon cancer patients who underwent laparoscopic left hemicolectomy were categorized into two groups, C-shaped group and Medial-to-lateral group. Baseline data, operative safety indices, operative quality indices and learning curve were subjected to statistical analysis. The complete mesocolic excision rate and R0 resection rate were 100% in both groups. In terms of surgical safety, C-shaped group experienced significantly less blood loss (50(20) mL vs. 50(50) mL, p = 0.002), shorter total operative time (252.65 ± 50.43 min vs. 280.12 ± 70.45 min, p = 0.004) and no organ damage occurred. All patients were classified into four BMI grades (I: BMI < 18.5 kg/m²; II: 18.5 ≤ BMI < 24 kg/m²; III: 24 ≤ BMI < 28 kg/m²; IV: BMI ≥ 28 kg/m²). The total operative time and estimated blood loss were significantly lower in obese patients (BMI grade III and IV) of C-shaped group. In addition, intra-group analysis further confirmed that this modified surgical technique could effectively enhance safety and efficiency for obese patients. Learning curve analysis revealed a significant reduction in total operative time after the completion of 20 surgeries. Utilization of the pancreas-guided C-shaped surgical procedure in obese patients ensures reliable surgical outcomes and significantly increases safety and efficiency. In addition, it is easier to learn and master.

PMID:39826041 | DOI:10.1007/s13304-025-02071-x

Intensive Care Med Exp. 2025 Jan 18;13(1):7. doi: 10.1186/s40635-025-00716-0.

ABSTRACT

PURPOSE: CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22). There is limited clinical data on the effect of CS on the plasma concentrations of beta-lactams. We aimed to evaluate the statistical and clinical impact of CS in a post-filter CKRT-CS setting on the plasma concentrations of the antibiotics meropenem and piperacillin in critically ill patients.

METHODS: Patients admitted to the intensive care unit (ICU) who received a prolonged infusion of piperacillin or meropenem with CS-combined CKRT were included in this retrospective analysis. TDM (therapeutic drug monitoring) plasma blood samples were collected at three different points. The differences in antibiotic concentrations between Pre, Intra, and Post were statistically compared to evaluate the total and isolated contributions of CKRT and CS to antibiotic removal. CS, CKRT and combined clearance (CL) values were calculated. The hypothesis was that the CS filter would have no clinically relevant impact on antibiotic levels.

RESULTS: 207 TDM samples were taken from 24 critically ill patients requiring beta-lactam antibiotics. Among these, 129 were meropenem samples, and 78 were piperacillin samples. A decrease in both antibiotic levels was observed between Pre and Intra, and Pre and Post, and the median relative difference between was >15% (meropenem: Pre-Intra 34.8%, Pre-Post 35.8%; piperacillin: Pre-Intra 41.1%, Pre-Post 34.7%), indicating a statistically and clinically significant effect of CKRT on both antibiotic exposures. No significant difference was observed between Intra and Post indicating no clinically relevant drug removal via the CS filter. Changes in CL attributed to CS were minimal, with combined CL differing by ≤8.60% compared to CKRT clearance.

CONCLUSION: The application of CS does not appear to significantly affect plasma concentrations of meropenem and piperacillin in critically ill patients.

PMID:39826040 | DOI:10.1186/s40635-025-00716-0

Clin Exp Nephrol. 2025 Jan 18. doi: 10.1007/s10157-024-02623-2. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear.

METHODS: The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013-2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies. Weighted generalized multivariate linear regression was employed to estimate the association between estradiol and eGFR and ACR, and a restricted cubic spline analysis was utilized to investigate potential nonlinear relationships.

RESULTS: A total of 8932 participants were included. Serum estradiol concentration was positively associated with eGFR after adjusting for potential covariates (β, 0.76; 95% CI 0.24 to 1.27) and with ACR (β, 5.99; 95% CI 1.62 to 10.36). A nonlinear positive association was found between estradiol and eGFR, while an inverse “V”-shaped relationship was seen with ACR. Sensitivity analyses confirmed the stability of the relationship between estradiol and eGFR but indicated a less robust association with ACR. Stratified analysis showed that the association between estradiol and eGFR was particularly significant in populations with CKD and hypertension. All forward MR analyses demonstrated a positive causal relationship between estradiol and eGFR, but no causality was found between estradiol and ACR. No reverse causal association was observed.

CONCLUSIONS: Serum estradiol concentration was causally associated with eGFR. Further longitudinal research is needed to validate these findings.

PMID:39826006 | DOI:10.1007/s10157-024-02623-2

Ann Nucl Med. 2025 Jan 18. doi: 10.1007/s12149-025-02016-9. Online ahead of print.

ABSTRACT

OBJECTIVE: Using ¹⁸F-FDG PET/CT metabolic parameters to differentiate post-transplant lymphoproliferative disorder (PTLD) and reactive lymphoid hyperplasia (RLH), and PTLD subtypes.

METHODS: ¹⁸F-FDG PET/CT and clinical data from 63 PTLD cases and 19 RLH cases were retrospectively collected. According to the 2017 WHO classification, PTLD was categorized into four subtypes: nondestructive (ND-PTLD), polymorphic (P-PTLD), monomorphic (M-PTLD), and classic Hodgkin. Metabolic parameters included maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and at different thresholds of SUVmax (2.5 and 41%), as well as gross tumor volume (GTV) was also collected. Nonparametric test and receiver operating characteristic (ROC) curves were used for statistics.

RESULTS: There were 42 ND-PTLD patients, 7 P-PTLD patients, and 14 M-PTLD patients. Ki-67 was significantly correlated with all metabolic parameters (P all < 0.01). SUVmean, SUVmax, MTV, TLG and GTV were all highest in M-PTLD, followed by P-PTLD, ND-PTLD, and RLH. ROC curves showed ¹⁸F-FDG PET/CT metabolic parameters all had moderate diagnostic efficacy in differentiating between PTLD and RLH, the area under the curves (AUC) range from 0.682 to 0.747. Diagnostic efficacy for P-PTLD + M-PTLD showed excellent performance (AUC for RLH + ND-PTLD vs P-PTLD + M-PTLD was 0.848 for SUVmax, 0.846 for SUVmean_41%, 0.834 for SUVmean_2.5, and 0.819 for GTV). For MTV_41%, TLG _41%, MTV_2.5, TLG_2.5, the AUC was 0.676, 0.761, 0.761, 0.787, respectively.

CONCLUSION: ¹⁸F-FDG PET/CT metabolic parameters at different thresholds of SUVmax (2.5 and 41%) exhibited comparable diagnostic efficacy for PTLD and its subtypes. All metabolic parameters demonstrated moderate diagnostic efficacy in distinguishing PTLD and RLH. SUVmax, SUVmean_41%, SUVmean_2.5 and GTV showed excellent performance in diagnosing P-PTLD + M-PTLD.

PMID:39826002 | DOI:10.1007/s12149-025-02016-9

Arch Dermatol Res. 2025 Jan 18;317(1):283. doi: 10.1007/s00403-024-03792-6.

ABSTRACT

Acne vulgaris is a common and challenging condition to treat. To assess the effect of botulinum toxin type A (BTX-A) in the treatment of mild to moderate acne vulgaris. This study included 30 patients with mild to moderate acne vulgaris treated with intradermal injections of diluted BTX-A (microbotox) on the cheek in a regular grid pattern using very small droplets (microbotox). Cases were assessed by acne grading of severity by Investigator’s Global Assessment of acne (IGAs) at baseline, at 1 month and after 4 months follow-up. IGA of acne at baseline ranged between 2 to 3 with a mean of 2.77 ± 0.430 and decreased significantly to 0.93 ± 0.868 after 4 months. There were highly statistically significant differences between different follow-up periods according to Investigator’s Global Assessment of acne. IGA on acne showed that 6 (20.0%) had fair improvement, 11 (36.7%) had good improvement and 9 (30.0%) demonstrated excellent improvement. Microbotox presents an approach to oily skin and acne vulgaris management. The multifaceted actions of BTX-A offer promising avenues for addressing the complex pathophysiology of this inflammatory condition pending verification by larger controlled multicenter studies.

PMID:39825998 | DOI:10.1007/s00403-024-03792-6

Clin Transl Oncol. 2025 Jan 18. doi: 10.1007/s12094-024-03839-0. Online ahead of print.

ABSTRACT

BACKGROUND: Immunosuppression might increase the risk of skin cancer in organ transplant recipients (OTRs), with azathioprine (AZA), exerting a fundamental role in the carcinogenesis of those tumors. This systematic review and meta-analysis aims to address the risk of developing malignant skin neoplasms in OTRs undergoing immunosuppression with AZA.

METHODS: PubMed, Cochrane and Embase were searched for studies with OTRs who have a treatment regimen involving Azathioprine therapy after transplantation and that analyzed the emergence of skin neoplasia. We performed the meta-analysis using RStudio v4.4.2 software.

RESULTS: A total of 17 studies comprising a total of 12,708 patients were included, of whom 3567 (28,06%) had a treatment regimen involving AZA therapy after transplantation. The majority of individuals were male 7298 (56,52%) and the median age of patients ranged from 41.5 to 63.2 years. The overall summary estimate showed a significantly increased risk of all types of skin cancer in relation to AZA exposure (OR 1.55; 95% CI 1.07-2.25; p = 0.018; I² = 82%). These results show that the overall result is statistically significant, which means that the observed effect is unlikely to be caused by chance.

CONCLUSION: This study highlights the increased risk of developing skin cancer, particularly squamous cell carcinoma (SCC), in OTRs receiving immunosuppressive therapy with AZA, which allows for rigorous screening and appropriate preventive and therapeutic interventions.

PMID:39825996 | DOI:10.1007/s12094-024-03839-0

Arch Dermatol Res. 2025 Jan 18;317(1):294. doi: 10.1007/s00403-024-03771-x.

ABSTRACT

UV-A exposure is a major risk factor for melanoma, nonmelanoma skin cancer, photoaging, and exacerbation of photodermatoses. Since people spend considerable time in cars daily, inadequate UV-A attenuation by car windows can significantly contribute to the onset or exacerbation of these skin diseases. Given recent market trends in the automobile industry and known impact of car windows on cumulative lifelong UV damage to the skin, there is a need to comparatively evaluate UV transmission across windows in electric vehicles (EV), hybrid vehicles (HV), and gas vehicles (GV) as well as variability based on year of manufacture and mileage to inform car manufacturers and consumers of the potential for UV exposure to the skin based on vehicle. To compare UV-A and UV-B transmission through EV, HV, and GV windows to evaluate differences in UV protection offered by various vehicle types. Comparative observational study that took place between June 10, 2024 and August 2, 2024. Outdoor setting with natural light exposure at car dealerships in Philadelphia, PA and New York, NY. 34 vehicles-15 gas vehicles (GV), 9 hybrid vehicles (HV), 10 electric vehicles (EV)-ranging from 2015 to 2025. Window status, with UV transmission measurements recorded with windows open and closed. UV-A and UV-B transmission through car windows was measured using UV transmission meters. The percent reduction in transmission was calculated. The front windshield and driver side window have statistically significant differences in UV-A attenuation across all vehicles with an average of 99.25% and 88.78% (p < 0.001), respectively. GV, HV, and EV all demonstrated significant differences in UV-A attenuation in most other vehicle windows compared to the front windshield. For GV, the front windshield, rear side windows (p = .176, p = .578) and back windshield (p = .457) blocked more UV-A than the front side windows. EV offered greater UV-A attenuation at the front and back windshield (p = .09) but not for any side windows, and HVs showed consistent differences in UV-A protection between the front windshield and all other windows. Domestic GV, trucks and luxury vehicles had no significant differences in UV-A attenuation across windows indicating reduced UV-A exposure for driver and passengers, whereas non-luxury vehicles had a notable difference in UV-A protection between the front windshield and all other windows. Regression analysis found mileage, not year of manufacture, to be a significant predictor of driver’s side UV-A attenuation, with more UV-A attenuation as vehicle mileage increases. Most vehicles evaluated offer effective UV-A and UV-B protection from the front windshield but lack sufficient UV-A protection for drivers nor consistently to other passengers with notable exceptions seen with domestic GV, trucks, and luxury vehicles. Mileage and not year of manufacture also contributed to additional UV-A attenuation. This underscores the importance of patient education on this known source for cumulative lifetime UV exposure and need for continued sun safety measures even while driving given potential UV-A impact on the skin.

PMID:39825984 | DOI:10.1007/s00403-024-03771-x

Arch Dermatol Res. 2025 Jan 18;317(1):276. doi: 10.1007/s00403-024-03674-x.

ABSTRACT

Morphea is a chronic inflammatory fibrosing disorder. Since fibrosis is the hallmark of both scars and morphea, our attention was raised for the possible use of Fractional Ablative CO₂ lasers and microneedling as treatment modalities for morphea. To compare the efficacy and safety of Fractional Ablative CO₂ lasers and microneedling in the treatment of morphea. This comparative cross-sectional study was conducted on 30 patients with morphea, diagnosed clinically and histopathologically. These patients were divided into two groups; Group 1 (n = 15) received treatment with Fractional Ablative CO₂ laser, and Group 2 (n = 15) received microneedling treatment. Each patient in both groups underwent a total of three sessions, one session per month. Treatment assessment was performed 1 month after the last session using Photographic documentation, clinical evaluation with the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), dermoscopic imaging and histopathological evaluation with Hematoxylin and Eosin (H&E) and Masson’s Trichrome stains. Additionally, patient satisfaction and side effects were evaluated at the end of treatment. A statistically significant decrease in the clinical score (LoSCAT) of morphea was observed in both the Fractional CO₂ laser and microneedling groups at the end of treatment. Furthermore, the histopathological score significantly improved in both groups regarding dermal vasculature, infiltrate, epidermal and dermal changes, and adnexal and periappendiceal fat. A high degree of satisfaction was reported among patients in both groups. Both factional CO₂ and microneedling are safe, effective, and well-tolerated modalities for the treatment of morphea.

PMID:39825977 | DOI:10.1007/s00403-024-03674-x