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Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis

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

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Association between estrogen and kidney function: population based evidence and mutual bidirectional Mendelian randomization study

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

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Utility of 18F-FDG PET/CT metabolic parameters on post-transplant lymphoproliferative disorder diagnosis

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 SUVmean41%, 0.834 for SUVmean2.5, and 0.819 for GTV). For MTV41%, TLG 41%, MTV2.5, TLG2.5, 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, SUVmean41%, SUVmean2.5 and GTV showed excellent performance in diagnosing P-PTLD + M-PTLD.

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

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Efficacy of diluted botulinum toxin type A (Microbotox) in treatment of mild to moderate acne vulgaris

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

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Azathioprine and risk of non-melanoma skin cancers in organ transplant recipients: a systematic review and update meta-analysis

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

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Evaluation of UV-A and UV-B transmission through the windows of gas, hybrid, and electric vehicles

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

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Comparative study between fractional CO2 laser (10,600 nm) and microneedling in treatment of morphea: dermoscopic and histopathological evaluation

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

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Unraveling the controversy: exploring the link between sex hormones and skin cancers through a meta-analysis and systematic review

Arch Dermatol Res. 2025 Jan 18;317(1):292. doi: 10.1007/s00403-024-03791-7.

ABSTRACT

Skin cancers continue to present unresolved challenges, particularly regarding the association with sex hormones, which remains a topic of controversy. A systematic review is currently warranted to address these issues. To analyze if sex hormones result in a higher incidence of skin cancers (cutaneous melanoma, basal cell carcinoma, squamous cell carcinoma). Data sources and study selection-The database of PubMed, Embase and Web of Science (WOS) was searched until July 3, 2024. The search yielded 1016 articles. 42 eligible studies were identified for meta-analysis. Data extraction and synthesis-Eligible trials reported skin cancer data and outcomes, confirming diagnoses and collecting hormone use information. Other extracted data included study methods, demographics, and reproductive factor. Relative risk (RR) and odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI), were synthesized after adjusting. The primary outcome was the incidence of cutaneous melanoma and non-cutaneous melanoma. 95% CI and OR are estimate effects. Participants using oral contraceptives (OCs) showed a higher incidence of cutaneous melanoma (CM) [OR 1.08, 95%CI 1.03-1.13, p < 0.01]. There is positively related statistic difference in Squamous cell carcinoma (SCC) [OR 1.37, 95%CI 1.15-1.63, p < 0.01]. Hormone replacement therapy (HRT) was associated with a higher incidence of CM [OR 1.18, 95%CI 1.13-1.24, p < 0.01]. And for non-melanoma skin cancer (NMSC), HRT also increased the incidence [OR 1.13, 95%CI 1.03-1.24, p = 0.01]. Menopausal hormone therapy (MHT) also showed an increased incidence of CM [OR 1.09, 95%CI 1.00-1.18, p < 0.05]. For age at first birth, > 30 years demonstrated a positive correlation with increased the incidence of CM [OR 1.21, 95%CI 1.00-1.46, p = 0.05]. OCs and HRT were associated with increased risks of skin cancers. MHT elevated the risk of CM. In women whose menopause age was older than 50 years, endogenous sex hormones decreased gradually, which caused higher risks of skin cancers. First birth aged older than 30 years indicated increasing effects of skin cancers.Trial registration number : CRD42024517445.

PMID:39825969 | DOI:10.1007/s00403-024-03791-7

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Vulvar lichen planus a retrospective analysis

Arch Dermatol Res. 2025 Jan 18;317(1):285. doi: 10.1007/s00403-025-03798-8.

ABSTRACT

Vulvar lichen planus (VLP) is a rare mucocutaneous disorder with significant impacts on quality of life and a potential risk of malignancy. Comprehensive data on its clinical features and treatment outcomes remain limited. To analyze the demographic and clinical characteristics of patients diagnosed with VLP and to evaluate the efficacy of current therapeutic approaches. A retrospective review was conducted on 70 female patients diagnosed with VLP at a single institution between January 2014 and August 2024. Clinical characteristics, treatment modalities, and outcomes were analyzed. Statistical comparisons were performed using Student’s t-test, Mann-Whitney U test, and χ² test as appropriate. The mean age at diagnosis was 59.3 ± 12.4 years, with a median disease duration of 2 years (range: 6 months-10 years). Pruritus (80.0%) and dyspareunia (62.9%) were the most prevalent symptoms. Corticosteroid therapy was the mainstay treatment, administered to 97.1% of patients, with superpotent topical corticosteroids being the most common (47.1%). Remission was achieved in 25.7% of cases, with younger patients exhibiting significantly higher remission rates (p = 0.005). Thyroid disease was the most common comorbid autoimmune condition, present in 32.9% of patients. VLP predominantly affects middle-aged women, with corticosteroids remaining the first-line therapy. Younger age appears to be associated with better treatment outcomes. These findings underscore the importance of early intervention and individualized therapeutic strategies. Further studies are warranted to explore the underlying mechanisms driving age-related differences in disease outcomes.

PMID:39825959 | DOI:10.1007/s00403-025-03798-8

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Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients

Arch Dermatol Res. 2025 Jan 18;317(1):280. doi: 10.1007/s00403-024-03784-6.

ABSTRACT

BACKGROUND: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

OBJECTIVE: We aimed to explore the potential effect of ritlecitinib on CeD serology levels before and after ritlecitinib treatment in research participants of clinical trials.

METHODS: The effect of ritlecitinib on CeD serology (tTG-IgA, DGP-IgA/IgG) levels was retrospectively evaluated in participants from three phase 2 and one phase 3 ritlecitinib clinical trials including participants with active AA, rheumatoid arthritis (RA) and vitiligo, whose serum samples at baseline and post-treatment were available. All statistical comparisons of the changes between initial and follow-up samples used the Wilcoxon matched pairs exact test.

RESULTS: Of 1146 research participants, 21 individuals had a positive tTG-IgA in their baseline samples (positivity rate, 0.018, 95% CI = 0.011-0.028). Among these 21 individuals, follow-up samples were available in 15 participants from the ritlecitinib group and in 3 from the placebo group. In follow-up samples, the values of tTG-IgA in the 15 participants treated with ritlecitinib significantly decreased from baseline (p < 0.01), while in the placebo group the tTGA-IgA levels remained close to the baseline values.

CONCLUSION: A decrease in CeD serology levels with ritlecitinib treatment suggests that ritlecitinib may provide beneficial effect in CeD.

PMID:39825945 | DOI:10.1007/s00403-024-03784-6