Category: Nevin Manimala

Dermatol Ther (Heidelb). 2025 Sep 23. doi: 10.1007/s13555-025-01547-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Atopic dermatitis (AD) is a common chronic inflammatory disease during adolescence, with severe forms having a particularly high impact on patients’ quality of life. Several therapeutic options are currently approved for the treatment of AD in individuals over 12 years of age. This study evaluated the efficacy and safety of tralokinumab in adolescent patients, with a particular focus on identifying which patient profiles may derive the greatest benefit from this therapy.

METHODS: A retrospective multicenter study was conducted across nine Spanish hospitals, including patients from 12 to 17 years old with moderate-to-severe AD treated with tralokinumab.

RESULTS: A total of 27 patients were included, with a mean age of 14.8 years. Nine had previously received treatment with dupilumab, five due to primary or secondary failure, and four due to adverse events. One patient had been treated with upadacitinib, which was discontinued because of primary failure and acne. A statistically significant reduction was achieved in Eczema Area and Severity Index (EASI), pruritus visual analog scale (VAS), and Investigator’s Global Assessment (IGA) scores. Palmoplantar involvement was observed in 44.4% of patients; after 24 weeks of treatment, 83.3% of those with palmoplantar involvement experienced complete resolution. Additionally, 37.0% of patients were overweight or obese, with no statistically significant differences in treatment efficacy.

CONCLUSION: Tralokinumab demonstrated efficacy and safety in the treatment of moderate-to-severe AD in patients aged 12-17 years. Notably, the treatment was effective in adolescent patients with palmoplantar involvement and/or obesity.

PMID:40986238 | DOI:10.1007/s13555-025-01547-3

Environ Sci Pollut Res Int. 2025 Sep 23. doi: 10.1007/s11356-025-36925-z. Online ahead of print.

ABSTRACT

The removal of contaminants of emerging concern (CECs) from water is vital due to their persistence and harmful effects on ecosystems and human health. This study developed a titanium-coconut shell based minerals (Ti-CSM) composite for the simultaneous removal of bisphenol S (BPS), carbamazepine (CBZ), and clonazepam (CZP) from water. Carbon material produced with coconut shell-a low-cost biomass-was used as support for titanium oxide in varying mass/mass Ti/biomass ratios (25:75, 50:50, and 75:25), with the Materials being calcined at 400 °C and 600 °C. The response surface methodology with central composite rotatable design (RSM-CCRD) optimized pH (5-9), adsorbate/adsorbent ratio (2.5-7.5 mg g⁻¹), and temperature (16-34 °C), while an artificial neural network (ANN) model was applied for performance prediction. The Ti-CSM 25:75 composite calcined at 600 °C achieved up to 99% removal for BPS and CZP, and 98.7% for CBZ under optimal conditions (pH 7.0, adsorbate/adsorbent ratio 2.5, and temperature 16 °C). Adsorption capacities reached 12.31 mg g⁻¹ (BPS), 8.02 mg g⁻¹ (CBZ), and 7.13 mg g⁻¹ (CZP). Kinetic studies followed a non-linear pseudo-second-order model, while Freundlich and Sips isotherms indicated monolayer adsorption. ANN model revealed higher predictive accuracy compared to RSM-CCRD (R² > 0.98 vs. R² > 0.85). Removal rates in ultrapure water exceeded 98%, while real wastewater treatment removed 89.5 ± 2.5%, 68.7 ± 1.9%, and 57.3 ± 2.0% of BPS, CBZ, and CZP, respectively. This result highlights the material’s potential in treating complex matrices and lessens risks of environmental toxicity, particularly for an endocrine disruptor like BPS. By minimizing titanium use and leveraging a biomass precursor for contaminants adsorption, Ti-CSM composites offer a sustainable, efficient solution for CECs removal, showcasing the potential of biomass modification in eco-friendly water treatment.

PMID:40986226 | DOI:10.1007/s11356-025-36925-z

Insights Imaging. 2025 Sep 23;16(1):201. doi: 10.1186/s13244-025-02086-3.

ABSTRACT

OBJECTIVES: To develop and validate an MRI-derived radiomics model for the prediction of intratumoral tertiary lymphoid structures (TLSs) status of soft tissue sarcoma (STS) and explore its prognostic value.

MATERIALS AND METHODS: This study retrospectively included 302 patients of three cohorts who underwent surgical resection of STS from two medical centers. Radiomics features were derived for both intratumoral and peritumoral regions from preoperative axial fat-suppressed T2-weighted and T1-weighted imaging sequences. Intratumoral, peritumoral, and combined radiomics models were constructed using a logistic regression algorithm. The area under the receiver operator characteristic curve (AUC) and the DeLong test were utilized to assess and compare the performances of three radiomics models. By applying a linear combination of the chosen features, the Rad-score for the optimal radiomics model was computed.

RESULTS: TLS positivity was identified in 114 (38%) of the 302 patients. No clinical, radiological, or pathological variable was found to show a statistically significant association with TLSs status. The combined radiomics model showed superior performance compared to both the intratumoral and peritumoral models, with an AUC of 0.878 (95% CI 0.812-0.927) in the development cohort, 0.778 (95% CI 0.649-0.876) in the internal validation cohort, and 0.772 (95% CI 0.679-0.850) in the external validation cohort. In the cohort for all patients, the 36-month cumulative PFS rate was 66.1% in the high Rad-score (≥ 0.5) group vs. 37.2% in the low Rad-score group (p < 0.05, log-rank test).

CONCLUSION: An MRI-derived radiomics model could predict intratumoral TLS status in patients with STS and demonstrated a correlation with PFS.

CRITICAL RELEVANCE STATEMENT: The MRI-derived radiomics model could predict intratumoral TLSs status in patients with STS accurately, which may help to screen patients who will benefit from immunotherapy and have a better prognosis.

KEY POINTS: Intratumoral tertiary lymphoid structure status in patients with soft tissue sarcomas was accurately predicted by an MRI-derived radiomics model. The combined radiomics model showed superior performance compared to both the intratumoral and peritumoral radiomics models. Progression-free survival was significantly longer in patients with a high Rad-score (≥ 0.5) in the development, internal validation, and external validation cohorts.

PMID:40986220 | DOI:10.1186/s13244-025-02086-3

Biol Trace Elem Res. 2025 Sep 23. doi: 10.1007/s12011-025-04823-7. Online ahead of print.

ABSTRACT

Factors affecting iron chelation therapy outcomes are complex and should be identified to tailor interventions to the needs of individuals with beta-thalassemia major (TM). The purpose of the study was to determine the effects of PON-1 or UGT1A1 single-nucleotide polymorphisms on therapeutic outcomes via deferasirox (DFX) and the antioxidant status. PON-1 (rs662) or UGT1A1 (rs887829) polymorphisms, iron chelation therapy outcomes (cardiac iron T2*, serum ferritin (SF)), and antioxidant-related nutritional indices (PON-1 activity, zinc, 25-hydroxyvitamin D) were determined in 44 Taiwanese TM patients receiving chronic blood transfusion and DFX therapy. Patients’ cardiac iron T2* values were negatively correlated with SF levels (r = – 0.38, p < 0.01). PON-1 AA/AG carriers had significantly greater PON-1 activity, whereas PON-1 GG carriers were prescribed significantly higher DFX doses. UGT1A1 CT and TT carriers had marginally significantly greater SF levels. Only four patients had normal levels of 25-hydroxyvitamin D (25(OH)D > 30 ng/mL). PON-1 activity in those with SF > 2500 (6.4 ± 1.9 units/mL) was significantly lower than that (7.7 ± 1.7 units/mL; p < 0.03) in patients with SF ≤ 2500. Although not statistically significant, variants in PON-1 or UGT1A1 were associated with increased odds ratios (2.44 and 2.899, respectively) for lower cardiac iron T2* values < 30 ms. Taiwanese TM patients with moderate iron overload status had significantly lower PON-1 activity and vitamin 25(OH)D levels, particularly those with T2* < 30 ms. Patients with PON-1 GG and UGT1A1 TT carriers may have an increased risk of cardiac iron overload.

PMID:40986213 | DOI:10.1007/s12011-025-04823-7

J Imaging Inform Med. 2025 Sep 23. doi: 10.1007/s10278-025-01670-9. Online ahead of print.

ABSTRACT

The application of artificial intelligence (AI) in medical imaging has revolutionized diagnostic practices, enabling advanced analysis and interpretation of radiological data. This study presents a comprehensive evaluation of radiomics-based and deep learning-based approaches for disease detection in chest radiography, focusing on COVID-19, lung opacity, and viral pneumonia. While deep learning models, particularly convolutional neural networks (CNNs) and vision transformers (ViTs), learn directly from image data, radiomics-based models extract handcrafted features, offering potential advantages in data-limited scenarios. We systematically compared the diagnostic performance of various AI models, including Decision Trees, Gradient Boosting, Random Forests, Support Vector Machines (SVMs), and Multi-Layer Perceptrons (MLPs) for radiomics, against state-of-the-art deep learning models such as InceptionV3, EfficientNetL, and ConvNeXtXLarge. Performance was evaluated across multiple sample sizes. At 24 samples, EfficientNetL achieved an AUC of 0.839, outperforming SVM (AUC = 0.762). At 4000 samples, InceptionV3 achieved the highest AUC of 0.996, compared to 0.885 for Random Forest. A Scheirer-Ray-Hare test confirmed significant main and interaction effects of model type and sample size on all metrics. Post hoc Mann-Whitney U tests with Bonferroni correction further revealed consistent performance advantages for deep learning models across most conditions. These findings provide statistically validated, data-driven recommendations for model selection in diagnostic AI. Deep learning models demonstrated higher performance and better scalability with increasing data availability, while radiomics-based models may remain useful in low-data contexts. This study addresses a critical gap in AI-based diagnostic research by offering practical guidance for deploying AI models across diverse clinical environments.

PMID:40986191 | DOI:10.1007/s10278-025-01670-9

Adv Ther. 2025 Sep 23. doi: 10.1007/s12325-025-03368-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Valoctocogene roxaparvovec is a single administration gene therapy treatment that enables endogenous factor VIII (FVIII) production to prevent bleeding in people with severe hemophilia A. Valoctocogene roxaparvovec is associated with a higher probability of being bleed-free, improvements in annualized bleed rates, and improvements in health-related quality of life compared with FVIII prophylaxis. The economic value of valoctocogene roxaparvovec will be determined, in part, by the duration of time over which the treatment effect is maintained, and the consequences associated with loss of response. Therefore, this analysis aimed to estimate the long-term durability of valoctocogene roxaparvovec treatment effect by extrapolating pivotal and longer-term trial data (Phase 3 GENEr8-1 4- to 5-year and a Phase 1/2 study 7-year data) to inform decision-making.

METHODS: Using data from the pivotal Phase 3 study GENEr8-1 and longer-term data from the 6E13 vg/kg cohort of Phase 1/2 Study 270-201, time to loss of response was analyzed within a time-to-event analysis framework. Loss of response was defined as a combination of: FVIII level decline < 5% and return to continuous prophylactic treatment and experiencing ≥ 2 treated bleed events in the previous 6 months at the time of return to prophylactic treatment.

RESULTS: Data were available for 134 participants from GENEr8-1, and 7 participants from Study 270-201. The main analysis results for predicted median durability ranged from 11.0 to 17.0 years considering the three statistically best-fitting parametric distributions; considering five plausible distributions, results ranged from 8.1 to 25.6 years. In scenario analyses using different definitions of loss of response, the results were broadly similar, with median durability ranging from 7.2 to 31.8 years.

CONCLUSION: This analysis demonstrates the potential therapeutic benefit of valoctocogene roxaparvovec may be sustained beyond the follow-up period in existing clinical trials and across all parametric extrapolations and definitions analyzed, indicating that gene therapy may offer long-term benefits beyond what has been previously reported (i.e., 7 years).

TRIAL REGISTRATION NUMBER: GENEr8-1: ClinicalTrials.gov identifier, NCT03370913. Study 270-201: ClinicalTrials.gov identifier NCT02576795.

PMID:40986187 | DOI:10.1007/s12325-025-03368-4

Adv Ther. 2025 Sep 23. doi: 10.1007/s12325-025-03348-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Four monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are approved for migraine prevention and commonly prescribed/reimbursed after the failure of repurposed anti-migraine medications. Participants achieving clinical response [e.g., ≥ 50% monthly migraine days (MMDs) reduction] during an anti-CGRP mAb trial are likely to continue treatment. We calculated number needed to treat (NNT) and quarterly cost per responder (CPR) across four anti-CGRP mAbs.

METHODS: Data were from randomized, double-blind, placebo-controlled phase 3b clinical trials that evaluated anti-CGRP mAbs (eptinezumab, fremanezumab, galcanezumab, erenumab) for migraine prevention in adults with episodic or chronic migraine for whom 2-4 prior preventive treatments have failed. NNT was calculated as 1 divided by absolute risk reduction (difference between active treatment and placebo in the proportion of participants with ≥ 50% or ≥ 75% MMD reduction over Weeks 1-12). CPR was calculated by multiplying NNT by the quarterly (3-month) drug acquisition CPR (£), based on the reimbursed list price in the United Kingdom (CPR could not be calculated for eptinezumab 300 mg). Statistical comparisons were not made.

RESULTS: All anti-CGRP mAbs demonstrated higher rates of ≥ 50% and ≥ 75% MMD reduction than their respective placebo (p < 0.05). The NNT to achieve ≥ 50% MMD reduction ranged from 2.7 (eptinezumab 300 mg) to 6.0 (erenumab 140 mg), and for ≥ 75%, 6.0 (eptinezumab 300 mg) to 16.2 (fremanezumab 675 mg/q). The cost per ≥ 50% responder ranged from £4647 (eptinezumab 100 mg) to £7009 (erenumab 140 mg), and for ≥ 75%, £9850 (eptinezumab 100 mg) to £21,862 (fremanezumab 675 mg/q).

CONCLUSIONS: These results show that, for most anti-CGRP mAbs, a low number of participants (< 10) with migraine need to be treated to achieve one person with a ≥ 50% or ≥ 75% reduction in MMDs over Weeks 1-12, with CPR ranging from £4647 (eptinezumab 100 mg) to £21,862 (fremanezumab 675 mg/q).

PMID:40986186 | DOI:10.1007/s12325-025-03348-8

Future Cardiol. 2025 Sep 23:1-9. doi: 10.1080/14796678.2025.2564029. Online ahead of print.

ABSTRACT

BACKGROUND: The triglyceride – glucose (TyG) index is a surrogate of insulin resistance and may predict vascular risk. We evaluated whether baseline TyG is associated with incident stroke and all-cause mortality in adults with diabetes.

METHODS: We analyzed 10,000 UK Biobank participants with diabetes and no baseline cardiovascular disease. TyG was calculated from fasting triglycerides and glucose and categorized into quartiles. Outcomes (stroke; all-cause mortality) were ascertained via hospital and death registries. Cox models estimated hazard ratios (HRs) adjusting for demographic, lifestyle, and clinical covariates.

RESULTS: Over a median 12.8 years, 620 strokes and 688 deaths occurred. Compared with Q1, Q4 had higher risks of stroke (HR 1.45, 95% CI 1.18-1.80) and mortality (HR 1.42, 95% CI 1.17-1.73). Each 1-SD higher TyG was associated with ~ 19% higher stroke risk (HR 1.19, 95% CI 1.07-1.32) and ~ 16% higher mortality risk (HR 1.16, 95% CI 1.05-1.29). Associations were consistent across age, sex, and BMI subgroups and robust in sensitivity analyses, including extended adjustment.

CONCLUSIONS: Higher TyG is independently associated with increased risks of stroke and all-cause mortality among individuals with diabetes. As an inexpensive measure derived from routine tests, TyG may aid risk stratification and inform targeted prevention in this high-risk population.

PMID:40985184 | DOI:10.1080/14796678.2025.2564029

Orthop Surg. 2025 Sep 23. doi: 10.1111/os.70179. Online ahead of print.

ABSTRACT

OBJECTIVE: Since the 1960s, although open reduction and internal fixation for ankle fractures has been widely used, it is associated with complications such as wound dehiscence, infection, prominent hardware, and failure. Closed reduction and internal fixation, on the other hand, offers greater biomechanical strength, requires minimal incisions, and features low-profile hardware. Our study compares the efficacy of elastic locking intramedullary nails (ELIN) fixation featuring minimally invasive microenvironmental protection microstress shielding versus rigid internal fixation (RIF) for trimalleolar fractures.

METHODS: This retrospective study included a total of 39 patients (2020-2024), comprising 10 men and 29 women (mean age, 55.9 years), who were assigned to the ELIN group or the RIF group. Comparing the different variables between the two groups, including surgical incision length, intraoperative blood loss, operative time, time until union, time to device removal, AOFAS scores, ankle dorsiflexion, and plantar flexion, postoperative complications, and patient satisfaction. The surgical incision length, intraoperative blood loss, and operative time conformed to a normal distribution, so the independent t-tests were used for statistical analysis. Time until union, time to device removal, AOFAS scores, ankle dorsiflexion, and plantar flexion, and patient satisfaction did not conform to a normal distribution; thus, the Mann-Whitney U test was adopted.

RESULTS: All 39 patients were completed the surgery successfully. ELIN fixation is superior to RIF in surgical incision length (p < 0.001), intraoperative blood loss (p = 0.047), operative time (p < 0.001), time until union (p = 0.003), and time to device removal (p < 0.001), with significant differences in the above parameters between the two groups. The AOFAS scores (p = 0.553), ankle dorsiflexion (p = 0.904), and plantar flexion (p = 0.799) were not significantly different between the two groups. One case of ankle pain was reported in each group at the sixth month postoperatively. By the end of the follow-up, the pain in these two cases had lessened or even disappeared after the patients reduced weight bearing on the injured ankle joint and took non-steroidal anti-inflammatory drugs under medical guidance. There was a surgical incision infection case in the RIF group, which healed after 3 weeks following daily wound dressing and use of sensitive antibiotics.

CONCLUSION: Compared with RIF, ELIN offers advantages including minimally invasive procedures, faster fracture union, shorter time to device removal, a more aesthetically pleasing appearance of the wound, and high patient satisfaction in treating trimalleolar fractures. These advantages well embody the concept of enhanced recovery after surgery. In contrast to traditional intramedullary fixation, ELIN realized locking fixation, reducing the risk of nail backing out and even nail fracture; however, it is more difficult to remove the nail.

PMID:40985157 | DOI:10.1111/os.70179

Clin Chem Lab Med. 2025 Sep 24. doi: 10.1515/cclm-2025-1011. Online ahead of print.

ABSTRACT

OBJECTIVES: The European Organization for External Quality Assurance Providers in Laboratory Medicine (EQALM) Haematology Working Group (WG) has previously provided two guidelines to support the standardization of haematology blood smear external quality assessment (EQA) (Vives CJL, Albarède S, Flandrin G, Heller S, Horvath K, Houwen B, et al. Guidelines for blood smear preparation and staining procedure for setting up an external quality assessment scheme for blood smear interpretation. Part I: control material. Clin Chem Lab Med 2004;42:922-6; Vives CJL, Van Blerk M, Albarède S, Gutierrez G, Heller S, Nordin G, et al. Guidelines for setting up an external quality assessment scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting. Clin Chem Lab Med 2006;44:1039-43) but these recommendations did not include analytical performance specifications. In this paper the WG provides advice on the performance specifications for the evaluation of blood cell identification, comments on morphological characteristics and diagnostic hypothesis.

METHODS: To develop these specifications, the WG made a survey of the practices in use by EQALM members and provided a standard set of EQA data, provided by one of the members, for performance evaluation.

RESULTS: The results of this exercise show a variation in the performance assessment outcomes from one EQA provider to another, suggesting that a degree of standardisation would be of benefit to participating laboratories.

CONCLUSIONS: The WG has provided advice on common performance specifications, based on model 1 of the Milan Consensus (Sandberg S, Fraser CG, Horvath AR, Jansen R, Jones G, Oosterhuis W, et al. Defining analytical performance specifications: consensus statement from the 1st strategic conference of the European federation of clinical chemistry and laboratory medicine. Clin Chem Lab Med 2015;53:833-5).

PMID:40985149 | DOI:10.1515/cclm-2025-1011