Nevin Manimala

Ophthalmol Ther. 2025 Nov 12. doi: 10.1007/s40123-025-01270-4. Online ahead of print.

ABSTRACT

INTRODUCTION: To report the 1-year efficacy of Myofix Defocus spectacles, designed to control the progression of myopia in childhood.

METHODS: A total of 47 children with myopia aged 7-15 years were enrolled. Cycloplegic objective refraction (spherical equivalent refraction, SE) and axial length (AL) were measured at baseline, 6 months, and 12 months. Linear regression models were used to identify risk factors of 12-month changes in SE and AL. For comparison, two virtual control groups of children were included. Tolerance was assessed through a questionnaire at each follow-up visit.

RESULTS: Of the initial cohort, 11 participants were lost to follow-up after 6 months due to reasons unrelated to lens design (77.1% retention rate). Over 12 months, the mean SE change in all eyes was – 0.21 ± 0.30 D, and AL change was 0.19 ± 0.13 mm. Progression was significantly different in participants who reported good compared to poor compliance (p < 0.001). At the 12-month follow-up, participants with good compliance had a mean SE progression of – 0.12 ± 0.25 D and a mean AL change of 0.17 ± 0.11 mm. In virtual controls, the mean annual SE progression was – 0.47 ± 0.36 D, and AL change was 0.26 ± 0.17 mm (both p < 0.001). In compliant participants, Myofix Defocus lens demonstrated a 75% reduction in SE and 37% reduction in AL compared to virtual controls.

CONCLUSIONS: After 1 year, Myofix Defocus spectacles slowed myopia progression in children, demonstrating comparable efficacy to other defocus-incorporated spectacle designs. Greater compliance resulted in better treatment effect. Further long-term studies are warranted to confirm these findings.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07092072. Registered retrospectively on July 29, 2025.

PMID:41222872 | DOI:10.1007/s40123-025-01270-4

Eur J Epidemiol. 2025 Nov 12. doi: 10.1007/s10654-025-01303-z. Online ahead of print.

NO ABSTRACT

PMID:41222860 | DOI:10.1007/s10654-025-01303-z

Clin Drug Investig. 2025 Nov 12. doi: 10.1007/s40261-025-01485-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Parkinson’s disease (PD) affects a large population worldwide with millions of people losing motor function control. Although there is no recognized cure for PD, current medications aim to manage the symptoms and slow down the progression of the disease. Amantadine is one such treatment option that can be used in both early and late stages of PD. The current study aimed to assess the relative bioequivalence of two test prototypes (Ta and Tb) of amantadine extended-release (ER) oral formulation manufactured by Sun Pharmaceuticals Industries Limited with the reference immediate-release (IR) formulation (R) of amantadine hydrochloride manufactured by Morton Grove Pharmaceuticals Inc.

METHODS: This was an open-label, balanced, randomized, three-treatment, six-sequence, three-period, single-dose once daily (OD) versus twice daily (BID), crossover relative bioavailability study in healthy adult male subjects under fasting condition with a total of 36 + 2 additional standby subjects meeting the eligibility criteria. The pharmacokinetic parameters including maximum concentration (C_max), time to achieve C_max (t_max), area under the plasma concentration-time curve from time zero to time t (AUC_0-t), area under the concentration-time curve from 0 to 24 h (AUC_0-24), area under the plasma concentration-time curve from time 0 to infinity (AUC_0-∞), and half-life (t_1/2) were assessed. Statistical analysis was performed using analysis of variance (ANOVA) and ratio of least square means (LSM) (log transformed) was used to calculate the relative bioequivalence of the test drugs with the reference drug. Safety monitoring was done by considering adverse and serious adverse events during the duration of the study.

RESULTS: Both Ta and Tb formulations demonstrated similar systemic exposure to the reference product, meeting the criteria for bioequivalence within acceptable limits (80.00-125.00%). The ratios of LSM for log-transformed pharmacokinetic parameters (90% confidence interval [CI]) for Ta versus R were 100.02% (96.75-103.40%) for C_max, and 107.27% (102.75-112.00%) for AUC_0-t; and for Tb versus R were 93.92% (90.38-97.60%) for C_max, and 101.12% (96.73-105.71%) for AUC_0-t. There were no adverse or serious adverse events observed during the study.

CONCLUSION: These findings confirm the bioequivalence of the two test prototypes of amantadine ER formulation manufactured by Sun Pharmaceutical Industries Limited with the IR BID formulation of amantadine manufactured by Morton Grove Pharmaceuticals Inc. The pharmacokinetic equivalence supports the use of OD amantadine ER as an alternative to the BID IR formulation, with the potential to improve patient adherence due to reduced dosing frequency.

PMID:41222848 | DOI:10.1007/s40261-025-01485-0

Ann Nucl Med. 2025 Nov 12. doi: 10.1007/s12149-025-02124-6. Online ahead of print.

ABSTRACT

OBJECTIVE: The primary role of ¹⁸F-FDG PET/CT at the initial diagnosis of breast cancer is to detect distant metastases. This study aimed to investigate locoregional characteristics associated with distant metastasis, based on clinicopathological factors, standard-of-care (SOC) imaging, and ¹⁸F-FDG PET/CT-including a novel PET parameter, subcutaneous/cutaneous uptake (SCU).

METHODS: This retrospective study included patients with newly diagnosed, unilateral invasive breast cancer who underwent pretreatment ¹⁸F-FDG PET/CT. Associations between distant metastasis and the following parameters-including age, SOC imaging-based clinical T and N stage, histology, histological grade, and subtype, as well as tumor SUVmax, subareolar SUV ratio (sSUVr), and subcutaneous/cutaneous uptake (SCU) on PET-were assessed using the Mann-Whitney U test, Fisher’s exact test, and logistic regression. Subgroup analyses were also performed after stratifying patients by locoregional clinical stage (I-IIIA vs. IIIB-C).

RESULTS: Among 197 women (mean age, 56 ± 14 years), distant metastasis was identified in 23 (11.6%). The prevalence of distant metastasis at each locoregional stage in SCU-positive versus SCU-negative patients was as follows: 0% vs. 0% for stage I; 22% vs. 1% for stage IIA; 25% vs. 14% for stage IIB; 25% vs. 13% for stage IIIA; 25% vs. 33% for stage IIIB; and 50% vs. 50% for stage IIIC, with a statistically significant difference observed at stage IIA. In the total cohort, univariate analysis showed that clinical T stage (p = .005), clinical N stage (p < .001), sSUVr (p = .002), and SCU (p < .001) were significantly associated with distant metastasis. In multivariate analysis, only clinical N stages (Odd ratio [OR], 6.5-32.6; p < .001-0.02) remained independent predictors. In the stage I-IIIA subgroup, SCU (OR, 4.86; p = .048) independently predicted distant metastasis, along with age (OR, 1.07; p = .01) and clinical N stages (OR, 8.40-30.26; p = .002-0.008). In the stage IIIB-C subgroup, none of the explanatory variables had significant associations with distant metastasis.

CONCLUSIONS: Age, clinical N stages, and SCU were associated with an elevated risk of distant metastasis in the stage I-IIIA disease. SCU may serve as a novel imaging marker of systemic disease and aid in the diagnosis of distant metastasis-particularly in patients with early-stage breast cancer, where such findings can critically influence treatment strategy.

PMID:41222829 | DOI:10.1007/s12149-025-02124-6

Clin Transl Oncol. 2025 Nov 12. doi: 10.1007/s12094-025-04106-6. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to evaluate whether brain metastases, which are one of the most critical factors that have a poor prognostic value and make treatment difficult in breast cancer cases, differ in HER2-low breast cancer and to evaluate the prognosis of HER2-low breast cancer.

METHOD: This retrospective study included 1134 female patients diagnosed with breast cancer between June 2012 and June 2023 from two tertiary healthcare centers in Türkiye. Molecular groups were examined in six categories according to hormone receptor (HR) and human epidermal growth factor receptor (HER2) status (HR(+) HER2(-), HR(+) HER2-low, HR(+) HER2(+), HR(-) HER2(-), HR(-) HER2-low, and HR(-) HER2(+)).

RESULTS: The median follow-up period was 56.6 months (IQR 29.9-90.5). We detected HER2-low disease in 155 (13.7%) cases. Among the six molecular groups, the highest brain metastasis rate was observed in the HR(-) HER2-low group (22.2%) (p = 0.001). In the HR(+) HER2-low group, the brain metastasis rate was 3.8%, with no statistically significant difference (p = 0.13). In the multivariate binary logistic regression model, there was a 32.4-fold increase in the risk of brain metastasis for the HR(-) HER2-low group compared to the HR(+) HER2(-) group (OR: 12.4, 95% CI 6.70-156.2, p < 0.001). The analysis reveals no significant increase in risk for the HR(+) HER2-low group (OR: 1.68, CI: 0.42-6.67, p = 0.46). In the Cox’s regression model, the highest risk for poor BMFS was found in the HR(-) HER2-low group compared to the HR(+) HER2(-) group, with a 32.8-fold increased risk (HR: 32.82, CI: 7.80-138.3, p < 0.001). In the Cox’s regression model, the highest risk for poor DFS was detected in the HR(-) HER2-low group compared to the HR(+) HER2(-) group, with a fourfold increase in risk (HR: 4.05, CI 1.34-12.30, p = 0.013). Shorter BMSS times were observed in the triple-negative and HR(-) HER2-low groups (1.33 and 3.9 months, respectively; p = 0.001).

CONCLUSION: Our study found that the risk of brain metastasis and disease recurrence increased significantly in the HR(-) HER2-low group, and contrary to some literature data, the risk of brain metastasis in the HR(+) HER2-low group did not differ from the HR(+) HER2(-) group. Both in our study and in many existing studies in the literature, it seems that the HR(+) HER2-low group has a similar prognosis with the HR(+) HER2(-) group, and the HR(-) HER2-low group is in an intermediate form between the HR(-) HER2(+) and HR(-) HER2(-) groups. Recurrence with brain metastasis and general disease recurrence were more common in the HR(-) HER2-low group. The study’s retrospective design and the limited number of patients, especially in the HR(-) HER2-low group, along with potential underreporting in 1 + HER2 cases, are notable limitations.

PMID:41222828 | DOI:10.1007/s12094-025-04106-6

Environ Sci Pollut Res Int. 2025 Nov 12. doi: 10.1007/s11356-025-37134-4. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) are persistent endocrine-disrupting chemicals widely detected in human serum. Epidemiological studies suggest that PFAS exposure may disrupt thyroid function by interfering with hormone production, transport, and metabolism; however, findings remain inconsistent, particularly regarding sex-specific effects. This study aimed to (1) examine associations between serum PFAS mixtures and thyroid hormone levels in adolescents and (2) identify mixture patterns and explore sex-specific associations using a nationally representative dataset. We investigated the association between serum PFAS mixtures and thyroid function markers-including thyroid-stimulating hormone (TSH), thyroid hormones, and thyroglobulin-among 12- to 20-year-olds in NHANES 2011-2012. Principal component analysis (PCA) identified three factors: Factor 1 (long-chain carboxylates: PFUnA, PFDA, PFNA), Factor 2 (sulfonates: PFHxS, PFOS, MeFOSAA, and PFOA), and Factor 3 (PFHpA). Multivariable linear regression estimated associations between PFAS factors and thyroid hormone concentrations. Higher exposure to Factor 1 was significantly positively associated with free T4 in males but negatively associated with total T4 in females. PFASs may alter hormone clearance or interfere with feedback regulation. Factor 2 exposure was negatively associated with total T4 and positively associated with TSH in males, with statistical significance. Greater exposure to Factor 3 was significantly associated with increased total T4 in males. Overall, exposure to Factors 1 and 2 was predominantly linked to lower thyroid hormone levels, whereas Factor 3 was positively associated with thyroid hormones. These findings highlight the importance of evaluating PFAS mixtures rather than individual compounds and suggest sex-specific thyroid hormone disruptions.

PMID:41222812 | DOI:10.1007/s11356-025-37134-4

Saudi Pharm J. 2025 Nov 12;33(6):43. doi: 10.1007/s44446-025-00042-2.

ABSTRACT

While several anti-tumor biosimilars have been approved in China, comprehensive nationwide analyses of their real-world utilization patterns remain limited, particularly regarding cross-regional adoption and indication-specific usage. We collected information on patients treated with bevacizumab, rituximab, trastuzumab and their biosimilars at 109 hospitals in nine Chinese cities from 2019 to 2023. Analysis of 264,527 prescriptions revealed rapid biosimilar adoption for bevacizumab (2023 originator share: 20.0%, -25.1%/year), moderate for rituximab (32.1%, -16.8%/year), and limited for trastuzumab (70.0%, -8.3%/year). Geographic variation was substantial (2023 city ranges: bevacizumab 2.3-43.0%; rituximab 6.7-70.3%; trastuzumab 42.4-92.4%). Tertiary hospitals showed faster biosimilar uptake than secondary hospitals (bevacizumab: + 23.7%). Free medical care patients preferred originators (bevacizumab: 64.1% vs 38-39% for other payers). Off-label use demonstrated significantly higher biosimilar adoption (bevacizumab: 69.0%; rituximab: 52.1%) versus approved indications (p < 0.00625). Cost distributions mirrored prescription trends but consistently favored originators. All trends were statistically significant (p < 0.05). The biosimilar market share showed steady annual growth, however the growth rates vary across different products. However, Patients with lower out-of-pocket costs remained more likely to choose original products. Enhanced regulatory oversight of both approved and off-label/extrapolated indications is needed to ensure appropriate biosimilar utilization.

PMID:41222808 | DOI:10.1007/s44446-025-00042-2

Clin Rheumatol. 2025 Nov 12. doi: 10.1007/s10067-025-07804-2. Online ahead of print.

ABSTRACT

BACKGROUND: Primary Sjögren’s syndrome (pSS), a systemic autoimmune disorder, is recognized by immune dysregulation and chronic inflammation. Though telomere attrition has been linked to various immune-related diseases, its relationship with pSS pathogenesis remains poorly understood. This research seeks to explore the relationship between peripheral blood leukocytes’ telomere length and the susceptibility to pSS, thereby offering insights into the potential role as a biomarker.

METHODS: 181 participants, comprising pSS patients (n = 87) and healthy controls (n = 94) were involved in this study. Relative length of leukocyte telomere (T/S ratio) was quantified by a validated quantitative PCR protocol. To define the independent effect of telomere length on pSS susceptibility, logistic regression analyses, including univariate and multivariable, were performed. In addition, generalized additive modeling (GAM) was applied to identify possible nonlinear dose-response patterns.

RESULTS: pSS patients demonstrated significantly shorter telomere lengths than healthy controls (mean T/S ratio: 0.8 ± 0.35 vs. 1.01 ± 0.49, P = 0.0019). Decreased length of telomere was strongly linked to a higher likelihood of pSS occurrence (OR = 0.31, 95% CI: 0.15-0.66, P = 0.0021). This relationship stayed statistically meaningful, albeit slightly weakened, after accounting for clinical characteristics and therapeutic variables. Moreover, nonlinear modeling suggested that progressive telomere shortening corresponded to a rising probability of developing pSS, implying a potential mechanistic contribution of telomere erosion to disease development.

CONCLUSION: This cross-sectional study indicates that reduced telomere length in peripheral blood leukocytes is linked to an elevated likelihood of developing pSS, suggesting that telomere dynamics could function as a promising biomarker for early detection and risk assessment. Future longitudinal studies are warranted to confirm causality and assess telomere-targeted interventions. Key Points • Leukocyte telomere shortening serves as a clinically relevant biomarker in pSS. • Nonlinear dynamics link telomere attrition to immune dysregulation. • Telomere length shows complex interaction with disease stage and therapeutics.

PMID:41222807 | DOI:10.1007/s10067-025-07804-2

Clin Rheumatol. 2025 Nov 12. doi: 10.1007/s10067-025-07768-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics, associated factors, and outcomes of posterior reversible encephalopathy syndrome (PRES) in patients with systemic lupus erythematosus (SLE).

METHODS: This retrospective case-control study, conducted from 2009 to 2022, included 32 patients with SLE who developed PRES and 50 matched controls with neuropsychiatric SLE (NPSLE). Controls were matched for age, sex, and disease duration. Clinical characteristics, laboratory indices, neuroimaging findings, and treatment approaches were systematically evaluated. Multivariate logistic regression was performed to identify factors associated with PRES in patients with SLE. In addition, survival outcomes were compared according to different glucocorticoid (GC) dosing regimens.

RESULTS: Patients with SLE who developed PRES had significantly longer hospitalizations and a higher frequency of hypertension compared with NPSLE controls (P < 0.05). Laboratory findings showed elevated white blood cell (WBC) and neutrophil (NE) counts, as well as increased levels of creatinine (Cr), blood urea nitrogen (BUN), and C-reactive protein (CRP); in contrast, serum albumin (Alb) and magnesium levels were markedly lower before the onset of neurological symptoms in the PRES group (all p < 0.05). PRES patients also demonstrated higher rates of nephritis and hypomagnesemia compared with NPSLE controls without PRES (p < 0.05). At the time of neurological symptom onset, seizures, visual impairment, and vomiting were more common in the PRES group, whereas acute confusional state were less frequent (p < 0.05). Neuroimaging revealed that patients with PRES more often exhibited lesions involving the parietal, occipital, frontal, and temporal lobes (p < 0.05). Multivariate logistic regression analysis identified several factors associated with an increased risk of PRES in patients with SLE: hypertension (OR 38.419, 95% CI: 6.073-243.037, p < 0.001), hypomagnesemia (OR 8.360, 95% CI: 1.542-45.322, p = 0.014), nephritis (OR 10.362, 95% CI:1.246-86.156, p = 0.030) and treatment with very-high-dose GC (OR 14.352, 95% CI: 1.927-106.921, p = 0.009). Furthermore, among SLE patients with PRES, survival rates differed significantly across GC dosing regimens (p = 0.045, Fisher’s exact test), with rates of 50.00% (6/12) in the very-high-dose group, 88.24% (15/17) in the high-dose group, and 100.00% (3/3) in the low-medium-dose group. During follow-up (1-6 months), disease relapse occurred in three patients (9.38%).

CONCLUSION: Hypertension, hypomagnesemia, nephritis, and the use of very-high-dose GC may represent potential factors associated with the development of PRES in patients with SLE. Moreover, treatment approaches, especially GC dosing, may influence patient survival outcomes.It should be emphasized, however, that the observed association involving hypomagnesemia, though statistically significant in this cohort, remains preliminary and necessitates further validation in larger, prospectively designed studies. Key Points • This study represents the largest case-control analysis of SLE-associated PRES to date (32 cases vs. 50 NPSLE controls), identifying multiple associated factors linked to PRES. • Hypomagnesemia and treatment with very-high-dose GCs were identified as novel associated factors for PRES in SLE, reported here for the first time. • Disease activity (SLE disease activity index (SLEDAI)) was compared between the SLE-PRES cohort (before and during the episode) and the NPSLE cohort. • Survival outcomes in SLE-PRES patients varied significantly according to GC dosing intensity (p = 0.045), with the highest mortality (50.0%) observed in the very-high-dose group.

PMID:41222806 | DOI:10.1007/s10067-025-07768-3

Mol Biol Rep. 2025 Nov 12;53(1):69. doi: 10.1007/s11033-025-11217-4.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is a complex disease influenced by genetic and environmental factors. Polymorphisms in RAAS genes have been implicated in kidney disease, though their influence on disease susceptibility varies across studies. The AGT and AGTR1 are key candidate genes of the RAAS cascade, essential for kidney function.

METHODS AND RESULTS: This study investigated the association of AGT (rs699) and AGTR1 (rs5186) polymorphisms with susceptibility to CKD. A total of 380 participants were recruited in this hospital-based case-control study and genotyping was performed using PCR- RFLP method. Statistical analyses were conducted using SPSS Statistics version 26.0. Computational analysis was done to predict the pathogenicity of missense variant rs699 and its effect on structure and function of AGT; however, rs5186, a 3′ UTR non-coding variant of the AGTR1 gene was excluded. Our findings showed that the AGT (rs699) T allele was more frequent in controls (46.9%) than in CKD cases (35.3%), suggesting a potential protective role against CKD (p = 0.001). No significant associations were observed in AGTR1 (rs5186) and CKD (p > 0.05). Furthermore, the studied polymorphisms did not significantly affect serum creatinine, urea, or eGFR levels in CKD patients. In silico analysis predicted the AGT rs699 variant to be likely benign, with slightly decreased AGT protein stability and binding affinity to renin.

CONCLUSIONS: The results suggest a significant association of the AGT (rs699) polymorphism with CKD. Computational findings support a limited functional impact of the rs699 variant. Further research, including functional studies and investigations in larger cohorts, is warranted to assess the potential of these polymorphisms as biomarkers for CKD risk.

PMID:41222805 | DOI:10.1007/s11033-025-11217-4