Tag: nevin manimala

Clin Pharmacokinet. 2025 Mar 27. doi: 10.1007/s40262-025-01484-6. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Navitoclax, an orally bioavailable B-cell lymphoma-2 (Bcl-2) family protein inhibitor, inhibits antiapoptotic Bcl-2 family proteins (with high affinity to Bcl-XL, Bcl-2, and Bcl-W). Navitoclax in combination with ruxolitinib has been investigated to treat patients with myelofibrosis (MF).

METHODS: Since navitoclax undergoes hepatic metabolism, we evaluated the pharmacokinetics (PK) and safety of single-dose navitoclax 50 mg in a phase 1 study in participants with mild (N = 6), moderate (N = 6), or severe (N = 1) hepatic impairment and matched participants with normal hepatic function (N = 7). All participants in this study were enrolled per Child-Pugh classification, with demographics matched per age, weight, and race.

RESULTS: Navitoclax maximum plasma concentration (C_max), area under the plasma concentration-time curve for time zero to infinity (AUC_0-∞), and terminal elimination half-life (t_1/2) in participants with mild or moderate hepatic impairment were comparable to participants with normal hepatic function. The change in C_max and AUC_0-∞ values in participants with mild and moderate hepatic impairment were within 25% of normal hepatic function. Overall, 2/20 (10%) participants receiving a 50 mg single dose reported grade 1 treatment-emergent adverse events of nausea (N = 1) and diarrhea (N = 1).

CONCLUSIONS: In summary, no new safety issues were identified. On the basis of the pharmacokinetic results, no dose adjustment is required for patients with MF with mild or moderate hepatic impairment.

PMID:40146460 | DOI:10.1007/s40262-025-01484-6

Discov Oncol. 2025 Mar 27;16(1):411. doi: 10.1007/s12672-025-02126-w.

ABSTRACT

PURPOSE: To investigate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in interim therapeutic and prognostic evaluation of patients with diffuse large B-cell lymphoma (DLBCL).

MATERIALS AND METHODS: Data of 86 patients with pathologically confirmed DLBCL who underwent ¹⁸F-FDG PET/CT imaging before chemotherapy, radiotherapy, and after interim chemotherapy, were retrospectively analyzed. Receive operating characteristic (ROC) curve analysis was performed to assess the predictive capacity of changes and change rates in PET/CT imaging parameters [maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum tumor dissemination (D_max)] for progression-free survival (PFS) and to identify optimal cutoff values. Kaplan-Meier survival curves were constructed, and the log-rank test was used to assess intergroup differences. Cox regression analysis was used to explore potential factors influencing PFS.

RESULTS: Among 86 patients [(45 men, 41 women, age: 57.8 ± 12.2 years)], the median PFS was 22.5 (14.5, 46) months. Until the last follow-up date, progression or recurrence occurred in 14 patients, while 9 patients died. The ROC curves indicated that the optimal cutoff values for predicting PFS were 99.10%, 99.72%, and 96.47% for ΔMTV%, ΔTLG%, and ΔD_max%, respectively (area under the curve = 0.786-0.849, all P < 0.05). Cox univariate analysis demonstrated that the alteration rates in metabolic and diffusion parameters before and after treatment, including SUV_max%, MTV%, TLG%, and D_max%, were predictive of PFS (hazard ratio [HR] = 6.213-13.430, all P < 0.05). The Cox multivariate analysis demonstrated that ΔMTV% and ΔD_max% independently predicted PFS, with HRs of 10.727 (95% confidence interval [CI] = 1.928-56.672, P = 0.007) and 7.178 (95%CI = 1.514-34.041, P = 0.013), respectively. We established a new prediction model by combining the ΔMTV% and ΔD_max% parameters, and the results of the model showed statistically significant differences in PFS between the high, intermediate, and low-risk groups. The model predicted higher effects than individual indicators.

CONCLUSION: The rate of change in metabolic and diffusion parameters on interim PET/CT can predict the prognosis of patients with DLBCL.

PMID:40146454 | DOI:10.1007/s12672-025-02126-w

Neurosurg Rev. 2025 Mar 27;48(1):333. doi: 10.1007/s10143-025-03479-0.

ABSTRACT

Deep brain stimulation in the subthalamic nucleus (STN-DBS) is a therapeutic intervention for patients with Parkinson’s disease (PD) primarily aimed at improving motor symptoms. However, the effects of STN-DBS on non-motor symptoms (NMS), such as olfactory dysfunction (OD), remain poorly understood. We performed a systematic review and single-arm meta-analysis to evaluate the effects of STN-DBS on OD in PD patients. We searched Medline, Scopus, and Web of Science databases. Eligible studies included observational studies with ≥ 4 patients reporting the effects of STN-DBS on OD in PD patients. Mean differences (MD) between pre- and post-operative, along with the final mean pooled analysis, olfactory scores values with 95% confidence intervals (CI) with a random effects model were used. The statistical analysis was performed using the software R Studio. The heterogeneity was assessed with I² statistics, and leave-one-out sensitivity analysis was used to address high heterogeneity. A total of seven studies, encompassing 188 PD patients, with a mean age of 60.8 years, were included in our analysis. There was a statistically significant difference between pre- and post-operative value in Odor discrimination (ODI) (MD 2.16; 95% CI 1.37 to 2.96; p < 0.01; I² = 0%) and Unified Parkinson’s Disease Rating Scale part III OFF medication (UPDRS III OFF_MED) (MD -11.96; 95% CI -22.57 to -1.35; p = 0.03; I² = 88%), showing improvement in OD and motor function after DBS, compared to baseline. In contrast, there was no statistically significant difference between the initial and final value in Odor thresholds (OT) (MD 1.54; 95% CI -0.22 to 3.30; p = 0.09; I² = 90%), and the University of Pennsylvania Smell Identification Test (UPSIT) (MD -0.37; 95% CI -3.40 to 2.66; p = 0.81; I² = 0%). Additionally, the pooled analysis for Odor identification (OI) showed a final mean of 7.06 (95% CI 4.39 to 9.72; I² = 100%), and for the TDI score (composite score derived from the sum of OD, OI, and OT results), a final mean of 25.96 (95% CI 17.31 to 34.62; I² = 94%). Despite the prior indication of STN-DBS for motor symptoms, it may improve OD in PD patients. Clinical trial number Not applicable.

PMID:40146437 | DOI:10.1007/s10143-025-03479-0

Breast Cancer Res Treat. 2025 Mar 27. doi: 10.1007/s10549-025-07671-0. Online ahead of print.

ABSTRACT

PURPOSE: Racial disparities exist regarding cardiovascular (CV) toxicities following breast cancer treatment; however, studies on racial differences in cardiac arrhythmias are lacking. This study examined associations between demographic and clinical factors and arrhythmia diagnosis in Black and White breast cancer survivors.

METHODS: This study included a retrospective cohort of Black and White women who were diagnosed with breast cancer and who received potentially cardiotoxic treatment. Cardiac arrhythmia data were captured via International Classification of Diseases, Tenth and Ninth Versions (ICD-10 and ICD-9). Experiences with cardiac arrhythmias were compared across racial groups. The associations of demographic and clinical factors with cardiac arrhythmias were evaluated using logistic regression for all women and in race-stratified models.

RESULTS: Thirty-three percent of the total 860 women in our study sample (mean (standard deviation) age 50.3 (10.7) years) old) experienced cardiac arrhythmias. In bivariate analyses, we observed a statistically discernible association between race and arrhythmia status following a breast cancer diagnosis (p = 0.004); however, this association was no longer significant in the multivariable model. In race-stratified multivariable analysis, the odds of experiencing arrhythmias in Black women over 50 years old are 51% lower than in Black women aged 50 years old or younger (adjusted odds ratio (OR): 0.49; 95% confidence interval (CI): 0.28, 0.86). All else being equal, Black women with hypertension had 2.68 times (95% CI: 1.51, 4.81) higher odds of experiencing arrhythmias than those without hypertension. White women with obesity had higher odds of experiencing arrhythmias than those with normal weight or underweight status. (adjusted OR 1.93: [1.17, 3.20]).

CONCLUSION: Survivors with chronic conditions like hypertension and obesity may require enhanced cardiac surveillance. Further investigation into hypertension management in Black survivors may shed light on its impact on CV toxicities in this group.

PMID:40146434 | DOI:10.1007/s10549-025-07671-0

Eur Radiol. 2025 Mar 27. doi: 10.1007/s00330-025-11489-1. Online ahead of print.

ABSTRACT

OBJECTIVES: Contrast-enhanced ultrasound (CEUS) assesses omental lesion nature, but CEUS-guided biopsy feasibility, effectiveness, and safety are uncertain.

METHODS: From January 2020 to January 2024, patients scheduled for ultrasound-guided omental biopsy at the First Hospital of China Medical University were enrolled. They were divided into CEUS-guided and conventional ultrasound-guided groups, balanced using propensity score matching (PSM). Success rate, diagnostic accuracy, and complication rate were compared. Subgroup analyses considered sonographic features, with significance at p < 0.05.

RESULTS: After PSM, 310 CEUS-guided and 160 conventional ultrasound-guided patients were analyzed. Groups were similar in demographics and omental characteristics (p > 0.05). CEUS-guided biopsy had higher sample acquisition (97.42% vs. 93.13%, p = 0.029) and diagnostic accuracy (96.03% vs. 87.92%, p = 0.002). Overall complication rate was 9.36% (44/470), with distant metastasis in 0.43% (2/470). Complication rates did not differ significantly between groups. In hyperechoic group, dense group, and non-nodule group, CEUS-guided biopsy had higher success (97.99% vs. 92.55%, p = 0.042) and accuracy (96.48% vs. 86.17%, p = 0.002). In non-nodule group, CEUS-guided accuracy was superior (93.41% vs. 84.11%, p = 0.015).

CONCLUSION: Ultrasound-guided omental biopsy is a safe and effective method for obtaining samples. CEUS-guided omental biopsy enhances sample acquisition and diagnostic accuracy, especially in hyperechoic group, dense group, and non-nodule group, suggesting it is a more accurate and effective diagnostic method.

KEY POINTS: Question Selecting a puncture site for diffuse lesions of the greater omentum presents challenges, as conventional ultrasound-guided biopsy often encounters difficulties in avoiding local necrotic tissue. Findings Ultrasound-guided biopsy of the greater omentum is a safe and effective diagnostic method, especially when augmented with CEUS, which can significantly enhance diagnostic accuracy. Clinical relevance CEUS can markedly enhance diagnostic accuracy by providing a robust foundation for selecting the biopsy site and pathway. Therefore, it is advisable to routinely employ CEUS-guided puncture pathways for atypical omental lesions.

PMID:40146426 | DOI:10.1007/s00330-025-11489-1

Eur Radiol. 2025 Mar 27. doi: 10.1007/s00330-025-11524-1. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to assess whether pharmacokinetic parameters derived from DCE-MRI can stratify Programmed Death-Ligand 1 (PD-L1) expression in NSCLC. The secondary aim was to identify a suitable pharmacokinetic model configuration for anisotropic temporally-spaced DCE-MRI sequences, considering Tofts variants, population-averaged arterial input functions (AIF), and bolus arrival time (BAT) estimation methods.

MATERIALS AND METHODS: From April 2021 to May 2023, patients with locally advanced non-small cell lung cancer (NSCLC) were prospectively enrolled. Tumors were categorized based on: PD-L1 absence/presence (threshold 1%) and hyperexpression/hypoexpression (threshold 50%). Pharmacokinetic parameters were extracted using several candidate configurations; fit quality was evaluated using coefficient of determination (R²). Mann-Whitney U-test and ROC-AUC were used to assess correlation with PD-L1 for the best-fit configuration.

RESULTS: Thirty-eight patients (mean age 68 ± 9 years, 28 men) were included. PD-L1 expression was present in 25 patients (66%) and absent in 13 (34%). PD-L1 was hyperexpressed in 13 (34%) patients and hypoexpressed in 25 (66%). Voxel-wise pharmacokinetic parameters were extracted using the best-fit configuration-extended Tofts model (ETM) with Georgiou AIF and Peak-Gradient (PG) BAT estimation (R² = 0.79). K^trans median (0.25 vs. 0.12 min^–¹, p = 0.02), K^trans standard deviation (0.32 vs. 0.23 min^–¹, p = 0.01) and K_ep median (1.09 vs. 0.59 min^–¹, p = 0.02) were significantly higher in PD-L1 < 50% group (ROC-AUC 0.71-0.76).

CONCLUSION: DCE-MRI pharmacokinetic parameters could stratify PD-L1 hypo/hyperexpression in NSCLC. The ETM with PG BAT estimation method and Georgiou AIF was the best-performing pharmacokinetic configuration.

KEY POINTS: Question Could Dynamic Contrast-Enhanced (DCE) MRI offer a safe and non-invasive way to assess Programmed Death-Ligand 1 (PD-L1) expression? Findings Quantitative DCE-MRI parameters K^trans (the volume transfer rate) and K_ep (the efflux rate constant) show potential for distinguishing PD-L1 hyperexpression from hypoexpression. Clinical relevance Preliminary results suggest that DCE-MRI could be a safe method to stratify PD-L1 hypo/hyperexpression in non-small cell lung cancer, potentially optimizing treatment decisions, given the high cost of immunotherapy.

PMID:40146425 | DOI:10.1007/s00330-025-11524-1

Eur Radiol. 2025 Mar 27. doi: 10.1007/s00330-025-11516-1. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the association between plaque characteristics and burden by coronary computed tomography angiography (CCTA) and ischemia determined by invasively measured fractional flow reserve (FFR), and whether the addition of plaque characteristics improves ischemia discrimination beyond coronary stenosis alone.

METHODS: A systematic literature review and meta-analysis of studies from PubMed, EMBASE, and the Cochrane Library databases, published between January 2005 and October 2024 were conducted to assess the relationship between quantitative and qualitative coronary plaque characteristics and invasive FFR. Pooled analyses were performed using weighted mean difference for plaque volumes with 95% confidence intervals and odds ratios for qualitative plaque findings.

RESULTS: A total of 29 studies involving 4416 patients (mean age 63 ± 9 years and 71% male) with predominantly stable coronary artery disease were included. Data on 3923 lesions and 3520 vessels were pooled. Total plaque, non-calcified plaque, and percent aggregate plaque volumes, as well as percent plaque burden, were inversely associated with FFR at both per-lesion and per-vessel levels (all, p-values < 0.05). The presence of high-risk plaque characteristics, including low-attenuation plaque, napkin-ring sign, and spotty calcification, were more frequently observed in lesions and vessels with FFR ≤ 0.80 (all, p-values < 0.05). Among plaque volumes, the percent aggregate plaque volume consistently improved ischemia discrimination independently of stenosis.

CONCLUSION: CCTA-derived quantification of plaque volumes and identification of high-risk plaque characteristics are associated with ischemia and significantly enhance discrimination of ischemia-causing lesions independently of coronary stenosis severity.

KEY POINTS: Question Plaque characteristics have been suggested as the missing link between coronary artery stenosis severity and ischemia. Findings High-risk plaque characteristics and larger coronary plaque volumes are associated with ischemia (FFR ≤ 0.80). Clinical relevance The addition of CCTA-derived plaque assessment improved the discrimination of ischemia compared with stenosis evaluation alone. Combining coronary stenosis and plaque assessment may improve the non-invasive assessment of patients with coronary artery disease and gatekeeping to the catheterization laboratory.

PMID:40146424 | DOI:10.1007/s00330-025-11516-1

Eur Radiol. 2025 Mar 27. doi: 10.1007/s00330-025-11527-y. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the therapeutic effect, adverse events, and hepatic artery injury (HAI) between gelatin spheres (GS) and nonspherical gelatin sponge particles (GP) in conventional transcatheter arterial chemoembolization (C-TACE).

MATERIALS AND METHODS: A total of 368 consecutive patients with hepatocellular carcinoma (HCC) who underwent C-TACE between September 2019 and May 2021 were included in this single center retrospective study. Adverse events, radiologic tumor response, local tumor recurrence, and HAI were evaluated.

RESULTS: Subsegmental C-TACE was performed using biodegradable GS in 165 patients and nonspherical biodegradable GP in 203 patients. No significant differences in patient background existed between the groups, and there was no significant difference in adverse event rate (p = 0.231). The CR and overall tumor response in the GS and GP groups were 73.3% vs 70.9%, and 99.4% vs 98.5%, respectively, with no significant between-group differences (p = 0.642 and p = 0.631). No significant difference in cumulative local tumor recurrence rate existed between the groups (p = 0.558). HAI was observed in 16% (20 of 125 patients) in the GS group and 37.4% (49 of 131 patients) in the GP group. The incidence of HAI was significantly higher in the GP group than in the GS group (p < 0.001). In multiple logistic regression analysis, risk factors for HAI were index tumor size ≥ 3 cm (p = 0.001) and use of GP (p < 0.001).

CONCLUSION: C-TACE with GS resulted in the same therapeutic and adverse effects as C-TACE with nonspherical GP while causing significantly less HAI.

KEY POINTS: Question Comparisons between GS and nonspherical GP are lacking, and the potential advantages of GS over nonspherical GP are not well studied. Findings HAI incidence was higher in the GP than the GS group, and risk factors of HAI were index tumor size ≥ 3 cm and GP use. Clinical relevance C-TACE with GS resulted in the same therapeutic and adverse effects as C-TACE with nonspherical GP while causing significantly less HAI.

PMID:40146423 | DOI:10.1007/s00330-025-11527-y

J Cancer Educ. 2025 Mar 27. doi: 10.1007/s13187-025-02617-y. Online ahead of print.

ABSTRACT

Effective cancer prevention requires early interventions to enhance health literacy, particularly for Opisthorchis viverrini (OV) and cholangiocarcinoma (CCA) in the Greater Mekong Subregion. This study developed and evaluated the Muk-KAMSComD Model, a structured learning management approach, to improve health literacy and preventive behaviors among primary school students in Mukdahan Province, a high-risk area in Thailand. A four-step research and development (R&D) framework was implemented: (1) situation and needs assessment, (2) model development, (3) implementation, and (4) refinement and presentation. Thirty-six Grade 6 students were selected through multi-stage sampling, and a one-group pretest-posttest design assessed health literacy using validated questionnaires. The 12-week intervention integrated the HALO Model (Healthy School, Active Learning, Lesson Study, and Open Class) with six key health literacy skills. Data were analyzed using qualitative content analysis, descriptive statistics, and paired t-tests. The Muk-KAMSComD Model consists of Knowledge provision, Awareness and belief creation, Motivation enhancement, Self-management practice, Communication, and Decision-making and forwarding. Post-intervention, students significantly improved (p < 0.001) in knowledge, communication, self-management, media literacy, information access, and decision-making skills. Information access showed the highest improvement, while self-management remained the lowest. The model was refined to strengthen parental engagement and instructional materials for enhanced effectiveness. The Muk-KAMSComD Model effectively strengthens health literacy and preventive behaviors for OV and CCA among primary school students. Its integration into school curricula and public health programs could contribute to sustainable CCA prevention in endemic regions.

PMID:40146421 | DOI:10.1007/s13187-025-02617-y

Eur J Orthop Surg Traumatol. 2025 Mar 27;35(1):136. doi: 10.1007/s00590-025-04253-0.

ABSTRACT

PURPOSE: The rising demand for primary total shoulder arthroplasty (TSA) has spurred interest in comparing the safety and cost-effectiveness of outpatient TSA in ambulatory surgical centers (ASCs) versus hospital-based centers (HSCs). This study evaluates ASCs and HSCs for medical complications, readmission rates, implant complications, and costs.

METHODS: This retrospective cohort study used the PearlDiver Mariner Database to identify patients undergoing primary TSA in ASCs or HSCs, assessing medical complications, readmissions, implant issues, and costs. ASC patients were matched in a 1:5 ratio to HSC patients by age, sex, region, and Elixhauser Comorbidity Index (ECI). Logistic regression analyzed the impact of ASC versus HSC settings on complications and readmissions, while Welch’s t-tests compared costs. Statistical significance was determined by a P value less than or equal to 0.05.

RESULTS: ASCs showed lower odds of pulmonary embolism (OR = 0.69; P = 0.04), total medical complications (OR = 0.89; P = 0.01), prosthetic joint dislocation (OR = 0.43; P = 0.05), and total implant-related complications (OR = 0.85; P = 0.03), but a higher 90-day readmission rate (OR = 1.22; P < 0.01). ASCs also offered significant cost savings on the day of surgery ($4600 vs. $11,100; P < 0.01) and for 90-day total costs ($6600 vs. $13,500; P < 0.01) compared to HSCs.

CONCLUSION: Outpatient primary TSA in ASCs offers comparable safety with substantially lower costs than HSCs. Despite higher readmission rates, ASCs represent a viable, cost-effective alternative.

PMID:40146416 | DOI:10.1007/s00590-025-04253-0