Nevin Manimala

Int Forum Allergy Rhinol. 2025 Oct 26. doi: 10.1002/alr.70058. Online ahead of print.

ABSTRACT

BACKGROUND: Botulinum toxin type A is a potent neurotoxin and was first approved for use in 1989; since there has been a surge in its uses. The latest international trend is the unapproved use of botulinum toxin for allergic and nonallergic rhinitis, being advertised as “Haytox.”

METHODS: A single-group open-label non-randomized Phase 1 clinical trial was completed. Rhinitis and nonallergic rhinitis were confirmed via formalized examination and testing with total IgE and radioallergosorbent test (RAST). Participants received 40 units of botulinum toxin type A, administered topically intranasally, 20 units per nostril, using the LMA MAD Nasal Intranasal Mucosal Atomization Device. Safety of the intervention was assessed with adverse event tracking logs. Symptom scores were used to assess symptom reduction, including total nasal symptom score (TNSS), visual analog scale (VAS) measurements at Weeks 0, 2, 4, and 12. In addition, peak nasal inspiratory flow (PNIF) was measured at Weeks 0 and 4, with the minimum clinically important difference (MCID) being used to demonstrate any clinically significant change in the TNSS score.

RESULTS: A TOTAL OF: 15 participants enrolled, of which 14 participants received treatment, with no serious adverse or related adverse events reported. There was a statistically and clinically significant reduction in TNSS and a statistically significant reduction in VAS from Weeks 0 to 12.

CONCLUSION: In this Phase 1 trial, topical application of botulinum toxin via spray was shown to be safe, without any significant adverse events. It reduced the TNSS and VAS across the cohort. However, the treatment efficacy should be taken in context as there was no blinding, alternative dosing, or comparison against placebo or recognized active treatment options. This safety data should embolden future research trials.

TRIAL REGISTRATION: TGA number: CT-2024-CTN-02905-1; ANZCTR number: ACTRN12624000772549.

PMID:41139237 | DOI:10.1002/alr.70058

Clin Transplant. 2025 Nov;39(11):e70359. doi: 10.1111/ctr.70359.

ABSTRACT

Our study includes 103 patients aged between 51 and 60 years who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling donors (MSDs) (n = 36), haploidentical donors (HIDs) (n = 56), and unrelated donors (URDs) (n = 11). Multivariate analysis exploring the relationship between risk factors and survival confirmed that survival outcomes were only independently impacted by Eastern Cooperative Oncology Group (ECOG) score (ECOG scores ≥2 vs. ECOG scores of 0-1, overall survival [OS] HR: 2.91 [95% CI 1.35-6.27], p = 0.006; failure free survival [FFS] HR: 2.93 [95% CI 1.33-5.88], p = 0.006; graft-versus-host disease-free/relapse-free survival [GRFS] HR: 2.80 [95% CI 1.33-5.88], p = 0.006), while age, specific donor source and hematopoietic cell transplantation-comorbidity index (HCT-CI) score did not significantly influence prognosis in this age group. After applying propensity score-matching (PSM) to balance the pretransplant clinical factors between patients with ECOG scores 0-1 cohort and those with ECOG scores ≥2 cohort, poor performance status remains a negative factor for survival outcomes (OS p = 0.04; FFS p = 0.03; GRFS p = 0.03). Further analysis in subgroup patients with HCT-CI scores 0-1 found the retained significance of ECOG score in predicting inferior survival. In conclusion, our results indicate good long-term results of allo-HSCT in elderly SAA adults regardless of donor type. Higher ECOG score is associated with poor post-transplant outcomes and has to be taken into account for patients, even at a low-risk comorbidly burden.

PMID:41139235 | DOI:10.1111/ctr.70359

Int J Neurosci. 2025 Oct 26:1-14. doi: 10.1080/00207454.2025.2580332. Online ahead of print.

ABSTRACT

Objective This study employs the Mendelian randomization (MR) approach to investigate the causal relationships among immune cells, cluster headache (CH), and potential mediation by serum metabolites. Methods Using genome-wide association study (GWAS) data, MR analyses were conducted on 731 immune cell phenotypes, 1400 serum metabolites, and CH. The inverse variance weighting (IVW) method was employed as the primary analytical approach, supplemented by MR-Egger and weighted median analyses. Stability of results was assessed using Cochran’s Q and other statistical tests. Results The analysis identified a negative causal relationship between CD39⁺ CD4⁺ %T cells and CH, supported by sensitivity analyses. Reverse MR analysis showed no effect of CH on CD39⁺ CD4⁺ T cells, suggesting a unidirectional role of these cells in reducing CH risk. Further mediation MR analysis indicated that CD39⁺ CD4⁺ T cells may influence CH risk through the regulation of either the adenosine 5′-diphosphate (ADP) to N-acetylneuraminate ratio or the choline phosphate to phosphoethanolamine ratio, with mediation effect ratios of 12.4% and 12.5%, respectively. Conclusion CD39⁺ CD4⁺ T cells may reduce CH risk by increasing the adenosine 5′-diphosphate (ADP) to N-acetylneuraminate ratio or the choline phosphate to phosphoethanolamine ratio. These findings provide novel insights into potential targets for the prevention and treatment of CH.

PMID:41139232 | DOI:10.1080/00207454.2025.2580332

Cancer. 2025 Nov 1;131(21):e70140. doi: 10.1002/cncr.70140.

ABSTRACT

BACKGROUND: In acute myeloid leukemia (AML), measurable residual disease (MRD) assessment is essential for predicting relapse and guiding therapy decision-making. Nucleophosmin 1 (NPM1) mutations are reliable MRD markers but apply to only ∼30% of patients with AML. Wilms tumor 1 (WT1) expression monitoring is applicable to a broader population but the European LeukemiaNet (ELN) threshold of 50 WT1 copies per 10⁴ ABL copies (0.5%) may be too high, which limits sensitivity.

METHODS: With WT1 expression data from 100 healthy controls, this study established a revised WT1 threshold of seven copies per 10⁴ ABL copies (0.07%). Its performance was retrospectively validated against NPM1 in 308 paired follow-up samples from 63 patients with NPM1-mutated AML, and against the core binding factor (CBF) β-MYH11 fusion transcripts in 83 samples from 12 patients. Statistical analyses included concordance, sensitivity/specificity, survival estimates, and model comparison with the Akaike information criterion.

RESULTS: Compared to the ELN cutoff, the revised threshold showed higher concordance with NPM1 (78.6% vs. 73%) and sensitivity (54% vs. 24%; p < .0001) and acceptable specificity (91% vs. 98%; p = .002). In survival analyses, the seven-copy cutoff demonstrated stronger prognostic value than the ELN threshold, particularly after consolidation therapy. In the CBFB::MYH11 cohort, the two thresholds showed similar concordance but WT1 positivity with the revised cutoff preceded relapse in selected patients.

CONCLUSIONS: In AML, the revised WT1 threshold of seven copies per 10⁴ ABL copies enhanced MRD sensitivity while maintaining specificity, improving concordance with NPM1, and showing prognostic relevance. These findings support the clinical value of locally optimized WT1 thresholds, and highlight the need for prospective multicenter validation and harmonization of WT1-based MRD monitoring.

PMID:41139231 | DOI:10.1002/cncr.70140

Cancer. 2025 Nov 1;131(21):e70133. doi: 10.1002/cncr.70133.

ABSTRACT

BACKGROUND: The high costs of cancer care may lead to medical debt for patients and families. This study examined the association of county-level medical debt and timely treatment initiation among individuals newly diagnosed with cancer.

METHODS: Individuals aged 19 years and older who were newly diagnosed with acute leukemias, diffuse large B-cell lymphoma, Hodgkin lymphoma, female breast cancer, colorectal cancer, and lung cancer with consecutive enrollment in the same insurance type from the month of diagnosis through 90 days afterward were identified from the 2012-2021 Colorado Central Cancer Registry linked to the Colorado All-Payer Claims Database with information about county-level medical debt from the Urban Institute (N = 35,789). The exposure was the county-level share of adults with medical debt in collections, categorized in four quartiles (Q1-Q4). The outcome was timely treatment initiation-defined as the receipt of any cancer-directed treatment within 90 days after cancer diagnosis. The association of county-level medical debt and time to treatment initiation was examined by using multivariable Cox models.

RESULTS: Higher county-level medical debt was associated with lower likelihood of timely treatment initiation for all selected cancers combined (Q4 [counties with the highest medical debt rate; n = 8652] vs. Q1 [counties with the lowest medical debt rate; n = 9042]: hazard ratio [HR], 0.916; 95% confidence interval [CI], 0.871-0.963; p for trend = .001), for female breast cancer (Q4 vs. Q1: HR, 0.910; 95% CI, 0.847-0.978; p for trend = .011), and among individuals aged 19-64 years with private health maintenance organization plans (Q4 vs. Q1: HR, 0.790; 95% CI, 0.699-0.893; p for trend = .002) or Medicaid coverage (Q4 vs. Q1: HR, 0.869; 95% CI, 0.786-0.960; p for trend = .013).

CONCLUSIONS: Policies aimed at preventing and alleviating medical debt could be effective strategies for improving access to timely treatment.

PMID:41139228 | DOI:10.1002/cncr.70133

Med Sci Monit. 2025 Oct 26;31:e950416. doi: 10.12659/MSM.950416.

ABSTRACT

BACKGROUND Foot biomechanics significantly influence weightlifting performance and injury prevention. Previous studies have indicated that intensive weightlifting impacts foot structure; however, comprehensive investigations into foot characteristics among weightlifters remain scarce. This study aims to compare the foot arch index (FAI), plantar load distribution (PLD), center of pressure (CoP), and rearfoot posture in 24 elite male weightlifters (77 kg and 85 kg classes) and 32 age- and body mass index-matched healthy men. MATERIAL AND METHODS A cross-sectional study was conducted involving 24 elite male weightlifters and 32 healthy controls. The JC Mat optical plantar pressure analyzer was used to assess FAI, PLD, and CoP during static stances, while rearfoot angles were measured through postural alignment analysis. Statistical comparisons were performed using independent samples t test or the Mann-Whitney U test. RESULTS Weightlifters exhibited significantly higher FAI values (P<0.05) and greater rearfoot valgus angles (P<0.01) for both feet, compared with the controls. Their PLD was predominantly concentrated at the medial longitudinal arches (P<0.05), medial heels (P<0.01), and lateral metatarsals (P<0.05), as well as the left medial metatarsals (P<0.05). CoP distribution was symmetrical across both feet. CONCLUSIONS Elite weightlifters in this study developed low-arched pronated foot postures, characterized by medial-dominant PLD patterns and bilateral symmetrical CoP. These biomechanical adaptations may enhance stability and balance during weightlifting, whereas increased rearfoot valgus may predispose athletes to lower limb injuries. Systematic assessment of foot biomechanics is essential for optimizing performance, preventing injuries, and designing weightlifting-specific footwear.

PMID:41139217 | DOI:10.12659/MSM.950416

BMC Cancer. 2025 Oct 25;25(1):1645. doi: 10.1186/s12885-025-14809-2.

ABSTRACT

BACKGROUND: Prostate cancer is the most prevalent cancer among men within the U.S. and globally, with rising incidence, including advanced-staged disease. Risk factors for aggressive prostate cancer are not well defined. This systematic review and meta-analysis provide an overview of the relationship between cardiometabolic diseases (diabetes, dyslipidemia, obesity, and hypertension) and aggressive prostate cancer.

METHODS: Aggressive prostate cancer was defined as disease that has spread or is at high risk of spreading: high-risk or very high-risk localized (T3-T4, Grade Group 4-5), node-positive (N1), or metastatic (M1). Using PRISMA guidelines, a total of 4,830 publications revealed 25 cohort studies of over 974,000 men. Following the systematic review of these prospective studies of men with prostate cancer, R was utilized to run a random effects model, yielding hazard ratios with 95% confidence intervals and generating forest plots with measures of heterogeneity.

RESULTS: Examination of these studies revealed that a positive association exists. Diabetes was associated with a significantly increased risk of aggressive prostate cancer (HR = 1.18; 95% CI: 1.07-1.30; p = 0.0008). Obesity also showed a significant association (HR = 1.15; 95% CI: 1.06-1.24; p = 0.0006), as did hypertension, though to a lesser degree (HR = 1.07; 95% CI: 1.00-1.14; p = 0.04). Dyslipidemia was not significantly associated with aggressive prostate cancer (HR = 1.03; 95% CI: 0.98-1.03; p = 0.26).

DISCUSSION: Three of the four cardiometabolic disease components (diabetes, obesity and hypertension) were shown to have statistical significance and offered intriguing evidence on their potential associations with aggressive prostate cancer. Dyslipidemia’s association was not statistically significant, which could be attributed to variations in methods of assessment and differing mechanistic effects. High heterogeneity and limited study availability remain key limitations.

CONCLUSION: If such associations between cardiometabolic diseases and prostate cancer aggressiveness are shown to be cause and effect, such controllable and treatable conditions can allow oncologists to work alongside primary care physicians to improve patient outcomes and reduce the incidence of aggressive disease. Through the promotion of lifestyle modifications, tighter cardiometabolic control, and targeted interventions, public health efforts might improve prostate cancer outcomes.

PMID:41139205 | DOI:10.1186/s12885-025-14809-2

Ann Surg Oncol. 2025 Oct 25. doi: 10.1245/s10434-025-18513-0. Online ahead of print.

ABSTRACT

BACKGROUND: Prognostication tools offer a way to combine diverse information and inform personalized survival predictions for patients and their providers. A review of tools aimed at prognostication for patients with esophagus and gastroesophageal junction (GEJ) cancers undergoing surgery did not identify many high-quality tools that may be used.

METHODS: This study developed and externally validated a prognostic model to estimate the probability of dying within 3 years of surgery for patients with resected esophageal or GEJ cancer diagnosed between 2004 and 2016, followed to 2020. We used population-based administrative health and pathology data in Ontario (development) and Manitoba (external validation) from cancer registries, physician billing data, and hospitalization records. Predictor variables included patient (e.g., age, sex), disease (tumor stage, lymph node status), treatment (e.g., extent of surgery, receipt of radiation), and pathology factors (e.g., lymphovascular invasion). Bootstrapped calibration-in-the-large and time-varying area under the curve (AUC) statistics were estimated.

RESULTS: Model development included 2124 patients from Ontario. External model validation included 318 patients from Manitoba. Internal validation demonstrated a calibration plot slope of 1.02, intercept of – 0.01, and AUC of 0.77. In comparison, the external validation reported a calibration plot slope of 1.11, intercept of 0.005, and AUC of 0.73. These results were robust across patient characteristics (e.g., age, sex, income), disease histology, and primary tumor location.

CONCLUSION: Our model demonstrated accurate prognostic capability and may be suitable for application in real-world clinical care. Development of a web-based interface and supporting documentation for communicating risk to personalize prognosis for patients or facilitate shared decision-making is under way.

PMID:41139180 | DOI:10.1245/s10434-025-18513-0

Eur Radiol. 2025 Oct 25. doi: 10.1007/s00330-025-12091-1. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop a personalized risk stratification nomogram, integrating clinicopathological, sonographic, and mammographic features, to identify high-risk patients who may benefit from postmastectomy radiotherapy (PMRT).

MATERIALS AND METHODS: A retrospective analysis was conducted on 408 patients from Medical Center 1 (January 2011 to June 2019) and 190 patients from Medical Center 2 (January 2017 to June 2019) with pathologically staged pT1-2N1M0 breast cancer following mastectomy, with preoperative mammography (MG) and ultrasound (US) imaging. After propensity score matching (PSM), the multimodal nomogram was developed using univariate and multivariate Cox regression analyses.

RESULTS: With multivariate analysis, independent risk factors were identified, including age, pathologic T stage, positive axillary lymph nodes, lymphovascular invasion, microcalcifications, and vascularity on US, architectural distortion, and suspicious calcifications on MG (all p < 0.05). The C-index for the multimodal nomogram was 0.816 (95% CI: 0.774-0.859) in the training and 0.846 (95% CI: 0.772-0.920) in the external validation cohort, demonstrating superior prognostic accuracy, discriminative ability, and clinical applicability than clinicopathological and imaging-only models. Risk stratification using this nomogram showed that PMRT significantly improved RFS in the high-risk group (training cohort: HR = 0.392; external validation cohort: HR = 0.358, both p < 0.05), while patients in the low-risk group did not derive benefit from PMRT (training cohort: HR = 0.173; external validation cohort: HR = 0, both p > 0.05).

CONCLUSION: This multimodal nomogram served as a clinical decision-support tool for clinicians to assess the risk-benefit balance of PMRT and had potential clinical application to guide further personalized adjuvant therapy for women with pT1-2N1M0 breast cancer.

KEY POINTS: Question Can the multimodal nomogram integrating clinicopathological, ultrasonic, and mammographic parameters identify high-risk pT1-2N1M0 patients who may benefit from postmastectomy radiation therapy? Findings By effectively risk-stratifying, the nomogram identified high-risk patients who derived significant benefit from PMRT while distinguishing low-risk patients who could potentially avoid unnecessary treatment. Clinical relevance The multimodal nomogram served as a clinical decision-support tool for clinicians to optimize personalized adjuvant therapeutic approaches and improve survival outcomes for patients with pT1-2N1M0 breast cancer.

PMID:41139173 | DOI:10.1007/s00330-025-12091-1

Eur Radiol. 2025 Oct 25. doi: 10.1007/s00330-025-12084-0. Online ahead of print.

ABSTRACT

OBJECTIVES: To identify MR imaging features of replacement histopathological growth patterns (rHGPs) of colorectal liver metastases (CRLMs) distinguishable from those of desmoplastic HGPs (dHGPs) and explore their relationships with prognosis.

MATERIALS AND METHODS: Seventy-nine patients with 104 CRLMs who underwent gadoxetic acid-enhanced MR followed by partial hepatectomy were included as a derivation cohort. The CRLMs were rHGPs or dHGPs. MR images of the CRLMs, focusing on the tumor and segmented tumor-liver interface zones (peritumoral area), were quantitatively evaluated and statistically analyzed. The statistically significant findings from the derivation cohort were validated in an independent external cohort.

RESULTS: In the derivation cohort, there were no significant differences among tumor sizes, contrast-to-noise ratios (CNRs), or enhancement ratios (ERs) of the tumors with rHGPs (n = 43) and dHGPs (n = 61) (p > 0.05). The peritumoral area was only identified during the arterial and portal phases. The thickness, CNR, and ER of the peritumoral area on the arterial and portal phase images of the rHGP group were significantly larger than those of the dHGP group (p < 0.05). The area under the ROC curve for predicting rHGP based on CNR during the arterial phase was the highest at 0.920. The peritumoral area CNR during the arterial phase was associated with a poor prognosis (p < 0.05). The usefulness of these parameters was confirmed in the validation cohort (p < 0.05).

CONCLUSION: The CRLMs with rHGPs had thicker peritumoral areas with higher CNR and ER during the arterial phase, and the CNR during the arterial phase was an independent indicator of poor prognosis.

KEY POINTS: Question Can MR imaging characteristics predict histopathological growth patterns (HGPs) of colorectal liver metastases (CRLMs), which have been established as independent predictors of prognosis? Findings CRLMs with replacement HGPs showed thicker, more enhanced peritumoral areas with higher contrast ratios than those with desmoplastic HGPs during the arterial phase. Clinical relevance Increased thickness and predominant enhancement of the peritumoral area during the arterial phase may serve as predictive markers for identifying replacement HGPs in CRLMs, which are linked to a poorer prognosis, in contrast to desmoplastic HGPs.

PMID:41139172 | DOI:10.1007/s00330-025-12084-0