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The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy

J Neuroinflammation. 2024 Aug 17;21(1):205. doi: 10.1186/s12974-024-03201-9.

ABSTRACT

INTRODUCTION: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia.

METHODS: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA).

RESULTS: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS.

CONCLUSION: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

PMID:39154085 | DOI:10.1186/s12974-024-03201-9

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A CT-based radiomics tumor quality and quantity model to predict early recurrence after radical surgery for colorectal liver metastases

Clin Transl Oncol. 2024 Aug 17. doi: 10.1007/s12094-024-03645-8. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to develop a tumor radiomics quality and quantity model (RQQM) based on preoperative enhanced CT to predict early recurrence after radical surgery for colorectal liver metastases (CRLM).

METHODS: A retrospective analysis was conducted on 282 cases from 3 centers. Clinical risk factors were examined using univariate and multivariate logistic regression (LR) to construct the clinical model. Radiomics features were extracted using the least absolute shrinkage and selection operator (LASSO) for dimensionality reduction. The LR learning algorithm was employed to construct the radiomics model, RQQM (radiomics-TBS), combined model (radiomics-clinical), clinical risk score (CRS) model and tumor burden score (TBS) model. Inter-model comparisons were made using area under the curve (AUC), decision curve analysis (DCA) and calibration curve. Log-rank tests assessed differences in disease-free survival (DFS) and overall survival (OS).

RESULTS: Clinical features screening identified CRS, KRAS/NRAS/BRAF and liver lobe distribution as risk factors. Radiomics model, RQQM, combined model demonstrated higher AUC values compared to CRS and TBS model in training, internal and external validation cohorts (Delong-test P < 0.05). RQQM outperformed the radiomics model, but was slightly inferior to the combined model. Survival curves revealed statistically significant differences in 1-year DFS and 3-year OS for the RQQM (P < 0.001).

CONCLUSIONS: RQQM integrates both “quality” (radiomics) and “quantity” (TBS). The radiomics model is superior to the TBS model and has a greater impact on patient prognosis. In the absence of clinical data, RQQM, relying solely on imaging data, shows an advantage in predicting early recurrence after radical surgery for CRLM.

PMID:39153176 | DOI:10.1007/s12094-024-03645-8

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Multivariate Data Analysis Assisted Mining of Nutri-rich Genotypes from North Eastern Himalayan Germplasm Collection of Perilla (Perilla frutescens L.)

Plant Foods Hum Nutr. 2024 Aug 17. doi: 10.1007/s11130-024-01220-8. Online ahead of print.

ABSTRACT

Understanding the nutritional diversity in Perilla (Perilla frutescens L.) is essential for selecting and developing superior varieties with enhanced nutritional profiles in the North Eastern Himalayan (NEH) region of India. In this study, we assessed the nutritional composition of 45 diverse perilla germplasm collected from five NEH states using standard protocols and advanced analytical techniques. Significant variability was observed in moisture (0.39-11.67%), ash (2.59-7.13%), oil (28.65-74.20%), protein (11.05-23.15%), total soluble sugars (0.34-3.67%), starch (0.01-0.55%), phenols (0.03-0.87%), ferric reducing antioxidant power (0.45-1.36%), palmitic acid (7.06-10.75%), stearic acid (1.96-2.29%), oleic acid (8.11-13.31%), linoleic acid (15.18-22.74%), and linolenic acid (55.47-67.07%). Similarly, significant variability in mineral content (ppm) was also observed for aluminium, calcium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, molybdenum, sodium, nickel, phosphorus, and zinc. Multivariate analyses, including hierarchical clustering analysis (HCA) and principal component analysis (PCA), revealed the enriched nutritional diversity within the germplasm. Correlation analysis indicated significant positive and negative relationships between nutritional parameters, indicating potential biochemical and metabolic interactions present in the perilla seeds. TOPSIS-based ranking identified promising genotypes for functional foods, pharmaceuticals, and nutritional applications. This study provides a first in-depth report of the nutritional composition and diversity of perilla germplasm in the NEH region, thus aiding in the identification of superior varieties for food and nutritional diversification and security.

PMID:39153163 | DOI:10.1007/s11130-024-01220-8

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Evaluation of Proximate Composition, Cooking Quality, and Texture Profile Analysis in Himalayan Landraces of Black Gram (Vigna mungo)

Plant Foods Hum Nutr. 2024 Aug 17. doi: 10.1007/s11130-024-01227-1. Online ahead of print.

ABSTRACT

The black gram is a traditional pulse crop and is a source of different nutritional components. Due to the scientific community’s preference for yield and its components, the area of nutritional composition remains unexplored. Therefore, the evaluation of various quality traits such as proximate composition, cooking quality, texture profile, and association between them is keen important for the identification of the traits influencing the selection of the genotypes. This research aimed at the evaluation of the 25 black gram genotypes for their proximate composition, the effect of different cooking methods (conventional and microwave) on cooking quality parameters, and texture profile analysis. The genotypes were screened on 17 parameters, mean and replicated value of each variable were subjected to statistical analysis. The results for proximate composition showed the range from 11.2-11.7%, 24.24-28.22%, 1.25-1.85%, 3.10-4.45%, 5.35-6.60%, 60.23-64.86% and 368.35-372.75 Kcal/100 g for moisture, protein, fat, dietary fiber, ash, utilizable carbohydrate, and gross energy respectively. Cooking time ranged from 33 to 55.5 min (traditional) to 29.5-48.5 min (microwave), L: B ratio from 1.35 to 1.85, WUR from 1.85 to 2.60, and GSL from 0.25 to 11.30%. TPA’s cohesiveness, gumminess, and chewiness ranged from 0.19 to 1.44 N, 0.14-1.30 N, 0.58-3.67 N, 1.14-10.81 N, and 0.58-5.29; 1.16-10.50 N in traditional and microwave cooking. Chewiness, gumminess, protein, ash, and cooking time were positively correlated. The first seven PCs have ≥ 1 eigenvalues, accounting for 23.30, 18.00, 13.50, 9.50, 7.40, 6.70%, and 6.40% of total variability. Mandi-2, Kinnour-1, Kirmour-1, Kangra-2, Bilaspur-1, Kangra-3, Kullu-1, Kullu-4, Chamba-3, and Chamba-7 to PCs 1-2 contributed the most to diversity, indicating good selection for subsequent upgrading initiatives.

PMID:39153162 | DOI:10.1007/s11130-024-01227-1

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Considerations Around the Inclusion of Children and Young People’s Time in Economic Evaluation: Findings from an International Delphi Study

Pharmacoeconomics. 2024 Aug 17. doi: 10.1007/s40273-024-01411-w. Online ahead of print.

ABSTRACT

BACKGROUND: People’s time is a finite resource and a valuable input that ought to be considered in economic evaluations taking a broad, societal perspective. Yet, evaluations of interventions focusing on children and young people (CYP) rarely account for the opportunity cost of time in this population. As a key reason for this, health economists have pointed to uncertainty around when it is appropriate to include CYP time-related costs in an economic evaluation and highlighted the lack of clear guidance on the topic.

METHODS: With this in mind, we carried out a Delphi study to establish a list of relevant considerations for researchers to utilise whilst making decisions about whether and when to include CYP time in their economic evaluations. Delphi panellists were asked to propose and rate a set of possible considerations and provide additional thoughts on their ratings. Ratings were summarised using descriptive statistics, and text comments were interrogated through thematic analysis.

FINDINGS: A total of 73 panellists across 16 countries completed both rounds of a two-round Delphi study. Panellists’ ratings showed that, when thinking about whether to include displaced CYP time in an economic evaluation, it is very important to consider whether: (1) inclusion would be in line with specified perspective(s) (median score: 9), (2) CYP’s time may already be accounted for in other parts of the evaluation (median score: 8), (3) the amount of forgone time is substantial, either in absolute or relative terms (median score: 7) and (4) inclusion of CYP’s time costs would be of interest to decision-makers (median score: 7). Respondents thought that considerations such as (1) whether inclusion would be of interest to the research community (median score: 6), (2) whether CYP’s time displaced by receiving treatment is ‘school’ or ‘play’ time (median score: 5), and (3) whether CYP’s are old enough for their time to be considered valuable (median score: 5) are moderately important. A range of views was offered to support beliefs and ratings, many of which were underpinned by compelling normative questions.

PMID:39153138 | DOI:10.1007/s40273-024-01411-w

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Report of climacturia and orgasmic disorders after radical prostatectomy in a Brazilian tertiary hospital: shedding light on a neglected condition

Int Urol Nephrol. 2024 Aug 17. doi: 10.1007/s11255-024-04181-8. Online ahead of print.

ABSTRACT

PURPOSE: After radical prostatectomy (RP), it is rarely acknowledged that several sexual dysfunctions can arise. These include issues in the orgasmic domain (e.g., decreased orgasm intensity, dysorgasmia), problems with ejaculation (e.g., absence of ejaculation), the development of penile deformities, and low sexual desire. This article aims to report the occurrence of orgasmic and ejaculatory dysfunction when actively investigated, documenting those rates and characterizing specific features of these conditions following RP.

METHODS: This study has analyzed retrospective data from men who underwent RP and were experiencing erectile dysfunction. During a structured visit, patients were systematically questioned about dysorgasmia, altered orgasmic sensation, climacturia, and arousal incontinence. Continuous variables were analyzed using the Student T or ANOVA tests, while categorical variables were analyzed using Chi-squared or Fisher’s exact tests. The associations were described as odds ratios with precise confidence intervals. All tests were two sided; a p value < 0.05 was considered statistically significant.

RESULTS: Sixty patients were included, out of which 3 (5%) reported dysorgasmia, while 33.3% presented a decrease in orgasm intensity. Climacturia was reported as the most common orgasmic disorder in 40 (66.6%) patients. However, only 14 patients (35%) reported that it frequently occurs, i.e., more than half of the time. Among the patients who reported climacturia, 72.5% classified it as mild losses. Additionally, arousal incontinence (AI) was noted in the study by 19 (26.3%) patients.

CONCLUSION: Our study highlights the importance of discussing orgasmic dysfunctions after RP, which can be frequent and bothersome but are often overlooked in preoperative counseling.

PMID:39153132 | DOI:10.1007/s11255-024-04181-8

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Patterns in use and tolerance of adjuvant neratinib in patients with hormone receptor (HR)-positive, HER2-positive early-stage breast cancer

Breast Cancer Res Treat. 2024 Aug 17. doi: 10.1007/s10549-024-07461-0. Online ahead of print.

ABSTRACT

PURPOSE: One year of neratinib therapy is known to derive a significant invasive disease-free survival (iDFS) benefit in early-stage, hormone receptor-positive (HR +), HER2 + , node-positive breast cancer after trastuzumab-based adjuvant therapy. Limitations to neratinib use include significant gastrointestinal side effects, which often result in treatment discontinuation. In this study, we aimed to identify clinicopathologic features associated with adjuvant neratinib use and factors impacting treatment completion.

METHODS: We performed a retrospective review of patients with early-stage HR + HER2 + breast cancer who were prescribed neratinib from 2017 to 2023 at our institution. We used the electronic medical record to extract information on patient characteristics, clinical features, and treatment information. Patients were identified as high risk based on definitions adapted from the standard high-risk definition in HR + HER2- breast cancer combined with studies correlating high Ki67 or high tumor grade with lower recurrence-free survival. Statistical analysis was performed using two-sided T-tests and chi-square tests.

RESULTS: We identified 62 eligible patients of whom 55% completed 1 year of neratinib and 45% did not. Sixty percent (N = 37) of patients offered neratinib were considered high risk at diagnosis. The most common reason for neratinib discontinuation was inability to tolerate side effects (54%) followed by pill burden (18%). The most common side effect experienced by patients was diarrhea despite anti-diarrheal prophylaxis (56%), followed by rash (8%). Patients who received an up-titration of neratinib were more likely to complete the full course of neratinib when compared to those who did not (76% vs. 40.5% p = 0.013). The median starting dose of those who completed neratinib treatment was 140 vs. 240 mg in those who did not (p = 0.016). Neither group experienced a statistically significant greater likelihood of treatment holds or dose reductions. In terms of outcomes, 10 patients had progression of disease of whom 7 did not complete neratinib treatment (p = 0.169). Interestingly, those 7 patients developed metastatic disease and 57% (N = 4) had central nervous system metastases.

CONCLUSION: Patients are more likely to complete 1 year of adjuvant neratinib with dose up-titration. Dose reductions and interruptions did not affect neratinib adherence in our patient population. Seven patients (11%) in our study developed metastatic disease, all of whom did not complete adjuvant neratinib treatment.

PMID:39153126 | DOI:10.1007/s10549-024-07461-0

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Robot-assisted versus conventional neck dissection: a propensity score matched case-control study on perioperative and oncologic outcomes

J Robot Surg. 2024 Aug 17;18(1):323. doi: 10.1007/s11701-024-02079-2.

ABSTRACT

The widespread acceptance of robotic surgery is extending to oral procedures. The demand for minimally invasive techniques is driving research into the cosmetic and oncologic benefits of robotic neck surgery. This study used propensity score matching to analyze the clinical course and postoperative outcomes of robot-assisted neck dissections for oncologic efficacy and surgical safety. Between May 2020 and April 2024, 200 OSCC patients underwent surgery and 42 were excluded. The cohort included 158 patients, 128 of whom underwent unilateral neck dissection and 30 of whom underwent bilateral neck dissection. Robotic-assisted neck dissection (RAND) was performed in 36 patients while conventional transcervical neck dissection (CTND) was performed in 122 patients. Data analysis included several factors, including lymph node retrieval and perioperative outcomes, with 1:1 propensity score matching to ensure fairness. Each of the 39 neck specimens with 36 patients was selected. The CTND group was 8 years older overall than the RAND group, but otherwise similar in terms of primary site and clinical stage. The RAND group had a 55-min longer operative time and 140 cc more hemovac drainage than the CTND group, but the hospital stay and intensive care unit duration were the same, and the number of lymph nodes retrieved was the same. Survival rates also showed no difference across all stages. This shows that RAND is in no way inferior to CTND in terms of perioperative or oncologic outcomes, and demonstrates the safety of robot-assisted surgery, even in patients who require flaps or in patients with advanced stages.

PMID:39153111 | DOI:10.1007/s11701-024-02079-2

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A retrospective study of prognostic factors and prostate-specific antigen dynamics in Japanese patients with metastatic hormone-sensitive prostate cancer who received combined androgen blockade therapy with bicalutamide

Int J Clin Oncol. 2024 Aug 17. doi: 10.1007/s10147-024-02597-x. Online ahead of print.

ABSTRACT

BACKGROUND: This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan.

METHODS: The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS.

RESULTS: The median observation period was 46.4 months, and the median age of patients at diagnosis was 71 years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29 months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2 ng/mL in a median time of 4.7 months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9 months.

CONCLUSION: These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.

PMID:39153094 | DOI:10.1007/s10147-024-02597-x

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Distinguishing glioblastoma progression from treatment-related changes using DTI directionality growth analysis

Neuroradiology. 2024 Aug 17. doi: 10.1007/s00234-024-03450-8. Online ahead of print.

ABSTRACT

BACKGROUND: It is difficult to distinguish between tumor progression (TP) and treatment-related abnormalities (TRA) in treated glioblastoma patients via conventional MRI, but this distinction is crucial for treatment decision making. Glioblastoma is known to exhibit an invasive growth pattern along white matter architecture and vasculature. This study quantified lesion development patterns in treated glioblastoma lesions and their relation to white matter microstructure to distinguish TP from TRA.

MATERIALS AND METHODS: Glioblastoma patients with confirmed TP or TRA with T1-weighted contrast-enhanced and DTI MR scans from two posttreatment follow-up timepoints were reviewed. The contrast-enhancing regions were segmented, and the regions were coregistered to the DTI data. Lesion increase vectors were categorized into two groups: parallel (0-20 degrees) and perpendicular (70-90 degrees) to white matter. FA-values were also extracted. To test for a statistically significant difference between the TP and TRA groups, a Mann‒Whitney U test was performed.

RESULTS: Of 73 glioblastoma patients, fifteen were diagnosed with TRA, whereas 58 patients suffered TP. TP had a 25.8% (95% CI 24.1%-27.6%) increase in parallel lesions, and TRA had a 25.4% (95% CI 20.9%-29.9%) increase in parallel lesions. The perpendicular increase was 14.7% for TP (95% CI 13.0%-16.4%) and 18.0% (95% CI 13.5%-22.5%) for TRA. These results were not significantly different (p = 0.978). FA value for TP showed to be 0.248 (SD = 0.054) and for TRA it was 0.231 (SD = 0.075), showing no statistically significant difference (p = 0.121).

CONCLUSIONS: Based on our results, quantifying posttreatment contrast-enhancing lesion development directionality with DTI in glioblastoma patients does not appear to effectively distinguish between TP and TRA.

PMID:39153088 | DOI:10.1007/s00234-024-03450-8