Search Results (375)

Background: Biological aging influences cancer outcomes, but its changes during chemotherapy and impact on chemotoxicity in colorectal cancer (CRC) remain underinvestigated. We examined (1) trajectories of biological aging (using Levine Phenotypic Age) during six months of chemotherapy, (2) sociodemographic and clinical risk factors for biological aging, and (3) links between biological aging and chemotoxicity. Methods: Using data from electronic health records (2013–2019) from 1129 adult CRC patients, we computed biological aging (raw Levine Phenotypic Age and its age acceleration [Levine Phenotypic Age–chronological age]) from routine blood tests (e.g., complete blood counts, hepatorenal/inflammatory markers). Chemotoxicity was identified primarily via International Classification of Diseases (ICD-9 and -10) codes. Results: Chemotherapy accelerated biological aging over time. Biological aging at baseline and changes over time predicted chemotoxicity. However, changes in biological aging over time showed stronger associations than baseline biological aging. Advanced cancer stages, higher comorbidity burden, and socioeconomic disadvantage (especially area-level deprivation) were associated with accelerated biological aging at baseline and over time. Biological aging occurred across both young and older adults. Conclusions: Levine Phenotypic Age, computed from routine blood tests in EHRs, offers a feasible clinical tool for aging-related chemotoxicity risk stratification. Validation in diverse cohorts and the development of predictive models are needed. Full article

The aim of this study was to compare the forces and moments exerted by thermoformed aligners (TFMs) and direct printed aligners (DPAs) on the maxillary left central incisor (21) and adjacent teeth (11, 22) during lingual bodily movement of tooth 21. Methods: An in vitro setup was used to quantify forces and moments on three incisors, which were segmented and fixed onto multi-axis force/moment transducers. TFM were fabricated using 0.76 mm-thick single-layer PET-G foils (ATMOS; American Orthodontics, Sheboygan, WI, USA) and multi-layer TPU foils (Zendura FLX; Bay Materials LLC, Fremont, CA, USA). DPAs were fabricated using TC-85 photopolymer resin (Graphy Inc., Seoul, Republic of Korea). Tooth 21 was planned for bodily displacement by 0.25 mm and 0.50 mm, and six force and moment components were measured on it and the adjacent teeth. Results: TC-85 generated lower forces and moments with fewer unintended forces and moments on the three teeth. TC-85 exerted 0.99 N and 1.53 N of mean lingual force on tooth 21 for 0.25 mm and 0.50 mm activations, respectively; ATMOS produced 3.82 N and 7.70 N, and Zendura FLX produced 3.00 N and 8.23 N of mean lingual force for the same activations, respectively. Bodily movement could not be achieved. Conclusions: The force systems generated by clear aligners are complex and unpredictable. DPA using TC-85 produced lower, more physiological force levels with fewer side effects, which may increase the predictability of tooth movement and enhance treatment outcome. The force levels generated by TFM were considered excessive and not physiologically compatible. Full article

This paper addresses the numerical evaluation of highly oscillatory integrals by developing a spectral Galerkin–Levin approach that efficiently solves Levin’s differential equation formulation for such integrals. The method employs Legendre polynomials as basis functions to approximate the solution, leveraging their orthogonality and favorable numerical properties. A key finding is that the Galerkin–Levin formulation is invariant with respect to the choice of polynomial basis—be it monomials or classical orthogonal polynomials—although the use of Legendre polynomials leads to a more straightforward derivation of practical quadrature rules. Building on this, this paper derives a simple and efficient numerical quadrature for both scalar and matrix-valued highly oscillatory integrals. The proposed approach is computationally stable and well-conditioned, overcoming the limitations of collocation-based methods. Several numerical examples validate the method’s high accuracy, stability, and computational efficiency. Full article

Discontinuous fibers are commonly added to matrix materials in additive manufacturing to enhance properties, but such benefits may be constrained by print and fiber orientation. The additive processes of forming rasters and layers in powder bed fusion inherently cause anisotropy in printed parts. Many print parameters, such as laser, temperature, and hatch pattern, influence the anisotropy of tensile properties. This study characterizes fiber orientation attributed to recoating non-encapsulated fibers and the resulting anisotropic tensile properties. Tensile and fracture properties of polyamide 12 reinforced with 0%, 2.5%, 5%, and 10% discontinuous carbon fibers by volume were characterized in two primary print/tensile loading orientations: tensile loading parallel to the recoater (“horizontal specimens”) and tensile load along the build axis (“vertical specimens”). Density and fractographic analysis indicate a homogeneous mixture with low porosity and primary fiber orientation along the recoating direction for both print orientations. Neat specimens (zero fiber) loaded in either direction have similar tensile properties. However, fiber-reinforced vertical specimens have significantly reduced consistency and tensile strength as fiber content increased, while the opposite is true for horizontal specimens. These datasets and results provide a mechanism to tune material properties and improve the functionality of selectively laser-sintered fiber-reinforced parts through print orientation selection. These datasets could be used to customize functionally graded parts with multi-material selective laser-sintering manufacturing. Full article

Background/Objectives: Children with cancer suffer due to the underlying disease and prescribed cancer-directed therapies, and non-pharmacologic modalities may offer improved symptom control without additional medications. We sought to elicit knowledge, attitudes, and beliefs of Pediatric Hematology Oncology (PHO) providers surrounding the incorporation of acupuncture for symptom management for their patients. Methods: A cross-sectional survey instrument was created, formatted, and delivered to physicians and advanced practice providers (APPs) at a single US pediatric cancer center. Survey responses were summarized by descriptive statistics. Results: A total of 78 PHO clinicians participated (response rate 29%). Most participants were interested in learning more about acupuncture (n = 42, 56.0%), yet rarely (n = 17, 22.7%) or never (n = 46, 61.3%) recommend acupuncture to patients. Most (n = 51, 73.9%) noted that they would support institutional development of an acupuncture program. Over half (n = 37, 52.2%) indicated their threshold for minimum hematologic indices for acupuncture includes a platelet count greater than 20,000 and absolute neutrophil count (ANC) greater than 500 (n = 37, 54.4%). Approximately two-thirds (n = 52, 66.7%) of participants noted that acupuncture could improve their patient’s quality of life, and most (n = 46, 67.6%) were not worried about harm. Conclusions: Acupuncture for symptom management is an evidenced-based, guideline-concordant recommendation for adults with cancer, but robust data in the pediatric oncology population are lacking. PHO providers do not routinely recommend acupuncture for patients but note that it may improve quality of life. Given their high symptom burden, rigorous studies of non-pharmacologic strategies for pediatric symptom management are vital. Acupuncture should be examined as a potential beneficial adjunct. Full article

B-cell maturation antigen (BCMA)-targeted therapies including both chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies (BsAbs), have revolutionized the treatment landscape for relapsed/refractory multiple myeloma (MM), offering both deep and durable responses, even in heavily pretreated patients. Despite these advances, most patients ultimately experience relapse. This is likely related to the development of resistance mechanisms that limit the long-term efficacy and durability of BCMA-targeted approaches. In this review, we examine the current landscape of BCMA-directed therapies, including Idecabtagene Vileucel, Ciltacabtagene Autoleucel, Teclistamab, and Elranatamab and explore the multifactorial mechanisms driving resistance. These mechanisms include tumor-intrinsic factors, host-related and tumor-extrinsic factors, and factors related to the tumor-microenvironment itself. We outline emerging strategies to overcome resistance, such as dual-targeting therapies, γ-secretase inhibitors, immune-checkpoint blockade, armored CAR T constructs, and novel combination regimens. Additionally, we discuss the role of therapy sequencing, emphasizing how prior exposure to BsAbs or CAR T-cell therapies may influence the efficacy of subsequent treatments. A deeper understanding of resistance biology, supported by integrated immune and genomic profiling, is essential to optimizing therapeutic durability and ultimately improve patient outcomes for patients with MM. Full article

Hepatitis C virus (HCV) infection is a major public health concern, with more than 58 million people chronically infected worldwide. The management of HCV, once the domain of specialists only, has been revolutionized by the advent of direct-acting antiviral therapies. To reduce the burden of HCV in the United States (US), emphasis is now being placed on the involvement of primary care physicians in the management of HCV patients. Inclusion of more primary care providers in the HCV diagnosis and treatment initiatives can assist in achieving the goal of HCV elimination, especially in the medically underserved areas. To actively engage in the management of HCV, primary care providers must understand its epidemiology, risk factors, natural history, current treatment regimen, and potential complications. This manuscript reviews these key areas, along with presenting the cost-effectiveness of treatment and evidence-based guidelines for follow-up care in adults with chronic HCV infection who have undergone HCV treatment. Equipped with this foundational knowledge about HCV management, primary care physicians can play a vital role in eliminating HCV. Full article

Background/Objectives: An accurate evaluation of variant actionability is essential in cancer management. In Von Hippel–Lindau Syndrome (VHL), the interpretation of the germline variants is confounded by the presence of non-syndromic component tumors, such as clear cell renal cell carcinoma (ccRCC), hemangioblastoma, pheochromocytoma, and neuroendocrine tumors. These tumors frequently occur sporadically, without any association with VHL syndrome. The presence of these tumors in a patient with a germline VHL variant could lead to inaccurate attribution of these tumors to the germline variant and VHL syndrome. In our previous INT²GRATE (INTegrated INTerpretation of GeRmline And Tumor gEnomes) programs, we demonstrated that integrating tumor-derived and germline evidence offers a comprehensive approach for the accurate assessment of the germline variants in cancer syndromes. Methods/Results: Here, we present a novel INT²GRATE variant evidence framework (VEF) for evaluating the clinical actionability of the germline variants in VHL syndrome, offering an integrated approach that incorporates both constitutional and tumor data. We analyzed 2672 variants in the VHL gene and their associated tumors and clinical evidence to effectively distinguish between constitutional, sporadic, VHL differentials, and VHL allelic genetic conditions. The germline INT²GRATE variants, along with their comprehensive associated evidence, were made accessible in the first open-access INT²GRATE Variant data Portal. Conclusions: This novel and integrated approach to variant assessment and data sharing in hereditary cancer syndromes is essential in the clinical evaluation of genomic variants, advancing precision oncology, and improving patient care. Full article

Background/Objectives: The presence of Ehlers–Danlos Syndromes (EDSs) has significant effects on overall health and results in varying levels of pain and disability. The effects of sleep are not well documented in this population. The purpose of this study is to report the sleep characteristics of people with EDS. Methods: An electronic survey regarding sleep characteristics was created and distributed through the EDS website. Results: Sleep disturbance is common in people with EDS, with 65.3% of respondents sleeping fewer than 8 h and 26.2% averaging fewer than 6 h. Those who slept fewer than 6 h reported more days of poor mental and physical health days. Sleep aids were commonly used with 41.40% of patients regularly taking prescription medication to get to sleep. Sleep latency of greater than 30 min was also found in 67.5% of subjects. Conclusions: The results demonstrate an association between people with EDS and poorer sleep duration, increased sleep latency, and increased use of sleep aids including prescription sleep medication compared to the general population. While more research needs to be completed in this area, sleep may be an important aspect to address in the management of EDS. Full article

Purpose: Intramedullary spinal cord tumors (IMSCTs) account for 2–8% of all primary CNS tumors, with ependymal tumors astrocytic tumors and hemangioblastoma being the most prevalent. Due to scarcity of large-scale studies, we aim to provide insights into the long-term neurological and functional outcomes following their resection. Methods: A single-center study where retrospective review of all patients’ medical records with IMSCT resection between October 2001 and March 2023 was conducted. Data on demographic characteristics, clinical presentations, and surgical outcomes were collected and analyzed. Results: This study included 253 patients (57.7% male) with a mean age of 36.2 ± 19. The cohort comprised ependymal tumors (45.1%), astrocytic tumors (35.6%), hemangioblastoma (11.1%), and miscellaneous tumors (n = 21; 8.3%). Differences were observed in age at surgery (p < 0.001) and mortality (p = 0.002) across tumor types. Gross total resection was more frequently achieved in hemangioblastoma (96.4%) and ependymal tumors (82.5%) compared to astrocytic tumors (55.6%) (p < 0.001). Long-term postoperative improvements were significant, with reductions in numbness from 74.7% to 52.2%, pain from 42.2% to 25.7%, and bladder incontinence from 23.7% to 11.6%, particularly in ependymal tumors and astrocytic tumors. Kaplan–Meier analysis showed that patients with ependymal tumors had the highest overall survival rates (94.8% at 5 years, 86.7% at 10 years, 76.3% at 15 years, and 65.4% at 20 years) compared to hemangioblastoma (88.7% at 5 and 10 years, and 53.2% at 15 years) and astrocytic tumors (67.8% at 5 years, 58.1% at 10 and 15 years) (p = 0.001). Conclusions: This study highlights the differences in survival and long-term functional outcomes among patients with IMSCTs based on tumor histology and grade. Full article

Background: Dilated Cardiomyopathy (DCM) is one of the leading causes of non-ischemic cardiomyopathy in the United States (US). The aim of our study is to analyze the general trends in DCM admissions between 2016 and 2021, and analyze social and healthcare disparities in terms of treatments and outcomes. Methods: National Inpatient Sample (NIS) data for the years 2016 to 2021 were used for the analysis. General population trends were analyzed. Normality of data distribution was tested using the Kolmogorov–Smirnov test and homogeneity was assessed using Levine’s test. One-way ANOVA was used after confirmation of normality of distribution to analyze social and healthcare disparities. Subgroup analysis was conducted, with the paired t-test for continuous variables and Fischer’s exact t-test for categorical variables to analyze statistical differences. Multivariate regression analysis was conducted to analyze the association of factors that were significant in the one-way ANOVA and paired t/chi square tests. A two-tailed p-value < 0.05 was used to determine statistical significance. Results: A total of 5262 admissions for DCM were observed between 2016 and 2021. A general declining trend was observed in the total number of DCM admissions, with a 33.51% decrease in total admissions in 2021 compared to 2016. All-cause in-hospital mortality remained stable across the years (between 3.5% and 4.5%). A total of 15.3% of admissions had CRT/ICD devices in place. A total of 425 patients (8.07%) for DCM underwent HT, and 214 admissions for DCM (4.06%) underwent LVAD placements between 2016 and 2021 In terms of interventions for DCM, namely Cardiac Resynchronization Therapy (CRT), Left Ventricular Assist Devices (LVADs) and Heart Transplantations (HTs), significant variance was observed in the mean age of the admissions with admissions over the mean age of 55 had lower number of interventions. Significant variance in terms of sex was observed for DCM admissions receiving HT, with lower rates observed for females. In terms of quarterly income, patients belonging to the lowest fourth quartile had higher rates of LVAD and HT compared to general DCM admissions. In the multivariate regression analysis, age at admission had significant association with lower chances of receiving LVADs and HT among DCM admissions, and significant association with higher chances of all-cause mortality during the hospital stay. Conclusions: A general declining trend in the total number of DCM admissions was observed between 2016 and 2021. Significant gender disparities were seen with lower rates of females with DCM receiving LVADs and HT. DCM admissions with mean age of 55 and above were found to have significantly lower rates of receiving LVADs and HT, and higher chances of all-cause mortality during the admission. Full article

Introduction: Prostate cancer with spinal metastases (PCSM) is associated with high morbidity and mortality. The impact of biomarkers on the prognosis of spinal metastases, however, remains unclear. Objective: This study explored associations between potential biomarkers, treatment modalities, survival, and neurological outcomes in PCSM patients. Methods: We conducted a retrospective analysis of 68 patients as part of a neurosurgical cohort with PCSM at a comprehensive cancer center from 2013 to 2023, examining the influence of potential biomarkers, treatment modalities, and demographics on prognosis. The primary outcomes were the identification of biomarkers, overall survival (OS) in years, survival after spinal metastasis in years, spinal metastasis recurrence, and postoperative neurological outcomes via Frankel scores. Results: All the patients (n = 68) had adenocarcinoma, and the median age was 69 years. The mortality rate was 66% with a median OS of 6 years. Seventy-two biomarkers were identified. An accelerated failure time model (AFT) showed that radiotherapy to the prostate increased the OS (TR = 1.805, p = 0.001), while smoking status (TR = 0.625, p < 0.001) and PTEN gene mutations (TR = 0.504, p = 0.006) were associated with decreased OS. Kaplan–Meier analysis associated PTEN mutations with reduced median OS using the Gehan–Breslow–Wilcoxon test (3.50 vs. 9.49 years; p = 0.001). PTEN mutations were trending towards but were not significant for decreased survival following spinal metastases (2.04 vs. 3.15 years; p = 0.08). Both PTEN (p = 0.02) and Tumor Protein 53 (TP53, p = 0.01) mutations were associated with increased spinal metastasis recurrence when analyzed using Fisher’s exact test. No differences were observed in the median OS or survival after spinal metastases among patients with or without androgen receptor splice variant-7 (AR-V7), prostate-specific membrane antigen (PSMA), TP53, or other analyzed biomarkers. Similarly, neither age, receipt of chemotherapy, nor radiotherapy to the spine correlated with OS. Only chemotherapy was associated with a decreased postoperative Frankel Score (p = 0.002). Conclusions: PTEN mutations and smoking status were associated with decreased OS in patients with PCSM. Both PTEN and TP53 mutations were associated with increased spinal metastasis recurrence. Receipt of radiotherapy to the prostate was correlated with prolonged survival, whereas receipt of radiotherapy to the spine was not. Chemotherapy was associated with decreased postoperative neurological outcomes. Full article

Background/Objectives: Insomnia is associated with immune function. This study evaluated the association between insomnia and febrile neutropenia in women treated with adjuvant chemotherapy for breast cancer. Methods: This secondary analysis used data from the Canadian Cancer Trial Group MA.21 trial, which compared three chemotherapy regimens (CEF, EC/T dose-dense, or AC/T) in 2104 women with high-risk locoregional breast cancer. A total of 1731 patients completed the EORTC QLQ-C30 questionnaire. We compared “insomnia patients” with patients considered “good sleepers” based on the sleep item of this questionnaire. The primary endpoint was the occurrence of febrile neutropenia. Secondary endpoints were the occurrences of leucopenia and infection. Chemotherapy dose reduction was added as a secondary outcome in an unplanned analysis. Results: Patients with insomnia (16.3%) had a significantly higher rate of febrile neutropenia than good sleepers (12.2%; p = 0.01). After controlling for various confounders, the contribution of insomnia in explaining febrile neutropenia remained statistically significant (OR 1.45, 95% CI 1.07–1.97, p = 0.02). Chemotherapy dose reductions were significantly more frequent in patients with insomnia (30.6%) than in good sleepers (21.8%; p < 0.0001). The relationship remained significant in the multivariate analysis (OR 1.67, 95% CI 1.30–2.15, p < 0.0001). Conclusions: In the MA21 trial, insomnia was associated with febrile neutropenia. Furthermore, chemotherapy dose reductions were more common in women with insomnia. These results suggest that the role of insomnia in potential cancer outcomes needs to be confirmed in other studies, given the possible implication of dose reductions on the prognosis of women receiving chemotherapy for breast cancer. Full article

Purpose: To investigate associations between 18F-FDG-PET/CT semiquantitative and radiomic features with pathologic axillary lymph node (ALN) status in stages I–III breast cancer patients. Methods: A search was conducted across MEDLINE, EMBASE, and CENTRAL databases. Quality assessment was performed with QUADAS-2 and the radiomics quality score (RQS). Descriptive statistical analysis was performed. Results: Most studies were retrospective cohort studies (27/28) and reported only on semiquantitative features (26/28). Most studies were at high risk of bias in patient selection (22/28) and feature extraction (26/28). Semiquantitative features included maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Although associations between tumour semiquantitative features and ALN status were reported, the mean/median reported values of tumour SUVmax (3.2–8.6 vs. 2.4–9.4), MTV (2.7–19.2 vs. 1.9–10.5), and TLG (10.6–59.3 vs. 5.6–29.6) in ALN+ vs. ALN− patients were inconsistent between studies. Fourteen studies reported a significantly higher ALN SUVmax in ALN+ patients. Two studies developed models using tumour radiomic features with high accuracy for predicting ALN metastases (81.2% and 80%) but scored low on the RQS. Conclusions: Feature-based analysis of PET/CT demonstrates potential for predicting pathologic ALN status in breast cancer patients. However, establishing a clinically meaningful relationship requires higher quality evidence. Full article