Search Results (35)

Background/Objectives: Patients with breast cancer who do not achieve a complete response to neoadjuvant chemotherapy (NAC) may benefit from intensified adjuvant systemic therapy. However, such treatment escalation is typically delayed until after tumour resection, which occurs several months into the treatment course. Quantitative ultrasound (QUS) can detect early microstructural changes in tumours and may enable timely identification of non-responders during NAC, allowing for earlier treatment intensification. In our previous prospective observational study, 100 breast cancer patients underwent QUS imaging before and four times during NAC. Machine learning algorithms based on QUS texture features acquired in the first week of treatment were developed and achieved 78% accuracy in predicting treatment response. In the current study, we aimed to validate these algorithms in an independent prospective cohort to assess reproducibility and confirm their clinical utility. Methods: We included breast cancer patients eligible for NAC per standard of care, with tumours larger than 1.5 cm. QUS imaging was acquired at baseline and during the first week of treatment. Tumour response was defined as a ≥30% reduction in target lesion size on the resection specimen compared to baseline imaging. Results: A total of 51 patients treated between 2018 and 2021 were included (median age 49 years; median tumour size 3.6 cm). Most were estrogen receptor–positive (65%) or HER2-positive (33%), and the majority received dose-dense AC-T (n = 34, 67%) or FEC-D (n = 15, 29%) chemotherapy, with or without trastuzumab. The support vector machine algorithm achieved an area under the curve of 0.71, with 86% accuracy, 91% specificity, 50% sensitivity, 93% negative predictive value, and 43% positive predictive value for predicting treatment response. Misclassifications were primarily associated with poorly defined tumours and difficulties in accurately identifying the region of interest. Conclusions: Our findings validate QUS-based machine learning models for early prediction of chemotherapy response and support their potential as non-invasive tools for treatment personalization and clinical trial development focused on early treatment intensification. Full article

Survivors of pediatric cancer are at risk for late effects and require risk-adapted long-term follow-up (LTFU) care. Yet less than 50% of survivors attend LTFU care. This study aimed to identify barriers and enablers of engaging with LTFU care as perceived by Canadian survivors of pediatric cancer and healthcare providers (HCPs). Survivors (n = 108) and HCPs (n = 20) completed surveys assessing barriers and enablers to attending LTFU care, summarized using descriptive statistics. Participants were invited to participate in survivor focus groups (n = 22) or HCP semi-structured interviews (n = 7). These were analyzed using reflexive thematic analysis and the Capability, Opportunity, and Motivation for Behaviour Change (COM-B) model, which explores how an individual’s capability, opportunity, and motivation influence a target behaviour. Structural barriers, transitioning from pediatric to adult care, and time constraints were highlighted as barriers that affect survivors’ physical opportunity to engage in LTFU care. Accessibility, financial support, HCPs and family support, and community resources were highlighted as enablers that better survivors’ physical and social opportunity to engage in LTFU care. In conclusion, Canadian survivors of pediatric cancer highlighted barriers that limited their physical opportunity to attend LTFU care, while factors that enhanced their physical and social opportunities facilitated greater engagement with LTFU care. Full article

Previous work has demonstrated quantitative ultrasound (QUS) analysis techniques for extracting features and texture features from ultrasound radiofrequency data which can be used to distinguish between benign and malignant breast masses. It is desirable that there be good agreement between estimates of such features acquired using different ultrasound devices. Handheld ultrasound imaging systems are of particular interest as they are compact, relatively inexpensive, and highly portable. This study investigated the agreement between QUS parameters and texture features estimated from clinical ultrasound images of breast tumors acquired using two different ultrasound scanners: a traditional cart-based system and a wireless handheld ultrasound system. The 28 patients who participated were divided into two groups (benign and malignant). The reference phantom technique was used to produce functional estimates of the normalized power spectra and backscatter coefficient for each image. Root mean square differences of feature estimates were calculated for each cohort to quantify the level of feature variation attributable to tissue heterogeneity and differences in system imaging parameters. Cross-system statistical testing using the Mann–Whitney U test was performed on benign and malignant patient cohorts to assess the level of feature estimate agreement between systems, and the Bland–Altman method was employed to assess feature sets for systematic bias introduced by differences in imaging method. The range of p-values was 1.03 × 10⁻⁴ to 0.827 for the benign cohort and 3.03 × 10⁻¹⁰ to 0.958 for the malignant cohort. For both cohorts, all five of the primary QUS features (MBF, SS, SI, ASD, AAC) were found to be in agreement at the 5% confidence level. A total of 13 of the 20 QUS texture features (65%) were determined to exhibit statistically significant differences in the sample medians of estimates between systems at the 5% confidence level, with the remaining 7 texture features being in agreement. The results showed a comparable magnitude of feature variation between tissue heterogeneity and system effects, as well as a moderate level of statistical agreement between feature sets. Full article

This work was conducted in order to validate a pre-treatment quantitative ultrasound (QUS) and texture derivative analyses-based prediction model proposed in our previous study to identify responders and non-responders to neoadjuvant chemotherapy in patients with breast cancer. The validation cohort consisted of 56 breast cancer patients diagnosed between the years 2018 and 2021. Among all patients, 53 were treated with neoadjuvant chemotherapy and three had unplanned changes in their chemotherapy cycles. Radio Frequency (RF) data were collected volumetrically prior to the start of chemotherapy. In addition to tumour region (core), a 5 mm tumour-margin was also chosen for parameters estimation. The prediction model, which was developed previously based on quantitative ultrasound, texture derivative, and tumour molecular subtypes, was used to identify responders and non-responders. The actual response, which was determined by clinical and pathological assessment after lumpectomy or mastectomy, was then compared to the predicted response. The sensitivity, specificity, positive predictive value, negative predictive value, and F1 score for determining chemotherapy response of all patients in the validation cohort were 94%, 67%, 96%, 57%, and 95%, respectively. Removing patients who had unplanned changes in their chemotherapy resulted in a sensitivity, specificity, positive predictive value, negative predictive value, and F1 score of all patients in the validation cohort of 94%, 100%, 100%, 50%, and 97%, respectively. Explanations for the misclassified cases included unplanned modifications made to the type of chemotherapy during treatment, inherent limitations of the predictive model, presence of DCIS in tumour structure, and an ill-defined tumour border in a minority of cases. Validation of a model was conducted in an independent cohort of patient for the first time to predict the tumour response to neoadjuvant chemotherapy using quantitative ultrasound, texture derivate, and molecular features in patients with breast cancer. Further research is needed to improve the positive predictive value and evaluate whether the treatment outcome can be improved in predicted non-responders by switching to other treatment options. Full article

Rationale: Neoadjuvant chemotherapy (NAC) is a key element of treatment for locally advanced breast cancer (LABC). Predicting the response of NAC for patients with LABC before initiating treatment would be valuable to customize therapies and ensure the delivery of effective care. Objective: Our objective was to develop predictive measures of tumor response to NAC prior to starting for LABC using machine learning and textural computed tomography (CT) features in different level of frequencies. Materials and Methods: A total of 851 textural biomarkers were determined from CT images and their wavelet coefficients for 117 patients with LABC to evaluate the response to NAC. A machine learning pipeline was designed to classify response to NAC treatment for patients with LABC. For training predictive models, three models including all features (wavelet and original image features), only wavelet and only original-image features were considered. We determined features from CT images in different level of frequencies using wavelet transform. Additionally, we conducted a comparison of feature selection methods including mRMR, Relief, Rref QR decomposition, nonnegative matrix factorization and perturbation theory feature selection techniques. Results: Of the 117 patients with LABC evaluated, 82 (70%) had clinical–pathological response to chemotherapy and 35 (30%) had no response to chemotherapy. The best performance for hold-out data splitting was obtained using the KNN classifier using the Top-5 features, which were obtained by mRMR, for all features (accuracy = 77%, specificity = 80%, sensitivity = 56%, and balanced-accuracy = 68%). Likewise, the best performance for leave-one-out data splitting could be obtained by the KNN classifier using the Top-5 features, which was obtained by mRMR, for all features (accuracy = 75%, specificity = 76%, sensitivity = 62%, and balanced-accuracy = 72%). Conclusions: The combination of original textural features and wavelet features results in a greater predictive accuracy of NAC response for LABC patients. This predictive model can be utilized to predict treatment outcomes prior to starting, and clinicians can use it as a recommender system to modify treatment. Full article

The relationship between indoor air quality and public health remains under-researched. WellHome is a transdisciplinary community-based study that will engage with residents to co-design feasible and acceptable research to quantify air pollution exposure in 100 homes in West London and examine its potential to exacerbate asthma symptoms in children. Sampling strategies such as using air quality monitors and passive samplers placed in kitchens, children’s bedrooms, and living rooms, will be developed in collaboration with local ambassadors and participating households to measure multiple physical, chemical, microplastic, and biological contaminants. This will provide a comprehensive understanding of indoor air quality across the city’s socio-economic gradient. Other data collected will include housing types and tenure, ventilation practices, occupant behaviours, time-activity, and airway symptoms. Epidemiological analysis will examine air pollution exposure impacts on children’s respiratory health. The particulate mixture’s relative hazard will be evaluated in toxicity studies based on source profiles and activity patterns of participants, focusing on asthma exacerbation related pathways. The study’s findings will be communicated to participants through co-designed reports and inform evidence-based recommendations for reducing indoor air pollution in London and urban areas worldwide. By raising awareness and providing actionable insights, WellHome seeks to contribute to global efforts to improve the health and well-being of vulnerable communities. Full article

Background: Headache is among the most common symptoms following concussion, yet headache after concussion (HAC) remains poorly characterized. This study describes headache characteristics over the first four weeks following pediatric sport-related concussion. Methods: This is a retrospective case series of 87 athletes (mean: 14.9 years; range: 8.4–18.8 years; 38% female) treated in a specialty sports concussion clinic within 28 days of injury. Primary outcomes of headache consistency, frequency, duration, and associated migrainous symptoms were assessed at immediate (0 to 48 h) and weekly time points over the first 28 days post-injury. Generalized mixed linear models compared headache characteristics across time points. Secondary analyses compared each outcome by as-needed analgesic use. Results: During the immediate post-injury period, headache was more often constant (p = 0.002) and associated with migrainous symptoms (p < 0.001). By the third week post-injury, episodic headache was more prevalent (p < 0.001). Most patients (54%) transitioned from constant, migrainous headache to episodic, non-migrainous headache. This finding was uninfluenced by as-needed analgesic medication use. Conclusions: These findings document the trajectory of HAC. Future studies should assess relationships between initial headache characteristics and recovery. Full article

Objectives: Perioperative blood transfusion (PBT) has been associated with worse survival after radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). Here, we evaluated the association between PBT and survival after RC that was preceded by neoadjuvant chemotherapy (NAC). Methods: A retrospective analysis was performed on 949 patients with cT2-4aN0M0 bladder cancer who received NAC prior to RC between 2000 and 2013 at 19 centers. Kaplan–Meier estimates of overall survival (OS) were made. Presumed risk factors for OS were analyzed using Cox regression analysis. PBT was defined by the administration of any packed red blood cells during surgery or during the post-operative hospital stay. Results: A transfusion was given to 608 patients (64%). Transfused patients were more likely to have adverse clinical and pathologic parameters, including clinical stage and performance status. Transfused patients had worse OS (p = 0.01). On multivariable Cox regression, PBT was found to be independently associated with worse OS (HR 1.53 (95% CI 1.13–2.08), p = 0.007). Conclusions: PBT is common after NAC and RC, which may be linked, in part, to the anemia induced by NAC. PBT was associated with several adverse risk factors that correlate with poor outcomes after NAC and RC, and it was an independent predictor of adverse OS on multivariable analysis. Further study should determine if measures to avoid blood loss can reduce the need for PBT and thereby improve patient outcomes. Full article

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0–1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a “high” exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context. Full article

The use of recycled concrete aggregates as a construction material is growing and this study was conducted to investigate the potential water quality issues that arise when concrete aggregates are exposed to water. The water used in the study was from a high-conservation-value wetland. It was dilute (17.8 µS cm⁻¹), acidic (pH 5.97) and poorly buffered. The ionic composition comprised sodium, bicarbonate and chloride ions. Water was recirculated for 60 min through a control treatment and three treatments containing recycled concrete aggregates (RCAs) of different fragment sizes (10 mm, 20 mm and 60 mm). The fragment size influenced the final water quality, but the response patterns varied between the attributes tested. Post-recirculation, the RCA treatments increased the electrical conductivity by 6 to 12 times; pH by 2.3 to 3.8 pH units; and concentrations of calcium, potassium, bicarbonate and sulphate. The water exposed to RCA materials also increased the concentrations of several metals (aluminium, arsenic, copper, lead and zinc), resulting in hazardous concentrations for aquatic species according to ecological water quality guidelines. Strontium concentrations in water exposed to RCAs increased by 30 to 120 times background levels. The results from this study added further support to a growing body of evidence that the exposure of concrete materials to water can produce environmentally hazardous water quality. Full article

Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes—except for lower IL-1β levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14⁺CD16⁺). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state. Full article

Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant. Full article

Objective: Many studies have shown that severe (hospitalized) bronchiolitis during infancy is a risk factor for developing childhood asthma. However, the population subgroups at the highest risk remain unclear. Using large nationwide pediatric cohort data, namely the NIH Environmental influences on Child Health Outcomes (ECHO) Program, we aimed to quantify the longitudinal relationship of bronchiolitis hospitalization during infancy with asthma in a generalizable dataset and to examine potential heterogeneity in terms of major demographics and clinical factors. Methods: We analyzed data from infants (age <12 months) enrolled in one of the 53 prospective cohort studies in the ECHO Program during 2001–2021. The exposure was bronchiolitis hospitalization during infancy. The outcome was a diagnosis of asthma by a physician by age 12 years. We examined their longitudinal association and determined the potential effect modifications of major demographic factors. Results: The analytic cohort consisted of 11,762 infants, 10% of whom had bronchiolitis hospitalization. Overall, 15% subsequently developed asthma. In the Cox proportional hazards model adjusting for 10 patient-level factors, compared with the no-bronchiolitis hospitalization group, the bronchiolitis hospitalization group had a significantly higher rate of asthma (14% vs. 24%, HR = 2.77, 95%CI = 2.24–3.43, p < 0.001). There was significant heterogeneity by race and ethnicity (P_interaction = 0.02). The magnitude of the association was greater in non-Hispanic White (HR = 3.77, 95%CI = 2.74–5.18, p < 0.001) and non-Hispanic Black (HR = 2.39, 95%CI = 1.60–3.56; p < 0.001) infants, compared with Hispanic infants (HR = 1.51, 95%CI = 0.77–2.95, p = 0.23). Conclusions: According to the nationwide cohort data, infants hospitalized with bronchiolitis are at a higher risk for asthma, with quantitative heterogeneity in different racial and ethnic groups. Full article

Despite the adverse effects of substance use on health among individuals with preexisting cardiovascular disease (CVD), little is known about trends and correlates for substance use among individuals with CVD. We examined trends of use in tobacco, alcohol, and cannabis among US adults with heart disease. Using nationally representative data from the 2015–2019 National Survey on Drug Use and Health (N = 7339), we conducted survey-adjusted logistic regression analyses to test the significance of trends in substance use while controlling for sociodemographic factors and related correlates. Results showed that the prevalence of cannabis use among adults with a heart condition significantly increased. Notably, the prevalence of cannabis use increased by 91% among non-Hispanic Whites, while the increasing trends were not present among other racial/ethnic groups. Our results also showed that increase in cannabis use was associated with easier access, lower disapproval, and risk perceptions of cannabis. Special attention is needed to raise awareness of the risk associated with cannabis use among individuals with CVD and the implementation of an early screening and treatment strategy among those with CVD. Full article

Purpose: Staphylococcus aureus is a leading cause of bacteremia with a 30-day mortality of 20%. This study evaluated outcomes after implementation of a pharmacist-driven Staphylococcus aureus bacteremia (SAB) initiative in a community hospital. Methods: This retrospective cohort analysis compared patients admitted with SAB between May 2015 and April 2018 (intervention group) to those admitted between May 2012 and April 2015 (historical control group). Pharmacists were notified of and responded to blood cultures positive for Staphylococcus aureus by contacting provider(s) with a bundle of recommendations. Components of the SAB bundle included prompt source control, selection of appropriate intravenous antibiotics, appropriate duration of therapy, repeat blood cultures, echocardiography, and infectious diseases consult. Demographics (age, gender, and race) were collected at baseline. Primary outcome was in-hospital mortality. Compliance with bundle components was also assessed. Results: Eighty-three patients in the control group and 110 patients in the intervention group were included in this study. Demographics were similar at baseline. In-hospital mortality was lower in the intervention group (3.6% vs. 15.7%; p = 0.0033). Bundle compliance was greater in the intervention group (69.1% vs. 39.8%; p < 0.0001). Conclusions: We observed a significant reduction in in-hospital mortality and increased treatment bundle compliance in the intervention cohort with implementation of a pharmacist-driven SAB initiative. Pharmacists’ participation in the care of SAB patients in the form of recommending adherence to treatment bundle components drastically improved clinical outcomes. Widespread adoption and implementation of similar practice models at other institutions may reduce in-hospital mortality for this relatively common and life-threatening infection. Full article