Modulation of back geometry in children with spastic diplegic cerebral palsy via hippotherapy training

Background and purpose: Controlled hippotherapy environment provides a foundation for improved neurologic function and sensory processing. This foundation can be generalized to a wide range of daily activities, making the horse a valuable therapeutic tool for rehabilitation. The purpose of this study was to examine the effects of a once weekly, twelve-week hippotherapy program on back geometry in children with spastic diplegic cerebral palsy.Subjects: Thirty spastic diplegic children from both sexes, ranging in age from six to eight years represented the sample of this study. The degree of spasticity ranged from 1 to 1+ according to the modified Ashworth scale. They were divided randomly into two groups of equal number A (control) and B (Study).Procedures: Evaluation of back geometry parameters was conducted for each child of the two groups before and after three months of treatment via using Formetric instrument system. Group A received a designed exercise program, while group B received hippotherapy training in addition to the same exercise program given to group A.Results: No significant difference was noticed when comparing the pre-treatment results of the two groups, while significant improvement was observed in all the measuring variables of the two groups when comparing their pre and post-treatment mean values. Significant difference was also observed when comparing the post-treatment results of the two groups in favor of group B.Discussion and conclusion: Hippotherapy utilizes the movement of the horse to provide sensory feedback and may be used as a therapeutic intervention for improving back geometry in children with spastic diplegia.Keywords: Cerebral palsy; Diplegia; Back geometry; Hippotherap

Role of treadmill training versus suspension therapy on balance in children with Down syndrome

Background and purpose: Maintaining balance is a subordinate but necessary requirement for most human actions. Most Down syndrome (DS) children, who constitute a large portion in our country, continue to evidence deficits in balance, co-ordination, and gait throughout childhood and adulthood. So, it is essential to seek an ideal physical therapy program to help in solving such a widespread problem. The present study was conducted to compare between the effect of treadmill training and suspension therapy on balance in children with DS.Subjects and methods: Thirty children born with DS from both sexes ranging in age from eight to ten years old were assigned into two groups of equal number. Study group I received treadmill training in addition to a designed exercises therapy program and study group II received suspension therapy in addition to the same exercises program given to the study group I. Stability indices were evaluated via using Biodex instrument system before and after three months of treatment.Results: The results revealed no significant difference when comparing the pre-treatment mean values of the two groups (study I and study II), while significant improvement was observed in all the measuring variables of the two groups when comparing their pre and post treatment mean values. Significant difference was also observed when comparing the post treatment results of the two groups in favor of the study group II.Conclusion: Suspension therapy for children with DS is an excellent supplement to regularly scheduled physical therapy intervention for the purpose of improving the degree of stability in those patients.Keywords: Down syndrome; Balance; Treadmill; Suspension therap

Liquid biopsy in ovarian cancer using circulating tumor DNA and cells: Ready for prime time?

Liquid biopsies hold the potential to inform cancer patient prognosis and to guide treatment decisions at the time when direct tumor biopsy may be impractical due to its invasive nature, inaccessibility and associated complications. Specifically, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have shown promising results as companion diagnostic biomarkers for screening, prognostication and/or patient surveillance in many cancer types. In ovarian cancer (OC), CTC and ctDNA analysis allow comprehensive molecular profiling of the primary, metastatic and recurrent tumors. These biomarkers also correlate with overall tumor burden and thus, they provide minimally-invasive means for patient monitoring during clinical course to ascertain therapy response and timely treatment modification in the context of disease relapse. Here, we review recent reports of the potential clinical value of CTC and ctDNA in OC, expatiating on their use in diagnosis and prognosis. We critically appraise the current evidence, and discuss the issues that still need to be addressed before liquid biopsies can be implemented in routine clinical practice for OC management

Stopping targeted therapy for complete responders in advanced BRAF mutant melanoma

BRAF inhibitors revolutionised the management of melanoma patients and although resistance occurs, there is a subgroup of patients who maintain durable disease control. For those cases with durable complete response (CR) it is not clear whether it is safe to cease therapy. Here we identified 13 patients treated with BRAF +/− MEK inhibitors, who cease therapy after prolonged CR (median = 34 months, range 20–74). Recurrence was observed in 3/13 (23%) patients. In the remaining 10 patients with sustained CR off therapy, the median follow up after discontinuation was 19 months (range 8–36). We retrospectively measured ctDNA levels using droplet digital PCR (ddPCR) in longitudinal plasma samples. CtDNA levels were undetectable in 11/13 cases after cessation and remained undetectable in patients in CR (10/13). CtDNA eventually became detectable in 2/3 cases with disease recurrence, but remained undetectable in 1 patient with brain only progression. Our study suggests that consideration could be given to ceasing targeted therapy in the context of prolonged treatment, durable response and no evidence of residual disease as measured by ctDNA

Supervised resistance exercise for women with ovarian cancer who have completed first-line treatment: a pragmatic study

Objectives: In ovarian cancer (OC), suboptimal muscle morphology (i.e., low muscle mass and density) is associated with poor clinical outcomes, yet little is known about the effect of interventions aimed at improving these measures. We investigated the effect of resistance exercise after first-line treatment on muscle mass and density, muscle strength and physical function, health-related quality of life (QoL), and pelvic-floor function in advanced-stage OC survivors. Methods: Fifteen OC survivors participated in supervised resistance exercise twice weekly for 12 weeks (in-clinic or by telehealth). Assessments included muscle mass and density (dual-energy X-ray absorptiometry, peripheral quantitative computed tomography), muscle strength (1-repetition maximum [1RM] chest press, 5RM leg press, handgrip strength), physical function (400-m walk, timed up-and-go [TUG]), QoL (QLQ-C30 questionnaire), and self-reported pelvic floor function (Australian Pelvic Floor Questionnaire). Results: The median age was 64 (range 33–72) years, 10 women underwent neoadjuvant chemotherapy and five underwent adjuvant chemotherapy. All participants completed the intervention (median attendance = 92%; range 79–100%). Post-intervention improvements were observed for whole-body lean mass (1.0 ± 1.4 kg, p = 0.015), appendicular lean mass (0.6 ± 0.9 kg, p = 0.013), muscle density (p = 0.011), upper and lower body strength (p ≤ 0.001), 400-m walk (p = 0.001), TUG (p = 0.005), and social and cognitive QoL domains (p = 0.002 and 0.007), with no change to pelvic floor symptoms (p \u3e 0.05). Conclusion: In this study, supervised resistance exercise effectively improved muscle mass and density, muscle strength, and physical functioning without deleterious effects on the pelvic floor. Considering the prognostic value of these outcomes, larger studies are needed to confirm the benefits of resistance exercise in OC supportive care

Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device.

Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches

KEYNOTE - D36: Personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma

Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes for patients with unresectable or metastatic melanoma remains. EVX-01, a personalized neoepitope vaccine, combined with pembrolizumab treatment, holds the potential to fulfill this need. Here we present the rationale and novel design behind the KEYNOTE - D36 trial: an open label, single arm, phase II trial aiming to establish the clinical proof of concept and evaluate the safety of EVX-01 in combination with pembrolizumab in CPI naive patients with unresectable or metastatic melanoma. The primary objective is to evaluate if EVX-01 improves best overall response after initial stable disease or partial response to pembrolizumab treatment, in patients with advanced melanoma. The novel end points ensure a decisive readout which may prove helpful before making major investments in phase III trials with limited phase I data. Clinical Trial Registration: NCT05309421 (ClinicalTrials.gov)

Associations of physical activity and exercise with health-related outcomes in patients with melanoma during and after treatment: A systematic review

Purpose: Although exercise medicine is recommended to counter treatment-related side-effects and improve health-related outcomes of patients affected by different cancers, no specific recommendations exist for patients with melanoma. As a result, we systematically examined the current evidence regarding the effects of physical activity and exercise on objectively-measured and patient-reported outcomes among patients with melanoma. Methods: Searches were conducted in PubMed, CINAHL, EMBASE, SPORTDiscus, and Web of Science databases. This review included published data involving physical activity or exercise and objectively-measured or patient-reported outcomes of patients with cutaneous melanoma. The quality of included studies was assessed using the McMaster University Critical Appraisal Tool for Quantitative Studies. Results: Six studies including 882 patients with melanoma were included. Studies presented heterogeneity of design with 2 cross-sectional surveys, 2 retrospective analyses, and 2 non-randomized intervention trials. No statistically significant change in quality of life, fatigue, physical function, cardiorespiratory fitness, body composition, psychological distress, cognitive function, or treatment-related side-effects were attributable to physical activity or exercise. Importantly, physical activity or exercise during melanoma treatment or into survivorship did not adversely impact patients/survivors. Conclusion: In summary, physical activity or exercise did not adversely impact quality of life, objectively-measured or patient-reported outcomes in patients with melanoma. In addition, there is a paucity of quality studies examining the effects of physical activity or exercise on patients with melanoma throughout the cancer care continuum

Genetic analysis of heterogeneous subsets of circulating tumour cells from high grade serous ovarian carcinoma patients

Circulating tumour cells (CTCs) are heterogenous and contain genetic information from the tumour of origin. They bear specific intra- and extra-cellular protein markers aiding in their detection. However, since these markers may be shared with other rare cells in the blood, only genetic testing can confirm their malignancy. Herein, we analyse different CTC subsets using single cell whole genome DNA sequencing to validate their malignant origin. We randomly selected putative CTCs identified by immunostaining that were isolated from 4 patients with high grade serous ovarian cancer (HGSOC) and one with benign cystadenoma. We specifically targeted CTCs positive for epithelial (CK/EpCAMpos), mesenchymal (vimentinpos), and pseudoendothelial (CK/EpCAMpos plus CD31pos) markers. We isolated these cells and performed whole genome amplification (WGA) and low-pass whole-genome sequencing (LP-WGS) for analysis of copy number alterations (CNA). Of the CK/EpCAMpos cells analysed from the HGSOC patients, 2 of 3 cells showed diverse chromosomal CNAs. However, the 4 pseudoendothelial cells (CK/EpCAMpos plus CD31pos) observed in the HGSOC cases did not carry any CNA. Lastly, two of the clusters of vimentin positive cells sequenced from those found in the benign cystadenoma case had CNA. Despite the low number of cells analysed, our results underscore the importance of genetic analysis of putative CTCs to confirm their neoplastic origin. In particular, it highlights the presence of a population of CK/EpCAMpos cells that are not tumour cells in patients with HGSOC, which otherwise would be counted as CTCs

Correlation between circulating tumour DNA and metabolic tumour burden in metastatic melanoma patients

Background: Circulating tumour DNA (ctDNA) may serve as a measure of tumour burden and a useful tool for non-invasive monitoring of cancer. However, ctDNA is not always detectable in patients at time of diagnosis of metastatic disease. Therefore, there is a need to understand the correlation between ctDNA levels and the patients\u27 overall metabolic tumour burden (MTB). Methods: Thirty-two treatment naïve metastatic melanoma patients were included in the study. MTB and metabolic tumour volume (MTV) was measured by 18F-fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT). Plasma ctDNA was quantified using droplet digital PCR (ddPCR). Results: CtDNA was detected in 23 of 32 patients. Overall, a significant correlation was observed between ctDNA levels and MTB (