scholarly journals Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy

Author(s):  
Nicole Chmielewski Stivers ◽  
Benoit Petit ◽  
Jonathan Ollivier ◽  
Virginie Monceau ◽  
Pelagia Tsoutsou ◽  
...  

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3973
Author(s):  
Nicole Chmielewski-Stivers ◽  
Benoit Petit ◽  
Jonathan Ollivier ◽  
Virginie Monceau ◽  
Pelagia Tsoutsou ◽  
...  

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female wild-type (WT) mice were treated with paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB-deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones, including estrogen. In females, RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by paclitaxel but enhanced cardiac sensitivity to radiotherapy. Conversely, rhoB-deficiency protected males from radiation toxicity. In sum, RhoB was identified as a molecular determinant driving estrogen-dependent cardioprotection in female mice, whereas neuroprotection was not sex hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mads G. Jørgensen ◽  
Navid M. Toyserkani ◽  
Frederik G. Hansen ◽  
Anette Bygum ◽  
Jens A. Sørensen

AbstractThe impact of breast cancer-related lymphedema (BCRL) on long-term quality of life is unknown. The aim of this study was to investigate the impact of BCRL on health-related quality of life (HRQoL) up to 10 years after breast cancer treatment. This regional population-based study enrolled patients treated for breast cancer with axillary lymph node dissection between January 1st 2007 and December 31th 2017. Follow up and assessments of the included patients were conducted between January 2019 and May 2020. The study outcome was HRQoL, evaluated with the Lymphedema Functioning, Disability and Health Questionnaire, the Disabilities of the Arm, Shoulder and Hand Questionnaire and the Short Form (36) Health Survey Questionnaire. Multivariate linear logistic regression models adjusted for confounders provided mean score differences (MDs) with 95% confidence intervals in each HRQoL scale and item. This study enrolled 244 patients with BCRL and 823 patients without BCRL. Patients with BCRL had significantly poorer HRQoL than patients without BCRL in 16 out of 18 HRQoL subscales, for example, in physical function (MDs 27, 95%CI: 24; 30), mental health (MDs 24, 95%CI: 21; 27) and social role functioning (MDs 20, 95%CI: 17; 23). Age, BMI, BCRL severity, hand and dominant arm affection had only minor impact on HRQoL (MDs < 5), suggesting a high degree of inter-individual variation in coping with lymphedema. This study showed that BCRL is associated with long-term impairments in HRQoL, especially affecting the physical and psychosocial domains. Surprisingly, BCRL diagnosis rather than clinical severity drove the largest impairments in HRQoL.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Rosie Barnett ◽  
Anita McGrogan ◽  
Matthew Young ◽  
Charlotte Cavill ◽  
Mandy Freeth ◽  
...  

Abstract Background/Aims  Axial spondyloarthritis (axSpA) is a chronic rheumatic condition, characterised by inflammatory back pain - often associated with impaired function and mobility, sleep disturbance, fatigue, and reduced quality of life. Despite the vast advances in pharmacological treatments for axSpA over the last few decades, physical activity and rehabilitation remain vital for effective disease management. At the Royal National Hospital for Rheumatic Diseases in Bath (RNHRD), the 2-week inpatient axSpA rehabilitation programme has been integral to axSpA care since the 1970’s. Prior research has demonstrated significant short-term improvements in spinal mobility (BASMI), function (BASFI) and disease activity (BASDAI) following course attendance. However, the long-term outcomes are yet to be evaluated in this unique cohort. Methods  Since the early 1990’s, clinical measures of spinal mobility, function and disease activity have been routinely collected at the RNHRD at all clinical appointments through administration of the BASMI, BASFI and BASDAI, respectively. Dates of attending the axSpA course and standard clinical and treatment follow-up data were also collected. Multiple linear regression models were used to investigate the impact of course attendance on final reported BASMI, BASDAI and BASFI scores (final score=most recent). Length of follow-up was defined as time between first and last recorded BASMI. Results  Of the 203 patients within the Bath SPARC200 cohort, 77.8% (158/203) had attended at least one rehabilitation course throughout follow-up. 70.0% (140/203) of patients were male. The mean duration of follow-up was 13.5 years (range 0-35 years); 28.1% (57/203) of individuals with 20+ years of follow-up. Course attendance (yes versus no) significantly reduced final BASMI score by 0.84 (p = 0.001, 95%CI -1.31 to -0.37) and final BASDAI score by 0.74 (p = 0.018, 95%CI -1.34 to -0.13). Although course attendance reduced final BASFI by 0.45 (95%CI -1.17 to 0.28), this relationship did not reach significance (p = 0.225). Whilst minimally clinically important difference (MCID) is, to our knowledge, yet to be defined for BASMI, MCIDs were achieved long-term for both BASDAI and BASFI - defined by van der Heijde and colleagues in 2016 as 0.7 and 0.4 for BASDAI and BASFI, respectively. Conclusion  These results provide novel evidence to support the integral role of education, physical activity and rehabilitation in the management of axSpA. Future work should investigate additional outcomes of critical importance to patients and clinicians, such as fatigue, quality of life and work productivity. Furthermore, a greater understanding of the factors that confound these outcomes may provide insights into those patients who may most benefit from attending a 2-week rehabilitation course. In addition to facilitating identification of those patients who may require additional clinical support. Disclosure  R. Barnett: None. A. McGrogan: None. M. Young: None. C. Cavill: None. M. Freeth: None. R. Sengupta: Honoraria; Biogen, Celgene, AbbVie, Novartis, MSD. Grants/research support; Novartis, UCB.


Sensors ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 1387
Author(s):  
Oswaldo Sebastian Peñaherrera-Pulla ◽  
Carlos Baena ◽  
Sergio Fortes ◽  
Eduardo Baena ◽  
Raquel Barco

Cloud Gaming is a cutting-edge paradigm in the video game provision where the graphics rendering and logic are computed in the cloud. This allows a user’s thin client systems with much more limited capabilities to offer a comparable experience with traditional local and online gaming but using reduced hardware requirements. In contrast, this approach stresses the communication networks between the client and the cloud. In this context, it is necessary to know how to configure the network in order to provide service with the best quality. To that end, the present work defines a novel framework for Cloud Gaming performance evaluation. This system is implemented in a real testbed and evaluates the Cloud Gaming approach for different transport networks (Ethernet, WiFi, and LTE (Long Term Evolution)) and scenarios, automating the acquisition of the gaming metrics. From this, the impact on the overall gaming experience is analyzed identifying the main parameters involved in its performance. Hence, the future lines for Cloud Gaming QoE-based (Quality of Experience) optimization are established, this way being of configuration, a trendy paradigm in the new-generation networks, such as 4G and 5G (Fourth and Fifth Generation of Mobile Networks).


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 960-960
Author(s):  
Sara Luck ◽  
Katie Aubrecht

Abstract Nursing home facilities are responsible for providing care for some of the most vulnerable groups in society, including the elderly and those with chronic medical conditions. In times of crisis, such as COVID-19 or other pandemics, the delivery of ‘regular’ care can be significantly impacted. In relation to COVID-19, there is an insufficient supply of personal protective equipment (PPE) to care for residents, as PPE not only protects care staff but also residents. Nursing homes across the United States and Canada have also taken protective measures to maximize the safety of residents by banning visitors, stopping all group activities, and increasing infection control measures. This presentation shares a research protocol and early findings from a study investigating the impact of COVID-19 on quality of care in residential long-term care (LTC) in the Canadian province of New Brunswick. This study used a qualitative description design to explore what contributes to quality of care for residents living in long-term care, and how this could change in times of crisis from the perspective of long-term care staff. Interviews were conducted with a broad range of staff at one LTC home. A semi-structured interview guide and approach to thematic analysis was framed by a social ecological perspective, making it possible to include the individual and proximal social influences as well as community, organizations, and policy influencers. Insights gained will improve the understanding of quality of care, as well as potential barriers and facilitators to care during times of crisis.


2017 ◽  
Vol 126 (2) ◽  
pp. 418-430 ◽  
Author(s):  
Sivashanmugam Dhandapani ◽  
Harminder Singh ◽  
Hazem M. Negm ◽  
Salomon Cohen ◽  
Mark M. Souweidane ◽  
...  

OBJECTIVE Craniopharyngiomas can be difficult to remove completely based on their intimate relationship with surrounding visual and endocrine structures. Reoperations are not uncommon but have been associated with higher rates of complications and lower extents of resection. So radiation is often offered as an alternative to reoperation. The endonasal endoscopic transsphenoidal approach has been used in recent years for craniopharyngiomas previously removed with craniotomy. The impact of this approach on reoperations has not been widely investigated. METHODS The authors reviewed a prospectively acquired database of endonasal endoscopic resections of craniopharyngiomas over 11 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, performed by the senior authors. Reoperations were separated from first operations. Pre- and postoperative visual and endocrine function, tumor size, body mass index (BMI), quality of life (QOL), extent of resection (EOR), impact of prior radiation, and complications were compared between groups. EOR was divided into gross-total resection (GTR, 100%), near-total resection (NTR, > 95%), and subtotal resection (STR, < 95%). Univariate and multivariate analyses were performed. RESULTS Of the total 57 endonasal surgical procedures, 22 (39%) were reoperations. First-time operations and reoperations did not differ in tumor volume, radiological configuration, or patients' BMI. Hypopituitarism and diabetes insipidus (DI) were more common before reoperations (82% and 55%, respectively) compared with first operations (60% and 8.6%, respectively; p < 0.001). For the 46 patients in whom GTR was intended, rates of GTR and GTR+NTR were not significantly different between first operations (90% and 97%, respectively) and reoperations (80% and 100%, respectively). For reoperations, prior radiation and larger tumor volume had lower rates of GTR. Vision improved equally in first operations (80%) compared with reoperations (73%). New anterior pituitary deficits were more common in first operations compared with reoperations (51% vs 23%, respectively; p = 0.08), while new DI was more common in reoperations compared with first-time operations (80% vs 47%, respectively; p = 0.08). Nonendocrine complications occurred in 2 (3.6%) first-time operations and no reoperations. Tumor regrowth occurred in 6 patients (11%) over a median follow-up of 46 months and was not different between first versus reoperations, but was associated with STR (33%) compared with GTR+NTR (4%; p = 0.02) and with not receiving radiation after STR (67% vs 22%; p = 0.08). The overall BMI increased significantly from 28.7 to 34.8 kg/m2 over 10 years. Six months after surgery, there was a significant improvement in QOL, which was similar between first-time operations and reoperations, and negatively correlated with STR. CONCLUSIONS Endonasal endoscopic transsphenoidal reoperation results in similar EOR, visual outcome, and improvement in QOL as first-time operations, with no significant increase in complications. EOR is more impacted by tumor volume and prior radiation. Reoperations should be offered to patients with recurrent craniopharyngiomas and may be preferable to radiation in patients in whom GTR or NTR can be achieved.


2017 ◽  
Vol 31 (1) ◽  
pp. 109-138 ◽  
Author(s):  
Mark J. Siedner

Objective: The number of people living with HIV (PLWH) over 50 years old in sub-Saharan Africa is predicted to triple in the coming decades, to 6-10 million. Yet, there is a paucity of data on the determinants of health and quality of life for older PLWH in the region. Methods: A review was undertaken to describe the impact of HIV infection on aging for PLWH in sub-Saharan Africa. Results: We (a) summarize the pathophysiology and epidemiology of aging with HIV in resource-rich settings, and (b) describe how these relationships might differ in sub-Saharan Africa, (c) propose a conceptual framework to describe determinants of quality of life for older PLWH, and (d) suggest priority research areas needed to ensure long-term gains in quality of life for PLWH in the region. Conclusions: Differences in traditional, lifestyle, and envirnomental risk factors, as well as unique features of HIV epidemiology and care delivery appear to substantially alter the contribution of HIV to aging in sub-Saharan Africa. Meanwhile, unique preferences and conceptualizations of quality of life will require novel measurement and intervention tools. An expanded research and public health infrastructure is needed to ensure that gains made in HIV prevention and treamtent are translated into long-term benefits in this region.


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