Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and its incidence is steadily rising. Currently, sorafenib remains the only approved standard treatment for patients with advanced HCC, as it has proven to increase survival in these patients. However, clinical and preclinical observations indicate that sorafenib treatment may have limited efficacy due to tumor progression from the rapid development of acquired resistance. Elucidation of the underlying mechanisms of evasive resistance to sorafenib is a major challenge in HCC research. In recent years, the role of epithelial-to-mesenchymal transition (EMT) in the advancement of HCC and development of drug resistance has gained increasing attention. EMT is a developmental multistep molecular and cellular reprogramming process that is hijacked by cancer cells to enable aggressiveness. In this review, we provide an overview of the currently available preclinical studies on the EMT mechanisms underlying resistance to sorafenib treatment. Recent studies report enrichment of cancer stem cells (CSCs) after sorafenib treatment. Interestingly, EMT process has been implicated in the generation of CSCs associated with therapy resistance. We discuss how combination of sorafenib with EMT inhibitors could enhance the clinical response to sorafenib, resulting in longer duration of responses, than observed with sorafenib monotherapy. In particular, we discuss how these new insights may facilitate rational development of combination therapies in the future to impact survival of patients with advanced HCC.
Background A majority of older adults with cancer develop malnutrition; however, the implications of malnutrition among this vulnerable population are poorly understood. The goal of this study was to quantify the prevalence of nutrition related‐symptoms and malnutrition among older adults with gastrointestinal (GI) malignancies and the association of malnutrition with geriatric assessment (GA) impairment, health‐related quality of life (HRQoL), and health care utilization. Methods We performed a cross‐sectional study of older adults (≥60 years) who were referred to the GI Oncology clinic at the University of Alabama at Birmingham. Participants underwent the Cancer & Aging Resilience Evaluation survey that includes the abbreviated Patient‐Generated Subjective Global Assessment of nutrition. Nutrition scores were dichotomized into normal (0‐5) and malnourished (≥6), and multivariate analyses adjusted for demographics, cancer type, and cancer stage were used to examine associations with GA impairment, HRQoL, and health care utilization. Results A total of 336 participants were included (men, 56.8%; women, 43.2%), with a mean age of 70 years (standard deviation, ±7.2 years) and colorectal cancer (33.6%) and pancreatic cancer (24.4%) being the most common diagnoses. Overall, 52.1% of participants were identified as malnourished. Malnutrition was associated with a higher prevalence of several GA impairments, including 1 or more falls (adjusted odds ratio [aOR], 2.1), instrumental activities of daily living impairment (aOR, 4.1), and frailty (aOR, 8.2). Malnutrition was also associated with impaired HRQoL domains; both physical (aOR, 8.7) and mental (aOR, 5.0), and prior hospitalizations (aOR, 2.2). Conclusion We found a high prevalence of malnutrition among older adults with GI malignancies that was associated with increased GA impairments, reduced HRQoL, and increased health care utilization.
Objectives: Patient-reported cognitive complaint (CI) is poorly described in older adults with cancer. The purpose of this study was to quantify the prevalence and examine the associations of patient-reported CI in older adults with gastrointestinal (GI) malignancies at diagnosis. Materials and Methods: Using participants ≥60 years with GI malignancies from the Cancer & Aging Resilience Evaluation (CARE) Registry that underwent a Geriatric Assessment (GA), we examined CI using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form 4a Cognitive Function. Cognition scores were dichotomized into normal (scores of 15-20) and impaired (4-14), and bivariate and multivariate analyses were used to examine associations. Results: A total of 264 participants with GI malignancy were included, mean age of 70.0 ± 7.1, 55.7% male, pancreatic cancer was the most common cancer (24.2%) and majority were stage III/IV (68.2%). 29.3% of participants endorsed CI. CI was not associated with demographic and clinical domains, but was associated with many GA impairments including instrumental Activities of Daily Living (iADL) impairment (adjusted odds ratio [aOR] 6.0, 95% confidence interval 3.0-11.8), falls (aOR 2.7, 1.4-5.4), anxiety (aOR 10.3, 5.2-20.4), and depression (aOR 10.2,. CI was also associated with reduced global mental (aOR 18.7,) quality of life, and prior hospitalizations (aOR 2.4, 1.2-4.8). Conclusion: We found a high prevalence of patient-reported CI in older adults with GI malignancies that was associated with increased GA impairments, reduced health-related quality of life, and increased healthcare utilization.Published by Elsevier Ltd.
Background Poor self-rated health (SRH) is a known predictor of frailty and mortality in the general population; however, its role among older adults with cancer is unknown. We evaluated the role of SRH as a potential screening tool to identify frailty and geriatric assessment (GA)-identified impairments. Materials and Methods Adults ≥60 years diagnosed with cancer in the UAB Cancer & Aging Resilience Evaluation (CARE) registry underwent a GA at the time of initial consultation. We measured SRH using a single-item from the Patient-Reported Outcomes Measurement Information System global health scale and dichotomized responses as poor (poor, fair) and good (good, very good, and excellent). We evaluated the diagnostic performance of SRH in measuring frailty, and GA impairment (≥2 deficits among a set of seven GA domains). We examined the impact of SRH with survival using a Cox model adjusting for confounders, exploring the mediating role of frailty. Results Six hundred and three older adults with cancer were included, with a median age of 69 years. Overall, 45% (n = 274) reported poor SRH. Poor SRH demonstrated high sensitivity and specificity for identifying frailty (85% and 78%, respectively) and GA impairment (75% and 78%, respectively). In a Cox regression model, poor SRH was associated with inferior survival (HR = 2.26; 95% CI 1.60-3.18) after adjusting for confounders; frailty mediated 69% of this observed relationship. Conclusion Self-rated health may be used as a screening tool to identify older adults with cancer with frailty and GA impairments. Poor SRH is associated with inferior survival, which is mediated by frailty.
As the current coronavirus pandemic continues and cases of COVID-19 critical illness rise, physicians and scientists across the globe are working to understand and study its pathophysiology. Part of the pathology of this illness may result from its prothrombotic potential as witnessed from derangements in coagulation and thrombotic complications reported in observational studies performed in China and Europe to findings of microthrombosis upon autopsy analysis of patients who succumbed to COVID-19. Multiple organizations, including the American Society of Hematology (ASH), recommend the routine use of prophylactic heparin to temper the thrombotic complications of this illness given its mortality benefit in severe COVID-19 infections. Reductions in circulating levels of Antithrombin III (AT), the primary mediator of heparin's action, is present in cases of coronavirus related critical illness. AT's use as a prognostic marker, an important effector of heparin resistance, and a potential therapeutic target for COVID-19 remains to be explored.
Background Individuals with sickle cell disease (SCD) are at risk for painful crises and long-term cardiopulmonary morbidity. Echocardiogram is recommended if signs or symptoms of cardiopulmonary disease develop in previously asymptomatic patients, or worsen in those with known disease. Second-generation echocardiogram contrast agents (ECAs) improve the diagnostic capacity of echocardiogram; however, these agents have risks in SCD populations that have yet to be investigated. Case summary We report a case series of two patients who experienced vaso-occlusive crises following administration of the ECA, Definity. Both patients were referred for echocardiogram from our institution’s sickle cell clinic because of concern for SCD-related cardiopulmonary complications. Both patients were in their usual state of health at the time of their exams. The first patient experienced acute back and hip pain minutes after receiving Definity and was diagnosed with acute vaso-occlusive crisis requiring admission for 6 days for pain management. The second patient developed dyspnoea and chest pain within 90 min of her echocardiogram. She was diagnosed with acute chest syndrome and admitted for further management. Her hospitalization was complicated by hyper-haemolysis and multiple organ failure syndrome. After 13 days, she was discharged home. Discussion The safety profile of ECAs has not been fully evaluated and warrants further study in individuals with SCD. Proposed mechanisms for our observations include the release of pro-inflammatory metabolites from Definity contrast agent’s shell and ultrasound-induced haemolysis secondary to ECA administration. Alternative imaging modalities and proper precautions should be considered when evaluating cardiopulmonary function in this patient population.
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