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Cachexia is a muscle-wasting syndrome that is known to impact the clinical course of several cancer populations but has not been specifically investigated in patients receiving chimeric antigen receptor T (CAR-T) cell therapy. In this study, we investigated the relationship between cachexia markers and several cancer and functional outcomes in a pilot population of aggressive B-cell non-Hodgkin lymphoma patients receiving CAR-T. We found that the prognostic nutritional index was linked to progression-free survival, overall survival, and disability-free survival, while several additional weight and serum-based markers of cachexia were also associated with negative outcomes. These data prompt further investigation of cachexia markers in populations receiving CAR-T cell therapy.
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Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Caquexia/etiología , Caquexia/terapia , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Linfoma no Hodgkin/terapia , Receptores de Antígenos de Linfocitos T , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: Cachexia is a devastating syndrome that impacts a majority of cancer patients. Early assessment of cachexia is critical to implementing cachexia treatments. Our aim was to summarize the existing cachexia assessment tools for their utility in both symptom and function evaluation. RECENT FINDINGS: Several tools now exist that provide a symptom-based approach for evaluating weight change, appetite, and nutrition impact symptoms in cancer patients with cachexia. However, current instruments used to assess physical function changes related to cachexia are limited in depth and breadth. Instead, we recommend a tiered approach to cachexia-related functional assessment that involves evaluation of activities of daily living, general mobility, and exercise tolerance in a prioritized sequence. Current tools for cancer-associated cachexia assessment are adept at symptom evaluation. New approaches to physical function evaluation are needed that efficiently and broadly evaluate the diverse functional needs of cachexia patients.
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Caquexia , Neoplasias , Actividades Cotidianas , Apetito , Caquexia/diagnóstico , Caquexia/etiología , Caquexia/terapia , Humanos , Neoplasias/complicaciones , Calidad de VidaRESUMEN
The mechanisms by which the extreme desmoplasia observed in pancreatic tumors develops remain unknown and its role in pancreatic cancer progression is unsettled. Chemokines have a key role in the recruitment of a wide variety of cell types in health and disease. Transcript and protein profile analyses of human and murine cell lines and human tissue specimens revealed a consistent elevation in the receptors CCR10 and CXCR6, as well as their respective ligands CCL28 and CXCL16. Elevated ligand expression was restricted to tumor cells, whereas receptors were in both epithelial and stromal cells. Consistent with its regulation by inflammatory cytokines, CCL28 and CCR10, but not CXCL16 or CXCR6, were upregulated in human pancreatitis tissues. Cytokine stimulation of pancreatic cancer cells increased CCL28 secretion in epithelial tumor cells but not an immortalized activated human pancreatic stellate cell line (HPSC). Stellate cells exhibited dose- and receptor-dependent chemotaxis in response to CCL28. This functional response was not linked to changes in activation status as CCL28 had little impact on alpha smooth muscle actin levels or extracellular matrix deposition or alignment. Co-culture assays revealed CCL28-dependent chemotaxis of HPSC toward cancer but not normal pancreatic epithelial cells, consistent with stromal cells being a functional target for the epithelial-derived chemokine. These data together implicate the chemokine CCL28 in the inflammation-mediated recruitment of cancer-associated stellate cells into the pancreatic cancer parenchyma.
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Carcinoma Ductal Pancreático/metabolismo , Quimiocinas/metabolismo , Quimiotaxis , Neoplasias Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/metabolismo , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Línea Celular , Línea Celular Tumoral , Células Cultivadas , Quimiocinas/genética , Técnicas de Cocultivo , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Ratones , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
As knowledge of growth-independent functions of cancer cells is expanding, exploration into the role of chemokines in modulating cancer pathogenesis, particularly metastasis, continues to develop. However, more study into the mechanisms whereby chemokines direct the migration of cancer cells is needed before specific therapies can be generated to target metastasis. Herein, we draw attention to the longstanding conundrum in the field of chemokine biology that chemokines stimulate migration in a biphasic manner; and explore this phenomenon's impact on chemokine function in the context of cancer. Typically, low concentrations of chemokines lead to chemotactic migration and higher concentrations halt migration. The signaling mechanisms that govern this phenomenon remain unclear. Over the last decade, we have defined a novel signaling mechanism for regulation of chemokine migration through ligand oligomerization and biased agonist signaling. We provide insight into this new paradigm for chemokine signaling and discuss how it will impact future exploration into chemokine function and biology. In the pursuit of producing more novel cancer therapies, we suggest a framework for pharmaceutical application of the principles of chemokine oligomerization and biased agonist signaling in cancer. © 2016 Wiley Periodicals, Inc.
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Antineoplásicos/farmacología , Quimiocinas/agonistas , Neoplasias/tratamiento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Animales , Antineoplásicos/uso terapéutico , Movimiento Celular/efectos de los fármacos , Quimiocinas/química , Progresión de la Enfermedad , Humanos , Modelos Moleculares , Neoplasias/inmunología , Neoplasias/patología , Multimerización de Proteína , Transducción de Señal/efectos de los fármacosRESUMEN
Aggressive dissemination and metastasis of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis and marked lethality. Rho monomeric G protein levels are increased in pancreatic cancer tissue. As the mechanisms underlying PDAC malignancy are little understood, we investigated the role for cAMP in regulating monomeric G protein regulated invasion and migration of pancreatic cancer cells. Treatment of PDAC cells with cAMP elevating agents that activate adenylyl cyclases, forskolin, protein kinase A (PKA), 6-Bnz-cAMP, or the cyclic nucleotide phosphodiesterase inhibitor cilostamide significantly decreased migration and Matrigel invasion of PDAC cell lines. Inhibition was dose-dependent and not significantly different between forskolin or cilostamide treatment. cAMP elevating drugs not only blocked basal migration, but similarly abrogated transforming-growth factor-ß-directed PDAC cell migration and invasion. The inhibitory effects of cAMP were prevented by the pharmacological blockade of PKA. Drugs that increase cellular cAMP levels decreased levels of active RhoA or RhoC, with a concomitant increase in phosphorylated RhoA. Diminished Rho signaling was correlated with the appearance of thickened cortical actin bands along the perimeter of non-motile forskolin or cilostamide-treated cells. Decreased migration did not reflect alterations in cell growth or programmed cell death. Collectively these data support the notion that increased levels of cAMP specifically hinder PDAC cell motility through F-actin remodeling.
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Carcinoma Ductal Pancreático/patología , AMP Cíclico/metabolismo , Neoplasias Pancreáticas/patología , 1-Metil-3-Isobutilxantina/farmacología , Amidas/farmacología , Apoptosis , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular , Colforsina/farmacología , AMP Cíclico/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Invasividad Neoplásica , Inhibidores de Fosfodiesterasa/farmacología , Piridinas/farmacología , Quinolonas/farmacología , Vasodilatadores/farmacología , Proteínas de Unión al GTP rho/antagonistas & inhibidores , Proteínas de Unión al GTP rho/metabolismo , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/metabolismo , Proteína rhoC de Unión a GTP , GemcitabinaRESUMEN
ABSTRACT: Nerve conduction studies (NCS) are a commonly performed procedure and a core competency for Physical Medicine and Rehabilitation (PM&R) residents. Nerve conduction studies are complex to learn and no standardized training protocols exist across PM&R programs. The aim of this study is to standardize training and assessment of resident proficiency in NCS skills and to evaluate the impact of an educational intervention on skills development. This was a repeated measures design wherein 36 PM&R residents underwent a pretest, followed by a mastery-learning-based intervention, including deliberate practice. Residents were then expected to meet or exceed a minimum passing score at post-test. Performance improved from a median score of 4.5/66 on the pretest to a median score of 63/66 on the posttest. 33/36 residents achieved the minimum passing score on the first attempt; three residents required additional deliberate practice and met the minimum passing score on the second attempt. A curriculum featuring deliberate practice dramatically increased checklist scores of residents performing NCS. This mastery learning program shows a reliable and reproducible method to achieve procedural competency within a PM&R residency program and can shift the curve to allow residents to immediately start performing NCS at the start of their clinical experience.
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Options for treatment of incurable cancer remain scarce and are largely focused on limited therapeutic mechanisms. A new approach specific to advanced cancers is needed to identify new and effective treatments. Morbidity in advanced cancer is driven by functional decline and a number of systemic conditions, including cachexia and fatigue. This review will focus on these clinical concepts, describe our current understanding of their underlying biology, and then propose how future therapeutic strategies, including pharmaceuticals, exercise, and rehabilitation, could target these mechanisms as an alternative route to addressing incurable cancer.
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OBJECTIVE: The establishment of rehabilitation goals for hospitalized cancer patients depends on accurate medical prognosis and matching goals to clinical timelines. Current tools for estimating prognosis are limited. We hypothesized that bed mobility is a predictor of mortality in cancer patients admitted to inpatient rehabilitation. DESIGN: In a retrospective cohort of 187 subjects with nonneurologic cancer admitted to inpatient rehabilitation, Functional Independence Measure scores and 6-mo mortality were analyzed. RESULTS: In the cohort, survival rate was 71% at 6 mos. In univariate analysis, discharge bed mobility score (odds ratio = 0.75, 95% confidence interval = 0.61-0.90, P = 0.003), bed mobility Functional Independence Measure gain (odds ratio = 0.66, 95% confidence interval = 0.51-0.85, P = 0.002), and bed mobility Functional Independence Measure efficiency (odds ratio = 0.011, 95% confidence interval = 0.00032-0.21, P = 0.006) were inversely associated with 6-mo mortality after discharge from inpatient rehabilitation facility. In multivariate analysis with additional motor Functional Independence Measure items, only bed mobility (odds ratio = 0.73, 95% confidence interval = 0.54-0.97, P = 0.029) and grooming (odds ratio = 0.79, 95% confidence interval = 0.63-0.99, P = 0.041) were independently associated with mortality. CONCLUSIONS: Lower discharge and lower change in bed mobility Functional Independence Measure scores are associated with mortality in cancer patients in inpatient rehabilitation. Bed mobility could serve as a clinical tool for estimating medical prognosis in hospitalized cancer patients and should be validated in prospective studies.
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Neoplasias , Alta del Paciente , Humanos , Masculino , Femenino , Neoplasias/rehabilitación , Neoplasias/mortalidad , Estudios Retrospectivos , Alta del Paciente/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Pronóstico , Limitación de la Movilidad , Pacientes Internos/estadística & datos numéricos , Centros de RehabilitaciónRESUMEN
Objective: Cancer cachexia is progressive weight loss due to muscle/adipose tissue wasting and inadequate intake that occurs in response to malignancy. It is an independent predictor of disease recurrence and reduced survival in several cancers. However, cachexia's relationship with gynecologic malignancy outcomes has only been examined in small studies with limited follow-up and inconsistent definitions of cachexia. This study investigated the impact of cachexia on disease recurrence and overall survival in high-risk endometrial carcinoma patients. Methods: This retrospective cohort study examined data from patients with high-risk non-metastatic primary endometrial carcinoma treated at a single institution from 2015 to 2020. Treatment for all subjects included total hysterectomy, surgical staging, pelvic external beam radiotherapy with or without adjuvant chemotherapy. Radiation planning CT datasets were used to measure skeletal musculature at the L3 vertebral level. Skeletal muscle index (SMI) was defined as total L3 skeletal muscle cross sectional area (cm2)/height2 (m2), and cachexia was defined based on SMI. Results: 55 patients were eligible for analysis. Several SMI thresholds were used to define cachexia, and analysis was performed for each definition. Kaplan-Meier and Cox-proportional hazards regression analysis yielded no significant reduction in overall survival (OS) or progression-free survival (PFS) in patients with cachexia, regardless of threshold chosen. However, 4 of 13 definitions of cachexia showed significantly improved OS in patients without cachexia, relative to those with cachexia. There were no significant differences in disease recurrence. Conclusions: Cachexia as defined in this study was not associated with poor outcomes in endometrial carcinoma patients based on OS, PFS, or disease recurrence.
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BACKGROUND: Progressive functional decline is a key element of cancer-associated cachexia. Major barriers to translating pre-clinical therapies into the clinic include lack of cancer models that accurately mimic functional decline, which develops over time, and use of non-specific measures, like grip strength, as surrogates for physical function. In this study, we aimed to extend the survival and longevity of a cancer model, in order to investigate cachexia-related function at the basic science level. METHODS: Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre (KPC) derived cells. 128 animals in this new model were assessed for cachexia syndrome phenotype using a battery of anatomical, biochemical, and behavioral techniques. RESULTS: We extended the survival of the KPC orthotopic model to 8-9 weeks post-implantation using a relatively low 100-cell dose of DT10022 KPC cells (p<0.001). In this Low-dose Orthotopic (LO) model, progressive muscle wasting was detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 weeks post-implantation compared to controls (p<0.001). Gait speed in LO animals declined as early 2-weeks post-implantation while grip strength change was a late event. Principle component and regression analyses revealed distinct cachectic and non-cachectic animal populations, which we leveraged to show that the gait speed decline was specific to cachexia (p<0.01) while grip strength decline was not (p=0.19). CONCLUSION: Gait speed represents an accurate surrogate for cachexia related physical function as opposed to grip strength.
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The circadian clock orchestrates vital physiological processes such as metabolism, immune function, and tissue regeneration, aligning them with the optimal time of day. This study identifies an intricate interplay between the circadian clock within muscle stem cells (SCs) and their capacity to modulate the immune microenvironment during muscle regeneration. We uncover that the SC clock provokes time of day-dependent induction of inflammatory response genes following injury, particularly those related to neutrophil activity and chemotaxis. These responses are driven by rhythms of cytosolic regeneration of the signaling metabolite NAD+. We demonstrate that genetically enhancing cytosolic NAD+ regeneration in SCs is sufficient to induce robust inflammatory responses that significantly influence muscle regeneration. Furthermore, using mononuclear single-cell sequencing of the regenerating muscle niche, we uncover a key role for the cytokine CCL2 in mediating SC-neutrophil crosstalk in a time of day-dependent manner. Our findings highlight a crucial intersection between SC metabolic shifts and immune responses within the muscle microenvironment, dictated by the circadian rhythms, and underscore the potential for targeting circadian and metabolic pathways to enhance tissue regeneration.
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ABSTRACT: Chimeric antigen receptor (CAR) T-cell (CAR-T) immunotherapy is an effective therapy for relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). However, data are limited on the impact of the convergence of race and social determinants of health on outcomes for patients treated with CAR-T therapy. We examined the impact of interactions between race and insurance type on health care use and outcomes in patients treated with CAR-T therapy for aggressive B-NHL. Adult patients with r/r B-NHL treated with CD19 CAR-Ts were identified between 2015 and 2021 across 13 US academic centers. Insurance type, demographic, and clinical data were collected and analyzed. In total, 466 adult patients were included in our analysis. Median follow-up after CAR-T therapy was 12.7 months. Median progression-free survival (mPFS) was longer for Caucasians (11.5 months) than for African Americans (3.5 months; hazard ratio [HR], 1.56 [1.03-2.4]; P = .04) or Asians (2.7 months; HR, 1.7 [1.02-2.67]; P = .04). Differences in median overall survival (mOS) were not significant. For Medicare (n = 206) vs Medicaid (n = 33) vs private insurance (n = 219) vs self-pay (n = 7): mPFS was 15.9 vs 4.2 vs 6.0 vs 0.9 months (P < .001), respectively; and mOS was 31.2 vs 12.8 vs 21.5 vs 3.2 months (P < .001), respectively. Our multicenter retrospective analysis showed that race and insurance status can affect outcomes for patients treated with CAR-T therapy.
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Inmunoterapia Adoptiva , Determinantes Sociales de la Salud , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Linfoma de Células B/terapia , Linfoma de Células B/mortalidad , Resultado del Tratamiento , Anciano , Estados Unidos , Estudios Retrospectivos , Grupos RacialesRESUMEN
PURPOSE: Although inpatient rehabilitation can improve functional independence in patients with cancer, the role of cachexia in this population is unknown. Our objectives were to:1) Establish prevalence of cachexia in a cohort of cancer patients receiving inpatient rehabilitation and its association with demographic and oncological history.2) Determine the relationship between the presence of cachexia and functional recovery and whether these patients in inpatient rehabilitation have a distinct prognosis. METHODS: This is a retrospective cohort study of 250 patients over 330 admissions to an inpatient rehabilitation facility. Body weight loss threshold and Weight Loss Grading Scale identified patients with and without cachexia. Main outcomes were functional independence measure scores, discharge destination, and 6-mo survival. RESULTS: Prevalence of cachexia in inpatient rehabilitation was 59% using consensus body weight loss criteria, and 77% of cancer patients had a Weight Loss Grading Scale score greater than 0. Patients with and without cachexia had similar motor and cognitive gains, although patients with severe cachexia had more limited functional gains ( P < 0.05) and increased odds of acute care return ( P < 0.01). Patients with a Weight Loss Grading Scale score of 4 had decreased survival at 6 mos ( P < 0.05) compared with noncachectic patients. CONCLUSIONS: These data suggest that there is a relationship between cachexia and recovery for cancer patients that should be further studied in rehabilitation settings.
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Pacientes Internos , Neoplasias , Humanos , Estudios Retrospectivos , Caquexia/etiología , Hospitalización , Recuperación de la Función , Neoplasias/complicaciones , Neoplasias/rehabilitación , Centros de Rehabilitación , Resultado del Tratamiento , Tiempo de InternaciónRESUMEN
Background: Progressive functional decline is a key element of cancer-associated cachexia. No therapies have successfully translated to the clinic due to an inability to measure and improve physical function in cachectic patients. Major barriers to translating pre-clinical therapies to the clinic include lack of cancer models that accurately mimic functional decline and use of non-specific outcome measures of function, like grip strength. New approaches are needed to investigate cachexia-related function at both the basic and clinical science levels. Methods: Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-ras LSL.G12D/+ ; Trp53 R172H/+ ; Pdx-1-Cre (KPC) derived cells. 128 animals in this new model were then assessed for muscle wasting, inflammation, and functional decline using a battery of biochemical, physiologic, and behavioral techniques. In parallel, we analyzed a 156-subject cohort of cancer patients with a range of cachexia severity, and who required rehabilitation, to determine the relationship between gait speed via six-minute walk test (6MWT), grip strength (hGS), and functional independence measures (FIM). Cachectic patients were identified using the Weight Loss Grading Scale (WLGS), Fearon consensus criteria, and the Prognostic Nutritional Index (PNI). Results: Using a 100-cell dose of DT10022 KPC cells, we extended the survival of the KPC orthotopic model to 8-9 weeks post-implantation compared to higher doses used (p<0.001). In this Low-dose Orthotopic (LO) model, both progressive skeletal and cardiac muscle wasting were detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 weeks post-implantation compared to controls (p<0.001). Gait speed in LO animals declined as early 2 week post-implantation whereas grip strength change was a late event and related to end of life. Principle component analysis (PCA) revealed distinct cachectic and non-cachectic animal populations, which we leveraged to show that gait speed decline was specific to cachexia (p<0.01) while grip strength decline was not (p=0.19). These data paralleled our observations in cancer patients with cachexia who required rehabilitation. In cachectic patients (identified by WLGS, Fearon criteria, or PNI, change in 6MWT correlated with motor FIM score changes while hGS did not (r 2 =0.18, p<0.001). This relationship between 6MWT and FIM in cachectic patients was further confirmed through multivariate regression (r 2 =0.30, p<0.001) controlling for age and cancer burden. Conclusion: Outcome measures linked to gait are better associated with cachexia related function and preferred for future pre-clinical and clinical cachexia studies.
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Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T. We conducted a multicenter retrospective analysis to describe peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post-CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post-CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post-CAR-T cell progression, which remains an unmet clinical need.
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Linfoma de Células B , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios Retrospectivos , Inmunoterapia Adoptiva/métodos , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Cancer patients undergoing inpatient rehabilitation often have high risk of complications leading to unplanned transfer to acute care. Prior studies have identified factors associated with these transfers but have been limited to examining factors that pertain to initial admission to rehabilitation and were not conducted in a freestanding inpatient rehabilitation facility. OBJECTIVE: The study aimed to include these prerehabilitation factors in addition to factors upon initial assessment in rehabilitation. It was hypothesized that specific factors from each of these periods would be associated with unplanned transfer to acute care. DESIGN: Retrospective cohort study. SETTING: Freestanding academic inpatient rehabilitation facility affiliated with an academic tertiary care facility with a comprehensive cancer center. PATIENTS: Retrospective review of 330 specific encounters unique to 250 patients from March 2017 to September 2018. MAIN OUTCOME MEASURES: The outcome measure was unplanned transfer to acute care. A binary logistic regression model was used to examine the relationship between factors from oncologic history, acute care course, and factors upon admission to rehabilitation to unplanned transfer to acute care. RESULTS: From 330 encounters, there were 111 unplanned transfers (34%). Unplanned transfer to acute care was independently associated with gastrointestinal malignancy (odds ratio [OR] 4.4, p = .01), 6-minute walk test less than 90 m (OR 4.6, p = .003), and prior unplanned transfer (OR 3.5, p = .007). CONCLUSIONS: The study suggests that oncologic and functional prerehabilitation markers are associated with an increased likelihood of unplanned transfer during inpatient cancer rehabilitation. These findings will provide a framework for creating predictive tools for unplanned transfers in cancer rehabilitation patients.
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Pacientes Internos , Neoplasias , Hospitalización , Humanos , Neoplasias/rehabilitación , Evaluación de Resultado en la Atención de Salud , Centros de Rehabilitación , Estudios RetrospectivosRESUMEN
Background: Older adults ≥65 years of age represent the majority of new cancer diagnoses and are vulnerable to developing depression-like symptoms. Evaluation and management of depression in older cancer patients is underappreciated despite its high prevalence and impact on health-related quality of life. Although antidepressants are the primary pharmacologics used to treat depressive-like symptoms, the efficacy and overall benefit(s) are not well-characterized in older adult patients with cancer. The objective of this investigation was to review what is known about the efficacy of pharmacologic treatment for older adults with depression and cancer. Methods: PubMed (Medline) and EMBASE (Elsevier) databases were analyzed for relevant literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: 1,919 unique studies were identified for title and abstract screening. Forty-eight publications were retrieved for full review. None of the identified studies evaluated the potential for benefit after pharmacological treatment among older adults with cancer and depression. Twenty-seven publications met all study criteria except for an analysis focused on older patients. Conclusion: We discovered a universal absence of literature with a relevance to pharmacologic antidepressant treatment effects in older adult patients with cancer. This included a lack of evaluation in patients with brain tumors who have an unusually high predilection for developing depression. Our findings suggest that new research is critically needed for understanding optimal clinical management strategies in older adults with cancer and depression who are treated with antidepressants.
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Objective: To evaluate whether manual wheelchair use and wheelchair tennis are associated with increased risk of lateral epicondylosis (LE). We hypothesized that the prevalence of LE would be highest in WC tennis players, followed by tennis players, WC users, and able-bodied subjects.Study design: Prospective cross-sectional pilot study.Setting: Milwaukee VAMC (clinic), National Veterans Wheelchair Games 2016 (medical event coverage).Participants: Wheelchair users, able-bodied controls, tennis players, non-tennis players.Interventions: Subjects meeting inclusion criteria underwent ultrasound examination of the dominant elbow evaluating for characteristics of LE (n = 83).Outcome measurements: Prevalence of LE between groups. Statistical analysis included odds ratios (OR), univariate and multivariate logistic regression.Results: There was no significant difference in diagnosis of LE between groups when comparing prevalence, unadjusted odds ratios, and predicted probabilities. When adjusted for age, able-bodied controls and tennis players had a similar increase in probability of LE with age; this effect was not seen for wheelchair users. Wheelchair users diagnosed with LE on US had spent significantly more time in a wheelchair (23 vs 13 years) than those with a negative diagnosis.Conclusions: Tennis playing in able bodied controls did not increase risk of LE. In wheelchair users, tennis playing does not appear to be associated with LE, though duration of wheelchair use appears to be a significant predictor of LE.Level of evidence: Level II.