Chronic diseases: Origin and cell mechanisms involved.

Chronic diseases are a worldwide health problem directly related to society, lifestyle, and the development of unhealthy habits over time. Cardiovascular disease, cancer, chronic respiratory disease, and diabetes are the main causes of death. Environmental factors, such as air pollutants, poor diet, genetic predisposition, or a combination of these, are related to the development of these diseases. These factors activate cell mechanisms, such as DNA damage, oxidative stress, endoplasmic reticulum stress, autophagy, inflammation, and cell death. Depending on the dose and duration of exposure to causative agents, this cell damage can be acute or chronic. Activating these cell mechanisms can rescue normal cell function and cause permanent damage, unleashing the degeneration of tissues and organs over time. A wide variety of treatments help control chronic diseases; however, they cannot be cured completely. This fact leads to complications, dysfunctions, and disabilities. Herein, we discuss some of the principal mechanisms involved and how cellular stress can lead to these diseases when they persist for a long time.

Immigrant Health and Changes to the Public-Charge Rule: Family Physicians' Response.

As the US federal government pursues immigration reform, changes to the federal public-charge rule have triggered confusion and concerns among patients who are immigrants. Although federal judges temporarily blocked implementation, a decision by the Supreme Court in January 2020 allowed the proposed changes to take effect. These policy changes have resulted in many legal immigrants and their family members becoming more reluctant to apply for health insurance, food, housing, and other benefits for which they are qualified. This article summarizes the changes and exclusions. Family physicians can effectively respond to patient and immigrant community concerns about these changes by providing outreach education, access to primary health care, and referrals to legal and social services.

Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer.

BACKGROUND: Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI < 85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. The purpose of this study is to determine if these biomarkers are associated with reduced RDI in women with stage I-III BC. METHODS: This study enrolled women with stage I-III BC. Prior to adjuvant or neoadjuvant chemotherapy, peripheral blood was collected for biomarker measurement. Dose reductions and delays were captured and utilized to calculate the RDI delivered. Univariate and multivariate analyses were performed to describe the association between pre-chemotherapy IL-6, CRP, and D-dimer levels and an RDI < 85%, controlling for relevant tumor and patient factors (age, stage, receptor status, chemotherapy regimen, and pre-chemotherapy physical function and comorbidity). RESULTS: A total of 159 patients (mean age 58 years, range 30-81, SD 11.3) with stage I-III BC were enrolled. An RDI < 85% occurred in 22.6% (N = 36) of patients and was associated with higher pre-chemotherapy IL-6 (OR 1.14, 95% CI 1.04-1.25; p = 0.006) and D-dimer (OR 2.32, 95% CI 1.27-4.24; p = 0.006) levels, increased age (p = 0.001), increased number of comorbidities (p = 0.01), and decreased physical function by the Medical Outcomes Survey Activities of Daily Living (ADL) Scale (p = 0.009) in univariate analysis. A multivariate model, including two biomarkers (IL-6 and D-dimer), age, ADL, BC stage, and chemotherapy regimen, demonstrated a significant association between the increased biomarkers and reduced RDI < 85% (OR 2.54; p = 0.04). CONCLUSIONS: Increased pre-chemotherapy biomarkers of aging (IL-6 and D-dimer) are associated with reduced RDI (<85%). Future studies are underway to validate these findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01030250 . Registered on 3 November 2016.

Association of Pre-Chemotherapy Peripheral Blood Pro-Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer.

BACKGROUND: Pro-inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. The purpose of this study was to determine if pro-inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]), and coagulation (D-dimer) factors were associated with pre-chemotherapy functional status in women with stage I-III breast cancer. PATIENTS AND METHODS: Prior to chemotherapy initiation in patients with stage I-III breast cancer, the following was captured: IL-6, CRP, D-dimer blood levels, and physical function measures including activities of daily living (ADL, subscale of Medical Outcomes Study Physical Health); instrumental activities of daily living (IADL, subscale of the Older Americans Resources and Services Program); Timed Up and Go (TUG); physician-rated Karnofsky Performance Status (KPS); and self-rated KPS. The association of these biomarkers with physical function measures was evaluated. RESULTS: One hundred sixty patients (mean age 58.3 years, range 30-81 years) with stage I-III breast cancer (stages I [n = 34; 21.5%], II [n = 88; 55.7%], III [n = 36; 22.8%]) were enrolled. The group with poorest physical function (defined by ADL <70, IADL <14, and TUG ≥10 seconds) had higher levels of IL-6 (p = .05), D-dimer (p = .0004), and CRP (p = .05). There was no significant association between these biomarkers and KPS. Patients with at least two biomarkers in the highest quartile were more likely to have poorer physical function (odds ration [OR] 18.75, p < .001). In multivariate analysis adjusting for age, stage, number of comorbidities, and body mass index, the association remained (OR 14.6, p = .002). CONCLUSION: Pre-chemotherapy biomarkers of aging are associated with poorer physical function among patients with breast cancer across the aging spectrum. The Oncologist 2017;22:1189-1196 IMPLICATIONS FOR PRACTICE: Commonly used physical function assessment tools may not reflect the diverse nature of physical function and risk for chemotherapy toxicity, particularly in older adults. No laboratory test reflects functional reserve. Pro-inflammatory and coagulation factors, such as IL-6, CRP, and D-dimer, can serve as biomarkers of aging and physical function; however, few studies have evaluated their utility in patients with cancer. This study was designed to understand the association between pre-chemotherapy biomarkers and physical function in women with early stage breast cancer undergoing adjuvant chemotherapy. Results indicate that elevated pre-chemotherapy levels in two of the three peripheral biomarkers are associated with the poorest physical function among patients with breast cancer across the aging spectrum.

The relationship between age, anxiety, and depression in older adults with cancer.

OBJECTIVE: In older men with prostate cancer, aging is associated with reduced anxiety and increased depression. The purpose of this study was to examine the association among age, anxiety, and depression in a cohort of older adults receiving chemotherapy. METHODS: This is a secondary analysis of a prospective longitudinal study investigating chemotherapy toxicity in older adults with cancer. Baseline data (pre-chemotherapy) included: age, sociodemographics, tumor and treatment factors, functional status, comorbidities, psychological state (measured by the Hospital Anxiety and Depression Scale), and social support. Univariate and multiple regression analyses were conducted to test the relationship between age, anxiety, and depression. RESULTS: The average age of the 500 patients (56% females) was 73.1. The majority had late stage disease: 22% Stage III and 61% stage IV. Clinically significant depression was reported in 12.6%. Clinically significant anxiety was reported in 20.9%. In univariate analyses, there was no association between anxiety and age, or depression and age. In multivariable analyses, older age (p=0.05) was associated with decreased anxiety, as well as lack of social support (p<0.01) and increased number of comorbidities (p<0.01). In multivariable analysis, depression was associated with lack of social support (p<0.01), increased number of comorbidities (p<0.01), and advanced stage (p<0.01). CONCLUSIONS: This study supports previous research that anxiety decreases with age in older adults with cancer. However, depression remained constant with increasing age. Greater resources and attention to identifying and treating the psychological sequelae of cancer in older adults are warranted.

Deseabilidad social, trastorno de conducta y callo emocional: estudio correlacional en adolescentes mexicanos / Social desirability, conduct disorder and callous- unemotional: a correlational study in Mexican adolescents / Desejabilidade social, desordem de conduta e insensibilidade emocional: um estudo correlacional em adolescentes mexicanos

El propósito principal de este estudio fue analizar la relación entre deseabilidad social (DS), el trastorno de conducta (TC) y el callo emocional (CE). En él participaron 150 adolescentes, entre los 13 y los 17 años (47% mujeres y 53% hombres), y se formaron dos grupos (con y sin probable TC). Se aplicó la escala de necesidad de aprobación social (ENAS), el cuestionario de detección del trastorno de conducta (CDTC), y el inventario de rasgos de insensibilidad emocional (IRIE). Se observó que el nivel de DS total resultó significativamente más bajo en el grupo con probable TC; también, una relación negativa baja entre la puntuación total del ENAS y las puntuaciones del CDTC, y negativas y moderadas con el IRIE. En conclusión se observó una relación negativa, aunque baja, entre la DS y el TC, y entre moderada y negativa con el CE. Las relaciones entre variables se modificaron en función de la edad y el género.

The main purpose of this study was to analyze the relationship between social desirability (SD), conduct disorder (CD) and callous unemotional (CU).. A total of 150 adolescents between 13 and 17 years of age (47% female and 53% male) participated in the study, and two groups were formed (with and without probable CD). The Need for Social Approval Scale (ENAS), the Conduct Disorder Screening Questionnaire (CDTC), and the Emotional Insensitivity Trait Inventory (IRIE) were applied. It was observed that the level of total SD was significantly lower in the group with probable CT; also, a low negative relationship between the ENAS total score and the CDTC scores, and negative and moderate ones with the IRIE. In conclusion, a negative, albeit low, relationship was observed between SD and CT, and moderate to negative with CE. The relationships between variables were modified by age and gender.

O objetivo principal deste estudo foi analisar a relação entre a desejabilidade social (SD), desordem de conduta (CD) e calo emocional (EC). Envolveu 150 adolescentes de 13-17 anos (47% mulheres e 53% homens), e foram formados dois grupos (com e sem provável CD). Foram administradas a Escala de Aprovação Social (ENAS), o Questionário de Avaliação de Distúrbios de Conduta (CDTC) e o Inventário de Traços de Insensibilidade Emocional (IRIE). Foi observado que o nível de SD total era significativamente menor no grupo com provável CD; também, uma relação negativa baixa entre a pontuação total do ENAS e a pontuação do CDTC, e relações negativas e negativas moderadas com o IRIE. Em conclusão, houve uma relação negativa, embora baixa, entre SD e CT, e moderada a negativa com CE. As relações entre as variáveis foram modificadas por idade e sexo.

Association between renal function and chemotherapy-related toxicity in older adults with cancer.

PURPOSE: To evaluate the association between renal function (RF) and chemotherapy-related toxicity (CRT) in older adults with cancer and to compare the effect of different RF formulas and body weight measurements on this association. METHODS: This is a secondary analysis of data from a prospective multicenter study of patients ≥ age 65 who were starting a new chemotherapy regimen. RF was estimated with 4 formulas (modified Jelliffe [Jelliffe], Cockcroft-Gault [CG], Wright, and Modification of Diet in Renal Disease [MDRD]), using actual, ideal and adjusted body weights for 492 patients. The association between baseline RF and grade 3-5 CRT was evaluated by unconditional logistic regression. RESULTS: As a continuous variable, decreased creatinine clearance (CrCl) calculated by CG with actual body weight was associated with increased odds of CRT (OR 1.12, P<0.01; 95% CI 1.04-1.20) indicating that on average for every 10mL/min decrease in CrCl the odds of CRT increased by 12%. Very low RF (in the lowest 10%) with all formulas (CG, Jelliffe, Wright and MDRD) was associated with increased odds for CRT. This association is independent of the type of chemotherapy received (those requiring dose adjustment for renal function vs not). Neither primary dose reduction nor chemotherapy duration was associated with CRT. Serum creatinine alone was not associated with increased odds of CRT (OR 0.67, P=0.15). CONCLUSIONS: Decreased RF is associated with increased odds of CRT and should be considered when assessing risk of CRT in older adults with cancer. Serum creatinine alone is not adequate for risk assessment.

Microbioma en los trastornos de la conducta alimentaria / Microbiome in eating disorders

Introducción: los trastornos de la conducta alimentaria (TCA) son enfermedades graves, con bases genéticas y neurobiológicas donde los principales sistemas afectados son el gastrointestinal y neurológico por lo cual el microbioma juega un papel importante. Objetivos: resumir los resultados de las últimas investigaciones en microbioma que pudieran ser futuras herramientas en el manejo de los TCA. Materiales y métodos: se realizó una búsqueda en PubMed sobre microbioma y TCA de publicaciones científicas de los últimos 10 años de estudios en humanos. Se incluyeron 10 estudios para una revisión tipo paraguas. Resultados: desde el descubrimiento del microbioma y su papel en el eje cerebro-intestinal se han realizado investigaciones que sugieren a los pre y probióticos como una herramienta útil en el manejo de diferentes enfermedades psiquiátricas a través de vías como nervio vago, liberación de metabolitos y neurotransmisores, y el sistema inmune asociados con síntomas presentados en anorexia. Conclusiones: los llamados psicobióticos, en referencia a probióticos que en cantidades adecuadas mejoran las funciones cognitivas, son una herramienta para el manejo de enfermedades psiquiátricas en las que los TCA pudieran ser beneficiados

Introduction: eating disorders are serious illnesses with genetic and neurobiological bases where the main organs affected are the gastrointestinal tract and the neurologic system making important the role of the microbiome. Objectives: summarize the results of the latest microbiome research that could be future tools in the management of eating disorders. Materials and methods: umbrella review of pubmed publications in humans of the last 10 years regarding microbiome and eating disorders.Results: since the discovery of the microbiome and the function on the cerebral-intestinal axis, through pathways such as vagal nerve, neurotransmitters and immune system, related to symptoms presented on anorexic patients. Conclusions: psychobiotics, live organisms that when ingested in adequate amounts produce health benefits in patients suffering from psychiatric illnesses are the new topic of future research in eating disorders

Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer.

PURPOSE: Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). PATIENTS AND METHODS: Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve. RESULTS: The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). CONCLUSION: This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.

Predictors of chemotherapy dose reduction at first cycle in patients age 65 years and older with solid tumors.

PURPOSE: Age-based reduction of chemotherapy dose with the first cycle (primary dose reduction, PDR) is not routinely guideline recommended. Few studies, however, have evaluated how frequently PDR is utilized in the treatment of older patients with cancer and which factors may be associated with this decision. METHODS: We conducted a secondary analysis of a multi-institutional prospective cohort study of patients age ≥65 years treated with chemotherapy. The dose and regimen were at the discretion of the treating oncologist. The prevalence of PDR and its association with treatment intent (palliative vs. curative), tumor type, patient characteristics (sociodemographics and geriatric assessment variables), and chemotherapy-associated toxicity were evaluated. RESULTS: Among 500 patients (mean age 73, range 65-91 years), 179 patients received curative intent chemotherapy and 321 patients received palliative intent chemotherapy, with PDR being more common in the latter sub-group (15% vs. 25%, p = 0.005). Increasing age was independently associated with PDR in both sub-groups. Comorbidity (prior cancer or liver/kidney disease) was independently associated with PDR in the palliative sub-group alone while Karnofsky Performance Status (KPS) was not associated with PDR in either subgroup. There was no significant difference in the rates of grades 3-5 toxicity, dose reductions, or delays with PDR. Patients in the palliative sub-group treated with PDR had higher rates of hospitalization compared to those treated with standard doses. CONCLUSION: PDR is more common in the palliative setting, but is also utilized among patients treated with curative intent. Factors associated with PDR include age and comorbid conditions, but not KPS.

Polypharmacy and potentially inappropriate medication use in older adults with cancer undergoing chemotherapy: effect on chemotherapy-related toxicity and hospitalization during treatment.

OBJECTIVES: To evaluate the prevalence of polypharmacy and potentially inappropriate medication (PIM) use and the association between these and chemotherapy-related adverse events in older adults with cancer undergoing chemotherapy. DESIGN: Secondary analysis of prospectively collected data. SETTING: Outpatient oncology clinics in seven academic medical centers. PARTICIPANTS: Adults aged 65 and older with cancer undergoing chemotherapy. MEASUREMENTS: Measures included number of daily medications (polypharmacy); PIM use based on three indices (Beers, Zhan, and Drugs to Avoid in the Elderly criteria), and use of six "high risk" medication classes for adverse drug events (anticoagulants, antiplatelet agents, opioids, insulin, oral hypoglycemics, antiarrhythmics). Using multivariate logistic regression, the relations were evaluated between these criteria and Grade 3 to 5 chemotherapy-related toxicity and between these criteria and hospitalization during chemotherapy. RESULTS: Participants (N=500; mean age 73, 61% Stage IV disease) took a mean of 5±4 daily medications (range 0-23). PIM use was common (up to 29% according to Beers criteria). No association was found between number of daily medications (reference 0-3 medications) and toxicity (4-9 medications, odds ratio (OR)=1.34, 95% confidence interval (CI)=0.92-1.97; ≥10 medications, OR=0.82, 95% CI=0.45-1.49) or hospitalization (≥4 medications, OR=1.34, 95% CI=0.82-2.18, P=.24). There was also no association between PIM use and toxicity (P=.93) or hospitalization (P=.98). No medication class was associated with either outcome. CONCLUSIONS: Polypharmacy and PIM use were common but were not associated with chemotherapy-related toxicity or hospitalization in older adults with cancer.