Validity of a self-administered G8 screening test for older patients with cancer.

INTRODUCTION: The Geriatric 8 (G8) is a brief cancer-specific tool which screens for patients who require a comprehensive geriatric assessment (CGA). The G8 test assesses patients on eight domains such as mobility, polypharmacy, age, and self-rated health. However, the current G8 requires a healthcare professional (nurse or physician) present to conduct the test, which limits its usefulness. The Self-G8 questionnaire (S-G8) is an adaptation of the original G8 test, assessing all the same domains, with questions modified to be appropriate for patients to self-complete. Our objective was to evaluate the performance of S-G8 compared to the G8 and CGA. MATERIALS AND METHODS: The initial S-G8 was designed by our team through review of the literature and questionnaire design principles, and was optimized through feedback from patients over the age of 70. The questionnaire subsequently underwent further refinement after undergoing pilot testing (N = 14). The diagnostic accuracy of the final iteration of the S-G8 was evaluated along with the standard G8 in a prospective cohort study (N = 52) in an academic geriatric oncology clinic at the Princess Margaret Cancer Centre, Toronto, Canada. Psychometric characteristics were evaluated including internal consistency, sensitivity, and specificity compared to the G8 and to the CGA. RESULTS: There was strong correlation between the G8 and S-G8 scores, with a Spearman correlation co-efficient of 0.76 (p < 0.001). Internal consistency was acceptable at 0.60. The frequency of abnormality (<14 score) for the G8 and S-G8 was 82.7% and 61.5%, respectively. The mean score for the original G8 and S-G8 was 11.9 and 13.5, respectively. The cut-off of 14 for the S-G8 yielded the best combination of sensitivity of 0.70 ± 0.07 and specificity of 0.78 ± 0.14 when compared to the G8. When compared to two or more abnormal domains on the CGA, the S-G8 performed at least as well as the G8 with a sensitivity of 0.77, specificity of 0.85, and a Youden's index of 0.62. DISCUSSION: The S-G8 questionnaire appears to be an acceptable alternative to the original G8 in identifying older adults with cancer who will benefit from a CGA. Large scale testing is warranted.

Autoantibody-mediated Macrophage Dysfunction in Patients with Severe Asthma with Airway Infections.

Rationale: Localized autoimmune responses have been reported in patients with severe eosinophilic asthma, characterized by eosinophil degranulation and airway infections. Objective: To determine the presence of autoantibodies against macrophage scavenger receptors within the airways and their effects on macrophage function and susceptibility to infection. Methods: Anti-EPX (eosinophil peroxidase), anti-MARCO (macrophage receptor with collagenous structure) IgG titers, and T1 and T2 (type 1/2) cytokines were measured in 221 sputa from 143 well-characterized patients with severe asthma. Peripheral monocytes and MDMs (monocyte-derived macrophages) isolated from healthy control subjects were treated with immunoprecipitated immunoglobulins from sputa with high anti-MARCO titers or nonspecific IgG to assess uptake of Streptococcus pneumoniae or response to the bacterial product LPS. Measurements and Main Results: Anti-MARCO IgG was detected in 36% of patients, with significantly higher titers (up to 1:16) in patients with mixed granulocytic sputa, indicative of airway infections. Multivariate regression analysis confirmed increased frequency of degranulation (free eosinophil granules), increased blood eosinophils (indicative of high T2 burden), increased sputum total cell count, peripheral blood leukocytes (indicative of infection), and lymphopenia were associated with increased anti-MARCO IgG titers; IL-15 (odds ratio [OR], 1.79; confidence interval [CI], 1.19-2.70), IL-13 (OR, 1.06; CI, 1.02-1.12), and IL-12p70 (OR, 3.34; CI, 1.32-8.40) were the associated cytokines. Patients with anti-MARCO antibodies had higher chances of subsequent infective versus eosinophilic exacerbations (P = 0.01). MDMs treated with immunoprecipitated immunoglobulins (anti-MARCO+ sputa) had reduced bacterial uptake by 39% ± 15% and significantly reduced release of IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.05) in response to an LPS stimulus. Conclusions: Autoantibodies against macrophage scavenger receptors in eosinophilic asthma airways may impede effective host defenses and lead to recurrent infective bronchitis.

Quality of care of consultations from the geriatric oncology clinic: "Are we addressing the needs of patients?"

INTRODUCTION: A comprehensive geriatric assessment (CGA) is recommended for older adults with cancer in the pre-treatment setting to optimize care. A CGA systematically evaluates multiple domains to develop a holistic view of the patient's health and facilitate timely interventions to ameliorate patient outcomes. For a CGA to be most effective, optimization of each abnormal domain should occur. However, there is limited literature exploring this issue. MATERIALS AND METHODS: Consultations of patients seen in a Geriatric Oncology clinic from June 2015 to June 2018 were reviewed. The percentage of "no recommendations made" in the consultation letter following the identification of impairment in each of eight geriatric domains was calculated. Trends over time were examined by stratifying the data into three periods ("Year 1", "Year 2", and "Year 3") and conducting a logistic regression analysis. RESULTS: A total of 365 consultation notes were reviewed. The patients were predominately older (mean age 79.9 years), male (66.9%), with genitourinary (38.6%) or gastrointestinal (23.3%) cancers. The most common stage was metastatic (40.6%). The most common treatment intent and modality were palliative (50.4%) and hormonal (50.9%), respectively. The geriatric domains that had the greatest frequency of impairments were medication optimization (76.2%), functional status (68.8%), and falls risk (64.9%). The domains that had the highest frequency of "no recommendations made" following identification of impairment were nutrition (39.8%), social support (39.5%), and mood (26.4%). The prevalence of "no recommendations made" decreased over time in social support (54.6% in Year 1 to 27.8% in Year 3, p = 0.043) and possibly nutrition (53.1% in Year 1 to 34.3% in Year 3, p = 0.088) but not for mood (p = 0.64). CONCLUSIONS: Nutrition, social supports and mood were the CGA domains with the highest proportion of "no recommendations made" following an identification of impairment. This is the first quality assurance study to identify social supports, mood, and nutrition domains as less frequently addressed following an identification of an impairment amongst older patients with cancer. Subsequent prospective research is required to understand reasons for these observations and identification of barriers to address these geriatric domains amongst older adults with cancer.

Hepatic Igf1-Deficiency Protects Against Atherosclerosis in Female Mice.

Atherosclerosis is the leading cause of cardiovascular disease (CVD), with distinct sex-specific pathogenic mechanisms that are poorly understood. Aging, a major independent risk factor for atherosclerosis, correlates with a decline in circulating insulin-like growth factor-1 (IGF-1). However, the precise effects of Igf1 on atherosclerosis remain unclear. In the present study, we assessed the essential role of hepatic Igf1, the major source of circulating IGF-1, in atherogenesis. We generated hepatic Igf1-deficient atherosclerosis-prone apolipoprotein E (ApoE)-null mice (L-Igf1-/-ApoE-/-) using the Cre-loxP system driven by the Albumin promoter. Starting at 6 weeks of age, these mice and their littermate controls, separated into male and female groups, were placed on an atherogenic diet for 18 to 19 weeks. We show that hepatic Igf1-deficiency led to atheroprotection with reduced plaque macrophages in females, without significant effects in males. This protection from atherosclerosis in females was associated with increased subcutaneous adiposity and with impaired lipolysis. Moreover, this impaired lipid homeostasis was associated with disrupted adipokine secretion with reduced circulating interleukin-6 (IL-6) levels. Together, our data show that endogenous hepatic Igf1 plays a sex-specific regulatory role in atherogenesis, potentially through athero-promoting effects of adipose tissue-derived IL-6 secretion. These data provide potential novel sex-specific mechanisms in the pathogenesis of atherosclerosis.