Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse transcription demonstrated a significant expression of AM mRNA in tumor samples from colorectal cancer (CRC) patients in clinical stage II, III, and IV when compared with normal colorectal tissue. AM, CLR, RAMP2, and RAMP3 proteins were immunohistochemically localized in the carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in lymph node and distant metastasis when compared with primary tumors. The human colon carcinoma cells HT-29 expressed and secreted AM into the culture medium with a significant increase under hypoxia. Treatment of HT-29 cells with synthetic AM stimulated cell proliferation and invasion in vitro. Incubation with anti-AM antibody (αAM), anti-AM receptors antibodies (αAMR), or AM antagonist AM22–52 inhibited significantly basal levels of proliferation of HT-29 cells, suggesting that AM may function as an autocrine growth factor for CRC cells. Treatment with αAM significantly suppressed the growth of HT-29 tumor xenografts in vivo. Histological examination of αAM-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial cells and pericytes, and increased tumor cell apoptosis. These findings highlight the potential importance of AM and its receptors in the progression of CRC and support the conclusion that αAM treatment inhibits tumor growth by suppression of angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic target.

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Background: Centenarians are known to be successful agers compared to other older adults.Objective: The objective of the present study was to compare coronavirus disease (COVID-19) symptoms and outcomes in centenarians and other residents living in nursing homes. Design-Setting-Subjects-Methods: A retrospective multicenter cohort study was conducted using data from 15 nursing homes in the Marseille area. Older residents with confirmed COVID-19 between March and June 2020 were enrolled. The clinical and biological characteristics, the treatment measures, and the outcomes in residents living in these nursing homes were collected from the medical records. Results: A total of 321 residents were diagnosed with COVID-19 including 12 centenarians. The median age was 101 years in centenarians and 89 years in other residents. The most common symptoms were asthenia and fever. Three centenarians (25%) experienced a worsening of pre-existing depression (vs. 5.5% of younger residents; p = 0.032). Mortality was significantly higher in centenarians than in younger residents (50% vs. 21.3%, respectively; p = 0.031). A quarter of the younger residents and only one centenarian were hospitalized. However, 33.3% of the centenarians received treatment within the context of home hospitalization. Conclusion: Worsening of pre-existing depression seems to be more frequent in centenarians with COVID-19 in nursing homes. This population had a higher mortality rate but a lower hospitalization rate than younger residents.

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Objectives To describe the clinical characteristics and management of residents in French nursing homes with suspected or confirmed coronavirus disease 2019 (COVID-19), and to determine the risk factors for COVID-19-related hospitalization and death in this population. Design A retrospective multicenter cohort study Setting and Participants Four hundred and eighty nursing home residents with suspected or confirmed COVID-19 between 1 March and 20 May 2020 were enrolled and followed until 2 June 2020 in 15 nursing homes in Marseille’s greater metropolitan area. Methods Demographic, clinical, laboratory, treatment type, and clinical outcome data were collected from patients’ medical records. Multivariable analyses were used to determine factors associated with COVID-19-related hospitalization and death. For the former, the competing risk analysis - based on Fine and Gray’s model - took death into account. Results 480 residents were included. Median age was 88 years (IQR 80-93), and 330 residents were women. A total of 371 residents were symptomatic (77.3%), the most common symptoms being asthenia (47.9%), fever or hypothermia (48.1%), and dyspnea (35.6%). One hundred and twenty-three patients (25.6%) were hospitalized and 96 (20%) died. Male gender (sHR 1.63, 95% CI 1.12-2.35), diabetes (sHR 1.69, 95% CI 1.15-2.50), an altered level of consciousness (sHR 2.36, 95% CI 1.40-3.98), and dyspnea (sHR 1.69, 95% CI 1.09-2.62) were all associated with a greater risk of COVID-19-related hospitalization. Male gender (OR 6.63, 95% CI 1.04-42.39), thermal dysregulation (OR 2.64, 95% CI 1.60-4.38), falls (2.21 95% CI 1.02-4.75), and being aged >85 years old (OR 2.36 95% CI 1.32-4.24) were all associated with increased COVID-19-related mortality risk, whereas polymedication (OR 0.46, 95% CI 0.27-0.77) and preventive anticoagulation (OR 0.46, 95% CI 0.27-0.79) were protective prognostic factors. Conclusions and Implications Male gender, being aged >85 years old, diabetes, dyspnea, thermal dysregulation, an altered level of consciousness, and falls, must all be considered when identifying and protecting nursing home residents who are at greatest risk of COVID-19-related hospitalization and death.