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Although frailty can arise in middle age, very few studies have investigated frailty before 65 years. Our objectives were to assess the prevalence of frailty parameters in middle-aged individuals and probe the association with future adverse events. We performed cross-sectional and longitudinal analyses of community-dwelling individuals aged 50 to 65 (n = 411, median age: 59.0) having undergone a multidomain geriatric assessment (2010–2015) in an outpatient clinic in the greater Paris area of France (SUCCEED cohort). The primary outcome was a composite measure of adverse events (non-accidental falls, fractures, unplanned hospitalizations, death), recorded in 2016/2017. Multivariable logistic regression models were built to identify independent predictors. Six frailty parameters were highly prevalent (> 20%): low activity (40.1%), exhaustion (31.3%), living alone (28.5%), balance impairment (26.8%), weakness (26.7%), and executive dysfunction (23.2%). Female sex (odds ratio: 2.67 [95% confidence interval: 1.17–6.11]), living alone (2.39 [1.32–4.33]), balance impairment (2.09 [1.16–3.78]), executive dysfunction (2.61, [1.18–5.77]), and exhaustion (2.98 [1.65–5.39]) were independent predictors of adverse events. Many frailty parameters are already altered in middle-aged individuals and are predictive of adverse health events. Our findings highlight a possible need for frailty screening and preventive programs targeting middle-aged individuals.

ATTRwt-CA occurs in elderly patients and leads to severe heart failure. The disease mechanism involves cardiac and extracardiac infiltration by amyloid fibrils. The objectives of this study are to describe the frailty phenotype in patients with ATTRwt-CA and to assess the associations between frailty parameters, the severity of cardiac involvement, and the course of amyloid disease. We used multidimensional geriatric tools to prospectively assess frailty in patients with ATTRwt-CA consulting (in 2018–2019) in the French National Reference Center for Cardiac Amyloidosis. We included 36 patients (35 males; median age: 82 years (76–86). A third of the patients were categorized as NYHA class III or IV, and 39% had an LVEF below 45%. The median serum NTproBNP was 3188 (1341–8883) pg/mL. The median duration of amyloidosis was 146 months (73–216). The frequency of frailty was 50% and 33% according to the physical frailty phenotype and the Short Emergency Geriatric Assessment questionnaire, respectively. Frailty affected a large number of domains, namely autonomy (69%), balance (58%), muscle weakness (74%), malnutrition (39%), dysexecutive syndrome (72%), and depression (49%). The severity of CA was significantly associated with many frailty parameters independently of age. Balance disorders and poor mobility were also significantly associated with a longer course of amyloid disease. Frailty is frequent in patients with ATTRwt-CA. Some frailty parameters were significantly associated with a longer course of amyloid disease and CA severity. Taking into account frailty in the assessment and management of ATTRwt should improve patients’ quality of life.

Background The expression of depressive symptoms in older people with cancer is heterogeneous because of specific features of age or cancer comorbidity. We aimed to identify depressive symptom profiles in this population and describe the associated features including survival. Materials and Methods Patients ≥70 years who were referred to geriatric oncology clinics were prospectively included in the ELCAPA study. In this subanalysis, depressive symptoms were used as indicators in a latent class analysis. Multinomial multivariable logistic regression and Cox models examined the association of each class with baseline characteristics and mortality. Results For the 847 complete‐case patients included (median age, 79 years; interquartile range, 76–84; women, 47.9%), we identified five depressive symptom classes: “no depression/somatic only” (38.8%), “no depression/pauci‐symptomatic” (26.4%), “severe depression” (20%), “mild depression” (11.8%), and “demoralization” (3%). Compared with the no depression/pauci‐symptomatic class, the no depression/somatic only and severe depression classes were characterized by more frequent comorbidities with poorer functional status and higher levels of inflammation. “Severe” and “mild” depression classes also featured poorer nutritional status, more medications, and more frequent falls. Severe depression was associated with poor social support, inpatient status, and increased risk of mortality at 1 year (adjusted hazard ratio, 1.62, 95% confidence interval, 1.06–2.48) and 3 years (adjusted hazard ratio, 1.49; 95% confidence interval, 1.06–2.10). Conclusion A data‐driven approach based on depressive symptoms identified five different depressive symptom profiles, including demoralization, in older patients with cancer. Severe depression was independently and substantially associated with poor survival. Implications for Practice Older patients with cancer present with distinct profiles of depressive symptomatology, including different severity levels of depression and the demoralization syndrome. Clinicians should use a systematic assessment of depressive symptoms to adequately highlight these distinct profiles. Geriatric and oncological features are differently associated with these profiles. For instance, severe depression was associated with more frequent comorbidities with poorer functional, poor nutritional status, polypharmacy, frequent falls, inpatient status and poor social support. Also, severe depression was independently and substantially associated with poor survival so that the identification and management of depression should be considered a high priority in this population.

Background Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. Results We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70–100) vs. 90% (60–100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04–1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12–1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1–3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38–1.26], p = 0.23). Conclusions In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 non-pregnant ITP women in a prospective, multicenter, observational cohort study. 131 pregnant ITP women were matched to 131 non-pregnant ITP women by history of splenectomy, ITP status (no response, response, complete response) and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite endpoint including bleeding events and/or severe thrombocytopenia (&lt;30x109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and non-pregnant ITP women (53.4 per 100 person-years [95%CI, 40.8-69.9] vs. 37.1 [27.5-50.0]; hazard ratio [HR], 1.35 [95%CI, 0.89-2.03], p=0.16). Pregnant ITP women were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95%CI, 1.41-5.23], p=0.003; HR, 2.01 [95%CI, 1.14-3.57], p=0.017, respectively). However, recurrence of severe bleeding events was not different between groups (p=0.4). Nineteen (14%) neonates showed NITP &lt;50´109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count &lt;50´109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95%CI, 1.72-17.89], p=0.004 and 4.07 [1.41-11.73], p=0.009). To conclude, ITP women do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling ITP women.