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Patrick Manckoundia,1 Amadou Konaté,2 Arthur Hacquin,1 Valentine Nuss,1 Anca-Maria Mihai,1 Jérémie Vovelle,1 Mélanie Dipanda,1 Sophie Putot,1 Jérémy Barben,1 Alain Putot1 1“Pôle Personnes Âgées”, Hospital of Champmaillot, University Hospital of Dijon Burgundy, Dijon, France; 2Unit of Diagnosis and Rapid Orientation (DIAGORA), Internal Medicine Department, Hospital of Saint-Eloi, University Hospital of Montpellier, Montpellier, FranceCorrespondence: Patrick Manckoundia Service de Médecine Interne GériatrieHôpital de Champmaillot CHU, 2, Rue Jules Violle, Dijon Cedex 21079, FranceTel + 333 80 29 39 70Fax + 333 80 29 36 21Email patrick.manckoundia@chu-dijon.frAbstract: Iron is involved in many types of metabolism, including oxygen transport in hemoglobin. Iron deficiency (ID), ie a decrease in circulating iron, can have severe consequences. We provide an update on iron metabolism and ID, highlighting the particularities in older adults (OAs). There are three iron compartments in the human body: 1) the functional compartment, which consists of heme proteins including hemoglobin, myoglobin and respiratory enzymes; 2) iron reserves (IR), which consist mainly of liver stocks and are stored as ferritin; and 3) transferrin. There are two types of ID. Absolute ID is characterized by a decrease in IR. Its main pathophysiological mechanism is bleeding, which is often digestive and can be due to neoplasia, frequent in OAs. Biological assessment shows low serum ferritin and transferrin saturation (TS) levels. Furthermore, hypochromic microcytic anemia is frequent, and the serum-soluble transferrin receptor (sTfR) level is high. Functional ID, in which IR are high or normal, is due to inflammation, which is also frequent in OAs, particularly in its chronic form. Biological assessments show high serum ferritin, normal or low TS, and normal sTfR levels. Moreover, C-reactive protein is elevated, and there is moderate non-regenerative non-macrocytic anemia. The main characteristics of iron metabolism anomalies in the elderly are the high frequency of ID (20% of ID with anemia in adults ≥ 85 years) and the severity of its consequences, which include cognitive impairment in case of ID or iron overload and decrease of physical activity in case of ID. In conclusion, causes of ID are frequently intertwined in OAs as a result of the polymorbidity that characterizes them. ID can have dramatic consequences, especially in frail OAs. Thus, measuring the appropriate biological markers prevents errors in the positive diagnosis of ID type, clarifies etiology, and informs treatment-related decision-making.Keywords: anemia, iron deficiency, iron metabolism, older adults

Abstract Both underweight and obesity have been associated with poor prognosis in COVID-19. In an older populations of patients hospitalized for SARS-CoV-2 infection, we aimed to evaluate the association between body mass index (BMI) and short and long-term prognosis. Among 434 consecutive patients aged ≥ 70 years and hospitalized for suspected COVID-19 at a university hospital, 219 patients (median age of 83 years, 53% male) testing positive for COVID-19 and for whom BMI was recorded at admission, agreed to participate. Among them, 39 had a BMI

Objectives: To assess health-related quality of life (QoL) in caregivers of elderly patients with chronic disabilities receiving, or not receiving, social worker support.Methods: This multicenter open-label randomized study assigned caregivers to receive an information booklet, exclusively, or with social worker support. Caregivers completed Short Form-36 (SF-36) and Hospital Anxiety Depression Scale quarterly, and Zarit Burden Interview each semester, for 24 months. We reported caregiver QoL mean changes at 12 and 24 months (M12, M24). Longitudinal QoL analysis up to M24 used mixed models for repeated measures (MMRM).Results: Among the 179 caregivers randomized from 2015 to 2019, the SF-36 physical and mental component summary showed no significant changes at M12 and M24, in terms of neither anxiety nor burden. However, depression significantly increased (M12: 1.4 ± 4.0; M24: 1.7 ± 4.1) with significant adjusted mean increase using MMRM at M24: 3.4 [0.6–2.5] in the control group, exclusively.Conclusion: These findings call for better recognition of the social support to prevent caregiver QoL deterioration and alleviate their depression early in the course of the disease.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT02626377.

IntroductionThe impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC).MethodsTo determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints.ResultsNo global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden.DiscussionThese results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Abstract Aims Recent guidelines recommend a systolic blood pressure (SBP) target below 130 mmHg in heart failure patients with preserved ejection fraction (HFpEF), whatever their age. We investigated whether this intensive SBP control was associated with better survival in very old adults hospitalized for acute HFpEF. Methods and results We conducted an observational study in an acute geriatric unit: all consecutive patients discharged from hospital for acute heart failure from 1 March 2019 to 29 February 2020 with a diagnosis of HFpEF were included. Re‐hospitalization and all‐cause mortality at 1 year were compared according to the mean SBP at discharge (patients with a mean SBP

(1) Anemia often predisposes older patients to type 2 myocardial infarction (T2MI). However, the management of this frequent association remains uncertain. We aimed to evaluate the impact of red blood cell transfusion during the acute phase of T2MI in older anemic inpatients. (2) Methods and results: We performed a retrospective study using a French regional database. One hundred and seventy-eight patients aged 65 years or older, presenting with a T2MI and anemia, were selected. Patients were split into two groups: one that received a red blood cell transfusion (≥1 red blood cell unit) and one that did not. A propensity score was built to adjust for potential confounders, and the association between transfusion and 30-day mortality was evaluated with an inverse propensity score weighted Cox model. Transfusion was not associated with 30-day all-cause mortality (propensity score weighted hazard ratio (HR) 1.59 (0.55–4.56), p = 0.38). However, 1-year all-cause mortality was significantly higher in the transfusion group (propensity score weighted HR 2.47 (1.22–4.97), p = 0.011). (3) Conclusion: Our findings in older adults with anemia suggest that blood transfusion in the acute phase of T2MI could not be associated with improved short-term prognosis. Prospective studies are urgently needed to assess the impact of transfusion on longer-term prognosis.

Lymphoid neoplasms are a heterogeneous group of lymphoid neoplastic diseases with multiple presentations, and varying prognoses. They are especially frequent in older patients (OPs) and the atypism of this frail elderly population can make the diagnostic process even more difficult. Blood lymphocyte immunophenotyping (BLI) is essential in rapid noninvasive diagnosis orientation and guides complementary investigations. To our knowledge, BLI prescription has never been evaluated in OPs. We hypothesized that, when there is a suspicion of lymphoid neoplasm in the geriatric population, a BLI is performed in view of various clinical or biological abnormalities. This study aimed to: (1) describe the characteristics of hospitalized OPs having undergone BLI for suspected lymphoid neoplasm, (2) identify the causes leading to BLI prescription, and (3) identify the most profitable criteria for BLI prescription. This was a descriptive retrospective study on 151 OPs aged ≥75 years who underwent BLI over a 2-year period. Regarding BLI prescriptions, eight had lymphocytosis, constituting the “lymphocytosis group” (LG+), while the 143 others had BLI prescribed for reasons other than lymphocytosis (LG−), mainly general weakness and anemia. In the LG−, we compared OPs with positive and negative BLI results. The criteria found to be profitable for BLI prescription were lymphadenopathy, splenomegaly, lymphocytosis, and thrombocytopenia. BLI identified circulating lymphoid neoplasms (positive BLI) in 21/151 OPs, mainly marginal zone lymphoma and chronic lymphocytic leukemia. In polymorbid OPs, as per our study population, the diagnostic and therapeutic complexity explained in part the sole use of indirect and minimally invasive diagnostic techniques such as BLI.

Abstract Background Frailty is highly prevalent in elderly people. While significant progress has been made to understand its pathogenesis process, few validated questionnaire exist to assess the multidimensional concept of frailty and to detect people frail or at risk to become frail. The objectives of this study were to construct and validate a new frailty-screening instrument named Frailty Groupe Iso-Ressource Evaluation (FRAGIRE) that accurately predicts the risk for frailty in older adults. Methods A prospective multicenter recruitment of the elderly patients was undertaken in France. The subjects were classified into financially-helped group (FH, with financial assistance) and non-financially helped group (NFH, without any financial assistance), considering FH subjects are more frail than the NFH group and thus representing an acceptable surrogate population for frailty. Psychometric properties of the FRAGIRE grid were assessed including discrimination between the FH and NFH groups. Items reduction was made according to statistical analyses and experts’ point of view. The association between items response and tests with “help requested status” was assessed in univariate and multivariate unconditional logistic regression analyses and a prognostic score to become frail was finally proposed for each subject. Results Between May 2013 and July 2013, 385 subjects were included: 338 (88%) in the FH group and 47 (12%) in the NFH group. The initial FRAGIRE grid included 65 items. After conducting the item selection, the final grid of the FRAGIRE was reduced to 19 items. The final grid showed fair discrimination ability to predict frailty (area under the curve (AUC) = 0.85) and good calibration (Hosmer-Lemeshow P-value = 0.580), reflecting a good agreement between the prediction by the final model and actual observation. The Cronbach's alpha for the developed tool scored as high as 0.69 (95% Confidence Interval: 0.64 to 0.74). The final prognostic score was excellent, with an AUC of 0.756. Moreover, it facilitated significant separation of patients into individuals requesting for help from others (P-value

Objective. To describe the demographic characteristics, socio-economic status, functional status (autonomy, strength), and health status (cognitive and thymic functions, cardiovascular risk factors, and nutritional status) of the oldest olds living on the Greek island of Ikaria. We also try to explain the longevity observed in this population. Methods. A cross-sectional observational study of people aged 90 and over living in both municipalities of north-western Ikaria (Evdilos and Raches) was conducted over one year, from October 21, 2012 to October 21, 2013. The participants were interviewed (medical history), had a brief clinical examination, and underwent standardized geriatric assessments including the Geriatric Depression Scale (GDS-15), the Mini-Mental-State Examination (MMSE), the Activities of Daily Living (ADL), the Instrumental ADL (IADL), and an assessment of grip strength. Results. Seventy-one persons (37 females, 34 males), aged 94.1 years on average, were interviewed at their homes. Seven percent were current smokers (females 5.4%, males 8.8%). Hypertension was diagnosed in 70.4% of participants, diabetes in 19.7%, hypercholesterolemia in 12.7%, and obesity in 17.2%; 66.0% of the population had one chronic disease or more. The mean score for the GDS-15 scale was 3.7/15.0, 23.7/30.0 for the MMSE, 4.0/6.0 for the ADL, and 4.2/8.0 in females and 3.6/5.0 in males for the IADL. Grip strength was 17.0 kg in females and 26.5 kg in males. Conclusions. This study provides an overview of the socio-demographic and medical characteristics of the oldest olds living in a longevity Blue Zone.

An 84-year-old man presented to the emergency department for acute vomiting associated with rotational vertigo and a sudden right sensorineural hearing loss. A left peripheral vestibular nystagmus was highlighted. The patient was afebrile, without respiratory signs or symptoms. Blood sampling at admission showed lymphopenia, thrombopenia and neutrophil polynucleosis, without elevation of C reactive protein. Cerebral magnetic resonance imaging eliminated a neurovascular origin. Vestibule, right semicircular canals and cochlear FLAIR hypersignals were highlighted, leading to the diagnosis of right labyrinthitis. A nasopharyngeal swab sampled at admission returned positive for SARS CoV2 by polymerase chain reaction. The etiologic investigation, including syphilitic and viral research, was otherwise negative. An oral corticotherapy (prednisone 70 mg daily) was introduced, followed by a progressive clinical recovery. Although acute otitis media have already been highlighted as an unusual presentation of COVID-19, radiology-proven labyrinthitis had to our knowledge, never been described to date.

In older patients, urinary tract infection (UTI) often has an atypical clinical presentation, making its diagnosis difficult. We aimed to describe the clinical presentation in older inpatients with UTI-related bacteremia and to determine the prognostic impact of atypical presentation. This cohort study included all consecutive patients older than 75 years hospitalized in a university hospital in 2019 with a UTI-related gram-negative bacillus (GNB) bacteremia, defined by blood and urine cultures positive for the same GNB, and followed up for 90 days. Patients with typical symptoms of UTI were compared to patients with atypical forms. Among 3865 inpatients over 75 with GNB-positive urine culture over the inclusion period, 105 patients (2.7%) with bacteremic UTI were included (mean age 85.3 ± 5.9, 61.9% female). Among them, UTI symptoms were reported in only 38 patients (36.2%) and 44 patients (41.9%) had no fever on initial management. Initial diagnosis of UTI was made in only 58% of patient. Mortality at 90 days was 23.6%. After adjustment for confounders, hyperthermia (HR = 0.37; IC95 (0.14–0.97)) and early UTI diagnosis (HR = 0.35; IC95 (0.13–0.94)) were associated with lower mortality, while UTI symptoms were not associated with prognosis. In conclusion, only one third of older patients with UTI developing bacteremia had UTI symptoms. However, early UTI diagnosis was associated with better survival.

We assessed the prescriptions of patients hospitalized in a geriatric unit and subsequently discharged. This prospective and observational study was conducted over a two-month period in the geriatrics department (acute and rehabilitation units) of a university hospital. Patients discharged from this department were included over a two-month period. Prescriptions were analyzed at admission and discharge from the geriatrics department (DGD), and six weeks after DGD. We included 209 patients, 63% female, aged 86.8 years. The mean number of medications prescribed was significantly higher at DGD than at admission (7.8 vs. 7.1, p = 0.003). During hospitalization, 1217 prescriptions were changed (average 5.8 medications/patient): 52.8% were initiations, 39.3% were discontinuations, and 7.9% were dose adjustments. A total of 156 of the 209 patients initially enrolled completed the study. Among these patients, 81 (51.9%) had the same prescriptions six weeks after DGD. In univariate analysis, medications were changed more frequently in patients with cognitive impairment (p = 0.04) and in patients for whom the hospital report did not indicate in-hospital modifications (p = 0.007). Multivariate analysis found that six weeks after DGD, there were significantly more drug changes for patients for whom there were changes in prescription during hospitalization (p < 0.001). A total of 169 medications were changed (mean number of medications changed per patient: 1.1): 52.7% discontinuations, 34.3% initiations, and 13% dosage modifications. The drug regimens were often changed during hospitalization in the geriatrics department, and a majority of these changes were maintained six weeks after DGD. Improvements in patient adherence and hospital-general practitioner communication are necessary to promote continuity of care and to optimize patient supervision after hospital discharge.

Influenza remains a major cause of illness and death in geriatric populations. While the influenza vaccine has successfully reduced morbidity and mortality, its effectiveness is suspected to decrease with age. The aim of this study was to assess the impact of influenza vaccination on all-cause mortality in very old ambulatory subjects. We conducted a prospective cohort study from 1 July 2016 to 31 June 2017 in a large unselected ambulatory population aged over 80 years. We compared all-cause mortality in vaccinated versus unvaccinated subjects after propensity-score matching, to control for age, sex and comorbidities. Among the 9149 patients included, with mean age 86 years, 4380 (47.9%) were vaccinated against influenza. In total, 5253 (57.4%) had at least one chronic disease. The most commonly vaccinated patients were those with chronic respiratory failure (76.3%) and the least commonly vaccinated were those suffering from Parkinson’s disease (28.5%). Overall, 2084 patients (22.8%) died during the study. After propensity score matching, the mortality was evaluated at 20.9% in the vaccinated group and 23.9% in the unvaccinated group (OR = 0.84 [0.75–0.93], p = 0.001). This decrease in mortality in the vaccinated group persisted whatever the age and Charlson Comorbidity index. In conclusion, nearly a half of this ambulatory elderly population received Influenza vaccine. After adjustment on comorbidities, influenza vaccination was associated with a significant decrease in all-cause mortality, even in the eldest multimorbid population. Improving immunization coverage in this frail older population is urgently needed.

In 2015, a major increase in incident hospital-onset Clostridioides difficile infections (HO-CDI) in a geriatric university hospital led to the implementation of a diagnosis-centered antibiotic stewardship program (ASP). We aimed to evaluate the impact of the ASP on antibiotic consumption and on HO-CDI incidence. The intervention was the arrival of a full-time infectiologist in the acute geriatric unit in May 2015, followed by the implementation of new diagnostic procedures for infections associated with an antibiotic withdrawal policy. Between 2015 and 2018, the ASP was associated with a major reduction in diagnoses for inpatients (23% to 13% for pneumonia, 24% to 13% for urinary tract infection), while median hospital stays and mortality rates remained stable. The reduction in diagnosed bacterial infections was associated with a 45% decrease in antibiotic consumption in the acute geriatric unit. HO-CDI incidence also decreased dramatically from 1.4‰ bed-days to 0.8‰ bed-days in the geriatric rehabilitation unit. The ASP focused on reducing the overdiagnosis of bacterial infections in the acute geriatric unit was successfully associated with both a reduction in antibiotic use and a clear reduction in the incidence of HO-CDI in the geriatric rehabilitation unit.

Acute infection is a frequent trigger of myocardial infarction (MI). However, whether percutaneous coronary intervention (PCI) improves post-infectious MI prognosis is a major but unsolved issue. In this prospective multicenter study from coronary care units, we performed propensity score-matched analysis to compare outcomes in patients with and without PCI for post-infectious MI with angiography-proven significant coronary stenosis (>50%). Among 4573 consecutive MI patients, 476 patients (10%) had a concurrent diagnosis of acute infection at admission, of whom 375 underwent coronary angiography and 321 patients had significant stenosis. Among the 321 patients, 195 underwent PCI. Before the matching procedure, patients without PCI had a similar age and sex ratio but a higher rate of risk factors (hypertension, diabetes, chronic renal failure, and prior coronary artery disease), pneumonia, and SYNTAX score than patients without PCI. After propensity score matching, neither in-hospital mortality (13% with PCI vs. 8% without PCI; p = 0.4) nor one-year mortality (24% with PCI vs. 19% without PCI, p = 0.5) significantly differed between the two groups. In this first prospective cohort of post-infectious MI in coronary care units, PCI might not improve short- and long-term prognosis in patients with angiography-proven significant coronary stenosis. If confirmed, these results do not argue for systematic invasive procedures after post-infectious MI.

Acute infection is suspected of involvement in the onset of acute myocardial infarction (MI). We aimed to assess the incidence, pathogenesis and prognosis of post-infectious MI. All consecutive patients hospitalized for an acute MI in coronary care units were prospectively included. Post-infectious MI was defined by a concurrent diagnosis of acute infection at admission. Type 1 MI (acute plaque disruption) or Type 2 MI (imbalance in oxygen supply/demand) were adjudicated according to the universal definition of MI. From the 4573 patients admitted for acute MI, 466 (10%) had a concurrent acute infection (median age 78 (66−85) y, 60% male), of whom 313 (67%) had a respiratory tract infection. Type 2 MI was identified in 72% of post-infectious MI. Compared with other MI, post-infectious MI had a worse in-hospital outcome (11 vs. 6% mortality, p < 0.01), mostly from cardiovascular causes. After adjusting for confounders, acute infections were no more associated with mortality (odds ratio 0.72; 95% confidence interval 0.43−1.20). In the group of post-infectious MI, Type 1 MI and respiratory tract infection were associated with a worse prognosis (respective odds ratio 2.44; 95% confidence interval: 1.12−5.29, and 2.89; 1.19−6.99). In this large MI survey, post-infectious MI was common, accounting for 10% of all MI, and doubled in-hospital mortality. Respiratory tract infection and Type 1 post-infectious MI were associated with a worse prognosis.

Neuroleptics may cause side effects, some of which are little known. We describe here a case of gastric dilation related to treatment with a neuroleptic in an elderly man. To our knowledge, such a case has never been reported in the literature. A 76-year-old man, living in a nursing home, was hospitalized for general weakness and abdominal pain. He had dementia with behavioral disorders treated with cyamemazine, a sedative and anxiolytic neuroleptic. Given a clinical suspicion of intestinal occlusion, an abdominopelvic computerized tomography scan was performed before the patient was admitted to our hospital. This computerized tomography scan did not show intestinal occlusion and there was no mention of gastric dilation in the computerized tomography scan report. Thus, acute gastroenteritis was suspected. The usual medications were stopped and symptomatic treatment for gastroenteritis was started. Quickly, his clinical state and biological parameters returned to normal and his usual treatment, including cyamemazine, was started again. The next day, the digestive symptoms, except for obstipation, reappeared. The abdominal X-ray showed gastric dilation without intestinal occlusion. The neuroleptic was stopped again and symptoms vanished the next day. This report underlines all of the necessary precautions and surveillance around drug prescription, especially in elderly persons.

Thrombosis due to heparin-induced thrombocytopenia (HIT) is rare but has a severe prognosis. Its management is not always easy, particularly in old patients with renal insufficiency. A 95-year-old woman was hospitalized for dyspnea. Curative treatment with unfractionated heparin was started because pulmonary embolism was suspected. Disseminated intravascular coagulation was then suspected because of thrombocytopenia, hypoprothrombinemia, hypofibrinogenemia, and a positive ethanol gelation test. The first immunoassay for HIT was negative. On the 12th day of hospitalization, bilateral cyanosis of the toes occurred associated with recent deep bilateral venous and arterial thrombosis at duplex ultrasound. New biological tests confirmed HIT and led us to stop heparin and to start argatroban with a positive clinical and biological evolution. Venous and arterial thrombosis associated with thrombocytopenia during heparin treatment must be considered HIT whatever the biological test results are. Argatroban is a good alternative treatment in the elderly.

Randall disease is an unusual cause of extraocular motor nerve (VI) palsy. A 35-year-old woman was hospitalized for sicca syndrome. The physical examination showed general weakness, weight loss, diplopia related to a left VIth nerve palsy, hypertrophy of the submandibular salivary glands, and peripheral neuropathy. The biological screening revealed renal insufficiency, serum monoclonal kappa light chain immunoglobulin, urinary monoclonal kappa light chain immunoglobulin, albuminuria, and Bence-Jones proteinuria. Bone marrow biopsy revealed medullar plasma cell infiltration. Immunofixation associated with electron microscopy analysis of the salivary glands showed deposits of kappa light chains. Randall disease was diagnosed. The patient received high-dose melphalan followed by autostem cell transplantation which led to rapid remission. Indeed, at the 2-month followup assessment, the submandibular salivary gland hypertrophy and renal insufficiency had disappeared, and the peripheral neuropathy, proteinuria, and serum monoclonal light chain had decreased significantly. The persistent diplopia was treated with nerve decompression surgery of the left extraocular motor nerve. Cranial nerve complications of Randall disease deserve to be recognized.