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Objective: We conducted a cross-sectional survey in France in a cohort over 55 years of age to characterize the impact of psychological dimensions on quality-of-life (QoL). Methods: The predictors of QoL in relation with aging were studied using an adapted quality-of-life model, based on emotional, cognitive and physical symptoms, functional status, and general health perception. Adding psychological dimensions such as self-esteem, psychological distress, perceptions of ageing and coping, was hypothesized to improve the QoL model. Responses were analyzed using structural equation modeling and path analysis. Results: The study involved 258 participants, mean age 66.9±7.9 years. Psychological distress and positive perception of aging exhibited the strongest direct impact on QoL (p<0.0001). Psychological distress also appeared to be mediator on QoL for perceived health status, self-esteem and negative perception of aging. Coping centred on emotion exhibited direct impact on self-esteem and so, indirect impact on QoL (p = 0.0002). Perception of personal financial situation (p = 0.0007) and coping centred on social support (p = 0.02) appeared as direct mediators influencing QoL. Conclusions: Psychological dimensions are predictors of QOL and have to be taken into account to maximize the resources with a view to successful aging. Further interventions targeting successful aging should focus on positive perception aging. [ABSTRACT FROM AUTHOR]

Simple Summary: Iron deficiency is common in individuals with cancer. The aim of our study was to determine whether iron deficiency is associated with survival in older patients with solid tumors. We found that iron deficiency in the absence of anemia is associated with better survival. However, when combined with anemia, iron deficiency is associated with increased mortality. This study questions the value of iron supplementation therapy in older patients with cancer. Background: iron deficiency (ID) is frequent in older patients. Purpose: to evaluate the association between ID and survival in patients ≥ 75 years old with confirmed solid tumors. Methods: a retrospective monocentric study including patients between 2009 and 2018. ID, absolute ID (AID) and functional ID (FID) were defined according to the European Society for Medical Oncology (ESMO) criteria. Severe ID was defined by a ferritin level < 30 µg/L. Results: in total, 556 patients were included, the mean age was 82 (±4.6) years, 56% were male, the most frequent cancer was colon cancer (19%, n = 104), and metastatic cancers were found in 38% (n = 211). Median follow-up time: 484 [190–1377] days. In anemic patients, ID and FID were independently associated with an increased risk of mortality (respectively, HR 1.51; p = 0.0065 and HR 1.73; p = 0.0007). In non-anemic patients, FID was independently associated with better survival (HR 0.65; p = 0.0495). Conclusion: in our study, ID was significantly associated with survival, and with better survival for patients without anemia. These results suggest that attention should be paid to the iron status in older patients with tumors and raise questions about the prognostic value of iron supplementation for iron-deficient patients without anemia. [ABSTRACT FROM AUTHOR]

Background: In a context of change in the demographic profile of the older population, to identify an age threshold for increased risk and burden of herpes zoster (HZ) in 70+ patients. Methods: Post hoc analysis of the 12-month French nationwide prospective observational ARIZONA cohort study. HZ was assessed by means of the following validated questionnaires: Neuropathic Pain Symptom Inventory (NPSI), Zoster Brief Pain Inventory (ZBPI), Short-Form health survey (SF-12), and Hospital Anxiety and Depression Scale (HADS). Results: 644 general practitioners included 1,358 volunteer patients with acute HZ in the ARIZONA study; 609 patients (45%) were 70+. In 70+ patients, age did not increase rash severity or HZ-related pain intensity at diagnosis, but increased by 64% the frequency of ophthalmic zoster (from 5.5% in 70–74 years age-group to 9.0% in 85+ patients, p = NS). Age was significantly associated with low physical health as assessed by the SF-12 Physical Component Summary (SF-12 PCS) score and bad mood as assessed by the HADS depression score (p < 0.001). Within the year following HZ, post-herpetic neuralgia (PHN) was systematically but not significantly more frequent in 85+ patients than in the 70–74, 75–79, or 80–84 years age-groups (19.0% vs. 13.3%/15.3%/11.6% at month 3; 15.1% vs. 7.3%/11.0%/12.2% at month 6; 15.2% vs. 6.0%/8.0%/6.0% at month 12, respectively). SF-12 PCS and HADS depression scores improved from day 0 to month 12 in all patients (p < 0.001). 85+ patients were more impaired than younger patients (p < 0.001), but without clear difference according to PHN. Conclusions: This study did not show in 70+ patients a clear and significant age threshold at which disease burden increased, although for some domains the impact seemed higher among the oldest patients; the cut-off of 70 years remains thus relevant for clinical and epidemiological studies. However, at individual level, assessment of the burden of HZ and HZ-related pain appears necessary to improve management and prevent functional decline in the most vulnerable 70+ patients. [ABSTRACT FROM AUTHOR]

Background: The control of translation, involving the kinases mTOR (mammalian target of rapamycin) and PKR (double-stranded RNA-dependent protein kinase), modulates cell survival and death and is altered in the brains of patients with Alzheimer’s disease (AD). In AD increased susceptibility of lymphocytes to apoptosis has been reported. Methods: We investigated the level of the kinases mTOR and PKR and the eukaryotic initiation factor 2α (eIF2α) in lymphocytes of patients with AD in comparison with controls. In AD patients we also looked for a correlation between activated proteins and cognitive and memory tests. Results: We report significant alterations of the levels of these kinases and eIF2α in lymphocytes of AD patients that were also significantly correlated with cognitive and memory test scores. Conclusion: These results suggest that the levels of mTOR, PKR and eIF2α in lymphocytes could follow the cognitive decline in AD. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We conducted a prospective study in a long-term care facility. Virologic diagnosis was assessed using viral isolation, polymerase chain reaction and serology for all patients with a flu-like syndrome. Albumin, vitamins and trace elements were also measured. Results. The risk of influenza increased 6.5-fold in patients with an antibody titer of 40 during the influenza outbreak ( P =0.04). Micronutriments and vitamins deficiencies were important. Patients with antibody titer >1:40 could still be infected by the virus without correlation with the nutritional status. Conclusion. Humoral protection with a titer >1:40 might not be protective in the elderly. Nutritional deficiencies were too prevalent to detect any effect on the results. [ABSTRACT FROM AUTHOR]

Since the prognosis of localized amyloidosis remains unclear, we conducted a survey to define the characteristics and the course of this disease. The charts of 35 patients with either laryngeal (14 patients), tracheobronchial (10 patients), colonic (1 patient), or lower urinary tract amyloidosis (10 patients) were analyzed. The average age at diagnosis was 52.7 ± 12 years (range 33–73 years). The amyloid protein type was specified to be amyloid light chain (AL) in 15 cases. All patients had undergone additional biopsies (accessory salivary glands, rectal, fat pad and bone marrow aspirates) to rule out a systemic disease. Symptomatic treatments included endoscopic excision and laser therapy. Colchicine and chemotherapy with prednisone and melphalan were prescribed with limited success. During a mean follow-up period of 6.1 ± 5.3 years no patient developed a systemic form of amyloidosis. Six deaths were reported, one related to the disease because of a fatal airway hemorrhage. We suggest that immunolabeling studies should be more routinely performed. There was no risk of developing a systemic disease from local amyloid deposits in our survey. However, local evolution can be life-threatening. Such patients should be referred to specialist centers for further evaluation. Management requires close follow-up to exclude recurrence and to determine the appropriate symptomatic treatment. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease, neuropathological hallmarks include the accumulation ofβ-amyloid peptides (Aβ) in senile plaques, phosphorylated tau in neurofibrillary tangles and neuronal death. Aβ is the major aetiological agent according to the amyloid cascade hypothesis. Translational control includes phosphorylation of the kinases mammalian target of rapamycin (mTOR) and p70S6k which modulate cell growth, proliferation and autophagy. It is mainly part of an anti-apoptotic cellular signalling. In this study, we analysed modifications of mTOR/p70S6k signalling in cellular and transgenic models of Alzheimer's disease, as well as in lymphocytes of patients and control individuals. Aβ 1–42 produced a rapid and persistent down-regulation of mTOR/p70S6k phosphorylation in murine neuroblastoma cells associated with caspase 3 activation. Using western blottings, we found that phosphorylated forms of mTOR and p70S6k are decreased in the cortex but not in the cerebellum (devoid of plaques) of double APP/PS1 transgenic mice compared with control mice. These results were confirmed by immunohistochemical methods. Finally, the expression of phosphorylated p70S6k was significantly reduced in lymphocytes of Alzheimer's patients, and levels of phosphorylated p70S6k were statistically correlated with Mini Mental Status Examination (MMSE) scores. Taken together, these findings demonstrate that the mainly anti-apoptotic mTOR/p70S6k signalling is altered in cellular and transgenic models of Alzheimer's disease and in peripheral cells of patients, and could contribute to the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer''s disease (AD) is clinically marked at the onset, by memory disturbances affecting explicit memory. Emotional explicit memory is enhanced in normal subjects and remained less affected at the beginning of AD. The kinase p70S6k participates in the control of protein translation and seems also implicated in the process of synaptic plasticity and the formation of memory at the molecular level. In a previous study, we have shown that peripheral p70S6k level is correlated with the decline of cognitive and memory functions in patients with AD. The goal of the present study was to analyse emotional and neutral explicit memory in AD patients and to evaluate the levels of active p70S6k in lymphocytes by western blots. The results reveal that the difference between emotional and neutral memories are correlated with the levels of peripheral p70S6k in patients with AD, as well as with the global cognitive scores assessed by the Mini Mental Status Examination. The decline of emotional memory in AD patients is reflected by the decrease of p70S6k levels. [Copyright &y& Elsevier]

Objective Few data are available on the epidemiology and management of GCA in real life. We aimed to address this situation by using health insurance claims data for France. Methods This retrospective study used the Echantillon Généraliste de Bénéficiaires (EGB) database, a 1% representative sample of the French national health insurance system. The EGB contains anonymous data on long-term disease status, hospitalizations and reimbursement claims for 752 717 people. Data were collected between 2007 and 2015. The index date was defined as the date of the first occurrence of a GCA code. Demographics, comorbidities, diagnostic tests and therapies were analysed. Annual incidence rates were calculated, and incident and overall GCA cases were studied. Results We identified 241 patients with GCA. The annual incidence was 7–10/100 000 people ⩾50 years old. Among the 117 patients with incident GCA, 74.4% were females, with mean age 77.6 years and mean follow-up 2.2 years. After the index date, 51.3% underwent temporal artery biopsy and 29.1% high-resolution Doppler ultrasonography. Among the whole cohort, 84.3% used only glucocorticoids. The most-prescribed glucocorticoid-sparing agent was methotrexate (12.0%). Conclusion The incidence of GCA in France is 7–10/100 000 people ⩾ 50 years old. Adjunct agents, mainly methotrexate, are given to only a few patients. The use of temporal artery biopsy in only half of the patients might reflect a shift toward the use of imaging techniques to diagnose GCA. [ABSTRACT FROM AUTHOR]

Background: Apathy and depression are two early behavioral symptoms in Alzheimer's disease (AD) and related disorders that often occur prior to the onset of cognitive decline and memory disturbances. Both have been associated with an increased risk of conversion to dementia, with a distinct neuropathology. Objective: The assessment of the trajectories of apathy and depression and their independent impact on dementia conversion. Methods: Apathy and Depression were measured using the Neuropsychiatric Inventory for caregiver (NPI) and clinician (NPI-C), among the nondemented individuals reporting subjective cognitive decline (SCD) at baseline. They were followed up over a 60-month period. Some converted to dementia, according to the methodology carried out by the French Memento Cohort. Results: Among individuals with SCD (n = 2,323), the levels of apathy and depression were low and did not evolve significantly over the 60-month period, despite a trend in apathy increasing as of month 24. Regarding SCD individuals who converted to dementia within the 60-month period (n = 27), the prevalence of depression remained globally steady, while the levels of apathy increased over time. Conclusion: Apathy and depression have different trajectories among individuals with SCD and apathy alone is more likely—compared to depression—to be associated with conversion to dementia. [ABSTRACT FROM AUTHOR]

Background: There is a lack of real‐life data regarding the frequency and predictive factors of hypoglycemia in older patients with type 2 diabetes (T2D). This study aimed to determine the frequency and predictors of hypoglycemia in older patients with insulin‐treated T2D. Methods: This prospective multicenter study included 155 insulin‐treated T2D patients aged 75 years and older with ≥2 self‐monitoring of blood glucose (SMBG) daily controls. Participants underwent a geriatric and diabetic assessment and received ambulatory blinded continuous glucose monitoring (CGM) for 28 consecutive days with FreeStyle Libre Pro® sensor. Study population (n = 141) has >70% CGM active time. Multivariable logistic regressions were used to identify factors associated with SMBG confirmed hypoglycemia (≥70 mg/dL) and with nocturnal level 2 time below range (glucose concentration <54 mg/dL during ≥15 consecutive min between 0.00 and 6.00 am). Results: The mean age of the 141 analyzed patients was 81.5 ± 5.3 years and 56.7% were male. The mean baseline HbA1c was 7.9% ± 1.0%. After geriatric assessment, 102 participants (72.3%) were considered as complex and 39 (27.7%) as healthy. The primary endpoint (confirmed SMBG <70 mg/dL) occurred in 37.6% patients. In multivariable analysis, the risk of SMBG‐confirmed hypoglycemia was positively associated with a longer duration of diabetes (OR (+1 year) =1.04, (1.00–1.08), p = 0.04) and glycemic variability assessed by CGM (CV %) (OR (+1%) = 1.12, [1.05–1.19], p = <0.001). Nighty‐two patients (65.2%) experienced nocturnal time in hypoglycemia (i.e., <54 mg/dL during ≥15 consecutive min between midnight and 6 a.m.). In multivariable analyses, cognitive impairment (OR: 9.31 [2.59–33.4]), heart failure (OR: 4.81 [1;48–15.6]), and depressive disorder (OR: 0.19 [0.06–0.53]) were associated with nocturnal time in hypoglycemia. Conclusion: Nocturnal hypoglycemia is very common and largely underdiagnosed in older patients with insulin‐treated T2D. CGM is a promising tool to better identify hypoglycemia and adapt diabetes management in this population. [ABSTRACT FROM AUTHOR]

Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer’s disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a brain with AD phenotype. Therefore, this study analyzed the chemokine levels in a human blood brain barrier model. A human endothelial cell line from the immortalized cerebral microvascular endothelial cell line (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype were used while PBMCs came from AD at mild or moderate stage and control patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and abluminal compartments with PBMCs from mild AD patients compared to controls. AD PBMCs can convert the chemokine signature towards that found in AD brain, targeting some chemokines as new biomarkers in AD. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding the observed memory disturbances in patients with Alzheimer disease.

Presents a letter to the editor commenting on a study about high response to intravenous immunoglobulin in the treatment of acquired hemophilia in an elderly patient.

Bacteria of the genus Shewanella are rarely implicated in bacteremia. We report a case of rupture of a primary aneurysm infected with Shewanella alga. [ABSTRACT FROM AUTHOR]

A 75-y-old woman with breast cancer presented with bacteremia due to Comamonas testosteroni. Evolution was favorable following adapted antimicrobial therapy and removal of a central venous catheter. This germ seems to be a rare pathogen; as reported in the literature, it is mostly encountered in patients with predisposing factors. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to describe hospital stays related to HZ and to evaluate the direct and indirect cost of hospitalizations due to HZ among patients aged over 50 years. Methods: The hospitalizations of people aged over 50 years were selected from the French national hospital 2011 database (PMSI) using ICD-10 diagnosis codes for HZ. Firstly, stays with HZ as principal or related diagnostic were described through the patient characteristics, type of hospitalization and the related costs. Secondly, a retrospective case–control analysis was performed on stays with HZ as comorbidity in 5 main hospitalizations causes (circulatory, respiratory, osteo-articular, digestive systems and diabetes) to assess the impact of HZ as co-morbidity on the length of stay, mortality rate and costs. Results: In the first analysis, 2,571 hospital stays were collected (60 % of women, mean age: 76.3 years and mean LOS: 9.5 days). The total health assurance costs were 10,8 M€. Mean cost per hospital stay was 4,206€. In the second analysis, a significant difference in LOS and costs was shown when HZ was associated as comorbidity in other hospitalization's causes. Conclusions: HZ directly impacts on the hospital cost. When present as comorbidity for other medical reasons, HZ significantly increases the length of hospital stay with subsequent economic burden for the French Health System. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to describe hospital stays related to HZ and to evaluate the direct and indirect cost of hospitalizations due to HZ among patients aged over 50 years. Methods: The hospitalizations of people aged over 50 years were selected from the French national hospital 2011 database (PMSI) using ICD-10 diagnosis codes for HZ. Firstly, stays with HZ as principal or related diagnostic were described through the patient characteristics, type of hospitalization and the related costs. Secondly, a retrospective case–control analysis was performed on stays with HZ as comorbidity in 5 main hospitalizations causes (circulatory, respiratory, osteo-articular, digestive systems and diabetes) to assess the impact of HZ as co-morbidity on the length of stay, mortality rate and costs. Results: In the first analysis, 2,571 hospital stays were collected (60 % of women, mean age: 76.3 years and mean LOS: 9.5 days). The total health assurance costs were 10,8 M€. Mean cost per hospital stay was 4,206€. In the second analysis, a significant difference in LOS and costs was shown when HZ was associated as comorbidity in other hospitalization’s causes. Conclusions: HZ directly impacts on the hospital cost. When present as comorbidity for other medical reasons, HZ significantly increases the length of hospital stay with subsequent economic burden for the French Health System. [ABSTRACT FROM AUTHOR]

Objective: to describe aminoglycoside use and nephrotoxicity in patients older than 75 years.Design: retrospective multicenter study.Setting: hospital department, rehabilitation, long-term care center.Population: patients ≥75 years old treated by aminoglycosides.Results: 184 patients, mean age: 84.4 years (range: 75–101). One hundred and twenty-seven patients received other nephrotoxic drug(s). Gentamicin (70%) and amikacin (30%) were used and the once-daily dosing was preferred (92%). Average treatment period was 2.75 (1–10) days for amikacin and 4.4 (1–30) for gentamicin with average dosage 13.5 and 3.5 mg/kg/day, respectively. The monitoring of maximal plasmatic concentration (Cmax) was done in 37 patients, 9 of them had probabilistic treatment. Only one had a Cmax fulfilling the objective of French recommendations (gentamicin >30 mg/l, amikacin >60 mg/l). When infection was documented, the objective of Cmax >10 × minimal inhibitory concentration of the strain was reached for 27%. Minimal plasmatic concentration was checked in 38% of cases, with adequate value (gentamicin <0.5 mg/l, amikacin <2.5 mg/l) for 37%. At the end of aminoglycoside course, 40 patients increased their serum creatinine >25% of the baseline value. In multivariate analysis, this was associated with treatment length ≥3 days and concomitant use of nephrotoxic drugs.Conclusion: aminoglycosides dosing used in elderly patients probably need therapeutic drug monitoring and dose adjustment. Aminoglycosides are used to treat severe infections. One of the most important side effects is nephrotoxicity in oldest patients. To minimise nephrotoxicity, short treatments are necessary and avoiding others nephrotoxic drugs could be relevant. [ABSTRACT FROM AUTHOR]

Objective: to describe aminoglycoside use and nephrotoxicity in patients older than 75 years.Design: retrospective multicenter study.Setting: hospital department, rehabilitation, long-term care center.Population: patients ≥75 years old treated by aminoglycosides.Results: 184 patients, mean age: 84.4 years (range: 75–101). One hundred and twenty-seven patients received other nephrotoxic drug(s). Gentamicin (70%) and amikacin (30%) were used and the once-daily dosing was preferred (92%). Average treatment period was 2.75 (1–10) days for amikacin and 4.4 (1–30) for gentamicin with average dosage 13.5 and 3.5 mg/kg/day, respectively. The monitoring of maximal plasmatic concentration (Cmax) was done in 37 patients, 9 of them had probabilistic treatment. Only one had a Cmax fulfilling the objective of French recommendations (gentamicin >30 mg/l, amikacin >60 mg/l). When infection was documented, the objective of Cmax >10 × minimal inhibitory concentration of the strain was reached for 27%. Minimal plasmatic concentration was checked in 38% of cases, with adequate value (gentamicin <0.5 mg/l, amikacin <2.5 mg/l) for 37%. At the end of aminoglycoside course, 40 patients increased their serum creatinine >25% of the baseline value. In multivariate analysis, this was associated with treatment length ≥3 days and concomitant use of nephrotoxic drugs.Conclusion: aminoglycosides dosing used in elderly patients probably need therapeutic drug monitoring and dose adjustment. Aminoglycosides are used to treat severe infections. One of the most important side effects is nephrotoxicity in oldest patients. To minimise nephrotoxicity, short treatments are necessary and avoiding others nephrotoxic drugs could be relevant. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies demonstrated that the PKR (double-stranded RNA-activated protein kinase) pathway was activated while the mTOR (mammalian target of rapamycin) pathway was inhibited in Alzheimer’s disease (AD). Here, we analysed upstream and downstream factors of mTOR in brain of APPSL/PS1 KI mice displaying a massive neuronal loss in hippocampus. While mTOR levels were not modified, we found a great activation of Akt with a robust accumulation of P-Akt(T308) in non-apoptotic neurons at 6 months of age. At the opposite, a significant decrease of the p70/85S6K activation was observed in brain of PS1 KI and APPSL/PS1 KI mice with a very weak or no nucleocytoplasmic P-p70/85S6K(T389) staining in apoptotic neurons of APPSL/PS1 KI mice. Furthermore, the activation of Erk1/2, 4E-BP1 and p70S6K(T421/S424) (substrate of Erk1/2), except eIF4E, was not modified. These findings demonstrate a clear dissociation between Akt and ribosomal S6K signaling markers in these mice which could be involved in the AD pathological process. [Copyright &y& Elsevier]

Elderly patients are often underrepresented in implantable cardioverter defibrillator (ICD) trials, and ICD implantation in patients ≥75 years consequently remains controversial. We aimed to evaluate mortality, appropriate ICD therapy rates and survival gain in an elderly population after risk stratification according to the Charlson Comorbidity Index (CCI). This monocentric retrospective study included elderly ICD patients ≥75 years. They were subdivided according to their CCI score into 3 categories (0–1, 2–3 or ≥4 points). Elderly patients were matched 1:2 with younger control ICD patients on gender, type of prevention (primary or secondary) and type of device (associated cardiac resynchronization therapy or not). Between January 2009 and July 2017, 121 elderly patients (mean age 78 ± 3; 83% male) matched with 242 controls (mean age 66 ± 5) were included. At 5 year follow-up after ICD implantation, overall survival was 78%, 57%, and 29% (P = 0.002) in the elderly with a CCI score of 0-1, 2-3 and ≥4 respectively, and 72% in controls. There was no significant difference regarding ICD appropriate therapy between the 3 subgroups despite a trend towards lower rates of therapy in CCI ≥ 4 points patients (34.2%, 39.7% and 22.8% respectively; P = 0.45). Median potential survival gain after an appropriate therapy was >5, 4.7 and 1.4 years, with a CCI score of 0-1, 2-3 and ≥4 respectively (P = 0.01). Elderly patients with CCI score ≥ 4 had the lowest survival after ICD implantation and little survival gain in case of appropriate defibrillator therapy. More than age alone, the burden of comorbidities assessed by the CCI could be helpful to better select elderly patients for ICD implantation. • 5-year survival rate was 29% in elderly with Charlson Comorbidity Index ≥ 4. • Elderly with Charlson Comorbidity Index ≥ 4 had the lowest cumulative incidence of appropriate therapy. • Survival was not different between elderly with Charlson Comorbidity Index 0–1 and youngers. • Appropriate therapy rates were not different between those 2 groups. • Charlson Comorbidity Index score is helpful to better select elderly candidates for ICD implantation. [ABSTRACT FROM AUTHOR]

To assess the 30-day mortality predictive markers in the oldest patients with Clostridioides difficile infection (CDI) and to analyze the accuracy of the European severity risk markers in this population. Observational prospective multicenter cohort study conducted by the French Infectious Diseases Society and Geriatrics Society networks. An electronic questionnaire was sent to members of both societies regarding their participation. Each investigator used an online survey to gather the data. Patients aged ≥75 years hospitalized in French geriatric or infectious wards with confirmed diagnosis of CDI between March 1, 2016 and May 1, 2017. Clinical and laboratory parameters included medical history and comorbidities with the Cumulative Illness Rating Scale (CIRS). Criteria increasing the risk of severe disease were recorded as listed in the European guidelines. Therapeutic management, recurrence, and mortality rates were assessed at day 30 after diagnosis. Included patients numbered 247; mean age was 87.2 years (SD 5.4). Most of the CDI incidences (66.4%) were health care–associated infections, with 81% diagnosed within 30 days of hospitalization; CIRS mean score was 16.6 (SD 6.6). Markers of severity ≥3 included 97 patients (39.3%). Metronidazole was the main initial treatment (51.0%). C difficile infection in the older adult was associated with a 30-day mortality of 12.6%. Multivariate analysis showed that baseline CIRS score [hazard ratio (HR) 1.06 per 1-point increase, 95% confidence interval (CI) 1.00-1.12] and evidence of cardiac, respiratory, or renal decompensation (HR 3.04, 95% CI 1.40-6.59) were significantly associated with mortality. European severity markers are adequate in the oldest old. Organ failure and comorbidities appeared to be the main markers of prognosis, and these should raise the awareness of practitioners. Although antibiotic treatment was not predictive of mortality, our results point out the lack of adherence to current guidelines in this population. [ABSTRACT FROM AUTHOR]

Objectives: The association between frailty, mortality and sex is complex, but a limited literature is available on this topic, particularly for older hospitalized patients. Therefore, the objective of our study was to prospectively evaluate sex differences in frailty, assessed by the Multidimensional Prognostic Index (MPI) and mortality, institutionalization, and re-hospitalization in an international cohort of older people admitted to hospital.Study Design: We used data from nine public hospitals in Europe and Australia, to evaluate sex differences in mortality, frailty and the risk of institutionalization and re-hospitalization, during one year of follow-up.Main Outcome Measures: People aged 65 years or more admitted to hospital for an acute medical condition or for a relapse of a chronic disease were included. A standardized comprehensive geriatric assessment, which evaluated functional, nutritional, and cognitive status, risk of pressure sores, comorbidities, medications and co-habitation status, was used to calculate the MPI to measure frailty in all hospitalized older people. Data regarding mortality, institutionalization and re-hospitalization were also recorded for one year.Results: Altogether, 1140 hospitalized patients (mean age = 84.2 years; 694 women = 60.9%) were included. The one-year mortality rate was 33.2%. In multivariate analysis, adjusted for age, MPI score, centre and diagnosis at baseline, although women had higher MPI scores than men, the latter had higher in-hospital (odds ratio, OR = 2.26; 95% confidence intervals, CI = 1.27-4.01) and one-year post-discharge mortality (OR = 2.04; 95%CI = 1.50-2.79). Furthermore, men were less frequently institutionalized in a care home than female patients (OR = 0.55; 95%CI: 0.34-0.91), but they were also more frequently re-hospitalized (OR = 1.42; 95%CI: 1.06-1.91) during the year after hospital discharge.Conclusion: Older hospitalized men were less frail, but experienced higher in-hospital and one-year mortality than women. Women were admitted more frequently to nursing homes and experienced a lower risk of re-hospitalization. These findings suggest important differences between the sexes and extends the 'male-female health-survival paradox' to acutely ill patient groups. [ABSTRACT FROM AUTHOR]

Background: Multidimensional Prognostic Index (MPI) is useful as a prognostic tool in hospitalized older patients, but our knowledge is derived from retrospective studies. We therefore aimed to evaluate in a multicenter, longitudinal, cohort study whether the MPI at hospital admission is useful to identify groups with different mortality risk and whether MPI at discharge may predict institutionalization, rehospitalization, and use of home care services during 12 months.Methods: This longitudinal study, carried out between February 2015 and August 2017, included nine public hospitals in Europe and Australia. A standardized comprehensive geriatric assessment including information on functional, nutritional, cognitive status, risk of pressure sores, comorbidities, medications, and cohabitation status was used to calculate the MPI and to categorize participants in low, moderate, and severe risk of mortality. Data regarding mortality, institutionalization, rehospitalization, and use of home care services were recorded through administrative information.Results: Altogether, 1,140 hospitalized patients (mean age 84.1 years, women = 60.8%) were included. In the multivariable analysis, compared to patients with low risk group at admission, patients in moderate (odds ratio [OR] = 3.32; 95% CI: 1.79-6.17; p < .001) and severe risk (OR = 10.72, 95% CI: 5.70-20.18, p < .0001) groups were at higher risk of overall mortality. Among the 984 older patients with follow-up data available, those in the severe-risk group experienced a higher risk of overall mortality, institutionalization, rehospitalization, and access to home care services.Conclusions: In this cohort of hospitalized older adults, higher MPI values are associated with higher mortality and other negative outcomes. Multidimensional assessment of older people admitted to hospital may facilitate appropriate clinical and postdischarge management. [ABSTRACT FROM AUTHOR]

As Alzheimer’s disease (AD) induces several cellular and molecular damages, it could be interesting to use multi-target molecules for therapeutics. We previously published that trans ε-viniferin induced the disaggregation of Aβ42 peptide and inhibited the inflammatory response in primary cellular model of AD. Here, effects of this stilbenoid were evaluated in transgenic APPswePS1dE9 mice. We report that trans ε-viniferin could go through the blood brain barrier, reduces size and density of amyloid deposits and decreases reactivity of astrocytes and microglia, after a weekly intraperitoneal injection at 10 mg/kg from 3 to 6 months of age. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is marked by several cellular and molecular damage. Therefore, the therapeutic interest of multi-target molecules is increasingly justified. Polyphenols presenting multiple pharmacological effects would be more efficient. In this study, beneficial effects of trans ε -viniferin, a natural polyphenol were thus evaluated. This study reported that this stilbenoid (1) induced the disaggregation of amyloid β (Aβ) peptide and (2) rescued inflammation in murine primary neuronal cultures. These both effects are higher than those of resveratrol, and so, trans ε -viniferin could be a good therapeutic multi-target candidate. [ABSTRACT FROM AUTHOR]

Peripheral inflammatory processes are involved in Alzheimer's disease (AD). We aimed to determine whether plasma inflammatory mediator levels at diagnosis are associated with cognitive decline through a 2-year follow-up in AD patients. Patients (n = 109, mean age 79.44 (6.82) years) were included at diagnosis with MMSE scores between 16 and 25, with C-reactive protein <10 mg/L, and without any acute or chronic inflammation status. Plasma IL-1β, IL-6, TNF-α, and CCL5 were measured using Luminex X-MAP technology at baseline, and after one year and two years of follow-up. The mean values of IL-1β, IL-6, TNF-α, and CCL5 at diagnosis were 0.3, 1.94, 6.57, and 69,615.81 pg/mL, respectively. Mean cognitive decline in MMSE was 3.35 points. No correlation between plasmatic value of IL-1β, IL-6, TNF-α, or CCL5 at diagnosis and cognitive decline during the two years of follow-up was found. Cognitive decline in AD does not appear to be predictable by the tested inflammatory mediators. [ABSTRACT FROM AUTHOR]

Objectives: There is today ample evidence that negative aging stereotypes impair healthy older adults' performance on cognitive tasks. Here, we tested whether these stereotypes also decrease performance during the screening for predementia on short cognitive tests widely used in primary care. Method: An experiment was conducted on 80 healthy older adults taking the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) under Threat or Reduced-threat condition. Results: Stereotype threat significantly impaired older adults' performance on both tests, resulting in 40% of older adults meet- ing the screening criteria for predementia, compared with 10% in Reduced-threat condition (MMSE and MoCA averaged). Discussion: Our research highlights the influence of aging stereotypes on short cognitive tests used to screen for predemen- tia. It is of critical importance that physicians provide a threat-free testing environment. Further research should clarify whether this socially induced bias may also operate in secondary care by generating false positives. [ABSTRACT FROM AUTHOR]

Background Selection of appropriate elderly who can benefit from transcatheter aortic valve implantation (TAVI) is challenging. We evaluated the prognosis of this procedure according to the comprehensive geriatric assessment (CGA) based on the multidimensional prognostic index (MPI). Methods Prospective observational monocentric study from January 2013 to December 2015. Consecutive patients aged ≥ 75 who underwent TAVI and a complete CGA were included. Baseline demographic, geriatric and cardiologic data were collected. CGA was used to calculate the MPI score that is divided in three groups according to the mortality risk. Follow up was performed until December 2016 and mortality rate was assessed at one, six and 12 months. Results 116 patients were included. Mean age was 86.2 ± 4.2 years, mean European system for cardiac operative risk evaluation (EuroSCORE) was 19.2 ± 11.3%, mean MPI score was 0.39 ± 0.13. Forty-five (38.8%) patients belonged to MPI-1 group, 68 (58.6%) to MPI-2 group and three to MPI-3 group. MPI score and Euroscore were moderately correlated (Spearman correlation coefficient r s = 0.27, p = 0.0035). Mortality rate was significantly different between MPI groups at six and 12 months ( p = 0.040 and p = 0.022). Kaplan Meier survival estimates at one year stratified by MPI groups was significantly different (hazard ratio HR = 2.83, 95%confidence interval (CI) 1.38–5.82, p = 0.004). Among variables retained to perform logistic regression analysis, the score of instrumental activities of daily living appeared the most relevant ( p < 0.001). Conclusion This study indicates that CGA based on MPI tool is accurate to predict prognosis in elderly patients undergoing TAVI procedure. [ABSTRACT FROM AUTHOR]

Background/Objective: although poorly documented, subcutaneous (SC) administration of antibiotics is common practice in France especially in Geriatrics Departments. The aim of this study was to determine the tolerance of such a practice. Design: prospective observational multicentre study. Methods: sixty-six physicians accepted to participate from 50 French Infectious Diseases and Geriatrics Departments. From May to September 2014, patients treated at least one day with SC antibiotics could be included. Modalities of subcutaneous administration, occurrence of local and systemic adverse effects (AE) and clinical course were collected until the end of the treatment. Results: two hundred-nineteen patients (83.0 [19-104] yo) were included. Ceftriaxone (n = 163, 74.4%), and ertapenem (n = 30, 13.7%) were the most often prescribed antibiotics. The SC route was mainly used because of poor venous access (65.3%) and/or palliative care (32.4%). Fifty patients (22.8%) experienced at least one local AE that led to an increased hospital stay for two patients (4.0%) and a discontinuation of the SC infusion in six patients (12.0%). A binary logistic regression for multivariate analysis identified the class of antibiotic (p = 0.002) especially teicoplanin and the use of rigid catheter (p = 0.009) as factors independently associated with AE. In over 80% of cases, SC antibiotics were well tolerated and associated with clinical recovery. Conclusions: SC administration of antibiotics leads to frequent but local and mild AE. Use of non-rigid catheter appears to be protective against AE. As it appears to be a safe alternative to the intravenous route, more studies are needed regarding efficacy and pharmacokinetics. [ABSTRACT FROM AUTHOR]

Objectives To investigate the relationship between warfarin treatment and different strata of all-cause mortality risk assessed using the Multidimensional Prognostic Index ( MPI) based on information collected using the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA) in community-dwelling older adults with atrial fibrillation ( AF). Design Retrospective observational study. Setting Older community-dwelling adults who underwent a SVa MA evaluation establishing accessibility to homecare services and nursing home admission from 2005 to 2013 in the Padova Health District, Italy. Participants Community-dwelling individuals with AF aged 65 and older (N = 1,827). Measurements Participants were classified as being at mild ( MPI- SVa MA-1), moderate ( MPI- SVa MA-2), or severe ( MPI- SVa MA-3) risk of mortality using the MPI- SVa MA, a validated prognostic tool based on age, sex, comorbidity, cognitive status, mobility and functional disability, pressure sore risk, and social support. The association between warfarin treatment and mortality was tested using multivariate- and propensity score-adjusted Cox regression models, controlling for age, sex, all SVa MA domains, concomitant diseases, and drug treatments. Results Higher MPI- SVa MA scores were associated with lower rates of warfarin treatment and higher 3-year mortality. After adjustment for propensity score quintiles, warfarin treatment was significantly associated with lower 2-year mortality in individuals with MPI- SVa MA-1 (hazard ratio ( HR) = 0.64, 95% confidence interval ( CI) = 0.50-0.82), MPI- SVa MA-2 ( HR = 0.68, 95% CI = 0.55-0.85), and MPI- SVa MA-3 ( HR = 0.55, 95% CI = 0.44-0.67). Heterogeneity analyses confirmed that the effect of warfarin treatment was not different between MPI- SVa MA groups ( P for heterogeneity = .48). Conclusion Community-dwelling older adults with AF benefitted from anticoagulation in terms of lower all-cause mortality over a mean follow-up of 2 years, regardless of poor health and functional condition. Although this benefit can be ascribed to the treatment, it may also reflect better overall care. [ABSTRACT FROM AUTHOR]

Recent findings indicate that microglia in Alzheimer’s disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1–42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA), and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3) were quantified by western blot and cytokines (Interleukin (IL)-1β, Tumor necrosis Factor (TNF)-α and IL-6) by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment. [ABSTRACT FROM AUTHOR]

Background Current evidence suggests a central role for autophagy in many neurodegenerative diseases including Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Furthermore, it is well admitted that inflammation contributes to the progression of these diseases. Interestingly, crosstalks between autophagy and inflammation have been reported in vitro and at the peripheral level such as in Crohn's disease. However, the impact of systemic inflammation on autophagic components in the brain remains to be documented. Therefore, this study monitored autophagy markers after acute and chronic lipopolysaccharide (LPS)-induced inflammatory stress in mice. Results We showed that acute inflammation, 24 h post-intraperitoneal 10 mg/kg LPS, substantially increased cytokine production (Interleukin(IL)-1β, Tumor necrosis factor (TNF)-α and IL-6), decreased the levels of autophagy markers (Beclin-1, p62 and LC3 II) and reduced p70S6K activation in cortex and hippocampus. In hippocampus, IL-1β levels and LC3 II expression were positively and highly correlated and a negative correlation was noted between TNF-α levels and p70S6K activation. Chronic inflammation by injection of 0.5 mg/kg LPS every three days during three months led to a moderate IL-1β production and decreased TNF-α levels. Interestingly, Beclin-1 and LC3 II levels decreased while those of p62 increased. Cortical IL-1β levels positively correlated with Beclin-1 and LC3 II and on the contrary inversely correlated with p62. Conclusion The present study is the first showing links between IL-1β-mediated inflammation and autophagy in the brain. It could open to new therapeutic strategies in brain diseases where regulation impairment of inflammation and autophagy progress with the severity of diseases. [ABSTRACT FROM AUTHOR]

Background In recent years, studies have sought to understand the mechanisms involved in the alteration of autophagic flux in Alzheimer's disease (AD). Alongside the recent description of the impairment of lysosomal acidification, we wanted to study the relationships between inflammation and autophagy, two physiological components deregulated in AD. Therefore, a longitudinal study was performed in APPswePS1dE9 transgenic mice at three, six and twelve months of age. Methods Autophagic markers (Beclin-1, p62 and LC3) and the activation of mammalian Target of Rapamycin (mTOR) signaling pathway were quantified by western blot. Cytokine levels (IL- 1β, TNF-α and IL-6) were measured by ELISA. Transmission electron microscopy was performed to detect autophagic vacuoles. Mann-Whitney tests were used to compare wildtype (WT) versus APPswePS1dE9 mice. Longitudinal changes in parameters were analyzed with a Kruskal-Wallis test followed by a post-hoc Dunn's test. Correlation between two parameters was assessed using a Spearman test. Results Compared to 12-month old WT mice, 12-month old APPswePS1dE9 mice had higher levels of IL-1β and TNF-α, a greater inhibition of the mTOR signaling pathway and lower levels of Beclin-1 expression both in cortex and hippocampus. Regarding the relationship of the various parameters in 12-month old APPswePS1dE9 mice, Beclin-1 rates were positively correlated with IL-1β and TNF-α levels. And, on the contrary, TNF-α levels were inversely correlated with the levels of mTOR activation. Altogether, these results suggest that inflammation could induce autophagy in APPswePS1dE9 mice. However, these transgenic mice displayed a large accumulation of autophagic vesicles within dystrophic neurons in cortex and hippocampus, indicating a terminal failure in the autophagic process. Conclusions This first demonstration of relationships between inflammation and autophagy in in vivo models of AD should be taken into account in new therapeutic strategies to prevent inflammation and/or stimulate autophagy in advanced neurodegenerative process such as AD. [ABSTRACT FROM AUTHOR]

Background Autophagy is a major pathway of protein and organelle degradation in the lysosome. Autophagy exists at basal constitutive level and can be induced as a defense mechanism under stress conditions. Molecular relationships between autophagy and inflammation at the periphery were recently evidenced, highlighting a role of autophagy in the regulation of inflammation. Impairment of autophagy (with accumulation of autophagic vacuoles) and substantial inflammation are found in neurodegenerative diseases such as Alzheimer's Disease (AD). However, the links between autophagy and inflammation in AD remain to be determined. Methods Here, we examined the inflammatory reaction and autophagy in murine tri-cultures of neurons, astrocytes, and microglia. Tri-cultures were exposed to various inflammatory stresses (lipopolysaccharide (LPS), amyloid peptide (Aβ42) with or without cytokines) for 48 hours. Furthermore, the relationships between inflammation and autophagy were also analyzed in astrocyte- and microglia-enriched cultures. Data for multiple variable comparisons were analyzed by a one-way ANOVA followed by a Newman-keuls' test. Results Aβ42 induced a low inflammation without accumulation of acidic vesicles contrary to moderate or severe inflammation induced by LPS or the cytokine cocktail (IL-1β, TNF-α, and IL-6) or IL-1β alone which led to co-localization of p62 and LC3, two markers of autophagy, with acidic vesicles stained with Lyso-ID Red dye. Moreover, the study reveals a major role of IL-1β in the induction of autophagy in tri-cultures in the presence or absence of Aβ42. However, the vulnerability of the autophagic process in purified microglia to IL-1β was prevented by Aβ42. Conclusion These findings show a close relationship between inflammation and autophagy, in particular a major role of IL-1β in the induction of the microglial autophagy which could be the case in AD. New therapeutic strategies could target inflammasome and autophagy in microglia to maintain its role in the amyloid immunosurveillance. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common form of dementia in the elderly individuals. Among the pathogenic mechanisms in AD, chronic systemic inflammation is described and characterized by massive production of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs), which may contribute to an altered immune response and exacerbation of neurodegeneration. Studies have also reported increased double-stranded RNA-dependent protein kinase (PKR) activation in the PBMCs of patients with AD. Interestingly, PKR could be involved in NF-κB activation, leading to production of a wide range of cytokines. We proposed to decrease proinflammatory cytokines production and release by treating the PBMCs in 25 patients with AD with a specific inhibitor of PKR. Our results showed that PKR inhibition greatly decreased tumor necrosis factor , interleukin (IL)-1α, IL-1β, and IL-6 production and release but did not affect the chemokine RANTES. Moreover, inhibition of the proinflammatory factors was correlated with prevention of caspase-3 activation. These results indicated that specific inhibition of PKR at the peripheral level might decrease the inflammatory response in AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common form of dementia in the elderly individuals. Among the pathogenic mechanisms in AD, chronic systemic inflammation is described and characterized by massive production of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs), which may contribute to an altered immune response and exacerbation of neurodegeneration. Studies have also reported increased double-stranded RNA-dependent protein kinase (PKR) activation in the PBMCs of patients with AD. Interestingly, PKR could be involved in NF-κB activation, leading to production of a wide range of cytokines. We proposed to decrease proinflammatory cytokines production and release by treating the PBMCs in 25 patients with AD with a specific inhibitor of PKR. Our results showed that PKR inhibition greatly decreased tumor necrosis factor α, interleukin (IL)-1α, IL-1β, and IL-6 production and release but did not affect the chemokine RANTES. Moreover, inhibition of the proinflammatory factors was correlated with prevention of caspase-3 activation. These results indicated that specific inhibition of PKR at the peripheral level might decrease the inflammatory response in AD. [ABSTRACT FROM AUTHOR]

Objectives: To study the effects of physical stimulation based on walking exercises, equilibrium and endurance on cognitive function and walking efficiency in patients with dementia. Methods: Randomized controlled trial including 31 subjects suffering from dementia (age: 81.8 ± 5.3 years). The intervention group (n = 16) benefited from a 15-week physical activity programme involving three 1-hour sessions per week. The control group (n = 15) did not practice any physical activities. Before and after rehabilitation, all subjects were evaluated with the Rapid Evaluation of Cognitive Functions test (ERFC French version) and walking analysis. Results: After the 15 weeks of rehabilitation, the subjects from the intervention group improved their overall ERFC score (p < 0.01), while those in the control group decreased their overall ERFC score. Interactions were also observed between walking parameters and groups (p < 0.01); the intervention group improved walking capacities through heightened walking speed, stride length and a reduction in double limb support time. Lastly, the subjects from the control group presented a reduction in both walking speed and stride length. Conclusion: This study shows that a physical activity programme can slow cognitive decline and improve quality of walking in elderly persons suffering from dementia. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

For 10 years, research has focused on signaling pathways controlling translation to explain neuronal death in Alzheimer Disease (AD). Previous studies demonstrated in different cellular and animal models and AD patients that translation is downregulated by the activation of double-stranded RNA-dependent protein kinase (PKR). Among downstream factors of PKR, the Fas-associated protein with a death domain (FADD) and subsequent activated caspase-8 are responsible for PKR-induced apoptosis in recombinant virus-infected cells. However, no studies have reported the role of PKR in death receptor signaling in AD. The aim of this project is to determine physical and functional interactions of PKR with FADD in amyloid-β peptide (Aβ) neurotoxicity and in APPSLPS1 KI transgenic mice. In SH-SY5Y cells, results showed that Aβ42 induced a large increase in phosphorylated PKR and FADD levels and a physical interaction between PKR and FADD in the nucleus, also observed in the cortex of APPSLPS1 KI mice, However, PKR gene silencing or treatment with a specific PKR inhibitor significantly prevented the increase in pT451-PKR and pS'94-FADD levels in SH-SY5Y nuclei and completely inhibited activities of caspase-3 and -8. The contribution of PKR in neurodegeneration through the death receptor signaling pathway may support the development of therapeutics targeting PKR to limit neuronal death in AD. [ABSTRACT FROM AUTHOR]

Abstract: The control of translation is disturbed in Alzheimer''s disease (AD). This study analysed the crosslink between the up regulation of double-stranded RNA-dependent-protein kinase (PKR) and the down regulation of mammalian target of rapamycin (mTOR) signalling pathways via p53, the protein Regulated in the Development and DNA damage response 1 (Redd1) and the tuberous sclerosis complex (TSC2) factors in two β-amyloid peptide (Aβ) neurotoxicity models. In SH-SY5Y cells, Aβ42 induced an increase of PT451-PKR and of the ratio p66/(p66+p53) in nuclei and a physical interaction between these proteins. Redd1 gene levels increased and PT1462-TSC2 decreased. These disturbances were earlier in rat primary neurons with nuclear co-localization of Redd1 and PKR. The PKR gene silencing in SH-SY5Y cells prevented these alterations. p53, Redd1 and TSC2 could represent the molecular links between PKR and mTOR in Aβ neurotoxicity. PKR could be a critical target in a therapeutic program of AD. [Copyright &y& Elsevier]

Provides information on a case of a woman with emphysematous cystitis. Medical examinations performed; Reason for conducting a barium contrast study; Description of the complication.

Background/Objective: The prevalence of postoperative delirium in elderly patients is >30%. The objective of this prospective study was to determine the usefulness of the short form of the Informant Questionnaire on COgnitive Decline in the Elderly (short IQCODE) to predict the occurrence of postoperative delirium after elective hip and knee arthroplasty in the elderly. Methods: Consecutive patients, 60 years and older, who were admitted for elective hip or knee arthroplasty were included. The preoperative cognitive status was determined using the Mini-Mental State Examination (MMSE) and the short IQCODE. Postoperative delirium was diagnosed using the Confusion Assessment Method. Logistic regression was used to analyze the links between the preoperative test scores and the outcome of postoperative delirium. Results: One hundred and one patients completed the study (mean age 73.6 ± 6.6 years). The mean ± SD MMSE score was 26 ± 3, and the mean short IQCODE score was 50.7 ± 6.2. Postoperative delirium developed in 15 patients (14.8%). A short IQCODE score >50 was significantly associated with postoperative delirium (OR 12.7, 95% CI 1.4–115.5; p = 0.02). Conclusions: The short IQCODE appears to be a useful tool to predict the risk of postoperative delirium in elderly patients undergoing elective surgery. Detecting this complication could be of great interest to improve the postoperative survey of elderly patients. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To describe the rationale for subcutaneous (SC) administration of antibiotics from available published data and to make propositions to help clinicians in daily practice. Narrative review. Hospitalized patients, persons in long-term care facilities and ambulatory care. We searched the MEDLINE/PubMed electronic database for evidence supporting SC administration of antibiotics up to September 2019; the results of this primary search were supplemented by searching the references of the identified articles, as well as by searching in Google Scholar. Regarding tolerability, efficacy, and pharmacokinetic/pharmacodynamic profiles, most studies suggest that the SC route could be an alternative to the intravenous route, particularly for time-dependent antibiotics and among certain patient populations, such as patients with poor venous access, swallowing disorders, or behavioral disturbance. However, clinical evidence of the benefits and risks of SC antibiotic administration is still scarce and of low level. SC administration of antibiotics may be useful in various settings such as in hospitalized patients and among those in long-term care facilities or being cared for at home. However, further clinical studies are needed to assess the pharmacokinetic/pharmacodynamic properties, as well as the risks and benefits of SC administration of antibiotics. In this review, we highlight the potential benefits of SC administration of antibiotics and address practical recommendations for its use. This information will enable improvement of treatment strategies and present the SC route as a potential option in specific situations. [ABSTRACT FROM AUTHOR]

A letter to the editor about vitamin D insufficiency and acute care in older patients is presented.

This study aimed to determine cancer prevalence occurring after the age of 75 in 45 French nursing homes (NH), as well as residents' characteristics and parameters associated with cancer‐specific management. Descriptive retrospective study including 214 residents (mean age, 89.7 years) with cancer diagnosed after age 75. The studied parameters were sociodemographic, functional, nutritional and cognitive data; comorbidity assessment; date of tumoral diagnosis; cancer type; tumoral stage; treatment plan; multidisciplinary staff decision and oncologic follow‐up. Our results showed that cancer prevalence in NH was 8.4 ± 1.1%, diagnosed before admission in 63% of cases. The most common tumoral sites were skin (26%), digestive tract and breast (18% for both); 12% had metastasis. Cognitive impairment was the most common comorbidity (42%), and 44% of the residents were highly dependent. Multivariate analysis showed that therapeutic decisions were associated with age. Older patients had less staging exploration (odd ratios [ORs], 0.90, 95% confidence interval [CI], 0.85–0.97) and underwent less cancer‐specific treatment (ORs, 0.92; 95%CI, 0.86–0.99). Oncologic follow‐up was more frequent in younger patients (ORs, 0.90; 95%CI, 0.81–0.99) and those with recent diagnosis (ORs, 0.37; 95%CI, 0.23–0.61). This study identified factors associated with substandard neoplastic management in elderly NH residents. It highlights needs for information, education and training in cancer detection to improve cancer consideration and care in NH. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning the use of single photon emission computed tomography (SPECT) to diagnose Lewy body dementia.

A letter to the editor about compliance with regulations for proton pump inhibitor prescriptions in a geriatrics department is presented.

This article presents a letter to the editor which discusses the Schnitzler syndrome in elderly people.