Older Persons Displaying Parkinsonian Gait: Prediction and Explanation of the Recurrent Falling Phenomenon and Its Related Poor Prognosis.

INTRODUCTION: Parkinsonian gait in older persons is a major risk factor for recurrent falling. This prospective, longitudinal study (named EVAMAR-AGEX) aimed to validate the threshold value of two or more falls per year for distinguishing non-recurrent (NRF) from recurrent fallers (RF), to explore predictive factors for recurrent falling, and to identify factors which underlie the transition of patients from NRF to RF. The study took place over 2 years, with an intermediate analysis at 1 year of follow-up. Herein, we report results after 2 years of follow-up. METHODS: Participants over the age of 65, diagnosed with parkinsonian gait, were followed over the course of 2 years. Induced parkinsonian syndrome and uncontrolled orthostatic hypotension were excluded. Assessments of motor, visual, and cognitive functions were carried out during visits at baseline. Between visits at 12 and 24 months of follow-up, data were collected by phone call every 2 months (falls, traumatic falls, hospitalizations, cognitive fluctuations, delirium, and mortality). Odds ratios (ORs) for a panel of predictive factors for recurrent falling were established using a Bayesian model. RESULTS: Sixty-six of the 79 initially enrolled participants progressed to the second year of the study, with a mean age of 80.57 (SD 6.3), 56% male, presenting parkinsonian gait (53% Parkinson's disease, 15% atypical neurodegenerative parkinsonism, 21% vascular parkinsonism, and 11% diffuse Lewy body disease). At 2 years of follow-up, 67% were RF. Univariate analysis revealed a previous history of falls to be the most significant predictive factor of recurrent falls (OR 13.16, credibility interval [CrI] [95%] 4.04-53.73), and this was reinforced at 2 years of follow-up compared to the intermediate 1-year analysis (OR 11.73, CrI [95%] 4.33-35.28). Multivariate analysis confirmed a previous history of falls (OR 13.20, CrI [95%] 3.29-72.08) and abnormal posture (OR 3.59, CrI [95%] 1.37-11.26) to be predictive factors for recurrent falling. Cognitive decline and fluctuating cognition were associated with the transition from NRF to RF (-3.5 MMSE points for participants transitioning from NRF to RF). CONCLUSION: Within this population of older persons presenting parkinsonian gait, a previous history of falls and abnormal posture may be used to easily identify individuals at risk of recurrent falls. Cognitive decline and fluctuations may underlie the transition of NRF to RF.

Gait Disorder among Elderly People, Psychomotor Disadaptation Syndrome: Post-Fall Syndrome, Risk Factors and Follow-Up - A Cohort Study of 70 Patients.

INTRODUCTION: Falls among older people are a major health issue and the first cause of accidental death after 75 years of age. Post-fall syndrome (PFS) is commonly known and yet poorly studied. OBJECTIVE: Identify risk factors for PFS and do a follow-up 1 year later. METHODS: We included all patients over 70 years of age hospitalized after suffering a fall in a case-control study, and then followed them in a cohort study. PFS was retained in case of functional mobility decline (transferring, walking) occurring following a fall in the absence of an acute neurological, orthopedic or rheumatic pathology directly responsible for the decline. The data initially collected were: clinical (anamnestic, emergency and departmental/ward evolution, medical history, lifestyle, treatments, clinical examination items); and imaging if the patient had been subjected to brain imaging in the last 3 years prior to inclusion. Regarding the follow-up at 1 year, we collected from the general physician the occurrence and the characteristics of new falls, functional mobility assessment, hospitalization and death. RESULTS: Inclusion took place from March 29, 2016 to June 7, 2016 and follow-up until June 30, 2017. We included 70 patients. A total of 29 patients exhibited a PFS (41.4 %). Risk factors for PFS included age, walking disorder prior to the fall, the use of a walking aid prior to the fall, no unaccompanied outdoor walk in the week before the fall, visual impairment making close reading impossible, stiffness in ankle dorsiflexion, grip strength and the fear of falling. Among patients with PFS, 52.9% could still perform a transfer at 1 year and 64.7% could still walk against 80.7% and 85.2%, respectively, for patients without PFS. CONCLUSION: The study showed the existence of body functions/structure impairments and activity limitations prior to the fall among patients exhibiting a PFS. This suggests the existence of a pre-fall syndrome, i.e., a psychomotor disadaptation syndrome existing prior to the fall. Among the 8 risk factors, fear of falling, vision impairment and muscle strength could be targeted for improvement. The diagnosis of PFS could be a marker of loss of functional mobility at 1 year.

Effect of high-intensity interval training and continuous endurance training on peak oxygen uptake among seniors aged 65 or older: A meta-analysis of randomized controlled trials.

BACKGROUND: Ageing is intrinsically associated with a progressive decline in cardiorespiratory fitness (CRF) as measured by peak oxygen uptake (VO2peak ). Improving CRF through physical activity contribute to better and healthy ageing. High-intensity interval training (HIIT) is a potent method of improving CRF among seniors, yet comparisons between this type of training and traditional endurance training (ET) are equivocal especially among older adults. PURPOSE: To analyse the effects of HIIT and ET on the VO2peak of seniors aged 65 years or older when compared with controls and also when the two types of training were compared with one another. METHODS: A comprehensive, systematic database search for manuscripts was performed in Embase, Medline, PubMed Central, ScienceDirect, Scopus and Web of Science using key words. Two reviewers independently assessed interventional studies for potential inclusion. Fifteen randomized controlled trials (RCTs) were included totalling 480 seniors aged 65 years or over. Across the trials, no high risk of bias was measured. RESULTS: In pooled analysis of the RCTs, the VO2peak was significantly higher after ET sessions compared with controls (mean difference-MD = 1.35; 95% confidence interval-CI: 0.73-1.96). Furthermore, VO2peak was found significantly higher not only when compared HIIT with controls (MD = 4.61; 95% CI: 3.21-6.01), but also when compared HIIT with ET (MD = 3.76; 95% CI: 2.96-4.56). CONCLUSION: High-intensity interval training and ET both elicit large improvements in the VO2peak of older adults aged 65 or over. When compared with ET, the gain in VO2peak was greater following HIIT. Nevertheless, further RCTs are therefore needed to confirm our results in senior's population.

Effects of a short-term Interval Aerobic Training Programme with active Recovery bouts (IATP-R) on cognitive and mental health, functional performance and quality of life: A randomised controlled trial in sedentary seniors.

BACKGROUND: Interval aerobic training programme with active recovery bouts (IATP-R) has shown to improve tolerance to IATP among seniors. However, data concerning its benefits for seniors' health are still limited. PURPOSE: The purpose of this study was to examine the effects of IATP-R on seniors' health status. METHODS: Sedentary volunteers (n = 60, aged ≥70 years) were randomly assigned to either IATP-R or maintained sedentary lifestyle for 9.5 weeks. IATP-R consisted of 30-minute cycling (6 × 4 minutes at first ventilatory threshold (VT1 ) intensity + 1 minute at 40% of VT1 ) twice a week. Cognitive and functional performances were assessed with the Trail Making Test (TMT-A; TMT-B); Paced Auditory Serial Addition Test (PASAT); Timed Up and Go (TUG) test; 6-Minute Walk Test (6-MWT); one-leg balance test; and the Short Physical Performance Battery (SPPB) tests, respectively. QoL and anxiety/depression status were measured by the Short Form-12 and the Goldberg's Scale, respectively. All participants were assessed at baseline and 9.5 weeks later. RESULTS: Compared to controls, IATP-R improved cognitive functions (TMT-A: +1.5% vs -21.5%; TMT-B: +0.9% vs -13.3%; PASAT: +1.4% vs -14.6%; semantic fluency: -1.1% vs +11.7%), functional performance (TUG: +5.4% vs -16.5%; 6-MWT: -3.2% vs +11.5%; SPPB: -3.2% vs +14.6%; One-leg balance: -16.3% vs +25.0%); QoL (physical health: -13.3% vs +23.1%; mental health: -7.1% vs +8.2%); and depressive symptoms (+26.3% vs -42.8%). Significant impacts were measured neither on letter modality of fluency tasks nor on anxiety score. CONCLUSION: These data showed that IATP-R is an effective training programme to improve functional and cognitive performances, mental health and well-being in sedentary seniors. Trial registration ClinicalTrials.gov NCT02263573. Registered October 1, 2014.

Local outbreak of Clostridioides difficile PCR-Ribotype 018 investigated by multi locus variable number tandem repeat analysis, whole genome multi locus sequence typing and core genome single nucleotide polymorphism typing.

The prevalence of Clostridioides difficile PCR-ribotype (RT) 018 is low in Europe but variations are observed across countries. We report here the first RT 018-related outbreak in France that took place in 4 geriatric units (GU) in Strasbourg, France. From January to December 2017, 38 patients were diagnosed with C. difficile infection (CDI). Strains were first characterized by PCR ribotyping: 19 out of 38 (50%) strains belonged to RT 018. These strains as well as 12 RT 018 isolated in other French healthcare facilities and 2 strains of RT 018 isolated in the GU in 2015 were characterized by multi locus variable-number tandem repeat (VNTR) analysis (MLVA), whole genome multi locus sequence typing (wgMLST) and core genome single nucleotide polymorphism typing (cgSNP). The MLVA indicated that 15 out of 19 epidemic strains of RT 018 were included in 2 Clonal Complexes (CC). Four RT 018 strains from the outbreak did not belong to the CC. The wgMLST and cgSNP typing analysis revealed a single CC that included 19 strains from the geriatric unit (17 from GU in 2017 and 2 from GU in 2015) and 4 strains (33%) from other healthcare facilities (HCF). Our results suggest that a specific RT 018 clone has spread in the geriatric unit and has evolved slowly over time. MLVA, wgMLST and cgSNP typing results provided fairly consistent information but wgMLST and cgSNP typing better separated epidemic strains from non-epidemic strains. Compared to wgMLST, the cgSNP typing did not provide additional information.

Effects of Interval Aerobic Training Program with Recovery bouts on cardiorespiratory and endurance fitness in seniors.

Interval aerobic training programs (IATP) improve cardiorespiratory and endurance parameters. They are, however, unsuitable to seniors as frequently associated with occurrence of exhaustion and muscle pain. The purpose of this study was to measure the benefits of an IATP designed with recovery bouts (IATP-R) in terms of cardiorespiratory and endurance parameters and its acceptability among seniors (≥70 years). Sedentary healthy volunteers were randomly assigned either to IATP-R or sedentary lifestyle. All participants performed an incremental cycle exercise and 6-minute walk test (6-MWT) at baseline and 9.5 weeks later. The first ventilatory threshold (VT1 ); maximal tolerated power (MTP); peak of oxygen uptake (VO2peak ); maximal heart rate (HRmax ); and distance walked at 6-MWT were thus measured. IATP-R consisted of 19 sessions of 30-minute (6 × 4-min at VT1  + 1-minute at 40% of VT1 ) cycling exercise over 9.5 weeks. With an adherence rate of 94.7% without any significant adverse events, 9.5 weeks of IATP-R, compared to controls, enhanced endurance (VT1 : +18.3 vs -4.6%; HR at baseline VT1 : -5.9 vs +0.2%) and cardiorespiratory parameters (VO2peak : +14.1 vs -2.7%; HRmax : +1.6 vs -1.7%; MTP: +19.2 vs -2.3%). The walk distance at the 6-MWT was also significantly lengthened (+11.6 vs. -3.1%). While these findings resulted from an interim analysis planned when 30 volunteers were enrolled in both groups, IATP-R appeared as effective, safe, and applicable among sedentary healthy seniors. These characteristics are decisive for exercise training prescription and adherence.

[The 'physical aptitude for health consultation' in a geriatric unit]. / La consultation de l'aptitude physique pour la santé dans un pôle de gériatrie.

The aim of the 'physical aptitude for health consultation' is to offer a validated physical reconditioning programme to adults with a stabilised chronic condition. It notably enables the absence of any contraindications to be established. A first of its kind in France, the programme has been implemented at Strasbourg university hospital.

[Association between the severity of neurocognitive disorders and the seriousness of falls in the elderly]. / Association entre la sévérité des troubles neurocognitifs et la gravité des chutes chez les personnes âgées.

Falls cause severe morbidity and mortality in people over 65 years old in all countries. Cognitive frailty is considered to be one of the risk factors for falls in the elderly. Approximately 60% of the elderly with neurocognitive disorders fall annually and this is two times more compared to elderly with no cognitive impairment. We already know that neurocognitive disorders and their severity are a risk factor for falls in older people. Few studies are conducted to investigate the association between the severity of neurocognitive disorders and the severity of falls. This study is therefore interested in investigating the association between the severity of neurocognitive disorders and the serious falls in the elderly. This is a non-interventional retrospective study of 100 patients admitted for fall in a geriatric hospital. The correlation between MMSE and fall severity remains uncertain. Serious falls are more frequent in patients with Parkinsonian syndromes, but this result is not statically significant. Polypharmacy remains very prevalent in our population with 70 % of patients having more than four drugs. Polydrug use in our study was very high, with 70% of patients taking more than four medications. We did not find a statistically significant association between the severity of neurocognitive disorders evaluated with the MMSE and the serious falls. More studies with tailored neurocognitive testing are needed to investigate the link between executive function disorders and the serious of falls.

Spatio-Temporal Gait Parameters of Hospitalized Older Patients: Comparison of Fallers and Non-Fallers.

Gait disorders are predisposing factors for falls. They are accessible to rehabilitation and can be analyzed using tools that collect spatio-temporal parameters of walking, such as the GAITRite® mat. The objective of this retrospective study was to find differences between the spatio-temporal parameters in patients who had fallen compared to patients who did not fall in a population of older patients hospitalized in acute geriatrics department. Patients over 75 years were included. For each patient, spatio-temporal parameters were collected using the GAITRite® mat. The patients were divided into two groups according to whether they had a history of fall. The spatio-temporal parameters were compared between the two groups and in relation to the general population. Sixty-seven patients, with an average age of 85.9 ± 6 years, were included. The patients had comorbidities, cognitive impairment and were polymedicated. The mean walking speed was 51.4 cm/s in non-fallers group and 47.3 cm/s in fallers group (p = 0.539), indicating pathological walking in comparison with the general population of the same age (average 100 cm/s). No association was found between the spatio-temporal parameters and fall, probably linked to many confounding factors such as the pathogenicity of walking of our patients and their comorbidities.

Diagnosis of vascular parkinsonism: A new tool for gait hypokinesia occurring in older persons.

INTRODUCTION: Reliable diagnosis of vascular parkinsonism (VaP) in the presence of a gait hypokinesia is an issue that is encountered in geriatrics. The EVAMAR-AGEX study was focusing on the phenomenon of recurrent falls in older persons (OP) with this parkinsonian gait. The present study is focusing on the diagnosis of VaP-related parkinsonian gait by developing a diagnostic guidance model adapted to OP. METHODS: Data from baseline and the 2-year follow-up visit were used to carry out univariate analysis and calculation of odds ratios, allowing to identify relevant variables to include in the diagnostic guidance model. To evaluate the model, confusion matrices were created, evaluating true positive, false negative, false positive and true negative incidences, sensitivity and specificity, and negative and positive predictive values. RESULTS: 79 patients included 58% male; average age 81.24 years. VaP diagnosis according to Zijlmans criteria occurred in 28%; neurodegenerative parkinsonian syndromes in 72%. A 4-criteria model was established to facilitate diagnostic: lack of prior hallucinations, lack of movement disorders tremor excluded, no cognitive fluctuations, and ≥75 years of age at diagnosis. In combination of 4/4 criteria, all of them were required to disclose a specificity of 91% in the diagnosis of VaP. In combination of 3/4, in case of negative test, a negative predictive value for VaP diagnosis of 0.97 was obtained. CONCLUSION: The challenge of our tool is both to be able to rule out what is probably not a VaP and to argue what makes a VaP diagnosis probable in OP.

Abnormal liver tests and non-alcoholic fatty liver disease predict disease progression and outcome of patients with COVID-19.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a serious public health issue that became rapidly pandemic. Liver injury and comorbidities, including metabolic syndrome, are associated with severe forms of the disease. This study sought to investigate liver injury, clinical features, and risk factors in patients with mild, moderate, and severe COVID-19. METHODS: We retrospectively included all consecutive patients hospitalized with laboratory-confirmed COVID-19 between February, 22 and May 15, 2020 at the emergency rooms of a French tertiary hospital. Medical history, symptoms, biological and imaging data were collected. RESULTS: Among the 1381 hospitalizations for COVID-19, 719 patients underwent liver tests on admission and 496 (68.9%) patients displayed abnormal liver tests. Aspartate aminotransferase was most commonly abnormal in 57% of cases, followed by gamma-glutamyl transferase, alanine aminotransferase, albumin, alkaline phosphatase, and total bilirubin in 56.5%, 35.9%, 18.4%, 11.4%, and 5.8%. The presence of hepatocellular type more than 2xULN was associated with a higher risk of hospitalization and a worse course of severe disease (odd ratio [OR] 5.599; 95%CI: 1.27-23.86; p = 0.021; OR 3.404; 95% CI: 2.12-5.47; p < 0.001, respectively). A higher NAFLD fibrosis score was associated with a higher risk of hospitalization (OR 1.754; 95%CI: 1.27-2.43, p < 0.001). In multivariate analyses, patients with high fibrosis-4 index had a 3-fold greater risk of severe disease (p < 0.001). CONCLUSION: Abnormal liver tests are common in patients with COVID-19 and could predict the outcome. Patients with non-alcoholic fatty liver disease and liver fibrosis are at higher risk of progressing to severe COVID-19.

Humoral immune response after COVID-19 infection or BNT162b2 vaccine among older adults: evolution over time and protective thresholds.

The objectives of this study were to assess the dynamics of the SARS-CoV-2 anti-RBD-IgG response over time among older people after COVID-19 infection or vaccination and its comparison with indicative levels of protection. Geriatric patients with SARS-CoV-2 serological test results were included and divided into three groups. A vaccine group (n = 34), a group of natural COVID-19 infection (n = 32), and a group who contracted COVID-19 less than 15 days after the first injection (n = 17). Eighty-three patients were included; the median age with IQR was 87 (81-91) years. In the vaccine group at 1 month since the first vaccination, the median titer of anti-RBD-IgG was 620 (217-1874) BAU/ml with 87% of patients above the theoretical protective threshold of 141 BAU/ml according to Dimeglio et al. (J Infec. 84(2):248-88, [7]). Seven months after the first vaccination, this titer decreased to 30 (19-58) BAU/ml with 9.5% of patients > 141 BAU/ml. In the natural COVID-19 infection group, at 1 month since the date of first symptom onset, the median titer was 798 (325-1320) BAU/ml with 86.7% of patients > 141 BAU/ml and fell to 88 (37-385) with 42.9% of patients > 141 BAU/ml at 2 months. The natural infection group was vaccinated 3 months after the infection. Five months after the vaccination cycle, the median titer was 2048 (471-4386) BAU/ml with 83.3% of patients > 141 BAU/ml. This supports the clinical results describing the decrease in vaccine protection over time and suggests that vaccination after infection can maintain significantly higher antibody titer levels for a prolonged period of time.

Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation.

The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)-beta receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-beta-dependent manner in mice and rats. Tumor cells are necessary and sufficient to convert DCs into regulatory cells that secrete bioactive TGF-beta and stimulate T reg cell proliferation. In conclusion, tumor expansion can stimulate T reg cells via a specific DC subset.

Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.

Systemic anticancer chemotherapy is immunosuppressive and mostly induces nonimmunogenic tumor cell death. Here, we show that even in the absence of any adjuvant, tumor cells dying in response to anthracyclins can elicit an effective antitumor immune response that suppresses the growth of inoculated tumors or leads to the regression of established neoplasia. Although both antracyclins and mitomycin C induced apoptosis with caspase activation, only anthracyclin-induced immunogenic cell death was immunogenic. Caspase inhibition by Z-VAD-fmk or transfection with the baculovirus inhibitor p35 did not inhibit doxorubicin (DX)-induced cell death, yet suppressed the immunogenicity of dying tumor cells in several rodent models of neoplasia. Depletion of dendritic cells (DCs) or CD8+T cells abolished the immune response against DX-treated apoptotic tumor cells in vivo. Caspase inhibition suppressed the capacity of DX-killed cells to be phagocytosed by DCs, yet had no effect on their capacity to elicit DC maturation. Freshly excised tumors became immunogenic upon DX treatment in vitro, and intratumoral inoculation of DX could trigger the regression of established tumors in immunocompetent mice. These results delineate a procedure for the generation of cancer vaccines and the stimulation of anti-neoplastic immune responses in vivo.

Presence of active myocarditis at the 6 month follow-up appointment for a severe form of COVID-19: a case report.

Here, we present the case of an 81-year-old male patient, who was hospitalized for a severe form of COVID-19. Transthoracic echocardiogram (TTE) performed 1 month after symptom onset was normal. Respiratory evolution was favourable, and the patient was discharged at Day 78. At 6 months, despite a good functional recovery, he presented pulmonary sequelae, and the TTE revealed a clear reduction of left ventricular ejection fraction (LVEF) and mild LV dilatation without cardiac symptoms. The cardiac magnetic resonance (CMR) using Lake Louise Criteria (LLC), T1 and T2 mapping showed focal infero-basal LV wall oedema, elevated T1 and T2 myocardial relaxation times especially in basal inferior and infero-lateral LV walls, and sub-epicardial late gadolinium enhancement in those LV walls. The diagnosis of active myocarditis was raised especially based on TTE abnormalities and CMR LLC, T1 and T2 mapping. Currently, we are not aware of published reports of a 6 month post-COVID-19 active myocarditis.

Therapeutic prevention of COVID-19 in elderly: a case-control study.

COVID-19 is a particularly aggressive disease for the elderly as 86% of deaths related to COVID-19 occur in people over 65 years of age. Despite the urgent need for a preventive treatment, there are currently no serious leads, other than the vaccination. The aim of this retrospective case-control study is to find a pharmacological preventive treatment of COVID-19 in elderly patients. One-hundred-seventy-nine patients had been in contact with other COVID-19 patients at home or in hospital, of whom 89 had tested RT-PCR-positive (COVID-pos) for the virus and 90 had tested RT-PCR-negative (COVID-neg). Treatments within 15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected. COVID-pos patients more frequently had a history of diabetes (P = .016) and alcoholism (P = .023), a lower leukocyte count (P = .014) and a higher mortality rate - 29.2% versus 14.4% - (P = .014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P = .0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-pos patients on antipsychotics (P = .0013) and OADs (P = .0153), particularly metformin (P = .0237), were less likely to die. Thus, patients on treatment with PPI were less likely to develop COVID-19 infection, and those on antipsychotics or metformin had a lower risk of mortality. However, prospective studies, including clinical trials, are needed to confirm or not these findings.

Effects of a short-term interval aerobic training program with recovery bouts on vascular function in sedentary aged 70 or over: A randomized controlled trial.

BACKGROUND: Interval aerobic training programs with active recovery bouts (IATP-R) are reported as being more adapted to seniors while improving cardiorespiratory and endurance parameters. Report of benefits on vascular function is still limited. PURPOSE: To measure the impact of IATP-R on vascular function among seniors. METHODS: Sedentary volunteers (≥70 years of age) were randomly assigned to either IATP-R (n = 30) or control group (n = 30). The IATP-R consisted of 2 weekly sessions of 30-min (6 × 4-min at first ventilatory threshold (VT1) intensity + 1-min at 40% of VT1) cycling exercise over 9.5-week. Controls remained their sedentary life over the same period. In all participants, the endothelial function was measured by flow-mediated dilation (FMD) in brachial artery and arterial stiffness through the carotid/radial and carotid/femoral pulse wave velocity (PWV). Systolic (SBP) and diastolic blood pressure (DBP) were measured at baseline and 9.5 weeks later. RESULTS: Resulting from a planned interim analysis, IATP-R improved SBP (IATP-R: from 133.7 ± 9.8 to 122.6 ± 9.4 mmHg vs. Controls: from 128.9 ± 12.5 to 132.6 ± 14.7 mmHg), DBP (IATP-R: from 80.2 ± 7.0 to 74.1 ± 6.7 mmHg vs. Controls: from 77.1 ± 6.8 to 80.3 ± 7.5 mmHg), and FMD (IATP-R: from 6.7 ± 2.0 to 7.5 ± 2.7% vs. Controls: from 7.9 ± 2.7 to 7.5 ± 2.5%). No significant impact on PWV was measured. CONCLUSION: Although these findings resulted from an interim analysis, IATP-R might be effective in regulating BP and improving endothelial function among sedentary seniors.

Heat shock protein 70 neutralization exerts potent antitumor effects in animal models of colon cancer and melanoma.

When overexpressed, the stress protein heat shock protein 70 (HSP70) increases the oncogenic potential of cancer cells in rodent models. HSP70 also prevents apoptosis, thereby increasing the survival of cells exposed to a wide range of otherwise lethal stimuli. These protective functions of HSP70 involve its interaction with and neutralization of the adaptor molecule apoptotic protease activation factor-1, implicated in caspase activation, and the flavoprotein apoptosis-inducing factor (AIF), involved in caspase-independent cell death. We have shown previously that a peptide containing the AIF sequence involved in its interaction with HSP70 (ADD70, amino acids 150-228) binds to and neutralizes HSP70 in the cytosol, thereby sensitizing cancer cells to apoptosis induced by a variety of death stimuli. Here, we show that expression of ADD70 in tumor cells decreases their tumorigenicity in syngeneic animals without affecting their growth in immunodeficient animals. ADD70 antitumorigenic effects are associated with an increase in tumor-infiltrating cytotoxic CD8+ T cells. In addition, ADD70 sensitizes rat colon cancer cells (PROb) and mouse melanoma cells (B16F10) to the chemotherapeutic agent cisplatin. ADD70 also shows an additive effect with HSP90 inhibition by 17-allylamino-17-demethoxygeldanamycin in vitro. Altogether, these data indicate the potential interest of targeting the HSP70 interaction with AIF for cancer therapy.

Clinical and paraclinical patterns of presentation, and sensitivity of diagnostic scores for pulmonary embolism at the emergencies: retrospective study on the impact of age at the University hospitals of Strasbourg (France).

The diagnosis of pulmonary embolism remains difficult. The objective of this study was to analyze the effect of age on the clinical presentation mode and the sensitivity of the diagnostic scores. METHODS: In retrospect, all patients discharged with a documented diagnosis of pulmonary embolism from the adult emergency service of the Regional university hospital of Strasbourg (France) over a year were considered. According to 4 age categories (<70, 70-74, 75-80 and >80 years) the data from the medical records were analyzed and compared. Diagnostic scores of Wells and modified Geneva were calculated. RESULTS: 117 patients met the inclusion criteria (mean age 71.8±13.8 years, women 54%). Chest pain was less common after 80 years; no difference was observed for syncope or dyspnea although the oxygen saturation is lower in old age. For diagnosis, 25% of patients had a lung scintigraphy with an increased recourse with age (<70 years: 10%, >80 years: 41%). Thoracic computed tomography angiography concerned 79% of patients with a significant decrease of his use in older. The sensitivity of the diagnostic scores was low but increased with age when the strong and intermediate probabilities of pulmonary embolism were combined. CONCLUSION: This study confirms the low specificity of the clinical signs of pulmonary embolism, whatever the age. It also shows the low sensitivity of the diagnostic scores in the 70 years or older.

Effect of Aerobic Training on Peak Oxygen Uptake Among Seniors Aged 70 or Older: A Meta-Analysis of Randomized Controlled Trials.

Older adults undergo a progressive decline in cardiorespiratory fitness and functional capacity. This lower peak oxygen uptake (VO2peak) level is associated with increased risk of frailty, dependency, loss of autonomy, and mortality from all causes. Regular physical activity and particularly aerobic training (AT) have been shown to contribute to better and healthy aging. We conducted a meta-analysis to measure the exact benefit of AT on VO2peak in seniors aged 70 years or older. A comprehensive, systematic database search for articles was performed in Embase, Medline, PubMed Central, Science Direct, Scopus, and Web of Science using key words. Two reviewers independently assessed interventional studies for potential inclusion. Ten randomized controlled trials (RCTs) were included totaling 348 seniors aged 70 years or older. Across the trials, no high risk of bias was measured and all considered open-label arms for controls. With significant heterogeneity between the RCTs (all p < 0.001), pooled analyses were computed for VO2peak. Not only was VO2peak found significantly higher in the training group compared to controls (mean difference [MD] = 1.56; 95% confidence interval [CI]: 0.90-2.23) in pooled analysis of the 10 RCTs but also when the analysis was adjusted on the participants' health statuses. MD among healthy and unhealthy seniors were, respectively, 1.72 (95% CI: 0.34-3.10) and 1.47 (95% CI: 0.60-2.34). This meta-analysis confirms the AT-associated benefits on VO2peak in healthy and unhealthy seniors.