TWIST1 a New Determinant of Epithelial to Mesenchymal Transition in EGFR Mutated Lung Adenocarcinoma

Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P<0.001), to low CDH1 expression (P<0.05) and low disease free survival (P = 0.044). To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup

J Am Med Dir Assoc

OBJECTIVES: Identifying risk factors for falls can improve outcomes in older patients without cognitive decline. Yet this has not been demonstrated in older people with mild cognitive impairment (MCI). We therefore sought to better identify risk factors for falls in this particular group. DESIGN: The analysis was conducted on the MEMENTO cohort, which is a large, French, prospective cohort. SETTING AND PARTICIPANTS: We included older people (>65 years old) with MCI (defined from neuropsychological scores) and a Short Physical Performance Battery (SPPB) score at baseline. METHODS: Fallers were defined as participants having fallen at least once during the study's 2-year follow-up period. We compared clinical, neuropsychological, and biological data at baseline in fallers vs nonfallers. Additional analyses were performed on the following subgroups: women, men, people aged ≥75 years. RESULTS: Of the 1416 people included in our study, 194 (13.5%) fell at least once. A bivariate analysis showed that fallers were older, predominantly women, less independent in activities of daily living, and more apathetic. Fallers performed less well in executive function, balance, and gait tests. In a multivariable analysis, only age, gender, the number of limitations in instrumental activities of daily living, and living alone were significantly associated with falls. In a multivariable analysis of the subgroup of oldest patients and of the subgroup of men, executive function was significantly worse in fallers than in nonfallers. CONCLUSION AND IMPLICATIONS: Our results demonstrate that easily attainable risk factors can be used to identify individuals with MCI with a higher risk of falls and for whom prevention could be beneficial. Future studies are needed to further evaluate the role of mild executive dysfunction in certain subgroups, such as men and oldest patients

The emerging role of Twist proteins in hematopoietic cells and hematological malignancies

International audienceTwist1 and Twist2 (Twist1-2) are two transcription factors, members of the basic helix-loop-helix family, that have been well established as master transcriptional regulators of embryogenesis and developmental programs of mesenchymal cell lineages. Their role in oncogenesis in epithelium-derived cancer and in epithelial-to-mesenchymal transition has also been thoroughly characterized. Recently, emerging evidence also suggests a key role for Twist1-2 in the function and development of hematopoietic cells, as well as in survival and development of numerous hematological malignancies. In this review, we summarize the latest data that depict the role of Twist1-2 in monocytes, T cells and B lymphocyte activation, and in associated hematological malignancies

Are Cerebrospinal Fluid Biomarkers Useful for the Diagnosis of Cognitive Disorders in Older Patients? A 10-Year Retrospective Study in a Geriatric Memory Clinic at Lille University Medical Center (Lille, France)

International audienceWe focused on the diagnostic value of Cerebrospinal Fluid (CSF) biomarker assays in older patients. Literature data on this topic are very scarce. CSF biomarkers now constitute an additional body of evidence in the diagnosis of Alzheimer Disease, along with clinical observations, neuropsychological data and imaging findings. We present data obtained in a geriatric memory clinic (Lille, France) over 10 years. We included solely patients having undergone Lumbar Puncture (LP) with diagnostic intent, i.e., when the clinical, neuropsychological and imaging data had not enabled the clinic’s physicians to establish a certain diagnosis. A total of 3,236 patients attended our memory clinics; 37 of them underwent LP. The application of CSF biomarker assays enabled rectification of the clinical diagnosis in 35.1% of cases. The diagnosis of cognitive disorders must always be based on a personalized approach

Hallucinations and parkinson's disease in the elderly: pitfalls and medical care

International audienceHallucinations are common neuropsychiatric symptoms in Parkinson's disease (PD), with a significant prognosis impact. It is necessary to rule out other diagnoses that can be mentioned when hallucinations occur in old patients with PD. The various etiological factors must be systematically checked and can help for diagnosis. Medical care will be focused on treating the primary cause (medical or iatrogenic origin) and will privilege non-pharmacological strategies. Due to their frequent adverse effects, antipsychotic medication should be limited and started at low dose in old patients with multiple comorbidities. Clozapine and quetiapine have the highest level of recommendation in this indication. In the future, defining fMRI-based targets for noninvasive brain stimulation tools should pave the way for innovative non-pharmacological treatment of hallucinations

Community-acquired acute kidney injury induced by drugs in older patients: a multifactorial event

International audiencePurpose: Community-acquired acute kidney injury (CA-AKI) is a frequent and severe adverse drug reaction (ADR) among older patients. The combination of drugs and other CA-AKI risk factors was barely evaluated. The objectives of our study were to both accurately identify CA-AKI induced by drugs in older patients, and to describe their combination with other risk factors.Patients and methods: We conducted a retrospective, single-center study in a general hospital over a two-year period. An automated detection identified CA-AKI according to KDIGO criteria, amongst 4,767 eligible inpatient stays among patients aged 75 years or older. Two independent experts reviewed all CA-AKI events to adjudicate drug involvement (Naranjo scale), identify inappropriate prescriptions (STOPP criteria), evaluate avoidability (Hallas criteria) and identify combined risk factors.Results: An expert review confirmed 713 CA-AKI (15.0% of inpatient stays) and determined that 419 (58.8%) CA-AKI were induced by drugs. A multifactorial cause (i.e., at least one drug with a precipitating factor) was found in 63.2% of drug-induced CA-AKI. Most of the drug-induced events were avoidable (66.8%), mainly in relation to a multifactorial cause.Conclusion: Drug-induced CA-AKI were frequent, multifactorial events in hospitalized older patients and their prevention should focus on combinations with precipitating factors

Underuse of Oral Anticoagulation for Individuals with Atrial Fibrillation in a Nursing Home Setting in France: Comparisons of Resident Characteristics and Physician Attitude

International audienceObjectivesTo describe the characteristics of nursing home residents diagnosed with atrial fibrillation (AF) and eligible for oral anticoagulants who did not receive these drugs and to detail the conditions that physicians who decide not to prescribe anticoagulants take into account.DesignCross-sectional.SettingNursing home.ParticipantsNursing home residents with a history of AF (N = 1,085).MeasurementsData were collected on clinical characteristics, geriatric syndromes, and antithrombotic regimen. Multivariate logistic regression was used to identify factors associated with nonprescription of anticoagulants. A standardized questionnaire was submitted to physicians in charge of patients with AF, to detail conditions associated with their medical decision not to prescribe anticoagulants.ResultsHistory of AF was present in 1,085 nursing home residents (10.1%), mean age 87, with a mean CHA2DS2-VASc score of 5.1 ± 1.4. Of these residents with AF, 544 (50.1%) did not receive anticoagulants. Recurrent falls (odds ratio (OR) = 4.9, 95% confidence interval (CI) = 2.4–9.9, P < .001), past history of bleeding (OR = 3.62, 95% CI = 1.54–8.51, P = .003), paroxysmal AF (OR = 3.5, 95% CI = 1.83–6.66, P < .001), and advanced age (OR = 1.1, 95% CI = 1.01–1.17, P = .02) were significantly associated with not prescribing anticoagulants. Recurrent falls (47%), cognitive impairment (22.6%), and advanced age (16.4%) were the main reasons for not prescribing anticoagulants.ConclusionThe prevalence of AF in a cohort of very old nursing home residents was 10%. Anticoagulation was prescribed in fewer than 50% of eligible cases despite high individual risk of stroke. Geriatric syndromes, especially falls and cognitive disorders, were the main reported contraindications for prescribing anticoagulants. Physicians caring for those residents wrongly thought that paroxysmal AF caused fewer thromboembolic events than permanent AF, which explains lower rates of anticoagulant prescription in individuals with paroxysmal A

Risk Factors for Hospital Readmission and Death After Discharge of Older Adults from Acute Geriatric Units: Taking the Rank of Admission into Account

International audienceObjective: To analyze the impact of the number of hospital readmissions on the risks of further hospital readmission and death after adjustment for a range of risk factors. Methods: We performed a multicentre prospective study of the DAMAGE cohort in the Hauts-de-France region of France. Patients aged 75 and over hospitalized initially in an acute geriatric unit (AGU) were included and followed up for 12 months. The risk of hospital readmission was analyzed using a Cox model, and its extension for recurrent events and the risk of death were analyzed using a Cox model for time-dependent variables. Results: A total of 3081 patients were included (mean (SD) age: 86.4 (5.5)). In the multivariate analysis, the relative risk (95% confidence interval [CI]) of hospital readmission rose progressively to 2.66 (1.44; 5.14), and the risk of death rose to 2.01 (1.23; 3.32) after five hospital admissions, relative to a patient with no hospital readmissions. The number of hospital readmissions during the follow-up period was the primary risk factor and the best predictor of the risk of hospital readmission and the risk of death. Conclusion: Hospital readmission is the primary risk factor for further hospital readmissions and for death in older subjects discharged from an AGU

Analysis of clinical pharmacist interventions in the COVID-19 units of a French university hospital.

International audienceObjectives The objectives were to compare clinical pharmacist interventions between two care groups: COVID-19-positive and COVID-19-negative patients, and to identify drugs that require particular attention, especially those involved in COVID-19 management.Methods A prospective cohort study was conducted on patients with positive and negative COVID-19 statuses admitted to Lille University Hospital over 1 month. Pharmaceutical analysis instigated interventions to rectify drug-related errors. For each pharmaceutical intervention (PI), the anatomical therapeutic chemical classification of the drug and the outcome of such an intervention were specified.Results The study included 438 patients. Prescription analysis led to 188 PIs performed on 118 patients (64 COVID-19-positive patients and 54 COVID-19-negative patients). Most drug-related problems were incorrect dosage representing 36.7% (69/188) of all interventions: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The most frequent PI in 34% (64/188) of cases was terminating a drug: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The main drug classes involved were antithrombotic agents (20.7%, 39/188), antibacterials for systemic use (13.8%, 26/188) and drugs for gastric acid-related disorders (6.4%, 12/188). Study population was limited to a single centre over 1 month.Conclusion No difference in PI was noted between the two groups. The presence of pharmacists led to a reduction in drug-related prescription problems, especially for antithrombotic and antibacterial drugs for both groups. Clinical pharmacy commitment in such a pandemic is therefore important

sj-pdf-1-jgp-10.1177_08919887221149142 – Supplemental Material for Assessment of a Suicide Prevention Gatekeeper Training Program for Nursing Home Staff

Supplemental Material, sj-pdf-1-jgp-10.1177_08919887221149142 for Assessment of a Suicide Prevention Gatekeeper Training Program for Nursing Home Staff by Alice Demesmaeker, Nicolas Baelde, Ali Amad, Jean Roche, Marie Playe, Guillaume Vaiva, Alina Amariei, Wanda Blervaque, Marguerite Marie Defebvre, Brigitte Caron, Francois Puisieux and Laurent Plancke in Journal of Geriatric Psychiatry and Neurology</p