MACVIA-LR,Reference site of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) in Languedoc Roussillon

The Région Languedoc-Roussillon is the umbrella organisation for an interconnected and integrated project on AHA covering the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing. All sub-activities (A1: electronic pharmaceutical file, A2: falls prevention initiative, A3: frailty, B3: chronic respiratory diseases, chronic diseases with comorbidities, oral health and hepatitis virus C chronic infection, C2 and D4 active and independent living and handicap) are included in MACVIA-LR that has a strong political commitment and includes all stakeholders (public, private, patients, policy makers). It is one of the Reference Sites of the European Innovation Partnership on Active and Healthy Ageing built around chronic diseases, ageing and handicap. The framework of MACVIA-LR has the vision that the prevention and management of CDs is essential for AHA promotion and for the reduction of handicap. The main objective of MACVIA-LR is to develop innovative solutions for a network of Living Labs in order to improve the care of patients affected by CDs in the Languedoc-Roussillon area and to disseminate the innovation.     

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

Sepsis is characterized by overlapping phases of excessive inflammation temporally aligned with an immunosuppressed state, defining a complex clinical scenario that explains the lack of successful therapeutic options. Here we tested whether the formyl-peptide receptor 2/3 (Fpr2/3)—ortholog to human FPR2/ALX (receptor for lipoxin A4)—exerted regulatory and organ-protective functions in experimental sepsis. Coecal ligature and puncture was performed to obtain nonlethal polymicrobial sepsis, with animals receiving antibiotics and analgesics. Clinical symptoms, temperature, and heart function were monitored up to 24 h. Peritoneal lavage and plasma samples were analyzed for proinflammatory and proresolving markers of inflammation and organ dysfunction. Compared with wild-type mice, Fpr2/3^−/− animals exhibited exacerbation of disease severity, including hypothermia and cardiac dysfunction. This scenario was paralleled by higher levels of cytokines [CXCL1 (CXC receptor ligand 1), CCL2 (CC receptor ligand 2), and TNFα] as quantified in cell-free biological fluids. Reduced monocyte recruitment in peritoneal lavages of Fpr2/3^−/− animals was reflected by a higher granulocyte/monocyte ratio. Monitoring Fpr2/3^−/− gene promoter activity with a GFP proxy marker revealed an over threefold increase in granulocyte and monocyte signals at 24 h post-coecal ligature and puncture, a response mediated by TNFα. Treatment with a receptor peptido-agonist conferred protection against myocardial dysfunction in wild-type, but not Fpr2/3^−/−, animals. Therefore, coordinated physio-pharmacological analyses indicate nonredundant modulatory functions for Fpr2/3 in experimental sepsis, opening new opportunities to manipulate the host response for therapeutic development.Sepsis is a clinical syndrome expression of the host reaction to pathogen invasion, as a consequence of either direct dissemination into the bloodstream or postsurgical trauma and gut ischemia/reperfusion-mediated pathogen translocation. The complexity of sepsis is due to multiple local and systemic immune responses that involve release of soluble mediators such as cytokines, bioactive lipid mediators, and cell stress markers, leading to multiple organ failure and ultimately death (1). Originally believed to result exclusively from an overzealous inflammatory response (e.g., cytokine storm), the lack of efficacy of anticytokine therapy in several clinical trials demonstrated that the pathogenesis of sepsis is complex. Notwithstanding the difficulty in clinical cases to establish the beginning of the infection (and the temporal recruitment of failing organs), it is now appreciated that the systemic inflammatory response syndrome (SIRS) can overlap with a compensatory anti-inflammatory response syndrome (CARS) (2). Immunosuppression associated with CARS may explain the failure of classical anti-inflammatory strategies in patients (3, 4).The acute inflammatory reaction against pathogens is in many cases successful, leading to healing and recovery of biological function. To achieve this end point, specific mediators and pathways of endogenous protection must be engaged by the host to promote what is now referred to as “resolution of inflammation” (5). Proresolving mediators share a set of properties that are emerging as paradigmatic (6); these include modulation of immune cell recruitment [inhibition of polymorphonuclear (PMN) migration and promotion of monocyte influx], augmentation of phagocytosis (leading to bacteria containment), promotion of apoptosis and efferocytosis, and eventually tissue/organ repair with restoration of physiological function (6, 7). It is perhaps for these organic and multifactorial biological actions that proresolving mediators like the protein annexin A1 (AnxA1) and the bioactive lipids lipoxin A₄ (LXA₄) and resolvin D₂ exert protection in models of experimental sepsis (8–10). Of relevance, the receptor target for AnxA1 and LXA₄ is a G protein-coupled receptor that belongs to the formyl-peptide receptor (FPR) family, termed FPR2/ALX. To establish the validity of FPR2/ALX for the development of innovative therapeutic approaches, proof-of-concept data within loss-of-function settings should be established.In the mouse, the human FPR2/ALX gene corresponds to two genes, termed Fpr2 and Fpr3, which share the first of the two exons (11). LXA₄ and AnxA1 are largely inactive in a transgenic mouse that lacks both murine genes (12) as shown in models of acute inflammation and ischemia-reperfusion injury (12–15). Herein we establish the patho-pharmacology of Fpr2/3 in experimental polymicrobial sepsis as a way to validate the human ortholog as a genuine receptor target for innovative treatments in sepsis.     

Transvaginal mesh,gender and the ethics of clinical innovation

On 10 October 2018, Australian Health Minister Greg Hunt issued a national apology to the Australian women who experienced ‘horrific outcomes’ following surgery using transvaginal mesh—acknowledging the ‘historic agony and pain that has come from mesh implantation’. This apology followed many decades of ‘innovative’ use of transvaginal mesh for the treatment of pelvic organ prolapse. We use the case of transvaginal mesh to explore how clinical innovation may not only harm patients, but also entrench vulnerability and exacerbate existing inequities—in this case, those relating to gender.     

Factors affecting independence in eating among elderly with Alzheimer's disease

Aim: In elderly patients with dementia, disturbed eating behavior is understood to be a core symptom or a behavioral and psychological symptom of dementia (BPSD). The purpose of the present study was to investigate the factors affecting self‐feeding in elderly patients with Alzheimer's disease (AD). Methods: A total of 150 AD patients who were hospitalized in dementia wards, or were residents of institutions or group homes were enrolled. The patients underwent an eating behavior examination, cognitive assessment, neurological examination and vital function tests. The eating behavior examination consisted of observation of the patients at mealtime. Items assessing eating behavior included the number of feeding cycles, stopping of eating or agitation and dysfunction. Results: Logistic regression analysis carried out to identify factors with a significant effect on decreased independence in eating were difficulty in beginning a meal (OR = 14.498, CI = 2.067–101.690), presence of dysphagia signs (OR = 5.214, CI = 1.031–26.377) and the severity of dementia (OR = 4.538, CI = 1.154–17.843). Conclusion: The present study is the first to generate objective data showing that difficulty in beginning a meal is a factor that hinders independence in eating in AD, in addition to the presence of dysphagia signs and the severity of dementia. Assisting AD patients in maintaining eating independence might be effectively achieved by eliminating environmental factors that interfere with beginning a meal, and by providing assistance that will promote beginning a meal. The present results show the necessity of developing effective methods for assisting elderly patients with AD. Geriatr Gerontol Int 2012; 12: 481–490.     

Safety of ESWL in elderly: Evaluation of independent predictors and comorbidity on stone‐free rate and complications

Aim: Urinary stone disease affects people of all ages. With its satisfactory efficacy ranges in all age groups and lack of side‐effects, extracorporeal shock wave lithotripsy (ESWL) has become the preferred treatment modality for uncomplicated renal and proximal calculi ≤20 mm. In the present study, we aimed to assess the safety and efficacy of the ESWL treatment in elderly patients. Methods: A retrospective study was carried out on patients aged over 65 years who underwent shock wave lithotripsy at our Department from 2009 to 2011, with a Siemens Lithostar electromagnetic shockwave lithotripter. A total of 231 patients (157 males, 74 females) out of 1694 (13.6%) were studied. The patients were divided into two groups (group 1 = 65–70; group 2 >70). The effect of age and other possible predicting factors (sex, stone localization and stone size) were investigated. Concomitant diseases and related complications were also evaluated. Results: An overall stone‐free rate (SFR) of 82.2% was found. The influence of sex on SFR was non‐significant. There was no significant difference when comparing SFR between the age groups. When patients were divided into those with renal and ureteral stones, the SFR were 94.4% and 67.6% (P < 0.01), respectively. The SFR of the stone size groups, ≤10 mm and >10 mm were 80% and 84.4%, respectively. Comorbidity was present in 148 patients. Complications were noted in 56 of 231 patients. Of 56 patients, 43 had minor complications and 13 major complications. Conclusion: ESWL seems to be an effective first‐line treatment choice for urinary stones in elderly patients with careful patient selection and personalized preparation. Geriatr Gerontol Int 2012; 12: 413–417.