"The least significant change on bone mineral density scan increased in patients with higher degrees of obesity".

BACKGROUND: The least significant change (LSC) threshold of 0.03 g/cm² is used to interpret bone mineral density (BMD) scans in the general population. Our working hypothesis was that the current LSC threshold would not be applicable in obese populations. AIMS: The aim of this study was to calculate the LSC in an obese population. METHODS: We performed an interventional study among 120 obesity patients, in whom two measurements of BMD were performed at 3 sites. Pairs of measures were used to calculate the LSC, using the Bland and Altman method. RESULTS: We calculated that the LSC was 0.046 g/cm² at the lumbar spine, 0.069 g/cm² at the femoral neck, and 0.06 g/cm² at the total hip. We also calculated the LSC for each class of obesity and observed an increase in LSC with increasing body mass index (BMI). We calculated a LSC of 0.05 g/cm² in patients with class 2 or class 3 obesity, whereas the LSC in patients with class 1 obesity is similar to the threshold used in the general population. DISCUSSION: In obese population, like BMD, LSC is higher than the threshold value of the general population, and increases with increasing BMI. CONCLUSION: LSC of 0.05 g/cm² could be used in clinical practice in patients with class 2 or 3 obesity. These findings should help to improve the interpretation of BMD scans in these patients and optimize their management. TRIAL REGISTRATION NUMBER: Comité de Protection des Personnes Ile-de France VII, France.

Fatigue and quality-of-life in the year following SARS-Cov2 infection.

BACKGROUND: The SARS-COV2 pandemic has been ongoing worldwide since at least 2 years. In severe cases, this infection triggers acute respiratory distress syndrome and quasi-systemic damage with a wide range of symptoms. Long-term physical and psychological consequences of this infection are therefore naturally present among these patients. The aim of this study was to describe the state of health of these patients at 6 (M6) and 12 months (M12) after infection onset, and compare quality-of-life (QOL) and fatigue at these time-points. METHODS: A prospective cohort study was set up at Reims University Hospital. Patients were clinically assessed at M6 and M12. Three scores were calculated to describe patient's status: the modified Medical Research Council score (mMRC) used to determine dyspnoea state, the Fatigue Severity Scale (FSS) and the Short Form 12 (SF12) that was carried out to determine the QOL both mentally and physically (MCS12 and PCS12). Descriptive analysis and comparison of scores between M6 and M12 were made. RESULTS: 120 patients completed both follow-up consultations. Overall, about 40% of the patients presented dyspnoea symptoms. The median mMRC score was 1 Interquartile ranges (IQR) = [0-2] at the two assessment. Concerning FSS scores, 35% and 44% of patients experienced fatigue at both follow-ups. The two scores of SF12 were lower than the general population standard scores. The mean PCS12 score was 42.85 (95% confidence interval (95% CI [41.05-44.65])) and mean MCS12 score of 46.70 (95% CI [45.34-48.06]) at 6 months. At 12 months, the mean PCS12 score was 42.18 (95% confidence interval (95% CI [40.46-43.89])) and mean MCS12 score of 47.13 (95% CI [45.98-48.28]). No difference was found between SF12 scores at 6 and 12 months. CONCLUSIONS: This study pinpoints the persistence of fatigue and a low mental and physical QOL compared to population norms even after 1 year following infection. It also supports the claims of mental or psychological alterations due to infection by this new virus, hence a lower overall QOL in patients.

Excess Soluble fms-like Tyrosine Kinase 1 Correlates With Endothelial Dysfunction and Organ Failure in Critically Ill Coronavirus Disease 2019 Patients.

Excess soluble fms-like tyrosine kinase 1 (sFlt-1), a soluble inhibitor of vascular endothelial growth factor pathway, has been demonstrated to promote endothelial dysfunction. Here, we demonstrate that sFlt-1 plasma levels correlate with respiratory symptom severity, expression of endothelial dysfunction biomarker, and incidence of organ failure in coronavirus disease 2019 patients. Clinical Trials Registration: NCT04394195.

A prognostic index predicting survival in transformed Waldenström macroglobulinemia.

Histological transformation into diffuse large B-cell lymphoma is a rare complication in patients with Waldenström macroglobulinemia (WM) usually associated with a poor prognosis. The objective of this study was to develop and validate a prognostic index for survival in transformed WM patients. Through this multicenter, international collaborative effort, we developed a scoring system based on data from 133 patients with transformed WM who were evaluated between 1995 and 2016 (training cohort). Univariate and multivariate analyses were used to propose a prognostic index with 2-year survival after transformation as an end-point. For external validation, a data set of 67 patients was used to evaluate the performance of the model (validation cohort). By multivariate analysis, three adverse covariates were identified as independent predictors of 2-year survival after transformation: elevated serum LDH (2 points), platelet count < 100 x 109/L (1 point) and any previous treatment for WM (1 point). Three risk groups were defined: low-risk (0-1 point, 24% of patients), intermediate-risk (2-3 points, 59%, hazard ratio (HR) = 3.4) and high-risk (4 points, 17%, HR = 7.5). Two-year survival rates were 81%, 47%, and 21%, respectively (P < 0.0001). This model appeared to be a better discriminant than the International Prognostic Index (IPI) and the revised IPI (R-IPI). We validated this model in an independent cohort. This easy-to-compute scoring index is a robust tool that may allow identification of groups of transformed WM patients with different outcomes and could be used for improving the development of risk-adapted treatment strategies.

Lack of admission biomarkers' clinical utility in outcomes prediction in patients suspected with infection in the emergency department.

INTRODUCTION: Initial procalcitonin (PCT) levels may fail in mortality and septic shock prediction and raise cost-effectiveness issues. Since measurement of lactate, C-reactive protein (CRP), white blood cells and neutrophils is common in the emergency department (ED), we compared prediction abilities of these biomarkers to PCT. METHODS: From January 1st to December 31st, 2018, an observational, single center, retrospective study was conducted in the adult ED of the Reims University Hospital (France). Endpoints were bacteremia, septic shock, and in-hospital mortality, related to the same ED visit. RESULTS: Over one year, 459 patients suspected with infection were included, of mean age 60.4 years (SD: 22.0), with 50.8% male, and 364 (79.3%) were hospitalized following ED visit. Overall, 45 (9.8%) patients had a bacteremia, 39 (8.5%) a septic shock and 54 (11.8%) died during their hospitalization. PCT and CRP showed the best discrimination for bacteremia, with an area under curve (AUC) of 0.68 for PCT and 0.65 for CRP. PCT and lactate showed similar good discriminative power for septic shock, with an AUC of 0.78 for both, and poor discrimination for in-hospital mortality, with an AUC of 0.62 for PCT and 0.69 for lactate. Systolic blood pressure and pulse oximetry showed similar discrimination for septic shock as PCT or lactate, while they showed higher discrimination for in-hospital mortality than PCT. CONCLUSION: Usual admission biomarkers lack clinical utility in predicting septic shock or in-hospital mortality. CRP and PCT are poorly efficient in predicting bacteremia.

Optic Nerve and Perioptic Sheath Diameter (ONSD), Eyeball Transverse Diameter (ETD) and ONSD/ETD Ratio on MRI in Large Middle Cerebral Artery Infarcts: A Case-Control Study.

BACKGROUND: Despite recent progress in the multidisciplinary management of large middle cerebral artery infarcts, the neurological prognosis remains worrying in a non-negligible number of cases. The objective of this study is to analyze the contribution of optic nerve and perioptic sheath measurement on MRI to the acute phase of large middle cerebral artery infarcts. METHODS: A retrospective case-control study between January 2008 and December 2019 in a single academic medical center was performed. Cases and controls were selected by interrogation of International Classification of Diseases (ICD), 10th edition, with ischemic stroke as criterion (code I64). Decompressive hemicraniectomy was a criterion for large middle cerebral artery infarcts (cases). Cases were matched with controls (1:3) based on age (± 5 years), sex, and year of hospitalization (± 2 years) The examinations were performed on 3T MRI (Siemens IRM 3T Magnetom).Optic nerve and perioptic sheath diameter was calculated using electronic calipers, 3 mm behind retina and in a perpendicular vector with reference to the orbit in axial 3D TOF sequence. RESULTS: Of 2612 patients, 22 patients met all the criteria of large middle cerebral artery infarcts and they were paired with 44 controls. Patients were mainly women, mean age of 53.6 years. There is a significant difference in the size of the optic nerve and perioptic sheath diameter measured on MRI at patient's admission (right: 5.13 ± 0.2 mm vs. 4.80 mm ± 0.18, p <0. 0001, left: 5.16 ± 0.17 vs 4.78 ± 0.20, p<0.0001). The AUC of optic nerve and perioptic sheath diameter was 0.93 (95%IC [0.85-1.00]), for a threshold at 5.03 mm, the sensitivity was 0.82 (95%IC [0.6-0.93]), specificity 0.94 (95%IC [0.85-0.98]). The Odds Ratio of large middle cerebral artery infarcts was 46.4 for optic nerve and perioptic sheath diameter the (95%IC [6.15-350.1] p=0.0002). CONCLUSION: Optic nerve and perioptic sheath diameter in the first MRI can predict the risk of developing large middle cerebral artery infarcts requiring a decompressive hemicraniectomy.

Hypercalcemia at diagnosis of diffuse large B-cell lymphoma is not uncommon and is associated with high-risk features and a short diagnosis-to-treatment interval.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event-free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high-risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, ß2-microglobulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was significantly shorter for hypercalcemic patients (P = .001). These associations with adverse prognostic factors translated into lower rates of EFS24 (HR = 1.66; 95% CI, 1.08-2.54) and shorter PFS (P = .0059) and OS (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters. These data suggest that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL.

Unilateral nephrectomy versus renal arterial embolization and technique survival in peritoneal dialysis patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder associated with progressive enlargement of the kidneys and liver. ADPKD patients may require renal volume reduction, especially before renal transplantation. The standard treatment is unilateral nephrectomy. However, surgery incurs a risk of blood transfusion and alloimmunization. Furthermore, when patients are treated with peritoneal dialysis (PD), surgery is associated with an increased risk of temporary or definitive switch to haemodialysis (HD). Unilateral renal arterial embolization can be used as an alternative approach to nephrectomy. METHODS: We performed a multicentre retrospective study to compare the technique of survival of PD after transcatheter renal artery embolization with that of nephrectomy in an ADPKD population. We included ADPKD patients treated with PD submitted to renal volume reduction by either surgery or arterial embolization. Secondary objectives were to compare the frequency and duration of a temporary switch to HD in both groups and the impact of the procedure on PD adequacy parameters. RESULTS: More than 700 patient files from 12 centres were screened. Only 37 patients met the inclusion criteria (i.e. treated with PD at the time of renal volume reduction) and were included in the study (21 embolized and 16 nephrectomized). Permanent switch to HD was observed in 6 embolized patients (28.6%) versus 11 nephrectomized patients (68.8%) (P = 0.0001). Renal artery embolization was associated with better technique survival: subdistribution hazard ratio (SHR) 0.29 [95% confidence interval (CI) 0.12-0.75; P = 0.01]. By multivariate analysis, renal volume reduction by embolization and male gender were associated with a decreased risk of switching to HD. After embolization, a decrease in PD adequacy parameters was observed but no embolized patients required temporary HD; the duration of hospitalization was significantly lower [5 days [interquartile range (IQR) 4.0-6.0] in the embolization group versus 8.5 days (IQR 6.0-11.0) in the surgery group. CONCLUSIONS: Transcatheter renal artery embolization yields better technique survival of PD in ADPKD patients requiring renal volume reduction.

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.

Prevalence of geophagy and knowledge about its health effects among native Sub-Saharan Africa, Caribbean and South America healthy adults living in France.

Geophagy is widespread among women from Sub-Saharan Africa, South America and the Caribbean and may persist in western countries. This practice may be associated with adverse effects such as anaemia, constipation or intestinal occlusion. We aimed to determine the prevalence of geophagy and the level of knowledge about its health effects among healthy adults originating from these countries and attending a travel medicine and international vaccination consultation in France. Among 101 travellers enrolled in the study, 83 (82.1%) were born in Sub-Saharan Africa and 13 (12.8%) in South America or the Caribbean. The mean duration of residence in France was 15.6 ± 10.4 years. Previous or current geophagy was present in 42 travellers [previous geophagy in 31 (30.7%) and current consumption in 11 (10.9%)]; 38 (90.5%) were women. The rate of awareness of harmful effects of geophagy as the risk of iron-deficient anaemia (18.8%) and soil-transmitted intestinal parasitic infections (11.9%) was low overall. Women with previous or current geophagy more often had history of iron therapy compared to those who never consumed, both during pregnancy (50.0 versus 14.3%; p = 0.0009) and outside pregnancy (47.4 versus 2.8%; p < 0.0001). Despite a long period of residence in France, geophagy was still a current practice among 10.9% of Sub-Saharan, South American and Caribbean travellers, who are poorly informed of its harmful effects. Therefore, specific information tailored to Sub-Saharan, South American and Caribbean about the risks of geophagy should be implemented in western countries.Level of evidence Level V, descriptive cross-sectional survey.

In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia.

BACKGROUND: Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their efficacy. METHODS: MSCs were obtained from CLI-patients BMCs. Stimulated- (S-) MSCs were cultured in endothelial growth medium. Cells were characterized by the expression of cell surface markers, the relative expression of 6 genes, the secretion of 10 cytokines and the ability to form vessel-like structures. The cell proangiogenic properties was analysed in vivo, in a hindlimb ischemia model. Perfusion of lower limbs and functional tests were assessed for 28 days after cell infusion. Muscle histological analysis (neoangiogenesis, arteriogenesis and muscle repair) was performed. RESULTS: S-MSCs can be obtained from CLI-patients BMCs. They do not express endothelial specific markers but can be distinguished from MSCs by their secretome. S-MSCs have the ability to form tube-like structures and, in vivo, to induce blood flow recovery. No amputation was observed in S-MSCs treated mice. Functional tests showed improvement in treated groups with a superiority of MSCs and S-MSCs. In muscles, CD31+ and αSMA+ labelling were the highest in S-MSCs treated mice. S-MSCs induced the highest muscle repair. CONCLUSIONS: S-MSCs exert angiogenic potential probably mediated by a paracrine mechanism. Their administration is associated with flow recovery, limb salvage and muscle repair. The secretome from S-MSCs or secretome-derived products may have a strong potential in vessel regeneration and muscle repair. Trial registration NCT00533104.

Long-term survival and clinical forms in the acute phase of Chikungunya virus infection in older Caribbeans.

OBJECTIVE: To investigate whether the long-term survival in elderly patients with prior Chikungunya virus infection (CVI) is associated with the clinical form presented in the acute phase, as defined by the WHO classification. METHODS: Retrospective cohort study performed in Martinique University Hospitals. Patients who attended the emergency department for suspected CVI, and who had a positive biological diagnosis of CVI by reverse transcription-polymerase chain reaction on a plasma sample between 10 January and 31 December 2014 were eligible for inclusion. Time-to-death was the primary outcome. The independent relationship between clinical forms and time-to-death was analysed using a Cox model. RESULTS: In total, 268 patients were included. Mean age was 80 ± 8 years, 53% were women. Median length of follow-up was 28 months (range: 0-39). During follow-up, 53 (19.8%) patients died. Median survival time was 13.2 months (range: 0-33.6). At the end of follow-up, death rates were 4.6% for acute clinical cases, 19.0% for atypical cases, 19.2% for severe acute cases and 23.5% for unclassifiable cases. By multivariable analysis, the clinical form of CVI at admission was found to be independently associated with long-term survival (atypical form: HR = 2.38; 95% CI = 2.15-2.62; severe acute form: HR = 2.40; 95% CI = 2.17-2.64; unclassifiable form: HR = 2.28; 95% CI = 2.06-2.51). CONCLUSION: The clinical form at presentation with CVI has a significant impact on long-term survival. Management of CVI patients should be tailored according to their clinical form at admission.

OBJECTIF: Etudier si la survie à long terme chez les patients âgés avec une infection antérieure par le virus du chikungunya (IVC) est associée à la forme clinique présente dans la phase aiguë, telle que définie par la classification de l'OMS. MÉTHODES: Etude de cohorte rétrospective réalisée dans les hôpitaux universitaires de la Martinique. Les patients qui se présentaient au service des urgences en cas de suspicion d'IVC et qui avaient un diagnostic biologique positif d'ICV par la PCR à transcription inverse sur un échantillon plasmatique entre le 10 janvier et le 31 décembre 2014 étaient éligibles à l'inclusion. Le temps jusqu'au décès était le résultat principal. La relation indépendante entre les formes cliniques et le temps jusqu'au décès a été analysée à l'aide d'un modèle de Cox. RÉSULTATS: Au total, 268 patients ont été inclus. L'âge moyen était de 80 ± 8 ans, 53% étaient des femmes. La durée médiane du suivi était de 28 mois (intervalle: 0 à 39 ans). Au cours du suivi, 53 patients (19,8%) sont décédés. La durée médiane de survie était de 13,2 mois (intervalle: 0 à 33,6). A la fin du suivi, les taux de décès étaient de 4,6% pour les cas cliniques aigus, 19,0% pour les cas atypiques, 19,2% pour les cas aigus sévères et 23,5% pour les cas non classifiables. L'analyse multivariée a révélé que la forme clinique de l'IVC à l'admission était indépendamment associée à la survie à long terme (forme atypique: HR = 2,38; IC95%: 2,15-2,62; forme aiguë sévère: HR = 2,40; IC95%: 2,17-2,64; forme inclassable: HR = 2,28; IC95%: 2,06-2,51). CONCLUSION: La forme clinique lors de la présentation avec IVC a un impact significatif sur la survie à long terme. La prise en charge des patients atteints d'ICV devrait être adaptée à la forme clinique lors de l'admission.

Outcome of autosomal dominant polycystic kidney disease patients on peritoneal dialysis: a national retrospective study based on two French registries (the French Language Peritoneal Dialysis Registry and the French Renal Epidemiology and Information Network).

Background: Pathological features of autosomal dominant polycystic kidney disease (ADPKD) include enlarged kidney volume, higher frequency of digestive diverticulitis and abdominal wall hernias. Therefore, many nephrologists have concerns about the use of peritoneal dialysis (PD) in ADPKD patients. We aimed to analyse survival and technique failure in ADPKD patients treated with PD. Methods: We conducted two retrospective studies on patients starting dialysis between 2000 and 2010. We used two French registries: the French Renal Epidemiology and Information Network (REIN) and the French language Peritoneal Dialysis Registry (RDPLF). Using the REIN registry, we compared the clinical features and outcomes of ADPKD patients on PD (n = 638) with those of ADPKD patients on haemodialysis (HD) (n = 4653); with the RDPLF registry, those same parameters were determined for ADPKD patients on PD (n = 797) and compared with those of non-ADPKD patients on PD (n = 12 059). Results: A total of 5291 ADPKD patients and 12 059 non-ADPKD patients were included. Analysis of the REIN registry found that ADPKD patients treated with PD represented 10.91% of the ADPKD population. During the study period, PD was used for 11.2% of the non-ADPKD population. Compared with ADPKD patients on HD, ADPKD patients on PD had higher serum albumin levels (38.8 ± 5.3 versus 36.8 ± 5.7 g/dL, P < 0.0001) and were less frequently diabetic (5.31 versus 7.71%, P < 0.03). The use of PD in ADPKD patients was positively associated with the occurrence of a kidney transplantation but not with death [hazard ratio 1.15 (95% confidence interval 0.84-1.58)]. Analysis of the RDPLF registry found that compared with non-ADPKD patients on PD, ADPKD patients on PD were younger and had fewer comorbidities and better survival. ADPKD status was not associated with an increased risk of technique failure or an increased risk of peritonitis. Conclusions: According to our results, PD is proposed to a selected population of ADPKD patients, PD does not have a negative impact on ADPKD patients' overall survival and PD technique failure is not influenced by ADPKD status. Therefore PD is a reasonable option for ADPKD patients.

Reduction of the Anticholinergic Burden Makes It Possible to Decrease Behavioral and Psychological Symptoms of Dementia.

OBJECTIVE: The aim of this study was to evaluate the impact of a reduction of the anticholinergic burden (AB) on the frequency and severity of behavioral and psychological symptoms of dementia (BPSD) and their repercussions on the care team (occupational disruptiveness). METHODS: In this prospective, single-center study in an acute care unit for Alzheimer disease (AD) and related disorders, 125 elderly subjects (mean age: 84.4 years) with dementia presented with BPSD. The reduction of the AB was evaluated by the Anticholinergic Cognitive Burden Scale. BPSD were evaluated with the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). The effect of the reduction of the AB on the BPSD was studied using logistic regression adjusting for the variables of the comprehensive geriatric assessment. RESULTS: Seventy-one subjects (56.8%) presenting with probable AD, 32 (25.6%) mixed dementia (AD and vascular), 17 (13.6%) vascular dementia, and 5 (4.0%) Lewy body dementia were included. Reducing the AB by at least 20% enabled a significant decrease in the frequency × severity scores of the NPI-NH (adjusted odds ratio: 3.5; 95% confidence interval: 1.6-7.9) and of the occupational disruptiveness score (adjusted odds ratio: 9.9; 95% confidence interval: 3.6-27.3). CONCLUSION: AB reduction in elderly subjects with dementia makes is possible to reduce BPSD and caregiver burden. Recourse to treatments involving an AB must be avoided as much as possible in these patients, and preferential use of nonpharmacologic treatment management plans is encouraged.

Antimicrobial peptide gene expression in periodontitis patients: A pilot study.

AIM: Antimicrobial peptides (AMPs) are one of the most active components of innate immunity and have characteristics that could place them at the heart of the pathogenesis of periodontal disease. This study investigated differences in the expression of AMP coding genes obtained using a simple harvesting technique, gingival smear, between two groups of patients: chronic periodontitis subjects versus healthy ones. MATERIALS AND METHODS: Twenty-three patients were enrolled in two groups: 12 were diagnosed with moderate or severe generalized chronic periodontitis, and 11 were diagnosed as clinically healthy. Gingival smears were retrieved and studied using reverse transcription-quantitative PCR (RT-qPCR) after mRNA purification. RESULTS: Fifteen gene expressions were obtained using real-time RT-qPCR. Three AMP genes, histatin 3 (HTN3), α-defensin 4 (DEFA4) and lysozyme C (LYZ), presented different expression levels in periodontitis patients compared with healthy subjects. The relative expression level of DEFA4 appeared to be a protective factor against periodontitis. CONCLUSION: Gingival smears studied by RT-qPCR may be used to assess the expression of AMPs coding genes. A lack of expression of DEFA4 could be a potential indicator of periodontitis status.

Transformed Waldenström macroglobulinaemia: clinical presentation and outcome. A multi-institutional retrospective study of 77 cases from the French Innovative Leukemia Organization (FILO).

Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy-proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement. Fluorodeoxyglucose-positron emission tomography was performed in half of the patients and the median maximum standardized uptake value was 15 for transformed disease. More than 80% of cases with available data for assessment by the Hans' algorithm harboured a non-germinal centre B-cell phenotype. First-line treatment for transformation consisted of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimen in 85% of patients. The overall response rate after first-line treatment was 61% and the median overall survival was only 16 months for the entire cohort. Time to transformation above 5 years (P = 0·0004) and elevated LDH (P = 0·02) were associated with worse outcome. Based on these findings, HT should be considered and lead to a biopsy in WM patients presenting with extranodal involvement, elevated LDH and constitutional symptoms. The optimal therapeutic approaches remain to be defined.

Risk Factors for Adverse Drug Reactions in Older Subjects Hospitalized in a Dedicated Dementia Unit.

OBJECTIVE: To identify risk factors for the occurrence of adverse drug reactions (ADRs) based on geriatric evaluation. DESIGN: Longitudinal prospective study from May 2010 to November 2011. SETTING: Dedicated acute geriatric care unit specializing in the management of patients with dementia syndrome (Alzheimer disease or related syndromes) at the University Hospital of Reims, France. PARTICIPANTS: Older patients with dementia syndrome (Alzheimer disease or related syndromes). MEASUREMENTS: Sociodemographic variables and comprehensive geriatric assessment were recorded. Occurrence of ADRs was noted. Risk factors for ADR were identified by multivariate logistic regression. RESULTS: During the study period, 293 patients were included; average age was 82 ± 8 years; the majority were women (61.4%). Average Mini-Mental State Examination score was 13 ± 8; average activities of daily living (ADL) score was 3.6 ± 2.1. Independent risk factors for occurrence of at least one ADR were polypharmacy (≥5 drugs/day) (OR: 4.0, 95% CI: 1.1-14.1) and dependence on at least 1 ADL (OR: 2.6, 95% CI: 1.1-6.5). CONCLUSIONS: Risk factors for ADRs were polypharmacy and dependence on at least one ADL. Our findings underline the importance of taking into consideration the characteristics of the patients when prescribing drugs in this specific population. Prescriptions should be re-evaluated at each follow-up.

Autologous Bone Marrow Mononuclear Cell Implantation and Its Impact on the Outcome of Patients With Critical Limb Ischemia　- Results of a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Cell therapy is a therapeutic option for patients presenting with nonrevascularizable critical limb ischemia (CLI). However there is a lack of firm evidence on its efficacy because of the paucity of randomized controlled trials.Methods and Results:The BALI trial was a multicenter, randomized, controlled, double-blind clinical trial that included 38 patients. For all of them, 500 mL of bone marrow were collected for preparation of a BM-MNC product that was implanted in patients assigned to active treatment. For the placebo group, a placebo cell-free product was implanted. Within 6 months after inclusion, major amputations had to be performed in 5 of the 19 placebo-treated patients and in 3 of the 17 BM-MNC-treated patients. According to a classical logistic regression analysis there was no significant difference. However, when using the jackknife analysis, 6 months after inclusion BM-MNC implantation was associated with a lower risk of major amputation (odds ratio (OR): 0.55; 95% confidence interval (CI): 0.52-0.58; P<0.0001) and of occurrence of any event (major or minor amputation, or revascularization) (OR: 0.30; 95% CI: 0.29-0.31; P<0.0001). The secondary endpoints (i.e., pain, ulcers, TcPO2, and ankle-brachial index value) were not statistically different between groups. CONCLUSIONS: Our results suggested that cell therapy reduced the risk of major amputation in patients presenting with nonrevascularizable CLI.

[Adverse drug reactions in pediatrics: Experience of a regional pharmacovigilance center]. / Les effets indésirables médicamenteux en pédiatrie : expérience d'un centre régional de pharmacovigilance.

AIM: To describe the adverse drug reactions (ADR) and the drugs involved in pediatrics. METHODS: An observational study on all ADR notifications recorded in the French pharmacovigilance database by the Regional Pharmacovigilance Center of Champagne-Ardenne between 1 January 1985 and 31 December 2014 involving children from 0 to 17 years inclusive was performed. For all notifications, we studied the patient and the ADR characteristics. RESULTS: During the study period, 632 notifications were collected. The most frequently reported ATC (anatomical, therapeutic and chemical) classes were vaccines (15.9%), antineoplastics (12%) and antibiotics (11.1%). Forty-six percent of the notifications were serious. For serious ADRs, the most involved drugs were paracetamol, asparaginase and ibuprofen. Skin reactions were the most often reported ADRs. The most common lowest level terms (LLT) were urticaria (4.9%), hypersensitivity (4.1%), fever (2.9%) and vomiting (2.8%). CONCLUSION: ADR reporting to the pharmacovigilance system, in particular pediatric ADRs, should be encouraged. Information on the use of medicinal products, especially on self-medication use, need to be improve.