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Introduction: Hairy-cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with a favorable outcome thanks to treatment with purine analogues (PNA) like cladribine and pentostatin. Here, we updated the French national retrospective cohort of HCL after 10 years of follow-up, in order to evaluate the risk of second cancers in these patients. Methods: Data were collected up to June 2018 through a questionnaire sent to the members of the Société Française d'Hématologie, and centralized in the cohort database. We described the second malignancies observed during the follow-up, distinguishing second 'solid' cancers from second hematological malignancies. Then, using a Fine and Gray model, we performed a multivariate analysis in order to identify second cancer risk factors. Finally, to evaluate the excess of cancers in our cohort in comparison with the French general population, we calculated the standardized incidence ratio (SIR). Results: 279 patients (pts) from 19 centers were included in our retrospective cohort. The median age was 59 years old (range 29-88). 21% had an infectious disease at diagnosis, 23% had a familial history of cancer and 11% a personal history of cancer before HCL diagnosis. The median number of lines of treatments was 1 (0-7). PNA (cladribine or pentostatin) were the first therapeutic choice in frontline (75% of pts) and at relapse (69%). With a median follow-up of 127 months (2-413), the median overall survival for the overall study population was 328 months (95% CI 299-357) and the median relapse-free survival (RFS) was 136 months (95% CI 109-163). Pts treated with cladribine or pentostatin in first line had a statistically significant better RFS than pts treated with 'other' treatments (log rank test, p < 0.001). The 10-year cumulative incidence of relapse was 39% (95% CI 33-46). Pts who received treatments other than PNA in first line had a higher risk of relapse (Gray's test, p < 0.001). For pts receiving PNA in first and second lines, there was no difference in outcomes between those who switched PNA and those who did not. In this cohort, we observed 68 second malignancies during the follow-up: 49 solid cancers (most prevalent: prostate and non-melanoma skin cancers) and 19 hematological malignancies (most prevalent: monoclonal gammopathy of undetermined significance (MGUS) and myelodysplastic syndromes (MDS)). The median onset of second cancer, second solid cancer and second hematological malignancy from HCL diagnosis was 81 months, 99 months and 78 months, respectively. The median age at diagnosis of cancer, solid cancer and hematological malignancy was 70, 69 and 77 years old, respectively. Considering death as a competing risk, the 10-year cumulative incidence of cancer, solid cancer and hematological malignancy was 15% (95% CI 11-19), 11% (95% CI 7.2-15), and 5.0% (95% CI 2.8-8.2), respectively. In multivariate analyses, IFN treatment was associated with a decreased risk for all cancers (Fine and Gray regression model, subdistribution Hazard Ratio (sdHR) 0.53 (95% CI 0.29-0.97); p = 0.038), a familial history of cancer was a risk factor for solid cancers (sdHR 2.12 (95% CI 1.15-3.91); p = 0.017), a personal history of cancer was a risk factor for hematological malignancies (sdHR 3.47 (95% CI 1.14-10.55); p = 0.028). Even after excluding non-melanoma skin cancers and MGUS, there was an excess of cancers (SIR = 2.22), solid cancers (SIR = 1.81) and hematological malignancies (SIR = 6.67). Conclusions: In this updated real-world retrospective cohort with a long follow-up and most pts treated with PNA, we highlighted the importance and the excess of second cancers in HCL patients, in particular hematological malignancies. Figure Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Hermine:AB Science: Membership on an entity's Board of Directors or advisory committees. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Troussard:Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Research Support; Sysmex: Other: Research Support.

Depression is often overlooked in elderly nursing home residents because symptoms may be masked or dismissed as an inevitable consequence of ageing. Current tools for the detection of depression in institutionalised older people are not always specific. Aims To construct and verify an instrument with which to detect depression in elderly nursing home residents (NH-SDI). Method Firstly for the construction, 328 elderly people were selected at random from the residents of 17 nursing homes in France, and examined by a single investigator. The examination included a psychiatric assessment, an evaluation of cognitive function using the MMSE, an evaluation of depressive state using four different instruments (mini-GDS, Goldberg, DMAS, CSDD), and assessment of any changes in behaviour in those suffering from dementia, using the NPI. A second stage was to confirm NH-SDI in 99 institutionalised subjects. Results Following the selection of items, we created a scale of 16 dichotomous items (NH-SDI). The internal consistency was satisfactory (α Cronbach = 0.85), as was its reliability with a sensitivity of 85.1% and a specificity of 86.5% for a cut-off score above 5. Conclusions The NH-SDI appears to be a useful instrument for the detection of depression in nursing homes and can easily be applied by healthcare staff as part of routine procedures. Copyright © 2010 John Wiley & Sons, Ltd.

International audience; Few studies report a protective role of childhood solar exposure to multiple sclerosis. Our objective was to confirm the protective role of childhood solar exposure in multiple sclerosis in Cuba, Martinique and Sicily. This was a matched case- control study, and cases met Poser criteria for clinically, laboratory (definite, probable) multiple sclerosis. Controls were resident population, without neurological disorder, living close to cases (within 100 km), matched for sex, age (+/-5 years), residence before age 15. We recruited 551 subjects during a 1-year period (193 cases, Cuba n = 95, Sicily n = 50, Martinique n = 48; 358 controls). Some (89%) met definite clinical multiple sclerosis criteria (relapsing remitting form (with and without sequel) (74%), secondary progressive (21%), primary progressive (5%)). Odds ratios in a uni-variate analysis were: family history of multiple sclerosis (5.1) and autoimmune disorder (4.0); wearing shirt (3.5), hat (2.7), pants (2.4); sun exposure causing sunburn (1.8); sun exposure duration (1 h more/day; weekends 0.91, weekdays 0.86); bare-chested (0.6); water sports (0.2). Independent factors in the multivariate analysis were family history of multiple sclerosis (4.8 (1.50-15.10)), wearing pants under sunlight (1.9 (1.10-3.20)), sun exposure duration (1 h more/ day, weekdays 0.90 (0.85-0.98), weekends 0.93 (0.87-0.99)), water sports (0.23 (0.13-0.40)). We conclude that outdoor leisure activities in addition to sun exposure reports are associated with a reduced multiple sclerosis risk, with evidence of dose response.

Although several prognostic factors have been identified in ALS, there remains some discordance concerning the prognostic significance of the age and clinical form at onset. In order to clarify these findings, we have analysed already known prognostic factors using a multi-state model. Two hundred and twenty-two sporadic ALS patients were followed. A simple unidirectional three-states model was used to summarize clinical course of ALS. States 1 and 2 reflected the progression of neurological impairment and state 3 represented the end of follow-up (tracheotomy or death). Gender, diagnostic delay, body mass index (BMI) and slow vital capacity (SVC) were also recorded. A time-inhomogeneous Markov model with piecewise constant transition intensities was used to estimate the effect of the covariates in each transition. The bulbar form at onset was only correlated with a more rapid clinical progression between state 1 and state 2. In contrast, an advanced age at diagnosis affected only survival from state 2. This methodological approach suggests that these two factors have a different prognostic significance: age at onset is related to patient's survival and the clinical form at onset predicts the progression of motoneuronal impairment in different regions.

Purpose: To assess the prevalence of epilepsy in a rural district of Lao PDR and to describe the clinical and epidemiological profile of the disease. Methods: Door-to-door screening was performed on the entire population of 8 randomly selected villages in the Hinheub district, using an internationally validated and standardized questionnaire. Additional passive case detection was performed through village key informants. Suspected epilepsy patients identified by the questionnaire were revisited and examined by an experienced neurologist on two follow-up visits. The confirmation of epilepsy was based only on an in-depth clinical examination. Electroencephalograms were performed at the district health care center. Results: In the 8 villages, 277 suspected cases of epilepsy were identified among 4,310 interviewed subjects; 194 of whom (70%) underwent a clinical examination by a neurologist during the first visit while 65 of 83 remaining suspected cases were seen on the second confirmation visit. Twenty-seven persons with epilepsy were identified. Six additional patients were diagnosed in 219 self-referred subjects. An overall prevalence of 7.7 cases of epilepsy per thousand inhabitants was calculated (95% CI 5.3–10.7). Generalized epilepsy (21 cases, 63.6%) was commoner than partial epilepsy (9 cases, 27.3%). The remaining 3 cases (9.1%) were not-classifiable as either generalized or partial. EEG abnormal findings were found in 12 of the 24 patients (50.0%) who had an EEG registration. Conclusions: This is the first study in Lao PDR to estimate the prevalence of epilepsy. Compared to Western countries it shows a pattern towards a higher prevalence.

International audience; Background: Diffuse large B-cell lymphoma (DLBCL) is a fatal malignancy that needs to identify new targets for additional therapeutic options. This study aimed to clarify the clinical and biological significance of endogenous neurotrophin (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) in DLBCL biopsy samples and cell lines.METHODS: We analysed expression of NGF, BDNF, and their receptors (Trk, p75(NTR)) in 51 biopsies and cell lines by immunohistochemistry, immunofluorescence, and western blotting. To investigate the biological role of BDNF/TrkB/p75(NTR) axis, effects of neurotrophin signalling inhibition were determined on tumour cell survival and vascular endothelial growth factor (VEGF) secretion. The pharmacological pan-Trk inhibitor K252a was used for in vitro and in vivo studies.RESULTS: A BDNF/TrkB axis was expressed in all biopsies, which was independent of the germinal centre B-cell (GCB)/non-GCB profile. p75(NTR), TrkB, and BDNF tumour scores were significantly correlated and high NGF expression was significantly associated with MUM1/IRF4, and the non-GCB subtype. Diffuse large B-cell lymphoma cell lines co-expressed neurotrophins and their receptors. The full-length TrkB receptor was found in all cell lines, which was also phosphorylated at Tyr-817. p75(NTR) was associated to Trk and not to its cell death co-receptor sortilin. In vitro, inhibition of neurotrophin signalling induced cell apoptosis. K252a caused cell apoptosis, decreased VEGF secretion, and potentiated rituximab effect, notably in less rituximab-sensitive cells. In vivo, K252a significantly reduced tumour growth and potentiated the effects of rituximab in a GCB-DLBCL xenograft model.CONCLUSIONS: This work argues for a pro-survival role of endogenous neurotrophins in DLBCLs and inhibition of Trk signalling might be a potential treatment strategy for rituximab resistant subgroups.

International audience; Epilepsy is a heterogeneous disorder, the symptoms of which are preventable and controllable to some extent. Significant inter- and intra-country differences in incidence and prevalence exist because multiple etiologic factors are implicated. Many past reviews have addressed sole etiologies. We considered a comprehensive view of all etiologies (genetic/structural/metabolic) to be significant for both the developing and the developed world as well as routine clinical/epidemiology practice. We therefore carried out a comprehensive search for peer-reviewed articles (irrespective of year, region and language; chosen based on novelty and importance) for each etiology. This article was felt to be essential since newer etiologic knowledge has emerged in recent years. Many new genetic links for rarer epilepsy forms have emerged. Epilepsy risk in limbic encephalitis, mechanisms of Alzheimer's-related epilepsy and the genetic basis of cortical malformations have been detailed. An etiological approach to epilepsy in combination with the conventional classification of epilepsy syndromes is required to gain knowledge.

Behavioral and psychological symptoms in dementia (BPSD) are very common, with 90% of patients experiencing at least one during the course of the disease. One-third of persons with dementia have depressive symptoms, and concomitant BPSD are very likely. Objective This study aimed to characterize the psychological and behavioral manifestations of depression in patients with dementia. Methods We recruited patients with dementia from several nursing homes in the Limousin region of France. Depression was as diagnosed by the Cornell Scale for Depression in Dementia (CSDD) with a cut-off of 7, and BPSD were assessed using the Neuropsychiatric Inventory (NPI). Results Of 319 patients with dementia, 42.9% (n = 137) were depressed and 75.9% (n = 242) had BPSD. All BPSD were significantly (p

Chantier qualité GA; International audience; BACKGROUND: To determine whether proapoptotic proteins were associated with clinicopathologic heterogeneity and influenced survival in patients with diffuse large B-cell lymphoma (DLBCL), we evaluated patterns of expression of the BCL-2 family member BAD, PP1alpha (the catalytic subunit of PP1 involved in activation of BAD), and apoptosis-inducing factor (AIF). PATIENTS AND METHODS: We retrospectively analyzed 46 patients all treated with standard chemotherapy ([CHOP] cyclophosphamide/doxorubicin/vincristine/prednisone-like); of these, 16 received rituximab. Immunohistochemical analyses were performed from biopsy samples of nodal DLBCL that were performed at initial diagnosis. Normal reactive lymph nodes were used as controls. RESULTS: BAD expression was found in 38 of 46 DLBCL cases and, though variable, was often strong. PP1alpha and AIF were detected in all tumors tested with a relative strong expression. Lower BAD expression was shown to be significantly associated with advanced clinical stages (Ann Arbor stage III + IV and International Prognostic Index intermediate-high to high; P = .006 and P = .0008, respectively). Moreover, BAD staining was positively correlated with BCL-2 (P = .022) and PP1alpha (P = .013) staining. Finally, high AIF expression proved to be predictive of a longer overall survival in non-rituximab-treated patients. CONCLUSION: Our study shows for the first time in DLBCL that differential BAD expression might play a role in the development of the disease, possibly reflecting its function as a tumor suppressor. Furthermore, our data highlight the interest in targeting BAD phosphatases and AIF-mediated mitochondrial apoptosis for new therapeutic strategies.

Background Taenia solium cysticercosis is an important zoonosis in many developing countries. Human neurocysticercosis is recognised as an important cause of epilepsy in regions where the parasite occurs. However, it is largely underreported and there is a lack of data about the disease burden. Because a body of information on human and porcine cysticercosis in Cameroon is becoming available, the present study was undertaken to calculate the impact of this neglected zoonosis. Methods Both the cost and Disability Adjusted Life Year (DALY) estimations were applied. All necessary parameters were collected and imported in R software. Different distributions were used according to the type of information available for each of the parameters. Findings Based on a prevalence of epilepsy of 3.6%, the number of people with neurocysticercosis-associated epilepsy was estimated at 50,326 (95% CR 37,299–65,924), representing 1.0% of the local population, whereas the number of pigs diagnosed with cysticercosis was estimated at 15,961 (95% CR 12,320–20,044), which corresponds to 5.6% of the local pig population. The total annual costs due to T. solium cysticercosis in West Cameroon were estimated at 10,255,202 Euro (95% CR 6,889,048–14,754,044), of which 4.7% were due to losses in pig husbandry and 95.3% to direct and indirect losses caused by human cysticercosis. The monetary burden per case of cysticercosis amounts to 194 Euro (95% CR 147–253). The average number of DALYs lost was 9.0 per thousand persons per year (95% CR 2.8–20.4). Interpretation This study provides an estimation of the costs due to T. solium cysticercosis using country-specific parameters and including the human as well as the animal burden of the zoonotic disease. A comparison with a study in South Africa indicates that the cost of inactivity, influenced by salaries, plays a predominant role in the monetary burden of T. solium cysticercosis. Therefore, knowing the salary levels and the prevalence of the disease might allow a rapid indication of the total cost of T. solium cysticercosis in a country. Ascertaining this finding with additional studies in cysticercosis-endemic countries could eventually allow the estimation of the global disease burden of cysticercosis. The estimated number of DALYs lost due to the disease was higher than estimates already available for some other neglected tropical diseases. The total estimated cost and number of DALYs lost probably underestimate the real values because the estimations have been based on epilepsy as the only symptom of cysticercosis., Author Summary Taenia solium cysticercosis is a zoonotic disease occurring in many developing countries. A relatively high prevalence in humans and pigs has been reported in several parts of the world, but insufficient data are available on the disease burden. Disease impact assessment needs detailed information on well-defined epidemiological and economic parameters. Our work conducted in West Cameroon over several years allowed us to collect the necessary information to estimate the impact of the parasite on the human and animal populations in this area using both cost and Disability Adjusted Life Year (DALY) estimations. This study identified the professional inactivity caused by the disease as the major loss factor in comparison to the cost of health care and losses due to infected pigs. These findings should allow a simpler estimation of the global disease burden based on information on salary levels and human cysticercosis prevalence in endemic areas of the world. In addition, the number of DALYs lost was higher than estimates already available for some other neglected tropical diseases in sub-Saharan Africa.

Objective: To determine the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in the Republic of Uruguay.Methods: The study was performed in Uruguay (3,241,003 inhabitants) during a 2-year period (2002–2003). To ensure complete case ascertainment, multiple sources of information were used, including all the neurologists, other medical specialties, general physicians, neurophysiology laboratories, hospital medical records and death certificates. ALS diagnosis was based on El Escorial criteria. Although all patients with motor neuron disease were enrolled in the follow-up, only probable and definite cases are included in the study. Results: Between January 1st, 2002, and December 31st, 2003, 89 new patients were diagnosed with probable or definite ALS. The mean annual incidence rate was 1.37 per 100,000 persons. The incidence was higher for men (1.95) than for women (0.84) with a male to female ratio of 2:1. For both, the incidence increased throughout the years showing a peak in the 65–74 age group among men and the 55–64 age group among women. Mean age at onset of ALS disease was 58.7 years. The estimated mean annual incidence for ALS calculated by the capture recapture method was 1.42 (95% CI, 1.13–1.72). On December 31st, 2002, the crude prevalence was 1.9 per 100,000 inhabitants. Conclusions: ALS incidence is within a narrow range across countries despite the genetic, environmental and socioeconomic differences when similar prospective design, diagnosis criteria and data analyses are applied.

Objective. We evaluated beliefs about, attitudes toward, and stigma associated with epilepsy in four districts of central Laos. Method. For this study, 83 people with epilepsy, 83 family members, and 166 matched villagers in Vientiane Province were interviewed. Results. From patients to families to villagers, there existed a significantly increasing gradient of misbeliefs. Dubbed locally as ‘‘mad pig disease,’’ epilepsy was viewed as having a supernatural origin by 25–42% of respondents, a life-threatening disease by 60%, a disease transmissible by consumption of pork meat by 10–21%, and a disease transmissible by contact with patients’ saliva by 14.5% of patients and 44% of villagers (P < 0.01). Stigma was high. People thought that they should avoid contact or sharing meals with patients (15% of patients, 62% of family members, P < 0.001), and that persons with epilepsy should not get a job, get married (29 and 42%, P < 0.016), or raise children (33–42%). Conclusion. Wrong beliefs may lead to stigma and hamper access to or compliance with modern epilepsy treatment. In traditional countries, education is the cornerstone of epilepsy management. 2007 Elsevier Inc. All rights reserved.

Epilepsy and onchocerciasis (river blindness) constitute serious public health problems in several tropical countries. There are four main mechanisms that might explain a relationship between these two diseases: (i) the presence of Onchocerca volvulus in the central nervous system; (ii) the pathogenicity of various O. volvulus strains; (iii) immunological mechanisms involving cross-reactive immunization or cytokine production during infection; and (iv) the triggering role of insomnia due to itching.

International audience

In this issue, Carpio and colleagues1 report on a randomised, double blind, placebo controlled trial on patients with neurocysticercosis (see page 1050) . Their findings, published on behalf of the Ecuadorian Neurocysticercosis Group, add to the vividly debated issue of treatment of neurocysticercosis.2 Albendazole treatment was evaluated to reduce active brain cysts of neurocysticercosis and seizure recurrence. Carpio and colleagues1 found that in significantly more patients, active brain cysts were cured and a higher reduction of number of brain cysts was achieved. These findings confirm previous reports. However, although a significant reduction in brain cysts …