A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011

Air Drep—A Retrospective Study Evaluating the Influence of Weather Conditions and Viral Epidemics on Vaso-Occlusive Crises in Patients with Sickle Cell Disease Living in French Guiana

(1) Objectives: French Guiana is the French territory most affected by sickle cell disease (SCD). This study investigates the associations between different environmental factors relative to climate, infectious outbreaks, and emergency visits or weekly hospital admissions for vaso-occlusive crisis (VOC). The identification of risk factors would lead to better patient care and patient management, and more targeted prevention and therapeutic education for patients with SCD in French Guiana. (2) Methods: This study was performed using data collected from the medicalized information system and emergency medical records of Cayenne General Hospital, between 1 January 2010 and 31 December 2016. ARIMA models were used to investigate the potential impact of weather conditions and flu epidemics on VOC occurrence. (3) Results: During the study period, 1739 emergency visits were recorded among 384 patients, of which 856 (49.2%) resulted in hospitalization, 811 (46.6%) resulted in hospital discharge, and 72 (4.2%) in another orientation. Decreased temperature and decreased humidity were both independent factors associated with an increase of VOC cases (p = 0.0128 and p = 0.0004, respectively). When studying severe VOC (leading to hospitalization, with or without prior emergency visit), 2104 hospital admissions were recorded for 326 patients. The only factor associated with severe VOC, in the multivariate analysis, was flu epidemics (p = 0.0148). (4) Conclusions: This study shows a link between climate, flu epidemics, and VOC in French Guiana. Patient’s awareness of risks related to climate and flu epidemics should be encouraged, as home prevention measures can help avoid painful crises. Moreover, physicians should encourage patients to get immunized for influenza every year

Factors associated with sexual risk taking behavior by precarious urban migrants in French Guiana

International audienceBackground: French Guiana is highly affected by HIV. The migrant population is particularly susceptible. The objective of this study was to evaluate the level of risk of HIV transmission and its perception among migrants in French Guiana and to identify predictive factors. Methods: An HIV/AIDS Knowledge, Attitudes, Behaviors and Practices study was conducted in 2012 among migrants living in precarious neighborhoods of French Guiana. Results: Of the 1039 participants surveyed, 893 were analyzed, of which 35.6% had risky sex during the past 12 months. Sexual risk taking was higher among the migrant population than in the general population. The predictors of sexual risk taking behavior were: younger age groups, males, having a job, not living with a spouse, having first had sex before age 16, using alcohol or drugs before sex, and having engaged in commercial sex recently. The factors associated with not being aware of one's risk were: being a woman, being from Guyana or Suriname, non-systematic use of condoms with a regular partner, and never or not recently having been tested for HIV. Conclusions: The results suggest there is still a need for information on HIV risks in a highly vulnerable population

Penile implants and other high risk practices in French Guiana’s correctional facility: A cause for concern

International audienceBACKGROUND: Prisoners in French Guiana, a French territory located in South America, have a HIV and hepatitis B prevalence of 4%. Body modifications such as penile implants, tattoos, and body piercings are common among detainees, increasing the risk of blood-borne virus transmission.METHODS: We conducted a cross-sectional randomised survey in which the primary objective was to estimate the prevalence of high risk 'bloody practices' (penile implants, tattoos, body piercings) in French Guiana's only correctional facility. The secondary objective was to describe the risk factors for penile implants, the procedures and motivations for insertion, the reported complications, their risk factors and adverse impact on condom use.RESULTS: Of the 221 male inmates interviewed, 19% had tattoos or body piercings while incarcerated, and 68% had penile implants, of which, 85% had been inserted inside the correctional facility. Addictive behaviors such as cannabis use and alcohol addiction (positive AUDIT-C score), early age at first sexual intercourse, and the number of incarcerations correlated positively with having inserted one or more penile implants while incarcerated. In contrast, having reported previous psychiatric hospitalizations and having a high knowledge score for HIV/AIDS and sexually transmitted infections (STIs) were negatively correlated with the insertion of penile implants while incarcerated. Penile implants were inserted in poor hygienic conditions, usually using the sharp lid of a canned food container, with 18% of early complications, mostly haemorrhage and edema. Condom use was negatively impacted for 52% of men with penile implants.CONCLUSIONS: Our results highlight the need for prevention interventions which should aim at increasing knowledge levels and at implementing comprehensive risk-reduction measures

Renouncing care in French Guiana: the national health barometer survey

Abstract Background In French Guiana, health inequalities are patent for a broad range of pathologies for all age groups. The objective of the present study was to quantify the proportion of the population that had renounced care in the past year, to study predictive factors, and to compare results with other French territories. Methods A two-stage random sample of 2015 individuals aged 15 to 75 years was surveyed by telephone. A descriptive analysis of variables relative to renouncing care, use of health care, screening, and vaccination was initially performed. Multivariate analysis was then used to determine variables associated with renouncing care for financial reasons and renouncing for reasons linked to time were directly estimated using a Poisson model on weighted data. Variables with a significance level < 0.2 in the bivariate analysis were included in the full multivariate model. Results In French Guiana, during the past 12 months, 30.9% of surveyed persons renounced care whatever the type for financial reasons. Results of the multivariate analysis showed that gender, perceived financial situation, perceived health and complementary insurance status were independent predictive factors of care renouncement for financial reasons. Overall, 24% of the surveyed population declared having renounced to care for time-related motives. The independent predictors for time-related renouncing were different than those for renouncing care for financial reasons: a higher education level and a poor perceived health were independently associated with time-related renouncement; retired persons and students were found to renounce care less frequently than persons with a job. Conclusions Renouncing for financial reasons, a major target of the 2016 health law, represented a public health problem in French Guiana. Renouncing for lack of time was an important motive for renouncing, which is aggravated by the insufficient number of health professionals, but may benefit from organizational solutions. There are avenues for improvement of health for the most vulnerable: promote health, act on risk factors, and facilitate the readability and accessibility of the health system. Recent reforms to stabilize health insurance may however have some adverse consequences for migrants

Relations between influenza, dengue outbreaks, and subsequent bacterial sepsis in French Guiana: a time series analysis

Objective : Infuenza has been shown to increase the risk for severe bacterial infection, in the tropics the seasonality of in uenza epidemics is less marked and this may not be the case. Dengue is often followed by prolonged asthenia and some physicians hypothesized increased susceptibility to infections based on anecdotal observations. Time series of in uenza and dengue surveillance were confronted with bacterial sepsis admissions to test the hypotheses. Monthly surveillance data on in uenza and dengue and aggregated sepsis data in Cayenne hospital were matched between 24/10/2007 and 27/09/2016. An ARIMA (1,0,1) model was used. Results : The series of the number of monthly cases of sepsis was positively associated with the monthly number of cases of in uenza at time t (β=0.001, p=0.0359). Forecasts were imperfectly correlated with sepsis since in uenza is not the only risk factor for sepsis. None of the ARIMA models showed a signi cant link between the dengue series and the sepsis series. There was thus no link between dengue epidemics and sepsis but it was estimated that for every 1000 cases of u there was one additional case of sepsis. In this tropical setting, in uenza was highly seasonal, and improved vaccination coverage could have bene ts on sepsis

Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study

International audienceBackground Fungal infections remain a major contributor to the opportunistic infections that affect people living withHIV. Among them, histoplasmosis is considered neglected, often being misdiagnosed as tuberculosis, and isresponsible for numerous deaths in Latin America. The objective of this study was to estimate the burden ofHIV-associated histoplasmosis compared with tuberculosis in Latin American countries.Methods For this modelling study, we estimated prevalence of previous exposure to Histoplasma capsulatum, HIVassociatedhistoplasmosis annual incidence, and number of deaths in 2012 in Latin American countries based onhistorical histoplasmin skin test studies in the general population, with an antigen dilution level of more than 1/10.Studies were identified in a literature search. Data on HIV-associated tuberculosis were extracted from the WHOnotifications and outcomes tables and data on people living with HIV were extracted from the UNAIDS report for theyear 2012. We systematically propagated uncertainty throughout all the steps of the estimation process.Findings Among 1310 articles identified as of June 1, 2015, 24 articles were included in the study, representing129 histoplasmin skin test studies led in the general population of Latin American countries. For the year 2012, weestimated a range of 6710 (95% CI 5680–7867) to 15 657 (13 254–18 357) cases of symptomatic HIV-associatedhistoplasmosis in Latin America. Hotspot areas for histoplasmosis prevalence (>30%) and incidence (>1·5 cases per100 people living with HIV) were Central America, the northernmost part of South America, and Argentina. Accordingto realistic scenarios, we estimated a range of 671 (95% CI 568–787) to 9394 (7952–11 014) deaths related tohistoplasmosis, compared with 5062 (3777–6405) deaths related to tuberculosis reported in Latin America.Interpretation Our estimates of histoplasmosis incidence and deaths are high and consistent with published data. Forthe first time, the burden of histoplasmosis is estimated to be equivalent in incidence and even higher in deaths whencompared with tuberculosis among people living with HIV in Latin America

Relationship between influenza and dengue outbreaks, and subsequent bacterial sepsis in French Guiana: A time series analysis

International audienceBackground: Influenza has been shown to increase the risk for severe bacterial infection, in the tropics the seasonality of influenza epidemics is less marked, and this may not be the case. Dengue is often followed by prolonged asthenia and some physicians hypothesized increased susceptibility to infections based on anecdotal observations. Design and Methods: Time series of influenza and dengue surveillance were confronted bacterial sepsis admissions to test the hypotheses. Monthly surveillance data on influenza and dengue and aggregated sepsis data in Cayenne hospital were matched between 24/10/2007 and 27/09/2016. An ARIMA (1,0,1) model was used. Results: The series of the number of monthly cases of sepsis was positively associated with the monthly number of cases of influenza at time t (β=0.001, p=0.0359). Forecasts were imperfectly correlated with sepsis since influenza is not the only risk factor for sepsis. None of the ARIMA models showed a significant link between the dengue series and the sepsis series. Conclusions: There was thus no link between dengue epidemics and sepsis, but it was estimated that for every 1,000 cases of flu there was one additional case of sepsis. In this tropical setting, influenza was highly seasonal, and improved vaccination coverage could have benefits on sepsis