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Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα.

Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs’ aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8+-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.

Summary Background There is limited information regarding the efficacy and long term safety of intrathecal injection of liposomal cytarabine in leukemic or lymphomatous meningitis. Design and Methods We studied 20 consecutive HIV-negative patients with leukemic or lymphomatous meningitis who were treated with intrathecal liposomal cytarabine between 2004 and 2007. We focused on efficacy and on any late effects of the drug. Results Twenty patients who received intrathecal liposomal cytarabine injection as part of their treatment; of these, 9 were alive and in complete remission at the end of the study. Median survival from the time of the first injection was 22.7 months (range, 0.5 to 64 months). Short-term toxicity related to intrathecal of liposomal cytarabine was observed in 2 cases; headache in 1 case and regressive facial palsy and diplopy in 1 case. Long-term toxicity was seen in 2 cases; clinical symptoms were urinary and fecal dysfunction with confusion in 1 case, and urinary dysfunction in 1 case. Both patients had been heavily pre-treated with neurotoxic drugs and neuraxis irradiation. Conclusion In our experience, intrathecal liposomal cytarabine injections were convenient in the management of leukemic and lymphomatous meningitis, and can lead to long-term survival. Although neurotoxicity was rare, clinicians should exercise caution when retreatment is required in relapsing patients.

Water losses from water distribution means have a high environmental impact in terms of natural resource depletion (water, energy, ecosystems). This work aims to develop an optical airborne surveillance service for the detection of water leaks (WADI—Water-tightness Airborne Detection Implementation) to provide water utilities with adequate and timely information on leaks in water transportation mains outside urban areas. Firstly, a series of measurement campaigns were performed with two hyperspectral cameras and a thermal infrared camera in order to select the most appropriate wavelengths and combinations thereof for best revealing high moisture areas, which are taken as a proxy for water leakage. The Temperature-Vegetation-Index method (T-VI, also known as Triangle/Trapezoid method) was found to provide the highest contrast-to-noise ratio. This preliminary work helped select the most appropriate onboard instrumentation for two types of aerial platforms, manned (MAV) and unmanned (UAV). Afterwards, a series of measurement campaigns were performed from 2017 to 2019 in an operational environment over two water distribution networks in France and Portugal. Artificial leaks were introduced and both remote sensing platforms successfully detected them when excluding the unfavorable situations of a recent rain event or high vegetation presence. With the most recent equipment configuration, known and unknown real leaks in the overflown part of a water transportation network in Portugal have been detected. A significant number of false alarms were also observed which were due either to natural water flows (groundwater exfiltration, irrigation runoff and ponds) or to vegetation-cover variability nearby water-distribution nodes. Close interaction with the water utilities, and ancillary information like topographic factors (e.g., slope orientation), are expected to reduce the false alarm rates and improve WADI’s methodology performance.

BRAF (V600) mutations are frequent in melanomas, and BRAF(V600)-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ≥2 mm according to BRAF (V600) mutations and other previously reported prognostic criteria. This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF (V600) mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60 % melanoma cells. BRAF mutations (p.V600E and p.V600K in 83 and 14 % of cases, respectively) were detected in 40 % of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3 %, with a median OS of 1.4 and 2.8 years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P = 0.005, hazard ratio 2.2, 95 % confidence interval 1.3-3.9) and BRAF status (P = 0.005, hazard ratio 1.9, 95 % confidence interval 1.2-3.1). BRAF (V600) status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.

Several lines of evidence indicate that immature oocyte retrieval and subsequent in vitro maturation (IVM) without ovarian stimulation may be a reliable option in assisted reproductive technologies (ART). However, few outcome data are available for children born following this technique. We assessed height and weight development of French children conceived after IVM. All children conceived after IVM at Antoine Beclere Hospital (Clamart, France) and born between June 2003 and October 2008 (n = 38) were included in a prospective cohort study and compared with a control group of children conceived by ICSI without IVM, matched for maternal age, gestational age and singleton/twin pregnancies. Follow-up included clinical examination at one year and a questionnaire completed by parents when the children were two years old (97% follow-up rate). No statistical differences between IVM and control groups were found for boys. Mean weight, height and head circumference at birth were significantly greater for IVM than for ICSI girls (3.236 kg vs 2.701 kg (p = 0.03); 49 cm vs 47 cm (p = 0.01) and 34 cm vs 33 cm (p = 0.04), respectively). At one year, IVM girls remained heavier (mean weight 10.2 kg vs 8.6 kg (p = 0.001)) and taller (76 cm vs 73 cm (p = 0.03)), and there was a two-point difference in BMI between the two groups of girls (18 vs 16 (p = 0.01)). Our results in girls born after IVM should be interpreted with caution. It remains unclear whether the observed sexual dimorphism is due to IVM technology or to maternal characteristics such as underlying infertility in patients with polycystic ovary syndrome (PCOS). Further monitoring of the outcomes of these infants is required.

Purpose The impact of human activities on marine environments is poorly addressed by the scope of life cycle impact assessment (LCIA). The aim of this study is to provide characterization factors to assess impacts of sea use such as fishing activities or seafloor destruction and transformation on the life support functions of marine ecosystems. Methods The consensual framework of land use for ecosystem services damage potential assessment was applied, according to the recent United Nations Environment Programme-Society for Environmental Toxicology and Chemistry (UNEP-SETAC) guidelines, using the free net primary production as a quality index of life support functions. Results and discussion The impact of shading, biomass removal, seafloor destruction, and artificial habitat creation on the available quantity of organic biomass for the ecosystem functioning was quantified at the midpoint level with a common unit (kg of organic carbon equivalent). It included effects of human interventions on both the ecosystem production potential and the stock of biomass present within the ecosystem. Characterization factors (CF) for biomass removal vary from 0.1 kgCeq kg−1 for seaweed to 111.1 kgCeq kg−1 for tunas, bonitos, and billfishes. CF for seafloor destruction range from 0.164 kgCeq m−2 for a temperate seagrass ecosystem to 0.342 kgCeq m−2 for an intertidal tropical rocky habitat. Conclusions This study provides an operational method in order to compute sea use impact assessment.