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Introduction: At the onset of the 20th century, ancient clinical observations of cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They were reported from 1914 to 1960, but remained unexplained. In 1983, in San Francisco, Calif., USA, cancer epidemics were related to infections by the human immunodeficiency virus type 1 (HIV-1) known as AIDS disease. Yet since 1996, it is known that HIV-1 strains are not the only ones involved. In Sub-Saharan Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1) and genital recurrent herpes simplex virus type 2 (HSV-2) appeared many times prior to infection by HIV-1. Case Reports: Data on these ancient medical observations regarding African cancer epidemics can today be referred to as the relationship between the unfortunate immune deficiency of herpes in Bantu populations and HIV-1 viral strains. For centuries, the Bantu populations dispersed in forests were living in close proximity to chimpanzees infected by simian immunodeficiency virus (SIV) and were exposed to SIV contamination which became HIV-1 in human beings. Presently, these unexplained Bantu cancer epidemics can be linked to the viral partnership of HSV-1/HSV-2 to HIV-1 strains. Conclusion: The key issue is now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment administered early during childhood to Bantu populations will offer a mean of preventing herpes diseases related to HIV-1 infection and hence avoid cancer epidemics.

This systematic review and meta-analysis is the first to evaluate the effects of group-based social skills training (SST) on parent-report social responsiveness in adults with autism spectrum disorder (ASD). A total of 18 studies were included in the narrative review and among them five randomized-controlled trials (n = 145) were included in the meta-analysis. SST had large positive effects on social responsiveness. The narrative review identified that SST could improve patients' outcomes in adults with ASD. These results should be interpreted with caution due to the moderate quality of the existing evidence, which could have inflated effect sizes. The absence of active comparator control groups makes unclear whether improvements at post-treatment are treatment-specific or are attributable to common factors to all psychotherapies.

This systematic review and meta-analysis is the first to evaluate the effects of group-based social skills training (SST) on parent-report social responsiveness in adults with autism spectrum disorder (ASD). A total of 18 studies were included in the narrative review and among them five randomized-controlled trials (n = 145) were included in the meta-analysis. SST had large positive effects on social responsiveness. The narrative review identified that SST could improve patient's outcomes in adults with ASD. These results should be interpreted with caution due to the moderate quality of the existing evidence, which could have inflated effect sizes. The absence of active comparator control groups makes unclear whether improvements at post-treatment are treatment-specific or are attributable to common factors to all psychotherapies., Author(s): J Dubreucq [sup.1] [sup.2] [sup.3] [sup.4] , F Haesebaert [sup.6] [sup.7] , J Plasse [sup.6] [sup.7] , M Dubreucq [sup.2] [sup.3] , N Franck [sup.1] [sup.5] [sup.6] Author Affiliations: [...]

We investigated the specific contribution of efferent information in a self-recognition task. Subjects experienced a passive extension of the right index finger, either as an effect of moving their left hand via a lever ('self-generated action'), or imposed externally by the experimenter ('externally-generated action'). The visual feedback was manipulated so that subjects saw either their own right hand ('view own hand' condition) or someone else's right hand ('view other's hand condition) during the passive extension of the index finger. Both hands were covered with identical gloves, so that discrimination on the basis of morphological differences was not possible. Participants judged whether the right hand they saw was theirs or not. Self-recognition was significantly more accurate when subjects were themselves the authors of the action, even though visual and proprioceptive information always specified the same posture, and despite the fact that subjects judged the effect and not the action per se. When the passive displacement of the participants right index finger was externally generated, and only afferent information was available, self-recognition performance dropped to near-chance levels. Differences in performance across conditions reflect the distinctive contribution of efferent information to self-recognition, and argue against a dominant role of proprioception in self-recognition.

IntroductionMouse models of human filarial infections are not only urgently needed to investigate the biology of the nematodes and their modulation of the host’s immunity, but will also provide a platform to screen and test novel anti-filarial drugs. Recently, murine Loa loa infection models have been stablished using immunocompromised mouse strains, whereas murine Mansonella perstans infections have not been implemented until now.MethodsTherefore, we aim to establish experimental M. perstans infections using the immunocompromised mouse strains RAG2IL-2Rγ-/- (lack B, T and natural killer cells), IL-4Rα/IL-5-/- (impaired IL-4/5 signalling and eosinophil activation) and NOD.Cg-PrkdcscidIl2rgtm1Wj l/SzJ (NOD scid gamma, NSG) BALB/c mice (lack mature lymphocytes) through subcutaneous (s.c.) or intraperitoneal (i.p.) inoculation of infective stage 3 larvae (L3) isolated from engorged vectors.ResultsIn total, 145 immunocompromised mice have been inoculated with 3,250 M. perstans, 3,337 O. volvulus, and 2,720 Loa loa L3 to comparatively analyse which immunocompromised mouse strain is susceptible to human filarial infections. Whereas, no M. perstans and O. volvulus L3 could be recovered upon 2-63 days post-inoculation, a 62-66% Loa loa L3 recovery rate could be achieved in the different mouse strains. Gender of mice, type of inoculation (s.c. or i.p.) or time point of analysis (2-63 days post inoculation) did not interfere with the success of L3 recovery. In addition, administration of the immune suppressants hydrocortisone, prednisolone and cyclophosphamide did not restore M. perstans L3 recovery rates.DiscussionThese findings show that RAG2IL-2Rg-/-BALB/c and C57BL/6, IL-4Rα/IL-5-/- BALB/c and NSG mice were not susceptible to M. perstans and O. volvulus L3 inoculation using the applied methods, whereas Loa loa infection could be maintained. Further studies should investigate if humanized immunocompromised mice might be susceptible to M. perstans. and O. volvulus.

In one case, skin biopsy displayed a superficial and deep perivascular and perieccrine lymphocytic infiltrate similar to those of chilblains or chilblain-like lesions. Relapse or new skin manifestations occurred in 2 patients following the second dose without worsening of symptoms. Patient 2 presented with 2 erythematous nodules 4 days after the first dose and chilblains 5 days after the second dose without nodules relapse. [Extracted from the article]

Background and Aims: There is evidence that some species can withstand a stress event better when experienced previously. This capacity could help to increase stress tolerance and resilience under recurrent stresses. To test the effect of a previous season drought imprint on the tolerance to a subsequent drought event, we compared the growth and physiological performance of young cv. Cabernet Sauvignon grapevines growing in a semi‐arid zone in Chile. Methods and Results: Treatments were single drought (SD; stressed during the second season) and double drought (DD; stressed during the first and second season). During the second season, DD vines budburst earlier, and leaves were smaller. During the drought period, DD showed a higher rate of photosynthesis despite a similar reduction in the stem water potential and stomatal conductance compared to that of SD. Such difference was associated to a higher maximum Rubisco carboxylation rate observed in DD. Conclusions: Our results suggest that grapevines exposed to drought are primed for an upcoming second drought event, the priming lasting from one season to the next, involving contrasting growth and physiological performance. Significance of the Study: Our study results contribute information to the emerging debate regarding drought‐priming effects on the tolerance of grapevines to recurrent drought events. [ABSTRACT FROM AUTHOR]

Summary: Background: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T‐cell (CTCL) and B‐cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. Objectives: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. Methods: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. Results: The calculated incidence was unprecedently high at 1·06 per 100 000 person‐years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal‐zone CBCL increased over time. Conclusions: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases. What is already known about this topic?Primary cutaneous lymphomas (PCLs) are a heterogeneous group of diseases.Little is known about changes over time in their epidemiology and about patients' characteristics and disease stages at the initial presentation. What does this study add?In this population‐based study we present changes over time in PCL epidemiology over a 15‐year period and show an unprecedentedly high incidence in Europe.The relative frequency of rare PCL remained stable over time, while other PCL subtypes were better stratified.This study suggests that the diagnosis of PCL should be evoked more frequently, and delivers up‐to‐date information on patients' characteristics at initial diagnosis in a European population. Linked Comment: Vermeer. Br J Dermatol 2021; 184:993–994. [ABSTRACT FROM AUTHOR]

Background. People suffering from schizophrenia cannot easily access employment in European countries. Different types of vocational programs coexist in France: supported employment, sheltered employment (ShE), and hybrid vocational programs. It is now acknowledged that the frequent cognitive impairments constitute a major obstacle to employment for people with schizophrenia. However, cognitive remediation (CR) is an evidence-based nonpharmacological treatment for these neurocognitive deficits. Methods. RemedRehab was a multicentric randomized comparative open trial in parallel groups conducted in eight centers in France between 2013 and 2018. Participants were recruited into ShE firms before their insertion in employment (preparation phase). They were randomly assigned to cognitive training Cognitive Remediation for Schizophrenia (RECOS) or Treatment As Usual (TAU). The aim of the study was to compare with the benefits of the RECOS program on access to employment and work attendance for people with schizophrenia, measured by the ratio: number of hours worked on number of hours stipulated in the contract. Results. Seventy-nine patients were included in the study between October 2018 and September 2019. Fifty-three patients completed the study. Hours worked / planned hours equal to 1 or greater than 1 were significantly higher in the RECOS group than in the TAU group. Conclusions. Participants benefited from a RECOS individualized CR program allows a better rate of work attendance in ShE, compared to the ones benefited from TAU. Traditional vocational rehabilitation enhanced with individualized CR in a population of patients with schizophrenia is efficient on work attendance during the first months of work integration. [ABSTRACT FROM AUTHOR]

Biting midges belonging to the genus Culicoides are tiny stout-shaped hematophagous insects and are thought to transmit the filarial nematode Mansonella perstans. Little is known about the Culicoides fauna in the rain forest belt of the Littoral Region of Cameroon. This study was designed to investigate the diversity, abundance and distribution of Culicoides spp. and their role as the purported vector(s) of M. perstans. Overnight light trap collections and human landing catches (HLCs) revealed eight species of Culicoides with C. grahamii being the most abundant species followed by C. milnei. Four anthropophilic species (C. inornatipennis, C. grahamii, C. fulvithorax and C. milnei) were determined by the HLCs with a higher abundance in the 4–6 p.m. collections. The drop trap technique and Mp419 LAMP assay confirmed C. milnei to be the most efficient vector in enabling the development of the microfilarial stage to the infective larval form of M. perstans. The LAMP assay also revealed that natural transmission of this nematode is fostered by C. milnei and C. grahamii in the wild. In conclusion, C. milnei was shown to be the main vector of M. perstans in the rain forest belt of the Littoral Region of Cameroon.

Immune checkpoint inhibitors (ICI) nivolumab and pembrolizumab, antiprogrammed cell death protein 1 antibodies, and ipilimumab, an anti-cytotoxic T-lymphocyte-associated antigen 4 antibody, are widely used in metastatic melanoma. Median time from ICI initiation to encephalitis onset was 42 days (range: 5-640) and was longer in patients receiving pembrolizumab than in patients receiving combined nivolumab and ipilimumab. Patients displaying ICI-induced encephalitis presented with a non-specific pattern of encephalitis with focal symptoms, confusion, meningeal syndrome, with exclusion of infectious or carcinomatous meningitis or new brain metastasis. [Extracted from the article]

Two well-established numerical representations of the coagulation cascade either initiated by the intrinsic system (Chatterjee et al., PLOS Computational Biology 2010) or the extrinsic system (Butenas et al., Journal of Biological Chemistry, 2004) were compared with thrombin generation assays under realistic pathological conditions. Biochemical modifications such as the omission of reactions not relevant to the case studied, the modification of reactions related to factor XI activation and auto-activation, the adaptation of initial conditions to the thrombin assay system, and the adjustment of some of the model parameters were necessary to align in vitro and in silico data. The modified models are able to reproduce thrombin generation for a range of factor XII, XI, and VIII deficiencies, with the coagulation cascade initiated either extrinsically or intrinsically. The results emphasize that when existing models are extrapolated to experimental parameters for which they have not been calibrated, careful adjustments are required.

Abstract 2D metal–organic frameworks have been recently proposed as a flexible platform for realizing new functional materials including quantum phases. Here, we present a method to create metal‐organic dimer complexes by on‐surface assembly on a metal substrate using low‐temperature scanning tunneling microscopy (STM) and spectroscopy (STS). We demonstrate that a dimer of Mn‐Phthalocyanine (MnPc)2 on a Ag(111) surface can be switched between two stable configurations upon a small conformational change controlled by STM manipulation. By means of density‐functional theory calculations, it is found that the two conformations correspond to an antiferromagnetic (AFM) and a ferromagnetic (FM) state respectively. Directly coordinated Mn atoms of the dimer lead to an AFM‐coupling whereas indirectly coordinated (shifted) Mn atoms lead to a FM‐coupling. Rarely seen in a molecular‐dimers with transition‐metal atoms, the FM‐AFM‐FM transition is thus readily on‐surface accessible. Furthermore, the two configurations of the switch are easily identified by their Kondo states, opening interesting routes in terms of both, writing (FM versus AFM states) and reading. These results pave the experimental route toward dimer‐based materials with complex magnetic structures of potential interest for application in spintronics, logics and computing.

Counting and sizing blood cells in hematological analyzers is achieved using the Coulter principle. The cells flow in a micro-aperture in which a strong electrical field is imposed, so that an electrical perturbation, called pulse, is measured each time a cell crosses the orifice. The pulses are expected to contain information on the shape and deformability of Red Blood Cells (RBCs), since recent studies state that RBCs rotate and deform in the micro-orifice. By implementing a dedicated numerical model, the present study sheds light on a variety of cells dynamics, which leads to different associated pulse signatures. Furthermore, simulations provide new insights on how RBCs shapes and mechanical properties affect the measured signals. Those numerical observations are confirmed by experimental assays. Finally, specific features are introduced for assessing the most relevant characteristics from the various pulse signatures and shown to highlight RBCs alterations induced by drugs. In summary, this study paves the way to a characterization of RBC rheology by routine hematological instruments.

Abstract Background The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used. Methods To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions. Results A total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y; 47% female; 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs); median follow-up, 37.3 months). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors. Conclusions This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 ( https://clinicaltrials.gov/ct2/show/NCT01207440 ).

Digital twins in the mechanics of materials usually involve multimodal data in the sense that an instance of a mechanical component has both experimental and simulated data. These simulations aim not only to replicate experimental observations but also to extend the data. Whether spatially, temporally, or functionally, augmentation is needed for various possible uses of the components to improve the predictions of mechanical behavior. Related multimodal data are scarce, high-dimensional and a physics-based causality relation exists between observational and simulated data. We propose a data augmentation scheme coupled with data pruning, in order to limit memory requirements for high-dimensional augmented data. This augmentation is desirable for digital twining assisted by artificial intelligence when performing nonlinear model reduction. Here, data augmentation aims at preserving similarities in terms of the validity domain of reduced digital twins. In this article, we consider a specimen subjected to a mechanical test at high temperature, where the as-manufactured geometry may impact the lifetime of the component. Hence, an instance is represented by a digital twin that includes 3D X-Ray tomography data of the specimen, the related finite element mesh, and the finite element predictions of thermo-mechanical variables at several time steps. There is, thus, for each specimen, geometrical and mechanical information. Multimodal data, which couple different representation modalities together, are hard to collect, and annotating them requires a significant effort. Thus, the analysis of multimodal data generally suffers from the problem of data scarcity. The proposed data augmentation scheme aims at training a recommending system that recognizes a category of data available in a training set that has already been fully analyzed by using high-fidelity models. Such a recommending system enables the use of a ROM-net for fast lifetime assessment via local reduced-order models.

Abstract: Background: A distinctive eruption referred to as ‘insect bite‐like reaction’ or ‘eosinophilic dermatosis of haematological malignancy’ has been described during the course of haematological B‐cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. Objectives: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. Methods: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo‐vesicles and/or nodules were included. Clinical, histopathological, immunohistochemical and molecular data were reviewed. Results: No significant insect bite history or seasonal predominance was recorded. Patients had pruritic papules (81%), papulo‐vesicles (43%) and nodules (38%), often predominated in the head and neck region (84%), without complete remission periods in most cases (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%). Histological and immunohistochemical review showed a dense dermal lymphocytic infiltrate predominantly composed of T lymphocytes (100%), with frequent eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic) pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides; clusters of tumour B cells were identified in 47% of cases using appropriate phenotyping markers. In 10/14 cases (71.4%) tested for B‐cell IgH gene rearrangement, a B‐cell clone was identified in skin lesions (identical to the blood clone in nine cases), whereas no T‐cell clone was present. Conclusion: We propose the denomination ‘T‐cell papulosis associated with B‐cell malignancy’ (TCP‐BCM) for this distinctive eruption. Although resulting in various histopathological pictures, it can be easily recognized by clinicians and may be identified by informed pathologists relying on some key features. An extravasation of tumour B cells with skin‐homing properties associated with a secondary, predominant, T‐cell immune reaction could explain the clinicopathologic aspect and the prolonged regressive and recurrent course of the disease. [ABSTRACT FROM AUTHOR]

Abstract Background The mass drug administration of ivermectin for onchocerciasis control has contributed to a significant drop in Loa loa microfilaria loads in humans that has, in turn, led to reduction of infection levels in Chrysops vectors. Accurate parasite detection is essential for assessing loiasis transmission as it provides a potential alternative or indirect strategy for addressing the problem of co-endemic loiasis and lymphatic filariasis through the Onchocerciasis Elimination Programme and it further reflects the true magnitude of the loiasis problem as excess human mortality has been reported to be associated with the disease. Although microscopy is the gold standard for detecting the infection, the sensitivity of this method is compromised when the intensity of infection is low. The loop-mediated isothermal amplification (LAMP) assay of parasite DNA is an alternative method for detecting infection which offers operational simplicity, rapidity and versatility of visual readout options. The aim of this study was to validate the Loa loa LAMP assay for the detection of infected Chrysops spp. under experimental and natural field conditions. Methods Two sets of 18 flies were fed on volunteers with either a low ( 30,000mf/ml) microfilarial load. The fed flies were maintained under laboratory conditions for 14 days and then analysed using LAMP for the detection of L. loa infection. In addition, a total of 9270 flies were collected from the north-west, east, and south-west regions (SW 1 and 2) of Cameroon using sweep nets and subjected to microscopy (7841 flies) and LAMP (1291 flies plus 138 nulliparous flies) analyses. Results The LAMP assay successfully detected parasites in Chrysops fed on volunteers with both low and high microfilariaemic loads. Field validation and surveillance studies revealed LAMP-based infection rates ranging from 0.5 to 31.6%, with the lowest levels in SW 2 and the highest infection rates in SW 1. The LAMP assay detected significantly higher infection rates than microscopy in four of the five study sites. Conclusion This study demonstrated the potential of LAMP as a simple surveillance tool. It was found to be more sensitive than microscopy for the detection of experimental and natural L. loa infections in Chrysops vectors.

This study aims at analysing the technical efficiency of the tourism industry worldwide. Using a sample of 111 countries worldwide from 2008 to 2016, we estimated the tourism industry technical efficiency score to measure of the industry performance from a translog output distance function modelling. Our results showed that high-income countries are more efficient because of higher qualified labour, and higher productivity of natural and cultural resources. Besides, our results support that African and Asian countries are less efficient than those from Europe and America. For international comparison purposes, our findings suggested that the level of income and the location of destinations should be incorporated as determinants and inputs of the tourism production function to the technical efficiency. In the political view, policymakers are encouraged to be aware of the income level of their citizens to improve the performance of their tourism sector.

Neutrophilic eccrine hidradenitis ( NEH) is a rare neutrophilic dermatosis, first described in patients undergoing chemotherapy for a malignant haemopathy. It has polymorphous clinical features and the association of both clinical and histological features is necessary to make a diagnosis. We report the first two cases of NEH in patients treated with a BRAF inhibitor ( BRAFi), either dabrafenib or vemurafenib, for a stage IV metastatic melanoma. Disseminated erythematous plaques associated with fever and polyarthralgia occurred early after the initiation of treatment and were badly tolerated. Histological analyses confirmed the diagnosis of NEH. Symptoms disappeared a few days after the cessation of treatment and introduction of topical steroids. The replacement of one BRAFi with another is a therapeutic alternative as it is not necessarily associated with a relapse of NEH. NEH can be added to the spectrum of neutrophilic dermatoses induced by BRAFis. It occurs earlier (3-4 days) than previously described drug-induced NEH (9-12 days) and may be an earlier stage of eccrine squamous syringometaplasia, which has already been reported in the context of BRAFi-treated patients. [ABSTRACT FROM AUTHOR]

Dear Editor, Controversy exists regarding the risk and prognosis of lymphomas during treatment with biologics.[1] Risk evaluation must consider the underlying medical condition - as chronic inflammatory diseases are associated with an excess risk of lymphoma[[2]] - and ongoing treatments (azathioprine, ciclosporin).[[4]] To date, a few isolated cases and two small series of primary cutaneous lymphoma (PCL) - mostly mycosis fungoides (MF) - have been reported in patients treated with biologics.[[6]] Our aim was to describe PCL in patients during treatment with biologics from two national registries in order to evaluate their behaviour and to propose management recommendations. Fifteen patients with CTCL had a past of benign dermatosis, eczema or psoriasis, confirmed by skin biopsy in six patients (including one with T-MF). Psoriasis in patients with mycosis fungoides: a clinicopathological study of 25 patients. [Extracted from the article]

The registered dose for imatinib is 400 mg/d, despite high inter-patient variability in imatinib plasmatic exposure. Therapeutic drug monitoring (TDM) is routinely used to maximize a drug’s efficacy or tolerance. We decided to conduct a prospective randomized trial (OPTIM-imatinib trial) to assess the value of TDM in patients with chronic phase chronic myelogenous treated with imatinib as first-line therapy (NCT02896842). Eligible patients started imatinib at 400 mg daily, followed by imatinib [C]min assessment. Patients considered underdosed ([C]min < 1000 ng/mL) were randomized in a dose-increase strategy aiming to reach the threshold of 1000 ng/mL (TDM arm) versus standard imatinib management (control arm). Patients with [C]min levels ≥ 1000 ng/mL were treated following current European Leukemia Net recommendations (observational arm). The primary endpoint was the rate of major molecular response (MMR, BCR::ABL1IS ≤ 0.1%) at 12 months. Out of 133 evaluable patients on imatinib 400 mg daily, 86 patients had a [C]min < 1000 ng/mL and were randomized. The TDM strategy resulted in a significant increase in [C]min values with a mean imatinib daily dose of 603 mg daily. Patients included in the TDM arm had a 12-month MMR rate of 67% (95% CI, 51–81) compared to 39% (95% CI, 24–55) for the control arm (p = 0.017). This early advantage persisted over the 3-year study period, in which we considered imatinib cessation as a censoring event. Imatinib TDM was feasible and significantly improved the 12-month MMR rate. This early advantage may be beneficial for patients without easy access to second-line TKIs.

Introduction: At the onset of the 20th century, ancient clinical observations of cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They were reported from 1914 to 1960, but remained unexplained. In 1983, in San Francisco, Calif., USA, cancer epidemics were related to infections by the human immunodeficiency virus type 1 (HIV-1) known as AIDS disease. Yet since 1996, it is known that HIV-1 strains are not the only ones involved. In Sub-Saharan Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1) and genital recurrent herpes simplex virus type 2 (HSV-2) appeared many times prior to infection by HIV-1. Case Reports: Data on these ancient medical observations regarding African cancer epidemics can today be referred to as the relationship between the unfortunate immune deficiency of herpes in Bantu populations and HIV-1 viral strains. For centuries, the Bantu populations dispersed in forests were living in close proximity to chimpanzees infected by simian immunodeficiency virus (SIV) and were exposed to SIV contamination which became HIV-1 in human beings. Presently, these unexplained Bantu cancer epidemics can be linked to the viral partnership of HSV-1/HSV-2 to HIV-1 strains. Conclusion: The key issue is now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment administered early during childhood to Bantu populations will offer a mean of preventing herpes diseases related to HIV-1 infection and hence avoid cancer epidemics. [ABSTRACT FROM AUTHOR]