Can a targeted psychological intervention be effective for young people following a first manic episode? Results from an 18-month pilot study.

Aim: There is a scarce literature describing psychological interventions for a young, first-episode cohort who have experienced psychotic mania. This study aimed to assess whether a manualized psychological intervention could be effective in reducing symptomatology and relapse, and improve functional outcome in this population. Methods: The study was an open-label design, drawn from a larger pharmacotherapy trial. All participants in the pharmacotherapy trial were offered a manualized psychological intervention in addition to case management. Inclusion in the psychotherapy group was based on participant's choice, and on completion of four or more of the eight modules offered. All clinical files were audited to ensure accuracy of group allocation. Forty young people aged 15 to 25 years old who had experienced a manic episode with psychotic features were recruited into the study, with 20 people in the combined treatment as usual plus psychotherapy group (P+TAU), and an equal number of matched control participants who received treatment as usual (TAU) within the same service. All participants were prescribed antipsychotic and mood-stabilizing medication. Symptomatic, functional and relapse measures were taken both at baseline and at 18-month follow-up. Results: Manic symptoms improved significantly for both groups, with no differences between groups. Depression scores and overall symptom severity were significantly lower in the P + TAU group. No differences were evident between groups with regard to numbers or type of relapse. The P + TAU group had significantly better social and occupational functioning after 18 months. Conclusion: This study suggests that a manualized psychological intervention targeted to a first-episode population can be effective in reducing depression and overall symptom severity, and can improve functional outcome following a first episode of psychotic mania.

Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon β-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial.

Recent studies have demonstrated the immunomodulatory properties of vitamin D, and vitamin D deficiency may be a risk factor for the development of MS. The risk of developing MS has, in fact, been associated with rising latitudes, past exposure to sun and serum vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels have also been associated with relapses and disability progression. The identification of risk factors, such as vitamin D deficiency, in MS may provide an opportunity to improve current treatment strategies, through combination therapy with established MS treatments. Accordingly, vitamin D may play a role in MS therapy. Small clinical studies of vitamin D supplementation in patients with MS have reported positive immunomodulatory effects, reduced relapse rates and a reduction in the number of gadolinium-enhancing lesions. However, large randomized clinical trials of vitamin D supplementation in patients with MS are lacking. SOLAR (Supplementation of VigantOL(®) oil versus placebo as Add-on in patients with relapsing-remitting multiple sclerosis receiving Rebif(®) treatment) is a 96-week, three-arm, multicenter, double-blind, randomized, placebo-controlled, Phase II trial (NCT01285401). SOLAR will evaluate the efficacy of vitamin D(3) as add-on therapy to subcutaneous interferon beta-1a in patients with RRMS. Recruitment began in February 2011 and is aimed to take place over 1 calendar year due to the potential influence of seasonal differences in 25(OH)D levels.

Rapid diagnostic tests for non-malarial febrile illness in the tropics.

The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.

Comparable Survival Between HIV+ and HIV- non-Hodgkin and Hodgkin Lymphoma Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation.

Autologous stem cell transplantation (ASCT) has been successfully used in HIV-related lymphoma (HIV-Ly) patients on highly active antiretroviral therapy. We report the first comparative analysis between HIV-Ly and a matched cohort of HIV(-) lymphoma patients. This retrospective European Group for Blood and Marrow Transplantation study included 53 patients (66% non-Hodgkin and 34% Hodgkin lymphoma) within each cohort. Both groups were comparable except for the higher proportion of males, mixed-cellularity Hodgkin lymphoma and patients receiving granulocyte colony-stimulating factor before engraftment and a smaller proportion receiving total body irradiation-based conditioning within the HIV-Ly cohort. Incidence of relapse, overall survival, and progression-free survival were similar in both cohorts. A higher nonrelapse mortality within the first year after ASCT was observed in the HIV-Ly group (8% vs 2%), predominantly because of early bacterial infections, although this was not statistically significant and did not influence survival. Thus, within the highly active antiretroviral therapy era, HIV patients should be considered for ASCT according to the same criteria adopted for HIV(-) lymphoma patients.

Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer.

BACKGROUND: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population. METHODS: We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05. RESULTS: In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation. CONCLUSIONS: The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in others having limited prognostic value. However, in the subpopulations where it is prognostic, it represents a marker of much higher risk than previously considered. KRAS mutation status does not seem to represent a strong prognostic variable.

Severe occlusive vasculitis as a complication of cat scratch disease

BACKGROUND: The purpose of this communication is to report a severe occlusive vasculitis as a complication of cat scratch. HISTORY AND SIGNS: A 34-year-old Hispanic woman presented with a sudden visual loss of the right eye associated with shivers, high fever and arthritis which developed 2 months after a cat's bite. Fundus examination showed papillitis and a palor of the paramacular zone of the retina. Fluorescein angiography revealed multiple arterial and venous vasculitic occlusions. THERAPY AND OUTCOME: Auto-immune disease and endocarditis were ruled out by an extensive medical work-up.The diagnosis of Bartonella henselae was confirmed by a positive serology. A systemic antibiotherapy with azithromycin, doxycyclin, rifampicin and steroid therapy resulted in a good clinical response, including a rapid visual recovery with a visual acuity of 20/20 and no relapse of the disease at 6 months follow-up. CONCLUSIONS: Ocular complications associated with cat scratch disease may include vasculitis with both arterial and venous occlusions causing severe visual loss.

Molecular pathology of colorectal cancer.

Colorectal cancer (CRC) is one of the most intensively studied cancer types, partly because of its high prevalence but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently (sessile) serrated adenomas, which can be detected endoscopically and removed. The morphological steps in the adenoma-carcinoma sequence have been elucidated at a molecular level, which has been facilitated by identification of the genes responsible for familial intestinal cancer. However, apart from early detection of familial forms of CRC and its use in genetic counseling, until recently such detailed molecular knowledge has had little impact on clinical management of the disease. This has dramatically changed in the last decade. With drugs specifically targeting the epidermal growth factor receptor (EGFR) having been shown effective in CRC, mechanisms responsible for resistance have been explored. The finding that KRAS mutated cancers do not respond to anti-EGFR treatment has had a profound impact on clinical management and on molecular diagnostics of CRC. Additional genetic tests for mutations in NRAS, BRAF and PIK3CA contribute to determining who to treat, and others will follow. New therapies effective in patients with advanced CRC are under investigation. Remaining burning questions for optimal management are which patients will relapse after resection of the primary tumor and which patients will respond to the standard 5FU-oxaliplatin adjuvant treatment regimen. Predictive tests to address these issues are eagerly awaited. New classifications of CRC, based on molecular parameters, are emerging, and we will be confronted with new subtypes of CRC, for which the definition is based on combinations of gene expression patterns, chromosomal alterations, gene mutations and epigenetic characteristics. This will be instrumental in designing new approaches for therapy but will also be translated into molecular diagnostics. Both will contribute to improved clinical management of CRC.

Best practice in the management of mild-to-moderately active ulcerative colitis and achieving maintenance of remission using mesalazine.

Optimizing treatment goals in ulcerative colitis requires recognizing the needs of patients. It is increasingly recognized that adapting treatment strategies aligned with patient needs can improve patient compliance and consequently minimize relapse rates. Tailoring of treatment strategies can improve not only patient quality of life, and decrease the number harmed by adverse events from more potent drugs, but can also save valuable healthcare costs by avoiding high-cost treatment interventions associated with acute ulcerative colitis. This review will consider several elements of mesalazine management from the patient perspective based on a range of clinical and patient-focused evidence. By highlighting patient preferences in disease management it is envisaged that this review will aid physicians to optimize treatment decisions with the different mesalazine preparations available.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

Altering in vivo fate of heart-infiltrating progenitors from pro-fibrotic into F4/80+macrophages prevents progression of myocarditis into inflammatory dilated cardiomyopathy

Rationale: Experimental autoimmune myocarditis (EAM) mirrors important pathogenic aspects of inflammatory cardiomyopathy, a common cause of heart failure. In EAM, TGF-β-dependent conversion of heart-infiltrating prominin-1+ progenitors into myofibroblasts is critical for development of fibrosis and the end-stage heart failure phenotype. Therapeutic strategies modulating the in vivo fate of prominin-1+ progenitors might therefore prevent TGF-β-mediated cardiac fibrosis and pathological remodelling. Methods and Results: EAM was induced in BALB/c mice using alpha-myosin heavy chain (aMyHC) peptide/complete Freund's adjuvant (CFA) immunization. Prominin-1+ cells were isolated from the inflamed hearts at day 21 after immunization, expanded and treated with Macrophage Colony-Stimulating Factor (M-CSF) or Transforming Growth Factor-beta (TGF-β). Herein, we demonstrated that M-CSF turns, ex vivo and in the EAM, heart-infiltrating prominin-1+ progenitors into immunosuppressive F4/80/CD11b/CD16/32/NOS2-expressing, nitric oxide producing and E.coli bacteria phygocyting macrophages, and protect further TGF-β-stimulated differentiation into pathogenic myofibroblasts. Systemic M-CSF treatment during myocarditis completely prevented post-inflammatory fibrosis, T cell relapse and left ventricular dysfunction. Mechanistically, M-CSF-induced macrophage differentiation from prominin-1+ progenitors critically required nitric oxide synthase 2. Accordingly, M-CSF treatment failed to reduce myocardial fibrosis development in Nos2-/- mice. Conclusions: Altering the in vivo fate of inflammatory prominin-1 expressing progenitors from pro-fibrotic into the F4/80 expressing macrophage phenotype protects from myocarditis progression, cardiac fibrosis, and heart failure. These findings offer a modern therapeutic model and challenge former concepts, which attributed macrophages a detrimental role in inflammatory cardiomyopathy progression.

Accuracy of sentinel lymph node dissection for melanoma staging in the presence of a collision tumour with a lymphoproliferative disease.

Sentinel lymph node dissection (SLND) identifies melanoma patients with metastatic disease who would benefit from radical lymph node dissection (RLND). Rarely, patients with melanoma have an underlying lymphoproliferative disease, and melanoma metastases might develop as collision tumours in the sentinel lymph node (SLN). The aim of this study was to measure the incidence and examine the effect of collision tumours on the accuracy of SLND and on the validity of staging in this setting. Between 1998 and 2012, 750 consecutive SLNDs were performed in melanoma patients using the triple technique (lymphoscintigraphy, gamma probe and blue dye). The validity of SLND in collision tumours was analysed. False negativity was reflected by the disease-free survival. The literature was reviewed on collision tumours in melanoma. Collision tumours of melanoma and chronic lymphocytic leukaemia (CLL) were found in two SLN and in one RLND (0.4%). Subsequent RLNDs of SLND-positive cases were negative for melanoma. The patient with negative SLND developed relapse after 28 months with an inguinal lymph node metastasis of melanoma; RLND showed collision tumours. The literature review identified 12 cases of collision tumours. CLL was associated with increased melanoma incidence and reduced overall survival. This is, to our knowledge, the first assessment of the clinical value of SLND when collision tumours of melanoma and CLL are found. In this small series of three patients with both malignancies present in the same lymph node basin, lymphocytic infiltration of the CLL did not alter radioisotope uptake into the SLN. No false-negative result was observed. Our data suggest the validity of SLND in collision tumours, but given the rarity of the problem, further studies are necessary to confirm this reliability.

La régression tumorale n'est pas un facteur de risque d'atteinte du ganglion sentinelle dans les mélanomes fins (indice de Breslow < or = 1 mm) [Tumour regression is not predictive for higher risk of sentinel node involvement in thin melanomas (Breslow thickness < or = 1 mm)]

Background: Thin melanomas (Breslow thickness <= 1 mm) are considered highly curable. The aim of this study was to evaluate the correlation between histological tumour regression and sentinel lymph node (SLN) involvement in thin melanomas. Patients and methods: This was a retrospective single-centre study of 34 patients with thin melanomas undergoing SLN biopsy between April 1998 and January 2005. Results: The study included 14 women and 20 men of mean age 56.3 years. Melanomas were located on the neck (n = 3), soles (n = 4), trunk (n = 13) and extremities (n = 14). Pathological examination showed 25 SSM, four acral lentiginous melanomas, three in situ melanomas, one nodular melanoma and one unclassified melanoma with a mean Breslow thickness of 0.57 mm. Histological tumour regression was observed in 26 over 34 cases and ulceration was found in one case. Clark levels were as follows: I (n = 3), II (n = 20), III (n = 9), IV (n = 2). Growth phase was available in 15 cases (seven radial and eight vertical). Mitotic rates, available in 24 cases, were: 0 (n = 9), 1 (n = 11), 2 (n = 2), 3 (n = 1), 6 (n = 1). One patient with histological tumour regression (2.9% of cases and 3.8% of cases with regressing tumours) had a metastatic SLN. One patient negative for SLN had a lung relapse and died of the disease. Mean follow-up was 26.2 months. Conclusion: The results of the present study and the analysis of the literature show that histological regression of the primary tumour does not seem predictive of higher risk of SLN involvement in thin melanomas. This suggests that screening for SLN is not indicated in thin melanomas, even those with histological regression.

Role of disease activity for decision making ability in early multiple sclerosis

Background and purpose: Decision making (DM) has been defined as the process through which a person forms preferences, selects and executes actions, and evaluates the outcome related to a selected choice. This ability represents an important factor for adequate behaviour in everyday life. DM impairment in multiple sclerosis (MS) has been previously reported. The purpose of the present study was to assess DM in patients with MS at the earliest clinically detectable time point of the disease. Methods: Patients with definite (n=109) or possible (clinically isolated syndrome, CIS; n=56) MS, a short disease duration (mean 2.3 years) and a minor neurological disability (mean EDSS 1.8) were compared to 50 healthy controls aged 18 to 60 years (mean age 32.2) using the Iowa Gambling Task (IGT). Subjects had to select a card from any of 4 decks (A/B [disadvantageous]; C/D [advantageous]). The game consisted of 100 trials then grouped in blocks of 20 cards for data analysis. Skill in DM was assessed by means of a learning index (LI) defined as the difference between the averaged last three block indexes and first two block indexes (LI=[(BI-3+BI-4+BI-5)/3-(BI-1+B2)/2]). Non parametric tests were used for statistical analysis. Results: LI was higher in the control group (0.24, SD 0.44) than in the MS group (0.21, SD 0.38), however without reaching statistical significance (p=0.7). Interesting differences were detected when MS patients were grouped according to phenotype. A trend to a difference between MS subgroups and controls was observed for LI (p=0.06), which became significant between MS subgroups (p=0.03). CIS patients who confirmed MS diagnosis by presenting a second relapse after study entry showed a dysfunction in the IGT in comparison to the other CIS (p=0.01) and definite MS (p=0.04) patients. In the opposite, CIS patients characterised by not entirely fulfilled McDonald criteria at inclusion and absence of relapse during the study showed an normal learning pattern on the IGT. Finally, comparing MS patients who developed relapses after study entry, those who remained clinically stable and controls, we observed impaired performances only in relapsing patients in comparison to stable patients (p=0.008) and controls (p=0.03). Discussion: These results raise the assumption of a sustained role for both MS relapsing activity and disease heterogeneity (i.e. infra-clinical severity or activity of MS) in the impaired process of decision making.

Chemotherapy induces tumor metastasis and dormancy

Chemotherapy is widely used as a systemic treatment modality in cancer patients and provides survival benefits for a significant fraction of treated patients H However, some patients suffer from cancer relapse and rapidly progress to metastasis, suggesting that following chemotherapy their residual tumor developed a more aggressive phenotype 4 5. Although some molecular mechanisms involved in chemo-resistance and chemotherapy-induced metastatic relapse have been reported, more investigations and understanding of these processes are necessary before any translation into the clinic might be considered. By using the syngeneic metastatic 4T1 murine breast cancer model, we observed that chemotherapy treatment and selection of chemotherapy-resistant cancer cells in vitro can induces two opposite phenotypes: a dormant one and a relapsing-metastatic one. Previous studies in our laboratory demonstrated that irradiation of mammary gland promotes tumor metastasis, at least in part, by inducing the recruitment of CD11b+ cells to both the primary tumor and the lungs at a pre-metastatic stage. In this study we found that CD11b+ cells may also play important roles in chemotherapy-induced tumor metastasis and dormancy in vivo. Tumor cells expressing the stem cell marker Sca-1 were enriched by chemotherapy treatment in vitro, as well as in tumor metastasis in vivo. Furthermore, tumor-derived CD11b+ cells were capable to maintain and expand this population in vitro. These results suggest that the expansion of a tumor cell population with stem cell features might be a mechanism by which chemotherapy induces metastasis. On the other hand, the same drug treatment in vitro generated resistant cells with a dormant phenotype. Dormant tumor cells were able to induce an in vivo immune- inflammatory response in the draining lymph node, which is normally absent due to the immunosuppressive effects of tumor-recruited myeloid derived- suppressor cells (MDSCs). Genome-wide gene expression analysis revealed the enrichment of invasion and metastasis-related genes in the relapsing metastatic tumor cells and immune response-related genes in the dormant tumor cells. Interestingly, CD11b+ cells derived from the microenvironment of growing-metastatic tumors, but not CD11b+ cells derived from the spleen of tumor-free mice, were able to instigate outgrowth of dormant tumor cells in vivo. Also, dormant cells formed growing and metastatic tumors when injected into immune-compromised NGS mice. These results point to a role of chemotherapy in enabling treated tumor cells to acquire immune response-inducing capabilities, while impairing the recruitment of CD11b+ cells and their differentiation into an immune-suppressive cell. The molecular mechanisms underneath these effects are being further investigated. In conclusion, results obtained in this model indicate that chemotherapy can induce a dormant phenotype in cancer cells and that this state of dormancy can be broken by MDSCs educated by relapsing tumors. Understanding the mechanism beyond these effects, in particular unraveling the genetic or epigenetic determinants of dormancy vs relapse, might open the way to therapies aimed and maintaining residual cells escaping chemotherapy in a state of sustained dormancy. - La chimiothérapie est un traitement systémique largement utilisé chez les patients cancéreux qui donne un avantage de survie significatif pour une bonne partie de patients traités (1-3). Cependant, certains patients souffrent d'une rechute et progressent ensuite vers la métastase. Ceci suggère que leur tumeur résiduelle a développé un phénotype agressif suite à la chimiothérapie (4-5). Bien que certains mécanismes moléculaires impliqués dans la chimiorésistance et la rechute métastatique ont été identifiés, d'avantage d'études sont nécessaires afin de mieux comprendre ce phénomène et de développer des nouvelles thérapies cliniques. En utilisant un modèle syngénique de cancer du sein métastatique chez la sourie (4T1), nous avons observé que la sélection des cellules cancéreuses résistantes à la chimiothérapie in vitro peut induire deux phénotypes opposés: un phénotype de dormance et un phénotype de progression métastatique. Une étude précédente issue de notre laboratoire a démontré que l'irradiation de la glande mammaire favorise la métastase de tumeurs recourants suite au recrutement de cellules CD11b+ dans la tumeur primaire et dans les poumons pré-métastatiques. Dans notre étude nous avons constaté que les cellules CD11b+ peuvent également jouer un rôle important dans la formation de métastases induites par la chimiothérapie ainsi que dans le maintien de la dormance in vivo. Nous avons également observé un enrichissement de cellules tumorales exprimant le marqueur de cellule souche Sca-1 parmi les cellules tumorales résistantes à la chimiothérapie et dans les cellules qui on formé des métastases in vivo. Des cellules CD11b+ dérivées du microenvironnement tumorale favorisent l'expansion de la population de cellules tumorales Sca-1+ in vitro. Ces résultats suggèrent que l'expansion d'une population de cellules tumorales avec des caractéristiques de cellules souches pourrait constituer un mécanisme par lequel la chimiothérapie induit des métastases dans des tumeurs récurrentes. D'autre part le même traitement de chimiothérapie peut générer des cellules résistantes avec un phénotype dormant. Les expériences in vivo indiquent que les cellules tumorales dormantes induisent une réponse immunitaire inflammatoire dans le ganglion lymphatique de drainage, qui est normalement réprimée par des cellules myéloïdes suppressives de tumeur (MDSC). Une analyse d'expression de gènes a révélé l'enrichissement de gènes liés à l'invasion et à la métastase dans les cellules tumorales récurrentes et des gènes liés à la réponse immunitaire dans les cellules tumorales dormantes. Les cellules CD11b+ issues du microenvironnement des tumeurs récurrents ont incité la croissance des cellules tumorales dormantes in vivo, tandis que les cellules CD11b+ dérivées de la rate de souris non porteuses de tumeur ne l'étaient pas. Les mécanismes moléculaires sous-jacents restent à découvrir. En conclusion, les résultats obtenus dans ce modèle indiquent que la chimiothérapie pourrait favoriser non seulement l'induction d'une dormance cellulaire, mais également que les cellules dormantes seraient adroits de induire une réponse immunitaire capable les maintenir dans un état de dormance prolongé. Un déséquilibre dans cette réponse immunitaire pourrait des lors briser cet état de dormance et induire une progression tumorale. Comprendre les mécanismes responsables de ces effets, en particulier l'identification des déterminants génétiques ou épigénétiques liés à la dormance vs la rechute, pourraient ouvrir la voie à des nouvelles thérapies visant le maintien d'un état de dormance permanente des cellules résiduelles après chimiothérapie.

Colite à Clostridium difficile: nouvelles recommandations de prise en charge [Clostridium difficile infections: update on new European recommendations].

Clostridium difficile infections: update on new European recommandations While metronidazole and vancomycin have been the only drug options to date for the treatment of C. difficile infection, new therapeutic approaches with promising results have recently emerged for the treatment of the first episode and relapses. Fidaxomicin is a new macrocyclic antibiotic more active against C. difficile and with a narrow spectrum allowing preservation of the intestinal microbiota. While having the same efficacy as vancomycin for the treatment of the first episode, this agent is associated with a lower rate of relapse. The highest relapse-free cure rate is achieved through fecal microbiota transplantation, which should be considered for patients with multiple relapses.