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Although many more eyes of children with retinoblastoma are salvaged now compared to just 10 years ago, the control of vitreous seeding remains a challenge. The introduction of intravitreal injection of melphalan has enabled more eyes to be salvaged safely but with definite retinal toxicity. Intensive treatment with high-dose intravitreal topotecan may be a strategy to control tumor burden because of its cell cycle-dependent cytotoxicity and the proven safety in humans. Therefore, we evaluated the ocular and systemic safety of repeated high-dose intravitreal injections of topotecan in rabbits. Systemic and ocular toxicity was assessed in non-tumor-bearing rabbits after four weekly injections of three doses of topotecan (10 μg, 25 μg, and 50 μg) or vehicle alone. Animals were evaluated weekly for general and ophthalmic clinical status. One week after the last injection, vitreous and plasma samples were collected for drug quantification and the enucleated eyes were subjected to histological assessment. Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. Eyes injected with all topotecan doses or vehicle showed no signs of anterior segment inflammation, clinical or histologic evidence of damage to the retina, and ERG parameters remained unaltered throughout the study. Vitreous and plasma topotecan lactone concentrations were undetectable. Four weekly intravitreal injections of topotecan up to 50 μg in the animal model or a 100 μg human equivalent dose were not toxic for the rabbit eye. High doses of topotecan may show promising translation to the clinic for the management of difficult-to-treat retinoblastoma vitreous seeds.

Background Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). Objectives This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. Methods This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. Results Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. Conclusions In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253)

Objectives The French ENT Society (SFORL) created a workgroup to draw up guidelines for the management of immunodeficient patients with head and neck cancer of cutaneous origin. The present guidelines cover diagnostic and therapeutic management and prevention of head and neck cancer of cutaneous origin in immunodeficient patients, and in particular in transplant patients and those with HIV infection. Materials and methods The present guidelines were based on a critical multidisciplinary reading of the literature. Immunosuppression and its varieties are defined. The usual risk factors for skin cancer and those specific to immunodeficiency are presented. The prevention, assessment and management of cutaneous carcinoma, melanoma, Kaposi's sarcoma and lymphoma are dealt with. The level of evidence of the source studies was assessed so as to grade the various guidelines. When need be, expert opinions are put forward. Results Immunodeficient patients are at higher risk of head and neck skin tumors. The level of risk depends on the type of deficiency; there is an especially high risk of squamous cell carcinoma in transplant patients and of Kaposi's sarcoma in HIV-positive subjects. Various viruses are associated with skin cancers. Skin tumors are often evolutive in case of immunodeficiency, requiring rapid treatment. Management is generally the same as in immunocompetent subjects and should be discussed in a multidisciplinary team meeting. Immunosuppression may need to be modulated. In organ transplant patients, the only class of immunosuppressants with proven antitumoral efficacy are mTOR inhibitors, particularly in cutaneous squamous cell carcinoma. The rhythm of clinical surveillance should be adapted according to the risk of recurrence. Preventive measures should be undertaken. Conclusion Skin cancers in immunodeficiency are highly evolutive, requiring the earliest possible treatment. Immunosuppression may need modulating. As the risk of recurrence may be elevated, careful surveillance should be implemented. Preventive measures should also be undertaken.

Resume Objectifs La Societe francaise d’otorhinolaryngologie (SFORL) a organise un groupe de travail charge de la redaction de recommandations pour la prise en charge des patients immunodeprimes atteints de tumeurs de la tete et du cou de point de depart cutane. Ces recommandations abordent la prise en charge diagnostique et therapeutique ainsi que les mesures de prevention des tumeurs de la tete et du cou a point de depart cutane survenant chez les immunodeprimes, en particulier les transplantes et les patients infectes par le VIH. Materiels et methodes L’elaboration de ces recommandations repose sur une lecture critique multidisciplinaire de la litterature. L’immunosuppression et les differents types d’immunosuppression ont ete definis. Les facteurs de risque habituels des tumeurs cutanees et ceux specifiques a l’immunodeprime sont presentes. La prevention, le bilan et la prise en charge des carcinomes cutanes, du melanome, de la maladie de Kaposi et des lymphomes sont traites. Le niveau de preuve des etudes a ete estime, permettant de grader le niveau des recommandations. Le cas echeant, des avis d’experts ont ete proposes. Resultats Les immunodeprimes ont un risque accru de developper des tumeurs cutanees de l’extremite cervico-cephalique. Le risque de developper ces tumeurs varie en fonction du type d’immunosuppression ; il existe un risque particulierement eleve de carcinomes epidermoides chez les transplantes et de maladie de Kaposi chez les patients seropositifs pour le VIH. Differents virus sont associes a ces cancers cutanes. Les tumeurs cutanees de l’immunodeprime sont souvent caracterisees par leur evolutivite justifiant une prise en charge therapeutique rapide. La prise en charge specifique, en general similaire a celle du sujet immunocompetent, doit etre discutee en RCP. La modulation de l’immunosuppression doit etre envisagee. Chez le transplante d’organe, la seule classe d’immunosuppresseurs ayant un effet anti-tumoral documente est celle des inhibiteurs de mTOR en particulier pour les carcinomes epidermoides cutanes. La frequence de la surveillance clinique doit etre adaptee au risque de recidive. Des mesures de prevention doivent etre proposees. Conclusion Les tumeurs cutanees de l’immunodeprime sont souvent caracterisees par leur evolutivite justifiant une prise en charge therapeutique la plus precoce possible. Une modulation de l’immunosuppression doit etre discutee. En raison d’un risque souvent eleve de recidive, une surveillance attentive doit etre proposee. Les mesures de prevention doivent egalement etre respectees.

We report the crystal structure together with the electric field gradient (EFG) tensor at the Hf site in Sr 0.5 Ba 0.5 HfO 3 as a function of temperature. High-temperature X-ray diffraction data show a second-order tetragonal-to-cubic phase transition at 700 K. The hyperfine interaction measured at 181 Ta probe corresponds to a static, asymmetric and disordered EFG. The hyperfine parameters V zz and η also display evident changes close to 673 K confirming the phase transition observed by XRD. The line width of the quadrupole interaction is relatively small compared with other perovskite-type compounds.

Rheological and sedimentation studies were used to determine floc structure in aqueous alumina suspensions in which the degree of flocculation was varied by modifying the pH of the suspensions. A slip-casting technique was developed to allow fabrication of alumina bodies with differential porosities by varying the degree of flocculation of the suspensions during the forming period. The porosity and density of the pre-sintered bodies were determined. The results show that the conditions of the starting suspensions influence the density of the bodies and that their variation during the slip-casting process enable samples to be fabricated with differential porosity.

Resume Parmi les nombreuses formes de neurofibromatose (NFM), deux sont actuellement bien caracterisees: la NFM1 ou maladie de Von Recklinghausen ou NFM peripherique, et la NFM 2 ou NFM centrale. La NFM 2 , dont notre patient presentait une forme typique, est definie par l'existence soit d'un neurinome bilateral de l'acoustique, soit l'association d'un neurinome unilateral de l'acoustique, de tumeurs du systeme nerveux central (neurinome, gliome, schwannome, meningiome) et d'antecedents familiaux de NFM 2 . il s'agit d'une maladie rare, liee a la perte d'un gene situe sur le bras long du chromosome 22. Elle s'oppose a la NFM 1 ou maladie de Von Recklinghausen, beaucoup plus frequente, liee a une anomalie situee sur le chromosome 17. Au cours de la NFM 2 , les signes cliniques apparaissent le plus souvent dans la deuxieme decennie, comportant une hypoacousie et plus rarement une baisse de l'acuite visuelle. La symptomatologie se complete en fonction des diverses localisations tumorales. Les neurinomes bilateraux de l'acoustique sont histologiquement des schwannomes, developpes dans la partie vestibulaire du nerf (« schwannomes vestibulaires ). La demarche diagnostique comprend un examen cutane soigneux a la recherche de tâches cafe au lait ou de neurofibromes cutanes, un examen oto-rhino-laryngologique pour depister une atteinte du VIII et un examen ophtalmologique pour depister une cataracte sous capsulaire et eliminer un nodule de Lish. L'imagerie par resonnance magnetique nucleaire est actuellement la plus performante pour rechercher un neurinome de l'acoustique ou d'autres tumeurs intracraniennes. Le diagnostic porte chez un patient impose un depistage systematique dans la fratrie et la descendance, meme chez les sujets asymptomatiques. Les patients qui sont pour la plupart, en âge de procreer, doivent connaitre le risque de transmission de 50 %, quelque soit le sexe de l'enfant. Dans un avenir proche, la localisation precise de l'anomalie chromosomique devrait permettre un diagnostic ante-natal.

We report 40 cases of malignant centrofacial ulcerations included in the SNFMI/GMCF protocol because of negative first biopsies. A performing biopsy protocol enabled to identify 27 of them as malignant lymphomas, which proced to be extraordinarily difficult to treat, except for those able to be given radiation therapy.