Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600mut melanoma patients.

BACKGROUND: Dabrafenib (D) and trametinib (T) improved survival in patients with BRAFV600mut melanoma. High plasma concentration of D (PCD) is weakly associated with adverse events (AE). We investigated the relationship between PCD/T and tumour control or AE. METHODS: We analysed PCD/T in patients treated with D+T for metastatic melanoma. We collected data of tumour response (RECIST 1.1) and AE (CTCAE 4.0) blinded to PCD/T results. RESULTS: We analysed 71 D and 58T assays from 34 patients. High inter-individual variability of PCD (median: 65.0ng/mL; interquartile range (IQR) [4-945]) and of PCT (median: 8.6ng/mL; IQR [5-39]) was observed. We found a weak relationship between PCD and progression-free survival, taking follow-up time into account (hazard ratio 0.991; 95%CI, 0.981 to 1.000; P=0.06). However, no difference was observed between mean PCD/T of progressing patients (n=21; 125±183ng/mL and 9.3±3.6ng/mL, respectively) and responders (complete, partial or stable response) (n=13; 159±225ng/mL, P=0.58 and 10.6±24.4ng/mL, P=0.29, respectively). No significant relationship was found between PCD/T and most common AEs (fever, lymphopenia, CPK increase, and hepatic cytolysis), body mass index, or age. Mean CPT (n=16) was significantly higher for female subjects (n=18; 11.5±4.8ng/mL) than for male subjects (8.8ng/mL±2.9, P=0.01), but no difference was observed between sex and CPD (P=0.32). CONCLUSION: Our study showed a weak relationship between PCD and progression-free survival, but no relationship between PCD/T and AE was found. Monitoring PCD and PCT alone is unlikely to be useful in assessing response to treatment.

Experimental and computational diagnosis of the fluxional nature of a benzene-1,3,5-tricarboxamide-based hydrogen-bonded dimer.

Precise characterization of the hydrogen bond network present in discrete self-assemblies of benzene-1,3,5-tricarboxamide monomers derived from amino-esters (ester BTAs) is crucial for the construction of elaborated functional co-assemblies. For all ester BTA dimeric structures previously reported, ester carbonyls in the side chain acted as hydrogen bond acceptors, yielding well-defined dimers stabilized by six hydrogen bonds. The ester BTA monomer derived from glycine (BTA Gly) shows a markedly different self-assembly behaviour. We report herein a combined experimental and computational investigation aimed at determining the nature of the dimeric species formed by BTA Gly. Two distinct dimeric structures were characterized by single-crystal X-ray diffraction measurements. Likewise, a range of spectroscopic and scattering techniques as well as molecular modelling were employed to diagnose the nature of dynamic dimeric structures in toluene. Our results unambiguously establish that both ester and amide carbonyls are involved in the hydrogen bond network of the discrete dimeric species formed by BTA Gly. The participation of roughly 4.5 ester carbonyls and 1.5 amide carbonyls per dimer as determined by FT-IR spectroscopy implies that several conformations coexist in solution. Moreover, NMR analysis and modelling data reveal rapid interconversion between these different conformers leading to a symmetric structure on the NMR timescale. Rapid hydrogen bond shuffling between conformers having three (three), two (four), one (five) and zero (six) amide carbonyl groups (ester carbonyl groups, respectively) as hydrogen bond acceptors is proposed to explain the magnetic equivalence of the amide N-H on the NMR timescale. When compared to other ester BTA derivatives in which only ester carbonyls act as hydrogen bond acceptors, the fluxional behaviour of the hydrogen-bonded dimers of BTA Gly likely originates from a larger range of energetically favorable conformations accessible through rotation of the BTA side chains.

Probing halogen-halogen interactions in solution.

Halogen-halogen interactions are a particularly interesting class of halogen bonds that are known to be essential design elements in crystal engineering. In solution, it is likely that halogen-halogen interactions also play a role, but the weakness of this interaction makes it difficult to characterize or even simply detect. We have designed a supramolecular balance that allows detecting BrBr interactions between CBr3 groups in solution and close to room temperature. The sensitivity and versatility of the chosen platform have allowed accumulating consistent data. In halogenoalkane solvents, we propose estimates for the free energy of these weak halogen bond interactions. In toluene solutions, we show that the interactions between Br atoms and the solvent aromatic groups dominate over the BrBr interactions.

Catheterization of post-traumatic parotid duct sialocele.

INTRODUCTION: Parotid duct sialocele is a salivary cavity arising at the expense of the parotid duct. Many cases of parotid sialocele have been published, but very few cases of parotid duct sialocele have been reported. CASE REPORT: We report a case of post-traumatic parotid duct sialocele that was assessed by MR sialography. The parotid duct was catheterized via the oral cavity and the catheter was left in place for ten days. No recurrence was observed. DISCUSSION: Published cases of parotid duct sialocele are rare, as only seven cases were identified in the literature. Several treatment options are available for sialocele involving the parotid gland or parotid duct. Subcutaneous injection of botulinum toxin is commonly used, with good results. Parotid duct catheterization has also been reported, mainly for parotid gland sialoceles. To the best of our knowledge, apart from the present case, the use of this technique for parotid duct sialocele has only been reported once before. This technique is minimally invasive, with very low morbidity and good results.

[Peripheral facial nerve palsy]. / La paralysie faciale périphérique.

Facial palsy can be defined as a decrease in function of the facial nerve, the primary motor nerve of the facial muscles. When the facial palsy is peripheral, it affects both the superior and inferior areas of the face as opposed to central palsies, which affect only the inferior portion. The main cause of peripheral facial palsies is Bell's palsy, which remains a diagnosis of exclusion. The prognosis is good in most cases. In cases with significant cosmetic sequelae, a variety of surgical procedures are available (such as hypoglossal-facial anastomosis, temporalis myoplasty and Tenzel external canthopexy) to rehabilitate facial aesthetics and function.

[Nasal polyposis and olfactory function: results of the surgical treatment]. / La polypose nasosinusienne et l'odorat: intérêt de la chirurgie.

INTRODUCTION: Hyposmia is a common cause of functional complaint in patients with nasal polyposis. The aim of the current study was to report the olfactory functional results after sinus surgery. MATERIALS AND METHODS: A systematic review of the scientific literature was achieved in the Pubmed database. RESULTS: Overall, 10 series published between 1989 and 2013, involving 959 patients, were selected. The surgery for nasal polyposis, adjuvant medical treatment, may allow olfactory improvement. The results are even better than surgery is as wide as possible and the evolutionary stage is low.

[Diagnosis and therapeutic pathways in head and neck cancers]. / Parcours de soins du patient présentant un carcinome epidermoïdes des voies aéro-digestives supérieures.

BACKGROUND: Cancers of uppers aero-digestives tracts represent, infrequency, the 5th cancer in the French population. Most of them (about 70%) are diagnosed at an advanced stage (stage III or IV) while they are associated with a poor prognosis (only 40% five year survival). The objective of our study was to analyze the care pathway of patients with cancers of uppers aero-digestives tracts in order to target efforts to improve the survival of these patients. METHODS: It was a descriptive and retrospective study, on medical files, on the health care pathway of patients with cancers of uppers aero-digestives tracts cared in the Head and Neck surgery department of Val de Grâce in Paris and Percy in Clamart between January 2004 and December 2006. The patients were adults with squamous cell carcinoma of uppers aero-digestives tracts. RESULTS: One hundred thirty-eight files of patients were analyzed. Fifty-five percent of patients were diagnosed at an advanced stage. On average patients have waited two months and twenty-one days before consulting a doctor for the first time. The time interval between the specialist consultation and the start of treatment was on average 7 weeks. The overall 5-year survival rate was 61%. CONCLUSION: Squamous cell carcinoma of uppers aero-digestives tracts remains serious and has a poor diagnosis, even in a population with a high social-cultural level. The long time interval before the first consultation may be reduced by improving health education among the general practitioner (primary and secondary prevention), and by establishing health care public campaigns. This would allow earlier diagnosis, more conservative therapeutic opportunities and therefore a better prognosis.

Diagnosis and radiological treatment of digestive haemorrhage following supramesocolic surgery.

Digestive haemorrhage following supramesocolic abdominal surgery (cephalic duodenopancreatectomy, cholecystectomy, total oesogastrectomy) is a rare but serious complication, which can be life-threatening. Improvement in scanning techniques has made it possible to modify the diagnostic strategy and improve the therapeutic management of the patients. The aim of this iconographic review is to recall the causes of digestive haemorrhage following supramesocolic surgery and to illustrate the dominant role of tomodensitometry in diagnosing it and in planning and controlling the efficacy of endovascular treatment.

MR Imaging of sclerosing cholangitis.

MRCP is a non-invasive cholangiographic technique used in detection and characterization of bile ducts abnormalities. MRCP features of primary sclerosing cholangitis are randomly distributed annular strictures alternating with slightly dilated bile ducts. Secondary sclerosing processes including ascending, ischemic, caustic, AIDS-related, eosinophilic and autoimmune cholangitis can mimic PSC at MRCP.

[Management of ear, nose, and throat diseases in district hospital centers in Madagascar]. / Prise en charge de la pathologie ORL dans les centres hospitaliers de district à Madagascar.

The purpose of this report is to describe the experience of a specialized medico-surgical ENT team sent to hospital centers in Atalaha and Tulear, Madagascar by a nonprofit organization called "Terre rouge" from the Reunion Island. In three separate short-term missions, a total of 93 patients received care. Discussion focuses on the particular pathological, cultural, and pedagogical features of the Island and on the resources that were deployed during the missions. Providing ENT care in district hospitals in Madagascar requires adaptation to the difficult climatic conditions, poor hospital facilities (infrastructure, equip ment, and personnel), and advanced stage of diseases. To ensure continuous access to ENT care, it will be necessary to provide practical and didactic training for healthcare personnel in the country.

[Diffusion-weighted MR imaging of liver pathology: principles and clinical applications]. / Imagerie par résonance magnétique de diffusion (IRMD) en pathologie hépatique: principe et applications cliniques.

Due to ongoing technological advances, the range of clinical applications for diffusion-weighted MR imaging has expanded to now include abdominal pathology. Current applications for liver pathology include two main directions. First, oncologic imaging with detection, characterization and follow-up of lesions. Second, evaluation of diffuse liver diseases, including hepatic fibrosis. The diagnostic impact and role of diffusion-weighted MR imaging remain under investigation, but appear promising. Because of its short acquisition time, sensitivity, and additional information it provides, diffusion-weighted MR imaging should be included in routine liver imaging protocols.

[Post-traumatic carotid cavernous fistula: report of two cases]. / Fistule carotido-caverneuse post-traumatique: à propos de deux cas.

Carotid cavernous fistula (CCF) is an abnormal communication between the cavernous sinus and the carotid arterial system. The authors reported the clinical presentation and therapeutic procedure of two cases. The physician has to be aware of this diagnosis when a patient is referred for a posttraumatic exophthalmia. The medical behaviour is multidisciplinary (ENT, ophthalmologist, radiologist and neurosurgeon). The imaging of choice is the angiography but angio-MRI and angio-CT can help to confirm the diagnosis. The endovascular embolization is the treatment of choice. It presents an acceptable risk of complication and a low risk of failure. In this paper the authors report 2 posttraumatic CCF cases treated with success by endovascular embolization.

Otoacoustic detection of risk of early hearing loss in ears with normal audiograms: a 3-year follow-up study.

INTRODUCTION: Distortion product otoacoustic emissions (DPOAEs) are known to represent the contractile amplifier function of cochlear outer hair cells. It is known that low or absent DPOAEs are associated with hearing loss on audiograms. However, low DPOAEs can also be found associated with normal audiograms. It is unknown whether low DPOAEs in normal hearing ears are risk markers for subsequent early hearing loss when subjects are exposed to noise. MATERIALS AND METHODS: A 3-year follow-up study was carried out on a population of pilots aged 20-40 years (n=521). Data collection consisted of tonal audiograms, DPOAEs measurements with a calculation of an index of abnormality (the IaDPOAE). Of the 521 pilots enrolled, 350 (67%) had follow-up data 3 years later. In pilots with normal audiograms (n=219, all frequencies=10dB HL), we observed the occurrence of hearing threshold shifts after 3 years depending on whether the IaDPOAE was initially high (group 1) or low (group 2). We used this index to test the hypothesis that reduced DPOAEs levels are potential ear vulnerability biomarkers in apparent normal hearing ears. After a 3-year follow-up, the initial IaDPOAE in normal hearing subjects was correlated with final noise-induced hearing threshold shifts at high frequencies (p<0.01). The occurrence of abnormal audiograms was significantly higher in group 1 compared to group 2 (p=0.003). In group 1, 13% of audiograms were found with at least one frequency 25dB HL compared to 3% of audiograms in group 2. In both groups, impairments occurred at high frequencies and hearing in the 4kHz frequency range was significantly more impaired in group 1 (p=0.035). Group 1 was associated with a relative risk of 2.29 (95% CI 1.26-4.16, p=0.005) of sustaining early hearing loss. There was no significant differences between groups for age and noise exposure. DISCUSSION: In adults with a normal audiogram, ear vulnerability to noise could be elicited by the use of objective DPOAE measurements. A high IaDPOAE that corresponded to reduced DPOAE levels constitutes a risk for early hearing loss. This study emphasised the interest of DPOAE measurements in public health and occupational noise prevention policies. The IaDPOAE calculation may also be interesting for clinicians because no DPOAE index of abnormality is currently available.

[Cataract surgery and its impact on balance and autonomy in elderly]. / Incidence d'une chirurgie de la cataracte sur l'équilibre et l'autonomie du sujet âgé.

PURPOSE: Cataract is a major cause of visual impairment among elderly. Cataract surgery improves visual afferencies and can have an impact on balance. The present study assessed the impact of cataract surgery upon balance and autonomy in elderly. We realized clinical examinations and objective tests the day before surgery and 2-months later. METHODS: The initial cohort consisted of 66 patients that had to undergo a cataract surgery. Their mean age was 79 +/- 0.5. For logistic reasons, only 33 patients have been completely evaluated before and after surgery. Each patient underwent a history and examination that have assessed autonomy, walking, visual and then cochleo-vestibular functions including bone vibratory test and dynamic computerized posturography (Equitest). RESULTS: After 2 months, cataract surgery had no incidence on balance. The fear of falling has stayed the same whereas the number of falls has been noticeably reduced by surgery. The overall score of Equitest has shown an increase in visual dependence after surgery. Although cataract surgery has no incidence on autonomy, it may improve the quality of life among older people by leisure activities recovery. CONCLUSION: An early physical rehabilitation facilitated by visual improvement after surgery can also prevent visual dependence and autonomy loss. We recommend vestibular rehabilitation in elderly with major visual dependence.

[Identity vigilance and implementation of transfusion software in hospitals]. / Identitovigilance et intégration de l'informatique transfusionnelle dans les établissements de santé.

In hospitals, patients' identity mismatch is the cause of serious incidents during transfusion or other healthcare processes. With a wider use of healthcare software, new dysfunctions and risks may occur in case of ID mismatch between different software and for transfusion between blood bank and hospital. Four critical stages are to be considered when using software management of hospital care: initial patients' identification, modifications of identification data during hospital stay and then synchronization of all different software, proper use of patient's identification means by hospital staff and share of patient's identification data with others such as the Etablissement français du sang (EFS) for transfusional purposes. Perpignan Hospital has put in place an identity vigilance group whose role is to enforce a safe patients' identification policy. It has to inform and train hospital staff, make sure that all software requiring patients' ID are correctly synchronized, especially when sharing data with EFS and monitor improvement with a surveillance system. As transfusion care is one of the more patients' ID sensitive, particularly when computer assisted, haemovigilance officers are highly involved in identity vigilance.

[Imaging of incidental cystic lesions of the pancreas]. / Imagerie des lésions kystiques du pancréas de découverte fortuite.

Cystic lesions of the pancreas, with an estimated prevalence of 20%, frequently are incidental findings at imaging on asymptomatic patients. Pseudocysts, typically in a setting of pancreatitis, should first be excluded. Characterization of cystic tumors is more complicated. Still, it is important to differentiate between benign and malignant lesions. Multi-detector row CT and MRI allow characterization of such lesions in over 75% of cases. Indeterminate lesions should undergo endoscopic US with biopsy/aspiration and fluid analysis, especially for mucin producing tumors (rounded with thick enhancing wall). When imaging fails to fully characterize a lesion, follow-up may be proposed for lesions less than 3 cm in size, that are either unilocular with thin nonenhancing wall (simple cyst) or lobulated multilocular with thin nonenhancing wall (serous cystadenoma, isolated side branch IPMTP). Follow-up imaging shows that these tumors usually show very little change over time. Management is based on comparing estimated patient survival without treatment to surgical risks (morbidity, mortality, functional sequelae from the procedure).