Percutaneous closure of patent foramen ovale: head-to-head comparison of two different devices

Percutaneous closure of patent foramen ovale (PFO) has been proposed as the treatment of choice for young high-risk patients who suffered cryptogenic stroke and/or peripheral paradoxical embolism. We sought to compare prospectively two different devices used for percutaneous PFO closure.Prospective data were collected on 40 high risk patients (females: 38%, mean age : 44 +/- 11 years, interatrial septal aneurysm >10 mm: 68%) who underwent percutaneous PFO closure after cryptogenic stroke (n = 38) or peripheral paradoxical embolism (n = 2). Chronologically, 20 patients were first treated by a PFO-Star (Cardia, Burnsville, MI) device. Then, 20 other patients received a Starflex occluder (NMT, Boston, MA). The primary endpoint was complete PFO closure at 6 months as assessed by transthoracic contrast echocardiography. Secondary endpoints were major peri- or post procedural complications and clinical recurrence at 1 year follow-up.Baseline clinical and anatomical characteristics were comparable for both groups. Complete PFO closure was observed in 50% (PFO-Star) and 90% (Starflex) of patients (p=0.001) respectively. Major peri-procedural complications occurred in the PFO-star group only: right-sided device thrombus (1 patient) and aorto-right atrial fistula (1 patient). At 1 year follow-up, no clinical recurrence occurred.In conclusion, despite the absence of clinical recurrence in this high-risk population with presumed paradoxical embolism, complete PFO closure at 6 months follow-up was significantly related to the type of closure device used

Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma.

Tumor-infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3(+) T cells, and relatively high levels of BDCA2(+) and FOXP3(+) cells in stromal (peripheral) regions of the tumors. Tumor-infiltrating (intraepithelial) FOXP3(+) T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase-II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase-2 by 43%, and B-cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c(+) myeloid dendritic cells, and high numbers of FOXP3(+) T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease-free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.

Dexamethasone therapy and endogenous cortisol production in severe pediatric head injury.

A prospective randomised study was performed on 25 children aged 1.4 to 15.8 years with severe head injury (Glasgow Coma Scale less than or equal to 7) to determine the clinical effectiveness and the impact on endogenous cortisol production of high-dose steroid therapy. Thirteen patients (group 1) received dexamethasone 1 mg/kg/day during the first 3 days and 12 (group 2) not. All patients were treated with a standardized regimen. Urinary free cortisol was measured by radioimmunoassay, and the clinical data were recorded at hourly intervals. Outcome was assessed 6 months later using the Glasgow Outcome Scale. We found a higher frequency of bacterial pneumonias in the dexamethasone-treated patients (7/13 versus 2/12). Group 1 showed a suppression of endogenous cortisol production from day 1 to day 6. In group 2, mean free cortisol was up to 5-fold higher than under basal conditions. The results in group 2 showed that the endogenous steroid production reacts adequately to the stress of severe head injury. It probably is sufficient to elicit maximum glucocorticoid effects. There was no other statistically significant difference in the clinical and laboratory data between the two groups. We conclude that dexamethasone in high doses suppresses endogenous cortisol production up to 6 days and may increase the risk of bacterial infection without affecting the outcome or the clinical and laboratory data.

Combined modality treatment with full-dose chemotherapy and concomitant boost radiotherapy for advanced head and neck carcinoma

Résumé Le but de cette étude est d'évaluer la faisabilité et l'efficacité d'un traitement des carcinomes pharyngo-laryngés avancés par combinaison de chimiothérapie intensive associé à une radiothérapie accélérée. Vingt-trois patients ont été inclus (age médian 54 ans, entre 35 et 70 ans). Les localisations tumorales étaient l'hypopharynx (n=7), base de langue (n=10), nasopharynx (n=2) ou l'oesophage proximal (n.1), ou sans porte d'entrée (n=3). Le traitement comprend trois cycles de chimiothérapie (cisplatin 100mg/m2 à J1 ; 5-FU 1000mg/m2 par jour pendant 5 jours en perfusion continue, précédé par de l'amifostine 910mg/m2 ; répété toutes les trois semaines). La radiothérapie concomitante, accélérée (dose totale de 70Gy en 6 semaines) a été débuté au premier jour du deuxième cycle de chimiothérapie. Vingt et un patients ont pu achever la radiothérapie. Dix-huit patients étaient en rémission complète à la fin du traitement. Avec un suivi médian de 45 mois, le taux de survie globale atteint 56% (95% Cl, 32-79%). Le contrôle loco-régional était de 71% (95% CI, 52-91%). La toxicité associée au traitement consistait en une insuffisance rénale réversible (≥grade II) chez 9 patients (43%) et une agranulocytose fébrile chez 9 patients (43%). Tous les patients ont présenté une mucite modérée à sévère (grade II/III) et 19 patients ont montré une toxicité cutanée de grade III. En conclusion, le traitement combiné de radiothérapie accélérée avec une chimiothérapie concomitante à base de Cisplatin/5-FU full-dose avec amifostine est faisable. La toxicité est importante mais reste maîtrisable dans le cadre d'un centre multidisciplinaire. Le taux de survie globale à 4 ans est prometteur, la recherche en vue de traitements moins toxiques doit se poursuivre. Abstract The purpose of this study was to evaluate the feasibility and efficacy of a treatment concept combining three cycles of full-dose chemotherapy (CT) with concomitant accelerated uninterrupted radiotherapy (RI). Twenty- three patients (median age: 54 years, range: 35-70) with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were included. The primary tumor involved the hypopharynx (n=7), base of the tongue (n=10), nasopharynx (n=2) or upper esophagus (n=1) or its location was unknown (n=3). Treatment consisted of three cycles of chemotherapy (cisplatin 100 mg/m2 on day 1; 5-FU 1,000 mg/m2 per day for 5 days as a continuous infusion, preceded by amifostine 910 mg/m2). repeated every 3 weeks. Uninterrupted concomitant boost-accelerated RI (total dose of 70 Gy in 6 weeks) started together on day 1 of the second cycle. All but two patients received the full course of RT. Eighteen patients achieved complete remission (78%). At a median follow-up of 45 months the overall survival was 56% (95% c.i. 32-79%) and the loco-regional control 71% (95% c.i. 52-91%). Toxicity involved reversible renal insufficiency of grade II in 9 patients (39%) and neutropenic fever in 9 patients (39%). All patients suffered from moderate to severe mucositis (grade HMI), and 19 patients presented cutaneous toxicity grade III. Concomitant boost-accelerated RI combined with concurrent full-dose cisplatin/5-FU chemotherapy and amifostine is feasible with manageable, although substantial, toxicity. The overall survival of 4 years is promising. Newer regimens causing less acute mucosal and skin toxicity are needed.

Une méthode simplifiée de mesure du volume atrial gauche sur les scanners de score calcique. Cardiovasculaire diagnostique et interventionnel. Séance Cardiovasculaire diagnostique et interventionnel. Séance ''L21 - Imagerie cardiaque non invasive''

Objectifs : Evaluer une méthode simple et rapide de mesure du volume atrial gauche. Matériels et méthodes : Cinquante patients ont été examinés avec un CT gaté pour mesure du score calcique. Trois méthodes ont été utilisées pour calculer le volume atrial gauche : 1) une méthode orthogonale avec mesure des surfaces/diamètres dans les plans axiaux/coronaux/sagittaux, 2) une méthode biplan inspirée de l'échocardiographie et 3) une méthode volumétrique. Les mesures ont été faites par le même observateur un mois plus tard et ont été répétées par trois autres observateurs. L'axe cardiaque a aussi été mesuré. La méthode Bland-Altmann et les corrélations de Spearman ont été utilisées. Résultats : La méthode volumétrique montre les variations intra/interobservateur les plus basses avec une variabilité de 6,1/7,4 ml, respectivement. Pour les mesures avec la méthode orthogonale (surfaces/diamètres), les variations intra/interobservateur sont 12,3/13,5 ml et 14,6/11,6 ml, respectivement. Pour la méthode biplan, les variations intra/interobservateur sont plus hautes : 23,9/19,8 ml. Comparée à la méthode de référence volumétrique, la méthode orthogonale avec les surfaces est mieux corrélée (R=0,959, p<0,001) que les autres méthodes. Il y a une faible influence de l'axe du coeur sur la méthode orthogonale avec les surfaces. Conclusion : La méthode volumétrique est le gold standard en terme de variabilité. Cependant elle est longue à metttre en oeuvre. La méthode orthogonale avec les surfaces est une alternative simple, sauf chez les patients obèses avec un coeur horizontalisé.

Neurally Adjusted Ventilatory Assist (NAVA) improves the matching of diaphragmatic electrical activity and tidal volume in comparison to pressure support (PS) under non invasive ventilation

INTRODUCTION. Patient-ventilator asynchrony is a frequent issue in non invasivemechanical ventilation (NIV) and leaks at the patient-mask interface play a major role in itspathogenesis. NIV algorithms alleviate the deleterious impact of leaks and improve patient-ventilator interaction. Neurally adusted ventilatory assist (NAVA), a neurally triggered modethat avoids interferences between leaks and the usual pneumatic trigger, could further improvepatient-ventilator interaction in NIV patients.OBJECTIVES. To evaluate the feasibility ofNAVAin patients receiving a prophylactic postextubationNIV and to compare the respective impact ofPSVandNAVAwith and withoutNIValgorithm on patient-ventilator interaction.METHODS. Prospective study conducted in 16 beds adult critical care unit (ICU) in a tertiaryuniversity hospital. Over a 2 months period, were included 17 adult medical ICU patientsextubated for less than 2 h and in whom a prophylactic post-extubation NIV was indicated.Patients were randomly mechanically ventilated for 10 min with: PSV without NIV algorithm(PSV-NIV-), PSV with NIV algorithm (PSV-NIV+),NAVAwithout NIV algorithm (NAVANIV-)and NAVA with NIV algorithm (NAVA-NIV+). Breathing pattern descriptors, diaphragmelectrical activity, leaks volume, inspiratory trigger delay (Tdinsp), inspiratory time inexcess (Tiexcess) and the five main asynchronies were quantified. Asynchrony index (AI) andasynchrony index influenced by leaks (AIleaks) were computed.RESULTS. Peak inspiratory pressure and diaphragm electrical activity were similar in thefour conditions. With both PSV and NAVA, NIV algorithm significantly reduced the level ofleak (p\0.01). Tdinsp was not affected by NIV algorithm but was shorter in NAVA than inPSV (p\0.01). Tiexcess was shorter in NAVA and PSV-NIV+ than in PSV-NIV- (p\0.05).The prevalence of double triggering was significantly lower in PSV-NIV+ than in NAVANIV+.As compared to PSV,NAVAsignificantly reduced the prevalence of premature cyclingand late cycling while NIV algorithm did not influenced premature cycling. AI was not affectedby NIV algorithm but was significantly lower in NAVA than in PSV (p\0.05). AIleaks wasquasi null with NAVA and significantly lower than in PSV (p\0.05).CONCLUSIONS. NAVA is feasible in patients receiving a post-extubation prophylacticNIV. NAVA and NIV improve patient-ventilator synchrony in different manners. NAVANIV+offers the best patient-ventilator interaction. Clinical studies are required to assess thepotential clinical benefit of NAVA in patients receiving NIV.

Effects of propranolol on resting metabolic rate after severe head injury.

Postabsorptive resting metabolic rate (RMR), measured by indirect calorimetry, and the effect of iv propranolol administration were studied in 12 nonseptic patients with severe head injury by means of indirect calorimetry. Before propranolol RMR was moderately increased (126 +/- 10.4% of predicted values) whereas urinary excretion of catecholamines was markedly elevated (p less than .01 vs. normal values). RMR was significantly correlated with both resting heart rate (HR) (r = .72, p less than .01) and 24-h urinary N excretion (r = .85, p less than .001). The administration of iv propranolol (0.1 mg/kg) produced a rapid decrease in HR (-10 +/- 4%, p less than .001) and in RMR (-6.1 +/- 2.3%, p less than .001). Further administration of propranolol produced no additional reduction in either HR or RMR. We conclude that severely head-injured patients are moderately hypermetabolic in resting and postabsorptive conditions, and that acute iv propranolol administration induces a reduction of about one quarter of the resting hypermetabolism.

Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Improvement of saliva production in ENT cancer patients treated by IMRT

Intensity modulated radiotherapy (IMRT) is a conformal radiotherapy that produces concave and irregular target volume dose distributions. IMRT has a potential to reduce the volume of healthy tissue irradiated to a high dose, but this often at the price of an increased volume of normal tissue irradiated to a low dose. Clinical benefits of IMRT are expected to be most pronounced at the body sites where sensitive normal tissues surround or are located next to a target with a complex 3D shape. The irradiation doses needed for tumor control are often markedly higher than the tolerance of the radiation sensitive structures such as the spinal cord, the optic nerves, the eyes, or the salivary glands in the treatment of head and neck cancer. Parotid gland salivary flow is markedly reduced following a cumulative dose of 30 50 Gy given with conventional fractionation and xerostomia may be prevented in most patients using a conformal parotid-sparing radiotherapy technique. However, in cohort studies where IMRT was compared with conventional and conformal radiotherapy techniques in the treatment of laryngeal or oropharyngeal carcinoma, the dosimetric advantage of IMRT translated into a reduction of late salivary toxicity with no apparent adverse impact on the tumor control. IMRT might reduce the radiation dose to the major salivary glands and the risk of permanent xerostomia without compromizing the likelihood for cure. Alternatively, IMRT might allow the target dose escalation at a given level of normal tissue damage. We describe here the clinical results on postirradiation salivary gland function in head and neck cancer patients treated with IMRT, and the technical aspects of IMRT applied. The results suggest that the major salivary gland function can be maintained with IMRT without a need to compromise the clinical target volume dose, or the locoregional control.

Right coronary artery flow velocity and volume assessment with spiral K-space sampled breathhold velocity-encoded MRI at 3 tesla: accuracy and reproducibility.

PURPOSE: To evaluate accuracy and reproducibility of flow velocity and volume measurements in a phantom and in human coronary arteries using breathhold velocity-encoded (VE) MRI with spiral k-space sampling at 3 Tesla. MATERIALS AND METHODS: Flow velocity assessment was performed using VE MRI with spiral k-space sampling. Accuracy of VE MRI was tested in vitro at five constant flow rates. Reproducibility was investigated in 19 healthy subjects (mean age 25.4 +/- 1.2 years, 11 men) by repeated acquisition in the right coronary artery (RCA). RESULTS: MRI-measured flow rates correlated strongly with volumetric collection (Pearson correlation r = 0.99; P < 0.01). Due to limited sample resolution, VE MRI overestimated the flow rate by 47% on average when nonconstricted region-of-interest segmentation was used. Using constricted region-of-interest segmentation with lumen size equal to ground-truth luminal size, less than 13% error in flow rate was found. In vivo RCA flow velocity assessment was successful in 82% of the applied studies. High interscan, intra- and inter-observer agreement was found for almost all indices describing coronary flow velocity. Reproducibility for repeated acquisitions varied by less than 16% for peak velocity values and by less than 24% for flow volumes. CONCLUSION: 3T breathhold VE MRI with spiral k-space sampling enables accurate and reproducible assessment of RCA flow velocity.

Early investigational drugs that target epidermal growth factor receptors for the treatment of head and neck cancer.

INTRODUCTION: Squamous-cell carcinoma of the head and neck (SCCHN) remains a challenging clinical problem, due to the persistent high rate of local and distant failures and the occurrence of secondary primaries. For locally advanced SCCHN, a combination of chemotherapy (CT), radiation or surgery is often used, but there are limitations, which may reduce compliance. Molecular targeted therapies, namely anti-EGFR treatments, are in development with the aim of improving clinical outcomes and mitigating treatment-related toxicities. AREAS COVERED: This review provides an overview of early investigational drugs that target EGFR for the treatment of SCCHN and discusses the ongoing trials in this domain. EXPERT OPINION: Targeted therapies are increasingly used in oncology, especially in SCCHN. Cetuximab has demonstrated a significant improvement in the treatment outcome, both as a curative treatment in combination with radiation therapy and as a palliative treatment in combination with CT; however, it failed to show any benefit in combination with concomitant chemoradiotherapy. Presently, there are many new agents, including monoclonal antibodies and small-molecule tyrosine kinase inhibitors, which are either currently under investigation for or which warrant further investigation for treating SCCHN. The discovery of predictive factors that help to identify patients most likely to respond to EGFR inhibitors as well as patient-customized therapies would help to improve patient outcomes in the future.