Human papillomavirus (HPV) vaccines as an option for preventing cervical malignancies: (how) effective and safe?

We carried out a systematic review of HPV vaccine pre- and post-licensure trials to assess the evidence of their effectiveness and safety. We find that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate. Additionally, we note evidence of selective reporting of results from clinical trials (i.e., exclusion of vaccine efficacy figures related to study subgroups in which efficacy might be lower or even negative from peer-reviewed publications). Given this, the widespread optimism regarding HPV vaccines long-term benefits appears to rest on a number of unproven assumptions (or such which are at odd with factual evidence) and significant misinterpretation of available data. For example, the claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer (let alone cervical cancer death), nor that the current overly optimistic surrogate marker-based extrapolations are justified. Likewise, the notion that HPV vaccines have an impressive safety profile is only supported by highly flawed design of safety trials and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities). We thus conclude that further reduction of cervical cancers might be best achieved by optimizing cervical screening (which carries no such risks) and targeting other factors of the disease rather than by the reliance on vaccines with questionable efficacy and safety profiles.

Management of Pharyngeal Fistulas After Anterior Cervical Spine Surgery: A Treatment Algorithm for Severe Complications.

STUDY DESIGN:: Retrospective database- query to identify all anterior spinal approaches. OBJECTIVES:: To assess all patients with pharyngo-cutaneous fistulas after anterior cervical spine surgery. SUMMARY OF BACKGROUND DATA:: Patients treated in University of Heidelberg Spine Medical Center, Spinal Cord Injury Unit and Department of Otolaryngology (Germany), between 2005 and 2011 with the diagnosis of pharyngo-cutaneous fistulas. METHODS:: We conducted a retrospective study on 5 patients between 2005 and 2011 with PCF after ACSS, their therapy management and outcome according to radiologic data and patient charts. RESULTS:: Upon presentation 4 patients were paraplegic. 2 had PCF arising from one piriform sinus, two patients from the posterior pharyngeal wall and piriform sinus combined and one patient only from the posterior pharyngeal wall. 2 had previous unsuccessful surgical repair elsewhere and 1 had prior radiation therapy. In 3 patients speech and swallowing could be completely restored, 2 patients died. Both were paraplegic. The patients needed an average of 2-3 procedures for complete functional recovery consisting of primary closure with various vascularised regional flaps and refining laser procedures supplemented with negative pressure wound therapy where needed. CONCLUSION:: Based on our experience we are able to provide a treatment algorithm that indicates that chronic as opposed to acute fistulas require a primary surgical closure combined with a vascularised flap that should be accompanied by the immediate application of a negative pressure wound therapy. We also conclude that particularly in paraplegic patients suffering this complication the risk for a fatal outcome is substantial.

Techniques de "non-fusion" en chirurgie rachidienne [Non fusion techniques in spinal surgery]

In order to prevent adjacent segment degeneration following spinal fusion new techniques are being used. Lumbar disc arthroplasty yields mid term results equivalent to those of spinal fusion. Cervical disc arthroplasty is indicated in the treatment of cervicobrachialgia with encouraging initial results. The ability of arthroplasty to prevent adjacent segment degeneration has yet to be proven. Although dynamic stabilization had not been proven effective in treating chronic low back pain, it might be useful following decompression of lumbar spinal stenosis in degenerative spondylolisthesis. Interspinal devices are useful in mild lumbar spinal stenosis but their efficacy in treating low back pain is yet to be proven. Confronted with a growing number of new technologies clinicians should remain critical while awaiting long term results.

Intravenous thrombolysis in stroke attributable to cervical artery dissection.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Whether this is also true for cervical artery dissection (CAD) is addressed in this study.METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated patients with CAD with IVT-treated patients with other etiologies (non-CAD patients). Main outcome and complication measures were favorable 3-month outcome, intracranial cerebral hemorrhage, and recurrent ischemic stroke. Modified Rankin Scale score <or=1 at 3 months was considered favorable.RESULTS: Fifty-five (5.2%) of 1062 IVT-treated patients had CAD. Patients with CAD were younger (median age 50 versus 70 years) but had similar median National Institutes of Health Stroke Scale scores (14 versus 13) and time to treatment (152.5 versus 156 minutes) as non-CAD patients. In the CAD group, 36% (20 of 55) had a favorable 3-month outcome compared with 44% (447 of 1007) non-CAD patients (OR, 0.72; 95% CI, 0.41 to 1.26), which was less favorable after adjustment for age, gender, and National Institutes of Health Stroke Scale score (OR, 0.50; 95% CI, 0.27 to 0.95; P=0.03). Intracranial cerebral hemorrhages (asymptomatic, symptomatic, fatal) were equally frequent in CAD (14% [7%, 7%, 2%]) and non-CAD patients (14% [9%, 5%, 2%]; P=0.99). Recurrent ischemic stroke occurred in 1.8% of patients with CAD and in 3.7% of non-CAD-patients (P=0.71).CONCLUSIONS: IVT-treated patients with CAD do not recover as well as IVT-treated non-CAD patients. However, intracranial bleedings and recurrent ischemic strokes were equally frequent in both groups. They do not account for different outcomes and indicate that IVT should not be excluded in patients who may have CAD. Hemodynamic compromise or frequent tandem occlusions might explain the less favorable outcome of patients with CAD.

Cervical nerve root synovial sarcoma in a child with chromosomal (X;18) translocation. Case report and review of the literature.

We report on an 11-year-old female with a history of cervicobrachialgia and progressive weakness of the right arm. Cervical spine MRI showed an enhancing heterogeneous intradural mass occupying the right C6-C7 foramen. She underwent a right C6-C7 foraminotomy with a complete macroscopic removal of the lesion. Pathological examination revealed a synovial sarcoma. Treatment was completed by chemotherapy and proton radiotherapy, and the girl remained free of symptoms for 3 years. After appearance of new symptoms, a local recurrence was confirmed, and despite aggressive treatment with salvage chemotherapy and radiotherapy, the disease progressed beyond medical control, and the child died, 6 years after diagnosis. Early recognition of this rare entity compared to its more benign differential diagnosis is crucial, as an aggressive management is needed.

Raeder's paratrigeminal syndrome due to spontaneous dissection of the cervical and petrous internal carotid artery.

The combination of pain, ipsilateral oculosympathetic defect (ptosis and miosis), and ipsilateral trigeminal dysfunction constitutes Raeder's syndrome. We describe a patient with an acute presentation of Raeder's syndrome due to spontaneous internal carotid artery dissection. True trigeminal dysfunction due to carotid dissection is rare, and the potential mechanisms for its involvement are reviewed in this paper. Finally, we remind clinicians to consider dissection in the differential diagnosis of Raeder's syndrome because of its potential for ischemic cerebral neurologic sequelae and suggest early cranial and neck imaging in the evaluation of such patients.

Indications à la coronarographie en urgence. Partie I: syndromes coronariens aigus avec élévation du segment ST [Indications for urgent coronary angiography. Part I: ST-segment elevation acute coronary syndromes]

The indications for urgent coronary angiography are stated in the guidelines for treatment of acute coronary syndromes. An invasive approach is considered the treatment of choice for patients presenting with ST elevation myocardial infarction within 12 hours of the beginning of symptoms. In the absence of contraindication, intravenous thrombolysis continues to be a valuable alternative to primary angioplasty within 3 hours of the beginning of clinical symptoms. Urgent coronary angiography continues to be recommended following the failure of thrombolysis, persistent myocardial ischemia after 12 hours of symptoms, recurrent myocardial ischemia following myocardial infarction or in the case of cardiogenic shock.

Risk factor impact on blood flow velocities and clinical outcomes of stented cervical and intracranial stenoses: preliminary observations.

OBJECTIVES: The role of angioplasty/stenting procedures, neurointerventionist experience, vascular risk factors, medical treatment and blood flow velocities were analysed to identify possible causes of intra-stent restenosis (ISR) following stenting of cervical and/or intracranial arteries, assuming progressive atherosclerosis to be the shared mechanism in both territories. Patients. 26 cerebrovascular patients subjected to stenting of severe (≥85%) symptomatic or asymptomatic carotid stenoses or moderate-to-severe (≥50%) intracranial or vertebral stenoses were included. METHODS: Clinical, radiological and ultrasonographic follow-up data were analysed retrospectively. RESULTS: Overall, stenting of the internal carotid artery (ICA) induced significant reductions in peak systolic velocities at 2 years (96±31cm/s vs. 358.2±24.9cm/s at baseline). The procedure-related ischemic complications rate was 7.4% (one hemispheric stroke and one TIA). The rate of ISR≤50% was 8% in the ICA at 2 years; was 50% in the common carotid artery (CCA) at 1 year, with concomitant distal ICA stenosis in 75% of CCA stenting, but all ISR were asymptomatic. Patients with ISR of the ICA were significantly younger (56.8±4.5 vs. 71.3±3.6 years, P=0.042) and had significantly more risk factors (5.5±0.9 vs. 3±0.3, P=0.012). No ISR≥70% was detected. CONCLUSIONS: ISR is relatively infrequent and, when present, it is mild and asymptomatic. Restenosis is more frequent in younger patients and those with several risk factors, and it may also be related to stenting of previous carotid endarterectomy.

Événements et déformations tardi-métamorphiques dans le segment Ossola-Ticino (Val Vigezzo-Centovalli, Italie-Suisse)

RESUME: Une zone tectonique large et complexe, connue sous le nom de ligne des Centovalli, traverse le secteur des Alpes Centrales compris entre Domodossola et Locarno. Cette région, formée par le Val Vigezzo et la vallée des Centovalli, constitue la terminaison méridionale du dôme Lepontin et représente une portion de la zone des racines des nappes alpines. Elle fait partie d’une grande et complexe zone de cisaillement, en partie associée à des phénomènes hydrothermaux d’âge alpin (<20 Ma), qui comprend le système tectonique Insubrien et celui du Simplon. Le Val Vigezzo et les Centovalli constituent un vrai carrefour entre les principaux accidents tectoniques des Alpes ainsi qu'une zone de juxtaposition du socle Sudalpin avec la zone des racines de l’Austroalpin et du Pennique. Les phases de déformation et les structures géologiques qui peuvent être étudiées s'étalent sur une période comprise entre environ 35 Ma et l'actuel. L’étude détaillée de terrain a mis en évidence la présence de nombreuses roches et structures de déformation de type ductile et cassant tels que des mylonites, des cataclasites, des pseudotachylites, des kakirites, des failles minéralisées, des gouges de faille et des plis. Sur le terrain on a pu distinguer au moins quatre générations de plis liés aux différentes phases de déformation. Le nombre et la complexité de ces structures indiquent une histoire très compliquée, selon plusieurs étapes distinctes, parfois liées, voire même superposées. Une partie de ces structures de déformation affectent aussi les dépôts sédimentaires d’âge quaternaire, notamment des limons et des sables lacustres. Ces sédiments constituent les restes d'un bassin lacustre attribué à l'époque interglaciaire Riss/Würm (éemien, 67.000-120.000 ans) et ils affleurent dans la partie centrale de la zone étudiée, à l'Est de la plaine de Santa Maria Maggiore. Ces sédiments montrent en leur sein toute une série de structures de déformation tels que des plans de faille inverses, des structures conjuguées de raccourcissement et des véritables plis. Ces failles et ces plis représenteraient les évidences de surface d’une déformation probablement active en époque quaternaire. Une autre formation rocheuse a retenu tout notre attention; il s'agit d'un corps de brèches péridotitiques monogéniques qui affleure en discontinuité le long du versant méridional et le long du fond de la vallée Vigezzo sur environ 20 km. Ces brèches se posent indifféremment sur le socle (unités Finero, Orselina) ou sur les sédiments lacustres. Elles sont traversées par des plans de failles qui développent des véritables stries de faille et des gouges de faille; l’orientation de ces plans est la même que celle affectant les failles à gouges du socle. La genèse de cette brèche est liée à l'altération et au modelage glacier (rock-glaciers) d'une brèche tectonique originelle qui borde la partie externe du Corps de Finero. Les structures de déformation de cette brèche, pareillement à celles des sédiments lacustres, ont été considérées comme les évidences de surface d'une tectonique quaternaire active dans la région. La dernière phase de déformation cassante qui affecte cette région peut donc être considérée comme active en époque quaternaire. Une vue d’ensemble de la région étudiée nous permet de reconnaître à l’échelle régionale une zone de cisaillement complexe orientée E-W, parallèlement à l’axe de la vallée Centovalli-Val Vigezzo. Les données de terrain, indiquent que cette zone de cisaillement débute sous conditions ductiles et évolue en plusieurs étapes jusqu’à des conditions de failles cassantes de surface. La reconstruction de l'évolution géodynamique de la région a permis de définir trois étapes distinctes qui marquent le passage, de ce secteur de socle cristallin, de conditions P-T profondes à des conditions de surface. Dans ce contexte, on a reconnu trois phases principales de déformation à l’échelle régionale qui caractérisent ces trois étapes. La phase la plus ancienne est constituée par des mylonites en faciès amphibolite, associées à des mouvements de cisaillement dextre, qui sont ensuite remplacés par des mylonites en faciès schistes verts et des plis rétrovergentes liés au rétrocharriage des nappes alpines. Une deuxième étape est identifiée par le développement d’une phase hydrothermale liée à un système de failles extensives et décrochantes dextres à direction principale E-W, NE-SW et NW-SE. Leur caractérisation minéralogique a permis la mise en évidence des phases cristallines de néoformation liées à cet événement constituées par : K-feldspath (microcline), chlorites (Fe+Mg), épidotes, prehnite, zéolites (laumontite), sphène, calcite. Dans ce contexte, pour obtenir une meilleure caractérisation de cet événement hydrothermal on a utilisé des géothermomètres sur chlorites, sensible aussi à la pression et a la a(H2O), qui ont donné des valeurs descendantes comprises entre 450-200°C. Les derniers mouvements sont mis en évidence par le développement d’une série de plans majeurs de failles à gouge, qui forment une structure en sigmoïdes d’épaisseur kilométrique reconnaissable à l’échelle de la vallée et caractérisée par des mouvements transpressifs avec une composante décrochante dextre toujours importante. Cette phase de déformation forme un système conjugué de failles avec direction moyenne E-W qui coupent la zone des racines des nappes alpines, la zone du Canavese et le corps ultramafique de Finero. Ce système se déroule de manière subparallèle à l'axe de la vallée le long de plusieurs dizaines de kilomètres. Une analyse complète et détaillée des gouges de faille par XRD a montré que la fraction argileuse (<2 µm) de ces gouges contient une partie de néoformation très importante constituée par, des illites, des chlorites et des interstratifiés de type illite/smectite ou chlorite/smectite. Des datations avec méthode K-Ar sur ces illites ont donné des valeurs comprises entre 12 et 4 Ma qui représentent l'âge de cette dernière déformation cassante. L'application de la méthode de la cristallinité de l'illite (C.I.) a permis d'évaluer les conditions thermiques qui caractérisent le déroulement de cette dernière phase tectonique qui se produit sous conditions de température caractéristiques de l'anchizone et de la diagenèse. L'ensemble des structures de déformation qu'on vient de décrire s'insère parfaitement dans le contexte de convergence oblique entre la plaque adriatique et celle européenne qui à produit l'orogène alpin. On peut considérer les structures tectoniques du Val Vigezzo-Centovalli comme l'expression d'une zone majeure de cisaillement "Simplo-Insubrienne". L'empilement structural et les structures tectoniques affleurantes dans la région sont le résultat de l'interaction entre un régime tectonique transpressif et un régime transtensif. Ces deux champs de tension sont antagonistes entre eux mais sont reliés, de toute façon, à une seule phase décrochante dextre principale, due à une convergence oblique entre deux plaques. À l'échelle de l'évolution géodynamique on peut distinguer différentes étapes au cours desquelles les structures de ces deux régimes tectoniques interagissent en manière différente. En accord avec les données géophysiques et les reconstructions paléodynamiques prises dans la littérature on considère que la ligne Rhône-Simplon-Centovalli représente l'évidence de surface de la suture majeure profonde entre la plaque Adriatique et celle Européenne. Les vitesses de soulèvement qui ont été calculées dans cette étude pour cette région des Alpes donnent une valeur moyenne de 0.8 mm/a qui est tout à fait comparable avec les données proposées par la littérature sur cette zone. La zone Val Vigezzo-Centovalli peut être donc considérée comme un carrefour géologique où se croisent différentes phases tectoniques qui représentent les évidences de surface d'une suture profonde majeure entre deux plaques dans un contexte de collision continentale. ABSTRACT: A wide and complex tectonic zone known as Centovalli line, crosses the Central Alps sector between Domodossola and Locarno. This area, formed by the Vigezzo Valley and Centovalli valley, constitutes the southernmost termination of the Lepontin dome and represents a portion of the alpine nappes root zone. It belongs to a large and complex shear-zone, partly associated with hydrothermal phenomena of alpine age (<20 My), which includes the Insubric Line and the Simplon fault zone. Vigezzo Valley and Centovalli constitute a real crossroads between the mains alpines tectonics lines as well as a zone of juxtaposition of the Southalpine basement with the Austroalpin and Pennique root zone. The deformation phases and the geological structures that can be studied between approximately 35 My and the present. The detailed field study showed the presence of many brittle and ductile deformation structures and fault rocks such as mylonites, cataclasites, pseudotachylites, kakirites, mineralized faults, fault gouges and folds. In the field we could distinguish at least four folds generations related to the various deformation phases. The number and the complexity of these structures indicate a very complicated history, comprising several different stages, that sometimes are related and even superimposed. Part of these deformation structures affect also the sedimentary deposits of quaternary age, in particular the silts and sands lake deposit. These sediments constitute the remainders of a lake basin ascribed to the interglacial Riss/Würm (Eemien, 67.000-120.000 years) and outcroping in the central part of the studied area, in the Eastern part of Santa Maria Maggiore plain. These sediments show a whole series of deformation structures such as inverse fault planes, combined shortening structures and true folds. These faults and folds would represent the surface evidence of a probably active tectonic deformation in quaternary time. Another rock formation attracted all our attention. It is a body of monogenic peridotite breccia which outcrops in discontinuity along the southernmost slope and the bottom of the Vigezzo valley on approximately 20 km. This breccia lies indifferently on the basement (Finero and Orselina units) or on the lake sediments. They are crossed by fault planes which developed slikenside and fault gouges whose orientation is the same of the faults gouges in the alpine basement. This breccia results from the weathering and the surface modelling of an original tectonic breccia which borders the external part of Finero peridotite body. This breccia deformation structures, like those of the lake sediments, were regarded as the surface interaction of active quaternary tectonics in the area. So the last brittle deformation phases which affects this area seems to be actives in quaternary time. Theoverall picture of the studied area on a regional scale enables us to point out a complex shear-zone directed E-W, parallel to the axis of the Centovalli and Vigezzo Valley. The field analysis indicates that this shear-zone began under ductile conditions and evolved in several stages to brittle faulting under surface conditions. The analysis of the geodynamic evolution of the area allows to define three different stages which mark the transition of this alpine basement root zone, from deep P-T conditions to P-T surface conditions. In this context on regional scale three principal deformation phases, which characterize these three stages can be distinguished. The oldest phase consisted of the amphibolitie facies mylonites, associated to dextral strikeslip movements. They are then replaced by green-schists facies mylonites and backfolds related to the backthrusting of the alpines nappes. A second episode is caracterized by the development of an hydrothermal phase bound to an extensive fault and dextral strike-slip fault system, with E-W, NW-SE and SE-NW principal directionsThe principal neoformed mineral phases related to this event are: K-feldspar (microcline), chlorites (Fe+Mg), epidotes prehnite, zéolites (laumontite), sphene and calcite. In this context, to obtain a better characterization of this hydrothermal event, we have used an chlorite geothermometer, sensitive also to the pressure and has the a(H2O), which gave downward values ranging between 450-200°C. The last movements are caracterized by the development of important gouge fault plans, which form a sigmoid structure of kilometric thickness which is recognizable at the valley scale, and is characterized by transpressive movements always with a significant dextral strike-slip component. This deformation phase forms a combined faults system with an average E-W direction, which cuts trough the alpine root zone, the Canavese zone and the Finero ultramafic body. This fault system takes place subparallel to the axis of the valley over several tens of kilometers. A complete and detailed XRD analysis of the gouges fault showed that the clay fraction (<2µm) contains a very significant neo-formation of illite, chlorites and mixed layered clays such as illite/smectite or chlorite/smectite. The K-Ar datings of the illite fraction <2µm gave values ranging between 12 and 4 My and the illite fraction <0.2µm gave more recents values until to 2,4-0 My.This values represent the age of this last brittle deformation. The application of the illite crystallinity method (C.I.) allowed evaluating the thermal conditions which characterize this tectonic phase that occured under temperature conditions of the anchizone and diagenesis. The whole set of deformation structures which we just described, perfectly fit the context of oblique convergence between the Adriatic and the European plate that produced the alpine orogen. We can regard the Vigezzo valley and Centovalli tectonic structures as the expression of a major "Simplo-Insubric" shear-zone. Structural stacking and tectonic structures that outcrop in the studied area, are the result of the interaction between a transpressive and a transtensve tectonic phases. These two tension fields are antagonistic but they are also connected, in any event, with only one principal dextral strike-slip movement, caused by an oblique convergence between two plates. On the geodynamic evolution scale we can distinguish various stages during which these two tectonic structures fields interact in various ways. In agreement with the geophysical data and the paleodynamic recostructions taken in the literature we considers that the Rhone-Simplon-Centovalli line are the surface feature of the major collision between the Adriatique and the European plate at depth. The uplift speeds we calculated in this study for this Alpine area give an average value of 0.8 mm/a, which is in good agreement with the data suggested by the literature on this zone. TheVigezzo Valley and Centovalli zone can therefore be regarded as a geological crossroad where various tectonic phases are superimposed. They represent the evidences of a major and deeper suture between two plates in a continental collision context.