The von Hippel-Lindau tumour suppressor gene: uncovering the expression of the pVHL172 isoform.

BACKGROUND: The von Hippel-Lindau (VHL) gene encodes two mRNA variants. Variant 1 encodes two protein isoforms, pVHL213 and pVHL160, that have been extensively documented in the literature. Variant 2 is produced by alternative splicing of exon 2 and encodes a pVHL isoform of 172 amino acids with a theoretical molecular weight of 19 kDa (pVHL172), the expression of which has never been demonstrated so far due to the absence of suitable antibodies. METHODS: We have generated an anti-pVHL monoclonal antibody (JD-1956) using pVHL172 recombinant protein. We tested the antibody against exogenous or endogenous expressed proteins in different cell lines. We identified the pVHL172 using a silencing RNA strategy. The epitope of the antibody was mapped using a peptide array. RESULTS: We efficiently detected the three different isoforms of pVHL in cell lines and tumorigenic tissues by western blotting and immunohistochemistry and confirmed for the first time the endogenous expression of pVHL172. CONCLUSIONS: The endogenous expression of the three isoforms and particularly the pVHL172 has never been shown before due to a lack of a highly specific antibody since none of the available commercial antibodies distinguish the three isoforms of pVHL in cells or in both normal and cancerous human tissues. Evidence of pVHL172 expression emphasises the need to further study its implication in renal tumorigenesis and VHL disease.

Sprint mechanics in world-class athletes: a new insight into the limits of human locomotion.

The objective of this study was to characterize the mechanics of maximal running sprint acceleration in high-level athletes. Four elite (100-m best time 9.95-10.29 s) and five sub-elite (10.40-10.60 s) sprinters performed seven sprints in overground conditions. A single virtual 40-m sprint was reconstructed and kinetics parameters were calculated for each step using a force platform system and video analyses. Anteroposterior force (FY), power (PY), and the ratio of the horizontal force component to the resultant (total) force (RF, which reflects the orientation of the resultant ground reaction force for each support phase) were computed as a function of velocity (V). FY-V, RF-V, and PY-V relationships were well described by significant linear (mean R(2) of 0.892 ± 0.049 and 0.950 ± 0.023) and quadratic (mean R(2) = 0.732 ± 0.114) models, respectively. The current study allows a better understanding of the mechanics of the sprint acceleration notably by modeling the relationships between the forward velocity and the main mechanical key variables of the sprint. As these findings partly concern world-class sprinters tested in overground conditions, they give new insights into some aspects of the biomechanical limits of human locomotion.

Spatially resolved imaging of human macular capillaries using adaptive optics-enhanced optical coherence tomography angiography.

Documenting the organization of the retinal capillaries is of importance to understand the visual consequences of vascular diseases which may differentially affect the microvascular layers. Here we detailed the spatial organization of the macular capillaries in ten healthy human subjects using a prototypic adaptive optics-enhanced optical coherence tomography angiography (AO-OCTA) system. Within the central 6° × 6°, the radial peripapillary capillaries and the superficial, intermediate and deep vascular plexuses (SVP, IVP and DVP, respectively) were consistently resolved. In 8 out of the 10 eyes, the capillary segments composing the perifoveal arcade (PFA) were perfused only by the SVP, while drainage of the PFA showed more variability, comprising a case in which the PFA was drained by the DVP. Around the center, a distinct central avascular zone could be documented for each layer in 7 of the 10 cases; in three eyes, the IVP and SVP merged tangentially around the center. In all eyes, the foveal avascular zone was larger in the DVP than in the SVP and IVP. In one eye with incomplete separation of the inner foveal layers, there was continuity of both the SVP and the IVP; a central avascular zone was only present in the DVP. The diversity of perfusion and drainage patterns supported a connectivity scheme combining parallel and serial organizations, the latter being the most commonly observed in perifoveal vessels. Our results thus help to further characterize the diversity of organization patterns of the macular capillaries and to robustly analyze the IVP, which will help to characterize early stages of microvascular diseases.

Intrinsic ankle and hopping leg-spring stiffness in distance runners and aerobic gymnasts.

The objective of this study was to examine the contribution of intrinsic ankle stiffness to leg-spring stiffness in high level athletes using various musculotendinous solicitations. 8 aerobic gymnasts (G), 10 long-distance runners (R) and 7 controls (C) were evaluated using quick-release and sinusoidal perturbation tests in order to quantify their respective plantarflexor musculotendinous ( SI(MT)), ankle musculoarticular active ( SI(MA)) and passive ( K(P)) stiffness. Leg-spring stiffness ( K(leg)) was measured during vertical hopping. Runners and gymnasts presented significantly higher SI(MT) values ( P < 0.01) than controls: 60.4 (± 14.1) rad (-1).kg (2/3) for G, 72.7 (± 23.8) rad (-1).kg (2/3) for R and 38.8 (± 6.5) for C. In addition, normalized K(leg) was not significantly different between G, R and C. It appeared that intrinsic ankle stiffness had no influence on leg-spring stiffness. The adaptation of SI (MT) seems to concern specifically the active part of the series elastic component in runners. The results suggested that the number of stretch-shortening cycles during daily practice sessions, rather than their intensity, act as the determinant for this component.

[Treatment of exudative age-related macular degeneration: Consensus of French experts for first-line treatment selection and the importance of long-term risk/benefit ratio]. / Consensus d'experts français sur les critères de choix d'un traitement de 1re intention dans la DMLA néovasculaire et importance du ratio bénéfice/risque à long terme.

Choosing a first-line treatment to optimize long-term outcomes is a major challenge for treating patients with neovascular age-related macular degeneration (AMD). The development of several new molecules makes it critical to identify the relevant factors to consider so as to provide an optimal risk-benefit ratio when initiating a treatment in naïve patients with neovascular AMD. This paper proposes a consensus established with the Delphi method (which includes a gradation in a consensus based on an analysis of the convergence rate of answers) to provide criteria that guide the ophthalmologist's decision for treatment initiation and follow-up in neovascular AMD patients. Fourteen questions were submitted to 93 French retina experts. Thirteen (93%) of the questions reached a consensus (≥50% of answers consensual). The criteria recommended to take into account were both efficacy and onset of action of the molecules, their safety, and the ability to decrease injection frequency. The primary criterion of expected efficacy of a molecule is a combination of the gain in visual acuity and resorption of retinal fluid. With regard to safety, experts recommend tighter follow-up for molecules currently in development, and at every scheduled visit, patients should be screened to identify early any potential adverse effects such as intraocular inflammation, retinal vasculitis or vascular occlusion. Experts also emphasize the importance of the packaging of the biological, with a preference toward prefilled syringes. Injection frequency is a key factor, and the authors recommended aiming for a maximal injection interval of 12 to 16 weeks. The stability of that maximum interval is also an important factor to consider in treatment selection.

Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population.

AIM: To assess the cardiovascular and cerebrovascular (CCV) safety of the dipeptidyl peptidase-IV inhibitor vildagliptin. METHODS: Data were pooled from 25 Phase III studies of vildagliptin, used either as monotherapy or combination therapy, with durations of 12 weeks to > or = 2 years. The safety of vildagliptin [50 mg qd (N = 1393) or 50 mg bid (N = 6116)] was assessed relative to a pool of all comparators [both placebo and active comparators (N = 6061)]. CCV events were adjudicated in a prospective, blinded fashion by an independent CCV adjudication committee. Meta-analysis of confirmed CCV events was performed with Mantel-Haenszel risk ratios (RRs); categories included in the composite endpoint were acute coronary syndrome, transient ischaemic attack (with imaging evidence of infarction), stroke and CCV death. Subgroup analyses by age (< and > or = 65 years), gender and cardiovascular (CV) risk status [high CV risk status defined as a previous history of events in the Standard MedDRA Queries of ischaemic heart disease, cardiac failure, ischaemic cerebrovascular conditions and/or embolic/thrombotic events, arterial) were also carried out. In addition, unadjusted and exposure-adjusted incidences are presented for both the composite endpoint and its components. RESULTS: Relative to all comparators, the RRs for the composite endpoint were < 1 for both vildagliptin 50 mg qd [RR = 0.88; 95% CI (0.37, 2.11)] and vildagliptin 50 mg bid [RR = 0.84; 95% CI (0.62, 1.14)]. The results were consistent across subgroups defined by age, gender and CV risk status, including the higher CV risk subgroups of elderly patients [RR for vildagliptin 50 mg bid vs. all comparators = 1.04; 95% CI (0.62, 1.73)], males [RR = 0.87; 95% CI (0.60, 1.24)] or patients with a high CV risk status [RR = 0.78; 95% CI (0.51, 1.19)]. The exposure-adjusted incidences of each component of the composite endpoint for vildagliptin 50 mg bid were also lower than or similar to those of all comparators. CONCLUSIONS: In a large meta-analysis, vildagliptin was not associated with an increased risk of adjudicated CCV events relative to all comparators in the broad population of type 2 diabetes including patients at increased risk of CCV events.

An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials.

AIM: To assess the safety of vildagliptin versus all comparators (ACs) with regard to organs, systems or tissues of particular interest in type 2 diabetes (T2DM) and areas of potential concern with dipeptidyl peptidase-IV (DPP-4) inhibitors. METHODS: Data were pooled from 38 studies where vildagliptin was given for > or =12 to > 104 weeks in patients with T2DM. Absolute and exposure-adjusted incidence rates and Peto odds ratios (ORs) versus ACs with corresponding 95% confidence intervals (CI) were calculated. RESULTS: There were > 7000 subject-years of exposure (SYE) to vildagliptin 50 mg bid and > 6500 SYE to ACs. For mild hepatic enzyme elevations with and without elevated bilirubin levels, the ORs for vildagliptin 50 mg bid were 1.24 (95% CI: [0.80, 1.93]) and 1.19 (95% CI: [0.29, 4.90]), respectively. The exposure-adjusted incidences of markedly elevated hepatic enzymes and for enzyme elevations with bilirubin > or = 2x ULN with vildagliptin 50 mg bid were < or = those in the ACs group. For hepatic and pancreatitis-related AEs, the ORs for vildagliptin 50 mg bid were 0.87 (95% CI: [0.64, 1.19]) and 0.70 (95% CI: [0.26, 1.88]), respectively, and for any AE in the infections and infestations SOC, this was 1.04 (95% CI: [0.96, 1.13]). The incidences of skin-related AEs were low and the risk with vildagliptin 50 mg bid was not significantly different from ACs [(OR = 1.10 (95% CI: [0.80, 1.51])]. CONCLUSIONS: The present meta-analyses indicate that vildagliptin was not associated with increased risk of hepatic events or hepatic enzyme elevations indicative of drug-induced liver injury, pancreatitis, infections or skin-related toxicity.

Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study.

AIM: To show that vildagliptin added to metformin is non-inferior to glimepiride in reducing HbA1c levels from baseline over 2 years. METHODS: A randomized, double-blind, active-comparator study of patients with type 2 diabetes mellitus inadequately controlled (HbA1c 6.5-8.5%) by metformin monotherapy. Patients received vildagliptin (50 mg twice daily) or glimepiride (up to 6 mg/day) added to metformin. RESULTS: In all, 3118 patients were randomized (vildagliptin, n = 1562; glimepiride, n = 1556). From similar baseline values (7.3%), after 2 years adjusted mean (s.e.) change in HbA1c was comparable between vildagliptin and glimepiride treatment: -0.1% (0.0%) and -0.1% (0.0%), respectively. The primary objective of non-inferiority was met. A similar proportion of patients reached HbA1c <7% (36.9 and 38.3%, respectively), but with vildagliptin more patients reached this target without hypoglycaemia (36.0% vs. 28.8%; p = 0.004). The initial response (IR) was sustained for a mean (s.d.) of 309 (244) days with vildagliptin versus 270 (223) days for glimepiride (p < 0.001) (IR = nadir HbA1c where change from baseline > or =0.5% or HbA1c < or =6.5% within the first six months of treatment. After IR was detected, sustained response = time between nadir and an increase of >0.3% above IR). Independent of disease duration, age was a predictor of effect sustainability. Fewer patients experienced hypoglycaemia with vildagliptin (2.3% vs. 18.2% with glimepiride) with a 14-fold difference in the number of hypoglycaemic events (59 vs. 838). Vildagliptin had a beneficial effect on body weight [mean (s.e.) change from baseline -0.3 (0.1) kg; between-group difference -1.5 kg; p < 0.001]. Overall, both treatments were well tolerated and displayed similar safety profiles. CONCLUSIONS: Vildagliptin add-on has similar efficacy to glimepiride after 2 years' treatment, with markedly reduced hypoglycaemia risk and no weight gain.

[Treatment switch in diabetic macular edema: Literature review and management algorithm]. / Les switchs de traitement dans l'œdème maculaire diabétique : revue de la littérature et algorithme de prise en charge.

Initial management of diabetic macular edema (DME) is well-defined, but there is a lack of national or international consensus for patients who do not respond or respond only partially to these treatments. Several studies, mostly retrospective, have assessed medication switches, but currently, the literature contains no randomized studies. The goal of this article is to present an algorithm for switching medications, which can be proposed to DME patients treated with anti-VEGF agents, as defined by a group of French retina experts, supported by the existing literature on the subject. After initiation of an anti-VEGF treatment for DME, the response is usually assessed after 5 monthly injections. A partial anatomical response (reduction of central retinal thickness between 10 and 20%), seen in 30 to 40% of patients, is associated with a favorable visual prognosis according to randomized studies. Continuation of the anti-VEGF injections after the induction phase is thus possible. If the response remains incomplete after 3 additional anti-VEGF injections, a complete ophthalmologic examination should be performed, and a switch to another therapeutic class (corticosteroids) may be proposed in the absence of contraindications. If a complete non-response is seen initially (reduction of central retinal thickness<10%), the switch is proposed immediately after the induction phase.

Influence of different racing positions on mechanical and electromyographic patterns during pedalling.

The aim of this study was to test the hypothesis that, in comparison with standard postures, aero posture (AP) would modify the coordination of lower limb muscles during pedalling and consequently would influence the pedal force production. Twelve triathletes were asked to pedal at an intensity near the ventilatory threshold (VT+Delta20%) and at an intenisty corresponding to the respiratory compensation point (RCP). For each intensity, subjects were tested under three positions: (1) upright posture (UP), (2) dropped posture (DP), and (3) AP. Gas exchanges, surface electromyography and pedal effective force were continuously recorded. No significant difference was found for the gas-exchange variables among the three positions. Data illustrate a significant increase [gluteus maximus (GMax), vastus medialis (VM)] and decrease [rectus femoris (RF)] in electromyography (EMG) activity level in AP compared with UP at RCP. A significant shift forward of the EMG patterns (i.e. later onset of activation) was observed for RF (at VT+Delta20% and RCP), GMax, VL, and VM (at RCP) in AP compared with UP. These EMG changes are closely related to alteration of force profile in AP (higher downstroke positive peak force, lower upstroke negative peak force, and later occurrence of these peaks along the crank cycle).

Accuracy and repeatability of the Polar RS800sd to evaluate stride rate and running speed.

The purpose of this study was to evaluate the accuracy and the repeatability of a new running computer system (RS800sd, Polar, Kempele, Finland) which included the measurement of running speed (RS) and stride rate (SR). Eight well-trained triathletes participated in this study. First, they completed an incremental continuous maximum test on a treadmill (from 12 km x h (-1) to 18 km x h (-1)) at 0% grade. Then the subjects took part in a second test to determine RS800sd intra-reproducibility to evaluate running speed. They ran twice during 5 min at a pace corresponding to their maximal lactate steady-state. During these two tests, RS and SR were recorded by the RS800sd system, by an optical sensor system (for RS) and a force-sensitive device (for SR). No difference was found between the RS800sd system and the reference systems both for RS (ICC=0.95) and SR (ICC=0.69). Moreover RS measures were statistically repeatable. This study provided evidence for the validity of the RS800sd system for measuring the kinematic characteristics of running (speed and frequency). Further investigations are needed to replicate these findings at lower running speeds, notably during walking to assess its capacity to evaluate physical activity in natural conditions.

Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea.

AIM: To compare the efficacy and tolerability of vildagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled [haemoglobin A(1c) (HbA(1c)) 7.5 to 11%] with prior sulphonylurea (SU) monotherapy. METHODS: This 24-week, multicentre, randomized, double-blind, placebo-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (50 mg given once or twice daily) vs. placebo added to glimepiride (4 mg once daily) in 515 patients with T2DM. Adjusted mean changes from baseline to end-point (AMDelta) in HbA(1c), fasting plasma glucose, fasting lipids and body weight were compared by analysis of covariance. RESULTS: The between-group difference (vildagliptin - placebo) in AMDelta HbA(1c) was -0.6 +/- 0.1% in patients receiving vildagliptin 50 mg daily and -0.7 +/- 0.1% in those receiving 100 mg daily (p < 0.001 vs. placebo for both). Greater efficacy was seen in patients > or =65 years of age (-0.7 +/- 0.1% and -0.8 +/- 0.2% for 50 and 100 mg daily respectively) and in patients with baseline HbA(1c) > 9% (Delta = -1.0 +/- 0.2% and -0.9 +/- 0.2% for 50 and 100 mg daily respectively). Relative to placebo, patients receiving vildagliptin also had improvements in beta-cell function and postprandial glucose, with small changes in fasting lipids and body weight. The incidences of adverse events (AEs) (67.1, 66.3 and 64.2%) and serious AEs (2.9, 2.4 and 5.1%) were similar in patients receiving 50 mg vildagliptin, 100 mg vildagliptin or placebo respectively. The incidence of hypoglycaemic events was low but slightly higher in the group receiving vildagliptin 100 mg (3.6%) than in the group receiving vildagliptin 50 mg (1.2%) or placebo (0.6%). CONCLUSIONS: In patients with T2DM inadequately controlled with prior SU monotherapy, addition of vildagliptin (50 or 100 mg daily) to glimepiride (4 mg once daily) improves glycaemic control and is well tolerated. Addition of vildagliptin 50 mg daily to SU monotherapy may be a particularly attractive therapy in elderly patients.

Measurement of full-thickness macular hole size using en face optical coherence tomography.

PurposeTo assess the feasibility and interest of measuring macular hole (MH) size using en face optical coherence tomography (OCT) compared with manual diameter measurements on B-scans.MethodsAmong our previously published series of 100 patients operated for primary MH, patients whose images were acquired with Cirrus 5000 HD-OCT (Carl Zeiss Meditec) with a quality signal strength >5/10 were included. Three segmentations (internal limiting membrane, horizontal, and retinal pigment epithelium (RPE)) were compared for obtaining the most appropriate en face image. MH surface areas were measured using ImageJ software. Mean diameters calculated from surface areas (diameter=2 × âˆš(surface area/π)) were compared with those measured on B-scans.ResultsNineteen patients were included with a mean age of 72±8 years (56-86) and a female predominance (3/16). The mean absolute difference between horizontal and vertical diameters measured on B-scans was of 54±47 µm (0-180) without reaching significance (P=0.874). RPE segmentation provided the best en face image and was feasible without and with adjustment, respectively, in 79% and 100% (cases with vitreomacular traction) of cases. No significant difference in mean diameters was observed between those calculated from en face images (435±143 µm (195-693)) and those measured on horizontal B-scans (426±139 µm (214-705), P=0.482).ConclusionMeasuring MH size on en face OCT images is feasible, reliable, and eliminates the potential bias related to manual measurements on B-scans. Its integration into OCT devices would offer an automated and easy-to-use option for clinical practice.

[Variability of chloroquine and hydroxychloroquine retinopathy among various ethnicities]. / Différences ethniques parmi les patients souffrant de toxicité maculaire aux antipaludéens de synthèse.

INTRODUCTION: Current screening recommendations for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are based on central 10°C static perimetry and a high-resolution SD-OCT with a special attention to the inferior part of the macula where the toxicity usually starts by ellipsoid zone disruption. However, Melles and Marmor, have recently shown a great variability in the topography of the initial toxicity observed among various ethnicities, which is important to keep in mind so as not to miss early toxicity in certain subgroups of patients. METHODS: Review of the literature. RESULTS: Ethnic differences have been shown regarding the topography of the initial retinal toxicity of CQ and HCQ, particularly between Caucasian and Asian subjects. In Caucasians, the first signs of toxicity are more often localized in the inferior para-foveal area associated with a decrease in retinal sensitivity in the upper 10°C visual field. However, in Asian subjects, the first signs of toxicity appear more pericentral (still inferior) with an extramacular pattern that could be missed by the usual 10°C visual field screening. DISCUSSION/CONCLUSION: The pathophysiology of these ethnic differences is unknown and may be due to distinct genetic predisposition to CQ and HCQ toxicity. Screening strategies should be adjusted to the ethnicity and performed in Asian subjects with larger visual fields (30°C), along with SD-OCT, looking for ellipsoid disruption≥8°C from the fovea. The recognition of this pericentral topography and an adjusted screening protocol should avoid late diagnosis in Asians treated with CQ and HCQ.

Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein.

By differential screening of a Xenopus egg cDNA library, we selected nine clones (Eg1 to Eg9) corresponding to mRNAs which are deadenylated and released from polysomes soon after fertilization. The sequence of one of these clones (Eg5) revealed that the corresponding protein has the characteristic features of a kinesin-related protein. More specifically, Eg5 was found to be nearly 30% identical to a kinesin-related protein encoded by bimc, a gene involved in nuclear division in Aspergillus nidulans.

Craniofacial fibrous dysplasia: A 10-case series.

OBJECTIVES: Fibrous dysplasia of bone is a rare sporadic benign congenital condition in which normal cancellous bone is replaced by fibro-osseous tissue with immature osteogenesis. Sarcomatous transformation is exceptional. Lesions may involve one bone (monostotic) or several (polyostotic). Fibrous dysplasia may be associated with café-au-lait skin macules and endocrinopathy in McCune-Albright syndrome, or with myxoma in Mazabraud's syndrome. METHODS: We report ten cases of patients followed up for craniofacial fibrous dysplasia in our center between 2010 and 2015. RESULTS: Mean age was 43 years (range, 10-72 years). Clinical symptoms comprised headache (n=3) and sensorineural disorder: recurrent anterior uveitis (n=1), visual acuity loss, epiphora and vestibular syndrome (n=1), and hearing loss (n=1). All cases were monostotic. The sphenoid bone was most commonly involved (n=5), followed by the ethmoid (n=1), frontal (n=1), fronto-ethmoid (n=1), temporal (n=1) and fronto-ethmoido-sphenoid (n=1) bones. Five patients were treated with intravenous pamidronate, a bisphosphonate: evolution was favorable for 3 of them at 1-6 months after treatment initiation, with resolution of headache or vestibular syndrome; the other 2 patients were stable. Two patients were operated on. CONCLUSION: Diagnosis of craniofacial fibrous dysplasia should be considered in case of headache, neuralgia, sensory disorder, functional disorder or infectious ENT complications. A medico-surgical approach is useful for these patients.

[Update on recommendations for screening for hydroxychloroquine retinopathy]. / Mise à jour des recommandations sur la toxicité rétinienne des antipaludéens de synthèse.

INTRODUCTION: Recommendations for screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy have recently been changed by the American Academy of Ophthalmology, taking into account new published data on toxicity prevalence, risk factors, location of onset in the retina and the efficacy of screening tests. METHODS: Literature review. RESULTS AND DISCUSSION: The risk of developing CQ or HCQ retinopathy depends on the daily dose and duration of treatment. At recommended doses, the risk is<1 % at 5 years, <2 % at 10years but increases to about 20 % after 20years of treatment. The maximum recommended daily dose is 5.0mg/kg for HCQ and 2.3mg/kg for CQ. The two main risk factors are the daily dose and duration of treatment. The presence of kidney failure and treatment with tamoxifen are also significant risk factors. A baseline examination should be performed at the initiation of treatment to rule out pre-existing maculopathy. The screening is then annual and starts from the 5th year of treatment. The two tests recommended for screening are the automated visual field and spectral domain OCT. Multifocal ERG and autofluorescence fundus imaging are only carried out secondarily to confirm the pathology.

[A "fast track" to improve management of neovascular age related macular degeneration]. / Un « circuit court ¼ pour améliorer la prise en charge des patients atteints de dégénérescence maculaire liée à l'âge néovasculaire.

OBJECTIVE: To evaluate the role of a fast track for management of patients with neovascular age- related macular degeneration (nARMD) treated by intravitreal injection of anti-VEGF. PATIENTS: The records of 100 patients in the chronic maintenance phase of intravitreal anti-VEGF followed in the fast track and 63 patients followed in the standard protocol for at least 12 months were retrospectively analyzed. METHOD: Patients in the fast track underwent visual acuity (VA) testing by ETDRS, optical coherence tomography (OCT) and a physician assessment. The injection was performed the same day whenever possible. The primary endpoint to evaluate patient adherence was the time between the ideal date of visit or injection prescribed by the physician and the actual date of administration. RESULTS: The mean time between the ideal date of visit or injection prescribed by the physician and the actual date of administration was 4.1±7.5 days for the patients followed in the fast track and 5.6±18.7 days for the patients followed in the standard protocol. Mean VA remained stable for the patients followed in the fast track: 20/50 (20/800 to 20/20) at baseline vs. 20/50 (20/800 to 20/16) at the conclusion of follow-up. It dropped from 40/50 at baseline to 20/63 at the conclusion of follow-up for the patients followed in the standard protocol. CONCLUSION: In the context of a fast track, it was possible to improve the adherence of nARMD patients and maintain their VA gain or stabilization achieved after the induction phase.

Relation between preferred and optimal cadences during two hours of cycling in triathletes.

OBJECTIVES: To determine whether the integrated electromyographic signal of two lower limb muscles indicates preferred cadence during a two hour cycling task. METHODS: Eight male triathletes performed right isometric maximum voluntary contraction (MVC) knee extension and plantar flexion before (P1) and after (P2) a two hour laboratory cycle at 65% of maximal aerobic power. Freely chosen cadence (FCC) was also determined, also at 65% of maximal aerobic power, from five randomised three minute sessions at 50, 65, 80, 95, and 110 rpm. The integrated electromyographic signal of the vastus lateralis and gastrocnemius lateralis muscles was recorded during MVC and the cycle task. RESULTS: The FCC decreased significantly (p<0.01) from P1 (87.4 rpm) to P2 (68.6 rpm), towards the energetically optimal cadence. The latter did not vary significantly during the cycle task. MVC of the vastus lateralis and gastrocnemius lateralis decreased significantly (p<0.01) between P1 and P2 (by 13.5% and 9.6% respectively). The results indicate that muscle activation at constant power was not minimised at specific cadences. Only the gastrocnemius lateralis muscle was affected by a two hour cycling task (especially at 95 and 110 rpm), whereas vastus lateralis remained stable. CONCLUSION: The decrease in FCC observed at the end of the cycle task may be due to changes in the muscle fibre recruitment pattern with increasing exercise duration and cadence.

[Craniofacial fibrous dysplasia]. / La dysplasie fibreuse osseuse cranio-faciale.

Fibrous dysplasia of bone is a benign, uncommon, sporadic, congenital skeletal disorder resulting in deformity. This disease arises from activating somatic mutation in GNAS which encodes the α subunit of the G stimulatory protein associated with proliferation of undifferentiated osteogenic cells resulting in marrow fibrosis, abnormal matrix production, and stimulation of osteoclastic resorption upon overproduction of IL-6 observed in dysplastic cells. Fibrous dysplasia may be monostotic or polyostotic. This mutation affecting many tissues, café au lait skin macules and endocrinopathies (precocious puberty, hyperthyroidism, growth hormone excess, Cushing syndrome) may be associated in McCune-Albright syndrome, but also myxoma in Mazabraud syndrome or phosphate diabetes. Diagnosis of craniofacial fibrous dysplasia should be considered in the presence of headache, neuralgia, sensory disorders (vision, hearing, balance, smelling), functional disorders (nasal obstruction, nasolacrimal duct obstruction, non-matching occlusion), infectious complications (sinusitis, otitis, mastoiditis). Such symptoms should lead to perform craniofacial CT scan completed with MRI. Bone biopsy is not systematic. Surgical treatment is discussed in cases of nervous complication, facial deformity or active lesions. In case of pain resistant to conventional analgesics, intravenous bisphosphonates can be proposed. In non-responder patients, several case reports suggest the efficacy of a monoclonal antibody directed against the IL-6 receptor which requires to be confirmed by randomized studies.