Alendronate after denosumab discontinuation in women previously exposed to bisphosphonates was not effective in preventing the risk of spontaneous multiple vertebral fractures: two case reports.

At denosumab discontinuation, an antiresorptive agent is indicated to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report two cases of postmenopausal women, previously exposed to bisphosphonates, treated with alendronate at denosumab discontinuation. Alendronate was ineffective to avoid spontaneous clinical vertebral fractures. They presented three and nine spontaneous vertebral fractures 8 and 12 months after denosumab discontinuation, respectively. Ineffectiveness of alendronate was attributed to insufficient control of the rebound as assessed by B-crosslaps measures in the first case, and partially to the high risk of fractures in the later. In both situations, the increased fracture risk may have favoured these new fractures. It is urgent to define effective therapeutic strategies to avoid spontaneous vertebral fractures after denosumab discontinuation.

The lumbar spine age-related degenerative disease influences the BMD not the TBS: the Osteolaus cohort.

We evaluated the influence of degenerative disease and fractured vertebra on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) in 1500 women aged 50-80 years. TBS was not affected by a degenerative disease. While BMD increases after 62.5 years, TBS continues to decline. TBS should play a leading role in lumbar spine evaluation. INTRODUCTION: After menopause, lumbar spine (LS) BMD and TBS values decrease. Degenerative disease (DD) increases with age and affect LS BMD. The aim of this study was to measure changes in LS BMD and TBS in women 50 to 80 years old, taking into account the impact of fractured vertebrae and DD. METHODS: LS BMD, TBS, and vertebral fracture assessment were evaluated in the OsteoLaus cohort (1500 women, 50-80 years old). The exams were analyzed following ISCD guidelines to identify vertebrae with fractures or DD (Vex). RESULTS: 1443 women were enrolled: mean age 66.7 ± 11.7 years, BMI 25.7 ± 4.4. LS BMD and TBS were weakly correlated (r2 = 0.16). The correlation (Vex excluded) between age and BMD was +0.03, between age and TBS -0.34. According to age group, LS BMD was 1.2 to 3.2% higher before excluding Vex (p < 0.001). TBS had an insignificant change of <1% after excluding Vex. LS BMD (Vex) decreased by 4.6% between 52.5 and 62.5 years, and increased by 2.6% between 62.5 and 77.5 years. TBS (Vex excluded) values decreased steadily with age with an overall loss of 8.99% between 52.5 and 77.5 years. Spine TBS, femoral neck, and total hip BMD gradually decreased with age, reaching one SD between the oldest and youngest group. CONCLUSIONS: TBS is not affected by DD. While BMD increases after 62.5 years, TBS continues to decline. For lumbar spine evaluation, in view of its independence from DD, TBS should play a leading role in the diagnosis in complement to BMD.

Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports.

Osteoporosis treatments are usually given for a limited period of time in order to balance benefits and risks. We report three cases of postmenopausal women without any previous fragility fracture who presented severe spontaneous vertebral fractures after denosumab discontinuation. We think that the occurrence of these fractures could be explained by the severe rebound effect observed after denosumab discontinuation and that a consensus regarding the end of treatment with denosumab has to be defined.

[Improvement of fracture healing with teriparatide: series of 22 cases and review of the literature]. / Accélération de la guérison fracturaire par le tériparatide: série de 22 cas et revue de la littérature.

Pseudoarthrosis is defined as a non healing fracture 9 months after trauma and without radiological progression within the last three months. Osteoporotic fractures have a greater risk of chirurgical complications. The question of giving a medical treatment in the purpose of accelerating fracture healing is an increasing concern. There are data showing that with teriparatide (bone anabolic treatment derived from the parathyroid hormone) bone healing and functional status are improved, with or without surgery, in the case of either typical or atypical fractures. The risks of this treatment are low but health insurance agreement is needed in this indication. We report our experience with the use of this molecule, out of the official indication, in complex situations of non healing fractures.

Can one or two high doses of oral vitamin D3 correct insufficiency in a non-supplemented rheumatologic population?

SUMMARY: We evaluated the effectiveness of supplementation with high dose of oral vitamin D3 to correct vitamin D insufficiency. We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients and that the patients who benefited more from supplementation were those with the lowest baseline levels. INTRODUCTION: Adherence with daily oral supplements of vitamin D3 is suboptimal. We evaluated the effectiveness of a single high dose of oral vitamin D3 (300,000 IU) to correct vitamin D insufficiency in a rheumatologic population. METHODS: Over 1 month, 292 patients had levels of 25-OH vitamin D determined. Results were classified as: deficiency <10 ng/ml, insufficiency ≥10 to 30 ng/ml, and normal ≥30 ng/ml. We added a category using the IOM recommended cut-off of 20 ng/ml. Patients with deficient or normal levels were excluded, as well as patients already supplemented with vitamin D3. Selected patients (141) with vitamin D insufficiency (18.5 ng/ml (10.2-29.1) received a prescription for 300,000 IU of oral vitamin D3 and were asked to return after 3 (M3) and 6 months (M6). Patients still insufficient at M3 received a second prescription for 300,000 IU of oral vitamin D3. Relation between changes in 25-OH vitamin D between M3 and M0 and baseline values were assessed. RESULTS: Patients (124) had a blood test at M3. Two (2%) had deficiency (8.1 ng/ml (7.5-8.7)) and 50 (40%) normal results (36.7 ng/ml (30.5-5.5)). Seventy-two (58%) were insufficient (23.6 ng/ml (13.8-29.8)) and received a second prescription for 300,000 IU of oral vitamin D3. Of the 50/124 patients who had normal results at M3 and did not receive a second prescription, 36 (72%) had a test at M6. Seventeen (47%) had normal results (34.8 ng/ml (30.3-42.8)) and 19 (53%) were insufficient (25.6 ng/ml (15.2-29.9)). Of the 72/124 patients who receive a second prescription, 54 (75%) had a test at M6. Twenty-eight (52%) had insufficiency (23.2 ng/ml (12.8-28.7)) and 26 (48%) had normal results (33.8 ng/ml (30.0-43.7)). At M3, 84% patients achieved a 25-OH vitamin D level >20 ng/ml. The lowest the baseline value, the highest the change after 3 months (negative relation with a correlation coefficient r = -0.3, p = 0.0007). CONCLUSIONS: We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients.

[Diabetic retinopathy and diabetic foot syndrome in patients of a sub-Saharan megacity (Kinshasa, DR Congo)]. / Diabetische Retinopathie und diabetisches Fußsyndrom bei Diabetikern in Kinshasa (Demokratische Republik Kongo).

PURPOSE: The prevalence of diabetes mellitus is increasing worldwide especially in developing countries. Foot ulcerations in patients with diabetic neuropathy have a high impact in the overall amputation rate. In the present study we looked for the severity of diabetic retinopathy in patients with diabetic foot syndrome in a diabetic care unit in a sub-Sahara megacity (Kinshasa, Democratic Republic of Congo). METHOD: Forty-one patients with diabetes-related foot ulcerations (26 male, 15 female, mean age 45.6 years) were enrolled in the study. All patients underwent visual acuity evaluation and slit lamp biomicroscopy. Incidence and stage of retinopathy were evaluated by retinal funduscopy and documented by fundus photography. RESULTS: Twenty-seven eyes showed no signs of diabetic retinopathy. Forty-seven eyes were diagnosed as non-proliferative diabetic retinopathy (16 mild, 16 moderate, 15 severe). Seven eyes showed proliferative diabetic retinopathy. One patient had a unilateral central venous occlusion. In this case the classification of diabetic retinopathy was not possible because of the massive retinal bleedings. CONCLUSION: It was evident that there is a considerable discrepancy between partly extensive foot ulcerations and only mild to moderate diabetic retinopathy in most of the patients. This indicates that neuropathy-induced foot problems and microangiopathy-induced diabetic retinopathy are diabetic complications whose formal pathogenesis is only loosely correlated. Additional risk factors in local African conditions compared to Europe may play a major role in this discrepancy.

[Therapeutic goal of vitamin D: optimal serum level and dose requirements]. / Aspects thérapeutiques de la vitamine D: quels taux cibler avec quels traitements?

Therapeutic goal of vitamin D: optimal serum level and dose requirements Results of randomized controlled trials and meta-analyses investigating the effect of vitamin D supplementation on falls and fractures are inconsistent. The optimal serum level 25(OH) vitamin D for musculoskeletal and global health is > or = 30 ng/ml (75 nmol/l) for some experts and 20 ng/ml (50 nmol/l) for some others. A daily dose of vitamin D is better than high intermittent doses to reach this goal. High dose once-yearly vitamin D therapy may increase the incidence of fractures and falls. High serum level of vitamin D is probably harmful for the musculoskeletal system and health at large. The optimal benefits for musculoskeletal health are obtained with an 800 UI daily dose and a serum level of near 30 ng/ml (75 nmol/l).

[Seven cases of inverted nasosinusal papilloma treated at Cotonou]. / Sept cas de papillome inversé nasosinusien pris en charge à Cotonou.

OBJECTIVE: Sinonasal inverted papilloma is a rare benign tumor with a high recurrence rate and potential malignant transformation. The purpose of this study was to analyze the clinical and radiological aspects and to identify the suitable surgical approaches to be used in developing countries. METHODOLOGY: In 3 years, 7 cases have been analyzed in a retrospective study. Patients presented with unilateral nasal obstruction and epitasis, a whitish unilateral polypoid mass, sinonasal opacity with osteolysis on CT scan or on sinus X-ray. Using these data we adopted the Krouse staging which classifies the disease in four stages and accordingly the appropriate surgical approach was used. The diagnosis was confirmed by histological examination of the biopsied specimen. RESULTS: Average age 48.28 years, predominant sex male. Symptom: unilateral nasal obstruction 5, bilateral nasal obstruction 1, epistaxis 5. The average time-delay before consultation was 73 months. The combined endonasal endoscopic and vestibular was the most commonly used approach (4 cases). The results were satisfying. After a minimal follow up of 2 years, one case of recurrence was detected after 4 years. CONCLUSION: CT scan is an essential tool for the diagnosis and detecting the extension of sinonasal inverted papillomas. Better results were obtained with a surgical approach that combined a vestibular approach and an endonasal endoscopic approach in our region.

[OsteoLaus: prediction of osteoporotic fractures by clinical risk factors and DXA, IVA and TBS]. / La cohorte OstéoLaus: évaluation des outils de routine clinique pour la prédiction de la fracture ostéoporotique.

OsteoLaus is a cohort of 1400 women 50 to 80 years living in Lausanne, Switzerland. Clinical risk factors for osteoporosis, bone ultrasound of the heel, lumbar spine and hip bone mineral density (BMD), assessment of vertebral fracture by DXA, and microarchitecture evaluation by TBS (Trabecular Bone Score) will be recorded. TBS is a new parameter obtained after a re-analysis of a DXA exam. TBS is correlated with parameters of microarchitecture. His reproducibility is good. TBS give an added diagnostic value to BMD, and predict osteoporotic fracture (partially) independently to BMD. The position of TBS in clinical routine in complement to BMD and clinical risk factors will be evaluated in the OsteoLaus cohort.

Long-term single-center results of management of ethmoid adenocarcinoma: 95 patients over 28 years.

OBJECTIVES: To assess management options for ethmoid adenocarcinoma. STUDY DESIGN: Retrospective review over 28 years. PATIENTS AND METHODS: Ninety-five patients were included. Statistical analysis using the Kaplan-Meier method was performed to establish survival rates, and univariate analysis to determine prognostic factors. Independent chi(2) test was used to compare survival rates between T3 and T4a stages operated by transfacial and craniofacial approaches, respectively. RESULTS: Mean age was 64 years, and 76% patients were stage T3 or T4. Three patients had node metastasis, none of whom had distant metastases at time of diagnosis. Eighty-three percent of patients received surgery and adjuvant radiotherapy on tumor bed. Mean follow-up was 5 years. The recurrence and metastasis rate were 31 and 9% at median time of 3 years, respectively. The disease-specific 5- and 10-year survival rates were 78 and 64%, respectively. The disease-free survival rate was 61 and 44%, respectively, at the same time points. Meningo-encephalic (P = 10(-8)), orbit or infratemporal fossae (P = 0.046), and frontal sinus extension (P = 0.02) negatively impacted survival. There was no statistically significant difference in survival rate between T3 and T4a. CONCLUSIONS: Our data suggest that less surgical treatment may be needed than is usually advocated for T1-T4a tumors and that surgery alone may be appropriate for T1-T3 tumors that have been resected with adequate margins in those patients for whom excellent follow-up is anticipated. No neck irradiation is indicated for N0 disease.

[Resorption of cartilage grafts in rhinoplasty: fundamental basis]. / La résorption des greffons cartilagineux en rhinoplastie: bases fondamentales.

Resorption of the autologous cartilage graft of the nasal dorsum is a problem which concerns all rhinoplasticians. Their rate of resorption is estimated between 20 to 30% of the graft volume and can occur with no means of prevention from the side of the surgeon. The goal of this article is to highlight, through a short review of the literature, the current data regarding the composition of the septal cartilage, its healing process and the progress made in cartilaginous tissue engineering to adapt our surgical technique. Cartilaginous tissue engineering does not yet have the abilities to provide a replacement septal cartilage with the same molecular composition, the same mechanical properties and devoid of volume loss after implantation and in spite of a certain progress, autologous cartilage grafts are still making the headlines. However to avoid the resorption of the latter and to preserve their volume, it seems necessary to avoid crushing them so as not to compromise chondrocyte viability and proliferation. Cutting-out millimeter-length dices seems more adapted to preserve cellular viability but remains insufficient because of the low healing capacities of the cartilage. Diced-cartilage wrapped with connective tissue seems an elegant and efficient solution over the long run to safeguard their volume and to harmonize contours and irregularities of the dorsum.

Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment Among Patients With Advanced Pancreatic Cancer: A Phase 1b/2 Pilot Clinical Trial.

Importance: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations, indicating a DNA repair deficiency associated with sensitivity to DNA damaging agents, such as platinum. Objective: To determine response rate following treatment with nab-paclitaxel plus gemcitabine plus platinum-based cisplatin for patients with metastatic pancreatic ductal adenocarcinoma (PDA). Design, Setting, and Participants: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus cisplatin treatment in which 25 patients with previously untreated metastatic PDA were enrolled. The trial was conducted from December 2013 to July 2016 at 3 US sites, with the last patient receiving study treatment at the end of October 2016, and the study closing January 2018. Interventions: Patients were treated with nab-paclitaxel plus gemcitabine plus various doses of cisplatin, 25 mg/m2, 37.5 mg/m2, and 50 mg/m2, on days 1 and 8 of a 21-day cycle. Main Outcomes and Measures: Primary end point was complete response rate as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and levels of carbohydrate antigen 19-9 (or in nonexpressers, carbohydrate antigen 125 or carcinoembryonic antigen). Efficacy analysis included evaluable patients (those who received at least 1 dose of study treatment and had at least 1 postbaseline tumor assessment). Results: Of 25 patients enrolled in the study, the median (range) age was 65.0 (47.0-79.0) years, 14 (56%) were men, and most (24) were white (96%). The maximum tolerable dose of cisplatin was 25 mg/m2. The most common treatment-related adverse events grade 3 or higher were thrombocytopenia (17 patients [68%]), anemia (8 patients [32%]), and neutropenia (6 patients [24%]). Fatal events occurred for 3 patients (12%); 2 were related to study participation. A median (range) of 8 (1-15) cycles was completed. The RECIST responses in 24 evaluable patients included 2 complete responses (8%), which was below the primary end point of 25%, 15 partial responses (62%), 4 stable disease (17%), and 3 progressive disease (12%), with median overall survival of 16.4 (95% CI, 10.2-25.3) months; 16 patients (64%) were alive at 1 year, 10 (40%) at 2 years, 4 (16%) at 3 years, and 1 (4%) at 4 plus years. Overall survival ranged from 36 to 59 months. Median progression-free survival was 10.1 (95% CI, 6.0-12.5) months. Thus, the overall response rate was 71%, and the disease control rate was 88%. Conclusions and Relevance: This triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging. The regimen is being studied in patients with PDA in the neoadjuvant setting and in patients with advanced biliary cancers. Trial Registration: ClinicalTrials.gov identifier: NCT01893801.

[Carcinogenesis of the ethmoidal adenocarcinoma due to wood dust]. / La carcinogenèse de l'adénocarcinome de l'ethmoïde aux poussières de bois.

OBJECTIVES: To recognize the mechanisms and the different oncogenic pathways of ethmoid adenocarcinoma (EADC) in woodworkers. METHODS: A systematic review of the literature and evaluation according to scientific evidences. RESULTS: Wood dust less than 10 microm settles on the external aspects of the ethmoid sinus that is the middle turbinate, the middle meatus and the olfactory cleft. The risk of developing an EADC is important from the first year. It is impossible to know what determines the latency period. Usually, this period exceeds 30 years and only 10% of patients are younger than 50 years of age. Chromosomal instability of the respiratory mucosa appears to be one of the major phases in the oncogenic process. Certain biomolecular and genetic factors are shared with the adenocarcinoma of the colon but they are not activated with the same importance and in the same context suggesting two distinct mechanisms of evolution. The local anatomo-clinical setting in the nasal cavity and carcinogenic substances in the wood dust play a key specific role in the development of EADC. No oncoproteins or immunohistochemistry features were identified in the process suggesting a cascade of genetic or molecular series of events.

Use of gutta percha cores in CT scan imaging for patent nasopalatine duct.

Gutta percha cores were inserted in nasopalatine ducts to improve their visualization on CT scans. This simple method enhances the diagnostic quality of these images so that surgery can be performed more precisely.

[Treatment by enlargement of septal perforations]. / Traitement par agrandissement des perforations septales.

OBJECTIVE: Assessment of surgical posterior enlargement for septal perforation. MATERIAL: Ten patients included had a symptomatic perforation in area 2 and/or 3 of Cottle. The size of the perforations was superior at 10 mm. METHOD: This is a retrospective study. The surgical procedure has consisted of an initial corection of anterior septal deviation, nasal deviation and supra-lobular depression. Afterwards, perforations were extended towards the back by respecting the choanal arch. Nasal obstruction, headache, epistaxis, crusting and nasal profil were assessed in preoperative and post surgical period at 2 months and at the time of a sent questionnaire. A visual analogue scale for nasal obstruction and headache was used. RESULTS: The patient's mean age was 53.9 years. The mean follow-up period was 16 months. The average hospital stay was 24 hours. In first step, two supra-lobular depresion and one nasal deviation were corected. The mean score of nasal obstruction was 7.6. All patient's were free of this symptom after surgery (10/10) (p < 0.00016). The mean score of headache was 7.8 and only five of the six patients were free of symptom (p < 0.01). Crusting and epistaxis were diseappared in seven of the height patients. The rate of success for the different symptom were 100% for nasal obstruction, 83.3% for headache and 87.5% for crusting and epistaxis. CONCLUSION: The surgical posterior enlargement for septal perforation is an effective procedure, reliable, simple, with very low morbidity.

[Immunohistochemistry expression of 3 markers (CEA, UEA-I and Ki-67) in nasal inverted papillomas]. / Expression immunohistochimique de l'ACE, de l'UEA-I et du Ki-67 dans les papillomes inversés naso-sinusiens.

OBJECTIVES: Immunohistochemistry evaluation of the expression of degeneration and proliferation markers of the benign form of Schneiderian inverted papillomas in the ORL sphere, in the nondysplastic, dysplastic and degenerated forms. Seeking out an expression profile with a prognostic value. MATERIALS AND METHOD: 44 surgical specimens were analyzed in two groups: A= 33 benign and B= 11 degenerated. Group A included: 10 dysplastic lesions, 4 septal lesions and 2 isolated sphenoidal lesions. A simultaneous bipolar localization belonged to the two groups (nasal, benign and otologic malignant). A control group consisted often biopsies of healthy mucous membranes harvested during septoplasties. The carcinoembryonic antigen (CEA), the ulex europaeus agglutinin I (UEA-I) and the monoclonal antibody Ki-67 were revealed by immunoreaction with peroxidase and enhanced by streptavidine-biotine. RESULTS: There was a significant difference in the marking of the CEA between the control group and groups A (p< 0.023) and B (p< 0.045). This expression was fulfilled only in the superficial layers in 84.1% of cases. There was no difference in expression between groups A and B, the dysplastic and non-dysplastic inverted papillomas and between the various degrees of dysplasias. There was no significant statistical difference in expression of UEA-I between all the groups and the sub-groups. The expression of Ki-67 was significantly increased in groups A (p< 0.00023) and B (p< 0.05) when compared to the control group. But, no difference existed between groups A and B, the various sub-groups and the benign specific localizations. This expression was present in the basal cells. An expression encompassing all the thickness of the epithelium was generally associated with a degenerated or dysplastic lesion, without being systematic. CONCLUSION: It was not possible using this specimen and for these three glycoproteins to extricate immunohistochemistry profiles of expression associated to the studied clinical and histological forms. However the expression of Ki-67 in more than 50% of the cells involving the full epithelium thickness would seem to suggest a particular cellular behavior Whereas the expression of the protein remains generally confined to the basal and suprabasal layers, a more significant population of Ki-67+ cells disseminated in the epithelium, would signify a tendency of the epithelium to escape the regulation mechanisms. This cellular behavior could constitute a prognostic histological marker but it would require a broader study to be confirmed.

Is ethmoidal adenocarcinoma screening in employees exposed to wood dust justified?

INTRODUCTION: Since 1995, the means which are used for the follow-up of wood-workers in France are obsolete. Based on experts' opinions, they have never been assessed as effective in the detection of adenocarcinoma of the ethmoid sinus. OBJECTIVE: Collecting the data present in the literature to justify the necessity and the means of a screening protocol that would help detect ethmoidal adenocarcinoma among the wood worker population. METHOD: This is a review of the literature from three data bases: the National Library of Medicine, the French National Institute for Research and Security and the French National Centre for Scientific Research. Only English and French articles were reviewed and they were classified in four categories according to proof tools purposed by the French High Authority for Health. RESULTS: There is a direct statistical relationship between the amount of wood dust and the development of ethmoidal adenocarcinoma, but threshold doses cannot actually be calculated. The relative risk is high starting the first year of exposure and the exposed population is well recognized. Despite the means presently available for follow-up, this lesion is always diagnosed at an advanced stage. Survival rates at 5-years would increase if the tumour were to be detected at stages T1 or T2. The CT scan is not suited for this aim because of its low sensibility in separating soft tissue contrast. On the other hand, the MRI allows the detection of small nasal or sino-nasal tumours with intact osseous boundaries with a 98% sensibility. However, the data from experimental models and healthy human volunteers show that wood-dust settles over the olfactory cleft and the adjacent mucosa. Moreover in the large majority of cases the implantation pedicle of these tumours is coming from within these areas. Therefore, nasal fibroscopic examination represents the best tool to detect adenocarcinoma of the ethmoid sinuses at its earlier stages. It is well tolerated and its cost is low. CONCLUSION: A screening of ethmoidal adenocarcinoma seems to be possible with simple means in specific population. An early detection could improve the prognosis of this lesion.

Mechanical stretch implications for vascular endothelial cells: Altered extracellular matrix synthesis and remodeling in pathological conditions.

AIMS: Cardiovascular diseases such as hypertension, thrombosis and atherosclerosis are responses to mechanical forces applied to the endothelium. Endothelial cells respond to hemodynamic mechanical forces such as cellular mechanical stretching. We investigated the expression of glycosaminoglycans, proteoglycans and other extracellular matrix molecules in endothelial cells subjected to various mechanical stimuli. MAIN METHODS: Endothelial cells were subjected to mechanical stretch in a vacuum system FlexCell™ to 5% (physiological condition) and 15% (pathological condition), for 4 h or 24 h. Culture plates not subjected to strain were used as controls. Subsequently, ECs were subjected to immunofluorescence, real-time PCR, PCR array, glycosaminoglycans biosynthesis using metabolic radiolabeling with 35S-sulfate and cell behavior assays (adhesion, migration and capillary tube formation). KEY FINDINGS: Mechanical stretch induced changes in endothelial cell morphology. Pathological consequences of mechanical stretch included inhibited migration in 2-fold and capillary-like tube formation in 2-fold, when compared to physiological condition after 4 h of ECs exposure; it also reduced total sulfated glycosaminoglycans synthesis thereabout 1.5-fold. Pathological mechanical stretch conditions induced higher expression after 24 h of ECs exposure to mechanical stretch of syndecan-4 (3.5-fold), perlecan (9.1-fold), decorin (5.7-fold), adhesive proteins as fibronectin (5.6-fold) and collagen III α1 (2.2-fold) and growth factors, including VEGF-A (7.3-fold) and TGFß-1 (14.6-fold) and TGFß-3 (4.3-fold). SIGNIFICANCE: Exposure of endothelial cells to mechanical stretch influenced remodeling of the extracellular matrix as well as cell-matrix interactions. These studies improve understanding of how vascular biology is affected by mechanical forces and how these molecules behave in cardiovascular diseases.

A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors.

BACKGROUND: The role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. The aim of this study was to characterize pharyngeal and esophageal pH-impedance reflux patterns in a group of patients with suspected laryngopharyngeal reflux and to determine predictive factors of response to proton pump inhibitors. METHODS: Patients with chronic pharyngolaryngeal symptoms were evaluated with a symptom score questionnaire, laryngoscopy, and 24-hour pharyngeal and esophageal pH-impedance monitoring at baseline and after 8-week treatment with esomeprazole 40 mg b.i.d. Response to treatment was defined by a diminution of more than 50% of the score for the primary symptom. Reflux patterns and baseline impedance values were compared to those obtained in 46 healthy subjects. KEY RESULTS: Twenty-four patients were included (17 women, median age 54 years), all previously refractory to antisecretory therapy. Symptom scores were 46 (32-62) and 40 (27-76) off and on therapy, respectively (P=.1). There was no significant difference between patients and controls for pH-impedance reflux parameters and baseline values off and on therapy in distal and proximal esophagus and in the pharynx. Median numbers of pharyngeal reflux were 0 and 0 off and on therapy, respectively. Only two patients were responders to treatment, both with excessive distal reflux but no pharyngeal reflux. Only one patient had abnormal pharyngeal reflux but did not respond to proton pump inhibitors. CONCLUSIONS: Patients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH-impedance reflux. In these patients, laryngopharyngeal reflux is unlikely.

[Rhinoplasty: advantages and indications of the external approach]. / Rhinoplastie : intérêts et indications de la voie externe.

Described for the first time in the 1930s by Rethi, the external approach would not have survived without its obvious advantages. It is practiced exclusively by certain authors giving the belief of better, more reliable or more durable results. This is in contrast to those who use this technique only for particular indications. This controversy emphases the need of evaluating the theoretical advantages and disadvantages of this approach relying on research. Indeed, it is clear to everybody that whatever the approach, the results initially depend more on the clinical analysis then on the qualification of the surgeon. So, if this controversy has no reason to be, moderate indications are probably useful to be set for the guidance of young rhinoplasticians.