Highlights and conclusions from the technical consultative meeting on novel coronavirus infection, Cairo, Egypt, 14-16 January 2013.

The emergence of a novel strain of coronavirus in the Arabian Peninsula raised a global health concern in 2012, partly because the majority of human infections were fatal and partly due to its presumed animal origin. An urgent meeting of scientific and public health experts was convened by WHO in January 2013 in view of the limited knowledge available on the epidemiological and natural history of infection with this novel virus. The meeting reviewed current evidence and identified critical knowledge gaps to improve better understanding of the public health risk associated with the virus so as to improve preparedness and to safeguard and protect global health.

Challenges of global surveillance during an influenza pandemic.

Surveillance is an essential foundation for monitoring and evaluating any disease process, and is especially critical when new disease agents appear. The H1N1 influenza pandemic of 2009 tested the capacities of countries to detect, assess, notify and report events as required by the 2005 International Health Regulations (IHR). As detailed in the IHR, the World Health Organization drew on official reports from Member States as well as unofficial sources (e.g., media alerts) to quickly report and disseminate information about the appearance of the novel influenza virus. The pre-existing Global Influenza Surveillance Network for virological surveillance also provided crucial information for rapid development of a vaccine and for detection of changes in the virus. However, the pandemic also highlighted a number of shortcomings in global epidemiological surveillance for respiratory disease. These included the lack of standards for reporting illness, risk factor and mortality data, and a mechanism for systematic reporting of epidemiological data. Such measures would have facilitated direct comparison of data between countries and improved timely understanding of the characteristics and impact of the pandemic. This paper describes the surveillance strategies in place before the pandemic and the methods that were used at global level to monitor the pandemic. Enhancements of global surveillance are proposed to improve preparedness and response for similar events in the future.

[Influenza vaccine: globalization of public health stakes]. / Vaccin grippal: mondialisation des enjeux de Santé Publique.

On June 11, 2009, Dr. Margaret Chan, Director-General of the World Health Organization (WHO), declared the first influenza pandemic of the 21st century. It was the first time in history that an influenza outbreak had been tracked in real-time from the emergence of a new strain of influenza A (H1N1) up to its spread to all continents over a period of 9 weeks. In recent years the international community has been working closely to prepare for such situations. A notable example of this cooperation occurred in response to the threat posed by the highly pathogenic avian influenza A virus (H5N1). Vaccine availability is a major challenge that will require increasing worldwide production and ensuring a widespread access. In this regard it is important to underline the fact that 70% of influenza vaccine is produced in Europe and the United States. In 2006 WHO implemented a global pandemic influenza action plan (GAP) aiming at increasing the world's production capacity for pandemic vaccine. The GAP contains three elements: (1) increased use of seasonal influenza vaccination in industrialized and developing countries (resolution WHA 56.19). (2) technology transfer. (3) development of new production technologies. Nevertheless numerous barriers still prevent people living in developing countries from rapid and fair access to pandemic influenza vaccine. Capacity for production of pandemic vaccine is limited and advanced purchase agreements between industrialized countries and vaccine manufacturers reduce potential access of developing countries to pandemic vaccine. Economic and logistic factors also limit global access to pandemic vaccine. Therefore, WHO is working with industrialized countries, pharmaceutical companies and the international community as a whole to promote global solidarity and cooperation and thus ensure distribution of pandemic vaccine in poor countries with no local production. The current pandemic situation highlights the increasing globalization of public health stakes with regard to influenza vaccination. The purpose of this presentation is to review the various challenges for production and distribution of vaccines and underline the progress that has been accomplished since 2005.

Postoperative infections after limb-sparing surgery for primary bone tumors of the pelvis: Incidence, characterization and functional impact.

INTRODUCTION: Surgical site infections (SSI) represent the most common postoperative complication after limb sparing surgery for primary malignant bone tumors, with incidence ranging from 10 to 47%. There is no consensus concerning about the optimal surgical strategy, or the adequate antibiotic prophylaxis in pelvic resections. A greater knowledge of these infections and their surgical trajectories seem essential to obtain. MATERIALS AND METHODS: We retrospectively studied 45 cases of pelvic resection, including at least the periacetabular zone 2 of Enneking, performed between 1989 and 2013 in the same center. Infection rate, risk factors and surgical trajectories were analyzed. The impact of a postoperative infection on the quality of life and functional recovery was evaluated by the Musculoskeletal Tumor Society scoring system (MSTS). RESULTS: Sixteen patients presented a SSI in the first post-operative year (35.6%). We found as risk factors the pre-operative ASA score, the age at surgery and the number of packed red cells transfused during surgery. In case of failure of an initial washout, an iterative procedure is responsible for a high failure rate of 88.9%. Irrespective of the type of reconstruction, our functional results show that this surgery is often a source of handicap with a MSTS score of 13.77 in infected patients versus 17.70 in non-infected patients, at two-year follow-up. DISCUSSION: In case of failure of an initial wash, prosthetic material must be removed and a hip transposition procedure should be preferred to a second-look surgery. Concerning prophylactic antibiotherapy, a dual therapy for at least 48 h after surgery should probably be preferred.

Giant cell tumor of tendon sheath: Open surgery or arthroscopic synovectomy? A systematic review of the literature.

PURPOSE: Giant cell tumor of tendon sheath (GCTTS), formerly known as pigmented villonodular synovitis (PVNS), is a benign, locally aggressive, proliferative disorder of the synovium involving a joint, bursa, or tendon sheath. Treatment of GCTTS involves early surgical resection to limit articular destruction and the risk of recurrence. Synovectomy remains the treatment of choice for GCTTS, but without clear consensus to make an open or arthroscopic synovectomy and no certainty on the responsibility of surgery in the evolution towards the degenerative osteoarthritis. The aim of this study was to evaluate the long-term clinical outcomes and the rate of recurrence of open or arthroscopic excision of GCTTS of the four most frequently involved joints: the shoulder, hip, knee and ankle. METHODS: We performed a systematic review of literature in September 2015. The keywords were "villonodular synovitis" AND "surgical treatment". The two authors analyzed 413 articles, according to title and abstract. Forty articles were selected, read entirely and references were analyzed. RESULTS: Thirty-three articles were selected. CONCLUSION: Our review of literature showed that arthroscopic excision is effective for localized type of GCTTS for all four joints. In diffuse type GCTTS, the efficacy of arthroscopic synovectomy has only been shown for the knee joint. In the other joints, early diagnosis can improve clinical outcomes, but we cannot certify that surgical treatment avoids osteoarthritis degradation. STUDY DESIGN: Review of literature, level of evidence IV.

[Nephrolithiasis of adult: From mechanisms to preventive medical treatment]. / Lithiase rénale de l'adulte : des mécanismes au traitement médical préventif.

Nephrolithiasis is a very common (prevalence around 10 to 12% in France) and recurrent disorder. Nephrolithiasis is associated to chronic kidney disease and is responsible for 2 to 3% of cases of end-stage renal disease, mainly if it is associated to nephrocalcinosis or to a monogenic disorder (1.6% of nephrolithiasis in adults, among them 1% of cystinuria). To understand the underlying pathophysiological processes, stone analysis (morphology and using infrared spectrophotometry) as well as minimal biological assessment including urine crystal research are required. The calcic nephrolithiasis is the more frequent subtype (>80%). Its medical treatment relies on simple dietary rules: non-alkaline hyperdiuresis>2 liters/day, calcium intake normalization (1 gram per day divided between the three principal meals), normalization of sodium (6 to 7 grams per day) and protein intake (1g/kg of theoretical body weight/day), and eviction of foods rich in oxalate. In case of persistent hypercalciuria (>0.1mmol/kg of theoretical body weight/day on free diet), a thiazide diuretic can be started while being aware to correct iatrogenic decrease in plasma potassium and urine citrate excretion. Measurement of bone mineral density must systematically be performed in patients with high 24 h-urinary calcium excretion. The medical treatment of uric acid nephrolithiasis relies on alkaline hyperdiuresis (goal of urine pH: 6.2 to 6.8). The use of allopurinol is justified only if urine uric acid is over 4mmol/day. Thanks to a well-managed preventive medical treatment, one can expect to stop the activity of nephrolithiasis in more than 80% of cases, making it one of the most accessible renal pathologies to preventive medical treatment.

Toll-like receptors 2, 4 and 9 expression in cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome).

The aim of this work was to study Toll-like receptors (TLRs) 2, 4 and 9 expression patterns in parapsoriasis and in cutaneous T-cell lymphoma (CTCL): Mycosis fungoides (MF) and Sézary syndrome (SS) at different stages of the illness. The expression of TLRs was examined by immunohistochemistry on paraffin-embedded biopsies. Normal skin, atopic dermatitis and psoriasis, were used as controls. In cutaneous lesions of inflammatory diseases (atopic dermatitis, psoriasis) the expression of TLR2, TLR4 and TLR9 was low compared to normal skin. In parapsoriasis the expression of the three TLRs was similar to control. By contrast, in MF skin we observed a strong intensity of labelling with the three TLRs in the epidermis. Concerning SS, the expression of TLR2, TLR4 and TLR9 was intermediate between inflammatory lesions and MF. Thus, the development of skin lesions in MF appears associated with an increase of TLR2, TLR4 and TLR9 expression by keratinocytes in cutaneous lesions, which could play a role in the chronic activation of T lymphocytes in the skin.

ACL reconstruction in 11 children using the Clocheville surgical technique: Objective and subjective evaluation.

INTRODUCTION: The over-the-top position of the femoral metaphyseal tunnel during extraphyseal ligament reconstruction of the anterior cruciate ligament (ACL) according to Clocheville may be responsible for negative anisometry. Until now, the follow-up of children operated using this pediatric technique was limited to screening for iatrogenic epiphysiodesis and the search for postoperative clinical instability. The objective of this study was to measure residual laxity using objective tests, to quantify muscle recovery, and to evaluate the quality of life of these patients in terms of the sports activities. MATERIAL AND METHODS: Eleven patients with a mean age of 13.5years were seen at a mean 2.1years of follow-up. They underwent objective clinical tests (GNRB(®) arthrometer and CON-TREX(®) dynamometer) as well as subjective questionnaires (IKDC and KOOS). RESULTS: No significant difference was found between the healthy knee and the operated knee for either the GNRB(®) at 134N (P=0.79) or at 200N (P=0.98). The CON-TREX(®) system allowed us to measure a median percentage of quadriceps recovery of 80.7% (range, 52.2-114.5) in terms of muscle power (60°/s) and 81.2% (range, 51.6-109.6) for muscle response (180°/s). The median subjective IKDC score was 94.73/100 (range, 73.68-98.93); 72.7% of the patients resumed competitive sports. DISCUSSION: This study's lack of statistical power did not show a significant difference in terms of residual laxity at rest of GNRB(®) transplants, while a mean differential of +0.4mm was observed. Although pediatric transphyseal ligament reconstruction techniques are increasingly used, the Clocheville technique remains, in our opinion, an attractive surgical alternative in the youngest subjects, with no major risk of iatrogenic epiphysiodesis even though it is theoretically anisometric. LEVEL OF EVIDENCE: IV.

[Perceptions of quality in health sectors and impact on quality assurance]. / Perceptions de la qualité dans le secteur sanitaire et impact sur la démarche qualité.

According to the ordinances dated April, 24.1996, clinics and hospitals should launch an internal accreditation process. There are many organizations which are about to develop a quality improvement process in order to be prepared to such an evaluation. The success of such approach lies on the involvement of the members of the organization concerned. This survey intends to sort out the actors' perceptions of quality, in order to adapt the process development to the internal cultural context. The data collection was realized through thirty pre-oriented interviews with physicians, nurses, administrative managers and private consultants in charge of implementing the quality process in health structures. The recorded interviews were later on analyzed in order to determine meaningful categories of perceptions of quality. The analysis reveals that quality is perceived in different ways. Three categories of perception can be found: Quality related to "a mean to change the organization" Quality as a "tool to control and limit the expenses" Quality as a way "to improve the relationship with the patients". Administrative managers rather consider the quality process as an expense control tool, whereas physicians and consultants perceive it as a mean to change the organization. Nurses rather adopt the quality process as a way to improve the relationship with the patient. The understanding of how the quality concept is perceived by the different personnel categories helps to initiate appropriately the improvement quality process in services.

[Evaluation of epidemiologic surveillance systems: analysis of different approaches in a study in Ecuador]. / Evaluation des systèmes de surveillance épidémiologique: analyse de différentes approches à partir d'une étude en Equateur.

Based on the experience of the assessment of public health surveillance systems, this paper explores the relationship between knowledge and action. Like research, evaluation is a cognitive process however oriented to a specific aim. Thus it is possible to compare the various approaches of evaluating these systems using the frame of paradigms in sciences (positivism, post positivism, critical theory and constructivism). In addition, evaluation aims to improve the functioning of the system, to introduce changes in it. The fourth generation evaluation, as it has been done in Ecuador, is an interesting way of acquiring understanding of the system while solving its malfunctionings. In this experience, the evaluator seeks the participation of the actors of the system at each steps of the evaluation process. He searches to involved them through three levels: intellectual, affective and ontological.

[Mothers' perceptions about their children's acute diarrhea in the Quito suburbs]. / Représentations de la diarrhée aiguë de l'enfant chez les mères d'une banlieue de Quito.

This study was performed in an urban marginal neighborhood of Quito (Ecuador). It aims to understand how the mothers with children (less than five years old) suffering from diarrhea are using the health center. We did 48 semi-directed interviews with mothers coming to the health center. The results show the various representations of diarrhea (symptomatic patterns and explanatory models: e.g. diarrhea due to supernatural cause, diarrhea related to heat and cold balance...) and the related processes of therapeutic search; For example, when the mother thinks that the diarrhea is due to a supernatural cause, she immediately goes to the traditional practitioner. The existing cultural gap between health practitioners of the center and the population of this neighborhood incite to consider differently the content of health education messages.

Pathogenetic mechanisms of vitiligo in a patient with Sézary syndrome.

Patients exhibiting association between vitiligo and cutaneous T-cell lymphoma (CTCL) remain rare and it is not known whether some T-cell subpopulations of CTCL in the skin are able to recognize specific melanocytic epitopes and thus induce vitiligo. The aim of our study was to determine whether T cells specific to melanocyte differentiation antigens were detectable among tumour-infiltrating lymphocytes (TIL) in the hypopigmented skin of a patient with Sézary syndrome (SS). A 71-year-old patient presented with SS and developed vitiligo during the course of her disease. Immunohistochemical studies showed staining with HMB45 and MelanA antibodies in the pigmented skin biopsy, whereas no staining was observed in the hypopigmented skin biopsy. To analyse responses to melanocyte differentiation antigens, we used a transient COS transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/antigen combinations. This technique allowed the detection of melanocyte differentiation antigen-specific T lymphocytes, directed mainly against Melan-A/MART1 antigen in the HLA-A*23 context. Our study supports the concept that vitiligo that has developed during the evolution of a CTCL is related to the presence of a T-lymphocyte subpopulation reactive against melanocyte differentiation antigens (mainly Melan-A/MART1) present in skin lesions. The role of interferon in the induction of this T-lymphocyte subpopulation is discussed.

Calcium-calmodulin plays a major role in bradykinin-induced arachidonic acid release by bovine aortic endothelial cells.

We provided evidence that calcium-calmodulin plays a major role in bradykinin-induced arachidonic acid release by bovine aortic endothelial cells. In cells labeled for 16 hr with 3H-arachidonic acid, ionomycin and Ca2(+)-mobilizing hormones such as bradykinin, thrombin and platelet activating factor induced arachidonic acid release. However, arachidonic acid release was not induced by agents known to increase cyclic AMP (forskolin, isoproterenol) or cyclic GMP (sodium nitroprusside). Bradykinin induced the release of arachidonic acid in a dose-dependent manner (EC50 = 1.6 +/- 0.7 nM). This increase was rapid, reaching a maximal value of fourfold above basal level in 15 min. In a Ca2(+)-free medium, bradykinin was still able to release arachidonic acid but with a lower efficiency. Quinacrine (300 microM), a blocker of PLA2, completely inhibited bradykinin-induced arachidonic acid release. The B2 bradykinin receptor antagonist HOE-140 completely inhibited bradykinin-induced arachidonic acid release. The B1-selective agonist DesArg9-bradykinin was inactive and the B1-selective antagonist [Leu8] DesArg9-bradykinin had no significant effect on bradykinin-induced arachidonic acid release. The phospholipase C inhibitor U-73122 (100 microM) decreased bradykinin-induced arachidonic acid release. The calmodulin inhibitor W-7 (50 microM) drastically reduced the bradykinin- and ionomycin-induced arachidonic acid release. Also, forskolin decreased bradykinin-induced arachidonic acid release. These results suggest that the activation of PLA2 by bradykinin in BAEC is a direct consequence of phospholipase C activation. Ca2(+)-calmodulin appears to be the prominent activator of PLA2 in this system.

Agonist-dependent AT(4) receptor internalization in bovine aortic endothelial cells.

Recent studies have characterized a specific binding site for the C-terminal 3-8 fragment of angiotensin II (Ang IV). In the present study we looked at the internalization process of this receptor on bovine aortic endothelial cells (BAEC). Under normal culture conditions, BAEC efficiently internalized (125)I-Ang IV as assessed by acid-resistant binding. Internalization of (125)I-Ang IV was considerably decreased after pretreatment of cells with hyperosmolar sucrose or after pretreatment of BAEC with inhibitors of endosomal acidification such as monensin or NH(4)Cl. About 50% of internalized (125)I-Ang IV recycled back to the extracellular medium during a 2 h incubation at 37 degrees C. (125)I-Ang IV remained mostly intact during the whole process of internalization and recycling as assessed by thin layer chromatography. As expected, internalization of (125)I-Ang IV was completely abolished by divalinal-Ang IV, a known AT(4) receptor antagonist. Interestingly, (125)I-divalinal-Ang IV did not internalize into BAEC. These results suggest that AT(4) receptor undergoes an agonist-dependent internalization and recycling process commonly observed upon activation of functional receptors.

Study on the functionality and molecular properties of the AT4 receptor.

Whereas the role of angiotensin II (Ang II) has been clarified in numerous tissues and cell types, the physiological relevance of its C-terminal (3-8) degradation fragment, angiotensin IV (Ang IV), is unclear. Previously, we characterized a specific binding site for Ang IV in the bovine adrenal cortex and on bovine aortic endothelial cells (BAEC). In the present study, we tried to assess the functionality and mechanism of action of this receptor for Ang IV (AT4 receptor). Our results revealed that none of the classical second messengers (i.e., cAMP, Ca2+, inositol phosphates, nitric oxide or arachidonic acid derivatives) was modified significantly during acute (less than 1 h) stimulation of cells with Ang IV. Under normal culture conditions, BAEC efficiently internalized 125I-Ang IV. After a 2 h incubation at 37 degrees C, acid-resistant binding corresponded to about 50% of total cell-associated radioactivity. This rapid internalization process suggests that the AT4 receptor is a functional protein. With a photoaffinity labeling approach, we revealed some properties of the AT4 receptor that are consistent with those of a growth factor or cytokine receptor.