Dermatological adverse effects of anti-glaucoma eye drops: a review.

Many patients are treated for glaucoma. Like other drugs, anti-glaucoma eye drops may induce dermatological adverse effects. We aim to review the dermatological adverse effects secondary to the active agents in anti-glaucoma eye drops through a literature review. In January 2020, we queried PubMed using the following MeSH terms: glaucoma/drug therapy or glaucoma, open angle/drug therapy cross-referenced with parasympathomimetics/adverse effects or adrenergic agonists/adverse effects or carbonic anhydrase inhibitors/adverse effects or prostaglandins F, synthetic/adverse effects or adrenergic beta antagonists/adverse effects or ophthalmic solutions/adverse effects. The initial search identified 1128 studies, of which 49 were excluded for being in a foreign language, 15 for not involving eye drops, 968 for not focusing on adverse dermatological effects, and 11 for insufficient documentation or redundancy. After adding 38 linked studies, we finally analyzed 123 studies. The ocular and periocular dermatological adverse effects of eye drops are contact dermatitis, hyperpigmentation, prostaglandin analog periorbitopathy, mucous membrane pemphigoid, eyelash depigmentation, skin hypertrichosis, and rare cases of melanoma and skin depigmentation. The reported distant dermatological adverse effects are psoriasis, excessive sweating, lichen planus, alopecia, toxic epidermal necrolysis, erythema multiforme, erythroderma, subacute cutaneous lupus erythematosus, nail pigmentation, and bullous pemphigoid. Most of the cutaneous adverse effects of anti-glaucoma eye drops are ocular and periocular and induced by prostaglandin analogs. Distant adverse effects are rare and sometimes questionable but should be kept in mind, especially mucous membrane pemphigoid, which could lead to blindness. The role of preservatives, such as benzalkonium chloride, should also be considered.

[How I explore a non-traumatic gonalgia]. / Comment j'explore une gonalgie non traumatique.

Because the knee is the joint of the human body with the largest surface, it is no wonder that gonalgia is one of the most common complaints in the general population. Although the management of a painful traumatic knee is relatively well standardized, that of a non-traumatic knee pain is less codified. History and a rigorous systematic clinical examination play a key role in the management of nontraumatic gonalgia. The diagnostic approach is mainly guided by the inflammatory or mechanical nature of the pain and its topography. This article aims to clarify the diagnostic approach to gonalgia without notion of prior trauma.

Le genou étant la plus grosse articulation du corps humain en termes de surface, il n'est pas étonnant que la gonalgie compte parmi les plaintes les plus fréquentes de la population générale. Bien que la prise en charge d'un genou douloureux traumatique soit relativement bien standardisée, celle d'une gonalgie non traumatique est moins codifiée. L'anamnèse systématique et un examen clinique rigoureux jouent un rôle clé dans la prise en charge de la gonalgie non traumatique. L'orientation diagnostique est principalement guidée par le caractère inflammatoire ou mécanique de la douleur et sa topographie. Cet article vise à éclaircir la démarche diagnostique face à des gonalgies sans notion de traumatisme.

[Knee pain in a child : watch out for the hip !] / Gonalgie chez l'enfant : vérifier la hanche !

This is a case report of a 13-year old patient presenting with knee pain after a bike accident. Multiple investigations and medical examinations focused on the knee. They did not show any abnormality. About one year later, the patient comes back with increased hip pain, limited internal rotation and shortening of the left limb. Hip X-Ray exams reveal a bilateral slipped capital femoral epiphysis requiring already an osteotomy. Slipped capital femoral epiphysis is a disorder of the proximal femoral epiphysis. The femoral neck is displaced anteriorly and rotates externally while the epiphysis remains in the acetabulum. This pathology is more common in preadolescent boys and can be associated with hormonal disorders. Patients present with an externally rotated gait, a limited internal rotation, associated hip and knee pain. Diagnosis might be missed when patients present with knee pain and can lead to delayed treatment. When facing knee pain, it is essential to perform a clinical examination of the hip. Radiography is the first medical imaging. Surgical treatment by in situ fixation is recommended and prevents further slip with a high rate of success. When delayed, a much more invasive approach is required. A delay in diagnosis adversely affects long-term outcomes.

Il s'agit d'un patient de 13 ans présentant des gonalgies comme principale plainte. Vu l'apparition des douleurs suite à une chute, les investigations se sont focalisées sur le genou. De multiples examens complémentaires ont été réalisés sans mise en évidence de lésion. Après un an d'évolution, le patient se présente en consultation d'orthopédie en chaise roulante avec une impotence fonctionnelle majeure et des douleurs importantes au niveau des membres inférieurs. On note une boiterie, une inégalité des membres inférieurs et une raideur des hanches. Une radiographie du bassin démontre une épiphysiolyse fémorale supérieure bilatérale. Il s'agit d'un glissement de l'épiphyse par rapport au col fémoral, retrouvé plus fréquemment chez le garçon entre 10 et 15 ans. Le tableau clinique peut être caractérisé par des gonalgies, entrainant des retards diagnostiques. En cas de diagnostic précoce, un vissage in situ, peu invasif, empêche la progression de la déformation. Si le diagnostic est retardé, un traitement plus lourd et plus invasif comportant plus de risques et de moins bons résultats à long terme doit être pratiqué. En cas de mauvaise évolution, une arthroplastie précoce doit être réalisée. Une prise en charge rapide permet d'éviter cette escalade thérapeutique.

[Arthroscopy of the hip : management of femoro-acetabular conflicts before the osteoarthritic stage]. / Actualités en arthroscopie de la hanche : prise en charge des conflits fémoro-acétabulaires avant le stade arthrosique.

Hip arthroscopy is a technique that has been shown to be effective in the treatment of femoro-acetabular lesions. These are related either to an anomaly on the anterior aspect of the femoral neck ("cam effect") or an anomaly at the level of the acetabular margin ("pincer effect") or a combination of both. The main arthroscopic gesture for the cam conflict consists of a femoroplasty, i.e. a regularization of the anterior bone bump. Other gestures, such as reinsertion of the labrum and cartilage repair, can be contemplated during the same operation. In a pincer conflict, an acetabuloplasty associated with re-insertion of the labrum can be performed. Hip arthroscopy is a technique in progress in terms of the surgical technique as well as the number of skilled surgeons. It aims to slow down the osteoarthritic evolution of the hip joint in the context of femoro-acetabular conflicts. However, it remains a tech¬nique with a long learning curve and possible side effects or complications are not to be neglected.

L'arthroscopie de hanche est une technique qui s'est révélée efficace pour le traitement de certains conflits fémoro-acétabulaires. Ces derniers sont liés soit à une anomalie du col fémoral sur son versant antérieur («effet came¼), soit à une anomalie du bord du cotyle («effet tenaille¼), soit l'association des deux. Le geste arthrosco¬pique principal consiste en une fémoroplastie lors du conflit de type came, c'est-à-dire une régularisation du «bump osseux¼; d'autres gestes, tels que la réinsertion du labrum et une réparation cartilagineuse peuvent être réalisés au cours du même geste opératoire. Lors d'un conflit de type tenaille, une acétabuloplastie associée à une réinsertion du labrum peut être réalisée. L'arthroscopie de hanche est une technique en progression, tant au niveau des gestes qui peuvent être réalisés ainsi qu'au niveau du nombre d'opérateurs. Elle cherche à ralentir l'évolution arthrosique de l'articulation de la hanche dans le cadre des conflits fémoro-acétabulaires. Elle reste, cependant, une technique grevée d'une courbe d'apprentissage longue et d'effets secondaires ou de complications non négligeables.

[Osteosynthesis for proximal humeral fractures : plate or nail ? Results of a retrospective monocentric study]. / Ostéosynthèse des fractures de l'humérus proximal : plaque ou clou? Résultats d'une étude rétrospective monocentrique.

Locking intramedullary nails and locking plates are widely used. There is a lack of consensus about optimal surgical treatment. We compare these techniques. This retrospective study included 97 patients : 51 with nail, 46 with plate. Absolute and relative Constant-Murley scores and Simple Shoulder Test (SST) were used to assess postoperative function. Time of fracture union and complications were recorded. Two fragment fractures were preferentially treated by nails and 4 fragment fractures by plates. There is no difference for union except advantage for nails in 2 fragment fractures. The functional outcome is similar, relative Constant-Murley score is 72,7 ± 0,3 %, SST 6,7 ± 3,9 after nailing and relative Constant-Murley score is 65,4 ± 0,3 %, SST 6,0 ± 3,6 after plating. Number of complications is similar after plating (67,4 %) and nailing (62,7 %). We propose to promote nailing for 2 fragment fractures and treatment with plates for 4 fragment fractures. Three fragment fractures can be treated by both techniques.

L'ostéosynthèse par enclouage et par plaque sont répandus dans le traitement des fractures de l'humérus proximal. Il n'y a pas de consensus concernant le traitement chirurgical optimal. Nous avons comparé ces deux techniques. Cette étude rétrospective comprend 97 patients : 51 enclouages, 46 traitements par plaque. Les scores de Constant-Murley absolu et relatif et le Simple Shoulder Test (SST) ont été utilisés pour évaluer la fonction. Le temps de consolidation et les complications ont été évalués. Les fractures 2 fragments ont été préférentiellement enclouées et les 4 fragments traitées par plaque. Il n'y a pas de différence si ce n'est un temps de consolidation plus court après enclouage pour les fractures 2 fragments. Le résultat fonctionnel est similaire, le score de Constant-Murley relatif est de 72,7 ± 0,3 % et le SST de 6,7 ± 3,9 après enclouage. Le score de Constant-Murley relatif est de 65,4 ± 0,3 % et le SST 6,0 ± 3,6 après ostéosynthèse par plaque. Le nombre de complications est équivalent entre le traitement par plaque (67,4 %) et par clou (62,7 %). Nous proposons de favoriser l'ostéosynthèse par enclouage pour les fractures 2 fragments et par plaque pour les fractures 4 fragments. Les fractures 3 fragments peuvent être traitées selon le choix du chirurgien.

[Thinking differently about health care after COVID-19]. / Repenser les soins de santé post-COVID-19.

The health crisis linked to the coronavirus pandemic (COVID-19) has forced society and hospitals in particular to adapt and reform. Teamwork between hospitals, even beyond the networks, helped them to deal with the crisis. The medical and nursing staff had to learn to work differently and differentiate urgent from non-urgent care. But the patient also had to change his/her behaviour. Access to hospitals has been divided between a separate COVID and non-COVID route in order to avoid contamination. Telemedicine has become a daily way of communicating between doctors and patients. Telephone consultations have been set up with reimbursement by social security. However, these actions and innovations should not end with the crisis but, on the contrary, be a lever to rethink the role of hospitals, and our health care system more generally.

La crise sanitaire liée à la pandémie du coronavirus (COVID-19) a obligé la société, et les hôpitaux en particulier, à s'adapter et se réformer. Le travail en équipe entre hôpitaux, même au-delà des réseaux, a permis de faire face à la crise. Le corps médical et infirmier a dû apprendre à travailler différemment et faire la distinction entre les soins urgents et non urgents. Mais le patient aussi a dû changer ses comportements. L'accès aux hôpitaux s'est vu diviser entre un trajet COVID et non-COVID, bien distincts, afin d'éviter des contaminations. La télémédecine est devenue un moyen quotidien de communiquer entre le monde médical et les patients. Des consultations téléphoniques ont été instaurées avec, à la clef, un remboursement par l'INAMI. Cependant, ces actions et innovations ne devraient pas se terminer avec la crise liée à la COVID-19, mais, au contraire, être un levier pour repenser le rôle des hôpitaux, et notre système de soins de santé plus globalement.

[The COVID-19 breaker : PCR to the rescue !] / La déferlante COVID-19 : la PCR à la rescousse ! Chronique d'une gestion de crise au Laboratoire de Microbiologie clinique du CHU de Liège.

Chronicle of a crisis management at the Clinical Microbiology Laboratory of CHU Liège The SARS-CoV-2 outbreak in December 2019 in China and its expansion across the world and Europe have requested the participation of clinical laboratories as major players in the diagnosis of COVID-19, to perform PCR tests mainly on nasopharyngeal swabs. In Belgium, the first confirmed COVID-19 patient was diagnosed in early February, the first of many, especially travelers returning from winter sports. In order to meet the ever-increasing demands for testing, the Clinical Microbiology Laboratory of the CHU of Liege had to adapt to this situation: firstly, by developing manual PCR tests and then automated solutions, permitting to increase the number of analyzes by ensuring a short turnaround time of results. Then, a system for the communication of results on a large scale has been set up, and finally solutions to deal with the lack of sampling devices have been found. This first wave of the pandemic has also highlighted an unprecedented solidarity within the institution. In this article, we recount the chronology of the management of this unprecedented health crisis within the Clinical Microbiology Laboratory of the CHU of Liege.

L'émergence du virus SARS-CoV-2 en décembre 2019 en Chine et son expansion à travers le monde et l'Europe ont sollicité la participation des laboratoires de Biologie clinique en tant qu'acteurs majeurs dans le diagnostic de la COVID-19, via la réalisation de tests PCR principalement sur des prélèvements nasopharyngés. En Belgique, le premier patient confirmé COVID-19 a été diagnostiqué début février, avant d'être suivi par de nombreux cas d'infections, initialement chez des vacanciers revenant des sports d'hiver. Afin de répondre à l'augmentation du nombre de tests, le laboratoire de Microbiologie clinique du CHU de Liège a dû s'adapter en développant des tests PCR, d'abord manuels puis automatisés. Ceux-ci ont permis d'augmenter le nombre d'analyses, tout en garantissant un temps de rendu des résultats court, en mettant en place un système de communication des résultats à grande échelle et en trouvant des solutions pour faire face à la pénurie des dispositifs de prélèvement. Cette première vague de la pandémie a aussi révélé une solidarité sans précédent au sein de l'institution. Dans cet article, nous retraçons la chronologie de la gestion de cette crise sanitaire inédite au sein du laboratoire de Microbiologie clinique du CHU de Liège.

The structure of the asteroid 4 Vesta as revealed by models of planet-scale collisions.

Asteroid 4 Vesta seems to be a major intact protoplanet, with a surface composition similar to that of the HED (howardite-eucrite-diogenite) meteorites. The southern hemisphere is dominated by a giant impact scar, but previous impact models have failed to reproduce the observed topography. The recent discovery that Vesta's southern hemisphere is dominated by two overlapping basins provides an opportunity to model Vesta's topography more accurately. Here we report three-dimensional simulations of Vesta's global evolution under two overlapping planet-scale collisions. We closely reproduce its observed shape, and provide maps of impact excavation and ejecta deposition. Spiral patterns observed in the younger basin Rheasilvia, about one billion years old, are attributed to Coriolis forces during crater collapse. Surface materials exposed in the north come from a depth of about 20 kilometres, according to our models, whereas materials exposed inside the southern double-excavation come from depths of about 60-100 kilometres. If Vesta began as a layered, completely differentiated protoplanet, then our model predicts large areas of pure diogenites and olivine-rich rocks. These are not seen, possibly implying that the outer 100 kilometres or so of Vesta is composed mainly of a basaltic crust (eucrites) with ultramafic intrusions (diogenites).

[Preoperative planning interest of a total hip prosthesis]. / L'intérêt de la planification préopératoire d'une prothèse totale de hanche.

Total hip arthroplasty (THA) is the standard surgical procedure for the treatment of severe hip osteoarthritis. THA can be subject to surgical and medical complications. One of the main expectations of our patients is to be able to resume all their daily activities. Preoperative planning of a THA is an essential step in the procedure. The reference method remains the 2D technique using «templates¼ positioned on an anteroposterior digital radiograph of the pelvis. It can also be done in 3D. In addition to the type and size of prosthetic components (cup, stem and prosthetic head), the planning allows the surgeon to restore the function through correction of any limb length and/or offset discrepancy, and soft tissue tensioning in order to reach the objectives set and to limit the risks of complications. In the opposite case, the surgeon exposes the patient to complications during or after surgery with probable negative consequences on the functional result. The positioning of the acetabular and femoral components is an important factor influencing the short- and long-term survival of THA. All patients undergoing total hip arthroplasty should have rigorous preoperative planning.

La prothèse totale de hanche (PTH) est l'intervention chirurgicale de référence dans le traitement de la coxarthrose sévère. La PTH peut s'accompagner de complications chirurgicales et médicales. Une des principales attentes de nos patients est de pouvoir reprendre l'ensemble de leurs activités quotidiennes. La planification préopératoire d'une PTH est une étape essentielle de l'intervention. La méthode de référence reste la technique en 2D utilisant des «calques¼ positionnés sur une radiographie digitalisée de bassin de face. Elle peut également être réalisée en 3D. Outre le choix du type et de la taille des composants (cupule, tige et tête prothétique), la planification permet de se poser les questions propres à chaque patient (restauration de la longueur du membre inférieur et de l'offset fémoral, …) afin d'atteindre les objectifs fixés et de limiter les risques de complication. Dans le cas contraire, le praticien expose le patient à des complications en per- ou post-opératoire, avec de probables conséquences péjoratives sur le résultat fonctionnel. Le positionnement du composant acétabulaire et du composant fémoral est un facteur important influençant la survie à court et à long termes d'une PTH. Tous les patients qui subiront une arthroplastie totale de la hanche doivent bénéficier d'une planification préopératoire rigoureuse.

[TeleSPOT Project : early detection of melanoma by teledermoscopy in general practice]. / Le projet TeleSPOT : Détection précoce du mélanome par télédermoscopie en Médecine générale.

Since decades the incidence of skin cancer is clearly rising. This alarming trend also applies to melanoma. It represents the 4th most common cancer in women and 6th in men in 2015. Early recognition and treatment reduce both morbidity and mortality. Screening is the cornerstone of secondary prevention. However, access to reliable and rapid diagnosis is hampered by several factors, including accessibility to specialized medicine. One of the solutions to this problem is to collaborate with the first-line medical care through a teledermatology system. The TeleSPOT project, Teledermoscopy Smartphone-based Pigmented lesion diagnosis Online Taskforce, aims to provide a remote diagnostic aid by dermatologists to distinguish suspect pigmented skin lesions and accelerate their management.

Depuis des décennies, l'incidence des cancers cutanés est en nette augmentation. Cette tendance alarmante s'applique également au mélanome. Il représente le 4ème cancer le plus fréquent chez la femme en 2015. Une prise en charge précoce permet de réduire la morbidité et la mortalité. Le dépistage représente la pierre angulaire de la prévention secondaire. Néanmoins, l'accès au diagnostic fiable et rapide est entravé par plusieurs facteurs limitants, notamment l'accessibilité à une Médecine spécialisée. Une des solutions à cette problématique est de collaborer avec la Médecine de première ligne par le biais de la télédermatologie. Le projet TeleSPOT, acronyme de Teledermoscopy Smartphone-based Pigmented lesion diagnosis Online Taskforce, a pour objectif de fournir une aide diagnostique à distance par des dermatologues afin de trier les lésions cutanées pigmentées suspectes et d'en accélérer la prise en charge.

[Telemonitoring of severe COPD patients]. / Expérience liégeoise dans le télé-monitoring de patients BPCO sévères.

Following a solicitation of INAMI in 2016, a team of the CHU Liège pneumology department has proposed a telemonitoring pilot project in severe chronic obstructive pulmonary disease (COPD) patients. The main objective of the study was to reduce the number of hospitalizations for COPD exacerbation. The patients included in the study had been at least hospitalized once in 12 months before the beginning of the telemonitoring. A close collaboration with the general practitioner was required. Patients were educated in the manipulation of the application and connected objects. The numerous technical difficulties encountered limited the number of patients studied within the short time allowed by INAMI. However, some interesting observations could be made and a first experience in the field acquired. A project on a large scale seems necessary.

Suite à un appel lancé par l'INAMI en 2016, une équipe de soins du Service de Pneumologie du CHU de Liège a proposé un projet pilote de télé-monitoring de patients souffrant de bronchopneumopathie chronique obstructive (BPCO) sévère dont l'objectif principal était de réduire le nombre de ré-hospitalisations pour exacerbation de BPCO. Les patients sélectionnés étaient des patients sévèrement atteints et ayant été au moins hospitalisés une fois dans les 12 mois précédant la mise en place de la surveillance à distance. Une collaboration étroite avec le médecin généraliste était requise. Les patients ont été éduqués à la manipulation de l'application et des objets connectés proposés. Les nombreuses difficultés techniques rencontrées ont limité le nombre de patients étudiés dans les délais courts autorisés par l'INAMI. Cependant, quelques observations intéressantes ont pu être faites et une première expérience dans le domaine a été acquise. Un projet à plus grande échelle paraît nécessaire.

Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012.

BACKGROUND: Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs) with an IgE-mediated mechanism. In France, this life-threatening condition is reported by anesthetists and allergologists, and two safety alerts concerning suxamethonium were raised in 2011 and 2012. This led to start a national survey over the 2000-2012 period which objectives were to provide a descriptive analysis, to estimate incidence rates, and to analyze the trends over this period. METHODS: The French pharmacovigilance database was retrospectively queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and positive skin tests were qualified as "confirmed cases." Subgroup analysis compared atracurium and cisatracurium vs suxamethonium and rocuronium. RESULTS: A total of 680 confirmed cases and 944 nonconfirmed cases were identified. Suxamethonium was the most implied NMBA (64%). Incidence rates (according to sales data) of suxamethonium and rocuronium were, respectively, 10- and 13-folds higher than those of the others NMBAs, regardless the confirmed/nonconfirmed status. Cisatracurium incidence rates remained stable over the period, while suxamethonium and atracurium increased and rocuronium first decreased but re-increased after 2006. Male patients were more frequent in the subgroup "atracurium-cisatracurium" (P = .019), whereas obesity and emergency setting were more frequent in the subgroup "rocuronium-suxamethonium." Shared characteristics were the poorly documented previous exposure to NMBA(s) and an insufficient adherence of patients to perform skin tests, showing the need to improve this procedure. CONCLUSION: Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences.

[Erysipelas without fever or biologic inflammation during tocilizumab therapy]. / Érysipèle sans fièvre ni syndrome inflammatoire lors d'un traitement par tocilizumab.

BACKGROUND: Tocilizumab (TCZ) is a monoclonal antibody that inhibits the interleukin 6 (IL-6) signalling pathway. This treatment is extremely effective in rheumatoid arthritis (RA), which may well be accompanied by serious infections presenting misleading clinical pictures. Herein we report a case of a typical bacterial dermo-hypodermitis in a female patient treated with TCZ. PATIENTS AND METHODS: An 80-year-old woman treated with methotrexate (MTX) and TCZ for RA presented dermo-hypodermitis on her left leg 8 days after receiving her 13th infusion of TCZ. She exhibited neither fever nor biological inflammatory syndrome. Oral amoxicillin (3g/d) was initiated on an outpatient basis. Two weeks later, the patient was apyretic and her laboratory results were normal, although local inflammatory signs persisted. TCZ infusion was postponed and she was given intravenous amoxicillin (4g/d) for 2days, followed by oral amoxicillin, resulting in rapid recovery. Subsequent courses of TCZ were administered without incident. DISCUSSION: During the course of treatment with TCZ, this patient presented delineated bacterial cellulitis in the form of erysipelas, which was noteworthy on account of the absence of fever and of biological inflammatory syndrome. While there have been reports of severe cases of cellulitis during TCZ treatment, to our knowledge, there have been none of erysipelas. Attenuation of local and systemic inflammatory symptoms is widely reported, and is directly associated with the anti-IL-6 action of TCZ. Patients with RA are especially susceptible to opportunistic or severe infections as a result of the disease itself and of associated treatments, and increased vigilance is called for with regard to infections that may be transformed and potentially more severe as a result of TCZ.

[Management of chronic osteomyelitis by long-term antibiotic suppression]. / Prise en charge de l'ostéomyélite chronique par antibiothérapie suppressive au long cours.

Chronic osteomyelitis is a chronic inflammatory disease induced by bone infection. It may be limited to a single portion of bone or involve several areas such as marrow, cortical, periosteum and adjacent soft tissues. Being able to persist for weeks, months or even years, it remains a therapeutic challenge in spite of the important medical and surgical advances, with a prolonged and complex management given the nature of the surgical interventions and the antibiotherapies required. We report a case of chronic osteomyelitis treated by long-term suppressive antibiotic therapy, which may be a reasonable alternative to surgery in inoperable clinical situations, but taking into account the risks associated with it in terms of side effects and selection of resistant organisms, as well as the cost of treatment and the quality of life of the patient.

L'ostéomyélite chronique est une pathologie inflammatoire chronique induite par une infection osseuse. Elle peut être limitée à une seule portion d'os ou impliquer plusieurs zones telles que la moelle, la corticale, le périoste et les tissus mous adjacents. Pouvant persister pendant des semaines, des mois voire des années, elle reste un challenge thérapeutique en dépit des importantes avancées médicales et chirurgicales, avec une prise en charge prolongée et complexe compte tenu de la nature des interventions chirurgicales et des antibiothérapies requises. Nous rapportons un cas d'ostéomyélite chronique pris en charge par antibiothérapie suppressive au long cours, qui peut être une alternative raisonnable à la chirurgie dans des situations cliniques inopérables, mais en prenant en considération les risques qui y sont associés en termes d'effets secondaires et de sélection des germes résistants, ainsi que le coût du traitement et la qualité de vie du patient.

Long-term stability of dexamethasone and alizapride or ondansetron in sodium chloride 0.9% polyolefin bag at 5±3°C.

INTRODUCTION: The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C. METHOD: Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend. RESULTS: The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r2) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days. CONCLUSION: The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.

Physical stability of highly concentrated injectable drugs solutions used in intensive care units.

BACKGROUND: The intensive care department of the institution use drug solutions within higher concentration to avoid fluid overload. The purpose of the study is to prove the physical stability of different injectable drugs within high concentration (amiodarone 25mg/mL, isosorbide 0.60mg/mL, lorazepam 0.16mg/mL, noradrenalin 0.120 and 0.240mg/mL, salbutamol 0.06mg/mL and sodium valproate 12mg/mL) to ensure the patients safety. METHODS: Five of 30 or 50mL polypropylene syringes were prepared for each solution under aseptic conditions and stored at room temperature. Immediately after the preparation (hour 0) and after 1, 4, 8, 24 and 48hours, 2mL of each solution were withdrawn from each syringe and placed in glass tubes to proceed to the stability test. All specimens were visually inspected in front of a black and of a white background and aliquots of each solution were centrifuged to proceed to microscopic inspection with a ten-fold magnification. The pH of each solution was measured with glass electrode pH-meter (Inolab level 1, WTW Weilhem, Germany with biotrode electrode, Hamilton, Bonaduz, Switzerland) and spectrophotometric measurements (Genesys 10 series, New-York, USA) were performed at three wavelengths (350, 410 and 550nm) to avoid the apparition of turbidity. RESULTS: For all the drugs included in the study, there was no significant change in pH, no color change, no turbidity or opacity and no precipitation observed in the solutions during the storage at room temperature for 48hours. No microaggregates were detected by microscope neither revealed by a change of absorbance. CONCLUSION: Within these limits, the preparations of amiodarone in 5% glucose polypropylene syringes and isosorbide, lorazepam, noradrenalin, salbutamol, valproate in 0.9% sodium chloride polypropylene syringes are physically stable at room temperature for 48hours. These results allow us to consider a study of chemical stability by high-performance liquid chromatography (HPLC).

A new method for the separation and purification of the osteogenic compounds of nacre Ethanol Soluble Matrix.

Nacre is able to induce bone-forming cells mineralization, and gains widely interest in bone regeneration. While, the osteoinductive compounds are not yet identified. ESM (Ethanol Soluble Matrix), a nacre extract from powder of Pinctada margaritifera pearl oyster shell, has been firstly proven having the capacity to induce mineralization and to restore mineralization defect in vitro. It is suitable to treat ESM as a source of osteoinductive compounds. Herein, we develop a new method for separating and purifying nacre extracts by an ionic approach. At first, cationic ESM (ESMc) and anionic ESM (ESMa) were achieved with ion-exchange resin. Then, ESM was separated and collected on cation exchange HPLC. Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectrometry (EDS) was used to reveal the concentrated elements in ESM fractions. A coupled cell models were used to test the ESM fractions. Alizarin Red staining was performed and quantified to evaluate the mineralization level. ESMc and 2 HPLC fractions stimulated the mineralization in both cells. EDS demonstrated the abundant presence of calcium and chloride in the osteogenic fractions. To validate, pure CaCl2 was tested and proven having an osteogenic effect in both cells, but less stable than ESM. The mineralization nodules induced by ESM fractions and CaCl2 differed in both cells. In conclusion, a new method was developed for separating and purifying nacre extracts by an ionic approach. By which, the osteoinductive compounds in ESM were proven cationic, and calcium in ESM was demonstrated to play a role in inducing the cell mineralization.

Restriction of spontaneous and prednisolone-induced leptin production to dedifferentiated state in human hip OA chondrocytes: role of Smad1 and ß-catenin activation.

OBJECTIVE: The aetiology of OA is not fully understood although several adipokines such as leptin are known mediators of disease progression. Since leptin levels were increased in synovial fluid compared to serum in OA patients, it was suggested that joint cells themselves could produce leptin. However, exact mechanisms underlying leptin production by chondrocytes are poorly understood. Nevertheless, prednisolone, although displaying powerful anti-inflammatory properties has been recently reported to be potent stimulator of leptin and its receptor in OA synovial fibroblasts. Therefore, we investigated, in vitro, spontaneous and prednisolone-induced leptin production in OA chondrocytes, focusing on transforming growth factor-ß (TGFß) and Wnt/ß-catenin pathways. DESIGN: We used an in vitro dedifferentiation model, comparing human freshly isolated hip OA chondrocytes cultivated in monolayer during 1 day (type II, COL2A1 +; type X, COL10A1 + and type I collagen, COL1A1 -) or 14 days (COL2A1 -; COL10A1 - and COL1A1+). RESULTS: Leptin expression was not detected in day1 OA chondrocytes whereas day14 OA chondrocytes produced leptin, significantly increased with prednisolone. Activin receptor-like kinase 1 (ALK1)/ALK5 ratio was shifted during dedifferentiation, from high ALK5 and phospho (p)-Smad2 expression at day1 to high ALK1, endoglin and p-Smad1/5 expression at day14. Moreover, inactive glycogen synthase kinase 3 (GSK3) and active ß-catenin were only found in dedifferentiated OA chondrocytes. Smad1 and ß-catenin but not endoglin stable lentiviral silencing led to a significant decrease in leptin production by dedifferentiated OA chondrocytes. CONCLUSIONS: Only dedifferentiated OA chondrocytes produced leptin. Prednisolone markedly enhanced leptin production, which involved Smad1 and ß-catenin activation.

Expression of the semicarbazide-sensitive amine oxidase in articular cartilage: its role in terminal differentiation of chondrocytes in rat and human.

OBJECTIVE: Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the oxidation of primary amines into ammonia and reactive species (hydrogen peroxide, aldehydes). It is highly expressed in mammalian tissues, especially in vascular smooth muscle cells and adipocytes, where it plays a role in cell differentiation and glucose transport. The study aims at characterizing the expression and the activity of SSAO in rat and human articular cartilage of the knee, and to investigate its potential role in chondrocyte terminal differentiation. DESIGN: SSAO expression was examined by immunohistochemistry and western blot. Enzyme activity was measured using radiolabeled benzylamine as a substrate. Primary cell cultures of rat chondrocytes were treated for 21 days by a specific SSAO inhibitor, LJP 1586. Terminal chondrocyte differentiation markers were quantified by RT-qPCR. The basal and IL1ß-stimulated glucose transport was monitored by the entrance of (3)[H]2-deoxyglucose in chondrocytes. RESULTS: SSAO was expressed in chondrocytes of rat and human articular cartilage. SSAO expression was significantly enhanced during the hypertrophic differentiation of chondrocytes characterized by an increase in MMP13 and in alkaline phosphatase (ALP) expressions. SSAO inhibition delayed the late stage of chondrocyte differentiation without cell survival alteration and diminished the basal and IL1ß-stimulated glucose transport. Interestingly, SSAO activity was strongly increased in human osteoarthritic cartilage. CONCLUSIONS: SSAO was expressed as an active form in rat and human cartilage. The results suggest the involvement of SSAO in rat chondrocyte terminal differentiation via a modulation of the glucose transport. In man, the increased SSAO activity detected in osteoarthritic patients may trigger hypertrophy and cartilage degeneration.

Relationships between population density, fine-scale genetic structure, mating system and pollen dispersal in a timber tree from African rainforests.

Owing to the reduction of population density and/or the environmental changes it induces, selective logging could affect the demography, reproductive biology and evolutionary potential of forest trees. This is particularly relevant in tropical forests where natural population densities can be low and isolated trees may be subject to outcross pollen limitation and/or produce low-quality selfed seeds that exhibit inbreeding depression. Comparing reproductive biology processes and genetic diversity of populations at different densities can provide indirect evidence of the potential impacts of logging. Here, we analysed patterns of genetic diversity, mating system and gene flow in three Central African populations of the self-compatible legume timber species Erythrophleum suaveolens with contrasting densities (0.11, 0.68 and 1.72 adults per ha). The comparison of inbreeding levels among cohorts suggests that selfing is detrimental as inbred individuals are eliminated between seedling and adult stages. Levels of genetic diversity, selfing rates (∼16%) and patterns of spatial genetic structure (Sp ∼0.006) were similar in all three populations. However, the extent of gene dispersal differed markedly among populations: the average distance of pollen dispersal increased with decreasing density (from 200 m in the high-density population to 1000 m in the low-density one). Overall, our results suggest that the reproductive biology and genetic diversity of the species are not affected by current logging practices. However, further investigations need to be conducted in low-density populations to evaluate (1) whether pollen limitation may reduce seed production and (2) the regeneration potential of the species.