Primary venous aneurysms: A 20-year retrospective analysis.

OBJECTIVE: Primary venous aneurysms are unusual vascular occurrences. Our aim is to document our institution's experience with this pathology; describing frequency, diagnosis, outcomes and medical histories of patients with primary venous aneurysms within a 20-year time frame. METHODS: A retrospective study at our institution using its radiology database was conducted. Results were isolated to primary venous aneurysms diagnosed between 1997 and 2017. Basic demographics and medical history were collected. RESULTS: We identified 32 patients with primary venous aneurysms. Eighteen were male and 14 were female. The average age of presentation was 54 years old, with a range of 17-86. None of these patients reported a family history of aneurysmal disease. The majority were incidental. Of these aneurysms, 3 were of the head and neck, 1 was contained in the thorax, 17 were intra-abdominal and 11 were peripheral. Diagnosis was made by computed tomography, duplex ultrasound, or magnetic resonance imaging. Conservative management was most frequently employed, but four patients underwent surgical repair. Three aneurysms required operation for symptom management (external jugular, subclavian, inferior vena cava), whereas one aneurysm of the popliteal vein was prophylactically managed, given the high risk for pulmonary embolism. CONCLUSIONS: Primary venous aneurysms present infrequently. Despite their rarity, primary venous aneurysms have been reported to occur throughout the venous system. The majority of primary venous aneurysms in this series were found incidentally and can present both symptomatically or asymptomatically. The findings of our 20-year experience were consistent with the existing literature. Because the risk of rupture is negligible, the indications for surgical management remain for cosmesis, symptom management or high risk of thromboembolic events.

Small molecular exogenous modulators of active forms of MMPs.

Matrix metalloproteinases (MMPs) are endopeptidases, and their activity depends on calcium and zinc metal ions. These enzymes are expressed originally in zymogenic form, where the active site of proteins is closed by a prodomain which is removed during activation. A homeostatic balance of their activity is primarily regulated by a 'cysteine switch' located on a consensus sequence of the prodomain and natural endogenous inhibitors, called tissue inhibitors of metalloproteinases (TIMPs). Breakage of this homeostasis may lead to various pathological conditions, which may require further activation and/or inhibition of these enzymes to regenerate that balance. Here, we report four modulators, more specifically, three inhibitors (I1, I2 and I3), and one exogenous activator (L) of the active form of human collagenase MMP-1 (without prodomain). The results were confirmed by binding studies using fluorescence-based enzyme assays.

Association Between Sarcopenia and Adverse Events Following Transcatheter Aortic Valve Implantation.

BACKGROUND: Sarcopenia, the age-related loss of skeletal muscle mass/function, has been identified as a marker of frailty. We examined the association between sarcopenia and adverse events following transcatheter aortic valve implantation (TAVI). METHODS: A retrospective cohort study was conducted at Toronto General Hospital. All patients who underwent TAVI in the time period 2007-2017 with preoperative computed tomography were included. Skeletal muscle index (SMI) was calculated radiographically using psoas muscle area at the L3 vertebral level, divided by height. Various measures of sarcopenia, including mean SMI, SMI below the sex-specific median, and SMI in the lowest sex-specific quartile were calculated. The primary outcome was postoperative adverse events, defined as a composite of in-hospital mortality and morbidity including cardiovascular, pulmonary, neurologic, access-related, and gastrointestinal complications. Univariate and multivariate logistic regression were performed to determine the association between sarcopenia and adverse events. RESULTS: A total of 468 patients (mean age: 80.7 years) were included. Baseline comorbidity burden was high, particularly congestive heart failure (93.4%). Postoperative adverse events occurred in 62 patients (13.2%). Univariate logistic regression demonstrated that postoperative adverse events were correlated with mean SMI (odds ratio [OR] 0.81, 95% confidence interal [CI] 0.66-0.97), events were less than the SMI (OR 2.16, 95% CI 1.24-3.84), and SMI in the sex-specific lowest quartile (OR 2.34, 95% CI 1.33-4.07). On multivariate analysis, SMI in the sex-specific lowest quartile was an independent predictor of adverse events (OR 2.53, 95% CI 1.41-4.50). CONCLUSIONS: Sarcopenia defined by radiologic psoas muscle measurements was independently associated with in-hospital mortality and morbidity following TAVI.

CONTEXTE: La sarcopénie, soit la perte de masse et de fonction des muscles squelettiques liée à l'âge, a été identifiée comme un marqueur de fragilité. Nous avons examiné l'association entre la sarcopénie et les événements indésirables suivant l'implantation valvulaire aortique par cathéter (IVAC). MÉTHODOLOGIE: Une étude de cohorte rétrospective a été menée au Toronto General Hospital. Tous les patients ayant subi une IVAC avec tomodensitométrie préopératoire au cours de la période 2007-2017 ont été inclus. L'indice de masse musculaire squelettique (IMMS) a été calculé par radiographie en utilisant la surface du psoas au niveau de la vertèbre L3, divisée par la taille. Diverses mesures de la sarcopénie, y compris l'IMMS moyen, l'IMMS sous la médiane selon le sexe et l'IMMS dans le quartile inférieur selon le sexe, ont été calculées. Le critère d'évaluation principal était les événements indésirables postopératoires, définis comme un critère composite comprenant la mortalité et la morbidité à l'hôpital, notamment les complications cardiovasculaires, pulmonaires, neurologiques, gastro-intestinales et liées à l'accès vasculaire. Des régressions logistiques univariée et multivariée ont été effectuées pour déterminer l'association entre la sarcopénie et les événements indésirables. RÉSULTATS: Un total de 468 patients (âge moyen : 80,7 ans) ont été inclus. Le fardeau de comorbidité au départ était élevé, en particulier pour ce qui est de l'insuffisance cardiaque congestive (93,4 %). Des événements indésirables postopératoires sont survenus chez 62 patients (13,2 %). La régression logistique univariée a montré que les événements indésirables postopératoires étaient en corrélation avec un IMMS moyen (rapport des cotes [RC] : 0,81, intervalle de confiance [IC] à 95 % : 0,66 à 0,97), un IMMS sous la médiane selon le sexe (RC : 2,16; IC à 95 % : 1,24 à 3,84) et un IMMS dans le quartile inférieur selon le sexe (RC : 2,34; IC à 95 % : 1,33 à 4,07). Lors de l'analyse multivariée, un IMMS situé dans le quartile inférieur selon le sexe était un prédicteur indépendant d'événements indésirables (RC : 2,53; IC à 95 % : 1,41 à 4,50). CONCLUSIONS: La sarcopénie définie par les mesures radiologiques du psoas était indépendamment associée à la mortalité et à la morbidité à l'hôpital à la suite d'une IVAC.

Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents.

The magA gene was sought in hypermucoviscous isolates of Klebsiella spp., the Klebsiella K serotype reference strains and in isolates of the K1 serotype of Klebsiella pneumoniae from the UK, Hong Kong, Israel, Taiwan and Australia. Only K1 isolates were PCR positive for magA; this gene was found in all such isolates tested. Hypermucoviscosity was not confined to magA positive isolates, nor was it found in all magA positive isolates. Comparison of XbaI PFGE profiles revealed that most (19/23) of the magA positive isolates clustered within 72 % similarity, with a further subcluster of isolates, from three different continents, clustering within >80 %. All of the 16 isolates tested within the main cluster had the same sequence type (ST 23) by multilocus sequence typing, with the exception of one isolate, which had a single nucleotide difference at one of the seven loci. This study indicates that a genotype strongly associated with highly invasive disease in Taiwan, where large numbers of cases have been reported, is geographically very widespread.

Improved and targeted delivery of bioactive molecules to cells with magnetic layer-by-layer assembled microcapsules.

Despite our increasing knowledge of cell biology and the recognition of an increasing repertoire of druggable intracellular therapeutic targets, there remain a limited number of approaches to deliver bioactive molecules to cells and even fewer that enable targeted delivery. Layer-by-layer (LbL) microcapsules are assembled using alternate layers of oppositely charged molecules and are potential cell delivery vehicles for applications in nanomedicine. There are a wide variety of charged molecules that can be included in the microcapsule structure including metal nanoparticles that introduce physical attributes. Delivery of bioactive molecules to cells with LbL microcapsules has recently been demonstrated, so in this study we explore the delivery of bioactive molecules (luciferase enzyme and plasmid DNA) to cells using biodegradable microcapsules containing a layer of magnetite nanoparticles. Interestingly, significantly improved intracellular luciferase enzyme activity (25 fold) and increased transfection efficiency with plasmid DNA (3.4 fold) was observed with magnetic microcapsules. The use of a neodymium magnet enabled efficient targeting of magnetic microcapsules which further improved the delivery efficiency of the cargoes as a consequence of increased microcapsule concentration at the magnetic site. Microcapsules were well tolerated by cells in these experiments and only displayed signs of toxicity at a capsule : cell ratio of 100 : 1 and with extended exposure. These studies illustrate how multi-functionalization of LbL microcapsules can improve and target delivery of bioactive molecules to cells.