534 SIX-MONTH EFFICACY OF INTRA-ARTICULAR HYALURONIC ACID FOR CARPOMETACARPAL JOINT OSTEOARTHRITIS

n/

Polymer-drug conjugates as inhalable drug delivery systems: A review

Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetic profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety in the lungs, which is closely linked to lung retention times. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments for several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps

Prenatal diagnosis of total and partial anomalous pulmonary venous connection: multicenter cohort study and meta-analysis

Objectives: The aims of this study were to review systematically literature on and describe the sonographic features and associated anomalies of total (TAPVC) and partial (PAPVC) anomalous pulmonary venous connection and scimitar syndrome (SS). Methods: A retrospective cohort study was carried out of cases of TAPVC, PAPVC and SS that underwent comprehensive ultrasound examination, seen over a 20-year period at two tertiary referral centers. Assessed variables included TAPVC subtype, gestational age at diagnosis, area behind the left atrium, ventricular disproportion, vertical vein, pulmonary venous obstruction, mode of diagnosis, association with cardiac and extracardiac conditions, and pregnancy and fetoneonatal outcomes. The outcome was considered favorable if the individual was alive and well (no functional impairment from surgery or cardiac or extracardiac conditions). Cases associated with right isomerism were excluded from the analysis, as TAPVC in these cases was only one of several major cardiac anomalies affecting sonographic signs. A systematic review was performed in order to obtain a synthesis of characteristics associated with TAPVC, PAPVC and SS. The literature search of PubMed and EMBASE (1970–2016) included reviews, case series and case reports. A meta-analysis was conducted only for TAPVC. Random-effects models were used to obtain pooled estimates of the frequencies of clinical characteristics and sonographic features. Results: For TAPVC, a total of 15 studies involving 71 patients (including 13 from the current cohort study) were included in the systematic review and meta-analysis. The pooled estimate for the association of TAPVC with congenital heart disease was 28.3% (95% CI, 18.1–41.3%) and with extracardiac anomalies it was 18.5% (95% CI, 10.5–30.6%). Of TAPVC cases, obstructed venous return was observed in 34.1% (95% CI, 22.7–47.7%), a favorable outcome in 43.8% (95% CI, 24.0–65.8%), ventricular disproportion in 59.2% (95% CI, 45.1–72.0%), increased area behind the left atrium in 58.1% (95% CI, 41.1–73.5%) and a vertical vein in 59.3% (95% CI, 41.1–75.3%). Diagnosis was established by using color or power Doppler in 84.9% (95% CI, 67.3–93.9%) of cases. For SS, there were only three studies describing eight cases, to which the current study added another five. Ventricular disproportion was present in three out of nine SS cases for which data were available, but for two of these, there was a concurrent heart anomaly. Color Doppler was used for all SS diagnoses, and four-dimensional echocardiography was useful in two out of six cases in which it was used. Outcome for SS cases was generally good. For PAPVC, there were only five studies describing five cases, to which the current study added another two. Major cardiac anomalies were associated in four out of seven of these cases, and extracardiac anomalies in three out of six cases for which data were available. Conclusions: TAPVC can be associated with other cardiac and extracardiac anomalies in a significant percentage of cases. Leading sonographic signs are ventricular disproportion, increased area behind the left atrium and the finding of a vertical vein. Color/power Doppler is the key mode for diagnosis of TAPVC. Obstructed venous return can be expected in roughly one-third of cases of TAPVC and outcome is favorable in less than half of cases. Data for SS and PAPVC are too few to synthesize. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd

Drivers of extinction risk in African mammals: the interplay of distribution state, human pressure, conservation response and species biology

Although conservation intervention has reversed the decline of some species, our success is outweighed by a much larger number of species moving towards extinction. Extinction risk modelling can identify correlates of risk and species not yet recognized to be threatened. Here, we use machine learning models to identify correlates of extinction risk in African terrestrial mammals using a set of variables belonging to four classes: species distribution state, human pressures, conservation response and species biology. We derived information on distribution state and human pressure from satellite- borne imagery. Variables in all four classes were identified as important predictors of extinction risk, and interactions were observed among variables in different classes (e.g. level of protection, human threats, species distribution ranges). Species biology had a key role in mediating the effect of external variables. The model was 90% accurate in classifying extinction risk status of species, but in a few cases the observed and modelled extinction risk mismatched. Species in this condition might suffer from an incorrect classification of extinction risk (hence require reassessment). An increased availability of satellite imagery combined with improved resolution and classification accuracy of the resulting maps will play a progressively greater role in conservation monitoring.JRC.H.5-Land Resources Managemen

Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus

Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response

Metastatic gastric cancer presenting with shoulder-hand syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Shoulder-hand syndrome is a relatively rare clinical entity classified as a complex regional pain syndrome type 1 and consisting essentially of a painful 'frozen shoulder' with disability, swelling, vasomotor or dystrophic changes in the homolateral hand. The pathophysiology is not completely clear but a predominant 'sympathetic' factor affecting the neural and vascular supply to the affected parts seems to be involved. Shoulder-hand syndrome has been related to many surgical, orthopedic, neurological and medical conditions; it is more often seen after myocardial infarction, hemiplegia and painful conditions of neck and shoulder, such as trauma, tumors, cervical discogenic or intraforaminal diseases and shoulder calcific tendinopathy, but has also been associated with herpetic infections, brain and lung tumors, thoracoplasty and drugs including phenobarbitone and isoniazid. The diagnosis of shoulder-hand syndrome is primarily clinical, but imaging studies, particularly bone scintigraphy, may be useful to exclude other disorders.</p> <p>Case presentation</p> <p>We report the case of a 67-year-old woman who presented with shoulder-hand syndrome as the initial manifestation of gastric cancer which had metastasized to bone.</p> <p>Conclusion</p> <p>Wider investigations are advisable in patients with atypical shoulder-hand syndrome. To the best of the authors' knowledge this is the first case of shoulder-hand syndrome associated with metastatic gastric cancer.</p

Nailfold videocapillaroscopy and serum VEGF levels in scleroderma are associated with internal organ involvement

Purpose: Nailfold videocapillaroscopy (NVC) identifies the microvascular hallmarks of systemic sclerosis (SSc) and vascular endothelial growth factor (VEGF) and may play a pivotal role in the associated vasculopathy. The aim of the present study was to compare NVC alterations with clinical subsets, internal organ involvement, and serum VEGF levels in a cohort of selected SSc cases. Methods: We studied 44 patients with SSc who were evaluated within 3\ua0months from enrollment by NVC, skin score, severity index, pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography, pulmonary high-resolution computed tomography (HRCT), gastroesophageal (GE) endoscopy or manometry or X-ray, and serum autoantibodies. Serum VEGF-A levels were determined by ELISA in 72 SSc patients and 31 healthy controls. Results: Giant capillaries were inversely correlated with age (p\ua0=\ua00.034, r\ua0=\ua0 120.34) and to the extent of reticular pattern at HRCT (p\ua0=\ua00.04, r\ua0=\ua0 120.5). Avascular areas were directly correlated with capillaroscopy skin ulcer risk index (CSURI) (p\ua0=\ua00.006, r\ua0=\ua0+0.4) and severity index (p\ua0=\ua00.004, r\ua0=\ua0+0.5). The mean capillary density was directly correlated to the ulcer number (p\ua0=\ua00.02, r\ua0=\ua0+0.4) and to DLCO/alveolar volume (p\ua0=\ua00.02, r\ua0=\ua0+0.4) and inversely correlated with severity index (p\ua0=\ua00.01, r\ua0=\ua0 120.4) and skin score (p\ua0=\ua00.02, r\ua0=\ua0 120.4). Serum VEGF levels were higher in the SSc population vs controls (p\ua0=\ua00.03) and inversely correlated with DLCO (p\ua0=\ua00.01, r\ua0= 120.4) and directly with ground-glass and reticular pattern at HRCT (p\ua0=\ua00.04, r\ua0=\ua0+0.4 for both). Conclusions: Our data suggest the importance of NVC not only for the diagnosis, but also for the global evaluation of SSc patients. Of note, serum VEGF levels may act as a biomarker of interstitial lung involvement