Thinking outside the glenohumeral box: Hierarchical shape variation of the periarticular anatomy of the scapula using statistical shape modeling

Variation in the shape of the glenoid and periarticular anatomy of the scapula has been associated with shoulder pathology. The goal of this study was to identify the modes of shape variation of periarticular scapular anatomy in relation to the glenoid in nonpathologic shoulders. Computed tomography scans of 31 cadaveric scapulae, verified to be free of pathology, were three-dimensionally reconstructed. Statistical shape modeling and principal component analysis identified the modes of shape variation across the population. Corresponding linear and angular measurements quantified the morphometric variance identified by the modes. Linear measures were normalized to the radius of the inferior glenoid to account for differences in the scaling of the bones. Five modes captured 89.7% of total shape variation of the glenoid and periarticular anatomy. Apart from size differences (mode 1: 33.0%), acromial anatomy accounted for the largest variation (mode 2: 32.0%). Further modes described variation in glenoid inclination (mode 3: 11.8%), coracoid orientation and size (mode 4: 9.0%), and variation in coracoacromial (CA) morphology (mode 5: 3.1%). The average scapula had a mean acromial tilt of 49 ± 7°, scapular spine angle of 61 ± 6°, the glenoid inclination of 84 ± 4°, coracoid deviation angle of 26 ± 4°, coracoid length of 3.7 ± 0.3 glenoid radii, and a CA base length of 5.6 ± 0.5 radii. In this study, the identified shape modes explain almost all of the variance in scapular anatomy. The acromion exhibited the highest variance of all periarticular anatomic structures of the scapula in relation to the glenoid, which may play a role in many shoulder pathologies.     

Predictors of Early Complications of Total Shoulder Arthroplasty

The authors hypothesized that age, body mass index (BMI), and medical comorbidities (graded with the Charleson Comorbidiy index [CCI]) could be used to predict early complications after TSA. The authors performed a retrospective review of primary TSAs with a minimum of 90-day follow-up. One hundred twenty-seven patients met the inclusion criteria. Complications occurred in 12 (9.4%) of patients. Major complications occurred in 1 patient (0.8%), medical in 8 (6.3%), and surgical in 4 (3.1%). CCI significantly correlated with complication rates and multivariate regression analysis demonstrated CCI to be the only significant determinant of overall complication rates (P = 0.005) and medical complication rates (P = 0.015). While BMI subgroup did not affect complication rates, transfusion rates, intra-operative blood loss, or operative time, our study may have been underpowered for this variable.     

Potential use of NOACs in developing countries: pros and cons

Purpose

Although vitamin K antagonists (VKAs) are effective for long-term thromboprophylaxis in atrial fibrillation (AF), their limitations have led to widespread underutilisation, especially in the developing world. Novel oral anticoagulants (NOACs) have emerged as promising alternatives to VKAs, although there are some particular considerations and challenges to their introduction in developing countries. This review summarises the current state of antithrombotic management of AF in the developing world, explores the early evidence for the NOACs and describes some of the special considerations that must be taken into account when considering the role of the NOACs within developing countries’ health care systems.

Methods

A literature search was conducted via PubMed and Google Scholar to find articles published in English between the years 2000 to 2014. Search terms used were “atrial fibrillation”, “oral anticoagulants”, “warfarin”, “NOACs”, “dabigatran”, “rivaroxaban”, “apixaban”, “edoxaban”, “time in therapeutic range”, “International Normalized Ratio” “cost-effectiveness”, “stroke”, “adverse-drug reactions” and “drug–drug interactions”, together with the individual names of developing countries as listed by the World Bank. We reviewed the results of randomized clinical trials, relevant retrospective and prospective studies, case-studies and review articles.

Results

Many developing countries lack or have sporadic data on the quality of AF management, making it difficult to anticipate the potential impact of NOACs in these settings. The utilisation of anticoagulants for AF appears highly variable in developing countries. Given the issues associated with VKA therapy in many developing countries, NOACs offer some potential advantages; however, there is insufficient evidence to advocate the widespread replacement of warfarin at present. VKAs may continue to have a role in selected patients or countries, especially if alternative monitoring strategies can be utilised.

Conclusion

The evaluation of the introduction of NOACs should consider safety, budget concerns and the quality of oral anticoagulation care achieved by each country. Prospective registries will be important in developing countries to better elucidate the comparative safety, efficacy and cost-effectiveness of NOACs and VKAs as NOACs are introduced into practice.     

Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial

BACKGROUND & AIMS: Tumor necrosis factor (TNF) is a pivotal cytokine in intestinal inflammation. Controlled trials using a chimeric anti-TNF antibody (infliximab) have shown its efficacy in refractory Crohn's disease. METHODS: Endoscopic and histological response to infliximab was investigated in a multicenter, randomized, double-blind, and placebo-controlled trial including 30 patients with active Crohn's disease undergoing ileocolonoscopy before and 4 weeks after intravenous administration of 5, 10, or 20 mg/kg of infliximab or placebo as a single infusion. Lesions were scored by means of the validated Crohn's Disease Endoscopic Index of Severity (CDEIS). Endoscopic biopsy specimens were taken during both procedures from 9 of 30 patients and scored by a single gastrointestinal pathologist. RESULTS: CDEIS scores decreased significantly in most infliximab-treated patients without an apparent dose response. No endoscopic improvement was observed in the placebo group. The changes in CDEIS correlated highly with those of the Crohn's Disease Activity Index. At a histological level, disappearance of the inflammatory infiltrate was observed in infliximab-treated patients but not in placebo-treated ones; however, architectural changes persisted in most patients. Strictures developed in several patients. CONCLUSIONS: Clinical improvement after infliximab therapy in active Crohn's disease is accompanied by significant healing of endoscopic lesions and disappearance of the mucosal inflammatory infiltrate.     

Prediction of the tissue-specificity of selective estrogen receptor modulators by using a single biochemical method

Here, we demonstrate that a single biochemical assay is able to predict the tissue-selective pharmacology of an array of selective estrogen receptor modulators (SERMs). We describe an approach to classify estrogen receptor (ER) modulators based on dynamics of the receptor-ligand complex as probed with hydrogen/deuterium exchange (HDX) mass spectrometry. Differential HDX mapping coupled with cluster and discriminate analysis effectively predicted tissue-selective function in most, but not all, cases tested. We demonstrate that analysis of dynamics of the receptor-ligand complex facilitates binning of ER modulators into distinct groups based on structural dynamics. Importantly, we were able to differentiate small structural changes within ER ligands of the same chemotype. In addition, HDX revealed differentially stabilized regions within the ligand-binding pocket that may contribute to the different pharmacology phenotypes of the compounds independent of helix 12 positioning. In summary, HDX provides a sensitive and rapid approach to classify modulators of the estrogen receptor that correlates with their pharmacological profile.     

Comparison and potential of hypo-osmotic and iso-osmotic erythrocyte ghosts and carrier erythrocytes as drug and enzyme carriers

Preparation, characteristics and properties of the three types of erythrocyte ghost are compared. These include light scattering properties, morphology, retention of cellular components and biochemical function including membrane transport. In vivo studies in the BALB/c mouse and Beagle dog have allowed the potential to be assessed of these erythrocyte ghosts as drug and enzyme cellular carriers in the treatment of human diseases. The development of the carrier erythrocyte with restored cellular ATP content and properties, including in vivo survival, that are closely similar to those of the normal erythrocyte is also described and its potential discussed.     

Structural domains of IS10 transposase and reconstitution of transposition activity from proteolytic fragments lacking an interdomain linker.

All of the DNA cleavage and strand transfer events required for transposition of insertion sequence IS10 are carried out by a 46-kDa IS10-encoded transposase protein. Limited proteolysis demonstrates that transposase has two principal structural domains, a 28-kDa N-terminal domain (N alpha beta; aa 1-246) and a 17-kDa C-terminal domain (C; aa 256-402). The two domains are connected by a 1-kDa proteolytic-sensitive linker region (aa 247-255). The N-terminal domain N alpha beta can be further subdivided into domains N alpha and N beta by a weaker protease-sensitive site located 6 kDa (53 aa) from the N terminus. The N beta and N alpha beta fragments are capable of nonspecific DNA binding as determined by Southwestern blot analysis. None of the fragments alone is capable of carrying out the first step of transposition, assembly of a synaptic complex containing a pair of transposon ends. Remarkably, complete transposition activity can be reconstituted by mixing fragment N alpha beta and fragment C, with or without the intervening linker region. We infer that the structural integrity of transposase during the transitions involved in the chemical steps of the transposition reaction is maintained independent of the linker, presumably by direct contacts between and among the principal domains. Reconstitution of activity in the absence of the linker region is puzzling, however, because mutations that block strand transfer or affect insertion specificity alter linker region residues. Additional reconstitution experiments demonstrate that the N alpha region is dispensable for formation of a synaptic complex but is required for complexes to undergo cleavage.