Citations

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

Background National prevalence and outcomes of Fontan operation in the USA is unknown. Study objective was to determine trends (temporal change) in the annual volume of Fontan operations, in-hospital mortality, postoperative complications and type of hospital discharge. Methods Review of the Nationwide Inpatient Sample for patients that underwent Fontan operation from 2001 to 2014 using the International Classification of Diseases-Ninth Revision, Clinical Modification procedure code for Fontan operation, that is, 35.94. To evaluate for change in patients’ demographics over the years, we divided the patient population into four groups based on procedure year (2001–2004, 2005–2008, 2009–2011 and 2012–2014). Results An estimated 15 934 Fontan operations were performed in the USA from 2001 to 2014. Median (Q1–Q3) age was 3 (2–4) years and 39.8% were female. Hypoplastic left heart syndrome was the most common (29%) congenital heart disease diagnosis. An estimated 1175 procedures were performed in 2001 and 1340 in 2014, but there was no significant change in the number of procedures per year (p=0.47). There was significant decline in in-hospital mortality from 4.5% (53/1175) in 2001 to 1.1% (15/1340) in 2014 (p=0.009). When we compared event rates between 2001–2004 and 2012–2014 periods, there was significant decline in postoperative cardiac complications (12.6% (459/3640) to 8% (378/4706), p=0.007) and respiratory complications (17.1% (623/3640) to 10.2% (481/4706), p<0.001). However, there was increase in the number of patients discharged to home with healthcare assistance or transferred to another acute care facility (5.8% (211/3640) to 9.4% (443/4706), p=0.01) and inflation-adjusted hospitalisation cost (US$46 978 to US$60 383, p<0.001), but no significant change in length of stay (p=0.73). Conclusion On the average, 1062 Fontan operations are performed annually in the USA with no change in volume of procedures but a decrease in in-hospital mortality and postoperative complications over a 15-year period.

Background Tachyarrhythmias and bradyarrhythmias affect 20%–50% of adult patients with tetralogy of Fallot (TOF) and some of these patients will require cardiac implantable electronic devices (CIED) such as pacemaker and/or internal cardioverter defibrillator. Methods The Mayo Adult Congenital Heart Disease database was queried for patients with repaired TOF and history of CIED implantation, 1990–2017. The study objectives were: (1) determine the occurrence of device-related complications defined as lead failure, lead recall, device infection and lead thrombus; and (2) determine the occurrence and risk factors for defibrillator shock. Results There were 99 patients (age 46±14 years and 66 (66%) men) with CIED, and the CIEDs were 41 (41%) pacemakers and 73 (73%) defibrillators. Indication for defibrillator implantation was for primary prevention in 28 (38%) and secondary prevention in 45 (62%). Device-related complications occurred in 20 (20%) patients (lead failure 17, lead recall 4, device infection 12 and thrombus 3). Twenty-five per cent of all device infections occurred within 30 days from the time of device generator change. Annualised rates of appropriate and inappropriate shocks were 5.7% and 6.2%, respectively. The use of class III antiarrhythmic drug was protective against defibrillator shock. Conclusion The current study provides useful outcome data to aid patient counselling and clinical decision-making. Further studies are required to explore ways to decrease the risk of postprocedural infection after device generator change, and to determine which patients will benefit from empirical antiarrhythmic therapy as a strategy to decrease incidence of inappropriate defibrillator shock.

The term “idiopathic calcifying tenosynovitis” (ICT) refers to a clinically and radiologically defined syndrome of pain and tendinous calcifications, most often involving the shoulder joint. A distinctive subset of ICT cases, termed “tenosynovitis with psammomatous calcifications” (TPC), occurs in the distal extremities and shows characteristic morphology, in particular psammomatous calcifications. As only 14 cases have been reported to date, TPC remains poorly recognized by both pathologists and clinicians. Twenty-three well-characterized cases of TPC along with all available radiologic and clinical information, including follow-up, were collected. Cases occurred in 21 females and 1 male (1 patient of unknown sex), aged 16 to 75 years (mean: 41), and almost exclusively involved the fingers and toes, except for one case in the elbow and one in the knee joint. The lesions ranged from 2 to 30 mm in size (mean: 10 mm). Pain was the most common presenting symptom (12/16 patients). A history of trauma or repetitive activity was present in 6 of 15 patients. None of the individuals was known to have disorders in calcium or phosphate metabolism. Radiographic studies showed a nonspecific, calcified mass. Typical morphologic features of TPC were invariably present, with degenerating tendinous tissue containing psammomatous calcifications, surrounded by a variably cellular, CD68/CD163/CD4-positive histiocyte-rich granulomatous host reaction. HUMARA assay in one case showed a polyclonal pattern. Clinical follow-up (19 patients; mean: 5.2 y; range: 1 to 14 y) showed no local recurrences. In this, the largest study of TPC to date, we confirm striking predilection of this distinctive pseudoneoplasm for the fingers and toes of young to middle-aged women. TPC should be rigorously distinguished from other forms of ICT, which typically involve large, proximal joints, and show simply dystrophic calcification involving tendinous tissues, and from tumoral calcinosis, which also involves large joints and often is associated with calcium and/or phosphate abnormalities. TPC appears to be related to trauma and/or repetitive activity and is cured with simple excision.

Abstract The frequent von Willebrand factor (VWF) variant p.Phe2561Tyr is located within the C4 domain, which also harbors the platelet GPIIb/IIIa-binding RGD sequence. To investigate its potential effect on hemostasis, we genotyped 865 patients with coronary artery disease (CAD), 915 with myocardial infarction (MI), and 417 control patients (Ludwigshafen Risk and Cardiovascular Health Study) and performed functional studies of this variant. A univariate analysis of male and female carriers of the Tyr2561 allele aged 55 years or younger revealed an elevated risk for repeated MI (odds ratio, 2.53; 95% confidence interval [CI], 1.07-5.98). The odds ratio was even higher in females aged 55 years or younger, at a value of 5.93 (95% CI, 1.12-31.24). Cone and plate aggregometry showed that compared with Phe2561, Tyr2561 was associated with increased platelet aggregate size both in probands’ blood and with the recombinant variants. Microfluidic assays revealed that the critical shear rate for inducing aggregate formation was decreased to 50% by Tyr2561 compared with Phe2561. Differences in C-domain circular dichroism spectra resulting from Tyr2561 suggest an increased shear sensitivity of VWF as a result of altered association of the C domains that disrupts the normal dimer interface. In summary, our data emphasize the functional effect of the VWF C4 domain for VWF-mediated platelet aggregation in a shear-dependent manner and provide the first evidence that a functional variant of VWF plays a role in arterial thromboembolism.