External loop recorders: determinants of diagnostic yield in patients with syncope

Objectives

The purpose of the current study was to determine the optimal duration of external loop recorder (ELR) monitoring in patients with presyncope or syncope and to identify factors that predict failure to activate the device effectively.

Design

A multivariate analysis was performed using data from the Comparison Of Loop Recorders Against Holter in Patients with Syncope (COLAPS) trial, a prospective study comparing diagnostic utility of ELRs and Holter monitors for assessment of syncope.

Methods

Patients with failure to effectively activate ELRs were compared to those who were successful. This analysis was performed separately for failure of test transmission and for failure to successfully record and transmit data from symptomatic episodes. Patient characteristics were compared among the groups to determine risk factors for device failure.

Results

Among 78 patients who received ELRs, a test transmission was successfully performed by 84.5% of patients. Twenty-one percent of diagnoses were made within 48 hours, 50% at 15 days, and 90% at 33 days. Patients performing a successful test transmission were more familiar with technology, with ability to use a bank automatic teller machine being a significant independent predictor. Patients with a successful test transmission were, in turn, significantly more likely to record and transmit data from symptomatic episodes. Patients living alone were much less likely to use the loop recorder effectively. The presence of factors that may influence motivation to reach a diagnosis (degree of worry/fear of symptoms and impact on daily life) were associated with successful use of the device in a univariate analysis.

Conclusion

ELRs should be worn for at least 30 days to maximize their diagnostic yield. Patients who are unfamiliar with technology, live alone, or have low motivation to reach a diagnosis have a lower diagnostic yield from ELRs for assessment of syncope.     

Evidence of vector-borne disease of Early Cretaceous reptiles

A blood-filled sand fly, Palaeomyia burmitis, was recently described from Early Cretaceous Burmese amber. Within the alimentary canal of this sand fly were the amastigotes and promastigotes of a digenetic leishmanial trypanosomatid. Inside the lumen of the thoracic midgut of the fossil sand fly were nucleated blood cells, some of which were intact and others in various stages of lysis and disintegration. The present study identifies these blood cells as reptilian and describes putative developing amastigotes inside spherical to oval whitish vacuoles within some of the fossil blood cells. The significance of this find is discussed, especially regarding the high possibility that Cretaceous dinosaurs were infected by trypanosomatids.     

Sleepiness, Troika of Consciousness Cycle, and the Epworth Sleepiness Scale

Excessive daytime sleepiness (EDS) is an important indicator when diagnosing sleep-disordered breathing and evaluating its treatment results. However, there appears to be some confusion as to what exactly is sleepiness; Dorlands Illustrated Medical Dictionary does not help. The medical literature was reviewed in order to assemble a schematic model that would suggest a definition of sleepiness and how it can be measured. The derived model is entitled the troika of consciousness cycle (TCC). It assumes that the presence of wakefulness, nonrapid eye movement sleep (NREMS), and rapid eye movement sleep (REMS) is determined by the interactions of four drives: two promoting wakefulness and one each for the two sleep states. The TCC illustrates that inadequate sleep results in sleep debt, but that sleepiness is determined solely by the nearness of the secondary wake drive line to the NREMS drive line. Contact of these lines indicates dozing, a change in consciousness state, an observable event. The probability of this event may be defined as objective sleepiness; this is what the Epworth sleepiness scale (ESS) attempts to measure. Studies indicate that the ESS can determine EDS with greater sensitivity and selectivity than either the multiple sleep latency test or the maintenance of wakefulness test.     

Morphological disruption of colonic mucosa by free or cholestyramine-bound bile acids

In order to assess the effects of free or resin-bound bile acids on colonic topography, adult rats were surgically provided with an indwelling infusion catheter in the proximal cecum, which exited at the neck behind the head. Conscious, unrestrained rats were allowed chowad libitum and were administered 1 ml of an infusion mixture twice daily for five days. The infusion mixtures included either carrier saline, 100 mg cholestyramine, 165 μmol mixed bile acids, or the bile acids bound to cholestyramine. Additional groups of rats were fed defined diets with and without 2% cholestyramine. Compared to fed controls, colonic infusions of saline had little effect on colon topography. Infusions of 100 mg of cholestyramine in saline twice each day did cause some apparent damage to surface morphology of the colon, but not to the extent observed during feeding of the resin as 2% of the diet. In contrast, extensive surface damage of the colon was observed by twice daily infusions of either 165 μmol of an equimolar mixture of cholic, deoxycholic, and chenodeoxycholic acids, or by the bile acids mixed previously with the ion-exchange resin. The data suggest that topographical damage of the colon observed during feeding of bile acid-sequestering resins is in large part due to increased concentrations of either bound or unbound bile acids in the large bowel.     

The 'Open-Artery Hypothesis': new clinical and pathophysiologic insights

The open-artery hypothesis states that myocardial reperfusion, even if late for myocardial salvage, provides benefits and prevents adverse cardiac remodeling. While observational data in humans regarding the deleterious impact of a permanent infarct-related artery occlusion and the benefits of spontaneous reperfusion are quite consistent, the reports regarding late revascularization are inconclusive in order to prove such a hypothesis. The observational studies tend to have selection biases, while randomized trials to date are too small to be conclusive. Moreover, the pathophysiological mechanisms underlying presumed benefits of reperfusion are still unclear. However, although the open-artery hypothesis remains unproven, the current evidence suggesting benefits calls for additional studies. Limitations of ischemic left ventricular dilatation and myopathy could markedly reduce cardiovascular morbidity and mortality after acute myocardial infarction.     

Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans

Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of cross-reactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg-produced split influenza vaccine. CR antibodies accounted for 73% ± 18% of the serum vaccine responses in a cohort of elderly donors, 65% ± 15% in late middle-aged donors, and only 13% ± 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccine-H1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Galβ1-4GalNAcβ), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza.     

Selection and evaluation of single domain antibodies toward MS2 phage and coat protein

MS2 phage (MS2 Ø) is a coli phage, non-pathogenic to eukaryotic cells, which has been used as a simulant for viral biothreats, such as those causing smallpox and hemorrhagic fever. MS2 Ø consists of an icosahedral capsid, 28 nm in diameter, and a single stranded RNA genome; the viral capsid is composed of 180 copies of coat protein (CP). In this study, we isolated anti-MS2 Ø single domain antibodies (sdAbs) for the sensitive detection of the MS2 Ø. To achieve this, a first immune sdAb library was prepared from llamas immunized with purified coat protein and a second from animals immunized with MS2 Ø. By panning the two libraries against CP, MS2 Ø, or alternating between the two targets, anti-MS2 Ø and anti-CP sdAbs were selected, sequenced, and characterized for their binding affinity. Both direct binding assays and capture sandwich assays were performed on the MAGPIX platform. One of the best anti-MS2 Ø sdAb, Lib2CP12H, could detect MS2 Ø concentrations as low as 1.45 ng/mL (～5.0E+6 pfu/mL), providing equivalent detection to conventional antibodies. This sdAb is thermally stable with a melting temperature around 60 °C and recovered 80% of its secondary structure after heat denaturation.