Gas flow during bronchoscopic ablation therapy causes gas emboli to the heart: a comparative animal study

BACKGROUND: Thermal ablation is one of the most commonly used modalities to treat central airway obstruction. Both laser and argon plasma coagulation (APC) have been reported to cause gas emboli and cardiac arrest. We sought to determine whether bronchoscopic ablation therapy can result in systemic gas emboli, correlate their presence with the rate of gas flow, and establish whether a zero-flow (ZF) modality would result in the significant reduction or elimination of emboli. METHODS: CO(2) laser delivered through a photonic bandgap fiber (PBF) and APC were applied in the trachea and mainstem bronchi of six anesthetized sheep at varying dosages and gas flow rates. Direct epicardial echocardiography was used to obtain a four-chamber view and detect gas emboli. RESULTS: The presence of gas flow accompanying APC and the CO(2) laser with forward flow correlated significantly with the appearance of gas bubbles in the atria. A definite dose response was observed between the gas flow rate and the number of bubbles seen. When the CO(2) laser was delivered through a PBF with ZF to the trachea or bronchi, no bubbles were observed. CONCLUSION: Bronchoscopic thermal ablation therapy using gas flow is associated with gas emboli in a dose-dependent fashion. The use of the flexible PBF with ZF is not associated with the development of gas emboli. Further study is required to determine whether a clinically safe threshold of gas emboli exists, and the relationships among the pathologic depth of tissue destruction, gas flow, pulse duration, and the development of gas emboli.     

Isolated superior mesenteric artery dissection in the emergency department: A rare cause of abdominal pain

Acute onset abdominal pain constitutes a significant proportion of emergency department visits, but only a small fraction of these cases are attributable to vascular pathologies (Bauersfeld, 1947 [1]). In this case, report, we present an incidental diagnosis of Spontaneous Isolated Superior Mesenteric Artery Dissection (SISMAD). A 69-year-old man was admitted to the emergency department complaining of fever, loss of appetite, vague epigastric pain, dysuria, and a productive cough for several days. A lower extremity venous Doppler ultrasound was performed, and a deep venous thrombosis (DVT) was identified in the left main femoral vein and in the proximal segment of the superficial vein. The patient also had no blood flow in the distal part of left external iliac vein. A contrast-enhanced computerized tomography angiography of the thorax and abdomen was performed to detect pulmonary embolism and the etiology of the abdominal pain. No pulmonary embolism was found; however, multiple metastatic nodules were identified in both lungs, as well as infiltration on the posterobasal field of the right lung, metastases on the liver, focal dilatation, and an intimal flap on the middle-distal part of the superior mesenteric artery (SMA) at 2?cm, with a segment that was compatible with isolated dissection. There was a contrast passage on the distal part of SMA, and no sign of bowel ischemia.     

Molecular dynamics simulations provide molecular insights into the role of HLA‐B51 in Behçet's disease pathogenesis

Behçet's disease is an inflammatory disorder of unknown etiology. Genetic tendency has an important role in its pathogenesis, and HLA‐B51, a class I MHC antigen, has been recognized as the strongest susceptibility factor for Behçet's disease. Despite the confirmation of the association of HLA‐B51 with Behçet's disease in different populations, its pathogenic mechanisms remain elusive. HLA‐B51 differs in only two amino acids from HLA‐B52, other split antigen of HLA‐B5, which is not associated with Behçet's disease. These two amino acids are located in the B pocket of the antigen‐binding groove, which occupies the second amino acids of the bound peptides. To understand the nature of the HLA–peptide interactions, differences in structure and dynamics of two HLA alleles were investigated by molecular dynamics simulations using YAYDGKDYI, LPRSTVINI, and IPYQDLPHL peptides. For HLA‐B51, all bound peptides fluctuated to larger extent than HLA‐B52. Free energy profiles of unbinding process for YAYDGKDYI by steered molecular dynamics simulations showed that unbinding from HLA‐B52 results in greater free energy differences than HLA‐B51. These results suggest the possibility of an instability of HLA‐B51 associated with the repertoire of peptides, and this finding may provide significant insight to its pathogenic role in Behçet's disease.     

Extreme conformational diversity in human telomeric DNA

DNA with tandem repeats of guanines folds into G-quadruplexes made of a stack of G-quartets. In vitro, G-quadruplex formation inhibits telomere extension, and POT1 binding to the single-stranded telomeric DNA enhances telomerase activity by disrupting the G-quadruplex structure, highlighting the potential importance of the G-quadruplex structure in regulating telomere length in vivo. We have used single-molecule spectroscopy to probe the dynamics of human telomeric DNA. Three conformations were observed in potassium solution, one unfolded and two folded, and each conformation could be further divided into two species, long-lived and short-lived, based on lifetimes of minutes vs. seconds. Vesicle encapsulation studies suggest that the total of six states detected here is intrinsic to the DNA. Folding was severely hindered by replacing a single guanine, showing only the shortlived species. The long-lived folded states are dominant in physiologically relevant conditions and probably correspond to the parallel and antiparallel G-quadruplexes seen in high-resolution structural studies. Although rare under these conditions, the short-lived species determine the overall dynamics because they bridge the different long-lived species. We propose that these previously unobserved transient states represent the early and late intermediates toward the formation of stable G-quadruplexes. The major compaction occurs between the early and late intermediates, and it is possible that local rearrangements are sufficient in locking the late intermediates into the stably folded forms. The extremely diverse conformations of the human telomeric DNA may have mechanistic implications for the proteins and drugs that recognize G-rich sequences.     

Thrombus aspiration during primary percutaneous coronary intervention associated with reduced platelet activation

Objectives:

To determine the effect of thrombectomy on platelet function in patients undergoing primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction (STEMI).

Methods:

This retrospective study included 413 consecutive STEMI patients who underwent PPCI between March 2012 and September 2013 at Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey that were assigned to the thrombus aspiration (TA) group or the non-TA group. Platelet count and mean platelet volume (MPV) were obtained at baseline and 24 hours (h), 48 h, and 72 h post PPCI.

Results:

Baseline MPV was similar in both groups, whereas the baseline platelet count was higher in the TA group (p=0.42 and p=0.002). The platelet count was higher in the TA group 24 h post PPCI (p=0.02), but was similar in both groups 48 h and 72 h post PPCI (p=0.18 and p=0.07). The MPV 48 h and 72 h post PPCI was higher in the non-TA group than in the TA group (8.4 ± 1.3 fL versus 8.7 ± 1.6 fL [p=0.04] and 8.5 ± 1.1 fL versus 8.9 ± 1.5 fL [p=0.04]).

Conclusion:

Thrombectomy reduced platelet activity via removal of thrombi from the coronary arteries in patients undergoing PPCI for STEMI.In acute ST-segment elevation myocardial infarction (STEMI), the main initiating factor is atherosclerotic plaque rupture or erosion, then platelets become activated and aggregated leading to acute coronary artery occlusion.1 Primary percutaneous coronary intervention (PPCI) is the standard treatment in patients with STEMI.2 In recent years, implementation of adjunctive mechanical and pharmacological therapies during PPCI, including manual thrombus aspiration (TA), has improved myocardial reperfusion and clinical outcome in STEMI patients.3-5 In daily practice, thrombectomy devices are used to remove thrombi or to prevent embolization of thrombi and plaque during PPCI.6 Platelet volume is a marker of platelet activation and is measured via mean platelet volume (MPV).7 An increase in MPV can occur in cases of acute myocardial ischemia, acute myocardial infarction, coronary atherosclerosis,8,9 and early stent thrombosis (ST).10 The Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS) study5 showed that TA therapy during PPCI decreases mortality and reinfarction rate.5 We speculate that the good results obtained with TA therapy are not only related to improved tissue perfusion but also may be related to reduced platelet activation. Therefore, the present study aimed to determine the effect of thrombectomy on platelet function and ST in patients undergoing PPCI for STEMI.     

Body position and obstructive sleep apnea syndrome

In adults, influence of body position on the occurrence of respiratory events during sleep is recognized, and increased numbers of respiratory events occur when the supine position is assumed.1-4 In 1985, Orr et al. showed that body position did not influence respiratory events during sleep in children.5 Recently, Fernandes do Prado et al. showed that children had a lower obstructive apnea hypopnea index (AHI) in supine position.6 Results of these two studies are different from others performed on adults. Moreover, upper airway abnormalities were not considered in these studies.The aim of the present study was to evaluate the effect of body position on obstructive respiratory events in children with different upper airway findings.