Distinctive Roles and Mechanisms of Human Neutrophil Peptides in Experimental Sepsis and Acute Respiratory Distress Syndrome.

OBJECTIVES: To examine the effects and mechanisms of human neutrophil peptides in systemic infection and noninfectious inflammatory lung injury. DESIGN: Prospective experimental study. SETTING: University hospital-based research laboratory. SUBJECTS: In vitro human cells and in vivo mouse models. INTERVENTIONS: Wild-type (Friend virus B-type) and conditional leukocyte human neutrophil peptides transgenic mice were subjected to either sepsis induced by cecal ligation and puncture or acute lung injury by intratracheal instillation of hydrochloric acid followed by mechanical ventilation. Using human neutrophil peptides as bait, the basal cell adhesion molecule (CD239) and the purinergic P2Y purinoceptor 6 receptor were identified as the putative human neutrophil peptides receptor complex in human lung epithelial cells. MEASUREMENTS AND MAIN RESULTS: In the cecal ligation and puncture sepsis model, Friend virus B-type mice exhibited higher systemic bacterial load, cytokine production, and lung injury than human neutrophil peptides transgenic mice. Conversely, an increased lung cytokine production was seen in Friend virus B-type mice, which was further enhanced in human neutrophil peptides transgenic mice in response to two-hit lung injury induced by hydrochloric acid and mechanical ventilation. The human neutrophil peptides-mediated inflammatory response was mediated through the basal cell adhesion molecule-P2Y purinoceptor 6 receptor signal pathway in human lung epithelial cells. CONCLUSIONS: Human neutrophil peptides are critical in host defense against infectious sepsis by their cationic antimicrobial properties but may exacerbate tissue injury when neutrophil-mediated inflammatory responses are excessive in noninfectious lung injury. Targeting the basal cell adhesion molecule/P2Y purinoceptor 6 signaling pathway may serve as a novel approach to attenuate the neutrophil-mediated inflammatory responses and injury while maintaining the antimicrobial function of human neutrophil peptides in critical illness.

Three-dimensional localization versus fluoroscopically only guided ablations: a meta-analysis.

OBJECTIVES: Data regarding efficacy and safety of three-dimensional localization systems (3D) are limited. We performed a meta-analysis of randomized trials comparing combined fluoroscopy- and 3D guided to fluoroscopically-only guided procedures. DESIGN: A systematic search was performed using multiple databases between 1990 and 2010. Outcomes were acute and long-term success, ablation, procedure and fluoroscopic times, radiation dose (RD), and complications. RESULTS: Thirteen studies involving 1292 patients were identified. 3D were tested against fluoroscopic guidance in 666 patients for supraventricular tachycardia (SVT), atrial flutter (AFL), atrial fibrillation (AF), and ventricular tachycardia (VT). Acute and long-term freedom from arrhythmia was not significantly different between 3D and control for AFL (acute success, 97% vs. 93%, p = 0.57; chronic success, 93% vs. 96%, p = 0.90) or for SVT (acute success, 94% vs. 100%, p = 0.36; chronic success, 88% vs. 88%, p = 0.80). A shorter fluoroscopic time was achieved with 3D in AFL (p < 0.001) and in SVT (p = 0.002). RD was significantly less for both AFL (p = 0.002) and SVT (p = 0.01). Ablation and procedure time and complications were not statistically different. CONCLUSIONS: Success, procedure time, and complications were similar between fluoroscopy- and 3D-guided ablations. Fluoroscopic time and RD were significantly reduced for ablation of AFL and SVT with 3D.

Teaching NeuroImages: acute cerebellitis caused by Salmonella typhimurium.

A 63-year-old woman presented with 24 hours of dysarthria, confusion, and appendicular ataxia preceded by watery diarrhea, without fever, nausea, vomiting, meningeal signs, recent travel, or antibiotic use. She had type II diabetes and gastroesophageal reflux disease (on proton pump inhibitor). She had consumed inadequately cooked beef stew left at room temperature for 24 hours. Blood cultures were positive for Salmonella typhimurium. CSF showed 15 nucleated cells, 72% monocytoid; remainder of CSF was normal. MRI was consistent with cerebellitis (figure). At 3 months, after 3 weeks of IV ceftriaxone, she remained dysarthric with bilateral dysmetria.

Approaches to empiric ablation of slow pathway: results from the Canadian EP web survey.

AIM: Dual atrioventricular nodal physiology (DAVNP) is a frequent finding in patients with suspected or documented supraventricular tachycardia (SVT). Empiric slow pathway ablation (ESPA) is sometimes performed in patients with DAVNP without inducible SVT at the time of electrophysiological study. Evidence to guide this practice in the adult population is limited. This study was aimed to assess the practice of ESPA by adult electrophysiologists in Canada. METHODS: All Canadian interventional electrophysiologists (n = 81) were invited to complete a web-based questionnaire assessing their practice of ESPA in patients with suspected and documented SVT. Operator experience, reimbursement models, diagnostic, and treatment decisions regarding ESPA were assessed with case scenarios. RESULTS: Forty-one responses (50 %) were obtained. Ninety-five percent of the responders stated that the evidence for ESPA is lacking or limited. Responders were more likely to perform ESPA in the setting of non-inducible SVT when there was documentation of the clinical arrhythmia (64 vs. 31 % (p = 0.017)). The threshold to perform ESPA was highly variable. Longer time in practice (r = 0.38, p = 0.017) and less perceived complications with ESPA (r = 0.31, p = 0.05) were correlated with the practice of ESPA, whereas length of ablation waiting lists (r = -0.15, p = 0.38), number of procedures performed per day (r = 0.11, p = 0.51) and type of reimbursement (p = 0.24) were not associated with the practice of ESPA. The perceived complication rate with ESPA was <1 %. CONCLUSION: Variability in the practice of ESPA in cases of non-inducible SVT exists. Documentation of the clinical arrhythmia, operator experience, and perceived low complication rates positively influence this practice.

Interatrial block in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder that affects 5% of the adult North American population. It is associated with atrial arrhythmias and stroke. The mechanisms of this association remain unclear. The aim to the study was to identify the factors associated with interatrial block (IAB) among patients with OSA. METHODS: Patients referred for polysomnography were studied. Sleep apnea severity (apnea-hypopnea index [AHI]) was measured in each subject. 12-lead ECGs were scanned and amplified (× 10); P-wave duration and dispersion were measured using a semi-automatic caliper. IAB was defined as a P-wave duration ≥ 120 ms. RESULTS: Data from 180 consecutive patients was examined. Moderate-severe OSA (mean AHI = 56.2 ± 27.9) was present in 144 (OSA group). The remaining 36 had mild or no OSA (mean AHI = 5.6 ± 3.6) and were used as controls. Age distribution between the groups did not differ and there were more males in the OSA group (69.4% vs 47.2%, p = 0.01). Obesity (78.5% vs 39.4%, p < 0.001) and hypertension (51.4% vs 27.8%, p < 0.01) were more prevalent in the OSA group. IAB was more prevalent in patients with moderate-severe OSA (34.7% OSA vs 0% controls, p < 0.001). In linear regression, age and AHI > 30 were independent predictors of maximum P-wave duration (p = 0.001 and p < 0.001, respectively). P-wave dispersion was significantly higher in the severe OSA group (14.6 ± 7.5 for OSA, 8.9 ± 3.1 controls, p < 0.001). CONCLUSIONS: Older age and moderate-severe OSA are predictors of IAB. P-wave dispersion is increased in patients with moderate-severe OSA. This may partly explain the high prevalence of atrial arrhythmias in patients with OSA.