Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients.

BACKGROUND After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels. OBJECTIVE To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning. PATIENTS / METHODS This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy. RESULTS Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83. CONCLUSIONS When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5-2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.

The deglaciation history of the Simplon region (southern Swiss Alps) constrained by 10Be exposure dating of ice-molded bedrock surfaces

The deglaciation history of the Swiss Alps after the Last Glacial Maximum involved the decay of several ice domes and the subsequent disintegration of valley glaciers at high altitude. Here we use bedrock exposure dating to reconstruct the temporal and spatial pattern of ice retreat at the Simplon Pass (altitude: ∼2000 m) located 40 km southwest of the ‘Rhône ice dome’. Eleven 10Be exposure ages from glacially polished quartz veins and ice-molded bedrock surfaces cluster tightly between 13.5 ± 0.6 ka and 15.4 ± 0.6 ka (internal errors) indicating that the Simplon Pass depression became ice-free at 14.1 ± 0.4 ka (external error of mean age). This age constraint is interpreted to record the melting of the high valley glaciers in the Simplon Pass region during the warm Bølling–Allerød interstadial shortly after the Oldest Dryas stadial. Two bedrock samples collected a few hundred meters above the pass depression yield older 10Be ages of 17.8 ± 0.6 ka and 18.0 ± 0.6 ka. These ages likely reflect the initial downwasting of the Rhône ice dome and the termination of the ice transfluence from the ice dome across the Simplon Pass toward the southern foreland. There, the retreat of the piedmont glacier in Val d’Ossola was roughly synchronous with the decay of the Rhône ice dome in the interior of the mountain belt, as shown by 10Be ages of 17.7 ± 0.9 ka and 16.1 ± 0.6 ka for a whaleback at ∼500 m elevation near Montecrestese in northern Italy. In combination with well-dated paleoclimate records derived from lake sediments, our new age data suggest that during the deglaciation of the European Alps the decay of ice domes was approximately synchronous with the retreat of piedmont glaciers in the foreland and was followed by the melting of high-altitude valley glaciers after the transition from the Oldest Dryas to the Bølling–Allerød, when mean annual temperatures rose rapidly by ∼3 °C.

Use of antiarrhythmic drugs during ablation of persistent atrial fibrillation: observations from a large single-centre cohort

Catheter ablation of complex fractionated atrial electrograms (CFAE), also known as defragmentation ablation, may be considered for the treatment of persistent atrial fibrillation (AF) beyond pulmonary vein isolation (PVI). Concomitant antiarrhythmic drug (AAD) therapy is common, but the relevance of AAD administration and its optimal timing during ablation remain unclear. Therefore, we investigated the use and timing of AADs during defragmentation ablation and their possible implications for AF termination and ablation success in a large cohort of patients. Retrospectively, we included 200 consecutive patients (age: 61 ± 12 years, LA diameter: 47 ± 8 mm) with persistent AF (episode duration 47 ± 72 weeks) who underwent de novo ablation including CFAE ablation. In all patients, PVI was performed prior to CFAE ablation. The use and timing of AADs were registered. The follow-ups consisted of Holter ECGs and clinical visits. Termination of AF was achieved in 132 patients (66 %). Intraprocedural AADs were administered in 168/200 patients (84 %) 45 ± 27 min after completion of PVI. Amiodarone was used in the majority of the patients (160/168). The timing of AAD administration was predicted by the atrial fibrillation cycle length (AFCL). At follow-up, 88 patients (46 %) were free from atrial arrhythmia. Multivariate logistic regression analysis revealed that administration of AAD early after PVI, LA size, duration of AF history, sex and AFCL were predictors of AF termination. The administration of AAD and its timing were not predictive of outcome, and age was the sole independent predictor of AF recurrence. The administration of AAD during ablation was common in this large cohort of persistent AF patients. The choice to administer AAD therapy and the timing of the administration during ablation were influenced by AFCL, and these factors did not significantly influence the moderate single procedure success rate in this retrospective analysis.

Interventional management of recurrent paroxysmal atrial fibrillation despite isolated pulmonary veins: impact of an ablation strategy targeting inducible atrial tachyarrhythmias

AIMS Pulmonary vein isolation (PVI) is an effective treatment option for paroxysmal atrial fibrillation (PAF). Reconnection of pulmonary veins (PVs) is the predominant cause for recurrence of PAF. However, treatment of patients with recurrence of PAF despite isolated PV in the absence of extra-PV foci remains challenging. METHODS AND RESULTS Of 265 patients undergoing repeat catheter ablation (CA) for recurrence of PAF 21 (8%) patients (14 men, age 58 ± 14 years) showed no reconnection of PV. Therefore, inducibility of sustained atrial arrhythmias was tested. If sustained atrial fibrillation (AF) or sustained atrial tachycardia (AT) was induced, patients underwent CA. During follow-up (FU), Holter- and Tele-electrocardiogram were performed. In 19 (91%) of 21 patients, sustained atrial arrhythmias [16 (84%) AF; 3 (15%) patients AT] were induced. One patient showed PAF. Eighteen patients underwent CA aiming for termination of induced arrhythmia. In 14 (77%) patients, termination into sinus rhythm was achieved. Despite extensive CA, three (16%) patients were externally cardioverted. No periprocedural complications occurred. During 21.2 ± 6.8-month FU, 10 (53%) patients were free of any arrhythmia. Paroxysmal atrial fibrillation recurred in 4 (21%) and AT in 5 (26%) patients. One patient showed persistent AF. Repeat CA was scheduled and successfully performed for these patients. CONCLUSION In patients with recurrence of PAF despite isolated PV, termination of induced atrial arrhythmias can be achieved in most patients by defragmentation and AT ablation. Moreover, this ablation strategy results in favourable mid-term outcome results.

Clinical and pharmacokinetic evaluation of S-ketamine for intravenous general anaesthesia in horses undergoing field castration.

BACKGROUND Intravenous anaesthetic drugs are the primary means for producing general anaesthesia in equine practice. The ideal drug for intravenous anaesthesia has high reliability and pharmacokinetic properties indicating short elimination and lack of accumulation when administered for prolonged periods. Induction of general anaesthesia with racemic ketamine preceded by profound sedation has already an established place in the equine field anaesthesia. Due to potential advantages over racemic ketamine, S-ketamine has been employed in horses to induce general anaesthesia, but its optimal dose remains under investigation. The objective of this study was to evaluate whether 2.5 mg/kg S-ketamine could be used as a single intravenous bolus to provide short-term surgical anaesthesia in colts undergoing surgical castration, and to report its pharmacokinetic profile. RESULTS After premedication with romifidine and L-methadone, the combination of S-ketamine and diazepam allowed reaching surgical anaesthesia in the 28 colts. Induction of anaesthesia as well as recovery were good to excellent in the majority (n = 22 and 24, respectively) of the colts. Seven horses required additional administration of S-ketamine to prolong the duration of surgical anaesthesia. Redosing did not compromise recovery quality. Plasma concentration of S-ketamine decreased rapidly after administration, following a two-compartmental model, leading to the hypothesis of a consistent unchanged elimination of the parent compound into the urine beside its conversion to S-norketamine. The observed plasma concentrations of S-ketamine at the time of first movement were various and did not support the definition of a clear cut-off value to predict the termination of the drug effect. CONCLUSIONS The administration of 2.5 mg/kg IV S-ketamine after adequate premedication provided good quality of induction and recovery and a duration of action similar to what has been reported for racemic ketamine at the dose of 2.2 mg/kg. Until further investigations will be provided, close monitoring to adapt drug delivery is mandatory, particularly once the first 10 minutes after injection are elapsed. Taking into account rapid elimination of S-ketamine, significant inter-individual variability and rapid loss of effect over a narrow range of concentrations a sudden return of consciousness has to be foreseen.

Prospective analysis of adrenal function in patients with acute exacerbations of COPD: the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial

OBJECTIVE To analyze prospectively the hypothalamic-pituitary-adrenal (HPA) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease (COPD). DESIGN Prospective observational study. SUBJECTS AND METHODS Patients presenting to the emergency department were randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner. The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline, on day 6 before blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of the test results. Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment. RESULTS A total of 311 patients were included in the analysis. Mean basal and stimulated serum total cortisol levels were highest on admission (496±398 and 816±413 nmol/l respectively) and lowest on day 6 (235±174 and 453±178 nmol/l respectively). Pathological stimulation tests were found in 63, 38, 9, 3, and 2% of patients on day 6, at discharge, and on days 30, 90, and 180 respectively, without significant difference between treatment groups. Clinical indicators of hypocortisolism did not correlate with stimulation test results, but cortisol levels were inversely associated with re-exacerbation risk. There were no hospitalizations or deaths as a result of adrenal crisis. CONCLUSION Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD. In hypocortisolemic patients who were provided with instructions about stress prophylaxis, the abrupt termination of prednisone appeared safe.

Enhanced depth imaging optical coherence tomography of congenital cavitary optic disc anomaly (CODA).

AIM To report the finding of extension of the 4th hyper-reflective band and retinal tissue into the optic disc in patients with cavitary optic disc anomalies (CODAs). METHODS In this observational study, 10 patients (18 eyes) with sporadic or autosomal dominant CODA were evaluated with enhanced depth imaging optical coherence tomography (EDI-OCT) and colour fundus images for the presence of 4th hyper-reflective band extension into the optic disc. RESULTS Of 10 CODA patients (18 eyes), five patients (8 eyes) showed a definite 4th hyper-reflective band (presumed retinal pigment epithelium (RPE)) extension into the optic disc. In these five patients (seven eyes), the inner retinal layers also extended with the 4th hyper-reflective band into the optic disc. Best corrected visual acuity ranged from 20/20 to 20/200. In three patients (four eyes), retinal splitting/schisis was present and in two patients (two eyes), the macula was involved. In all cases, the 4th hyper-reflective band extended far beyond the termination of the choroid into the optic disc. The RPE extension was found either temporally or nasally in areas of optic nerve head excavation, most often adjacent to peripapillary pigment. Compared with eyes without RPE extension, eyes with RPE extension were more myopic (mean dioptres -0.9±2.6 vs -8.8±5, p=0.043). CONCLUSIONS The RPE usually stops near the optic nerve border separated by a border tissue. With CODA, extension of this hyper-reflective band and retinal tissue into the disc is possible and best evaluable using EDI-OCT or analogous image modalities. Whether this is a finding specific for CODA, linked to specific gene loci or is also seen in patients with other optic disc abnormalities needs further evaluation.

Adrenal insufficiency after glucocorticoid withdrawal in children with rheumatic diseases

?Glucocorticoids (GCs) are often used for the treatment of rheumatic disorders. However, doses are prescribed, which may suppress the hypothalamic-pituitary-adrenal (HPA) axis. After GC withdrawal, recovery of the HPA axis may be delayed putting the patient at risk for adrenal insufficiency. We assessed adrenal function and factors influencing adrenal responsiveness after termination of GC therapy in paediatric patients with rheumatic diseases.

Ca(2+) release from the sarcoplasmic reticulum activated by the low affinity Ca(2+) chelator TPEN in ventricular myocytes

The Ca(2+) content of the sarcoplasmic reticulum (SR) of cardiac myocytes is thought to play a role in the regulation and termination of SR Ca(2+) release through the ryanodine receptors (RyRs). Experimentally altering the amount of Ca(2+) within the SR with the membrane-permeant low affinity Ca(2+) chelator TPEN could improve our understanding of the mechanism(s) by which SR Ca(2+) content and SR Ca(2+) depletion can influence Ca(2+) release sensitivity and termination. We applied laser-scanning confocal microscopy to examine SR Ca(2+) release in freshly isolated ventricular myocytes loaded with fluo-3, while simultaneously recording membrane currents using the whole-cell patch-clamp technique. Following application of TPEN, local spontaneous Ca(2+) releases increased in frequency and developed into cell-wide Ca(2+) waves. SR Ca(2+) load after TPEN application was found to be reduced to about 60% of control. Isolated cardiac RyRs reconstituted into lipid bilayers exhibited a two-fold increase of their open probability. At the low concentration used (20-40muM), TPEN did not significantly inhibit the SR-Ca(2+)-ATPase in SR vesicles. These results indicate that TPEN, traditionally used as a low affinity Ca(2+) chelator in intracellular Ca(2+) stores, may also act directly on the RyRs inducing an increase in their open probability. This in turn results in an increased Ca(2+) leak from the SR leading to its Ca(2+) depletion. Lowering of SR Ca(2+) content may be a mechanism underlying the recently reported cardioprotective and antiarrhythmic features of TPEN.

Hereditary hydrocephalus in laboratory-reared golden hamsters (Mesocricetus auratus)

A colony of golden hamsters had an ongoing problem with hydrocephalus. In an attempt to clear the colony of the problem, new breeders from another supplier had been purchased. At termination of a behavioral study, the brain was collected from 35 animals (four of which had died with hydrocephalus during the study) and was examined macroscopically and by light microscopy. Although no animals manifested obvious behavioral changes, 31 of 35 (88.6%, 13/15 males and 18/20 females in control and manipulated groups) had hydrocephalus. Twenty-five animals had macroscopically identifiable hydrocephalus, and six had hydrocephalus identified microscopically. Neither teratogenic concentrations of metals nor mycotoxins were detected in tissues or food, and sera from breeders tested negative for antibodies to Sendai virus, reovirus 3, and lymphocytic choriomeningitis virus. Trial matings of breeders expected to produce hydrocephalic offspring resulted in affected offspring, and mating of breeders expected to produce normal offspring resulted in normal or less-affected offspring. Hydrocephalus was confirmed retrospectively in some breeders. Hereditary hydrocephalus appears to be widespread in hamster stocks in Central Europe. Affected animals do not manifest signs of disease and usually die without obvious premonitory signs. Despite severe hydrocephalus, the animals can breed, and animal handlers do not identify motor deficits or abnormal behavioral activity. This entity is unlike the previously described, hereditary hydrocephalus of hamsters that is phenotypically identifiable and usually is lethal before they attain breeding age.

Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis

BACKGROUND: We assessed the incidence of early recurrent ischemic stroke in stroke patients treated with intravenous tissue-type plasminogen activator (tPA) and the temporal pattern of its occurrence compared with symptomatic intracranial hemorrhage (ICH). METHODS AND RESULTS: Prospectively collected, population-based data for 341 consecutive acute stroke patients (62% men; mean age, 66 years) treated with tPA according to the National Institute of Neurological Disorders and Stroke study protocol at 8 medical centers in Switzerland (3 academic and 5 community) between January 2001 and November 2004 were retrospectively analyzed. The primary outcome measure was neurological deterioration > or = 4 points on the National Institutes of Health Stroke Scale occurring within 24 hours of tPA treatment and caused either by recurrent ischemic stroke (defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography scans, in the absence of ICH) or by ICH. Early recurrent ischemic stroke was diagnosed in 2 patients (0.59%; 95% confidence interval, 0.07% to 2.10%) and symptomatic ICH in 15 patients (4.40%; 95% confidence interval, 2.48% to 7.15%). Both recurrent ischemic strokes occurred during thrombolysis, whereas symptomatic ICHs occurred 2 to 22 hours after termination of tPA infusion. CONCLUSIONS: Recurrent ischemic stroke is a rare cause of early neurological deterioration in acute stroke patients undergoing intravenous thrombolysis, with a different temporal pattern compared with that of symptomatic ICH.

Efalizumab-associated papular psoriasis

BACKGROUND: Efalizumab is a human anti-CD11a monoclonal antibody used in the treatment of patients with moderate to severe plaque psoriasis. Some of the patients develop new papular lesions during treatment, which are predominantly located in the flexural regions. OBSERVATION: Four patients with recalcitrant psoriasis undergoing treatment with efalizumab presented with erythematous, partly scaly papules and small plaques on previously unaffected areas after 4 to 10 weeks of efalizumab therapy. Tissue sections of biopsy specimens were stained with hematoxylin-eosin, and immunohistochemical staining was performed using monoclonal antibodies against CD3, CD4, CD8, T-cell-restricted intracellular antigen 1, granzyme B, neutrophil elastase, CD68, CD1a, CD11c, HLA-DR, CD25, CD20, and CD56. Histopathological and immunohistochemical examination of the lesions showed features consistent with psoriasis and activation of various leukocyte subtypes including T cells, dendritic cells, macrophages, and neutrophils. CONCLUSIONS: Papular eruptions appearing during efalizumab therapy represent new psoriatic lesions and could be referred to as efalizumab-associated papular psoriasis (EAPP). They usually do not necessitate termination of efalizumab therapy and may optionally be treated with topical corticosteroids. Dermatologists should be aware of these lesions and inform their patients accordingly.

Dextran sulfate modulates MAP kinase signaling and reduces endothelial injury in a rat aortic clamping model

OBJECTIVE: Mitogen-activated protein kinases (MAPKs), including JNK, p38, and ERK1/2, noticeably influence ischemia/reperfusion injury (IRI). The complement inhibitor dextran sulfate (DXS) associates with damaged endothelium denudated of its heparan sulfate proteoglycan (HSPG) layer. Other glycosaminoglycan analogs are known to influence MAPK signaling. Hypothetically therefore, targeted intravascular cytoprotection by DXS may function in part through influencing MAPK activation to reduce IRI-induced damage of the vasculature. METHODS: IRI of the infrarenal aorta of male Wistar rats was induced by 90 minutes clamping followed by 120 minutes reperfusion. DXS (5 mg/mL) or physiologic saline (NaCl controls) was infused locally into the ischemic aortic segment immediately prior to reperfusion. Ninety minutes ischemia-only and heparinase infusion (maximal damage) experiments, as well as native rat aorta, served as controls. Aortas were excised following termination of the experiments for further analysis. RESULTS: DXS significantly inhibited IRI-induced JNK and ERK1/2 activation (P = .043; P =.005) without influencing the p38 pathway (P =.110). Reduced aortic injury, with significant inhibition of apoptosis (P = .032 for DXS vs NaCl), correlated with decreased nuclear factor kappaB translocation within the aortic wall. DXS treatment clearly reduced C1q, C4b/c, C3b/c, and C9 complement deposition, whilst preserving endothelial cell integrity and reducing reperfusion-induced HSPG shedding. Protection was associated with binding of fluorescein labeled DXS to ischemically damaged tissue. CONCLUSIONS: Local application of DXS into ischemic vasculature immediately prior to reperfusion reduces complement deposition and preserves endothelial integrity, partially through modulating activation of MAPKs and may offer a new approach to tackle IRI in vascular surgical procedures. CLINICAL RELEVANCE: The purpose of the present study was to determine the role of dextran sulfate (DXS), a glycosaminoglycan analog and complement inhibitor, in modulating intracellular MAPK signaling pathways, reducing complement activation and ultimately attenuating ischemia/reperfusion injury (IRI) in a rat aortic-clamping model, in part a surrogate model to study the microvasculature. The study shows a role for DXS in ameliorating endothelial injury by reducing IRI-mediated damage and intravascular, local inflammation in the affected aortic segment. DXS may be envisaged as an endothelial protectant in vascular injury, such as occurs during vascular surgical procedures.

Chronic schizophrenics with positive symptomatology have shortened EEG microstate durations

OBJECTIVE: In young, first-episode, never-treated schizophrenics compared with controls, (a) generally shorter durations of EEG microstates were reported (Koukkou et al., Brain Topogr 6 (1994) 251; Kinoshita et al., Psychiatry Res Neuroimaging 83 (1998) 58), and (b) specifically, shorter duration of a particular class of microstates (Koenig et al., Eur Arch Psychiatry Clin Neurosci 249 (1999) 205). We now examined whether older, chronic schizophrenic patients with positive symptomatology also show these characteristics. METHODS: Multichannel resting EEG (62.2 s/subject) from two subject groups, 14 patients (36.1+/-10.2 years old) and 13 controls (35.1+/-8.2 years old), all males, was analyzed into microstates using a global approach for microstate analysis that clustered the microstates into 4 classes (Koenig et al., 1999). RESULTS: (a) Hypothesis testing of general microstate shortening supported a trend (P=0.064). (b) Two-way repeated measure ANOVA (two subject groupsx4 microstate classes) showed a significant group effect for microstate duration. Posthoc tests revealed that a microstate class with brain electric field orientation from left central to right central-posterior had significantly shorter microstates in patients than controls (68.5 vs. 76.1 ms, P=0.034). CONCLUSIONS: The results were in line with the results from young, never-treated, productive patients, thus suggesting that in schizophrenic information processing, one class of mental operations might intermittently cause deviant mental constructs because of premature termination of processing.

Frequent ventricular tachycardias: antiarrhythmic drug treatment or catheter ablation?

Antiarrhythmic drugs are used in at least 50% of patients who received an implantable cardioverter defibrillator (ICD). The potential indications for antiarrhythmic drug treatments in patients with an ICD are generally the following: reduction of the number of ventricular tachycardias (VTs) or episodes of ventricular fibrillation and therefore reduction of the number of ICD therapies, most importantly, the number of disabling ICD shocks. Accordingly, the quality of life should be improved and the battery life of the ICD extended. Moreover, antiarrhythmic drugs have the potential to increase the tachycardia cycle length to allow termination of VTs by antitachycardia pacing and reduction of the number of syncopes. In addition, supraventricular arrhythmias can be prevented or their rate controlled. Recently published or reported trials have shown the efficacy of amiodarone, sotalol and azimilide to significantly reduce the number of appropriate and inappropriate ICD shocks in patients with structural heart disease. However, the use of antiarrhythmic drugs may also have adverse effects: an increase in the defibrillation threshold, an excessive increase in the VT cycle length leading to detection failure. In this situation and when antiarrhythmic drugs are ineffective or have to be stopped because of serious side effects, catheter ablation of both monomorphic stable and pleomorphic and/or unstable VTs using modern electroanatomic mapping systems should be considered. The choice of antiarrhythmic drug treatment and the need for catheter ablation in ICD patients with frequent VTs should be individually tailored to specific clinical and electrophysiological features including the frequency, the rate, and the clinical presentation of the ventricular arrhythmia. Although VT mapping and ablation is becoming increasingly practical and efficacious, ablation of VT is mostly done as an adjunctive therapy in patients with structural heart disease and ICD experiencing multiple shocks, because the recurrence and especially the occurrence of "new" VTs after primarily successful ablation with time and disease progression have precluded a widespread use of catheter ablation as primary treatment.