The frozen elephant trunk technique for the treatment of extensive thoracic aortic aneurysms: operative results and follow-up.

OBJECTIVE: The 'frozen' elephant trunk technique allows for single-stage repair of combined aortic arch and descending aortic aneurysms using a 'hybridprosthesis' with a stented and a non-stented end. This report summarizes the operative- and follow-up data (mean follow-up 14 months) with this new treatment. METHODS: Between 09/01 and 4/04, 22 patients (62+/-9 years; 9 female) with different aortic pathologies (15 aortic dissections, 7 aneurysms) were operated on after approval from the local institutional review board. The stented end of the hybridprosthesis was deployed in the descending aorta through the opened aortic arch during hypothermic circulatory arrest and selective antegrade cerebral perfusion. RESULTS: All patients survived the procedure but one patient died of acute hemorrhage due to rupture of the false lumen in the descending aorta on the second postoperative day. Two patients required reexploration of the chest for bleeding complications. In 2 of 4 patients who developed neurological dysfunction, symptoms resolved completely. In one of them, the descending aorta was perforated intraoperatively due to misplacement of the stented end of the hybridprosthesis. In all follow-up CT-scans thrombus formation in the descending aortic aneurysm excluded by the stented end of the hybridprosthesis has been observed. CONCLUSIONS: This procedure is performed through median sternotomy and combines the concepts of the elephant trunk operation and endovascular stenting of descending aortic aneurysms. Favourable intraoperative and postoperative results during follow-up with regard to thrombus formation around the stented descending aortic segment encourage us to evaluate all patients with thoracic aneurysms extending to proximal and distal of the left subclavian artery for this treatment.     

Decreased phenylalanine uptake and turnover in patients with vitiligo

The human epidermis has the full machinery for autocrine L-phenylalanine turnover to L-tyrosine in keratinocytes and melanocytes. Phenylalanine hydroxylase (PAH) activities increase linearly with inherited skin colour (skin phototype I-VI, Fitzpatrick classification) yielding eightfold more activities in black skin compared to white skin. Moreover, UVB irradiation (1 MED) significantly increases epidermal PAH activities 24 h after exposure. Importantly, L-phenylalanine uptake and turnover in the pigment forming melanocytes is vital for initiation of melanogenesis. In this context it was shown that the uptake of this amino acid is regulated by calcium. The depigmentation disorder vitiligo provides a unique model to follow impaired L-phenylalanine turnover in the skin as well as in serum because affected individuals hold an impaired epidermal 6BH4 de novo synthesis/recycling and regulation including low epidermal PAH activities. After overnight fasting and oral loading with L-phenylalanine (100 mg/kg body weight), 29.6% of 970 patients tested (n=287/970) yielded serum phenylalanine/tyrosine ratios >or=4 and 35.3% (n=342/970) had mild to moderate hyperphenylalaninaemia (HPA), while 9.3% (n=90/970) had both serum L-phenylalanine levels >or=2.0 mg/dl and phe/tyr ratios >or=4.0. Isolated HPA was found in 26% (n=252/970), whereas 20.3% had only increased ratios (n=197/970). None of the patients had phenylketonuria and the family history for this metabolic disease was negative. The IQ followed normal Gaussian distribution. In vitro L-phenylalanine uptake/turnover studies on primary epidermal melanocytes originating from these patients demonstrated a significantly decreased calcium dependent L-phenylalanine uptake and turnover compared to healthy control cells. Based on our observation, we would like to propose that phenylalanine uptake/turnover is under tight control by calcium which in turn could offer an additional novel mechanism in the aetiology of HPA.     

“Locking in” a rare pathogen

Since its identification as a unique species in 1982, Escherichia hermannii has only recently been implicated as a pathogenic organism in human diseases. Literature search indicates removal of hemodialysis catheter as being essential to the success of treatment for bacteremia with this organism. However, having no alternative access for hemodialysis led to the attempt to salvage the catheter with the use of Antibiotic lock therapy. This case highlights Antibiotic lock therapy as an indication in Escherichia hermanii Catheter related Bloodstream infection.     

Ultrasensitive and bifunctional ZnO nanoplates for an oxidative electrochemical and chemical sensor of NO2: implications towards environmental monitoring of the nitrite reaction

Herein, we focused on the one pot synthesis of ZnO nanoplates (NP edge thickness of ∼100 nm) using a chemical emulsion approach for chemical (direct) and electrochemical (indirect) determination of NO₂. The structural and morphological elucidation of the as-synthesized ZnO NPs was carried out by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive analysis of X-ray (EDAX), thermogravimetric analysis (TGA) and BET-surface area measurements. The XRD studies of the as-synthesised NPs reveal that ZnO NPs have a Wurtzite type crystal structure with a crystallite size of ∼100 nm. Such ZnO NPs were found to be highly sensitive to NO₂ gas at an operating temperature of 200 °C. Electrocatalytic abilities of these ZnO NPs towards NO₂/NO₂⁻ were verified through cyclic voltammetry (CV) and linear sweep voltammetry (LSV) using aqueous 1 mM NO₂⁻ (nitrite) in phosphate buffer (pH 7) solution. The results revealed enhanced activity at an onset potential of 0.60 V vs. RCE, achieved at a current density of 0.14 mA cm⁻². These ZnO NPs show selective NO₂ detection in the presence of other reactive species including CO, SO₂, CH₃OH and Cl₂. These obtained results show that this chemical route is a low cost and promising method for ZnO NPs synthesis and recommend further exploration into its applicability towards tunable electrochemical as well as solid state gas sensing of other toxic gases.

Herein, we focused on the one pot synthesis of ZnO nanoplates (NP edge thickness of ∼100 nm) using a chemical emulsion approach for chemical (direct) and electrochemical (indirect) determination of NO₂.      

Impact of dosing regimen of custirsen,an antisense oligonucleotide,on safety,tolerability and cardiac repolarization in healthy subjects

Aims

Custirsen (OGX-011/TV-1011), a second-generation antisense oligonucleotide (ASO) that reduces clusterin production, is under investigation with chemotherapy in patients with solid tumours. Custirsen is associated with constitutional symptoms (CS) that may interfere with clinical pharmacology investigations, such as QT interval studies. Experience with other ASOs suggests NSAID premedication may ameliorate CS, but we observed suboptimal outcomes in healthy subjects given custirsen and NSAIDs. We sought to establish a custirsen regimen for future clinical pharmacology studies in healthy subjects.

Methods

Subjects received custirsen (640 mg intravenously over 120 min) with dexamethasone premedication or increasing doses (320, 480, 640 mg over 6 days) of custirsen with dexamethasone premedication, then one full custirsen dose without premedication on day 8. Incidence/severity of adverse events (AEs) and extensive electrocardiogram readings were evaluated. Pharmacokinetic parameters were estimated.

Results

AEs included CS, elevated transaminases and prolonged activated partial thromboplastin time (aPTT) that were predominantly grade 1/2. Administration of increasing custirsen doses and dexamethasone premedication reduced the incidence of CS associated with full dose custirsen. Transaminase elevation showed a dose-dependent effect (0% at days 2, 4, 27% at day 6) with the highest custirsen doses. Increasing doses of custirsen may have mitigated the severity but not incidence of aPTT prolongation. Neither regimen was associated with cardiac repolarization changes in QT values or concentration–effect analyses. The custirsen pharmacokinetic profile was consistent with previous experience.

Conclusion

Escalation of custirsen dose combined with dexamethasone premedication reduced CS associated with full dose custirsen and should be considered in future clinical pharmacology studies of custirsen.     

A prolonged observational study of tracheal tube displacements: Benchmarking an incidence <0.5-1% in a medical-surgical adult intensive care unit

Background and Aims:

Tracheal tubes are commonly used in intensive care unit (ICU) and lead to complications like displacements. The primary aim of the study was to evaluate if the rate of tracheal tube displacement benchmarked at <1% per patient and <0.5% per tracheal tube day, could be sustained over a prolonged period. The secondary aim was to document the patterns of all forms airway accident and to evaluate their consequences.

Subjects and Methods:

This was a prospective observational study of Intubated and ventilated patients in a General Medical-Surgical Adult ICU. The incidence of accidental extubation, self extubation, partial displacement and blockages of tracheal tubes were recorded.

Results:

The overall tracheal tube displacement rate was 61/10,112 (0.6%) per patient and 61/28,464 (0.22%) per tracheal tube day. There were 30 additional incidents of blockage, kinking or biting of the tracheal tube. Physiological consequences-69 were mild, 10 moderate, 12 major and one death. Of the 91 accidents, 30 were partly and 30 were completely preventable. 76 incidents involved an endotracheal tube (54 displaced, 12 blocked and 10 bitten-kinked) and 15 a tracheostomy tube (seven displaced and eight blocked). Accidents were more common in medical than surgical patients (medical = 48, cardiac surgical = 17 and other surgical/trauma = 26).

Conclusion:

Tracheal tube displacement rate in a mixed medical-surgical adult ICU was maintained below the pre-set benchmark of <1% per patient and <0.5% per intubated day over nearly a decade.