Transcatheter Aortic valve implantation in a patient with circulatory collapse,using the lucas® chest compression system

We describe a case of Transcatheter Aortic Valve Implantation (TAVI) using the LUCAS® Chest Compression System in an elderly high risk patient with severe aortic stenosis and heart failure. In this case, the patient developed severe aortic regurgitation following predilatation of the native aortic valve and automated cardiopulmonary resuscitation (A‐CPR) was initiated. The procedure was performed under ongoing A‐CPR for a total of 28 min. The patient was transferred to the intensive care unit and to a step down unit the following day. At follow‐up 30 days later, she showed no signs of neurologic or cardiac damage. This case report shows, that it is possible to perform the TAVI procedure under ongoing A‐CPR and that A‐CPR, judged by invasive blood pressures, was capable of maintaining a satisfactory perfusion pressure even with a damaged aortic valve. © 2013 Wiley Periodicals, Inc.     

Hepatic excretory function in sepsis: implications from biophotonic analysis of transcellular xenobiotic transport in a rodent model

Introduction

Hepatobiliary elimination of endo- and xenobiotics is affected by different variables including hepatic perfusion, hepatocellular energy state and functional integrity of transporter proteins, all of which are altered during sepsis. A particular impairment of hepatocellular transport at the canalicular pole resulting in an accumulation of potentially hepatotoxic compounds would have major implications for critical care pharmacology and diagnostics.

Methods

Hepatic transcellular transport, that is, uptake and hepatobiliary excretion, was studied in a rodent model of severe polymicrobial sepsis by two different biophotonic techniques to obtain insights into the handling of potentially toxic endo- and xenobiotics in sepsis. Direct and indirect in vivo imaging of the liver was performed by intravital multifluorescence microscopy and non-invasive whole-body near-infrared (NIRF) imaging after administration of two different, primarily hepatobiliary excreted xenobiotics, the organic anionic dyes indocyanine green (ICG) and DY635. Subsequent quantitative data analysis enabled assessment of hepatic uptake and fate of these model substrates under conditions of sepsis.

Results

Fifteen hours after sepsis induction, animals displayed clinical and laboratory signs of multiple organ dysfunction, including moderate liver injury, cholestasis and an impairment of sinusoidal perfusion. With respect to hepatocellular transport of both dyes, excretion into bile was significantly delayed for both dyes and resulted in net accumulation of potentially cytotoxic xenobiotics in the liver parenchyma (for example, specific dye fluorescence in liver at 30 minutes in sham versus sepsis: ICG: 75% versus 89%; DY635 20% versus 40% of maximum fluorescence; P < 0.05). Transcutaneous assessment of ICG fluorescence by whole body NIRF imaging revealed a significant increase of ICG fluorescence from the 30th minute on in the bowel region of the abdomen in sham but not in septic animals, confirming a sepsis-associated failure of canalicular excretion.

Conclusions

Hepatocytes accumulate organic anions under conditions of sepsis-associated organ dysfunction. These results have potential implications for monitoring liver function, critical care pharmacology and the understanding of drug-induced liver injury in the critically ill.     

Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

Background: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide‐stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. Methods: Ten healthy male volunteers (21–28 years) participated in a placebo‐controlled, double‐blind, cross‐over study. In random order and on two separate days each volunteer ingested either 50?mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. Results: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. Conclusion: A single dose of 50?mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.     

IKZF1 deletion is an independent predictor of outcome in pediatric acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol

IKZF1 gene deletions have been associated with a poor outcome in pediatric precursor B-cell acute lymphoblastic leukemia. To assess the prognostic relevance of IKZF1 deletions for patients treated on Berlin-Frankfurt-Münster Study Group trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia samples by Multiplex Ligation-dependent Probe Amplification. Patients whose leukemic cells bore IKZF1 deletions had a lower 5-year event-free survival (0.69±0.05 vs. 0.85±0.01; P<0.0001) compared to those without, mainly due to a higher cumulative incidence of relapses (0.21±0.04 vs. 0.10±0.01; P=0.001). Although IKZF1 deletions were significantly associated with the P2RY8-CRLF2 rearrangement, their prognostic value was found to be independent from this association. Thus, IKZF1 deletion is an independent predictor of treatment outcome and a strong candidate marker for integration in future treatment stratification strategies on ALL-BFM protocols.Clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00430118","term_id":"NCT00430118"}}NCT00430118     

The Cryo-Needle: A New Tool for Histological Biopsies. A Feasibility Study

Purpose

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure for intrathoracic lymph node biopsies. The newly developed cryo-needle operates in a similar way to the EBUS-TBNA but is able to obtain specimens for histological evaluation. The purpose of this animal study was to evaluate the feasibility, effect, and safety of the cryo-needle biopsies.

Methods

Four EBUS-guided cryo-needle biopsies were obtained from a mediastinal lymph node of a healthy pig. In an open surgery approach, cryo-needle biopsies using activation times of 1, 2, and 3 s (A1/A2/A3) and needle biopsies using a 21-gauge EBUS-TBNA needle were obtained from mesenteric lymph nodes. Cryo-needle biopsies A2 were performed with (A2+) and without (A2?) an oversheath. The size, weight, percentage of lymphatic tissue and artefact-free area of each cryobiopsy were evaluated. Smears were made with the TBNA-needle aspirates to determine the number of lymphocytes per high-power field (HPF). The bleeding duration was measured.

Results

We successfully obtained EBUS-guided cryo-needle biopsies. The area and weight of the biopsies A3 and A2+ were significantly larger compared with A1 (1.7 ± 0.8 and 1.4 ± 0.3 vs. 0.9 ± 0.4 mm²; 5.2 ± 2.4 and 3.4 ± 1.8 vs. 1.5 ± 0.7 mg). The percentage of lymphatic tissue of the cryobiopsies was 90 ± 25 and 98 % of samples were artefact-free. The number of lymphocytes/HPF of TBNA-needle smears was 128 ± 54.3. There was no difference in bleeding duration between the techniques.

Conclusions

The cryo-needle yields large histological specimens of high quality.     

Sarcoidosis‐associated pulmonary hypertension: acute vasoresponsiveness to inhaled nitric oxide and the relation to long‐term effect of sildenafil

Background: Severe pulmonary sarcoidosis is often complicated by pulmonary hypertension (PH) caused by different pathophysiological mechanisms. Objectives: To assess the acute vasoresponsiveness in patients with sarcoidosis and PH and the relation to the therapeutic effect of sildenafil. Methods: A retrospective chart review of 25 patients with recalcitrant pulmonary sarcoidosis being evaluated for lung transplantation at our centre. Haemodynamics were evaluated by right heart catheterisation in 24 patients of whom 19 had PH. Eight of the 19 patients received vasodilator challenge with inhaled nitric oxide (iNO). Results: The study group of eight patients (seven men) had a median age of 51 years (range 38 years–58 years). During iNO we observed a reduction in all patients’ mean pulmonary arterial pressure (MPAP) of median 9 mmHg (range 1 mmHg–20 mmHg) (P = 0.01) and in all patients’ pulmonary vascular resistance of median 2.0 Wood Units (0.7 Wood Units–5.8 Wood Units) (P = 0.01). Acute vasoresponsiveness defined as reduction in MPAP of ≥10 mmHg to a MPAP of ≤40 mmHg without reduction in cardiac output was achieved in two of eight patients. Seven patients were subsequently started on sildenafil and had haemodynamics measured during treatment. There was no relationship between the acute vasoresponsiveness and the response to treatment. One patient had similar responses, but in six patients, the responses were reversed. Conclusions: Approximately a quarter of the tested patients with end‐stage pulmonary sarcoidosis and PH displayed acute vasoresponsiveness to iNO. However, the degree of vasoresponsiveness appears to be a poor predictor of the response to treatment of PH with sildenafil. Please cite this paper as: Milman N, Svendsen CB, Iversen M, Videbæk R and Carlsen J. Sarcoidosis‐associated pulmonary hypertension: acute vasoresponsiveness to inhaled nitric oxide and the relation to long‐term effect of sildenafil. The Clinical Respiratory Journal 2009; 3: 207–213.     

Interobserver Delineation Variation Using CT versus Combined CT + MRI in Intensity–Modulated Radiotherapy for Prostate Cancer

Purpose:  

To quantify interobserver variation of prostate and seminal vesicle delineations using CT only versus CT + MRI in consensus reading with a radiologist.