The effect of high-dose selenium on mortality and postoperative organ dysfunction in post-cardiotomy cardiogenic shock patients supported with mechanical circulatory support - A post-hoc analysis of the SUSTAIN CSX trial.

PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial. METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients. PRIMARY OUTCOME: duration of tMCS therapy. SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality. RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62). CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.

Catheter directed thrombolysis for a pulmonary arterial thrombus on VA ECMO in a child - a case report.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) as a bridge to cardiac transplantation is considered a high risk support strategy in the paediatric population. METHODS: We describe the case of a 12 year old boy who required V-A ECMO support for rapidly deteriorating cardiomyopathy and developed a massive pulmonary embolus (PE) peri-cannulation. Subsequent investigations were also positive for heparin induced thrombocytopenia. RESULTS: We elected to treat the PE with ultrasound accelerated catheter directed thrombolysis using the advantages of this minimally invasive targeted method to try and resolve the PE and avoid a cerebral haemorrhage, both of which would have taken the patient off the urgent transplant list. CONCLUSION: The PE resolved in 24 h and he went on to receive a cardiac transplant and have a favourable outcome.

Anesthetic gas consumption with target-controlled administration versus a semi-closed circle system with automatic end-tidal concentration control in an artificial lung model.

The use of volatile anesthetics as sedatives in the intensive care unit is relevant to the patient's outcome. We compared anesthetic gas consumption of the conventional semi-closed Aisys CSTM with the MIRUSTM system, which is the first anesthetic gas reflector system that can administer desflurane in addition to isoflurane and sevoflurane. We connected an artificial lung model to either a MIRUSTM system and a Puritan BennettTM 840 ventilator or an Aisys CSTM anesthesia machine. We found that consumption of 0.5% isoflurane, which corresponds to the target concentration 0.5 MAC, was averaged to 2 mL/h in the MIRUSTM system, which is identical to the Aisys CSTM at a fresh gas flow (FGF) of 1.0 L/min. MIRUSTM consumption of 1% sevoflurane was averaged to 10 mL/h, which corresponds to 8.4 mL/h at FGF 2.5 L/min. The MIRUSTM system consumed 3% or 4% desflurane at an average of 13.0 mL/h or 21.3 mL/h, which is between the consumption at 1.0 L/min and 2.5 L/min FGF. Thus, the MIRUSTM system can effectively deliver volatile anesthetics in clinically relevant concentrations in a similar rate as a conventional circular breathing system at FGFs between 1.0 L/min and 2.5 L/min.

In vitro performance evaluation of AnaConDaTM-100 and AnaConDaTM-50 compared to a circle breathing system for control and consumption of volatile anaesthetics.

To identify the better volatile anaesthetic delivery system in an intensive care setting, we compared the circle breathing system and two models of reflection systems (AnaConDa™ with a dead space of 100 ml (ACD-100) or 50 ml (ACD-50)). These systems were analysed for the parameters like wash-in, consumption, and wash-out of isoflurane and sevoflurane utilising a test lung model. The test lung was connected to a respirator (circle breathing system: Aisys CS™; ACD-100/50: Puriton Bennett 840). Set parameters were volume-controlled mode, tidal volume-500 ml, respiratory rate-10/min, inspiration time-2 sec, PEEP-5 mbar, and oxygen-21%. Wash-in, consumption, and wash-out were investigated at fresh gas flows of 0.5, 1.0, 2.5, and 5.0 l/min. Anaesthetic target concentrations were 0.5, 1.0, 1.5, 2.0, and 2.5%.  Wash-in was slower in ACD-100/-50 compared to the circle breathing system, except for fresh gas flows of 0.5 and 1.0 l/min. The consumption of isoflurane and sevoflurane in ACD-100 and ACD-50 corresponded to the fresh gas flow of 0.5-1.0 l/min in the circle breathing system. Consumption with ACD-50 was higher in comparison to ACD-100, especially at gas concentrations > 1.5%. Wash-out was quicker in ACD-100/-50 than in the circle breathing system at a fresh gas flow of 0.5 l/min, however, it was longer at all the other flow rates. Wash-out was comparable in ACD-100 and ACD-50. Wash-in and wash-out were generally quicker with the circle breathing system than in ACD-100/-50. However, consumption at 0.5 minimum alveolar concentration was comparable at flows of 0.5 and 1.0 l/min.

Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial.

BACKGROUND: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC's reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0-awake N_Index 100), might drift downward over time despite constant MAC values. METHODS: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. RESULTS: Thirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 - 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation's duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43-0.9, 45-0.8, and 43-0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group. CONCLUSIONS: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration. TRIAL REGISTRATION: NCT03860129.

How Does a Tumor Get Its Shape? MicroRNAs Act as Morphogens at the Cancer Invasion Front.

The generation and organization of the invasion front shape of neoplasms is an intriguing problem. The intimate mechanism is not yet understood, but the prevailing theory is that it represents an example of morphogenesis. Morphogenesis requires the presence of specific molecules, known as morphogens (activators and inhibitors), which can diffuse and elicit dose-dependent responses in their target cells. Due to their ability to modulate most of the coding transcriptome, their well-established role in embryogenesis, and their capacity to rapidly move between neighboring and distant cells, we propose microRNAs as inhibitors that could shape the cancer invasion front. In order to explain the genesis of the tumor border, we use Alan Turing's reaction diffusion model, refined by Meinhardt and Gierer. This assumes the existence of an activator called a, and an inhibitor called h, which we hypothesize could be a freely moving microRNA. We used the fractal dimension as a measure of tumor border irregularity. We observed that the change in fractal dimension associates with variations in the diffusion coefficient of the activator (Da) or the inhibitor (Dh). We determined that the fractal dimension remains constant (i.e., the irregularity of the tumor border does not change) across a Dh interval, which becomes narrower as Da rises. We therefore conclude that a change in fractal dimension occurs when the balance between Da and Dh is disrupted. Biologically, this could be explained by a faulty distribution of the inhibitor caused by an abnormal density of the intercellular connection network. From a translational perspective, if experimentally confirmed, our observations can be used for a better diagnosis of cancer aggressiveness.

Use of the MIRUS™ system for general anaesthesia during surgery: a comparison of isoflurane, sevoflurane and desflurane.

The MIRUS™ system enables automated end-expired control of volatile anaesthetics. The device is positioned between the Y-piece of the breathing system and the patient's airway. The system has been tested in vitro and to provide sedation in the ICU with end-expired concentrations up to 0.5 MAC. We describe its performance in a clinical setting with concentrations up to 1.0 MAC. In 63 ASA II-III patients undergoing elective hip or knee replacement surgery, the MIRUS™ was set to keep the end-expired desflurane, sevoflurane, or isoflurane concentration at 1 MAC while ventilating the patient with the PB-840 ICU ventilator. After 1 h, the ventilation mode was switched from controlled to support mode. Time to 0.5 and 1 MAC, agent usage, and emergence times, work of breathing, and feasibility were assessed. In 60 out of 63 patients 1.0 MAC could be reached and remained constant during surgery. Gas consumption was as follows: desflurane (41.7 ± 7.9 ml h-1), sevoflurane (24.3 ± 4.8 ml h-1) and isoflurane (11.2 ± 3.3 ml h-1). Extubation was faster after desflurane use (min:sec): desflurane 5:27 ± 1:59; sevoflurane 6:19 ± 2:56; and isoflurane 9:31 ± 6:04. The support mode was well tolerated. The MIRUS™ system reliable delivers 1.0 MAC of the modern inhaled agents, both during mechanical ventilation and spontaneous (assisted) breathing. Agent usage is highest with desflurane (highest MAC) but results in the fastest emergence. Trial registry number: Clinical Trials Registry, ref.: NCT0234509.

Robot-assisted surgery for gastric cancer.

Minimally invasive surgery for gastric cancer is a relatively new research field, with convincing results mostly stemming from Asian countries. The use of the robotic surgery platform, thus far assessed as a safe procedure, which is also easier to learn, sets the background for a wider spread of minimally invasive technique in the treatment of gastric cancer. This review will cover the literature published so far, analyzing the pros and cons of robotic surgery and highlighting the remaining study questions.

Open vs robotic radical gastrectomy for locally advanced gastric cancer.

BACKGROUND: This study aims to evaluate the immediate outcomes of robotic and open gastrectomy for patients with locally advanced gastric adenocarcinomas. METHODS: A retrospective analysis was performed on patients undergoing curative intent gastrectomies between 2004 and 2013 in our department. Operative and postoperative outcomes as well as long-term survival data were analysed. RESULTS: Two groups of patients were analysed: the robotic group (n = 18) and the open surgery group (n = 29). Operating time in the robotic group (320.833 ± 85.186 min) was significantly longer (p = 0.0004) as compared with the open group (243.366 ± 57.973 min). The number of retrieved lymph nodes was not statistically different between the two groups (p = 0.108) and neither was the rate of postoperative complications (p = 0.294). CONCLUSIONS: Robotic gastrectomy is a safe procedure, with satisfactory short- and long-term outcomes in locally advanced gastric cancer. Studies on a larger number of patients are necessary in order to confirm whether an immediate benefit in survival exists due to robotic surgery. Copyright © 2015 John Wiley & Sons, Ltd.