Predictors of survival after prolonged weaning from mechanical ventilation.

PURPOSE: Weaning from mechanical ventilation is a key component of intensive care treatment; however, this process may be prolonged as some patients require care at specialised centres. Current data indicate that weaning from invasive mechanical ventilation is successful in approximately 65% of patients; however, data on long-term survival after discharge from a weaning centre are limited. MATERIALS AND METHODS: We analysed predictors of survival among 597 patients (392 men, mean age 68 ± 11) post-discharge from a specialised German weaning centre. RESULTS: Complete weaning from mechanical ventilation was achieved in 407 (57.8%) patients, and 106 patients (15.1%) were discharged with non-invasive ventilation; thus, prolonged weaning was successful in 72.9% of the patients. The one-year and five-year survival rates post-discharge were 66.5% and 37.1%, respectively. Age, duration of mechanical ventilation, certain clusters of comorbidities, and discharged with mechanical ventilation significantly influenced survival (p < .001). Completely weaned patients who were discharged with a tracheostomy had a significantly reduced survival rate than did those who were completely weaned and discharged with a closed tracheostomy (p = .004). CONCLUSIONS: The identified predictors of survival after prolonged weaning could support therapeutic strategies during patients' intensive care unit stay. Patients should be closely monitored after discharge from a weaning centre.

Spatial control of the energy metabolism of yeast cells through electrolytic generation of oxygen.

The metabolic dynamics of yeast cells is controlled by electric pulses delivered through a spatially extended yeast cell/Au electrode interface. Concomitant with voltage pulses, oxygen is generated electrolytically at the electrode surface and delivered to the cells. The generation of oxygen was investigated in dependence of the applied voltage, width of the voltage pulses and temperature of the electrolytic solution. The local oxygen pulses at the electrodes lead to a transient activation of the aerobic energy metabolism of the yeast cells causing a perturbation in their energy balance. The effect of these local perturbations on the temporal dynamics of glycolysis in yeast cells is quantified in dependence of the energy state of cells.

Long-term safety and outcome of intravenous treprostinil via an implanted pump in pulmonary hypertension.

BACKGROUND: We examined safety and long-term outcomes of intravenous treprostinil administered via the implantable LENUS Pro pump in patients with severe pulmonary hypertension (PH). METHODS: Patients with PH undergoing pump implantation between December 2009 and October 2016 in German referral centers were retrospectively analyzed (end of follow-up: May 2017). The primary objective was to determine long-term safety of the implantable pump. Secondary end points were 3-year survival and prognostic relevance of pre-implantation hemodynamics. RESULTS: We monitored 129 patients (120 with pulmonary arterial hypertension, 1 with PH due to lung diseases, and 8 with inoperable chronic thromboembolic PH) for 260 patient-years (median follow-up, 19 months; interquartile range, 11-34 months). There were 82 complications/peri-procedural events in 60 patients; of these, 57 were serious adverse events (0.60 per 1,000 treatment-days), including 2 periprocedural deaths due to right heart failure. The incidence of complications related to the pump, catheter, infection, and pump pocket per 1,000 treatment-days was 0.074, 0.264, 0.032 (3 local infections; no bloodstream infections), and 0.380, respectively. Three-year overall and transplant-free survival were 66.5% and 55.7%, respectively (39 patients died; 16 underwent lung transplantation). Baseline cardiac index independently predicted transplant-free survival (multivariate hazard ratio, 1.90; 95% confidence interval, 1.11-3.28; p = 0.019; n = 95). CONCLUSIONS: Our data suggest that intravenous treprostinil via the LENUS Pro pump in advanced PH is associated with a very low risk of bloodstream infections, but other serious adverse events may occur. Therefore, this therapy needs standardization and should be offered in specialized PH centers only. Further technical advances of the pump system and prospective studies are needed.

Procedural safety of a fully implantable intravenous prostanoid pump for pulmonary hypertension.

BACKGROUND: In patients with severe pulmonary arterial hypertension, subcutaneous or catheter-based intravenous application of prostanoids carries a risk of local side effects or systemic infections, which limits their use and acceptance. Recently, a fully implantable pump for continuous application of intravenous treprostinil was approved in Germany. However, surgery is a major risk for patients with severe pulmonary arterial hypertension. The purpose of this study was to investigate the safety of a fully implantable pump inserted under local or general anesthesia in patients with severe pulmonary hypertension. METHODS: All patients with pulmonary hypertension undergoing pump implantation for the continuous application of intravenous treprostinil were included from two German centers. Surgery was performed under local or general anesthesia according to the protocol of the recruiting center. Intra-operative safety and in-hospital complications were analyzed for the two different implantation regimens. RESULTS: In total, 51 patients were included. No major intra-operative complications were recorded. During the observation period, two patients died of progressive right heart failure, and two patients required treatment in the intensive care unit for acute right heart decompensation and respiratory failure. In total, major complications occurred in 8 out of 51 patients. CONCLUSIONS: Our observational study provides preliminary evidence supporting the procedural safety of a fully implantable pump inserted under local or general anesthesia for patients with severe pulmonary hypertension. The observation of major complications in a subset of patients requires extensive pre- and post-operative assessments. Future trials are required to provide further evidence for the long-term safety and efficacy of the pump using this approach.

Intravenous treprostinil infusion via a fully implantable pump for pulmonary arterial hypertension.

OBJECTIVES: Parenteral prostanoids infused via external pumps are well-established pulmonary arterial hypertension (PAH) treatments. However, local side-effects and systemic infections restrict their use. The purpose of this study was to investigate the safety of a fully implantable treprostinil infusion pump (LENUS Pro®) in patients with PAH. METHODS: Thirty patients with PAH undergoing pump implantation (with stable PAH therapy for ≥3 weeks pre-implantation) were included in this prospective, multicenter, observational study (NCT01979822). Primary endpoints were predefined adverse events (AEs) during implantation, in-hospital and/or during 6-month follow-up. Refill-related AEs were a secondary endpoint. RESULTS: Twenty-nine patients completed 6-month follow-up (one underwent lung transplantation). During implantation, one pneumothorax (not requiring drainage) occurred. Four patients had an in-hospital AE (including one catheter revision). During 6-month follow-up, AEs were most frequent at the first refill (10); the most common AE was seroma around the pump. No infections occurred. One pump required replacement because of a defective septum caused by use of a non-approved refill needle (associated with extravasation). Apart from the extravasation, no refill-related AEs were recorded. Post hoc efficacy analyses showed significant improvements in functional class [number in functional class I/II/III/IV: 0/5/21/2 (baseline) versus 3/8/17/0 (6 months); p = 0.012] and 6-min walk distance (mean ± standard deviation: 407 ± 122 m versus 445 ± 127 m; n = 17; p = 0.014). CONCLUSIONS: This study supports use of a fully implantable treprostinil infusion pump in patients with PAH requiring parenteral prostanoids. Refills should be performed by specialized healthcare professionals at patients' homes or at experienced centers using approved equipment.

Pulmonary hypertension in patients with idiopathic pulmonary fibrosis - the predictive value of exercise capacity and gas exchange efficiency.

Exercise capacity and survival of patients with IPF is potentially impaired by pulmonary hypertension. This study aims to investigate diagnostic and prognostic properties of gas exchange during exercise and lung function in IPF patients with or without pulmonary hypertension. In a multicentre setting, patients with IPF underwent right heart catheterization, cardiopulmonary exercise and lung function testing during their initial evaluation. Mortality follow up was evaluated. Seventy-three of 135 patients [82 males; median age of 64 (56; 72 years)] with IPF had pulmonary hypertension as assessed by right heart catheterization [median mean pulmonary arterial pressure 34 (27; 43) mmHg]. The presence of pulmonary hypertension was best predicted by gas exchange efficiency for carbon dioxide (cut off ≥152% predicted; area under the curve 0.94) and peak oxygen uptake (≤56% predicted; 0.83), followed by diffusing capacity. Resting lung volumes did not predict pulmonary hypertension. Survival was best predicted by the presence of pulmonary hypertension, followed by peak oxygen uptake [HR 0.96 (0.93; 0.98)]. Pulmonary hypertension in IPF patients is best predicted by gas exchange efficiency during exercise and peak oxygen uptake. In addition to invasively measured pulmonary arterial pressure, oxygen uptake at peak exercise predicts survival in this patient population.

Control of glycolytic oscillations by temperature.

External control of oscillatory glycolysis in yeast extract has been performed by application of either homogeneous temperature oscillations or stationary, spatial temperature gradients. Entrainment of the glycolytic oscillations by the 1/2- and 1/3-harmonic, as well as the fundamental input frequency, could be observed. From the phase response curve to a single temperature pulse, a distinct sensitivity of NADH-oxidizing processes, compared with NAD-reducing processes, is visible. Determination of glycolytic intermediates shows that the feedback-regulated phosphofructokinase as well as the glyceraldehyde-3-phosphate dehydrogenase are the most temperature-sensitive steps of glycolysis. We also find strong concentration changes in ATP and AMP at varying temperatures and, accordingly, in the energy charge. Construction of a feedback loop for spatial control of temperature by means of a Peltier element allowed us to apply a temperature gradient to the yeast extract. With this setup it is possible to initiate traveling waves and to control the wave velocity.