The Ongoing Debate: Longevity of Biological Valves in Pulmonary Position.

BACKGROUND: In patients with tetralogy of Fallot (ToF) or ToF-like anatomy, factors possibly impacting the longevity of biological valves in the pulmonary position were investigated. METHOD: Between 1997 and 2017, 79 consecutive hospital survivors with a median age of 8.7 years (range: 0.2-56.1 years; interquartile range [IQR]: 14.8 years) with ToF or ToF-like anatomy underwent surgical implantation of Contegra (n = 34), Hancock (n = 23), Perimount (n = 9), pulmonary homograft (n = 9), and miscellaneous (n = 4) conduits. The median internal graft diameter was 19 mm (range: 11-29 mm; IQR: 8 mm) which refers to a median z-score of 0.6 standard deviation (SD) (range: -1.8 to 4.0 SD; IQR: 2.1 SD). RESULTS: The median time of follow-up was 9.4 years (range: 1.1-18.8 years; IQR: 6.0 years). Thirty-nine patients (49%) underwent surgical (n = 32) or interventional (n = 7) pulmonary valve re-replacement. Univariate Cox regression revealed patient age (p = 0.018), body surface area (p = 0.004), internal valve diameter (p = 0.005), and prosthesis z-score (p = 0.018) to impact valve longevity. Multivariate Cox regression analysis, however, did not show any significant effect (likely related to multicollinearity). Subgroup analysis showed that valve-revised patients have a higher average z-score (p = 0.003) and younger average age (p = 0.007). CONCLUSION: A decreased longevity of biological valves in the pulmonary position is related to younger age, lower valve diameter, and higher z-score. Because valve size (diameter and z-score) can be predicted by age, patient age is the crucial parameter influencing graft longevity.

Antimicrobial effects of inhaled sphingosine against Pseudomonas aeruginosa in isolated ventilated and perfused pig lungs.

BACKGROUND: Ex-vivo lung perfusion (EVLP) is a save way to verify performance of donor lungs prior to implantation. A major problem of lung transplantation is a donor-to-recipient-transmission of bacterial cultures. Thus, a broadspectrum anti-infective treatment with sphingosine in EVLP might be a novel way to prevent such infections. Sphingosine inhalation might provide a reliable anti-infective treatment option in EVLP. Here, antimicrobial potency of inhalative sphingosine in an infection EVLP model was tested. METHODS: A 3-hour EVLP run using pig lungs was performed. Bacterial infection was initiated 1-hour before sphingosine inhalation. Biopsies were obtained 60 and 120 min after infection with Pseudomonas aeruginosa. Aliquots of broncho-alveolar lavage (BAL) before and after inhalation of sphingosine were plated and counted, tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Immunostainings were performed. RESULTS: Sphingosine inhalation in the setting of EVLP rapidly resulted in a 6-fold decrease of P. aeruginosa CFU in the lung (p = 0.016). We did not observe any negative side effects of sphingosine. CONCLUSION: Inhalation of sphingosine induced a significant decrease of Pseudomonas aeruginosa at the epithelial layer of tracheal and bronchial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated pig lungs.

Custodiol-MP for ex vivo lung perfusion - A comparison in a porcine model of donation after circulatory determination of death.

INTRODUCTION: Ex vivo lung perfusion (EVLP) is an established technique to evaluate and eventually recondition lungs prior to transplantation. Custodiol-MP (C-MP) solution is a new solution, designed for clinical machine perfusion, that has been used for kidneys. The aim of this study was to compare the effects of EVLP with Custodiol-MP on lung functional outcomes to the gold standard of EVLP with Steen Solution™. MATERIAL AND METHODS: In a porcine EVLP model of DCDD (Donation after Circulatory Determination of Death), lungs were perfused with Steen Solution™ (SS, n = 7) or Custodiol-MP solution supplemented with 55 g/l albumin (C-MP, n = 8). Lungs were stored cold for 4 h in low potassium dextran solution and subsequently perfused ex vivo for 4 h. During EVLP pulmonary gas exchange, activities of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) as well as levels of lactate in the perfusate were recorded hourly. RESULTS: Oxygenation capacity differed significantly between groups (averaged over 4 h: SS 274 ± 178 mmHg; C-MP 284 ± 151 mmHg p = 0.025). Lactate dehydrogenase activities and lactate concentrations were significantly lower in Custodiol-MP perfused lungs.In a porcine model of DCDD with 4 h of EVLP the use of modified Custodiol-MP as perfusion solution was feasible. The use of C-MP showed at least comparable lung functional outcomes to the use of Steen SolutionTM. Furthermore C-MP perfusion resulted in significantly lower lactate dehydrogenase activity and lactate levels in the perfusate and higher oxygenation capacity.

Impact of left ventricular unloading using a peripheral Impella®-pump in eCPR patients.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (eCPR) is a rapidly growing treatment strategy due to increasing survival rates in selected patients. Additional left ventricular mechanical unloading, using a transfemoral micro-axial blood pump (Impella® Denver, Massachusetts, USA), might improve patients' outcomes. In this regard, we sought to investigate patients who suffered OHCA (out-of hospital cardiac arrest) or IHCA (in-hospital cardiac arrest) with subsequent eCPR via VA-ECMO (veno-arterial extracorporeal membrane oxygenation) and concomitant Impella® implantation based on survival and feasibility of ECMO weaning. METHODS: From January 2016 until December 2020, 108 patients underwent eCPR at our institution. Data prior to eCPR and early outcome parameters were analyzed comparing patients who were supported with an additional Impella® (2.5 or CP) (ECMO+Impella®, n = 18) and patients without additional (ECMO, n = 90) support during V-A ECMO therapy. The primary endpoint was in-hospital mortality; secondary endpoints were, among others: ECMO explantation, need for hemodialysis, stroke, and need for blood transfusions. RESULTS: Low-flow time was significantly lower in the ECMO+Impella group (60 min vs. 55 min, p = .01). All-cause mortality was significantly lower in the ECMO+Impella® group (82% vs. 56%, p = .01). The time of circulatory support was shorter in the ECMO cohort (2.0 ± 1.73 vs. 4.76 ± 2.88 p = .05). ECMO decannulation was significantly more feasible in patients with ECMO+Impella® (72% vs. 32%, p = .01). Patients treated with additional Impella® showed significantly more acute kidney injury with the need for dialysis (72% vs. 18%, p ≤ .01). CONCLUSION: Concomitant Impella® support might positively influence survival and ECMO weaning in eCPR patients. Treatment-associated complications such as the need for dialysis were more common in this highly selected patient group. Further studies with larger numbers are necessary to evaluate the clinical relevance of concomitant LV-unloading in eCPR patients using an Impella® device.

Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs.

Ex-vivo lung perfusion (EVLP) systems like XVIVO are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial cultures (46-89%) which leads to a donor-to-recipient transmission and after a higher risk of lung infection with reduced posttransplant outcome. We have previously shown that sphingosine very efficiently kills a variety of pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and epidermidis, Escherichia coli or Haemophilus influenzae. Thus, sphingosine could be a new treatment option with broadspectrum antiinfective potential, which may improve outcome after lung transplantation when administered prior to lung re-implantation. Here, we tested whether sphingosine has any adverse effects in the respiratory tract when applied into isolated ventilated and perfused lungs. A 4-h EVLP run using minipig lungs was performed. Functional parameters as well as perfusate measurements where obtained. Biopsies were obtained 30 min and 150 min after inhalation of sphingosine. Tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Hemalaun, TUNEL as well as stainings with Cy3-coupled anti-sphingosine or anti-ceramide antibodies were implemented. We demonstrate that tube-inhalation of sphingosine into ex-vivo perfused and ventilated minipig lungs results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea without morphological side effects up to very high doses of sphingosine. Sphingosine also did not affect functional lung performance. In summary, the inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated minipig lungs.

Porcine slaughterhouse lungs for ex vivo lung perfusion - a pilot project.

Ex vivo lung perfusion (EVLP) is an emerging technique for evaluation and eventual reconditioning of donor lungs. Before clinical use experiments with laboratory animals are standard. It was the aim of this study to compare lungs evaluated with EVLP from laboratory animals with slaughterhouse lungs and to investigate the potential use of a slaughterhouse lung model for ex vivo lung perfusion as an alternative for the use of laboratory animals. In a porcine model of Donation after Circulatory Determination of Death (DCDD) 16 lungs were obtained either from regular slaughterhouse animals (SL n = 8) or from laboratory animals in organ procurements (SS n = 8). Lungs were flushed and stored cold for four hours in Perfadex Plus™ and subsequently perfused ex vivo with Steen Solution™ for up to four hours. During 4 hours of EVLP lung functional parameters and activities of lactate, lactate dehydrogenase (LDH) and alkaline phosphatase (AP) in the perfusate were recorded hourly. Histological samples were taken and evaluated fur Lung Injury. Lungs showed no significant difference in oxygen capacity in between groups (∆ PO2 averaged over 4 hours: SL 293 ± 187 mmHg SS 247 ± 199 mmHg). LDH concentration was significantly higher in slaughterhouse lungs (SL 438,5 ± 139,8 U/l, SS 258,42 ± 108,4 U/l P ≤ 0,01). We conclude that the use of slaughterhouse lungs for EVLP was feasible with no significant disadvantages compared to standard organ procurement lungs regarding lung functional outcomes. With the use of slaughterhouse lungs animal experiments in EVLP research could be successfully reduced.

Prediction of acute kidney injury after left ventricular assist device implantation: Evaluation of clinical risk scores.

Acute kidney injury (AKI) is frequent in patients scheduled for implantation of a left ventricular assist device (LVAD) and associated with increased mortality. Although several risk models for the prediction of postoperative renal replacement therapy (RRT) have been developed for cardiothoracic patients, none of these scoring systems have been validated in LVAD patients. A retrospective, single center analysis of all patients undergoing LVAD implantation between September 2013 and July 2016 was performed. Primary outcome was AKI requiring RRT within 14 days after surgery. The predictive capacity of the Cleveland Clinic Score (CCS), the Society of Thoracic Surgeons Score (STS), and the Simplified Renal Index Score (SRI) were evaluated. 76 patients underwent LVAD implantation, 19 patients were excluded due to preoperative RRT. RRT was associated with a prolonged ventilation time, length of stay on the ICU and 180 day mortality (14(60.9%) vs 6(17.6%), P < .01). Whereas the Thakar Score (7.43 ± 1.75 vs 6.44 ± 1.44, P = .02) and the Mehta Score (28.12 ± 15.08 vs 21.53 ± 5.43, P = .02) were significantly higher in patients with RRT than in those without RRT, the SRI did not differ between these groups (3.96 ± 1.15 vs 3.44 ± 1.05, P = .08). Using ROC analyses, CCS, STS, and SRI showed moderate predictive capacity for RRT with an AUC of 0.661 ± 0.073 (P = .040), 0.637 ± 0.079 (P = .792), and 0.618 ± 0.075 (P = .764), respectively, with comparable accuracy in the Delong test. Using univariate logistic regression analysis, only the De Ritis Ratio (OR 2.67, P = .034) and MELD (OR 1.11, P = .028) were identified as predictors of postoperative RRT. Risk scores which are predictive in general cardiac surgery cannot predict RRT in patients after LVAD implantation. Therefore, it seems to be necessary to develop a specific risk score for this patient population.

Clinical Development of Sphingosine as Anti-Bacterial Drug: Inhalation of Sphingosine in Mini Pigs has no Adverse Side Effects.

BACKGROUND/AIMS: Pulmonary infections with Pseudomonas aeruginosa (P. aeruginosa) or Staphylococcus aureus (S. aureus) are of utmost clinical relevance in patients with cystic fibrosis, chronic obstructive pulmonary disease, after trauma and burn, upon ventilation or in immuno-compromised patients. Many P. aeruginosa and S. aureus strains are resistant to many known antibiotics and it is very difficult or often impossible to eradicate the pathogens in patient´s lungs. We have recently shown that the sphingoid base sphingosine very efficiently kills many pathogens, including for instance P. aeruginosa, S. aureus or Acinetobacter baumannii, in vitro. In vivo experiments of our group on cystic fibrosis mice indicated that inhalation of sphingosine prevents or eliminates existing acute or chronic pneumonia with P. aeruginosa or S. aureus in these mice. We also demonstrated that sphingosine is safe to use for inhalation up to high doses, at least in mice. To facilitate development of sphingosine to an anti-bactericidal drug that can be used in humans for inhalation, safety data on non-rodents, larger animals are absolutely required. METHODS: Here, we inhaled mini pigs with increasing doses of sphingosine for 10 days and analyzed the uptake of sphingosine into epithelial cells of bronchi as well as into the trachea and lung and the systemic circulation. Moreover, we measured the generation of ceramide and sphingosine 1-phosphate that potentially mediate inflammation, the influx of leukocytes, epithelial cell death and disruption of the epithelial cell barrier. RESULTS: We demonstrate that inhalation of sphingosine results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea, but not in systemic accumulation. Inhaled sphingosine had no side effects up to very high doses. CONCLUSION: In summary, we demonstrate that inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no systemic or local side effects.

The aspartate transaminase/alanine transaminase (DeRitis) ratio predicts mid-term mortality and renal and respiratory dysfunction after left ventricular assist device implantation.

OBJECTIVES: Preoperative liver dysfunction is a well-known risk factor for adverse events after major surgery. However, there is only little data regarding the precise role of the Model of End-Stage Liver Disease (MELD) score and the De Ritis ratio (DRR, alanine transaminase/aspartate aminotransferase) as a predictor for outcome after left ventricular assist device (LVAD) implantation. METHODS: A retrospective analysis of all patients undergoing LVAD implantation at our institution between January 2012 and August 2014 was performed. The primary outcome was survival at 180 days after surgery. RESULTS: During the observation period, 63 patients underwent LVAD implantation (mean age 59.9 ± 8.3 years, 50% male). Mean preoperative ejection fraction was 16.3 ± 7.7, 13 patients required preoperative renal replacement therapy and 9 patients were on extracorporeal life support. Mean Interagency Registry for Mechanically Assisted Circulatory Support level was 2.8 ± 1.3, mean preoperative MELD was 12.7 ± 7.2, mean preoperative DRR was 2.01 ± 4.4. Aspartate aminotransferase (102 ± 220.8 vs 57.8 ± 123.4 U/l, P = 0.041), MELD score (16.1 ± 8.8 vs 11.4 ± 6.1, P = 0.017) and DRR (4.2 ± 7.8 vs 1.1 ± 1.1, P = 0.001) were significantly higher in non-survivors than in survivors after 180 days. Using logistic regression analyses, a DRR >1.37 was an independent predictor for 30-day mortality [odds ratio (OR) 4.5] and 180-day mortality (OR 4.1). In addition, the DRR was associated with postoperative acute kidney injury with need for renal replacement therapy (OR 4.2) and prolonged postoperative ventilation time >72 h (OR 3.8). Using receiver operator characteristics analyses, DRR showed a sensitivity of 0.80 and a specificity of 0.81 (area under the curve 0.834, cut-off 1.37) for 180-day mortality. CONCLUSIONS: The DRR is predictive of early and mid-term mortality as well as relevant morbidities in patients undergoing LVAD implantation. Therefore, the DRR should be considered within the preoperative risk stratification and patient selection for LVAD implantation.

Does Traumatic Donor Cause of Death Influence Outcome after Lung Transplantation? A Single-Centre Analysis.

Background Owing to the shortage of donor organs in lung transplantation (LuTX), liberalization of donor selection criteria has been proposed. However, some studies suggested that donor traumatic brain damage might influence posttransplantation allograft function. This article aimed to investigate the association of donor cause of death (DCD) and outcome after LuTX. Methods A retrospective analysis of 186 consecutive double LuTXs at our institution from January 2000 to December 2008 was performed. DCD was categorized into traumatic brain injury (TBI) and nontraumatic brain injury (NTBI). In addition, NTBI was sub classified as spontaneous intracerebral bleeding (B), hypoxic brain damage (H), and intracerebral neoplasia (N). Results DCD was classified as TBI in 50 patients (26.9%) and NTBI in 136 patients (73.1%): B in 112 patients (60.2%), H in 21 patients (11.3%), and N in 3 patients (1.6%). Young male donors predominated in group TBI (mean age 36.0 ± 14.5 vs. 42.8 ± 10.7, p < 0.01; 29 males in the TBI group [58.0%] vs. 48 males in the NTBI group [35.3%], p < 0.01). Groups of DCD did not differ significantly by recipient age or gender, recipient diagnosis, donor ventilation time, or paO2/FiO2 before harvesting. TBI donors received significantly more blood (3.4 ± 3.8 vs. 1.8 ± 1.9, p = 0.03). A chest trauma was evident only in group T (n = 7 [3.7%] vs. 0 [0%], p < 0.001). Mode of donor death did not affect the following indices of graft function: length of postoperative ventilation, paO2/FiO2 ratio up to 48 hours, and lung function up to 36 months. One- and three-year survival was comparable with 84.4 and 70.4% for TBI donors versus 89.4% and 69.2% for NTBI donors. Five-year survival tended to be lower in the TBI group but did not reach statistical significance (43.4 vs. 53.9%). Conclusion This study indicates that traumatic DCD does not affect outcome after LuTX. These results can be achieved with an ideal donor management combined with an individual case-to-case evaluation by an experienced LuTX surgeon.

Is universal antifungal prophylaxis mandatory in adults after lung transplantation? A review and meta-analysis of observational studies.

BACKGROUND: Lung transplant (LTX) recipients are at high risk of invasive Aspergillus infections (IAI). However, no randomized-controlled trials (RCT) or international guidelines on antifungal prophylaxis (AFP) in the LTX population exist. METHODS: A meta-analysis was performed to determine whether AFP reduces the rate of IAI after LTX. A total of six eligible observational studies (five with no prophylaxis, one with targeted prophylaxis, three studies including heart/lung transplantation) with a total of 748 patients were included. RESULTS: The pooled odds ratio (OR) for IAI (62 IFI in the intervention arm and 82 in the control group) was 0.234 (95% confidence interval [CI] 0.097-0.564, P=0.001, z=-3.237). Pooled studies were characterized by substantial heterogeneity (I2 =66.64%); number needed to treat was 6.8. A subgroup analyses with exclusion of heart transplant recipients also showed a statistically significant reduction in IAI with AFP (OR 0.183, 95% CI 0.0449-0.744, P=0.018). CONCLUSION: This study suggests that universal antifungal prophylaxes reduces incidence of IAI after LTX. However, included studies are limited by small sample size, single-center structure without randomization, mixed population (including heart/heart-lung transplant), and heterogeneity due to variations in immunosuppression, type, and duration of AFP. Therefore, there is a clear need for an adequately powered RCT.

Safety and Efficiency of Percutaneous Dilatational Tracheostomy With Direct Bronchoscopic Guidance for Thoracic Transplant Recipients.

BACKGROUND: Percutaneous dilatational tracheostomy (PDT) is the standard airway access in critically ill patients who require prolonged mechanical ventilation. However, the literature lacks reports about the effectiveness and safety of this procedure in thoracic organ transplant recipients, who have increased risks of bleeding and infection. METHODS: We retrospectively reviewed the records of subjects who underwent thoracic organ transplantation at our institution between January 2004 and March 2011 followed by PDT (using the Ciaglia Blue Rhino technique with direct bronchoscopic guidance). RESULTS: From a total of 312 thoracic transplant recipients, we identified 93 (29.8%) subjects with PDT. Of these, 79 had undergone double lung transplant, 11 had undergone heart transplant, 2 had undergone combined heart-lung transplant, and 1 had undergone combined heart-kidney transplant. Mean age was 49.5 ± 11.2 y, and 58% of subjects were female. The mean time from intubation to PDT was 3.7 ± 3.4 d, and mean time from transplant to PDT was 12.6 ± 28.3 d. Thirty-two subjects (34.4%) underwent PDT after re-intubation. Thirty-nine subjects were receiving renal replacement therapy (41.9%), and 28 had a coagulopathy (30.1%). Moderate but not significant bleeding was observed in 3 subjects. There were no major complications during PDT procedures. Forty-five subjects (48.4%) could be weaned successfully from the ventilator and the tracheostoma could be removed. Forty-eight subjects (51.6%) died due to sepsis, multi-organ failure, or transplant failure. No procedure-related deaths were noted. There were no significant late complications. Among the 45 who survived their stay in the ICU, the functional and cosmetic outcomes of PDT were excellent. CONCLUSIONS: PDT can be safely performed on patients with acute respiratory failure after thoracic organ transplantation. Therefore, we recommend the use of this technique for prolonged airway management in these patients.

Extraction of enhanced, ultrashort laser pulses from a passive 10-MHz stack-and-dump cavity.

Periodic dumping of ultrashort laser pulses from a passive multi-MHz repetition-rate enhancement cavity is a promising route towards multi-kHz repetition-rate pulses with Joule-level energies at an unparalleled average power. Here, we demonstrate this so-called stack-and-dump scheme with a 30-m-long cavity. Using an acousto-optic modulator, we extract pulses of 0.16 mJ at 30-kHz repetition rate, corresponding to 65 stacked input pulses, representing an improvement in three orders of magnitude over previously extracted pulse energies. The ten times longer cavity affords three essential benefits over former approaches. First, the time between subsequent pulses is increased to 100 ns, relaxing the requirements on the switch. Second, it allows for the stacking of strongly stretched pulses (here from 800 fs to 1.5 ns), thus mitigating nonlinear effects in the cavity optics. Third, the choice of a long cavity offers increased design flexibility with regard to thermal robustness, which will be crucial for future power scaling. The herein presented results constitute a necessary step towards stack-and-dump systems providing access to unprecedented laser parameter regimes.

Large-mode enhancement cavities.

In passive enhancement cavities the achievable power level is limited by mirror damage. Here, we address the design of robust optical resonators with large spot sizes on all mirrors, a measure that promises to mitigate this limitation by decreasing both the intensity and the thermal gradient on the mirror surfaces. We introduce a misalignment sensitivity metric to evaluate the robustness of resonator designs. We identify the standard bow-tie resonator operated close to the inner stability edge as the most robust large-mode cavity and implement this cavity with two spherical mirrors with 600 mm radius of curvature, two plane mirrors and a round trip length of 1.2 m, demonstrating a stable power enhancement of near-infrared laser light by a factor of 2000. Beam radii of 5.7 mm × 2.6 mm (sagittal × tangential 1/e(2) intensity radius) on all mirrors are obtained. We propose a simple all-reflective ellipticity compensation scheme. This will enable a significant increase of the attainable power and intensity levels in enhancement cavities.

1 MHz repetition rate hollow fiber pulse compression to sub-100-fs duration at 100 W average power.

We report on nonlinear pulse compression at very high average power. A high-power fiber chirped pulse amplification system based on a novel large pitch photonic crystal fiber delivers 700 fs pulses with 200 µJ pulse energy at a 1 MHz repetition rate, resulting in 200 W of average power. Subsequent spectral broadening in a xenon-filled hollow-core fiber and pulse compression with chirped mirrors is employed for pulse shortening and peak power enhancement. For the first time, to our knowledge, more than 100 W of average power are transmitted through a noble-gas-filled hollow fiber. After pulse compression of 81 fs, 93 µJ pulses are obtained at a 1 MHz repetition rate.

Preferential gain photonic-crystal fiber for mode stabilization at high average powers.

We report on the design and experimental investigation of a preferential gain photonic-crystal fiber with a mode-field diameter of 47 µm. This few-mode fiber design confines the doping of Ytterbium-ions just to the center of the core and, therefore, promotes fundamental mode operation. In a chirped-pulse amplification system we extracted up to 303 W of average power from this fiber with a measured M2 value of 1.4.

Fiber chirped-pulse amplification system emitting 3.8 GW peak power.

We report on the experimental demonstration of a fiber chirped- pulse amplification system capable of generating nearly transform-limited sub 500 fs pulses with 2.2 mJ pulse energy at 11 W average power. The resulting record peak power of 3.8 GW could be achieved by combining active phase shaping with an efficient reduction of the acquired nonlinear phase. Therefore, we used an Ytterbium-doped large-pitch fiber with a mode field diameter of 105 µm as the main amplifier.