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Controlled donation after circulatory death (cDCD) has become a standard in liver, kidney, and lung transplantation (LTx). Based on recent innovations in ex vivo heart preservation, heart transplant centers have started to accept cDCD heart allografts. Because the heart has very limited tolerance to warm ischemia, changes to the cDCD organ procurement procedures are needed. These changes entail delayed ventilation and prolonged warm ischemia for the lungs. Whether this negatively impacts lung allograft function is unclear.A retrospective analysis of cDCD lungs transplanted between 2012 and February 2022 at the Medical University of Vienna was performed. The heart + lung group consisted of cases in which the heart was procured by a cardiac team for subsequent normothermic ex vivo perfusion. A control group (lung group) was formed by cases where only the lungs were explanted. In heart + lung group cases, the heart procurement team placed cannulas after circulatory death and a hands-off time, collected donor blood for ex vivo perfusion, and performed rapid organ perfusion with Custodiol solution, after which the heart was explanted. Up to this point, the lung procurement team did not interfere. No concurrent lung ventilation or pulmonary artery perfusion was performed. After the cardiac procurement team left the table, ventilation was initiated, and lung perfusion was performed directly through both stumps of the pulmonary arteries using 2 large-bore Foley catheters. This study analyzed procedural explant times, postoperative outcomes, primary graft dysfunction (PGD), duration of mechanical ventilation, length of intensive care unit (ICU) stay, and early survival after LTx.A total of 56 cDCD lungs were transplanted during the study period. In 7 cases (12.5%), the heart was also procured (heart + lung group); in 49 cases (87.5%), only the lungs were explanted (lung group). Basic donor parameters were comparable in the 2 groups. The median times from circulatory arrest to lung perfusion (24 minutes vs 13.5 minutes;Although prioritized cDCD heart explantation is associated with delayed ventilation and significantly longer warm ischemic time to the lungs, post-LTx outcomes within the first year are unchanged. Prioritizing heart perfusion and explantation in the setting of cDCD procurement can be considered acceptable.

Tracheobronchial injury is a rare but potentially life-threatening condition. Various surgical treatment options have been described for symptomatic patients with full-thickness injury. However, studies comprising a meaningful number of patients are sparse.We retrospectively analyzed all patients who received surgical repair of tracheobronchial injury between January 1999 and May 2021 at the Department of Thoracic Surgery, Medical University of Vienna. Patient characteristics, surgical variables, postoperative morbidity, and mortality were retrieved and analyzed.Fifty patients with a median age of 68 years (range, 17-88) were included in the analysis. The etiologies of the iatrogenic tracheobronchial injuries were emergency intubation (48%), elective percutaneous dilatation tracheostomy (38%), or elective intubation (14%). The most common location of tracheobronchial injuries was distal third (28%) with a median length of 50 mm (range, 20-100 mm). The surgical approach was cervicotomy in 52%, thoracotomy in 38%, sternotomy in 2%, and combined approaches in 8% of cases. Moreover, intraoperative venovenous (n = 4) or venoarterial (n = 2) extracorporeal membrane oxygenation support was required in 12% of cases. Procedure-related mortality was 0%. However, as patients with tracheobronchial injury usually have severe comorbidities, the rate of patients discharged alive from the intensive care unit was only 66%. The median follow-up period of discharged patients was 5.5 months (range, 0.7-209). Airway stenosis or dehiscence was not observed in any patient.Surgical repair of tracheobronchial injuries can be performed safely with a low procedure-related morbidity. If possible, the less-invasive cervical access should be preferred for patients with tracheobronchial injury, even for injuries extending to the main bronchi.

Dual-lumen extracorporeal membrane oxygenation (ECMO) cannulation is considered technically challenging and harbors the risk of potential life-threatening complications during cannulation. Dual-lumen cannula insertion is performed under either ultrasound or fluoroscopy guidance. Both techniques have significant disadvantages, such as examiner dependence or the necessity for transportation of the patient from the intensive care unit to the operating room.Digital, mobile x-ray devices provide a novel, examiner-independent imaging modality for bedside dual-lumen ECMO cannulation.From November 2019 to November 2021, 23 dual-lumen cannulations were performed in 20 patients at the Department of Thoracic Surgery, Medical University of Vienna. Twelve of 23 (52.2%) were inserted in the intensive care unit using a mobile x-ray device. The remaining patients (47.8%) were cannulated in the operating room with conventional fluoroscopy guidance. In none of the procedures did cardiovascular injuries occur. Insertion site bleeding was the most common ECMO-related complication (n = 2).Dual-lumen cannulation using sequential x-rays can be performed safely. Especially for infectious patients or patients who require an awake ECMO, this technique overcomes disadvantages of established imaging modalities.

ZusammenfassungIn der pädiatrischen Atemwegschirurgie sind zahlreiche anatomische Besonderheiten, spezifische Krankheitsbilder sowie spezielle Operationstechniken zu beachten. Auch an spezialisierten Zentren sind diese Eingriffe bei pädiatrischen Patienten eher selten. Ätiologisch handelt es sich meist um erworbene Stenosen als Folge von Frühgeburtlichkeit, Langzeitintubation oder -tracheotomie, welche typischerweise in Kindern mit zahlreichen Komorbiditäten auftreten. Kongenitale Fehlbildungen der Atemwege gehen häufig mit weiteren Malformationen einher, welche die erfolgreiche Behandlung zusätzlich erschweren. Voraussetzung zur Behandlung dieser Kinder sollte daher ein multidisziplinäres Team sein. An erfahrenen Zentren mit entsprechender Infrastruktur kann die chirurgische Behandlung dieser Kinder mit sehr guten Ergebnissen durchgeführt werden. So wird bei den meisten Patienten nach chirurgischer Behandlung eine sehr gute Lebensqualität ohne Notwendigkeit einer Langzeittracheostomie erreicht. Diese Übersichtsarbeit fasst die wichtigsten Indikationen, sowie die häufigsten Operationstechniken in der pädiatrischen Atemwegschirurgie zusammen.

OBJECTIVES Traditionally, patients on bridge-to-transplant extracorporeal membrane oxygenation were kept sedated and intubated. However, awake bridging strategies have evolved during recent years. This study aims to elaborate differences in physical activity and postoperative outcomes after lung transplantation (LTx), depending on bridging strategy and duration. METHODS Bridged patients receiving LTx between March 2013 and April 2021 were analysed. Awake bridging was defined as a Richmond Agitation-Sedation Scale score of ≥−1 until 24 h before transplantation. Patients were grouped in awake and sedated cohorts. RESULTS A total of 88 patients (35 awake, 53 sedated bridging) were included. After LTx, mobilization to standing position was achieved earlier in awake bridged patients (7 vs 15 days, P < 0.001). Postoperative ventilation time (247 vs 88 h, P = 0.005) and intensive care unit stay (30 vs 16 days, P = 0.004) were longer in the sedated cohort. Awake patients with bridging duration >6 days showed shorter postoperative ventilation time (108 vs 383 h, P = 0.003), less intensive care unit days (23 vs 36, P = 0.003) and earlier mobilization to standing position (9 vs 17 days, P < 0.001). In contrast, postoperative ventilation time and days in intensive care unit in patients with bridge-to-transplant duration ≤6 days were comparable between cohorts. Mobilization to standing position was achieved faster in the awake (≤6 days) bridged cohort (5 vs 9 days, P = 0.024). CONCLUSIONS Despite the complex management of bridged patients, excellent survival rates after LTx can be achieved. Especially in patients with more than 1 week on extracorporeal membrane oxygenation, awake bridging concepts are associated with significantly faster recovery.

Alemtuzumab is a monoclonal antibody targeting CD52, used as induction therapy after lung transplantation (LTx). Its engagement produces a long-lasting immunodepletion; however, the mechanisms driving cell reconstitution are poorly defined. We hypothesized that miRNAs are involved in this process. The expression of a set of miRNAs, cytokines and co-signaling molecules was measured with RT-qPCR and flow cytometry in prospectively collected serum samples of LTx recipients, after alemtuzumab or no induction therapy. Twenty-six LTx recipients who received alemtuzumab and twenty-seven matched LTx recipients without induction therapy were included in the analysis. One year after transplantation four miRNAs were differentially regulated: miR-23b (p = 0.05) miR-146 (p = 0.04), miR-155 (p p p p p

Background: For endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) under general anaesthesia, both rigid bronchoscopy and laryngeal masks (LMAs) with superimposed high-frequency jet ventilation can be used. Despite the fact that in Europe rigid bronchoscopy for EBUS-TBNA is still widely used, an increasing number of centres use jet ventilation via the LMA for this procedure. To our knowledge no clinical trials have ever been made to compare these two methods. This trial aimed to evaluate whether patients recover from the procedure more quickly when a LMA is used for ventilation compared with rigid bronchoscopy where muscle relaxants and deep anaesthesia are required. Objectives: We wanted to test the hypothesis that there is no difference in the postoperative recovery of patients in the postanaesthesia care unit (PACU) after EBUS-TBNA with jet ventilation via a rigid bronchoscope and a LMA. Secondary outcomes were the difference of duration of anaesthesia, the diagnostic outcome of the procedure and drug quantities for both groups. Design: Prospective randomised single blinded two centre controlled trial. Setting: Two centres in Austria participated. Patients were enrolled from December 2016 until January 2018. Patients: Ninety patients for elective EBUS-TBNA were enrolled and assigned to one of two intervention groups. Two patients were excluded before and eleven patients were excluded after EBUS-TBNA. Seventy-seven were analysed. Interventions: Patients assigned to group 1 were ventilated with a LMA; those assigned to group 2 were ventilated via a rigid bronchoscope. Vital signs, drug dosage, duration of anaesthesia, recovery, PACU stay and Aldrete score at the PACU were recorded. Main outcome measures: The primary endpoint was an integral over time of a modified Aldrete score. Secondary endpoints were the durations of the interventions, the recovery from anaesthesia and PACU stay, initial and mean Aldrete values at PACU, the effect site concentration of Propofol according to the Schnider pharmacokinetic model, the peak ultiva rates and the diagnostic outcome. Results: We were not able to show any significant difference regarding the postoperative recovery criteria based on the Aldrete score, the durations measured and the diagnostic outcomes. Vital signs remained stable and in an equal range in both groups. There were no differences in the mean effect site propofol concentration and the peak ultiva rates. Conclusion: EBUS-TBNA under general anaesthesia using a LMA with SHJV is equal to rigid bronchoscopy with superimposed high-frequency jet ventilation for the variables analysed. Trial registration: ISRCTN (ISRCTN58911367).

Surgical treatment of benign subglottic stenoses can be challenging. It requires the close cooperation of an experienced team that includes various specialist disciplines. The treatment success will be evaluated with an extensive documentation of voice quality, lung function and swallowing function. The stenosis has to be analyzed in terms of its etiology, severity and pretreatment. Endoscopic removal of the stenotic tissue often leads to good short-term results. However, the proportion of re-stenoses is very high, which are often even more severe. Long-term treatment success can often only be achieved by surgical resection. The surgical technique used must be strictly adapted to the individual stenosis. In principle, a distinction can be made between classic cricotracheal resections and those that receive an expanded operative component. Particularly in the case of high-grade side-to-side stenoses, complex reconstruction with cartilage graft may be necessary. It is important not just to restore the airway flow. Maintaining the vocal function is an equally important treatment goal. Experienced centers can achieve very satisfactory long-term results with regard to functional outcome and voice quality.

Alemtuzumab is a monoclonal antibody targeting CD52, increasingly used as induction therapy after transplantation. The aim of this study was to analyze the outcomes of alemtuzumab induction therapy followed by a low-dose maintenance immunosuppression in a large single-center cohort of lung transplant recipients. All patients, who received alemtuzumab induction followed by a low-dose maintenance immunosuppression were included in the analysis. Short- and long-term outcomes were analyzed. 721 lung transplant recipients, transplanted between January 2008 and June 2019, were included in this retrospective study. Freedom from higher-grade ACR at 1, 5, and 10 years was 98%, 96%, and 96%, respectively. Thirty-nine patients (5%) developed clinical AMR. Twenty-one percent of patients developed high-grade CKD. A total of 1488 infections were recorded. Sixteen percent were diagnosed within the first 3 months. Sixty-two patients (9%) developed a malignancy during follow-up. Freedom from CLAD at 1, 5, and 10 years was 94%, 72%, and 53%, respectively. Overall survival rates at 1, 5, and 10 years were 85%, 71%, and 61%, respectively. Alemtuzumab induction combined with a low-dose tacrolimus protocol is safe and associated with low rates of acute and chronic rejection, as well as an excellent long-term survival.

Introduction: The world-wide experience with lung transplantation (LT) for COVID-19 induced ARDS is limited and it is unknown if and when such a treatment should be offered. Aims & Methods: Aim of the study was a) to highlight the proportion of COVID-19 ARDS patients who can be considered for LT and b) to assess the outcome after LT. Clinical data were collected for COVID-19 patients who had been referred to our institution for the evaluation of a LT (Figure 1). For the subgroup of transplanted patients, postoperative outcome was determined (30-days survival rate, length of ICU stay and overall survival in days). Findings: Until February 2021, 48 patients were referred to our center. 28 (58%) were rejected due to comorbidities, 8 (17%) were considered too good and recovered without LT. 8 (17%) patients underwent bilateral LT, 4 (8%) additional candidates were still under evaluation for LT. 30-days survival rate after LT was 100% with a median length of ICU stay of 59 (55-63) days. With a follow up ranging between 14 and 275 days, all transplanted patients are alive. Conclusion: LT is feasible for COVID-19 induced ARDS and should be considered for carefully selected patients with irreversible lung injury.

Purpose Preoperative assessment of benign subglottic stenosis is usually performed by endoscopy and a computed tomography scan. Both diagnostic modalities have relevant limitations and sometimes an accurate assessment of the extent of disease is challenging. Description Based on computed tomography scans of benign glotto-subglottic stenosis and a control airway, color-coded three-dimensional (3D) models were produced using a commercially available 3D printer. The diagnostic relevance of 3D models was tested by means of a quiz. Evaluation 52 thoracic surgeons from 4 North American and 1 European institution with different levels of experience in airway surgery were invited to test the diagnostic accuracy of 3D models against endoscopy films and computed tomography scans. 3D models were found to be superior to the other two diagnostic tools in terms of grading the extent of the stenosis and selecting the correct surgical strategy. The group of residents benefited the most from the 3D models. Conclusions 3D models of complex glotto-subglottic airway stenosis are a useful supplement of the preoperative assessment. In addition, they can serve as a teaching tool for residents and fellows.

Background: Pulmonary metastasectomy is one of the cornerstones in the treatment of oligometastatic colorectal cancer (CRC). However, the selection of patients who benefit from a surgical resection is difficult. Mutational profiling has become an essential part of diagnosis and treatment of malignant disease. Despite this, comprehensive data on the mutational profile of CRC and its clinical impact in the context of pulmonary metastasectomy is sparse. We therefore aimed to provide a complete mutational status of CRC pulmonary metastases (PM) and corresponding primary tumors by targeted next-generation sequencing (tNGS), and correlate sequencing data with clinical outcome variables. Methods: Case-matched, formalin-fixed paraffin embedded surgical specimens of lung metastases (n=47) and matched primary CRC (n=24) were sequenced using the TruSeq Amplicon Cancer Panel (Illumina platform). Penalized Cox regression models were applied to identify mutations with prognostic impact. Results: Mutations were found most frequently in APC, TP53 and KRAS , in both PM and matched primary tumors. Concordance between primary tumors and PM was 83.5%. Adaptive elastic-net regularized Cox regression models identified mutations being prognostic for time to pulmonary recurrence ( EGFR, GNAQ, KIT, MET , and PTPN11 ) and for overall survival (OS) ( PDGFRA, SMARCB1 , and TP53 ). Conclusions: Our findings suggest that CRC PM harbor a variety of conserved and de novo mutations. We could identify a mutational profile predicting clinical outcome after pulmonary metastasectomy. Moreover, our data provide a rationale for future targeted therapies of patients with CRC lung metastases.

Objectives In patients with idiopathic pulmonary arterial hypertension, cardiac function can be impaired in the early postoperative phase after lung transplantation because the chronically untrained left ventricle is prone to fail. Thus, restrictive fluid management is pivotal to unload the left heart. In our institution, continuous renal replacement therapy is implemented liberally whenever a patient cannot be balanced negatively. It remains unclear whether such strategy impairs long-term kidney function. Methods We retrospectively reviewed our institutional database for patients with idiopathic pulmonary arterial hypertension who underwent transplantation between 2000 and 2018. The impact of postoperative continuous renal replacement therapy on long-term outcomes was investigated using a linear mixed model and multivariable Cox regression. Results A total of 87 idiopathic pulmonary arterial hypertension lung transplant recipients were included in this analysis. In 38 patients (43%), continuous renal replacement therapy was started in the early postoperative period for a median of 16 days (10-22). In this group, urine production significantly decreased and patients began to acquire a positive fluid balance; however, homeostatic functions of the kidney were still preserved at the time of continuous renal replacement therapy initiation. All patients were successfully weaned from continuous renal replacement therapy and fully recovered their kidney function at the time of hospital discharge. No difference in kidney function was found between continuous renal replacement therapy and noncontinuous renal replacement therapy in patients within 5 years. Conclusions Early implementation of continuous renal replacement therapy for perioperative volume management does not impair long-term kidney function in idiopathic pulmonary arterial hypertension lung transplant recipients. Our data suggest that such a strategy leads to excellent long-term outcomes.

OBJECTIVES A tension-free anastomosis is crucial to minimize the risk of airway complications after laryngotracheal surgery. The ‘guardian’ chin stitch is placed to prevent hyperextension of the neck in the early postoperative period. This manoeuvre was introduced early in tracheal surgery and is now routinely performed by many airway surgeons. However, the evidence for or against is sparse. METHODS We performed a retrospective analysis of all adult patients receiving a (laryngo-)tracheal resection at our department from October 2011 to December 2019. According to our institutional standard, none of the patients received a chin stitch. Instead, a head cradle was used to obtain anteflexion of the neck during the first 3 days and patients were instructed to avoid hyperextension of the neck during the hospital stay. The postoperative outcome and the rate of anastomotic complications were analysed. RESULTS A total of 165 consecutive patients were included in this study. Median age at surgery was 53 years (18–80). Seventy-four patients received a tracheal resection, 24 a cricotracheal resection, 52 an extended cricotracheal resection including dorsal mucosectomy and 15 a single-stage laryngotracheal reconstruction. The median resection length was 25 mm (range 10–55 mm). One hundred and sixty-two out of 165 (98.2%) patients had an unremarkable postoperative course. One patient (0.6%) had partial anastomotic rupture after a traumatic reintubation, which required revision surgery and re-anastomosis. Two patients (1.2%) after previous radiation therapy (>60 Gy) developed a partial necrosis of the anastomosis, resulting in prolonged airleak and fistulation. At follow-up, bronchoscopy 3 months after surgery, 92.7% (127/137) of the patients had a proper anastomosis, 6.6% (9/137) had minor granuloma formations at the site of the anastomosis, which were all treated successfully by endoscopic removal. One patient received dilatation for restenosis (0.7%). CONCLUSIONS After sufficient mobilization of the central airways, postoperative anteflexion of the neck supported by a head cradle is sufficient to prevent excessive anastomotic tension and dehiscence. Considering the risk for severe neurological complications associated with the chin stitch, the routine use of this manoeuvre in laryngotracheal surgery should not be recommended.

BACKGROUND The evaluation of donor lungs heavily depends on the subjective judgment of the retrieval surgeon. As a consequence, acceptance rates vary significantly among transplant centers. We aimed to determine donor ventilation parameters in a prospective study and test if they could be used as objective quality criteria during organ retrieval. METHODS A prospective evaluation of lung donors was performed in 3 transplant centers. Ventilation parameters were collected at the time of retrieval using a standardized ventilation protocol. Recipient length of mechanical ventilation (LMV) was defined as the primary end point, and collected data was used to build linear models predicting LMV. RESULTS In total, 166 donors were included in this study. Median LMV after transplantation was 32 hours (interquartile range: 20–63 hours). Peak inspiratory pressure and dynamic compliance (Cdyn) at the time of retrieval, but not the partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio, correlated with recipient LMV in Spearman correlations (r = 0.280, p = 0.002; r = −0.245, p = 0.003; and r = 0.064, p = 0.432, respectively). Linear models were built to further evaluate the impact of donor ventilation parameters on LMV. The first model was based on donor P/F ratio, donor age, donor intubation time, donor smoking history, donor partial pressure of carbon dioxide, aspiration, chest trauma, and pathologic chest X-ray. This model performed poorly (multiple R-squared = 0.063). In a second model, donor ventilation parameters were included, and Cdyn was identified as the strongest predictor for LMV. The third model was extended by recipient factors, which significantly improved the robustness of the model (multiple R-squared = 0.293). CONCLUSION In this prospective evaluation of donor lung parameters, currently used donor quality criteria poorly predicted recipient LMV. Our data suggest that Cdyn is a strong donor-bound parameter to predict short-term graft performance; however, recipient factors are similarly relevant.

Laryngotracheal resections have become a clinical routine in experienced airway centers and even extended glotto-subglottic resections and reconstructions can be performed with low complication rates and excellent long-term airway patency. However, reports on the functional outcome after laryngotracheal resections are sparse and there is no general agreement among airway surgeons, which functional evaluations should be performed before and after surgery. The following review provides an overview on basic assessment tools, which can be used to objectively report functional outcome after laryngotracheal surgery.

OBJECTIVE Single-stage laryngotracheal reconstruction (SSLTR) provides a definite surgical treatment for patients with complex glotto-subglottic stenosis. To date, the influence of SSLTR on the functional outcome after surgery has not been analyzed. METHODS A retrospective analysis of all patients receiving a SSLTR between November 2012 and October 2019 was performed. Preoperatively and 3 months postoperatively, patients received a full functional evaluation, including spirometry; voice measurements (eg, fundamental frequency; dynamic range, singing voice range, and perceptual voice evaluation using the Roughness-Breathiness-Hoarseness [RBH] score, and fiberoptic endoscopic evaluation of swallowing [FEES]). RESULTS A total of 15 patients with a mean age of 45 ± 17 years underwent SSTLR. Two (13%) patients were men and 13 (87%) were women. The majority of patients (67%) had undergone previous surgical or endoscopic treatment attempts that had failed. At the 3-month follow-up visit, none of the patients had signs of penetration or aspiration in their swallowing examination. Voice measurements revealed a significantly lower fundamental voice frequency (201.0 Hz vs 155.5 Hz; P = .006), whereas voice range (19.1 semitones vs 14.9 semitones; P = .200) and dynamic range (52.5 dB vs 53.0 dB; P = .777) was hardly affected. The median RBH score changed from R1 B0 H1 to R2 B1 H2. In spirometry, breathing capacity increased significantly (peak expiratory flow, 44% vs 87% [P

BACKGROUND: Lung transplantation is increasingly performed in recipients aged ≥65 years. However, the risk factors for mortality specific to this population have not been well studied. In lung transplant recipients aged ≥65 years, we sought to determine post-transplant survival and clinical factors associated with post-transplant mortality. METHODS: We investigated 5,815 adult lung transplants recipients aged ≥65 years in the Scientific Registry of Transplant Recipients. Mortality was defined as a composite of recipient death or retransplantation. The Kaplan–Meier method was used to estimate the median time to mortality. Univariable and multivariable Cox proportional hazards regression models were used to examine the association between time to mortality and 23 donor, recipient, or center characteristics. RESULTS: Median survival in lung transplant recipients aged ≥65 years was 4.41 years (95% CI: 4.21–4.60 years) and significantly worsened by increasing age strata. In the multivariable model, increasing recipient age strata, creatinine level, bilirubin level, hospitalization at the time of transplantation, single lung transplant operation, steroid use at the time of transplantation, donor diabetes, and cytomegalovirus mismatch were independently associated with increased mortality. CONCLUSIONS: Among the 8 risk factors we identified, 5 factors are readily available, which can be used to optimize post-transplant survival by informing risk during candidate selection of patients aged ≥65 years. Furthermore, bilateral lung transplantation may confer improved survival in comparison with single lung transplantation. Our results support that after careful consideration of risk factors, lung transplantation can provide life-extending benefits in individuals aged ≥65 years.

This paper presents a completely new approach to measure the jitter at the output of a sample-and-hold circuit. A cyclostationary stochastic process is used to model the entire noise of the measurement system. This approach relies on the calculation of a cyclostationary variance, representing a complete description of the noise of the measurement system. This provides the basis for conducting powerful analyses of how the various noise sources contribute to the cyclostationary variance, enabling the user to gain a deep insight into the noise behavior of the system. A new jitter estimator is derived that provides some new and unprecedented features. First, it is robust against the second harmonic of the input signal, and second, it allows for the elimination of cyclostationary noise contributed by the data acquisition device. A stochastic model of the method is derived and a thorough analysis of the uncertainty of the proposed estimator is presented. This results in a formula that allows for the prediction of the measurement uncertainty and another formula that allows for the calculation of the required number of samples in order to meet a given uncertainty. The method proved to be accurate in Monte Carlo simulations and in measurements as well. A jitter in the range of 22 fs out of a 10-GS/s sample-and-hold integrated circuit was successfully measured with a standard deviation of 230 as.

The management of pediatric airway pathology can be challenging and requires a dedicated team, consisting of thoracic surgeons, phoniatricians, logopedics, pediatricians and anesthetists. It necessitates a tailored treatment approach for each individual patient in order to address the minor variances that exist between cases. The majority of pediatric airway problems are a sequela of prematurity and prolonged post-partal intubation/tracheostomy. Surgical repair is often complicated by additional malformation or severe comorbidities. This comprehensive review should give an overview on most common airway problems in neonates and children as well as available surgical techniques.

Chronic lung allograft dysfunction (CLAD), presenting as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) is the major limiting factor of long-term survival in lung transplantation. Its pathogenesis is still obscure. In BOS, persistent alloimmune injury and chronic airway inflammation are suggested. One of the main tasks of the lymphatic vessel (LV) system is the promotion of immune cell trafficking. The formation of new LVs has been shown to trigger chronic allograft rejection in kidney transplants. We therefore sought to address the role of lymphangiogenesis in CLAD.Formalin-fixed paraffin-embedded tissue samples of 22 patients receiving a lung retransplantation due to BOS or RAS were collected. Lymphatic vessel density (LVD) was determined by immunohistochemical staining for podoplanin. Lung tissue obtained from 13 non-CLAD patients served as control. The impact of LVD on graft survival was assessed.Lymphatic vessel density in CLAD patients did not differ from those in control subjects (median number of LVs per bronchiole: 4.75 (BOS), 6.47 (RAS), 4.25 (control), P = 0.97). Moreover, the number of LVs was not associated with regions of cellular infiltrates (median number of LVs per bronchiole: with infiltrates, 5.00 (BOS), 9.00 (RAS), 4.00 (control), P = 0.62; without infiltrates, 4.5 (BOS), 0.00 (RAS), 4.56 (control), P = 0.74). Lymphatic vessel density did not impact the time to development of BOS or RAS in lung transplantation (low vs high LVD: 38.5 vs 86.0 months, P = 0.15 [BOS]; 60.5 vs 69.5 months, P = 0.80 [RAS]).Unlike chronic organ failure in kidney transplantation, lymphangiogenesis is not altered in CLAD patients. Our findings highlight unique immunological processes leading to BOS and RAS.

Purpose The diagnosis and treatment of antibody-mediated rejection (AMR) after LTx has gained increasing recognition within the transplant community. Extracorporeal photopheresis (ECP) modulates various pathways of the immune system and is currently used to treat CLAD. In AMR, adding ECP to established AMR treatments could potentially prevent rebound of DSA. This study aimed to analyze the role of ECP as adjunct treatment of AMR. Methods Patients who developed antibody-mediated rejection between 2009 and 2019 were included in this single-center retrospective analysis. The following parameters were evaluated: DSAs, C4d deposition and lung histology. Results A total of 39 patients developed clinical AMR during follow-up. Nineteen (48%) patients had positive DSA against HLA Class I and eighteen (46%) HLA Class II. Median time to diagnosis of AMR was 180 days (IQR: 2-2477). First line treatment was immunoadsorption (IA) in 34 (87%) patients, intravenous immunoglobulins with concomitant immunoadsorption in 3 (8%) patients and in 2 cases ATG. Twenty (51%) patients primarily treated with IA and the two patients treated with ATG received ECP. Among the patients treated with ECP, 12 had DSA against HLA Class I and 13 against HLA Class II. ECP treatment was initially performed twice a week. After stabilization of lung function and improvement of clinical situation, ECP was then performed once a month for a minimum of 6 months. Median length of treatment was 12 months. Patients who received ECP after first line treatment had 1-year survival rate of 62% compared to 27% of other AMR patients. In all patients treated with IA followed by ECP, DSA disappeared or MFI reduced below our institutional threshold of 5000. Conclusion Extracorporeal photopheresis is associated with a reduction of de novo DSA after antibody-mediated rejection. Prospective studies are necessary to confirm the beneficial effect of ECP as an add-on therapy after AMR.

A 55-year-old woman was referred to our department with a bilateral stenosis of both main bronchi starting at the level of the carina and a blind-ended pouch originating from the carina. Differential diagnosis of diffuse narrowing of the intrathoracic central airways was excluded during the diagnostic workup. Recurrent infection of the blind-ended pouch remained a possible explanation of this unusual type of stenosis. Carinal resection and reconstruction by end-to-end anastomosis of the trachea to the right main bronchus and reimplantation of the left main bronchus to the intermediate bronchus with intraoperative extracorporeal membrane oxygen support resulted in an excellent long-term outcome.

Background Airway management during repair of laryngotracheal stenosis is demanding, and there is currently no accepted standard of care. Recently an increasing number of airway centers have started to use a laryngeal mask until the airway is surgically exposed and cross-table ventilation can be initiated. However detailed data on this approach are missing in the literature. Methods Patients receiving laryngotracheal surgery from November 2011 until October 2018 were retrospectively included in this single-center study, except for patients who presented with a preexisting tracheostomy at time of surgery. Airway management uniformly consisted of laryngeal mask ventilation until cross-table ventilation was established. Clinical variables, perioperative complications, and airway complications were analyzed. Results One hundred eight patients (65 women, 43 men) receiving tracheal resection (n = 50), cricotracheal resection (n = 49), or single-stage laryngotracheal reconstruction (n = 9) were included in the analysis. Of the included patients 23 (21.3%) had malignant disease and 85 (78.7%) a benign pathology. In the subgroup of patients with subglottic disease 85.1% had high-grade stenosis (Myer-Cotton III°). Airway management with a laryngeal mask was successful in all except 1 patient (99.1%). Mean pulse oximetry and mean end-tidal CO2 during laryngeal mask ventilation was 98.7% ± 2.4% and 34.8 ± 7.6 mm Hg, respectively. At the end of surgery 95 patients (88%) were successfully weaned from the respirator using the laryngeal mask. Conclusions The laryngeal mask as the primary airway device is feasible and safe in patients undergoing laryngotracheal surgery even in cases with high-grade stenosis.

Background Lung transplantation has evolved to a routinely performed surgical procedure in patients with end-stage pulmonary disease. Bronchial healing problems are rare but represent a potential life-threatening complication. Herein, we aimed to define the incidence, classification, and treatment of bronchial complications after lung transplantation. Material and Methods All patients receiving lung transplantation between January 1999 and December 2017 were included in this retrospective study. All bronchial anastomoses were performed in a standardized technique using a single, polydioxanone running suture. The rate of anastomotic complications requiring an intervention, type of complication according the 2018 International Society for Heart and Lung Transplantation classification, and the clinical management were retrospectively analyzed. Results A total of 2941 anastomoses were performed in 1555 patients. The overall incidence of relevant anastomotic complications was 1.56%, 0.68% for left anastomoses, and 2.44% for right anastomoses. In 6 patients, a surgical revision or retransplantation was performed, whereas endoscopic treatment alone was sufficient in 39 patients. One patient underwent right-sided retransplantation 6 months after the first lung transplantation after failed endoscopic treatment attempts. International Society for Heart and Lung Transplantation grade “S Lc Ec” was the most common type of anastomotic complication. The overall incidence decreased within the study period from 2.4% in the era 1999 to 2003 to 0.8% in the era 2014 to 2017. We found no significant difference in overall survival of patients with and without anastomotic complications (P = .995; hazard ratio, 0.99; 95% confidence interval, 0.63-1.58). Conclusions The single running suture technique is associated with a very low rate of true anastomotic complications. Close follow-up and early endoscopic treatment of patients with anastomotic complications result in excellent long-term outcomes.

Objective Intraoperative extracorporeal membrane oxygenation (ECMO) is usually reserved to support patients during complex lung transplantation. We hypothesized that a routine application of intraoperative ECMO in all patients improves primary graft function. Methods Patients receiving a bilateral lung transplantation between November 2016 and July 2018 at the Medical University of Vienna were included in this prospective, single-center observational study. All transplantations were uniformly performed on central venoarterial ECMO support, with the possibility to extend ECMO into the early postoperative period whenever graft function did not meet established quality criteria at the end of implantation. Primary graft dysfunction (PGD) grades were evaluated at 24, 48, and 72 hours after transplantation. Perioperative complications and survival outcome were assessed. Results A total of 159 patients were included in the study. At 24 hours post-transplantation, 38.4% (n = 61) of patients were already extubated, 48.4% (n = 77) were classified as PGD0, 4.4% (n = 7) as PGD1, 3.1% (n = 5) as PGD2, 2.5% (n = 4) as PGD3, and 3.1% (n = 5) were “ungradable” due to prophylactic postoperative prolongation of ECMO. At 72 hours after transplantation, 76.7% (n = 122) of the patients were extubated, as opposed to only 1.3% (n = 2) of patients classified as PGD3. The median time of mechanical ventilation was 29 hours (interquartile range, 17-58). The 90-day-mortality was 3.1%, and 2-year survival was 86%. Conclusions Routine use of intraoperative ECMO resulted in excellent primary graft function and mid-term outcome in patients undergoing lung transplantation. To the best of our knowledge, the herein measured PGD rates are the lowest reported in the literature to date. Our results advocate a routine intraoperative use of ECMO in bilateral lung transplantation.

Purpose In patients suffering from idiopathic pulmonary arterial hypertension (iPAH), cardiac function can be impaired in the early postoperative phase after lung transplantation as the chronically untrained left ventricle is prone to fail. Thus, restrictive fluid management is pivotal to unload the left heart. In our institution, continuous renal replacement therapy (CRRT) is implemented liberally, whenever a patient cannot be balanced negatively. It remains unclear whether such strategy impairs long-term kidney function. Methods iPAH patients transplanted between 2000 and 2018 were included in this retrospective study. The influence of hemofiltration in the peri-operative phase on long-term outcomes was investigated. Results A total of 87 iPAH lung transplant recipients were included in this analysis. In 38 patients (44%) CRRT was started in the early postoperative period for a median of 16 days (3-45). In this group, urine production had significantly decreased and patients began to acquire a positive fluid balance, however, hemostatic functions of the kidney were still preserved at the time of CRRT initiation. All patients were successfully weaned from CRRT and fully recovered their kidney function at the time of hospital discharge (Figure 1). No difference in kidney function was found between CRRT and non-CRRT patients at 1, 3, and 5 years. Long-term survival was excellent with 10-year survival rates of 75%. Conclusion Early implementation of CRRT for perioperative volume management does not impair long-term kidney function in iPAH recipients. Our data suggest that such a strategy leads to excellent long-term outcomes.

Background Several activities are attributed to antimicrobial peptides (AMPs), including bacterial killing, leucocyte recruitment and angiogenesis. Despite promises of advanced cellular therapies for treatment of diabetic foot ulcer, it is currently accepted that paracrine factors rather than cellular components are causative for the observed effects. Whether AMPs are present in the mononuclear cell (MNC) secretome (MNC‐sec) of white blood cells that are beneficial in experimental wound healing is not known. Materials and methods Antimicrobial activity of the secretomes of nonirradiated (MNC‐sec) and γ‐irradiated MNCs (MNC‐sec rad) was analysed by microdilution assay. AMPs were determined by quantitative real‐time PCR (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA). Whether human MNC‐sec rad causes AMP secretion in vivo was examined in an experimental rat model. Image flow cytometry was used to determine the type of cell death induced in MNCs after exposure to γ‐radiation. Results The antimicrobial activity assay revealed a bactericidal activity of MNC‐sec rad and to a lesser degree also of MNC‐sec. Image flow cytometry showed that γ‐irradiation of MNCs induced early apoptosis followed mainly by necroptosis. RT‐PCR and ELISA revealed a high abundance of different AMPs in the secretome of MNCs. In addition, human MNC‐sec elicited an increase in de novo endogenous AMP production in rats in vivo. Conclusion We provide evidence that the secretome of MNCs has direct and indirect positive effects on the immune defence system, including augmentation of antibacterial properties. Our data further suggest that necroptosis could play a key role for the release of paracrine factors and the therapeutic action of MNC‐sec rad.

Background Anastomotic failure is a rare but severe complication after airway surgery. A sufficient blood supply is crucial for the healing of the anastomosis. Currently, judging the appearance of the mucosa by conventional bronchoscopy is the only available technique to monitor the anastomosis. Near-infrared imaging using indocyanine green (ICG) as an intravasal fluorescent can be used to directly assess tissue perfusion. For technical reasons, bronchoscopic ICG angiography to evaluate blood supply of airway anastomosis was unavailable in the past. We sought to investigate the technical feasibility of ICG perfusion using a newly developed bronchoscopy unit with an integrated near-infrared filter to monitor perfusion during the healing of tracheal anastomosis. Methods Twelve patients who underwent elective airway surgery were included in this prospective, single-center feasibility study. The ICG was administered intravenously at 0.2 mg/kg body weight at three timepoints: at the end of surgery; 3 to 5 days postoperatively; and 2 months postoperatively. A custom-made bronchoscopy unit (Karl Storz, Tuttlingen, Germany) was used to assess the anastomosis with white light and additionally with near-infrared light to monitor the distribution and intensity of the fluorescence signal. Results A total of 32 ICG fluorescence bronchoscopies were performed in our study cohort. In all measurements, a sufficient fluorescence signal was detected. A lack of perfusion was detected in all patients confined to the anastomotic suture line immediately after the operation. This malperfusion resolved gradually after 3 to 5 days and disappeared completely after 2 months. No anastomotic complication developed in our series of patients during follow-up (median 7 months). Conclusions To the best of our knowledge, this is the first report on ICG fluorescence bronchoscopy in the literature. It is an easy and effective method to evaluate the perfusion at the tracheal anastomosis. In the future, it might contribute to an early detection of anastomotic failure and reduce morbidity and mortality after airway surgery.

On 7 August 1974, the 24-year-old French tightrope walker, Philippe Petit, captivated the world when he walked across a steel high wire suspended between the New York City's Twin Towers—without a safety net ( Figure 1 ). More than four decades later this coup is still considered as one of the most extreme tightrope walks ever…