Interstitial Pulmonary Fibrosis and Extensive Dendriform Ossification with Persistent Viral Load: A Rare Presentation of Post-COVID-19 Condition in Need of Lung Transplantation.

The incidence, presentation, and predisposing factors of post-acute sequelae of COVID-19 (PASC) are currently poorly understood. Lung explants may provide a rare insight into terminal SARS-CoV-2-associated lung damage and its pathophysiology. A 62-year-old man presented with progressively worsening respiratory symptoms after recovering from mild COVID-19 3 months earlier. No underlying pulmonary comorbidities were reported. A chest CT revealed bilateral extensive ground-glass and reticular opacities, suspicious of pulmonary fibrosis. Despite initial high-dose glucocorticoid therapy, the interstitial lung disease progressed, and after exhausting all viable therapeutic options, bilateral lung transplantation was successfully conducted. Histological analysis revealed extensive end-stage interstitial fibrosis with diffuse dendriform ossification and bronchiolar and transitional cell metaplasia. Signs of interstitial remodeling such as an increased interstitial collagen deposition, a pathological accumulation of CD163+/CD206+ M2-polarized macrophages with an increased expression of phosphorylated ERK, and an increased density of CD105+ newly formed capillaries were observed. qRT-PCR and immunohistochemistry for SARS-CoV-2 N-protein in the endothelium of medium-sized vessels confirmed a persistence of SARS-CoV-2. Our findings highlight a highly unusual presentation of SARS-CoV-2-associated lung fibrosis, implying that incomplete viral clearance in the vascular compartment may play a vital pathophysiological role in the development of PASC.

External validation of risk prediction scores in patients undergoing anatomic video-assisted thoracoscopic resection.

BACKGROUND: EuroLung Risk scores were established to predict postoperative morbidity and mortality in patients undergoing anatomic lung resections. We aimed to perform an external validation of the EuroLung scores, which were calculated from data of the European Society of Thoracic Surgeons database, in our video-assisted thoracoscopic surgery cohort. METHODS: All available EuroLung scores were calculated for 718 patients scheduled for anatomic video-assisted thoracoscopic surgery resections between 2009 and 2019. Morbidity and mortality according to the definitions of the EuroLung scores were analyzed in a prospectively maintained database. RESULTS: Overall observed complication rate was 10.45%. Scores showed weak individual correlation (η = 0.155-0.174). The EuroLung1 app score showed the biggest area under the receiver operative characteristic (ROC) curve with 0.660. Binary logistic regression analysis showed that predicted postoperative forced expiratory volume in 1 s was associated with increased complications in both EuroLung1 and parsimonious EuroLung1 scores. Thirty-day mortality was 0.7% (predicted 1.10-1.40%) and was associated with predicted postoperative forced expiratory volume in 1 s for both EuroLung2 and parsimonious EuroLung2 scores. The EuroLung2 (2016) showed the biggest area under the ROC curve with 0.673. Only a very weak eta correlation between predicted and observed mortality was found for both aggregate EuroLung2, EuroLung2 (2016), EuroLung2 (2019), and parsimonious EuroLung2 (2016) (η = 0.025/0.015/0.011/0.009). CONCLUSION: EuroLung scores help to estimate postoperative morbidity. However, even with the highest aggregate EuroLung scores possible only 50% suffer from postoperative morbidity. Although calibration of the scores was acceptable, discrimination between predicted and observed events was poor. Therefore, individual correlation between predicted and observed events is weak. Therefore, EuroLung scores may be best used to compare institutional quality of care to the European Society of Thoracic Surgeons database but should not be used to preclude patients from surgical treatment.

Clinical relevance of lung transplantation for COVID-19 ARDS: a nationwide study.

BACKGROUND: Although the number of lung transplantations (LTx) performed worldwide for COVID-19 induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of most severly ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx to the pandemic are unknown. METHODS: A retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-Cov-2) infection admitted between January 1, 2020 and May 30, 2021 in Austria. Patients referred to one of the two Austrian LTx centers were analyzed and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared to patients who underwent LTx for other indications. RESULTS: Between January 1, 2020 and May 30, 2021, 39.485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation, 183 received extra-corporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. With a median follow-up of 134 (47-450) days, 14/19 patients are alive. CONCLUSIONS: Early referral of ECMO patients to a LTx center is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS.

A spark of hope: histopathological and functional recovery after critical COVID-19.

BACKGROUND: There are substantial concerns about fibrotic and vascular pulmonary sequelae after coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS).AQ1 Histopathology reports of lung biopsies from COVID-19 survivors are scarce. CASE: We herein report results of functional and histopathological studies in a 70 year-old man undergoing a co-incidental tumor lobectomy six months after long-term mechanical ventilation for COVID-19 pneumonia. CONCLUSION: Despite several unfavorable risk factors, this case presentation shows a completed pulmonary recovery process within a few months.

Thoracotomy versus video-assisted thoracoscopic surgery (VATS) in stage III empyema-an analysis of 217 consecutive patients.

BACKGROUND: Pleural empyema is an infectious disease of the chest cavity, with a high morbidity and mortality. According to the American Thoracic Society, pleural empyema gets graduated into three stages, with surgery being indicated in intermediate stage II and chronic stage III. Evidence for the feasibility of a minimally-invasive video-assisted thoracoscopic approach in stage III empyema for pulmonary decortication is still little. METHODS: Retrospective single-center analysis of patients conducted to surgery for chronic stage III pleural empyema from 05/2002 to 04/2014 either by video-assisted thoracoscopic surgery (VATS, n = 110) or conventional open surgery by thoracotomy (n = 107). Multiple regression analysis and propensity score matching was used to evaluate the influence of operation technique (thoracotomy versus VATS) on the length of post-operative hospitalization. RESULTS: Operation time was longer in the thoracotomy-group (p = 0.0207). Conversion rate from VATS to open surgery by thoracotomy was 4.5%. Post-operative complication- (61 patients in thoracotomy- and 55 patients in VATS-group), recurrence- (3 patients in thoracotomy- and 5 in VATS-group) and mortality-rates (6.5% in thoracotomy- and 9.5% in VATS-group) did not differ between both groups; the length of (post-operative) stay at intensive care unit was longer in the VATS-group (p = 0.0023). Duration of chest tube drainage and prolonged air leak rate were similar among both groups, leading to a similar overall and post-operative length of hospital stay in both groups. Adjusted to clinically and statistically relevant confounders, multiple regression analysis showed an influence of the surgical technique on length of post-operative stay after pair matching of the patients (n = 84 in each group) by propensity score (B = - 0.179 for thoracotomy = 0 and VATS = 1, p = 0.032) leading to a reduction of 0.836 days after a VATS-approach compared to thoracotomy. CONCLUSIONS: VATS in late stage (III) pleural empyema is feasible and safe. The decrease in post-operative hospitalization demonstrated by adjusted multiple regression analysis may indicate the minimally-invasive approach being safe, more tolerable for patients, and more effective.

VATS Partial Pleurectomy Versus VATS Pleural Abrasion: Significant Reduction in Pneumothorax Recurrence Rates After Pleurectomy.

INTRODUCTION: Surgical treatment of primary spontaneous pneumothorax (PSP) usually consists of bullectomy and any form of pleurodesis to reduce risk of disease recurrence. Whether pleurectomy is superior to pleural abrasion is still a matter of debate with recurrence rates especially high when performed with a video-assisted thoracoscopic (VATS) approach. Aim of this study was to compare the efficacy of the two methods in prevention of recurrence of pneumothorax in a minimally invasive setting. MATERIALS AND METHODS: Between 01/2005 and 12/2015, 107 patients younger than 40 years with PSP underwent VATS bullectomy and either partial pleurectomy or pleural abrasion. Medical records of patients were reviewed retrospectively. RESULTS: Pleural abrasion was performed in 34/107 patients, 73/107 patients underwent partial pleurectomy. There were no statistically significant differences in age, sex, body mass index or smoking history at time of surgery. There was no significant difference in major postoperative complications (p = 0.3022). Nine (8.4%) patients had a recurrence of pneumothorax during follow-up. Incidence of recurrence in those undergoing pleural abrasion was significantly higher than those undergoing apical pleurectomy (8/34 vs. 1/73, p < 0.001). Surgical technique was the only factor associated with a recurrence of PSP after surgical intervention. DISCUSSION: In our analysis, a VATS partial pleurectomy proved to be effective for prevention of recurrent PSP. Recurrence rates were low despite a minimally invasive approach and significantly lower than in the pleural abrasion group. According to these findings, VATS pleurectomy might be considered as the primary choice for surgical pleurodesis in patients with PSP.

Measures to Prevent Air Embolism in Transthoracic Biopsy of the Lung.

OBJECTIVE: Systemic air embolism (AE) is a rare but feared complication of transthoracic biopsy with potentially fatal consequences. The aim of the study was to assess the effect of patient positioning during transthoracic biopsy on preventing systemic AE. MATERIALS AND METHODS: We compared a historical control group of 610 patients (group 1) who underwent transthoracic biopsy before the implementation of measures to prevent systemic AE during transthoracic biopsy and a group of 1268 patients (group 2) who underwent biopsy after the measures were implemented. The patients in group 2 were placed in the ipsilateral-dependent position so that the lesion being biopsied was located below the level of the left atrium. RESULTS: The rate of systemic AE was reduced from 3.77% to 0.16% (odds ratio [OR], 0.040; 95% CI, 0.010-0.177; p < 0.001). Logistic regression analyses identified needle penetration depth, prone position of the patient during biopsy, location above the level of the left atrium, needle path through ventilated lung, and intubation anesthesia as independent risk factors for systemic AE (p < 0.05). Propensity score-matched analyses identified the number of biopsy samples obtained as an additional risk factor (p = 0.003). The rate of pneumothorax was reduced from 15.41% in group 1 to 5.99% in group 2 (OR, 0.374; 95% CI, 0.307-0.546; p < 0.001). CONCLUSION: Performing transthoracic biopsy with the patient in an ipsilateral-dependent position so that the lesion is located below the level of the left atrium is an effective measure for preventing systemic AE. Needle path through ventilated lung and intubation anesthesia should be avoided whenever possible.

Causes, predictors and consequences of conversion from VATS to open lung lobectomy.

BACKGROUND: To analyze causes, predictors and consequences of conversions from intended VATS lobectomy to open surgery. METHODS: This is a retrospective analysis of a prospectively maintained database. RESULTS: From 2009 until December 2012, 232 patients were scheduled for anatomical VATS resection. Conversion to open surgery was necessary in 15 (6.5 %) patients. Reasons for conversion were bleeding in six, oncologic in five and technical in four patients (adhesions after pleuritis or radiotherapy for other tumors: 3; limited space: 1). In a univariable exact logistic regression analysis, conversion rate was significantly higher in patients after induction therapy (p = 0.019). There was also a statistical trend to a higher conversion rate in patients with larger tumor size (<3 vs. ≥3 cm, p = 0.117) and during the first half of our series (p = 0.107). Conversion rate was not influenced by patient age, nodal stage (pN0 vs. pN+), body mass index, the presence of chronic obstructive pulmonary disease, lung function (FEV1) or benign disease. In a multivariable exact logistic regression, induction treatment (p = 0.013) and tumor size (p = 0.04) were independent significant risk factors for conversion. Conversion did not translate into higher overall postoperative complication rate (33.3 vs. 29.5 %), longer chest drain duration (median, 5 vs. 5 days) or in-hospital mortality (0 vs. 1 %). However, length of hospital stay was significantly longer in the conversion group (median 11 vs. 9 days, p = 0.028). CONCLUSIONS: Induction therapy was an independent risk factor for conversion to thoracotomy in this VATS lobectomy series. Following induction therapy, patients should be carefully selected for a VATS approach. Conversion to thoracotomy did not increase the postoperative rate of complications or mortality, but significantly increased length of hospital stay.

Extended minimally invasive lung resections: VATS bilobectomy, bronchoplasty, and pneumonectomy.

PURPOSE: The aim of the present study was to analyze feasibility, morbidity, mortality, and oncologic outcome of extended video-assisted thoracoscopic surgery (VATS) anatomic lung resections in a single-center experience. Extended resections include bilobectomies, bronchoplasties, and pneumonectomies. METHODS: The present study is a retrospective analysis of a prospectively maintained institutional database. Between 2009 and 2014, 390 patients were scheduled for anatomical VATS resections. VATS resection was completed in 370 patients giving an overall conversion rate of 5.1 %. Extended VATS resections were performed in 29 patients (7.8 %): bilobectomy in 8, bronchoplastic resection in 15 (2 bronchial sleeve resections, 11 wedge bronchoplasties, 2 simple bronchoplasties), and pneumonectomy in 6. RESULTS: Median operative time was 217 min (117-390 min). Median chest tube duration was 4 days (range, 2-50 days). Median length of hospital stay was 9 days (6-63 days). There was no in-hospital mortality. Major complications with need for reinterventions occurred in three patients (10.3 %): one air leakage from bronchial stump after pneumonectomy, one hematothorax after completion pneumonectomy, and one chylothorax. All complications were treated with VATS procedures. Minor complications included two persistent air leaks that were treated with an additional chest drain and resolved, one urinary tract infection, one atelectasis with need for bronchoscopy, and one pleural fluid collection with the need for drainage. After a median follow-up of 26 months, no local tumor recurrence occurred. Two patients had a second lung primary cancer and four patients with advanced tumor stages had distant recurrent disease. CONCLUSIONS: With growing experience, extended VATS resections are feasible in selected cases with low perioperative morbidity and mortality.

Anatomic lung resections for benign pulmonary diseases by video-assisted thoracoscopic surgery (VATS).

PURPOSE: Based on increasing evidence of its benefits regarding perioperative and oncologic outcome, video-assisted thoracoscopic surgery (VATS) has gained increasing acceptance in the surgical treatment of early stage non-small cell lung cancer (NSCLC). However, the evidence for a VATS approach in anatomic lung resection for benign pulmonary diseases is still limited. METHODS: Between March 2011 and May 2014, data from 33 and 63 patients who received VATS anatomic lung resection for benign diseases (VATS-B) and early stage NSCLC (VATS-N), respectively, were analyzed retrospectively. For subgroup analyses, VATS-B was subdivided by operation time and underlying diseases. Subgroups were compared to VATS-N. RESULTS: Three patients from VATS-B and four from VATS-N experienced conversion to open surgery. Causes of conversion in VATS-B were intraoperative complications, whereas conversions in VATS-N were elective for oncological concerns (p < 0.05). Operation time and duration of postoperative mechanical ventilation were longer by tendency; postoperative stay on intensive care unit and chest tube duration were significantly longer in VATS-B. Subgroup analyses showed a longer operation time as a predictor for worse perioperative outcome regarding postoperative mechanical ventilation, postoperative stay on intensive care unit, chest tube duration, and length of hospital stay. Patients with longer operation time suffered from more postoperative complications. Differences in perioperative outcome data were not significantly dependent on the underlying benign diseases compared to VATS-N. CONCLUSIONS: VATS is feasible and safe in anatomic lung resection for benign pulmonary diseases. Not the underlying disease, but a longer operation time is a factor for worse postoperative outcome.

Video-assisted thoracoscopic anatomic lung resections in Germany-a nationwide survey.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is an accepted alternative to thoracotomy for anatomic lung resection (AR) and literature suggests benefits over the conventional open approach. However, it's routine clinical application is still low and varies within different countries. METHODS: Nationwide survey among thoracic surgical units in Germany, evaluating the departmental structure, volume of the VATS program, experience with VATS-AR (lobectomies and other-than-lobectomies-anatomic-resections), surgical technique and learning curve data. RESULTS: Response rate among the 269 surgical units practicing thoracic surgery in Germany was 84.4 % (n = 227). One hundred twenty-two (53.7 %) units do have experience with any type of VATS-AR. The majority of units started the VATS program only within the last 5 years and 17.2 % (n = 21) of the units have performed more than 100 procedures by now. In 2013, 78.7 % of the units performed less than 25 % of their institutional AR via a VATS approach. Indications for VATS-AR were non-small cell lung cancer in 93.4 % (up to UICC-stage IA, IB, IIA, IIB, IIIA in 7 %, 22.8 %, 33.3 %, 17.5 %, 7 %, respectively), benign diseases in 57.4 %, and pulmonary metastases in 50.8 %. 43.4 % of the departments had experience with extended VATS-AR and 28.7 % performed VATS-AR after induction-therapy. CONCLUSIONS: Every second thoracic surgical unit in Germany does have experience in VATS-AR though only about 20 % of them perform it routinely and also in extended procedures.

The impact and relevance of techniques and fluids on lung injury in machine perfusion of lungs.

Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols.

Intercostal Catheters Reduce Long-Term Pain and Postoperative Opioid Consumption after VATS.

Background/Objectives: Pain after video-assisted thoracoscopic surgery (VATS) leads to impaired postoperative recovery, possible side effects of opioid usage, and higher rates of chronic post-surgery pain (CPSP). Nevertheless, guidelines on perioperative pain management for VATS patients are lacking. The aim of this study was to analyze the effectiveness of intercostal catheters in combination with a single shot intraoperative intercostal nerve block (SSINB) in comparison to SSINB alone with respect to opioid consumption and CPSP. Methods: Patients receiving an anatomic VATS resection between 2019 and 2022 for primary lung cancer were retrospectively analyzed. A total of 75 consecutive patients receiving an ICC and SSINB and 75 consecutive patients receiving only SSINB were included in our database. After enforcing the exclusion criteria (insufficient documentation, external follow-ups, or patients receiving opioids on a fixed schedule; n = 9) 141 patients remained for further analysis. Results: The ICC and No ICC cohort were comparable in age, gender distribution, tumor location and hospital stay. Patients in the ICC cohort showed significantly less opioid usage regarding the extent (4.48 ± 6.69 SD vs. 7.23 ± 7.55 SD mg, p = 0.023), duration (0.76 ± 0.97 SD vs. 1.26 ± 1.33 SD days, p = 0.012) and frequency (0.90 ± 1.34 SD vs. 1.45 ± 1.51 SD times, p = 0.023) in comparison to the No ICC group. During the first nine months of oncological follow-up assessments, no statistical difference was found in the rate of patients experiencing postoperative pain, although a trend towards less pain in the ICC cohort was found. One year after surgery, the ICC cohort expressed significantly less often pain (1.5 vs. 10.8%, p = 0.035). Conclusions: Placement of an ICC provides VATS patients with improved postoperative pain relief resulting in a reduced frequency of required opioid administration, less days with opioids, and a reduced total amount of opioids consumed. Furthermore, ICC patients have significantly lower rates of CPSP one year after surgery.

Is limited surgery justified in the treatment of T1 colorectal cancer?

BACKGROUND: Surgical treatment of colorectal cancer (CRC) should be aimed primarily at achieving a combination of surgical-oncologic radicalness and the highest possible quality of life. In recent years, surgical therapy for T1 CRC has tended toward less radical interventions. The question regarding changes in survival and recurrence rates still is unanswered. METHODS: A retrospective medical chart review of patients surgically treated in our department for T1 CRC from January 1990 to December 2010 (n = 223) was performed. Charts were reviewed for tumor-specific parameters, local recurrence, distant metastasis, and patient survival. The different treatment options used were strictly separated for a more detailed workup. RESULTS: Radical resection (RR) was performed for 57.1 %, local resection (LR) for 14.8 %, and an endoscopic approach (EA) for 28.1 % of the study population. After receipt of the histology report, 35.7 % of the patients initially resected nonradically underwent reoperation, mostly using RR. Seven patients experienced a local recurrence over time (3.6 %): one after initial RR, three after LR, and three after EA. Systemic recurrence occurred for nine patients (4.6 %) over time, six of whom had undergone initial RR. High-risk criteria were shown for 20 T1 CRCs. For 60 % (12/20) of the patients, initial RR was performed. Radical reoperation was performed for 75 % of the nonradically treated high-risk tumors. One high-risk patient without reoperation experienced metastatic disease over time. The 5-year overall survival rate was 87.2 %, itemized for the defined subgroups as follows: 83.9 % for RR, 82.8 % for LR, and 58.2 % for EA. CONCLUSION: Patients with T1 CRC had a distinctly higher incidence of local recurrence after EA or LR. Explicit workup in terms of risk classification is crucial to reducing the risk of local and systemic recurrence. A nonradical approach should be only a second option for patients with T1 CRC, namely, those solely in clearly low-risk situations or those with distinct comorbidities.

Robotic-assisted minimally invasive vs. thoracoscopic lung lobectomy: comparison of perioperative results in a learning curve setting.

PURPOSE: Minimally invasive lung lobectomy was introduced in the late 1990s. Since that time, various different approaches have been described. At our institution, two different minimally invasive approaches, a robotic and a conventional thoracoscopic one, were performed for pulmonary lobectomies. This study compares perioperative outcome of the two different techniques in a learning curve setting. METHODS: Between 2001 and 2008, 26 patients underwent lung lobectomy with a robotic-assisted thoracoscopic surgery (RATS) technique. In 2009, the minimally invasive approach was changed to a conventional video-assisted thoracoscopic surgery (VATS) technique. Perioperative results of the first 26 VATS patients were compared to the results of the robotic group. RESULTS: There were significantly more patients with clinical stage >IB in the VATS group than in the robotic-assisted group (23.1 vs. 0 %). Otherwise, demographic data were equal between the groups. Operative time was significantly longer in the robotic group (215 vs. 183 min, p = 0.0362). Median difference between preoperative hemoglobin levels and levels on postoperative day 1 was higher in the RATS group, suggesting a higher blood loss. No difference was found in conversion rate, acute phase protein levels (C-reactive protein), chest drain duration, postoperative morbidity and mortality, and length of hospital stay. Procedural costs were higher for the robotic approach (difference, 770.55 , i.e., 44.4 %). CONCLUSIONS: Shorter operative times, a lower drop of postoperative hemoglobin levels indicating less blood loss, and lower procedural costs suggest a benefit of the VATS approach over the robotic approach for minimally invasive lung lobectomy.

Risk factors, complications and costs of prolonged air leak after video-assisted thoracoscopic surgery for primary lung cancer.

Background: Prolonged air leak (PAL) represents a common complication after lung resection. This study aims to analyze the risk factors for the development of a PAL, its impact on the postoperative outcome and to estimate additional treatment costs. Methods: A single center database was queried for all patients scheduled for video-assisted thoracoscopic surgery for primary lung cancer. In total, 957 patients between 2009 and 2021 were analyzed. Exclusion criteria was pneumonectomy. Collected data included demographics and perioperative data (e.g., duration of surgery, postoperative infections, air leak duration etc.). PAL was defined as an air leak lasting for 5 days or longer. The PAL cohort included 103 patients, the non-PAL included 854 patients. Univariate analysis and binomial logistic regression were performed. Cost calculation was performed using available data from prior publications to estimate treatment costs. Results: Male sex, chronic obstructive pulmonary disease (COPD) and low body mass index (BMI) showed to be risk factors for the development of postoperative PAL (P<0.001). Using these risk factors, a risk prediction score for PAL has been established. A subgroup analysis showed a significantly higher rate of sarcopenia in patients with PAL (P<0.001). The mean duration until removal of chest drains and length of stay (LOS) was significantly longer in the PAL cohort (14.2 vs. 4.4 days, P<0.001; 19.8 vs. 9.3 days, P<0.001). Also, the duration of the operation was longer in PAL patients (179.1 vs. 161.2 minutes, P=0.001). Patients with PAL had an elevated risk for postoperative infections [odds ratio (OR) 3.211, 31.1% vs. 12.3%, P<0.001]. As a result of a prolonged LOS, estimated treatment costs were significantly higher for PAL, ranging from 2,888.2 to 12,342.8 € depending on available cost bases compared to the non-PAL cohort, which ranged from 1,370.5 to 5,856.8 € (P<0.001). Conclusions: PAL is a frequent complication that prolongs the LOS after thoracic surgery and, according to the literature, results in elevated readmission rates, leading to excess health care costs. Risk factors for PAL are well established. Preoperative treatment of sarcopenia and dismal nutritional status might alter the risk. As measures to prevent PAL are otherwise limited, guidelines for effective management of PAL need to be established.

Using machine learning surrogate modeling for faster QSP VP cohort generation.

Virtual patients (VPs) are widely used within quantitative systems pharmacology (QSP) modeling to explore the impact of variability and uncertainty on clinical responses. In one method of generating VPs, parameters are sampled randomly from a distribution, and possible VPs are accepted or rejected based on constraints on model output behavior. This approach works but can be inefficient (i.e., the vast majority of model runs typically do not result in valid VPs). Machine learning surrogate models offer an opportunity to improve the efficiency of VP creation significantly. In this approach, surrogate models are trained using the full QSP model and subsequently used to rapidly pre-screen for parameter combinations that result in feasible VPs. The overwhelming majority of parameter combinations pre-vetted using the surrogate models result in valid VPs when tested in the original QSP model. This tutorial presents this novel workflow and demonstrates how a surrogate model software application can be used to select and optimize the surrogate models in a case study. We then discuss the relative efficiency of the methods and scalability of the proposed method.

Sarcopenia and Mediastinal Adipose Tissue as a Prognostic Marker for Short- and Long-Term Outcomes after Primary Surgical Treatment for Lung Cancer.

Surgical resection remains the gold standard of treatment for early-stage lung cancer. Several risk models exist to predict postoperative morbidity and mortality. Psoas muscle sarcopenia has already successfully been used for morbidity prediction in lung transplantation and is not yet included in the available risk scores for pulmonary resections. We hypothesized that the skeletal muscle index and mediastinal adipose tissue might also have an impact on postoperative outcomes after primary surgery for primary lung cancer. The institutional database was queried for patients with primary lung cancer who were treated with primary lobectomy or segmentectomy between February 2009 and November 2018. In total, 311 patients were included for analysis. Patients receiving neo-/adjuvant chemotherapy or with a positive nodal status were excluded to rule out any morbidity or mortality due to (neo-)adjuvant treatment. Sarcopenia was defined as a skeletal muscle index of <34.4 cm2/m2 for women and <45.4 cm2/m2 for men. Mediastinal adipose tissue was defined with a radiodensity of -150 to -30 Hounsfield units. Sarcopenia was diagnosed in 78 (25.1%) of the 311 patients. Male patients were significantly more likely to suffer from sarcopenia (31.5% vs. 18.1%, p = 0.009). Comorbidities, lung function, tumour histology, pathologic tumour staging, mediastinal adipose tissue and age did not differ between groups with or without sarcopenia. Sarcopenic patients had a significantly longer length of stay, with 13.0 days vs. 9.5 (p = 0.003), and a higher rate of any postoperative complications (59.0% vs. 44.6%, p = 0.036). There was no difference in recurrence rate. Five-year overall survival was significantly better in the patient cohort without sarcopenia (75.6% vs. 64.5%, p = 0.044). Mediastinal adipose tissue showed no significant impact on length of stay, postoperative complications, recurrence rate, morbidity or survival. Sarcopenia, quantified with the skeletal muscle index, is shown to be a risk factor for postoperative morbidity and reduced survival in primary lung cancer. Efforts should be taken to pre-emptively screen for sarcopenia and start countermeasures (e.g., physical prehabilitation, protein-rich nutrition, etc.) during the preoperative workup phase.

Analysis of Pain Management after Anatomic VATS Resection in Austrian Thoracic Surgery Units.

BACKGROUND: Postoperative pain influences rehabilitation, postoperative complications and quality of life. Despite its impact, there are no uniform treatment guidelines. Different centers seem to use various strategies. This study aims to analyze pain management regimens used after anatomic VATS resections in Austrian thoracic surgery units, with a special interest in opioid usage and strategies to avoid opioids. METHODS: A questionnaire was designed to assess the use of regional anesthesia, postoperative pain medication and characteristics of individual pain management regimens. The questionnaire was sent to all thoracic surgery units in Austria, with nine out of twelve departments returning them. RESULTS: All departments use regional anesthesia during the procedure. Four out of nine centers use epidural analgesia or an intercostal catheter for postoperative regional anesthesia in at least 50% of patients. Two departments follow an opioid restrictive regimen, five depend on the visual analogue scale (VAS) and two administer opioids on a fixed schedule. Three out of nine departments use NSAIDs on a fixed schedule. The most used medication is metamizole (eight out of nine centers; six on a fixed schedule, two depending on VAS) followed by piritramide (six out of nine centers; none as a fixed prescription). CONCLUSIONS: This study reflects the heterogeneity in postoperative pain treatment after VATS anatomic lung resections. All departments use some form of regional anesthesia in the perioperative period; prolonged regional anesthesia is not utilized uniformly to reduce opioid consumption, as suggested in enhanced recovery after surgery programs. More evidence is needed to optimize and standardize postoperative pain treatment.

Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC.

Cancer associated fibroblasts (CAF) are known to orchestrate multiple components of the tumor microenvironment, whereas the influence of the whole stromal-fibroblast compartment is less understood. Here, an extended stromal fibroblast signature was investigated to define its impact on immune cell infiltration. The lung cancer adenocarcinoma (LUAD) data set of the cancer genome atlas (TCGA) was used to test whole stroma signatures and cancer-associated fibroblast signatures for their impact on prognosis. 3D cell cultures of the NSCLC cancer cell line A549 together with the fibroblast cell line SV80 were used in combination with infiltrating peripheral blood mononuclear cells (PBMC) for in-vitro investigations. Immune cell infiltration was assessed via flow cytometry, chemokines were analyzed by immunoassays and RNA microarrays. Results were confirmed in specimens from NSCLC patients by flow cytometry or immunohistochemistry as well as in the TCGA data set. The TCGA analyses correlated the whole stromal-fibroblast signature with an improved outcome, whereas no effect was found for the CAF signatures. In 3D microtumors, the presence of fibroblasts induced infiltration of B cells and CD69+CD4+ T cells, which was linked to an increased expression of CCL13 and CXCL16. The stroma/lymphocyte interaction was confirmed in NSCLC patients, as stroma-rich tumors displayed an elevated B cell count and survival in the local cohort and the TCGA data set. A whole stromal fibroblast signature was associated with an improved clinical outcome in lung adenocarcinoma and in vitro and in vivo experiments suggest that this signature increases B and T cell recruitment via induction of chemokines.