Long-Term Outcome of Chest Wall and Diaphragm Repair with Biological Materials.

INTRODUCTION: Chest wall and/or diaphragm reconstruction aims to preserve, restore, or improve respiratory function; conserve anatomical cavities; and upkeep postural and upper extremity support. This can be achieved by utilizing a wide range of different grafts made of synthetic, biological, autologous, or bioartificial materials. We aim to review our experience with decellularized bovine pericardium as graft in the past decade. PATIENTS AND METHODS: We conducted a retrospective analysis of patients who underwent surgical chest wall and/or diaphragm repair with decellularized bovine pericardium between January 1, 2012 and January 13, 2022 at our institution. All records were screened for patient characteristics, intra-/postoperative complications, chest tube and analgesic therapy duration, length of hospital stay, presence or absence of redo procedures, as well as morbidity and 30-day mortality. We then looked for correlations between implanted graft size and postoperative complications and gathered further follow-up information at least 2 months after surgery. RESULTS: A total of 71 patients either underwent isolated chest wall (n = 51), diaphragm (n = 12), or pericardial (n = 4) resection and reconstruction or a combination thereof. No mortality was recorded within the first 30 days. Major morbidity occurred in 12 patients, comprising secondary respiratory failure requiring bronchoscopy and invasive ventilation in 8 patients and secondary infections and delayed wound healing requiring patch removal in 4 patients. There was no correlation between the extensiveness of the procedure and extubation timing (chi-squared test, p = 0.44) or onset of respiratory failure (p = 0.27). CONCLUSION: A previously demonstrated general viability of biological materials for various reconstructive procedures appears to be supported by our long-term results.

Management and outcome of obstructive airway complications after lung transplantation - a 12-year retrospective cohort study.

BACKGROUND: Obstructive airway complications (OACs) represent a significant problem after lung transplantation (LTx). Bilateral OACs after double lung transplantation are infrequently reported. OBJECTIVES: The aim of this study was to investigate management and outcome of OAC. DESIGN: Retrospective single-center cohort study. METHODS: Adult patients with bilateral LTx performed between 2010 and 2021 were included. Patients with follow-ups of less than 3 months and after heart-lung transplantation were excluded. OAC was defined either as the need for stenting, surgical revision, or balloon dilatation. Outcome parameters included graft survival, graft function, quality of life, and management. RESULTS: During the study period, 1,170 patients were included. Hundred thirty-five (11.5%) patients developed OAC. Forty-six (4.4%) patients had significant bilateral OAC. Thirty-seven (80%) bilateral OAC patients were treated by stent insertion; in 34 patients, biodegradable stents were used. The median number of bronchoscopies in bilateral OAC was 26 during the first postoperative year compared with nine in controls (p < 0.001). Fourteen OAC patients (n = 10 bilateral) underwent surgical revision including six re-do transplantations. Graft loss occurred significantly more frequently in patients with bilateral OAC with a graft survival of 63% and 50% in these after 3 and 5 years compared with 83% and 73% in controls without OAC (p < 0.001). Baseline forced expiratory volume in 1 s (FEV1) in patients with bilateral OAC was median 58% predicted in comparison with 90% in controls (p < 0.001). Quality of life was significantly reduced. CONCLUSION: Bilateral OACs impose a high burden of disease on patients after lung transplantation and were associated with early and late graft loss. Affected patients' OAC demonstrated reduced graft function and impaired quality of life. Most OACs were managed by bronchoscopy preferably by non-permanent stenting. Surgery including re-do transplantation was used in selected cases.

Comparison of uniportal robotic-assisted thoracic surgery pulmonary anatomic resections with multiport robotic-assisted thoracic surgery: a multicenter study of the European experience.

Background: Robotic-assisted thoracic surgery (RATS) has seen increasing interest in the last few years, with most procedures primarily being performed in the conventional multiport manner. Our team has developed a new approach that has the potential to convert surgeons from uniportal video-assisted thoracic surgery (VATS) or open surgery to robotic-assisted surgery, uniportal-RATS (U-RATS). We aimed to evaluate the outcomes of one single incision, uniportal robotic-assisted thoracic surgery (U-RATS) against standard multiport RATS (M-RATS) with regards to safety, feasibility, surgical technique, immediate oncological result, postoperative recovery, and 30-day follow-up morbidity and mortality. Methods: We performed a large retrospective multi-institutional review of our prospectively curated database, including 101 consecutive U-RATS procedures performed from September 2021 to October 2022, in the European centers that our main surgeon operates in. We compared these cases to 101 consecutive M-RATS cases done by our colleagues in Barcelona between 2019 to 2022. Results: Both patient groups were similar with respect to demographics, smoking status and tumor size, but were significantly younger in the U-RATS group [M-RATS =69 (range, 39-81) years; U-RATS =63 years (range, 19-82) years; P<0.0001]. Most patients in both operative groups underwent resection of a primary non-small cell lung cancer (NSCLC) [M-RATS 96/101 (95%); U-RATS =60/101 (59%); P<0.0001]. The main type of anatomic resection was lobectomy for the multiport group, and segmentectomy for the U-RATS group. In the M-RATS group, only one anatomical segmentectomy was performed, while the U-RATS group had twenty-four (24%) segmentectomies (P=0.0006). All M-RATS and U-RATS surgical specimens had negative resection margins (R0) and contained an equivalent median number of lymph nodes available for pathologic analysis [M-RATS =11 (range, 5-54); U-RATS =15 (range, 0-41); P=0.87]. Conversion rate to thoracotomy was zero in the U-RATS group and low in M-RATS [M-RATS =2/101 (2%); U-RATS =0/101; P=0.19]. Median operative time was also statistically different [M-RATS =150 (range, 60-300) minutes; U-RATS =136 (range, 30-308) minutes; P=0.0001]. Median length of stay was significantly lower in U-RATS group at four days [M-RATS =5 (range, 2-31) days; U-RATS =4 (range, 1-18) days; P<0.0001]. Rate of complications and 30-day mortality was low in both groups. Conclusions: U-RATS is feasible and safe for anatomic lung resections and comparable to the multiport conventional approach regarding surgical outcomes. Given the similarity of the technique to uniportal VATS, it presents the potential to convert minimally invasive thoracic surgeons to a robotic-assisted approach.

Surgical management of large tracheoesophageal fistula in infants after button battery ingestion.

OBJECTIVES: In recent years, an increase in severe and even fatal outcomes related to oesophageal or airway button battery (BB) ingestion by infants and small children has been reported. Extensive tissue necrosis caused by lodged BB can lead to major complications, including tracheoesophageal fistula (TEF). In these instances, best treatment remains controversial. While small defects may warrant a conservative approach, surgery often remains inevitable in highly complex cases with large TEF. We present a series of small children that underwent successful surgical management by a multidisciplinary team in our institution. METHODS: This is a retrospective analysis of n = 4 patients <18 months undergoing TEF repair from 2018 to 2021. RESULTS: Surgical repair under extracorporeal membrane oxygenation (ECMO) support was feasible in n = 4 patients by reconstructing the trachea with decellularized aortic homografts that were buttressed with pedicled latissimus dorsi muscle flaps. While direct oesophageal repair was feasible in 1 patient, 3 required esophagogastrostomy and secondary repair. The procedure was completed successfully in all 4 children with no mortality and acceptable morbidity. CONCLUSIONS: Tracheo-oesophageal repair after BB ingestion remains challenging and is associated with major morbidity. Bioprosthetic materials in conjunction with the interposition of vascularized tissue flaps between trachea and oesophagus appear to be a valid approach to manage severe cases.

Uniportal video-assisted thoracic surgery basal segmentectomy: a single-center retrospective cohort study.

Background: Uniportal video-assisted thoracic surgery (VATS) basal segmentectomy is technically challenging and requires a deep understanding of the segmental anatomy of the lung. This report describes the uniportal VATS segmentectomy of basal segments using a single-direction approach. Methods: A total of 49 patients who underwent uniportal VATS basal segmentectomy between April 2019 and April 2021 were included in this retrospective study. All the surgeries were conducted using a single-direction approach. The resections of segments 7-8 were mainly performed using the interlobar fissure approach, while the resections of segments 9-10 were performed using the inferior pulmonary ligament approach. Results: A total of 33 patients underwent a single basal segmentectomy and 16 patients underwent combined basal segmentectomy/sub-segmentectomy. The median operative time was 120 min (range, 60-180 min), and the median blood loss was 20 mL (range, 10-100 mL). The median chest tube duration was 2 days (range, 1-5 days), and the median hospital stay after surgery was 4 days (range, 2-15 days). The morbidity rate after surgery was 6.1% (3/49). There were no perioperative deaths. The pathological examinations revealed 3 cases of adenocarcinoma in situ (AIS), 33 cases of minimally invasive adenocarcinoma, and 13 cases of lepidic-predominant invasive adenocarcinoma. No recrudescence or mortality was reported during the median follow-up time of 7 months (range, 2-25 months). Conclusions: Uniportal VATS basal segmentectomy is a feasible and reliable technique based on our experience. This single-direction method allows the uniportal VATS basal segmentectomy to be performed in an easy manner with the targeted segmental bronchi and vessels exposed from superficial to deep in order of their appearance while avoiding the repeated turnover of the lung.

Surgical Lung Biopsy for Interstitial Lung Disease: A Two Center Propensity Score Matching Analysis.

BACKGROUND: Surgical lung biopsy (SLB) is recommended for patients with nonclassified interstitial lung disease (nILD) if high resolution computed tomography and/or transbronchial lung biopsy did not achieve a definitive diagnosis. Current literature suggests better patient tolerability and less postoperative complications if surgery is performed under spontaneous ventilation. OBJECTIVES: We conducted a propensity score matching (PSM) analysis of our nILD patients undergoing SLB under spontaneous ventilation or general anesthesia to investigate postprocedural AE-ILD, 30-/90-day mortality and perioperative variables in two academic high-volume centers (Hannover, Heidelberg). METHODS: All patients undergoing SLB for nILD under general anesthesia (GAVATS) and spontaneous ventilation (NIVATS) at both centers from February 2013 until April 2021 were analyzed retrospectively. Data of 132 patients were used for PSM resulting in 40 pairs. RESULTS: There was one death in the NIVATS group 60 days after SLB and one AE-ILD in each cohort. Chest tube indwelling time, chest tube total effusion, length of hospital stay, and operative time were all in favor of NIVATS. CONCLUSIONS: In our PSM analysis, NIVATS is associated with faster postprocedural recovery. However, a reduction in postoperative AE-ILD or 30-/90-day mortality was not observed.

The strategy of non-intubated spontaneous ventilation anesthesia for upper tracheal surgery: a retrospective case series study.

Background: Upper tracheal surgery is used to treat patients who with tracheal tumors or tracheal stenosis. The non-intubated spontaneous ventilation anesthesia (NSVA) may have advantages over endotracheal intubation and surgical cross-field intubation in upper tracheal surgery. This study aimed to illustrate and assess the feasibility of NSVA strategy for upper tracheal surgery. Methods: This is a retrospective case series study in which 51 patients (from May 2015 to August 2020) who met the criteria in NSVA strategy were analyzed. Anesthesia was performed using total intravenous anesthesia (TIVA) combined with bilateral superficial cervical plexus block (CPB) or thoracic epidural anesthesia (TEA). Patients received spontaneous ventilation through laryngeal mask airway (LMA) during the surgery. Anesthesia conversion technique was applied to patients who met the anesthesia conversion criteria. Results: In total, 51 patients met the NSVA criteria and were included in this study. Forty-six out of 51 patients (90%) had TIVA + bilateral superficial CPB and five patients (10%) had TIVA + TEA + CPB. During the airway-opened period, 46 patients had stable spontaneous ventilation. Five patients need anesthesia conversion, two patients had high-frequency ventilation (HFV), and three patients required cross-field intubation. Postoperative complications occurred in seven (14%) patients, no reintubation was needed after surgery. The median postoperative hospital stay was 6.31±4.30 days. Conclusions: This NSVA strategy includes criteria for patient selection, preoperative assessment, surgical technique, airway management, criteria and technique for anesthesia conversion. The NSVA strategy is a feasible procedure in upper tracheal surgery.

Role of Pre-Operative Brain Imaging in Patients with NSCLC Stage I: A Retrospective, Multicenter Analysis.

Background: Lung cancer is the worldwide leading oncological cause of death in both genders combined and accounts for around 40-50% of brain metastases in general. In early-stage lung cancer, the incidence of brain metastases is around 3%. Since the early detection of asymptomatic cerebral metastases is of prognostic value, the aim of this study was to analyze the incidence of brain metastases in early-stage lung cancer and identify possible risk factors. Methods: We conducted a retrospective multicentric analysis of patients with Stage I (based on T and N stage only) Non-Small Cell Lung Cancer (NSCLC) who had received preoperative cerebral imaging in the form of contrast-enhanced CT or MRI. Patients with a history of NSCLC, synchronous malignancy, or neurological symptoms were excluded from the study. Analyzed variables were gender, age, tumor histology, cerebral imaging findings, smoking history, and tumor size. Results were expressed as mean with standard deviation or median with range. Results: In total, 577 patients were included in our study. Eight (1.4%) patients were found to have brain metastases in preoperative brain imaging. Tumor histology was adenocarcinoma in all eight cases. Patients were treated with radiotherapy (five), surgical resection (two), or both (one) prior to thoracic surgical treatment. Other than tumor histology, no statistically significant characteristics were found to be predictive of brain metastases. Conclusion: Given the low incidence of brain metastases in patients with clinical Stage I NSCLC, brain imaging in this cohort could be avoided.

[Case Series Report: Management of Anesthesia in Children Undergoing Complex Surgery of Tracheoesophageal Fistula after Ingestion of Button Batteries]. / Fallberichte: Kinder mit tracheoösophagealer Fistel nach Knopfbatterieningestion.

Button battery ingestions in children increased in recent years and may lead to life-threatening complications, especially if the battery is impacted in the esophagus. The pH close to the negative pole of the battery can rise in a very alkalotic range (pH > 10) leading to severe tissue damage. Therefore, in this case series report, the clinical courses of four children with button battery ingestion leading to tracheoesophageal fistulas are presented. The diagnosis and removal of the button battery was delayed in all cases. The surgical reconstruction of the trachea was performed in intravenous anesthesia and with extended monitoring. The intraoperative oxygenation was maintained using a combination of extracorporeal membrane oxygenation (ECMO) and mechanical ventilation via an endobronchial tube. To prevent these life-threatening complications, the awareness of the parents and child care providers should be raised, and the manufacturers should redesign their products to secure the battery compartment. In children with suspected battery ingestions, the immediate localization and removal of the battery (< 2 h) is of highest importance. Local administration of honey or sucralfate can be considered in ingestions < 12 h but should not delay an endoscopic removal.

Monitoring excimer laser-guided cardiac lead extractions by uniportal video-assisted thoracoscopy: A single center experience.

BACKGROUND: Though laser guided extractions of cardiac implantable electronic devices leads have become a routine procedure, the severe complications are associated with a high mortality. Here, we report our single center experience using uniportal video-assisted thoracoscopy for laser lead extraction and compare it to stand-alone laser lead extraction. METHODS: The intraoperative data and postoperative clinical outcomes of patients undergoing laser lead extraction with concomitant thoracoscopy (N = 28) or without (N = 43) in our institution were analyzed retrospectively. RESULTS: Neither the median x-ray time (612.0 s for the thoracoscopy group vs. 495.5 s for the non-thoracoscopy group, p = 0.962), length of the operation (112.5 vs. 100.0 min, p = 0.676) or the median length of hospital stay (9.0 vs. 10.0 days, p = 0.990) differed significantly. The mean intensive care unit stay was longer for patients in the non-thoracoscopy group (0.8 vs. 2.5 days, p = 0.005). The 30-day-mortality in the thoracoscopy group was zero, whereas five patients died in the non-thoracoscopy group. Furthermore, four patients in the non-thoracoscopy group had encountered haemothorax, while none were observed in the thoracoscopy group (p = 0.148). CONCLUSIONS: The adoption of uniportal video-assisted thoracoscopy during laser-guided lead extraction of cardiac implantable electronic devices can be considered safe and does not lengthen the operating time or hospital stay. It might be useful in the detection of severe complications and, in experienced hands, possibly allow direct bleeding control.

Surgical treatment of non-cystic fibrosis bronchiectasis in Central Europe.

BACKGROUND: Bronchiectasis is a mostly irreversible bronchial dilatation induced by the destruction of elastic and muscular fibers of the bronchial wall. Surgical treatment is usually reserved for focal disease, and whenever complications, like hemoptysis or secondary aspergilloma, arise. In this study, we report our experience and outcomes in surgical bronchiectasis management between 2016 and 2020. METHODS: We retrospectively searched our database for patients admitted for surgical treatment of bronchiectasis between 2016 and 2020. All records were screened for pre-surgical management. Age, gender, distribution of bronchiectatic lesions, type of surgery, perioperative complications, chest tube duration, length of hospital stay as well as 30-day-mortality were recorded, and a brief follow-up was made. RESULTS: A total of n=34 patients underwent pulmonary resection with bronchiectasis. Mean age on admission was 56.2±15.1 years and n=21 patients (62%) were female. In n=23 cases the right lung was affected, in n=9 cases the left side and in two cases both lungs. Indications for surgery included persistent major alterations after conservative therapy (n=9), massive hemoptysis (n=4), and full-blown "destroyed lobe" (n=7). All patients received anatomical lung resection (n=21 lobectomies, n=2 bilobectomies and n=11 segmentectomies), either by uniportal video assisted thoracoscopic surgery (n=28) or by lateral thoracotomy (n=6). Average length of hospital stay was 7.9±6.3 days; one patient died on POD 7 due to myocardial infarction. CONCLUSIONS: In spite of a decreasing number of patients with bronchiectasis referred to surgery due to improvements in preventing and managing the disease, pulmonary resection still plays a significant role in treating this pathology in Central Europe. Surgery remains a viable approach for localized forms of bronchiectasis, and the only option in treating acute deterioration and complications like massive hemoptysis.

Analysis of pH and electrolytes in blood and ruminal fluid, including kidney function tests, in sheep undergoing long-term surgical procedures.

BACKGROUND: The physiology of sheep as small ruminants is remarkably different from monogastric animals especially regarding the forestomach system. Using sheep for surgical procedures during scientific research thereby presents an exceptional setting for the anaesthetist. Long-term anaesthesia generally demands deprivation of food to reduce the risk of bloat in sheep. This might influence the energy and electrolyte balance. In horses and companion animals, close monitoring of mean arterial blood pressure, capnography and blood gas analysis are common procedures during long-term surgery. However, few data are available on reference ranges for blood gas in sheep and these cover only short periods of anaesthesia. To the authors' knowledge, there is no study available that includes the monitoring of electrolytes and pH in ruminal fluid and kidney function tests in sheep undergoing long term anaesthesia. Thereby, the aim of the present study was to gather data on blood parameters, and data on ruminal fluid and kidney function during long-term anaesthesia in sheep. Data were obtained from eight sheep undergoing the invasive surgical procedure of left pneumonectomy and auto-transplantation or isolated left lung perfusion. After a 19-h fasting period, the animals were administered xylazine and ketamine and then intubated and maintained in general anaesthesia under artificial ventilation using isoflurane in oxygen. Blood samples were evaluated during 9 h of anaesthesia; ruminal fluid and kidney function tests were evaluated during 7 h of anaesthesia. RESULTS: Blood parameters such as electrolytes and partial pressure of carbon dioxide revealed few changes, yet blood glucose decreased and beta-hydroxybutyric acid increased significantly. All animals showed an elevated arterial pH and bicarbonate concentration despite artificial ventilation. In ruminal fluid, the pH significantly decreased and no significant changes in electrolytes occurred. Kidney function tests revealed no significant changes in any of the animals. However, fractional excretion of water and phosphate was slightly increased. One animal showed severe complications due to hypokalaemia. CONCLUSION: Invasive surgery under long-term anaesthesia in sheep is possible without great imbalances of arterial pH and electrolytes. Nevertheless, potassium concentrations should be monitored carefully, as a deficiency can lead to life-threatening complications. The operated sheep tended not to develop metabolic acidosis and the mean kidney function could be maintained within the physiological range throughout anaesthesia. However, slight elevations in renal fractional water and phosphate excretion could suggest an early tubular reabsorption dysfunction. In ruminal fluid, acidification occurred, though no significant changes were observed in L- and D-lactate levels or in electrolyte concentrations. To our knowledge, the role of the rumen in storing fluids and balancing electrolytes in the blood has not yet been documented during anaesthesia. However, the importance of the rumen for fluid equilibrium in sheep indicates the necessity for routine monitoring and further research.

α1-Antitrypsin attenuates acute rejection of orthotopic murine lung allografts.

BACKGROUND: α1-Antitrypsin (AAT) is an acute phase glycoprotein, a multifunctional protein with proteinase inhibitory, anti-inflammatory and cytoprotective properties. Both preclinical and clinical experiences show that the therapy with plasma purified AAT is beneficial for a broad spectrum of inflammatory conditions. The potential effects of AAT therapy have recently been highlighted in lung transplantation (LuTx) as well. METHODS: We used a murine fully mismatched orthotopic single LuTx model (BALB/CJ as donors and C57BL/6 as recipients). Human AAT preparations (5 mg, n = 10) or vehicle (n = 5) were injected to the recipients subcutaneously prior to and intraperitoneally immediately after the LuTx. No immune suppressive drugs were administered. Three days after the transplantation, the mice were sacrificed, and biological samples were assessed. RESULTS: Histological analysis revealed significantly more severe acute rejection in the transplanted lungs of controls than in AAT treated mice (p < 0.05). The proportion of neutrophil granulocytes, B cells and the total T helper cell populations did not differ between two groups. There was no significant difference in serum CXCL1 (KC) levels. However, when compared to controls, human AAT was detectable in the serum of mice treated with AAT and these mice had a higher serum anti-elastase activity, and significantly lower proportion of Th1 and Th17 among all Th cells. Cleaved caspase-3-positive cells were scarce but significantly less abundant in allografts from recipients treated with AAT as compared to those treated with vehicle. CONCLUSION: Therapy with AAT suppresses the acute rejection after LuTx in a mouse model. The beneficial effects seem to involve anti-protease and immunomodulatory activities of AAT.

Impact of sarcopenia in advanced and metastatic soft tissue sarcoma.

INTRODUCTION: Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. METHODS: 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. RESULTS: 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9-6.0] vs. 16 months [95%CI 8.8-23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4-4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). CONCLUSION: This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.

[Multidisciplinary Management of Non-cystic-fibrosis Bronchiectasis - State of the Art]. / Interdisziplinäre Behandlung der Non-Cystic-Fibrosis-Bronchiektasie ­ State of the Art.

Bronchiectasis is a mostly irreversible bronchial dilatation induced by a destruction of elastic and muscular fibers of the bronchial wall. Radiological criteria of bronchiectasis are met, when the inner diameter of the bronchial wall surpasses the outer diameter of the accompanying pulmonary artery. Its incidence increases with age, even though it often lacks true clinical signs of disease. Only when it is accompanied by cough, expectorations and recurring bronchopulmonary infections, it can be considered a true bronchiectatic disease. Cystic fibrosis (CF) is one of its preeminent triggers, but certainly plays a particular role in this entity, which is why the terminus of "non-CF-bronchiectasis" was coined in the first place.Multidisciplinary management consists in extensive diagnostic work-up, treatment of potential triggers of bronchiectasis and supportive care in form of vaccination programs, secretolysis and pulmonary rehabilitation, as well as antibiotic treatment of pulmonary exacerbations.Surgical treatment has to be considered a last resort in case of hemoptysis, recurring severe pneumonia or secondary aspergilloma with complete resection of all pathological findings, ideally by minimally-invasive approach.

Rhinovirus-induced Human Lung Tissue Responses Mimic Chronic Obstructive Pulmonary Disease and Asthma Gene Signatures.

Human rhinovirus (RV) is a major risk factor for chronic obstructive pulmonary disease (COPD) and asthma exacerbations. The exploration of RV pathogenesis has been hampered by a lack of disease-relevant model systems. We performed a detailed characterization of host responses to RV infection in human lung tissue ex vivo and investigated whether these responses are disease relevant for patients with COPD and asthma. In addition, impact of the viral replication inhibitor rupintrivir was evaluated. Human precision-cut lung slices (PCLS) were infected with RV1B with or without rupintrivir. At Days 1 and 3 after infection, RV tissue localization, tissue viability, and viral load were determined. To characterize host responses to infection, mediator and whole genome analyses were performed. RV successfully replicated in PCLS airway epithelial cells and induced both antiviral and proinflammatory cytokines such as IFNα2a, CXCL10, CXCL11, IFN-γ, TNFα, and CCL5. Genomic analyses revealed that RV not only induced antiviral immune responses but also triggered changes in epithelial cell-associated pathways. Strikingly, the RV response in PCLS was reflective of gene expression changes described in patients with COPD and asthma. Although RV-induced host immune responses were abrogated by rupintrivir, RV-triggered epithelial processes were largely refractory to antiviral treatment. Detailed analysis of RV-infected human PCLS and comparison with gene signatures of patients with COPD and asthma revealed that the human RV PCLS model represents disease-relevant biological mechanisms that can be partially inhibited by a well-known antiviral compound and provide an outstanding opportunity to evaluate novel therapeutics.

miRNAs in lung cancer. A systematic review identifies predictive and prognostic miRNA candidates for precision medicine in lung cancer.

Lung cancer (LC) is the leading cause of cancer-related death worldwide and miRNAs play a key role in LC development. To better diagnose LC and to predict drug treatment responses we evaluated 228 articles encompassing 16,697 patients and 12,582 healthy controls. Based on the criteria of ≥3 independent studies and a sensitivity and specificity of >0.8 we found blood-borne miR-20a, miR-10b, miR-150, and miR-223 to be excellent diagnostic biomarkers for non-small cell LC whereas miR-205 is specific for squamous cell carcinoma. The systematic review also revealed 38 commonly regulated miRNAs in tumor tissue and the circulation, thus enabling the prediction of histological subtypes of LC. Moreover, theranostic biomarker candidates with proven responsiveness to checkpoint inhibitor treatments were identified, notably miR-34a, miR-93, miR-106b, miR-181a, miR-193a-3p, and miR-375. Conversely, miR-103a-3p, miR-152, miR-152-3p, miR-15b, miR-16, miR-194, miR-34b, and miR-506 influence programmed cell death-ligand 1 and programmed cell death-1 receptor expression, therefore providing a rationale for the development of molecularly targeted therapies. Furthermore, miR-21, miR-25, miR-27b, miR-19b, miR-125b, miR-146a, and miR-210 predicted response to platinum-based treatments. We also highlight controversial reports on specific miRNAs. In conclusion, we report diagnostic miRNA biomarkers for in-depth clinical evaluation. Furthermore, in an effort to avoid unnecessary toxicity we propose predictive biomarkers. The biomarker candidates support personalized treatment decisions of LC patients and await their confirmation in randomized clinical trials.

Developing a minimally-invasive anaesthesiological approach to non-intubated uniportal video-assisted thoracoscopic surgery in minor and major thoracic surgery.

BACKGROUND: Non-intubated uniportal video-assisted thoracoscopic surgery (niVATS) is a novel approach to major and minor lung resection. It benefits from a holistic anesthesiological concept with adequate pain relief and sedation in a minimal-invasive setup allowing thoracic procedures under spontaneous breathing. At present no anesthesiological gold standard for niVATS exists. The primary aim of our retrospective observational study was to evaluate feasibility and safety of minimally invasive niVATS for both minor and major pulmonary resections at our institution. METHODS: All 88 consecutive patients scheduled for niVATS minor or major thoracic procedures were included into the study. Anaesthesia was performed according to a departmental niVATS algorithm including both regional anaesthesia and sedation. Patient characteristics and early outcome data including intraoperative and postoperative findings were compared between groups. Prediction scores for postoperative complications (LAS VEGAS, ARISCAT, ThRCRI) were calculated and compared. RESULTS: No early mortality and a low overall morbidity rate of 28.4% were encountered. Conversion to orotracheal intubation was required in 6.8% of all cases. Postoperative pulmonary complications occurred in 15.9% of total cases and were lower than predicted by both LAS VEGAS and ARISCAT respectively. Cardiac complications were found in 1.1% and lower than predicted by ThRCRI. A persistent air leak occurred in 11.4% of total cases and was significantly higher in major resection. Postoperative chest tube duration and hospital length of stay in the major resection group exceeded times reported by other groups. CONCLUSIONS: niVATS appears to be safe in both minor and major thoracic procedures. A minimally invasive anaesthesiological approach foregoing central iv lines, arterial blood pressure measurement and urinary catheterization is feasible. Our niVATS protocol appears to be a viable alternative for both minor and major thoracic procedures in selected patients.