[SARS-CoV-2-associated pneumothorax, pneumomediastinum and soft tissue emphysema. Clinical implications based on a case series]. / SARS-CoV-2-assoziierter Pneumothorax, Pneumomediastinum und Weichteilemphysem. Klinische Implikationen anhand einer Fallserie.

The new coronavirus (SARS-CoV-2) that arose in 2019 causes a wide spectrum of symptoms and different courses of disease. Pneumothorax, pneumomediastinum and soft tissue emphysema are rare complications in patients with pulmonary involvement. They are the sequelae of severe, virus-induced structural changes of the pulmonary architecture. High pressure artificial ventilation aggravates the problem. Hence pneumothorax and ectopic air in soft tissues are indicators of extensive pulmonary damage. Therefore, efforts should be made to treat even very small or multiply recurrent pneumothorax by drainage procedures.

Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells.

BACKGROUND: Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrations in order to study responses to hypoxia in a model that mimics human lung cancer in vivo. METHODS: Non-small cell lung cancer (NSCLC) fragments from altogether 70 patients were maintained ex vivo in normoxia or hypoxia in short-term culture. Viability, apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were studied using Affymetrix GeneChip 1.0 ST microarrays. RESULTS: Apoptosis rates were comparable in normoxia and hypoxia despite different oxygenation levels, suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in hypoxic compared to normoxic fragments largely overlapped with published hypoxia-signatures. While most of these genes were up-regulated by hypoxia also in NSCLC cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated fibroblasts isolated from non-small cell lung cancers. High MME expression was significantly associated with poor overall survival in 342 NSCLC patients in a meta-analysis of published microarray datasets. CONCLUSIONS: The novel ex vivo model allowed for the first time to analyze hypoxia-regulated gene expression in preserved human lung cancer tissue. Gene expression profiles in human hypoxic lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines, however, the elastase MME was identified as a novel hypoxia-induced gene in lung cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma fibroblast MME expression under hypoxia might contribute to enhanced aggressiveness of hypoxic cancers.

Incidental finding of Clostridium perfringens on human corpses used for the anatomy course.

Post-mortem specimens used for anatomy teaching are commonly embalmed using compositions of chemicals, with the objective to maintain tissue quality and to avoid putrefaction. Monitoring for bacterial or fungal contamination is becoming increasingly important especially when measures are taken to minimize exposure by chemicals such as formaldehyde. In this case, random swabs were taken from six corpses embalmed with ethanol-glycerin and Thiel embalming. Cultures and MALDI-TOF analyses yielded four cases of Clostridium perfringens contamination. C. perfringens is of special interest as a human pathogen. A potential source was identified in the containers filled with the moistening solution. Cross contamination with Clostridium species has likely occurred between corpses sharing the moistening solution and soaking the cover linen directly within the containers. To minimize any risk for those exposed, the moistening solutions were discarded and all equipment thoroughly disinfected. The specimens had to be cremated as they formed a potential source of Clostridium spores. Deviating from previous routines it was formalized that the cover linen must not be submerged in the moistening contains rather than moistening the specimens directly with dedicated vessels. Follow-up analyses yielded no further contamination with C. perfringens.

Prognostic Impact of Pulmonary Metastasectomy in Bone Sarcoma Patients: A Retrospective, Single-Centre Study.

This retrospective study aimed at analyzing the impact of metastasectomy on post-metastasis survival (PMS) in bone sarcoma patients with lung metastases. Altogether, 47 bone sarcoma patients (24 males, median age at diagnosis of lung metastases: 21.8 (IQR: 15.6-47.3) years) with primary (n = 8) or secondary (n = 39) lung metastases treated at a single university hospital were retrospectively included. Based on a propensity score, inverse probability of treatment weight (IPTW) was calculated to account for selection bias whether patients had undergone metastasectomy or not. The most common underlying histology was osteosarcoma (n = 37; 78.7%). Metastasectomy was performed in 39 patients (83.0%). Younger patients (p = 0.025) with singular (p = 0.043) and unilateral lesions (p = 0.024), as well as those with an interval ≥ 9 months from primary diagnosis to development of lung metastases (p = 0.024) were more likely to undergo metastasectomy. Weighted 1- and 3-year PMS after metastasectomy was 80.8% and 58.3%, compared to 88.5% and 9.1% for patients who did not undergo metastasectomy. Naive Cox-regression analysis demonstrated a significantly prolonged PMS for patients with metastasectomy (HR: 0.142; 95%CI: 0.045-0.450; p = 0.001), which was confirmed after IPTW-weighting (HR: 0.279; 95%CI: 0.118-0.662; p = 0.004), irrespective of age, time to metastasis, and the number of lesions. In conclusion, metastasectomy should be considered in bone sarcoma patients with lung metastases, after carefully considering the individual risks, to possibly improve PMS.

High complication rate with titanium plates for chest wall reconstruction following tumour resection.

OBJECTIVES: The reconstruction of the chest wall defect after tumour resection presents a challenge. Titanium rib plates were presented as a reconstruction option due to its biocompatibility, flexibility and pliability. The aim of this study was to evaluate the outcome of single-centre cohort treated with chest wall reconstruction after tumour resections, with a focus on the titanium rib plates reconstruction. METHODS: We retrospectively reviewed the data of 26 patients who underwent wide resection for malignancies of the chest wall, where reconstruction was performed using polypropylene mesh, porcine dermal collagen mesh with or without titanium rib plates, operated on between 2012 and 2019. Events being associated with the surgery requiring revision were rated as complications. RESULTS: Most of the patients had primary tumours (n = 19; 73%). A mean of 3.7 ribs (range: 1-7) was resected. Reconstruction was performed with titanium rib plates (13 patients, 50%), of these 11 were performed with additional mesh grafts. The remaining 13 patients (50%) underwent reconstruction with mesh grafts only. Fourteen patients (54%) developed a complication requiring surgical revision, after a median of 5.5 months. The most common complication was wound healing deficit (n = 4), plate fracture (n = 2), mesh rupture (n = 2), infection (n = 2) and local recurrence (n = 2). The only factor being associated with the development of complications was the usage of a plate (P = 0.015), irrespective of defect size (P = 0.29). CONCLUSIONS: The high complication rate is found when using titanium plates for chest wall reconstruction after tumour resection. A high caution is recommended in choosing the chest wall reconstruction method.

Benefit of Metastasectomy in Renal Cell Carcinoma: A Propensity Score Analysis.

INTRODUCTION: To quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: We therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone. RESULTS: The most frequent metastasectomy procedures were lung resections (n = 13) and craniotomies (n = 6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P = .00007; Hazard ratio (HR) = 0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR = 0.62, 95%CI: 0.39-1.00, P = .050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P = .001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases. CONCLUSION: Within the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit.

Efficacy and safety of current drug therapies for invasive aspergillosis.

Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients. The therapeutic goals are to restore leucocyte function and to reduce the fungal burden by effective antifungal agents and, contingently, by surgery. Several drugs for the treatment of IA are currently licensed. The longest known among them is amphotericin B (AmB). In well-performed clinical trials, approximately 30-50% of participants treated with AmB showed complete or partial response. However, this drug is associated with considerable acute and chronic toxicity which was somewhat mitigated by the development of lipid-based formulations. In contrast, voriconazole (VRC) is better tolerated, penetrates well into the central nervous system and may be given intravenously and orally in a sequential manner. The overall rates of favourable response to VRC were similar to that for AmB. Most notably, double-digit rates of complete remission were observed in studies including extraordinarily high proportions of patients with proven IA and specific risk factors. Disadvantages of VRC include the genetically determined interindividual variability of pharmacokinetics and the potential for drug-drug interactions that may require therapeutic drug monitoring. The recently introduced caspofungin (CPF) offers an excellent safety profile, but underperformed in terms of efficacy against mold infections. Other antifungals such as itraconazole and posaconazole are presently recommended as second-line option for the therapy or prophylaxis of (non-)IA. The value of micafungin and anidulafungin remains to be investigated in randomized clinical trials. In guidelines released by relevant medical societies, VRC is recommended as the first choice in the treatment of IA. AmB, preferably given as a liposomal preparation, or combinatory antifungal regimens combining VRC or liposomal AmB with CPF are stated as alternative options.

Interdisciplinary Radical "En-Bloc" Resection of Ewing Sarcoma of the Chest Wall and Simultaneous Chest Wall Repair Achieves Excellent Long-Term Survival in Children and Adolescents.

Introduction: Ewing sarcomas of the chest wall, historically known as "Askin tumors" represent highly aggressive pediatric malignancies with a reported 5-year survival ranging only between 40 and 60% in most studies. Multimodal oncological treatment according to specific Ewing sarcoma protocols and radical "en-bloc" resection with simultaneous chest wall repair are key factors for long-term survival. However, the surgical complexity depends on tumor location and volume and potential infiltrations into lung, pericardium, diaphragm, esophagus, spine and major vessels. Thus, the question arises, which surgical specialties should join their comprehensive skills when approaching a child with Ewing sarcoma of the chest wall. Patients and Methods: All pediatric patients with Ewing sarcomas of the chest wall treated between 1990 and 2020 were analyzed focusing on complete resection, chest wall reconstruction, surgical complications according to Clavien-Dindo (CD) and survival. Patients received neo-adjuvant chemotherapy according to the respective Ewing sarcoma protocols. Depending on tumor location and organ infiltration, a multi-disciplinary surgical team was orchestrated to perform radical en-bloc resection and simultaneous chest wall repair. Results: Thirteen consecutive patients (seven boys and six girls) were included. Median age at presentation was 10.9 years (range 2.2-21 years). Neo-adjuvant chemotherapy (n = 13) and irradiation (n = 3) achieved significant reduction of the median tumor volume (305.6 vs. 44 ml, p < 0.05). En-bloc resection and simultaneous chest wall reconstruction was achieved without major complications despite multi-organ involvement. Postoperatively, one patient with infiltration of the costovertebral joint and laminectomy required surgical re-intervention (CD IIIb). 11/13 patients were treated with clear resections margins (R1 resection in one patient with infiltration of the costovertebral joint and marginal resection <1 mm in one child with multiple pulmonary metastases). All patients underwent postoperative chemotherapy; irradiation was performed in four children. Two deaths occurred 18 months and 7.5 years after diagnosis, respectively. Median follow-up for the remaining patients was 8.8 years (range: 0.9-30.7 years). The 5-year survival rate was 89% and the overall survival 85%. Conclusion: EWING specific oncological treatment and multi-disciplinary surgery performing radical en-bloc resections and simultaneous chest wall repair contribute to an improved survival of children with Ewing sarcoma of the chest wall.

Phospholipid dynamics in ex vivo lung cancer and normal lung explants.

In cancer cells, metabolic pathways are reprogrammed to promote cell proliferation and growth. While the rewiring of central biosynthetic pathways is being extensively studied, the dynamics of phospholipids in cancer cells are still poorly understood. In our study, we sought to evaluate de novo biosynthesis of glycerophospholipids (GPLs) in ex vivo lung cancer explants and corresponding normal lung tissue from six patients by utilizing a stable isotopic labeling approach. Incorporation of fully 13C-labeled glucose into the backbone of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylinositol (PI) was analyzed by liquid chromatography/mass spectrometry. Lung cancer tissue showed significantly elevated isotopic enrichment within the glycerol backbone of PE, normalized to its incorporation into PI, compared to that in normal lung tissue; however, the size of the PE pool normalized to the size of the PI pool was smaller in tumor tissue. These findings indicate enhanced PE turnover in lung cancer tissue. Elevated biosynthesis of PE in lung cancer tissue was supported by enhanced expression of the PE biosynthesis genes ETNK2 and EPT1 and decreased expression of the PC and PI biosynthesis genes CHPT1 and CDS2, respectively, in different subtypes of lung cancer in publicly available datasets. Our study demonstrates that incorporation of glucose-derived carbons into the glycerol backbone of GPLs can be monitored to study phospholipid dynamics in tumor explants and shows that PE turnover is elevated in lung cancer tissue compared to normal lung tissue.

Creation of a prevascularized site for cell transplantation in rats.

INTRODUCTION: Transplanted cells, especially islet cells, are likely to become apoptotic due to local hypoxia leading to graft dysfunction. Isolated pancreatic islet cells depend on the diffusion of oxygen from the surrounding tissue; therefore, access to sufficient oxygen supply is beneficial, particularly when microcapsules are used for immunoisolation in xenotransplantation. The aim of this study was to create a prevascularized site for cell transplantation in rats and test its effectiveness with microencapsulated HEK293 cells. METHODS: The combination of implantation of a foam dressing, vacuum-assisted wound closure (foam+VAC) and hyperbaric oxygenation (HBO) was used in 40 Sprague-Dawley rats. Blood flow and vascular endothelial growth factor (VEGF) levels were determined. Sodium cellulose sulphate (SCS)-microencapsulated HEK293 cells were xenotransplanted into the foam dressing in rats pre-treated with HBO, and angiogenesis and apoptosis were assessed. RESULTS: Vessel ingrowth and VEGF levels increased depending on the duration of HBO treatment. The area containing the foam was perfused significantly better in the experimental groups when compared to controls. Only a small amount of apoptosis occurs in SCS-microencapsulated HEK293 cells after xenotransplantation. CONCLUSION: As ischemia-damaged cells are likely to undergo cell death or loose functionality due to hypoxia, therefore leading to graft dysfunction, the combination foam+VAC and HBO might be a promising method to create a prevascularized site to achieve better results in xenogeneic cell transplantation.

Is There an Impact of Sex on Acute Postthoracotomy Pain? A Retrospective Analysis.

BACKGROUND: Current knowledge about sex-related differences states that pain is generally more frequent and intense in women. Because severe postthoracotomy pain is associated with complications, sufficient pain control is essential. Data on sex-related aspects in the context of pain after thoracotomy are scarce. The study attempted to determine whether sex significantly affects pain and pain treatment after thoracotomy. METHODS: This retrospective study assessed visual analogue scale (VAS) scores and analgesic consumption (opioids and diclofenac) during the first 5 days after surgery and the point in time when analgesics were changed from the intravenous to the oral route in patients who had open lung surgery. The influences of sex, PCEA (patient-controlled epidural analgesia), age, and surgical factors were evaluated with mixed-model analysis. RESULTS: The study was able to include 344 patients (130 female, 214 male). The VAS scores model did not consider sex as relevant. The opioid model showed a PCEA-time-sex interaction with increasing opioid demand after day 3 that predominantly affected male patients (P < .001). Diclofenac doses where significantly higher in an interaction of female sex and small extent of surgery (P = .007). Posterolateral thoracotomy led to significantly higher VAS scores (P < .001) and higher demand for opioids (P = .007) and diclofenac (P = .012). CONCLUSIONS: The study concluded that there are no general sex-related differences in pain intensity and analgesic requirement after thoracotomy. Anterolateral thoracotomy was the less painful surgical approach. PCEA had favorable results, although there seemed to a rebound pain phenomenon after epidural catheter removal on postoperative day 3 that mainly affected male patients.

Multi-channel lung sound classification with convolutional recurrent neural networks.

In this paper, we present an approach for multi-channel lung sound classification, exploiting spectral, temporal and spatial information. In particular, we propose a frame-wise classification framework to process full breathing cycles of multi-channel lung sound recordings with a convolutional recurrent neural network. With our recently developed 16-channel lung sound recording device, we collect lung sound recordings from lung-healthy subjects and patients with idiopathic pulmonary fibrosis (IPF), within a clinical trial. From the lung sound recordings, we extract spectrogram features and compare different deep neural network architectures for binary classification, i.e. healthy vs. pathological. Our proposed classification framework with the convolutional recurrent neural network outperforms the other networks by achieving an F-score of F1≈92%. Together with our multi-channel lung sound recording device, we present a holistic approach to multi-channel lung sound analysis.

Transdiaphragmatic repositioning of the heart in the setting of emergency laparotomy after blunt trauma.

Cardiac luxation after blunt trauma is a rare condition that carries a high mortality rate. We report a case of a left pericardial rupture with partial dislocation of the heart into the left pleural cavity and cardiac strangulation in a polytraumatized patient after a severe motor vehicle accident. This case is of special interest because the patient not only had cardiovascular compromise but was also actually in cardiac arrest and being resuscitated when an emergency repositioning of the heart through the diaphragm in the setting of damage control laparotomy restored circulation. This report stresses the need for a high index of suspicion for accurate early diagnosis of pericardial rupture.

Surgery for metachronous metastasis of soft tissue sarcoma - A magnitude of benefit analysis using propensity score methods.

INTRODUCTION: Metastasectomy is hypothesised to improve OS in metastatic STS, but evidence in favour of this approach derives from non-controlled single-arm cohorts affected by selection bias. The objective was to quantify the effect of metastasectomy vs. non-surgical management on overall survival (OS) in patients with metachronous metastases from extremity- and trunk soft tissue sarcoma (STS). MATERIALS AND METHODS: From a population of 1578 STS patients, 135 patients who underwent surgery for localised STS at two European centres between 1998 and 2015 and developed metachronous STS metastases were included. Propensity score analyses with inverse-probability-of-treatment-weights (IPTW) and landmark analyses were performed to control for selection and immortal time bias, respectively. RESULTS: OS was significantly longer in the 68 patients undergoing metastasectomy than in the 67 patients who were treated non-invasively for their metastasis (10-year OS: 23% vs. 4%; hazard ratio (HR) = 0.34, 95% CI: 0.22-0.53, p < 0.0001). This association prevailed after IPTW-weighting of the data to control for the higher prevalence of favourable prognostic factors in the surgery group (adjusted 10-year OS: 17% vs. 3%, log-rank p < 0.0001; HR = 0.33, 95% CI: 0.20-0.52, p < 0.0001). Five-year OS estimates were 27.8% in patients who had and 14.5% in patients who had not undergone metastasectomy within the first 3 months after diagnosis of a metastasis (p < 0.0001). CONCLUSION: In this observational bi-centre study, metastasectomy was associated with prolonged survival in patients with metachronous STS metastases. In the absence of randomized studies, our results indicate that metastasectomy should be considered as an important treatment option for metachronous STS metastases.

Crackle and Breathing Phase Detection in Lung Sounds with Deep Bidirectional Gated Recurrent Neural Networks.

In this paper, we present a method for event detection in single-channel lung sound recordings. This includes the detection of crackles and breathing phase events (inspiration/expiration). Therefore, we propose an event detection approach with spectral features and bidirectional gated recurrent neural networks (BiGRNNs). In our experiments, we use multichannel lung sound recordings from lung-healthy subjects and patients diagnosed with idiopathic pulmonary fibrosis, collected within a clinical trial. We achieve an event-based F-score of F1 ≈ 86% for breathing phase events and F1 ≈ 72% for crackles. The proposed method shows robustness regarding the contamination of the lung sound recordings with noise, bowel and heart sounds.

Emergency treatment of chest trauma--an e-learning simulation model for undergraduate medical students.

OBJECTIVE: Appropriate emergency measures are essential in improving the outcome of patients with thoracic injuries. Pathophysiological background and basic principles of emergency treatment decisions should be already taught in undergraduate medical curricula. The effectiveness of a computer simulation model on thoracic trauma management was evaluated. METHODS: Forty-one students were enrolled in this pre-test/post-test self-controlled study. Learning experience was based on a complex computer simulation model demonstrating basic mechanisms of thoracic injuries and facilitating the interactive application of various emergency measures. RESULTS: Pre-test multiple-choice results were 72.2% (66.9-77.5) correct answers, which increased significantly to 86.5% (82.6-90.4) in the post-test (p<0.001). The students spent 30 min (23-36) with the interactive learning object. Content analysis of open-ended feedback revealed a highly significant overall positive judgement (p<0.001), where the importance of 'trial and error' learning, the possibility of being able to 'view a process' and the simplicity of the model were particularly stressed. CONCLUSIONS: Computer simulation of chest trauma emergency treatment options is a safe and efficient learning approach in undergraduate medical education, which is highly appreciated by the students.

AIRFIX: the first digital postoperative chest tube airflowmetry--a novel method to quantify air leakage after lung resection.

OBJECTIVE: Prolonged air leak after pulmonary resection is a common complication and a major limiting factor for early discharge from hospital. Currently there is little consensus on its management. The aim of this study was to develop and evaluate a measuring device which allows a simple digital bed-side quantification of air-leaks compatible to standard thoracic drainage systems. PATIENTS AND METHODS: The measuring device (AIRFIX) is based upon a 'mass airflow' sensor with a specially designed software package that is connected to a thoracic suction drainage system. Its efficacy in detecting pulmonary air-leaks was evaluated in a series of 204 patients; all postoperative measurements were done under standardized conditions; the patients were asked to cough, to take a deep breath, to breathe out against the resistance of a flutter valve, to keep breath and to breathe normally. As standard parameters, the leakage per breath or cough (ml/b) as well as the leakage per minute (ml/min) were displayed and recorded on the computer. RESULTS: Air-leaks within a range of 0.25-45 ml/b and 5-900 ml/min were found. Removal of the chest tubes was done when leakage volume on Heimlich valve was less than 1.0 ml/b or 20 ml/min. After drain removal based upon the data from chest tube airflowmetry none of the patients needed re-drainage due to pneumothorax. CONCLUSION: The AIRFIX device for bed-side quantification of air-leaks has proved to be very simple and helpful in diagnosis and management of air-leaks after lung surgery, permitting drain removal without tentative clamping.

Direct reconstruction of tissue parameters from differential multifrequency EIT in vivo.

The basic purpose of electrical impedance tomography (EIT) is the reconstruction of conductivity distributions. While multifrequency measurements are of common use, the majority of reconstructed images are still conductivity distributions from one single frequency. More interesting than conductivities at each frequency are electrical tissue parameters, which describe the frequency-dependent conductivity changes of tissue. These parameters give information about physiological or electrical properties of tissues. By using this spectral information, a classification of different tissue types is possible. To get a distribution of tissue parameters, usually a posterior fitting of a tissue model to the conductivity spectra obtained with classical reconstruction algorithms at various frequencies is used. In this work, a single-step reconstruction algorithm for differential imaging was developed for the direct estimation of Cole parameters. This method is termed differential parametric reconstruction. The Cole model was used as the underlying tissue model, where only the relative changes of the two conductivity parameters sigma(0) and sigma(infinity) were reconstructed and the other two parameters of the model which are less identifiable were set to constant values. The reconstruction algorithm was tested with simulated noisy datasets and real measurement data from EIT measurements on the human thorax. These measurements were taken from healthy subjects and from patients with a serious lung injury. The new method yields a good image quality and higher robustness against noise compared to conventional reconstruction methods.