A practical approach to uveitis screening in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis typically presents as a silent chronic anterior uveitis and can lead to blindness. Adherence to current screening guidelines is hampered by complex protocols which rely on the knowledge of specific JIA characteristics. The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to simplify screening to enable local eye care professionals (ECPs), who carry the main burden, to screen children with JIA appropriately and with confidence. METHODS: A consensus meeting took place in January 2023 in Barcelona, Spain, with an expert panel of 10 paediatric rheumatologists and 5 ophthalmologists with expertise in paediatric uveitis. A summary of the current evidence for JIA screening was presented. A nominal group technique was used to reach consensus. RESULTS: The need for a practical but safe approach that allows early uveitis detection was identified by the panel. Three screening recommendations were proposed and approved by the voting members. They represent a standardised approach to JIA screening taking into account the patient's age at the onset of JIA to determine the screening interval until adulthood. CONCLUSION: By removing the need for the knowledge of JIA categories, antinuclear antibody positivity or treatment status, the recommendations can be more easily implemented by local ECP, where limited information is available. It would improve the standard of care on the local level significantly. The proposed protocol is less tailored to the individual than the 'gold standard' ones it references and does not aim to substitute those where they are being used with confidence.

[Prehospital chest tube placement: Which factors are associated with feeling confident to perform the procedure?] / Prähospitale Anlage von Thoraxdrainagen: Welche Faktoren sind mit einem subjektivem Sicherheitsgefühl assoziiert?

BACKGROUND: The prehospital placement of chest tubes is a rare but potentially life-saving procedure. A high level of subjective confidence with the procedure is essential for emergency medical doctors. This study aims to identify if there is a statistically significant difference in the subjective sense of confidence in prehospital chest tube placement regarding medical experience and qualification, clinical routine, and attendance at simulation courses. METHODS: Prehospital emergency physicians of three emergency medical services in Southwest Saxony, Greifswald, and Vechta, Germany, were invited to participate in an online survey from January to March 2022 using the online survey service limesurvey. The question "Do you feel confident in chest tube placement?" was used to measure the subjective level of confidence. Answers were compared with data concerning medical qualification, experience in prehospital emergency medicine, clinical routine, and attendance at simulation courses. Statistical analysis was performed using chi-squared test and Fisher's exact test. RESULTS: Three out of four participants felt confident in chest tube placement (53/71; 74.6%). More than half of the participants reported that they did not perform this procedure regularly (35/53, 66%). Subjective confidence was highest in physicians who regularly place chest tubes during their non-prehospital work (34/37; 91,9%; p<0.001), and more often when participants had clinical routine and attended simulation courses than when none of this applied (p=0.012). Attendance at simulation courses alone was not associated with a higher level of confidence (p=0.002). Specialists showed significantly more often subjective confidence in chest tube placement (p=0.0401). CONCLUSION: Prehospital chest tube placement is rare, but potentially lifesaving. An adequately high level of subjective confidence in the placement of chest tubes is a key condition for prehospital emergency doctors. Inhospital clinical routine and attendance at simulation courses are significantly associated with high levels of confidence. Our data indicate that working only in prehospital emergency settings without further clinical routine or medical specialization is not sufficient for achieving and ensuring subjective confidence in chest tube placement.

Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers.

BACKGROUND: T-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clinical activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA). METHODS: We present here the generation and preclinical development of NILK-2301, a BsAb composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format). RESULTS: NILK-2301 binds CD3ɛ on T-cells with its lambda light chain arm with an affinity of ≈100 nM, and the CEACAM5 A2 domain on tumor cells by its kappa light chain arm with an affinity of ≈5 nM. FcγR-binding is abrogated by the "LALAPA" mutation (Leu234Ala, Leu235Ala, Pro329Ala). NILK-2301 induced T-cell activation, proliferation, cytokine release, and T-cell dependent cellular cytotoxicity of CEACAM5-positive tumor cell lines (5/5 colorectal, 2/2 gastric, 2/2 lung), e.g., SK-CO-1 (Emax = 89%), MKN-45 (Emax = 84%), and H2122 (Emax = 97%), with EC50 ranging from 0.02 to 0.14 nM. NILK-2301 binds neither to CEACAM5-negative or primary colon epithelial cells nor to other CEACAM family members. NILK-2301 alone or in combination with checkpoint inhibition showed activity in organotypic tumor tissue slices and colorectal cancer organoid models. In vivo, NILK-2301 at 10 mg/kg significantly delayed tumor progression in colon- and a pancreatic adenocarcinoma model. Single-dose pharmacokinetics (PK) and tolerability in cynomolgus monkeys at 0.5 or 10 mg/kg intravenously or 20 mg subcutaneously showed dose-proportional PK, bioavailability ≈100%, and a projected half-life in humans of 13.1 days. NILK-2301 was well-tolerated. Data were confirmed in human FcRn TG32 mice. CONCLUSIONS: In summary, NILK-2301 combines promising preclinical activity and safety with lower probability of ADA-generation due to its format compared to other molecules and is scheduled to enter clinical testing at the end of 2023.

Organotypic 3D Co-Culture of Human Pleura as a Novel In Vitro Model of Staphylococcus aureus Infection and Biofilm Development.

Bacterial pleural infections are associated with high mortality. Treatment is complicated due to biofilm formation. A common causative pathogen is Staphylococcus aureus (S. aureus). Since it is distinctly human-specific, rodent models do not provide adequate conditions for research. The purpose of this study was to examine the effects of S. aureus infection on human pleural mesothelial cells using a recently established 3D organotypic co-culture model of pleura derived from human specimens. After infection of our model with S. aureus, samples were harvested at defined time points. Histological analysis and immunostaining for tight junction proteins (c-Jun, VE-cadherin, and ZO-1) were performed, demonstrating changes comparable to in vivo empyema. The measurement of secreted cytokine levels (TNF-α, MCP-1, and IL-1ß) proved host-pathogen interactions in our model. Similarly, mesothelial cells produced VEGF on in vivo levels. These findings were contrasted by vital, unimpaired cells in a sterile control model. We were able to establish a 3D organotypic in vitro co-culture model of human pleura infected with S. aureus resulting in the formation of biofilm, including host-pathogen interactions. This novel model could be a useful microenvironment tool for in vitro studies on biofilm in pleural empyema.

[Pathophysiology, Diagnostics and Therapy of Pulmonary Contusion - Recommendations of the Interdisciplinary Group on Thoracic Trauma of the Section NIS of the German Society for Trauma Surgery (DGU) and the German Society for Thoracic Surgery (DGT)]. / Pathophysiologie, Diagnostik und Therapie der Lungenkontusion ­ Empfehlungen der interdisziplinären Arbeitsgruppe der Sektion NIS der DGU und DGT zur Thoraxtraumaversorgung.

Pulmonary contusion usually occurs in combination with other injuries and is indicative of a high level of force. Especially in multiply injured patients, pulmonary contusions are frequently detected. The injury is characterised by dynamic development, which might result in difficulties in recognising the actual extent of the injury at an early stage. Subsequently, correct classification of the extent of injury and appropriate initiation of therapeutic steps are essential to achieve the best possible outcome. The main goal of all therapeutic measures is to preserve lung function as best as possible and to avoid associated complications such as the development of pneumonia or Acute Respiratory Distress Syndrome (ARDS).The present report from the interdisciplinary working group "Chest Trauma" of the German Society for Trauma Surgery (DGU) and the German Society for Thoracic Surgery (DGT) includes an extensive literature review on the background, diagnosis and treatment of pulmonary contusion. Without exception, papers with a low level of evidence were included due to the lack of studies with large cohorts of patients or randomised controlled studies. Thus, the recommendations given in the present article correspond to a consensus of the aforementioned interdisciplinary working group.Computed tomography (CT) of the chest is recommended for initial diagnosis; the extent of pulmonary contusion correlates with the incidence and severity of complications. A conventional chest X-ray may initially underestimate the injury, but is useful during short-term follow-up.Therapy for pulmonary contusion is multimodal and symptom-based. In particular, intensive care therapy with lung-protective ventilation and patient positioning are key factors of treatment. In addition to invasive ventilation, non-invasive ventilation should be considered if the patient's comorbidities and compliance allows this. Furthermore, depending on the extent of the lung injury and the general patient's condition, ECMO therapy may be considered as an ultima ratio. In particular, this should only be performed at specialised hospitals, which is why patient assignment or anticipation of early transfer of the patient should be anticipated at an early time during the course.

[Thoracic Surgery Without Chest Tube: The Current Situation in Germany]. / Thoraxchirurgie ohne Thoraxdrainage ­ aktuelle Situation in Deutschland.

BACKGROUND: Over the last decades, several techniques have been implemented to reduce the invasiveness of thoracic surgery. Omitting chest tubes can lead to less postoperative pain and a shorter length of hospital stay. This study examines the extent to which German surgeons use the tubeless technique and what experience they have had with it. MATERIALS AND METHODS: We conducted a nationwide survey, supported by the German Society of Thoracic Surgery (DGT). A digital questionnaire was sent to all leading thoracic surgeons with DGT membership between July and September 2020. RESULTS: 63 of 161 surgeons (39%) returned the questionnaires. The tubeless technique was used in 1.9% of thoracic surgery procedures performed last year. 59% of hospitals have implemented the technique; 24% of them also performed lung resections that way. The majority of respondents (79%) believe that the tubeless technique causes less postoperative pain; 16% see no advantage. Pleural effusion was ranked as the most important contraindication (76%). All participating surgeons agree that the absence of an air fistula is a prerequisite for performing lung resections using the tubeless technique - commonly checked by an underwater leak test (73%), and/or with a digital drainage system (53%), partially under pressure controlled ventilated lungs. Almost half of the respondents (46%) have not observed any complications using the tubeless technique. CONCLUSION: Most German thoracic surgeons consider the tubeless technique safe and advantageous over the conventional technique. However, the case load is low and only 59% of the surgeons surveyed have experience with this technique. Randomised clinical trials concerning selection criteria and the procedural pathway may help increase the use.

[Occult and Retained Haemothorax - Recommendations of the Interdisciplinary Thoracic Trauma Task Group of the German Trauma Society (DGU - Section NIS) and the German Society for Thoracic Surgery (DGT)]. / Okkulter und residueller Hämatothorax nach Thoraxtrauma ­ Empfehlungen der interdisziplinären Arbeitsgruppe Thoraxtrauma der Sektion NIS der Deutschen Gesellschaft für Unfallchirurgie (DGU) und der Deutschen Gesellschaft für Thoraxchirurgie (DGT).

The management of occult and retained haemothorax is challenging for all involved in the care of polytrauma patients in terms of diagnosis and treatment. The focus of decision making is preventing sequelae such as pleural empyema and avoiding a trapped lung. An interdisciplinary task force of the German Society for Thoracic Surgery (DGT) and the German Trauma Society (DGU) on thoracic trauma offers recommendations for post-trauma care of patients with occult and/or retained haemothorax, as based on a comprehensive literature review.

Pectus excavatum in motion: dynamic evaluation using real-time MRI.

OBJECTIVES: The breathing phase for the determination of thoracic indices in patients with pectus excavatum is not standardized. The aim of this study was to identify the best period for reliable assessments of morphologic indices by dynamic observations of the chest wall using real-time MRI. METHODS: In this prospective study, patients with pectus excavatum underwent morphologic evaluation by real-time MRI at 3 T between January 2020 and June 2021. The Haller index (HI), correction index (CI), modified asymmetry index (AI), and modified eccentricity index (EI) were determined during free, quiet, and forced breathing respectively. Breathing-related differences in the thoracic indices were analyzed with the Wilcoxon signed-rank test. Motion of the anterior chest wall was analyzed as well. RESULTS: A total of 56 patients (11 females and 45 males, median age 15.4 years, interquartile range 14.3-16.9) were included. In quiet expiration, the median HI in the cohort equaled 5.7 (4.5-7.2). The median absolute differences (Δ) in the thoracic indices between peak inspiration and peak expiration were ΔHI = 1.1 (0.7-1.6, p < .001), ΔCI = 4.8% (1.3-7.5%, p < .001), ΔAI = 3.0% (1.0-5.0%, p < .001), and ΔEI = 8.0% (3.0-14.0%, p < .05). The indices varied significantly during different inspiratory phases, but not during expiration (p > .05 each). Furthermore, the dynamic evaluation revealed three distinctive movement patterns of the funnel chest. CONCLUSIONS: Real-time MRI reveals patterns of chest wall motion and indicate that thoracic indices of pectus excavatum should be assessed in the end-expiratory phase of quiet expiration. KEY POINTS: • The thoracic indices in patients with pectus excavatum depend on the breathing phase. • Quiet expiration represents the best breathing phase for determining thoracic indices. • Real-time MRI can identify different chest wall motion patterns in pectus excavatum.

CT texture analysis and node-RADS CT score of mediastinal lymph nodes - diagnostic performance in lung cancer patients.

BACKGROUND: Texture analysis derived from computed tomography (CT) can provide clinically relevant imaging biomarkers. Node-RADS is a recently proposed classification to categorize lymph nodes in radiological images. The present study sought to investigate the diagnostic abilities of CT texture analysis and Node-RADS to discriminate benign from malignant mediastinal lymph nodes in patients with lung cancer. METHODS: Ninety-one patients (n = 32 females, 35%) with a mean age of 64.8 ± 10.8 years were included in this retrospective study. Texture analysis was performed using the free available Mazda software. All lymph nodes were scored accordingly to the Node-RADS classification. All primary tumors and all investigated mediastinal lymph nodes were histopathologically confirmed during clinical workup. RESULTS: In discrimination analysis, Node-RADS score showed statistically significant differences between N0 and N1-3 (p < 0.001). Multiple texture features were different between benign and malignant lymph nodes: S(1,0)AngScMom, S(1,0)SumEntrp, S(1,0)Entropy, S(0,1)SumAverg. Correlation analysis revealed positive associations between the texture features with Node-RADS score: S(4,0)Entropy (r = 0.72, p < 0.001), S(3,0) Entropy (r = 0.72, p < 0.001), S(2,2)Entropy (r = 0.72, p < 0.001). CONCLUSIONS: Several texture features and Node-RADS derived from CT were associated with the malignancy of mediastinal lymph nodes and might therefore be helpful for discrimination purposes. Both of the two quantitative assessments could be translated and used in clinical routine.

[Safety aspects of prehospital thoracic emergency procedures: Results of a survey among German emergency physicians]. / Sicherheitsaspekte invasiver thorakaler Maßnahmen in der prähospitalen Notfallmedizin ­ Ergebnisse einer Umfrage unter deutschen Notärzt:innen.

BACKGROUND: The safe indication and performance of thoracic emergency procedures are crucial and potentially lifesaving in prehospital emergency care. This study aims to investigate issues of patient safety and quality assurance of prehospital invasive thoracic interventions. The survey does not represent the actual medical care situation but explores reasons for security concerns among emergency physicians. METHODS: Using a pre-validated questionnaire, prehospital emergency physicians of three prehospital rescue associations (Zweckverband) in Southwest Saxony, Greifswald, and Vechta, Germany, were queried via the online survey service limesurvey. The survey was conducted between January and March 2022. RESULTS: 104 emergency physicians participated (response rate 42.4%) 71 of which fully completed the survey (68%). 79% of the participants stated that they felt safe in performing pleural punction. Common reasons for postponing prehospital thoracic interventions included fear of complications or individual patient characteristics. 90% said that they were familiar with the on-board equipment options, and 60% reported that resources were sufficient to perform double-sided procedures. While in all three regions there is sufficient on-board equipment to perform procedures on two sides, one out of two participants said that lack of equipment deters them from performing prehospital invasive thoracic procedures. Emergency physicians who graduated from trauma courses and/or participate in air rescue are more likely to perform invasive thoracic procedures. More than half of the participants wanted more training in chest tube placement or pleural punction. CONCLUSION: Safety in prehospital invasive thoracic procedures needs improvement in structural, procedural, as well as human factors aspects. Safe handling of these rare but vital techniques requires more training. A lack of knowledge of equipment is a significant safety gap. Prehospital ultrasound constitutes a structural element of prehospital diagnostics.

Chest Tube Placement in Mechanically Ventilated Trauma Patients: Differences between Computed Tomography-Based Indication and Clinical Decision.

The rate of occult pneumothorax in intubated and mechanically ventilated trauma patients until initial computed tomography (CT) remains undetermined. The primary aims of this study were to analyze initial chest CTs with respect to the thoracic pathology of trauma, the clinical injury severity, and chest tube placement (CTP) before and after CT. In a single-center retrospective analysis of 616 intubated and mechanically ventilated adult patients admitted directly from the scene to the emergency department (ED), 224 underwent CTP (36%). Of these, 142 patients (62%) underwent CTP before CT, of which, 125 (88%) had significant chest injury on CT. Seventeen patients had minor or absent chest injuries, most of which were associated with transient or unrecognized tracheal tube malposition. After CT, CTP was performed in another 82 patients, of which, 56 (68.3%) had relevant pneumothorax and 26 had minor findings on CT. Sixty patients who had already undergone CTP before CT received another CTP after CT, of which, 15 (25%) had relevant pneumothorax and 45 (75%) had functionality issues or malposition requiring replacement. Nine patients showed small pneumothorax on CT, and did not undergo CTP (including four patients with CTP before CT). The physiological variables were unspecific, and the trauma scores were dependent on the CT findings for identifying patients at risk for CTP. In conclusion, the clinical decisions for CTP before CT are associated with relevant false-negative and false-positive cases. Clinical assessment and CT imaging, together, are important indicators for CTP decisions that cannot be achieved by using clinical assessment or CT alone.

Chest Compression-Related Flail Chest Is Associated with Prolonged Ventilator Weaning in Cardiac Arrest Survivors.

Chest compressions during cardiopulmonary resuscitation (CPR) may be associated with iatrogenic chest wall injuries. The extent to which these CPR-associated chest wall injuries contribute to a delay in the respiratory recovery of cardiac arrest survivors has not been sufficiently explored. In a single-center retrospective cohort study, surviving intensive care unit (ICU) patients, who had undergone CPR due to medical reasons between 1 January 2018 and 30 June 2019, were analyzed regarding CPR-associated chest wall injuries, detected by chest radiography and computed tomography. Among 109 included patients, 38 (34.8%) presented with chest wall injuries, including 10 (9.2%) with flail chest. The multivariable logistic regression analysis identified flail chest to be independently associated with the need for tracheostomy (OR 15.5; 95% CI 2.77−86.27; p = 0.002). The linear regression analysis identified pneumonia (ß 11.34; 95% CI 6.70−15.99; p < 0.001) and the presence of rib fractures (ß 5.97; 95% CI 1.01−10.93; p = 0.019) to be associated with an increase in the length of ICU stay, whereas flail chest (ß 10.45; 95% CI 3.57−17.33; p = 0.003) and pneumonia (ß 6.12; 95% CI 0.94−11.31; p = 0.021) were associated with a prolonged duration of mechanical ventilation. Four patients with flail chest underwent surgical rib stabilization and were successfully weaned from the ventilator. The results of this study suggest that CPR-associated chest wall injuries, flail chest in particular, may impair the respiratory recovery of cardiac arrest survivors in the ICU. A multidisciplinary assessment may help to identify patients who could benefit from a surgical treatment approach.

Iatrogenic Tracheal Rupture Related to Prehospital Emergency Intubation in Adults: A 15-Year Single Center Experience.

OBJECTIVE: Iatrogenic tracheal rupture is an unusual and severe complication that can be caused by tracheal intubation. The frequency, management, and outcome of iatrogenic tracheal rupture due to prehospital emergency intubation in adults by emergency response physicians has not yet been sufficiently explored. METHODS: Adult patients with iatrogenic tracheal ruptures due to prehospital emergency intubation admitted to an academic referral center over a 15-year period (2004-2018) with consideration of individual risk factors were analyzed. RESULTS: Thirteen patients (eight female) with a mean age of 67 years met the inclusion criteria and were analyzed. Of these, eight tracheal ruptures (62%) were caused during the airway management of cardiopulmonary resuscitation (CPR). Stylet use and difficult laryngoscopy requiring multiple attempts were documented in eight cases (62%) and four cases (30%), respectively. Seven patients (54%) underwent surgery, while six patients (46%) were treated conservatively. The overall 30-day mortality was 46%; five patients died due to their underlying emergencies and one patient died of tracheal rupture. Three survivors (23%) recovered with severe neurological sequelae and four (30%) were discharged in good neurological condition. Survivors had significantly smaller mean rupture sizes (2.7cm versus 6.3cm; P <.001) and less cutaneous emphysema (n = 2 versus n = 6; P = .021) than nonsurvivors. CONCLUSIONS: Iatrogenic tracheal rupture due to prehospital emergency intubation is a rare complication. Published risk factors are not consistently present and may not be applicable to identify patients at high risk, especially not in rescue situations. Treatment options depend on individual patient condition, whereas outcome largely depends on the underlying disease and rupture extension.

Risk factors and outcomes of unrecognised endobronchial intubation in major trauma patients.

BACKGROUND: Emergency tracheal intubation during major trauma resuscitation may be associated with unrecognised endobronchial intubation. The risk factors and outcomes associated with this issue have not previously been fully defined. METHODS: We retrospectively analysed adult patients admitted directly from the scene to the ED of a single level 1 trauma centre, who received either prehospital or ED tracheal intubation prior to initial whole-body CT from January 2008 to December 2019. Our objectives were to describe tube-to-carina distances (TCDs) via CT and to assess the risk factors and outcomes (mortality, length of intensive care unit stay and mechanical ventilation) of patients with endobronchial intubation (TCD <0 cm) using a multivariable model. RESULTS: We included 616 patients and discovered 26 (4.2%) cases of endobronchial intubation identified on CT. Factors associated with an increased risk of endobronchial intubations were short body height (OR per 1 cm increase 0.89; 95% CI 0.84 to 0.94; p≤0.001), a high body mass index (OR 1.14; 95% CI 1.04 to 1.25; p=0.005) and ED intubation (OR 3.62; 95% CI 1.39 to 8.90; p=0.006). Eight of 26 cases underwent tube thoracostomy, four of whom had no evidence of underlying chest injury on CT. There was no statistically significant difference in mortality or length of stay although the absolute number of endobronchial intubations was small. CONCLUSIONS: Short body height and high body mass index were associated with endobronchial intubation. Before considering tube thoracostomy in intubated major trauma patients suspected of pneumothorax, the possibility of unrecognised endobronchial intubation should be considered.

[Molecule pathology in the treatment of lung cancer-Interdisciplinary view of the importance in thoracic surgery]. / Molekularpathologie in der Behandlung des Lungenkarzinoms ­ interdisziplinärer Blick auf die thoraxchirurgische Bedeutung.

Treatment modalities of lung cancer have rapidly evolved in recent years by the establishment of tumor-specific targeted drugs and immunomodulatory concepts and the complexity has rapidly increased. This development is accompanied by improved survival data and knowledge of other spectra of side effects and recurrence characteristics. This development requires that clinicians maintain a constant vigilance in the stratification of treatment options. This article gives an overview of the current clinically relevant approaches of targeted treatment of lung cancer and points out possible links to thoracic surgery. The presentation of the options of targeted therapy demonstrates which role they play in the adjuvant treatment in cases of proven mutations of epidermal growth factor receptor (EGFR), when a salvage operation can be used and how a curative treatment concept can be elaborated in individual cases through targeted treatment. Every lung cancer ultimately requires a molecular analysis of treatment-relevant mutation patterns at the earliest possible time in the diagnostics. Interdisciplinary concepts can individually guarantee the long-term survival of the patient.

Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-ß.

Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-ß (TGF-ß) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-ß, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-ß signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-ß.

Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition.

Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients' responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/or assays to determine individual prediction of treatment response and investigate resistance mechanisms. Here, we describe a standardized ex vivo tissue culture model to investigate individual tumor responses. NSCLC tissue cultures preserve morphological characteristics of the baseline tumor specimen for up to 12 days ex vivo and also maintain T-cell function for up to 10 days ex vivo. A semi-automated analysis of proliferating and apoptotic tumor cells was used to evaluate tissue responses to the PD-1 inhibitor nivolumab (n = 12), from which two cases could be successfully correlated to the clinical outcome. T-cell responses upon nivolumab treatment were investigated by flow cytometry and multispectral imaging. Alterations in the frequency of the Treg population and reorganization of tumor tissues could be correlated to nivolumab responsiveness ex vivo. Thus, our findings not only demonstrate the functionality of T cells in NSCLC slice cultures up to 10 days ex vivo, but also suggests this model for stratifying patients for treatment selection and to investigate in depth the tumor-associated T-cell regulation.

[How severe is the effect of the coronavirus pandemic on the department of surgery of a university hospital? : An analysis of the first 7 weeks]. / Wie stark trifft die Corona-Pandemie die chirurgische Klinik eines universitären Maximalversorgers? : Eine Analyse der ersten 7 Wochen.

BACKGROUND: The corona pandemic poses enormous financial challenges for hospitals. Using the example of a clinic for visceral, transplantation, thorax and vascular surgery (VTTG), the performance development of inpatient care in the first 7 weeks in comparison to the previous year as well as an evaluation of the compensation measures laid down by law were evaluated. METHODOLOGY: Based on the performance figures, a comparison was made between the period from 16 March to 3 May 2019 and the same period in 2020. Changes in the number of cases, case mix, case mix index and day mix index as well as the bed occupancy days were recorded. The monetary measures from the COVID-19 Hospital Relief Act were applied to these changes and the adequacy was evaluated. RESULTS: Compared to the previous year there was a decrease in inpatient admissions of 120 patients during the observation period. As a result there was a decrease of 370 points in case mix and 1433 days of occupancy. For the whole VTTG this resulted in a decrease in revenue of approximately 0.8 million €, which was completely compensated by the flat rate payment for empty beds. The individual areas of the VTTG showed a heterogeneous picture in relation to the compensation for the loss of revenue. Elective units in particular showed a shortfall up to 128,163 € with respect to inpatient treatment for 7 weeks. CONCLUSION: The measures taken by the Government are an important support for the economic security of German hospitals. The lack of differentiation of measures by specialty leads to a heterogeneous picture in compensation for VTTG revenues and has to be understood as an alarm signal especially for elective surgical healthcare.

Prognostic Factors for Iatrogenic Tracheal Rupture: A Single-Center Retrospective Cohort Study.

Iatrogenic tracheal ruptures are rare but severe complications of medical interventions. The main goal of this study was to explore prognostic factors for all-cause mortality and rupture-related (adjusted) mortality. We retrospectively analyzed patients admitted to an academic referral center over a 15-year period (2004-2018). Fifty-four patients met the inclusion criteria, of whom 36 patients underwent surgical repair and 18 patients were treated conservatively. In a 90-day follow-up, the all-cause mortality was 50%, while the adjusted mortality was 13%. Rupture length was identified as a predictor for all-cause mortality (area under the curve, 0.84; 95% confidence interval (CI) 0.74-0.94) with a cutoff rupture length of 4.5 cm (sensitivity, 0.70; specificity, 0.81). Multivariate analysis confirmed rupture length as a prognostic factor for all-cause mortality (adjusted hazard ratio (HR) 1.5; 95% CI 1.2-1.9; p = 0.001), but not for adjusted mortality (HR 1.5; 95% CI 0.97-2.3; p = 0.068), while mediastinitis predicted adjusted mortality (HR 5.8; 95% CI 1.1-31.7; p = 0.042), but not all-cause mortality (HR 1.6; 95% CI 0.7-3.5; p = 0.243). The extent of iatrogenic tracheal rupture and mediastinitis might be relevant prognostic factors for all-cause mortality and adjusted mortality, respectively.

Thoracotomy for emergency repair of iatrogenic tracheal rupture: single center analysis of perioperative management and outcomes.

BACKGROUND: Iatrogenic tracheal ruptures are rare but life-threatening airway complications that often require surgical repair. Data on perioperative vital functions and anesthetic regimes are scarce. The goal of this study was to explore comorbidity, perioperative management, complications and outcomes of patients undergoing thoracotomy for surgical repair. METHODS: We retrospectively evaluated adult patients who required right thoracotomy for emergency surgical repair of iatrogenic posterior tracheal ruptures and were admitted to a university hospital over a 15-year period (2004-2018). The analyses included demographic, diagnostic, management and outcome data on preinjury morbidity and perioperative complications. RESULTS: Thirty-five patients who met the inclusion criteria were analyzed. All but two patients (96%) presented with critical underlying diseases and/or emergency tracheal intubations. The median time (interquartile range) from diagnosis to surgery was 0.3 (0.2-1.0) days. The durations of anesthesia, surgery and one-lung ventilation (OLV) were 172 (128-261) min, 100 (68-162) min, and 52 (40-99) min, respectively. The primary airway management approach to OLV was successful in only 12 patients (34%). Major complications during surgery were observed in 10 patients (29%). Four patients (11%) required cardiopulmonary resuscitation, one of whom received extracorporeal membrane oxygenation, and another one of these patients died during surgery. Major complications were associated with significantly higher all-cause 30-day mortality (p = 0.002) and adjusted mortality (p = 0.001) compared to patients with minor or no complications. CONCLUSIONS: Surgical repair of iatrogenic tracheal ruptures requires advanced perioperative care in a specialized center due to high morbidity and potential complications. Airway management should include early anticipation of alternative OLV approaches to provide acceptable conditions for surgery.