[Pneumology in the Model Degree Program of the Medical Faculty Ostwestfalen Lippe, Germany]. / Das Fach Pneumologie im Modellstudiengang der Medizinischen Fakultät Ostwestfalen-Lippe (OWL).

The specialist field of "pneumology" is still underrepresented in university clinics in Germany, but this is not the case at the newly founded medical faculty Ostwestfalen-Lippe (OWL) in Bielefeld. This is linked to representing pneumology and internal intensive care medicine in patient care, teaching and research across the board and the opportunity to actively help shape the development of the human medicine faculty in an exciting environment.The early anchoring of the subject "Pneumology" in the model degree program of medical school in OWL (begin winter semester 2021/22) contributes to further visibility and a university medical orientation. In this overview various issues of Pneumology in the Model Degree Program are explored by basic scientists, clinical teachers, members of the medical faculty and a student.In today's Evangelisches Klinikum Bethel (EvKB), pulmonary medicine has a long tradition. The hospital's first lung and infection center was opened in 1927. The EvKB's department for internal medicine, pneumology and intensive care medicine, which has been independent since 2009, is becoming a university clinic for pneumology within the medical faculty OWL. Relevant translational and interdisciplinary research can be intensified.There are 30 "Pneumology" teaching units in the model degree program, which are divided into two study sections using different formats, such as lectures, seminars, hands on courses and skills lab. It is represented in particular in the module complex "Circulation and Respiration". The content of the first phase of teaching was carried out by a module commission, with members representing the subjects involved in the module.Knowledge of the basics from, for example, physiology, pathophysiology, anatomy and pathology are taught to the students in the run-up to the pneumology course. Using the example of physiology, the presentation of the learning content of a basic subject is elaborated in this article.Half of all teaching units on pneumology of the entire course took place in the 2nd semester (in March and April 2022), so that students experienced the clinical relevance of the content at an early stage. There was a particular focus on obstructive airway and restrictive lung diseases. After imparting the basic knowledge of the physical examination of the lungs in the Skills Lab, the most important pathological findings in the above-mentioned diseases on inspection, palpation, auscultation and percussion are demonstrated and practised in patients as part of bedside teaching under supervision.Communication training is also longitudinally integrated into the modular teaching, with a total of more than 200 teaching hours and is performed interdisciplinary. In the "Circulation and Breathing" module eight hours are devoted to this with simulated patients, the anamnesis and therapy advice on classic cardiopulmonary diseases. For the students, integrating the teaching of basic theory and its clinical application for each organ systems represents a challenge in the model degree program, the advantages outweigh from today's perspective.

Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA.

Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors.

Minimally-Invasive Diaphragmatic Plication in Patients with Unilateral Diaphragmatic Paralysis.

Background: Diaphragm eventration (DE) represents a frequent problem with consecutive major impacts on respiratory function and the quality of life of the patients. The role of diaphragmatic plication (DP) is still underestimated. The aim of the present study is to evaluate the efficacy of minimally-invasive surgical diaphragmatic plication for the management of unilateral diaphragmatic eventration, to the best of our knowledge, this is the largest series reported in the literature using a non-resectional technique. Methods: All patients with unilateral diaphragmatic paralysis admitted for diaphragmatic plication (DP) between January 2008 and December 2022 formed the cohort of this retrospective analysis. DP procedure was done to plicate the diaphragm without resection or replacement with synthetic materials. Patients were divided into two groups: Group I included patients who underwent DP through an open thoracotomy, and Group II included patients who underwent DP through video-assisted thoracoscopic surgery (VATS). Data from all patients were collected prospectively and subsequently analyzed retrospectively. Patients' characteristics, lung function tests, radiological findings, type of surgical procedures, complications, and postoperative follow-up were compared. The primary outcome measure was the postoperative result (deeper position of the paralyzed diaphragm) and improvement of dyspnea. The secondary outcome was lung function values over a long-term follow-up. Results: The study included a total of 134 patients who underwent diaphragmatic plication during the study period. 94 (71.7%) were males, mean age of 64 (SD ± 14.0). Group I (thoracotomy group) consisted of 46 patients (35 male). Group II (VATS-group) consisted of 88 patients (69 male). The majority of patients demonstrated impaired lung functions (n = 126). The mean length of diaphragmatic displacement was 8 cm (SD ± 113.8 cm). The mean duration of the entire procedure, including placement of the epidural catheter (EDC), was longer in group I than in group II (p = 0.016). This was also observed for the mean length of the surgical procedure itself (p = 0.031). Most patients in group I had EDC (n = 38) (p = 0.001). Patients in group I required more medication for pain control (p = 0.022). A lower position of the diaphragm was achieved in all patients (p < 0.001). The length of hospital stay was 7 (SD ± 4.5) days in group I vs. 4.5 (SD ± 3.2) days in group II (p = 0.036). Minor complications occurred in 3% (n = 4) in group I vs. 2% (n = 3) in group II. No mortality was observed in any of the groups. Postoperative follow-up of patients at 6, 12, and 24 months showed a significant increase in forced vital capacity (FVC) up to 25% (SD ± 10%-35%) (p = 0.019), in forced expiratory volume in 1 s (FEV1) up to 20% (SD ± 12%-38%) in both groups (p = 0.026), also in the diffusion capacity of carbon monoxide (DLCO) up to 15% (SD ± 10%-20%) was noticed in both groups. Chronic pain symptoms were noted in 13% (n = 6) in group I vs. 2% (n = 2) in group II (p = 0.014). Except for one patient in group II, no recurrence of DE was observed. Conclusions: Diaphragm plication is an effective procedure to reduce debilitating dyspnea and improve lung function in patients suffering from diaphragm eventration. Minimally invasive diaphragmatic plication using VATS procedures is a safe and feasible procedure for the management of unilateral diaphragmatic paralysis. VATS-DP is superior to open procedure in terms of pain management and length of hospital stay, hence, accelerated recovery is more likely. Careful patient selection is crucial to achieving optimal outcomes. Prospective studies are needed to validate these results.

[Cardiac arrest and hypothermia caused by suicidal intoxication with butane: a case report]. / Kasuistik - Reanimation unter Hypothermie nach suizidaler Butangasintoxikation.

In the emergency medicine field cases of intoxication by sniffing agents do not occur very often. Nevertheless, considering the easy availability of butane the option of abuse especially by adolescent persons cannot be ignored. Although many cases of accidental death caused by malignant arrhythmia are described ("Sudden sniffing death syndrome"), suicide attempts using butane are a rarity. In this case the emergency treatment has to allow for special pathophysiological changes explained by physicochemical characteristics of butane. The following case report describes the symptomatology and pre-hospital treatment of an intoxication by butane with a suicidal intention.

Huge typical pulmonary carcinoid presented with gigantism syndrome.

A 27-year-old male patient presented with cough and right-sided, light thoracic pain. His physical appearance showed typical features of gigantism. Subsequently, further diagnostic work-up showed elevated level of growth hormone and a huge tumor of the right lung, identifying a typical pulmonary carcinoid tumor (TPCT). Curative surgery was performed leading to normalization of the elevated growth hormone levels few days after surgery. Two- and five-year follow-up showed no signs of recurrence. Respected to tumor size, we determined the largest TPCT to be reported in medical literature history.

Nanopore Sequencing Reveals Global Transcriptome Signatures of Mitochondrial and Ribosomal Gene Expressions in Various Human Cancer Stem-like Cell Populations.

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term "NF-kB binding" was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.

Analysis of risk factors in thoracic trauma patients with a comparison of a modern trauma centre: a mono-centre study.

OBJECTIVES: Thoracic trauma (TT) is the third most common cause of death after abdominal injury and head trauma in polytrauma patients. Its management is still a very challenging task. The purpose of this study was to analyse the risk factors affecting the outcome in a high-volume trauma centre and the efficacy of a specialised trauma team in level 1 trauma centres. PATIENTS AND METHODS: Between January 2003 and December 2012, data of all patients admitted to the accident and emergency (A&E) department were prospectively collected at the German Trauma Registry (GTR) and thereafter retrospectively analysed. Patients with chest trauma, an Injury Severity Score (ISS) ≥ 18 and an Abbreviated Injury Scale (AIS) > 2 in more than one body region were included. Patients were divided into two groups: group I included patients presenting with thoracic trauma between January 2003 and December 2007. The results of this group were compared with the results of another group (group II) in a later 5-year period (Jan. 2008-Dec. 2012). Univariate and multivariate analyses were performed, and differences with p < 0.05 were considered statistically significant. RESULTS: There were 630 patients (56%) with thoracic trauma. A total of 540 patients (48%) had associated extrathoracic injuries. Group I consisted of 285 patients (197 male, mean age 46 years). Group II consisted of 345 patients (251 male, mean age 49 years). Overall 90-day mortality was 17% (n = 48) in group I vs. 9% (n = 31) in group II (p = 0.024). Complication rates were higher in group I (p = 0.019). Higher Injury Severity Scores (ISSs) and higher Abbreviated Injury Acale (AIS) scores in the thoracic region yielded a higher rate of mortality (p < 0.0001). Young patients (< 40 years) were frequently exposed to severe thoracic injury but showed lower mortality rates (p = 0.014). Patients with severe lung contusions (n = 94) (15%) had higher morbidity and mortality (p < 0.001). Twenty-three (8%) patients underwent emergency thoracotomy in group I vs. 14 patients (4%) in group II (p = 0.041). Organ replacement procedures were needed in 18% of patients in group I vs. 31% of patients in group II (p = 0.038). CONCLUSIONS: The presence of severe lung contusion, a higher ISS and AISthoracic score and advanced age are independent risk factors that are directly related to a higher mortality rate. Management of blunt chest trauma with corrective chest tube insertion, optimal pain control and chest physiotherapy results in good outcomes in the majority of patients. Optimal management with better survival rates is achievable in specialised centres with multidisciplinary teamwork and the presence of thoracic surgical experience.

A typical carcinoid of the lung - a case report with pathological correlation and propagation of the cancer stem cell line BKZ1 with synaptophysin expression.

RATIONALE: Neuroendocrine tumors (NETs) of the lung account for 5% of all cases of lung cancer, which itself is the leading cause of cancer-related death worldwide. In accordance to its rarity, only few cell lines of NETs exist, which even often lack key characteristics of the primary tumor, making it difficult to study underlying molecular mechanisms. PATIENT CONCERNS: The patient reported in this case is a 71-year old woman, which never smoked but suffered under dry cough. DIAGNOSES: Chest CT-scan showed a paracardiac nodule of the lingula with 2 × 1.8 cm in diameter. INTERVENTIONS: The detected paracardiac nodule of the lingula was anatomically resected using video assisted thoracic surgery. OUTCOMES: Histopathological diagnostic of the removed tissue identified the tumor as a well-differentiated typical carcinoid (TC), which represents one of the four subgroups of pulmonary NETs. Next to the successful treatment of the patient, we were able to propagate cancer stem cells (CSCs) out of the resected tumor tissue. To the best of our knowledge, we firstly isolated CSCs of a typical carcinoid, which were positive for the prominent CSC markers CD44, CD133 and nestin, confirming their stem cell properties. Additionally, CSCs, further referred as BKZ1, expressed the neuroendocrine marker synaptophysin, verifying their neuroendocrine origin. However, nuclear synaptophysin protein was also present in other stem cell populations, suggesting a role as general stem cell marker. LESSON: In line with the importance of CSCs in cancer treatment and the lack of CSC-models for neuroendocrine neoplasms, the here described BKZ1 cancer stem cell line of a typical carcinoid represents a promising new model to study pulmonary carcinoids and particular NETs.

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells.

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

The direct thrombin inhibitor argatroban: a review of its use in patients with and without HIT.

Argatroban is a synthetic direct thrombin inhibitor with a relative short elimination half-life of 45 minutes and elimination which is predominantly performed via hepatic metabolism. Argatroban anticoagulation has been systematically studied in patients exhibiting the heparin-induced thrombocytopenia (HIT)/thrombosis syndrome and demonstrated to be a safe and effective therapy in this indication. Moreover, in smaller studies argatroban has also been assessed in special clinical settings in non-HIT patients. The current review presents the pharmacology of argatroban, data regarding monitoring of the agent, and an overview of the results of the major clinical trials assessing argatroban anticoagulation in HIT patients. Additionally, data from clinical trials with argatroban use outside HIT, in more special indications such as in percutaneous coronary intervention, stroke, renal replacement therapy, and intensive care medicine, are reviewed.

Assessing errors in the determination of base excess.

UNLABELLED: We compared estimates for base excess of extracellular fluid (BE(ecf); mmol/L) obtained in five clinically used blood gas analyzers: AVL Compact 2 (Roche Diagnostics, Mannheim, Germany), Ciba-Corning 860 (Bayer Diagnostics, Fernwald, Germany), IL 1620 (Instrumentation Laboratories, Lexington, MA), Stat Profile Ultra (Nova Biomedical, Waltham, MA), and ABL 510 (Radiometer, Copenhagen, Denmark). A total of 134 measurements per analyzer were obtained in arterial and venous blood samples from 10 patients undergoing cardiac surgery and 65 measurements per analyzer in venous blood samples from 2 healthy volunteers. The blood samples were equilibrated in a tonometer with gases of known composition (37 degrees C). Additional theoretical studies were performed to evaluate the relationship between pH and calculated BE(ecf) value (with varied PCO(2)) using the formulas of the various analyzers. The standard deviations of repeated measurements were 0.24 mmol/L for ABL 510 and approximately 0.45 mmol/L for the other 4 analyzers. The maximal systematic difference between the average of all measurements of each analyzer was 3.7 mmol/L; this was primarily attributable to differences in measuring pH, and, to a lesser extent, to differences in calculation and determination of PCO(2). Comparison of the results from samples with different oxygen saturation showed that the relative alkalinity of deoxygenated hemoglobin (Haldane effect) can also influence the determinations of BE(ecf). IMPLICATIONS: A clinically useful way to quantify nonrespiratory disturbances of the acid-base balance is calculation of the base excess of extracellular fluid by using blood gas analyzers. In this study, we found significant variability in estimates of base excess of extracellular fluid obtained with five analyzers from different manufacturers. This variability is attributable to multiple factors, including lack of correction for deoxygenated hemoglobin (Haldane effect).