Publications by authors named "Biruta Witte"

Influenza A virus (IAV) infection mobilizes bone marrow-derived macrophages (BMDM) that gradually undergo transition to tissue-resident alveolar macrophages (TR-AM) in the inflamed lung. Combining high-dimensional single-cell transcriptomics with complex lung organoid modeling, in vivo adoptive cell transfer, and BMDM-specific gene targeting, we found that transitioning ("regenerative") BMDM and TR-AM highly express Placenta-expressed transcript 1 (Plet1). We reveal that Plet1 is released from alveolar macrophages, and acts as important mediator of macrophage-epithelial cross-talk during lung repair by inducing proliferation of alveolar epithelial cells and re-sealing of the epithelial barrier.

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Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role in tumor-associated macrophages (TAMs) is still largely unknown. We found that the lncRNA ADPGK-AS1 was substantially upregulated in artificially induced M2-like human macrophages, macrophages exposed to lung cancer cells in vitro, and TAMs from human lung cancer tissue. ADPGK-AS1 is partly located within mitochondria and binds to the mitochondrial ribosomal protein MRPL35.

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Article Synopsis
  • Tobacco smoking and air pollution are major contributors to chronic obstructive pulmonary disease (COPD), yet not all smokers develop the condition, highlighting the need to explore protective mechanisms against oxidative stress.
  • The study investigated various cohorts by analyzing sputum, lung tissue, and blood samples to measure levels of 3-nitrotyrosine (3-NT), an indicator of oxidative stress, and established a new cell model resistant to cigarette smoke extract (CSE) to understand the relationship between oxidative stress and COPD.
  • Findings suggest that high levels of HO-1 (heme oxygenase-1) are linked to reduced oxidative stress in CSE-resistant cells, while increased expression of CEACAM6 in epithelial cells appears to exacerbate oxidative stress and
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Background: Lung cancer is frequently diagnosed among elderly patients. However, this patient group is under-represented in or excluded from clinical trials and, therefore, evidence-based treatment is challenging. It is uncertain whether there are differences in the feasibility of adjuvant therapies between older and younger patients with NSCLC.

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During surgery, ATP from damaged cells induces the release of interleukin-1β, a potent pro-inflammatory cytokine that contributes to the development of postoperative systemic inflammation, sepsis and multi-organ damage. We recently demonstrated that C-reactive protein (CRP) inhibits the ATP-induced release of monocytic interleukin-1β, although high CRP levels are deemed to be a poor prognostic marker. Here, we retrospectively investigated if preoperative CRP levels correlate with postoperative CRP, leukocyte counts and fever in the context of anatomical lung resection and systematic lymph node dissection as first line lung cancer therapy.

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While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases.

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Background: In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly.

Methods: We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53).

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Persistent air leaks (PALs) are regarded as a frequent complication after thoracic surgery resulting in prolonged hospitalization and increased morbidity. Several more or less invasive therapeutic approaches are available for treatment of PAL with varying degrees of success. The endoscopic placement of one-way intrabronchial valves in the segment(s) in which the air leak has been located offers a highly effective and well-tolerated minimal invasive option for patients with PAL.

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Purpose: Intensivists and surgeons are often confronted with critically ill patients suffering from pleural empyema. Due to it' s multifactorial pathogenesis and etiology, medicals should be sensitized to recognize the different stages of the disease. Besides a whole bundle of different established classification systems, the progress of pleural effusions can be subdivided into the early exudative, the intermediate fibropurulent and the late organized phase according to the classification of the American Thoracic Society.

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Objectives: To compare the video-assisted thoracoscopic surgery (VATS) with the open thoracotomy access to pulmonary segmentectomy by the clinical outcomes and long-term survival in lung carcinoma.

Methods: Non-randomized comparative intention-to-treat study of prospective institutional registry data and survival data of 100 consecutive patients undergoing segmentectomy.

Results: Within one decade (2002-12), 100 patients with proven or highly suspected lung carcinoma underwent 100 anatomical sub-lobar pulmonary resections (52 typical and 20 atypical segmentectomies, 28 split-lobe procedures).

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Objectives: To compare left upper split-lobe procedures, being upper trisegmentectomy and resection of the lingula, with left upper lobectomy for surgical treatment of lung carcinoma originating from the left upper lobe.

Methods: A pair-matched control study comparing the clinical and oncological outcomes of 22 consecutive patients after left upper split-lobe resections with those of 44 pair-matched controls that received left upper lobectomy for non-small-cell lung carcinomas. The control group was matched 1:2 for tumour diameter, histology, nodal status and patient age.

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Objective: The aim of this study was to identify resorption, clinical performance, and safety of cotton-derived oxidized cellulose gauze applied as a hemostat in minimally invasive oncologic thoracic surgery.

Methods: This is a pilot prospective noncomparative observational human in vivo study. A piece of cotton-derived oxidized cellulose gauze measuring 5 × 20 cm was inserted into the subcarinal space of patients with potentially resectable lung carcinoma at the time of video-assisted mediastinoscopic lymphadenectomy and reexamined several days later for macroscopic and histologic evaluation at the time of subsequent lung resection.

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Objectives: To describe the diagnostic value of selective extended cervical mediastinoscopy (ECM) in combination with video-assisted mediastinoscopic lymphadenectomy (VAMLA) in mediastinal staging of potentially resectable left-sided lung carcinoma.

Methods: Institutional report on 110 ECM procedures indicated for enlarged lymph nodes within the aorto-pulmonary (AP) zone on computed tomography. Staging sensitivity, negative predictive value (NPV) and specificity of ECM, combined VAMLA and ECM, VAMLA alone and systematic dissection for lung resection via left-sided video-assisted thoracoscopic surgery (VATS) or thoracotomy were calculated from a subset of 92 patients with left-sided lung carcinoma.

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This paper describes a prospective, observational, single-centre study of 20 consecutive patients with clinical stage I lung carcinoma undergoing anatomical sublobar resections using complete video-assisted thoracoscopic surgery (cVATS). Thirteen male and seven female patients with a median age of 68 (range 57-84) years and a median of four (range 0-9) relevant comorbid conditions presented with five right-sided and 15 left-sided tumours, with a median diameter of 2.3 (range 1.

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Background: Mediastinal lymphadenectomy is usually performed at thoracotomy together with lung resection. It is a prerequisite for accurate nodal staging and has an impact on survival.

Methods: VAMLA (video-assisted mediastinoscopic lymphadenectomy) dissection is guided by anatomical landmarks.

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Objectives: To assess the feasibility and radicality of a combined thoracoscopic and mediastinoscopic approach to mediastinal lymphadenectomy compared to thoracoscopy only for minimally invasive management of early stage lung carcinoma.

Methods: Prospective observational study of patients undergoing anatomical thoracoscopic lung resection for lung carcinoma in our department in 2007. Mediastinal lymphadenectomy was performed either thoracoscopically (VATS group) or by a combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy (VAMLA+VATS group).

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Objective: To determine the impact of endoesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) on management of thoracic malignancies.

Methods: One hundred and twenty patients referred for invasive diagnostic and resection of thoracic malignancies were studied prospectively. Negative and inconclusive EUS-FNA findings were assessed by video-assisted mediastinoscopic lymphadenectomy (VAMLA) or open lymphadenectomy.

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Routine use of pedicled thymus or pericardial fat pad flap for prophylactic bronchial stump coverage in neoadjuvant treated non-small cell lung cancer (NSCLC) is challenged by the observation of synchronous lymph node metastases to the flap. As a consequence, we suggest local muscle flaps, and histological examination of the pericardial fat pad.

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Background: The development of a two-bladed spreadable videomediastinoscope in 1992 allowed increased exposure and bimanual dissection of mediastinal structures. Concurrent with technical progress in mediastinoscopy, neoadjuvant treatment of stage III lung cancer was introduced, and accuracy of pretreatment mediastinal staging became a topic at issue. In this setting, development of a videomediastinoscopic technique for complete mediastinal lymphadenectomy was the obvious thing to do.

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Objectives: Pretherapeutic T4 staging of centrally located lung cancer is crucial for the treatment strategy, but non-invasive imaging techniques are of low accuracy. We have developed the new imaging technique of intraoperative mediastinoscopic ultrasound (MUS) to predict technical resectability in tumors staged cT4 based on computed tomographic scanning.

Methods: Intraoperatively, a sterilizable fingertip ultrasound probe is introduced and guided through the video mediastinoscope with a modified grasper during staging mediastinoscopy.

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Systematic mediastinal lymphadenectomy is usually done at thoracotomy together with lung resection. It is a prerequisite for accurate nodal staging and has an impact on survival. With the introduction of neoadjuvant therapy for stage III lung carcinoma, mediastinal staging before therapy became more important.

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Background: This study was conducted to assess indications, procedures, complications, and clinical feasibility of video-assisted mediastinoscopic surgery (VAMS). It also assessed the accuracy of mediastinal lymph node staging by video-assisted mediastinoscopic lymphadenectomy (VAMLA) with bimanual dissection through the twin-bladed, expanding Linder-Dahan mediastinoscope.

Methods: From 2000 to 2004, we documented and assessed 226 consecutive procedures in a prospective database.

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