Effect of Nasal High Flow (NHF) on Right Heart Function in Stable Patients with Pulmonary Hypertension of Different WHO Classes.

Background: Nasal high flow (NHF) has various effects on the respiratory system in acute and chronic conditions. There are initial reports that NHF is also able to influence cardiac function in acute decompensation. This study was designed to clarify whether NHF has an influence on the right heart in stable patients with chronic pulmonary hypertension. Methods: Forty-one stable patients from different pulmonary hypertension (PH) WHO classes were recruited. Most patients were assigned to WHO classes 1 and 3. All received a right heart catheterization and blood gas analysis. Oxygenation was kept constant. The mean pulmonary arterial pressure (mPAP), wedge pressure (PC), cardiac output (CO), diastolic pulmonary gradient (DPG), pulmonary arterial resistance (PVR) and other parameters were determined. The patients then used NHF at 35 L/min for 20 min, after which the right heart catheter measurements were repeated with ongoing NHF therapy. Results: In the entire cohort and in the subgroups, there were no changes in right heart function or cardiac ejection fraction. The blood gases did not change either. Conclusions: Thus, there is no effect of NHF on right heart function in stable patients with PH.

Outcomes of oncological intended thoracic surgery after lung transplantation.

Background: Lung cancer following lung transplantation (LT) may require thoracic surgery (TS). There is an urgent need for data on surgical feasibility, clinical and surgical characteristics, as well as outcome data. Methods: We reviewed the medical records of LT patients who had undergone TS at the University Hospital Leipzig between the years 2000 and 2022. Data on medical and surgical history, pulmonary function test, arterial blood gas analysis, six-minute walking distance test, and surgical approach, perioperative management, anesthesiologic, and surgical procedures were analyzed. Results: Among 248 LT patients, 13 patients (5.2%) developed lung cancer after 4.2 years on average and on 6 of them (46.2%), major TS procedure was performed for the resection of lung cancer. In one patient who underwent TS for a suspicious pulmonary nodule, it turned out to be a parenchymal scar. TS was carried out in 57.1% on the native lung and 42.9% on the transplant lung. Pneumonia and acute renal failure were predominantly observed postoperative complications. We found that the capacity of gas exchange either before or after TS was related to the degree of postoperative complications. The in-hospital survival was 71.4%. Conclusions: Incidence of lung cancer is increased after LT. Follow-up care allows early diagnosis with a comparably high share of operable tumor stage. Cancer as well as postoperative complications were more likely after single lung transplantation (SLT). Postoperative morbidity and mortality are higher in this scarce group of patients and hence, warrants a centered and experienced interdisciplinary approach.

Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin-angiotensin-aldosterone system on COVID-19 disease.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19. METHODS: Our preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19. RESULTS: Our study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels. CONCLUSIONS: Although there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response. CLINICAL TRIAL REGISTRATION: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.

Comparative bioinformatic analysis of KRAS, STK11 and KEAP1 (co-)mutations in non-small cell lung cancer with a special focus on KRAS G12C.

OBJECTIVES: Mutations in STK11 (STK11MUT) and KEAP1 (KEAP1MUT) occur frequently in non-small cell lung cancer (NSCLC) and are often co-mutated with KRAS. Several studies linked the co-occurrence of KRASMUT + STK11MUT, as well as KRASMUT + KEAP1MUT to reduced response to immune checkpoint inhibitors (ICI) and even a negative impact on survival. Data focusing STK11 + KEAP1 co-mutations or the triple mutation (KRAS + STK11 + KEAP1) are scarce. The recent availability of KRAS-G12C inhibitors increases the clinical relevance of those co-mutations in KRAS-mutated NSCLC. MATERIALS AND METHODS: We present a comprehensive bioinformatic analysis encompassing six datasets retrieved from cBioPortal. RESULTS: Independent of the treatment, triple mutations and STK11MUT + KEAP1MUT were significantly associated with a reduced overall survival (OS). Across treatments, OS of patients with a KRAS G12C triple mutation was significantly reduced compared to patients with KRAS G12C-only. Under ICI-therapy, there was no significant difference in OS between patients harboring the KRAS G12C-only and patients with the KRAS G12C triple mutation, but a significant difference between patients harboring KRAS non-G12C and KRAS non-G12C triple mutations. Triple mutated primary tumors showed a significantly increased frequency of distant metastases to bone and adrenal glands compared to KRAS-only mutated tumors. Additionally, our drug response analysis in cancer cell lines harboring the triple mutations revealed the WNT pathway inhibitor XAV-939 as a potential future drug candidate for this mutational situation. CONCLUSION: The triple mutation status may serve as a negative prognostic and predictive factor across treatments compared to KRASMUT-only. KRAS G12C generally seems to be a negative predictive marker for ICI-therapy.

Nasal High-Flow (NHF) Improves Ventilation in Patients with Interstitial Lung Disease (ILD)-A Physiological Study.

INTRODUCTION: Acute hypercapnic respiratory failure has a poor prognosis in patients with interstitial lung disease (ILD). Recent data demonstrated a positive effect of nasal high-flow (NHF) in patients with acute hypoxemic respiratory failure. Preliminary data also show benefits in several hypercapnic chronic lung diseases. OBJECTIVES: The aim of this study was to characterize flow-dependent changes in mean airway pressure, breathing volumes, and breathing frequency and decreases in PCO2. METHODS: Mean airway pressure was measured in the nasopharyngeal space. To evaluate breathing volumes, a polysomnographic device was used (16 patients). All subjects received 20, 30, 40, and 50 L/min and-to illustrate the effects-nCPAP and nBiPAP. Capillary blood gas analyses were performed in 25 hypercapnic ILD subjects before and 5 h after the use of NHF. Additionally, comfort and dyspnea during the use of NHF were surveyed. RESULTS: NHF resulted in a small flow-dependent increase in mean airway pressure. Tidal volume was unchanged and breathing rate decreased. The calculated minute volume decreased by 20 and 30 L/min NHF breathing. In spite of this fact, hypercapnia decreased at a flow rate of 24 L/min. Additionally, an improvement in dyspnea was observed. CONCLUSIONS: NHF leads to a reduction in paCO2. This is most likely achieved by a washout of the respiratory tract and a reduction in functional dead space. NHF enhances the effectiveness of breathing in ILD patients by the reduction in respiratory rate. In summary, NHF works as an effective ventilatory support device in hypercapnic ILD patients.

IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients.

The insulin-like growth factor (IGF)-pathway is involved in tumor cell proliferation, metastasis, and survival. We aimed to find out what effects IGF binding protein 3 (IGFBP3) exerted on H1299 lung cancer (LC) cells in terms of tumor growth and invasion and whether IGFBP3 was associated with clinical and pathological parameters in a prospective cohort of LC patients. H1299 cells were transfected with an IGFBP3-expressing vector. Its influence on apoptosis induction via flow cytometry annexin V FITC assay, cell proliferation in 2D and 3D cell culture, and invasion were examined. Expression of several matrix metalloproteinases (MMPs) and inhibitors (TIMP-1) were also investigated in IGFBP3-transfected LC cells. Further, data on LC patients (n = 131), tumor characteristics, and survival were prospectively collected and correlated with IGFBP3 plasma levels. IGFBP3 did not influence apoptosis induction and 2D cell proliferation. However, both spheroid growth (3D proliferation) and invasion of IGFBP3-transfected cells planted in an extracellular matrix-based gel were significantly inhibited. IGFBP3 inhibited MMP-1 release, and the total MMP activity. In LC patients, higher IGFBP3 plasma levels correlated with both lower clinical tumor stage, grading, Ki-67 staining, and the absence of necrosis (P < 0.05, respectively). Increased IGFBP3 plasma levels were associated with improved overall survival (hazard ratio 0.37, P = 0.01). In conclusion, overexpressed IGFBP3 in a LC cell line inhibited tumor growth and invasion. Translating from bench to bedside, investigation of clinicopathological parameters confirmed these experimental results showing that higher IGFBP3 plasma levels were associated with less aggressive tumor growth, reduced tumor spread, and improved survival of LC patients.

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.

Cardiac function in relation to functional status and fatigue in patients with post-COVID syndrome.

Patients with Post-COVID syndrome (PCS) are frequently referred for cardiologic evaluation. We assessed cardiac function and biomarkers in relation to functional status and fatigue in patients with PCS. This prospective single-center cohort study included 227 patients with persisting symptoms after COVID-19 infection. Most frequent complaints were fatigue (70%), dyspnea (56%), neurocognitive symptoms (34%) and chest pain (28%). Standardized questionnaires were used to assess Post-COVID-Functional-Scale (PCFS) and fatigue (MFI-20). The fatigue severity was inversely related to age and did not correlate with cardiovascular diseases, echocardiographic findings, or biomarkers. Similarly, mild to moderate functional impairment (PCFS 1-3) did not correlate with cardiovascular alterations. However, the subgroup of patients with significant functional impairment (PCFS = 4) had more frequent cardiovascular comorbidities, biomarkers and impaired global longitudinal strain (GLS). Patients with elevated troponin T showed abnormal GLS, reduced left ventricular ejection fraction and impaired tricuspid annular plane systolic excursion. The majority of patients with PCS shows a normal cardiac function. Only the small subgroup of patients with severe functional impairment and patients with elevated troponin T is at risk for impaired cardiac function and likely to benefit from specialized care by a cardiologist.

Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients.

The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

Disease Progression and Age as Factors Underlying Multimorbidity in Patients with COPD: Results from COSYCONET.

Background: Multimorbidity plays an important role in chronic obstructive pulmonary disease (COPD) but is also a feature of ageing. We estimated to what extent increases in the prevalence of multimorbidity over time are attributable to COPD progression compared to increasing patient age. Methods: Patients with COPD from the long-term COSYCONET (COPD and Systemic Consequences - Comorbidities Network) cohort with four follow-up visits were included in this analysis. At each visit, symptoms, exacerbation history, quality of life and lung function were assessed, along with the comorbidities heart failure (HF), coronary artery disease (CAD), peripheral arterial disease (PAD), hypertension, sleep apnea, diabetes mellitus, hyperlipidemia, hyperuricemia and osteoporosis. Using longitudinal logistic regression analysis, we determined what proportion of the increase in the prevalence of comorbidities could be attributed to patients' age or to the progression of COPD over visits. Results: Of 2030 patients at baseline, 878 completed four follow-up visits (up to 4.5 years). CAD prevalence increased over time, with similar effects attributable to the 4.5-year follow-up, used as indicator of COPD progression, and to a 5-year increase in patients' age. The prevalence of HF, diabetes, hyperlipidemia, hyperuricemia, osteoporosis and sleep apnea showed stronger contributions of COPD progression than of age; in contrast, age dominated for hypertension and PAD. There were different relationships to patients' characteristics including BMI and sex. The results were not critically dependent on the duration of COPD prior to enrolment, or the inclusion of patients with all four follow-up visits vs those attending only at least one of them. Conclusion: Analyzing the increasing prevalence of multimorbidity in COPD over time, we separated age-independent contributions, probably reflecting intrinsic COPD-related disease progression, from age-dependent contributions. This distinction might be useful for the individual assessment of disease progression in COPD.

Reversibility of Hypercapnia after an Acute Exacerbation of COPD.

BACKGROUND: After an episode of hypercapnic AECOPD, some patients show reversible, prolonged or persistent hypercapnic respiratory failure. However, at the time of patient discharge, it is uncertain whether patients will remain hypercapnic or may return to a physiologic gas status. METHODS: Data were retrospectively collected from COPD patients with an acute hypercapnic exacerbation (AECOPD). Out of 143 total COPD inpatients, complete data set was available for 82 patients in stable condition. According to the first available capillary or arterial pCO2, patients were divided into those with persistent hypercapnia (PHG) and those with reversible hypercapnia. RESULTS: In this study, 51% of patients with acute hypercapnic AECOPD and follow-up (FUP) visits developed normocapnia after a time period of several weeks. These patients were characterized by lower carbon dioxide partial pressure (PaCO2), HCO3-, and BE levels prior to the AECOPD event, at discharge and at FUP. pH was higher at discharge and FUP in this group. Greater disease severity and lower forced vital capacity were prominent in patients with PHG. Binary logistic regression revealed GOLD D and higher PaCO2 at discharge as predicting factors for PHG. CONCLUSIONS: A large percentage of patients has prolonged hypercapnia following acute hypercapnic COPD exacerbation. The risk profile of patients with irreversible hypercapnia should be carefully evaluated following AECOPD in order to choose selected patients for home-noninvasive ventilation.

Risk Assessment for Patients with Chronic Respiratory Conditions in the Context of the SARS-CoV-2 Pandemic Statement of the German Respiratory Society with the Support of the German Association of Chest Physicians.

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases.

Nasal high-flow compared to non-invasive ventilation in treatment of acute acidotic hypercapnic exacerbation of chronic obstructive pulmonary disease-protocol for a randomized controlled noninferiority trial (ELVIS).

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a major negative impact on health status, rates of hospitalization, readmission, disease progression and mortality. Non-invasive ventilation (NIV) is the standard therapy for hypercapnic acidotic respiratory failure in AECOPD. Despite its beneficial effects, NIV is often poorly tolerated (11-34 % failure rate). An increasing number of studies have documented a beneficial effect of nasal high-flow (NHF) in acute hypercapnia. We designed a prospective, randomized, multi-centre, open label, non-inferiority trial to compare treatment failure in nasal NHF vs NIV in patients with acidotic hypercapnic AECOPD. METHODS: The study will be conducted in about 35 sites in Germany. Patients with hypercapnic AECOPD with respiratory acidosis (pH < 7.35) will be randomized 1:1 to NIV or NHF. The primary outcome is the combined endpoint of intubation, treatment failure or death at 72 h. The switch from one to the other device marks a device failure but acts as a rescue treatment in absence of intubation criteria. A sample size of 720 was calculated to have 80% power for showing that NHF is non-inferior to NIV with a margin of 8 percentage points. Linear regression will be used for the confirmatory analysis. DISCUSSION: If NHF is shown to be non-inferior to NIV in acidotic hypercapnic AECOPD, it could become an important alternative treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04881409 , Registered on May 11, 2021.

Predictors of psychiatric comorbidity in cancer patients at the time of their discharge from the hospital.

PURPOSE: A cancer diagnosis can have a substantial impact on one's mental health. The present study investigated the prevalence and predictors of psychiatric comorbidities in cancer patients at the time of their discharge from the hospital. METHODS: Psychiatric comorbidities were assessed shortly before hospital discharge and half a year after hospitalization using a structured clinical interview (SCID), based on the diagnostic and statistical manual of mental disorders (DSM-IV). Frequencies at both time points were estimated using percentages and corresponding 95% confidence intervals. Predictors of mental disorders were identified using binary logistic regression models. RESULTS: At time of hospital discharge, 39 out of 334 patients (12%) were diagnosed with a psychiatric comorbidity, and 15 (7%) were diagnosed half a year later. Among the diagnoses, adjustment disorders (3%) were most frequent at the time of hospital release, while major depression (3%) was the most frequent 6 months later. Having a mental disorder was associated with unemployment (odds ratio (OR) 3.4, confidence interval (CI) 1.1-10.9, p = 0.04). There was no evidence that school education (OR 2.0, CI 0.4-9.0, p = 0.38), higher education (OR 0.7, CI 0.2-2.4, p = 0.60), income (OR 1.0, CI 1.0-1.0, p = 0.06), tumor stage (OR 1.1, CI 0.4-3.2, p = 0.85), type of disease (OR 0.6, CI 0.2-2.1, p = 0.47), pain (OR 1.0, CI 1.0-1.0, p = 0.15), fatigue (OR 1.0, CI 1.0-1.0, p = 0.77), or physical functioning (OR 1.0, CI 1.0-1.0, p = 0.54) were related to the presence of a psychiatric comorbidity. CONCLUSIONS: Unemployment was associated with at least a threefold increased risk of mental disorder, which highlights the need for special attention to be given to this subgroup of cancer patients.

A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation.

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6-32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p = .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients.

[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.

CT Texture Analysis of Pulmonary Neuroendocrine Tumors-Associations with Tumor Grading and Proliferation.

Texture analysis derived from computed tomography (CT) might be able to provide clinically relevant imaging biomarkers and might be associated with histopathological features in tumors. The present study sought to elucidate the possible associations between texture features derived from CT images with proliferation index Ki-67 and grading in pulmonary neuroendocrine tumors. Overall, 38 patients (n = 22 females, 58%) with a mean age of 60.8 ± 15.2 years were included into this retrospective study. The texture analysis was performed using the free available Mazda software. All tumors were histopathologically confirmed. In discrimination analysis, "S(1,1)SumEntrp" was significantly different between typical and atypical carcinoids (mean 1.74 ± 0.11 versus 1.79 ± 0.14, p = 0.007). The correlation analysis revealed a moderate positive association between Ki-67 index with the first order parameter kurtosis (r = 0.66, p = 0.001). Several other texture features were associated with the Ki-67 index, the highest correlation coefficient showed "S(4,4)InvDfMom" (r = 0.59, p = 0.004). Several texture features derived from CT were associated with the proliferation index Ki-67 and might therefore be a valuable novel biomarker in pulmonary neuroendocrine tumors. "Sumentrp" might be a promising parameter to aid in the discrimination between typical and atypical carcinoids.

[S1 Guideline Post-COVID/Long-COVID]. / S1-Leitlinie Post-COVID/Long-COVID.

The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.