Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkpoint inhibition yielded improved overall survival. Although there are promising molecular pathways with potential therapeutic impacts, targeted therapies are still not an integral part of routine treatment. Against this background, we evaluated current literature for potential new molecular candidates such as surface markers (e.g., DLL3, TROP-2 or CD56), apoptotic factors (e.g., BCL-2, BET), genetic alterations (e.g., CREBBP, NOTCH or PTEN) or vascular markers (e.g., VEGF, FGFR1 or CD13). Apart from these factors, the application of so-called ‘poly-(ADP)-ribose polymerases’ (PARP) inhibitors can influence tumor repair mechanisms and thus offer new perspectives for future treatment. Another promising therapeutic concept is the inhibition of ‘enhancer of zeste homolog 2’ (EZH2) in the loss of function of tumor suppressors or amplification of (proto-) oncogenes. Considering the poor prognosis of SCLC patients, new molecular pathways require further investigation to augment our therapeutic armamentarium in the future.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is primarily characterised by a respiratory disease. However, SARS-CoV-2 can directly infect vascular endothelium and subsequently cause vascular inflammation, atherosclerotic plaque instability and thereby result in both endothelial dysfunction and myocardial inflammation/infarction. Interestingly, up to 50% of patients suffer from persistent exercise dyspnoea and a post-viral fatigue syndrome (PVFS) after having overcome an acute COVID-19 infection. In the present study, we assessed the presence of coronary microvascular disease (CMD) by cardiovascular magnetic resonance (CMR) in post-COVID-19 patients still suffering from exercise dyspnoea and PVFS. N = 22 patients who recently recovered from COVID-19, N = 16 patients with classic hypertrophic cardiomyopathy (HCM) and N = 17 healthy control patients without relevant cardiac disease underwent dedicated vasodilator-stress CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as velocity-encoded (VENC) phase-contrast imaging of the coronary sinus flow (CSF) at rest and during pharmacological stress (maximal vasodilation induced by 400 µg IV regadenoson). Using CSF measurements at rest and during stress, global myocardial perfusion reserve (MPR) was calculated. There was no difference in left ventricular ejection-fraction (LV-EF) between COVID-19 patients and controls (60% [57–63%] vs. 63% [60–66%], p = NS). There were only N = 4 COVID-19 patients (18%) showing a non-ischemic pattern of LGE. VENC-based flow measurements showed that CSF at rest was higher in COVID-19 patients compared to controls (1.78 ml/min [1.19–2.23 ml/min] vs. 1.14 ml/min [0.91–1.32 ml/min], p = 0.048). In contrast, CSF during stress was lower in COVID-19 patients compared to controls (3.33 ml/min [2.76–4.20 ml/min] vs. 5.32 ml/min [3.66–5.52 ml/min], p = 0.05). A significantly reduced MPR was calculated in COVID-19 patients compared to healthy controls (2.73 [2.10–4.15–11] vs. 4.82 [3.70–6.68], p = 0.005). No significant differences regarding MPR were detected between COVID-19 patients and HCM patients. In post-COVID-19 patients with persistent exertional dyspnoea and PVFS, a significantly reduced MPR suggestive of CMD—similar to HCM patients—was observed in the present study. A reduction in MPR can be caused by preceding SARS-CoV-2-associated direct as well as secondary triggered mechanisms leading to diffuse CMD, and may explain ongoing symptoms of exercise dyspnoea and PVFS in some patients after COVID-19 infection.
Objectives PSMA (prostate-specific membrane antigen) is overexpressed in prostate cancer cells and is reported to be a promising target for antibody-based radioligand therapy in patients with metastasized prostate cancer. Since PSMA expression is not restricted to prostate cancer, the underlying study investigates PSMA expression in non-small cell lung cancer (NSCLC). Material and methodsImmunohistochemistry was used to identify PSMA expression in n = 275 samples of NSCLC tissue specimens. By means of CD34 co-expression, the level of PSMA expression in tumor associated neovasculature was investigated. The impact of PSMA expression on clinicopathologic parameters and prognosis was evaluated.
Background: Severe pulmonary hemorrhage is a life-threatening complication in critically ill patients. Due to tracheobronchial obstruction, ventilation is often impaired. Traditionally, rigid bronchoscopy is an option for recanalization. However, in comparison to flexible bronchoscopy, the application of rigid bronchoscopy is more complex. Against this background we evaluated the use of flexible cryo-probes for blood clot removal in critically ill patients. Methods: Retrospectively, we identified 16 patients (median age: 60 years, 69% male patients), who suffered from severe airway obstruction due to blood clots. All patients required invasive ventilation and 11 patients depended on extracorporeal membrane oxygenation (ECMO). To remove blood clots, flexible bronchoscopic cryoextraction was performed in n=27 cases, whereas rigid bronchoscopy was only needed in two cases. Results: Whereas in 9 cases single flexible cryoextraction was successful immediately, the procedure had to be repeated again in 7 patients. In all cases, tracheobronchial obstruction was treated with success and conditions of invasive ventilation were improved. In no case severe complications were observed. Conclusions: In consideration of the underlying evaluation, we highly recommend flexible cryoextraction as both a safe and less complex technique for blood clot removal in critically ill patients.
Background Recent studies have highlighted Coronavirus disease 2019 (COVID-19) as a multisystemic vascular disease. Up to 60% of the patients suffer from long-term sequelae and persistent symptoms even 6 months after the initial infection. Methods This prospective, observational study included 58 participants, 27 of whom were long COVID patients with persistent symptoms > 12 weeks after recovery from PCR-confirmed SARS-CoV-2 infection. Fifteen healthy volunteers and a historical cohort of critically ill COVID-19 patients (n = 16) served as controls. All participants underwent sublingual videomicroscopy using sidestream dark field imaging. A newly developed version of Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell velocity (VRBC) and the microvascular health score (MVHS™) in sublingual microvessels with diameters 4–25 µm. Measurements and main results Although dimensions of the glycocalyx were comparable to those of healthy controls, a µm-precise analysis showed a significant decrease of vascular density, that exclusively affected very small capillaries (D5: − 45.16%; D6: − 35.60%; D7: − 22.79%). Plotting VRBC of capillaries and feed vessels showed that the number of capillaries perfused in long COVID patients was comparable to that of critically ill COVID-19 patients and did not respond adequately to local variations of tissue metabolic demand. MVHS was markedly reduced in the long COVID cohort (healthy 3.87 vs. long COVID 2.72 points; p = 0.002). Conclusions Our current data strongly suggest that COVID-19 leaves a persistent capillary rarefication even 18 months after infection. Whether, to what extent, and when the observed damage might be reversible remains unclear.
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