Early mortality in German patients with lung cancer: risk factors associated with 30-and 60-day mortality.

Despite therapeutic advances, early mortality in lung cancer is still prevalent. In this study, we aimed to assess risk factors for 30- and 60-day mortality in German lung cancer patients. In this retrospective cross-sectional analysis, we used data of lung cancer patients treated at LMU Hospital Munich between 2015 and 2019. We categorized patients into 30-day mortality, 60 day-mortality, and longer survival. We used Student's t-test and ANOVA to compare means and Chi2-test to compare frequencies. We used logistic regression analysis to identify factors associated with a risk for early mortality. Of the 2454 lung cancer patients, 2.0% (n = 50) died within 30 and 1.7% (n = 41) within 30 to 60 days of diagnosis. Older age and advanced stage at diagnosis were significantly associated with early mortality in the univariate and the multivariate analysis. Patients in the 30-day mortality group significantly more often did not receive tumor-directed therapy. They were also more likely to die in an acute care setting compared to the 60-day mortality group. The group of patients who died unexpectedly (12.0%) was dominantly female, with a high proportion of patients with unintentional weight loss at the time of diagnosis. Our results suggest that in the treatment of patients with lung cancer there is a need for a greater focus on older patients. Moreover, physicians should pay special attention to females with recent weight loss and patients with a comorbidity of diabetes mellitus or renal impairment. Engaging a case manager focused on detecting patients with the above characteristics could help improve overall care.

Response to high-altitude triggers in seasonal asthmatics on and off inhaled corticosteroid treatment.

Background: Due to the effects of climate change, winter sport enthusiasts will be increasingly forced to stay at higher altitudes. High altitude (HA) environmental factors such as cold temperature, physical exertion, and hypoxia with subsequent hypocapnia due to hyperventilation have been shown to induce bronchoconstriction. With bronchial asthma being highly prevalent, asthmatics also will be increasingly exposed to HA environment and might experience increasing symptoms. Methods: We analysed the effects of HA factors at around 2600 m a.s.l. (metres above sea level) on lung function in mild seasonal asthmatics while they were routinely off (January) and on (March, after start of lowland pollen season) low-dose inhaled corticosteroid (ICS) treatment (n = 10), and matched healthy controls (n = 11). Results: Without inhaled corticosteroid (ICS) treatment mean FEV1 in asthmatics was 230 ml lower after exercise at HA compared to low altitude (LA, p < 0.05), while in healthy controls there was no significant difference. This decrease was mainly induced by cold and exercise at HA. During ICS treatment, this decrease was prevented. Methacholine response was reduced at HA compared to LA. Conclusions: The decrease of FEV1 in response to a combination of hypoxia, cold, and exercise is prevented by ICS treatment in mild, seasonal asthmatics. However, the FEV1 response to high altitude factors was overall small.

Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease.

Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils "plucked" intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events.

Follow-up lung ultrasound to monitor lung failure in COVID-19 ICU patients.

OBJECTIVES: Point-of-care lung ultrasound (LU) is an established tool in the first assessment of patients with coronavirus disease (COVID-19). To assess the progression or regression of respiratory failure in critically ill patients with COVID-19 on Intensive Care Unit (ICU) by using LU. MATERIALS AND METHODS: We analyzed all patients admitted to Internal Intensive Care Unit, Ludwig-Maximilians-University (LMU) of Munich, from March 2020 to December 2020 suffering lung failure caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). LU was performed according to a standardized protocol at baseline and at follow up every other day for the first 15 days using a lung ultrasound score (LUSS). Ventilation data were collected simultaneously. RESULTS: Our study included 42 patients. At admission to ICU, 19 of them (45%) were mechanically ventilated. Of the non-invasive ventilated ones (n = 23, 55%), eleven patients required invasive ventilation over the course. While LUS did not differ at admission to ICU between the invasive ventilated ones (at baseline or during ICU stay) compared to the non-invasive ventilated ones (12±4 vs 11±2 points, p = 0.2497), LUS was significantly lower at d7 for those, who had no need for invasive ventilation over the course (13±5 vs 7±4 points, p = 0.0046). Median time of invasive ventilation counted 18 days; the 90-day mortality was 24% (n = 10) in our cohort. In case of increasing LUS between day 1 (d1) and day 7 (d7), 92% (n = 12/13) required invasive ventilation, while it was 57% (n = 10/17) in case of decreasing LUS. At d7 we found significant correlation between LU and FiO2 (Pearson 0.591; p = 0.033), p/F ratio (Pearson -0.723; p = 0.005), PEEP (Pearson 0.495; p = 0.043), pplat (Pearson 0.617; p = 0.008) and compliance (Pearson -0.572; p = 0.016). CONCLUSION: LUS can be a useful tool in monitoring of progression and regression of respiratory failure and in indicating intubation in patients with COVID-19 in the ICU.

Osimertinib rechallenge under steroid protection following osimertinib-induced pneumonitis: three case studies.

Osimertinib is a third-generation tyrosine kinase inhibitor that became the preferred first-line treatment option for metastatic non-small cell lung cancer with sensitizing epidermal growth factor receptor mutations. Drug-induced pneumonitis is known to occur with osimertinib. In case of severe pneumonitis, discontinuation of treatment and therapy with corticosteroids is recommended, and a treatment switch is usually performed. We herein report the treatment course in three patients who were rechallenged with osimertinib under steroid protection following an osimertinib-induced pneumonitis. All our patients were initially re-exposed to a lower dose of osimertinib. Two patients were successfully rechallenged under prednisolone protection. The third patient, who was initially retreated with osimertinib without steroid protection, suffered from a recurrent pneumonitis, and was later rechallenged successfully under steroid protection. Our case series indicates that rechallenge with osimertinib following recovery from osimertinib-induced pneumonitis allows a successful rechallenge in individual cases when alternative treatment options are lacking. Concomitant steroids appear to protect against flares of pneumonitis during rechallenge.

Lung ultrasound predicts clinical course but not outcome in COVID-19 ICU patients: a retrospective single-center analysis.

BACKGROUND: Point-of-care lung ultrasound (LU) is an established tool in the first assessment of patients with coronavirus disease (COVID-19). Purpose of this study was to evaluate the value of lung ultrasound in COVID-19 intensive care unit (ICU) patients in predicting clinical course and outcome. METHODS: We analyzed lung ultrasound score (LUS) of all COVID-19 patients admitted from March 2020 to December 2020 to the Internal Intensive Care Unit, Ludwig-Maximilians-University (LMU) of Munich. LU was performed according to a standardized protocol at ICU admission and in case of clinical deterioration with the need for intubation. A normal lung scores 0 points, the worst LUS has 24 points. Patients were stratified in a low (0-12 points) and a high (13-24 points) lung ultrasound score group. RESULTS: The study included 42 patients, 69% of them male. The most common comorbidities were hypertension (81%) and obesity (57%). The values of pH (7.42 ± 0.09 vs 7.35 ± 0.1; p = 0.047) and paO2 (107 [80-130] vs 80 [66-93] mmHg; p = 0.034) were significantly reduced in patients of the high LUS group. Furthermore, the duration of ventilation (12.5 [8.3-25] vs 36.5 [9.8-70] days; p = 0.029) was significantly prolonged in this group. Patchy subpleural thickening (n = 38; 90.5%) and subpleural consolidations (n = 23; 54.8%) were present in most patients. Pleural effusion was rare (n = 4; 9.5%). The median total LUS was 11.9 ± 3.9 points. In case of clinical deterioration with the need for intubation, LUS worsened significantly compared to baseline LU. Twelve patients died during the ICU stay (29%). There was no difference in survival in both LUS groups (75% vs 66.7%, p = 0.559). CONCLUSIONS: LU can be a useful monitoring tool to predict clinical course but not outcome of COVID-19 ICU patients and can early recognize possible deteriorations.

Late-onset severe pneumonitis under osimertinib.

Pneumonitis is a rare and possibly life threatening side effect of TKI-treatment. We present a patient with adenocarcinoma of the lung harboring an uncommon EGFR Exon 21 mutation treated with osimertinib as second-line therapy. After nine months of treatment, the patient developed progressing shortness of breath and night sweats. A severe late-onset predominantly eosinophilic pneumonitis was diagnosed, osimertinib treatment was discontinued and immunosuppressive treatment was initiated. This case report highlights late-onset pneumonitis as a side effect of third-generation TKI-treatment and possible options for subsequent tumor treatment.

Effect of Acute Altitude Exposure on Serum Markers of Platelet Activation.

Background: Platelets are the key factor in primary hemostasis. It has been shown that chronic altitude exposure increases platelets' aggregability. Nevertheless, data about acute effects and the underlying mechanisms are sparse. Methods: Sixteen healthy volunteers were examined in our hospital (519 m alt.) and 30 minutes after arrival in the environmental research station on the Zugspitze Mountain (2656 m alt.). Serum levels of soluble p-selectin were examined to elucidate platelet activation. In addition, serum levels of chromogranin A (CGA) as a measure of adrenergic activation, endothelin 1 (ET-1) representing pulmonary vascular tone and monocyte chemoattractant protein-1 (MCP-1) as a measure of inflammatory response were examined. Results: Acute altitude exposure induced a significant increase of p-selectin (116 ± 4.8 pg/mL vs. 132 ± 6.2 pg/mL; p < 0.01). Whereas MCP-1 was significantly lowered (538 ± 50.6 pg/mL to 470 ± 41.1 pg/mL; p = 0.02) and CGA was not altered significantly (88 ± 47.4 ng/mL vs. 79 ± 44 ng/mL; p = 0.22), ET1 was increased significantly from 0.8 ± 0.07 pg/mL to 1.15 ± 0.09 pg/mL (p < 0.01). Conclusion: Our study could demonstrate relevant platelet activation that was accompanied by a 44% increase of ET-1. This activation might obtain clinical relevance in patients with pre-existing cardiovascular disease as a trigger for acute events.

Daily Chronic Intermittent Hypobaric Hypoxia Does Not Induce Chronic Increase in Pulmonary Arterial Pressure Assessed by Echocardiography.

Chronic hypoxia causes pulmonary vascular remodeling resulting in persistently increased pulmonary arterial pressures (PAP) even after return to normoxia. Recently, interest in chronic intermittent hypobaric hypoxia (CIHH) was raised because it occurs in subjects working at high altitude (HA) but living in lowland. However, effects of daily CIHH on PAP are unknown. In this pilot study, we included 8 healthy subjects working at (2650 m) each workday for 8-9 h while living and sleeping at LA and 8 matched control subjects living and working at LA. Cardiorespiratory measurements including echocardiography at rest and during exercise were performed at LA (Munich, 530 m) and HA (Zugspitze, 2650 m). Hemoglobin was higher in CIHH subjects. LA echocardiography showed normal right and left cardiac dimensions and function in all subjects. Systolic PAP (sPAP) and tricuspid annular plane systolic excursion (TAPSE) at rest were similar in both groups. Resting blood gas analysis (BGA) at HA revealed decreased pCO2 in CIHH compared to controls (HA: 28.4 versus 31.7 mmHg, p=0.01). During exercise, sPAP was lower in CIHH subjects compared to controls (LA: 28.7 versus 35.3 mmHg, p=0.02; HA: 26.3 versus 33.6 mmHg, p=0.04) and peripheral oxygen saturation (SpO2) was higher. In sum, subjects exposed to CIHH showed no signs of pulmonary vascular remodeling.

Perception of climate change in patients with chronic lung disease.

BACKGROUND: Climate change affects human health. The respective consequences are predicted to increase in the future. Patients with chronic lung disease are particularly vulnerable to the involved environmental alterations. However, their subjective perception and reactions to these alterations remain unknown. METHODS: In this pilot study, we surveyed 172 adult patients who underwent pulmonary rehabilitation and 832 adult tourists without lung disease in the alpine region about their perception of being affected by climate change and their potential reaction to specific consequences. The patients' survey also contained the COPD Assessment Test (CAT) to rate the severity of symptoms. RESULTS: Most of the patients stated asthma (73.8%), COPD (9.3%) or both (11.0%) as underlying disease while 5.8% suffered from other chronic lung diseases. Patients and tourists feel equally affected by current climate change in general, while allergic subjects in both groups feel significantly more affected (p = 0.04). The severity of symptoms assessed by CAT correlates with the degree of feeling affected (p<0.01). The main disturbing consequences for patients are decreased air quality, increasing numbers of ticks and mosquitos and a rising risk for allergy and extreme weather events such as thunderstroms, while tourists are less disturbed by these factors. Increasing number of heat-days is of little concern to both groups. CONCLUSION: Overall patients are more sensitive to health-related consequences of climate change. Yet, the hazard of heat-days seems underestimated and awareness should be raised.