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Aim: To analyze immune cell populations in non-small-cell lung cancer (NSCLC) tumors and matched tumor-bearing and non-tumor-bearing lymph nodes (ntbLNs) to predict prognosis. Patients & methods: 71 patients with long-term disease-free survival and 80 patients with relapse within 3 years were included in this study. We used Cox regression to identify factors associated with overall survival (OS) and progression-free survival (PFS). Results: Sinus histiocytosis and tumor-infiltrating lymphocyte density in the tumor were positively associated with PFS and OS. CD4 expression in node 1 (hazard ratio = 0.72; p = 0.02) and node 2 (hazard ratio = 0.91; p = 0.04) ntbLNs were positively correlated with OS and PFS, respectively. Discussion: Immunological markers in ntbLNs could be used to predict survival in NSCLC.

BackgroundThe novel coronavirus SARS-CoV-2 has caused a global COVID-19 pandemic, leading to worldwide changes in public health measures. In addition to changes in the public sector (lockdowns, contact restrictions), hospitals modified care to minimize risk of infection and to mobilize resources for COVID-19 patients. Our study aimed to assess the impact of these measures on access to care and behaviour of patients with thoracic malignancies.MethodsThoracic oncology patients were surveyed in October 2020 using paper-based questionnaires to assess access to ambulatory care services and tumor-directed therapy during the COVID-19 pandemic. Additionally, behaviour regarding social distancing and wearing of face masks were assessed, as well as COVID-19 exposure, testing and vaccination. Results are presented as absolute and relative frequencies for categorical variables and means with standard deviation for numerical variables. We used t-test, and ANOVA to compare differences in metric variables and Chi2-test to compare proportions between groups.Results93 of 245 (38%) patients surveyed completed the questionnaire. Respiration therapy and physical therapy were unavailable for 57% to 70% of patients during March/April. Appointments for tumor-directed therapy, tumor imaging, and follow-up care were postponed or cancelled for 18.9%, 13.6%, and 14.8% of patients, respectively. Patients reported their general health as mostly unaffected. The majority of patients surveyed did not report reducing their contacts with family. The majority reduced contact with friends. Most patients wore community masks, although a significant proportion reported respiratory difficulties during prolonged mask-wearing. 74 patients (80%) reported willingness to be vaccinated against SARS-CoV-2.ConclusionsThis survey provides insights into the patient experience during the second wave of the COVID-19 pandemic in Munich, Germany. Most patients reported no negative changes to cancer treatments or general health; however, allied health services were greatly impacted. Patients reported gaps in social distancing, but were prepared to wear community masks. The willingness to get vaccinated against SARS-CoV-2 was high. This information is not only of high relevance to policy makers, but also to health care providers.

Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation.We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19).The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p .0001) and having cystic fibrosis (CF) (OP = 10.1, p .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES.Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.

The model heterocyst-forming filamentous cyanobacterium Anabaena sp. PCC 7120 (Anabaena) is a typical example of a multicellular organism capable of simultaneously performing oxygenic photosynthesis in vegetative cells and O

In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality differs between men and women. We therefore aimed to examine sex differences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome, referring to pulmonary disorders. The study population comprised 1044 women and 1531 men with the diagnosis of COPD from COSYCONET, among them 2175 of GOLD grades 1–4 and 400 at risk. Associations of comorbidities with mortality were studied using Cox regression analysis for men and women separately. During the follow-up (median 3.7 years) 59 women and 159 men died. In men, obesity, hypertension, coronary artery disease, liver cirrhosis, osteoporosis, kidney disease, anaemia and increased heart rate (HR) predict mortality, in women heart failure, hyperuricemia, mental disorders, kidney disease and increased HR (p Clinical Trial Registration: ClinicalTrials.gov NCT01245933.

Background: In light of political discussions about minimum case volumes and certified lung cancer centers, this observational study investigates differences in therapy and survival between high vs. low patient volume hospitals (HPVH vs. LPVH).Methods: We identified 12,374 lung cancer patients treated in HPVH (>67 patients) and LPVH in 2013 from German health insurance claims. Stratified by metastasis status (no metastases, nodal metastases, systemic metastases), we compared HPVHs and LPVHs regarding likelihood of resection and systemic therapy, type of systemic therapy, and surgical outcomes, using multivariate logistic models. Three-year survival was modeled using Cox regression. We adjusted all regression models for age, gender, comorbidity, and residence area, and included a cluster variable for the hospital.Results: Around 24 % of patients were treated in HPVHs. Irrespective of stratum and subgroup, three-year survival was significantly better in HPVHs. In patients with systemic metastases (OR = 1.84, CI=[1.22,2.76]) and without metastases (OR = 3.28, CI=2.13, 5.04]), resection was more likely in HPVHs. Among patients with systemic therapy, the odds of receiving pemetrexed was higher in HPVHs, in patients with nodal metastases (OR = 1.57, CI=1.01,2.45]). In resected patients without metastases the odds ratio of receiving a thoracoscopic lobectomy was 2.28 (CI=1.04,4.99]) in HPVHs.Conclusion: Our data suggests that case volume is clinically relevant in resected and non-resected lung cancer patients, but optimal minimum case volumes may differ for subgroups. (C) 2020 Published by Elsevier B.V.

Litter decomposition is a key process of nutrient and carbon cycling in terrestrial ecosystems. The decomposition process will likely be altered under ongoing climate change, both through direct effects on decomposer activity and through indirect effects caused by changes in litter quality. We studied how hydrological change indirectly affects decomposition via plant functional community restructuring caused by changes in plant species’ relative abundances (community‐weighted mean (CWM) traits and functional diversity). We further assessed how those indirect litter quality effects compare to direct effects. We set up a mesocosm experiment, in which sown grassland communities and natural turf pieces were subjected to different hydrological conditions (dryness and waterlogging) for two growing seasons. Species‐level mean traits were obtained from trait databases and combined with species’ relative abundances to assess functional community restructuring. We studied decomposition of mixed litter from these communities in a common “litterbed.” These indirect effects were compared to effects of different hydrological conditions on soil respiration and on decomposition of standard litter (direct effects). Dryness reduced biomass production in sown communities and natural turf pieces, while waterlogging only reduced biomass in sown communities. Hydrological stress caused profound shifts in species’ abundances and consequently in plant functional community composition. Hydrologically stressed communities had higher CMW leaf dry matter content, lower CMW leaf nitrogen content, and lower functional diversity. Lower CWM leaf N content and functional diversity were strongly related to slower decomposition. These indirect effects paralleled direct effects, but were larger and longer‐lasting. Species mean traits from trait databases had therefore considerable predictive power for decomposition. Our results show that stressful soil moisture conditions, that are likely to occur more frequently in the future, quickly shift species’ abundances. The resulting functional community restructuring will decelerate decomposition under hydrological stress., We show for the first time not only that community‐weighted mean functional traits and functional diversity rapidly change under hydrological stress (dryness and waterlogging), but also that these shifts strongly decelerate litter decomposition. These indirect effects on litter decomposition via changes in litter quality parallel direct effects on decomposer activity, but are even larger in magnitude and last longer. To our knowledge, this is the first study showing a link between effects of hydrological conditions on functional community structure with consequences for an ecosystem process, such as litter decomposition.

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.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).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.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.

BackgroundTumor tissue as well as regional lymph nodes are removed during curative surgery for early-stage non-small cell lung cancer (NSCLC). These tissues provide a unique snapshot of the immune cell composition at the time of surgery. We investigated the immune landscape in matched tumor tissue, tumor bearing (tb) and non-tumor bearing (ntb) N1 as well as N2 lymph nodes (LNs) in patients with NSCLC and its relation to survival.MethodsInternal hospital databases were screened for surgically treated NSCLC patients for whom tumor tissue, tbLNs as well as N1 and N2 ntbLNs were available. Clinical as well as demographic data were extracted from hospital records. Expression profiling of 770 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies.ResultsWe identified 190 surgically treated patients of whom 16 fulfilled inclusion criteria and had sufficient archived tissue. The Tumor Immune Dysfunction and Exclusion (TIDE) score in N1 tumor-free lymph nodes was associated with OS. TIM-3 expression was inversely correlated with TIDE scores in affected LNs, N1 and N2 ntbLNs. Levels of CD8 expression were significantly higher in TIDE High compared to TIDE Low patients. TIM-3 and PD-L1 were selected for the final model for OS in multivariate regression in more than one tissue.ConclusionLevels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC.

Background Surgery is the treatment of choice for early and for some locally advanced non-small cell lung cancer (NSCLC). Ipsilateral hilar and mediastinal lymph nodes are generally removed at the time of tumor resection. There is now increased awareness about the physiological role of lymph nodes in cancer. We investigated the expression profiles of immune-related markers in matched tumor tissue, affected and unaffected N1 and N2 lymph nodes in patients with NSCLC and their relation to survival. Materials and Methods Internal hospital databases were screened for surgically-treated NSCLC patients with documented relapse or long-term disease-free survival (defined as 3 years). Data on patients’ age, sex, surgery, (neo)adjuvant therapy, tumor characteristics and time and location of relapse was extracted. FFPE tissue blocks of primary tumor, affected and unaffected lymph nodes were collected. mRNA was extracted from these tissues and expression profiling of 751 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies. Results A total of 754 NSCLC patients were screened. Of these, 71 patients showed long-term disease-free survival and 80 patients had local or systemic relapse within 3 years after surgery. Expression profiles of immune-related genes in tumor and lymph node immune populations differed between patients with and without 3-year disease-free survival. Conclusions Expression profiles of immune-related genes differ between patients with and without relapse. Our findings show that differences in expression profiles of immune-related genes in tumor and lymph nodes should be taken into account when assessing patient prognosis. Disclosure Information L. Sellmer: None. J. Kovacs: None. J. Kumbrink: None. J. Neumann: None. J. Walter: None. D. Kauffmann-Guerrero: None. C. Schneider: None. A. Tufman: None.

Hydrology is a major environmental factor determining plant fitness, and hydrological niche segregation (HNS) has been widely used to explain species coexistence. Nevertheless, the distribution of plant species along hydrological gradients does not only depend on their hydrological niches but also depend on their seed dispersal, with dispersal either weakening or reinforcing the effects of HNS on coexistence. However, it is poorly understood how seed dispersal responds to hydrological conditions. To close this gap, we conducted a common‐garden experiment exposing five wind‐dispersed plant species (Bellis perennis, Chenopodium album, Crepis sancta, Hypochaeris glabra, and Hypochaeris radicata) to different hydrological conditions. We quantified the effects of hydrological conditions on seed production and dispersal traits, and simulated seed dispersal distances with a mechanistic dispersal model. We found species‐specific responses of seed production, seed dispersal traits, and predicted dispersal distances to hydrological conditions. Despite these species‐specific responses, there was a general positive relationship between seed production and dispersal distance: Plants growing in favorable hydrological conditions not only produce more seeds but also disperse them over longer distances. This arises mostly because plants growing in favorable environments grow taller and thus disperse their seeds over longer distances. We postulate that the positive relationship between seed production and dispersal may reduce the concentration of each species to the environments favorable for it, thus counteracting species coexistence. Moreover, the resulting asymmetrical gene flow from favorable to stressful habitats may slow down the microevolution of hydrological niches, causing evolutionary niche conservatism. Accounting for context‐dependent seed dispersal should thus improve ecological and evolutionary models for the spatial dynamics of plant populations and communities., To test how seed dispersal by wind responds to abiotic contexts, we estimate fecundity and seed dispersal of five plant species under various hydrological conditions by combining common‐garden experiments and mechanistic modeling, and quantified the relationship between seed production and seed dispersal. There was a general positive relationship between seed production and dispersal distance. The positive relationship between seed production and dispersal may reduce the concentration of each species to the environments favorable for it, thus counteracting species coexistence.

A real-time polymerase chain reaction (qPCR) is considered the gold standard for the laboratory diagnosis of canine parvovirus (CPV) infection but can only be performed in specialized laboratories. Several point-of-care tests (POCT), detecting CPV antigens in faeces within minutes, are commercially available. The aim of this study was to evaluate eight POCT in comparison with qPCR. Faecal samples of 150 dogs from three groups (H: 50 client-owned, healthy dogs, not vaccinated within the last four weeks, S: 50 shelter dogs, healthy, not vaccinated within the last four weeks, p = 50 dogs with clinical signs of CPV infection) were tested with eight POCT and qPCR. Practicability, sensitivity, specificity, positive (PPV) and negative predictive values (NPV), as well as overall accuracy were determined. To assess the differences between and agreement among POCT, McNemar’s test and Cohen’s Kappa statistic were performed. Specificity and PPV were 100.0% in all POCT. Sensitivity varied from 22.9–34.3% overall and from 32.7–49.0% in group P. VetexpertRapidTestCPVAg® had the highest sensitivity (34.3% overall, 49.0% group P) and differed significantly from the 3 POCT with the lowest sensitivities (Fassisi®Parvo (27.7% overall, 36.7% group P), Primagnost®ParvoH+K (24.3% overall, 34.7% group P), FASTest®PARVOCard (22.9% overall, 32.7% group P)). The agreement among all POCT was at least substantial (kappa &gt, 0.80). A positive POCT result confirmed the infection with CPV in unvaccinated dogs, whereas a negative POCT result did not definitely exclude CPV infection due to the low sensitivity of all POCT.

Most SCLC patients are diagnosed with extensive disease (ED) and the prognosis in this cohort remains poor. However, some patients are diagnosed with limited (LD) or very limited (VLD, T1-2, N0-1, M0) disease and previous data suggest that surgical resection might improve outcomes in these patients. Most of the existing evidence comes from small case series. For this reason, we investigated clinical features and surgical outcomes in a large cohort of resected SCLC patients.We used a large pseudomized dataset (n = 32432) provided by the Munich Cancer Registry to analyze all documented SCLC patients (n = 5043) between 2002 and 2015. We correlated patients' characteristics as well as surgery modalities with survival data and describe trends in the role of surgery in SCLC over the time.We analyzed 5043 SCLC patients. A total of 161 (3.2%) received either oncological (lobectomy, bilobectomy and pneumonectomy) or limited resection (segmentectomy and wedge resection). We found a significant trend suggesting that resections in SCLC patients become less common in all stages of disease, accompanied by an increased proportion of oncological resections. This suggests a more accurate preoperative staging. In VLD resection was significantly associated with longer survival compared to nonsurgical management (log-rank P = .013). Survival was better with oncological resection compared to atypical resection. Administration of adjuvant chemotherapy was associated with better outcome in all resected patients (P = .01).VLD SCLC patients benefit from oncological resection. We recommend invasive staging in these patients to ensure VLD. Furthermore, adjuvant chemotherapy should be offered to all resected patients.

INTRODUCTION Chronic kidney disease (CKD) is associated with significant morbidity and mortality after lung transplantation (LTX). Calcineurin inhibitor (CNI) nephrotoxicity is the leading cause of CKD. After kidney transplantation, polyomavirus-associated nephropathy (PyVAN) is a well-recognized problem. This study aims to evaluate the role of polyomavirus in patients after LTX. METHODS From January 2017 to January 2020, all lung transplant recipients who performed follow-up visits in our center were included in the study and retrospectively assessed. We measured renal function (creatinine levels before and after transplantation), JCPyV, and BKPyV load by polymerase chain reaction (PCR) in serum and urine samples after transplantation. RESULTS In total, 104 consecutive patients (59 males, 56.7%) with a mean age of 49.6 ± 11.1 years were identified. JCPyV was found in urine of 36 patients (34.6%) and serum of 3 patients (2.9%). BKPyV was found in urine of 40 patients (38.5%) and serum of 4 patients (3.8%), respectively. Urine evidence for JCPyV (p

OBJECTIVES A video-assisted thoracoscopic surgery (VATS) is an accepted alternative to open thoracotomy (OT) in lung cancer patients undergoing lobectomy, but evidence of the benefits of VATS remains inconsistent. The aim of this study was to compare VATS and OT regarding survival, costs and length of hospital stay (LOS). METHODS We identified lung cancer patients (incident 2013) undergoing VATS or OT from German insurance claims data and performed 1:2 propensity score matching. A 3-year survival was analysed using the Kaplan–Meier curves and a univariable Cox model. Group differences in the 3-year lung cancer-related costs and costs of hospital stay with lobectomy were compared via univariable generalized linear gamma models. LOS was compared using the Mann–Whitney–Wilcoxon test. RESULTS After propensity score matching, we compared 294 patients undergoing VATS and 588 receiving OT. We found no differences in the 3-year survival (VATS: 73.8%, OT: 69.2%, P = 0.131) or costs for hospital stay with lobectomy (VATS: €11 921, OT: €12 281, P = 0.573). However, VATS patients had significantly lower lung cancer-related costs (VATS: €20 828, OT: €23 723, P = 0.028) and median postoperative LOS (VATS: 9 days, OT: 11 days, P CONCLUSIONS From a payer's perspective, extending the use of VATS is beneficial, as it shows economic benefits without affecting survival. However, for a more comprehensive assessment of the benefits of VATS from a society’s point of view, further aspects such as patient-reported outcomes and provider-related standby costs need to be investigated further.

Ca2+ is a potent signalling molecule that regulates many cellular processes. In cyanobacteria, Ca2+ has been linked to cell growth, stress response and photosynthesis, and to the development of specialist heterocyst cells in certain nitrogen-fixing species. Despite this, the pathways of Ca2+ signal transduction in cyanobacteria are poorly understood, and very few protein components are known. The current study describes a previously unreported Ca2+-binding protein which was called the Ca2+ Sensor EF-hand (CSE), which is conserved in filamentous, nitrogen-fixing cyanobacteria. CSE is shown to bind Ca2+, which induces a conformational change in the protein structure. Poor growth of a strain of Anabaena sp. PCC 7120 overexpressing CSE was attributed to diminished photosynthetic performance. Transcriptomics, biophysics and proteomics analyses revealed modifications in the light-harvesting phycobilisome and photosynthetic reaction centre protein complexes.

Successful alien plant invasion is influenced by both climate change and plant-plant interactions. We estimate the single and interactive effects of competition and extreme weather events on the performance of the global legume invader Lupinus polyphyllus (Lindl.). In three experimental studies we assessed (i) the stress tolerance of seedling and adult L. polyphyllus plants against extreme weather events (drought, fluctuating precipitation, late frost), (ii) the competitive effects of L. polyphyllus on native grassland species and vice versa, and (iii) the interactive effects of extreme weather events and competition on the performance of L. polyphyllus. Drought reduced growth and led to early senescence of L. polyphyllus but did not reduce adult survival. Fluctuating precipitation events and late frost reduced the length of inflorescences. Under control conditions, interspecific competition reduced photosynthetic activity and growth of L. polyphyllus. When subjected to competition during drought, L. polyphyllus conserved water while simultaneously maintaining high assimilation rates, demonstrating increased water use efficiency. Meanwhile, native species had reduced performance under drought. In summary, the invader gained an advantage under drought conditions through a smaller reduction in performance relative to its native competitors but was competitively inferior under control conditions. This provides evidence for a possible invasion window for this species. While regions of high elevation or latitude with regular severe late frost events might remain inaccessible for L. polyphyllus, further spread across Europe seems probable as the predicted increase in drought events may favour this non-native legume over native species.

Background Protecting against CMV infection and maintaining CMV in latent state are largely provided by CMV-specific T-cells in lung transplant recipients. The aim of the study was to assess whether a specific T-cell response is associated with the risk for CMV infection in seronegative patients who are at high risk for delayed CMV infection. Methods All CMV-seronegative recipients (R-) from CMV-seropositive donors (D+) between January 2018 and April 2019 were included and retrospectively screened for CMV infection before and after assessment of CMV-specific cell-mediated immunity. Results Thirty-one of the 50 patients (62%) developed early-onset CMV infection. Lower absolute neutrophil counts were significantly associated with early-onset CMV infection. Antiviral prophylaxis was ceased after 137.2 ± 42.8 days. CMV-CMI were measured at a median of 5.5 months after LTx. 19 patients experienced early and late-onset CMV infection after prophylaxis withdrawal within 15 months post transplantation. Positive CMV-CMI was significantly associated with lower risk of late-onset CMV infection after transplantation in logistic and cox-regression analysis (OR=0.05, p = .01; OR=2,369, p = .026). Conclusion D+/R- lung transplant recipients are at high risk of developing early and late-onset CMV infection. Measurement of CMV-CMI soon after transplantation might further define the CMV infection prediction risk in LTx recipients being at high risk for CMV viremia.

Climate change is altering precipitation patterns, with higher frequency and magnitude of extreme events. Specifically, longer and more pronounced waterlogged conditions are predicted after rain spells as well as more frequent droughts, especially in Central Europe. Such hydrological changes can severely affect species performance and alter the function of ecosystems, as well as favor plant invasions. Competition with native communities may change depending on water stress. Bunias orientalis is an invasive plant that may benefit from disturbance or precipitation changes. We conducted a 3-year mesocosm experiment in a common garden to investigate how invasion success of B. orientalis in native German grassland communities is affected by varying hydrological conditions (from very dry to waterlogged). We measured the establishment and growth of B. orientalis in varying water table depths in bare soil (simulating disturbance) vs. in the community. Establishment and biomass of B. orientalis was generally highest under non-stress conditions. The species was also highly tolerant to dry conditions, but only when growing in bare soil. However, performance of B. orientalis was generally low, whereby interspecific competition in communities greatly limited invasion success. This might be due to the low competitive ability of the species in conditions of hydrological stress and the near-natural grassland communities with an extensive mowing regime used in our experiment. Our results suggest that invasion success of B. orientalis in grasslands will not increase if precipitation patterns change toward more extreme events. However, disturbance that creates bare soil patches might favor B. orientalis under drought conditions.

Treatment with single agent immune checkpoint inhibitors (ICIs) has tremendously changed second line therapy in NSCLC. However, there are still no reliable biomarkers predicting response and survival in this group of patients. PD-L1 revealed to be a correlating, but no perfect marker. Therefore, we sought to investigate in this prospective study, whether inflammation status and cytokine profile could serve as additional biomarkers guiding treatment decision for single agent ICIs in NSCLC. 29 stage IV NSCLC patients receiving single agent PD-1 checkpoint-inhibitor in second line were prospectively enrolled. Inflammatory scores and cytokine profiles (IL-6, IL-8, IL-10, IFN-γ and TNFα) have been obtained before treatment and at the time of the first staging. Cytokine profiles were correlated with response and survival. Patients with signs of pre-therapeutic inflammation (elevated, NLR, SII, IL-6, IL-8) showed significantly lower response to ICI treatment and reduced PFS. Contrary, elevated levels of IFN-γ revealed to characterize a subgroup of patients, who significantly benefits from ICI treatment. Furthermore, low systemic inflammation and high levels of IFN-γ characterized patients with long term-response to ICI treatment. Pre-therapeutic assessment of inflammation and cytokine profiles has the ability to predict response and survival in NSCLC patients treated with single agent ICIs.

Objective Evaluation of pulmonary function impairment after COVID-19 in persistently symptomatic and asymptomatic patients of all disease severities and characterisation of risk factors. Methods Patients with confirmed SARS-CoV-2 infection underwent prospective follow-up with pulmonary function testing and blood gas analysis during steady-state cycle exercise 4 months after acute illness. Pulmonary function impairment (PFI) was defined as reduction below 80% predicted of DLCOcSB, TLC, FVC, or FEV1. Clinical data were analyzed to identify risk factors for impaired pulmonary function. Results 76 patients were included, hereof 35 outpatients with mild disease and 41 patients hospitalized due to COVID-19. Sixteen patients had critical disease requiring mechanical ventilation, 25 patients had moderate–severe disease. After 4 months, 44 patients reported persisting respiratory symptoms. Significant PFI was prevalent in 40 patients (52.6%) occurring among all disease severities. The most common cause for PFI was reduced DLCOcSB (n = 39, 51.3%), followed by reduced TLC and FVC. The severity of PFI was significantly associated with mechanical ventilation (p p p = 0.014) and in hospitalized patients CT score. A decrease of paO2 > 3 mmHg during cycle exercise occurred in 1/5 of patients after mild disease course. Conclusion We characterized pulmonary function impairment in asymptomatic and persistently symptomatic patients of different severity groups of COVID-19 and identified further risk factors associated with persistently decreased pulmonary function. Remarkably, gas exchange abnormalities were revealed upon cycle exercise in some patients with mild disease courses and no preexisting pulmonary condition.

Dear Editor, The novel coronavirus, SARS-CoV-2, has caused the global COVID-19 pandemic, leading countries all over the world to implement public health measures. In addition to public lockdowns, hospitals have modified care to minimize risk of infection and mobilize resources for treating COVID-19 patients. The intended as well as unintended effects of these measures, and of the pandemic itself, on patients with lung cancer and other thoracic malignancies have not yet been described. Thoracic oncology patients may be particularly vulnerable to COVID-19 due to immunosuppression and preexisting comorbid diseases. Data on Chinese COVID-19 cases suggest that COVID-19 patients with cancer have a higher risk of severe events like admission to intensive care, requiring ventilation, and mortality compared to COVID-19 patients without cancer [1]. As such, it is particularly important to understand how well the measures to control infection are accepted and implemented by patients in this setting. In addition, most thoracic oncology patients are in regular contact with health care providers and require frequent medical assessments and treatment. The impact of the pandemic on the provision of regular health care is as yet unclear. In order to avoid undue gaps in regular thoracic oncology care, it is necessary to understand how thoracic oncology patients can access health care during the COVID-19 pandemic. This information would allow health care providers and cancer centers to better adapt to patient needs in this demanding situation and also adjust previous measures to deal with a second wave. In our study, we aimed to document the changes made to daily routines and access to health care as well as the physical and mental well-being of thoracic oncology patients at the Munich Lung Cancer Center during the first wave of the COVID-19 pandemic. We assessed patients' experiences during the CO­VID-19 pandemic using questionnaire-based telephone interviews of ambulatory patients seen for thoracic malignancy at our center in the 3-month period preceding the onset of the COVID-19 crisis in Germany. Patients were contacted by a thoracic oncology physician and their verbal consent was obtained by telephone. Baseline telephone interviews were conducted by 1 of 3 study assistants between the 8th of April and the 5th of May 2020. Additional medical history details were obtained from electronic patient records. Our questionnaire was designed to evaluate the impact of public health measures implemented during the COVID-19 pandemic on daily routines, access to care, acceptance of infection control measures, and the physical and mental well-being of lung cancer patients. A total of 67 patients were reached by interviewers to conduct baseline interviews. The average age of the patients was 62.9 years, and 38.8% of patients were male. We found that while 80% of patients with a thoracic malignancy reduced the number of times they left their home to run errands during the lockdown, only 42% reduced the number of times they left home for the purpose of taking walks or other exercise. Two-thirds of patients walked or exercised outside their homes more than once a week, with 36% reporting daily exercise outside the home. We recorded that 70% of patients did not go grocery shopping themselves; most of these patients reported that they received support from a spouse or partner. Of those who did go grocery shopping themselves, only 1 reported wanting help from another person; the remaining patients were planning to continue shopping independently. Many patients reported changes in ambulatory care. Access to ambulatory respiratory therapy and physiotherapy, particularly, decreased significantly. Nearly two-thirds of those receiving ambulatory respiratory therapy were unable to continue this during the pandemic. As the production of droplets during respiratory therapy is likely quite high, limiting such therapy may be necessary to control the spread of infection. For patients in need of regular respiratory therapy, this represents an area for which alternative forms of therapy and novel forms of patient and therapist protection should be developed. A total of 16 patients reported making changes to their medication during the pandemic. Out of these 16, only 4 made changes to their medication due to reasons related to the pandemic. These 4 patients received double their normal dosages of the anti-PD-L1 antibody pembrolizumab at doubled intervals (i.e., 400 mg every 6 weeks instead of 200 mg every 3 weeks). This strategy was intended to reduce the frequency of clinic visits and thus reduce the need for patients to travel outside their home; it was recommended by the European Society for Medical Oncology (ESMO) [2]. Although 34% of patients reported postponements of physician appointments (e.g., surveillance imaging) or a switch to telephone appointments instead of clinic visits, the majority of those interviewed did not worry about the COVID-19 pandemic having a strong negative impact on their lung cancer care. Interestingly, the patients with a higher comorbidity burden worried less about the impact of the pandemic on their care. Patients with a poor performance status (PS) reported more worry about contracting COVID-19 than patients with an ECOG PS of 0. Five patients reported having direct contact with a person positive for COVID-19, and all of them plus 1 other patient were tested for COVID-19. Tests for 4 of them were negative and the results were not yet available for the other 2 at the baseline interview, but were confirmed as being negative in a follow-up interview. Levels of worry about contracting the virus were highly variable. A quarter of all patients said they did not worry at all about contracting COVID-19, but almost 30% ranked their worry as high or very high. Patients with lower levels of worry frequently indicated that they felt safe due to the precautions they were taking. Over 50% of patients indicated that the stay-at-home order had no/only a limited effect on their mental well-being and around 12% reported a very strong effect. Only a minority of patients (9%) reported a strong impact of the stay-at-home order on their physiological well-being whereas >50% reported no effect at all. The COVID-19 pandemic represents an unprecedented and unexpected challenge for medical care providers and indirectly or directly impacts on care in almost every health care setting. We were encouraged to find that many patients significantly reduced errands and grocery shopping during the lockdown but were nevertheless able to maintain a moderate level of physical activity and exercise outdoors. Previous work has shown that lung cancer patients benefit greatly from aerobic exercise, with a significant positive impact on their symptoms, quality of life, and pulmonary function [3, 4]. For this reason, we find it important that any future lockdowns continue to allow for physical activity outside the home. Additionally, exercise could be potentially improved using telephone- and internet-based strategies involving experts in physical therapy. In line with this, the use of telephone interviews was intended to support patients to stay at home, avoiding the need for patients to leave their homes to return paper surveys. By conducting telephone interviews, we were able to directly address patients' questions and concerns regarding any changes in their care due to the COVID-19 pandemic. We will continue to survey our thoracic oncology patients longitudinally during the COVID-19 pandemic to assess the evolving impact of the restrictions on access to cancer care and treatment outcomes. Statement of Ethics Approval for this prospective noninterventional study was obtained from the ethics committee of the Ludwig Maximilian University. The study was conducted in accordance with the Declaration of Helsinki, good clinical practice guidelines, and local ethical and legal requirements. Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources This research received funding from Stiftungen der Medizinische Fakultat Ludwig-Maximilians-Universitat Munchen. Author Contributions A.T.: conceptualization, methodology, resources, writing of the original draft, and supervision. K.K., Z.S., D.K.-G., F.M., C.S., and J.B.: writing of the review and editing. R.Z.: investigation and data curation. L.S.: methodology, investigation, data curation, and writing of the original draft. J.W.: methodology, investigation, data curation, formal analysis, and writing of the original draft.

Due to climate change, the amount, frequency, and intensity of precipitation worldwide are changing. There is increasing evidence that hydrological change severely affects species interactions and that these effects might overrule direct autecological responses, although this is currently understudied. Here, I synthesize published data on 405 interactions to show how changes in soil moisture affect the frequency or strength of plant-mediated biotic interactions. Despite substantial variation among published responses, general patterns have emerged. A recurrent finding in the synthesized studies is that dryness impedes beneficial interactions between plants and other organisms (decreased mycorrhization and infection with other symbiotic endophytes, less pollinator visits, less active decomposers) and increases detrimental interactions (increased performance of sucking insects, pathogen infection and competition between functionally similar plants). For increased wetness, which is far less studied, stress intensity seems to matter: Slightly increased precipitation often benefits plants and thereby associated interaction partners (increased mycorrhization and infection with symbiotic endophytes, increased herbivore performance), while extreme waterlogging or flooding impedes many interactions (decreased decomposer activity and mycorrhization). Legacy effects of changed soil moisture on plant community composition can amplify or reverse short-term effects on interactions. Although some concepts acknowledge the role of stress intensity (mild versus severe) and stress type (permanent versus pulsed) empirical research testing-related hypotheses is largely lacking, as is research on the role of soil moisture legacies for interactions.

Sopotlieva, Desislava/0000-0002-9281-7039; Guler, Behlul/0000-0003-2638-4340; Velev, Nikolay/0000-0001-6812-3670; De Boeck, Hans/0000-0003-2180-8837; Kreyling, Juergen/0000-0001-8489-7289; Bahn, Michael/0000-0001-7482-9776; Dengler, Jurgen/0000-0003-3221-660X; Nijs, Ivan/0000-0003-3111-680X; Wellstein, Camilla/0000-0001-6994-274X; Apostolova, Iva/0000-0002-2701-175X; Stampfli, Andreas/0000-0002-5517-1363; Picon-Cochard, Catherine/0000-0001-7728-8936; Bloor, Juliette M.G./0000-0002-8668-1323; Arfin Khan, Mohammed Abu Sayed/0000-0001-6275-7023; Campetella, Giandiego/0000-0001-6126-522X WOS:000413145900006 PubMed ID: 28941071 Biodiversity can buffer ecosystem functioning against extreme climatic events, but few experiments have explicitly tested this. Here, we present the first multisite biodiversityxdrought manipulation experiment to examine drought resistance and recovery at five temperate and Mediterranean grassland sites. Aboveground biomass production declined by 30% due to experimental drought (standardised local extremity by rainfall exclusion for 72-98 consecutive days). Species richness did not affect resistance but promoted recovery. Recovery was only positively affected by species richness in low-productive communities, with most diverse communities even showing overcompensation. This positive diversity effect could be linked to asynchrony of species responses. Our results suggest that a more context-dependent view considering the nature of the climatic disturbance as well as the productivity of the studied system will help identify under which circumstances biodiversity promotes drought resistance or recovery. Stability of biomass production can generally be expected to decrease with biodiversity loss and climate change. ERA-Net BiodivERsA [01LC1201]; Belgian Federal Science Policy Office (BELSPO)Belgian Federal Science Policy Office; German Federal Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF); Bulgarian Science Found; Ministere de l'Ecologie, du Developpement durable et de l'Energie (France) This work is part of the project SIGNAL which is funded by the ERA-Net BiodivERsA (http://www.biodiversa.org; Funding ID 01LC1201), with the national funders Belgian Federal Science Policy Office (BELSPO), German Federal Ministry of Education and Research (BMBF), Bulgarian Science Found and Ministere de l'Ecologie, du Developpement durable et de l'Energie (France) as part of the 2011-2012 BiodivERsA call for research proposals. For site FR, we thank P. Pichon, A. Salcedo, J. Pottier, M.E. Lefranc, M. Michaux, A. Vernay and G. Zannin for help during the course of the experiment. We thank three anonymous referees for insightful and constructive comments on an earlier version of this manuscript.

Background Filamentous cyanobacteria represent model organisms for investigating multicellularity. For many species, nitrogen-fixing heterocysts are formed from photosynthetic vegetative cells under nitrogen limitation. Intracellular Ca2+ has been implicated in the highly regulated process of heterocyst differentiation but its role remains unclear. Ca2+ is known to operate more broadly in metabolic signalling in cyanobacteria, although the signalling mechanisms are virtually unknown. A Ca2+-binding protein called the Ca2+ Sensor EF-hand (CSE) is found almost exclusively in filamentous cyanobacteria. Expression of asr1131 encoding the CSE protein in Anabaena sp. PCC 7120 was strongly induced by low CO2 conditions, and rapidly downregulated during nitrogen step-down. A previous study suggests a role for CSE and Ca2+ in regulation of photosynthetic activity in response to changes in carbon and nitrogen availability. Results In the current study, a mutant Anabaena sp. PCC 7120 strain lacking asr1131 (Δcse) was highly prone to filament fragmentation, leading to a striking phenotype of very short filaments and poor growth under nitrogen-depleted conditions. Transcriptomics analysis under nitrogen-replete conditions revealed that genes involved in heterocyst differentiation and function were downregulated in Δcse, while heterocyst inhibitors were upregulated, compared to the wild-type. Conclusions These results indicate that CSE is required for filament integrity and for proper differentiation and function of heterocysts upon changes in the cellular carbon/nitrogen balance. A role for CSE in transmitting Ca2+ signals during the first response to changes in metabolic homeostasis is discussed.

Effects of molecular crowding on structural and dynamical properties of biological macromolecules do depend on the concentration of crowding agents but also on the molecular mass and the structural compactness of the crowder molecules. By employing fluorescence correlation spectroscopy (FCS), we investigated the translational mobility of several biological macromolecules ranging from 17 kDa to 2.7 MDa. Polyethylene glycol and Ficoll polymers of different molecular masses were used in buffer solutions to mimic a crowded environment. The reduction in translational mobility of the biological tracer molecules was analyzed as a function of crowder volume fractions and was generally more pronounced in PEG as compared to Ficoll solutions. For several crowding conditions, we observed a molecular sieving effect, in which the diffusion coefficient of larger tracer molecules is reduced to a larger extent than predicted by the Stokes–Einstein relation. By employing a FRET-based biosensor, we also showed that a multiprotein complex is significantly compacted in the presence of macromolecular crowders. Importantly, with respect to sensor in vivo applications, ligand concentration determining sensors would need a crowding specific calibration in order to deliver correct cytosolic ligand concentration.

SummaryCa2+is a potent signalling molecule that regulates many cellular processes. In cyanobacteria, Ca2+has been linked to cell growth, stress response and photosynthesis, and to the development of specialist heterocyst cells in certain nitrogen-fixing species. Despite this, the pathways of calcium signal transduction in cyanobacteria are poorly understood, and only a few protein components are known. The current study describes a previously unreported calcium-binding protein which was called the Calcium Sensor EF-hand (CSE), which is conserved in filamentous, nitrogen-fixing cyanobacteria. CSE is shown to bind calcium, which induces a conformational change in the protein structure. Poor growth of a strain ofAnabaenasp. PCC 7120 overexpressing CSE was attributed to diminished photosynthetic performance. Transcriptomics, biophysics and proteomics analyses revealed modifications in the light-harvesting phycobilisome and photosynthetic reaction center-protein complexes, and downregulated respiration.

Ca

BackgroundAlthough lung cancer is most commonly diagnosed in elderly patients, evidence about tumor-directed therapy in elderly patients is sparse, and it is unclear to what extent this affects treatment and care. Our study aimed to discover potential disparities in care between elderly patients and those under 65 years of age.MethodsWe studied claims from 13 283 German patients diagnosed with lung cancer in 2009 who survived for at least 90 days after diagnosis. We classified patients as "non-elderly" (= 85). We compared receipt of tumor-directed therapy (6 months after diagnosis), palliative care, opioids, antidepressants, and pathologic diagnosis confirmation via logistic regression. We used generalized linear regression (gamma distribution) to compare group-specific costs of care for 3 months after diagnosis. We adjusted all models by age, nursing home residency, nursing care need, comorbidity burden, and area of residence (urban, rural). The age group "non-elderly" served as reference group.ResultsCompared with the reference group "non-elderly", the likelihood of receiving any tumor-directed treatment was significantly lower in all age groups with a decreasing gradient with advancing age. Elderly lung cancer patients received significantly fewer resections and radiotherapy than non-elderly patients. In particular, treatment with antineoplastic therapy declined with increasing age ("young-old" (OR = 0.76, CI = [0.70,0.83]), "middle-old" (OR = 0.45, CI = [0.36,0.50]), and "old-old" (OR = 0.13, CI = [0.10,0.17])). Patients in all age groups were less likely to receive structured palliative care than "non-elderly" ("young-old" (OR = 0.84, CI = [0.76,0.92]), "middle-old" (OR = 0.71, CI = [0.63,0.79]), and "old-old" (OR = 0.57, CI = [0.44,0.73])). Moreover, increased age was significantly associated with reduced quotas for outpatient treatment with opioids and antidepressants. Costs of care decreased significantly with increasing age.ConclusionThis study suggests the existence of age-dependent care disparities in lung cancer patients, where elderly patients are at risk of potential undertreatment. To support equal access to care, adjustments to public health policies seem to be urgently required.

Leaf litters commonly interact during decomposition in ways that can synergistically increases rates of decay. These interactions have been linked to moisture availability, suggesting that drought could slow decomposition rates by disrupting litter interactions. Slowed decomposition may reduce competitive ability of exotic species that exploit rapid decomposition rates as part of niche construction mechanisms. Here, we evaluated the impacts of drought on interactions between native and exotic species' litter decomposition. We considered litter mixtures of Lupinus polyphyllus (exotic N-fixing forb), Trifolium pratense (native N-fixing forb), Senecio inaequidens (exotic non-N-fixing forb), and Senecio jacobaea (native non-N-fixing forb) with the native grass Alopecurus pratensis and evaluated the difference between the observed rate of decay and the one expected based on species decomposing in monocultures. Litters were deployed in Belgium and Germany and exposed to a 56 day drought, which resembled local millennium drought (statistical recurrence of duration in local precipitation series > 1000 years). Litter interactions reduced mass remaining by 81% in Belgium and 15% in Germany, averaged across mixtures. Similarly, litter interactions reduced N remaining by 93% in Belgium and 14% in Germany. Drought consistently removed these interactions and resulted in additive litter decay. Litters of native and exotic species did not differ in their response to drought. These findings support moisture availability as a key regulator of interactions between litters during decomposition. Thus, increasing frequency of drought may slow nutrient cycling to a greater extent than previously thought.

Extreme drought events challenge ecosystem functioning. Ecological response to drought is studied worldwide in a growing number of field experiments by rain-out shelters. Yet, few meta-analyses face severe challenges in the comparability of studies. This is partly because build-up of drought stress in rain-out shelters is modified by ambient weather conditions. Rain-out shelters can further create confounding effects (radiation, temperature), which may influence plant responses. Yet, a quantification of ecophysiological effects within rain-out shelters under opposing ambient weather conditions and of microclimatological artifacts is missing. Here, we examined phytometers—standardized potted individuals of Plantago lanceolata—under rain-out shelter, rain-out shelter artifact control, and ambient control during opposing outside microclimatological conditions. Furthermore, we tested for artifacts of rain-out shelters on plant responses in a long-term semi-natural grassland experiment. Phytometer plants below the rain-out shelters showed lower stomatal conductance, maximum quantum efficiency, and leaf water potential during warm ambient conditions with high evaporative demand than during cold conditions with low evaporative demand. Plant performance was highly correlated with ambient temperature and vapor pressure deficit (VPD). Rain-out shelter artifacts on plant responses were nonsignificant. Rain-out shelters remain a viable tool for studying ecosystem responses to drought. However, drought manipulations using rain-out shelters are strongly modified by ambient weather conditions. Attributing the results from rain-out shelter studies to drought effects and comparability among studies and study years therefore requires the quantification of the realized drought stress, for example, by relating ecosystem responses to measured microclimatological parameters such as air temperature and VPD.

Summary Climate change is predicted to increase the frequency and magnitude of extreme climatic events. These changes will directly affect plant individuals and populations and thus modify plant community composition. Little is known, however, about transgenerational effects (i.e. the influence of the parental environment on offspring phenotype and performance beyond the effects of transmitted genes) of climate extremes and community composition. Perennial plants have been particularly neglected. This impedes projections on species adaptations and population dynamics under climate change. Maternal plants of two widespread dwarf-shrub species (Genista tinctoria and Calluna vulgaris) recurrently experienced extreme weather event manipulations each year (drought and heavy rain). To test for transgenerational effects of community composition, C. vulgaris maternal plants were grown in communities differing in the number of neighbouring species. After 6 years, seeds of maternal plants were collected at least 2 months after the final weather treatments. We assessed transgenerational effects of the extreme events and of altered community composition on germination and monitored the development of offspring over 2 years. We show that extreme events experienced by maternal plants influence offspring germination and growth beyond the seedling stage. Seeds produced by maternal plants experiencing stress, indicated by increased tissue dieback, germinated earlier in both observed species. We observed differences in leaf stoichiometry and growth rates for G. tinctoria offspring throughout the first year: Offspring from heavy rain-treated mothers showed reduced leaf C:N ratio and higher growth rates. Results further indicate that not only community density, as investigated in prior studies, but also community composition trigger transgenerational effects. Synthesis. Our findings show that variation in the maternal environment not only affects the number, but also the performance of offspring. Extreme climatic events, terminated before seed set, induce transgenerational effects. Species richness of mother communities can affect the stress level of target species and thereby germination regardless of community density. In contrast to prior studies, which revealed direct effects of chronic stress on plant individuals, this study emphasizes the importance of addressing transgenerational effects of extreme weather events when projecting future ecological responses and adaptation to climate change.

Drought stress is one of the major stressors for plants under climate change, depressing growth through inhibition of photosynthesis and causing oxidative cell damage. It has been shown that plants can form a drought stress memory, improving their performance under recurring drought stress after they have been primed by drought before. Mechanisms underlying such a drought stress memory and possible cross-stress tolerance (improved performance to drought after plants have been stressed by other stressors) are currently unclear. We aimed to test whether previous waterlogging stress and drought stress leads to improved performance and changes in morphological, photosynthetic and anti-oxidative parameters under recurring drought. Therefore, we repeatedly subjected Alopecurus pratensis grass plants to waterlogging and drought over two years. In the third year, plants were well-watered for three weeks to recover and then subjected to drought stress for two weeks. Plants primed with drought before showed less tissue damage and higher levels of Rubisco content, anti-oxidative enzymes (POX, SOD) and chlorophyll b after the recovery and the drought period. We show for the first time a long-term drought stress memory in a grass species, lasting over several weeks. Our results indicate that drought priming enhances the activity of anti-oxidative enzymes, which is key for depressing oxidative damage and for improving tolerance to subsequent drought stress in A. pratensis.

Bacterial periplasmic binding proteins (PBPs) undergo a pronounced ligand-induced conformational change which can be employed to monitor ligand concentrations. The most common strategy to take advantage of this conformational change for a biosensor design is to use a F&ouml, rster resonance energy transfer (FRET) signal. This can be achieved by attaching either two fluorescent proteins (FPs) or two organic fluorescent dyes of different colors to the PBPs in order to obtain an optical readout signal which is closely related to the ligand concentration. In this study we compare a FP-equipped and a dye-labeled version of the glucose/galactose binding protein MglB at the single-molecule level. The comparison demonstrates that changes in the FRET signal upon glucose binding are more pronounced for the FP-equipped sensor construct as compared to the dye-labeled analog. Moreover, the FP-equipped sensor showed a strong increase of the FRET signal under crowding conditions whereas the dye-labeled sensor was not influenced by crowding. The choice of a labeling scheme should therefore be made depending on the application of a FRET-based sensor.

Background When patients die in a hospital their quality of life is lower than when they die at home or in a hospice. Despite efforts to improve palliative care supply structures, still about 60% of lung cancer patients die in a hospital. Studies have examined factors related to inhospital death in lung cancer patients, yet none used data of a representative German population, additionally including economic aspects. This study aimed to identify factors related to inhospital death in German lung cancer patients and analysed resulting costs. Methods We analysed a dataset of health insurance claims of 17,478 lung cancer patients (incident 2009) with 3 year individual follow-up. We grouped patients into inhospital death and death elsewhere. Studied factors were indicators of healthcare utilization, palliative care, comorbidities and disease spread. We used logistic regression models with LASSO selection method to identify relevant factors. We compared all-cause healthcare expenditures for the last 30 days of life between both groups using generalized linear models with gamma distribution. Results Twelve thousand four hundred fifty-seven patients died in the observation period, thereof 6965 (55.9%) in a hospital. The key factors for increased likelihood of inhospital death were receipt of inpatient palliative care (OR = 1.85), chemotherapeutic treatments in the last 30 days of life (OR = 1.61) and comorbid Congestive Heart Failure (OR = 1.21), and Renal Disease (OR = 1.19). In contrast, higher care level (OR = 0.16), nursing home residency (OR = 0.25) and receipt of outpatient palliative care (OR = 0.25) were associated with a reduced likelihood. All OR were significant (p-values

Numerous target agents promising longer survival with fewer adverse events have recently been approved for the treatment of NSCLC and are associated with high drug prices. Using the reference years 2009 and 2013, we aimed to detect changes in the therapy with targeted agents and resulting costs, in the year after the initial diagnosis. We analyzed German health insurance claims of 6,822 and 7,414 patients with advanced lung cancer diagnosed in 2009 or 2013, respectively. We used procedural and ATC codes to identify therapy with targeted agents, and claims for in- and outpatient visits and for drug prescriptions to calculate daily therapy costs. 2009 costs were inflated and compared with 2013 costs using generalized linear models with gamma distribution, adjusted by age, gender, comorbidities and area of residence. The proportion of patients receiving targeted therapies remained stable at around 11%. There was an increase in the usage of bevacizumab (1.5% to 2.6%) and gefitinib (0.6% to 1.3%), whereas usage decreased for cetuximab (0.5% to 0.1%) and erlotinib (8.2% to 5.3%). Crizotinib and afatinib were approved after 2009 only and received by 0.4% and 0.1% of patients in 2013, respectively. Daily costs were 4% (p Therapy in lung cancer is changing due to new targeted therapies. Costs are increasing especially for the drugs themselves. However, usage is limited to only around 11% of patients so far.

Objectives: In presence of lung cancer, the additional impact of comorbidity on survival is often neglected, although comorbidities are likely to be prevalent. Our study examines the comorbidity profile and the impact of distinct conditions on survival in German lung cancer patients.Material and methods: We investigated claims data from a large nationwide statutory health insurance fund of 16,202 patients initially diagnosed with lung cancer in 2009. We calculated the prevalence of comorbidities grouped according to an extension of the Elixhauser Comorbidity Index (EI). Effects of distinct comorbidities on 5-year survival were examined using multivariate Cox proportional hazards models, adjusted for sex, age and metastases at baseline. Ail analyses were stratified by initial lung cancer-related treatment regimen (Surgery, Chemotherapy/Radiotherapy, No treatment). Findings were visualized in the form of a comorbidome.Results: Our study population was predominantly male (70.6%) with a mean age of 68.6 years, and a mean EI score of 3.94. Patients without treatment were older (74.4 years), and their comorbidity burden was higher (mean EI = 4.59). Median survival varied by subgroup (Surgery: 24.4 months, Chemotherapy/Radiotherapy: 8.8 months, No treatment: 2.0 months), and so did the comorbidity profile and the impact of distinct conditions on survival. Generally, the effect of comorbidities on survival was detrimental and the negative association was most pronounced for 'Weight Loss' and' Paralysis'. In contrast, 'Lipid Metabolism Disorders' and 'Obesity' were positively associated with survival. Noteworthily, highly prevalent conditions tended not to show any significant association.Conclusion: We found specific comorbidity profiles within the distinct treatment regimens. Moreover, there were negative but also some positive associations with survival, and the strength of these effects varied by stratum. Particularly the positive effects of 'Obesity" and 'Lipid Metabolism Disorders' which were robust across strata need to be further investigated to elucidate potential biomedical explanations.

Under climate change, both wetter and drier conditions, as well as an increase in extreme events like floods or droughts are projected for many areas. So far, studies only investigate the impact of drier or wetter conditions at a single stress severity level but do not consider how different intensities and types of changes affect insect herbivores feeding on stressed plants. Further, how effects of acute stress pulses differ from milder, chronic soil moisture stress is unclear. We investigated how changing soil moisture conditions affect a generalist insect herbivore feeding on grassland plants. We transplanted multi-species sections of grassland into pots and subjected them to different intensities and durations of flooding and drying stress. We compared effects of short, extreme drought and flooding pulses against the effects of milder, but chronic stress. Constantly drier conditions decreased plant and herbivore performance at all levels of stress severity. Severe permanent wetness did not affect plant growth, but decreased pupal weight (− 23%) and survival of larvae (− 34%). Extreme pulsed drought exacerbated negative effects of chronic drying, as most larvae died before they could benefit from rewetting plants after the drought (94% mortality). Pulsed flooding did not affect plants or larval development more than chronic severe wetness. Our findings imply that plant stress negatively affects generalist chewing herbivores, even with mixed diets. Both drier and severely wet, but not mildly wetter conditions, will reduce survival of some species. Especially, extreme droughts appear to have strong negative effects on generalist grassland herbivores.

PURPOSE: To assess rural-urban differences in healthcare utilization and supportive care at the end-of-life in German lung cancer patients. METHODS: We identified 12,929 patients with incident lung cancer in 2009 from claims data and categorized them to four district types (major city, urban, rural, remote rural). We compared site of death, unplanned hospitalizations, hospital days, outpatient doctor, general practitioner (GP) and home visits, structured palliative care, therapy with antidepressants, pain relief medication and chemotherapy, and therapeutic puncturing in the last 30 and 14days of life using mixed models with logistic link function for binary outcomes and log link function for count data. We adjusted all models by age, sex, comorbidities, metastases location and presence of multiple tumors at diagnosis, survival in months, and type of tumor-directed treatment. RESULTS: We found significant differences in two of the outcomes measured. The likelihood of > 14 hospital days in the last 30days was significantly higher in rural districts than in remote rural districts (1.27 [1.05, 1.52], p = 0.0003). The number of visits to the GP in the last 30days of life was significantly lower in urban districts than in remote rural districts (β = - 0.19 [- 0.32, - 0.06], p =&thinsp