The Landsteiner lung cancer research platform (LALUCA) : Objectives, methodology and implementation of a real-world clinical lung cancer registry.

BACKGROUND: Lung cancer is a major health burden in Austria; however, limited real-world data exist on the diagnostic and treatment reality of lung cancer patients in Austria. The collection of high-quality data in a clinical setting is needed to gain insights into the real-world diagnostic and therapeutic management of lung cancer patients. METHODS: The Karl Landsteiner Institute for Lung Research and Pulmonary Oncology implemented the Landsteiner lung cancer research platform (LALUCA), recruiting unselected lung cancer patients from two high volume centers in Vienna. This article describes the objectives, design, methodology of the registry and the process of implementation. RESULTS: A multidisciplinary team of lung cancer specialists created a custom designed variable catalogue for the LALUCA platform consisting of 17 categories with 180 variables. Detailed information on clinical characteristics, diagnostic interventions, molecular pathology as well as curative and palliative treatment modalities are collected. During an implementation phase in 2020, the platform was optimized using the data of 50 patients. Since then a total of 1200 patients have been enrolled. Recruitment for the registry is ongoing with a recruitment rate of approximately 400 patients per year. CONCLUSION: The LALUCA registry is a web-based platform for the collection of real-world clinical data of lung cancer patients. Combining a large number of patients with a focus on gathering comprehensive data on diagnosis and treatment, the LALUCA registry provides a tool for investigation, evaluation, and improvement of the clinical management, survival and quality of care of Austrian lung cancer patients.

Assessing the Performance of a Novel Stool-Based Microbiome Test That Predicts Response to First Line Immune Checkpoint Inhibitors in Multiple Cancer Types.

The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice.

Insulin resistance may contribute to vascular dysfunction in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at an increased cardiovascular risk; however, the underlying mechanisms for this relationship are ill defined. Altered glucose metabolism may increase cardiovascular risk via impaired endothelial function. METHODS: We conducted a longitudinal pilot study to assess the interrelationship between systemic vascular function, glucose metabolism, and lung function in patients with COPD. Eighteen non-smoking patients with stable moderate-to-severe COPD [67 % male; median (first to third quartiles) Forced Expiratory Volume in 1 second (FEV1) % predicted: 38 % (28-55 %); body mass index: 26 kg/m(2) (24-28 kg/m(2))] free from cardiovascular risk factors were evaluated. Systemic vascular function was assessed by means of flow-mediated dilation technique of the brachial artery. Laboratory measurements included fasting blood glucose levels, circulating concentrations of insulin, C-reactive protein, and fibrinogen. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined. Measurements were performed at baseline and were repeated after 12 months. RESULTS: Flow-mediated dilation significantly decreased from 13.5 % (11-15 %) at baseline to 9.8 % (6-12 %; p = 0.002) at the follow-up visit, whereas both fasting blood glucose concentrations and HOMA-IR increased from 94 mg/dl (86-103 mg/dl) to 102 mg/dl (94-111 mg/dl; p = 0.027) and from 1.2 (0.8-2.1) to 1.7 (1.2-3.0; p = 0.023), respectively. There was a significant relationship between changes in endothelial function and changes in fasting serum glucose (r = - 0.483, p = 0.009), HOMA-IR (r = - 0.441, p = 0.019), and FEV1 (r = 0.336, p = 0.05). CONCLUSION: Altered glucose metabolism may be associated with progression of endothelial dysfunction in patients with COPD.

Thrombin generation in type 2 diabetes with albuminuria and macrovascular disease.

BACKGROUND: Albuminuria is an indicator of cardiovascular morbidity and mortality in patients with type 2 diabetic mellitus (T2DM). MATERIALS AND METHODS: In our cross-sectional study, we measured thrombin generation (TG), a key process in haemostasis and a tool to detect an individual's coagulation potential, in normo-, micro- and macroalbuminuria in T2DM with and without macrovascular disease (MVD). The TG-assay was performed, and the TG-curve [including the lag phase, peak thrombin and area under the curve (AUC)] was analysed. RESULTS: A total of 160 patients (62 women; mean age ± SD: 67 ± 11 years) with T2DM and normo-, micro- or macroalbuminuria were investigated. Of those, 90 (56%) patients had normoalbuminuria, 40 (25%) microalbuminuria and 30 (19%) macroalbuminuria. The AUC between the groups of patients with normo-, micro- and macroalbuminuria was statistically significantly different [3297 (2785; 3764) vs. 3222 (2381; 3678) vs. 3726 (3153; 4235) nM Thrombin; P = 0AE019]. T2DM patients with MVD (n = 121) had a significantly shorter lag phase [12 (9; 16) vs. 20 (15; 25) min; P < 0AE001], a significantly higher peak thrombin [233 (130; 339) vs. 133 (82; 187) nM; P < 0AE001] and a significantly higher AUC [3464 (2969; 3868) vs. 3091 (2384; 3619) nM Thrombin; P = 0AE01] than T2DM patients without MVD (n = 39), indicating an earlier and higher thrombin generation. CONCLUSION: Our results support the hypothesis that TG may be involved in the pathogenesis of MVD in diabetic nephropathy as for the first time, we could show that patients with T2DM in different stages of diabetic nephropathy had disturbances in thrombin generation.

Myotoxicity of telbivudine in pre-existing muscle damage.

OBJECTIVES: It is unknown if telbivudine causes muscle damage only in patients with pre-existing muscle pathology. CASE REPORT: A 27 yo male of African origin received telbivudine for hepatitis B during 3 months. Three weeks after initiation of the drug he developed myalgia, and tiredness. Creatine-kinase increased from 278 U/l (n, <170 U/l) at baseline to 3243 U/l. Shortly after discontinuation of telbivudine muscle symptoms and hyper-CK-emia disappeared. The findings suggest that pre-existing muscle damage favored the myotoxic effect of telbivudine. CONCLUSIONS: Telbivudine appears to cause accelerated muscle toxicity if given to patients who already have muscle damage. Patients under telbivudine should be closely monitored for muscular side effects and those with pre-existing muscle damage should not receive the drug.