Effect of Indacaterol/Glycopyrronium on Pulmonary Perfusion and Ventilation in Hyperinflated Patients with Chronic Obstructive Pulmonary Disease (CLAIM). A Double-Blind, Randomized, Crossover Trial.

Rationale: In the CLAIM study, dual bronchodilation with indacaterol/glycopyrronium (IND/GLY) significantly reduced hyperinflation, which translated into improved cardiac function, measured by left ventricular end-diastolic volume and cardiac output. Pulmonary microvascular blood flow (PMBF) is reduced in chronic obstructive pulmonary disease (COPD); however, the effect of reduced lung hyperinflation on PMBF remains unknown. Objectives: To determine the effect of lung deflation with IND/GLY on PMBF and regional pulmonary ventilation using magnetic resonance imaging (MRI) in hyperinflated patients with COPD. Methods: In this double-blind, randomized, two-period crossover study, gadolinium-enhanced MRI and phase-resolved functional lung MRI were used to measure PMBF and regional ventilation, respectively, in patients with COPD receiving IND/GLY versus placebo. Measurements and Main Results: Sixty-two patients were randomized to receive once-daily IND/GLY (110/50 µg) for 14 days, followed by 14 days of placebo, or vice versa. Treatment periods were separated by a 14-day washout. Sixty patients were included in the per-protocol analysis. MRI measurements showed significant improvements in total PMBF (P = 0.006) and regional PMBF (P values for individual lobes were between 0.004 and 0.022) in response to IND/GLY versus placebo. Regional ventilation was also significantly improved with IND/GLY, as evidenced by a 12.4% increase versus placebo (P = 0.011), a 14.3% relative decrease in ventilation defect percentage of nonventilated/hypoventilated lung tissue (cutoff was defined as 0.075 regional ventilation; P = 0.0002), and a 15.7% reduction in the coefficient of variation of regional ventilation compared with placebo (P < 0.0001). Conclusions: Pharmacologic intervention with IND/GLY improves pulmonary microvascular blood flow and regional ventilation in patients with COPD with hyperinflation. Clinical trial registered with www.clinicaltrials.gov (NCT02442206).

Breath-hold and free-breathing 2D phase-contrast MRI for quantification of oxygen-induced changes of pulmonary circulation dynamics in healthy volunteers.

PURPOSE: To evaluate the effect of inhaled 100% oxygen on pulmonary circulation dynamics in healthy volunteers using 2D phase-contrast magnetic resonance imaging (2D PC MRI). MATERIALS AND METHODS: Twenty-one healthy volunteers were examined at 1.5T. Through-plane 2D PC MRI measurements were performed in the main pulmonary artery during free-breathing and breath-hold. Acceleration time and volume, maximum and minimum area, area change, average and maximum mean velocity, forward volume, heart rate, as well as blood pressure were determined. At baseline, subjects breathed room air. After application of a closed-fit full face mask, three further measurements were conducted: at room air (control), directly after starting 15 L/min 100% oxygen (wash-in), and after 5 minutes during continuous oxygen supply (saturation). Data were analyzed with a mixed linear model. Skewed distributed variables were rank-transformed. Tukey contrasts with family-wise adjusted P-values were applied for pairwise comparisons. RESULTS: Inhaled oxygen affected several hemodynamic parameters. Average mean velocity (P < 0.01: breath-hold during wash-in and saturation, P = 0.03: free-breathing during saturation) and maximum mean velocity (P < 0.01: breath-hold and free-breathing during saturation) decreased. When obtained during free-breathing, acceleration volume (P = 0.02: saturation), area change (P = 0.02: saturation), and maximum area (P = 0.02: wash-in, P = 0.03: saturation) increased, while minimum area and forward volume did not change. CONCLUSION: Oxygen alters pulmonary circulation dynamics in the main pulmonary artery of healthy volunteers, which can be reliably detected using 2D phase-contrast MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1698-1706.

Histamine induces chemotaxis and phagocytosis in murine bone marrow-derived macrophages and RAW 264.7 macrophage-like cells via histamine H4-receptor.

OBJECTIVE: Expression and function of histamine H4-receptor, an immunomodulatory receptor involved in inflammatory diseases, on murine macrophages, which are vital for immunity, were investigated. MATERIALS AND METHODS: The expression pattern of histamine receptors on bone marrow-derived macrophages of BALB/c mice and on RAW 264.7 cells was studied at the mRNA level by reverse transcription polymerase chain reaction. The functional relevance of histamine receptors was investigated by analyzing histamine-induced chemotaxis and phagocytosis in the presence of histamine receptor antagonists mepyramine (histamine H1-receptor), famotidine (histamine H2-receptor), thioperamide (histamine H3/4-receptors) and JNJ7777120 (histamine H4-receptor). RESULTS: Both bone marrow-derived macrophages and RAW 264.7 cells express mRNA for histamine H1-receptor and histamine H4-receptor. Residual amounts of histamine H2-receptor mRNA are found in bone marrow-derived macrophages only. In both cellular models, histamine induced chemotaxis and phagocytic activity, which was reduced by thioperamide as well as by JNJ 7777120, but not by mepyramine or famotidine. CONCLUSION: In murine bone marrow-derived macrophages and RAW 264.7 macrophage-like cells histamine H4-receptor mediates chemotaxis and phagocytic activity.

[Positron emission tomography in oncology]. / Positronenemissionstomographie in der Onkologie.

Positron emission tomography (PET) is a highly sensitive imaging tool that noninvasively characterizes metabolic processes and molecular targets. PET has become an integral part of oncological diagnostics and an increasingly important tool for oncological therapy management. PET assessment, for example, directly influences treatment escalation or de-escalation in context of Hodgkin lymphomas or is, in case of lung cancer, able to reduce unnecessary surgeries. Hence, molecular PET imaging represents an indispensable tool in the development of personalized treatments. Furthermore, the development of new radiotracers for specific cell surface structures offers a promising potential for diagnostics and-combined with therapeutic nuclides-also for therapies. One recent example are radioligands targeting prostate-specific membrane antigen, which are relevant in prostate cancer.

[Hereditary kidney cancer - easily clarified and diagnosed with ToSCaNA]. / Hereditäre Nierentumore ­ einfach abgeklärt mit ToSCaNA.

BACKGROUND: In recent years great improvements in the diagnosis and differentiation of hereditary syndroms with predisposition for kidney cancer have been achieved. It has been assumed that 5-8% of all kidney cancer have a hereditary origin. In reality, this number will probably be much higher as many genetic aspects of kidney cancer are still not entirely known. Hereditary kidney cancer usually shows two characteristic properties: While the median age of diagnosis of sporadic renal cell carcinoma is 64 years, patients with a hereditary tumor predisposition are about 20 years younger at the time of diagnosis. Additionally, their tumors often occur multifocal/bilateral. Therefore, a special management with extended diagnostics is necessary for these young kidney cancer patients. In literature many reports on hereditary syndromes with kidney cancer predisposition exist. Though, these papers usually put their focus on single syndromes rather than on the aspects of kidney cancer. The goal of this article is to present the practicing urologist with a compact overview of the most important hereditary syndromes with kidney cancer predisposition and by this improve the primary diagnostic and treatment of renal cancer patients and their relatives. MATERIAL/METHODS: We conducted a literature search on the five most important hereditary syndromes with kidney cancer association and summarized the results in a chart. Additionally, we formed the acronym ToSCaNA combining the most important extrarenal manifestations of the syndromes. Based on this data, a diagnostic workflow and treatment path was established. RESULTS: All in all, hereditary kidney cancer is a rare entity, which nonetheless could present as a significant number in high-volume centers. For doctors who scarcely get in contact with these types of tumors, the acronym and workflow could pose a valuable asset for their clinical diagnostic portfolio. An early identification and diagnostic work-up of affected patients and their relatives is crucial for appropriate treatment and surveillance and allows the identification/treatment of additionally affected relatives. CONCLUSION: In patients with young age of onset and multifocal/bilateral occurrence of kidney cancer, hereditary syndromes should always be considered. The initial suspicion of a hereditary genesis of the cancer can be further evaluated by the acronym ToSCaNA and the presented workflow.

Perioperative CTEPH patient monitoring with 2D phase-contrast MRI reflects clinical, cardiac and pulmonary perfusion changes after pulmonary endarterectomy.

Magnetic resonance imaging (MRI) is an emerging tool for diagnosis and treatment monitoring of chronic thromboembolic pulmonary hypertension (CTEPH). The current study aims to identify central pulmonary arterial hemodynamic parameters that reflect clinical, cardiac and pulmonary changes after PEA. 31 CTEPH patients, who underwent PEA and received pre- and postoperative MRI, were analyzed retrospectively. Central pulmonary arterial blood flow, lung perfusion and right heart function data were derived from MRI. Mean pulmonary arterial pressure (mPAP) and 5-month follow-up six-minute walk-distance (6MWD) were assessed. After PEA, mPAP decreased significantly and patients achieved a higher 6MWD. Central pulmonary arterial blood flow velocities, pulmonary blood flow (PBF) and right ventricular function increased significantly. Two-dimensional (2D) phase-contrast (PC) MRI-derived average mean velocity, maximum mean velocity and deceleration volume changes after PEA correlated with changes of 6MWD and right heart ejection fraction (RVEF). Deceleration volume is a novel 2D PC MRI parameter showing further correlation with PBF changes. In conclusion, 2D PC MRI-derived main pulmonary hemodynamic changes reflect changes of RVEF, PBF and 5-month follow-up 6MWD and may be used for future CTEPH patient monitoring after PEA.