Tumor mutational load, CD8 T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients.

Objectives: A minority of NSCLC patients benefit from anti-PD1 immune checkpoint inhibitors. A rational combination of biomarkers is needed. The objective was to determine the predictive value of tumor mutational load (TML), CD8 T cell infiltration, HLA class-I and PD-L1 expression in the tumor.

Right ventricular diastolic impairment in patients with pulmonary arterial hypertension.

Background: The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH patients.

Methods And Results: Single-beat RV pressure-volume analyses were performed in 21 PAH patients and 7 control subjects to study RV diastolic stiffness.

Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension.

Rationale: Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are up-regulated, but this may have long-term negative effects on the progression of iPAH.

Objectives: Assess systemic and pulmonary RAAS activity in patients with iPAH and determine the efficacy of chronic RAAS inhibition in experimental PAH.

Pulmonary arterial hypertension in systemic sclerosis is associated with profound impairment of microvascular endothelium-dependent vasodilatation.

Objective: Impaired microvascular function may contribute to organ complications in patients with systemic sclerosis (SSc). We investigated whether SSc patients with and without pulmonary arterial hypertension (PAH) show a graded impairment of microvascular function compared to healthy controls.

Methods: Twenty-two patients with SSc and 22 controls were studied.

Familial multiple discoid fibromas: a look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus.

Background: Previously, we proposed that familial multiple trichodiscomas (OMIM 190340) is distinct from Birt-Hogg-Dubé syndrome (BHD) (OMIM #135150). BHD is characterized by multiple fibrofolliculomas/trichodiscomas, lung cysts, pneumothorax, and renal cell cancer. Germline FLCN mutations can be detected in most but not all BHD families.

Diaphragm muscle fiber weakness in pulmonary hypertension.

Rationale: Recently it was suggested that patients with pulmonary hypertension (PH) suffer from inspiratory muscle dysfunction. However, the nature of inspiratory muscle weakness in PH remains unclear.

Objectives: To assess whether alterations in contractile performance and in morphology of the diaphragm underlie inspiratory muscle weakness in PH.

Exercise stroke volume and heart rate response differ in right and left heart failure.

Aims: In pulmonary arterial hypertension (PAH), the exercise-induced increase in stroke volume (SV) is limited by the increase in pulmonary artery pressure. In left heart failure (LHF), systemic arterial pressure increases little during exercise, and the SV increase is limited by the left ventricle itself. These differences might be reflected by a dissimilar SV and heart rate (HR) response to exercise, which could have important therapeutic implications, for example in beta-blocker therapy.

[Spontaneous pneumothorax as the first manifestation of a hereditary condition with an increased renal cancer risk].

Spontaneous pneumothorax can be due to Birt-Hogg-Dubé syndrome (BHD syndrome), an autosomal dominant predisposition for fibrofolliculomas, multiple lung cysts, pneumothorax and renal cancer. The syndrome is the result of germline mutations in the FLCN (folliculin) gene. Its clinical presentation is highly variable.

Quantification of right ventricular afterload in patients with and without pulmonary hypertension.

Right ventricular (RV) afterload is commonly defined as pulmonary vascular resistance, but this does not reflect the afterload to pulsatile flow. The purpose of this study was to quantify RV afterload more completely in patients with and without pulmonary hypertension (PH) using a three-element windkessel model. The model consists of peripheral resistance (R), pulmonary arterial compliance (C), and characteristic impedance (Z).

Bilateral pulmonary infiltrates in a patient with ulcerative colitis receiving mesalazine.

A 36-year-old woman presented with a 2-month history of dry cough, bilateral pain in the upper chest, and low-grade fever. She had a 1-year history of ulcerative colitis (UC), which was treated with mesalazine. Cultures of sputum and bronchoalveolar lavage (BAL) fluid were negative.