Previous phase I studies demonstrated safety and some beneficial effects of mesenchymal stem cells (MSCs) in patients with mild to moderate idiopathic pulmonary fibrosis (IPF). The aim of our study was to evaluate the safety, tolerability, and efficacy of a high cumulative dose of bone marrow MSCs in patients with rapid progressive course of severe to moderate IPF. Twenty patients with forced ventilation capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide (DLCO) ≥20% with a decline of both >10% over the previous 12 months were randomized into two groups: one group received two intravenous doses of allogeneic MSCs (2 × 10 8 cells) every 3 months, and the second group received a placebo. A total amount of 1.6 × 10 9 MSCs had been administered to each patient after the study completion. There were no significant adverse effects after administration of MSCs in any patients. In the group of MSC therapy, we observed significantly better improvement for the 6-minute walk distance in 13 weeks, for DLCO in 26 weeks, and for FVC in 39 weeks compared with placebo.FVC for 12 months in the MSCs therapy group increased by 7.8% from baseline, whereas it declined by 5.9% in the placebo group. We did not find differences between the groups in mortality (two patients died in each group) or any changes in the high-resolution computed tomography fibrosis score. In patients with IPF and a rapid pulmonary function decline, therapy with high doses of allogeneic MSCs is a safe and promising method to reduce disease progression.

Background:The diagnosis of pulmonary alveolar proteinosis (PAP) is based on computed tomography, histology, and antibodies to granulocyte-macrophage colony-stimulating factor. The role of a novel technique for imaging cells and elastin during endoscopy, probe-based confocal laser endomicroscopy (pCLE), has not yet been investigated in PAP patients. The aim of the present study was to estimate the value of pCLE in the PAP diagnosis and treatment in comparison with the findings of high-resolution computed tomography (HRCT) before and after whole-lung lavage.Methods:In vivo pCLE was performed during bronchoscopy in 6 male patients with PAP before and after whole-lung lavage. In certain lung segments, pCLE was followed by HRCT.Results:During the in vivo pCLE, we found characteristic signs of PAP: a fluorescent floating amorphous substance in the alveoli lumen sticking to conglomerates along with alveolar macrophages. These features were present to a lesser extent after a whole-lung lavage. pCLE revealed specific PAP features not only in segments with crazy-paving and ground-glass opacity, but also in segments without HRCT findings.Conclusions:The alveolar imaging in PAP patients is able to reveal characteristic changes, both in the presence and in the absence of HRCT findings. Therefore, pCLE may be a helpful tool for the diagnosis and whole-lung lavage therapy. Our data prove that accumulation of lipoproteinaceous substances within the alveoli at PAP is a diffuse but not a patchy process.

We present a case of 41-year-old patient with invasive pulmonary aspergillosis (IPA) in which probe-based confocal laser endomicroscopy (pCLE) imaging of central and distal airways was first performed in vivo. pCLE imaging showed the signs of complete or partial destruction of elastin network of alveolar wall with fibrillar branching fluorescent structures in the zone with typical IPA changes on HRCT.

The aim of the present work was to study the structure of nocturnal sleep in patients who had sustained brain insults, and to relates sleep structure to the stage of disease and the location of the focal lesion. Studies were performed on 18 patients with ischemic insult, 8 affected in the right hemisphere, 6 affected in the left hemisphere, and 4 with brainstem lesions; controls consisted of 5 healthy subjects. Diagnoses were in all cases confirmed by computer tomography. Clinical and neurological studies were performed, along with recording of polygraph traces of nocturnal sleep (electroencephalograms, electrooculograms, electromyograms). Sleep parameters were analyzed using a program developed at the Sleep Studies Center, I. M. Sechenov Moscow Medical Academy; along with standard parameters, this program included analysis of the segmental structure of sleep. Sleep quality-the level of normality or disturbance to its structure-was assessed using a sleep index (SI). Patients showed profound disorganization of nocturnal sleep structure, with disruption of the mechanisms organizing sleep as a whole and generating and maintaining the individual stages. The greatest sleep disturbances were seen in ischemic insult in the right hemisphere and in patients with lesions in medial deep structures.