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Background-The rate of failure of noninvasive mechanical ventilation (NIMV) in patients with chronic obstructive pulmonary disease (COPD) with acute respiratory insuYciency ranges from 5% to 40%. Most of the studies report an incidence of "late failure" (after >48 hours of NIMV) of about 10-20%. The recognition of this subset of patients is critical because prolonged application of NIMV may unduly delay the time of intubation. Methods-In this multicentre study the primary aims were to assess the rate of "late NIMV failure" and possible associated predictive factors; secondary aims of the study were evaluation of the best ventilatory strategy in this subset of patients and their outcomes in and out of hospital. The study was performed in two respiratory intensive care units (ICUs) on patients with COPD admitted with an episode of hypercapnic respiratory failure (mean (SD) pH 7.23 (0.07), PaCO 2 85.3 (15.8) mm Hg). Results-One hundred and thirty seven patients initially responded to NIMV in terms of objective (arterial blood gas tensions) and subjective improvement. After 8.4 (2.8) days of NIMV 31 patients (23%; 95% confidence interval (CI) 18 to 33) experienced a new episode of acute respiratory failure while still ventilated. The occurrence of "late NIMV failure" was significantly associated with functional limitations (ADL scale) before admission to the respiratory ICU, the presence of medical complications (particularly hyperglycaemia), and a lower pH on admission. Depending on their willingness or not to be intubated, the patients received invasive ventilation (n=19) or "more aggressive" (more hours/day) NIMV (n=12). Eleven (92%) of those in this latter subgroup died while in the respiratory ICU compared with 10 (53%) of the patients receiving invasive ventilation. The overall 90 day mortality was 21% and, after discharge from hospital, was similar in the "late NIMV failure" group and in patients who did not experience a second episode of acute respiratory failure.Conclusions-The chance of COPD patients with acute respiratory failure having a second episode of acute respiratory failure after an initial (first 48 hours) successful response to NIMV is about 20%. This event is more likely to occur in patients with more severe functional and clinical disease who have more complications at the time of admission to the ICU. These patients have a very poor inhospital prognosis, especially if NIMV is continued rather than prompt initiation of invasive ventilation.

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Mesenchymal stem cells (MSC) possess anti-inflammatory properties and participate in tissue repair. We used MSC to heal therapy-induced tissue toxicity. Ten consecutive patients, treated with MSC due to tissue toxicity following allogeneic hematopoietic stem cell transplantation, (ASCT) were included. Their median age was 48 (13-64) years. Seven had hemorrhagic cystitis grades 2-5, two had pneumomediastinum and one had perforated colon and peritonitis. MSC donors were mainly third-party, HLA-mismatched (n=11), HLA-haploidentical (n=3) and, in two cases, the HLA-identical ASCT sibling donors. MSC were given intravenously, the median cell dose was 1.0 (range 0.7-2)x10(6)/kg. In five patients, the severe hemorrhagic cystitis cleared after MSC infusion. Gross hematuria disappeared after median 3 (1-14) days. Two patients had reduced transfusion requirements after MSC infusion, but died of multiorgan failure. In one of them, MSC donor DNA was demonstrated in the urinary bladder. In two patients, pneumomediastinum disappeared after MSC infusions. A patient with steroid-resistant graft-versus-host disease of the gut experienced perforated diverticulitis and peritonitis that was reversed twice by MSC. MSC is a novel treatment for therapy-induced tissue toxicity.