Effects of intratracheal mesenchymal stromal cell therapy during recovery and resolution after ventilator-induced lung injury.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been demonstrated to attenuate acute lung injury when delivered by intravenous or intratracheal routes. The authors aimed to determine the efficacy of and mechanism of action of intratracheal MSC therapy and to compare their efficacy in enhancing lung repair after ventilation-induced lung injury with intravenous MSC therapy. METHODS: : After induction of anesthesia, rats were orotracheally intubated and subjected to ventilation-induced lung injury (respiratory rate 18(-1) min, P insp 35 cm H2O,) to produce severe lung injury. After recovery, animals were randomized to receive: (1) no therapy, n = 4; (2) intratracheal vehicle (phosphate-buffered saline, 300 µl, n = 8); (3) intratracheal fibroblasts (4 × 10 cells, n = 8); (4) intratracheal MSCs (4 × 10(6) cells, n = 8); (5) intratracheal conditioned medium (300 µl, n = 8); or (6) intravenous MSCs (4 × 10(6) cells, n = 4). The extent of recovery after acute lung injury and the inflammatory response was assessed after 48 h. RESULTS: Intratracheal MSC therapy enhanced repair after ventilation-induced lung injury, improving arterial oxygenation (mean ± SD, 146 ± 3.9 vs. 110.8 ± 21.5 mmHg), restoring lung compliance (1.04 ± 0.11 vs. 0.83 ± 0.06 ml · cm H2O(-1)), reducing total lung water, and decreasing lung inflammation and histologic injury compared with control. Intratracheal MSC therapy attenuated alveolar tumor necrosis factor-α (130 ± 43 vs. 488 ± 211 pg · ml(-1)) and interleukin-6 concentrations (138 ± 18 vs. 260 ± 82 pg · ml(-1)). The efficacy of intratracheal MSCs was comparable with intravenous MSC therapy. Intratracheal MSCs seemed to act via a paracine mechanism, with conditioned MSC medium also enhancing lung repair after injury. CONCLUSIONS: Intratracheal MSC therapy enhanced recovery after ventilation-induced lung injury via a paracrine mechanism, and was as effective as intravenous MSC therapy.

Paramediastinal air cyst with traumatic bronchial injury: a rare complication of neonatal resuscitation.

Paramediastinal air cysts and pneumatoceles are known complications of chest trauma and mechanical ventilation. After an initial period of enlargement, these lesions tend to resolve completely with conservative management. We present a case of a premature newborn who developed an enlarging paramediastinal air cyst as a result of resuscitation around the time of delivery that ultimately required surgical excision via a right thoracotomy. To our knowledge, this is the first reported case in a neonate.

Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat.

BACKGROUND: Bone-marrow derived mesenchymal stem cells (MSCs) reduce the severity of evolving acute lung injury (ALI), but their ability to repair the injured lung is not clear. A study was undertaken to determine the potential for MSCs to enhance repair after ventilator-induced lung injury (VILI) and elucidate the mechanisms underlying these effects. METHODS: Anaesthetised rats underwent injurious ventilation which produced severe ALI. Following recovery, they were given an intravenous injection of MSCs (2×10(6) cells) or vehicle immediately and a second dose 24 h later. The extent of recovery following VILI was assessed after 48 h. Subsequent experiments examined the potential for non-stem cells and for the MSC secretome to enhance VILI repair. The contribution of specific MSC-secreted mediators was then examined in a wound healing model. RESULTS: MSC therapy enhanced repair following VILI. MSCs enhanced restoration of systemic oxygenation and lung compliance, reduced total lung water, decreased lung inflammation and histological lung injury and restored lung structure. They attenuated alveolar tumour necrosis factor α concentrations while increasing concentrations of interleukin 10. These effects were not seen with non-stem cells (ie, rat fibroblasts). MSC-secreted products also enhanced lung repair and attenuated the inflammatory response following VILI. The beneficial effect of the MSC secretome on repair of pulmonary epithelial wounds was attenuated by prior depletion of keratinocyte growth factor. CONCLUSION: MSC therapy enhances lung repair following VILI via a paracrine mechanism that may be keratinocyte growth factor-dependent.

Early mortality rate of morbidly obese patients after tracheotomy.

OBJECTIVES: To 1) determine the early mortality rate (within 30 days) of morbidly obese patients after tracheotomy; 2) determine the difference between the mortality rate after tracheotomy of morbidly obese patients and patients who are not morbidly obese; and 3) determine the difference between the mortality rate after tracheotomy adjusted for case mix index (CMI) of morbidly obese patients and patients who are not morbidly obese. STUDY DESIGN: Retrospective cohort study of 278 patients who had undergone a tracheotomy by the otolaryngology head and neck surgery department from 2004 to 2006. The patients were subdivided into two groups: 1) body mass index (BMI) <35 (n = 229) and 2) BMI > or =35 (morbidly obese) (n = 49). METHODS: Charts reviewed for age, sex, weight, height, BMI, indication for tracheotomy, date of tracheotomy, type of tracheotomy, date of discharge, date of death, length of hospital stay, and CMI. RESULTS: There is a trend toward significance (P = .09) between the mortality rate after tracheotomy of morbidly obese patients (29%) and patients who are not morbidly obese (18%). There is less significance between the adjusted mortality rate based on CMI after tracheotomy when the patient population is divided into morbidly obese patients and patients who are not morbidly obese (P = .12). CONCLUSION: The mortality rate after tracheotomy of morbidly obese patients is greater than patients who are not morbidly obese.