Bone continually adapts to meet changing physical and biological demands. Osteoblasts, osteoclasts, and osteocytes cooperate to integrate these physical and biochemical cues to maintain bone homeostasis. Although TGFβ acts on all three of these cell types

Although recipients of donor lungs from smokers have worse clinical outcomes, the underlying mechanisms are unknown. We tested the association between donor smoking and the degree of pulmonary edema (as estimated by lung weight), the rate of alveolar fluid clearance (AFC; measured by airspace instillation of 5% albumin) and biomarkers of lung epithelial injury and inflammation (bronchoalveolar lavage [BAL] surfactant protein-D (SP-D) and IL-8) in ex vivo lungs recovered from 298 organ donors. The extent of pulmonary edema was higher in current smokers (n = 127) compared to nonsmokers (median 408 g, interquartile range [IQR] 364-500 vs. 385 g, IQR 340-460, p = 0.009). Oxygenation at study enrollment was worse in current smokers versus nonsmokers (median PaO2 /FiO2 214 mm Hg, IQR 126-323 vs. 266 mm Hg, IQR 154-370, p = 0.02). Current smokers with the highest exposure (≥20 pack years) had significantly lower rates of AFC, suggesting that the effects of cigarette smoke on alveolar epithelial fluid transport function may be dose related. BAL IL-8 was significantly higher in smokers while SP-D was lower. These findings indicate that chronic exposure to cigarette smoke has important effects on inflammation, gas exchange, lung epithelial function and lung fluid balance in the organ donor that could influence lung function in the lung transplant recipient.

Although recipients of donor lungs from smokers have worse clinical outcomes, the underlying mechanisms are unknown. We tested the association between donor smoking and the degree of pulmonary edema (as estimated by lung weight), the rate of alveolar fluid clearance (AFC; measured by airspace instillation of 5% albumin) and biomarkers of lung epithelial injury and inflammation (bronchoalveolar lavage [BAL] surfactant protein-D (SP-D) and IL-8) in ex vivo lungs recovered from 298 organ donors. The extent of pulmonary edema was higher in current smokers (n=127) compared to nonsmokers (median 408g, interquartile range [IQR] 364-500 vs. 385g, IQR 340-460, p=0.009). Oxygenation at study enrollment was worse in current smokers versus nonsmokers (median PaO2/FiO2 214mm Hg, IQR 126-323 vs. 266mm Hg, IQR 154-370, p=0.02). Current smokers with the highest exposure (≥20 pack years) had significantly lower rates of AFC, suggesting that the effects of cigarette smoke on alveolar epithelial fluid transport function may be dose related. BAL IL-8 was significantly higher in smokers while SP-D was lower. These findings indicate that chronic exposure to cigarette smoke has important effects on inflammation, gas exchange, lung epithelial function and lung fluid balance in the organ donor that could influence lung function in the lung transplant recipient.

Purpose

Previous studies have suggested an association between increased thoracic kyphosis and neural axis abnormalities in patients with adolescent idiopathic scoliosis (AIS). However, the basis for this finding is unclear, and this association has been mainly noted in retrospective studies on a non-consecutive series of patients. The purpose of this study was to assess the relationship between thoracic kyphosis and neural axis abnormalities in patients with AIS.

Methods

We studied a consecutive series of AIS patients treated with spinal fusion. Thoracic kyphosis (T2 to T12) was measured from preoperative lateral radiographs. All patients underwent a spine magnetic resonance imaging (MRI) prior to surgery, and MRI reports were reviewed to determine the presence of neural axis abnormalities. Statistical analyses included descriptive statistics and chi-squared analysis.

Results

This study included 210 patients with AIS. There were no significant differences in age or gender between patients with thoracic hypokyphosis (kyphosis < 20°), normal thoracic kyphosis (kyphosis 20° to 40°) and thoracic hyperkyphosis (kyphosis > 40°) (p > 0.05). Neural axis abnormalities were present in 17.9% of patients with thoracic hypokyphosis, 9.8% of patients with normal thoracic kyphosis and 13.6% of patients with thoracic hyperkyphosis (p = 0.60). There were no significant differences in rates of Chiari malformation, syrinx, intra-spinal masses and other central nervous system abnormalities between groups (p > 0.05).

Conclusions

Thoracic kyphosis was not associated with neural axis abnormalities in our consecutive series of patients with AIS. Increased thoracic kyphosis may not be a reliable indicator for the presence of neural axis abnormalities in patients with AIS.

Level of evidence

IV.

Prior studies have demonstrated associations between beta-adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001-2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg) and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The β1AR1165 and β2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 μg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n¼260) and placebo (n¼246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p¼0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p¼0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs. 0%,p<0.001) for tachycardia. In summary, treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia.High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema.