A review of the potential applications and controversies of non-invasive testing for biomarkers of aspiration in the lung transplant population.

Despite improvements in one-yr survival following lung transplantation, five-yr survival lags significantly behind the transplantation of other solid organs. The contrast in survival persists despite advancements in anti-rejection regimens, suggesting a non-alloimmune mechanism to chronic lung transplant failure. Notably, markers of aspiration have been demonstrated in bronchoalveolar lavage (BAL) fluid concurrent with bronchiolitis obliterans syndrome (BOS). This recent evidence has underscored gastroesophageal reflux (GER) and its associated aspiration risk as a non-alloimmune mechanism of chronic lung transplant failure. Given the suggested safety and efficacy of laparoscopic anti-reflux procedures in the lung transplant population, identifying those at risk for aspiration is of prime importance, especially concerning the potential for long-term improvements in morbidity and mortality. Conventional diagnostic methods for GER and aspiration, such as pH monitoring and detecting pepsin and bile salts in BAL fluid, have gaps in their effectiveness. Therefore, we review the applications and controversies of a non-invasive method of defining reflux injury in the lung transplant population: the detection of biomarkers of aspiration in the exhaled breath condensate. Only by means of assay standardization and directed collaboration may such a non-invasive method be a realization in lung transplantation.

Lung allograft donors with excessive alcohol use have increased levels of human antimicrobial peptide LL-37.

The relatively low long-term survival rate of lung transplant recipients as compared to other organ recipients serves as an impetus to identify potential lung dysfunction as early as possible. There is an association between donor heavy alcohol use and acute lung injury in the lung allograft after transplant, known as primary graft dysfunction. Excessive alcohol use (EAU) can induce pulmonary immune dysregulation in response to an infection. Antimicrobial peptides (AMPs) are an important component of the innate immune response to pulmonary infections, but the impact of EAU on AMPs in the allograft lung has not been evaluated. Our hypothesis is that specific lung AMPs, LL-37, α-defensin-1,2,3, and ß-defensin-2, are dysregulated in the lungs from organ donors who had EAU. In this prospective observational investigation, we measured AMPs via ELISA and inflammatory cytokines via multiplex bead array, in bronchoalveolar lavage (BAL) fluid of lung allograft donors, comparing results based on their alcohol consumption. LL-37 levels in lung donors with EAU were found to be increased compared to nondrinker (ND) donors [median 7.7 ng/mL (IQR 4.1-37.0) vs. 2.3 ng/mL (IQR 1.1-7.9), p = 0.004], whereas α-defensins-1,2,3 were decreased only in the presence of an infection in donors with EAU compared to ND donors [median 2.2 ng/mL (IQR 1.6-2.4) vs. 3.2 ng/mL (IQR 2.3-3.8), p = 0.049]. There was no difference in ß-defensin-2 levels. Gene expression levels of these AMPs were not different. Elevated levels of CXCL8 were noted in bronchial washings of donors with EAU compared to ND donors, [median 4372 pg/mL (IQR 3352-13180) vs. 867.3 pg/mL (IQR 163.6-3675), p = 0.04], suggesting a potentially heightened inflammatory response. At 1 month post-transplant, LL-37 and CXCL8 levels are decreased compared to levels at time of transplant. In lung donors with EAU, LL-37 and α-defensins-1,2,3 dysregulated levels in the presence of an infection may be a harbinger of dysfunction of the lungs through the transplant process.

Genetic analysis of sympatric char populations in western Alaska: Arctic char (Salvelinus alpinus) and Dolly Varden (Salvelinus malma) are not two sides of the same coin.

The North Pacific Ocean has been of great significance to understanding biogeography and speciation in temperate faunas, including for two species of char (Salmonidae: Salvelinus) whose evolutionary relationship has been controversial. We examined the morphology and genetics (microsatellite and mitochondrial DNA) of Arctic char (Salvelinus alpinus) and Dolly Varden char (Salvelinus malma) in lake systems in western Alaska, the eastern and western Arctic, and south of the Alaskan Peninsula. Morphologically, each lake system contained two forms: one (Arctic char) largely confined to lake habitats and characterized by greater numbers of pyloric caeca, gill rakers, and shallower bodies, and another (Dolly Varden) predominated in adjacent stream habitats and was characterized by fewer pyloric caeca, gill rakers, and deeper bodies. MtDNA partial (550 bp) d-loop sequences of both taxa were interspersed with each other within a single 'Bering' clade and demographic inferences suggested historical gene flow from Dolly Varden to Arctic char had occurred. By contrast, the taxa were strongly differentiated in sympatry across nine microsatellite loci in both lakes. Our data show that the two taxa are highly genetically distinct in sympatry, supporting their status as valid biological species, despite occasional hybridization. The interaction between these species highlights the importance of the North Pacific, and Beringia in particular, as an evolutionary wellspring of biodiversity.

How much does a regional immunization registry increase documented immunization rates at primary care sites in rural colorado?

OBJECTIVE: To determine increases in immunization up-to-date (UTD) rates at a rural pediatric practice with the sequential addition of records from other sites in a 2-county region. DESIGN/METHODS: UTD rates for children aged 3 months to 35 months (n = 876) were determined for the index practice and then recalculated after sequential addition of records from 1) the other private practice in the region, 2) 7 public primary care sites, and 3) 2 public health clinics in the region. RESULTS: Adding records from all sites increased documented UTD rates in the index practice from 49% to 64% at 3 months (N = 33, P = 0.025), 50% to 68% at 5 months (N = 38, P = 0.008), 28% to 45% at 7 months (N = 113, P <.01), 29% to 54% at 12 months (N = 200, P <.001), 11% to 35% at 19 months (N = 124, P <.001), and 10% to 33% at 24 months (N = 368, P <.001). CONCLUSIONS: Regional registries will be valuable tools for immunization delivery if there is an ongoing commitment to effective collection of current and historical immunization data.

Challenges in the diagnosis of 2009 H1N1 in a lung transplant patient and the long-term implications for prevention and treatment: a case report.

Although respiratory viral infections have been associated with acute rejection and bronchiolitis obliterans syndrome, the long-term impact of the novel pandemic influenza A (2009 H1N1) virus on lung transplant patients has not been defined. We describe the diagnostic challenges and long-term consequences of 2009 H1N1 infection in a lung transplant patient, discuss the potential implications for prevention and treatment, and conclude that even timely antiviral therapy may be insufficient to prevent long-term morbidity.

Unstable fracture-dislocations of the thoracolumbar spine: results of surgical treatment.

In a review of 22 patients with unstable fractures or fracture-dislocations of the thoracolumbar spine, treated by Harrington rod instrumentation and spinal arthrodesis, all arthrodeses became solid. All patients with incomplete neurologic lesions regained some function. No patient was made neurologically worse by the procedure. Solid arthrodesis was achieved whether laminectomy was performed or not. Harrington rods offer a method of reduction of compression fractures, offer partial stability to the spine, and serve as an adjunct to spine arthrodesis.

Orthopaedic aspects of prune belly syndrome.

Prune belly syndrome is a relatively uncommon disorder that is characterized by intrauterine urinary obstruction associated with cryptorchisdism, oligohydramnios, and orthopaedic deformations. The oligohydramnios is believed to produce limited intrauterine space, which in turn leads to fetal compression and the resultant deformities. The deformities observed in our patients were developmental dislocation of the hip (DDH), clubfeet, metatarsus adductus, vertical talus, and congenital muscular torticollis. These deformations should be treated aggressively because children with prune belly syndrome may be expected to have a relatively normal life if their renal function is good. The one exception is that as infants these children are very susceptible to pulmonary infections because of their inability to cough. Therefore, treatment of the hip and other deformations should be delayed until the children are old enough to be able to clear pulmonary secretions easily.