The Role of TGF‐β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome

Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly understood. Based on the association of TGF‐β with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single‐center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF‐β and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF‐β and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76–5.38) for the most severe form of PGD. TGF‐β and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF‐β and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF‐β biology.     

Radiation dose reduction during hysterosalpingography: an application of scanning-beam digital radiography

Hysterosalpingography was performed in 31 patients by means of a low-dose scanning-beam digital radiographic system. The technique permits adequate evaluation of gynecologic abnormalities while allowing significant reduction in radiation: 2.4-mR (6.1 X 10(-7) C/kg) exposure to the skin and 0.7-mrad (7 X 10(-6) Gy) mean dose to the ovaries per image obtained. Sixteen patients demonstrated readily recognizable and documented abnormalities, corroborated by laparoscopy, laparotomy, or other supportive evidence.     

In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection: comparison with other imaging modalities

When infection of prosthetic orthopedic implants is suspected, optimal management requires accurate confirmation or exclusion of infection. The authors retrospectively studied 98 patients with possible infection who underwent scanning with indium-111-labeled white blood cells (WBCs) and subsequently underwent surgery within 14 days. At surgery, 50 patients had infections, as determined by means of culture or histologic results. The diagnostic accuracy of In-111 scanning was compared with that of plain radiography, arthrography, three-phase bone scanning, and various clinical and laboratory findings classically associated with infection. Positive findings on In-111 WBC scans and elevated erythrocyte sedimentation rates were found to be the most predictive variables in the diagnosis of septic prostheses (P less than or equal to .001 and P less than or equal to .002, respectively). Likelihood ratio analysis more clearly demonstrated the superiority of In-111 WBC scanning, with positive and negative scans yielding likelihood ratios of 5.0 and 0.16, respectively.     

A meta-analytic approach to quantify the dose–response relationship between melatonin and core temperature

A melatonin-mediated reduction in body temperature could be useful as a “pre-cooling” intervention for athletes, as long as the melatonin dose is optimised so that substantial soporific effects are not induced. However, the melatonin-temperature dose–response relationship is unclear in humans. Individual studies have involved small samples of different sexes and temperature measurement sites. Therefore, we meta-analysed the effects of exogenous melatonin on body core temperature to quantify the dose–response relationship and to explore the influence of moderating variables such as sex and measurement site. Following a literature search, we meta-analysed 30 data-sets involving 193 participants and 405 ingestions of melatonin. The outcome was the mean difference (95 % confidence limits) in core temperature between the melatonin and placebo-controlled conditions in each study, weighted by the reciprocal of each standard error of the difference. The mean (95 % confidence interval) pooled reduction in core temperature was found to be 0.21 °C (0.18–0.24 °C). The dose–response relationship was found to be logarithmic (P < 0.0001). Doses of 0–5 mg reduced temperature by ~0.00–0.22 °C. Any further reductions in temperature were negligible with doses >5 mg. The pooled mean reduction was 0.13 °C (0.05–0.20 °C) for oral temperature vs 0.26 °C (0.20–0.32 °C) for tympanic and 0.22 °C (0.19–0.25 °C) for rectal temperature. In conclusion, our meta-regression revealed a logarithmic dose–response relationship between melatonin and its temperature lowering effects. A 5-mg dose of melatonin lowered core temperature by ~0.2 °C. Higher doses do not substantially increase this hypothermic effect and may induce greater soporific effects.     

Colonization With Small Conidia Aspergillus Species Is Associated With Bronchiolitis Obliterans Syndrome: A Two‐Center Validation Study

Aspergillus colonization after lung transplantation may increase the risk for bronchiolitis obliterans syndrome (BOS), a disease of small airways. We hypothesized that colonization with small conidia Aspergillus species would be associated with a greater risk of BOS, based upon an increased likelihood of deposition in small airways. We studied adult primary lung recipients from two large centers; 298 recipients at University of California, Los Angeles and 482 recipients at Duke University Medical Center. We grouped Aspergillus species by conidia diameter ≤3.5 μm. We assessed the relationship of colonization with outcomes in Cox models. Pre‐BOS colonization with small conidia Aspergillus species, but not large, was a risk factor for BOS (p = 0.002, HR 1.44, 95% CI 1.14–1.82), along with acute rejection, single lung and Pseudomonas. Colonization with small conidia species also associated with risk of death (p = 0.03, HR 1.30, 95% CI 1.03–1.64). Although other virulence traits besides conidia size may be important, we have demonstrated in two large independent cohorts that colonization with small conidia Aspergillus species increases the risk of BOS and death. Prospective evaluation of strategies to prevent Aspergillus colonization of small airways is warranted, with the goal of preserving lung allograft function as long as possible.