The significance of a single episode of minimal acute rejection after lung transplantation

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains the leading obstacle to better long-term outcomes after lung transplantation. Acute rejection has been identified as the primary risk factor for BOS, but the impact of minimal acute rejection, especially a solitary episode, has usually been discounted as clinically insignificant. METHODS: We performed a retrospective cohort study of 259 adult lung transplant recipients to determine the risk of BOS associated with a single episode of A1 rejection, without recurrence or subsequent progression to a higher grade. The cohort was divided into 3 groups based on the severity of acute rejection (none, single episode of A1, and single episode of A2). We determined the risks of BOS stages 1, 2, 3, and death for each group using univariate and multivariate Cox regression analyses. RESULTS: A solitary episode of A1 rejection was a significant risk factor for BOS stages 1 and 2, but not stage 3 or death, in the univariate analysis. Multivariate Cox regression models confirmed that the risk of BOS attributable to a single episode of A1 rejection was independent of other potential risk factors, such as community acquired respiratory viral infections, number of HLA mismatches, and cytomegalovirus pneumonitis. Likewise, univariate and multivariate analyses demonstrated that a single episode of A2 rejection was a significant risk factor for all stages of BOS but not death. CONCLUSIONS: A single episode of minimal acute rejection without recurrence or subsequent progression to a higher grade is a significant predictor of BOS independent of other risk factors.     

Reliability for grading acute rejection and airway inflammation after lung transplantation.

BACKGROUND: The Lung Rejection Study Group (LRSG) created a scheme for grading acute allograft rejection in 1990 and then revised it in 1996, but virtually no studies have evaluated the reliability of this formulation. This investigation assessed the reliability of the current LRSG system by determining inter- and intrareader agreement for grading transbronchial biopsy samples from lung transplant recipients. METHODS: Biopsy samples from a cohort of 204 recipients were reviewed and classified by a single pathologist who was blinded to original interpretations. The "A" and "B" rejection grades from this contemporary review were compared with original grades by the kappa statistic. RESULTS: For "A" grading, weighted kappa was 0.65 (95% confidence interval [CI] 0.60-0.70) for interreader agreement (n = 529 specimens) and 0.65 (95% CI 0.53-0.76) for intrareader agreement (n = 97 specimens). For "B" grading, weighted kappa was 0.26 (95% CI 0.14-0.39) for interreader agreement (n = 164 specimens) and 0.33 (95% CI 0.15-0.51) for intrareader agreement (n = 58 specimens). CONCLUSIONS: On the basis of the analysis of the LRSG scheme, "A" grades exhibit very good reliability, but "B" grades have only fair reliability, and steps to improve this shortcoming should be taken.     

Sentinel lymph node biopsy for ductal carcinoma in situ: an evolving approach at the University of Florida

While sentinel lymph node biopsy (SLNB) has virtually replaced axillary dissection as the initial diagnostic procedure for invasive breast cancer, the role of SLNB in ductal carcinoma in situ (DCIS) remains controversial. The purpose of this study was to review our experience with SLNB in DCIS. All patients with DCIS or DCIS with microinvasion (DCISM) who underwent SLNB from June 1997 to April 2002 at the University of Florida were included for analysis. The indications for SLNB were at the discretion of the treating surgeon. Lymphatic mapping involved a sequential dermal-peritumoral radiocolloid injection and dynamic lymphoscintigraphy followed by an intraoperative assessment of radioactivity with a handheld gamma probe. All sentinel lymph nodes (SLNs) with radioactive counts>or=10% of the ex vivo counts of the most radioactive SLN were removed. Pathologic analysis consisted of slicing the SLN at 2 mm intervals for permanent section. All paraffin blocks of the SLNs were step sectioned in 4 microm sections (92 microm spacing) through the entire lymph node. Slides were then stained with an immunohistochemical stain for cytokeratin (AE1/AE3) and evaluated by microscopy. Nodal metastases were classified using the 6th edition of the American Joint Committee on Cancer (AJCC) staging manual. From April 1998 to April 2002, 43 patients with DCIS underwent SLNB at the University of Florida. Seven patients (16%) with multifocal or extensive DCIS (five patients) or DCISM (two patients) who underwent SLNB had a positive sentinel node. Two of the three patients considered positive by immunohistochemistry alone had either DCISM or invasive disease. Four (80%) of the five patients with extensive DCIS and a positive sentinel node were ultimately determined to have invasive or microinvasive disease. While SLNB remains controversial in DCIS, our data suggest that patients with extensive DCIS should undergo SLNB at the initial procedure to avoid the need for a second operation. Data from clinical trials are needed to determine the impact of SLNB results on overall survival in patients with DCIS.     

Closure of a surgically created arteriovenous fistula with a covered stent-graft in a patient with venous ambulatory hypertension--a case report

The purpose of this paper is to report the use of a covered stent-graft in the endovascular treatment of a surgically created arteriovenous fistula. A 37-year-old woman with symptomatic venous ambulatory hypertension underwent a left common femoral vein-to-right common iliac vein bypass using 10 mm ringed polytetrafluoroethylene (PTFE) with creation of an arteriovenous (AV) fistula from the superficial femoral artery to the PTFE graft. At 1 year postoperatively, recurrent symptoms thought to be due to the arteriovenous fistula were treated by placement of an 8 mm x 10 cm Viabahn covered stent-graft. Placement was via crossover technique from the right common femoral artery using a 9 French sheath. At 2 months' follow-up symptoms had resolved, the AV fistula was occluded, and venous bypass remained patent. Focal arteriovenous fistulas of the proximal superficial femoral artery can be treated safely with a covered stent-graft via an endovascular approach.     

Persistence of antidepressant treatment effects in a pharmacotherapy plus psychotherapy trial for active injection drug users

The objective of this study was to determine if combined psychotherapy and pharmacotherapy reduces reported depressive symptoms compared to an assessment only condition for active drug injectors over nine months. Using a randomized controlled trial at an outpatient academic research office, the researchers applied psychotherapy (eight sessions of cognitive behavioral therapy) plus pharmacotherapy (citalopram) to active injection drug users with a DSM-IV diagnosis of major depression, dysthymia, substance-induced mood disorder with symptoms persisting for at least three months, or major depression plus dysthymia, and a Modified Hamilton Rating Scale for Depression (MHRSD) score greater than 13. The MHRSD scale scores were then assessed at the completion of three, six, and nine months. Participants (n = 109) were 64% male and 82% Caucasian, with a mean baseline MHRSD score of 20.7. Depression subtypes included major depression only (63%), substance-induced depression (17%), and double-depression (17%). Study retention at nine months was 89%. At the completion of three months of acute treatment, 26% of combined treatment patients (n = 53), compared to 12% of control patients (n = 56), were in remission (p = .047). At both six and nine months, the between-group differences in remission rates and mean MHRSD scores were insignificant, although the overall mean MHRSD score decreased from baseline (p < .01). At all follow-up assessments, depression remission was significantly associated with lower heroin use. Among active drug injectors diagnosed with depression, symptoms decline over time. Combined treatment is superior to an assessment-only condition in depression remission rates at the end-of-treatment, but this difference does not persist.     

Function of striatum beyond inhibition and execution of motor responses

We used functional magnetic resonance imaging (fMRI) to study the role of the striatum in inhibitory motor control. Subjects had to refrain from responding to designated items (STOP trials) within a similar series of motor stimuli. Striatal activation was increased significantly compared to that when responding to all targets within a series of motor stimuli, indicating that the striatum is more active when inhibitory motor control over responses is required. The likelihood of a STOP trial was varied parametrically by varying the number of GO trials before a STOP trial. We could thus measure the effect of expecting a STOP trial on the fMRI response in the striatum. We show for the first time in humans that the striatum becomes more active when the likelihood of inhibiting a planned motor response increases. Our findings suggest that the striatum is critically involved in inhibitory motor control, most likely by controlling the execution of planned motor responses.     

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes

OBJECTIVE: We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes. STUDY DESIGN: We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks' gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed. RESULTS: The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P = .94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P = .03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P = .03). CONCLUSIONS: The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.