Use of fractional flow reserve versus stress perfusion scintigraphy in stent restenosis

BackgroundFractional flow reserve (FFR) is a valid surrogate for hemodynamic significance in stenotic native coronary arteries. The aim of this study was to examine the value of FFR compared to stress perfusion myocardial scintigraphy (SPMS) in patients with coronary stent restenosis.MethodsWe studied 42 patients, aged 62 ± 10 years, with stent restenosis 5.3 ± 1.6 months after coronary stent implantation. All patients had a single coronary lesion of intermediate severity (diameter stenosis 40–70%). FFR measurement, SPMS, and quantitative angiography of the stent stenosis were performed in all patients.ResultsThe mean percentage in stent diameter stenosis was 53 ± 9%. FFR was 0.77 ± 0.15. In 20 patients FFR was below 0.75. Nineteen patients had reversible perfusion defects in SPMS. FFR showed good diagnostic accuracy for the detection of reversible perfusion defects in SPMS (AUROC 0.86, 95% CI 0.74–0.98). The percentage of agreement of SPMS and FFR was 88%, with the best cutoff value of 0.75 for FFR.ConclusionsA FFR value of 0.75 is not only valid for diagnosing significant native coronary stenosis, but also for stent restenosis. Thus, FFR measurement should be taken into account when making decisions regarding patients with stent restenosis.     

Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics

The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 10(9) particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 10(8) particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics.     

Low incidence of neurologic events during long-term support with the HeartMate XVE left ventricular assist device

Neurologic events during left ventricular assist device (LVAD) support are associated with significant morbidity and death. To evaluate this problem, we analyzed neurocognitive function and the frequency and incidence of neurologic events in 21 consecutive patients who were undergoing long-term support with the HeartMate XVE LVAD (Thoratec Corporation; Pleasanton, Calif). The mean duration of LVAD support was 531 days (range, 55-1, 309 d); the cumulative support time was 11,188 days (30.7 yr). No patients received anticoagulant therapy, and most received aspirin. None experienced strokes or transient ischemic attacks. Twenty patients were discharged from the hospital; 2 were later readmitted because of transient changes in neurologic status (metabolic encephalopathy) that ultimately resolved. Neurologic function, as measured by the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Score (MRS), was abnormal before LVAD implantation but normal 6 and 12 months after (mean NIHSS, 23.6 before vs 0 after; mean MRS, 0.68 before vs 0.18 after). Neurocognitive function, as evaluated by the Boston Naming Test, Trail Making Test part B, and Block Design Test, also improved during LVAD support. Together, these findings indicate that few neurologic events occur during long-term HeartMate XVE LVAD support in the absence of anticoagulation therapy. They also suggest that modifications made to the HeartMate LVAD since the REMATCH trial have resulted in fewer complications, and that better patient selection and supportive care have improved outcomes.     

Octreotide increases thresholds of colonic visceral perception in IBS patients without modifying muscle tone

Effects of octreotide (1.25 µg/kg subcutaneously) on colonic tone and visceral perception were evaluated in 10 IBS patients, using a barostat and compared to placebo in a double-blind crossover study. Colonic sensory thresholds were also studied in healthy controls for comparison with IBS patients. Colonic tone was reflected by variations in volume of the barostat balloon. Baseline volume was 117±38 ml and was not modified by placebo (122±40 ml) or octreotide (106±42 ml). After the meal, maximal decrease in balloon volume was 75±4% following placebo (P<0.001) beginning after 9±3 min and lasting 136±17 min. Following octreotide, the maximal decrease was 69±16% (NS vs placebo), after 10±3 min and lasting 140±22 min. In the second part, discomfort and pain thresholds were evaluated during isobaric distensions (4 mm Hg increments, 5-min duration, 5-min interval with return to pressure 0 between each). The pressure inducing discomfort was 21.2±5.9 mm Hg following placebo vs 29.6±6.6 mm Hg following octreotide (P<0.01). The pressure inducing pain was 24.8±7.3 mm Hg following placebo vs 33.2±7.3 mm Hg following octreotide (P<0.01). In healthy subjects, discomfort and pain were induced by colonic distensions at a mean intraballoon pressure of 32.7±5.8 mm Hg and 36.7±3.9 mm Hg, respectively. Compliance curves were not different following placebo and octreotide. Octreotide significantly increases thresholds for visceral perception in IBS patients without modifying compliance during distension nor colonic tone.     

Evaluation and Therapy of the Patient with Fecal Occult Blood Loss: A Decision Analysis

We performed a decision analysis to evaluate cost per cancer detected, cost per neoplasm detected, and cost per treatable lesion of two common diagnostic strategies, barium enema-proctoscopy or colonoscopy as the first diagnostic test, for patients with fecal occult blood loss. The prevalence of polyps, cancer, and angiodysplasia, and the colonoscopy success rate were obtained from consecutive colonoscopy records. Costs were estimated from hospital charges; sensitivity and specificity of barium enema and colonoscopy were obtained from the literature. For treatable lesions (cancer, polyps, and angiodysplasia), the colonoscopy first strategy had a higher sensitivity (80% vs. 57%) and a higher specificity (95% vs. 80%) than the barium enema first strategy. Cost effectiveness measures were similar for the two strategies. Colonoscopy as the first diagnostic test had a lower cost per treatable lesion ($2,319 vs. $2,895) and a lower cost per neoplasm detected ($2,694 vs. $2,896), whereas the barium enema first strategy had a lower cost per cancer detected ($10,050 vs. $10,297). The lower cost per treatable lesion of the colonoscopy first strategy was not affected by changes in the prevalence of lesions, test characteristics, costs of tests, or colonoscopy success rate over clinically relevant ranges. The higher cost of colonoscopy was offset by its greater sensitivity and its capacity for biopsy and therapy. Therefore, since the cost per treatable lesion is lower and the sensitivity, specificity, and predictive value is superior, colonoscopy is recommended as the preferred initial test in evaluating a patient with fecal occult blood loss.     

Ethnicity and psychiatric comorbidity among alcohol-dependent persons who receive inpatient treatment: African Americans,Alaska natives,Caucasians, and Hispanics

This study examined ethnic and gender differences of psychiatric comorbidity among alcohol dependent men and women from four ethnic groups: Alaska Native, Caucasians, African Americans, and Hispanics. The data were obtained through individual standardized interview; DSM-III-R diagnoses were obtained via a computer algorithm. The subjects included 1177 Caucasians, 361 African Americans, 93 Hispanics and 486 Alaska Natives. Significant ethnic differences were found in relation to age of onset of alcohol and multiple substance dependence and psychiatric comorbidity. Ethnic differences were also noted with regard to the health care utilization.     

Patterns of Puumala virus infection in Finland

Puumala hantavirus infection is prevalent throughout most of Europe, and in endemic areas it may be the most common cause of acute renal failure. To evaluate trends in incidence of Puumala virus infections in Finland, we analysed national surveillance data in 12-month periods from March 1995 to February 2002. During this time, 8184 laboratory-confirmed cases were notified to the National Infectious Disease Register. Three epidemic periods were identified, for which the number of cases was more than 1400 (there were approximately 600-900 cases per non-epidemic period). The incidence of Puumala hantavirus infection varied by geographic region during the study period, and the overall number of cases may be increasing.