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CAP Home > CAP Reference Resources and Publications > CAP TODAY > CAP TODAY 2011 Archive > Clinical Abstracts
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  Clinical Abstracts

 

 

 

 

February 2011

Editor:
Michael Bissell, MD, PhD, MPH

Creatinine in acute pancreatitis Creatinine in acute pancreatitis

The fate of a patient suffering from acute pancreatitis depends on whether one or more organs fail at the outset or in the course of the disease or whether and to what extent pancreatic necroses develop. Organ failure and pancreatic necrosis are not parallel processes. Necrotizing pancreatitis may not involve organ failure, whereas non-necrotizing, or interstitial, pancreatitis may be accompanied by organ failure. The Atlanta classification lists the following as the principal organ failures in acute pancreatitis: shock (systolic blood pressure of less than 90 mm Hg), pulmonary insufficiency (PaO2 of 60 mm Hg or less), renal failure (creatinine of 2 mg/dL or more after rehydration), and gastrointestinal bleeding (more than 50 cc/24 hours). The gold standard for demonstrating pancreatic necrosis is contrast-enhanced computed tomography (CT) using Balthazar’s well-established classification of interstitial and necrotizing pancreatitis (now officially termed the Computed Tomography Severity Index). The consensus is that contrast-enhanced CT is the most reliable way to confirm pancreatic necrosis. Pancreatic necroses may develop in the course of acute pancreatitis and are then associated with a high rate of morbidity or mortality. In general, however, necroses can be detected by contrast-enhanced CT within 96 hours of the onset of necrotizing pancreatitis, and only a very small proportion of cases of interstitial pancreatitis evolve into necrotizing pancreatitis. Independent of these discussions, contrast-enhanced CT is an expensive diagnostic procedure, and it would be useful to have simple parameters to determine the presence and extent of the necrotizing form of pancreatitis. An increase in creatinine concentration within 48 hours of admission to the hospital is strongly associated with developing pancreatic necrosis. Blood urea nitrogen and creatinine, both well-known markers of renal function, differ in their accuracy as markers of pancreatic necrosis. It has been hypothesized that creatinine levels may be less sensitive to small changes in intravascular volume and may better reflect visceral organ injury than blood urea nitrogen. The authors conducted a prospective multi-center study of 462 patients with a first attack of acute pancreatitis to determine the value of an elevated serum creatinine concentration as a marker for pancreatic necrosis. Serum creatinine was determined on admission and at 24 and 48 hours thereafter and compared with the findings of contrast-enhanced CT performed within 96 hours of admission. The authors found that pancreatic necrosis was present in 62 (13 percent) of the patients. Serum creatinine levels (abnormal, 2 mg/dL or more) on admission and after 24 and 48 hours were evaluated against the presence or absence of pancreatic necrosis. Sensitivity rates varied between 14 percent and 23 percent, specificity between 95 percent and 97 percent, positive predictive values between 41 percent and 50 percent, and negative predictive values between 87 percent and 89 percent. Receiver operating characteristic curves revealed an area under the curve of between 0.604 and 0.669. The authors concluded that an elevated serum creatinine concentration at any time during the first 48 hours after hospital admission is not a marker for pancreatic necrosis in a first attack of acute pancreatitis. If serum creatinine is normal, necrotizing pancreatitis is unlikely, and contrast-enhanced CT need not be performed unless complications occur or if the patient’s condition deteriorates.

Lankisch PG, Weber-Dany B, Maisonneuve P, et al. High serum creatinine in acute pancreatitis: a marker for pancreatic necrosis? Gastroenterol. 2010;105:1196–1200.

Correspondence: Dr. Paul Georg Lankisch at paulgeorg.lankisch@t-online.de

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A new TSI biomarker in Graves disease A new TSI biomarker in Graves disease

The autoantibodies of clinical relevance in Graves disease stimulate the thyroid-stimulating hormone receptor and directly influence the metabolic activity of the thyroid gland, leading to hyperthyroidism. The TSH-receptor (TSH-R) stimulating Igs (TSIs) with inflammatory cytokines mediate met-a-bolic changes in TSH-R–positive fibroblasts, target cells of orbital tissues, and supposedly lead to Graves orbitopathy. Evidence of the coexpression of TSH and IGF-I receptors on lymphocytes and specialized subsets of fibroblasts indicates that other self-antigens and TSI not linked to thyroid hormone production may contribute to extrathyroid inflammation in Graves disease. Identifying TSIs and differentiating them from nonfunctional TSH-R remain important goals. The tests for detecting TSH-R autoantibodies in Graves disease patients do not necessarily identify the pathogenic TSH-R antibodies that determine the clinical outcome of thyroid autoimmunity. Methods that measure the binding of antibodies in patient sera to TSH-R immobilized on the surface of plastic-coated tubes, plates, or beads display high analytical sensitivity and specificity. However, these methods do not measure the functional activity of Igs, nor do they discriminate between the Igs with stimulating, blocking, or neutral activity. Over the past 30 years, biological assays to detect TSI in the sera of Graves disease patients have been developed in individual laboratories. These experimental cell-based systems assess TSI activity on human thyroid cells, FRTL-5 primary rat thyrocytes, and Chinese hamster ovary cells transfected with recombinant human TSH-R. The protocols involve several days of cell culture with cell lines that are not quality controlled and require measuring radioactive cAMP released into the supernatant of cell lysates. Despite these limitations, the monitoring of TSI in Graves disease patients undergoing treatment with antithyroid medication and B-cell depletion indicate a promising role for TSI bioassays in evaluating response to therapy. To assess the relevance of TSI in the pathogenesis of Graves disease and its extrathyroid manifestations, the authors performed a controlled cross-sectional trial in a large cohort of Graves disease subjects. Two commercial TSI bioassays with quality-controlled cell lines that employ a luciferase reporter readout were compared with anti-TSH-R binding assays for their clinical sensitivity and specificity in Graves disease and Graves orbitopathy. The authors tested TSI in two reporter cell lines designed to measure Igs binding the TSH-R and transmitting signals for cAMP/CREB/cAMP regulatory element complex-dependent activation of luciferase gene expression. The responsiveness of the novel chimeric (Mc4) TSH-R (amino acid residues 262–335 of human TSH-R replaced by rat LH-R) to TSI was compared with the wild-type TSH-R. The authors found that all hyperthyroid Graves disease/Graves orbitopathy patients were TSI positive. TSIs were detected in 150 of 155 (97 percent, Mc4) and 148 of 155 (95 percent, wild type) Graves orbitopathy patients, six of 45 (13 percent, Mc4) and 20 of 45 (44 percent, wild type) mostly treated Graves disease subjects, and none of 40 (Mc4) and one of 40 (wild type) controls. Serum TSI titers were three- and eight-fold higher in Graves orbitopathy versus Graves disease and controls, respectively. All patients with diplopia and optic neuropathy, as well as smokers, were TSI positive. TSI strongly correlated with Graves orbitopathy activity (r=0.87 and r=0.7; both P<0.001) and severity (r=0.87 and r=0.72; both P<0.001) in the Mc4 and wild-type bioassays, respectively. Clinical sensitivity (97 versus 77 percent; P<0.001) and specificity (89 versus 43 percent; P<0.001) of the Mc4/TSI were greater than TSH-R antibody (TRAb) in Graves orbitopathy. All 11 of 200 (5.5 percent) TSI-positive/TRAb-negative patients had Graves orbitopathy, whereas all seven of 200 (3.5 percent) TSI-negative/TRAb-positive subjects had only Graves disease. The authors concluded that the novel Mc4/TSI is a functional indicator of Graves orbitopathy activity and severity.

Lytton SD, Ponto KA, Kanitz M, et al. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. J Clin Endocrinol Metab. 2010;95:2123–2131.

Correspondence: George J. Kahaly at kahaly@ukmainz.de

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Detecting MRSA from positive blood cultures Detecting MRSA from positive blood cultures

Hospital-acquired and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections have caused elevated morbidity and mortality rates and substantially increased health care costs. First isolated in the 1960s, hospital-acquired (HA)-MRSA is now endemic in most U.S. hospitals and long-term–care facilities. Classically associated with skin and soft tissue infections, community-acquired (CA)-MRSA has been involved in an increasing number of cases of bacteremia and sometimes fatal invasive disease. Regardless of its origin, a major financial burden has been placed on the health care industry due to MRSA-related bacteremia that stem from extended hospital stays. The authors conducted a multi-center study to compare the performance of a novel chromogenic medium, Spectra MRSA agar (Remel), with that of traditional culture to screen for MRSA from positive blood cultures. Blood specimens were inoculated into aerobic and anaerobic blood culture bottles (site A, BacT/Alert FA [aerobic] and BacT/Alert FN [anaerobic]; site B, Standard Aerobic/F and Bactec Peds Plus/F [aerobic] and Lytic/10 Anaerobic/F [anaerobic]; site C, VersaTrek Redox 1 [aerobic] and VersaTrek Redox 2 [anaerobic]; site D, Plus Aerobic/F and Lytic/10 An-aerobic/F). This was followed by incubation in an automated blood culture system (site A, BioMérieux BacT/Alert; sites B and D, BD Bactec; site C, Trek Diagnostics VersaTrek) for up to five days. Positive blood cultures, defined as Gram-positive cocci upon Gram staining, were subcultured onto Spectra MRSA agar and blood agar, which is the gold standard. Following aerobic incubation at 35°C, Spectra MRSA plates were observed for denim blue colony growth at 24- and 48-hour time intervals, indicating MRSA. Blood agar plates were observed for up to 48 hours for suspected S. aureus colonies that were typically yellow, catalase positive, and composed of Gram-positive cocci often demonstrating beta-hemolysis. Suspected MRSA colonies from Spectra MRSA and blood agar plates were tested with the Oxoid PBP2’ latex agglutination test (Remel) and the oxacillin Etest (BioMérieux) according to an established protocol for MRSA confirmation. The minimal inhibitory concentrations (MICs) were determined as defined by guidelines of the Clinical Laboratory Standards Institute. True positives were defined as denim blue colonies on Spectra MRSA agar that were identified as MRSA by the Oxoid PBP2’ test and oxacillin Etest (at least 4 µg/mL) or S. aureus PBP2’-negative colonies with an oxacillin MIC of 4 to 6 µg/mL. False positives were defined as denim blue methicillin-susceptible S. aureus (MSSA) colonies on Spectra MRSA agar. True negatives were defined as the absence of denim blue colonies on Spectra MRSA agar that was confirmed negative for MRSA by blood agar and standard techniques. False negatives were defined as confirmed MRSA colonies on blood agar that did not grow on Spectra MRSA agar. The combined sensitivity and specificity of Spectra MRSA agar for detecting MRSA were 96 percent and 99.6 percent at 24 hours and 99.4 percent and 98.5 percent at 48 hours. The authors concluded that the data presented in their report demonstrate that Spectra MRSA agar can, with high sensitivity and specificity, rapidly identify and differentiate MRSA from other Gram-positive cocci recovered from positive blood cultures, providing guided antimicrobial therapy in a timely fashion.

Peterson JF, Dionisio AA, Riebe KM, et al. Alternative use for Spectra MRSA chromogenic agar in detection of methicillin-resistant Staphylococcus aureus from positive blood cultures. J Clin Microbiol. 2010;48:2265–2267.

Correspondence: Nathan A. Ledeboer at nledeboe@mcw.edu

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444444444444444444 Troponin turnaround time and the emergency department

The number of patients presenting for emergency department care has been rapidly increasing. A consequence of increasing numbers of patients and decreasing numbers of facilities for treating these patients is crowding in the nation’s emergency departments. ED crowding is associated with poorer patient satisfaction, lower quality of care, treatment delays, and nontreatment of acute painful conditions. Ambulance diversion secondary to crowding is associated with increased door-to-needle time for patients receiving thrombolytic therapy for acute myocardial infarction, and prolonged ED boarding has been associated with a higher risk of death in critically ill patients. Increases in the number of ED visits may tax hospital-based laboratories. Studies have identified laboratory turnaround time as a barrier to patient processing times and have indicated that it increases lengths of stay. Furthermore, critical laboratory results may be delayed during episodes of ED crowding, leading to treatment delays and worse outcomes. To study the relationship between ED crowding and hospital laboratory turnaround time, the authors evaluated the association between ED patient volume and troponin TAT (TTAT). It is worthwhile to evaluate TTAT because the timely availability of these results guides clinicians in patient care decisionmaking, initiation of hospital admissions, and treatment for conditions such as acute coronary syndromes. The authors conducted a retrospective cohort review of patients at five academic, tertiary care emergency departments in the United States. They collected data on all adult patients seen in each ED for troponin laboratory testing during January, April, July, and October 2007. Primary predictor variables were two ED patient volume measures at the time the troponin test was ordered—number of all patients in the ED/number of beds (occupancy) and number of admitted patients waiting for beds/beds (boarder occupancy). The outcome variable was the troponin turnaround time. Adjusted covariates included patient characteristics, triage severity, season (month of the laboratory test), and site. Multivariable adjusted quantile regression was used to assess the association of ED volume measures with TTAT. The authors reviewed 9,492 troponin tests. They determined that median TTAT for this cohort was 107 minutes (interquartile range [IQR], 73–148 minutes). Median occupancy for this cohort was 1.05 patients (IQR, 0.78–1.38 patients), and median boarder occupancy was 0.21 (IQR, 0.11–0.32). Adjusted quantile regression demonstrated a significant association between increased ED patient volume and longer times to TTAT. For every 100 percent increase in census, or number of boarders over the number of ED beds, respectively, there was a 12-minute (95 percent confidence interval [CI], 9–14) or 33-minute (95 percent CI, 24–42) increase in TTAT. The authors concluded that increased ED patient volume is associated with longer hospital laboratory processing times. Prolonged laboratory turnaround time may delay recognition of conditions in the acutely ill, potentially affecting clinician decisionmaking and the initiation of timely treatment. Laboratory turnaround time as a patient throughput measure and factors that may be associated with prolonging laboratory TAT should be further investigated.

Hwang U, Baumlin K, Berman J, et al. Emergency department patient volume and troponin laboratory turnaround time. Acad Emerg Med. 2010;17:501–507.

Correspondence information not available.

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Clinical pathology abstracts editor: Michael Bissell, MD, PhD, MPH, professor, Department of Pathology, Ohio State University, Columbus.
 
 
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