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How to diagnose axial spondyloarthritis early.

BACKGROUND: Chronic low back pain (LBP), the leading symptom of ankylosing spondylitis (AS) and undifferentiated axial spondyloarthritis (SpA), precedes the development of radiographic sacroiliitis, sometimes by many years. OBJECTIVE: To assign disease probabilities and to develop an algorithm to help in the early diagnosis of axial SpA. METHODS: Axial SpA comprises AS and undifferentiated SpA with predominant axial involvement. Clinical features include inflammatory back pain (IBP), alternating buttock pain, enthesitis, arthritis, dactylitis, acute anterior uveitis, a positive family history, psoriasis, inflammatory bowel disease, and good response to NSAIDs. Associated laboratory findings include raised acute phase reactions, HLA-B27 association, and abnormalities on skeletal imaging. Sensitivities, specificities, and likelihood ratios (LRs) of these parameters were determined from published studies. A 5% prevalence of axial SpA among patients with chronic LBP was used. The probability of the presence of axial SpA, depending on the presence or absence of the above clinical features of SpA, was determined. A probability of > or = 90% was used to make a diagnosis of axial SpA. RESULTS: The presence of inflammatory back pain features increased the probability of axial SpA from the background 5% prevalence to 14%. The presence of 2-3 SpA features was necessary to increase the probability of axial SpA to 90%. The highest LRs were obtained for HLA-B27 and MRI. Diagnostic algorithms to be used in daily practice were suggested. CONCLUSIONS: This approach can help clinicians to diagnose with a high degree of confidence axial SpA at an early stage in patients with IBP who lack radiographic sacroiliitis.

Axis, Cervical Vertebra↗

The effect of saliva specimen collection, handling and storage protocols on hepatitis C virus (HCV) RNA detection by PCR.

OBJECTIVES: Commercial assays can now be adapted to detect salivary anti-hepatitis C virus (HCV) antibodies, increasing the potential of saliva as a non-invasive diagnostic specimen suited to surveillance and epidemiological studies. However, current diagnostic algorithms involve confirmation of HCV infection by RT-PCR. Manipulation and storage conditions of serum can influence the stability of viral RNA. This study examined whether varying specimen collection, handling and storage protocols also affected subsequent HCV RNA detection by RT-PCR applied to saliva specimens. METHODS: Whole unstimulated saliva, together with saliva samples collected in two commercially available devices (Salivette and Omnisal) were obtained from 50 HCV seropositive intravenous drug users. The specimens were subjected to a number of handling and storage conditions, including heat treatment and prolonged storage, then examined for HCV RNA by RT-PCR using primers derived from the 5' non-coding region (5'NCR). RESULTS: HCV RNA was detected in saliva samples from 25 (50%) of the patients. No single collection device or handling procedure identified all the subjects with HCV RNA positive saliva though whole saliva yielded the greatest number of positive results. CONCLUSIONS: Collection and processing of saliva specimens for RT-PCR analysis is complex. At present, detection of salivary HCV RNA by PCR is not sufficiently sensitive for use as a diagnostic tool in epidemiological studies.

Adult↗

[Pathological features of light chain nephropathy].

OBJECTIVE: To investigate the pathologic features and diagnostic algorithm of light chain nephropathy (LCN). METHODS: Seven cases of LCN were studied by light microscopy, electron microscopy and immunolabeling of light chains (kappa, lambda) by immunofluorescence and immunoelectron microscopy. RESULTS: The histopathology of 7 cases by light microscopy was variable, with 3 cases showing nodular glomerulosclerosis, 1 case showing mild to moderate mesangial proliferation, and 3 cases showing cast nephropathy with minimal glomerular change. Immunofluorescence study revealed positive staining of a single type of light chain in mesangium (nodular pattern) or along glomerular basement membrane (linear), along tubular basement membrane and around arteriolar walls in all the 7 cases. Ultrastructurally, electron-dense granular deposits were identified in mesangium, subendothelial aspect of glomerular basement membrane, outer aspect of tubular basement membrane and arteriolar walls. Immunogold labeling of light chains showed distinct labeling of a single type light chain in the granular electron-dense materials (5 cases being kappa-positive and 2 being lambda-positive). CONCLUSIONS: LCN typically shows nodular glomerulosclerosis. The ultrastructural change is characteristic and important for diagnosis. Immunolabeling of light chains by immunofluorescence and immunoelectron microscopy carries further diagnostic value, especially in cases with minimal light microscopic change.

Adult↗

Potential impact of pediatric MR urography on the imaging algorithm in patients with a functional single kidney.

OBJECTIVE: The purpose of this study was to evaluate the potential of MR urography in the assessment of children with a suspected "functional single kidney." SUBJECTS AND METHODS: Sixty patients (age range, 2.7 weeks to 15.7 years) who had been referred for assessment of a suspected functional single kidney underwent MR urography in addition to detailed sonography of the urinary tract and the currently indicated standard imaging. The results of the conventional imaging ((99m)Tc-dimer captosuccinic acid scintigraphy, voiding cystourethrography, and genitography) were compared with the results of sonography and MR urography; surgical findings served as the gold standard if available. RESULTS: Twenty-six patients had a single kidney. The other diagnoses were six contralateral multicystic dysplastic kidneys, two normal ectopic kidneys, one crossfused double system, and 25 ectopic or dysplastic renal buds. Scintigraphy detected all normal kidneys, two ectopic kidneys, and two dysplastic renal buds. Detailed sonography missed two ectopic kidneys and two orthotopic dysplastic renal buds, but one additional renal bud that could not be confirmed on other imaging techniques (accuracy, 91.7%; sensitivity, 88.2%; specificity, 96.2%) was suspected. MR urography results were correct in all patients and verified in all 13 with surgical correlation. CONCLUSION: MR urography allows a reliable assessment of renal and ureteral anatomy and of dysplastic or ectopic renal buds, even in non- or poorly functioning systems. MR urography therefore has the potential to replace the currently used excretory urography and scintigraphy. In patients with a suspected functional single kidney a detailed sonographic study and MR urography should be considered the diagnostic algorithm of choice.

Adolescent↗

[Pathologic feature and diagnosis of pulmonary alveolar proteinosis].

OBJECTIVE: To describe the pathologic features and diagnostic algorithm of pulmonary alveolar proteinosis (PAP). METHODS: Thirty-nine biopsy and postmortem cases of PAP were studied by light microscopy and histochemical staining using periodic acid-Schiff (with digestion) (PAS-D), mucicarmine (with digestion) (mucicarmine-D) and alcian blue. RESULTS: Histologically, the affected lung tissue displayed the following characteristic features: (1) alveoli and some of the small bronchioles were filled with eosinophilic and fine granular proteinaceous material with needle-like clefts; (2) proteinaceous material was seen admixed with various numbers of degenerated and sometimes exfoliated pneumocytes; (3) pneumocytes were hyperplastic; (4) alveolar capillaries and alveolar septa had become hyperemic, but pulmonary interstitial inflammation was not obvious; (5) no significant inflammation was identified in the bronchial wall; (6) compensating emphysema was noted in the surrounding lung parenchyma. Fragments of eosinophilic, finely granular proteinaceous material with needle-like clefts were also found in the bronchoalveolar lavage fluid under light microscopy. The proteinaceous material was stained red by PAS-D. The staining for mucicarmine-D was negative, while alcian blue staining was either weakly positive (faint blue staining) or negative. Pathologic examination of lung biopsies and bronchoalveolar lavage fluid thus remaines the gold standard for diagnosis of PAP. CONCLUSIONS: Identification of homogeneous, eosinophilic, finely granular and PAS-D-positive proteinaceous material with needle-like clefts in alveolar spaces or bronchoalveolar lavage fluid is of diagnostic importance in PAP. Bronchoalveolar lavage, being a relatively safe and non-invasive procedure, can be a useful adjunct in arriving at the final conclusion.

Adult↗

The presence of microscopic hematuria detected by urine dipstick test in the evaluation of patients with renal colic.

Urolithiasis is a common diagnosis in patients presenting at our hospital with flank pain. One of the most important steps in the diagnostic algorithm of renal colic is the presence of hematuria, but this fact has been challenged by authors reporting a negative urinalysis for microscopic hematuria in about 9-18% of such patients. Our aim was to investigate whether the same results are obtained when a sample of urine is tested with a urine dipstick test (UDT) at the time of the initial examination. Data from patients with the clinical diagnosis of renal colic examined at the emergency department of our hospital were reviewed, and the sensitivity of hematuria in urine samples tested by UDT was recorded in a group consisting of patients for whom imaging showed evidence of a stone >3 mm in size. In cases in which UDT was negative, or showed only traces of red blood cells (RBCs), a formal urinalysis was performed. A total of 609 patients were finally included in the study, with a mean age of 49.2 years. Average stone size was 5.8 mm, located mainly in the lower part of the ureter. Dipstick analysis was positive for hematuria in 92.9%. A urinalysis, with a cut-off point of less than three red blood cells per high power field, was used as a means to verify the results of the UDT in 17.8% of cases: in 7.1% of UDT negative patients and 10.7% of patients with traces of blood. The urinalysis was negative in 5.1% of patients, adding only 2% to the diagnostic accuracy of UDT. Therefore, our findings suggest that the sensitivity of a UDT for hematuria in cases of suspected renal colic has a high degree of accuracy when performed at the emergency department, and can be used as a first-line, low cost examination. A microscopic analysis may be useful when the UDT is negative or not clear enough, to verify the results.

Adult↗

Immunohistochemical estimation of cell cycle entry and phase distribution in astrocytomas: applications in diagnostic neuropathology.

An immunohistochemical method for assessing cell cycle phase distribution in neurosurgical biopsies would enable such data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in glial neoplasms, without the requirement for flow cytometric analysis. Paraffin-embedded sections of intracerebral gliomas (n = 48), consisting of diffuse astrocytoma (n = 9), anaplastic astrocytoma (n = 8) and glioblastoma (n = 31), were analysed by immunohistochemistry using markers of cell cycle entry, Mcm-2 and Ki67, and putative markers of cell cycle phase, cyclins D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis). Double labelling confocal microscopy confirmed that the phase markers were infrequently coexpressed. Cell cycle estimations by immunohistochemistry were corroborated by flow cytometric analysis. There was a significant increase in Mcm-2 (P < 0.0001), Ki67 (P < 0.0001), cyclin A (P < 0.0001) and cyclin B1 (P = 0.002) expression with increasing grade from diffuse astrocytoma through anaplastic astrocytoma to glioblastoma, suggesting that any of these four markers has potential as a marker of tumour grade. In a subset of glioblastomas (n = 16) for which accurate clinical follow-up data were available, there was a suggestion that the cyclin A:Mcm-2 labelling fraction might predict a relatively favourable response to radical radiotherapy. These provisional findings, however, require confirmation by a larger study. We conclude that it is feasible to obtain detailed cell cycle data by immunohistochemical analysis of tissue biopsies. Such information may facilitate tumour grading and may enable information of prognostic value to be obtained in the routine diagnostic laboratory.

Adult↗

The occult head and neck primary: to treat or not to treat?

In patients with cervical node metastases from an unknown primary malignancy, there is unresolved controversy regarding the utility of elective irradiation of putative pharyngeal primary sites as part of the management plan. We analysed the experience of the Peter MacCallum Cancer Institute to assess the risk of withholding mucosal irradiation in relation to the diagnostic algorithm used to exclude a primary lesion at the time of initial presentation. Between 1983 and 1992, 69 patients were seen with metastatic squamous or undifferentiated carcinoma in cervical nodes from an unknown primary site. Neck nodal stage was NX or N1 13%; N2 52%; N3 35%. Nodal disease was bilateral in 12% of patients. Investigations included examination under anaesthesia, with or without random biopsies, in 84%, and CT scanning of the head and neck in 55%. Treatment was by surgery alone in four patients, by radiotherapy alone in 23, and by combined modalities in 40. Two patients received no treatment. Seventeen were treated with palliative intent. The radiotherapy fields provided comprehensive coverage of the pharynx in only eight patients and partial coverage in five. The estimated overall 5-year survival was 36%. Eleven primary tumours were detected between 7 months and 7 years after the initial treatment, of which nine were in head and neck sites. This yielded an estimated incidence of 30% at 10 years, which is similar to the risk of the development of a second primary after the successful treatment of a known head and neck cancer. Only three patients (none of whom had a CT scan as part of their initial evaluation) manifested a primary in an unirradiated pharyngeal site within 2 years of treatment. As the accuracy of imaging improves, the risk of missing an occult primary lesion will decrease further. We conclude that the use of standardized diagnostic investigations incorporating modern imaging substantially eliminates the indication for comprehensive elective mucosal irradiation with its consequent morbidity. The overriding priority in patients who present with advanced neck disease is to secure regional control.

Actuarial Analysis↗

Examining the obstructed ureter with intraluminal sonography.

PURPOSE: Intraluminal sonography was used to define, differentiate and direct better treatment of obstructing ureteral lesions. MATERIALS AND METHODS: A total of 63 patients with a history of ureteral obstruction and suspected stricture were accrued for evaluation. All patients underwent retrograde contrast imaging, ureteroscopy and intraluminal sonography as part of a diagnostic algorithm. Specific sonographic criteria to differentiate lesions and stricture types were developed. Associated complicating variables defined on sonography included foreign bodies, submucosal stone fragments, ureteral wall fibrosis, mass lesions and adjacent vasculature. Endoscopic treatment was then performed with ultrasound guidance if technically feasible. RESULTS: A total of 63 ureters were evaluated with the preoperative diagnosis of ureteral stricture disease. All ureters were narrowed on contrast imaging in the segment where a stricture was suspected. On sonography 24 ureters (36%) had wall fibrosis with normal periureteral tissues. In general these strictures did well with endoscopic incision. Of the 67 ureters 13 (19%) were thickened or had edematous walls with normal architecture and without fibrosis. These patients all did well with expectant therapy. In contrast, 7 ureters (10%) were obstructed by segmental retroperitoneal fibrosis which did not respond to minimally invasive therapies. In addition, 8 ureters (12%) were obstructed by ureteral wall scarring and periureteral fibrosis, and required open surgical intervention. Ten ureteral strictures had adjacent vasculature, and endoscopic incisions under ultrasound guidance were directed safely away from these structures without associated morbidity. Calculi, stone fragments and foreign bodies embedded in the ureteral wall with associated inflammation were defined with sonography and responded to endoscopic therapies. The intraluminal sonographic diagnosis of ureteral endometriosis was made in 6 patients with a range of lesions from bright, hyperechoic blood filled cysts to an inhomogeneous fluid filled scar involving the wall and periureteral tissues. Primary ureteral carcinoma was also demonstrated in 2 patients after other diagnostic techniques failed. In 1 of these patients intraluminal sonography directed biopsies diagnosed submucosal tumor. Finally, 1 patient had a small periureteral urinoma on intraluminal sonography which was missed on other imaging studies. CONCLUSIONS: Intraluminal sonography is useful in patients with ureteral obstruction of unclear etiology as well as for selecting patients who may benefit from minimally invasive therapies and safely directing these treatments.

Adolescent↗

[The diagnostic and therapeutic procedures in pulmonary embolism: a survey in the Veneto Region].

BACKGROUND: Pulmonary embolism is one of the most frequent cardiopulmonary diseases, but it is often under- or misdiagnosed. In order to address this issue and to identify flow charts that are commonly used in pulmonary embolism diagnosis and treatment, 191 clinical wards of internal medicine, cardiology, geriatrics, pneumology and intensive care units, located in the Veneto Region, were surveyed. METHODS: An anonymous questionnaire was mailed to each ward in order to collect clinical diagnostic information on all pulmonary embolisms which occurred during 1993. Among the returned questionnaires, 114 (59.6%) had usable information for the analysis. RESULTS: The vast majority of participating centers reported in 1993 less than 10 pulmonary embolism events. No significant differences were observed between internal medicine, geriatrics, pneumology wards and intensive care units. The reported events, however, were slightly higher in the divisions of cardiology with an annual average of 12 events per center. First level diagnostic procedures, such as ECG, chest X-ray and arterial blood gas analysis were chosen and performed in all patients. Interestingly, Doppler echocardiography, which is often not included in official guidelines for pulmonary embolism diagnosis, was performed in 56% of the participating centers. On the contrary, ventilation-perfusion lung scanning, which is considered highly predictive in many diagnostic algorithms, was underutilized (35% perfusion scan, 20% ventilation scan). This underuse was probably due to technical and organizational difficulties. Pulmonary angiography, the most accurate procedure for the diagnosis of pulmonary embolism, was performed in 28% of the patients. During the acute phase, intravenous heparin was commonly used; 91% of patients received the infusion continuously, 4% intermittently. Thrombolysis was performed in 25% of the patients. The preferred drugs were recombinant tissue-plasminogen activator (67%), followed by urokinase (20%) and streptokinase (13%). To start thrombolytic therapy, 20% of the interviewed clinicians considered sufficient the evidence of clinical manifestations of pulmonary embolism confirmed by echocardiographic data. At discharge, prescription of oral anticoagulant drugs was common (78%) for at least 6 months (47%). Standardized procedures for the diagnosis and treatment of pulmonary embolism were already implemented in 13% of the participating centers. CONCLUSIONS: These data suggest a common effort to define unanimous conventional protocols in the management of pulmonary embolism. It should be underlined, however, that a particular attention to the clinical manifestations and a productive collaboration among clinicians with different expertise are required to improve the diagnosis and treatment of pulmonary embolism.

Diagnostic Imaging↗

[Therapy and prevention of deep venous thrombosis and pulmonary embolism in gynecology and obstetrics].

AIM: The aim of this paper is to present the latest developments in therapy and prophylaxis of deep vein thrombosis in gynecology and obstetrics. DATA EXTRACTION: The data presented in the paper have been extracted from the Current Contents database. In the introduction, the coagulation cascade is described, and certain coagulation abnormalities caused by deficiency or decreased activity of coagulation factors are highlighted. The most prominent signs of deep vein thrombosis in pregnant women are swelling and tenderness of the affected leg, sometimes accompanied with fever and leucocytosis. In pelvic thrombosis, swelling of the leg is often absent and such a condition may be mistaken for other abdominal emergencies. The diagnostic algorithm for deep vein thrombosis starts with the clinical Wells criteria. To confirm the diagnosis it is necessary to visualize the thrombus by one of the imaging methods. The value of D-dimer is limited by its low positive predictive value, particularly in pregnant women. Low weight molecular heparin's have lately almost replaced standard heparin in the treatment of the deep vein thrombosis in pregnant women for providing advantages of subcutaneous application, no need of laboratory control of coagulation parameters, lower risk of bleeding, and lower incidence of osteoporosis and heparin-induced thrombocytopenia. We list the recommendations of the American College of Chest Physicians published in 1991, which stratify pregnant women with deep vein thrombosis according to their medical history and laboratory parameters. We have specified the proposed approach according to: history of deep vein thrombosis due to transient risk factors; previous idiopathic deep vein thrombosis without anticoagulant therapy; previous deep vein thrombosis with thrombophylia; previous idiopathic deep vein thrombosis on anticoagulant therapy; laboratory-proven thrombophilia with no history of deep vein thrombosis; and recurrent deep vein thrombosis. Pregnant women with artificial heart valves may undergo one of three proposed treatments. Long preoperative hospitalization, prolonged operative procedures, extensive injuries of blood vein vessels on radical procedures, frequently present accompanying malignant disease or previous irradiation therapy and postoperative bed-ridden period after major gynecologic procedures increase the risk of perioperative development of deep vein thrombosis. It is necessary to appraise this risk, classify patients in one of the four groups, and administer appropriate measures. Patients at a low risk of developing thromboembolic incidents are those younger than 40, undergoing procedures lasting less than 30 minutes and without other risk factors. The risk is moderate in patients aged 40-60 without other risk factors, or those aged under 40 having malignancy have high risk. Patients at a very high risk are those with a history of deep vein thrombosis, thrombophilia or pelvic exenteration. In the last decade there has been a great advancement in the diagnostics and treatment of deep vein thrombosis. The discovery of genetic disorders predisposing the patient to the development of a thromboembolic incident (thrombophilia) has changed our position concerning the duration of anticoagulant therapy, and nowadays it can last from several months to a lifetime regimen, depending on the underlying mechanism causing the incident. A significant improvement in therapy has occurred with the introduction of low molecular weight heparins in clinical practice. Their therapeutic value is equal to standard heparin, and their advantages include easier dosage and less nursing time as well as in a lower incidence of side effects such as haemorrhage. For these reasons, low molecular weight heparin has almost completely replaced standard heparin in the western world.

Adult↗

[False aneurysms of lower extremity arteries: noninvasive preop diagnosis with magnetic resonance angiography and Doppler ultrasonography].

The purpose of this study was to work out a diagnostic algorithm to be used in patients surgically treated because of a false aneurysm of arteries supplying the lower limb. The study includes preoperative vessel evaluation as well as treatment results assessment with MRA and US methods. Examinations included until now 16 patients with clinical false aneurysm suspicion. Most cases presented false aneurysms being complications after arterial graft implantation, in two patients, who were not previously operated, diagnosed false aneurysms were the result of injury. We performed 23 examinations (7 of which were postoperative treatment result evaluation examinations). Examinations were performed on MR equipment with a 1.5 T field induction. The 2D TOF with traveling presaturation method was used. Primary data and reconstructed (MIP) angiograms were analyzed by a radiologist having no access to clinical information and previous examination results. Ultrasound duplex doppler examinations were performed with 7 MHz linear probe. The MRA examinations visualized 7 false aneurysms of the lower Y-graft junction. Clinical verification, ultrasonography examinations and surgery confirmed the existence of 6 aneurysms of the Y-graft as well as 5 out of 6 diagnosed in the ileofemoral graft junctions area. The post-traumatic aorta aneurysm and the postarteriographic femoral aneurysm were also confirmed. Two false positive MRA diagnoses were due to dilatation of the artery below the graft junction, in one case it was a dilatation of the vessel below a stenosis. Furthermore, the MRA helped diagnosing stenoses and occlusions in femoral arteries and common iliac artery.

Adult↗

Comparative multicentre study of a panel of thyroid tests using different automated immunoassay platforms and specimens at high risk of antibody interference.

The introduction of automation for immunoassays in recent years has brought about important and evident improvements in assay precision. Increasing standardization and comparability between platforms should enable the development of clinical guidelines and diagnostic algorithms for appropriate clinical decision making. A continuing source of variation between different automated immunoassay platforms is the sporadic effect of interfering antibodies or substances, thus causing aberrant results not supporting the patient's clinical status. The aim of this study was to describe current thyroid panel variation between automated immunoassay platforms including population specimens at risk of antibody interference. A multisite design with laboratories in three different countries using four different automated immunoassay platforms (Roche-Boehringer Mannheim Elecsys (Italy), Roche-Boehringer Mannheim ES300 (Wales), Bayer Immuno 1 and the Bayer ACS:180 evaluated the thyroid panel of thyrotropin (TSH), triiodothyromine (T3), free thyroxine (FT4) and free triiodothyronine (FT3). A common set of 158 randomly selected patient samples of non-thyroid and thyroid disorders, with and without treatment, was tested. Included were 62 patient samples at risk for endogenous antibody interference with high antimicrosomal antibody, anti-TSH receptor antibody and increased rheumatoid factor sub-populations. Across all controls and between platforms, precision measurements were comparable and varied between 0.7% and 12.8% for TSH, 2.8% and 13% for FT4, 1.8% and 10.5% for FT3 and 3.1% and 16% for T3 assay. Acceptable correlation and reproducibility were found between the three Bayer Immuno 1 platforms at each country's site with all four thyroid panel assays demonstrating r-values of 0.989 to 1.000 and slopes of 0.915 to 1.078. Comparisons between the different platforms showed acceptable correlation for all thyroid panel assays. Specimens containing rheumatoid factor were associated with a significantly increased variation between systems for the FT4 and FT3 assays (p < 0.01). This effect did not appear to be selective for a given platform. For specimens with raised autoimmune antibodies and therefore at risk of assay antibody interference, no variation could be observed between the platforms.

Antibodies↗

Excess triiodothyronine as a risk factor of coronary events.

BACKGROUND: Abnormalities in cardiac function, eg, arrhythmias and congestive heart failure, often accompany thyrotoxicosis. A relationship between thyroid hormone excess and the cardiac complications of angina pectoris and myocardial infarction (MI) remains largely speculative. METHODS: The results of thyroid function studies on blood samples drawn from a total of 1049 patients (aged 40 years or older) immediately on emergency medical admission were related to frequencies of angina pectoris and myocardial infarction as determined according to current diagnostic algorithms. After 3 years, those patients who had initially presented with angina pectoris or acute MI were observed for subsequent coronary events; of these (n=185), 98% of the subjects (n=181) could be reevaluated. RESULTS: On hospital admission, the relative rate of angina pectoris and MI was markedly high (odds ratio, 2.6; 95% confidence interval, 1.3-5.2; P=.007) in patients with elevated serum free and total triiodothyronine (T(3)) levels. An initially elevated free T(3) level was a risk factor for subsequent coronary events during the 3-year follow-up (adjusted odds ratio, 4.8; 95% confidence interval, 1.3-17.4; P=.02). CONCLUSIONS: An elevation of serum free T(3) levels at hospital admission is associated with a 2.6-fold greater likelihood of the presence of a coronary event. Moreover, an initially elevated T(3) level is associated with a 3-fold higher risk of developing a subsequent coronary event during the next 3 years. Excess T(3) seemed to be a factor associated with the development and progression of acute myocardial ischemia.

Adult↗

Overuse of transthoracic echocardiography in the diagnosis of native valve endocarditis.

BACKGROUND: Infective endocarditis (IE) is a diagnostic challenge due to its variable presentation and nonspecific clinical findings. The use of transthoracic echocardiography (TTE) has greatly improved the ability to diagnose IE early, and therefore reduce high mortality and morbidity rates. However, reliance on TTE to exclude IE may lead to overuse of this technology in patients with a low pretest probability of IE. METHODS: Prospective observational study of all patients referred for TTE to diagnose IE. Clinical factors were used to determine likelihood of IE based on the Von Reyn criteria, and the resulting diagnostic probabilities were correlated with abnormal TTE findings as well as duration of antibiotic therapy. RESULTS: One hundred eleven TTEs performed on 98 patients were included in the analysis. Over 70% of TTEs were obtained in patients in whom the diagnosis of IE was rejected by Von Reyn criteria. Therapeutic management (prolonged antibiotic administration) was associated significantly with Von Reyn categorization, and not significantly affected by TTE results. CONCLUSIONS: Most TTEs are obtained in patients with a low pretest probability of IE and do not contribute to therapeutic decision making. We propose a diagnostic algorithm to direct the use of TTE to patients with intermediate or high pretest probability of IE.

Adolescent↗

Plasma D-dimers in the diagnosis of venous thromboembolism.

Clinical suspicion for venous thromboembolism (VTE) mandates objective testing to confirm or exclude the diagnosis. However, current imaging modalities are imperfect because of a small but important risk of complications with invasive techniques or limited sensitivity with noninvasive ones. A diagnostic tool for VTE is needed that is noninvasive and highly accurate, allowing immediate treatment decisions to be made in most cases. Plasma D-dimers (D-ds), specific cross-linked fibrin derivatives, partially fulfill these criteria in that they are sensitive markers for thrombosis but lack specificity. They therefore cannot be used to make a positive diagnosis of VTE; however, they generally have high negative predictive value and are useful as an exclusionary test, a potentially important role given that VTE is eventually ruled out in most patients investigated. Clinical management studies are clarifying the role of D-ds in the diagnostic paradigm of VTE: negative ultrasound and D-d findings obviate the need for serial imaging in suspected deep vein thrombosis, and anticoagulant therapy can be safely withheld in patients with non-high clinical suspicion for pulmonary embolism and non-high probability ventilation perfusion scan if D-d test results are negative. More recently, the combination of a negative SimpliRED (AGEN Biomedical Ltd, Brisbane, Australia) D-d result and low clinical suspicion derived using a formal scoring system has been shown to exclude deep vein thrombosis and pulmonary embolism and to obviate the need for imaging. Several different D-d assays are now available, and clinicians should be aware of the performance characteristics of the test used before incorporation into diagnostic algorithms as these will differ between assays, and the results of clinical management studies cannot necessarily be safely extrapolated to assays other than those specifically evaluated. If alternative assays are to be substituted, these should consistently have been shown to possess equivalent or greater sensitivity.

Biomarkers↗

Accuracy of ultrasonography in predicting celiac disease.

BACKGROUND: Various ultrasonographic (US) signs have been reported in overt celiac disease (CD). The aim of this study was to investigate the diagnostic accuracy of 6 US parameters in predicting CD. METHODS: One hundred sixty-two consecutive patients with chronic diarrhea (n=105), iron deficiency anemia (n=25), or dyspepsia (n=32) underwent anti-endomysial IgA antibody determination and duodenal biopsy. Moreover, US evaluation of 6 parameters (ie, fasting gallbladder volume, transverse diameter of small bowel loops, thickness of the small bowel wall, pattern of peristalsis, presence of free abdominal fluid, and diameter of the mesenteric lymph nodes) was done by 2 operators blind to the serological and histological findings. The pretest probability of CD was estimated to be between 5% and 10%. The percentage of agreement between US and histologic findings, the sensitivity, specificity, positive and negative likelihood ratios, and the posttest probability for positive and negative results were calculated. RESULTS: Celiac disease was diagnosed in 12 patients (7.4%). An increased gallbladder volume, the presence of free fluid in the abdominal cavity, and enlarged mesenteric lymph nodes showed a specificity of 96%, 96%, and 97%, respectively (95% confidence intervals [CIs], 92%-99%, 93%-99%, and 95%-99%), whereas the presence of dilated small bowel loops with increased fluid content and increased peristalsis had a sensitivity of 92% and 83%, respectively (95% CIs, 76%-100% and 62%-100%). Eleven (92%) of the 12 patients with celiac disease and 35 (23%) of the 150 patients who did not have the disease had at least 1 US sign (P=.001); all of the US signs were concomitantly present in 4 patients with CD (33%) and 1 patient without CD (0.6%) (P=.001). CONCLUSION: Ultrasonographic evaluation can accurately predict CD but its place in the diagnostic algorithm depends upon the probability of the disease in the considered population.

Adolescent↗

A rapid test for infectious and inflammatory enteritis.

BACKGROUND: Inflammatory illnesses are an indication for specific diagnostic studies and possible antimicrobial therapy. The presence of fecal leukocytes has been used as a marker of inflammatory diarrhea; however, microscopic examination of the fecal smear is unreliable if the specimen is transported, refrigerated, frozen, or collected by swab. OBJECTIVE: To evaluate a rapid, sensitive, semiquantitative test for detection of fecal leukocytes using antilactoferrin latex bead agglutination (LFLA), a test that remains sensitive even after specimens are refrigerated, frozen, or stored on swabs. METHODS: LFLA titers were determined in stool specimens from previously healthy volunteers before and after experimental infection with different enteric pathogens and from patients with nosocomial diarrhea caused by Clostridium difficile. RESULTS: Healthy controls and subjects with noninflammatory diarrhea caused by Vibrio cholerae consistently demonstrated LFLA titers less than 1:50. In contrast, subjects with inflammatory diarrhea caused by Shigella species and C difficile had markedly elevated titers. Titers for subjects with experimental shigellosis ranged from 1:50 to 1:3200, with seven (78%) of nine at 1:400 or greater. Titers for patients with C difficile enteritis ranged as high as 1:1200, with six (50%) of 12 at 1:400 or greater. Subjects with experimental enteropathogenic Escherichia coli infection also had elevated titers, ranging from 1:100 to 1:1600, with three (43%) of seven at 1:400 or greater. Titers for subjects with experimental enterotoxigenic E coli infection were moderately elevated, with nine (53%) of 17 ranging from 1:50 to 1:200 (only one [6%] of 17 was > or = 1:400), suggesting a mild inflammatory process. CONCLUSIONS: The fecal LFLA assay distinguishes inflammatory from noninflammatory diarrhea, may provide new information on mildly inflammatory processes, and may be a useful, rapid test in a diagnostic algorithm for acute, infectious diarrheal illnesses.

Communicable Diseases↗