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Controlled oral food challenges in children--when indicated, when superfluous?

The diagnostic work-up of suspected food allergy includes the skin prick test (SPT), the measurement of food specific immunoglobulin E (IgE) antibodies using serologic assays, and more recently the atopy patch test (APT). For specific serum IgE and the SPT, decision points have been established for some foods allowing prediction of clinical relevance in selected cases. The APT may be helpful, especially when considered in combination with defined levels of specific IgE. Controlled oral food challenges still remain the gold standard in the diagnostic work-up of children with suspected food allergy. Most food allergic children will lose their allergy over time. As there is no laboratory parameter, which can accurately predict when clinical tolerance has been developed, controlled oral food challenges are the measure of choice. In this article, the current knowledge of predictors for the outcome of oral food challenges is reviewed and proposals for the daily practical work-up in the case of suspected food related clinical symptoms are presented.

Algorithms↗

Diagnostic and prognostic use of DNA image cytometry in cervical squamous intraepithelial lesions and invasive carcinoma.

In the fight against cervical malignancy and its precursors, several adjuvant diagnostic methods have been proposed to increase the accuracy of cytologic and histologic diagnoses. Because chromosomal aneuploidy has been accepted as an early key event in tumorigenesis caused by genetic instability, the cytometric equivalent of chromosomal aneuploidy detected by DNA image cytometry (DNA-ICM) may serve as a marker of neoplasia. During the last decade, the appearance of a new generation of hardware with high processing and storage capacities, together with the development of appropriate software, has facilitated the development of high-performance DNA-ICM systems. International consensus on the clinical application of DNA-ICM has been reached. According to the statements of Task Force 8 of the International Consensus Conference on the Fight Against Cervical Cancer, indications for DNA-ICM include the identification of prospectively malignant cells in squamous intraepithelial lesions (SILs) and atypical squamous cells of undetermined significance (ASCUS). The European Society of Analytical Cellular Pathology consensus reports on DNA-ICM have provided standardized technical details on performance, terms, and algorithms for diagnostic data interpretation and quality-assurance procedures. Increasing biologic evidence and clinical data have confirmed the utility of DNA-ICM as an adjuvant method suitable for determining the diagnosis and prognosis of cervical intraepithelial lesions and invasive carcinoma. Patients with ASCUS and low-grade SIL diagnoses that reveal DNA euploidy may return for normal screening intervals, whereas the detection of DNA aneuploidy indicates that these lesions should be removed. Formerly a research tool, today, standardized DNA-ICM has become a useful and low-cost laboratory method to establish objectively and reproducibly an early diagnosis of prospectively progressive cervical intraepithelial lesions at a high-quality level. DNA-ICM may further contribute to the monitoring of treatment in patients with invasive cervical malignancies.

Adult↗

[The role of non-invasive diagnostics of pulmonary embolism in the optimization of treatment].

177 patients with pulmonary embolism (PE) were examined to study the information value of transthoracal echoCG in early diagnostics of the disease, the possibility of noninvasive evaluation of its severity, and possibility of determining indications for thrombolytic therapy (TLT) on basis of such evaluation. The results show that the sensitivity of such a sign as elevation of pulmonary artery pressure (PAP) by 30 mmHg, is 95%, provided that the patient does not have severe or moderate concomitant diseases cousing PAP elevation (postinfarction cardiosclerosis, chronic obstructive lung disease, valvular diseases etc.). The specificity of this sign, vs the control group, was 5%. Thus, elevation of PAP in patients with clinical manifestations of PE and without concomitant pathology, is a highly informative symptom of acute PE. The sensitivity of the parameter of right ventricular (RV) dilatation was 85%, of paradoxial ventricular septum motion--54%. In patients with PE of various degree of severity and concomitant diseases, high sensitivity of the above-listed sonographic signs of RVoverload goes together with their low specificity, which is not higher than 25%. This does not allow evaluating the degree of embolism and determining indications for TLT in these patients on basis of echoCG data. The authors of the article have developed an algorithm of diagnostic and therapeutic measures in patients with suspected PE.

Echocardiography, Doppler↗

Pathologic diagnosis of acute lymphocytic leukemia.

With present knowledge, the optimal management of individual patients with acute leukemia requires that every case be studied by morphology, cytochemistry, cytogenetic, immunologic and molecular techniques. An algorithm for diagnostic evaluation and classification of ALL is provided in Fig. 11. Other techniques, such as DNA or cDNA [figure: see text] microarray, are at present important research tools but have not yet had a major effect on patient care. More detailed studies of individual patients need to be conducted at specialized cancer centers, where preservation of cells, DNA, RNA, or protein is possible. Such investigations will yield important information on the clinical importance of the expression of various markers, the prevalence and relevance of bilineage and biphenotypic leukemias, and above all will reveal the mechanisms of leukemogenesis and of disease evolution. Such insights will further aid clinicians in treating ALL and in preventing refractory disease.

Adult↗

Strategies for surgical treatment of gallbladder carcinoma based on information available before resection.

HYPOTHESIS: Precise preoperative staging for gallbladder carcinoma is difficult, despite recent advances in hepatobiliary imaging. However, the most accurate preoperative staging may be possible by integrating preoperative key data. OBJECTIVE: To establish useful strategies for the surgical treatment of gallbladder cancer based on information available before resection. DESIGN: Retrospective review. SETTING: University hospital and tertiary referral cancer center. PATIENTS AND METHODS: From January 1, 1978, through March 31, 2001, 152 patients with gallbladder cancer underwent surgical resection with curative intent. Preoperative diagnoses of the T factor (image-T) and N factor (image-N) in the TNM classification were determined by evaluating all findings of diagnostic imaging, including ultrasonography, enhanced computed tomography, endoscopic ultrasonography, and angiography. The distribution of lymph node metastasis and prognostic factors were also analyzed. RESULTS: The overall diagnostic accuracy for image-T was 52.6% (95% confidence interval, 44.7%-60.6%) and was lower in patients with pT1 and pT2 disease (37.2% and 33.9%, respectively). However, image-T was a significant predictor of lymph node metastasis and patient outcome. Preoperative staging for N was more difficult, with only 24.5% (95% confidence interval, 12.4%-36.5%) of the node-positive patients being correctly diagnosed. An analysis of harvested lymph nodes showed that the cystic, pericholedochal, and posterosuperior peripancreatic nodes were the most prevalent sites of metastasis, and these were considered key nodes for the lymphatic spread of gallbladder cancer. By combining data on image-T and positivity of these key nodes, more accurate TNM staging was possible. Although an extended lymph node dissection provided significantly better survival in patients with pN2 disease, there was no survival advantage to more radical operations, including bile duct resection or pancreaticoduodenectomy. CONCLUSIONS: Although precise preoperative TNM staging for gallbladder carcinoma was difficult, the most accurate staging before resection was possible by integrating image-T classification and data from the intraoperative histopathologic examination of key lymph nodes. Based on this staging, we propose algorithms for the surgical treatment of gallbladder carcinoma.

Adult↗

New real-time strain imaging concepts using diagnostic ultrasound.

Two real-time strain imaging concepts and systems are presented. Both systems are based on a conventional ultrasound scanner that is connected to a PC with an A/D converter card for real-time data acquisition of rf data. Differential strain between successively acquired rf frames are estimated using phase root seeking. The first concept uses a special real-time implementation of manual elastography. In the second concept, denoted 'vibrography', the static compression is replaced by low-frequency axial vibration of the probe, still operating in quasistatic acquisition mode. The properties of both concepts are discussed with regard to noise and motion artefacts, and it is shown, using simulations and phantom experiments, that both imaging concepts yield the same kind of strain images. Vibrography has the advantage that no manual compression has to be applied, total compression can be very low and some motion artefacts are better suppressed.

Algorithms↗

Risk factors evaluation in some cardiovascular diseases.

Cardiovascular risk factors are associated with limitations of blood fluidity. Rheological behaviour of blood in transient flow may result from the internal organization, which in turn depends upon many parameters, which may be considered as possible elements of a profiling algorithm for diagnostic and prognostic values in various pathophysiological states. This study was designed to investigate haemorheological parameters in patients being treated for hypertension, coronary heart disease and myocardial infarct. On the basis of plasma viscosity, whole blood viscosity, haematocrit, red cell aggregation and red cell deformation, the risk was evaluated. In cases of hypertension there was a significant rise in plasma viscosity, whole blood viscosity, red cell aggregation and a fall in red cell deformability. In cases of coronary disease, plasma viscosity and red cell aggregation was increased, while in patients with myocardial infarcts, where the degree of severity is greater it was found that there was a significant rise in both plasma and whole blood viscosity. Haematocrit values were unaffected in all three groups.

Adult↗

Initial work-up and long-term follow-up in patients with phaeochromocytomas and paragangliomas.

Catecholamine-producing tumours may arise in the adrenal medulla (phaeochromocytomas) or in extra-adrenal chromaffin cells (paragangliomas). The most specific and sensitive diagnostic test is the determination of plasma or urinary metanephrine levels. The tumour can be located by computed tomography, magnetic resonance imaging and metaiodo-benzylguanidine scintigraphy. Patients are treated by tumour resection. Phaeochromocytomas and paragangliomas may be sporadic or the result of several genetic diseases: multiple endocrine neoplasia type 2, neurofibromatosis 1, von Hippel-Lindau disease, succinate dehydrogenase-phaeochromocytoma-paraganglioma syndrome. Familial cases are diagnosed earlier and are more frequently bilateral and recurrent than sporadic cases. About 10% of tumours are malignant, either at initial surgery or during follow-up. Recurrences and malignancy are more frequent in cases with large or extra-adrenal tumours and in the succinate dehydrogenase subunit B-related phaeochromocytoma-paraganglioma syndrome. Patients should be followed up indefinitely, particularly if they have familial or extra-adrenal tumours.

Adrenal Gland Neoplasms↗

Massive pulmonary embolism. Diagnostic and therapeutic strategies.

Massive PE is a devastating clinical entity often undiscovered until autopsy. Acute right ventricular failure may progress to death within minutes to hours after the embolic event and prompt diagnostic and therapeutic intervention are imperative. The diagnosis heavily relies on clinical suspicion together with ventilation-perfusion scanning. Echocardiography may have a role in select patients to aid in the recognition of PE with right ventricular failure and to guide therapy. Clinical instability may hinder the diagnostic evaluation and delay therapeutic intervention. Oxygen is administered and, when necessary, intubation and mechanical ventilation are undertaken. In the setting of hypotension supportive therapy includes vasoactive medications, such as norepinephrine. Intravenous fluids should be administered cautiously. Therapeutic options aimed directly at reducing the embolic burden include systemic thrombolytic therapy, surgical embolectomy, and the use of intrapulmonary arterial catheter techniques. In the absence of contraindications, thrombolytic therapy should be strongly considered in hypotensive patients. Surgical embolectomy for acute PE is controversial, but this modality appears to have a role in select patients. Various intrapulmonary arterial catheter techniques, with or without low-dose thrombolytic therapy, have been used successfully to reduce the embolic burden, although no particular technique appears to have clear advantages over others. Placement of an inferior vena caval filter may prevent additional, potentially fatal emboli and appears appropriate in select patients with massive emboli.

Algorithms↗

Assessment of deep vein thrombosis or pulmonary embolism by the combined use of clinical model and noninvasive diagnostic tests.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are relatively common diseases and are amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with use of the noninvasive imaging tests, but limitations exist. The standard first choice of investigation in patients with suspected DVT is compression ultrasonography (CUS). As with all tests, there is a potential for false-positive and false-negative results. The latter are especially an issue for calf vein thrombi, and this in part has led to the concept of serial CUS testing of the proximal venous system and not imaging of the calf. The premise of the repeat (serial) CUS test is that only thrombi that extend to the proximal system are clinically relevant, and these thrombi will be detected during subsequent testing. However, despite the safety of the serial CUS testing concept, it is inconvenient and expensive. The standard first choice of investigation in patients with suspected PE, the ventilation-perfusion (V/Q) lung scan is nondiagnostic in most cases. In the past few years, the diagnostic process has improved because of the validation of clinical models that accurately categorize patients as having low (5%), moderate (20% to 30%), or high probability (>60%) for venous thromboembolic disease. Among the improvements this provides is the elimination of serial CUS testing if the ultrasound results are normal and the clinical probability is low in patients with suspected DVT. In patients with suspected PE in whom further testing is necessary, determination of clinical probability allows selection of invasive (angiography) or noninvasive testing (serial ultrasound) in patients with non-high-probability V/Q scans. The fibrin degradation product D-dimer has had a high negative predictive value; negative results with enzyme-linked immunosorbent assay (ELISA) tests effectively rule out DVT or PE. In addition, a negative result with less-sentive D-dimer testing and a low clinical probability excludes DVT or PE.

Algorithms↗

Insights into latent class analysis of diagnostic test performance.

Latent class analysis is used to assess diagnostic test accuracy when a gold standard assessment of disease is not available but results of multiple imperfect tests are. We consider the simplest setting, where 3 tests are observed and conditional independence (CI) is assumed. Closed-form expressions for maximum likelihood parameter estimates are derived. They show explicitly how observed 2- and 3-way associations between test results are used to infer disease prevalence and test true- and false-positive rates. Although interesting and reasonable under CI, the estimators clearly have no basis when it fails. Intuition for bias induced by conditional dependence follows from the analytic expressions. Further intuition derives from an Expectation Maximization (EM) approach to calculating the estimates. We discuss implications of our results and related work for settings where more than 3 tests are available. We conclude that careful justification of assumptions about the dependence between tests in diseased and nondiseased subjects is necessary in order to ensure unbiased estimates of prevalence and test operating characteristics and to provide these estimates clinical interpretations. Such justification must be based in part on a clear clinical definition of disease and biological knowledge about mechanisms giving rise to test results.

Algorithms↗

Magnetic resonance direct thrombus imaging: a novel technique for imaging venous thromboemboli.

Invasive testing is now seldom required in patients with suspected venous thromboembolism (VTE). However, a corollary of noninvasive imaging is increased complexity as results are often yielded as probabilities rather than definitive answers and additional testing is frequently required following initial imaging. This creates a milieu in which misunderstandings and protocol violations are common, potentially leading to diagnostic errors. A highly accurate noninvasive imaging technique which allows immediate treatment decisions to be made is needed. Magnetic resonance direct thrombus imaging (MRDTI) is a novel technique which detects methaemoglobin in clot, allowing visualisation of thrombus without using intravenous contrast. It has two major advantages over conventional modalities which identify it as having the potential to fill this role. Firstly, direct visualisation of thrombus overcomes many of the pitfalls of conventional techniques, which have either identified thrombus as a filling defect or in terms of surrogates. Secondly, simultaneous imaging of the legs and chest allows a comprehensive assessment of thrombus load, minimising the importance of overlooked subsegmental pulmonary embolism (PE) and potentially facilitating more titrated treatment. Early data suggest MRDTI is highly accurate for the detection of both deep vein thrombosis (DVT) and PE, and ongoing out-come studies are evaluating the safety of withholding treatment in suspected DVT and PE on the basis of negative MRDTI alone. If favorable, a multi-centre outcome study evaluating cost-effectiveness as well as safety would be justified. Subject to further evaluation, this technique has the potential greatly to simplify and standardise the investigation of suspected VTE.

Algorithms↗

Comparing filtered backprojection and ordered-subsets expectation maximization for small-lesion detection and localization in 67Ga SPECT.

UNLABELLED: Iterative reconstruction of SPECT images has recently become clinically available as an alternative to filtered backprojection (FBP). However, there is conflicting evidence on whether iterative reconstruction, such as with the ordered-subsets expectation maximization (OSEM) algorithm, improves diagnostic performance over FBP. The study objective was to determine if the detection and localization of small lesions in simulated thoracic gallium SPECT images are better with OSEM reconstruction than with FBP, both with and without attenuation correction (AC). METHODS: Images were simulated using an analytic projector acting on the mathematic cardiac torso computer phantom. Perfect scatter rejection was assumed. Lesion detection accuracy was assessed using localization receiver operating characteristic methodology. The images were read by 5 nuclear medicine physicians. For each reconstruction strategy and for each observer, data were collected in 2 viewing sessions of 100 images. Two-way ANOVA and, when indicated, the Scheffé multiple comparisons test were applied to check for significant differences. RESULTS: Little difference in the accuracy of detection or localization was seen between FBP with and without AC. OSEM with AC extended the contrast range for accurate lesion detection and localization over that of the other methods investigated. Without AC, no significant difference between OSEM and FBP reconstruction was detected. CONCLUSION: OSEM with AC may improve the detection and localization of thoracic gallium-labeled lesions over FBP reconstruction.

Algorithms↗

Preoperative endoscopic sphincterotomy and laparoscopic cholecystectomy for the management of cholecystocholedocholithiasis: 10-year experience.

No procedure has yet been identified as the "gold standard" for the detection and treatment of common bile duct stones (CBDS) in patients undergoing laparoscopic cholecystectomy (LC). This prospective study involves 2137 patients undergoing elective laparoscopic cholecystectomy. The algorithm for diagnostic management in place until July 1997 involved routine intravenous cholangiography and selective endoscopic retrograde cholangiography (ERC). Subsequently, assessment of the bile duct was not routinely performed, but a scoring system was applied to single out those patients at risk of CBDS who should undergo intravenous cholangiography and/or ERC (see Fig. 2). Whenever bile duct stones were found, endoscopic sphincterotomy (ES) was performed, and LC was performed with a standardized four-cannula technique after endoscopic bile duct stone clearance. Common bile duct stones were suspected in 340 patients who were referred for preoperative ERC; 250 patients were referred for ES; 21 patients were referred for open surgery because of failure of ERC or sphincterotomy. Common bile duct stones, detected in 283 cases (13.2%), were removed before surgery in 250 cases (88.3%) and during surgery in 28 cases (9.9%). Self-limited pancreatitis occurred in 4.2% of the patients after sphincterotomy. Laparoscopic cholecystectomy was performed in 98.4% of the cases. The conversion rate was 8.3% if sphincterotomy had been performed previously and 3.4% after standard laparoscopic cholecystectomy (p < 0.001). The morbidity rate was 4.5%; mortality, 0.09%. During follow-up five patients (0.2%) had retained stones endoscopically treated. Future trials of novel strategies for detecting and treating CBDS should compare the results of novel strategies with those of the strategy employed in this study, which includes selective ERC, preoperative ES, and LC.

Adolescent↗

Three hundred consecutive emergent celiotomies in general surgery patients: influence of advanced diagnostic imaging techniques and procedures on diagnosis.

OBJECTIVES: To assess the utility of advanced tests performed before surgery on patients who needed emergent abdominal operations, and to assess the outcomes of these patients relative to their diagnoses. SUMMARY BACKGROUND DATA: Patients with a potential abdominal catastrophe may have various presentations, contributing to the difficulty of the decision about whether an operation is indicated. Advanced tests can be valuable, but the use of these adjuncts should be appropriate to the clinical status of the patient so that treatment is not delayed. The role of these tools in the evaluation of the patient who may need an emergent abdominal operation is less well defined. METHODS: Data were reviewed on adult patients undergoing emergent abdominal operations. Entrance criteria included patients who had an emergent abdominal operation, defined as one performed for presumed gastrointestinal perforation, infarction, or hemorrhage within 6 hours of admission or surgical consultation. Advanced tests were those that were time-consuming or invasive or required scheduling with other departments so that the risk/benefit ratio of these tests could be questioned. A useful test was one that provided information that contributed to a change in the patient's management. RESULTS: During a 5-year period, 300 consecutive adult patients (158 perforations, 66 hemorrhage, 53 ischemia/infarction, and 23 "other") underwent emergent nontrauma celiotomies. Overall, the death rate was 20%. Advanced preoperative tests were performed in 135 (45%) of the 300 patients, and 40 of these patients had delayed treatments. Preoperative localization of bleeding sites was accomplished in 77% of patients with upper gastrointestinal bleeding and 86% of patients with lower gastrointestinal bleeding. CONCLUSIONS: Most patients in need of emergent abdominal operations should not undergo advanced tests. The primary role of advanced tests in these patients is in the localization of a bleeding site. With the exception of patients who present with hemorrhage, advanced tests frequently cause a delay in treatment.

Abdomen, Acute↗

A primary care approach to the adult patient with nodular thyroid disease.

Nodular thyroid disease can be defined as the presence of one or more nodules in a thyroid gland of normal or increased size. To diagnose and treat patients with nodular goiters cost-effectively is often challenging because many thyroid illnesses present with a nodule; often the patient is unaware of its presence. Although most thyroid nodules are benign, it is occasionally difficult to exclude malignant neoplasm in an enlarged gland. It is essential for the primary care physician to be comfortable with examining and treating patients with thyroid nodules. A rational, stepwise approach to the evaluation of nodular thyroid disease was developed.

Adult↗

Incidence of air travel-related pulmonary embolism at the Madrid-Barajas airport.

BACKGROUND: Prolonged air travel and the associated immobilization are risk factors for venous thromboembolism. The occurrence of pulmonary thromboembolism (PTE) under these circumstances is referred to as economy class syndrome. We assessed the incidence of symptomatic PTE in passengers on long-haul flights arriving at Madrid-Barajas Airport, Madrid, Spain, and the association with the number of flight hours. METHODS: We retrospectively reviewed cases of PTE among international travelers arriving at Madrid-Barajas Airport between January 1995 and December 2000. Patients presenting with symptoms of deep venous thrombosis but without symptoms of PTE were excluded. Pulmonary thromboembolism was identified using an algorithm of diagnostic tests. The incidence of PTE and the association with flight duration was assessed. RESULTS: The average number of passengers per year who arrived at the airport on flights originating abroad in the period analyzed was 6 839 222. Sixteen cases of PTE were detected over the 6-year period. All patients with travel-associated PTE had flight durations of greater than 6 hours. The overall incidence of PTE was 0.39 per 1 million passengers (95% confidence interval [CI], 0.20-0.58). On flights that lasted between 6 and 8 hours, the incidence was 0.25 per 1 million passengers (95% CI, 0-0.75), while on flights longer than 8 hours, the incidence was 1.65 per 1 million passengers (95% CI, 0.81-2.49) (P<.001). CONCLUSIONS: Air travel is a risk factor for PTE, and the incidence of PTE increases with the duration of the air travel. However, the low incidence of PTE among long-distance passengers, similar to that observed in other international airports, does not justify social alarm.

Aged↗