The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): A review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals.

Progressive pseudorheumatoid dysplasia (PPRD) is a genetic, non-inflammatory arthropathy caused by recessive loss of function mutations in WISP3 (Wnt1-inducible signaling pathway protein 3; MIM 603400), encoding for a signaling protein. The disease is clinically silent at birth and in infancy. It manifests between the age of 3 and 6 years with joint pain and progressive joint stiffness. Affected children are referred to pediatric rheumatologists and orthopedic surgeons; however, signs of inflammation are absent and anti-inflammatory treatment is of little help. Bony enlargement at the interphalangeal joints progresses leading to camptodactyly. Spine involvement develops in late childhood and adolescence leading to short trunk with thoracolumbar kyphosis. Adult height is usually below the 3rd percentile. Radiographic signs are relatively mild. Platyspondyly develops in late childhood and can be the first clue to the diagnosis. Enlargement of the phalangeal metaphyses develops subtly and is usually recognizable by 10 years. The femoral heads are large and the acetabulum forms a distinct "lip" overriding the femoral head. There is a progressive narrowing of all articular spaces as articular cartilage is lost. Medical management of PPRD remains symptomatic and relies on pain medication. Hip joint replacement surgery in early adulthood is effective in reducing pain and maintaining mobility and can be recommended. Subsequent knee joint replacement is a further option. Mutation analysis of WISP3 allowed the confirmation of the diagnosis in 63 out of 64 typical cases in our series. Intronic mutations in WISP3 leading to splicing aberrations can be detected only in cDNA from fibroblasts and therefore a skin biopsy is indicated when genomic analysis fails to reveal mutations in individuals with otherwise typical signs and symptoms. In spite of the first symptoms appearing in early childhood, the diagnosis of PPRD is most often made only in the second decade and affected children often receive unnecessary anti-inflammatory and immunosuppressive treatments. Increasing awareness of PPRD appears to be essential to allow for a timely diagnosis. © 2012 Wiley Periodicals, Inc.

Diagnostic concordance of DSM-IV and DSM-5 Posttraumatic Stress Disorder (PTSD) in a clinical sample

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Use of a latest-generation vascular plug for peripheral vascular embolization with use of a diagnostic catheter: preliminary clinical experience

The latest-generation Amplatzer vascular plug (AVP), the AVP 4, is designed for embolization of smaller vessels without a sheath or guiding catheter. This study evaluated the AVP 4 in peripheral vascular embolization.

[Early genetic testing in nephrology - a diagnostic aid in ambiguous clinical situations]

Despite a growing number of identified genetic causes of monogenetic disorders, early molecular testing is rarely applied in daily nephrologic practice. In selected cases and to answer specific questions, molecular testing however can be helpful for the specialist. The future significance of genetic testing most likely lies in the area of individual risk profiling for polygenetic disorders. The basis for this testing however has yet to be established.

Clinical aspects, diagnostic challenges and management of patients with neuroendocrine tumors (NETs)

Neuroendocrine tumor (NET) entities are rare malignancies. Higher awareness and improved diagnostic methods have led to an increasing incidence of these diseases, and most oncologists deal with such patients in their daily practice. The symposium on NETs that was held in Merano (Italy) in October 2009 was organized by the German-speaking European School of Oncology (dESO) and gathered specialists from different disciplines of transalpine countries to bring together experiences and observations regarding these tumors. The goal of the meeting and of this review was to illustrate both well- and poorly differentiated NETs and to encourage interdisciplinary approaches.

Clinical presentation and diagnostic delay in bullous pemphigoid: a prospective nationwide cohort

Prospective systematic analyses of the clinical presentation of bullous pemphigoid (BP) are lacking. Little is known about the time required for its diagnosis. Knowledge of the disease spectrum is important for diagnosis, management and inclusion of patients in therapeutic trials.

Leydig-cell tumour in children: variable clinical presentation, diagnostic features, follow-up and genetic analysis of four cases

BACKGROUND: Testicular tumours are relatively uncommon in infants and children, accounting for only 1-2% of all paediatric solid tumours. Of these approximately 1.5% are Leydig-cell tumours. Further, activating mutations of the luteinizing hormone receptor gene (LHR), as well as of the G protein genes, such as Gsalpha (gsp) and Gialpha (gip2) subunits, and cyclin-dependent kinase gene 4(CDK4) have been associated with the development of several endocrine neoplasms. AIMS/METHODS: In this report, the clinical variability of Leydig-cell tumours in four children is described. The LHR-, gsp-, gip2- and CDK4 genes were investigated to establish the possible molecular pathogenesis of the variable phenotype of the Leydig-cell tumours. RESULTS: No activating mutations in these genes were found in the four Leydig-cell tumours studied. Therefore, the absence of activating mutations in LHR, as well as in both the 'hot spot' regions for activating mutations within the G-alpha subunits and in the regulatory 'hot spot' on the CDK4 genes in these tumours indicates molecular heterogeneity among Leydig-cell tumours. CONCLUSION: Four children with a variable phenotype caused by Leydig-cell tumours are described. A molecular analysis of all the 'activating' genes and mutational regions known so far was performed, but no abnormalities were found. The lessons learnt from these clinically variable cases are: perform ultrasound early and most importantly, consider discrepancies between testicular swelling, tumour size and androgen production.

[The importance of clinical information in diagnostic imaging in the febrile patient]

From conventional radiography to cross-sectional imaging methods, modern radiology offers a wide range of diagnostic tools for investigating patients with fever. To achieve the best results and to yield a correct diagnosis, the radiologist must tailor the diagnostic protocol individually for every patient. The decision on the most suitable imaging method, and the type and timing of contrast media strongly depends on the suspected diagnosis. Based on patient history and laboratory data, some modalities may be contraindicated or the patient may need a premedication. The authors give a short overview of diagnostic strategies in evaluating the most important causes of fever and point to the need of discussion and co-operation between clinicians and radiologists.

Diagnostic workup of patients with acute transverse myelitis: spectrum of clinical presentation, neuroimaging and laboratory findings

STUDY DESIGN: Retrospective 9-year survey. OBJECTIVES: Clinical presentation of acute myelitis syndromes is variable, and neuroimaging and laboratory findings are not specific enough to establish the diagnosis with certainty. We evaluated the spectrum clinical features and paraclinical findings encountered during diagnostic workup and aiding the diagnosis. SETTING: Department of Neurology, Inselspital Bern, Switzerland. MATERIAL: Charts and magnetic resonance imaging (MRI) of 63 patients discharged with the diagnosis of acute transverse myelitis. RESULTS: The diagnosis was supported by abnormal MRI and cerebrospinal fluid (CSF) findings in 52 patients (82.5%) and suspected in the remaining either because of a spinal cord MRI lesion suggestive of myelitis (n=5), or abnormal CSF findings (n=4), or electrophysiological evidence of a spinal cord dysfunction (n=2). Clinical impairment was mild (ASIA D) in the majority. All patients had sensory disturbances, whereas motor deficit and autonomic dysfunction were less frequent. Neurological levels were mainly located in cervical or thoracic dermatomes. Spinal cord lesions were visualized by MRI in 90.4% of the patients and distributed either in the cervical or thoracic cord, or both. Multiple lesions were present in more than half of the patients, and lateral, centromedullary and posterior locations were most common. A high percentage of multiple sclerosis (MS)-typical brain lesions and CSF findings suggested a substantial number of MS-related myelitis in our cohort. CONCLUSION: The diagnostic workup of acute myelitis discloses a broad spectrum of CSF or MRI findings, and may be associated with diagnostic uncertainty due to lack of specific CSF or MRI features, or pathological findings.

Clinical presentation of celiac disease and the diagnostic accuracy of serologic markers in children

There has been growing recognition of a changing clinical presentation of celiac disease (CD), with the manifestation of milder symptoms. Serologic testing is widely used to screen patients with suspected CD and populations at risk. The aim of this retrospective analysis was to evaluate the clinical presentation of CD in childhood, assess the diagnostic value of serologic tests, and investigate the impact of IgA deficiency on diagnostic accuracy. We evaluated 206 consecutive children with suspected CD on the basis of clinical symptoms and positive serology results. Ninety-four (46%) had biopsy-proven CD. The median age at diagnosis of CD was 6.8 years; 15% of the children were <2 years of age. There was a higher incidence of CD in girls (p = 0.003). Iron deficiency and intestinal complaints were more frequent in children with CD than those without CD (61% vs. 33%, p = 0.0001 and 71% vs. 55%, p = 0.02, respectively), while failure to thrive was less common (35% vs. 53%, p = 0.02). The sensitivity of IgA tissue transglutaminase (IgA-tTG) was 0.98 when including all children and 1.00 after excluding children with selective IgA deficiency. The specificity of IgA-tTG was 0.73 using the recommended cut-off value of 20 IU, and this improved to 0.94 when using a higher cut-off value of 100 IU. All children with CD and relative IgA deficiency (IgA levels that are measurable but below the age reference [n = 8]) had elevated IgA-tTG. In conclusion, CD is frequently diagnosed in school-age children with relatively mild symptoms. The absence of intestinal symptoms does not preclude the diagnosis of CD; many children with CD do not report intestinal symptoms. While the sensitivity of IgA-tTG is excellent, its specificity is insufficient for the diagnostic confirmation of a disease requiring life-long dietary restrictions. Children with negative IgA-tTG and decreased but measurable IgA values are unlikely to have CD.

Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability, d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis: A Prospective Management Study.

BACKGROUND Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE None.

Clinical findings and diagnostic value of post-traumatic thoracic radiographs in dogs and cats with blunt trauma

Objective: To characterize the clinical findings in dogs and cats that sustained blunt trauma and to compare clinical respiratory examination results with post-traumatic thoracic radiography findings. Design: Retrospective clinical study. Setting: University small animal teaching hospital. Animals, interventions and measurements: Case records of 63 dogs and 96 cats presenting with a history of blunt trauma and thoracic radiographs between September 2001 and May 2003 were examined. Clinical signs of respiratory distress (respiratory rate (RR), pulmonary auscultation) and outcome were compared with radiographic signs of blunt trauma. Results: Forty-nine percent of dogs and 63.5% of cats had radiographic signs attributed to thoracic trauma. Twenty-two percent of dogs and 28% of cats had normal radiographs. Abnormal auscultation results were significantly associated with radiographic signs of thoracic trauma, radiography score and presence and degree of contusions. Seventy-two percent of animals with no other injuries showed signs of thoracic trauma on chest radiographs. No correlation was found between the radiographic findings and outcome, whereas the trauma score at presentation was significantly associated with outcome and with signs of chest trauma but not with the radiography score. Conclusion: Thoracic trauma is encountered in many blunt trauma patients. The RR of animals with blunt trauma is not useful in predicting thoracic injury, whereas abnormal chest auscultation results are indicative of chest abnormalities. Thorough chest auscultation is, therefore, mandatory in all trauma animals and might help in the assessment of necessity of chest radiographs.

Diagnostic Performance and Additional Value of Elastosonography in Focal Breast Lesions: Statistical Correlation between Size-Dependant Strain Index Measurements, Multimodality-BI-RADS Score, and Histopathology in a Clinical Routine Setting

Objective. To evaluate the diagnostic benefit of real-time elastography (RTE) in clinical routine. Strain indices (SI) for benign and malignant tumors were assessed. Methods. 100 patients with 110 focal breast lesions were retrieved. Patients had mammography (MG), ultrasound (US), and, if necessary, MRI. RTE was conducted after ultrasound. Lesions were assessed with BI-RADS for mammography and ultrasound. Diagnosis was established with histology or follow-up. Results. SI for BI-RADS 2 was 1.71 ± 0.86. Higher SI (2.21 ± 1.96) was observed for BI-RADS 3 lesions. SI of BI-RADS 4 and 5 lesions were significantly higher (16.92 ± 20.89) and (19.54 ± 10.41). 31 malignant tumors exhibited an average SI of 16.13 ± 14.67; SI of benign lesions was 5.29 ± 11.87 (P value <0.0001). ROC analysis threshold was >3.8 for malignant disease. Sensitivity of sonography was 90.3% (specificity 78.5%). RTE showed a sensitivity of 87.1% (specificity 79.7%). Accuracy of all modalities combined was 96.8%. In BI-RADS 3 lesions RTE was able to detect all malignant lesions (sensitivity 100%, specificity 92.9%, and accuracy 93.9%). Conclusions. RTE increased sensitivity and specificity for breast cancer detection when used in combination with ultrasound.