Integrated diagnostics: proceedings from the 9th biennial symposium of the International Society for Strategic Studies in Radiology

The International Society for Strategic Studies in Radiology held its 9th biennial meeting in August 2011. The focus of the programme was integrated diagnostics and massive computing. Participants discussed the opportunities, challenges, and consequences for the discipline of radiology that will likely arise from the integration of diagnostic technologies. Diagnostic technologies are increasing in scope, including advanced imaging techniques, new molecular imaging agents, and sophisticated point-of-use devices. Advanced information technology (IT), which is increasingly influencing the practice of medicine, will aid clinical communication and the development of “population images” that represent the phenotype of particular diseases, which will aid the development of diagnostic algorithms. Integrated diagnostics offer increased operational efficiency and benefits to patients through quicker and more accurate diagnoses. As physicians with the most expertise in IT, radiologists are well placed to take the lead in introducing IT solutions and cloud computing to promote integrated diagnostics. To achieve this, radiologists must adapt to include quantitative data on biomarkers in their reports. Radiologists must also increase their role as participating physicians, collaborating with other medical specialties, not only to avoid being sidelined by other specialties but also to better prepare as leaders in the selection and sequence of diagnostic procedures. Key Points ? New diagnostic technologies are yielding unprecedented amounts of diagnostic information. ? Advanced IT/cloud computing will aid integration and analysis of diagnostic data. ? Better diagnostic algorithms will lead to faster diagnosis and more rapid treatment.     

Validation of a Condition-Specific Measure for Women Having an Abnormal Screening Mammography

OBJECTIVES: The aim of this study is to assess the validity of a new condition-specific instrument measuring psychosocial consequences of abnormal screening mammography (PCQ-DK33). METHODS: The draft version of the PCQ-DK33 was completed on two occasions by 184 women who had received an abnormal screening mammography and on one occasion by 240 women who had received a normal screening result. Item Response Theories and Classical Test Theories were used to analyze data. Construct validity, concurrent validity, known group validity, objectivity and reliability were established by item analysis examining the fit between item responses and Rasch models. RESULTS: Six dimensions covering anxiety, behavioral impact, sense of dejection, impact on sleep, breast examination, and sexuality were identified. One item belonging to the dejection dimension had uniform differential item functioning. Two items not fitting the Rasch models were retained because of high face validity. A sick leave item added useful information when measuring side effects and socioeconomic consequences of breast cancer screening. Five "poor items" were identified and should be deleted from the final instrument. CONCLUSIONS: Preliminary evidence for a valid and reliable condition-specific measure for women having an abnormal screening mammography was established. The measure includes 27 "good" items measuring different attributes of the same overall latent structure-the psychosocial consequences of abnormal screening mammography.     

Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease

The article explores the finding that high shear alone applied to normal, native blood results in platelet aggregation. A filter with tortuous capillary-sized channels permits a study of the effect of shearing forces at different pressures. Native, heparinized, citrated and EDTA blood and platelet-rich plasma (PRP) were forced through the filter. Normal and von Willebrand's blood were studied, as were the effects of antibodies to platelet glycoproteins (GPr) and to von Willebrand's factor (vWf) and of "membrane-active" drugs. Normally, the filter blocked at 40 mmHg but not at 5 mmHg. Transmission electronmicroscopy of the filter at 40 mmHg showed blockage by platelet aggregates. Initially, the mean transit time through the filter was 8 milliseconds. Platelet retention in the filter occurred in two phases. From 0 to 3 seconds, only high-shear, vWf, and GPrIIb/IIIa were required. From 10 to 20 seconds, retention presumably involved these three attributes, but divalent cations were also essential. Only this phase was inhibited by some membrane-active drugs. ADP- and thrombin- induced aggregation requires GPrIIb/IIIaand fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPrIIb/IIIa and vWf. This indicates a different type of exposure of GPrIIb/IIIa. The long bleeding time in vW disease highlights the absolute requirement for vWf and emphasizes the difference in exposure of GPrIIb/IIIa induced by shear stress. Evidently, a process similar to that occurring in the filter is required in normal capillary hemostasis.     

Stem cell factor enhances interleukin-3 dependent induction of 68-kD calmodulin-binding protein and thymidine kinase activity in NFS-60 cells

Stem cell factor (SCF) is known to act synergistically with other hematopoietic factors in increasing the colony formation of hematopoietic progenitor cells. We have shown that interleukin-3 (IL-3)- dependent proliferation of NFS-60 cells is associated with the induction of a specific calmodulin-binding protein of about 68 kD (CaM- BP68). To evaluate the relationship between proliferative stimulation and the induction of CaM-BP68 by cytokines, we examined whether the increased proliferative potential of NFS-60 cells in response to SCF is reflected in an increased induction of the CaM-BP68. We observed that SCF alone has a limited effect on proliferative stimulation and on the induction of CaM-BP68 in factor-deprived NFS-60 cells. However, when combined with IL-3, granulocyte colony-stimulating factor (G-CSF), or IL-6, it caused a significant increase in cytokine-dependent proliferative stimulation, as well as in the induction of CaM-BP68. Furthermore, an increase in IL-3-dependent induction of CaM-BP68 in the presence of SCF coincided with a corresponding increase in thymidine kinase activity, whose expression is linked to G1/S transition of the cells. At low concentrations SCF caused a synergistic increase in IL-3- dependent induction of both CaM-BP68 and thymidine kinase activity. In contrast to the changes in CaM-BP68 and thymidine kinase activity, no significant changes in DNA polymerase alpha were observed in factor- deprived NFS-60 cells in response to IL-3 and/or SCF. These observations suggest an increased expression of CaM-BP68 and thymidine kinase are associated with the synergistic effect of SCF on factor- dependent proliferation of hematopoietic progenitor cells.     

Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ara-C and recombinant human granulocyte-macrophage colony- stimulating factor

We administered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) (120 micrograms/m2/d by continuous intravenous [IV] infusion) to 12 patients with newly diagnosed acute myeloid leukemia (AML) at relatively high risk of early death during remission induction. GM-CSF began 3 days after completion of induction chemotherapy (ara-C 1.5 g/m2 d x 4 days by continuous IV infusion after a 3 g/m2 bolus). Rates of fatal infection (42%), pneumonia and/or sepsis (83%), and CR (50%) did not differ significantly (P less than .05) from those observed after administration of the identical chemotherapy without GM-CSF to 53 historical controls with newly diagnosed AML at similarly high risk of early death. There were no significant differences between the GM-CSF-treated and the historical groups in the time required to reach neutrophil counts of 500 or 1,000/microL after administration of chemotherapy. Four patients died of infection before they could have benefited from the earliest recovery of neutrophil count observed in patients who entered CR. Growth of leukemia after GM-CSF administration was observed in only 1 of the 8 patients who survived long enough for response to induction therapy to be fully evaluated. This observation suggests that it might be safe to undertake larger, randomized studies, perhaps using earlier administration of GM-CSF, to definitively determine the role of GM-CSF added to chemotherapy in patients with newly diagnosed AML.     

Standard versus user-interactive assessment of significant coronary stenoses with multislice computed tomography coronary angiography

Forty-four patients in sinus rhythm with suspected coronary artery disease underwent 16-row multislice computed tomography coronary angiography and conventional coronary angiography. Two protocols for image analysis were applied to the multislice computed tomographic images: standard projections versus interactive postprocessing. The diagnostic accuracy of both methods for the detection of significant lesions (>50% lumen reduction) was compared with quantitative coronary angiography. Sensitivity and specificity were 58% and 96% and 96% and 97%, for standard projections and interactive postprocessing protocol, respectively.     

Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin's disease: long-term analysis of risk factors and outcome

The survival of patients with Hodgkin's disease has dramatically improved over the past 30 years because of advances in treatment. However, concern for the risk of long-term complications has resulted in a number of trials to evaluate reduction of therapy. The consequences of these trials on recurrence, development of long-term complications, and survival remain unknown. One major consequence of successful treatment of Hodgkin's disease is the development of second malignant neoplasms. We sought to determine the factors most important for development of second tumors in pathologically staged and treated Hodgkin's disease patients followed for long intervals to provide background information for future clinical trials and guidelines for routine patient follow-up. Between April 1969 and December 1988, 794 patients with laparotomy staged (PS) IA-IIIB Hodgkin's disease were treated with radiation therapy (RT) alone or combined radiation therapy and chemotherapy (CT). There were 8,500 person-years of follow-up (average of 10.7 person-years per patient). Age and gender-specific incidence rates were multiplied by corresponding person-years of observation to obtain expected numbers of events. Observed to expected results were calculated by type of treatment, age at treatment, sex, and time after Hodgkin's disease. Absolute (excess) risk was expressed as number of excess cases per 10,000 person-years. Seventy-two patients have developed a second malignant neoplasm. Eight patients developed acute leukemia, 10 had non-Hodgkin's lymphoma (NHL), and 53 patients developed solid tumors at a median time of 5 years, 7.25 years, and 12.2 years, respectively, after Hodgkin's disease. One patient developed multiple myeloma 16.5 years after Hodgkin's disease. The relative risk (RR) of developing a second malignancy was 5.6. The absolute excess risk per 10,000 person-years (AR) of developing a second malignancy was 69.6 (7.0% excess risk per person per decade of follow-up). The highest RR occurred for the development of leukemia (RR = 66.2), however because of the low expected risk, the AR was only 9.3. The RR of solid tumors after Hodgkin's disease was lower (4.7); however, the AR was greater (49) than for acute leukemia. Among the solid tumors, breast, gastrointestinal, lung, and soft tissue cancers had the highest absolute excess risks. The risk for developing breast cancer after Hodgkin's disease was greatest in women who were under the age of 25 at treatment. The most significant risk factor for the development of both leukemia and solid tumors was the combined use of radiation therapy and chemotherapy. The RR following RT alone was 4.1 (AR = 51.1); for RT + CT (initially or at relapse) the RR was 9.75 (P < 0.05, nonoverlapping confidence limits, AR = 123.9). Survival following development of a second malignancy was poor in patients with leukemia, gastrointestinal tumors, lung cancer, and sarcoma. Survival from other malignancies including NHL and breast cancer was more encouraging. Second malignant neoplasms are a major cause of late morbidity and mortality following treatment for Hodgkin's disease. The most significant risk factor for the development of second tumors is the extent of treatment for Hodgkin's disease. Recommendations are presented for both prevention and early detection of these tumors.     

The appropriate use criteria: Improvements for its integration into real world clinical practice

The purpose of this position statement is to suggest ways in which future appropriate use criteria (AUC) for coronary revascularization might be restructured to: (1) incorporate improvement in quality of life and angina relief as primary goals of therapy, (2) integrate the findings of recent trials into quality appraisal, (3) employ the combined information of the coronary angiogram and invasive physiologic measurements together with the results of stress test imaging to assess risk, and (4) recognize the essential role that patient preference plays in making individualized therapeutic decisions. The AUC is a valuable tool within the quality assurance process; it is vital that interventionists ensure that percutaneous coronary intervention case selection is both evidence-based and patient oriented. Appropriate patient selection is an important quality indicator and adherence to evidence-based practice should be one metric in a portfolio of process and outcome indicators that measure quality.