Prospective evaluation of the clinical usefulness of an antigen- specific assay (MAIPA) in idiopathic thrombocytopenic purpura and other immune thrombocytopenias

The diagnosis of idiopathic immune thrombocytopenia remains a clinical diagnosis based on the exclusion of other causes of immune and nonimmune thrombocytopenia. Measurement of platelet-associated Ig (PAIg), while sensitive, is nonspecific for the diagnosis of immune thrombocytopenia. Published experience of antigen capture assays (including monoclonal antibody immobilization of platelet antigens or MAIPA) suggest a high sensitivity and specificity (70% to 80%) in selected groups of patients. In a prospective evaluation of 158 patients with thrombocytopenia from all causes, we report a sensitivity of 51% and specificity of 80% for direct MAIPA assays. MAIPA was considerably better in discriminating immune from nonimmune thrombocytopenia than two assays of PAIgG. Antiplatelet antibodies detected by MAIPA were more frequently directed against the glycoprotein (GP) IIb/IIIa than the GP Ib/IX complex. Our experience suggests that MAIPA assays are useful in the laboratory assessment of thrombocytopenia, should be performed before therapy, and that some patients with 'nonimmune' thrombocytopenia may have genuine antiplatelet antibodies.     

The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)

OBJECTIVE: To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden. RESEARCH DESIGN AND METHODS: The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15-34 years in Sweden. In 1987-1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8-10 years later. The assessment was based on retinal photographs in most cases (86%). RESULTS: Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA(1c) 8.1 +/- 1.5% and 6.8 +/- 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA(1c) (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001). CONCLUSIONS: Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.     

Novel Factors to Improve Prediction of Nodal Positivity in Patients with Clinical T1/T2 Breast Cancers

Background

Memorial Sloan Kettering Cancer Center (MSKCC) and MD Anderson Cancer Center (MDACC) have established nomograms to predict sentinel node positivity. We propose the addition of two novel variables—distance of tumor from the nipple and from the skin—can improve their performance.

Methods

Ultrasounds of clinical T1/T2 tumors were reviewed. Distances of the tumor from the skin and from the nipple were measured. MSKCC and MDACC nomogram predictions and the AUC–ROC for each model were calculated. The added utility of the two variables was then examined using multiple logistic regression.

Results

Of 401 cancers studied, 79 (19.7 %) were node positive. The mean distance of tumors from the nipple in node-positive patients was 4.9 cm compared with 6.0 cm in node-negative patients (p = 0.0007). The mean distance of tumors from the skin was closer in node-positive cases (0.8 cm) versus node-negative cases (1.0 cm, p = 0.0007). The MSKCC and MDACC nomograms AUC–ROC values were 0.71 (95 % CI 0.64–0.77) and 0.74 (95 % CI 0.68–0.81). When adjusted for the MSKCC predicted probability, addition of both distance from nipple (p = 0.008) and distance from skin (p = 0.02) contributed significantly to prediction of nodal positivity and improved the AUC–ROC to 0.75 (95 % CI 0.70–0.81). Similarly, distance from nipple (p = 0.002), but not distance from skin (p = 0.09), added modestly to the MDACC nomogram performance (AUC 0.77; 95 % CI 0.71–0.83).

Conclusions

Distance of tumor from the nipple and from the skin are important variables associated with nodal positivity. Adding these to established nomograms improves prediction of nodal positivity.     

Multigland Disease and Slower Decline in Intraoperative PTH Characterize Mild Primary Hyperparathyroidism

Background

Many patients with primary hyperparathyroidism (PHPT) present with less severe biochemical parameters. The purpose of this study was to compare the presentation, operative findings, and outcomes of these patients with “mild” PHPT to patients with “overt” disease.

Methods

A retrospective review of a prospectively collected parathyroid database was performed to identify cases of PHPT undergoing an initial neck operation. Patients were classified as mild when either the preoperative calcium or PTH was within the normal limits. Comparisons were made with the Student’s t test, Chi-squared test, or Wilcoxon rank-sum test where appropriate. Kaplan–Meier estimates were plotted for disease-free survival and compared by the log-rank test.

Results

Of the 1,429 patients who met inclusion criteria, 1,049 were classified as overt and 388 (27.1 %) were mild. Within the mild group, 122 (31.4 %) presented with normocalcemic PHPT and 266 (68.6 %) had a normal PTH. The two groups had similar demographics and renal function. Interestingly, the mild group had more than double the rate of kidney stones (3.1 vs. 1.3 %, p = 0.02). The mild group was less likely to localize on sestamibi scan (62.4 vs. 78.7 %, p < 0.01). Intraoperatively, more mild patients exhibited multigland disease (34.3 vs. 14.1 %, p < 0.01). When examining intraoperative PTH (IoPTH) kinetics where single adenomas were excised, the IoPTH fell at a rate of 6.9 pg/min in mild patients compared with 11.5 pg/min in the overt group (p < 0.01). Accordingly, 62.2 % of patients in the overt group and 53.3 % in the mild group were cured at 5 min postexcision (p < 0.01). There was no difference in the rates of persistence or recurrence between the groups, and disease-free survival estimates were identical (p = 0.27).

Conclusions

Patients with mild PHPT were more likely to have multigland disease and a slower decline in IoPTH, but these patients can be successfully treated with surgery.     

Bone stiffness and failure load are related with clinical parameters in men with chronic obstructive pulmonary disease

Osteoporosis is frequently seen in patients with chronic obstructive pulmonary disease (COPD). Because research on bone structure and bone strength in COPD patients is limited, the objectives of this pilot study were as follows: (1) to compare bone structure, stiffness, and failure load, measured at the peripheral skeleton, between men with and without COPD after stratification for areal bone mineral density (aBMD); and (2) to relate clinical parameters with bone stiffness and failure load in men with COPD. We included 30 men with COPD (normal aBMD, n = 18; osteoporosis, n = 12) and 17 men without COPD (normal aBMD, n = 9; osteoporosis, n = 8). We assessed pack‐years of smoking, body mass index (BMI), fat free mass index (FFMI), pulmonary function (forced expiratory volume in 1 second [FEV₁], FEV₁/forced vital capacity [FVC], diffusion capacity for carbon monoxide [DLCO], and transfer coefficient for carbon monoxide [KCO]), and extent of emphysema. Bone structure of the distal radius and tibia was assessed by high‐resolution peripheral quantitative computed tomography (HR‐pQCT), and bone stiffness and failure load of the distal radius and tibia were estimated from micro finite element analysis (µFEA). After stratification for aBMD and COPD, men with osteoporosis showed abnormal bone structure (p < 0.01), lower bone stiffness (p < 0.01), and lower failure load (p < 0.01) compared with men with normal aBMD, and men with COPD had comparable bone structure, stiffness, and failure load compared with men without COPD. In men with COPD, lower FFMI was related with lower bone stiffness, and failure load of the radius and tibia and lower DLCO and KCO were related with lower bone stiffness and failure load of the tibia after normalization with respect to femoral neck aBMD. Thus, this pilot study could not detect differences in bone structure, stiffness, and failure load between men with and without COPD after stratification for aBMD. FFMI and gas transfer capacity of the lung were significantly related with bone stiffness and failure load in men with COPD after normalization with respect to femoral neck aBMD. © 2013 American Society for Bone and Mineral Research.     

Three-dimensional water/fat separation and T2* estimation based on whole-image optimization--application in breathhold liver imaging at 1.5 T

The chemical shift of water and fat resonances in proton MRI allows separation of water and fat signal from chemical shift encoded data. This work describes an automatic method that produces separate water and fat images as well as quantitative maps of fat signal fraction and T2* from complex multiecho gradient-recalled datasets. Accurate water and fat separation is challenging due to signal ambiguity at the voxel level. Whole-image optimization can resolve this ambiguity, but might be computationally demanding, especially for three-dimensional data. In this work, periodicity of the model fit residual as a function of the off-resonance was used to modify a previously proposed formulation of the problem. This gives a smaller solution space and allows rapid optimization. Feasibility and accurate separation of water and fat signal were demonstrated in breathhold three-dimensional liver imaging of 10 volunteer subjects, with both acquisition and reconstruction times below 20 s.