Interference in HbA1c measurement: a case of electropherogram shift due to hyperleukocytosis leading to the discovery of leukemic mantle cell lymphoma.

HbA1c is a pivotal biomarker in diabetes management, reflecting long-term glycaemic control. HbA1c is often measured with capillary electrophoresis, which generally is a very precise technique, but there can be interference, especially in the case of haemoglobin diseases. Thus, in patients with underlying conditions, the accurate measurement of HbA1c can be challenging. We present a case of special interference in a 74-year-old female patient referred to a HbA1c test, in whom the measurement was thought to be significantly affected by hyperleukocytosis and led to an unexpected diagnosis of leukemic low-grade lymphoma. This case report highlights the underrecognized potential interference of leukocytosis in HbA1c measurement. It underscores the importance of clinical vigilance when interpreting HbA1c results in patients with underlying haematological conditions.

The Ability of the Toe-Brachial Index to Predict the Outcome of Treadmill Exercise Testing in Patients with a Normal Resting Ankle-Brachial Index.

BACKGROUND: Peripheral arterial disease (PAD) in the presence of a normal ankle-brachial index (ABI) can be diagnosed noninvasively by measuring a postexercise ABI or by measuring the toe-brachial index (TBI). METHODS: This was a prospective comparative study. Over a period of 30 months, a total of 415 patients who were referred with the suspicion of vascular claudication and resting values of 0.91 ≤ ABI<1.40 were further evaluated for the resting TBI and postexercise ABI by treadmill testing. RESULTS: A total of 325 (39%) of the 830 investigated limbs had a low TBI (≤0.70), and 505 (61%) had a normal TBI. Of the limbs with a low TBI, 160 (49%) had PAD according to a postexercise ABI versus 165 (33%) of the limbs with normal TBI. The overall agreement in PAD classification between the two methods was 500/830 (60%) with a Cohen's kappa = 0.166 (95% CI: 0.096-0.232). The data showed an inverse correlation between the magnitude of the TBI decrease, as well as the resting ABI, and the probability of an abnormal postexercise ABI. On average, limbs with a low TBI had a lower resting ABI than patients with a normal TBI (1.07 ± 0.09 vs. 1.13 ± 0.10, P < 0.001). The groups with a low TBI had a significantly higher ratio of abnormal test results than patients with a normal TBI, in limbs with ABI (0.96-1.00) and ABI >1.10 (P ≤ 0.022 for both), but there were no statistically significant differences found in other ABI intervals (P > 0.200 for all). CONCLUSIONS: The magnitude of the TBI reduction correlates with an increased probability of an abnormal postexercise ABI. However, this is due in part to limbs with a low TBI having a lower resting ABI on average than limbs with a normal TBI, which also correlates with the probability of an abnormal exercise test result. This study shows that the TBI and the postexercise ABI are not interchangeable for establishing a PAD diagnosis.

Reporting and handling of equivocal imaging findings in diagnostic studies of bone metastasis in prostate cancer.

BACKGROUND: Equivocal scanning results occur. It remains unclear how these results are presented and their management influence diagnostic characteristics. PURPOSE: To investigate the reporting and handling of equivocal imaging findings in diagnostic studies of bone metastases, and to assess the impact on diagnostic performance of the methods used to analyze equivocal findings. The conceptual issue was reified based on two actual observations. MATERIAL AND METHODS: A recent meta-analysis of bone metastases in prostate cancer was conducted and data were obtained from a large clinical trial with a true reference of bone metastasis, where diagnostic characteristics were calculated with equivocal scans handled by: removal; considered malignant; considered benign; and intention-to-diagnose. RESULTS: The meta-analysis included 18 trials where the median proportion of reported equivocal results was 27%. Eleven (61%) studies reported an equivocal option for the index test, 42% reported equivocal results and described how these were analyzed. The clinical trial included 583 prostate cancer patients with 20% equivocal results. The different methods of managing equivocal findings resulted in highly variable outcomes: sensitivity = 85%-100%; specificity = 78%-99%; and positive and negative predictive values = 44%-94% and 97%-100%, respectively. The diagnostic performances obtained using the four methods were differentially susceptible to the proportion of equivocal imaging findings and the prevalence of bone metastases. CONCLUSION: Reporting of equivocal results was inadequate in bone imaging trials. The handling of equivocal findings strongly influenced diagnostic accuracy.

Combined oral contraceptives may activate the contact system in healthy women.

Background: The contact system (CAS) is part of the coagulation system, consisting of a group of plasma proteins stimulating inflammation, coagulation, and fibrinolysis when activated. CAS can be triggered by several activating surfaces, and CAS may play a potential role in thrombus formation. Combined oral contraceptives (COCs) are known to increase the risk of venous thromboembolism, and COCs induce various prothrombotic changes in the coagulation system, whereas the effect of COC on CAS has not been thoroughly investigated. Objectives: To investigate CAS in COC users compared with nonusers. Methods: Blood samples from 62 study subjects, 30 COC users, and 32 nonusers, were analyzed. Coagulation factor XII (FXII), prekallikrein (PK), H-Kininogen (HK), cleaved HK (cHK), C1-esterase inhibitor (C1-inh), and the endogenous kallikrein potential (EKP) were measured. Results: COC users had significantly higher FXII (median, 38.4 vs 28.9 mg/L) and lower C1-inh levels (0.20 vs 0.23 g/L) than nonusers. The levels of PK and HK were not significantly different. Measurement of EKP indicated an increased capacity of CAS in COC users (1860 vs 1500 nmol/L × min), and increased plasma levels of cHK (2.02 vs 1.07 µg/L) indicated an increased activity in vivo. Conclusion: This study demonstrates an increased CAS capacity in women using COC compared with nonusers and also an increased activity in vivo. The results indicate that increased contact activation may contribute to the increased thrombotic risk caused by COC.

Reporting and Handling of Indeterminate Bone Scan Results in the Staging of Prostate Cancer: A Systematic Review.

Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled in clinical trials are not known. A systematic review was conducted using electronic databases up to October 2016. The main outcome of interest was the reporting of indeterminate bone scans, analyses of how such scans were managed, and exploratory analyses of the association of study characteristics and the reporting of indeterminate bone scan results. Seventy-four eligible clinical trials were identified. The trials were mostly retrospective (85%), observational (95%), large trials (median 195 patients) from five continents published over four decades. The majority of studies had university affiliation (72%), and an author with imaging background (685). Forty-five studies (61%) reported an indeterminate option for the bone scan and 23 studies reported the proportion of indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to handle indeterminate scans. Most trials (n = 39) used add-on supplementary imaging, follow-up bone scans, or both. Exploratory analyses showed a significant association of reporting of indeterminate results and number of patients in the study (p = 0.024) but failed to reach statistical significance with other variables tested. Indeterminate bone scan for staging of prostate cancer was insufficiently reported in clinical trials. In the case of indeterminate scans, most studies provided adequate measures to obtain the final status of the patients.

Avid 18F-FDG Uptake in Idiopathic Tumoral Calcinosis Mimicking Lymph Node Metastasis.

Tumoral calcinosis is a benign condition characterized by periarticular calcified lesions that is frequently observed in patients with chronic renal failure. Tumoral calcinosis often presents with subcutaneous masses and joint swelling. We present a case of tumoral calcinosis with dramatically increased 18F-fluoro-2-deoxy-d-glucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT) that mimicked lymphoma or lymph node metastases.