Establish pre-clinical diagnostic efficacy for parathyroid hormone as a point-of-surgery-testing-device (POST).

Measuring the Parathyroid hormone (PTH) levels assists in the investigation and management of patients with parathyroid disorders. Rapid PTH monitoring is a valid tool for accurate assessment intraoperatively. Rapid Electro-Analytical Device (READ) is a point-of-care device that uses impedance change between target and capture probe to assess the PTH concentration in undiluted patient plasma samples. The aim of this work focuses on evaluating the analytical performance of READ platform to Roche analyzer as a prospective clinical validation method. The coefficient of variation (CV) for intra-assay imprecision was < 5% and inter-assay imprecision CV was < 10% for high (942 pg/mL) and low (38.2 pg/mL) PTH concentration. Functional sensitivity defined at 15% CV was 1.9 pg/mL. Results obtained from READ platform correlated well (r = 0.99) with commercially available clinical laboratory method (Roche Diagnostics) to measure PTH concentrations with a turn-around time of less than 15 min. Furthermore, the mean bias of 7.6 pg/mL determined by Bland-Altman analysis, showed good agreement between the two methods. We envision such a sensing system would allow medical practitioners to facilitate targeted interventions, thereby, offering an immediate prognostic approach as the cornerstone to delivering successful treatment for patients suffering from primary hyperparathyroidism.

Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study.

BACKGROUND: Therapeutic humanized IgG1 kappa monoclonal antibody (t-mAb), daratumumab (DARA) is a Food and Drug Administration approved drug for the treatment of relapsed/refractory plasma cell myeloma (PCM). DARA appears on serum protein electrophoresis (SPEP) and on serum immunofixation (sIFE) as an IgG kappa monoclonal immunoglobulin protein (M-protein), complicating the assessment of the patients' response to therapy. A more ominous threat to patient safety can occur with the misinterpretation of the presence of a small t-mAb spike as being the residual product of the patient's neoplastic clone, presented either as oligoclonality or new clonality, which could result in incorrect interpretation of failure to achieve remission. METHODS: In this report, we describe a novel and cost-effective technique based on biotinylated recombinant CD38 and streptavidin-coated magnetic beads to capture and remove residual DARA present in PCM patient serum samples. The treated samples are then run like regular samples on SPEP and sIFE. We validated this simple technique in DARA-spiked PCM samples and patient samples on DARA treatment. RESULTS: Our simple capture technique completely extracted DARA in all of the tested serum specimens and allowed the assessment of residual M-protein without DARA interference. The results were reproducible and highly specific for DARA, and did not have any impact on endogenous M-protein migration and quantification by SPEP and sIFE. The cost of this technique is much lower and it can be performed in-house with a very short turnaround time compared to the currently available alternative methods. There is a great need for such reflex technologies to avoid interpretation errors. CONCLUSIONS: This method is an effective way to eliminate DARA interference in SPEP and sIFE, and can be easily implemented in any clinical laboratory without any patent restriction. This simple technique can be adopted for other t-mAbs using their respective ligands and will help to reduce additional doses of toxic treatment and further testing in patients on t-mAbs with a false positive M-protein spike.

Assessment of Risk for Interference by Circulating Biotin in Samples Received for High Sensitivity Troponin-T, Thyrotropin, and for Prostate Specific Antigen Testing by Immunoassays.

BACKGROUND: Biotin interference in streptavidin-based immunoassays is known and may lead to erroneous results and thus to diagnostic error. The recent increase in reports of biotin interference in immunoassay-based testing has been attributed to increased intake of biotin supplements by the public and to the high dose biotin therapy in patients with neurological and inherited disorders. Circulating biotin levels greater than 20 ng/mL are reported to exhibit interference in high sensitivity troponin T (hs-TnT), thyroid stimulating hormone (TSH), and in prostate specific antigen (PSA) among other assays when using our Cobas® 6000 immunoassay analyzer (Roche Diagnostics, IN, USA). This study aims to examine the risk for biotin interference among our patient population. METHODS: Serum and plasma leftover samples from 183 different patients were collected following completion of hs-TnT (53 samples), TSH (45 samples), and PSA (85 samples) testing. Aliquots were stored frozen at -20°C until analysis. Biotin concentrations in these samples were measured using an ELISA (ALPCO, Salem, NH, USA) according to the manufacture's protocol. Samples with biotin levels of 20 ng/mL or greater were considered as high-risk samples (HRS) for biotin interference. RESULTS: The overall concentrations of biotin in our patients' samples ranged from 0.02 ng/mL to 11.38 ng/mL (median 0.42 ng/mL). The median and (range) biotin concentrations in hs-TnT, TSH, and PSA samples were 0.27 ng/mL (0.02 - 6.86 ng/mL), 0.39 ng/mL (0.08 - 11.38 ng/mL), and 0.47 ng/mL (0.09 - 7.73 ng/mL), respectively. Although there was no significant difference between biotin levels in samples for TSH or PSA measurement (p = 0.85), biotin in samples for PSA and for hs-TnT and in samples for TSH and hs-TnT were significantly different (p = 0.049 and 0.089), respectively. None of the samples had biotin levels greater than or equal to 20 ng/mL. CONCLUSIONS: Using representative samples with requests for hs-TnT, TSH, and PSA testing, where reliable performance for the selected assays at their lowest measurement range is required for clinical intervention, among our study population the risk was considered minimal as their circulating biotin levels were less than 20 ng/mL. However, educating clinicians and laboratory users regarding the potential of biotin interference is always recommended.

Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline.

OBJECTIVE: To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. PARTICIPANTS: The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. EVIDENCE: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. CONCLUSIONS: Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.

Association of troponin T, detected with highly sensitive assay, and outcomes in infective endocarditis.

Troponin levels have been correlated with adverse outcomes in multiple disease processes, including congestive heart failure, acute coronary syndromes, sepsis, and, in a few small series, infective endocarditis. We hypothesized that a novel measurement of troponin using a highly sensitive assay would correlate with adverse outcomes when prospectively studied in patients with infective endocarditis. At a single center in the International Collaboration on Endocarditis, 42 patients met the inclusion criteria and underwent testing for cardiac troponin T (cTnT) using both a standard and a highly sensitive precommercial assay. The cTnT levels were associated with the prespecified primary composite outcome of death, central nervous system event, and cardiac abscess. Secondary outcomes included the individual components of the composite outcome and the need for cardiac surgery. A receiver operating characteristic curve was derived and used to identify the optimal cutpoint for cTnT using the highly sensitive assay. cTnT was detectable with the highly sensitive assay in 39 (93%) of 42 patients with infective endocarditis and with the standard assay in 25 (56%) of 42 (p <0.05). Of the 42 patients, 15 experienced the composite outcome, 4 died, 9 had a central nervous system event, and 5 had a cardiac abscess. With the hs-cTnT assay, the median cTnT was greater in the patients who experienced the primary outcome (0.12 vs 0.02 ng/ml, p <0.05). According to the receiver operating characteristic curve analysis (area under the curve of 0.74), cTnT levels of ≥0.08 ng/ml produced optimal specificity (78%) for the primary outcome. The patients with a cTnT level of ≥0.08 ng/ml were more likely to experience the primary outcome (odds ratio 7.0, 95% confidence interval 1.7 to 28.6, p <0.01) and a central nervous system event (odds ratio 9.3, 95% confidence interval 1.3 to 24.1, p = 0.02). In conclusion, cTnT is detectable in 93% of patients with infective endocarditis using a novel highly sensitive assay, with higher levels correlating with poor clinical outcomes.

Elevated cerebrospinal fluid beta-2 microglobulin as a tumor marker in a patient with myeloma of the central nervous system.

Myeloma involvement of the nervous system is rare. Extensive literature review revealed only a few cases reported from different parts of the world. The presence of CNS symptoms and detection of plasma cells in the CSF is the usual basis of diagnosis. In addition, immunoelectrophoresis and immunofixation for detection of monoclonal protein confirm the diagnosis in some cases, while some authors used flow cytometry and cytogenetic studies on CSF. Reports of multiple myeloma also include unfavorable cytogenetic abnormalities of chromosome 13. We report a case with relapsed CNS multiple myeloma with the detection of elevated beta-2 microglobulin (beta2M) as a tumor marker in the CSF.

Elevated cerebrospinal fluid b-2 microglobulin as a tumor marker in a patient with myeloma of the central nervous system.

Myeloma involvement of the nervous system is rare. Extensive literature review revealed only a few cases reported from different parts of the world. The presence of CNS symptoms and detection of plasma cells in the CSF is the usual basis of diagnosis. In addition, immunoelectrophoresis and immunofixation for detection of monoclonal protein confirm the diagnosis in some cases, while some authors used flow cytometry and cytogenetic studies on CSF. Reports of multiple myeloma also include unfavorable cytogenetic abnormalities of chromosome 13. We report a case with relapsed CNS multiple myeloma with the detection of elevated b-2 microglobulin (b2M) as a tumor marker in the CSF.