Modular-integrative modeling: a new framework for building brain models that blend biological realism and functional performance.

This Perspective presents the Modular-Integrative Modeling approach, a novel framework in neuroscience for developing brain models that blend biological realism with functional performance to provide a holistic view on brain function in interaction with the body and environment.

Emerging Biomarkers in the Laboratory and in Practice: A Novel Approach to Diagnosing Heart Failure in Diabetes.

The Biomarkers for the Diagnosis of Heart Failure in Diabetes webinar was hosted by Diabetes Technology Society on September 20, 2023, with the objective to review current evidence and management practices of biomarker screening for heart failure in people with diabetes. The webinar discussed (1) the four stages of heart failure, (2) diabetes and heart failure, (3) natriuretic peptide and troponin for diagnosing heart failure in diabetes, (4) emerging composite and investigational biomarkers for diagnosing heart failure, and (5) prevention of heart failure progression. Experts in heart failure from the fields of clinical chemistry, cardiology, and diabetology presented data about the importance of screening for heart failure as an often-unnoticed complication of people with type 1 and type 2 diabetes.

Comparison of Sampson and extended Martin/Hopkins methods of low-density lipoprotein cholesterol calculations with direct measurement in pediatric patients with hypertriglyceridemia.

OBJECTIVE: The Friedewald equation is the commonly used method of low-density lipoprotein cholesterol (LDL-C) calculation, requiring reflex to direct LDL-C measurement when triglycerides (TG) ≥ 400 mg/dL. Recently formulated Sampson and extended Martin/Hopkins methods have been validated with TG up to 800 mg/dL and thus have the potential to replace direct LDL-C measurement. Given the growing prevalence of childhood dyslipidemia, the objective of this study was to compare Sampson and extended Martin/Hopkins methods of LDL-C calculation with the direct measurement in a pediatric cohort with 400 ≤ TG ≤ 799 mg/dL. METHODS: This study retrieved standard lipid panels and corresponding direct LDL-C measurements of 131 patients with 400 ≤ TG ≤ 799 mg/dL from a pediatric population. Following the application of Sampson and extended Martin/Hopkins calculations, calculated values were compared with direct LDL-C measurements using ordinary least squares linear regression analysis and bias plotting. RESULTS: Both Sampson and extended Martin/Hopkins LDL-C calculations exhibited a strong correlation with the direct measurements (Pearson r = 0.89) in patients with 400 ≤ TG ≤ 800 mg/dL. Average percentages of bias of 45% and 21% were found between the direct LDL-C measurements and Sampson or extended Martin/Hopkins calculations, respectively. CONCLUSION: Both Sampson and extended Martin/Hopkins calculations are applicable as clinical alternatives of direct LDL-C measurement in pediatric patients given 400 ≤ TG ≤ 799 mg/dL.

Biomarkers for the Diagnosis of Heart Failure in People with Diabetes: A Consensus Report from Diabetes Technology Society.

Diabetes Technology Society assembled a panel of clinician experts in diabetology, cardiology, clinical chemistry, nephrology, and primary care to review the current evidence on biomarker screening of people with diabetes (PWD) for heart failure (HF), who are, by definition, at risk for HF (Stage A HF). This consensus report reviews features of HF in PWD from the perspectives of 1) epidemiology, 2) classification of stages, 3) pathophysiology, 4) biomarkers for diagnosing, 5) biomarker assays, 6) diagnostic accuracy of biomarkers, 7) benefits of biomarker screening, 8) consensus recommendations for biomarker screening, 9) stratification of Stage B HF, 10) echocardiographic screening, 11) management of Stage A and Stage B HF, and 12) future directions. The Diabetes Technology Society panel recommends 1) biomarker screening with one of two circulating natriuretic peptides (B-type natriuretic peptide or N-terminal prohormone of B-type natriuretic peptide), 2) beginning screening five years following diagnosis of type 1 diabetes (T1D) and at the diagnosis of type 2 diabetes (T2D), 3) beginning routine screening no earlier than at age 30 years for T1D (irrespective of age of diagnosis) and at any age for T2D, 4) screening annually, and 5) testing any time of day. The panel also recommends that an abnormal biomarker test defines asymptomatic preclinical HF (Stage B HF). This diagnosis requires follow-up using transthoracic echocardiography for classification into one of four subcategories of Stage B HF, corresponding to risk of progression to symptomatic clinical HF (Stage C HF). These recommendations will allow identification and management of Stage A and Stage B HF in PWD to prevent progression to Stage C HF or advanced HF (Stage D HF).

The Continued Need for the Routine Assessment of Folate Status.

OBJECTIVE: The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. METHODS: Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. RESULTS: Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. A total of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. CONCLUSION: This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

The yield of neuroimaging in patients presenting to the emergency department with isolated neuro-ophthalmological complaints: A retrospective chart review.

Neuro-ophthalmological emergencies require prompt assessment and management to avoid vision or life-threatening sequelae. The decision to perform a neuroimaging procedure is based on the clinical judgment of the medical team, without defined indications. This study aims to identify presenting symptoms and physical exam findings associated with relative positive findings on neuroimaging studies. Electronic medical records of patients presenting to the emergency department (ED) with isolated neuro-ophthalmologic complaints between January 1, 2013 and September 30, 2019 were reviewed. We collected data on the clinical presentation, neuroimaging procedures and results, consults, and diagnoses. Two hundred eleven patients' charts were reviewed. Most presented with unilateral eye complaints (53.6%), and the most common symptoms were blurred vision (77.3%) and headaches (42.2%). A total of 126 imaging procedures were performed of which 74.6% were normal, while 25.4% showed relevant abnormal findings. Complaining of blurry vision (P = .038) or visual field changes (P = .014) at presentation as well as having a visual field defect (P = .016), abnormal pupil reactivity (P = .028), afferent pupillary defect (P = .018), or abnormal optic disc exam (P = .009) were associated with positive findings on imaging. Neuroimaging is more likely to yield positive findings in patients presenting to the ED with visual field irregularities, afferent pupillary defects, or abnormal optic discs. These findings - when combined with the proper clinical setting - should lower the threshold to proceed with neuroimaging in the emergency department. Based on our results, larger-scale studies might lead to a well-structured algorithm to be followed by ED physicians in decision making.

A Comparison of the Long-Term Surgical Outcomes of Horizontal Strabismus Surgery between Resident Clinic and Private Clinic Patients.

PURPOSE: To compare the long-term surgical outcomes of patients with horizontal strabismus whose surgery was performed in an outpatient department (OPD) setting (by residents-in-training) to those whose surgery was performed in a private clinic (PC) setting (by staff-ophthalmologists) in the same operating room/institution. METHODS: Two hundred and forty-four patients' charts who had horizontal strabismus surgeries from January 2007 to 2020 were reviewed retrospectively. A total of 92 patients were operated on by residents and followed in OPD, and 152 patients by staff-surgeons and followed in PC. Demographic data and eye exam parameters were collected. Distance and near deviation (in prism diopters, PD) were extracted and compared between groups at baseline and postoperatively (6 months and yearly for up to 6 years). Success was defined as a postoperative motor alignment of 10PD or less. RESULTS: The mean age of the 244 patients was 10.5 ± 11.7 years, with no significant differences between groups. A longer follow-up duration was reported in the PC group (34.9 ± 24.3 months vs 25.3 ± 20.2 months). Patients had similar success rates in both groups in the early postoperative period (6 months and 1 year); however, a higher success rate was observed in the PC group compared to OPD at 3, 5 and 6 years with the following respective values: 72.2% vs 50% (p < .001), 75% vs. 66.7% (p = .02), and 68.6% vs. 66.7% (p = .03). The difference was more pronounced in the esotropia subgroup mostly at 3 years follow-up. CONCLUSION: This study showed a similar success rate of horizontal strabismus surgery performed in a PC setting by staff surgeons as compared to that performed in an OPD setting by residents at 6 months and 1 year. A significantly higher success rate was observed at long term follow-up (after 2 years) in the PC group compared to the OPD group, possibly related to the difference in compliance with post-operative follow-up management and not to surgery itself.

Comparison between D-dimer levels in diabetic and non-diabetic positive COVID-19 adult patients: A hospital-based study.

BACKGROUND: Diabetes is one of the most common associated comorbidity with severe acute respiratory syndrome coronavirus (SARS-CoV-2) pneumonia patients. Coagulation disorders with D-dimer levels are increased in both diseases. This study aimed to compare the levels of D-dimer in DM and non-DM patients with coronavirus disease (COVID-19) and correlate it with the disease severity. METHODS: This is a cross-sectional hospital-based study. It was conducted at royal care hospital, isolation COVID-19 Centre in 2021. The study included 130 patients with COVID-19 who fulfilled the inclusion criteria. Data were collected through a structured datasheet. The disease was diagnosed by a nasal swab polymerase chain reaction (PCR) Participants were divided into diabetics and non-diabetics depending on the history from the datasheet. The data were analysed with Statistical Package of Social Science (SPSS) version 23. RESULTS: The study showed that 73.1% of the participants were males and 26.9% were females. The most frequent age group was >65 years. The percentages of diabetics and non-diabetics, among the study participants, were found to be 41.5% and 58.5%, respectively. Moreover, 52.3% were admitted to the intensive care unit (ICU). This study revealed that D-dimer was higher compared with diabetes mellitus. The diabetics were associated with higher levels of D-dimer compared to non-diabetics. Regarding the correlation between the level of D-dimer and severity of COVID-19, it was found that there is a significant association, as the ICU patients were associated with higher levels of D-dimer in comparison with non-ICU patients. CONCLUSION: This study concluded that there is a significant association between the high D-dimer level and severity of COVID-19 among diabetic patients.

Conglomeratin: a new antibacterial flavonol derivative from Macaranga conglomerata Brenan (Euphorbiaceae).

A new prenylated kaempferol, conglomeratin (1), alongside 7 known compounds including flavonoids (2 and 3), ellagic acid derivatives (4 and 5), triterpenoids (6 and 7), and a coumarin (8) were isolated from the leaves (1 - 5) and stem bark (6 - 8) of Macaranga conglomerata. Their structures were elucidated using spectroscopic and spectrometric techniques. The antibacterial assay was performed using disc diffusion method against Gram-positive and Gram-negative microorganisms. Compound 1 was significantly active against Pseudomonas aeruginosa ATCC 27853 (MIC = 7.8 µg/mL) and moderately active towards Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 31488 (MIC = 62.5 µg/mL). Compound 2 showed potency against P. aeruginosa ATCC 27853 (MIC = 1.0 µg/mL) while 4 and 7 were selective towards K. pneumoniae ATCC 31488 (MIC = 7.8 and 1.0 µg/mL, respectively). These findings suggest that prenylation of flavonoids may contribute to improving their broad-spectrum antimicrobial activities.

Methods of Low-Density Lipoprotein-Cholesterol Measurement: Analytical and Clinical Applications.

Among the five major classes of lipoprotein particles, low-density lipoprotein-cholesterol (LDL-C) is the primary lipoprotein risk factor for the development of cardiovascular diseases (CVD) through the promotion of atherosclerotic pathogenesis. Therefore, it is of paramount importance to accurately measure the plasma concentration of LDL-C using an appropriate method to examine the risk of CVD and determine the efficacy of therapeutic interventions to reduce the cholesterol level and examine the risk assessment strategy. At present, there is a wide variety of methods available for LDL-C measurement. In this review, we have outlined the commonly used methods of LDL-C measurement. These methods have been classified into non-automated analytical methods, calculation methods, and automated direct measurement of LDL-C. We have also described some recently proposed promising calculation methods which are being considered for clinical adoption. This current review could assist the clinicians to have a better understanding regarding the measurement techniques and comparative utilities of different methods of LDL-C measurement and guide them to select an appropriate method based on accuracy, turnaround time, and cost of test.

Cytotoxic alkaloids from the root of Zanthoxylum paracanthum (mildbr) Kokwaro.

Chemical investigation of the root of Zanthoxylum paracanthum afforded 1 new alkamide derivative, (2E,4E)-6-oxo-N-isobutyldeca-2,4-dienamide (1) together with 10 known congeners including one phenolic amide (2), four benzophenanthridines (3 - 6), three indolonaphthyridines (7 - 9) and two lignans (10 and 11). Their structures were elucidated by a combination of spectroscopic and spectrometric data. Using resazurin reduction assay, the crude extract (10 µg/mL) and isolates (10 µM) were screened for their cytotoxic activities against the drug-sensitive (CCRF-CEM) leukemia cell line and its multidrug-resistant counterpart (CEM/ADR5000). Compounds 3, 4 and 6 showed cytotoxicity against CCRF-CEM with IC50 values of 2.00 ± 0.33, 2.31 ± 0.20 and 0.11 ± 0.04 µM, respectively. Only compound 6 exhibited strong cytotoxic activity against CEM/ADR5000 with an IC50 value of 2.34 ± 0.34 µM in comparison with the standard drug doxorubicin which showed IC50 values of 0.01 ± 0.14 (CCRF-CEM) and 26.78 ± 3.30 µM (CEM/ADR5000).

Scleral Perforation as a Complication of Strabismus Surgery: A Literature Review.

The aim of this review was to report the existing literature on the incidence, risk factors, treatment, and outcomes of scleral perforation as a vision-threatening complication of strabismus surgery. The current literature reported an incidence range of scleral perforation/penetration between 3 in 1,000 and 7.8%. Rectus muscle recession was the most commonly mentioned risk factor among the studies. Other risk factors were myopia, previous extraocular muscle surgery, surgeon experience, S-24 needle use, muscle reattachment posterior to the original insertion site, operating on a horizontal rectus muscle, and young age. Different views existed in the literature regarding scleral perforation management. Some ophthalmologists advocated management by cryopexy or indirect ophthalmoscopic laser uniformly, whereas others reserved it for more complicated cases. Antibiotic therapy for endophthalmitis prophylaxis was recommended by one study and shown to be practiced by some ophthalmologists. [J Pediatr Ophthalmol Strabismus. 2022;59(4):214-223.].

Assessment of mortality from COVID-19 in a multicultural multi-ethnic patient population.

BACKGROUND: Studies indicate that ethnicity and socioeconomic disparity are significant facilitators for COVID-19 mortality. The United Arab Emirates, distinctly has a population of almost 12% citizens and the rest, immigrants, are mainly unskilled labourers. The disparate socio-economic structure, crowded housing conditions, and multi-ethnic population offer a unique set of challenges in COVID-19 management. METHODS: Patient characteristics, comorbidities, and clinical outcomes data from the electronic patient medical records were retrospectively extracted from the hospital information system of the two designated public COVID-19 referral hospitals. Chi-square test, logistic regression, and odds ratio were used to analyse the variables. RESULTS: From, the total of 3072 patients, less than one-fifth were females; the Asian population (71.2%);followed by Middle Eastern Arabs (23.3%) were the most infected by the virus. Diabetes Mellitus (26.8%), hypertension (25.7%) and heart disease (9.6%) were the most prevalent comorbidities observed among COVID-19 patients. Kidney disease as comorbidity significantly diminished the survival rates (Crude OR 9.6, 95% CI (5.6-16.6), p < 0.001) and (Adjusted OR 5.7 95% CI (3.0 - 10.8), p < 0.001), as compared to those patients without kidney disease. Similarly, the higher age of patients between 51 and 65 years, significantly decreased the odds for survival (Crude OR 14.1 95% CI (3.4-58.4), p < 0.001) and (Adjusted OR 12.3 95% CI (2.9 - 52.4), p < 0.001). Patient age beyond 66 years, further significantly decreased the odds for survival (Crude OR 36.1 95% CI (8.5-154.1), p < 0.001), and (Adjusted OR 26.6 95% CI (5.7 - 123.8), p < 0.001). CONCLUSION: Our study indicates that older ages above 51 years and kidney disease increased mortality significantly in COVID-19 patients. Ethnicity was not significantly associated with mortality in the UAE population. Our findings are important in the management of the COVID-19 disease in the region with similar economic, social, cultural, and ethnic backgrounds.

Teaching the Scleral Pass in Strabismus Surgery.

The authors describe a method to improve teaching the most critical step in strabismus surgery, the scleral pass. The attending surgeon fashions a "scleral tunnel" by performing the scleral pass and retracting the needle so the resident can pass it through the same tunnel. This ultimately helps decrease complications during surgical training. [J Pediatr Ophthalmol Strabismus. 2021;58(5):e34-e35.].

Circulating macroprolactin exhibits molecular heterogeneity and is not exclusively an antibody complex.

BACKGROUND: Macroprolactin (macPRL) is considered to be solely a prolactin antibody complex. We examined macPRL heterogeneity in samples from thirteen patients suspected of macroprolactinemia. METHODS: Polyethylene glycol (PEG) precipitation, gel permeation (GPC), protein-G affinity, and Lectin affinity chromatography were used to investigate the nature of macPRL. RESULTS: Using PEG, 8, 3, and 2 samples were macPRL positive, negative, and indeterminate respectively. Using GPC, prolactin appeared at high (H) (≥150 kDa), mid (M) (≥30 < 150 kDa), and low (L) (<30 k Da) forms. For macPRL positive samples, 52.3 to 95.0%, 3.6 to 34.1%, and 1.4 to 34.5% appeared at the (H), (M), and (L) regions respectively, compared with samples negative for macPRL with 1.2 to 5.1%, 60.0 to 79.4%, and 15.4 to 38.9% prolactin activity respectively. macPRL positive samples showed 30.4 to 86.5% binding to protein G column compared with negative samples at 1.2 to 5.1%. GPC-separated forms showed macPRL is heterogenous being either antibody bound (protein G studies) or glycosylated aggregates (lectin studies). Samples with identified macPRL forms were analysed using 4 immunoassay analysers. CONCLUSIONS: Samples with (H) and (M) macPRL forms showed significant positive bias in 2 immunoassays. The study is limited by the small number of samples and a larger scale study is required.

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.

Association of a Novel Protocol for Rapid Exclusion of Myocardial Infarction With Resource Use in a US Safety Net Hospital.

Importance: High-sensitivity cardiac troponin T (hs-cTnT) protocols for the evaluation of chest pain in the emergency department (ED) may reduce unnecessary resource use and overcrowding. Objective: To determine whether the implementation of a novel hs-cTnT protocol, which incorporated troponin values drawn at 0, 1, and 3 hours after ED presentation and the modified HEART score (history, electrocardiogram, age, risk factors), was associated with improvements in resource use while maintaining safety. Design, Setting, and Participants: This retrospective cohort study from Parkland Health and Hospital System, a large safety net hospital in Dallas, Texas, included data on 31 543 unique ED encounters in which patients underwent electrocardiographic and troponin testing from January 1, 2017, to October 16, 2018. The hs-cTnT protocol was implemented in December 2017. Main Outcomes and Measures: Resource use outcomes included trends in ED dwell time, troponin to disposition decision time (the difference between the first troponin draw time and the time an order was placed for inpatient admission, admission to observation, or discharge), and final patient disposition. Safety outcomes included readmission for myocardial infarction and death. Results: In 31 543 encounters, mean (SD) patient age was 54 (14.4) years and 14 675 patients (48%) were female. Department dwell time decreased by a mean of -1.09 (95% CI, -2.81 to 0.64) minutes per month in the preintervention period. The decline was steeper after the intervention (-4.69 [95% CI, -9.05 to -0.33] minutes per month) (P for interaction = .007). The troponin to disposition time was increasing in the preintervention period by 1.72 (95% CI, 1.08 to 2.36) minutes per month; postintervention, the mean difference increased more slowly (0.37 [95% CI, -1.25 to 1.99 minutes per month; P value for interaction = .007]). The proportion of patients discharged from the ED increased after the intervention (48% vs 54%, P < .001). Thirty-day major adverse cardiac event rates were low and did not differ before and after the intervention. Conclusions and Relevance: Implementation of a novel protocol incorporating serial hs-cTnT measurements over 3 hours with the Modified HEART Score was associated with reduction in ED dwell times and attenuation of temporal increases in time from troponin measurement to disposition. This or similar protocols to rule out myocardial infarction have the potential to reduce ED overcrowding and improve health care quality while maintaining safety.

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.

Validation and implementation of the fifth-generation high sensitivity Troponin T (hs-TnT) assay at a large teaching county hospital. A laboratory-driven multi-speciality effort.

We describe the validation and implementation of the new 5th generation high sensitivity Troponin T assay (Roche Diagnostics®). In addition to the assay improved sensitivity, the numerical values, reporting units, reference intervals, and critical limits are markedly different. We describe the use of clinical correlation as the basis for implementation and validation of the fifth-generation hs-TnT assay at a large teaching county hospital.