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BACKGROUND: Serum kappa, lambda, the K/λ light chain concentrations are used for screening, diagnosis, and monitoring of patients with multiple myeloma and other plasma cell disorders. Biological variation studies conducted on healthy subjects showed that free light chains have a low within and high between-individual variation. We determined if this variation were genetically linked. METHODS: We obtained a single serum sample from 16 pairs of identical twins, 8 neonate twins, and 19 presumed directly-related siblings children, measured Κ and λ light chains and computed the Κ/λ ratio. RESULTS: As expected, Κ/λ results from each twin neonate were near identical (reflecting maternal/placental transfer). For older children and adult twins, the Κ/λ ratio form a cluster of results that were a subset of the reference range. There was one outlier, a female with a high, different from her twin sister. She likely had a monoclonal gammopathy (no followup was possible). Excluding this pair, results from neonate twins (14.4% ±10.3%) and non-neonate twins (18.0 ± 15.3%) were not significantly different. Results between non-twin siblings were more scattered (53.2%±53.4%) and different from neonate and non-neonate twin adult and children. CONCLUSION: We suggest that the Κ/λ free light chains may be genetically linked.
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Cadeias Leves de Imunoglobulina , Irmãos , Gêmeos , Adolescente , Adulto , Criança , Feminino , Humanos , Recém-Nascido , Cadeias kappa de Imunoglobulina , Cadeias lambda de Imunoglobulina , Paraproteinemias/diagnóstico , PlacentaRESUMO
OBJECTIVES: The destruction of red cells during blood collection or with the processing of the sample continues to occur at a high rate, especially among emergency department (ED) patients. This can produce pre-analytical laboratory errors, particularly for potassium. We determined the incidence of hemolyzed samples and discuss the potential medical impact for hypokalemic patients who potassium level is artificially normal (pseudoeukalemia). METHODS: Potassium results were obtained for a 6-month period. Using a measured hemolysis index (HI), hemolysis was present in 3.1â¯% for all potassium ordered (n=94,783) and 7.5â¯% for ED orders (n=22,770). Most of these samples were reported as having high normal result or were hyperkalemic. There were 22 hemolytic samples with a potassium of <3.5â¯mmol/L, and 57 hemolytic samples with a potassium in lower limit of normal (3.5-3.8â¯mmol/L). From this group, we examined the medical histories of 8 selected patients whose initially normal potassium levels were subsequently confirmed to have a potassium values that were below, at, or just above the lower limit of normal due to hemolysis. RESULTS: The primary complaint for these patients were: necrotizing soft tissue infection, pancreatitis, volume overload from heart failure with reduced ejection fraction, hypertension treated with hydrochlorothiazide, and presence of a short bowel syndrome. A subsequent non-hemolyzed sample was collected demonstrating hypokalemia in all of these patients. Within these cases, there was a potential for harm had hemolysis detection not been performed. CONCLUSIONS: We demonstrate the medical importance of detecting hemolysis for patients who have pseudoeukalemia. This is relevant because the HI cannot be obtained when electrolytes are tested using whole blood samples, and a normal potassium may lead to inappropriate patient management.
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A 78-year-old male was seen in the emergency department (ED) with chest pain. Fifteen months earlier, he had presented to the ED with shoulder and elbow pain. High-sensitivity cardiac troponin I (hs-cTnI) testing was conducted at that time, which produced normal results of 10 and 13 ng/L (cutoff <48 ng/L). During the current admission, his electrocardiogram was unremarkable, with a borderline prolonged PR interval noted. The patient's hs-cTnI results were 25, 47, and 254 ng/L at 0, 1, and 7 hours, respectively. He was diagnosed with demand ischemia and admitted to the hospital. The detection of acute myocardial infarction in this case was made during the first sample collection (t = 0), despite the fact that this result was well within the normal range.
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BACKGROUND: Mild traumatic brain injury (mTBI) is defined as a Glascow Coma Score of between 13 and 15. The diagnosis and rule out of individuals suffering from mTBI on an acute basis is imperfect and involves subjective measures. Serum biomarkers that exhibit narrow within-individual biological variation can be used for the early rule-out of mTBI, when baseline levels are compared during health. METHODS: This is a descriptive study that applies published biological variation data of serum mTBI biomarkers for early rule out of sports-related injury. RESULTS: Laboratory tests such as glial fibrillary acidic protein, fatty acid binding protein 7, and phosphorylated protein enriched in astrocytes have low within-individual variances and are potential candidates. Aldolase C also rises early in blood but the biological variation is of this marker is currently unknown. CONCLUSIONS: The use of blood-based biomarkers, measured in real time using point-of-care testing devices when compared to a pre-competition baseline instead of a population-based reference interval, can provide early rule out of mTBI, and possibly enable on-field evaluations and a medical decision for a return to competition.
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BACKGROUND: Artificial intelligence (AI) promises to become an important tool in the practice of laboratory medicine. AI programs are available online that can provide concise medical and laboratory information within seconds after a question is submitted. METHODS: We posed the following contemporary and relevant question for clinical chemists using an AI program: "Should labs eliminate CK-MB testing?" The results of this inquiry were critically reviewed by a cardiologist, emergency department physician, and clinical laboratorians for accuracy and appropriateness. RESULTS: An AI report answering this question was generated within 15 s. The experts felt that the information was inaccurate with the statements that CK-MB results are released earlier than cardiac troponin (cTn), and are more useful for detection of myocardial injury in patients with renal insufficiencies. The summary omitted discussion on the ongoing debate for periprocedural detection of acute myocardial infarction (MI), the perceived value for detection of reinfarction, the value in risk stratification compared to cTn, the economic justification for testing both CK-MB and cTn, and medicolegal aspects of testing when results are discordant. CONCLUSIONS: At this time, AI does not appear to be ready to be used by clinical laboratories for answering important practice questions.
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Serviços de Laboratório Clínico , Infarto do Miocárdio , Humanos , Inteligência Artificial , Laboratórios , Laboratórios Clínicos , Infarto do Miocárdio/diagnósticoRESUMO
BACKGROUND: Serum level of microRNA-122 (miR-122) has been reported as a sensitive diagnostic biomarker for detecting liver injury, comparable to the aminotransferases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities are increased in other conditions, such as acute skeletal muscle injury (ASMI). We determined whether miR-122 is nonspecifically increased in patients suffering from ASMI. METHODS: We measured ALT, AST, creatine kinase (CK), and miR-122 in 3 groups: healthy controls (n = 24), patients with ASMI (total n = 29, 11 with recreational drug use and 18 without recreational drug use), and patients with acute liver injury (ALI; n = 14). RESULTS: Levels of ALT, AST, and CK increased 83%, 97%, and 100% for patients with ASMI and 100% for all 3 enzymes in ALI patients. In contrast, miR-122 increased in 34% of patients with ASMI (44.4% with recreational drug use and 18.2% without recreational drug use) and 100% of ALI patients. In 2 drug-induced liver injury cases, miR-122 increased about 12-24 hours before ALT and AST. CONCLUSION: Recreational drug misuse is associated with both rhabdomyolysis and drug-induced liver injury (DILI). The traditional liver function markers AST and ALT were nonspecifically increased in the majority of patients with ASMI. miR-122 is only increased in patients at risk for DILI and demonstrates superior specificity for liver injury.
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BACKGROUND: People living with HIV have increased risk of cardiovascular disease, but few studies focus on women with HIV (WWH) and few account for the use of multiple substances. SETTING: We recruited WWH from San Francisco shelters, free meal programs, street encampments, and a safety net HIV clinic. METHODS: Between 2016 and 2019, participants completed 6 monthly interviews, specimen collection, and a transthoracic echocardiogram. We assessed associations between 3 echocardiographic indices of cardiac hypertrophy (concentric hypertrophy, concentric remodeling, and eccentric hypertrophy) and study factors, including cardiovascular risk factors, substance use, and HIV-specific factors (CD4 + count, viral load, HIV medication). RESULTS: Among 62 participants, the average age was 53 years and 70% were ethnic minority women. Just over 70% had elevated blood pressure. Toxicology-confirmed substance use included tobacco (63%), cannabis (52%), cocaine (51%), methamphetamine (29%), and alcohol (26%). Concentric hypertrophy was detected in 26% of participants. It was positively associated with cocaine use [adjusted relative risk (aRR) = 32.5, P < 0.01] and negatively associated with cannabis use (aRR = 0.07, P < 0.01). Concentric remodeling was detected in 40% of participants. It was positively associated with cocaine use (aRR = 11.2, P < 0.01) and negatively associated with cannabis use (aRR = 0.17, P = 0.02). Eccentric hypertrophy was not significantly associated with factors studied here. CONCLUSIONS: Routine evaluation of stimulant use as a contributing factor to cardiovascular risk may improve risk assessment in WWH. Whether cannabis use mitigates the impact of cocaine use on structural heart disease among WWH merits further investigation.
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Transtornos Relacionados ao Uso de Cocaína , Cocaína , Infecções por HIV , Cardiopatias , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Pessoa de Meia-Idade , Etnicidade , Infecções por HIV/complicações , Grupos Minoritários , Transtornos Relacionados ao Uso de Substâncias/complicações , Cardiopatias/epidemiologia , HipertrofiaRESUMO
This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.
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COVID-19 , Vacinas , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , COVID-19/diagnóstico , COVID-19/prevenção & controle , Anticorpos Antivirais , Imunoglobulina G , ImunoensaioRESUMO
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.
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Biomarcadores , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Peptídeos Natriuréticos/sangue , Troponina/sangueRESUMO
BACKGROUND: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. METHODS: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. RESULTS: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. CONCLUSIONS: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.
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Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.