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The pathogenesis of endometriosis is not well understood at the moment, and the lack of effective biomarkers often leads to delayed diagnosis of the disease. Lipidomics provides a new approach for the diagnosis and prediction of endometriosis. Sphingomyelin, phosphatidylcholine and phosphatidylserine in peripheral blood, endometrial fluid, peritoneal fluid and follicular fluid have good diagnostic value for endometriosis and disease classification; the lipid metabolites in the eutopic endometrium tissue are expected to be biomarkers of early endometriosis; and the lipid metabolites in peripheral blood are also of great value for predicting endometriosis-related infertility. The development of lipidomics technique will further advance the progress on the pathogenesis, prediction, diagnosis and treatment of endometriosis.

Background: Globally, few studies have examined the effect of the COVID-19 pandemic on routine patient care and follow-up., Objectives: To evaluate the effect of the COVID-19 response on biochemical test requests received from outpatient departments (OPDs) and peripheral clinics serviced by the National Health Laboratory Service Chemical Pathology Laboratory at Tygerberg Hospital, Cape Town, South Africa (SA). Request volumes were used as a measure of the routine care of patients, as clinical information was not readily available., Methods: A retrospective audit was conducted. The numbers of requests received from OPDs and peripheral clinics for creatinine, glycated haemoglobin (HbA1c), lipid profiles, thyroid-stimulating hormone (TSH), free thyroxine, free tri-iodothyronine (fT3), serum and urine protein electrophoresis, serum free light chains and neonatal total serum bilirubin were obtained from 1 March to 30 June for 2017, 2018, 2019 and 2020., Results: The biggest impact was seen on lipids, creatinine, HbA1c, TSH and fT3. The percentage reduction between 1 March and 30 June 2019 and between 1 March and 30 June 2020 was 59% for lipids, 64% for creatinine and HbA1c, 80% for TSH and 81% for fT3. There was a noteworthy decrease in overall analyte testing from March to April 2020, coinciding with initiation of level 5 lockdown. Although an increase in testing was observed during June 2020, the number of requests was still lower than in June 2019., Conclusions: This study, focusing on the short-term consequences of the SA response to the COVID-19 pandemic, found that routine follow-up of patients with communicable and non-communicable diseases was affected. Future studies are necessary to evaluate the long-term consequences of the pandemic for these patient groups.

Introduction: Vitamin D is a micronutrient that plays a large role in bone disease, and researchers are now discovering that it also does so in non-skeletal disease, thus making high-quality analytical determination necessary. To make this determination, a series of immunochemical and physical methods are used. These methods present a series of different ways of handling samples as well as different methodologies that bring a series of advantages and limitations based on the scope of work in which the vitamin D analysis methodology is applied. Although the Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) is the gold standard method of analytical vitamin D determination, and is the only one to offer a more complete and accurate view of all metabolites of this vitamin, it is necessary to standardize all the analysis methodologies that allow accurate, reliable and quality analytical determination, since it is essential to obtain results that can reliably be extrapolated to the population, and that can be decisive in assessing a large number of pathologies.

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for calcific aortic valve stenosis (CAVS) for which transcatheter aortic valve replacement (TAVR) is increasingly utilized as treatment. We evaluated the effect of a program to increase testing of and define the prevalence of elevated Lp(a) among patients undergoing TAVR. Educational efforts and incorporation of a "check-box" Lp(a) order to the preoperative TAVR order set were instituted. Retrospective chart review was performed in 229 patients requiring TAVR between May 2013 and September 2018. Of these patients, 57% had an Lp(a) level measured; testing rates increased from 0% in 2013 to 96% in 2018. Lipoprotein(a) testing occurred in 11% of patients before and in 80% of patients after the "check-box" order set ( P < .001). The prevalence of elevated Lp(a) (≥30 mg/dL) was 35%; these patients had a higher incidence of coronary artery disease requiring revascularization compared with patients with normal Lp(a) (65% vs 47%; P = .047). Patients with Lp(a) ≥30 mg/dL also had higher incidence of paravalvular leak compared with those with normal Lp(a) (13% vs 4%; P = .04). This study defines the prevalence of elevated Lp(a) in advanced stages of CAVS and provides a practice pathway to assess procedural complications and long-term outcomes of TAVR in patients with elevated Lp(a) levels.

Strong epidemiological evidence supports a causal relationship between dyslipidemia and atherosclerotic cardio-vascular disease, which remains the leading cause of death and morbidity worldwide. A lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) is recommended at the initial evaluation for the assessment of the cardio-vascular risk. A commentary of the lipid profile for the clinician and mostly for the patient should be stated on the lab report. Quantifying the cardio-vascular risk using the SCORE (systematic coronary risk estimation) system, as recommended by the Haute autorité de santé (HAS), is the starting point to establish therapeutic goals and treatment strategies. It may be important to emphasize therapeutic goals in lipid reports in order to better monitor lipid profiles at appropriate intervals to assess compliance and therapeutic efficacy for patients on lipid lowering therapy.

Aim: To study the regional variability of requests for anaemia chemistry tests in primary care in Spain and the associated economic costs of potential over-requesting., Methods: Requests for anaemia tests were examined in a cross-sectional study. Clinical laboratories from different autonomous communities (AACCs) were invited to report on primary care anaemia chemistry tests requested during 2014. Demand for iron, ferritin, vitamin B12 and folate tests per 1000 inhabitants and the ratios of the folate/vitamin B12 and transferrin/ferritin requests were compared between AACCs. We also calculated reagent costs and the number of iron, transferrin and folate tests and the economic saving if every AACC had obtained the results achieved by the AACC with best practice., Results: 110 laboratories participated (59.8% of the Spanish population). More than 12 million tests were requested, resulting in reagent costs exceeding €16.5 million. The serum iron test was the most often requested, and the ferritin test was the most costly (over €7 million). Close to €4.5 million could potentially have been saved if iron, transferrin and folate had been appropriately requested (€6 million when extrapolated to the whole Spanish population)., Conclusions: The demand for and expenditure on anaemia chemistry tests in primary care in Spain is high, with significant regional differences between different AACCs., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: To examine the effects of an educational meeting and subsequent computer reminders on the number of ordered laboratory tests., Methods: Using interrupted time series analysis we assessed whether trends in the number of laboratory tests ordered by rheumatologists between September 2012 and September 2015 at the Sint Maartenskliniek (the Netherlands) changed following an educational meeting (September 2013) and the introduction of computer reminders into the Computerised Physician Order Entry System (July 2014). The analyses were done for the set of tests on which both interventions had focussed (intervention tests; complement, cryoglobulins, immunoglobins, myeloma protein) and a set of control tests unrelated to the interventions (alanine transferase, anti-cyclic citrullinated peptide, C-reactive protein, creatine, haemoglobin, leukocytes, mean corpuscular volume, rheumatoid factor and thrombocytes)., Results: At the start of the study, 101 intervention tests and 7660 control tests were ordered per month by the rheumatologists. After the educational meeting, both the level and trend of ordered intervention and control tests did not change significantly. After implementation of the reminders, the level of ordered intervention tests decreased by 85.0 tests (95%-CI -133.3 to -36.8, p<0.01), the level of control tests did not change following the introduction of reminders., Conclusions: In summary, an educational meeting alone was not effective in decreasing the number of ordered intervention tests, but the combination with computer reminders did result in a large decrease of those tests. Therefore, we recommend using computer reminders in addition to education if reduction of inappropriate test use is aimed for.

Human fetuin A (HFA) plays a prominent pathophysiological role in numerous diseases and pathophysiological conditions with considerable biomedical significance; one example is the formation of calciprotein particles in osteoporosis and impaired calcium metabolisms. With impressive advances in in vitro diagnostic assays during the last decade, ELISAs have become a workhorse in routine clinical diagnostics. Recent diagnostic formats involve high-sensitivity immunoassay procedures, surface plasmon resonance, rapid immunoassay chemistries, signal enhancement, and smartphone detection. The current trend is toward fully integrated lab-on-chip platforms with smartphone readouts, enabling health-care practitioners and even patients to monitor pathological changes in biomarker levels. This review provides a critical analysis of advances made in HFA assays along with the challenges and future prospects., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The paper reviews the data available in the literature on existing laboratory markers for systemic bacterial infection, among which C-reactive protein, proinflammatory cytokines, procalcitonin test, and presepsin receive primary emphasis.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 5% of the elderly population. PD diagnosis is still based on the identification of neuromotor symptoms although nonmotor manifestations emerge years prior to diagnosis. The discovery of biomarkers at the earliest stages of PD is of extreme interest. miRNAs have been considered potential biomarkers for neurodegenerative diseases, but only a limited number have been found to be PD related. This review focuses on the current findings in the field of circulating miRNAs in PD and the challenges surrounding clinical utility and validation. We briefly describe the more established circulating biomarkers in PD and provide a more thorough review of miRNAs differentially expressed in PD. We highlight their potential for being considered as biomarkers for diagnosis while emphasizing the challenges for adequate validation of the findings and how miRNAs can be envisioned in a clinical setting satisfying regulatory bodies.

Using data from the National Health and Nutrition Examination Survey for the period 2003-2012, the objective of this study was to evaluate trends in blood lead levels (BLL) among children aged 1-5 and 6-11 years and smoker and nonsmoker adolescents aged 12-19 years. Regression models with log10 transformed values of BLLs as dependent variable were fitted to evaluate how gender, race/ethnicity, smoking, and exposure to secondhand smoke at home affect BLLs. Irrespective of age, gender, and race/ethnicity, BLLs declined over the study period (p ≤ 0.01). Overall, adjusted BLLs declined by 0.00114 μg/dL for every 2 years. Children aged 1-5 years had about 50 % higher BLLs than smoker adolescents, about 75 % higher BLLs than nonsmoker adolescents, and about 45 % higher BLLs than children aged 6-11 years. While overall, children aged 1-5 years with BLL ≥ 5 μg/dL made up 3.24 %, 7.8 % non-Hispanic Black children aged 1-5 years had BLL ≥ 5 μg/dL. Males were found to have higher adjusted BLLs than females, and non-Hispanic Blacks were found to have higher adjusted BLLs than non-Hispanic Whites. Higher poverty income ratio was associated with lower adjusted BLLs (β = -0.02916, p < 0.01). Children living in owner-occupied homes had lower adjusted BLLs than children living in renter-occupied homes. BLLs increased with increase in number of smokers smoking inside the home (β = 0.02496, p = 0.02). In conclusion, while BLLs have declined for all age groups, genders, and races/ethnicities, certain races/ethnicities like non-Hispanic Blacks continue to have substantially higher BLLs than non-Hispanic Whites.

Purpose: Sarcoidosis is a disease with heterogenous clinical presentations. Diagnosis of sarcoidosis is often challenging with the lack of gold standard tests. In this study, we investigated the diagnostic utility of angiotensin-converting enzyme (ACE) for diagnosis of sarcoidosis., Methods: A cohort of Olmsted County, Minnesota residents who were diagnosed with sarcoidosis between January 1, 1984 and December 31, 2013 was identified based on individual medical record review. ACE levels recorded in the medical records of all subjects at the time of diagnosis were extracted. Comparator subjects were residents of Olmsted County, Minnesota who had ACE levels tested the same time period but did not have a diagnosis of sarcoidosis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the c-statistic of high versus low/normal ACE to diagnose sarcoidosis were calculated., Results: A total of 3277 Olmsted County residents age ≥18 years had at least one ACE test in 1984-2013. The sarcoidosis incidence cohort contained 295 Olmsted County residents diagnosed with sarcoidosis in 1984-2013. Of these, ACE tests were obtained in 251. The sensitivity and specificity of high ACE for diagnosis of sarcoidosis were 41.4 % (95 % CI 35.3-47.8 %) and 89.9 % (95 % CI 88.8-91.0 %), respectively. The PPV and NPV in this population were 25.4 % (95 % CI 21.3-29.9 %) and 94.9 % (95 % CI 85.0-87.4 %)., Conclusions: This study demonstrated a poor sensitivity and insufficient specificity of high ACE for diagnosis of sarcoidosis suggesting a limited role of ACE in clinical practice.

Lactate is a product of anaerobic metabolism. Lactate concentration in blood is used clinically as an indicator of tissue hypoperfusion and hypoxia to determine disease severity, assess response to therapy, and predict outcome. This article reviews lactate physiology, sample collection and processing, and interpretation of lactate concentration in clinical practice., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Blood-based assays for various cardiac biomarkers can assist in the diagnosis of heart disease in dogs and cats. The two most common markers are cardiac troponin-I and N-terminal pro-B-type natriuretic peptide. Biomarker assays can assist in differentiating cardiac from noncardiac causes of respiratory signs and detection of preclinical cardiomyopathy. Increasingly, studies indicate that cardiac biomarker testing can help assess the risk of morbidity and mortality in animals with heart disease. Usage of cardiac biomarker testing in clinical practice relies on proper patient selection, correct interpretation of test results, and incorporation of biomarker testing into existing diagnostic methods., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Iron is an essential element and is used by every cell in the body. This article summarizes iron metabolism and disorders associated with iron metabolism in dogs and cats. The diagnostic tests currently in use for assessing iron status are discussed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Hyperglycemia, hypoglycemia and increased glucose variability are independently associated with increased risk of death in critically ill adults. The relationship between time in targeted blood glucose range (TIR) and mortality is not well described and may be a factor that has confounded the results of the major interventional trials of intensive insulin therapy., Methods: We conducted a retrospective analysis of prospectively collected data involving 3,297 patients with intensive care unit (ICU) lengths of stay (LOS) of ≥ 1.0 day who were admitted between 1 January 2009 and 31 December 2013 to a single mixed medical-surgical ICU. We investigated the relationship between TIR 70 to 140 mg/dl with mortality and compared outcomes of non-diabetics (NON) and individuals with diabetes mellitus (DM), including stratifying by TIR above (TIR-hi) and below (TIR-lo) the median value for the NON and DM groups., Results: There were 85,799 blood glucose (BG) values for the NON group and 32,651 for the DM group, and we found that 75.5% and 54.8%, respectively, were between 70 and 140 (P < 0.0001). The median (interquartile range) TIR (%) values for the NON and DM groups were 80.6% (61.4% to 94.0%) and 55.0% (35.5% to 71.1%), respectively (P < 0.0001). For the NON group, mortality was 8.47% and 15.71% for TIR-hi and TIR-lo, respectively (P < 0.0001). For the DM group, mortality was 16.09% and 14.44% for TIR-hi and TIR-lo, respectively (P = NS). We observed similar relationships for the NON group when we stratified by ICU LOS or severity of illness, especially in the most severely ill patients. There was a cumulative interaction of indices of hypoglycemia, hyperglycemia or glucose variability with TIR. Multivariable analysis demonstrated, for the NON group, that TIR-hi was independently associated with increased survival (P = 0.0019). For the NON group, the observed-to-expected mortality ratios for TIR-hi and TIR-lo, based on Acute Physiology and Chronic Health Evaluation IV methodology, were 0.53 and 0.78, respectively. In contrast, among those in the DM group, there was no clear relationship between TIR 70 to 140 mg/dl and survival., Conclusions: Independently of ICU LOS and severity of illness, TIR 70 to 140 mg/dl > 80% is strongly associated with survival in critically ill patients without diabetes. These findings have implications for the design of clinical protocols for glycemic control in critically ill patients as well for the design of future interventional trials of intensive insulin therapy.

An observational cohort analysis was conducted within the Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) DataLink, a consortium of 11 integrated health-care delivery systems with electronic health records in 10 US states. Among nearly 7 million adults aged 20 years or older, we estimated annual diabetes incidence per 1,000 persons overall and by age, sex, race/ethnicity, and body mass index. We identified 289,050 incident cases of diabetes. Age- and sex-adjusted population incidence was stable between 2006 and 2010, ranging from 10.3 per 1,000 adults (95% confidence interval (CI): 9.8, 10.7) to 11.3 per 1,000 adults (95% CI: 11.0, 11.7). Adjusted incidence was significantly higher in 2011 (11.5, 95% CI: 10.9, 12.0) than in the 2 years with the lowest incidence. A similar pattern was observed in most prespecified subgroups, but only the differences for persons who were not white were significant. In 2006, 56% of incident cases had a glycated hemoglobin (hemoglobin A1c) test as one of the pair of events identifying diabetes. By 2011, that number was 74%. In conclusion, overall diabetes incidence in this population did not significantly increase between 2006 and 2010, but increases in hemoglobin A1c testing may have contributed to rising diabetes incidence among nonwhites in 2011., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The study of utilization patterns can quantify potential overuse of laboratory tests and find new ways to reduce healthcare costs. We demonstrate the use of distributional analytics for comparing electronic health record (EHR) laboratory test orders across time to diagnose and quantify overutilization., Materials and Methods: We looked at hemoglobin A1c (HbA1c) testing across 119,000 patients and 15 years of hospital records. We examined the patterns of HbA1c ordering before and after the publication of the 2002 American Diabetes Association guidelines for HbA1c testing. We conducted analyses to answer three questions. What are the patterns of HbA1c ordering? Do HbA1c orders follow the guidelines with respect to frequency of measurement? If not, how and why do they depart from the guidelines?, Results: The raw number of HbA1c orderings has steadily increased over time, with a specific increase in low-measurement orderings (<6.5%). There is a change in ordering pattern following the 2002 guideline (p<0.001). However, by comparing ordering distributions, we found that the changes do not reflect the guidelines and rather exhibit a new practice of rapid-repeat testing. The rapid-retesting phenomenon does not follow the 2009 guidelines for diabetes diagnosis either, illustrated by a stratified HbA1c value analysis., Discussion: Results suggest HbA1c test overutilization, and contributing factors include lack of care coordination, unexpected values prompting retesting, and point-of-care tests followed by confirmatory laboratory tests., Conclusions: We present a method of comparing ordering distributions in an EHR across time as a useful diagnostic approach for identifying and assessing the trend of inappropriate use over time., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The acupuncture-moxibustion serum has received wide attention as a new idea and method. Its application on researches in vivo and the treatment of disease not only has an important theory value, but also provides new ideas for overcoming the limitations of researches in vivo and some disease's treatment. Literature regarding the basic research of acupuncture-moxibustion serum for last more than 10 years is reviewed, and the effects of acupuncture-moxibustion serum on respiratory system, digestive system, cardiovascular system, nervous system, immune system, anti-aging, bone metabolism and anti-cancer are summarized, hoping to provide references for clinical treatment and evidence-based medicine.

The analysis of intact parathyroid hormone (PTH) (PTH1-84) is useful in the diagnosis of hyper- and hypocalcaemia, hyperparathyroidism, and in the prevention of bone mineral disorders in renal patients. The analysis is complicated by the presence of PTH fragments, which may accumulate in renal failure and cross-react in immunoassays, including the most recent third-generation immunoassays. Large variability exists between different commercially available assays. This article reviews the current literature on PTH testing, with emphasis on the use of mass spectrometry-based methods, and considers the important sources of variation which still need to be addressed prior to the development of much needed candidate reference methods for PTH analysis. Recently, mass spectrometric methods have been developed for the quantitation of PTH1-84 using surrogate tryptic peptides, but even these methods are subject to significant interferences due to the presence of newly observed modified PTH species, such as oxidised and phosphorylated PTH variants, which can accumulate in patient samples. Further work, including: 1) the use of high-resolution mass spectrometry; and 2) the analysis of PTH without prior protease digestion, is required before these approaches can be considered as reference methods against which other methods should be harmonised.

Molecular diagnostics is crucial for prevention, identification, and treatment of disease. Traditional technologies for molecular diagnostics using blood are limited to laboratory use because they rely on sample purification and sophisticated instruments, are labor and time intensive, expensive, and require highly trained operators. This review discusses the frontiers of point-of-care (POC) diagnostic technologies using a drop of blood obtained from a finger prick. These technologies, including emerging biotechnologies, nanotechnologies, and microfluidics, hold the potential for rapid, accurate, and inexpensive disease diagnostics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Preoperative laboratory testing is commonplace in the clinical setting and is often utilized at surgeon discretion. We searched the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) data set to determine the impact of preoperative laboratory testing in ambulatory plastic surgery patients., Objective: The authors assess the utilization and predictive value of preoperative laboratory testing in outpatient plastic surgery procedures., Methods: Patients undergoing ambulatory plastic surgery were identified from the 2005 to 2010 NSQIP databases. Laboratory tests were categorized by group: hematologic, chemistry, coagulation, and liver function tests (LFT). We defined complications in 2 groups: major postoperative and wound complications. Multivariate analyses were used to identify patient characteristics associated with testing and to assess the ability of laboratory testing to predict postoperative complications., Results: A total of 5359 (62.0%) patients underwent testing; 881 (16.4%) tests were performed on the day of surgery. In patients with no defined NSQIP comorbidities, 59.4% underwent preoperative testing and had a significantly lower rate of abnormal findings (33.4% vs 25.3%, P < .0001). In multivariate analyses, testing was associated with older age, American Society of Anesthesiologists class >2, Hispanic or African American race, body contouring procedures, epidural or spinal procedures, and with diabetes, hypertension, and cancer. Major complications occurred in 0.34% of patients. Our analysis demonstrated that neither testing nor abnormal results were associated with postoperative complications, either major (P = .178) or wound (P = .150)., Conclusions: We found no association between abnormal laboratory testing and postoperative morbidity. Preoperative testing in low-risk ambulatory plastic surgery patients may be costly and has limited direct clinical benefit.

Background: More than 2.9 million serum vitamin B12 tests were performed in 2010 in Ontario at a cost of $40 million. Vitamin B12 deficiency has been associated with a few neurocognitive disorders., Objective: To determine the clinical utility of B12 testing in patients with suspected dementia or cognitive decline., Methods: Three questions were addressed: Is there an association between vitamin B12 deficiency and the onset of dementia or cognitive decline? Does treatment with vitamin B12 supplementation improve cognitive function in patients with dementia or cognitive decline and vitamin B12 deficiency? What is the effectiveness of oral versus parenteral vitamin B12 supplementation in those with confirmed vitamin B12 deficiency? A literature search was performed using MEDLINE, Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination database, from January 2002 until August 2012., Results: Eighteen studies (7 systematic reviews and 11 observational studies) were identified to address the question of the association between B12 and the onset of dementia. Four systematic reviews were identified to address the question of the treatment of B12 on cognitive function. Finally, 3 randomized controlled trials were identified that compared oral B12 to intramuscular B12., Conclusions: Based on very low quality evidence, there does appear to be an association between elevated plasma homocysteine levels (a by-product of B vitamins) and the onset of dementia. Based on moderate quality evidence, but with less than optimal duration of follow-up, treatment with B12 supplementation does not appreciably change cognitive function. Based on low to moderate quality of evidence, treatment with vitamin B12 and folate in patients with mild cognitive impairment seems to slow the rate of brain atrophy. Based on moderate quality evidence, oral vitamin B12 is as effective as parenteral vitamin B12 in patients with confirmed B12 deficiency., Plain Language Summary: Low levels of vitamin B12 have been associated with neurocognitive disorders. This evidence-based analysis assessed the usefulness of serum vitamin B12 testing as it relates to brain function. This review found very low quality evidence that suggests a connection between high plasma homocysteine levels (a by-product of B vitamin metabolism in the body) and the onset of dementia. Moderate quality of evidence indicates treatment with vitamin B12 does not improve brain function. Moderate quality of evidence also indicates treatment using oral vitamin B12 supplements is as effective as injections of vitamin B12.

Background: During the past decade, several clinical trials investigating the potential benefits of homocysteine-lowering therapy for the secondary prevention of vascular events were completed and published. The objective of the study was to determine trends in clinical laboratory testing for homocysteine at a single institution over the time period from 1997 to 2010., Methods: A single-center, retrospective analysis was performed at a large, academic, tertiary care medical center in the USA. The database was searched for clinical laboratory measurements of plasma or serum homocysteine between January 1, 1997 and December 31, 2010. Individual medical records were reviewed for a subset of 221 unique patients in the 10-year period from 2001 to 2010 who had homocysteine values ≥20 μmol/L., Results: From 1997 to 2003, there was a 16-fold increase in the annual number of homocysteine assays performed. Testing for homocysteine declined in 2004 and 2006, coinciding with the publication of intervention trials that failed to support a clinical benefit of homocysteine-lowering therapy for the secondary prevention of vascular events. Subgroup analysis suggested that homocysteine testing for the indication of suspected nutritional deficiency or hypercoagulability remained steady despite a decline in testing for the indication of cardiac risk assessment., Conclusions: The frequency of clinical laboratory testing for plasma or serum homocysteine changed bimodally over the time period from 1997 to 2010. These observations suggest that clinical practice was impacted by emerging evidence from association studies and intervention trials investigating homocysteine as a potentially treatable cardiac risk factor.

Clinical interest in Vitamin D and its purported roles not only in calcium and bone metabolism but in several other medical conditions (diabetes, cardiovascular disease, multiple sclerosis, cancer, psychiatric disorders, neuro-muscular disease) has led to a surge in laboratory requests for 25 hydroxy vitamin D and 1,25 dihydroxy vitamin D measurement. Circulating 25 hydroxy vitamin D concentration is routinely used as the best indicator of vitamin D status, but measurement of other metabolites, especially the physiologically active 1,25 dihyroxy vitamin D, are of clinical value. Over the last 40 years the development of assays for vitamin D and its metabolites from early competitive binding assays through to immunoassay and liquid chromatography aligned to mass spectrometry have demonstrated various analytical challenges, the advantages and disadvantages of each method are constantly changing with new technological developments. Immunoassay remains the predominant mode of measurement for 25-hydroxy vitamin D although problems with equimolar recovery of the D2 and D3 metabolites remain an issue. Standardisation of all assays has been improved but not resolved with the currently available reference materials as evidenced by the international vitamin D external quality assurance scheme, DEQAS. The choice of method for each laboratory remains a balance mainly between turn around time, convenience, cost and the specificity and accuracy of the information obtained. With increasing discussion and clinical interest surrounding other vitamin D metabolites the vitamin D assay debate is set to continue.

Background: We aimed to compare the variation in PSA test ordering behavior between ten different health centers according to patients' age and the tendencies in PSA testing during the period of study (2002 - 2009)., Methods: The study subjects attended 10 primary care centers in Alicante, Spain (2002 - 2009). Variables included: patient age, primary center, and year. We calculated percentages of PSA testing for each age group over the total PSA testing in each center and year., Results: A great variability has been shown between the different centers, mainly in patients where the controversy in PSA testing is higher: in the group including patients younger than 50 and those older than 85 years old. PSA testing percentages increased along the period of study for all the groups of age, except for the group of patients aged between 50 and 75 years old, where accordingly, PSA testing percentages decreased along the time., Conclusions: These results may contribute to the discussion about the use of PSA testing and show the importance of a consensus among healthcare providers to facilitate adoption of an approach while international recommendations come to an agreement.

The evaluation of glycated hemoglobin (HbA(1c)) is used in daily practice for monitoring the diabetes mellitus. HbA(1c) may be assayed by different methods, among which high-pressure liquid chromatography (HPLC). We have evaluated a new kit 2.0 available on HPLC Variant II(®) Turbo analyzer (Bio-Rad), which is characterized by an elution buffer containing sodium perchlorate. The correlation with the routine method used in our laboratory (HPLC Variant II(®) analyzer equipped with the NU kit) is good (r² = 0.997). Intra- and inter-assay coefficients of variation are respectively lower than 0.6 and 1.6%. Linearity is excellent from 3.2% (11 mmol/mol) to 18.3% (177  mmol/mol). There is no inter-sample contamination. This method provides a result quickly (96  seconds), but does not allow separating labile HbA(1c) from carbamylated hemoglobin, contrary to the NU kit. As the control of analytical quality is a major concern for validation and clinical use of HbA(1c) results, the characteristics of this new kit make it a well-suited tool for daily laboratory practice.

Introduction: National transplant registries routinely focus on centre-specific patient and graft survival rates following renal transplantation. However other outcomes such as graft function (as measured by eGFR), haemoglobin, biochemical variables and blood pressure are also important quality of care indicators., Methods: Renal transplant activity, incident graft survival data and donor information were obtained from NHS Blood and Transplant. Laboratory and clinical variables and prevalent survival data were obtained from the UK Renal Registry. Data were analysed separately for prevalent and one year post-transplant patients., Results: Increasing live and donor after cardiac death donors were responsible for the increasing transplant activity within the UK. During 2009, 2.9% of prevalent transplant patients experienced graft failure and transplant patient death rates remained stable at 2.5 per 100 patient years. There was centre variation in outcomes including eGFR, haemoglobin and biochemical variables in prevalent and 1 year posttransplant patients. Analysis of prevalent transplants by chronic kidney disease stage showed 14.3% with an eGFR <30 ml/min/1.73 m(2) and 1.9% with an eGFR <15 ml/min/1.73 m(2). Of those with CKD stage 5T, 33.3% had haemoglobin concentrations <10.5 g/dl, 22.4% phosphate concentrations ≥ 1.8 mmol/L and 7.7% adjusted calcium concentrations ≥ 2.6 mmol/L., Conclusion: Significant variations in clinical outcomes (unadjusted for patient-specific variables) amongst kidney transplant recipients continued to exist in the UK, and may reflect differences in healthcare delivery between renal centres., (Copyright © 2011 S. Karger AG, Basel.)

Since the early 1960s, dried blood spots (DBS) on filter paper have been used in clinical applications. The first key milestone in the use of DBS was the screening of phenylketonuria and other inborn errors of metabolism using microbiological and enzymatic analytical methods. 20 years after its introduction, advanced mass spectrometers and new soft ionization techniques have permitted the coupling of liquid chromatography with MS and tandem MS (MS/MS) and since the 1990s, DBS analysis by LC-MS/MS expanded screening to many inborn errors of metabolism simultaneously. Recently, DBS-LC-MS/MS analysis has been used in other fields such as pharmacology, toxicology and forensic sciences. Today, new ambient ionization techniques, coupled to MS, directly desorb/ionize molecules from solid samples. This presents new opportunities for the in situ analysis of DBS. Most likely, ambient MS methods will be used to analyze DBS, increasing the clinical applications of MS within the next 10 years.

Proteomics has brought new perspectives to the fields of hematology and transfusion medicine in the last decade. The steady improvement of proteomic technology is propelling novel discoveries of molecular mechanisms by studying protein expression, post-translational modifications and protein interactions. This review article focuses on the application of proteomics to the identification of molecular mechanisms leading to the deterioration of blood platelets during storage - a critical aspect in the provision of platelet transfusion products. Several proteomic approaches have been employed to analyse changes in the platelet protein profile during storage and the obtained data now need to be translated into platelet biochemistry in order to connect the results to platelet function. Targeted biochemical applications then allow the identification of points for intervention in signal transduction pathways. Once validated and placed in a transfusion context, these data will provide further understanding of the underlying molecular mechanisms leading to platelet storage lesion. Future aspects of proteomics in blood banking will aim to make use of protein markers identified for platelet storage lesion development to monitor proteome changes when alterations such as the use of additive solutions or pathogen reduction strategies are put in place in order to improve platelet quality for patients., ((c) 2009 Elsevier B.V. All rights reserved.)

The first umbilical cord blood (UCB) transplant to a sibling with Fanconi's anaemia in 1988 represented a breakthrough in the field of transplantation. Thereon, several transplants have been performed with UCB-derived hematopoietic stem cells (HSCs) and a plethora of studies have investigated the plasticity of UCB-derived stem and progenitor cells. However, these studies have not been hitherto translated into clinical trials and, although UCB is routinely used as an alternative source of HSCs, no substantial advances have been made in the field of clinical regenerative medicine. The real deal is the lack of knowledge about the molecular processes governing the events of differentiation which transform immature UCB stem cells into terminally-committed hematopoietic, muscle, bone and nervous cells. In order to fill this void, several studies have been recently focused on the identification of the peculiar proteomic profile of UCB-derived stem cells. Hereby, we concisely review recent proteomic surveys addressing UCB-derived stem and progenitor cells. Notably, comparative studies detected a wider spectrum of proteins in immature cells rather than in more differentiated populations, as if maturation events could represent a bottleneck to protein expression. Future research projects should try to shed light on these processes and their completion could pave the way for unprecedented treatments., ((c) 2009 Elsevier B.V. All rights reserved.)

Cardiac troponins play a major role in the diagnostic work-up of acute coronary syndrome/myocardial infarction. Elevations were demonstrated also in other, rather nonischemic diseases like pulmonary embolism or acute heart failure. Stepwise improvement in the accuracy of the commercially available assays allowed detection of low-level concentrations of cardiac troponins, which were previously partially classified to be normal (between the limit of detection and the 99 th percentile by < 10% coefficient of variance). These low concentrations were associated with the detection of chronic cardiovascular pathologies and an increased risk of future cardiovascular events. Recently, ten to 100 times more sensitive assays (so-called high sensitive or ultra sensitive assays) have been developed. The clinical importance of those now measurable troponin values is currently under intensive investigation. The expected additional clinical and prognostic information from such low- and even lowest-level troponin values pose a special challenge. Specifically, the question has been raised, whether the established single cutoff approach for diagnosing myocardial infarction should not be complemented by another, lower cutoff usable for the detection of other (stable) cardiovascular pathologies with lower but still substantial risk.

Preventive care has the aim to prevent the occurrence of disease and to detect disease at an early stage, in order to allow for timely interventions. Before tests can be implemented into routine prevention care, several criteria have to be satisfied. Laboratory tests such as fasting glucose, lipids, fecal occult blood testing are widely used within preventive programs. The use of other parameters, such as PSA, TSH, creatinine, urine albumin (albumin/creatinine ration, ACR) similarly might get an important role. This article focuses on the role of laboratory tests in preventive care with a special emphasis on recommendations on their use in Central Europe.

Some variant proteins cause diseases, and some diseases result in increases of proteins with abnormally modified structures. The detection, characterization, and estimation of the relative amounts of protein variants and abnormally modified proteins are important for clinical diagnosis and for elucidation of the mechanisms of the pathogenesis of diseases. Analysis of the covalent structures of proteins using matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography-electrospray ionization MS (LC-ESI-MS), which had been developed by the early 1990s, have largely replaced analyses by conventional protein chemistry. Here, we review the detection and characterization of hemoglobin variants, HbA1c measurement, detection of carbohydrate-deficient transferrin, and identification of variants of transthyretin (TTR) and Cu/Zn-superoxide dismutase (SOD-1) using soft ionization MS. We also propose the diagnostic application of the signals of modified forms of TTR, that is, S-sulfonated TTR and S-homocysteinyl TTR. The relative peak height ratio of the abnormal/normal components gives valuable information about the instability of variants and enables the detection of unstable Hb subunits or thalassemia heterozygotes. We found unique modified structures of TTR that suggested changes in amyloid fibrils.