The automated processing algorithm to correct the test result of serum neuron-specific enolase affected by specimen hemolysis.

INTRODUCTION: Serum neuron-specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test. METHODS: The reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots. RESULTS: The high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = -0.069, p = 0.640). The 95% confidence interval of mean difference (from -8.33% to 12.17%) was less than the acceptable bias range (±20%). CONCLUSION: The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.

Consensus of the Spanish society of laboratory medicine and the Spanish society of medical oncology on the methodology and criteria for evaluation of circulating tumour markers in breast cancer.

The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.

Establishment of improved review criteria for hematology analyzers in cancer hospitals.

BACKGROUND: Although hematologic review criteria for general hospitals have been established, they may be insufficient for cancer hospitals. This study aimed to establish the appropriate review criteria for hematology analyzers in cancer hospitals. METHODS: A total of 1003 samples from our hospital were randomly selected for blood smear preparation and microscopic review. The review criteria of the International Consensus Group for Hematology Review (ICGH) and Chinese consensus group were used to obtain the review, true-negative (TN), true-positive (TP), false-negative (FN), and false-positive (FP) rates, as well as the triggered rules. Our review criteria were established by comparing flag or numeric value information of TP and FP samples, adjusting rules to obtain better efficiency, a low slide review rate, and an acceptable FN rate. RESULTS: Overall, 197 (19.64%) samples showed positive smear findings. Compared to the ICGH criteria, the slide review rate of the newly established criteria declined from 51.25% to 39.28%, and the TP and TN rates increased from 17.85% and 46.06% to 23.13% and 55.83%, respectively. The FN rate of the newly established criteria was 3.69%. Another set of samples used to validate the newly established criteria yielded the review, FN, and FP rates as 33.49%, 1.86%, and 25.58%, respectively. CONCLUSION: The newly established review criteria for hematology analyzers enabled the prompt identification, smear, and further verification of doubtful specimens, without a significant increase in the workload, thus improving the efficiency of the review process. This study provided data support for other cancer hospitals to establish review criteria.

The integration of Sysmex XN-9100' WPC channel reflex testing in the detection of reactive versus malignant blood samples.

INTRODUCTION: Sysmex XN-9100™ (Sysmex, Kobe, Japan) system has an optional White Progenitor Cell (WPC) channel. While the White Differentiation (WDF) channel reports a combined flag for blasts/abnormal lymphocytes, WPC channel specifies flagging into a separate flag for each cell type or removes the flag entirely. Aim of this study was to evaluate the added value of this WPC channel in the detection of malignant samples. METHODS: Routine blood samples analyzed on Sysmex XE-5000 with flagging for either blasts, abnormal lymphocytes, or atypical lymphocytes (n = 630) were selected for testing on Sysmex XN-9100, resulting in a reflex WPC analysis in 420 samples. All samples were microscopically evaluated with DI-60 digital cell imaging analyzer. RESULTS: WPC reflex testing resulted in a suspect flag ("blasts" and/or "abnormal lymphocytes") in 334 samples, which was confirmed microscopically in 38% (128/334). In all true positive samples, WPC correctly classified the initial WDF flag in either "blasts" flag or "abnormal lymphocytes?" flag in 75%. Only 12% (50/420) of WDF "blasts/abnormal lymphocytes" positive samples became negative after WPC reflex testing. Subgroup analysis showed differences between the "pediatric" versus "adult" groups and the "hematological/chemotherapy" versus "nonhematological/nonchemotherapy" groups in specificity and smear reduction. CONCLUSION: Overall, WPC reflex testing showed good sensitivity (99%); however, the specificity remains poor (29%). Using reflex WPC to the WDF channel resulted in a 12% reduction of the smear review rate. Although the WPC channel offers different interesting advantages, additional topics and a specific workflow should be applied to optimize the use of this channel.

New trimester-specific reference intervals for clinical biochemical tests in Taiwanese pregnant women-cohort of TMICS.

BACKGROUND: Because there are no published biochemical reference intervals (RI) for pregnant Taiwanese women, we used an established islandwide birth cohort, the Taiwan Maternal and Infant Cohort Study, to establish RIs for important biochemical parameters in women during their 3rd trimester in Taiwan. Additionally, we compared the differences in these biochemical parameters between early third trimester (weeks 28 to 31) and late third trimester (weeks 37 to 40) of pregnant women as well as the differences in them between the third trimester and after delivery. METHODS: Between 2012 and 2015, we recruited a total of 2,136 pregnant women from nine hospitals located in northern (n = 3), central (n = 3), southern (n = 2), and eastern Taiwan (n = 1) to receive regular prenatal health examinations during their third trimester (weeks 28 to 40). After exclusion, samples obtained from 993 eligible pregnant women were analyzed. RESULTS: There were increases in both lower and upper normal limits for blood neutrophil, thyroid profile (triiodothyronine (T3) and thyroxine (T4)), testosterone, estradiol, and progesterone and decreases for RBC, hemoglobin (Hb), alanine aminotransferase (ALT) and creatinine (Cr) during their third trimesters. Women in their late third trimester (n = 378) had higher median RBC, Hb, aspartate aminotransferase (AST), Cr, thyroid-stimulating hormone (TSH), testosterone, estradiol, and progesterone and lower median platelet and insulin, compared with those in their early third trimester (n = 490). Twenty-three of the women had both third trimester and post-pregnancy data. After delivery, the women had lower median AST, ALT, insulin, T3, T4, testosterone, estradiol, and progesterone and higher median Cr, free T4, FSH, and luteinizing hormone (LH), compared to their third trimesters. CONCLUSIONS: Gestation-related changes in important biochemical parameters should be considered when evaluating clinical laboratory values in pregnant women.

Development and Validation of a Serum Metabolomic Signature for Endometrial Cancer Screening in Postmenopausal Women.

Importance: Endometrial carcinoma (EC) is the most commonly diagnosed gynecologic cancer. Its early detection is advisable because 20% of women have advanced disease at the time of diagnosis. Objective: To clinically validate a metabolomics-based classification algorithm as a screening test for EC. Design, Setting, and Participants: This diagnostic study enrolled 2 cohorts. A multicenter prospective cohort, with 50 cases (postmenopausal women with EC; International Federation of Gynecology and Obstetrics stage I-III and grade G1-G3) and 70 controls (no EC but matched on age, years from menopause, tobacco use, and comorbidities), was used to train multiple classification models. The accuracy of each trained model was then used as a statistical weight to produce an ensemble machine learning algorithm for testing, which was validated with a subsequent prospective cohort of 1430 postmenopausal women. The study was conducted at the San Giovanni di Dio e Ruggi d'Aragona University Hospital of Salerno (Italy) and Lega Italiana per la Lotta contro i Tumori clinic in Avellino (Italy). Data collection was conducted from January 2018 to February 2019, and analysis was conducted from January to March 2019. Main Outcomes and Measures: The presence or absence of EC based on evaluation of the blood metabolome. Metabolites were extracted from dried blood samples from all participants and analyzed by gas chromatography-mass spectrometry. A confusion matrix was used to summarize test results. Performance indices included sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy. Confirmation or exclusion of EC in women with a positive test result was by means of hysteroscopy. Participants with negative results were followed up 1 year after enrollment to investigate the appearance of EC signs. Results: The study population consisted of 1550 postmenopausal women. The mean (SD) age was 68.2 (11.7) years for participants with no EC in the training cohort, 69.4 (13.8) years for women with EC in the training cohort, and 59.7 (7.7) years for women in the validation cohort. Application of the ensemble machine learning to the validation cohort resulted in 16 true-positives, 2 false-positives, and 0 false-negatives, and it correctly classified more than 99% of samples. Disease prevalence was 1.12% (16 of 1430). Conclusions and Relevance: In this study, dried blood metabolomic profile was used to assess the presence or absence of EC in postmenopausal women not receiving hormonal therapy with greater than 99% accuracy.

[Diagnostic workup in front of an hypereosinophilia in 2020]. / Démarche diagnostique devant une hyperéosinophilie en 2020.

The discovery of eosinophilia above 1.5 G/L should not be considered innocuous, requiring monitoring for etiology and possible secondary organ damage. Among these, cardiac localization is the most worrying, sometimes indolent, to be systematically sought by ultrasound and magnetic resonance. The potential etiologies are very numerous, mostly reactive and corticosensitive, much more rarely clonal in relation to a malignant hemopathy usually chronic and myeloid, sometimes sensitive to tyrosine kinase inhibitors.

Evaluation of laboratory investigative methods of diagnosing clonal hematological disorders in a resource-poor setting.

BACKGROUND: The successful treatment of patients with clonal hematological disorders (CHDs) depends largely on making an accurate diagnosis, which is, in turn, is dependent on performing specific diagnostic tests that are necessary. OBJECTIVES: This study assessed the laboratory investigative methods of diagnosing CHDs with regard to the specific required tests (SRTs) that were needed to make a final diagnosis in a center with limited resources. METHODS: This is a descriptive hospital-based retrospective study. For the study, data about laboratory investigation details of adults diagnosed with CHDs from 1995 to 2015 were retrieved. The SRTs were determined and data analyzed using SPSS version 20. RESULTS: A total of 129 case notes of adults in the age range of 18-80 years, diagnosed with CHDs, were used. Out of the 671 SRTs needed for diagnosis, only 304 (45.3%) were conducted. When an SRT was requested to be done within the treatment facility, the patients were significantly more likely to do it in comparison with when they were requested to get it done from an external referral laboratory. All the patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) had all (100%) their SRTs done while patients with non-Hodgkin's lymphoma (NHL) had the least (15.3%) of their SRTs done. Full blood count (FBC) was the most frequently used (n = 129; 100%) SRT for diagnosis while immunophenotyping (IMPT) was the least (n = 4; 8.3%) used SRT. CONCLUSION: Most of our patients had CHD diagnosis without the complete SRT, and this may cast doubt on the accuracy of diagnosis. Therefore, there is a crucial need for availability of more comprehensive laboratory services, especially in government-owned hospitals.

Comparison of Hemoglobin Measurements by 3 Point-of-Care Devices With Standard Laboratory Values and Reliability Regarding Decisions for Blood Transfusion.

BACKGROUND: We compared the accuracy of 3 point-of-care testing (POCT) devices with central laboratory measurements and the extent to which between-method disagreements could influence decisions to transfuse blood. METHODS: Hemoglobin concentrations [Hb] were measured in 58 adult patients undergoing cardiothoracic surgery using 2 Ilex GEM Premier 3500 blood gas analyzers (BG_A and BG_B) and a HemoCue Hb-201 device (HemoCue). Measurements were compared with our central laboratory's Siemens Advia 2120 flow cytometry system (laboratory [Hb] [Lab[Hb]]), regarded as the gold standard. We considered that between-method [Hb] differences exceeding 10% in the [Hb] range 6-10 g/dL would likely erroneously influence erythrocyte transfusion decisions. RESULTS: The 70 Lab[Hb] measurements ranged from 5.8 to 16.7 g/dL, of which 25 (36%) were <10.0 g/dL. Measurements by all 4 devices numbered 57. Mean POCT measurements did not differ significantly (P > .99). Results of the Bland-Altman analyses revealed statistically significant bias, with predominant underestimations by all 3 POCTs predominating. HemoCue upper and lower limits of agreement (LOA) were narrower, and the 95% confidence intervals (95% CIs) of the LOAs did not overlap with those of BG_A and BG_B. Similarly, a narrow mountain plot demonstrated greater precision for the HemoCue. Comparing BG_A with BG_B revealed no bias and narrow LOA. Error grid analysis within the [Hb] range 6-10 g/dL revealed that 5.3% of HemoCue measurements were beyond the permissible 10.0% error zone in contrast to 19.0% and 16.0% of the blood gas measurements. Possible inappropriate transfusion decisions based on POCT values generally erred toward unnecessary transfusions. Calculations of Cohen κ statistic indicated better chance-corrected agreement between HemoCue and Lab[Hb] regarding erythrocyte transfusions than the blood gas analyzers. CONCLUSIONS: All 3 POCT devices underestimated the Lab[Hb] and cannot be used interchangeably with standard laboratory measurements. BG_A and BG_B can be considered to be acceptably interchangeable with each other. Whereas the HemoCue had little bias and good precision, the blood gas analyzers revealed large bias and poor precision. We conclude that the tested HemoCue provides more reliable measurements, especially within the critical 6-10 g/dL range, with reduced potential for transfusion errors. Decisions regarding erythrocyte transfusions should also be considered in the light of clinical findings.

Paraprotein implicated in hardware failures in nucleic acid testing of blood donors.

BACKGROUND AND OBJECTIVES: Analyser blockage due to gel formation by paraproteins leading to invalid results is a rare problem in viral nucleic acid testing (NAT) at New Zealand Blood Service (NZBS) despite many blood samples tested without problems from individuals with known paraproteins. This study aimed to identify common factors in samples causing blockages. METHOD: Retrospective data were gathered on blood samples known to have blocked analysers at NZBS testing sites. Patients with plasma cell dyscrasia undergoing haematopoietic stem cell (HSC) harvest formed the comparator arm. These patients were identified from registry data of individuals undergoing autologous stem cell transplantation at Auckland City Hospital between 2013 and 2017. RESULTS: Four individuals were identified as having blocked analysers between 2010 and 2018. A total of 184 HSC transplant patients were identified, with contemporaneous paraprotein levels available for 177 (96%). Patients with intact immunoglobulin subtypes (134, 73%) were further analysed. Of these, 119 patients (65%) also had total protein and globulin levels available. Mean paraprotein (37.5 g/l), total protein (95.3 g/l), globulin levels (51.5 g/l) and proportion of lambda subtype (75%) were higher in the blocker group compared with non-blocking comparators (4.7 g/l, 66.8 g/l, 27.7 g/l, 36.6% respectively) (P = 0·03, 0·02, 0·007, 0·12). The highest paraprotein and total protein levels from the non-blocking cohort overlapped with the lowest of the blocker group. DISCUSSION: High protein levels (paraprotein >20 g/l, total protein >75 g/l) and a trend towards lambda subtype were associated with NAT analyser blockage. The overlap with non-blocking donor samples suggests factors in addition to protein quantity that are also important.

Utility of Perioperative Laboratory Tests in Pediatric Patients Undergoing Spinal Fusion for Scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: We aimed to characterize the frequency of perioperative laboratory tests for posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and to assess whether test results affected clinical management. SUMMARY OF BACKGROUND DATA: Perioperative laboratory tests for PSF including complete blood count, coagulation laboratory tests, basic metabolic panels (BMPs), and type and screen, are commonly ordered based on providers' discretion or existing order sets. Studies have shown unnecessary laboratory tests as financially and physically costly in adults; however, no studies have examined the necessity of common perioperative laboratory tests in pediatric spinal deformity surgery. METHODS: Retrospective review of patients aged 10-18 years who underwent PSF for AIS at our center in the past three years. The clinical utility of perioperative laboratory tests was assessed based on detected incidence of anemia, blood transfusions, hematology/endocrinology/nephrology consultations, insulin administration, and postponed/canceled surgeries. RESULTS: A total of 234 patients were included (mean age 14.4 ± 1.8 years, 75% female). Of 105 (44.9%) patients with preoperative coagulation laboratory tests, 21 (20%) had abnormal results; however, none had subsequent hematology consultations or canceled/postponed surgeries. Postoperatively, only 5 (2.1%) patients and 30 (12.8%) patients had hemoglobin values less than 8 g/dL on postoperative day (POD) 1 and 2, respectively. Multivariate analysis identified POD1 hemoglobin ≤9.35 g/dL as the only predictor of hemoglobin <8 g/dL on POD2. Overall, there were 8 (3.4%) indicated blood transfusions postoperatively. Costs of unnecessary laboratory tests averaged $95.27 (range $49.72 to $240.27) per patient. CONCLUSIONS: Many perioperative laboratory orders may be unnecessary in pediatric spinal deformity surgery, subjecting patients to extraneous costs and needlesticks. In particular, preoperative coagulation laboratory tests, perioperative BMPs, and additional postoperative CBCs for those with hemoglobin >9.35 on POD1 may not be warranted. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

[D-dimer: how about it?] / D-dimeerbepaling: hoe zit het ook alweer?

This lab quiz presents some practical case studies on the correct use of D-dimer tests in patients suspected of venous thromboembolism. Elevated D-dimer levels are associated with clotting activation and fibrinolysis and can be used as indirect biomarkers of thrombosis. The D-dimer test is highly sensitive and is used to rule out the presence of venous thromboembolism (VTE) when clinical probability is low, based on Wells scores. However, sensitivity and specificity of cut-off values for D-dimer for ruling out VTE are strongly assay-dependent due to lack of standardisation. Because of low specificity, use of these cut-off values is problematic in cases of sepsis and inflammation, after recent surgery and in cases of trauma and active malignancy as well as during anticoagulant therapy and pregnancy. Agedependent cut-off values for patients > 50 years old might improve specificity and could be safely used if clinically validated assays (latex-agglutination assays) are used as described for the ADJUST-study.

Harmonization of Training, Training Requirements, Board Certification, and Practice of Hematopathology.

OBJECTIVES: Hematopathology (HP) is a rapidly changing field with insufficient data to provide guidance to program directors (PDs), the Accreditation Council for Graduate Medical Education, or the American Board of Pathology. METHODS: Two surveys were performed-one for HP PDs and one, given twice, for HP diplomates doing Maintenance of Certification/Continuing Certification reporting in 2017 to 2018. RESULTS: Bone marrow (BM), lymph node (LN), and flow cytometry interpretations and peripheral blood/fluid reviews are performed by more than 80% of hematopathologists and are the areas with the greatest amount of training. A smaller proportion of hematopathologists is involved in other HP-related activities. Most PDs believed fellows should perform BM procedures. Interpretation of 400 or more LNs and 500 BMs was PDs' median expectations for fellows. PDs and HP diplomates considered coagulation and benign RBC disorders overemphasized on the certification examination. CONCLUSIONS: These results highlight how varied the practice of HP is and can provide guidance to HP PDs, those responsible for assessing HP programs, and the American Board of Pathology.

Proposal for the International Society for Cell & Gene Therapy position statement on assays for the quality control and potency assessment of adoptive cellular immunotherapies.

Translation of cell and gene therapies from pre-clinical experiments to clinical trials and final drug licensing brings requires the development, verification and even validation of the assays essential for the definition of the drug product. The technical and scientific challenges in doing this are far greater than they seem at first and are compounded by a lack of approved standards for assays used to support (c)GMP manufacture. This paper highlights some of those challenges and proposes solutions based on the experience of our colleagues using similar assay platforms in regulated pathology laboratories.

Performance of the point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for follow-up after treatment of S. mansoni infection in Eritrean refugees.

BACKGROUND: Point-of-care circulating cathodic antigen (POC-CCA) urine cassette testing has become a popular approach to screen for Schistosoma infection. Since the test is also increasingly used for following-up of treatment success, we assessed the assay's diagnostic accuracy after praziquantel treatment of S. mansoni infection among Eritrean refugees in Switzerland. METHODS: In our preceding study, 107 asymptomatic Eritrean refugees in Switzerland were screened for schistosomiasis by stool microscopy, serology, and POC-CCA urine testing. Individuals screened positive by any method were treated with praziquantel and invited for a follow-up visit, repeating the same diagnostic procedures one year after treatment. The POC-CCA baseline and follow-up results were analyzed against the 'baseline microscopy positive cases' (= the most reliably true positive cases) and the 'baseline microscopy plus serology negative cases at baseline and follow-up' (= the most reliably true negative cases). RESULTS: Complete diagnostic baseline and follow-up sampling was available from 48 participants. Compared to most reliably true positive cases at baseline, POC-CCA testing had a sensitivity of 90%. Compared to most reliably true negative cases, POC-CCA testing had a specificity of 73.9%. CONCLUSION: We conclude that the POC-CCA urine test is valuable for screening but its use is not suitable for routine follow-up after treatment.

Utility of cell population data (VCS parameters) as a rapid screening tool for Acute Myeloid Leukemia (AML) in resource-constrained laboratories.

INTRODUCTION: Despite advances in diagnostic techniques, many cases of acute myeloid leukemia (AML) remain underdiagnosed in remote centers unequipped with these technologies. We hypothesized that the automated cellular indices with scatter plots and flags may aid in rapid and cost-effective screening of AML. METHODS: Cell population data (CPD) parameters from 100 de novo AML samples were analyzed by Coulter LH 780 automated analyzer and were compared with 100 age-matched controls. Similar parameters were also compared with 100 and 50 reactive cases of neutrophilia and monocytosis, respectively. System-generated flags and scatter plot patterns were also analyzed. RESULTS: Results were compared between AML cases and normal controls; AML FAB M2, M3, M4 vs reactive neutrophilia; AML FAB M4, M5 vs reactive monocytosis. Significant parameters were selected from all comparison groups. Using appropriate statistical tools, we calculated the cutoff values of these parameters and were able to screen out AML cases with 94% sensitivity and 95% specificity. Three statistical equations were generated using two of the most significant parameters which improved the sensitivity to 98% and specificity to 99%. Five hypothetical scatter plot patterns were devised and were classified according to FAB categories of AML. Most common pattern was selected in AML which was seen in 56% of the cases. Output was analyzed combining these patterns and flags with CPD parameters. CONCLUSION: CPD either alone or in the form of statistical equations along with scatter plots and flags can provide rapid and economic tool in preliminary diagnosis of AML in cost-constrained settings.

The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort.

BACKGROUND: Several blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) ≥ 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort. METHODS: The study-population consisted of 533 men in ages 45-75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information, protein levels and single nucleotide polymorphisms (SNP). RESULTS: 263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG ≥ 2. The Stockholm3 test discriminated better for GG ≥ 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95% CI 82.7-89.2) and AUC 74.8 (95% CI 70.3-79.3). Using a Stockholm3 cut-off of 10% risk of GG ≥ 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG ≥ 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG ≥ 2 cancer. CONCLUSION: A prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.

Applicability of papain solutions in immunohematology / Aplicabilidade de soluções de papaína em imuno-hematologia

ABSTRACT Objective: To compare the enzyme activity of different presentations of papain solution to validate in-house preparations. Methods: Two papain solutions were prepared, and the third presentation was a commercial solution. Tests were carried out with samples of red cells typed as weak RhD. Results: In-house prepared papain solutions showed similar enzyme reactivity, and statistically no differences compared to the enzyme activity of the commercial solution. Conclusion: Evaluating the cost-benefit ratio, the in-house prepared papain solutions present more economic advantages, and can be incorporated into immunohematological routines as a way to cope with periods of financial crisis and cost-containment policies.

RESUMO Objetivo: Comparar a atividade enzimática de diferentes apresentações de solução de papaína para validação de preparados in-house. Métodos: Foram preparadas duas soluções de papaína, e a terceira apresentação tratou-se de uma solução comercial. Os testes comparativos das reações enzimáticas foram realizados com amostras de hemácias tipadas como RhD fraco. Resultados: As soluções de papaína preparadas in-house apresentaram reatividade enzimática semelhante e estatisticamente sem diferenças em comparação com a atividade enzimática da solução comercial. Conclusão: Avaliando-se a relação entre custo e benefício, as soluções de papaína preparadas in-house são economicamente vantajosas, podendo ser incorporadas às rotinas imuno-hematológicas como forma de enfrentamento em períodos de crise financeira e em políticas de retenção de gastos.

The enhanced liver fibrosis (ELF) test in diagnosis and management of liver fibrosis.

Liver disease is a major cause of mortality both globally and in the UK. The earlier liver fibrosis is detected, the sooner interventions can be implemented, including lifestyle changes and medications. Non-invasive tests for liver fibrosis are beginning to augment and replace liver biopsy in assessment of liver fibrosis because of their ease of use, lack of complications and reproducibility. The enhanced liver fibrosis (ELF) test is a blood test that measures three molecules involved in liver matrix metabolism to give a score reflecting the severity of liver fibrosis. This article reviews the evidence supporting ELF as a diagnostic test, a prognostic marker and its use in disease monitoring. In doing so it highlights the important role ELF plays in the early recognition of liver fibrosis facilitating timely referral to a liver specialist. The ELF test is useful in primary, secondary and tertiary care, not only allowing earlier diagnosis and more accurate prognosis, but also providing the opportunity to personalize treatment based on the patient's response.