Novel serum protein biomarker panel for early diagnosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Late presentation of disease at the time of diagnosis is one of the major reasons for dismal prognostic outcomes for PDAC patients. Currently, there is a lack of clinical biomarkers, which can be used to diagnose PDAC patients at an early resectable stage. This study performed proteomic mass spectrometry to identify novel blood-based biomarkers for early diagnosis of PDAC. Serum specimens from 88 PDAC patients and 88 healthy controls (60 discovery cohort and 28 validation cohort) were analyzed using data independent acquisition high resolution mass spectrometry to identify candidate biomarker proteins. A total of 249 proteins were identified and quantified by the mass spectrometric analysis. Six proteins were markedly (>1.5 fold) and significantly (p < .05; q < 0.1) increased in PDAC patients compared to healthy controls in discovery cohort. Notably, four of these six proteins were significantly upregulated in an independent validation cohort. The top three upregulated proteins (i.e., Polymeric Immunoglobulin Receptor [PIGR], von Willebrand Factor [vWF], and Fibrinogen) were validated using enzyme linked immunosorbent assay, which led to selection of PIGR and vWF as a diagnostic biomarker panel for PDAC. The panel showed high ability to diagnose early stage (stage I and II) PDAC patients (area under the curve [AUC]: 0.8926), which was further improved after the addition of clinically used prognostic biomarker (Ca 19-9) to the panel (AUC: 0.9798). In conclusion, a novel serum protein biomarker panel for early diagnosis of PDAC was identified.

Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK.

BACKGROUND: Black men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited. METHODS: This retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis. The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors. RESULTS: 730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70-79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men. CONCLUSIONS: More prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.

Association Between Xanthelasma Palpebrarum with Cardiovascular Risk and Dyslipidemia: A Case Control Study.

PURPOSE: To determine whether xanthelasma palpebrarum (XP) is associated with dyslipidemia, cardiovascular disease (CVD), and other systemic conditions in a large population. DESIGN: Case-control study conducted at a single tertiary care center. PARTICIPANTS: Individuals who were examined at a medical screening institute from 2001 through 2020. METHODS: Medical records were reviewed to extract data on ophthalmic evaluations, blood test results, and systemic diagnoses. Patients identified with XP in at least 1 eye constituted the study group. A control group without XP was established matched by age and sex at a 10:1 ratio to allow robust statistical analysis. MAIN OUTCOME MEASURES: Associations between XP and dyslipidemia and CVD were determined. Lipid profiles and diagnoses of dyslipidemia and CVD were compared between the case and control groups. RESULTS: The database included 35 452 individuals, 24 287 of whom were male (69%), with a mean ± standard deviation age of 52.2 ± 12.2 years. The study population included 203 patients with XP (0.6%) and 2030 matched control participants. The prevalence of dyslipidemia diagnosis was similar between the two groups (42% XP vs. 46% controls, P = 0.29), as were the use rates of statins, fibrates, or other cholesterol-lowering medications (48% XP vs. 47% controls, P = 0.88). Lipid profiles were similar between the groups, including total cholesterol (controls median 187 [IQR, 163-211] vs. XP 192 [166-215], P = 0.093), high-density lipoprotein (controls median 48 [IQR, 41-57] vs. XP 47 [42-57], P = 0.65), low-density lipoprotein (controls median 120 [101-141] vs. XP 125 [104-145], P = 0.17), and triglyceride levels (controls median 111 [81-152] vs. XP 105 [81-139], P = 0.16). The rate of CVD was similar as well (10% control group vs. 8.9% XP group; P = 0.56). The prevalences of related conditions, including hypertension, diabetes mellitus, and history of cerebrovascular accident, were similar between groups (24% control group vs. 23% XP group, 14% control group vs. 10% XP group, and 1.3% control group vs. 1% XP group, respectively; P > 0.05). CONCLUSIONS: Xanthelasma palpebrarum was not associated with increased rates of dyslipidemia or CVD. This questions the extent to which XP serves as an indicative marker for heightened systemic risk. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A Review on Emerging Techniques for Diagnosis of Colorectal Cancer.

Common detection methods in practice for diagnosing colorectal cancer (CRC) are painful and invasive leading to less participation of individuals for CRC diagnosis. Whereas, improved or enhanced imaging systems and other minimally invasive techniques with shorter detection times deliver greater detail and less discomfort in individuals. Thus, this review is a summary of the diagnostic tests, ranging from the simple potential use in developing a flexible CRC treatment to the patient's potential benefits in receiving less invasive procedures and the advanced treatments that might provide a better assessment for the diagnosis of CRC and reduce the mortality related to CRC.

Donor Blood Tests do Not Predict Pancreas Graft Survival After Simultaneous Pancreas Kidney Transplantation; a National Cohort Study.

Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021). 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8 to 3300 U/L (median = 70), and this had no impact on pancreas graft survival when adjusting for multiple confounders (aHR = 0.944, 95% CI = 0.754-1.81). Peak alanine transaminases also did not influence pancreas graft survival in multivariable models (aHR = 0.967, 95% CI = 0.848-1.102). Restricted cubic splines were used to assess associations between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact pancreas transplant outcome. This is the largest, most statistically robust study evaluating donor blood tests and transplant outcome. Provided other factors are acceptable, pancreata from donors with mild or moderately raised amylase and transaminases can be accepted with confidence. The use of pancreas grafts from such donors is therefore a safe, immediate, and simple approach to expand the donor pool to reach increasing demands.

Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary.

AIM: Blood Sampling Guidelines have been developed to target European emergency medicine-related professionals involved in the blood sampling process (e.g. physicians, nurses, phlebotomists working in the ED), as well as laboratory physicians and other related professionals. The guidelines population focus on adult patients. The development of these blood sampling guidelines for the ED setting is based on the collaboration of three European scientific societies that have a role to play in the preanalytical phase process: EuSEN, EFLM, and EUSEM. The elaboration of the questions was done using the PICO procedure, literature search and appraisal was based on the GRADE methodology. The final recommendations were reviewed by an international multidisciplinary external review group. RESULTS: The document includes the elaborated recommendations for the selected sixteen questions. Three in pre-sampling, eight regarding sampling, three post-sampling, and two focus on quality assurance. In general, the quality of the evidence is very low, and the strength of the recommendation in all the questions has been rated as weak. The working group in four questions elaborate the recommendations, based mainly on group experience, rating as good practice. CONCLUSIONS: The multidisciplinary working group was considered one of the major contributors to this guideline. The lack of quality information highlights the need for research in this area of the patient care process. The peculiarities of the emergency medical areas need specific considerations to minimise the possibility of errors in the preanalytical phase.

Machine learning models based on routinely sampled blood tests can predict the presence of malignancy amongst patients with suspected musculoskeletal malignancy.

AIMS: This study explores the possibility of using routinely taken blood tests in the diagnosis and triage of patients with suspected musculoskeletal malignancy. METHODS: A retrospective study was performed on results of patients who had presented for assessment to a regional musculoskeletal tumour unit. Blood results of patients with a histologically confirmed diagnosis between 2010 and 2020 were retrieved. 33 distinct blood tests were available for model forming. Results were standardised by calculating z-scores. Data were split into a training set (70%) and a test set (30%). The training set was balanced by resampling underrepresented classes. The random forest algorithm performed best and was selected for model forming. Receiver operating characteristic curves were used to find the optimum threshold. Models were calibrated and performance metrics evaluated with confusion tables. RESULTS: 2371 patients formed the study population. 1080 had a malignant diagnosis in one of three categories: sarcoma, metastasis, or haematological malignancy. 1291 had a benign condition. Metastasis could be predicted with an accuracy of 79% (AUC 87%, sensitivity 79%, specificity 80% NPV 91%). Haematological malignancy accuracy 79% (AUC 81%, sensitivity 77%, specificity 79%, NPV 97%). Sarcoma accuracy 64% (AUC 73%, sensitivity 76%, specificity 61%, NPV 88%) and all malignancy accuracy 74% (AUC 80%, sensitivity 72%, specificity 75%, NPV 76%). CONCLUSION: Routinely performed blood tests can be useful in triage of musculoskeletal tumours and can be used to predict presence of musculoskeletal malignancy.

'Low' faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham '4F' protocol with FIT10 in symptomatic patients.

AIM: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. METHOD: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 µg Hb/g faeces. RESULTS: A single threshold of 10 µg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 µg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. CONCLUSION: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.

Click evoked otoacoustic emissions in occupational exposure to lead, concentrations of selected essential elements and markers of oxidative stress.

PURPOSE: This study focused on the selected markers of oxidative stress, impact of elevated lead levels on long-term hearing quality. We investigated whether the presence of certain essential minerals might provide protection to the auditory system against the effects of lead (and cadmium) compounds. METHODS: The research group included 280 male employees of the zinc and lead smelter, which was divided into: L-Pb-low blood lead concentration (PbB) subgroup, H-Pb-high PbB subgroup. Hearing tests were performed using the click evoked otoacoustic emission (CEOAE). RESULTS: Zinc protoporphyrin level was significantly higher in the H-Pb subgroup by 68%. Cd concentration was significantly higher in H-Pb by 33%. The Ca concentration was significantly lower in the H-Pb by - 2%. Selected oxidative stress markers concentration were significantly higher in the H-Pb group: malondialdehyde (MDA) by 4%, and lipofuscin (LPS) by 9%. In the CEOAE results showed statistically significant differences between the L-Pb and H-Pb subgroups. Larger negative changes in otoemission amplitude were observed in H-Pb subgroup. All otoemission results showed a statistically significant negative correlation with age, time of work, MDA concentration, and with PbB. Selected CEOAE parameters showed a significant negative correlation with cadmium blood concentration (CdB), and a positive correlation with Ca and Zn. CONCLUSION: Elevated blood lead content in occupational exposure is associated with an increase in MDA and LPS concentration, which negatively correlates with CEOAE parameters. This suggests an important role of oxidative stress in the long-term deterioration of hearing.

Prediction of pre-eclampsia at St. Mary's hospital lacor, a low-resource setting in northern Uganda, a prospective cohort study.

BACKGROUND: Pre-eclampsia is the second leading cause of maternal death in Uganda. However, mothers report to the hospitals late due to health care challenges. Therefore, we developed and validated the prediction models for prenatal screening for pre-eclampsia. METHODS: This was a prospective cohort study at St. Mary's hospital lacor in Gulu city. We included 1,004 pregnant mothers screened at 16-24 weeks (using maternal history, physical examination, uterine artery Doppler indices, and blood tests), followed up, and delivered. We built models in RStudio. Because the incidence of pre-eclampsia was low (4.3%), we generated synthetic balanced data using the ROSE (Random Over and under Sampling Examples) package in RStudio by over-sampling pre-eclampsia and under-sampling non-preeclampsia. As a result, we got 383 (48.8%) and 399 (51.2%) for pre-eclampsia and non-preeclampsia, respectively. Finally, we evaluated the actual model performance against the ROSE-derived synthetic dataset using K-fold cross-validation in RStudio. RESULTS: Maternal history of pre-eclampsia (adjusted odds ratio (aOR) = 32.75, 95% confidence intervals (CI) 6.59-182.05, p = 0.000), serum alkaline phosphatase(ALP) < 98 IU/L (aOR = 7.14, 95% CI 1.76-24.45, p = 0.003), diastolic hypertension ≥ 90 mmHg (aOR = 4.90, 95% CI 1.15-18.01, p = 0.022), bilateral end diastolic notch (aOR = 4.54, 95% CI 1.65-12.20, p = 0.003) and body mass index of ≥ 26.56 kg/m2 (aOR = 3.86, 95% CI 1.25-14.15, p = 0.027) were independent risk factors for pre-eclampsia. Maternal age ≥ 35 years (aOR = 3.88, 95% CI 0.94-15.44, p = 0.056), nulliparity (aOR = 4.25, 95% CI 1.08-20.18, p = 0.051) and white blood cell count ≥ 11,000 (aOR = 8.43, 95% CI 0.92-70.62, p = 0.050) may be risk factors for pre-eclampsia, and lymphocyte count of 800 - 4000 cells/microliter (aOR = 0.29, 95% CI 0.08-1.22, p = 0.074) may be protective against pre-eclampsia. A combination of all the above variables predicted pre-eclampsia with 77.0% accuracy, 80.4% sensitivity, 73.6% specificity, and 84.9% area under the curve (AUC). CONCLUSION: The predictors of pre-eclampsia were maternal age ≥ 35 years, nulliparity, maternal history of pre-eclampsia, body mass index, diastolic pressure, white blood cell count, lymphocyte count, serum ALP and end-diastolic notch of the uterine arteries. This prediction model can predict pre-eclampsia in prenatal clinics with 77% accuracy.

Using Alzheimer's disease blood tests to accelerate clinical trial enrollment.

INTRODUCTION: Screening potential participants in Alzheimer's disease (AD) clinical trials with amyloid positron emission tomography (PET) is often time consuming and expensive. METHODS: A web-based application was developed to model the time and financial cost of screening for AD clinical trials. Four screening approaches were compared; three approaches included an AD blood test at different stages of the screening process. RESULTS: The traditional screening approach using only amyloid PET was the most time consuming and expensive. Incorporating an AD blood test at any point in the screening process decreased both the time and financial cost of trial enrollment. Improvements in AD blood test accuracy over currently available tests only marginally increased savings. Use of a high specificity cut-off may improve the feasibility of screening with only an AD blood test. DISCUSSION: Incorporating AD blood tests into screening for AD clinical trials may reduce the time and financial cost of enrollment. HIGHLIGHTS: The time and cost of enrolling participants in Alzheimer's disease (AD) clinical trials were modeled. A web-based application was developed to enable evaluation of key parameters. AD blood tests may decrease the time and financial cost of clinical trial enrollment. Improvements in AD blood test accuracy only marginally increased savings. Use of a high specificity cut-off may enable screening with only an AD blood test.

Mass Spectrometric Blood Metabogram: Acquisition, Characterization, and Prospects for Application.

In metabolomics, many metabolites are measured simultaneously in a single run. Such analytical performance opens up prospects for clinical laboratory diagnostics. In this work, a mass spectrometric metabogram was developed as a simplified and clinically applicable way of measuring the blood plasma metabolome. To develop the metabogram, blood plasma samples from healthy male volunteers (n = 48) of approximately the same age, direct infusion mass spectrometry (DIMS) of the low molecular fraction of samples, and principal component analysis (PCA) of the mass spectra were used. The seven components of the metabogram defined by PCA, which cover ~70% of blood plasma metabolome variability, were characterized using a metabolite set enrichment analysis (MSEA) and clinical test results of participating volunteers. It has been established that the components of the metabogram are functionally related groups of the blood metabolome associated with regulation, lipid-carbohydrate, and lipid-amine blood components, eicosanoids, lipid intake into the organism, and liver function thereby providing a lot of clinically relevant information. Therefore, metabogram provides the possibility to apply the metabolomics performance in the clinic. The features of the metabogram are also discussed in comparison with the thin-layer chromatography and with the analysis of blood metabolome by liquid chromatography combined with mass spectrometry.

Hematologic tests and their association with the severity of COVID-19 and periodontitis in hospitalized patients: a case-control study.

BACKGROUND: The presence of comorbidities, especially those with a chronic inflammatory nature such as periodontitis, can facilitate COVID-19 progression toward more severe forms. Both of these diseases can affect systemic health and alter hematological test results. In this study, we decided to investigate COVID-19 and periodontitis' possible interaction with these alterations. METHODS: Hospitalized patients with a definitive diagnosis of COVID-19 were included. Controls had mild to moderate COVID-19, while cases had severe to critical COVID-19. Periodontal examination was done for each patient. Relevant medical and hematological data were extracted from patient's hospital files. RESULTS: A total of 122 patients entered the final analysis. The minimum white blood cell counts were associated with the severity of periodontitis. The interaction between periodontitis and COVID-19 was associated with increased minimum white blood cell counts and decreased platelet counts. COVID-19 severity was associated with increased venous oxygen saturation, prothrombin time, the maximum partial thromboplastin time, the maximum and average urea, the maximum creatinine, the maximum potassium, and lactate dehydrogenase, and decreased sodium levels. CONCLUSIONS: Results of this study showed that several blood parameters were associated with periodontitis, COVID-19, or the interaction between them.

Organic selenium supplementation on metabolic profile of dairy goats.

The aim of this study was to evaluate the effect of organic selenium (SE) supplementation on blood constituents related to hematology and serum biochemistry of dairy goats in the productive phase. A total of 16 lactating Saanen × Toggenburg crossbred goats, aged between 2 and 3, lactating, nonpregnant, clinically healthy, and having a body weight (BW) of 40.75 ± 8.31 kg were selected for this study. Higher SE concentrations were observed on the 42nd day of supplementation, and on the 63rd day, the SE concentrations were similar ([Formula: see text]) to the 21st and 42nd days. There was no interaction for plasma constituents comparing treatment effects and days of supplementation ([Formula: see text]). SE supplementation reduced ([Formula: see text]) plasma proteins with a gradual increase in available SE. There was no difference ([Formula: see text]) for the blood count comparing the effects of treatment and days of supplementation. There was no interaction ([Formula: see text]) for serum biochemical constituents between treatments and periods, except for urea ([Formula: see text]). Animals that received SE supplementation had similar plasma urea concentrations before and after supplementation, while animals that did not receive SE in the diet had increased serum urea concentrations. The main action of selenium in metabolism occurred in the reduction of plasma proteins and urea levels, which leads us to conclude that it influenced protein metabolism. Finally, hematology, liver function, and energy metabolism are not affected by selenium supplementation in dairy goats reared in semiarid conditions.

Equilibrium-based COVID-19 diagnosis from routine blood tests: A sparse deep convolutional model.

SARS-CoV2 (COVID-19) is the virus that causes the pandemic that has severely impacted human society with a massive death toll worldwide. Hence, there is a persistent need for fast and reliable automatic tools to help health teams in making clinical decisions. Predictive models could potentially ease the strain on healthcare systems by early and reliable screening of COVID-19 patients which helps to combat the spread of the disease. Recent studies have reported some key advantages of employing routine blood tests for initial screening of COVID-19 patients. Thus, in this paper, we propose a novel COVID-19 prediction model based on routine blood tests. In this model, we depend on exploiting the real dependency among the employed feature pool by a sparsification procedure. In this sparse domain, a hybrid feature selection mechanism is proposed. This mechanism fuses the selected features from two perspectives, the first is Pearson correlation and the second is a new Minkowski-based equilibrium optimizer (MEO). Then, the selected features are fed into a new 1D Convolutional Neural Network (1DCNN) for a final diagnosis decision. The proposed prediction model is tested with a new public dataset from San Raphael Hospital, Milan, Italy, i.e., OSR dataset which has two sub-datasets. According to the experimental results, the proposed model outperforms the state-of-the-art techniques with an average testing accuracy of 98.5% while we employ only less than half the size of the feature pool, i.e., we need only less than half the given blood tests in the employed dataset to get a final diagnosis decision.

EFFECT OF MAMMOGRAPHY IMAGING PROCEDURE ON SERUM INFLAMMATORY AND/OR TUMOR MARKER LEVELS.

Mammography is one of the gold standard screening tests for breast cancer. The effects of mammography procedure on blood parameters are not known. This study aimed to investigate whether the procedure-associated breast compression affects the widely and simultaneously performed blood measurements of C-reactive protein (CRP), carcinoembryonic antigen (CEA), and cancer antigen (CA) 15-3. According to breast ultrasound examination results, participants were divided into 3 groups as follows: group 1 (participants with breast mass size ≥20.0 mm, n=48); group 2 (participants with breast mass size <20.0 mm, n=17); and group 3 (participants with no breast mass, n=23). In groups 1 and 2, on the day of the mammographic imaging study, serum CRP, CEA, and CA 15-3 levels were measured before and after the imaging study. Participants in group 3 had their blood parameters measured without mammography and/or any breast compression. Post-mammography blood measurements displayed a significant increase in serum CRP levels, and a significant decrease in serum CEA and CA 15-3 levels in group 1 (in comparison with the same day pre-mammography blood sampling levels; p<0.05 all). Although pre-mammography serum CEA levels in group 1 participants were significantly higher than those in group 2 and 3 participants, this significant elevation became nonsignificant at post-mammography measurements (p<0.05 and p>0.05, respectively). On the day of the mammographic imaging study, the optimal time of blood sampling for testing CRP, CEA and CA 15-3 levels in persons with a breast mass is before, but not after the mammographic imaging procedure. This issue requires additional detailed studies.

Age Dependence of Liver Enzymes: An Analysis of Over 1,300,000 Consecutive Blood Samples.

BACKGROUND & AIMS: Upper levels of normal for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) generally take sex into account, but not age. This simplification may lead to misclassification and burden the patient and health system unnecessarily. METHODS: Consecutive blood samples were analyzed from a German laboratory. Subcohorts included samples from a prescribed routine check-up and a healthy cohort, defined as patients without increased GGT, triglyceride, cholesterol, glycated hemoglobin, or glucose levels, and without known hepatitis B. RESULTS: A total of 1,369,180 blood samples were analyzed from 601,779 participants (50.8% female; mean age, 58.5 y; SD, 18.0 y). There is an extreme age dependence in ALT values for men: increased values were seen in 20.0% (95% CI, 19.5%-20.4%) of patients in the age group of 25 to 34 years, but only 6.7% (95% CI, 6.4%-7.0%) for the ages of 65 to 74 years. The 95th percentile reaches values greater than 80 U/L instead of 50 U/L at the age of 35, and decrease to less than 50 U/L by the age of 75. Similar qualitative results were found in the healthy and prescribed routine check-up subcohorts. The age dependence is much weaker for ALT in women. The proportion of women with an increased AST level increases from approximately 6% to 12% at approximately age 50. The 95th percentile for GGT increases up to the age of 60 in men, and throughout life in women. CONCLUSIONS: Current guidelines and reference values for ALT imply that subsequent diagnostics are needed for a large proportion of young men. Our data strongly suggest that age adaptation should be considered.

Abnormal Liver Blood Tests: Primary Care Approach.

BACKGROUND: According to recent epidemiological data, annual deaths due to liver disease have increased dramatically, while predictions show that trends will continue to rise in the upcoming years. SUMMARY: Abnormal liver blood tests are one of the most common challenges encountered in the primary care setting. The prevalence of mildly elevated transaminase levels is around 10-20% in the general population. The most common causes for the rising burden of liver disease are nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD), and viral hepatitis. With improvements in the management of viral hepatitis over the last decades, the causes for the rising burden of liver disease are shifting toward ARLD and NAFLD. It is well-known that liver disease usually progresses silently for years or decades until the complications of cirrhosis occur. The majority of patients will not require referral to a specialist but will need further assessment in primary care. They should be evaluated for the etiology of liver disease irrespective of the duration of abnormal liver blood tests or unmarked clinical presentation. The evaluation should include a history of alcohol use, a history of medicines or herbal supplements, testing for viral hepatitis, and assessment for NAFLD, especially in obese patients and patients with type 2 diabetes. Abdominal ultrasound should be performed. Key Messages: The general practitioner may contribute significantly by identifying and screening patients at risk for chronic liver disease, as well as prioritize individuals with symptoms or signs of advanced liver disease to the specialist clinic.

Abnormal Liver Blood Tests: Hepatologist Approach.

BACKGROUND: Available data suggest that the prevalence of chronic liver disease (CLD) and primary liver cancer is rising in Europe and represents a major public health problem. Predictions are showing that these trends will continue to rise in the upcoming years. SUMMARY: Alcohol-related liver disease, nonalcohol fatty liver disease, and viral hepatitis B and hepatitis C are the leading causes of liver cirrhosis and primary liver cancer in Europe. Drug-induced liver injury represents a major cause of acute hepatitis, while liver transplantation is the second most common solid organ transplantation in the world. Patients with CLD have increasing rates of hospitalization, longer hospital stays, and more adverse outcomes compared to the other chronic conditions. Direct targeting of risk factors can prevent complications of advanced liver disease and improve outcome. Patients with CLD should be referred to a hepatologist for assessment of the stage of liver disease, for specific treatment and screening for hepatocellular carcinoma. Moreover, patients with unknown etiology of abnormal liver blood tests should be referred to a hepatologist for assessment of liver disease, as well as for prevention and treatment of complications of cirrhosis and/or portal hypertension. Key Messages: CLD is amenable to prevention and treatment, while disease management strategies need to improve in order to reduce the burden of liver disease and deaths due to end-stage liver diseases.

Blood tests in primary care: A qualitative study of communication and decision-making between doctors and patients.

OBJECTIVE: Blood tests are commonly used in primary care as a tool to aid diagnosis, and to offer reassurance and validation for patients. If doctors and patients do not have a shared understanding of the reasons for testing and the meaning of results, these aims may not be fulfilled. Shared decision-making is widely advocated; yet, most research focusses on treatment decisions rather than diagnostic decisions. The aim of this study was to explore communication and decision-making around diagnostic blood tests in primary care. METHODS: Qualitative interviews were undertaken with patients and clinicians in UK primary care. Patients were interviewed at the time of blood testing, with a follow-up interview after they received test results. Interviews with clinicians who requested the tests provided paired data to compare clinicians' and patients' expectations, experiences and understandings of tests. Interviews were analysed thematically using inductive and deductive coding. RESULTS: A total of 80 interviews with 28 patients and 19 doctors were completed. We identified a mismatch in expectations and understanding of tests, which led to downstream consequences including frustration, anxiety and uncertainty for patients. There was no evidence of shared decision-making in consultations preceding the decision to test. Doctors adopted a paternalistic approach, believing that they were protecting patients from anxiety. CONCLUSION: Patients were not able to develop informed preferences and did not perceive that choice is possible in decisions about testing, because they did not have sufficient information and a shared understanding of tests. A lack of shared understanding at the point of decision-making led to downstream consequences when test results did not fulfil patients' expectations. Although shared decision-making is recommended as best practice, it does not reflect the reality of doctors' and patients' accounts of testing; a broader model of shared understanding seems to be more relevant to the complexity of primary care diagnosis. PATIENT OR PUBLIC CONTRIBUTION: A patient and public involvement group comprising five participants with lived experience of blood testing in primary care met regularly during the study. They contributed to the development of the research objectives, planning recruitment methods, reviewing patient information leaflets and topic guides and also contributed to discussion of emerging themes at an early stage in the analysis process.