Seasonally adjusted laboratory reference intervals to improve the performance of machine learning models for classification of cardiovascular diseases.

BACKGROUND: Variation in laboratory healthcare data due to seasonal changes is a widely accepted phenomenon. Seasonal variation is generally not systematically accounted for in healthcare settings. This study applies a newly developed adjustment method for seasonal variation to analyze the effect seasonality has on machine learning model classification of diagnoses. METHODS: Machine learning methods were trained and tested on ~ 22 million unique records from ~ 575,000 unique patients admitted to Danish hospitals. Four machine learning models (adaBoost, decision tree, neural net, and random forest) classifying 35 diseases of the circulatory system (ICD-10 diagnosis codes, chapter IX) were run before and after seasonal adjustment of 23 laboratory reference intervals (RIs). The effect of the adjustment was benchmarked via its contribution to machine learning models trained using hyperparameter optimization and assessed quantitatively using performance metrics (AUROC and AUPRC). RESULTS: Seasonally adjusted RIs significantly improved cardiovascular disease classification in 24 of the 35 tested cases when using neural net models. Features with the highest average feature importance (via SHAP explainability) across all disease models were sex, C- reactive protein, and estimated glomerular filtration. Classification of diseases of the vessels, such as thrombotic diseases and other atherosclerotic diseases consistently improved after seasonal adjustment. CONCLUSIONS: As data volumes increase and data-driven methods are becoming more advanced, it is essential to improve data quality at the pre-processing level. This study presents a method that makes it feasible to introduce seasonally adjusted RIs into the clinical research space in any disease domain. Seasonally adjusted RIs generally improve diagnoses classification and thus, ought to be considered and adjusted for in clinical decision support methods.

Predicting Elective Surgical Patient Outcome Destination Based on the Preoperative Modified Frailty Index and Laboratory Values.

INTRODUCTION: To determine the accuracy of preoperative modified frailty index (mFI) with or without laboratory values (mFI-labs or labs-continuous) in predicting postoperative discharge destination. Discharge destination is important to providers and patients. The ability to accurately predict discharge destination preoperatively can improve hospital resource utilization and help set patient and family expectations. METHODS: Cohort analysis of the 2018 American College of Surgeon National Surgical Quality Improvement Project (ACS-NSQIP) Participant Use File of patients undergoing operations with complete data point sets: age, sex, operation work relative-value units; mFI-clinical based on 12 clinical findings, mFI-labs based on seven laboratory values. The nine hierarchical destinations: home, home with assistance, multi-level community, unskilled-care facility, rehabilitation facility, skilled-nursing facility, acute care hospital, hospice, or death, from best to worst outcome. Data were analyzed using univariate analysis, multiple logistic regression and supervised learning artificial neural networks. RESULTS: Univariate and multivariate in general showed that patients with higher mFI-clinical and mFI-lab scores, as well as older age and more complex operations were more likely to be discharged to facilities other than home. However, these statistical techniques could not predict the exact destination. An artificial neural network analysis demonstrated perfect location prediction in 64.9% of cases and within one level of prefect prediction is 87.4%. CONCLUSIONS: Using a limited number of preoperative factors, combining the mFI-clinical with laboratory values significantly improves the destination prediction performance significantly better than using the values separately. Preoperative knowledge of the likely discharge destination can benefit postoperative care planning and delivery.

Relationship Between Handgrip Strength and Laboratory Values in Adolescents With Non-Alcoholic Fatty Liver Disease.

INTRODUCTION: The worldwide prevalence of non-alcoholic fatty liver disease in adolescents is increasing. Measuring handgrip strength is a simple and non-invasive method for assessing sarcopenia in adolescents. However, the association between handgrip strength and laboratory values has not yet been evaluated in a clinical setting. This study proposes an association between handgrip strength and laboratory values of adolescents with non-alcoholic fatty liver disease. METHODOLOGY: Data were obtained from 100 adolescents (76 males; 24 females; age, 10-18 years) who had been diagnosed with non-alcoholic fatty liver disease. Anthropometric values and handgrip strength were measured, and blood test parameters were evaluated. The association between HGS and each laboratory value was evaluated. RESULTS: The handgrip strength of males and females was different between the low and high alkaline phosphatase level (275 U/L) groups. Regarding the handgrip-to-body weight ratio, there was a difference between the low and high groups based on alanine aminotransferase level < 24.1 U/L in males. CONCLUSION: Handgrip strength is easy to measure in schools and clinics. This is the first study to determine the usefulness of handgrip strength in Korean adolescents with non-alcoholic fatty liver disease. As more data are gathered, handgrip strength may be used to screen and manage adolescents with non-alcoholic fatty liver disease.

Association of Immediate Postoperative Hemodynamic and Laboratory Values in Predicting Norwood Admission Outcomes.

The primary objective of this study was to determine whether or not hemodynamic parameters and laboratory values at the time of admission to the pediatric cardiac intensive care unit after the Norwood operation were associated with a composite outcome of either need for extracorporeal membrane oxygenation or inpatient mortality. This was a single-center retrospective study of infants with functionally univentricular hearts admitted to intensive care after the Norwood procedure from January 2011 to January 2020. Data were obtained at a single point (after a Norwood procedure) and then compared between two subsets of patients based on the presence or not of the composite outcome of interest. In univariate and multiple regression analyses, a series of receiver operator curves were generated to assess the relationship between the variables of interest and the composite outcome. Eight (7.6%) experienced the composite outcome out of a total of 104 patients. Those who experienced the composite endpoint had significantly higher oxygen extraction ratio (0.43 vs. 0.31, p = 0.01), lower systemic blood flow (2.5 L/min versus 3.1 L/min, p = 0.01), and higher systemic vascular resistance (20.2 indexed woods units versus 14.8 indexed woods units, p = 0.01). Those with systemic blood flow of less than 2.5 L/min/m2 had a 17% risk of experiencing the composite endpoint AUC = 0.79. Those with systemic vascular resistance of greater than 19 indexed woods units had a 22% risk of experiencing the composite endpoint AUC 0.80. Systemic blood flow and systemic vascular resistance are independently associated with this composite outcome.

Validation of the Updated Hepatocellular Carcinoma Early Detection Screening Algorithm in a Community-Based Cohort of Patients With Cirrhosis of Multiple Etiologies.

BACKGROUND & AIMS: The Hepatocellular carcinoma (HCC) Early detection Screening (HES) algorithm has been proposed to improve the performance of the serum alpha-fetoprotein (AFP) test in surveillance for HCC. The HES algorithm incorporates data on age, level of alanine aminotransferase, platelet count, and rate of AFP change to increase likelihood of earlier detection and thereby reduce HCC-related mortality. We updated the HES algorithm to include etiology of cirrhosis and validated it in a community-based cohort. METHODS: We collected data from the Veterans Health Administration, from 2010 through 2015, on etiologies for HCC, including hepatitis C, hepatitis B, alcoholic liver disease, and non-alcoholic fatty liver disease. We used these data to update the HES algorithm and tested its accuracy using data from patients with cirrhosis in the Kaiser Permanente Northern California healthcare system (validation cohort). RESULTS: Among the 7432 patients with cirrhosis in the validation cohort, 1102 were diagnosed with HCC during a median follow-up time of 3.21 years; 709 patients had early-stage HCC. The HES algorithm identified patients who would receive a diagnosis of early-stage HCC within the next 6 months with 51.20% sensitivity and 90.00% specificity, compared with 46.02% sensitivity for the AFP test alone (5.18% absolute improvement; P = .0015). In HCC screening, a positive result from HES or AFP test leads to follow-up evaluation with more sensitive imaging methods. The number of early-stage HCC cases detected per 1000 imaging analyses were 136.46 with the HES algorithm vs 118.01 with the AFP test alone (P < .0005). The HES algorithm identified 56.00% of patients with HCC in the 6 months before their diagnosis despite no detection of nodules by surveillance ultrasound; the AFP test identified only 50.00% of these patients. CONCLUSIONS: We validated the HES algorithm using data from a diverse community-based cohort of patients with cirrhosis. The algorithm offers a modest but useful advantage over the AFP test alone in detection of early-stage HCC with virtually no added cost.

Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression.

BACKGROUND: To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease-2019 (COVID-19), a systematic review and meta-analysis were conducted on the association between admission laboratory values in hospitalized COVID-19 patients and subsequent disease severity and mortality. MATERIAL AND METHODS: Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta-analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta-regression techniques for 11 markers. RESULTS: In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 109 /L (2.76, 4.87), lymphocytes (ALC) at -0.34 × 109 /L (-0.45, -0.23), interleukin-6 (IL-6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C-reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D-dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non-severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta-regression. CONCLUSION: The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID-19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.

Comorbid diseases of vitiligo: A 10-year cross-sectional retrospective study of an urban US population.

BACKGROUND: Vitiligo is associated with medical conditions, primarily autoimmune disorders; however, only a few studies in the United States have investigated these associations. OBJECTIVE: Our purpose was to investigate the diseases associated with vitiligo in the New York, New York, population and evaluate if these associations differ by race/ethnicity and sex. METHODS: In this retrospective study, we analyzed data collected from the medical records of 1487 vitiligo patients seen at New York University during a 10-year period. RESULTS: Vitiligo patients had a statistically significant higher prevalence of hypothyroidism, multiple sclerosis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, seronegative arthritis, pernicious anemia, myasthenia gravis, inflammatory bowel disease, lymphoma, and systemic lupus erythematosus. Rates of comorbid autoimmune diseases varied by race and sex. LIMITATIONS: Medical charts did not consistently report race/ethnicity, type of vitiligo, and total body surface area affected. Information from nondermatology medical visits was also included. CONCLUSION: This study revealed multiple new disease associations for vitiligo, including multiple sclerosis, idiopathic thrombocytopenic purpura, and lymphoma, as well as confirmed previously reported associations with other autoimmune diseases, the most common being hypothyroidism followed by rheumatoid arthritis. Associations did vary by race/ethnicity and sex.

Veterans Affairs patient database (VAPD 2014-2017): building nationwide granular data for clinical discovery.

BACKGROUND: To study patient physiology throughout a period of acute hospitalization, we sought to create accessible, standardized nationwide data at the level of the individual patient-facility-day. This methodology paper summarizes the development, organization, and characteristics of the Veterans Affairs Patient Database 2014-2017 (VAPD 2014-2017). The VAPD 2014-2017 contains acute hospitalizations from all parts of the nationwide VA healthcare system with daily physiology including clinical data (labs, vitals, medications, risk scores, etc.), intensive care unit (ICU) indicators, facility, patient, and hospitalization characteristics. METHODS: The VA data structure and database organization represents a complex multi-hospital system. We define a single-site hospitalization as one or more consecutive stays with an acute treating specialty at a single facility. The VAPD 2014-2017 is structured at the patient-facility-day level, where every patient-day in a hospital is a row with separate identification variables for facility, patient, and hospitalization. The VAPD 2014-2017 includes daily laboratory, vital signs, and inpatient medication. Such data were validated and verified through lab value range and comparison with patient charts. Sepsis, risk scores, and organ dysfunction definitions were standardized and calculated. RESULTS: We identified 565,242 single-site hospitalizations (SSHs) in 2014; 558,060 SSHs in 2015; 553,961 SSHs in 2016; and 550,236 SSHs in 2017 at 141 VA hospitals. The average length of stay was four days for all study years. In-hospital mortality decreased from 2014 to 2017 (1.7 to 1.4%), 30-day readmission rates increased from 15.3% in 2014 to 15.6% in 2017; 30-day mortality also decreased from 4.4% in 2014 to 4.1% in 2017. From 2014 to 2017, there were 107,512 (4.8%) of SSHs that met the Center for Disease Control and Prevention's Electronic Health Record-based retrospective definition of sepsis. CONCLUSION: The VAPD 2014-2017 represents a large, standardized collection of granular data from a heterogeneous nationwide healthcare system. It is also a direct resource for studying the evolution of inpatient physiology during both acute and critical illness.

Comparative pharmacokinetics and a clinical laboratory evaluation of intravenous acetaminophen in Beagle and Galgo Español dogs.

OBJECTIVE: To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Español (GE) dogs. STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: A total of 20 healthy dogs - 10 Beagles and 10 GE (six males and four females in both groups). METHODS: Acetaminophen (10 and 20 mg kg-1) was administered intravenously (IV) to the dogs on two different occasions. Plasma concentrations were analysed by high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling with ADAPT 5 software. Simulations after multiple IV doses were investigated. Clinical laboratory values such as red blood cell (RBC) count, haemoglobin (Hb), haematocrit (Ht), white blood cell (WBC) count, platelet count, total proteins, alanine aminotransferase (ALT), aspartate aminotransferase, urea and creatinine were measured before and 24 hours after acetaminophen administration in combination with clinical examination to assess side effects resulting from the drug. RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. PK parameters were different as a result of a breed effect. For doses of 10 and 20 mg kg-1, respectively, clearance values were 1.70 (1.15-2.27) and 1.62 (1.06-2.86) L kg-1 hour-1 for Beagles and 1.18 (0.70-1.39) and 1.08 (0.67-1.35) L kg-1 hour-1 for GE; elimination half-life values were 2.64 (0.52-4.46) and 2.86 (0.87-4.63) hours for Beagles and 3.49 (1.89-7.80) and 4.57 (2.08-8.90) hours for GE. Significant differences were also found between GE and Beagles in the RBC count, Ht, Hb, WBC count and serum ALT before drug administration, and these differences were maintained 24 hours later, independent of the dosage used. For each breed, no side effects resulting from IV acetaminophen administration were observed at doses of either 10 or 20 mg kg-1. CONCLUSIONS AND CLINICAL RELEVANCE: IV PK of acetaminophen was different between Beagles and GE dogs. Side effects were not detected. Further studies are necessary to evaluate the PK in a clinical context.

The effect of anti-emetic doses of dexamethasone on postoperative blood glucose levels in non-diabetic and diabetic patients: a prospective randomised controlled study.

There are few data regarding postoperative hyperglycaemia in non-diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty-five non-diabetic patients and patients with type-2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non-diabetic patients, the mean (SD) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l(-1) vs. 7.8 (1.4) mmol.l(-1) , p = 0.04). In diabetic patients, the mean (SD) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l(-1) vs. 10.7 (2.4) mmol.l(-1) , p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non-diabetics and diabetics.

Gender-specific differences in therapy and laboratory parameters and validation of mortality predictors in severely injured patients--results of a German level 1 trauma center.

PURPOSE: Gender-specific differences in trauma patients have been reported in several studies. There is a lack of knowledge about differences in therapy and laboratory parameters. The objective of this study is to analyze differences between genders, confirming the therapy and laboratory parameters. Additionally, predictors for mortality were validated. METHODS: Patients on primary admission to the hospital between 2002 and 2012 with an Injury Severity Score (ISS) ≥ 16 were included. 1073 patients met the inclusion criteria. Comparisons and matched-pair analyses between deceased and survived females, males, and between deceased females and males were conducted. RESULTS: The analyzed laboratory parameters differed between genders, especially the base excess, lactate, and coagulation parameters. In particular, females presented values that were normal or only slightly pathological. The prothrombin ratio was 75.3% in female and 63.2% in male (p = 0.027) and lactate 2.5 mmol/l in female and 3.8 mmol/l in male (p = 0.049). No differences between genders could be found in the initial treatment of severely injured patients. Only the infused volume differed between genders with 1178.2 ml in male and 793.6 ml in female (p = 0.02). The known predictors for mortality, lactate, and prothrombin ratio could not be validated in female trauma patients. CONCLUSIONS: No gender differences, except the infused volume, in the treatment of severely injured patients could be found. Differences in laboratory tests, especially base excess, lactate, and coagulation parameters were found. As these parameters are also used as predictors of mortality in trauma patients, gender-specific cut-offs of these laboratory tests might be necessary to avoid underestimating injured women.

Impact of age on haematological markers pre- and post-marathon running.

This study investigated whether haematological markers differ between young and masters marathon participants, running at similar performance levels. Nine young (31.89 ± 4.96 years) and eight masters (63.13 ± 4.61 years) runners participated. At five time points (pre-race through 54 h post-race), a complete blood cell count, basic metabolic panel and creatine kinase (CK) isoenzyme panel were assessed. Race performance was standardised using the World Masters Association Age Grading Performance Tables. Total CK levels were elevated for all participants at all time points post-race (P < 0.001). The CK-isoenzyme MB% was elevated across groups at 6, 30 and 54 h post-race (P < 0.01, P < 0.01 and P < 0.05), with masters runners having a higher CK-MB% at 30 and 54 h (P < 0.05, P < 0.05). Total white blood cell and neutrophil counts were elevated through 6 h post-race (P < 0.001), with higher levels found in younger runners (P < 0.001). When considering all blood work, masters runners had a higher number of abnormal values at 6, 30 and 54 h post-race (P < 0.05, P < 0.01 and P < 0.05). In conclusion, masters runners demonstrated sustained CK-MB elevation, which may suggest greater cardiac stress. However, future studies using additional cardiac markers should be completed to confirm these findings. In addition, masters runners showed an increased number of laboratory values outside normal range, indicating the body's reduced capacity to respond to marathon running.

Quality and Safety of General Anesthesia with Propofol and Sevoflurane in Children Aged 1-14 Based on Laboratory Parameters.

INTRODUCTION: Knowledge of anatomic, physiological, biochemical and physical characteristics of children of all age groups, the existing illness and possible pathological response of the organism to the existing situation, require a pediatric anesthesiologist to participate in the preparation of a child for surgical treatment, to choose the best anesthesia technique and medications, and manipulative techniques to enable the scheduled surgical treatment with minimum anesthesia risks. The aim of this clinical study was to prove reliability and quality of propofol or sevoflurane general anesthesia in children in the age group of 1-14 years from the ASA I group and in the elective surgical treatments in duration of 60 minutes, based on preoperative and postoperative levels of laboratory findings (transaminases, blood sugar, urea and creatinine). MATERIALS AND METHODS: the study included 160 patients randomized in two groups based on different approaches: total intravenous anesthesia was used for the propofol group (n=80) (TIVA) and the inhalation technique was used for the sevoflurane group (n=80). RESULTS: statistical evaluation of the obtained results indicates stability of laboratory findings in the immediate postoperative course (after 24 hours) in respect to the preoperative period. Based on the Mann Whitney test (P), preoperative and postoperative blood sugar levels in the sevoflurane vs. propofol group were P=0.152 vs. 0.021; creatinine levels P=0.113 vs. 0.325; urea levels P= 0.016 vs. 0.900; AST levels P=0,031 vs. 0,268 and ALT levels P=0.021 vs. 0.058. Level of significance was P<0.5. CONCLUSION: Analysis of the examined laboratory parameters show that propofol and sevoflurane provide full security and quality of general anesthesia in children age group 1-14 years, from the ASA I group. All analyzed laboratory levels in the postoperative course remained in their referential values in both groups of participants.

Nutritional Data on Selected Food Products Consumed in Oman: An Update of the Food Composition Table and Use for Future Food Consumption Surveys.

Food composition data in the Eastern Mediterranean Region countries are often lacking, obsolete, or unreliable. The study aims to provide reliable nutrient data on food products consumed in Oman in order to evaluate their nutritional quality, the consistency of the nutrition labeling and claims, and, ultimately, the use for food consumption surveys and update the current food composition database. Contents of fat, fatty acids, carbohydrates, protein, sugars, and sodium were chemically analyzed in 221 foods and beverages. Products were classified according to their nutritional composition and the extent of processing and coded according to the FoodEx2 system. Labels and laboratory values were compared using the tolerance levels of the European Union. Results indicate that the nutrition labeling aligns with the values obtained in the laboratory, with the exception of 6.3% discrepancies in TFA content, where the reported values are higher than the appropriate reference values. The most frequent category (71.5%) was ultra-processed foods. In terms of inconsistencies in the nutritional claims, 5.1% of food products with claims did not comply with the statement "sugar-free" or "low salt". Our study provides evidence to support the necessity of comprehensive recommendations for consumers and food industries, which are aimed at enhancing the nutritional quality of products and augmenting consumer awareness.

Temporal trends in laboratory parameters in survivors and non­survivors of critical COVID­19 illness and the effect of dexamethasone treatment.

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P<0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment.

C-reactive protein as robust laboratory value associated with prognosis in patients with stage III non-small cell lung cancer (NSCLC) treated with definitive radiochemotherapy.

To evaluate the prognostic value of biomarkers from peripheral blood obtained as routine laboratory assessment for overall survival in a cohort of stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiochemotherapy at a high-volume cancer center. Seven blood biomarkers from 160 patients treated with definitive radiochemotherapy for stage III NSCLC were analyzed throughout the course treatment. Parameters were preselected using univariable and multivariable proportional hazards analysis and were assessed for internal validity using leave-one-out cross validation. Cross validated classifiers including biomarkers in addition to important clinical parameters were compared with classifiers containing the clinical parameters alone. An increased C-reactive protein (CRP) value in the final week of radiotherapy was found as a prognostic factor for overall survival, both as a continuous (HR 1.099 (1.038-1.164), p < 0.0012) as well as categorical variable splitting data at the median value of 1.2 mg/dl (HR 2.214 (1.388-3.531), p < 0.0008). In the multivariable analysis, the CRP value-maintained significance with an HR of 1.105 (1.040-1.173) and p-value of 0.0012. The cross validated classifier using CRP at the end of radiotherapy in addition to clinical parameters separated equally sized high and low risk groups more distinctly than a classifier containing the clinical parameters alone (HR = 2.786 (95% CI 1.686-4.605) vs. HR = 2.287 (95% CI 1.407-3.718)). Thus, the CRP value at the end of radiation therapy has successfully passed the crucial cross-validation test. The presented data on CRP levels suggests that inflammatory markers may become increasingly important during definitive radiochemotherapy, particularly with the growing utilization of immunotherapy as a consolidation therapy for stage III NSCLC.

Creatine and guanidinoacetate reference values in a French population.

Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays in body fluids may be used for detecting patients with primary creatine deficiency disorders (PCDD), a class of inherited diseases. Their laboratory values in blood and urine may vary with age, requiring that reference normal values are given within the age range. Despite the long known role of creatine for muscle physiology, muscle signs are not necessarily the major complaint expressed by PCDD patients. These disorders drastically affect brain function inducing, in patients, intellectual disability, autistic behavior and other neurological signs (delays in speech and language, epilepsy, ataxia, dystonia and choreoathetosis), being a common feature the drop in brain creatine content. For this reason, screening of PCDD patients has been repeatedly carried out in populations with neurological signs. This report is aimed at providing reference laboratory values and related age ranges found for a large scale population of patients with neurological signs (more than 6 thousand patients) previously serving as a background population for screening French patients with PCDD. These reference laboratory values and age ranges compare rather favorably with literature values for healthy populations. Some differences are also observed, and female participants are discriminated from male participants as regards to urine but not blood values including creatine on creatinine ratio and guanidinoacetate on creatinine ratio values. Such gender differences were previously observed in healthy populations; they might be explained by literature differential effects of testosterone and estrogen in adolescents and adults, and by estrogen effects in prepubertal age on SLC6A8 function. Finally, though they were acquired on a population with neurological signs, the present data might reasonably serve as reference laboratory values in any future medical study exploring abnormalities of creatine metabolism and transport.

Are admission laboratory values in isolation meaningful for predicting surgical outcome in patients with perforated peptic ulcers?

Background: The study aimed to calculate the predictive value of admission laboratory values in patients with perforated peptic ulcers. Methods: A retrospective, cohort analytical, observational study was performed, including patients with surgically confirmed perforated peptic ulcers over a 5-year period. Demographic data and admission laboratory values were collected from hospital electronic databases. Outcomes measured were in-hospital mortality, intensive care unit (ICU) admission and length of stay. The significance of categorical variables was calculated by chi-square and Fisher's exact test. Logistic regression analysis was performed to determine univariately statistically significant variables. Results: In total, 188 patients met the inclusion criteria. The median age was 46 (range 15-87) years with a male predominance of 71.3 % (n = 134). The median length of hospital stay was 7 (range 1-94) days and 31.4 % (n = 59) of patients were admitted to the ICU. Post-operative in-hospital mortality was 25.0 % (n = 47). Predicting the categorical outcome of in-hospital mortality, abnormal haemoglobin, platelet count, urea, creatinine and potassium levels were all found to be statistically significant in the univariate analysis. Age (odds ratio [OR] 1.03), haemoglobin (OR 4.36) and creatinine (OR 7.76) levels were significant in the multivariate analysis. Conclusions: Mortality rate among patients with perforated peptic ulcer disease is still substantial. Admission laboratory values showed statistical significance as outcome indicators and were valuable to assist in predicting the prognosis. An abnormally high serum creatinine level was the strongest single predictor of both mortality and ICU admission. Key message: Initial laboratory findings of patients admitted for perforated peptic ulcer showed that an abnormally high serum creatinine level was the strongest single predictor of both mortality and ICU admission.

Temporal evolution of laboratory characteristics in patients critically ill with COVID­19 admitted to the intensive care unit (Review).

In the context of coronavirus disease 2019 (COVID-19), laboratory medicine has played a crucial role in both diagnosis and severity assessment. Although the importance of baseline laboratory findings has been extensively reported, data regarding their evolution over the clinical course are limited. The aim of the present narrative review was to provide the dynamic changes of the routine laboratory variables reported in patients with severe COVID-19 over the course of their critical illness. A search was made of the literature for articles providing data on the time-course of routine laboratory tests in patients with severe COVID-19 during their stay in the intensive care unit (ICU). White blood cell, neutrophil and lymphocyte counts, neutrophil to lymphocyte ratio, platelet counts, as well as D-dimer, fibrinogen, C-reactive protein, lactate dehydrogenase and serum albumin levels were selected as disease characteristics and routine laboratory parameters. A total of 25 research articles reporting dynamic trends in the aforementioned laboratory parameters over the clinical course of severe COVID-19 were identified. During the follow-up period provided by each study, the majority of the laboratory values remained persistently abnormal in both survivors and non-survivors. Furthermore, in the majority of studies, the temporal trends of laboratory values distinctly differentiated patients between survivors and non-survivors. In conclusion, there are distinct temporal trends in selected routine laboratory parameters between survivors and non-survivors with severe COVID-19 admitted to the ICU, indicating their importance in the prognosis of clinical outcome.