Kinetics and prognostic significance of laboratory markers in patients with severe fever with thrombocytopenia syndrome: insight from a comprehensive analysis.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with significant mortality. Identifying prognostic factors that influence patient outcomes is crucial for effective clinical management. In this study, we assessed the dynamic changes of laboratory markers and their association with outcomes in 93 SFTS patients. We found that age and hypertension were significantly associated with poor outcomes in SFTS patients. The deceased group exhibited lower platelet counts, elevated liver and kidney function markers, coagulation profiles, inflammatory markers, and cytokines compared to the survival group. Kinetic analysis showed that these markers gradually normalized in the survival group, while they remained persistently abnormal in the deceased group. Furthermore, hypertension, elevated AST, PCT, and IL-10 were identified as independent risk factors for predicting poor prognosis of SFTS patients. These findings provide valuable insights into the prognostic significance of laboratory markers and highlight the importance of early identification of high-risk SFTS patients.

Machine learning prediction for COVID-19 disease severity at hospital admission.

IMPORTANCE: Early prognostication of patients hospitalized with COVID-19 who may require mechanical ventilation and have worse outcomes within 30 days of admission is useful for delivering appropriate clinical care and optimizing resource allocation. OBJECTIVE: To develop machine learning models to predict COVID-19 severity at the time of the hospital admission based on a single institution data. DESIGN, SETTING, AND PARTICIPANTS: We established a retrospective cohort of patients with COVID-19 from University of Texas Southwestern Medical Center from May 2020 to March 2022. Easily accessible objective markers including basic laboratory variables and initial respiratory status were assessed using Random Forest's feature importance score to create a predictive risk score. Twenty-five significant variables were identified to be used in classification models. The best predictive models were selected with repeated tenfold cross-validation methods. MAIN OUTCOMES AND MEASURES: Among patients with COVID-19 admitted to the hospital, severity was defined by 30-day mortality (30DM) rates and need for mechanical ventilation. RESULTS: This was a large, single institution COVID-19 cohort including total of 1795 patients. The average age was 59.7 years old with diverse heterogeneity. 236 (13%) required mechanical ventilation and 156 patients (8.6%) died within 30 days of hospitalization. Predictive accuracy of each predictive model was validated with the 10-CV method. Random Forest classifier for 30DM model had 192 sub-trees, and obtained 0.72 sensitivity and 0.78 specificity, and 0.82 AUC. The model used to predict MV has 64 sub-trees and returned obtained 0.75 sensitivity and 0.75 specificity, and 0.81 AUC. Our scoring tool can be accessed at https://faculty.tamuc.edu/mmete/covid-risk.html . CONCLUSIONS AND RELEVANCE: In this study, we developed a risk score based on objective variables of COVID-19 patients within six hours of admission to the hospital, therefore helping predict a patient's risk of developing critical illness secondary to COVID-19.

[A new screening method for the diagnosis of sarcopenia in people 65 years and older.]

Diagnosis of sarcopenia is difficult due to the limitations of measuring muscle mass, which requires specialized equipment. Simple screening tools can be useful in general practice. The aim of the study was to develop a new screening method for diagnosing sarcopenia based on risk factors and biomarkers of the disease. The study included 230 people over 65 years and older (70 men and 160 women, median age 75 [68; 79] years) examined in a medical institution in St. Petersburg. Sarcopenia was diagnosed according to the updated consensus of the European Working Group on Sarcopenia 2 (EWGSOP2, 2018). When constructing a mathematical model, such indicators as the number of falls, BMI, fatigue, and the level of C-reactive protein in the blood serum had the greatest diagnostic significance of sarcopenia. The calculations showed high sensitivity - 91,4%, specificity - 88,7% and accuracy - 89,9% of the screening method for diagnosing sarcopenia in people 65 years and older.

Association between Multi-Organ Involvement and Brain Injury in Cooled Newborns: A Statistical Approach.

INTRODUCTION: In the event of fetal hypoxia-ischemia, circulation to the brain and central organs is thought to be preserved. The objective of the study was to explore the relationship between the presence of brain injury on MRI and multi-organ involvement, as reflected in routinely collected laboratory (lab) values in babies who have undergone therapeutic hypothermia (TH) after hypoxic-ischemic encephalopathy (HIE). METHODS: Peak and trough values, and age at peak/trough, were obtained for 10 lab markers collected for clinical care, representing hematopoiesis, coagulation, inflammation, hepatic, and renal function, from 71 consecutively recruited newborns from four tertiary neonatal centers undergoing TH. Cerebral MR images obtained as part of clinical care were assessed by two raters with expertise, in a blinded fashion. RESULTS: There was no significant association between the presence of cerebral injury on MRI and systems involvement in newborns who have undergone TH. However, the peak/trough platelet ratio was significantly associated with cerebral injury. Also, the peak platelet, lymphocyte, and urea counts occurred significantly later in babies with substantial brain injury compared to those without. CONCLUSION: Using a statistical approach, we demonstrate that there is no clear relationship between multi-organ involvement and cerebral injury in babies with HIE who have undergone TH. We infer that babies may have cerebral injury in the absence of involvement of other organ systems. The platelet count ratio as an independent biomarker of cerebral injury in this group requires further investigation. Reference ranges of lab values for term newborns undergoing TH are provided.

The predictive ability of routinely collected laboratory markers for surgically treated spinal metastases: a retrospective single institution study.

PURPOSE: We aimed to identify effective routinely collected laboratory biomarkers for predicting postoperative outcomes in surgically treated spinal metastases and attempted to establish an effective prediction model. METHODS: This study included 268 patients with spinal metastases surgically treated at a single institution. We evaluated patient laboratory biomarkers to determine trends to predict survival. The markers included white blood cell (WBC) count, platelet count, neutrophil count, lymphocyte count, hemoglobin, albumin, alkaline phosphatase, creatinine, total bilirubin, calcium, international normalized ratio (INR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR). A nomogram based on laboratory markers was established to predict postoperative 90-day and 1-year survival. The discrimination and calibration were validated using concordance index (C-index), area under curves (AUC) from receiver operating characteristic curves, and calibration curves. Another 47 patients were used as a validation group to test the accuracy of the nomogram. The prediction accuracy of the nomogram was compared to Tomita, revised Tokuhashi, modified Bauer, and Skeletal Oncology Research Group machine-learning (SORG ML). RESULTS: WBC, lymphocyte count, albumin, and creatinine were shown to be the independent prognostic factors. The four predictive laboratory markers and primary tumor, were incorporated into the nomogram to predict the 90-day and 1-year survival probability. The nomogram performed good with a C-index of 0.706 (0.702-0.710). For predicting 90-day survival, the AUC in the training group and the validation group was 0.740 (0.660-0.819) and 0.795 (0.568-1.000), respectively. For predicting 1-year survival, the AUC in the training group and the validation group was 0.765 (0.709-0.822) and 0.712 (0.547-0.877), respectively. Our nomogram seems to have better predictive accuracy than Tomita, revised Tokuhashi, and modified Bauer, alongside comparable prediction ability to SORG ML. CONCLUSIONS: Our study confirmed that routinely collected laboratory markers are closely associated with the prognosis of spinal metastases. A nomogram based on primary tumor, WBC, lymphocyte count, albumin, and creatinine, could accurately predict postoperative survival for patients with spinal metastases.

Interpretable generalized neural additive models for mortality prediction of COVID-19 hospitalized patients in Hamadan, Iran.

BACKGROUND: The high number of COVID-19 deaths is a serious threat to the world. Demographic and clinical biomarkers are significantly associated with the mortality risk of this disease. This study aimed to implement Generalized Neural Additive Model (GNAM) as an interpretable machine learning method to predict the COVID-19 mortality of patients. METHODS: This cohort study included 2181 COVID-19 patients admitted from February 2020 to July 2021 in Sina and Besat hospitals in Hamadan, west of Iran. A total of 22 baseline features including patients' demographic information and clinical biomarkers were collected. Four strategies including removing missing values, mean, K-Nearest Neighbor (KNN), and Multivariate Imputation by Chained Equations (MICE) imputation methods were used to deal with missing data. Firstly, the important features for predicting binary outcome (1: death, 0: recovery) were selected using the Random Forest (RF) method. Also, synthetic minority over-sampling technique (SMOTE) method was used for handling imbalanced data. Next, considering the selected features, the predictive performance of GNAM for predicting mortality outcome was compared with logistic regression, RF, generalized additive model (GAMs), gradient boosting decision tree (GBDT), and deep neural networks (DNNs) classification models. Each model trained on fifty different subsets of a train-test dataset to ensure a model performance. The average accuracy, F1-score and area under the curve (AUC) evaluation indices were used for comparison of the predictive performance of the models. RESULTS: Out of the 2181 COVID-19 patients, 624 died during hospitalization and 1557 recovered. The missing rate was 3 percent for each patient. The mean age of dead patients (71.17 ± 14.44 years) was statistically significant higher than recovered patients (58.25 ± 16.52 years). Based on RF, 10 features with the highest relative importance were selected as the best influential features; including blood urea nitrogen (BUN), lymphocytes (Lym), age, blood sugar (BS), serum glutamic-oxaloacetic transaminase (SGOT), monocytes (Mono), blood creatinine (CR), neutrophils (NUT), alkaline phosphatase (ALP) and hematocrit (HCT). The results of predictive performance comparisons showed GNAM with the mean accuracy, F1-score, and mean AUC in the test dataset of 0.847, 0.691, and 0.774, respectively, had the best performance. The smooth function graphs learned from the GNAM were descending for the Lym and ascending for the other important features. CONCLUSIONS: Interpretable GNAM can perform well in predicting the mortality of COVID-19 patients. Therefore, the use of such a reliable model can help physicians to prioritize some important demographic and clinical biomarkers by identifying the effective features and the type of predictive trend in disease progression.

Longitudinal changes in inflammatory biomarkers among patients with COVID-19: A nationwide study in Iceland.

OBJECTIVES: All SARS-CoV-2-positive persons in Iceland were prospectively monitored and those who required outpatient evaluation or were admitted to hospital underwent protocolized evaluation that included a standardized panel of biomarkers. The aim was to describe longitudinal changes in inflammatory biomarkers throughout the infection period of patients with COVID-19 requiring different levels of care. DESIGN: Registry-based study. SETTING: Nationwide study in Iceland. PATIENTS: All individuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) from February 28 to December 31, 2020 in Iceland and had undergone blood tests between 5 days before and 21 days following onset of symptoms. MEASUREMENTS AND MAIN RESULTS: Data were collected from the electronic medical record system of Landspitali-The National University Hospital of Iceland. Data analyses were descriptive and the evolution of biomarkers was visualized using locally weighted scatterplot smoothing curves stratified by the worst clinical outcome experienced by the patient: outpatient evaluation only, hospitalization, and either intensive care unit (ICU) admission or death. Of 571 included patients, 310 (54.3%) only required outpatient evaluation or treatment, 202 (35.4%) were hospitalized, and 59 (10.3%) were either admitted to the ICU or died. An early and persistent separation of the mean lymphocyte count and plasma C-reactive protein (CRP) and ferritin levels was observed between the three outcome groups, which occurred prior to hospitalization for those who later were admitted to ICU or died. Lower lymphocyte count, and higher CRP and ferritin levels correlated with worse clinical outcomes. Patients who were either admitted to the ICU or died had sustained higher white blood cell and neutrophil counts, and elevated plasma levels of procalcitonin and D-dimer compared with the other groups. CONCLUSIONS: Lymphocyte count and plasma CRP and ferritin levels might be suitable parameters to assess disease severity early during COVID-19 and may serve as predictors of worse outcome.

Effects of prebiotic-rich yogurt on menopausal symptoms and metabolic indices in menopausal women: a triple-blind randomised controlled trial.

This study aimed to investigate the effects of prebiotics on metabolic indices and menopausal symptoms. This triple-blind randomised controlled trial was conducted on 60 menopausal women. The participants were assigned to two groups based on block randomisation. Over 6 weeks, the experimental group received 100 g of prebiotic-rich yogurt daily after lunch and the control group received regular yogurt. Menopausal symptoms and metabolic indices were assessed before and after the treatment. The mean total score of menopausal symptoms (p < 0.001), anxiety (p < 0.001), depression (p = 0.003), vasomotor (p < 0.001), and low-density lipoprotein (p = 0.028) was statistically lower in the experimental group than the control group. Moreover, the serum insulin level was statistically higher among those in the experimental group (p = 0.011). The study results demonstrated the positive effects of prebiotic-rich yogurt on menopausal symptoms and some metabolic indices. Trial registration: Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N52; Date of registration: 12/4/2019. URL: https://en.irct.ir/user/trial/41105/view; Date of first registration: 12/5/2019.

Laboratory-wide association study of survival with prostate cancer.

BACKGROUND: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory-wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer. METHODS: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false-discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts. RESULTS: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate-specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06-1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20-1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76-0.80]; and creatinine: HR, 1.05 [95% CI, 1.03-1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98-1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09-1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort. CONCLUSIONS: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making. LAY SUMMARY: This article examined routine laboratory tests associated with survival among veterans with prostate cancer. Using laboratory-wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making.

Demographic, clinical, and laboratory factors associated with renal parenchymal injury in Iranian children with acute pyelonephritis.

BACKGROUND: The association between renal parenchyma changes on dimercaptosuccinic acid (DMSA) scans and demographic, clinical, and laboratory markers was assessed in pediatric patients with acute pyelonephritis. METHODS: A retrospective study of 67 Iranian babies and children aged 1-month to 12-year with APN was conducted between 2012 and 2018. The presence of renal parenchymal involvement (RPI) during APN was determined using technetium-99m DMSA during the first 2 weeks of hospitalization. The association of DMSA results with demographic data, clinical features (hospitalization stay, fever temperature and duration), and laboratory parameters such as pathogen type, and hematological factors (ESR, CRP, BUN, Cr, Hb, and WBC) was evaluated. RESULTS: 92.5% of children with an average age of 43.76 ± 5.2 months were girls. Twenty-four children (35.8%) did not have renal parenchymal injury (RPI), while 26 (38.8%) and 17 (25.4%) patients showed RPI in one and both kidneys, respectively. There was no significant association between RPI and mean ESR, CRP, BUN, and WBC. However, there were significant associations between RPI and higher mean levels of Cr, Hb, and BMI. CONCLUSIONS: Low BMI and Hb levels and increased Cr levels might be indicative of the presence of RPI in children with APN.

Epidemiological and clinical characteristics of 3334 cases with prediagnosis coronavirus disease - 2019 (COVID-19) in Turkey.

AIM: This study aims to analyse the epidemiological and clinical features of the patients admitted to the hospital with the prediagnosis of coronavirus disease 19 (COVID-19) in Turkey. MATERIALS AND METHODS: In this retrospective study, epidemiological and clinical features, laboratory markers, radiological features, therapeutic approaches, and survival conditions of the patients with the prediagnosis of COVID-19 from March 11th to June 30th, 2020 have been analysed and reported. The data of the cases were divided into four groups and then compared with each other: first group includes confirmed cases with positive reverse transcriptase polymerase chain reaction (RT-PCR) and chest computed tomography (CT) imaging results considered as COVID-19 lung involvement, second group includes the clinically diagnosed cases with negative RT-PCR and positive CT imaging abnormalities, third group includes mild and asymptomatic cases with positive RT-PCR and negative CT findings, fourth group includes suspected cases with negative RT-PCR and negative CT findings. Post-hoc analysis was performed to evaluate the differences among the groups. RESULTS: In total, 3334 patients with the prediagnosis of COVID-19 admitted to the emergency department. Based on the post hoc analyses, significant differences were found among the four groups in terms of their test results of leukocytes, haemoglobin, platelet, neutrophils, urea and C-reactive protein (CRP) (P < .001). Furthermore, the factors of age groups, hospitalisation, intensive care unit follow-up and mortality rate of the four groups showed a significant difference among the groups (P = .001). CONCLUSION: The mean leukocytes, neutrophils and platelet counts of patients with positive RT-PCR were found to be lower than the ones with negative RT-PCR. The mean serum levels of CRP were found to be higher in patients with lung involvement compared with other patient groups.

Clinical Usefulness of Acute-Phase Markers in Distinguishing between PFAPA and Other Exudative Tonsillitis Causes: A Methodological Study.

BACKGROUND: We investigated the practical use of procalcitonin (PCT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and complete blood count (CBC) parameters in distinguishing periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA) attacks from exudative tonsillitis associated with group A streptococcus (GAS) and Epstein-Barre virus (EBV). METHODS: The study population consisted of cases with exudative tonsillitis who had been subsequently diagnosed as PFAPA, EBV, and GAS tonsillitis through a period of 6 years. We retrieved the CBC, ESR, CRP and PCT data from patients' medical records. RESULTS: Of the patients, 47 (35.6%) had PFAPA, 36 (27.3%) had GAS and 49 (37.1%) had EBV tonsillitis. Median CRP, ESR and PCT values of patients with PFAPA were 78 (17-92) mg/dl, 44 (11-83) mm/h, 0.16 (0.01-1.45) ng/ml, respectively. The CRP and ESR levels were significantly higher in PFAPA and GAS groups compared with the EBV group (p = 0.001). There was no significant difference between the groups regarding the PCT levels. CONCLUSION: The study indicated no benefit of PCT in distinguishing PFAPA from the others. However, we found that CRP, ESR, and CBC parameters could be useful in identifying PFAPA and GAS than EBV tonsillitis.

A Retrospective Analysis of Pain Etiology in Middle-Aged Patients with Peripheral Neuropathy.

Background and Objectives: Correct assessment and a multidisciplinary approach appear to be extremely important in preventing peripheral neuropathy and its complications. The purpose of this study was to find the correlations and dissimilarities between different types of peripheral neuropathy, the occurrence of pain, and laboratory results. Materials and Methods: This retrospective study assessed 124 patients who were hospitalized in our neurology department due to various types of sensory or motor disturbances. The patients were eventually diagnosed with peripheral neuropathy, based on the electrophysiological study, anamnesis, physical examination, and laboratory results. The whole group was subjected to statistical analysis. Results: The mean age of patients was over 56 years, with a slight woman predominance. A statistically significant (p < 0.05) relationship between the place of residence and gender was seen, where more men than women live in the rural area, while more women than men live in the urban area. Most often we observed symmetric, sensorimotor, demyelinating, inflammatory, and chronic neuropathy. More than 40% of patients reported pain. A statistically significant correlation between the evolution/severity and the occurrence of pain was seen in subacute type (p < 0.05) and small fibre neuropathy (p < 0.01). Conclusions: A higher incidence of peripheral neuropathy in middle-aged people will become essential in the aging society with lifestyle and chronic disorders. Peripheral neuropathy is slightly more common in women than men and its occurrence may be influenced by work performed or internal and external factors. In the study group, more than 40% of patients reported pain, therefore the pain measurement for each patient should be implemented and repeated at every visit. An assessment of sodium level and, in women, markers of neuroinflammation level in the various types of peripheral neuropathy may be an interesting direction for the future.

Biochemical Markers, Genotype, and Inflammation in Pediatric Inflammatory Bowel Disease: A Danish Population-Based Study.

BACKGROUND: Our aim was to characterize the biochemical markers at diagnosis in patients with inflammatory bowel disease (IBD), to assess the utility of these to predict disease course and investigate if genotype influences biochemical markers of inflammation. SUMMARY: Patients were included from a population-based pediatric IBD cohort from Eastern Denmark. Data on biochemical markers and medical as well as surgical treatment were registered at diagnosis, 30 days, 6 and 12 months after diagnosis. Fifty-two single nucleotide polymorphisms (SNPs) known to be associated with IBD were selected for genotyping based on previous genetic studies. Key messages: A total of 190 IBD patients (97 ulcerative colitis [UC], 87 Crohn's disease [CD], and 6 IBD unclassified) were included. UC patients with extensive disease had higher C-reactive protein, erythrocyte sedimentation rate, and platelet count at diagnosis compared to UC patients with less extensive disease. No similar differences between disease extent groups were found in CD. Low albumin at diagnosis was associated with an increased risk of surgery in both UC (OR 1.35; 95% CI: 1.05-1.75) and CD patients (OR 1.23; 95% CI: 1.01-1.48) and increased use of azathioprine and anti-tumor necrosis factor alpha use in the total IBD cohort (OR 1.15; 95% CI: 1.04-1.27 and OR 1.19 [1.08-1.34]). One SNP (rs4986791 in the TLR-4 locus) and 2 SNPs (rs6785049 in the Pregnane-x-receptor gene and rs10500264 in the SLCA10 gene) were associated with a change in albumin and hemoglobin over time respectively in our IBD cohort. Our study confirms albumin to be a marker of severe disease course. Furthermore, the patient's genotype possibly affects the inflammatory response. Future studies in larger pediatric cohorts are needed to confirm our findings.

Influence of ethnicity on population reference values for biochemical markers.

Reference intervals (RIs) for biochemical and hematological markers determined using healthy adult and/or pediatric populations are vital for clinical interpretation of laboratory test results. Most clinical laboratories commonly use age- and sex-specific RIs, but the effect of ethnicity as a covariate is often overlooked. Ethnic differences in serum biomarker concentrations can occur as a result of genetic and environmental factors, while the degree to which each factor influences serum levels depends on the specific biomarker. Numerous studies have investigated ethnic differences in routine chemistry, fertility, endocrine, cancer, and hematological markers, as well as in vitamins and carotenoids, in children, adolescents and adults. In the present review, we summarize and discuss ethnic-specific differences observed for these laboratory markers and their potential impact on the clinical interpretation of laboratory test results. We categorized the available data into seven major ethnic groups (i.e. Black, Caucasian, East Asian, Hispanic, South Asian, South East Asian, and West Asian) for ease of comparison. While certain biomarkers could not be compared between ethnic groups because of insufficient information or contradictory results between studies, significant differences between ethnic groups were reported by one or more studies for most of the biomarkers included in this review. The clinical significance of these differences and the potential need for ethnic-specific RIs for certain biochemical markers are also discussed.

Diagnosing Periprosthetic Joint Infection in Inflammatory Arthritis: Assumption Is the Enemy of True Understanding.

BACKGROUND: Despite concern over the interpretation of serum and synovial fluid tests to screen and diagnose periprosthetic joint infection (PJI) in patients with inflammatory arthritis, only a single study has investigated this area. We aimed to assess accuracy of clinical and laboratory markers for PJI diagnosis in the context of underlying inflammatory arthritis. METHODS: This multicenter study was conducted on total joint arthroplasty patients at 3 different centers between 2001 and 2016. PJI was defined based on Musculoskeletal Infection Society criteria. Acute PJI cases were excluded. Patients operated for a diagnosis other than infection, who did not subsequently fail at 1-year follow-up, were considered aseptic revisions. Serum C-reactive protein and erythrocyte sedimentation rate, synovial white blood cell and differential, as well as alpha-defensin and results of frozen section were documented. RESULTS: In total, 1220 patients undergoing revision total joint arthroplasty (567 PJI, 653 aseptic) were included. Fifty-five septic patients and 61 in the aseptic group had inflammatory arthritis. Although mean levels of serum C-reactive protein and synovial white blood cell in inflammatory arthritis patients were significantly higher compared to patients without inflammatory arthritis, there were no significant differences in PJI patients. The thresholds associated with increased risk for PJI in patients with and without inflammatory arthritis were similar and closely resembled traditional cut-points. CONCLUSION: We demonstrate higher baseline immune upregulation in aseptic revision cases with inflammatory arthritis, but no significant differences are seen for PJI. Conventional PJI thresholds for serum and synovial diagnostic markers should be adhered to. Assumptions about inflammatory arthritis patients needing differential diagnostic protocols should be avoided.

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed. Dysregulation of metabolism, as a result of ethanol exposure, in the intestine leads to colon carcinogenesis. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota have been suggested. The clinical aspects of NASH, as part of the metabolic syndrome in the aging population, have been presented. The symposium addressed mechanisms and biomarkers of alcohol induced damage to different organs, as well as the role of the microbiome in this dialog. The microbiota regulates and acts as a key element in harmonizing immune responses at intestinal mucosal surfaces. It is known that microbiota is an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. The signals at the sites of inflammation mediate recruitment and differentiation in order to remove inflammatory inducers and promote tissue homeostasis restoration. The change in the intestinal microbiota also influences the change in obesity and regresses the liver steatosis. Evidence on the positive role of moderate alcohol consumption on heart and metabolic diseases as well on reducing steatosis have been looked up. Moreover nutrition as a therapeutic intervention in alcoholic liver disease has been discussed. In addition to the original data, we searched the literature (2008-2016) for the latest publication on the described subjects. In order to obtain the updated data we used the usual engines (Pub Med and Google Scholar). The intention of the eighth symposia was to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications.

Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice.

BACKGROUND: Macrocytic anaemia (MCV ≥ 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. METHODS: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. RESULTS: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. CONCLUSION: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice.

Alcoholic and non-alcoholic steatohepatitis.

This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.