Laboratory Biomarkers Research Articles

Feasibility of plasma proteomics in patients with immune thrombocytopenia.

ITP is an acquired autoimmune bleeding disorder characterized by an isolated thrombocytopenia. The pathophysiology is highly multifactorial and involves antibody- and/or cytotoxic T cell-mediated killing of platelets and disruption of megakaryocyte function hampering platelet production. ITP remains a diagnosis of exclusion, and due to the high degree of variability between patients, it remains challenging to predict disease courses and responses to therapeutic agents. Hence, diagnostic and therapeutic laboratory biomarkers are highly warranted. To address this issue, in their paper, Jiang and colleagues have performed plasma proteomics in ITP patients (n = 40), in comparison to patients with thrombocytopenia due to other causes than ITP (non-ITP thrombocytopenia, n = 19) and healthy controls (n = 18). The data underscore that patients with ITP have a distinct plasma proteomic signature compared to non-ITP thrombocytopenia patients and healthy individuals. The findings should be further validated and investigated but suggest that the application of plasma proteomics is feasible and promising with respect to the search for potential biomarkers in patients with ITP. Commentary on: Jiang etal. Targeted proteomics profiling reveals valuable biomarkers in the diagnosis of primary immune thrombocytopenia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19760.

Prevalence and Risk Factors of Pulmonary Embolism in COPD Patients Complicated with Secondary Polycythemia.

This study aimed to establish the prevalence of pulmonary embolism (PE) in chronic obstructive pulmonary disease (COPD) patients with secondary polycythemia (SP) and explore the risk factors for PE in COPD patients with SP. We analyzed the prevalence of PE among COPD patients with SP who were hospitalized at Qinghai Provincial People's Hospital between January 2015 and December 2020. From January 2021 to January 2024, we enrolled patients into three groups (COPD+SP+PE, COPD+SP, and control) and performed laboratory measurements, biomarkers, echocardiography, and pulmonary function tests. Patients in the COPD+SP group received clinical treatment, and biomarkers were measured again seven days after treatment. The prevalence of PE in patients with COPD SP was 5.21%. We found that COPD+SP+PE group had significantly higher levels of erythrocyte distribution width (RDW), platelet volume distribution width (PDW), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), monocyte to large platelet ratio (MLPR), 5-hydroxytryptamine (5-HT), activated protein C (APC), urokinase-type plasminogen activator (u-PA), thrombomodulin (TM), interleukin-38 (IL-38), tissue factor (TF), and fractalkine (FKN) in contrast to COPD+SP group. Biomarkers, such as FKN, β-thromboglobulin (β-TG), APC, u-PA, TM, TF, and IL-38, were risk factors for COPD patients with SP who are complicated by PE. Clinical treatment significantly reduced the levels of β-TG, IL-38, APC, endothelin-1 (ET-1), u-PA, FKN, TM, 5-HT, and neutrophil extracellular traps (NETs) in patients with COPD+SP. PE incidence was significantly higher in patients with COPD and SP. In COPD patients with SP, routine joint detection of blood and cardiac markers, blood gas analysis, and pulmonary function tests can help to identify patients with PE. APC, u-PA, TF, FKN, TM, and IL-38 are risk factors for PE in patients with COPD and SP, and clinical treatment can effectively reduce this risk.

A single risk assessment for the most common diseases of ageing, developed and validated on 10 cohort studies

BackgroundWe aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors.MethodsData were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.0, 6.8, and 7.4, respectively. Disease-free participants at baseline were included, and 22 risk factors (sociodemographic, medical, lifestyle, laboratory biomarkers) were evaluated. Two risk tools (DemNCD and DemNCD-LR based on Fine and Gray sub-distribution and logistic regression [LR], respectively) were developed and validated. Predictive accuracies of these risk tools were assessed using Harrel’s C-statistics and area under the curve (AUC) and 95% confidence interval (CI). Model calibration was conducted using Hosmer–Lemeshow goodness of fit test along calibration plots.ResultsBoth the DemNCD and DemNCD-LR resulted in similar predictive accuracy for each outcome. The overall AUC (95% CI) for dementia, stroke, MI, and diabetes risk tool were 0·68 (0·65, 0·70), 0·58 (0·54, 0·61), 0·65 (0·61, 0·68), and 0·68 (0·64, 0·72), respectively, for males. For females, these figures were 0·65 (0·63, 0·67), 0·55 (0·52, 0·57), 0·65 (0·62, 0·68), and 0·61 (0·57, 0·65).ConclusionsThe DemNCD is the first tool to predict both dementia and multiple cardio-metabolic diseases using comprehensive risk factors and provided similar predictive accuracy to existing risk tools. It has similar predictive accuracy as tools designed for single outcomes in this age-group. DemNCD has the potential to be used in community and clinical settings as it includes self-reported and routinely available clinical measures.

Diagnosis of sepsis: which clinical and laboratory biomarkers are useful?

The quest for an unequivocal diagnostic tool for sepsis has persisted for decades, but this goal remains elusive. The diagnosis of sepsis is characterized by its complexity, which encompasses dozens of biochemical, hematologic, and immunologic parameters as well as complex microbiological diagnostics. During the last decade, the integration of omics technologies has further complicated this landscape. Despite these advancements, clinical diagnosis remains the gold standard for the diagnosis of sepsis. In the following review, we provide an overview of select diagnostic biomarkers that are deemed readily applicable in routine clinical practice, thus extending beyond the confines of university hospitals. Verification of the reliability and usefulness of a diagnostic parameter generally takes several years, and this process is more difficult in patients with sepsis compared with other patients because of the complexity of this clinical condition. Nevertheless, the introduction of new technologies, the intensive use of bedside diagnostics, and the contribution of omics technologies are moving us toward the realization of personalized medicine and theranostics.

Rank correlation between atopic comorbidity and laboratory parameters in allergic rhinitis

One of the current cutting-edge problems in allergy and ENT is the study of comorbidity in allergic rhinitis, which is the most common atopic disease among all other atopies. Two decades ago, a new endotype of the disease, local allergic rhinitis, was discovered. In the past, some patients with typical complaints of chronic nasal congestion, persistent runny nose, and other similar symptoms, did not display such characteristic diagnostic criteria as positive allergy skin tests and an increased value of serum total IgE and specific IgE antibodies. They were qualified by allergists and ENT specialists as individualists with non-allergic rhinitis and, accordingly, did not receive adequate treatment. However, their symptoms remained, prompting them to abuse decongestants and resulting in an increased burden on the cardiovascular system. This, along with the burden of concomitant pathology, including other atopies, can be considered a significant medical and social problem. With the purpose to study rank correlation between comorbidity and three laboratory biomarkers, 46 patients with allergic rhinitis were examined. The list of parameters included two routine items such as serum total IgE and eosinophilic cationic protein, and rarely studied IL-4 in skin exudate. Clinical analysis showed that significantly more often allergic rhinitis in patients was combined with bronchial asthma (in 39.1%, p 0.05), less often with food allergy (in 19.6%), atopic dermatitis (in 10.9%), insect allergy (in 8.7%), and allergic urticaria (in 4.5%). In one case, local perennial rhinitis was identified, accompanied by conventional seasonal rhinitis with a high content of serum total IgE and positive allergic skin tests with pollen allergens. Skin tests with household allergens, including house dust mite products, showed a negative result. This case was regarded as a manifestation of the so-called “double” allergic rhinitis. The Spearman correlation demonstrated a negative mean strength relationship between comorbidity and serum IgE and eosinophilic cationic protein (p 0.05). The seemingly paradoxical result can be interpreted quite logically, taking into account immunopathogenetic mechanisms of allergic inflammation. In particular, with an increase in the frequency of atopic comorbidity, the migration of eosinophils from the blood to sites of eosinophilic inflammation increases.

Feasibility of transcranial Doppler to evaluate vasculopathy among survivors of childhood brain tumors exposed to cranial radiation therapy.

The ability of transcranial Doppler (TCD) to detect asymptomatic cerebrovascular disease among childhood brain tumor survivors following exposure to cranial radiation therapy has not been established. Survivors of childhood brain tumors, more than 3years since diagnosis and exposed to greater than 30Gy cranial radiation, underwent a history and physical exam, laboratory biomarkers of cerebrovascular disease (cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), high-sensitivity CRP, hemoglobin A1C, apoprotein A, and apoprotein B), and a TCD evaluation of their cerebral arteries. In all 165 cerebral arteries from 13 patients (medulloblastoma=10; germ cell tumor=3; females=5; mean age at diagnosis=8.0years; mean age at time of study=20.9years) were examined. Twenty-eight of 165 (17%) were considered abnormal by pre-specified criteria. Total 114 cerebral arteries from 13 patients were assessed for greater than 50% stenosis velocities. Arteries most likely to be considered abnormal included the distal bilateral vertebral arteries (right 38%, left 30%), basilar artery 30%, bilateral siphon internal carotid arteries (right 30%, left 23%), bilateral middle cerebral arteries (23% bilaterally), and bilateral anterior cerebral arteries (7% bilaterally). Two vessels had mean flow velocities consistent with 50% stenosis (1.8%). No vessels were found to have greater than 80% stenosis. TCD may be a useful and practical tool to examine asymptomatic cerebrovascular disease among childhood brain tumor survivors after exposure to cranial radiation therapy. Posterior circulation vessels appear to have the highest burden of disease in this group of brain tumor survivors, a majority of whom had medulloblastoma.

Individuals Who Had a Lifetime History of Suicide Attempts and Their Relationships With Inflammation, Severity of Depressive Symptoms, and Childhood Maltreatments

Abstract Lifetime history of suicide attempts is associated with inflammatory mechanisms, severity of depressive symptoms, and childhood trauma. This cross-sectional study enrolled 54 suicide attempters and 154 nonsuicide attempters. All individuals were assessed through a questionnaire, a structured clinical interview, scales, anthropometric measures, and laboratory biomarkers. Individuals with a history of lifetime suicide attempts showed significant positive correlations regarding soluble tumor necrosis factor receptor 1 and severity of depressive symptoms (p = 0.013), interleukin-1 receptor antagonist and severity of depressive symptoms (p = 0.04), and absenteeism from work and childhood physical abuse (p = 0.012). Suicide attempters also experienced more childhood trauma (sexual abuse, physical abuse, emotional abuse, emotional neglect, and physical neglect) compared with nonsuicide attempters. IL-4 levels were significantly lower in individuals who attempted suicide than in nonsuicidal individuals. Lifetime suicide attempts in major affective disorders were associated with childhood trauma and proinflammatory and anti-inflammatory cytokines.

Trends of common laboratory biomarkers after SARS-CoV-2 infection

Most studies that explore the long-term effects of COVID-19 are based on subjectively reported symptoms, while laboratory-measured biomarkers are mainly examined in studies of relatively small cohorts. This study investigates the long-term effects of SARS-CoV-2 infection on common laboratory biomarkers. We utilized a retrospective cohort of SARS-CoV-2 infected individuals and rigorously matched controls based on demographic and clinical characteristics, examining 63 common laboratory biomarkers. Additional lab-specific cohorts were matched with an additional criterion of baseline biomarker values. Differences in biomarkers over a 12-month follow-up were analyzed using standardized mean difference-in-differences. The general cohort included 361,061 matched pairs, with 26M laboratory results. The effects on most biomarkers lasted 1-4 months and were consistent with anticipated changes after acute viral infections. Some biomarkers presented prolonged effects, consistent across the general and lab-specific cohorts. One group of such findings included a 7-8 month decrease in WBC counts, mainly driven by decreased counts of neutrophils, monocytes, and basophils. Potassium levels were decreased for 3-5 months. Vaccinated individuals' data suggested potentially smaller effects on WBCs, but cohort sizes limited this analysis. This study explores SARS-CoV-2 infection effects on common laboratory biomarkers, characterizing the direction and duration of these effects on the largest infected cohort to date. The effects of most biomarkers resolve in the first months following infection. The most notable longer-lasting effects involved the immune system. Further research is required to characterize the magnitude of these effects among specific individuals.

Platelet-to-Lymphocyte Ratio as Coagulopathy Predictor in COVID-19 Patients at Margono Soekarjo Hospital

Coronavirus Disease 2019 (COVID-19) is a disease possibly attacking various organs and systems of the body including the coagulation system causing coagulopathy. Various laboratory biomarkers have been developed to detect coagulopathy. This research aimed to determine the correlation and ability of Platelet-to-Lymphocyte Ratio (PLR) in predicting coagulopathy when compared to D-dimer. A cross-sectional research was conducted on 1580 data of COVID-19 patients at Margono Soekarjo Hospital. The research data were then analyzed using Spearman’s correlation test to figure out the correlation between PLR and D-dimer. This research was also intended to find the PLR Cut-Off Value (COV), Odds Ratio (OR), Area Under Receiver Operating Characteristic (AUROC), and diagnostic value. Platelet-to-lymphocyte ratio value had a significant correlation with D-dimer levels (r=0.260, p=0.000). The COV of PLR was 176.61 with the OR of 2.7 (2.2-3.3 95%CI), AUROC of 0.638, sensitivity of 62%, and specificity of 62%. PLR can be used as a screening biomarker to predict the occurrence of coagulopathy in COVID-19 patients.

Enhancing the accuracy and effectiveness of diagnosis of spontaneous bacterial peritonitis in cirrhotic patients: A machine learning approach utilizing clinical and laboratory data

PurposeSpontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid that develops naturally, without being triggered by any surgical conditions or procedures, and is a common complication of cirrhosis. With a potential mortality rate of 40 ​%, accurate diagnosis and prompt initiation of appropriate antibiotic therapy are crucial for optimizing patient outcomes and preventing life-threatening complications. This study aimed to expand the use of computational models to improve the diagnostic accuracy of SBP in cirrhotic patients by incorporating a broader range of data, including clinical variables and laboratory values. Patients and methodsWe employed 5 machine learning classification methods - Decision Tree, Support Vector Machine, Naive Bayes, K-Nearest Neighbor, and Random Forest, utilizing a variety of demographic, clinical, and laboratory features and biomarkers. ResultsAscitic fluid markers, including white blood cell (WBC) count, lactate dehydrogenase (LDH), total protein, and polymorphonuclear cells (PMN), significantly differentiated between SBP and non-SBP patients. The Random Forest model demonstrated the highest overall accuracy at 86 ​%, while the Naive Bayes model achieved the highest sensitivity at 72 ​%. Utilizing 10 key features instead of the full feature set improved model performance, notably enhancing specificity and accuracy. ConclusionOur analysis highlights the potential of machine learning to enhance the accuracy of SBP diagnosis in cirrhotic patients. Integrating these models into clinical workflows could substantially improve patient outcomes. To achieve this, ongoing multidisciplinary research is crucial. Ensuring model interpretability, continuous monitoring, and rigorous validation will be essential for the successful implementation of real-time clinical decision support systems.

Baseline level of interleukin-6 is associated with the risk of acute coronary syndrome development in SARS-CoV‐2 infection

BackgroundAcute coronary syndrome (ACS) is frequently reported in patients with coronavirus disease 2019 (COVID-19). Cytokine storm induced by interleukin-6 (IL-6) has been suggested to potentially cause myocardial injury in COVID-19. We investigated the association between baseline level of IL-6 and development of ACS in COVID-19 patients.MethodsDemographic and clinical data of hospitalized COVID-19 patients from 2020 to 2022 were reviewed. Extracted data including patient characteristics, laboratory biomarkers, and systemic inflammation indexes in patients with or without ACS were reviewed and analyzed. Logistic regression models were applied to analyze predictors of ACS development and receiver-operating characteristic (ROC) curves were used to assess discriminatory power of IL-6 and other risk factors for predicting ACS development.ResultsAmong 1,753 COVID-19 patients, 37 cases experienced ACS and 159 patients without main COVID-19 complications were randomly selected as controls. ACS patients were older (p = 0.001) and suffered from more comorbidities including diabetes (43% vs. 18%, p = 0.001), hypertension (40.5% vs. 24.5%, p = 0.050), ischemic heart disease (49% vs. 9%, p = 0.001), and hyperlipidemia (19% vs. 5%, p = 0.010). Also, decreased level of consciousness (31.6% vs. 2.5%, p = 0.001), ICU admission (65% vs. 2%, p = 0.001), and mortality events (70% vs. 0.6%, p = 0.001) were more prevalent in the ACS group. Baseline levels of IL-6 (p = 0.001), D-dimer (p = 0.026), troponin (p = 0.001), blood urea nitrogen (p = 0.002), and creatinine (p = 0.008) were higher in ACS patients but erythrocyte sedimentation rate (p = 0.013), hemoglobin (p = 0.033), and red blood cells (p = 0.028) were lower compared with controls. Also, age (OR: 1.06, p = 0.019), IL-6 (OR: 1.44, p = 0.047), and cardiovascular disease (CVD) (OR: 3.66, p = 0.043) were associated with ACS development. The area under the curve (AUC) of IL-6 and combined predictors respectively was 0.661 (p = 0.002) and 0.829 (p = 0.001).ConclusionsHigh IL-6 concentration at baseline is a strong predictor for ACS development in COVID-19 patients. Also, elderly and concurrent CVD are significantly associated with ACS development.

Investigation of Biochemical and Inflammatory Markers in COVID-19 Patients Hospitalized in the Intensive Care Unit: An Observational Study in Northern Iran

Background: Since the first documentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been a notable emphasis on it in a brief period, especially as the mortality rate and confirmed cases steadily rise. The rapid and accurate laboratory identification of an ongoing COVID-19 infection is essential for efficient pandemic control. For diagnostic purposes, various testing methods have been developed to detect the severity of COVID-19. These diagnostic methods play a crucial role in identifying and managing the spread of the virus within communities worldwide. Methods: This cross-sectional observational study was conducted from February to June 2020, spanning four months. Patient clinical records and laboratory biomarkers data were collected. Results: In this study, 263 patients were involved, with an average age of 59.38 ± 15.26 years, and 51.3% of them (135 patients) were male. The typical hospital stay was 9.25 ± 6.9 days. The patients were divided into three groups: Those who survived (49.4%), those receiving treatment (4.9%), and those who did not survive (45.6%), with all treated patients surviving. An important connection was observed between serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), urea, leukocytosis, lymphopenia, high polymorphonuclear neutrophil (PMN) counts, and poor patient outcomes (P-value < 0.05). Elevated aspartate transaminase (AST) levels also showed a close relationship with adverse outcomes (P-value = 0.05). Furthermore, most patients with hyponatremia, high fasting blood glucose, and elevated serum creatinine levels did not survive, despite lacking statistical significance. Conclusions: Serum biomarkers serve as prognostic indicators for the severity of COVID-19 patients. Leveraging these markers aids in promptly diagnosing patients at high mortality risk and facilitates more effective treatments in the disease's initial phases. These biomarkers can help healthcare providers identify patients at higher risk of complications and guide the implementation of targeted interventions to improve patient outcomes.

NT-proBNP Reflects Left Ventricular Hypertrophy Rather than Left Ventricular Dilatation or Systolic Dysfunction in Patients with Fabry Disease

Background: The diagnosis and follow-up of cardiac involvement in Fabry disease constitutes an important challenge for clinicians caring for affected patients. Combining cardiac imaging with laboratory biomarkers appears most appropriate for longitudinal monitoring. Therefore, we examined the use of NT-proBNP and its association with imaging findings in patients with Fabry disease. Methods: We analysed cardiac MRI and echocardiography data, as well as laboratory results, from a single-centre prospective registry. Results: Repetitive follow-ups of 38 patients with Fabry disease, of whom 18 presented with left ventricular hypertrophy (LVH), revealed a correlation of NT-proBNP with left ventricular (LV) interventricular septal thickness, LV maximum wall thickness, LV and right ventricular (RV) mass index and trabecular mass in patients with LVH. Patients without LVH did not exhibit any tangible association between NT-proBNP and the mentioned parameters. Conversely, we could not detect an association of NT-proBNP with impairment of LV or RV ejection fraction or diastolic volume. Conclusions: NT-proBNP plays a pivotal role as a biomarker for cardiac involvement in patients with Fabry disease. Interestingly, in this specific population with mostly preserved ejection fraction, it seems to reflect ventricular hypertrophy rather than ventricular dysfunction or dilatation. While strong associations were found in hypertrophic patients, NT-proBNP’s prognostic value appears limited in non- or pre-hypertrophic stages.

Clustering Based on Laboratory Data in Patients With Heart Failure Admitted to the Intensive Care Unit.

Heart failure (HF) is a common condition that imposes a significant burden on healthcare systems. We aimed to identify subgroups of patients with heart failure admitted to the ICU using routinely measured laboratory biomarkers. A large dataset (N = 1176) of patients with heart failure admitted to the ICU at the Beth Israel Deaconess Medical Center in Boston, USA, between June 1, 2001, and October 31, 2012, was analyzed. We clustered patients to identify laboratory phenotypes. Cluster profiling was then performed to characterize each cluster, using a binary logistic model. Two distinct clusters of patients were identified (N = 679 and 497). There was a significant difference in the mortality rate between Clusters 1 and 2 (50 [7.4%] vs. 109 [21.9%], respectively, p < 0.001). Patients in the Cluster 2 were significantly older (mean [SD] age = 72.35 [14.40] and 76.37 [11.61] years, p < 0.001) with a higher percentage of chronic kidney disease (167 [24.6%] vs. 262 [52.7%], respectively, p < 0.001). The logistic model was significant (Log-likelihood ratio p < 0.001, pseudo R2 = 0.746) with an area under the curve of 0.905. The odds ratio for leucocyte count, mean corpuscular volume (MCV), red blood cell (RBC) distribution width, hematocrit (HcT), lactic acid, blood urea nitrogen (BUN), serum potassium, magnesium, and sodium were significant (all p < 0.05). Laboratory data revealed two phenotypes of ICU-admitted patients with heart failure. The two phenotypes are of prognostic importance in terms of mortality rate. They can be differentiated using blood cell count, kidney function status, and serum electrolyte concentrations.

The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status.

Vitamin B12 (cobalamin; B12) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B12 deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B12 status include the measurement of serum B12 (also known as total B12 or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B12 status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B12 test, which is readily available and highly automated. In some cases, the sequential use of different B12 status biomarkers or the calculation of a composite B12 status score, derived from a panel of B12 biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarises the utility of B12-related biomarkers and describes approaches to their application and interpretation.

A-249 Monocyte distribution width (MDW) as a reliable diagnostic biomarker for sepsis in HIV-infected patients

Abstract Background Sepsis is the main cause of death in patients with acquired immunodeficiency syndrome (AIDS) and early diagnosis of sepsis in AIDS remains a significant challenge. Monocyte distribution width (MDW), as a new type of sepsis auxiliary diagnostic marker, has attracted widespread attention in the research and exploration of its clinical application. This study aims to evaluate the diagnostic efficacy of MDW in the occurrence of sepsis in HIV-infected patients and to construct a new clinical diagnostic model in combination MDW with other indicators. Methods A prospective cohort study was conducted at Shanghai Public Health Center with a total of 602 patients enrolled between December 2022 and August 2023. Sepsis-3 criteria were employed as the diagnostic standard for sepsis. MDW was measured at admission, using the hematology analyzer DxH900 (Beckman Coulter Inc.). Comprehensive clinical data, including complete blood counts and biochemical profiles, were collected. Enrolled participants received a follow-up about their survivals on day 30 and day 90. Five machine learning models were evaluated and compared to select the best performing model. Results The diagnostic performance of MDW for sepsis yielded an AUC of 0.818. With a cut-off value of 25.26, the sensitivity and specificity reached 0.822 and 0.754 respectively. The best performing variable among all five ML algorithms was Random Forest model. The top three variables with the highest importance ranking were platelet, albumin, and hemoglobin. Incorporating MDW and the top three laboratory indicators into a random forest model, the AUC value improved to 0.931. With a cut-off value of 0.5, the sensitivity was 1.00 while the specificity was 0.732. Conclusions MDW was an auxiliary diagnostic biomarker for sepsis in HIV-infected patients with reliable sensitivity and specificity. In combination MDW with other common laboratory biomarkers, a diagnostic model can be established to further improve the diagnostic efficiency of sepsis.

Complete blood count as a biomarker for preeclampsia with severe features diagnosis: a machine learning approach

ObjectiveThis study introduces the complete blood count (CBC), a standard prenatal screening test, as a biomarker for diagnosing preeclampsia with severe features (sPE), employing machine learning models.MethodsWe used a boosting machine learning model fed with synthetic data generated through a new methodology called DAS (Data Augmentation and Smoothing). Using data from a Brazilian study including 132 pregnant women, we generated 3,552 synthetic samples for model training. To improve interpretability, we also provided a ridge regression model.ResultsOur boosting model obtained an AUROC of 0.90±0.10, sensitivity of 0.95, and specificity of 0.79 to differentiate sPE and non-PE pregnant women, using CBC parameters of neutrophils count, mean corpuscular hemoglobin (MCH), and the aggregate index of systemic inflammation (AISI). In addition, we provided a ridge regression equation using the same three CBC parameters, which is fully interpretable and achieved an AUROC of 0.79±0.10 to differentiate the both groups. Moreover, we also showed that a monocyte count lower than 490/mm3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$490 /mm^{3}$$\\end{document} yielded a sensitivity of 0.71 and specificity of 0.72.ConclusionOur study showed that ML-powered CBC could be used as a biomarker for sPE diagnosis support. In addition, we showed that a low monocyte count alone could be an indicator of sPE.SignificanceAlthough preeclampsia has been extensively studied, no laboratory biomarker with favorable cost-effectiveness has been proposed. Using artificial intelligence, we proposed to use the CBC, a low-cost, fast, and well-spread blood test, as a biomarker for sPE.

A Prospective Comparative Study on the Clinical Diagnostic Performance of Blood Inflammatory Markers in Acute Appendicitis.

Despite the substantial advancements in imaging techniques for the diagnosis and differential diagnosis of acute appendicitis (AA) over recent decades, the specificity and sensitivity of widely utilized laboratory biomarkers in clinical practice remain inadequate.This study aimed to investigate the diagnostic utility of commonly employed blood inflammatory markers for AA. A total of 399 participants who either sought medical care or underwent health examinations were enrolled in this prospective study. The cohort comprised 200 patients diagnosed with AA (AA group), 100 patients presenting with abdominal pain but without AA (AP group), and 99healthy individuals undergoing routine health check-ups (HC group). For all subjects, the following biomarkers were measured: plasma neutrophil gelatinase-associated lipocalin (NGAL), white blood cell count (WBC), neutrophil count (NEU), percentage of neutrophils (NEU%), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). The diagnostic performance of the observed indicators, both individually and in combination, was assessed for the diagnosis of AA using Receiver Operating Characteristic (ROC) curves analysis and Delong's test. The laboratory indicators demonstrated a progressive increase from the HC group to the AP group, and further to the AA group (all p<0.05). Multifactorial logistic regression analysis identified NEU% and plasma NGAL as significant risk factors for the occurrence of AA. ROC curve analysis and Delong's test indicated that, in distinguishing the AA group from the HC group, the diagnostic performance of plasma NGAL, CRP, and NLR was equally substantial and superior to that of NEU and WBC. Within the AP group, plasma NGAL and CRP exhibited comparable diagnostic efficacy, outperforming NEU, WBC, and NLR. When differentiating AA in the non-appendicitis group (ie HC group + AP group), NGAL and CRP demonstrated comparable diagnostic efficacy, surpassing that of NEU, white WBC, and NLR. While the integration of multiple diagnostic tests can potentially improve overall diagnostic accuracy, the observed enhancement in the AUC is not statistically significant. NGAL, CRP, WBC, NEU% and NLR were significantly increased in patients with acute abdomen. NGAL and NEU% may function as independent risk factors for predicting the incidence of AA, with NGAL and CRP demonstrating similar and favorable diagnostic performance. While the combined evaluation of these biomarkers may enhance the diagnostic value for AA, the improvement in the area under the curve (AUC) is not substantial.

Outcomes of COVID-19 in 24 hospitalized liver transplant recipients: an observational study

BackgroundAlthough liver transplant (LT) recipients are considered a population at risk of severe features of coronavirus disease 2019 (COVID-19), data in this regard are scarce and controversial. In this study, we reported the outcome of 24 cases of LT recipients who were hospitalized due to COVID-19 and investigated the role-playing factors in the severity of the disease.MethodsIn this single-center, analytic case-series study, eligible patients were among LT recipients who were hospitalized due to the diagnosis of COVID-19 based on positive results of polymerase chain reaction. Participants were categorized as severe COVID-19 if they were admitted to the intensive care unit, experienced respiratory failure demanding mechanical ventilation, or eventually died. Demographic and clinical data, COVID-19 symptoms and specific treatments, laboratory biomarkers, and immunosuppressive regimens and their alteration during the admission were recorded. Analysis was done using SPSS software.ResultsTwenty-four hospitalized LT patients were included, of which nine had severe and fifteen had non-severe COVID-19. Out of 9 patients with severe COVID-19, four sadly died. The analysis and comparison between the two groups revealed longer hospital stays (P = 0.02), lower lymphocyte counts (P = 0.002), and higher levels of C-reactive protein (CRP) (P = 0.006) in patients with severe COVID-19. Patients with non-severe COVID-19 had higher doses of tacrolimus and mycophenolate in their baseline immunosuppressive regimen (both P = 0.02).ConclusionLymphopenia and high CRP levels are associated with more severe forms of COVID-19 in LT patients. Mycophenolate may have protective properties against severe COVID-19. The role of severity indicators in LT patients with COVID-19 needs to be systematically recognized.

Expert Consensus Statement on an Updated Definition of Unintended Weight Loss Among Persons With Human Immunodeficiency Virus in the Modern Treatment Era.

The era of modern antiretroviral therapy (ART) has markedly improved health and survival among persons with human immunodeficiency virus (HIV) (PWH). In the pre-ART era, wasting was associated with HIV disease progression to acquired immunodeficiency syndrome and death. Effective ART has reduced the prevalence and incidence of this pre-ART form of HIV-associated wasting. However, a subgroup of ART-treated virally suppressed PWH continue to lose weight, often accompanied by aging-related comorbidities and/or functional deficits. For this subgroup of patients, the older definition of HIV-associated wasting (HIVAW) cannot and should not be applied. An expert panel comprising the authors of this white paper convened to review the existing definition of HIVAW and to create an updated definition that they termed HIV-associated weight loss, based on clinically defined parameters among contemporary PWH receiving ART. Here, clinical features and laboratory biomarkers associated with HIV-associated weight loss are reviewed and approaches to screening and treatment are considered. Available management approaches, including the use of current US Food and Drug Administration-approved medications for HIVAW and other available therapies are discussed. The expert panel also identified knowledge gaps and provided recommendations for clinicians, payers, and researchers.