Laboratory Tests Research Articles

Complement 3 and 4 impact in osteoarthritis.

Aim: To investigate the association between serum complement 3 and 4 (C3 and C4) levels and clinical characteristics in osteoarthritis (OA) patients.Methods: This retrospective study included 361 OA patients divided into groups based on complement levels. Clinical data and laboratory test results, including C3, C4, ESR and CRP levels, were analyzed using non-parametric tests, Spearman correlation and multivariate regression.Results: The AC-OA group had lower PA, C3, C4, ESR, CRP and IgA levels compared with controls. C3 levels were positively correlated with ESR (r=0.260, p<0.001) and CRP (r=0.243, p<0.001). C4 levels also correlated with ESR (r=0.175, p=0.001) and CRP (r=0.263, p<0.001) and were significantly associated with the number of affected joints.Conclusion: Serum C4 levels are effective indicators of disease activity in OA, particularly in terms of joint involvement and CRP levels, while C3 levels showed no significant association. These findings suggest a potential role for C4 in predicting OA activity.

Trends in resource utilization for new-onset psychosis hospitalizations at children's hospitals.

Children with new-onset psychosis often require hospitalization for medical evaluation. The goal of this study was to assess variations in the management of children with new-onset psychosis and characterize trends in resource utilization. The study included index hospitalizations for children ages 7-18 admitted to children's hospitals with a primary diagnosis of psychosis from 2011 to 2022 using the Pediatric Health Information System (PHIS) database. Children with a complex chronic condition were excluded. Resource utilization categories included medication, imaging, laboratory, and other clinical resources. Variability in resource utilization was assessed using covariance tests for random intercepts with generalized linear modes after adjusting for age, sex, payor, and severity. Trends in resource utilization were examined using generalized estimating equations adjusting for the same factors and accounting for hospital clustering. Our data set included 7126 new-onset psychosis hospitalizations from 37 children's hospitals. Teenage males and non-Hispanic Whites were most likely to be hospitalized. There was a significant variation in resource utilization across hospitals in all categories (p < .001). The most frequently utilized resources were antipsychotic medications (76%), serum chemistry (77%), toxicology labs (72%), and brain magnetic resonance imaging (22%). The most notable increases in utilization were in the performance of laboratory tests, brain imaging, anesthetic use, and intravenous immunoglobulin use. Study findings suggest that there has been a stable rate of hospitalization for children with new-onset psychosis, yet a significant variation in the medical evaluation exists. Significant increases and variations in resource utilization across all categories suggest an emerging need for robust evidence and consensus-based practice guidelines.

Cranioplasty infection in porous hydroxyapatite: Potential antibacterial properties.

Intensive research is dedicated to the development of novel biomaterials and medical devices to be used as grafts in reconstructive surgery, with the purpose of enhancing their therapeutic effectiveness, safety, and durability. A variety of biomaterials, from autologous bone to polymethylmetacrylate, polyether ether ketone, titanium, and calcium-based ceramics are used in cranioplasty. Porous hydroxyapatite (PHA) is reported as a possible material for bone reconstruction, with good signs of biocompatibility, osteoconductive and osteointegrative properties. In the present paper we studied the possible antibacterial properties of PHA in a laboratory test in order to provide a possible overview of the occurrence of post-operative infections in PHA cranioplasty. The test method has been designed to evaluate the potential antimicrobial activity of specimens under dynamic contact conditions to overcome difficulties in ensuring contact of inoculum to the specimen surface. The test was conducted using Staphylococcus aureus ATCC6538 as a bacterial strain. Two experimental sets were performed to evaluate the antimicrobial properties of the specimens against two different Staphylococcus aureus concentrations. The first preliminary test (a) verified the antibacterial property at 0, 1, 2, and 4 h of contact time; the second confirmatory test (b) was repeated to verify the antibacterial property at 0, 4, 8 h. In the first experiment, after the first hour of contact, the bacterial inoculum was reduced by 7.96% compared to "inoculum only," which increased to 26.11% at the second hour, and up to 52.33% after 4 h. In the second experiment, the confirmation test showed that bacterial growth reaches maximum inhibition after 4 h of contact. At 4 h, there was a higher bacterial reduction of 72.93%, which decreased at 8 h (36.45%). Analyzing the growth trend of viable microorganisms under Dynamic Contact Conditions it can be seen that PHA cranioplasty appears to inhibit exponential growth by inducing bacterial stasis in the early hours of contact, reaching a maximum reduction within 4 h, in this adopted experimental condition.

Correlation of Platelet Indices with Severity of Gastroesophageal Varices in Patients of Liver Cirrhosis: A Research Protocol

Introduction: In India, liver cirrhosis is a significant public health concern, contributing to 2.95% of total deaths. Cirrhosis is the advanced stage of ongoing liver fibrosis, which poses substantial global health challenges due to its fatal consequences, such as gastroesophageal varices. Need of the study: Gastroesophageal varices are a potentially lethal complication of liver cirrhosis. The severity of these varices directly impacts the prognosis of the patient. Gastroesophageal varices are major contributors to both mortality and morbidity on a global scale. While various parameters have been explored to predict the progression and severity of these varices, platelet indices have not been extensively studied in cirrhosis patients with gastroesophageal varices in India. Aim: To study the association and correlation of platelet indices with the severity of gastroesophageal varices in patients with liver cirrhosis. Materials and Methods: A cross-sectional study will be conducted in the Medicine OPD/IPD of Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, Maharashtra, India from May 2023 to May 2025, involving 64 patients who meet the inclusion and exclusion criteria. Patients fulfilling the selection criteria will be informed about the study procedure in their native language. The diagnosis of liver cirrhosis will be established based on the patient’s detailed history, physical examination, laboratory tests, and ultrasound scan. Upon enrollment, a detailed history will be taken, and parameters will be recorded in a specifically designed proforma. Initial parameters will include age, gender, weight, co-morbidities (such as Diabetes Mellitus (DM), Hypertension (HTN), Heart Failure (HF), Cardiovascular Disease (CVS), Chronic Obstructive Pulmonary Disease (COPD), kidney failure, liver failure, and malignant conditions), and the aetiology of cirrhosis. Platelet count and indices-Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), and Plateletcrit (PCT)- will be assessed. The categorical and continuous variables will be represented as frequency (percentage) and mean (standard deviation, SD). The Chi-square test and Independent sample t-test will be used to evaluate the association between various categorical variables and continuous variables. The Pearson correlation test will be used to assess any correlation between platelet indices and oesophageal varices, with a significance level set at &lt;0.05.

Explainable machine learning and online calculators to predict heart failure mortality in intensive care units.

This study aims to develop explainable machine learning models and clinical tools for predicting mortality in patients in the intensive care unit (ICU) with heart failure (HF). Patients diagnosed with HF who experienced their first ICU stay lasting between 24h and 28days were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was all-cause mortality within 28days. Data analysis was performed using Python and R, with feature selection conducted via least absolute shrinkage and selection operator (LASSO) regression. Fifteen models were evaluated, and the most effective model was rendered explainable through the Shapley additive explanations (SHAP) approach. A nomogram was developed based on logistic regression to facilitate interpretation. For external validation, the eICU database was utilized. After selection, the study included 2343 records, with 1808 surviving and 535 deceased patients. The median age of the study population was 70.00, with ~3/5 males (60.31%). The median length of stay in the ICU was 6.00days. The median age of the survival group was younger than the non-survival group (69.00 vs. 73.00), and non-survival patients spent longer time in the ICU. Seventy-five features were initially selected, including basic information, vital signs, laboratory tests, haemodynamics and oxygen status. LASSO regression determined the shrinkage parameter α=0.020, and 44 features were chosen for model construction. The linear discriminant analysis (LDA) model showed the best performance, and the accuracy reached 0.8354 in the training cohort and 0.8563 in the testing cohort. It showed satisfying area under the curve (AUC), recall, precision, F1 score, Cohen's kappa score and Matthew's correlation coefficient. The concordance index (c-index) reached 0.7972 in the training cohort and 0.8125 in the testing cohort. In external validation, the LDA model achieved approximately 0.9 in accuracy, precision, recall and F1 score, with an AUC of 0.79. Univariable analysis was performed in the training cohort. Features that differed significantly between the survival and non-survival groups were subjected to multiple logistic regression. The nomogram built on multiple logistic regression included 14 features and demonstrated excellent performance. The AUC of the nomogram is 0.852 in the training cohort, 0.855 in the internal validation cohort and 0.770 in the external validation cohort. The calibration curve showed good consistency. The study developed an LDA and a nomogram model for predicting mortality in HF patients in the ICU. The SHAP approach was employed to elucidate the LDA model, enhancing its utility for clinicians. These models were made accessible online for clinical application.

An Updated Review on the Alarming Epidemic of the Monkeypox Virus

: After the COVID-19 pandemic, the world has been vulnerable due to another virus called monkeypox. Monkeypox is a very uncommon zoonotic infectious condition that occurs in both human and non-human primates with similar clinical characteristics as smallpox along with remarkable epidemic potential because of the increasing existence of human outbursts in recent scenarios. The increasing number of cases of this virus is developing curiosity among the people, hence scientists are aiming to become aware of various pathological characteristics and management of this virus before it becomes an epidemic. Currently, the monkeypox outbreak is a trending headline and has increased as an alarming tone after continuous upcoming cases. Previous studies revealed that the first human suspected case was found on September 1, 1970, when a 9-month-old baby was admitted to the Basankusu Hospital in the Democratic Republic of Congo. It is hard to distinguish monkeypox from the smallpox virus therefore, laboratory testing is the technique of disease identification and monitoring. Various new approaches and vaccines are being positioned for the prevention and clinical management of monkeypox through the entanglement of metallic and organic nanocarriers. However, more researchers suggested that virology and ecology of the virus in endemic areas is essential to recognize and avoid further worldwide occurrence of this virus. On behalf of an exhaustive literature survey, We are providing a rationalizing overview of monkeypox in the context of its present global outbreak, as well as its symptoms, prevention, treatment, assessment, and clinical studies.

Evaluation and analysis of efficacy in bisphosphonate treatment of chronic nonbacterial osteomyelitis.

This study aimed to analyze the influence of drug factors on the efficacy of bisphosphonate for chronic nonbacterial osteomyelitis to provide a reference for clinical treatment and promote clinical rational drug use by evaluation of effectiveness and safety of bisphosphonate treatment of chronic nonbacterial osteomyelitis. Literature on the treatment of chronic nonbacterial osteomyelitis by using bisphosphonate was collected and analyzed from PubMed, Medline, Embase, Cochrane, ISI Web of Knowledge, CNKI, VIP, and Wanfang databases. A total of 489 cases were collected, with an average complete response rate of clinical presentation, laboratory tests and imaging findings of 80.37%, 80.56% and 79.22%, respectively. Except for opadronate, risedronate, ibandronate, pamidronate, alendronate, neidronate and zoledronate showed good efficacy, and the average complete response rates were 100%, 100%, 81.64%, 87.50%, 69.23% and 69.23%, respectively.The study found that in the pamidronate group, the average complete response rate of 0.5-1 mg/kg (maximum single dose≤60 mg) subgroup and the frequency of administration once every 3 months subgroup were better than other subgroups. Bisphosphonate could be used to treat chronic nonbacterial osteomyelitis, which of efficacy were affected by different drug types, dose and frequency of administration. The optimal dose and frequency of administration of pamidronate were 0.5-1 mg/kg (maximum single dose≤60 mg) and once every 3 months, respectively.

The Impact of Hematologic Disorders on the Severity of Cerebral Venous Sinus Thrombosis: A Comparative Study.

Hematologic diseases are considered important contributors to cerebral venous sinus thrombosis (CVST) cases. This retrospective study aims to compare the difference of the clinical and radiological characters between CVST patients with and without hematologic diseases. Consecutive hospitalized CVST patients with hematologic disorders constituted the hematologic disorder group, while that without identifiable risk factors comprised the control group in this study. We systematically documented the various types of hematologic diseases associated with CVST, along with laboratory tests. Clinical manifestations, imaging findings, as well as treatment and prognosis, were recorded. A comparative analysis was conducted between the hematologic disorder group and the control group based on the aforementioned parameters. The final analysis included 97 CVST cases associated with hematologic diseases and 65 cases without any identified risk factors. The spectrum of hematologic diseases in our study ranged from iron-deficiency anemia to acute leukemia. Patients with hematologic disorder showed higher admission mRS, greater thrombotic burden, and higher incidence of stroke and cerebral hemorrhage (p < 0.05). The use of batroxobin significantly improved the prognosis of CVST caused by hematologic diseases, without causing major bleeding or death during the follow-up period. Patients with hematologic disorders who develop CVST tend to present with more severe conditions compared to those without identifiable risk factors. It is essential to conduct timely screening for CVST in patients with hematologic diseases who present with risk factors of thrombosis.

Negative Impact of Low Serum Cholinesterase on Short- and Long-term Outcomes in Elderly Patients Undergoing Scheduled Surgery for Colorectal Cancer.

Cholinesterase (ChE) is important for estimating nutritional status and can be easily measured. This study aimed to investigate the effect of ChE on the short- and long-term prognoses of elderly patients with colorectal cancer. This study included 120 elderly patients who underwent scheduled surgery for colorectal cancer. ChE is a biomarker that can be easily measured using blood tests. The optimal cut-off level of ChE was determined using receiver operating characteristic analysis. We investigated the relationship of ChE with disease-free and overall survival using univariate and multivariate analyses. Seventy-two (60%) patients had low ChE levels (<255 U/l). In the multivariate analysis, low ChE (p=0.04) was an independent and significant predictor of postoperative complications. Low ChE (p=0.049), low prognostic nutritional index (p=0.04), and lymph node metastasis (p<0.01) were independent and significant prognostic predictors of poor disease-free survival. American Society of Anesthesiologists Physical Status 3 (p<0.01), low ChE (p<0.01), and lymph node metastasis (p<0.01) were independent and significant predictors of poor overall survival. ChE level is a significant predictor of short- and long-term outcomes in elderly patients undergoing scheduled surgery for colorectal cancer.

The role of virtual wards in maternity in the United Kingdom.

Virtual wards are an initiative which aims to provide hospital care from the comfort of the patient's own home. Monitoring and additional services, such as intravenous drugs and fluids and blood tests can be undertaken through this system. Although virtual wards have been used in the UK since 2005 in specialties such as General Medicine, General Surgery and Paediatrics, their use in maternity has been more limited. This article aims to review their current use in the UK and beyond as well as to discuss some of the advantages and challenges they may pose to a maternity population.

Current trends in blood biomarkers detection and neuroimaging for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and cognitive impairments. A significant challenge in managing PD is the variability of symptoms and disease progression rates. This variability is primarily attributed to unclear biomarkers associated with the disease and the lack of early diagnostic technologies and effective imaging methods. PD-specific biomarkers are essential for developing practical tools that facilitate accurate diagnosis, patient stratification, and monitoring of disease progression. Hence, creating valuable tools for detecting and diagnosing PD based on specific biomarkers is imperative. Blood testing, less invasive than obtaining cerebrospinal fluid through a lumbar puncture, is an ideal source for these biomarkers. Although such biomarkers were previously lacking, recent advancements in various detection techniques related to PD biomarkers and new imaging methods have emerged. However, basic research requires more detailed guidelines on effectively implementing these biomarkers in diagnostic procedures to enhance the diagnostic accuracy of PD blood testing in clinical practice. This review discusses the developmental trends of PD-related blood biomarker detection technologies, including optical analysis platforms. Despite the progress in developing various biomarkers for PD, their specificity and sensitivity remain suboptimal. Therefore, the integration of multimodal biomarkers along with optical and imaging technologies is likely to significantly improve diagnostic accuracy and facilitate the implementation of personalized medicine. This review forms valid research hypotheses for PD research and guides future empirical studies.

ENSMBL-PASD: Spearheading early autism spectrum disorder detection through advanced genomic computational frameworks utilizing ensemble learning models.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by various genetic and environmental factors. Currently, there is no definitive clinical test, such as a blood analysis or brain scan, for early diagnosis. The objective of this study is to develop a computational model that predicts ASD driver genes in the early stages using genomic data, aiming to enhance early diagnosis and intervention. This study utilized a benchmark genomic dataset, which was processed using feature extraction techniques to identify relevant genetic patterns. Several ensemble classification methods, including Extreme Gradient Boosting, Random Forest, Light Gradient Boosting Machine, ExtraTrees, and a stacked ensemble of classifiers, were applied to assess the predictive power of the genomic features. TheEnsemble Model Predictor for Autism Spectrum Disorder (eNSMBL-PASD) model was rigorously validated using multiple performance metrics such as accuracy, sensitivity, specificity, and Mathew's correlation coefficient. The proposed model demonstrated superior performance across various validation techniques. The self-consistency test achieved 100% accuracy, while the independent set and cross-validation tests yielded 91% and 87% accuracy, respectively. These results highlight the model's robustness and reliability in predicting ASD-related genes. The eNSMBL-PASD model provides a promising tool for the early detection of ASD by identifying genetic markers associated with the disorder. In the future, this model has the potential to assist healthcare professionals, particularly doctors and psychologists, in diagnosing and formulating treatment plans for ASD at its earliest stages.

Abstract TMP75: Reduced thrombus immunoreactivity is transcriptionally associated with greater NIHSS severity at presentation of ischemic stroke: Analysis from the INSIGHT registry

Funding: The INSIGHT Registry is funded by Penumbra. Introduction: Thrombi have shown to modify and be modified by their microenvironment throughout the pathogenesis of ischemic stroke. The molecular mechanisms by which this occurs and how it corresponds to symptomatic presentation is unknown. Here, we identify a transcriptomic signature in thrombi associated with increased NIHSS severity at presentation, suggesting a mechanistic role for immune clearance in clinical severity of ischemic stroke. Methods: The INSIGHT registry is a prospective, multicenter, multi-omic registry focused on elucidating the molecular underpinnings of stroke from analysis of clot and interarterial blood. RNA sequencing of 10,990 genes from 292 thrombi from patients undergoing thrombectomy was aligned, normalized, and residualized using Rsubread, edgeR, sva, and limma/voom. Signed co-expression modules were constructed using WGCNA, and each module eigengene (a measure of a module’s principal component) was correlated with NIHSS at presentation using Pearson’s correlation. Networks were visualized and analyzed in cytoscape. Hub genes were determined by number of undirected edges. Network enrichments were conducted using Gene Ontology biological processes and cellular components. Results: The mean NIHSS in this cohort was 15.14± 7.45. 3 co-expression modules out of 26 total modules detected in the data significantly inversely correlated with NIHSS at presentation. These networks corresponded to downregulation of neuronal activation (p=0.042), interferon signaling (p=0.039), and T cell activation (p=0.023), respectively. Major hub genes in each module included KCNAB2, a potassium channel associated with epilepsy and implicated in susceptibility to poor stroke outcomes in aged mice brains, SRSF11, associated with cognitive decline, PNISR, associated with interferon signaling, and ZAP70, associated with T-cell differentiation. Conclusion: The association of immune downregulation with increased NIHSS severity suggests that robust immune clearance may mitigate poor outcomes in ischemic stroke, and that thrombi-mediated modification of the local immune environment may exacerbate symptomatic presentation. Conversely, the association of major hub genes with known cognitive decline suggests that thrombi are modified by the neurovascular unit and neurons of surrounding tissues and post-thrombectomy sequencing may provide insight into the underlying health of the surrounding parenchyma.

Abstract 14: A distinct clot transcriptomic signature is associated with atrial fibrillation-derived ischemic stroke in the INSIGHT Registry

Funding: The INSIGHT Registry is funded by Penumbra. Introduction: Rapid and precise determination of the etiology of acute ischemic stroke is crucial in long-term management and prevention of recurrence. Identification of etiology-associated molecular biomarkers following thrombectomy may allow for personalized intervention. Here, we examine the transcriptomics of cardioembolic thrombi as a result of atrial fibrillation, identifying a distinct transcriptomic signature relative to other causes of ischemic stroke. Methods: The INSIGHT registry is a prospective, multicenter, multi-omic registry focused on elucidating the molecular underpinnings of stroke from analysis of clot and interarterial blood. RNA sequencing of 10,990 genes from 292 thrombi from patients undergoing thrombectomy was analyzed using edgeR, sva, and limma/voom. 111 patients had a determined etiology of atrial fibrillation. Controls had unknown, atheroembolic, or coagulopathy stroke etiology. Significant association of thrombus gene expression with atrial fibrillation was conducted using the Wilcoxon Rank Sum test using Benjamini-Hochberg multiple testing correction (FDR &lt;5%). Gene set enrichment was performed using FGSEA using Gene Ontology biological processes gene sets. Co-expression modules were detected using WGCNA and analyzed using cytoscape. Results: 33 genes (27 upregulated, 6 downregulated) within thrombi were significantly associated with atrial fibrillation etiology. These included upregulated endothelial cell markers associated with cardiac endothelial cells (e.g. KDR , AMDHD2 , IL18BP ) compared to thrombi of other etiologies. In addition, upregulated genes were associated with oxidative stress (FDR= 8.46x10 -8 ) and metabolism (1.04x10 -6 ), while adaptive T-cell immunity was downregulated (FDR= 7.52x10 -3 ). Co-expressed gene networks upregulated by atrial fibrillation-associated thrombi included a module implicated in innate immune signaling and cytotoxic granule release (p=0.02), which included key hub genes GZMH and TBX21. Conclusion: Cardioembolic thrombi possess a distinct transcriptomic signature consistent with collection and retainment of cardiac endothelial tissue at origin, and display immunomodulatory activity associated with innate vs adaptive immune balance. This signature suggests the active role thrombi likely play in the vascular microenvironment and may ultimately be used to identify atrial fibrillation as an etiology in strokes of unknown origin.

Abstract TP359: Peripheral blood GATA2 expression increases RNF213 mutation penetrance and clinical severity in moyamoya disease

Background: The p.R4810K founder mutation in the RNF213 gene confers susceptibility to moyamoya disease (MMD) and non-MMD intracranial artery disease. However, penetrance is incomplete, and the underlying molecular mechanism remains unknown. Methods and Results: Transcriptome analysis of peripheral blood was conducted with 9 MMD patients and 5 unaffected mutation carriers from 4 familial MMD pedigrees. Bayesian network analysis identified upregulated gene modules associated with lipid metabolism and leukocyte development (including GATA2 and SLC45A3 ), and EGFR signaling ( UBTD1 ). It also identified downregulated gene modules related to mitochondrial ribosomal proteins ( RPS3A and RPL26 ), and cytotoxic T cell immunity ( GZMA and TRGC1 ). The GATA2 network was replicated through WGCNA analysis and further examined in a case-control study, comprising 43 MMD patients, 16 non-MMD patients, 19 unaffected carriers, and 35 healthy controls. GATA2 exhibited a significant linear correlation with SLC45A3 and was significantly higher in MMD patients compared to age- and sex-matched unaffected carriers or wild-type controls. Among patients with the p.R4810K mutation, higher GATA2 expression was associated with an earlier age of onset, bilateral involvement, and symptomatic disease onset. Conclusions: Peripheral blood GATA2 expression was associated with increased penetrance of the RNF213 mutation and more severe clinical manifestations in MMD.

Total cost of care of immune-oncology treatments for unresectable hepatocellular carcinoma: A Singapore healthcare perspective analysis.

642 Background: Tremelimumab + durvalumab (STRIDE) and atezolizumab + bevacizumab are recommended first-line immune-oncology treatment options for unresectable hepatocellular carcinoma (uHCC). This study aimed to quantify the total economic burden to the Singapore healthcare system of treating patients with uHCC using STRIDE versus atezolizumab + bevacizumab. Methods: A model was developed to estimate the total cost of care of using STRIDE or atezolizumab + bevacizumab, which followed patients with uHCC eligible for first-line systemic therapy, considering direct medical costs. Costs considered in the model included treatment acquisition and administration, endoscopy, healthcare resource use, and cost for treating grade ≥3 treatment-emergent adverse events (TEAEs). Data on treatment regimens and TEAEs were taken from the HIMALAYA (STRIDE) and IMbrave150 (atezolizumab + bevacizumab) trials. Resource use rates were based on an average of 168 days treatment for both regimens. All costs were obtained from Singaporean sources. Results: The total cost of care for STRIDE and atezolizumab + bevacizumab was estimated at SGD$40,277 (USD$30,932) and SGD$43,605 (USD$33,487) per patient, respectively. This translates into an average cost savings of SGD$3,328 (USD$2,555]) per patient when treated with STRIDE compared to atezolizumab + bevacizumab. The main driver of cost savings was treatment acquisition and administration (-SGD$1,917 [-USD$1,472], -6%) though lower costs were also associated with resource use (-SGD$927 [-USD$712], -8%), endoscopy (-SGD$342 [-USD$263], -77%) and TEAE management (-SGD$141 [-USD$108], -74%). Assuming an incident population of 260 patients eligible for treatment, the total burden was estimated at SGD$10,489,604 (USD$8,055,696) when all patients were treated with STRIDE, and SGD$11,356,273 (USD$8,721,271) when treated with atezolizumab + bevacizumab (Table). The incremental cost offset to the health plan was SGD$866,669 (USD$665,575) when treated with STRIDE. Conclusions: This study suggests that STRIDE offers cost savings over atezolizumab + bevacizumab for uHCC treatment in the Singapore healthcare system. Additional real-world evidence studies are warranted to capture the long-term survival benefits and associated treatment costs. Annual cost of care based on 260 patients receiving first-line immune-oncology treatment. Category STRIDE Atezolizumab + Bevacizumab Incremental difference Endoscopy costs $26,358 $115,555 -$89,197 Resource Use costs* $2,607,000 $2,848,307 -$241,307 Adverse events costs $12,899 $49,716 -$36,817 Treatment acquisition and administration $7,843,347 $8,342,696 -$499,349 TOTAL $10,489,604 $11,356,273 -$866,669 All costs in SGD$. *Includes: physician visits; laboratory and radiological tests; and hospitalisation.

Lactiplantibacillus plantarum TCCC11824 exerts hypolipidemic and anti-obesity effects through regulation of NF-κB-HMGCR pathway and gut microbiota in mice and clinical patients

A strong association exists between the high-fat diet (HFD) and the incidence of obesity, hyperlipidemia and cardiovascular disease, affecting an increasing number of individuals. More and more research has shown that probiotics and gut microbiota play important roles in dietary absorption, metabolism and host healthy. This study aims to evaluate the therapeutic effects and the underlying mechanisms of Lactiplantibacillus plantarum TCCC11824 (CGMCC 8198) on hyperlipidemia and obesity in mice and clinical. Fristly, there was a dose-dependent improvement in HFD-induced hyperlipidemia and obesity in mice which had been treated with L. plantarum TCCC11824 for 5 weeks thus restoring the balance of the gut microbiota. Furthermore, it showed that cell lysate of L. plantarum TCCC11824 could directly exhibit protective effects on the hepatocytes steatosis induced by oleic acid, and regulate the expression of HMGCR by inhibiting NF-κB pathway. Importantly, L.plantarum TCCC11824 ameliorated the expression of indicators of hyperlipidemia and inhibited the synthesis of SCFAs (short-chain fatty acids), as shown by blood and fecal tests in hyperlipidemic patients. In summary, L. plantarum TCCC11824 exerts anti-hyperlipidemic and anti-obesity effects through the regulation of HMGCR via NF-κB and modulating gut microbiota, indicating its potential as a dietary supplement for the treatment of hyperlipidemia and obesity.

Current Evidence on the Care of Young Infants With Hypothermia in the Emergency Department.

The presence of hypothermia among young infants in the emergency department may be a sign of serious or invasive bacterial infections, or invasive herpes simplex viral infection. However, hypothermia may also occur due to a variety of other infectious and noninfectious conditions or environmental exposure. In some settings, hypothermia may represent a protective, energy-conserving response to illness. Recent efforts have enhanced our understanding of the prevalence of serious infections among infants with hypothermia, although challenges remain due to lack of standardized definitions and comprehensive guidelines. There exists extensive variation in the care of young infants with hypothermia. Risk factors for serious bacterial infections in infants with hypothermia, as identified in single-center and multicenter retrospective studies, include lower temperatures, older age, and abnormalities in blood and urine testing. Given the absence of clear guidelines, management of infants with hypothermia relies heavily on clinician judgment and shared decision making, guided by individual patient assessments and risk factors. This review article summarizes existing evidence and identifies gaps in the management of infants (<90 days) with hypothermia in the emergency department.

Effects of Nickel Bioaccumulation on Hematological, Biochemical, Immune Responses, Neuroinflammatory, Oxidative Stress Parameters, and Neurotoxicity in Rats.

Nickel (Ni) exposure is linked to numerous health issues, including dermatitis, immunotoxicity, and cancer. Emerging evidence suggests Ni may cross the blood-brain barrier, accumulating in the brain and causing neuroinflammation, oxidative stress, and neuronal apoptosis. Herein, we investigated the effect of Ni exposure through the intraperitoneal route, studying the Ni effect in subacute and chronic toxicity, on various health parameters in Wistar rats. Rats were randomly divided into four groups (n = 10 per group): two groups received a daily intraperitoneal injection of NiCl₂ at a dose of 0.25mg/kg for subacute (21days) or chronic (60days) exposure periods, while the other two groups were treated with NaCl solution (0.9%) as a control for equivalent durations. The study assessed behavioral, biochemical, hematological, immunological, neurobiochemical, and histopathological effects over 21 and 60days. Neurobehavioral tests, blood and tissue analyses, and organ examinations were conducted. This study demonstrates that Ni bioaccumulation in subacute and chronic exposure has significant health impacts in Wistar rats, including hematological, immunological, biochemical, AchE activity, neuroinflammatory, oxidative stress, and neurobehavioral changes. Chronic exposure results in higher Ni accumulation, particularly in the brain, causing neurotoxicity, inflammation, and behavioral disorders such as anxiety, depression, and memory impairment. The findings highlight the importance of limiting Ni exposure to prevent adverse health effects.

Precision neurology.

Over the past several decades, high-resolution brain imaging, blood and cerebrospinal fluid analyses, and other advanced technologies have changed diagnosis from an exercise depending primarily on the history and physical examination to a computer- and online resource-aided process that relies on larger and larger quantities of data. In addition, randomized controlled trials (RCT) at a population level have led to many new drugs and devices to treat neurological disease, including disease-modifying therapies. We are now at a crossroads. Combinatorially profound increases in data about individuals has led to an alternative to population-based RCTs. Genotyping and comprehensive "deep" phenotyping can sort individuals into smaller groups, enabling precise medical decisions at a personal level. In neurology, precision medicine that includes prediction, prevention and personalization requires that genomic and phenomic information further incorporate imaging and behavioral data. In this article, we review the genomic, phenomic, and computational aspects of precision medicine for neurology. After defining biological markers, we discuss some applications of these "-omic" and neuroimaging measures, and then outline the role of computation and ultimately brain simulation. We conclude the article with a discussion of the relation between precision medicine and value-based care.