Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

SCN1A rs6732655A/T polymorphism: Diagnostic and therapeutic insights for drug-resistant epilepsy.

BACKGROUND: A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs, resulting in heightened mortality rates, psychosocial challenges, and a diminished quality of life. Genetic factors, particularly within the SCN1A gene, and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases. In this extended study, we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response. AIM: To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response. METHODS: The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases. We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique. The diagnostic performance of interleukin (IL)-1ß, IL-6, and high mobility group box 1 (HMGB1) protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis. RESULTS: AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy. Serum biomarkers IL-6, IL1ß and HMGB1 demonstrated diagnostic potential, with cutoff values of 4.63 pg/mL, 59.52 pg/mL and 7.99 ng/mL, respectively, offering valuable tools for epilepsy management. Moreover, specific genotypes (AA and AT) were found to be linked to the elevated levels of IL-1ß and IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy. CONCLUSION: SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk. These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.

External quality assessment performance in ten countries: an IFCC global laboratory quality project.

OBJECTIVES: This study aimed to assess the validity of external quality assessment (EQA) laboratory results across various cultural and environmental contexts and to identify potential improvement areas. METHODS: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a 2-year study (2022 and 2023) in which EQA materials, related software and online training was provided by a commercial vendor to 100 laboratories in ten IFCC member society countries. The results were analysed on a monthly basis by the TF-GLQ, to show the number of submissions per country, tests per lab, acceptability rates, random failures and to get a measure of which analytes performed poorly. RESULTS: The EQA material was dispatched on a quarterly basis. Some countries had problems with customs releasing the material in a timely manner, resulting in laboratories not receiving them on time leading to no submission. We report here the results for the second year of the survey. The number of examinations varied between laboratories, ranging from seven to 84 analytes. Of the ten countries surveyed, six averaged greater than 90 % acceptable results over the whole 12-months cycle, one had unacceptable results for two of the nine months they returned results and the other four were considered to not perform to an acceptable standard. CONCLUSIONS: All 100 participating laboratories indicated satisfaction with the EQA survey and related services, including on-site training, and report handling. However, specimen receiving issues, suggest benefits in dispatching materials for a full 12-month cycle. Significant discrepancies in EQA performance indicate that four countries require long-term assistance, training and guidance. To ensure reliable patient results, promoting EQA in certain countries is essential to achieve the required level of quality.

Role of lymphocyte-to-monocyte ratio as a predictive marker for diabetic coronary artery disease: A cross-sectional study.

BACKGROUND: The lymphocyte to monocyte ratio (LMR) is considered a marker of systemic inflammation in cardiovascular disease and acts as predictor of mortality in coronary artery disease. AIM: To investigate the predictive role of LMR in diabetic coronary artery disease patients. METHODS: This cross-sectional study was conducted at tertiary care super-specialty hospital at New Delhi, India. A total of 200 angiography-proven coronary artery disease (CAD) patients were enrolled and grouped into two categories: Group I [CAD patients with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) levels ≥ 6.5%], and Group II (CAD patients without T2DM and HbA1c levels < 6.5%). Serum lipoproteins, HbA1c, and complete blood count of enrolled patients were analyzed using fully automatic analyzers. RESULTS: The logistic regression analysis showed an odds ratio of 1.48 (95%CI: 1.28-1.72, P < 0.05) for diabetic coronary artery disease patients (Group I) in unadjusted model. After adjusting for age, gender, diet, smoking, and hypertension history, the odds ratio increased to 1.49 (95%CI: 1.29-1.74, P < 0.01) in close association with LMR. Further adjustment for high cholesterol and triglycerides yielded the same odds ratio of 1.49 (95%CI: 1.27-1.75, P < 0.01). Receiver operating characteristic curve analysis revealed 74% sensitivity, 64% specificity, and 0.74 area under the curve (95%CI: 0.67-0.80, P < 0.001), suggesting moderate predictive accuracy for diabetic CAD patients. CONCLUSION: LMR showed positive association with diabetic coronary artery disease, with moderate predictive accuracy. These findings have implications for improving CAD management in diabetics, necessitating further research and targeted interventions.

Urinary biomarkers NG AL and beta-2 microglobulin in children with type 1 diabetes mellitus.

OBJECTIVES: To study the urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (ß2M) levels as markers of tubular damage in children with type 1 diabetes (T1DM). METHODS: Forty T1DM children and 40 age-matched controls were enrolled. Subjects with coexisting kidney disorder, intake of oral glucose lowering drugs and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA1c), kidney function, urinary albumin-creatinine ratio (UACR), NGAL and ß2M were measured and compared in cases and controls. RESULTS: The median (IQR) age of cases and controls was 10.6 (8, 14.2) and 10.7 (8.4, 13.7) years, respectively. Cases had disease duration of 4 (3, 6.8) years and HbA1c 10.9 (9, 13.1) %. Microalbuminuria was seen in 14 (35 %). Median (IQR) levels of UACR were higher in cases than controls [19.38 (10.27, 35.26) and 6.49 (3.10, 11.65) µg/mg; p<0.001], similarly NGAL/creatinine [352.21 (191.49, 572.45) and 190.54 (125.91, 322.83) ng/mg; p=0.006], unlike ß2M/creatinine [1.7 (0.43, 6.02) and 2.12 (1.05, 4.47) µg/mg; p=0.637]. Children with higher HbA1c (≥10 %) had higher urinary ACR and tubular biomarkers than HbA1c<10 % (p>0.05). Urinary ACR showed positive correlation with NGAL/creatinine (r=0.38, p=0.019) and ß2M/creatinine (r=0.42, p=0.009). CONCLUSIONS: Urinary biomarkers NGAL and ß2M were elevated in the presence of normal urinary microalbumin levels suggestive of early tubular damage in T1DM.

Discovering hidden patterns: Association rules for cardiovascular diseases in type 2 diabetes mellitus.

BACKGROUND: It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), and studies are able to correlate their relationships with available biological and clinical evidence. The aim of the current study was to apply association rule mining (ARM) to discover whether there are consistent patterns of clinical features relevant to these diseases. ARM leverages clinical and laboratory data to the meaningful patterns for diabetic CAD by harnessing the power help of data-driven algorithms to optimise the decision-making in patient care. AIM: To reinforce the evidence of the T2DM-CAD interplay and demonstrate the ability of ARM to provide new insights into multivariate pattern discovery. METHODS: This cross-sectional study was conducted at the Department of Biochemistry in a specialized tertiary care centre in Delhi, involving a total of 300 consented subjects categorized into three groups: CAD with diabetes, CAD without diabetes, and healthy controls, with 100 subjects in each group. The participants were enrolled from the Cardiology IPD & OPD for the sample collection. The study employed ARM technique to extract the meaningful patterns and relationships from the clinical data with its original value. RESULTS: The clinical dataset comprised 35 attributes from enrolled subjects. The analysis produced rules with a maximum branching factor of 4 and a rule length of 5, necessitating a 1% probability increase for enhancement. Prominent patterns emerged, highlighting strong links between health indicators and diabetes likelihood, particularly elevated HbA1C and random blood sugar levels. The ARM technique identified individuals with a random blood sugar level > 175 and HbA1C > 6.6 are likely in the "CAD-with-diabetes" group, offering valuable insights into health indicators and influencing factors on disease outcomes. CONCLUSION: The application of this method holds promise for healthcare practitioners to offer valuable insights for enhancing patient treatment targeting specific subtypes of CAD with diabetes. Implying artificial intelligence techniques with medical data, we have shown the potential for personalized healthcare and the development of user-friendly applications aimed at improving cardiovascular health outcomes for this high-risk population to optimise the decision-making in patient care.

Unlocking new potential of clinical diagnosis with artificial intelligence: Finding new patterns of clinical and lab data.

Recent advancements in science and technology, coupled with the proliferation of data, have also urged laboratory medicine to integrate with the era of artificial intelligence (AI) and machine learning (ML). In the current practices of evidence-based medicine, the laboratory tests analysing disease patterns through the association rule mining (ARM) have emerged as a modern tool for the risk assessment and the disease stratification, with the potential to reduce cardio-vascular disease (CVD) mortality. CVDs are the well recognised leading global cause of mortality with the higher fatality rates in the Indian population due to associated factors like hypertension, diabetes, and lifestyle choices. AI-driven algorithms have offered deep insights in this field while addressing various challenges such as healthcare systems grappling with the physician shortages. Personalized medicine, well driven by the big data necessitates the integration of ML techniques and high-quality electronic health records to direct the meaningful outcome. These technological advancements enhance the computational analyses for both research and clinical practice. ARM plays a pivotal role by uncovering meaningful relationships within databases, aiding in patient survival prediction and risk factor identification. AI potential in laboratory medicine is vast and it must be cautiously integrated while considering potential ethical, legal, and pri-vacy concerns. Thus, an AI ethics framework is essential to guide its responsible use. Aligning AI algorithms with existing lab practices, promoting education among healthcare professionals, and fostering careful integration into clinical settings are imperative for harnessing the benefits of this transformative technology.

Validation and verification framework and data integration of biosensors and in vitro diagnostic devices: a position statement of the IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MBHLM) and the IFCC Scientific Division.

Advances in technology have transformed healthcare and laboratory medicine. Biosensors have emerged as a promising technology in healthcare, providing a way to monitor human physiological parameters in a continuous, real-time, and non-intrusive manner and offering value and benefits in a wide range of applications. This position statement aims to present the current situation around biosensors, their perspectives and importantly the need to set the framework for their validation and safe use. The development of a qualification framework for biosensors should be conceptually adopted and extended to cover digitally measured biomarkers from biosensors for advancing healthcare and achieving more individualized patient management and better patient outcome.

Potential Association of The Pathogenic Kruppel-like Factor 14 (KLF14) and Adiponectin (ADIPOQ) SNVs with Susceptibility to T2DM.

AIM: To evaluate the associations of the pathogenic variants in Kruppel-like Factor 14 (KLF 14) and Adiponectin (ADIPOQ) with susceptibility to type 2 diabetes mellitus (T2DM). BACKGROUND: Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease characterized by increased blood sugar and caused by resistance to insulin in peripheral tissues and damage to pancreatic beta cells. Kruppel-like Factor 14 (KLF-14) is proposed to be a regulator of metabolic diseases, such as diabetes mellitus (DM) and obesity. Adiponectin (ADIPOQ) is an adipocytokine produced by the adipocytes and other tissues and was reported to be involved in T2DM. OBJECTIVES: To study the possible association of the KLF-14 rs972283 and ADIPOQ-rs266729 with the risk of T2DM in the Saudi population. METHODS: We have evaluated the association of KLF-14 rs972283 C>T and ADIPOQ-rs266729 C>G SNV with the risk to T2D in the Saudi population using the Amplification Refractory Mutation System PCR (ARMS-PCR), and blood biochemistry analysis. For the KLF-14 rs972283 C>T SNV we included 115 cases and 116 healthy controls, and ADIPOQ-rs266729 C>G SNV, 103 cases and 104 healthy controls were included. RESULTS: Results indicated that the KLF-14 rs972283 GA genotype and A allele were associated with T2D risk with OR=2.14, p-value= 0.014 and OR=1.99, p-value=0.0003, respectively. Results also ADIPOQ-rs266729 CG genotype and C allele were associated with an elevated T2D risk with an OR=2.53, p=0.003 and OR=1.66, p-value =0.012, respectively. CONCLUSION: We conclude that SNVs in KLF-14 and ADIPOQ are potential loci for T2D risk. Future large-scale studies to verify these findings are recommended. These results need further verifications in protein functional and large-scale case control studies before being introduced for genetic testing.

Quality standards and internal quality control practices in medical laboratories: an IFCC global survey of member societies.

OBJECTIVES: The trueness and precision of clinical laboratory results are ensured through total quality management systems (TQM), which primarily include internal quality control (IQC) practices. However, quality practices vary globally. To understand the current global state of IQC practice and IQC management in relation to TQM the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a survey of IFCC member countries on IQC practices and management. METHODS: The survey included 16 questions regarding IQC and laboratory TQM practices and was distributed to IFCC full and affiliate member countries (n=110). A total of 46 (41.8 %) responses were received from all regions except North America. RESULTS: Of the responding countries, 78.3 % (n=36) had legislative regulations or accreditation requirements governing medical laboratory quality standards. However, implementation was not mandatory in 46.7 % (n=21) of responding countries. IQC practices varied considerably with 57.1 % (n=28) of respondents indicating that they run 2 levels of IQC, 66.7 % (n=24) indicating they run IQC every 24 h and 66.7 % (n=28) using assay manufacturer IQC material sources. Only 29.3 % (n=12) of respondents indicated that every medical laboratory in their country has written IQC policies and procedures. By contrast, 97.6 % (n=40) of responding countries indicated they take corrective action and result remediation in the event of IQC failure. CONCLUSIONS: The variability in TQM and IQC practices highlights the need for more formal programs and education to standardize and improve TQM in medical laboratories.

Insights on antioxidant therapeutic strategies in type 2 diabetes mellitus: A narrative review of randomized control trials.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disease of impaired glucose utilization. Imbalance in generation and elimination of free radicals generate oxidative stress which modulates glucose metabolism and insulin regulation, resulting in the occurrence and progression of diabetes and associated complications. Antioxidant supplements in T2DM can be seen as a potential preventive and effective therapeutic strategy. AIM: To compare randomized controlled trials (RCTs) in which antioxidants have been shown to have a therapeutic effect in T2DM patients. METHODS: We systematically searched the electronic database PubMed by keywords. RCTs evaluating the effect of antioxidant therapy on glycaemic control as well as oxidant and antioxidant status as primary outcomes were included. The outcomes considered were: A reduction in blood glucose; changes in oxidative stress and antioxidant markers. Full-length papers of the shortlisted articles were assessed for the eligibility criteria and 17 RCTs were included. RESULTS: The administration of fixed-dose antioxidants significantly reduces fasting blood sugar and glycated hemoglobin and is associated with decreased malondialdehyde, advanced oxidation protein products, and increased total antioxidant capacity. CONCLUSION: Antioxidant supplements can be a beneficial approach for the treatment of T2DM.

A new door to a different world: opportunities from the metaverse and the raise of meta-medical laboratories.

OBJECTIVES: In the digital age, the metaverse has emerged with impressive potential for many segments of society. The metaverse could be presented as a parallel dimension able to enhance the physical world as well as our actions and decisions in it with the objective to use a coalition between the natural and virtual worlds for value creation. Our aim was to elaborate on the impact of the metaverse on laboratory medicine. METHODS: Based on the available evidence, literature and reports, we analyzed the different perspectives of the metaverse on laboratory medicine and the needs for an efficient transition. RESULTS: The convergence and integration of technologies in the metaverse will participate to the reimagination of laboratory medicine services with augmented services, users' experiences, efficiency, and personalized care. The revolution around the metaverse offers different opportunities for laboratory medicine but also open multiple related challenges that are presented in this article. CONCLUSIONS: Scientific societies, multidisciplinary teams and specialists in laboratory medicine must prepare the integration metaverse and meta-medical laboratories, raise the awareness, educate, set guidance to obtain a maximum of value and mitigate potential adverse consequences.

External quality assessment practices in medical laboratories: an IFCC global survey of member societies.

OBJECTIVES: Clinical laboratory results are required for critical medical decisions, underscoring the importance of quality results. As part of total quality management, external quality assessment (EQA) is a vital component to ensure laboratory accuracy. The goal of this survey was to evaluate the current status of global laboratory quality systems and assess the need for implementation, expansion, or harmonization of EQA programs (EQAP) for Clinical Chemistry and Laboratory Medicine. METHODS: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a survey of IFCC full and affiliate members (n=110) on laboratory quality practice. A total of 41 (37.3%) countries representing all IFCC regions except North America provided responses about EQA availability and practices. RESULTS: All 41 countries perform EQA, 38 reported that their laboratories had EQA policies and procedures, and 39 further act/evaluate unacceptable EQA results. 39 countries indicated they have international and/or national EQAP and 30 use alternative performance assessments. EQA frequency varied among countries. Generally, an EQAP provided the EQA materials (40/41) with four countries indicating that they did not have an EQAP in their country. CONCLUSIONS: Globally, most laboratories participate in an EQAP and have defined quality procedures for EQA. There remain gaps in EQA material availability and implementation of EQA as a part of a total laboratory quality system. This survey highlights the need for education, training, and harmonization and will guide efforts of the IFCC TF-GLQ in identifying areas for enhancing global laboratory quality practices.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients.

BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide, and India contributes to about one-fifth of total CAD deaths. The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine (CML) in heart muscle, which correlates with fibrosis. AIM: To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes. METHODS: We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin (HbA1c) levels (group I: HbA1c ≥ 6.5; group II: HbA1c < 6.5). We analyzed the levels of lipoproteins, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nitric oxide. RESULTS: Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had more severe CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the left anterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter. Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide as compared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596, P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Odds ratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at unadjusted and adjusted levels with covariates. CONCLUSION: CML and inflammatory markers may play a significant role in the development of CAD, particularly in diabetic individuals, and may serve as potential biomarkers for the prediction of CAD in both diabetic and non-diabetic patients.

Target association rule mining to explore novel paediatric illness patterns in emergency settings.

BACKGROUND AND AIMS: To assess the hospitalized sick children admitted to the pediatric emergency department (ED) and to find new patterns of clinical and laboratory attributes using association rule mining (ARM). METHODS: In this observational study, 158 children with median (IQR) age 11 months and a PRISM III score of 5 (2-9) were enrolled. Hotspot data mining method was applied to assess clinical attributes, lab investigations and pre-defined outcome parameters of children and their association in sick hospitalized children aged 1 month to 12 years. RESULTS: We obtained 30 rules with value for outcome as discharge is given attributes as follows: duration of hospitalization > 4 days, lactate > 1.2 mmol/L, platelet = 3.67/µL, dur_ventil = 0 h, serum K = 5.2 mmol/L, SBP = 120 mmHg, pCO2 = 41.9 mmHg, PaO2 = 163 mmHg, age = 92 months, heart rate > 114-159 per minute, temperature > 98 °F, GCS (Glasgow Coma Scale) > 7-14, gas K = 4.14 mmol/L, gas Na = 138.1 mmol/L, BUN (Blood Urea Nitrogen) = 18.69 mg/dL, Diagnosis > 1-718, Creatinine = 1.2 mg/dL, serum Na = 148 mmol/L, shock = 2, Glucose = 144 mg/dL, Mg(i) > 0.23 meq/L, BUN > 6.54 mg/dL. CONCLUSION: ARM is an effective data analysis technique to find meaningful patterns using clinical features with actual numbers in pediatric critical illness. It can prove to be important while analysing the association of clinical attributes with disease pattern, its features, and therapeutic or intervention success patterns.

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease.

INTRODUCTION: The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. AIM: We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). METHODS: We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. RESULTS: The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females. CONCLUSIONS: ET-1 and ETA gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.

Artificial intelligence and thyroid disease management: considerations for thyroid function tests.

Artificial intelligence (AI) is transforming healthcare and offers new tools in clinical research, personalized medicine, and medical diagnostics. Thyroid function tests represent an important asset for physicians in the diagnosis and monitoring of pathologies. Artificial intelligence tools can clearly assist physicians and specialists in laboratory medicine to optimize test prescription, tests interpretation, decision making, process optimization, and assay design. Our article is reviewing several of these aspects. As thyroid AI models rely on large data sets, which often requires distributed learning from multi-center contributions, this article also briefly discusses this issue.

Daily v. weekly oral vitamin D3 therapy for nutritional rickets in Indian children: a randomised controlled open-label trial.

The aim of the study was to compare the efficacy of daily v. weekly oral vitamin D3 therapy in radiological healing of nutritional rickets. Children 6 months to 12 years (n 132) diagnosed with nutritional rickets were randomised into three groups (n 44): group A - 2000 IU daily vitamin D3 for 12 weeks, B - 60 000 IU weekly for 3 weeks, C - 60 000 IU weekly for 6 weeks. Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and X-ray score were estimated at baseline and 12 weeks (endline). The proportion of children who achieved complete radiological healing at endline was compared between three groups by χ2 and delta change in laboratory parameters by ANOVA (parametric data) or Kruskal Wallis test (non-parametric data), respectively. Baseline 25(OH)D ≤ 20 ng/ml was seen in 119 (90·2 %), hyperparathyroidism in 90 (68·8 %) and hypocalcaemia in 96 (72·7 %). A total of 120/132 children completed the study. Complete radiological healing seen in 30 (75 %) in group A, 23 (60·5 %) in group B and 26 (61·9 %) in group C; P = 0·15, with comparable endline X-ray scores; P = 0·31. The median (interquartile range (IQR)) delta X-ray score (baseline-endline) was 7 (4,9), 5 (2·25, 6) and 6 (4,7) in groups A, B and C, respectively; P = 0·019. Median (IQR) 25(OH)D endline levels in groups A, B and C were 50·0 (26·5, 66·5), 42·1 (28·4, 54·4) and 53·5 (33·7, 71·2) ng/ml, respectively; P = 0·045. Radiological scores were comparable at endline among daily and weekly vitamin D groups with greater change from baseline in daily supplemented group.

The Role of Inflammatory and Cytokine Biomarkers in the Pathogenesis of Frailty Syndrome.

Frailty is a conglomerated elderly disorder that includes multiple abnormalities, like anemia, an increased titer of catabolic hormones, and compromised physiology of most of the body systems. Many studies have established the biomarkers that correlate with physical function and immune aging; however, people can age differently, so chronological age is not a sufficient marker of susceptibility to disabilities, morbidities, and mortality. The pathophysiology of frailty is not clearly understood, but a critical role of enhanced inflammation in the body is hypothesized. Many factors contribute to the development of frailty syndrome, such as pro-inflammatory cytokines, inflammatory markers, inflammatory cytokines, and secosteroids, like vitamin D. This review aims to highlight the role of inflammatory and cytokine biomarkers and vitamin D in the pathogenesis of Frailty Syndrome.