Genetic Association of Transcription Factor 7-Like-2 rs7903146 Polymorphism With Type 2 Diabetes Mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) mainly results from the inability of muscle, fat, and liver cells to uptake glucose due to insulin resistance or deficiency of insulin production by the pancreas. Predisposition to T2DM may be due to environmental, hereditary, or both factors. Although there are many genes involved in causing T2DM, transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) single nucleotide polymorphism (SNP) found in genome-wide association studies (GWAS) is susceptible to T2DM. TCF7L2 is involved in pancreatic beta cell proliferation and differentiation via the Wnt signaling mechanism. OBJECTIVES: To find the genetic association of TCF7L2 rs7903146 (C/T) gene polymorphism in patients with T2DM. METHODS: A case-control study was conducted on 194 T2DM patients recruited from the endocrinology department at Indira Gandhi Institute of Medical Sciences, Patna, and 180 non-diabetic healthy controls that were age and sex-matched with the patients. All clinical examination and biochemical investigations like glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol; and determination of TCF7L2 gene polymorphism by allele-specific polymerase chain reaction (AS-PCR) were carried out for each subject. RESULTS:  The T allele of the rs7903146 (C/T) SNP was associated with a two-fold higher risk of T2DM and the heterozygous genotype (CT) with a 1.96 times higher risk. CONCLUSION: There is a high association of this SNP with the development of T2DM in the eastern Indian population. Serial monitoring of HbA1c should be done in an individual having this type of polymorphism for early detection of T2DM to prevent future complications.

Poor Glycemic Control Affecting Screening of Prostate Carcinoma.

Introduction Diabetes and cancer are commonly linked together. The possible links include insulin resistance, hyperinsulinemia, hyperglycemia, oxidative stress, and chronic inflammation. These are factors that have potential promoting effects on the progression of cancer in many ways. Measurement of prostate-specific antigen (PSA) is widely applied for early detection of prostate cancer. However, several factors influence serum PSA levels in men including age, benign prostatic hyperplasia, prostatitis, and body mass index (BMI). The risk of several malignancies is increased in diabetes but the risk of prostate carcinoma in diabetic patients is reduced secondary to lowering of testosterone levels during the state of hyperinsulinemia. A negative association between serum PSA levels and metformin use is also an explanation of low cancer prostate incidence with diabetes. Objective The study aims to evaluate the PSA levels in diabetic patients with poor glycemic control i.e., glycated hemoglobin (HbA1c) ≥ 7%) vs good glycemic control (HbA1c < 7%). Materials and methods Samples of PSA in diabetic patients collected in the Department of Biochemistry at Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, were included. The observational study was carried out on clinically diagnosed 318 cases of diabetes attending both the outpatient and inpatient Department, IGIMS, Patna. Six ml venous blood samples were collected from patients after obtaining informed consent and ethical clearance. Patient details regarding age, complete clinical details, and general physical examinations were recorded. Serum levels of PSA, fasting plasma glucose (FPG) and HbA1c were analyzed and values were compared. The serum level of PSA was estimated by the chemiluminescent immunoassay (CLIA) method on an automated immunoassay analyzer in the Department of Biochemistry, maintaining all the quality control precautions using a control, calibrator, and reagent kit. HbA1c estimation was by chromatography technique. Fasting plasma glucose was estimated using the hexokinase method on an automated chemistry analyzer. Statistical analyses were performed using SPSS software, version 16.0 (SPSS Inc., Chicago). The median and interquartile range were calculated for numerical variables. Covariance analysis was used in the comparisons among groups. The Mann-Whitney U test was applied to detect the comparison between the two groups. Significance was determined by the P value. P value<0.05 was considered significant. Result Serum PSA value was found to be higher in (the good glycemic control group) with a median of 0.99 with an interquartile range of 3.14, than in (the bad glycemic control group) with a median of 0.49 with an interquartile range of 3.9, and the difference is statistically significant. The difference is also statistically significant in the subgroup (i) with PSA value <4 ng/ml. In subgroups (ii) and (iii), PSA values 4 ng/ml-8 ng/ml and PSA values >8 ng/ml respectively, no significant differences were found. Conclusion It was found that serum prostate-specific antigen levels have been lower in diabetic patients with poor glycemic control than in good glycemic control. Future studies with a larger sample size and detailed information on diabetes duration and management are recommended.

Epidemiological trends of colorectal cancer cases in young population of Eastern India: A retrospective observational study.

BACKGROUND: Colorectal cancer (CRC) is a disease of the older population in developed countries where the incidence among the young is rising despite the decline in the overall incidence. Contrary to this, in India, which is a low-incidence country for CRCs, the incidence among all age groups including the young is rising. This study aimed at describing the clinico-demographic profile of young CRC cases and the epidemiological trend of the proportion of young cases from 2014 to 2021 in a tertiary cancer center in Eastern India. METHODS: This retrospective observational study was conducted at Department of Radiation Oncology, State Cancer Institute, IGIMS Patna, India a prominent tertiary cancer care center of Bihar. All histopathologically confirmed CRC cases in the 0-39 years age group were considered young and evaluated for the clinical, demographic profile as well as yearly trends in proportion out of total CRC cases. Microsoft Excel (2021) was used for statistical analysis. A P value of 0.05 was considered significant. RESULTS: Young colorectal (less than 40 years) patients constituted a third (n = 344, 33.4%) of total colorectal (n = 1028) cases. The median age among the young CRC cases was 30 years (range: 12 to 39 years). Rectum was the most common subsite noted (n = 255,74.1%) among this group of young patients. The most commonly encountered stage of the disease was III (n = 107, 31.1%) and chemotherapy was the most common treatment offered (n = 153, 44.5%). The proportion of young (0-39 years) CRC cases ranged between 29.4 and 37.4 (mean 33.5 ± 2.77, P value = 0.725) over the calendar years of the study period. CONCLUSION: The proportion of young (<40 years of age) cases out of total CRC cases in our study is higher than that in developed countries. However, the trends of this proportion have been consistent over the study period, i.e., from 2014 to 2021 without any significant change in our hospital-based cancer registry. Rectal cancer affected nearly three out of every four CRC patients in this age group. More advanced disease at presentation emphasizes the need for measures of screening, early diagnosis, and adequate infrastructure for treatment.

Study of analytical error in lipase assay.

Background: Lipase and amylase are the most frequently used biomarker for the diagnosis of pancreatic diseases, especially acute pancreatitis. Lipase has better diagnostic accuracy in comparison to amylase for the analysis of acute pancreatitis. However, lipase assay in random access analyzer is sometimes difficult to perform as it is exposed to different types of samples or reagents which may act as interference. Materials and Methods: In our laboratory, we found the raised values (>500 IU/L) of lipase with normal amylase in some samples. However, the immediate rerun of these samples for lipase only showed normal (<80 IU/L) lipase level. To root out this fallacy, we performed reagent and sample carryover studies. Results: The cause of the falsely raised value of lipase was revealed by reagent carryover studies. All samples which assayed triglyceride (TGL) followed by lipase immediately after it showed elevated (>500 IU/L) lipase value. This is due to the interference of microbial lipase used in TGL reagents. This was corrected by separating the analysis of lipase and TGL into two different instruments. Conclusion: If interference testing is not done, the laboratories are prone to have an analytical error in reporting and hence lead to diagnostic error. Hence, after analyzer installation, interference testing should be included in the validation protocol.

Résumé Contexte: La lipase et l'amylase sont les biomarqueurs les plus fréquemment utilisés pour le diagnostic des maladies pancréatiques, en particulier la pancréatite aiguë. La lipase a une meilleure précision diagnostique par rapport à l'amylase pour l'analyse de la pancréatite aiguë. Cependant, le dosage de la lipase dans un analyseur à accès aléatoire est parfois difficile à réaliser car il est exposé à différents types d'échantillons ou de réactifs qui peuvent agir comme des interférences. Matériels et méthodes: Dans notre laboratoire, nous avons trouvé des valeurs élevées (> 500 UI/L) de lipase avec une amylase normale dans certains échantillons. Cependant, la réexécution immédiate de ces échantillons pour la lipase n'a montré qu'un niveau de lipase normal (<80 UI/L). Pour éliminer cette erreur, nous avons effectué des études de transfert de réactifs et d'échantillons. Résultats: La cause de la valeur faussement élevée de la lipase a été révélée par des études de transfert de réactif. Tous les échantillons qui dosaient les triglycérides (TGL) suivis de la lipase immédiatement après présentaient une valeur de lipase élevée (> 500 UI/L). Cela est dû à l'interférence de la lipase microbienne utilisée dans les réactifs TGL. Cela a été corrigé en séparant l'analyse de la lipase et de la TGL dans deux instruments différents. Conclusion: Si les tests d'interférence ne sont pas effectués, les laboratoires sont susceptibles d'avoir une erreur analytique dans les rapports et donc de conduire à une erreur de diagnostic. Par conséquent, après l'installation de l'analyseur, les tests d'interférence doivent être inclus dans le protocole de validation. Mots-clés: Pancréatite aiguë, amylase, erreur diagnostique, laboratoires, lipase.

Correlation Between Circulating Cell-Free DNA Levels and Breast Cancer Subtypes: A Prospective Observational Study.

INTRODUCTION: Breast cancer (BC), a heterogeneous disease, is one of the leading causes of cancer-related deaths among women worldwide. Circulating cell-free DNA (cfDNA) levels have been persistently reported to be elevated in BC patients. In the current study, we evaluated the correlation between the cfDNA levels in patients with BC and its subtypes. METHODS: We recruited newly diagnosed, histopathologically confirmed BC patients aged >18 years (N=39), who did not have any previous malignancy, from the Department of Surgical Oncology, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. A total of 6 ml of venous blood was collected from each subject; of this, 1 ml was subjected to complete blood count (CBC), and 4 ml was transferred to a clot-activated collection vial for plasma separation and the cfDNA isolation thereof. In addition to the basic demographic history of each patient, the information on the cancer subtype was as also recorded from the medical records of each patient. All the data were analysed by GraphPad Prism Version 8 (Insightful Science, LLC, San Diego, California, United States). One-way ANOVA was used to test the difference between more than two groups. Pearson correlation was also estimated between cfDNA levels and various CBC indices. A two-tailed p-value<0.05 was considered statistically significant. RESULTS: The mean age of included patients was 48.6±8.20 years. The mean levels of cfDNA were 2.81±2.39 ng/µL. The mean counts of various blood cell types and other indices of CBC were in the normal range. Compared to BC patients with estrogen receptors (ER+), the cfDNA levels were significantly higher in patients with human epidermal growth factor receptor 2 (HER2+) and triple-negative BC (TNBC) (p<0.05).  Conclusion: The elevated levels of cfDNA in patients with BC can be a prognostic marker for the disease subtype. However, more replicative studies are warranted to substantiate our findings.

Assessment of Maternal Serum Biochemical Attributes and Fetal Ultrasound Scans in First-Trimester Low-Risk Noninvasive Prenatal-Tested Pregnant Women.

INTRODUCTION: The first trimester of pregnancy is marked by several important disrupting changes as a result of complex biological upshot of events required for the development of the fetus. These changes in the biological events result in changes in the maternal serum biomarkers that are associated with fetal growth. The aim of the present study was to evaluate the correlation between the maternal blood biochemical determinants such as pregnancy-associated plasma protein-A (PAPP-A) and alpha fetoprotein (AFP) with ultrasound scans during early pregnancy in the first trimester. METHODS: The study included 139 women whose fetus was alive between 11±1 weeks of gestation. The risk of fetal chromosomal abnormalities at first trimester was analyzed by the VeriSeq NIPT Solution v2 platform (Illumina, San Diego, CA, USA) for noninvasive prenatal testing (NIPT) assay. The PAPP-A and AFP levels were evaluated by chemiluminescent immunoassays. The levels of PAPP-A and AFP were correlated with the fetal heart rate (HR), crown rump length (CRL), and nuchal translucency (NT) by Pearson's correlation analysis. RESULTS: The mean age of the participants was 28.35±3.87 years (minimum=21, maximum=35). The mean AFP and PAPP-A levels in the maternal plasma were 14.76±1.04 ng/mL and 4.37±0.86 mIU/ml respectively. The mean FHR, CRL, and NT were 138±7.62 bpm, 59±3.24 mm, and 2.3±0.61 mm respectively. PAPP-A and AFP significantly (p<0.05) correlated with fetal HR, CRL, and NT at 11±1 weeks of gestation. The mean ratio of AFP:PAPP-A in low-risk pregnancies was 3.37. CONCLUSIONS: The maternal serum biochemical attributes correlated well with the fetal ultrasound scans. The findings of the present study can prove to be clinically useful for clinical research, obstetrics, and gynaecology, especially for examinations of first-trimester pregnancies.