Micro-RNAs With Prognostic Significance in Gallbladder Cancer: A Systematic Review and Meta-Analysis.

Gallbladder cancer (GBC) stands out as one of the most widespread malignancies impacting the biliary tract globally. Despite increasing interest, to the best of our knowledge, no meta-analysis has been undertaken to amalgamate the existing data concerning the prognostic significance of micro-RNAs (miRNAs) in GBC in comparison to studies on miRNAs in other cancers. Hence, this systematic review and meta-analysis aimed at determining the prognostic significance of miRNAs in GBC patients. Comprehensive literature searches were conducted across PubMed, Cochrane Library, Ovid, Scopus, and Science Direct databases. Studies that evaluated the association between miRNAs and overall survival in GBC patients were included. Random-effect meta-analysis was employed to pool hazard ratios (HRs) and their 95% confidence intervals (CIs) across studies. A total of 15 studies, encompassing 16 miRs, were included for our analysis. The pooled analysis revealed that a high expression of miR-204, miR-7-2-3p, miR-29c-3p, miR-125b, miR-20a, miR-139-5p, miR-141, miR-92b-3p, miR-335, and miR-372 was significantly associated with poor prognosis and increased risk (HR>1 and the upper bound of the 95% CI>1). Additionally, these miRNAs were associated with the overall survival (HR = 1.56, 95% CI = 0.91-2.20, I2 = 91.82%). Significant heterogeneity was observed and could be attributed to the limited number of studies available on the GBC and significant reliance on quantitative real-time PCR for the detection of miRNAs. In conclusion, specific miRNAs exhibit prognostic significance in GBC, with potential implications for patient stratification and targeted therapeutic interventions. However, due to the heterogeneity among studies, these findings should be interpreted cautiously and validated in larger cohorts.

Efficacy of jackfruit components in prevention and control of human disease: A scoping review.

The jackfruit (Artocarpus heterophyllus) is one of the natural remedies significantly used in folk medicine. The ethnopharmacological applications of jackfruit are mainly concerned with the management of inflammation, diarrhea, and diabetes mellitus. Flavonoids, stilbenoids, aryl benzofurans, and lectin jacalin are abundant in jackfruit species. Jacalin is a good indicator for evaluating the immunological state of HIV-1 patients. The extracts and metabolites of jackfruit, particularly those from the leaves, bark, stem, and fruit, contain several beneficial bioactive mixtures. New studies are focused on exploring these bioactive compounds used in various biological activities such as antiviral, antiplatelet, anticancer, antiatherosclerotic, immunomodulatory effects, inhibitors of 5-alpha reductase activity, and the formulation of fast-dissolving tablets (orodispersible, rapid melts porous). Multidisciplinary programs that integrate traditional and modern technology play a crucial role in the lies ahead expansion of jackfruit as the prospective inception of therapeutic compounds. This review aims to highlight significant results on the identification, production, and bioactivity of metabolites found in jackfruit, with current developments in jackfruit research in the control and prevention of human diseases.

Next generation sequencing uncovers multiple miRNAs associated molecular targets in gallbladder cancer patients.

Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.

Prognostic Significance of Diastolic Dysfunction in Type 2 Diabetes Mellitus Patients With Sepsis and Septic Shock: Insights From a Longitudinal Tertiary Care Study.

BACKGROUND: Sepsis is one of the leading contributors to global mortality and morbidity, causing multi-organ failure, mainly involving cardiovascular failure, both systolic and diastolic dysfunction, leading to adverse clinical outcomes. There is little clinical data on the correlation with the mortality of patients with type 2 diabetes mellitus (T2DM) with sepsis and septic shock and left ventricular diastolic dysfunction. Our study sought to assess whether the severity of diastolic dysfunction could predict 28-day mortality. METHODOLOGY: The study included T2DM patients admitted to the intensive care unit (ICU) with sepsis and septic shock defined according to the Third International Consensus Definitions for Sepsis and Septic Shock at a tertiary care center in northern India. A total of 132 patients (age = 61.01 ± 13.12 years; 62% male; mean APACHE II (Acute Physiology and Chronic Health Evaluation II) score = 25.74 ± 4.79; Sequential Organ Failure Assessment (SOFA) score = 12.34 ± 3.36) underwent transthoracic echocardiography within two hours of ICU admission till 28 days of admission or till mortality occurred. Clinical variables (APACHE II and SOFA score) and cardiac biomarkers, such as N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin I, and creatine phosphokinase-MB, were measured at the time of admission and after 72 hours to compare with mortality. Diastolic dysfunction was defined according to the American Society of Echocardiography (ASE) 2009 guidelines, classifying subjects into grade 0 (normal), if early diastolic velocity (e') ≥ 8 cm/s; grade 1 (impaired relaxation), if e' < 8 cm/s and early (E) to late (A) ventricular filling velocities (E/A) ratio < 0.8; grade 2 (pseudo normal), if e' < 8 cm/s, E/A = 0.8-1.5, and peak E-wave velocity by the peak e' velocity (E/e') ratio = 9-12; and grade 3 (restrictive), if e' < 8 cm/s, E/A > 2, deceleration time (DT) < 160 ms, and E/e' ≥ 13. RESULTS: Thirty-seven (40.65%) out of 132 patients had diastolic dysfunction on initial echocardiography, while 54 (59.34%) had diastolic dysfunction on at least subsequent echocardiography. Total mortality was 68.93% with the highest mortality (100%) observed among those with grade 3 diastolic dysfunction. The 28-day mortality with diastolic dysfunction in sepsis and septic shock patients showed significant results (p < 0.001), indicating that with a higher E/A ratio or higher grade of diastolic dysfunction with the increase in SOFA score, the early ICU mortality is the highest and have the shortest duration of ICU stay with mean ± SD = 6.2 ± 2.48, as compared to other grades with 100% mortality. Also, the cardiac biomarker NT-pro-BNP was markedly elevated with a mean ± SD value of 503 ± 269.3 pg/ml, indicating early predicted mortality. No correlation was detected between mortality and the mean levels of fasting blood sugar, postprandial blood sugar, and glycosylated hemoglobin. CONCLUSION: Our study concluded that diastolic dysfunction is an important and strongest independent mortality predictor in patients with T2DM with severe sepsis and septic shock, and the higher the grade of diastolic dysfunction, the higher the mortality with the lowest mean ICU stay.

Expression of ER, PR, and HER-2 Neu and correlation with tumor markers in gall bladder carcinoma.

Background: Females having a large proportion of gallbladder carcinoma (GBC) and a higher incidence of gallstones pointed toward the role of sex hormones in GBC development. In this study, we evaluated the expression of Estrogen receptor (ER), Progesterone receptor (PR), and Her2/neu and their correlation with tumor markers and clinicopathological parameters in the GBC. Methods: A total of 50 patients of GBC and 42 patients in control group undergoing surgery for other conditions were taken. The patient's biopsy sample's paraffin block was tested for ER, PR, and Her2/neu expression by immunohistochemistry. Results: ER and PR had no significant expression in GBC and control group, but Her2/neu had 16% expression in GBC, significantly associated with the degree of differentiation with 62.5% (n-5) being well-differentiated; 75% of Her2/neu positive were in stages III and IV. Her2/neu did not correlate with tumor markers despite expression. Conclusions: Her2/neu amplification is a small step in validating that option so it could be included in the treatment and prognostication of GBC.

Bilirubin in wound healing: A double-edged sword.

The impact of bilirubin levels on wound healing remains a topic of controversy. The present study is a literature review that examines the impact of increased levels of bilirubin in the bloodstream on the process of wound healing. The physiological pathways and their interrelationships, as well as the relevant research publications, were comprehensively addressed in our discussion. The present study undertook a comprehensive review of the extant literature pertaining to the impact of bilirubin concentration on the process of wound healing, with particular emphasis on its association with reactive oxygen species. This scholarly article provides an overview of several studies that elucidate the mechanisms and correlation between bilirubin and the process of wound healing. The impact of bilirubin on wound healing has been observed, and it appears to function as a modulator. This review demonstrates that there exists a spectrum of bilirubin concentrations that can function as precise regulators, although this range falls under pathological hyperbilirubinemia. Further research is required to determine the precise boundary of this range. Within a certain range, bilirubin serves as a positive regulator in the process of wound healing. Beyond this range, it has the potential to function as a negative regulator.

Effectiveness of Kabasura Kudineer tablets in the management of asymptomatic and mild cases of COVID-19: A pilot double-blinded, randomized controlled trial.

INTRODUCTION: COVID-19 was declared a pandemic in 2020. It has had a devastating effect on human life and the global economy. To date, there is no proven therapy for COVID-19, even though rigorous research is ongoing to test multiple compounds across all systems of medicine. A need was felt to systematically explore the Indian system of medicine to assess its efficacy against COVID-19. The objective of the present study was to examine the effect of Kabasura Kudineer as a standalone therapy on the following: time required to achieve symptom relief & resolution, virological clearance, and levels of IL6, CRP and IgG, and compare it to the standard therapy available for treatment of COVID-19. METHODOLOGY: A double-blinded randomized controlled trial was conducted in 110 participants. 55 participants were enrolled in the Kabasura Kudineer arm and 55 in the control (standard therapy + Kabasura Kudineer placebo) arm. Study participants were randomly allocated into the two study arms. They were assessed for symptoms at baseline, and on Day 5 and Day 10. RT PCR, CRP, IL6 and IgG levels were measured at baseline, Day 5 and Day 10. On day 28, participants were interviewed telephonically for symptom assessment alone. STATISTICAL ANALYSIS: A per-protocol approach was used. Significant difference between two groups was assessed at baseline, day 5 and day 10 using the Chi-square and Mann Whitney test. RESULT: A total of 110 patients participated in study. Four patients in the Kabasura Kudineer arm and 9 in the Standard therapy arm were lost to follow-up. Baseline characteristics for both the groups were matched at baseline. 83.9% and 93.9% patients were relieved of all symptoms by the 10th day in Kabasura and standard therapy groups respectively. Decrease in CRP level was more pronounced in the Kabasura group compared to standard therapy viz. 3 mg/l and 1.26 mg/l. No significant difference was found in IgG level and IL6 levels in both the study groups. However, it was noticed that among the unvaccinated group, the surge in IgG levels was much higher in Kabasura Kudineer group than the standard therapy group. CONCLUSION: Kabasura Kudineer as a standalone therapy was as effective and safe as the standard therapy among patients with asymptomatic to mild COVID-19.

Non-coding RNAs, cancer treatment and cardiotoxicity: A triad of new hope.

The global health landscape has experienced a shift towards non-communicable diseases, with cardiovascular diseases and cancer as leading causes of mortality. Although advancements in healthcare have led to an increase in life expectancy, they have concurrently resulted in a greater burden of chronic health conditions. Unintended consequences of anticancer therapies on various tissues, particularly the cardiovascular system, contribute to elevated morbidity and mortality rates that are not directly attributable to cancer. Consequently, the field of cardio-oncology has emerged to address the prevalence of CVD in cancer survivors and the cardiovascular toxicity associated with cancer therapies. Non-coding RNAs (ncRNAs) have been found to play a crucial role in early diagnosis, prognosis, and therapeutics within the realm of cardio-oncology. This comprehensive review evaluates the risk assessment of cancer survivors concerning the acquisition of adverse cardiovascular consequences, investigates the association of ncRNAs with CVD in patients undergoing cancer treatment, and delves into the role of ncRNAs in the diagnosis, treatment, and prevention of CVD in patients with a history of anti-cancer therapy. A thorough understanding of the pathogenesis of cancer therapy-related cardiovascular disease and the involvement of ncRNAs in cardio-oncology will enable healthcare professionals to provide anticancer treatment with minimized cardiovascular side effects, thereby improving patient outcomes. Ultimately, this comprehensive analysis aims to provide valuable insights into the complex interplay between cancer and cardiovascular diseases, facilitating the development of more effective diagnostic, therapeutic, and preventive strategies in the burgeoning field of cardio-oncology.

Association of Serum Leptin With Body Mass Index in Gallbladder Cancer Patients: A Pilot Study.

BACKGROUND: Leptin has been proposed to be a link between obesity and the increased incidence of various cancers like breast cancer, colon cancer, gastric cancer, etc. The role of leptin in gallbladder cancer is largely undetermined. Moreover, no study has evaluated serum leptin levels and their correlation with clinicopathological characteristics and serum tumour markers in gallbladder cancer (GBC). Therefore, the present study was planned. METHODS: A cross-sectional study was conducted in a tertiary care hospital in Northern India after obtaining ethical approval from the institution. Forty GBC patients staged as per American Joint Committee on Cancer (AJCC) 8th staging system were recruited along with 40 healthy controls. Serum leptin was assayed by sandwich enzyme-linked immunosorbent assay (ELISA) and tumour markers (CA19-9, CEA and CA125) by Chemiluminescence. ROC, Mann Whitney U test, Linear regression and Spearman correlation was performed using Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY). BMI was also assessed for both groups. RESULTS: Median BMI for GBC patients was 19.46 (IQR 17.61-22.36). Median serum leptin levels were significantly lower (2.09 (IQR 1.01-7.76) ng/mL) in GBC patients as compared to controls (12.32 (IQR 10.50-14.72) ng/mL). AUC was 0.84 with 100% sensitivity and 75% specificity at 7.57 ng/mL. Serum leptin was not associated with cancer stage, resectability, metastasis, liver infiltration, or tumour markers on linear regression (p=0.74, adjusted R square = -0.07). A significant positive correlation was found between BMI and serum leptin in GBC patients (p=0.00). CONCLUSIONS: Lower BMI and relatively lean presentation of GBC patients may account for low serum leptin levels.

Genetic Variations in IL-1ß, TNF-α, and TGF-ß Associated with the Severity of Chronic Cervical Spondylitis in Patients.

Chronic cervical spondylitis (CCS), a degenerative disorder of the spine, is known for causing disability among old and young people. Single-nucleotide polymorphisms (SNPs) in various cytokine genes have demonstrated an impactful association with several inflammatory disorders. In the present study, we have investigated the SNPs and allelic distribution of the three most prevalent cytokines genes, IL-1ß (-511C/T), TNF-α (-308G/A), and TGF-ß (-509C/T), along with serum levels of these cytokines in 252 subjects. SNPs were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and digested fragments were separated and visualized using agarose gel electrophoresis and Native Polyacrylamide gel electrophoresis (PAGE). The serum cytokine levels were analyzed with a flow cytometer using a customized multiplex bead-based assay. It was observed that these SNPs did not reflect the susceptibility to CCS but were associated with susceptibility to CCS. We found a significant association between the C/C and G/G genotypes and the C and G alleles of IL-1ß and TNF-α, respectively, suggesting a lower risk of CCS. The frequency distribution of risk alleles (-511T) and (-308A) were simultaneously higher in CCS compared to the control, reflecting the susceptibility to CCS. TGF-ß showed a significant association with disease susceptibility, along with a significant correlation between age and the chronicity of CCS. The serum cytokine levels were significantly different in CCS and controls.

Assessment of Vitamin D Levels and Other Bone Related Biochemical Markers in Healthy Adults in Rural Population of Uttarakhand, India.

Despite being close to equator and receiving sufficient sun rays, evidences revealed that Indians have severe deficiency of vitamin D (vit D) ranging from 41 to 100% in different geographical locations. Therefore, in this study levels of 25(OH)D (physiologically measurable form) along with other bone metabolism associated biochemical markers were determined in serum sample of 300 apparently healthy study subjects (rural) from Doiwala block of Dehradun district in the state of Uttarakhand. Demographic data was also obtained based on a structured questionnaire to establish an association between 25(OH)D levels and various dietary and socio-cultural factors. Results demonstrated that of all study subjects, 197 (65%) had 25(OH)D levels below < 12 ng/mL (deficient) and 65 (21%) had 25(OH)D levels between 12 and 20 ng/mL (insufficient) with all other markers falling within respectively established reference ranges. Further, in univariate analysis, gender, occupation (indoor and outdoor), education were independently associated with vitamin D status. Additionally, parathyroid hormone associated significantly with gender and occupation, while calcium associated significantly with gender, occupation and education. Lastly, regression analysis revealed that gender and occupation independently associated with vitamin D status of subjects. In conclusion, apparently healthy subjects showed considerable vitamin D deficiency thereby generating an urgent need for formulating and implementing better government policies for enrichment of vitamin D levels among rural adults of Uttarakhand in future. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01048-6.

Treatment Outcomes and Survival in Hypercalcemia of Malignancy: A Grave Metabolic Emergency.

BACKGROUND: Management of hypercalcemia is based on the manifestation of symptoms and serum calcium levels. It is considered an oncological emergency; therefore, management has to be done on an urgent basis. AIM: In the present study, we analyzed the clinicopathological profile, treatment, and outcome of patients with hypercalcemia in solid malignancies at our institute. METHODS: We retrospectively analyzed the medical records of patients diagnosed with cancer and admitted to the department of radiation oncology with hypercalcemia. The parameters studied were age, gender, performance status, date of diagnosis, the primary site of cancer, stage, histopathology, time of presentation of hypercalcemia since initial cancer diagnosis, clinical symptoms, parathyroid hormone levels, liver and renal function tests, bone metastases, management, outcome, and present status. RESULTS: In the present study, 47 patients of hypercalcemia from various solid malignancies were admitted during the study period between 1st January 2018 and 30th April 2022. Head and neck cancer (14, 29.7%) was the most common site of the primary malignancy. Twelve patients had incidental hypercalcemia and were asymptomatic. Management of hypercalcemia included intravenous saline hydration, bisphosphonates, and supportive medication. At the time of analysis, 17 patients were lost to follow-up, 23 patients died, and seven were alive and on follow-up. Median survival was 68.0 days (95% CI: 1.7-134.3 days). CONCLUSION: Hypercalcemia of malignancy is considered a metabolic oncological emergency and requires urgent and aggressive management. It gets complicated by a deranged kidney function test. Despite available treatment, it portends an abysmal prognosis.

Potential of Cytochrome P450, a Family of Xenobiotic Metabolizing Enzymes, in Cancer Therapy.

Significance: Targeted cancer therapy with minimal off-target consequences has shown promise for some cancer types. Although cytochrome P450 (CYP) consists of 18 families, CYP1-4 families play key role in metabolizing xenobiotics and cancer drugs. This eventually affects the process of carcinogenesis, treatment outcomes, and cancer drug resistance. Differential overexpression of CYPs in transformed cells, together with phenotypic alterations in tumors, presents a potential for therapeutic intervention. Recent Advances: Recent advances in molecular tools and information technology have helped utilize CYPs as cancer targets. The precise expression in various tumors, X-ray crystal structures, improved understanding of the structure-activity relationship, and new approaches in the development of prodrugs have supported the ongoing efforts to develop CYP-based drugs with a better therapeutic index. Critical Issues: Narrow therapeutic index, off-target effects, drug resistance, and tumor heterogeneity limit the benefits of CYP-based conventional cancer therapies. In this review, we address the CYP1-4 families as druggable targets in cancer. An emphasis is given to the CYP expression, function, and the possible mechanisms that drive expression and activity in normal and transformed tissues. The strategies that inhibit or activate CYPs for therapeutic benefits are also discussed. Future Directions: Efforts are needed to develop more selective tools that will help comprehend molecular and metabolic alterations in tumor tissues with biological end-points in relation to CYPs. This will eventually translate to developing more specific CYP inhibitors/inducers. Antioxid. Redox Signal. 38, 853-876.

Assessment of Dyslipidemia, Lipid Ratios, and Atherogenic Indices as Cardiovascular Risk Factors in Prediabetic and Diabetic Subjects.

Background Uttarakhand is a small state in northern India that comprises mixed population with people dwelling in both hilly and plain areas. Globally, diabetes mellitus (DM) has already been considered to be a pandemic. Furthermore, cardiovascular diseases (CVD) significantly increase mortality and morbidity in patients suffering from DM. Additionally, dyslipidemia has been identified as an important marker in the development of atherosclerosis and ultimately CVD in patients of prediabetes and diabetes. Thus, the identification of subjects with dyslipidemia in prediabetes might be fruitful in lowering their progression to diabetes and ultimately in decreasing incidences of CVD. Hence, this study was undertaken to assess dyslipidemia via the calculation of atherogenic indices (AI) and lipid ratios in prediabetic and diabetic groups attending tertiary care hospital in Uttarakhand. Materials and Methods This study reviewed retrospective biochemical data of 500 study subjects from e-hospital software of the All India Institute of Medical Sciences, Rishikesh. All study subjects were divided into three groups: 122 controls, 137 prediabetics, and 241 diabetics based on the American Diabetes Association criteria. Study subjects were evaluated for glycated hemoglobin (HbA1c), lipid profile, and AI (total cholesterol [TC]/high-density lipoprotein cholesterol [HDLc], low-density lipoprotein cholesterol [LDLc]/HDLc, TC-HDLc/HDLc, triglycerides [TG]/HDLc). Results Results showed that TC, TG, LDLc, and AI were significantly higher, and HDLc was significantly decreased in prediabetic and diabetic groups compared with controls. Furthermore, HbA1c showed significant positive correlation with lipid profile and AI except atherogenic coefficient (TC-HDL/HDL). Conclusion In conclusion, the current study showed the presence of dyslipidemia in both prediabetic and diabetic groups underlining their importance for screening at the prediabetic stage. Hence, we also recommend screening of the prediabetic group for dyslipidemia to arrest the development of early cardiovascular complications.

Comprehensive structured training on occupational health hazards and vaccination: A novel initiative toward employee safety.

Introduction: Healthcare providers are vulnerable to occupational health hazards. However, they do not appropriately apprehend the serious health consequences of occupational exposures. This study was conducted to assess the effectiveness of "Occupational health hazards and vaccination" workshop organized periodically in institute. Material and Methods: We validated the questionnaire prior to assess the effectiveness of workshop. Expert performed "key check" of questionnaire. Item analysis of one best item questions was performed using difficulty index (p value), discrimination indices (DI), distractor efficiency (DE), and reliability using Kuder-Richardson 20 coefficients (KR20). Pre-test and post-test scores of study participants were compared. Effectiveness of workshop was determined using class average normalized gain. Result: The 14 item one-best questions had acceptable difficulty level (60.35 ± 9.46%) and ideal discriminating power (0.75 ± 0.17) with mean DE 73.81 ± 22.46%. The test was found highly reliable with KR20 as 0.90. Mean score in pre-test and post-test were 6.47 ± 3.38 and 13.69 ± 1.51, respectively, and significant improvement in post-test score was found compared to pre-test score. Class average normalized gain was 0.84. Conclusion: The Occupational health hazards and vaccination workshop effectively improved healthcare providers' knowledge regarding workplace safety protocols. Questionnaire was found to be valid and reliable. Low baseline knowledge highlights the fact that implementation of such training on regular basis is the need of hour.

Single-Point Insulin Sensitivity Estimator (SPISE) as a Feasible Marker of Insulin Resistance in Adult Metabolic Syndrome: Evaluated in a Hospital Based Cross-Sectional Pilot Study at Tertiary Care Centre of Uttarakhand.

Insulin resistance (IR) plays an important role as a major determinant of Metabolic syndrome (MetS). Various methods are available for measuring insulin resistance but they are laborious, time-consuming, and costly. Therefore various surrogate markers and indices have been devised to simplify and improve the determination of insulin resistance. Recently, a new index, single point insulin sensitivity estimator (SPISE) was proposed in the European population and was found comparable to the gold standard test (hyperinsulinemic euglycemic glucose clamp).This study was planned to evaluate whether SPISE could be a useful potential low-cost indicator for predicting MetS with IR patients in Indian population. Eighty-three participants from outpatient care of AIIMS Rishikesh were evaluated after informed consent. They were divided into Metabolic syndrome (n = 56) and Non Metabolic Syndrome(n = 27), using South Asian Modified National Cholesterol Education Program- ATP-III criteria for metabolic syndrome. SPISE index, HOMA-IR, Insulin Resistance Index, Triglycerides to high-density lipoproteins cholesterol ratio (TG/HDL-C) were calculated for all the subjects. Receiver operating characteristic (ROC) curve was plotted to assess discriminatory ability of SPISE, HOMA-IR, TG/HDL-C ratio, IRI and hs-CRP to differentiate between IR(Metabolic syndrome) and non-IR (Non-Metabolic syndrome) subjects. SPISE has greater area under curve with better sensitivity and specificity compared to HOMA-IR, IRI, TG/HDL-C ratio and hs CRP. So, SPISE has better predictive ability than HOMA-IR, IRI, TG/HDL-C ratio and hs CRP to discriminate IR from non-IR cases. SPISE could be a useful potential low-cost indicator with high sensitivity and specificity for predicting IR in MetS patients.

Derivation of a Modified Friedewald's equation for LDL cholesterol estimation in Sub-Himalayan population: A comparative study.

Background: Despite the availability of alternative homogenous assays for LDL-C measurement, most of the laboratories still use Friedewald Equation (FE). However, various novel equations have shown better performance than FE specific to a particular population. Besides, no equation has been devised for use in Sub-Himalayan population. Methods: A cross-sectional laboratory data-based study was conducted by recruiting lipid profiles of 1851 samples to validate 10 different equations for calculating LDL and to devise a novel Modified Friedewald Equation (MFE) specific for Sub-Himalayan population. Results: The novel MFE is presented as: LDL-C = -2.421 + (0.752 × TC) - (0.047 × TG) - (0.350 × HDL). A significant difference was observed between direct LDL-C (118.84 ± 40.39 mg/dL) and all other equations except MFE (118.84 ± 37.96 mg/dl, P > 0.999) and Puavilai Equation (117.99 ± 49.05 mg/dL, P = 0.138). Additionally, MFE showed lowest mean percentage bias of 0.14% with 95% limits of agreement within ± 2SD on Bland-Altman analysis. On ROC analysis at cut-offs of clinical decision limits of 100 mg/dl, 130 mg/dl, 160 mg/dl, and 190 mg/dl, MFE outperformed all other equations with highest AUC (0.974, 0.978, 0.982, and 0.995) respectively with specificity >95% at higher levels. MFE also showed highest correlation (r = 0.954, P < 0.001) and least rMSE (13.8) with direct LDL although all the equations showed significant positive correlation with direct LDL (p < 0.001). Conclusion: MFE derived in this study showed a better diagnostic performance as compared to other 10 equations taking Direct LDL-C as gold standard for Sub-Himalayan Population and may be used as a substitute for FE in the study population.

Clinical and Biochemical Correlation With Cytomorphological Findings of Lymphocytic Thyroiditis: An Experience at a Tertiary Centre in the Himalayan Foothills.

Introduction Lymphocytic thyroiditis is an autoimmune disorder and one of the major causes of hypothyroidism. On cytomorphology, it is characterized by follicular destruction by lymphocytes with elevated biochemical markers, including a panel of autoantibodies against thyroid antigens. This study aimed to determine the prevalence of various cytological features of lymphocytic thyroiditis and their correlation with clinical presentation and biochemical parameters. Materials and methods We conducted a hospital-based cross-sectional study of 105 patients diagnosed with lymphocytic thyroiditis on cytology at our tertiary care center in the Himalayan foothills from December 2018 to December 2019. We recorded and analyzed baseline demographic characteristics, clinical features, and biochemical parameters to assess correlations between cytological findings and grades. Results The study included 105 patients with lymphocytic thyroiditis (90 females, 15 males). The study population age ranged from 11 years to 80 years, with the disease most common in patients aged 21 to 40 years. Grade II was the most common cytological presentation (n=65, 62%). Thyroid-stimulating hormone levels were elevated in 33.3% of cases, and anti-thyroid peroxidase levels were elevated in all 25 cases for whom data were available (p>0.05). Conclusion Cytological diagnosis of lymphocytic thyroiditis was compatible in all cases in the study. However, cytological grading did not correlate with the clinical presentation and biochemical parameters. The diagnosis of lymphocytic thyroiditis could be missed if clinicians use clinical findings and biochemical parameters alone.

Expression of Human epidermal growth factor receptor 2, Survivin, Enhancer of zeste homolog -2, Cyclooxygenase-2, p53 and p16 molecular markers in Gall bladder carcinoma.

INTRODUCTION: Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging. MATERIALS AND METHODS: This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry. RESULTS: Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 - 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ2 = 9.886, P = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ2 = 7.017, P = 0.037 and χ2 = 5.861, P = 0.033) respectively. CONCLUSIONS: The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.