Association of Thyroid Function and Severity of Illness in Liver Cirrhosis as Measured by Child-Pugh Score.

Objective The main aim of this study is to understand the existing knowledge gap between thyroid function tests and the severity of liver cirrhosis as measured by the Child-Pugh score. Materials and methods This is a cross-sectional study conducted on 100 patients diagnosed with cirrhosis of liver. Serum triiodothyronine (free T3), thyroxine (free T4), and thyroid stimulating hormone (TSH) levels were measured, and the severity of liver cirrhosis was measured by Child-Pugh score and statistical analysis were done to investigate the association of free T3, free T4 and TSH levels with Child-A, Child-B, and Child-C severity groups. Results The results revealed that there is a statistically significant positive correlation between TSH levels and Child-Pugh score, whereas a statistically significant negative correlation was associated between free T3 (fT3), free T4 (fT4) levels, and Child-Pugh Score. Further, we also observed that the Child-C group has 7.5-fold risk of increased TSH levels (odds ratio {OR} = 7.553, 95% CI = 2.869-19.883, p = 0.000), has 5-fold risk of decreased fT3 levels (OR = 5.023, 95% CI = 1.369-18.431, p = 0.009) and has 6.4-fold risk of decreased fT4 levels (OR = 6.402, 95% CI = 2.516-16.290, p = 0.000). Conclusion Our results demonstrated that there is a positive and direct correlation associated between increasing TSH with severity of liver cirrhosis as measured by Child-Pugh score, whereas a negative and inverse correlation was observed between decreasing fT3 and fT4 levels with the severity of liver cirrhosis as measured by Child-Pugh score. This suggests that the Child-Pugh score can be used as a prognostic indicator in cirrhotic patients.

The Association Between Microalbuminuria and QTc Prolongation in Patients With Type 2 Diabetes Mellitus: A Single-Centre Study From South India.

BACKGROUND: One of the most significant complications of type 2 diabetes mellitus (T2DM) is diabetic nephropathy, the leading cause of end-stage renal disease. Another important clinical marker in patients with type 2 diabetes is QTc interval prolongation. We aimed to study the association between QTc interval prolongation and microalbuminuria in patients with T2DM. OBJECTIVE: The primary objective of this study was to examine the association between QTc interval prolongation and microalbuminuria in patients with T2DM. The secondary objective was to correlate the prolongation of the QTc interval with the duration of T2DM. MATERIALS AND METHODS: This study was conducted as a single-centre, prospective, observational study in a tertiary-care centre in South India, Amrita Institute of Medical Sciences and Research Center. The study was conducted over two years, between April 2020 and April 2022. Patients aged more than 18 with T2DM with and without microalbuminuria were recruited into the study and control groups, and various parameters, including QTC intervals, were recorded. RESULTS: A total of 120 patients were enrolled in the study, with 60 patients with microalbuminuria forming the study group and 60 patients without microalbuminuria forming the control group. There was a statistically significant association between microalbuminuria with a prolonged QTc interval, hypertension, a longer duration of T2DM, higher haemoglobin AIc (HbA1c) levels, and higher serum creatinine values.

Cytochrome P450 2C19 Polymorphisms and Its Association With Major Adverse Cardiac Events in Post-coronary Intervention Patients on Clopidogrel in the Tertiary Care Center.

Background Clopidogrel has become essential in managing coronary artery disease and other atherothrombotic diseases. It is an inactive prodrug that needs biotransformation in the liver by various cytochrome P (CYP) 450 isoenzymes for its active metabolite formation. However, 4-30% of patients on clopidogrel have shown no or decreased antiplatelet response. This condition is called 'clopidogrel non-responsiveness' or 'clopidogrel resistance.' This is attributed to genetic heterogeneity causing interindividual variation and increased risk of major adverse cardiac events (MACEs). This study aimed to assess MACEs and their association with CYP450 2C19 polymorphisms in post-coronary intervention patients on clopidogrel. Methods This prospective observational study was conducted on acute coronary syndrome patients, started on clopidogrel following coronary intervention. After considering inclusion and exclusion criteria, 72 patients were enrolled, and a genetic analysis was done. Based on genetic analysis, patients were divided into two groups, normal (CYP2C19*1) and abnormal phenotypes (CYP2C19*2 & *3). These patients were followed for two years, and the MACE during the first year and second year was compared between these two groups. Results Of 72 patients, 39 (54.1%) were normal, and 33 (45.8%) were abnormal genotypes. The mean age of patients is 67.71 ± 9.968. A total of 19 and 27 MACEs were seen during first- and second-year follow-ups. During the first-year follow-up, three (9.1%) patients with abnormal phenotypes developed ST-elevation myocardial infarction (STEMI), and none of the phenotypically normal patients developed STEMI (p-value = 0.183). Non-ST elevation myocardial infarction (NSTEMI) was seen in three (7.7%) normal and seven (21.2%) abnormal phenotype patients (p-value=0.19). Other events, such as thrombotic stroke, stent thrombosis, and cardiac death, were seen in two (6.1%) abnormal phenotypic patients (p-value=0.401). During the second-year follow-up, STEMI was seen in one (2.6%) normal and three (9.7%) abnormal phenotypic patients (p-value=0.183). NSTEMI was seen in four (10.3%) normal and nine (29%) abnormal phenotype patients (p=0.045). Comparison of total MACEs between normal and abnormal phenotypic groups at the end of the first year (p-value=0.011) and second year (p-value=<0.01) has statistical significance. Conclusion We can infer that the risk of developing a recurrent MACE in post-coronary intervention patients on clopidogrel is significantly high in the abnormal phenotypic group (CYP2C19*2 & *3) than in normal phenotypic patients.

Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus: A Single-Centre Observational Study From a Tertiary Care Hospital in South India.

Background There is a high prevalence of left ventricular diastolic dysfunction (LVDD) in patients with type 2 diabetes mellitus (T2DM). The influencing factors of LVDD in T2DM are not fully understood.  Objective This study aimed at assessing the prevalence of LVDD in T2DM as well as looking at the association between various parameters related to T2DM with LVDD in patients with T2DM. Materials and methods This was a single-centre cross-sectional study in Kerala, India. The primary objective of the study was to assess the prevalence of LVDD in T2DM. The secondary objectives were to look for an association between higher glycated haemoglobin (HbA1c), complications of T2DM, age, and gender of the patient with the presence of LVDD. Results A total of 80 patients were included in the study. There were 40 patients with LVDD with a prevalence of 50%. There was a statistically significant positive association between increased age, longer duration of diabetes, higher HbA1C, the presence of diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy with the prevalence of LVDD. A logistic regression analysis demonstrated that the presence of diabetic retinopathy is a risk factor for LVDD in the study subjects.

Microalbuminuria as an Independent Risk Factor for Developing Concentric Left Ventricular Hypertrophy in Primary Hypertension: A Single-Center Observational Study From South India.

Introduction Microalbuminuria and concentric left ventricular hypertrophy (LVH) are both associated with primary hypertension. We aimed to study the correlation between these two parameters in a cohort of patients with primary hypertension. Methods We conducted a single-center observational comparative study involving patients suffering from primary hypertension in a tertiary care hospital in the southern state of Kerala in India. Patients aged more than 18 years who were diagnosed to have primary hypertension were enrolled in the study irrespective of duration of illness or treatment status. The primary objective of the study was to assess whether microalbuminuria was an independent risk factor for concentric LVH in patients with primary hypertension. The secondary objective of the study was to study the relationship between various other studied biomarkers with concentric LVH in patients with primary hypertension. Results Microalbuminuria was found to be associated with concentric LVH in patients with primary hypertension (p=0.003). Multivariate regression analysis showed that serum creatinine, high diastolic blood pressure, and microalbuminuria appeared to be independent risk factors for concentric LVH (p<0.001, 0.016, and 0.016 respectively). Conclusions Microalbuminuria is a reliable marker for predicting the prevalence of concentric LVH in patients with primary hypertension. A high serum creatinine and high diastolic blood pressure are also independent risk factors for having concentric LVH.

Red Cell Distribution Width As a Predictor of Mortality in Patients With Sepsis.

Introduction Sepsis is a common medical condition that is associated with very high mortality and, in survivors, long-term morbidity. Conventional inflammatory markers, such as CRP, erythrocyte sedimentation rate (ESR), and white blood cell count (WBC), have proven to have a limited utility in sepsis patients by virtue of their poor sensitivity and specificity for infections. Recently, the commonly used index of red cell distribution width (RDW) has been implicated as a prognostic marker in sepsis. This study aimed at assessing the role of RDW in predicting outcomes such as mortality in patients with sepsis and to study its role as a prognostic marker. Methods This was conducted as a prospective comparative observational study over a two year period between 2018 and 2020 in a tertiary care center in South India. In total, 60 adult patients above 18 years of age who were diagnosed to have severe sepsis and septic shock were selected to be part of the study. To find the survival probability on overall survival, Kaplan-Meier analysis was used and a comparison was done using the Log-rank test. To find the most significant predictors of mortality, cox regression analysis was applied. Results A total of 60 patients (n=60) were enrolled in this study out of which 30 (50%) patients had a rise in RDW and 30 (50%) patients had a fall in RDW. A total of 17 (28.3%) patients died during this study. In the rise in RDW group, there were 12 (40%) deaths while in the fall in the RDW group, there were five (16.7%) deaths. There was a statistically significant association found between mortality with rise and fall in RDW (p<0.05). A cox multivariate regression analysis demonstrated statistically significant associations between a rise in RDW (p<0.05, HR: 5.6, CI 1.4 to 21.9) and serum hemoglobin < 13.6 g/dL (p<0.05, HR: 3.6, CI 1.1 to 11.4) with mortality in this study. Kaplan-Meier analysis of rise and fall in RDW with survival trended towards better survival outcomes in the fall in the RDW group but was not significant (p=0.07). Conclusion We found that an increase in RDW from baseline during the initial 72 hours after admission is significantly associated with adverse clinical outcomes including mortality. The mortality in the rise in the RDW group, as well as overall mortality, were significantly higher than the mortality in the reduced RDW group. Hence, serial RDW measurements could be used as a prognostic factor in severe sepsis and septic shock.

Diagnostic Value and Prognostic Use of Presepsin Versus Procalcitonin in Sepsis.

BACKGROUND: Sepsis is a medical problem beyond belief despite the use of modern antibiotics and frequently updated guidelines on resuscitation therapies. It is at this crucial juncture where inflammatory biomarkers have been providing an incredible and easy way to detect sepsis. Various biomarkers have been used over the past decades in medicine to evaluate sepsis, each one better than the previous and having its own pros and cons. In this study, we assess the role of presepsin, which is a CD-14 polypeptide, and procalcitonin which has for some time been the inflammatory marker of choice in sepsis. This is the first study of presepsin as a sepsis biomarker in Indian adults. METHODS: A prospective observational study was conducted in 48 patients who were diagnosed to have sepsis either on admission to the hospital or during their stay in hospital according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) guidelines during the period from October 2015 to January 2017, after fulfilling all inclusion and exclusion criteria. Efficacy of both inflammatory markers was studied from blood drawn from the patient at the same time, with the same prick. RESULTS: A total of 48 patients were included in this study. The superiority of presepsin over procalcitonin was evident with presepsin having a sensitivity of 46.2 and specificity of 100 and procalcitonin having a sensitivity of 46.2 and specificity of 31.8. The P value of the presepsin results was significant at <0.001. Along with it, presepsin also proved to be a very reliable marker for 28-day mortality with all 12 patients in the presepsin positive group expiring (P value: <0.001). Receiver operating characteristic (ROC) curve was plotted to try and define an optimal normal value for presepsin in an Indian population and the value calculated was 93.71 with a sensitivity of 65.4 and a specificity of 68.2. CONCLUSION: This study shows the superiority of presepsin over procalcitonin as it has much better specificity and a similar sensitivity than procalcitonin and is a better indicator of 28-day mortality. The new cut off that we have postulated here for presepsin improves the efficiency of the inflammatory marker by increasing its sensitivity at the cost of decreasing its specificity slightly.

Enhanced selective cellular uptake and cytotoxicity of epidermal growth factor-conjugated liposomes containing curcumin on EGFR-overexpressed pancreatic cancer cells.

Pancreatic cancer is one of the most malignant cancers with a high mortality rate. Some types of pancreatic cancer cells overexpress epidermal growth factor receptor (EGFR), which is a potential target for anticancer agents. In this study, we examined the effect of epidermal growth factor (EGF)-conjugated liposomes containing curcumin (EGF-LP-Cur) on three different EGFR-expressed human pancreatic cancer cell lines, BxPC-3, Panc-1 and Mia Paca-2. We have demonstrated that it is feasible to prepare liposomal vesicles of EGF-LP-Cur and that it is stable in the liquid vehicle at ambient conditions for three weeks. In addition, the formulation of curcumin had higher cytotoxicity on BxPC-3 than on any other cells. It is also shown that the cellular uptake of curcumin on BxPC-3, which is essential for the cytotoxicity, is associated with EGFR-mediated mechanism of action. In summary, our results have showed that targeting EGFR with EGF-conjugated curcumin liposomes enhanced the antitumor activity of curcumin against human pancreatic cancer cells.

El Nino Southern Oscillation (ENSO) impact on tuna fisheries in Indian Ocean.

El Nino Southern Oscillation (ENSO) is an important driver of interannual variations in climate and ecosystem productivity in tropical regions. However, detailed information about this important phenomenon of the Indian Ocean is scarce. Consequently, the objective of this study is to improve understanding of the impact of warm event El Nino and cool event La Nina on annual tuna landings from the Indian Ocean from 1980 to 2010. In this study, maximum tuna landings were recorded during a weak El Nino year (1456054 t in 2006) and during a weak La Nina year (1243562 t in 2000), although the lowest tuna catch was followed during the strong El Nino year (1204119 t in 2009) and during a strong La Nina year (706546 t in 1988). Validation of predicted tuna landings and SST were showing a significant positive correlation (p < 0.01) was observed all the major tuna species except Southern Bluefin Tuna. Whereas the other relationships such as sea level pressure, Wind actions; Zonal Wind (U), Meridonial Wind (V), and Scalar Wind (W) are less well-defined. In contrast with principal component analysis we find that Principal Components 1 explains 75.5% of the total variance and suggest that sea surface temperature plays a major role in determining tuna availability in the region especially during warm event El Nino years; landings in Indian Ocean tend to be optimum SST 25 to 26°C in ENSO event. Our results confirm the ENSO impact on climate, tuna abundance and production in the Indian Ocean. However, among the oceanic variables SST explained the highest deviance in generalized additive models and therefore considered the best habitat predictor in the Indian Ocean followed by sea level pressure and Winds (U, V, W).

Science and technology of the emerging nanomedicines in cancer therapy: A primer for physicians and pharmacists.

Nanomedicine, the medical applications of devices based on nanotechnology, promises an endless range of applications from biomedical imaging to drug and gene delivery. The size range of the nanomaterials is strictly defined as 1-100 nm, although many marketed nanomedicines are in the submicron range of 100-1000 nm. The major advantages of using nanomaterials as a carrier for anticancer agents are the possibility of targeted delivery to the tumor; their physical properties such as optical and magnetic properties, which can be exploited for developing contrast agents for tumor imaging; their ability to hold thousands of molecules of a drug and deliver at the required site and also the ability to overcome solubility and stability issues. Currently, there are several nanotechnology-enabled diagnostic and therapeutic agents undergoing clinical trials and a few already approved by Food and Drug Administration. Targeted delivery of anticancer agents is achieved by exploiting a unique characteristic of the rapidly dividing tumor cells called "the enhanced permeability and retention effect." Nanoparticles with mean diameter between 100 and 200 nm or even above 200 nm have also been reported to be taken up by tumor cells via the enhanced permeability and retention effect. In addition to this passive targeting based on size, the nanoparticle surface may be modified with a variety of carefully chosen ligands that would interact with specific receptors on the surface of the tumor cells, thus imparting additional specificity for active targeting. Regional release of a drug contained in a nanoparticulate system by the application of external stimuli such as hyperthermia to a thermosensitive device is another innovative strategy for targeted delivery. Nanoparticles protect the enclosed drug from rapid elimination from the body, keep them in circulation for prolonged periods and often evade expulsion by the efflux pump mechanisms, which also leads to avoidance of development of resistance. This review focuses on the science and technology of Food and Drug Administration-approved cancer nanomedicines such as Abraxane, Doxil, DaunoXome and those drug-delivery systems that have reached an advanced stage of clinical development utilizing liposomes, albumin nanospheres, thermosensitive devices and gold nanoshells.

Prescribing patterns and utilization of antimicrobial drugs in a tertiary care teaching hospital of a Caribbean developing country.

This study aimed to evaluate the prescribing practices and utilization of antimicrobials in a tertiary care teaching hospital of a Caribbean developing country. A prospective observational cohort study was undertaken for a period of 12 weeks in the general wards and the intensive care unit (ICU) of the hospital. Demographic data, diagnoses on admission, antimicrobials prescribed, dosage and duration, route of administration, leukocyte count and microbiological culture and sensitivity reports were recorded. Hospital length of stay and final outcome were recorded. The usage was determined in terms of prescribed daily dose and the total costs of antimicrobials were calculated. Of 889 patients admitted, 335 (37.7 percent) received 22 different antimicrobial drugs. Overall, 67 percent of the prescriptions adhered to the hospital protocol. Median length of stay in the hospital was 7 days. Skin and soft tissue infections were the most common diagnoses for which antimicrobials were prescribed. Amoxicillin-clavulanate was the most common (32 percent) antimicrobial used. Eighty-nine percent of the antimicrobials were given through the intravenous route. Sixty percent of the patients received two antimicrobials, 26 percent received three, and 14 percent of patients were prescribed four or more antimicrobials during their stay at the hospital. There was significantly higher inappropriate choice of antimicrobials in ICU when compared with general wards (Mantel-Haenszel Odds Ratio 3.3; 95 percent Confidence Intervals 1.4, 7.7). Prescribing patterns did not strictly adhere to the hospital antimicrobial protocol. There is a need for monitoring and control of antimicrobial prescription.

Prescribing patterns and utilization of antimicrobial drugs in a tertiary care teaching hospital of a Caribbean developing country.

This study aimed to evaluate the prescribing practices and utilization of antimicrobials in a tertiary care teaching hospital of a Caribbean developing country. A prospective observational cohort study was undertaken for a period of 12 weeks in the general wards and the intensive care unit (ICU) of the hospital. Demographic data, diagnoses on admission, antimicrobials prescribed, dosage and duration, route of administration, leukocyte count and microbiological culture and sensitivity reports were recorded. Hospital length of stay and final outcome were recorded. The usage was determined in terms of prescribed daily dose and the total costs of antimicrobials were calculated. Of 889 patients admitted, 335 (37.7%) received 22 different antimicrobial drugs. Overall, 67% of the prescriptions adhered to the hospital protocol. Median length of stay in the hospital was 7 days. Skin and soft tissue infections were the most common diagnoses for which antimicrobials were prescribed. Amoxicillin-clavulanate was the most common (32%) antimicrobial used. Eighty-nine percent of the antimicrobials were given through the intravenous route. Sixty percent of the patients received two antimicrobials, 26% received three, and 14% of patients were prescribed four or more antimicrobials during their stay at the hospital. There was significantly higher inappropriate choice of antimicrobials in ICU when compared with general wards (Mantel-Haenszel Odds Ratio 3.3; 95% Confidence Intervals 1.4, 7.7). Prescribing patterns did not strictly adhere to the hospital antimicrobial protocol. There is a need for monitoring and control of antimicrobial prescription.

Prescribing patterns and utilization of antimicrobial drugs in a tertiary care teaching hospital of a Caribbean developing country

This study aimed to evaluate the prescribing practices and utilization of antimicrobials in a tertiary care teaching hospital of a Caribbean developing country. A prospective observational cohort study was undertaken for a period of 12 weeks in the general wards and the intensive care unit (ICU) of the hospital. Demographic data, diagnoses on admission, antimicrobials prescribed, dosage and duration, route of administration, leukocyte count and microbiological culture and sensitivity reports were recorded. Hospital length of stay and final outcome were recorded. The usage was determined in terms of prescribed daily dose and the total costs of antimicrobials were calculated. Of 889 patients admitted, 335 (37.7%) received 22 different antimicrobial drugs. Overall, 67% of the prescriptions adhered to the hospital protocol. Median length of stay in the hospital was 7 days. Skin and soft tissue infections were the most common diagnoses for which antimicrobials were prescribed. Amoxicillin-clavulanate was the most common (32%) antimicrobial used. Eighty-nine percent of the antimicrobials were given through the intravenous route. Sixty percent of the patients received two antimicrobials, 26% received three, and 14% of patients were prescribed four or more antimicrobials during their stay at the hospital. There was significantly higher inappropriate choice of antimicrobials in ICU when compared with general wards (Mantel-Haenszel Odds Ratio 3.3; 95% Confidence Intervals 1.4, 7.7). Prescribing patterns did not strictly adhere to the hospital antimicrobial protocol. There is a need for monitoring and control of antimicrobial prescription.