Evaluation of alpha-defensins as a marker of severity in chronic obstructive pulmonary disease.

BACKGROUND: Defensins are key effector molecules of innate immunity that can contribute towards the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). The present study was conducted to investigate the role of alpha-defensins in patients with COPD by quantifying serum and sputum samples. METHODS: A total of 180 patients were enrolled and divided into four groups, and sputum and serum values of alpha-defensins were assessed. The sensitivity, specificity, and accuracy of sputum alpha-defensin as a diagnostic biomarker were evaluated to assess its utility in diagnosing COPD. RESULTS: The mean value of sputum alpha-defensins was found to be statistically significant amongst the four groups (P < 0.001). The highest levels were found in subjects with AECOPD (385.76 ± 116.62 ng/mL). Sputum alpha-defensins were found to be negatively correlated with FEV 1 values (rho = -0.31, P < 0.001). CONCLUSION: Sputum alpha-defensins can be used as a potential marker for predicting acute exacerbation of COPD. In addition, they could serve as an indicator of disease severity in COPD patients.

Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study.

INTRODUCTION: The objective of this study was to compare the effects of teneligliptin-based regimens and other gliptin-based regimens with respect to insulin resistance and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: We enrolled T2DM subjects, inadequately controlled with metformin and glimepiride and taking one of the gliptins, and divided them into two groups, i.e. group 1 (teneligliptin-based regimens) and group 2 (other gliptin-based regimens). Fasting plasma insulin, adiponectin levels, homeostatic model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were measured and compared. Costs of different gliptins were noted, and mean cost of per day therapy was compared. RESULTS: Eighty-six subjects participated in this study (43 each in group 1 and group 2). No significant differences were observed in FBG, HbA1c, insulin levels, and HOMA-IR, but the trend was in favor of teneligliptin-based regimens. A significantly higher number of subjects achieved HbA1c target in group 1 (P < 0.001). Teneligliptin had significantly lower cost of per day therapy as compared to other dipeptidyl peptidase-4 inhibitors. CONCLUSION: Teneligliptin seems to be cost-effective and safer option in T2DM subjects who were not adequately controlled with metformin and sulfonylureas. However, further prospective studies are needed.

Population pharmacokinetics of ciprofloxacin in newborns with early onset neonatal sepsis and suspected meningitis.

BACKGROUND: Neonatal Sepsis accounts for significant proportion of neonatal mortality globally. Ciprofloxacin can be used as an effective antimicrobial against common causative agents of neonatal sepsis. However, there is only limited information about its pharmacokinetic distribution in plasma and Cerebrospinal fluid (CSF) of neonates. METHODS: Plasma and CSF samples were taken using a sparse sampling technique from neonates who received at least one dose of intravenous ciprofloxacin. Ciprofloxacin levels were analysed using high-performance liquid chromatography (HPLC). Population pharmacokinetic analysis was conducted using a non-linear mixed-effects modelling using Pumas® (Pharmaceutical Modelling and Simulation) package (Version 2.0). RESULTS: 53 neonates were enroled in the study of whom; 9 (17%) had meningitis. The median concentration of ciprofloxacin in CSF was 1.4 (0.94-2.06) ug/ml and plasma was 2.94 (1.8-5.0) ug/ml. A one-compartment model with first-order elimination fitted the data. Body weight was found to be a significant covariate on volume of distribution (Vd). Simulations based on the final model suggest that dose of 10 mg/kg, intravenous b.d may not be able to achieve the desirable indices. CONCLUSIONS: One compartment model with weight as a covariate explained the available data. Further studies with modified sampling strategy, larger sample size and variable dose levels are needed.

Serial evaluation of antibody titres in patients recovered from COVID-19 and their correlation with disease severity.

On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic. According to the findings of various studies conducted around the world, the serological response varies greatly among different populations, with the determinants of variable response still unknown, including the role of disease severity, which is thought to have a definite correlation. The purpose of this study was to assess serial SARS-CoV-2 IgG antibody response in COVID-19 patients and correlate it with disease severity. It was a longitudinal observational study in which 45 patients (age >18 yrs), were enrolled who had recovered from COVID-19 and were reporting to the post-COVID Care OPD Clinic. Patients who had been on long-term immunosuppressive therapy prior to SARS-CoV-2 infection were not eligible. All patients had not been immunized against SARS-CoV-2 and had no history of contact with recent COVID-19 cases. The patients underwent serial blood tests to determine serum IgG titers specific for SARS-CoV-2 at 30, 60, and 90 days after being diagnosed with COVID-19. Chemiluminescence was used to perform a semi-quantitative evaluation of the SARS-CoV-2 IgG antibody. At 30 days after confirmed SARS-CoV-2 infection, 98.78% had detectable serum IgG levels, and sero-reversion (loss of previously detectable antibodies) occurred in 2.5% at 60 days and 90 days. Serum IgG was found to peak at 30 days out of the three time points of measurement (30, 60, and 90 days from diagnosis). Serum IgG levels at 90 days were significantly lower than those at 30 days (p<0.0001) and 60 days (p=0.002). The current study's findings shed light on the presence and persistence of serum SARS-CoV-2-specific IgG antibodies following a natural infection. The findings point to a long-lasting immune response with increasing severity of initial COVID-19 disease.

Rates and determinants of fast chronic kidney disease progression distinguished by nutritional status, and the impact of malnutrition on mortality - evidence from a clinical population.

BACKGROUND & AIMS: Malnutrition is a serious problem that influences morbidity, mortality, functional activity, and quality of life in patients with chronic kidney disease (CKD). However, there has not been much research done on how nutritional status appears to affect mortality in non-dialysis CKD patients. This study aimed to recognize the rates and predictors of fast CKD progression distinguished by nutritional status, and also sought to determine the impact of malnutrition on mortality in non-dialysis CKD patients. METHODS: This prospective cohort study (n = 360) involved non-dialysis CKD patients with index estimated glomerular filtration rate (eGFR) between the range of 15-89 ml/min/1.73 m2. Nutritional status was evaluated by using the "Pt-Global web tool/PG-SGA". A loss of eGFR >4 ml/min/1.73 m2 per year was considered to be a sign of fast CKD progression. Kaplan-Meier plots were used to evaluate the cumulative survival, and Cox-proportional hazard models were used to analyze the renal outcomes. RESULTS: Around 244 (67.8%) of patients have experienced a fast decline in kidney function. In the malnourished group, systolic blood pressure and hyperphosphatemia were observed to have increased hazards for fast CKD progression. The overall incidence of mortality and composite endpoints were found to be 13.9% & 37.6%, respectively. Death rates (11.6%) and composite endpoints (29.8%) were higher in the malnourished (severe & moderate) group. Cox regression hazard model reported 4 times increased hazards for death [HR 4.41 (1.99-9.77) 95% CI; P ≤ 0.005] and 3 times increased hazards for composite endpoints [HR 3.29 (2.10-5.16) 95% CI; P ≤ 0.005] for 'severely malnourished' category in reference to 'normal nutrition' category. CONCLUSIONS: Fast CKD progression was observed to be more common in malnourished patients. Systolic blood pressure and hyperphosphatemia were recognized as potential predictors of fast CKD progression. Moreover, malnutrition was found to be a significant predictor of mortality among non-dialysis CKD patients. The findings of this study advocate for early nutritional evaluation and timely dietary interventions to halt the progression of CKD.

Association of blood donor characteristics and in vitro haemolysis of packed red blood cell concentrates during storage.

BACKGROUND AND OBJECTIVES: Blood donor variability can affect the storage properties of packed red blood cells (PRBCs). This study aimed to determine the association of donor characteristics with in vitro storage haemolysis of PRBCs. MATERIALS AND METHODS: In the prospective observational study, a total of 109 whole blood donors were enrolled using the purposive sampling method. A pre-donation sample was collected for haemoglobin (Hb) and serum uric acid (UA) levels. PRBC aliquots were tested for potassium, lactate dehydrogenase (LDH), Hb, haematocrit, plasma Hb and haemolysis on days 1, 21 and 35 of storage. The association of these parameters with donor age, sex, donation status, dietary pattern and body mass index was determined. RESULTS: Mean haemolysis was significantly higher in PRBCs from donors with UA levels ≤6 mg/dL than donors with UA levels >6 mg/dL on day 35 of storage (0.22 ± 0.11 vs. 0.18 ± 0.07, p = 0.03). Median plasma Hb (mg/L) was significantly higher in PRBCs from first-time donors on day 21 (586 vs. 509, p = 0.05) and day 35 (1507 vs. 1358, p = 0.02) of storage in comparison to frequent donors. Significantly higher mean potassium (p = 0.04 day 1; p = 0.02 day 21) and median LDH values (p = 0.02 day 1, p = 0.05 day 21) were observed in PRBCs from male donors. A statistically significant positive association was observed between donor UA and LDH levels of PRBCs on day 35 of storage (ß coefficient: 715.52, p-value: 0.003) on multiple regression analysis. CONCLUSION: In vitro haemolysis of PRBCs is affected by blood donor characteristics.

Nutritional status, symptom burden, and predictive validity of the Pt-Global web tool/PG-SGA in CKD patients: A hospital based cross sectional study.

BACKGROUND: Despite not being frequently recognized, malnutrition, a consequence of chronic kidney disease, negatively affects morbidity, mortality, functional activity, and patient's quality of life. Management of this condition is made more difficult by the dearth of knowledge regarding the symptom burden brought on by inadequate nutritional status. Additionally, there are multiple tools to evaluate nutritional status in CKD; but, Pt-Global web tool/PG-SGA used in oncology, has not been investigated in chronic kidney disease patients. This study aimed to explore the nutritional status, symptom burden and also investigate the predictive validity of Pt-Global web tool/PG-SGA among pre-dialysis diabetic and non-diabetic chronic kidney disease patients. METHODOLOGY: This cross-sectional study was carried out at a renal clinic of a tertiary care public teaching hospital. Nutritional status and symptom burden was evaluated by employing a 'Pt-Global web tool/PG-SGA' which is considered as a preeminent interdisciplinary tool in oncology and other chronic catabolic conditions. The predictive validity of the Pt-Global web tool/PG-SGA, referred as overall score for malnutrition was ascertained using Receiver Operating Curves (ROC). The conclusions were drawn using descriptive statistics, correlation, and regression analysis. RESULTS: In a sample of 450 pre-dialysis CKD patients, the malnutrition was present in 292(64.9%) patients. Diabetic CKD patients exhibit higher proportion of malnutrition 159(35.3%). The prevalence of malnutrition was exacerbated by eGFR reduction. The overall Pt-Global web tool/PGA-SGA score was significantly influenced by the symptoms of fatigue (81.5%), appetite loss (54.8%), physical pain (45.3%), constipation (31.78%), dry mouth (26.2%), and feeling full quickly (25.8%). The ROC analysis showed that the AUC for the total PG-SGA score was 0.988 (95% CI: 0.976-1.000), indicating that it is a reliable indicator of malnutrition. The sensitivity (84.2%) for identifying malnutrition was low when using the conventional tool cut off score of ≥9. Instead, it was discovered that a score of ≥3 had a greater sensitivity (99.3%) and specificity (44.3%) and was therefore recommended. CONCLUSIONS: This study not only presents empirical evidence of poor nutritional status in CKD patients but also reveals that it is worse in patients with diabetes, hypoalbuminemia, and poorer kidney function (well recognized risk factors for cardiovascular disease). Early diagnosis and management of symptoms contributing malnutrition will reduce mortality and CKD progression. The Pt-Global web tool/PG-SGA total score of 3 or more appears to be the ideal cut off score for identifying malnutrition, which can be utilized by dietician for improving malnutrition.

Relationship Between Statin-associated Muscle Symptoms, Serum Vitamin D and Low-density Lipoprotein Cholesterol - A Cross-sectional Study.

INTRODUCTION: Statin-associated muscle symptoms (SAMS) can lead to medication non-adherence among statin users. There is a complex relationship between SAMS, vitamin D and low-density lipoprotein cholesterol (LDL-C). The objective of this study was to evaluate the relationship between vitamin D, LDL-C and occurrence of SAMS. METHODS: This was a cross-sectional study in patients using statins. Thorough patient histories were taken, a clinical examination was conducted and SAMS were recorded. Levels of vitamin D, creatine phosphokinase (CPK) and LDL-C were measured. These parameters were compared amongst statin users with SAMS and those without SAMS. Levels of vitamin D and LDL-C were converted into percentiles and their relationship with SAMS was evaluated in terms of odds ratio. Receiver operating characteristics (ROC) were drawn, taking vitamin D and LDL-C as predictors of SAMS. RESULTS: A total of 121 statin users were enrolled in this study. Thirty-eight patients (31.4%) presented with SAMS. Significantly lower levels of serum vitamin D were observed amongst statin users with SAMS compared with those without SAMS (19.8 ± 9.67 ng/mL versus 25.0 ± 14.6 ng/mL; 95% confidence interval -10.4 to -0.07; p=0.04). With vitamin D levels less than or equal to 5th, 10th and 25th percentile, the chances of occurrence of SAMS were significantly higher, but not at the 50th percentile (corresponding vitamin D level of 20.21 ng/mL). LDL-C did not show any conclusive relationship with SAMS. ROC curves showed a significant discrimination for vitamin D levels, but not for LDL-C. CONCLUSION: Statin users with low levels of vitamin D are at increased risk of developing SAMS. However, LDL-C status of statin users failed to predict any meaningful association with SAMS. Given the small sample size of this study, these results should be regarded as preliminary.

Association of Adiponectin with Lung Function Impairment and Disease Severity in Chronic Obstructive Pulmonary Disease.

CONTEXT: Chronic obstructive pulmonary disease (COPD) is not only restricted to the pulmonary inflammation and airway obstruction but is also associated with comorbidities, which affect the therapeutic intervention and the quality of life and survival. Markers that can predict the systemic inflammation and a decline in the pulmonary function are of scientific interest. Adiponectin (APN) appears to be one such biomarker and can be used as a potential indicator of severity and response to treatment in patients of COPD. AIMS: The study aims to find out the role of APN as a marker of inflammation in the pathogenesis of COPD and explore its relationship with the severity of the disease. SETTINGS AND DESIGN: This was a cross-sectional study. SUBJECTS AND METHODS: The study group consisted of 60 patients of COPD, which included 30 males admitted with acute exacerbation of COPD (AECOPD) and 30 males with stable COPD. The study group was compared with 30 healthy, age-matched males. APN was estimated by commercially available ELISA kits. Pulmonary function tests were performed on all cases and controls using standardized protocols on SPIROLAB III. STATISTICAL ANALYSIS USED: Statistical analysis was performed using Student's t-test and Pearson's correlation coefficient. RESULTS: The levels of APN were found to be significantly higher in patients with COPD as compared to the controls and the levels increased with the severity of the disease were 16.10 ± 4.97 ng/ml and 11.43 ± 4.22 ng/ml, respectively, in AECOPD and COPD. A significant positive correlation was found between the levels of APN and interleukin (IL)-8 in patients of COPD, while the levels correlated negatively with percentage of forced expiratory volume in 1 s (FEV1%). CONCLUSIONS: The results reveal that APN is associated with the inflammatory process of COPD as suggested by its significant inverse relationship with FEV1% and positive correlation with a marker of inflammation such as IL-8. It can thus be used as a biomarker for disease severity and progression in patients of COPD, therefore aiding in risk stratification and therapeutic intervention.

Role of serum adenosine deaminase in pulmonary tuberculosis.

BACKGROUND: Definitive laboratory diagnosis and confirmation of tuberculosis remains a major challenge because of lack of specificity and sensitivity of diagnostic methods especially in sputum smear negative tuberculosis. Many studies have proved the role of ADA in diagnosis of tuberculosis in effusion fluids and a decrease in ADA activity after treatment. This study was aimed to investigate the role of serum ADA level as an early diagnostic and prognostic marker for pulmonary tuberculosis (PTB). MATERIAL AND METHODS: This was a cohort study done on patients visiting the OPD Clinics of the department of Pulmonary Medicine at GMCH, Chandigarh. 50 sputum positive and 50 sputum negative tuberculosis patients and 100 controls were recruited. Serum ADA levels were measured at the start of treatment and again after two months of treatment. Its correlation with severity of disease was seen. RESULTS: Mean serum ADA (IU/L) was found to be 35.293±30.941 in PTB patients and 11.819±8.023 in control groups and the difference was found to be highly significant (P<0.00). Mean ADA was 31.107±29.32 in sputum positive patients, 39.478±32.22 in sputum negative and 11.819±8.0235 in control groups. No statistically significant difference was observed amongst sputum positive and sputum negative patients. The levels decreased significantly after intensive phase of treatment. At the cut off values of 14.6IU/L, serum ADA had 78% sensitivity and 76% specificity (AUC=0.801, P value<0.00) to differentiate between PTB from healthy controls. CONCLUSION: Serum ADA levels may be used as a biomarker for diagnosis of PTB and to evaluate the response to treatment at follow up.

Concept maps: A tool for knowledge management and synthesis in web-based conversational learning.

Web-based conversational learning provides an opportunity for shared knowledge base creation through collaboration and collective wisdom extraction. Usually, the amount of generated information in such forums is very huge, multidimensional (in alignment with the desirable preconditions for constructivist knowledge creation), and sometimes, the nature of expected new information may not be anticipated in advance. Thus, concept maps (crafted from constructed data) as "process summary" tools may be a solution to improve critical thinking and learning by making connections between the facts or knowledge shared by the participants during online discussion This exploratory paper begins with the description of this innovation tried on a web-based interacting platform (email list management software), FAIMER-Listserv, and generated qualitative evidence through peer-feedback. This process description is further supported by a theoretical construct which shows how social constructivism (inclusive of autonomy and complexity) affects the conversational learning. The paper rationalizes the use of concept map as mid-summary tool for extracting information and further sense making out of this apparent intricacy.

Assessment for learning with Objectively Structured Practical Examination in Biochemistry.

CONTEXT: Despite a radical shift in assessment methodologies over the last decade, the majority of medical colleges still follow the Traditional Practical Examination (TPE). TPE raises concerns about examiner variability, standardization, and uniformity of assessment. To address these issues and in line with the notion of assessments as motivating what and how students learn, Objectively Structured Practical Examination (OSPE) was introduced, as an assessment modality. Despite its usefulness, awareness and motivation to use the same, still needs to be probed. AIMS: To implement OSPE in the assessment of practical skills in biochemistry, and to know student and faculty perspectives regarding OSPE. SETTINGS AND DESIGN: OSPE was introduced at the stage of formative assessment of practical skills, for 94 year one MBBS students. SUBJECTS AND METHODS: Students were divided into two groups; the first group was evaluated by the traditional method and the second by OSPE. Students were crossed over on a second examination. The mean score obtained by both the methods was compared statistically. Students and faculty perspectives regarding OSPE were obtained by a questionnaire. Student performance was compared using "Bland-Altman technique," and Student's t-test. RESULTS: The mean scores of students was found to be significantly higher (P < 0.0001) when assessed with OSPE as compared to TPE. Number of students achieving >70% marks was also significantly higher with OSPE. Validity was supported by a significant correlation coefficient of comparison of marks by the two methods. Feedback from students and faculty indicated that they endorsed OSPE. CONCLUSIONS: This evaluation demonstrated the need for a structured approach to assessment. Going in line with the notion that assessment drives learning, introducing OSPE would help tailoring teaching-learning to optimize student satisfaction and learning.

Mortality predictors in severe hyponatraemia in emergency inpatients.

Hyponatraemia, one of the most common electrolyte abnormality when severe (<120 meq/l), has poor prognosis and fatal outcome. Published data on identification of mortality predictors in severe hyponatraemia is however insufficient. The aim of the study was to determine the characteristics, causes and outcome of severe hyponatraemia (<120 meq/l) in hospitalised patients and to identify the mortality predictors. A retrospective case note review of patients (n=175) admitted in emergency ward of a tertiary care hospital during a period of 12 months having severely hyponatraemic (<120 meq/l) were undertaken. Both at the time of admission and those developing during their stay were included. Severe hyponatraemia was found to be common in elderly males. Aetiology was predominantly multifactorial (60.5%), and single aetiologies were mainly, congestive cardiac failure (9.7%), alcoholic liver disease (8.6%) and obstructive airway disease (7.4%). Overall mortality in study group was 25.7%. The mortality was found to be higher (30.8%) in patients developing severe hyponatraemia during hospitalisation as compared to that on admission (24.2%). Mortality was also found to be significantly (p<0.05) higher in patients whose sodium levels were not normalised after treatment. A strong relation between lowest sodium levels rather than admission sodium levels was seen. Severe hyponatraemia (<120meq/l) is a commonly encountered clinical problem, associated with a poor prognosis. The data suggest that outlook in severe hyponatraemia is governed by aetiology and by the serum sodium levels. Identification of mortality predictors should not be overlooked, as correct diagnosis of the aetiology and early recognition of risk factors is critical both to determine correct management and for better prognosis.

Lipoprotein (a) in type 2 diabetes mellitus: Relation to LDL:HDL ratio and glycemic control.

BACKGROUND: Increased lipoprotein (a) [Lp (a)] concentrations are predictive of coronary artery disease (CAD). Type 2 diabetes mellitus also leads to dyslipidemia, like elevated triglyceride levels and low HDL levels, which are known risk factors for CAD. This study was designed to investigate the levels of Lp (a) in type 2 diabetic patients and their association with LDL: HDL ratio and glycemic control. MATERIALS AND METHODS: The study included 60 patients of type 2 diabetes and 50 age and sex matched controls. The Lp(a) levels in the diabetic group were compared with the control group and the relationship between the Lp(a) levels and LDL: HDL ratio was evaluated. Diabetic group was further divided into three subgroups according to levels of glycated hemoglobin. Lp(a) levels and glycated hemoglobin in controlled and uncontrolled diabetes mellitus were also compared to find out any correlation between them. Statistical analysis was done using the students 't' test and Chi square test. RESULTS: Lp(a) levels were found to be significantly increased in the diabetic group as compared to the control group (P< 0.001). LDL: HDL ratio was also increased in the diabetic group as compared to the control group. Lp(a) levels showed no association with LDL: HDL ratio and degree of glycemic control in these patients. CONCLUSIONS: The results of the present study suggest that Lp(a) levels are increased in type 2 diabetic patients. The elevated Lp(a) levels do not reflect the glycemic status and are also independent of increase in LDL:HDL ratio suggesting different metabolic pathways and the genetic connection for LDL and Lp(a).

Antioxidant status in rheumatoid arthritis and role of antioxidant therapy.

BACKGROUND: Oxygen free radicals have been implicated as mediators of tissue damage in patients of rheumatoid arthritis (RA). This study was designed to elucidate plasma oxidant/antioxidant status in rheumatoid arthritis, with the aim of evaluating the importance of antioxidant therapy in the management of this disease. METHODS: The study included 40 patients of rheumatoid arthritis who were randomly divided into two subgroups of 20 each. One group received conventional treatment for 12 weeks and in the other group conventional treatment was supplemented with antioxidants for the same duration. Twenty age- and sex-matched normal individuals constituted the control group. Blood samples of controls and patients were collected at the time of presentation and analyzed for total thiols, glutathione, vitamin C and malondialdehyde (MDA-marker of oxidative stress). The investigations were repeated in the patients after 12 weeks. RESULTS: The blood concentrations of total thiols, glutathione and vitamin C were found to be significantly lower in rheumatoid arthritis patients as compared to healthy controls, while the concentrations of MDA were much higher. There was a statistically significant increase in the posttreatment concentrations of these antioxidants, along with a decrease in the concentrations of MDA. CONCLUSIONS: The antioxidant defense system is compromised in rheumatoid arthritis patients. There is a shift in the oxidant/antioxidant balance in favor of lipid peroxidation, which could lead to the tissue damage observed in the disease. The results suggest the necessity for therapeutic co-administration of antioxidants along with conventional drugs to such patients. However, due to the limited number of cases included in this study, more studies may be required to substantiate the results and arrive at a definite conclusion, in terms of safety and efficacy of adding on antioxidant therapy for the treatment of RA.