D-dimer - a multifaceted molecule.

D-dimer, a universally unique marker for fibrin degradation, is generated through the enzymatic interplay of thrombin, factor XIIIa, and plasmin. The emergence of D-dimer-containing fibrin molecules occurs in both intravascular and extravascular spaces during pivotal physiological processes like haemostasis, thrombosis, and tissue repair. Given the inherently physiological nature of fibrin formation and fibrinolysis, basal levels of D-dimer fragments are present in plasma. Beyond its role as a marker of routine physiological processes, aberrations in D-dimer levels are indicative of a spectrum of conditions, both non-pathological and pathological. The clinical utility of D-dimer has been firmly established, particularly in scenarios like venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). Additionally, recent applications have extended to assess the prognosis of COVID-19. While D-dimer is commonly associated with thrombotic conditions, its elevation is not confined to these conditions alone. Elevated D-dimer levels are observed across various diseases, where its significance extends beyond diagnostic indicators to prognostic implications.

Urinary lipoarabinomannan in individuals with sputum-negative pulmonary tuberculosis.

BACKGROUND OBJECTIVES: Tuberculosis (TB) is a major global cause of ill health. Sputum microscopy for confirmation of presumptive pulmonary TB (PTB) has a reportedly low sensitivity of 22-43 per cent for single smear and up to 60 per cent under optimal conditions. National TB Elimination Programme in India recommends the use of cartridge-based nucleic acid amplification test (CBNAAT) and culture for microbiological confirmation in presumptive PTB individuals with sputum smear negative test. The use of lateral flow urine lipoarabinomannan (LF-LAM) is usually recommended for the diagnosis of TB in HIV-positive individuals with low CD4 counts or those who are seriously ill. The objective of this study was to detect urinary LAM using cage nanotechnology that does not require a physiologic or immunologic consequence of HIV infection for LAM quantification in human urine in 50 HIV-seronegative sputum smear-negative PTB individuals. METHODS: To study the diagnostic value of urinary LAM in sputum smear negative PTB individuals, a cage based nanotechnology ELISA technique was used for urinary LAM in three different groups of participants. Fifty smears negative PTB clinically diagnosed, 15 smear positive PTB and 15 post TB sequel individuals. Sputum was tested by smear, CBNAAT, and culture along with urine LAM before treatment. The results were interpreted by ROC curve in comparison to the standard tests like CBNAAT and culture. RESULTS: The mean urinary LAM value was 0.84 ng/ml in 37 culture-positive [Mycobacterium tuberculosis (M.tb)] and 0.49 ng/ml in 13 culture-negative (M.tb) smear-negative individuals with PTB, respectively. In 47 smear-negative PTB cases with microbiologically confirmed TB by CBNAAT, the mean urinary LAM was 0.76 ng/ml. The mean urinary LAM in post-TB sequel individuals was 0.47 ng/ml. As per the receiver operating characteristic curve, cut-off value of urinary LAM in individuals with smear-negative PTB microbiologically confirmed by: (i) CBNAAT was 0.695 ng/ml and (ii) culture was 0.615 ng/ml. INTERPRETATION CONCLUSIONS: The findings of this study suggest that individuals with smear-negative PTB and a urinary LAM value of >0.615 ng/ml were most likely to have microbiological confirmed TB while those with a LAM value <0.615 ng/ml >0.478 ng/ml are less likely and those with a value <0.478 ng/ml are unlikely to have microbiological confirmed TB.

Diabetes mellitus in acute exacerbation of chronic obstructive pulmonary disease - the tip of the iceberg.

COPD is a chronic respiratory disease characterized by systemic inflammation caused primarily by tobacco use, and it is associated with an increased susceptibility to respiratory infections, both viral and bacterial, which are responsible for acute COPD exacerbations (AECOPD). Diabetes mellitus is one of the most common co-morbidities in COPD patients. In our study, we attempted to detect previously undiagnosed diabetes in AECOPD patients who presented to our Institute. The study included 100 patients who had been diagnosed with AECOPD. Pearson's coefficient correlation analysis was used to assess the relationship between various parameters. The vast majority of patients belonged to Group 3. (diagnosed at the time of admission as having type II diabetes). HbA1c had a significant positive correlation with BMI, cholesterol, and TLC, but a negative correlation with SpO2. Using HbA1C, nearly two-thirds of the AECOPD were newly diagnosed with diabetes mellitus. Our findings suggest that diabetes is significantly underdiagnosed in COPD patients.

Point-of-care test for tuberculosis: a boon in diagnosis.

Rapid diagnosis of tuberculosis (TB) is an effective measure to eradicate this infectious disease worldwide. Traditional methods for screening TB patients do not provide an immediate diagnosis and thus delay treatment. There is an urgent need for the early detection of TB through point-of-care tests (POCTs). Several POCTs are widely available at primary healthcare facilities that assist in TB screening. In addition to the currently used POCTs, advancements in technology have led to the discovery of newer methods that provide accurate and fast information independent of access to laboratory facilities. In the present article, the authors tried to include and describe the potential POCTs for screening TB in patients. Several molecular diagnostic tests, such as nucleic acid amplification tests, including GeneXpert and TB-loop-mediated isothermal amplification, are currently being used as POCTs. Besides these methods, the pathogenic component of Mycobacterium tuberculosis can also be utilized as a biomarker for screening purposes through immunological assays. Similarly, the host immune response to infection has also been utilized as a marker for the diagnosis of TB. These novel biomarkers might include Mtb85, interferon-γ inducible protein-10, volatile organic compounds, acute-phase proteins, etc. Radiological tests have also been observed as POCTs in the TB screening POCT panel. Various POCTs are performed on samples other than sputum, which further eases the screening process. These POCTs should not require large-scale manpower and infrastructure. Hence, POCT should be able to identify patients with M. tuberculosis infection at the primary healthcare level only. There are several other advanced techniques that have been proposed as future POCTs and have been discussed in the present article.

Prevalence of allergic bronchopulmonary aspergillosis in asthmatic patients: A prospective institutional study.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by an allergic inflammatory response to colonization by Aspergillus species, most commonly Aspergillus fumigatus. AIM: To study the prevalence of ABPA in asthmatic patients presenting to our institute. MATERIALS AND METHODS: All consecutive asthma patients attending our allergy clinic Out Patient Department (OPD) over a period of 20 months were tested with skin prick test (SPT) for Aspergillus antigens and those who were found positive were further evaluated for ABPA using Greenberger's criteria. RESULTS: Seventy consecutive asthmatic patients were screened by SPT using Aspergillus antigens. Thirteen patients (18.57%) were found to be SPT positive, out of which nine patients (12.9%) were diagnosed as having ABPA using Greenberger's criteria. ABPA was common among 25-35 age group with no gender predilection. ABPA patients had longer duration of illness, predominantly mixed pattern in PFT, higher mean absolute eosinophil count (AEC) and serum total IgE compared to non-ABPA asthmatic patients. Specific IgE for A. fumigatus was positive in all ABPA patients and serum precipitins were positive in seven patients (77.58%). Chest X-ray abnormalities were seen in five patients (55.6%) and HRCT showed central bronchiectasis in eight patients (88.9%) with varying other radiological features. None were sputum fungal culture positive and five patients (55.6%) have been misdiagnosed as pulmonary tuberculosis in the past. CONCLUSION: The prevalence of ABPA is significantly higher in bronchial asthma patients presenting to tertiary care centers and hence awareness is required among physicians for early diagnosis and management of ABPA to achieve better asthma control and to avoid permanent lung damage.

Association of inflammatory cytokines, lipid peroxidation end products and nitric oxide with the clinical severity and fetal outcome in preeclampsia in Indian women.

Preeclampsia is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. The various pathways involved in its etiology include endothelial dysfunction, inflammatory milieu, lipid peroxidation and immunological imbalance. The present study was conducted to evaluate the causative and predictive role of nitric oxide, lipid peroxidation end products (MDA) and inflammatory cytokines (IL-6, TNF-α) in clinical presentation, severity and fetal outcome in preeclampsia. The study population was divided into 3 groups- Non- pregnant females comprising the control population; G1 and G2 groups included normal pregnant and pregnant females with preeclampsia with 50 patients in each group. Nitric Oxide and MDA levels were found to be highest in the preeclamptic patients as compared to other two groups. ROC curve analysis shows the superiority of the inflammatory markers as determinants of severity of preeclampsia which suggests the emerging role of pro inflammatory markers in the various pathological changes in preeclampsia. TNF-α emerged as the best marker in multivariate analysis and thus, has the potential for being used as a marker for PIH. Our study illustrates the multifactorial etiology of preeclampsia involving oxidative stress, proinflammatory milieu and endothelial dysfunction.

Prevalence of metabolic syndrome in patients with angiographically proven coronary artery disease presenting to a tertiary care hospital in Delhi, India.

BACKGROUND: Coronary artery disease is fast emerging as the major concern for afflicting people across the globe. The Indian subcontinent is highly predisposed to this condition due to distinctive risk factor profile of this population. This fact has led to a condition where the current preventative and management protocols that have worked well in the non-Asian Indian Caucasian populations, have failed to bring about the anticipated control over the incidence and progression of CAD in Asian Indians. Metabolic syndrome has been identified as a major determinant of CAD in this population. MATERIALS AND METHODS: The prevalence of metabolic syndrome was determined in 431 patients undergoing coronary angiography through various diagnostic algorithms. The Asian modified diagnostic criteria were also implemented to estimate the metabolic syndrome prevalence in patients with different levels of stenosis. RESULTS: We observed a high incidence of metabolic syndrome in the patients with coronary artery disease. The prevalence of MS increased with increase in severity of coronary artery involvement. The IDF guideline with Asian modification was the most successful diagnostic algorithm. CONCLUSIONS: It is now imperative to acknowledge the unique pattern of CAD and risk factor profile prevalent among South Asians. This will facilitate more focused and individualized management protocols directed to this population. Metabolic syndrome is a major syndrome prevalent in this population. Hence, effective control of MS may help in reducing the morbidity and mortality due to CAD in a great way.

Paraoxonase: a multifaceted biomolecule.

BACKGROUND: Paraoxonase enzyme was first identified as a protective barrier against organophosphorus poisoning. After painstaking research spanning the last three decades, the knowledge about this enzyme has increased immensely. The present review attempts to elaborate the role of paraoxonase enzyme in normal physiology as well as provide an overview of the various disorders in which the enzyme may have a role in etiopathogenesis. METHODS: The literature was searched from the websites of the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) and Pub Med Central, the U.S. National Library of Medicine's digital archive of life sciences journal literature. RESULTS: Paraoxonase acts as an important antioxidant enzyme against oxidative stress. The enzyme has been implicated in the pathogenesis of a number of disorders including cardiovascular disorders, cancers etc. CONCLUSIONS: A better understanding of the molecular mechanism of the enzyme along with the regulatory circuits will help us to utilize agonists to potentiate the anti oxidant actions of the enzyme.

Pre-analytical factors that influence the interpretation of prothrombin time in the clinical laboratory: one year experience in a super speciality hospital in India.

BACKGROUND: Accuracy and precision of Laboratory results is a top most priority in a clinical laboratory. Errors in Laboratory results could be due to pre-analytical, analytical and postanalytical variables. Here, we have discussed about pre-analytical variables during estimation of prothrombin time. METHODS: 15,335 PT (prothrombin time) samples received in the department of clinical biochemistry from June 2008 to May 2009 were evaluated for the prevalence of pre-analytical errors. The prothrombin time (PT) was analyzed on automated coagulometer-ACL 7000 with thromboplastin reagent supplied by Trinity Biotech, Ireland. RESULTS: Out of the 15,335 samples received in one year for analysis by the department, 464 samples showed the presence of pre-analytical variables and therefore, could not be assayed. Among the pre-analytical variables, inappropriate proportion between blood and anticoagulant was the most common error with a frequency of approximately 60%. Clotted samples and illegible handwriting accounted for another 15% each of the rejections respectively. Around 6% of the samples were hemolysed and another 2% were rejected due to lipemia. CONCLUSION: Appropriate knowledge of blood sample collection is a need of an hour to have accuracy in Laboratory results.

Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects.

Thyroid hormones regulate the renal hemodynamics and basal metabolic rate of most cells. This hospital-based case-control study was done to evaluate the changes in biochemical markers of liver and kidney function in hypothyroid subjects before and after treatment. The study included 176 subjects randomly selected from Thyroid clinics. Serum T(3), T(4), TSH, Liver and Kidney Function tests were analysed using standard kits. Forty-six hypothyroid patients were re-evaluated 6 weeks after thyroxine substitution therapy. Hypothyroid subjects (n=80) showed significantly raised serum creatinine and uric acid levels as compared to euthyroid subjects (n=96). After 6 weeks of thyroxine replacement, serum creatinine and uric acid decreased significantly and were comparable to euthyroid group. A positive correlation of ALT, AST, uric acid, protein and albumin with TSH levels (p<0.05) and negative correlation of serum T(4) levels with ALT, AST, proteins (p<0.05) was observed in the hypothyroid group. Hypothyroidism results in reversible impairment of hepatorenal function.