Browsing by Author "Afzal Azim"

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An NMR based panorama of the heterogeneous biology of acute respiratory distress syndrome (ARDS) from the standpoint of metabolic biomarkers
(John Wiley and Sons Ltd, 2020) Akhila Viswan; Chandan Singh; Arvind M. Kayastha; Afzal Azim; Neeraj Sinha
Acute respiratory distress syndrome (ARDS), manifested by intricate etiology and pathophysiology, demands careful clinical surveillance due to its high mortality and imminent life support measures. NMR based metabolomics provides an approach for ARDS which culminates from a wide spectrum of illness thereby confounding early manifestation and prognosis predictors. 1H NMR with its manifold applications in critical disease settings can unravel the biomarker of ARDS thus holding potent implications by providing surrogate endpoints of clinical utility. NMR metabolomics which is the current apogee platform of omics trilogy is contributing towards the possible panacea of ARDS by subsequent validation of biomarker credential on larger datasets. In the present review, the physiological derangements that jeopardize the whole metabolic functioning in ARDS are exploited and the biomarkers involved in progression are addressed and substantiated. The following sections of the review also outline the clinical spectrum of ARDS from the standpoint of NMR based metabolomics which is an emerging element of systems biology. ARDS is the main premise of intensivists textbook, which has been thoroughly reviewed along with its incidence, progressive stages of severity, new proposed diagnostic definition, and the preventive measures and the current pitfalls of clinical management. The advent of new therapies, the need for biomarkers, the methodology and the contemporary promising approaches needed to improve survival and address heterogeneity have also been evaluated. The review has been stepwise illustrated with potent biometrics employed to selectively pool out differential metabolites as diagnostic markers and outcome predictors. The following sections have been drafted with an objective to better understand ARDS mechanisms with predictive and precise biomarkers detected so far on the basis of underlying physiological parameters having close proximity to diseased phenotype. The aim of this review is to stimulate interest in conducting more studies to help resolve the complex heterogeneity of ARDS with biomarkers of clinical utility and relevance. © 2019 John Wiley & Sons, Ltd.
Gender-specific association of oxidative stress and immune response in septic shock mortality using NMR-based metabolomics
(Royal Society of Chemistry, 2022) Swarnima Pandey; Mohd. Adnan Siddiqui; Surendra Kumar Trigun; Afzal Azim; Neeraj Sinha
Background: Sepsis and septic shock are still associated with a high mortality rate. The early-stage prediction of septic shock outcomes would be helpful to clinicians for designing their treatment protocol. In addition, it would aid clinicians in patient management by understanding gender disparity in terms of clinical outcomes of septic shock by identifying whether there are sex-based differences in sepsis-associated mortality. Objective: This study aimed to test the hypothesis that gender-based metabolic heterogeneity is associated with sepsis survival and identify the biomarkers of mortality for septic shock in an Indian cohort. Method: The study was performed in an Indian population cohort diagnosed with sepsis/septic shock within 24 hours of admission. The study group was 50 patients admitted to intensive care, comprising 23 females and 27 males. Univariate and multivariate analysis were performed to identify the biomarkers for septic shock mortality and the gender-specific metabolic fingerprint in septic shock-associated mortality. Results: The energy-related metabolites, ketone bodies, choline, and NAG were found to be primarily responsible for differentiating survivors and non-survivors. The gender-based mortality stratification identified a female-specific association of the anti-inflammatory response, innate immune response, and β oxidation, and a male-specific association of the pro-inflammatory response to septic shock. Conclusion: The identified mortality biomarkers may help clinicians estimate the severity of a case, as well as predict the outcome and treatment efficacy. The study underlines that gender is one of the most significant biological factors influencing septic shock metabolomic profiles. This understanding can be utilized to identify novel gender-specific biomarkers and innovative targets relevant for gender medicine. © The Royal Society of Chemistry.
Metabolic profiling of human lung injury by 1H high-resolution nuclear magnetic resonance spectroscopy of blood serum
(Springer Science and Business Media, LLC, 2015) Chandan Singh; Ratan Kumar Rai; Afzal Azim; Neeraj Sinha; Armin Ahmed; Kritika Singh; Arvind M. Kayastha; A.K. Baronia; Mohan Gurjar; Banani Poddar; Ratender K. Singh
Acute respiratory distress syndrome (ARDS) contributes substantially to mortality and morbidity in USA and worldwide. Due to limitations in early diagnostics of ARDS by classical methods, there has been need for discovery of novel methods and biomarkers for its characterization. We present here first high-resolution 1H nuclear magnetic resonance (NMR) metabolic profiling of serum from ARDS patients and non ARDS (NARDS) controls to search for novel biomarkers in blood serum for better diagnostics and prognostics. We have carried out study with serum samples from a total of 45 subjects, which included 26 ARDS patients and 19 NARDS controls. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were performed on 1H NMR spectra of serum for group discrimination between the two. PCA and PLS-DA on 1H NMR spectra of serum clearly discriminated between NARDS control and ARDS diseased samples. In our study, lipid resonances showed major contribution for this separation in loading plots. In order to highlight role of other small molecular weight metabolites, the analysis was also carried out after removing lipids resonances from NMR spectrum. There was significant increase in concentrations of N-acetylglycoproteins (NAC) (p = 0.001), acetoacetate (p = 0.001), lactate (p = 0.001), creatinine (p = 0.003), histidine (p = 0.03), formate (p = 0.04) and aromatic amino acids serum of ARDS patients. Along with small metabolites, lipids play a very important role in this discrimination and can differentiate between two classes. Our study has given new avenue in the metabolic profiling of lung injuries. © 2014, Springer Science+Business Media New York.
Metabolomics: An emerging potential approach to decipher critical illnesses
(Elsevier B.V., 2020) Mohd Adnan Siddiqui; Swarnima Pandey; Afzal Azim; Neeraj Sinha; Mohammed Haris Siddiqui
Critical illnesses contribute to the maximum morbidity and mortality of hospitalized patients. Acute respiratory distress syndrome (ARDS) and sepsis/septic shock are the two most common acute illnesses associated with intensive care unit (ICU) admission. Once triggered, both have an identical underlying mechanism, portrayed by inflammation and endothelial dysfunction. The diagnosis of ARDS is based on clinical findings, laboratory tests, and radiological imaging. Blood cultures remain the gold standard for the diagnosis of sepsis, with the limitation of time delay and low positive yield. A combination of biomarkers has been proposed to diagnose and prognosticate these acute disorders with strengths and limitations, but still, the gold standard has been elusive to clinicians. In this review article, we illustrate the potential of metabolomics to unravel biomarkers that can be clinically utilized as a rapid prognostic and diagnostic tool associated with specific patient populations (ARDS and sepsis/septic shock) based on the available scientific data. © 2020
Search for biomarkers in critically ill patients: A new approach based on nuclear magnetic resonance spectroscopy of mini-bronchoalveolar lavage fluid
(BioMed Central Ltd., 2014) Chandan Singh; Ratan K. Rai; Afzal Azim; Neeraj Sinha; Arvind K. Baronia
[No abstract available]
Serum metabolic profiles of septic shock patients based upon co-morbidities and other underlying conditions
(Royal Society of Chemistry, 2021) Swarnima Pandey; Mohd. Adnan Siddiqui; Afzal Azim; Surendra Kumar Trigun; Neeraj Sinha
Diagnosis and management of patients with septic shock is still a significant challenge for clinicians with its high mortality amongst hospitalized patients. Septic shock is a heterogeneous condition and is usually accompanied by various underlying disease conditions. Dissecting the specific metabolic changes induced by these underlying disease conditions through metabolomics has shown the potential to improve our understanding of the disease's relevant pathophysiological mechanisms, leading to improved treatment. This study has shown the metabolic alterations caused due to co-morbid conditions like diabetes, hypertension, CAD, and CKD in septic shock. It has also shown the distinct metabolic profiles of septic shock patients with underlying respiratory illnesses and encephalopathy. Metabolic profiling of sera obtained from 50 septic shock patients and 20 healthy controls was performed using high-resolution 1D1H CPMG and diffusion-edited NMR spectra. Univariate and multivariate statistical analyses were performed to identify the potential molecular biomarkers. Noted dysregulations in amino acids, carbohydrates, and lipid metabolism were observed in septic shock patients. Further stratification within the septic shock patients based on co-morbid conditions and primary diagnosis has shown their role in causing metabolic alterations. Evaluation of these compounds during treatment will help design a personalized treatment protocol for the patients, improving therapeutics. © The Royal Society of Chemistry 2021.