Advances in metabolomics in critically ill patients with Sepsis and Septic Shock.

Sepsis accounts for high cases of morbidity and mortality in hospitalized patients. It has a very complex pathophysiology and swiftly progresses to a severe form of the disease, such as septic shock leading to organ dysfunction, organ failure, and death. Metabolomics has transformed sepsis's clinical and research topography with its application in prognosis, diagnosis, and risk assessment in patients with sepsis and septic shock. Metabolites in blood and urine are detected and analyzed, which helps in understanding the pathogenesis of the disease and aid in better disease management by identifying biomarkers early on. Metabolomics, sepsis and septic shock were the keywords were searched in PubMed and Scopus, from its inception to Dec 2023. This article provides information regarding metabolic profiling performed in sepsis and septic shock We demonstrated that metabolomics will change the world of sepsis by analyzing and detecting the diagnosis, prognosis, mortality, and treatment response biomarkers.

Unveiling Pathophysiological Insights: Serum Metabolic Dysregulation in Acute Respiratory Distress Syndrome Patients with Acute Kidney Injury.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.

Metabolomics Characterization of Disease Markers in Diabetes and Its Associated Pathologies.

With the change in lifestyle of people, there has been a considerable increase in diabetes, which brings with it certain follow-up pathological conditions, which lead to a substantial medical burden. Identifying biomarkers that aid in screening, diagnosis, and prognosis of diabetes and its associated pathologies would help better patient management and facilitate a personalized treatment approach for prevention and treatment. With the advancement in techniques and technologies, metabolomics has emerged as an omics approach capable of large-scale high throughput data analysis and identifying and quantifying metabolites that provide an insight into the underlying mechanism of the disease and its progression. Diabetes and metabolomics keywords were searched in correspondence with the assigned keywords, including kidney, cardiovascular diseases and critical illness from PubMed and Scopus, from its inception to Dec 2023. The relevant studies from this search were extracted and included in the study. This review is focused on the biomarkers identified in diabetes, diabetic kidney disease, diabetes-related development of CVD, and its role in critical illness.

Biopolymeric nanoencapsulation of model drug: Its development and characterisation.

This research aimed to develop the phenytoin-loaded bionanosuspension by utilising the novel biopolymer from Juglans regia andreduce the long-term treatment cost of epilepsy and increase the efficiency of therapy. A novel biopolymer with remarkable inbuilt properties was isolated and used in the development of a nano capsulated dispersed system. The diverse proportions of phenytoin and biopolymer with different ratios 1:2, 1:3, 1:4, 1:5 and 1:8 were taken for the planning of details PJNC1-PJNC5. The bionanosuspension was assessed for dispersibility, pH, % entrapment efficiency, stability study and in vitro drug discharge. The formulation PJNC2 with 1:3 drug biopolymer proportion showed significant outcomes for various assessments with t50% of 16.51 h and r2 estimation of 0.9884. PJNC2 showed 92.07%±2.5 drug delivery in 36h and was stable. The bionanosuspension was found to be stable and safe for the delivery of nanosized phenytoin utilising the biopolymer having a remarkable stabiliser cum retardant property.

Sepsis, Management & Advances in Metabolomics.

Though there have been developments in clinical care and management, early and accurate diagnosis and risk stratification are still bottlenecks in septic shock patients. Since septic shock is multifactorial with patient-specific underlying co-morbid conditions, early assessment of sepsis becomes challenging due to variable symptoms and clinical manifestations. Moreover, the treatment strategies are traditionally based on their progression and corresponding clinical symptoms, not personalized. The complex pathophysiology assures that a single biomarker cannot identify, stratify, and describe patients affected by septic shock. Traditional biomarkers like CRP, PCT, and cytokines are not sensitive and specific enough to be used entirely for a patient's diagnosis and prognosis. Thus, the need of the hour is a sensitive and specific biomarker after comprehensive analysis that may facilitate an early diagnosis, prognosis, and drug development. Integration of clinical data with metabolomics would provide means to understand the patient's condition, stratify patients better, and predict the clinical outcome.

Longitudinal NMR Based Serum Metabolomics to Track the Potential Serum Biomarkers of Septic Shock.

Background: Septic shock, with a prolonged hospital stay, has the highest mortality rate worldwide. There is a need for better management of the disease, which requires time-dependent analysis of alteration occurring in the disease condition and subsequent planning of treatment strategies to curb mortality. Objective: The study aims to identify early metabolic signatures associated with septic shock before treatment and post-treatment. It also entails the progression of patients towards recovery, which clinicians could use to analyze treatment efficacy. Methods: The study was performed on 157 serum samples of patients with septic shock. We performed metabolomic, univariate, and multivariate statistics to identify the significant metabolite signature of patients prior to treatment and during treatment by collecting serum samples on the day I, day III, and day V of treatment. Results: We identified metabotypes of patients before treatment and post-treatment. The study showed time-dependent metabolite alteration in ketone bodies, amino acids, choline, and NAG in patients undergoing treatment. Conclusion: This study illustrates the metabolite's journey in septic shock and during treatment, which may be of prospective assistance to clinicians to monitor therapeutics.

Metabolic fingerprint of patients showing responsiveness to treatment of septic shock in intensive care unit.

OBJECTIVE: An early metabolic signature associated with the responsiveness to treatment can be useful in the better management of septic shock patients. This would help clinicians in designing personalized treatment protocols for patients showing non-responsiveness to treatment. METHODS: We analyzed the serum on Day 1 (n = 60), Day 3 (n = 47), and Day 5 (n = 26) of patients with septic shock under treatment using NMR-based metabolomics. Partial least square discriminant analysis (PLS-DA) was performed to generate the list of metabolites that can be identified as potential disease biomarkers having statistical significance (that is, metabolites that had a VIP score > 1, and p value < 0.05, False discovery rate (FDR) < 0.05). RESULTS: Common significant metabolites amongst the three time points were obtained that distinguished the patients being responsive (R) and non-responsive (NR) to treatments, namely 3 hydroxybutyrate, lactate, and phenylalanine which were lower, whereas glutamate and choline higher in patients showing responsiveness. DISCUSSION: The study gave these metabolic signatures identifying patients' responsiveness to treatment. The results of the study will aid in the development of targeted therapy for ICU patients.

Gender-specific association of oxidative stress and immune response in septic shock mortality using NMR-based metabolomics.

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 ß 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.

Serum metabolic profiles of septic shock patients based upon co-morbidities and other underlying conditions.

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 1D 1H 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.

Metabolomics: An emerging potential approach to decipher critical illnesses.

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.

Rapid Head Movements in Common Marmoset Monkeys.

Gaze shifts, the directing of the eyes to an approaching predator, preferred food source, or potential mate, have universal biological significance for the survival of a species. Our knowledge of gaze behavior is based primarily on visually triggered responses, whereas head orientation triggered by auditory stimuli remains poorly characterized. Common marmoset (Callithrix jacchus) is a diurnal, small-bodied (∼350 g), New World monkey species, known for its rich behavioral repertoires during social interactions. We used a lightweight head tracking system to measure marmosets' reflexive head orientations toward a natural stimulus presented from behind. We found that marmoset could rotate its head at angular velocities above 1,000°/s and maintained target accuracy for a wide range of rotation amplitudes (up to 250°). This unusual, saccadic head orienting behavior offers opportunities for understanding the many biological factors that have shaped the evolution of sensorimotor controls of gaze orientation by the primate brain.