Modified NUTRIC Score as a Predictor of All-cause Mortality in Critically Ill Patients: A Systematic Review and Meta-analysis.

Purpose: The purpose of our meta-analysis was to look at the impact of modified nutrition risk in the critically ill (mNUTRIC) on mortality in patients with critical illness. Materials and methods: Literature relevant to this meta-analysis was searched in PubMed, Web of Science, and Cochrane Library till 26 August 2023. Prospective or retrospective studies, patients >18 years of age, studies that reported on mortality and mNUTRIC (mNUTRIC cut-off score) were included. The QUIPS tool was used to evaluate the risk for bias in prognostic factors. Results: A total of 31 studies on mNUTRIC score, involving 13,271 patients were included. The summary area under the curve (sAUC) of 0.80 (95% CI: 0.76-0.83) illustrates the mNUTRIC score's strong discrimination. The pooled sensitivity was 0.79 (95% CI: 0.74-0.84) and pooled specificity was 0.68 (95% CI: 0.63-0.73). We found no discernible variation in the mNUTRIC's prediction accuracy among cut-off values of <5 and >5 in our subgroup analysis and sAUC values were 0.82 (95% CI: 0.78-0.85) and 0.78 (95% CI: 0.74-0.81), respectively. Conclusion: We observed that mNUTRIC can discriminate between critically ill individuals and predict their mortality. Prospero: CRD42023460292. How to cite this article: Prakash J, Verma S, Shrivastava P, Saran K, Kumari A, Raj K, et al. Modified NUTRIC Score as a Predictor of All-cause Mortality in Critically Ill Patients: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2024;28(5):495-503.

The Effect on Serum Electrolytes in Patients Undergoing Elective Craniotomy for Supratentorial Brain Tumors Using PlasmaLyte A and Normal Saline as Intravenous Replacement Fluid.

Background and aim The type of fluid which is administered to patients is very crucial and important. In this study normal saline is compared with PlasmaLyte A in patients undergoing craniotomy for supratentorial brain tumors. Generally normal saline is used in neurosurgical patients; it is seen to be associated with hyperchloremic acidosis. A balanced crystalloid, e.g. PlasmaLyte A, maintains a better metabolic status than normal saline. This study was planned to study the metabolic effects of using PlasmaLyte A as compared with normal saline as intravenous fluids in patients undergoing supratentorial brain tumour surgeries. Methods This is a prospective, randomized, double-blinded study in patients undergoing craniotomy for supratentorial brain tumors. Written informed consent was taken from patients and they were divided into two groups, Group A and B of 40 patients each by computer-generated random numbers. Group A received PlasmaLyte A and Group B received normal saline intra-operatively as maintenance fluid. Heart rate, mean arterial pressure, total fluid administered, serum sodium, serum potassium, chloride, lactate, pH, serum urea, serum creatinine, osmolarity, and urine output were assessed at different time intervals in both groups. Blood urea and creatinine were assessed to see acute kidney injury. Results There was no difference in mean values of serum sodium, potassium, lactate, serum urea, creatinine and serum osmolarity in both groups throughout the study period. However there was a rise in serum chloride and a low pH was noted in Group B. The urine output was also similar in both groups. The metabolic status of patients receiving PlasmaLyte was better than those receiving normal saline. Conclusion Normal saline may cause hyperchloremic metabolic acidosis which may be avoided by using balanced crystalloids. The use of balanced crystalloids should be preferred to normal saline in neurosurgical patients to ensure a better metabolic status and good clinical outcome.

Evaluation of Nebulised Dexmedetomidine Given Pre-operatively to Attenuate Hemodynamic Response to Laryngoscopy and Endotracheal Intubation: A Randomised Control Trial.

Background and aim A variety of medications have been studied to reduce the hemodynamic response to laryngoscopy and intubation. Dexmedetomidine has been used intravenously in many studies to reduce the hemodynamic response to laryngoscopy and intubation. In high-risk patients, this pressor response can increase morbidity and mortality. As dexmedetomidine has a good bioavailability via the nebulisation route, we formulated this study to evaluate the effect of nebulised dexmedetomidine on the hemodynamic response to laryngoscopy and endotracheal intubation. Methods This is a prospective, randomised controlled trial conducted on 100 patients with the American Society of Anesthesiologists grade I and II. The primary objective of the study was to see if nebulised dexmedetomidine at a dose of 1 microgram/kg could reduce the stress reaction to laryngoscopy and intubation. The secondary objective was to study the dose sparing effect of nebulised dexmedetomidine on the amount of propofol used during induction of general anaesthesia. The study population was randomly divided into two groups: group A (n = 50) included patients nebulised with dexmedetomidine 1 microgram/kg and group B (n = 50) included patients nebulised with 5 ml saline 30 minutes before induction of anaesthesia in a sitting position. Results The demographics were similar in both groups. Following laryngoscopy and intubation, the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate showed a significant increase in the control group B as compared to the treatment group A. In group A, there was attenuation in SBP (one minute = 113.2 ± 14.503, P < 0.001; five minutes = 109.86 ± 8.342, P < 0.001; 10 minutes = 114.24 ± 7.797, P = 0.010), DBP (one minute = 73.72 ± 10.986, P = 0.011; five minutes = 71.62 ± 9.934, P = 0.005; 10 minutes = 76.1 ± 8.006, P = 0.009), MAP (one minute = 86.80 ± 11.86, P = 0.001; five minutes = 84.44 ± 8.97, P = 0.006; 10 minutes = 88.72 ± 7.44, P = 0.018), and heart rate (one minute = 83.34 ± 12.325, P = 0.001; five minutes = 81.56 ± 13.33, P = 0.003; 10 minutes = 80.16 ± 14.086, P = 0.013) following laryngoscopy and intubation. Induction dose of propofol was significantly lower in the dexmedetomidine group (73 ± 19.509, P < 0.001). Conclusion Nebulised dexmedetomidine effectively blunts the hemodynamic response to laryngoscopy and intubation and also has a dose sparing effect on the induction dose of propofol.

Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues.

The Mycobacterium tuberculosis dihydrodipicolinate synthase (Mtb-dapA) is an essential gene. Mtb-DapA catalyzes the aldol condensation between pyruvate and L-aspartate-beta-semialdehyde (ASA) to yield dihydrodipicolinate. In this work we tested the inhibitory effects of structural analogues of pyruvate on recombinant Mtb-DapA (Mtb-rDapA) using a coupled assay with recombinant dihydrodipicolinate reductase (Mtb-rDapB). Alpha-ketopimelic acid (α-KPA) showed maximum inhibition of 88% and IC50 of 21 µM in the presence of pyruvate (500 µM) and ASA (400 µM). Competition experiments with pyruvate and ASA revealed competition of α-KPA with pyruvate. Liquid chromatography-mass spectrometry (LC-MS) data with multiple reaction monitoring (MRM) showed that the relative abundance peak of final product, 2,3,4,5-tetrahydrodipicolinate, was decreased by 50%. Thermal shift assays showed 1 °C Tm shift of Mtb-rDapA upon binding α-KPA. The 2.4 Å crystal structure of Mtb-rDapA-α-KPA complex showed the interaction of critical residues at the active site with α-KPA. Molecular dynamics simulations over 500 ns of pyruvate docked to Mtb-DapA and of α-KPA-bound Mtb-rDapA revealed formation of hydrogen bonds with pyruvate throughout in contrast to α-KPA. Molecular descriptors analysis showed that ligands with polar surface area of 91.7 Å(2) are likely inhibitors. In summary, α-hydroxypimelic acid and other analogues could be explored further as inhibitors of Mtb-DapA.

The structure of Rv3717 reveals a novel amidase from Mycobacterium tuberculosis.

Bacterial N-acetylmuramoyl-L-alanine amidases are cell-wall hydrolases that hydrolyze the bond between N-acetylmuramic acid and L-alanine in cell-wall glycopeptides. Rv3717 of Mycobacterium tuberculosis has been identified as a unique autolysin that lacks a cell-wall-binding domain (CBD) and its structure has been determined to 1.7 Šresolution by the Pt-SAD phasing method. Rv3717 possesses an α/ß-fold and is a zinc-dependent hydrolase. The structure reveals a short flexible hairpin turn that partially occludes the active site and may be involved in autoregulation. This type of autoregulation of activity of PG hydrolases has been observed in Bartonella henselae amidase (AmiB) and may be a general mechanism used by some of the redundant amidases to regulate cell-wall hydrolase activity in bacteria. Rv3717 utilizes its net positive charge for substrate binding and exhibits activity towards a broad spectrum of substrate cell walls. The enzymatic activity of Rv3717 was confirmed by isolation and identification of its enzymatic products by LC/MS. These studies indicate that Rv3717, an N-acetylmuramoyl-L-alanine amidase from M. tuberculosis, represents a new family of lytic amidases that do not have a separate CBD and are regulated conformationally.

Computational screening for new inhibitors of M. tuberculosis mycolyltransferases antigen 85 group of proteins as potential drug targets.

The group of antigen 85 proteins of Mycobacterium tuberculosis is responsible for converting trehalose monomycolate to trehalose dimycolate, which contributes to cell wall stability. Here, we have used a serial enrichment approach to identify new potential inhibitors by searching the libraries of compounds using both 2D atom pair descriptors and binary fingerprints followed by molecular docking. Three different docking softwares AutoDock, GOLD, and LigandFit were used for docking calculations. In addition, we applied the criteria of selecting compounds with binding efficiency close to the starting known inhibitor and showing potential to form hydrogen bonds with the active site amino acid residues. The starting inhibitor was ethyl-3-phenoxybenzyl-butylphosphonate, which had IC(50) value of 2.0 µM in mycolyltransferase inhibition assay. Our search from more than 34 million compounds from public libraries yielded 49 compounds. Subsequently, selection was restricted to compounds conforming to the Lipinski rule of five and exhibiting hydrogen bonding to any of the amino acid residues in the active site pocket of all three proteins of antigen 85A, 85B, and 85C. Finally, we selected those ligands which were ranked top in the table with other known decoys in all the docking results. The compound NIH415032 from tuberculosis antimicrobial acquisition and coordinating facility was further examined using molecular dynamics simulations for 10 ns. These results showed that the binding is stable, although some of the hydrogen bond atom pairs varied through the course of simulation. The NIH415032 has antitubercular properties with IC(90) at 20 µg/ml (53.023 µM). These results will be helpful to the medicinal chemists for developing new antitubercular molecules for testing.

Molecular docking of (5E)-3-(2-aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione on HIV-1 reverse transcriptase: novel drug acting on enzyme.

The study of Human immunodeficiency virus (HIV) in humans and animal models in last 31 years suggested that it is a causative agent of AIDS. This causes serious pandemic public health concern globally. It was reported that the HIV-1 reverse transcriptase (RT) played a critical role in the life cycle of HIV. Therefore, inhibition of HIV-1RT enzyme is one of the major and potential targets in the treatment of AIDS. The enzyme (HIV-1RT) was successfully targeted by non nucleotide reverse transcriptase inhibitors (NNRTIs). But frequent application of NNRTIs led drug resistance mutation on HIV infections. Therefore, there is a need to search new NNRTIs with appropriate pharmacophores. For the purpose, a virtually screened 3D model of unliganded HIV-1RT (1DLO) was explored. The unliganded HIV-1RT (1DLO) was docked with 4-thiazolidinone and its derivatives (ChemBank Database) by using AutoDock4. The best seven docking solutions complex were selected and analyzed by Ligplot. The analysis showed that derivative (5E)-3-(2- aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione (CID 3087795) has maximum potential against unliganded HIV-1RT (1DLO). The analysis was done on the basis of scoring and binding ability. The derivative (5E)-3-(2- aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione (CID 3087795) indicated minimum energy score and highest number of interactions with active site residue and could be a promising inhibitor for HIV-1 RT as Drug target.

Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry.

The genome sequencing of H37Rv strain of Mycobacterium tuberculosis was completed in 1998 followed by the whole genome sequencing of a clinical isolate, CDC1551 in 2002. Since then, the genomic sequences of a number of other strains have become available making it one of the better studied pathogenic bacterial species at the genomic level. However, annotation of its genome remains challenging because of high GC content and dissimilarity to other model prokaryotes. To this end, we carried out an in-depth proteogenomic analysis of the M. tuberculosis H37Rv strain using Fourier transform mass spectrometry with high resolution at both MS and tandem MS levels. In all, we identified 3176 proteins from Mycobacterium tuberculosis representing ~80% of its total predicted gene count. In addition to protein database search, we carried out a genome database search, which led to identification of ~250 novel peptides. Based on these novel genome search-specific peptides, we discovered 41 novel protein coding genes in the H37Rv genome. Using peptide evidence and alternative gene prediction tools, we also corrected 79 gene models. Finally, mass spectrometric data from N terminus-derived peptides confirmed 727 existing annotations for translational start sites while correcting those for 33 proteins. We report creation of a high confidence set of protein coding regions in Mycobacterium tuberculosis genome obtained by high resolution tandem mass-spectrometry at both precursor and fragment detection steps for the first time. This proteogenomic approach should be generally applicable to other organisms whose genomes have already been sequenced for obtaining a more accurate catalogue of protein-coding genes.