Multiple myeloma can be accurately diagnosed in acute kidney injury patients using a rapid serum free light chain test

Abstract Background Acute kidney injury (AKI) is common in patients with multiple myeloma (MM). Whether serum free light chain (sFLC) measurements can distinguish between myeloma and other causes of AKI requires confirmation to guide early treatment. A rapid and portable sFLC test (Seralite®) is newly available and could reduce delays in obtaining sFLC results and accelerate diagnosis in patients with unexplained AKI. This study evaluated the accuracy of Seralite® to identify MM as the cause of AKI. Method sFLCs were retrospectively analysed in patients with AKI stage 3 as per KDIGO criteria (i.e. serum creatinine ≥354 μmol/L or those on dialysis treatment) (n = 99); 45/99 patients had a confirmed MM diagnosis. Results The Seralite® κ:λ FLC ratio accurately diagnosed all MM patients in the presence of AKI: a range of 0.14–2.02 returned 100% sensitivity and specificity for identifying all non-myeloma related AKI patients. The sFLC difference (dFLC) also demonstrated high sensitivity (91%) and specificity (100%): an optimal cut-off of 399 mg/L distinguished between myeloma and non-myeloma AKI patients. We propose a pathway of patient screening and stratification in unexplained AKI for use of Seralite® in clinical practice, with a κ:λ ratio range of 0.14–2.02 and dFLC 400 mg/L as decision points. Conclusions Seralite® accurately differentiates between AKI due to MM and AKI due to other causes in patients considered at risk of myeloma. This rapid test can sensitively screen for MM in patients with AKI and help inform early treatment intervention

Not Available

Not AvailableNot AvailableNot Availabl

Incidence of central line-associated bloodstream infection in the intensive care unit: A prospective observational study

Aims: The aim of this study was to determine the incidence of central line-associated bloodstream infections (CLABSIs) in the medical and surgical intensive care units (ICUs) of a tertiary care hospital. Materials and Methods: One hundred and twenty patients admitted to medical and surgical ICU with an indwelling, nontunneled central venous catheter (CVC) inserted at admission in the department of emergency medicine or at medical and surgical ICU for more than 48 h were monitored. The patients were followed up daily for the development of new-onset sepsis after 48 h of insertion of CVC, by analyzing the culture of two sets of blood samples, over a span of 24 h. The data were evaluated statistically using Microsoft Excel version 11 and SPSS version 17 (IBM, USA). Results: Among 120 patients hospitalized for an aggregate of 972 days, 7 patients had acquired CLABSI with an incidence rate of 7.2/1000 central line days. The organisms isolated were Staphylococcus aureus, Acinetobacter spp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. Conclusion: The incidence rate of CLABSI in this study was in line with other studies on the CLABSI rate in India. The study found a significant association of CLABSI with duration of CVC catheterization, underlying comorbid conditions and diseases of patients, and indication of CVC insertion. However, there was no significant association of CLABSI with age of patients, their gender, and site of insertion

Structure model of ferrochelatase from Salmonella Typhi elucidating metalation mechanism

A homology model of ferrochelatase (HemH), the heme biosynthesis terminal step enzyme from Salmonella Typhi was generated to understand the mechanism of metal insertion into protoporphyrin IX for heme biosynthesis. The overall fold of membrane associated ferrochelatase (StFc) from S. Typhi is similar to human and Yeast ferrochelatase than Bacillus subtilis, and Bacillus anthracis. An insertion of 16 amino acid residues in helical switch having hydrophobic patch proposed to interact with membrane lipids and in opening and closing of heme binding cleft. The sequence analysis and the docking study revealed that the protoporphyrin binding site in StFc has a crucial replacement of Tyr/Met to Leu13 unique in comparison to other known structures, where Tyr13 observed in B. subtilis/B. anthracis while Met76 in human/yeast play important role in holding protoporphyrin in optimal orientation for metalation. A sitting-a-top (SAT) complex mechanism for metalation is proposed with His194 and Glu264 lie at the bottom and Leu13 on the top of the porphyrin ring. In addition, an entry and exit mechanism is also proposed for protoporphyrin binding into cavity by opening and closing of helical switch using molecular dynamics simulation studies of Apo and heme complexed model structure of S. Typhi HemH

Structural insights into the dual strategy of recognition by peptidoglycan recognition protein, PGRP-S: structure of the ternary complex of PGRP-S with lipopolysaccharide and stearic acid.

Peptidoglycan recognition proteins (PGRPs) are part of the innate immune system. The 19 kDa Short PGRP (PGRP-S) is one of the four mammalian PGRPs. The concentration of PGRP-S in camel (CPGRP-S) has been shown to increase considerably during mastitis. The structure of CPGRP-S consists of four protein molecules designated as A, B, C and D forming stable intermolecular contacts, A-B and C-D. The A-B and C-D interfaces are located on the opposite sides of the same monomer leading to the the formation of a linear chain with alternating A-B and C-D contacts. Two ligand binding sites, one at C-D contact and another at A-B contact have been observed. CPGRP-S binds to the components of bacterial cell wall molecules such as lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN) from both gram-positive and gram-negative bacteria. It also binds to fatty acids including mycolic acid of the Mycobacterium tuberculosis (Mtb). Previous structural studies of binary complexes of CPGRP-S with LPS and stearic acid (SA) have shown that LPS binds to CPGRP-S at C-D contact (Site-1) while SA binds to it at the A-B contact (Site-2). The binding studies using surface plasmon resonance showed that LPS and SA bound to CPGRP-S in the presence of each other. The structure determination of the ternary complex showed that LPS and SA bound to CPGRP-S at Site-1 and Site-2 respectively. LPS formed 13 hydrogen bonds and 159 van der Waals contacts (distances ≤4.2 Å) while SA formed 56 van der Waals contacts. The ELISA test showed that increased levels of productions of pro-inflammatory cytokines TNF-α and IFN-γ due to LPS and SA decreased considerably upon the addition of CPGRP-S

Serum free light chain level at diagnosis in myeloma cast nephropathy-a multicentre study.

Myeloma cast nephropathy (MCN) is a common cause of severe renal impairment in multiple myeloma (MM). The level of free light chain (FLC) that causes MCN varies substantially and there is uncertainty about the threshold level that should be used to inform clinical practice. In a multicentre cohort study of 103 patients with a diagnosis of MM and biopsy-confirmed MCN made between 2002-2014, we report prospectively measured levels of serum FLC at diagnosis obtained using a single nephelometric assay (Freelite®) and we explore the relationship between serum FLC level at diagnosis with renal outcome and patient survival. Using a landmark approach, overall survival (OS) was compared between patients who achieved independence from dialysis compared to those who remained dialysis dependent at 3-month, 6-month, 9-month, and 12-month time points. The median serum FLC level at diagnosis was 7531 mg/L (range 107-114600). Serum creatinine was 535 μmol/L (range 168-2993) and eGFR 7 ml/min/1.73 m (range 1-34). Six patients (5.8%) had an FLC level  500 mg/L should be considered the threshold level associated with the development of MCN

Crystal structure of the disintegrin heterodimer from saw-scaled viper (Echis carinatus) at 1.9 Åresolution

Disintegrins constitute a family of potent polypeptide inhibitors of integrins. Integrins are transmembrane heterodimeric molecules involved in cell-cell and cell-extracellular matrix interactions. They are involved in many diseases such as cancer and thrombosis. Thus, disintegrins have a great potential as anticancer and antithrombotic agents. A novel heterodimeric disintegrin was isolated from the venom of saw-scaled viper (Echis carinatus) and was crystallized. The crystals diffracted to 1.9 Å resolution and belonged to space group P43212. The data indicated the presence of a pseudosymmetry. The structure was solved by applying origin shifts to the disintegrin homodimer schistatin solved in space group I4122 with similar cell dimensions. The structure refined to the final Rcryst/Rfree factors of 0.213/0.253. The notable differences are observed between the loops, (Gln39-Asp48) containing the important Arg42-Gly43-Asp44, of the present heterodimer and schistatin. These differences are presumably due to the presence of two glycines at positions 43 and 46 that allow the molecule to adopt variable conformations. A comparative analysis of the surface-charge distributions of various disintegrins showed that the charge distribution on monomeric disintegrins occurred uniformly over the whole surface of the molecule, while in the dimeric disintegrins, the charge is distributed only on one face. Such a feature may be important in the binding of two integrins to a single dimeric disintegrin. The phylogenetic analysis developed on the basis of amino acid sequence and three-dimensional structures indicates that the protein diversification and evolution presumably took place from the medium disintegrins and both the dimeric and short disintegrins evolved from them