Clinical Utility of Blood Culture Identification 2 Panel in Flagged Blood Culture Samples from the Intensive Care Unit of a Tertiary Care Hospital.

Background: The availability of rapid diagnostic platforms for positive blood cultures has accelerated the speed at which the clinical microbiology laboratory can identify the causative organism and facilitate early appropriate antimicrobial therapy. There is a paucity of data regarding the clinical utility of the blood culture identification 2 (BCID2) panel test and its correlation with phenotypic drug susceptibility testing (DST) in flagged blood culture bottles from intensive care units (ICUs) in countries such as India, which have high rates of multidrug-resistant gram-negative bacteria (MDR-GNB). Materials and methods: We conducted a retrospective observational study in a tertiary care ICU on 200 patients above 18 years of age in whom a BCID2 test was ordered when blood cultures flagged positive. Results: We found 99% concordance between BCID2 and cultures in the identification of bacteria and yeasts and 96.5% concordance between phenotypic and genotypic DST. Furthermore, BCID2 was available about 1.5 days earlier than conventional ID and DST and played a key role in tailoring antimicrobials in 82.5% of the patients. Polymyxin-based therapy was discontinued earlier after an empiric dose in 138 patients (69%) based on BCID2 reports. Conclusion: In critically ill patients with monomicrobial bacteremia, BCID2 rapidly identifies bacteria and antimicrobial resistance (AMR) genes and is significantly faster than conventional culture and sensitivity testing. Antibiotics were escalated in more than a third of patients and de-escalated in almost a fifth on the same day. We recommend that all ICUs routinely incorporate the test in their antibiotic decision-making process and in antimicrobial stewardship. How to cite this article: Vineeth VK, Nambi PS, Gopalakrishnan R, Sethuraman N, Ramanathan Y, Chandran C, et al. Clinical Utility of Blood Culture Identification 2 Panel in Flagged Blood Culture Samples from the Intensive Care Unit of a Tertiary Care Hospital. Indian J Crit Care Med 2024;28(5):461-466.

Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Bacteremia Caused by Enterobacteriaceae.

Introduction and background: Rapid molecular diagnostics to predict carbapenem resistance well before the availability of routine drug sensitivity testing (DST) can serve as an antimicrobial stewardship tool in the context of high rates of Carbapenem-resistant Enterobacteriaceae (CRE). Materials and methods: A retrospective observational study of patients more than 18 years of age on whom Xpert Carba-R (FDA approved for rectal swab specimen) was done on gram-negative bacteria (GNB) flagged blood culture samples, in an Indian intensive care unit between January 2015 and November 2018. We analyzed the performance of Xpert Carba-R in comparison with routine DST. Results: A total of 164 GNBs were isolated from 160 patients. Klebsiella pneumoniae and Escherichia coli were the predominant isolates. Carba-R was positive in 35.36% of samples and 45.34% were carbapenem-resistant (CR) on routine DST. The distribution of the CR gene was: Oxacillinase (OXA) (50%), NDM (32.7%) followed by OXA and NDM co-expression (15.51%). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of Carba-R were 90.74, 93.15, 13.25, 0.10, 83.58 and 96.31% for Enterobacteriaceae. The median time to obtain the Carba-R report was 30 hours 34 minutes vs 74 hours and 20 minutes for routine DST. Based on the Carba-R report, 9.72% of patients had escalation and 27.08% had de-escalation of antibiotics. Conclusion: Xpert Carba-R serves as a rapid diagnostic tool for predicting carbapenem resistance in intensive care unit patients with bacteremia caused by Enterobacteriaceae. How to cite this article: Rajendran S, Gopalakrishnan R, Tarigopula A, Kumar DS, Nambi PS, Sethuraman N, et al. Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Bacteremia Caused by Enterobacteriaceae. Indian J Crit Care Med 2023;27(9):655-662.

Unmasking Resident Physician Burnout During the COVID-19 Era.

Burnout is not a new concept in the health care field. Most, if not all, resident physicians (residents) experience burnout at least once during their training. However, the COVID-19 pandemic placed a large strain on the health care system and exacerbated stressors that contribute to burnout, including anxiety, depression, and work overload. The authors reviewed the literature on resident burnout in the era of COVID-19 to elucidate common stressors across the specialties and identify successful interventions or initiatives that may be most effective for residency programs.

Increased maternal non-oxidative energy metabolism mediates association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and offspring autism spectrum disorder symptoms in early life: A birth cohort study.

Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study (BIS), a population-based birth cohort of 1,074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord serum at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured in 596 and 674 children by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) prospective associations between higher prenatal di-(2-ethylhexyl) phthalate (DEHP) levels and upregulation of maternal non-oxidative energy metabolism pathways, and (ii) prospective associations between upregulation of these pathways and increased offspring ASD symptoms at 2 and 4 years of age. Counterfactual mediation analyses indicated that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. These results highlight the importance of the prenatal period and suggest that further investigation of maternal energy metabolism as a molecular mediator of the adverse impact of prenatal environmental exposures such as phthalates is warranted.

Pathological Spectrum of Dura-Based Nonmeningothelial Lesions: 5 Years' Experience from a Tertiary Care Centre.

Introduction Nonmeningothelial lesions arising from the dura comprise a wide spectrum of pathologies ranging from neoplastic to infective etiologies. They have overlapping clinical and radiologic findings necessitating histopathological evaluation for the final diagnosis which in turn dictates management and prognosis. Therapeutic strategies are different for each of the lesion. There is scarcity of large case series detailing clinicopathological spectrum of dura-based nonmeningothelial lesions. Materials and Methods In this study, we analyzed the neuropathological spectrum of dura-based nonmeningothelial lesions diagnosed over a period of 5 years in our tertiary care center. Results There were 79 cases of dura-based nonmeningothelial lesions constituting 7.3% of all dura-based lesions (age range: 2-75 years; M:F = 2:3). Basal region was more frequently involved than the convexities. On histopathology, neoplastic lesions predominated (92.4%) and included in order of frequency solitary fibrous tumor/hemangiopericytoma (35.6%), gliomas (27.4%), metastasis (27.4%), mesenchymal tumors (4%), primitive neuroectodermal tumor (2.73%), and medulloblastoma (2.73%). Infective lesions were less frequent (7.6%), included fungal infections and Rosai-Dorfman disease. Conclusion Awareness of the spectrum of nonmeningothelial dural lesions is useful for pathologists as well as the treating surgeon.

EGFR mutations and ROS1 and ALK rearrangements in a large series of non-small cell lung cancer in South India.

BACKGROUND: Driver mutations are seen in 80% of lung adenocarcinomas, and they influence prognosis and choice of therapy. AIM: Aim of this study was to analyse the frequency of epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements and their association with age and gender in non-small cell lung cancer reported from a tertiary care center in South India. METHODS: Tumors from patients with non-small cell carcinoma of lung were evaluated for EGFR mutations, ALK and ROS1 rearrangements and their association with age and gender were studied. RESULTS: Two thirds of non-small cell carcinomas had driver mutations or rearrangements. EGFR mutation was common and seen in 34.1%, whereas ALK rearrangement was seen in 11.1% and ROS1 rearrangement in 2% patients. Among EGFR mutations, most common were Exon 19 deletion and L858R seen in 21.3% and 11% of patients, respectively. Adenocarcinoma was the histologic diagnosis in 81% to 85% of patients with exon 19 deletion and L858R mutation, respectively. EGFR mutation frequency in patients less than 36 years was 13.6%, whereas in older patients, it varied from 34% to 36%. Exon 19 deletion was seen in 29.8% females and 17.2% of males. CONCLUSION: EGFR mutations are more common than ALK and ROS1 rearrangements. They are more common in females. Patients less than 36 years have reduced frequency of EGFR mutations. Exon 19 deletion and L858R are most common and are more prevalent in lung adenocarcinomas. Rare EGFR mutations are seen in patients aged more than 50 years.

Microcystic Meningiomas: MRI-Pathologic Correlation.

BACKGROUND AND PURPOSE: Microcystic meningiomas (MM) are a distinctive, rare subtype of Grade I meningiomas with limited radiological descriptions. We intend to identify unique imaging phenotypes and seek radiopathological correlations. METHODS: Retrospective analysis of histopathologically proven MM was undertaken. Clinicodemographic profiles, imaging, and histopathological characteristics were recorded. Spearman rank correlations among radiological and pathological attributes were performed. RESULTS: Twenty-eight cases were analyzed (mean age = 45.5 years; M:F = 1:1.54; mean volume = 50.1 mL; supratentorial n = 27). Most lesions were markedly T2 hyperintense (higher than peritumoral brain edema-a unique finding) (89.3%) and showed invariable diffusion restriction, severe peritumoral brain edema (edema index >2 in 64.3%), a "storiform" pattern on T2-weighted images (T2WI) (75%), reticular pattern on postcontrast T1 (78.6%)/diffusion-weighted images (DWI) (65.4%), hyperperfusion, T1 hypointensity (84.6%), and absence of blooming on susceptibility-weighted image (80.9%). Storiform/reticular morphology correlated with large cysts on histopathology (ρ = .56; P = .005753).  Lesion dimension positively correlated with reticular morphology on imaging (ρ = .59; P = .001173), higher flow voids (ρ = .65; P = .00027), and greater microcystic changes on histopathology (ρ = .51; P = .006778). Peritumoral brain edema was higher for lesions demonstrating greater angiomatous component (ρ = .46; P = .014451). CONCLUSIONS: We have elucidated varied neuroimaging features and highlighted pathological substrates of crucial imaging findings of MM. MM ought to be considered as an imaging possibility in an extra-axial lesion with a marked hypodensity on noncontrast computed tomography, markedly T2-hyperintense/T1-hypointense signal, and a storiform/reticular pattern on T2W/GdT1w//DWI.

Utility of multiplex polymerase chain reaction (PCR) in diarrhea-An Indian perspective.

BACKGROUND: Infective diarrhea causes morbidity worldwide. Polymerase chain reaction (PCR)-based pathogen diagnostics of diarrheal stool specimens are shown to be highly sensitive and rapid as opposed to conventional diagnostics. METHODS: We analyzed the performance of FilmArray gastrointestinal (GI) panel, one such multiplex PCR test, on stool specimens in patients presenting with diarrhea to our hospital from March 2016 to September 2017 and compared the results with conventional diagnostic tests. RESULTS: A total of 106 patients were included. The panel detected at least one target in 54 out of 106 patients (50.9%) with results available on the same day. Multiple targets were detected in 26 out of 54 patients who tested positive (48.1%). Bacteria as an isolated etiology for diarrhea was present in 34 patients (62.9%), viruses (16.7%, nine patients), parasites (7.4%, four patients), and multiple pathogens in seven patients (12.9%). Enteroaggregative Escherichia coli (EAEC) was the commonest pathogen detected (in 23, 24% patients). Conventional diagnostic investigations, undertaken in 68/106 (64.1%) patients were positive in 12 (17.65%) as compared to 54/106 (50.9%) (p < 0.0001). Conventional  investigations detected a pathogen not included in the study panel in 11 of 52 patients (21.1%). CONCLUSION: FilmArray multiplex PCR panel detects a wide array of GI pathogens including viruses and co-infections at a shorter time with more sensitivity compared to conventional diagnostics. Henceforth, it may facilitate treatment decisions, isolation policy, and antimicrobial stewardship in patients with diarrhea requiring hospitalization.

Granular cells in oligodendroglioma suggest a neoplastic change rather than a reactive phenomenon: case report with molecular characterisation.

Oligodendrogliomas are diffuse gliomas characterised by IDH mutation and 1p/19q co-deletion. Classical oligodendrocytes, minigemistocytes, gliofibrillary oligodendrocytes, granular cells, and mucocytes are morphologic cell types described in oligodendroglioma. Even though the occurrence of granular cells in oligodendroglioma is known, exact nature of these cells and their molecular characteristics remain undetermined. We describe a case of oligodendroglioma with granular cells, in which we have attempted to molecularly characterise the granular cells. These granules were stained blue on Luxol fast blue and red on Masson's trichrome. The cells showed a distinct pattern of immunoreactivity to GFAP and IDH1. In addition, they exhibited mitotic activity and increased Ki-67 labelling. Molecularly, both the granular cells and classical oligodendroglial cells in the tumor showed 1p/19q co-deletion which is the diagnostic hallmark of an oligodendroglioma. Thus, we opine that granular cells are neoplastic and represent a morphological variant of neoplastic oligodendrocyte.