External quality assurance schemes (EQAS) are invaluable tools used by medical laboratories to assess the performance of their testing systems. EQA is an exercise conducted by the EQA provider to compare the testing performance of a laboratory with other laboratories, identify areas of improvement and provide insights into laboratory quality standards. This retrospective study evaluates the continuous improvement of the CMC EQAS Clinical Biochemistry program and the benefits of the program to the overall performance of the Indian medical laboratories over the last four and a half decades in terms of the increase in participants, programs, analytes, lab types, lab sizes, and performance. The CMC EQAS program with 50 participating laboratories in 1978, increased to 13,883 laboratories in 2024, with increase in programs and analytes. 70

Prematurity has been postulated to have adverse effects on nephron endowment. The objectives of the study was to study the kidney consequences of prematurity in childhood. We also studied the serum uromodulin levels in children with premature birth and its correlation with kidney growth. This cross-sectional study was conducted from January to December 2019 included children aged 3 to 6 years with history of premature birth from 2014 to 2016. Impact of prematurity on clinical parameters such as growth, blood pressure, kidney volume were studied. In addition serum uromodulin estimated by enzyme linked immunoassay kit was used to correlate with mean kidney volume (MKV), hypertension and chronic kidney disease (CKD). In this single centre cross-sectional study outcomes of 37 children with history of prematurity were analysed. Median (IQR) age of the cohort was 5.8 years(4 to 6.6). The mean (SD) gestational age of the cohort was 30 (2) weeks with mean (SD) birth weight of 1359.7 g(333.8). Premature rupture of membranes(12/3,32.4

Background: Serum Vitamin B12 level is routinely analyzed using total Vitamin B12 assay. It can also be analyzed by active B12 assay. In this study, we compared the association of total and active Vitamin B12 levels with maternal medical complications associated with Vitamin B12 in pregnancy. Materials and Methods: Blood sera of 217 pregnant women in their first trimester were included to conduct this retrospective study. The levels of active B12 and total B12 were analyzed by Roche cobas e 801. The distribution of active and total B12 among the anemic groups was analyzed using the Mann–Whitney U-test. Categorical associations of complications with active and total B12 were done using Chi-square statistics. The discriminating ability of active and total B12 was analyzed by the receiver operating characteristic (ROC) curve. Results: The hemoglobin levels and the maternal medical complications associated with Vitamin B12, in the total and active Vitamin B12-deficient groups were found to be similar when compared to the corresponding nondeficient groups. There is a positive correlation between total and active Vitamin B12 assay (r = 0.52, P < 0.01). The predictive ability of total and active B12 for both neonatal and maternal outcomes assessed using the ROC curve reported an AUC <0.70. Conclusions: Total B12 assay was strongly positively correlated with active B12 assay. However, neither of these predicted maternal medical complications or neonatal complications associated with B12 deficiency. Therefore, we suggest a continuation of the standard practice of total Vitamin B12 assay over active B12 assay for the estimation of B12 deficiency in pregnancy especially in low- and middle-income countries like India.

Abstract Introduction: Cholestasis may increase the difficulty of diagnosing Wilson’s disease (WD). We aimed to compare Leipzig score including hepatic parenchymal copper concentration or rhodanine stain, to diagnose hepatic WD, in noncholestatic patients with fibrosis. Materials and Methods: We defined cholestasis by biochemical and/or histological criteria. Of noncholestatic patients who had liver fibrosis and liver copper estimation, those with isolated hepatic WD comprised WD study group and those with liver disease other than WD, with either low serum ceruloplasmin, high urinary copper, or Kayser–Fleischer ring, were controls. WD diagnosis by Leipzig score was labeled highly likely, probable, or unlikely. Results: Twenty WD study group patients (12 males; 21 [6–52] years; median [range]) and 18 controls (13 males; 32 [10–69] years, all had high urinary copper) were recruited. Rhodanine stain was positive in 60% WD patients and in 33% of controls. With rhodanine stain, Leipzig score had sensitivity of 100% (95% confidence interval: 83.2%–100%), specificity of 66.7% (41%–86.7%), and positive likelihood ratio of 3 (1.56–5.77) to diagnose probable/highly likely WD. In contrast, on adding hepatic parenchymal copper concentration, Leipzig score had sensitivity of 100% (83.2%–100%), but specificity was 38.9% (17.3%–64.2%). In controls, Leipzig score (including rhodanine stain) of ≤ 2 ruled out WD. Conclusion: On excluding cholestatic patients, rhodanine stain performs better than hepatic parenchymal copper concentration to diagnose hepatic WD using Leipzig score in patients with fibrosis. Widespread availability is an added advantage of rhodanine stain.

Abstract Background Securing definitive airway with minimal complications is a challenging task for high-volume emergency departments (ED) that deal with patients with compromised airway. Materials and methods We conducted a prospective observational study between September 2019 and March 2020. Cohort of adults presenting to the ED requiring rapid sequence induction (RSI) were recruited to determine the prevalence and risk factors for the development of aspiration pneumonia(AP) in patients intubated in the ED. Results During the study period, a total of 154 patients with a mean age of 44.5 years required RSI in the ED. Male (61%) predominance was noted among the study cohorts. We did not find any association between RSI performed in the ED and the risk of developing AP. The first attempt success rate of RSI was 76.7%, and 33(21.4%) patients had immediate adverse events following RSI. Rescue intubation was required for 11(7.1%) patients. The prevalence of AP following RSI in the ED was 13.4%. Endotracheal tube (ET) aspirate pepsin was positive in 45(29.2%) samples collected. The ET aspirate pepsin assay had low sensitivity (44.44%), specificity (73.53%), positive predictive value (18%), and negative predictive value (91%) in predicting the occurrence of AP. On multivariate logistic regression analysis, male gender (AOR: 7.29, 95%CI: 1.51−35.03, p = 0.013) and diabetes mellitus (AOR: 3.75, 95%CI: 1.23-11.51, p = 0.02) were found to be independent risk factors for developing AP. Conclusion We identified male gender and diabetes mellitus to be independent predictors of risk of developing AP after RSI in the ED. ET aspirate pepsin levels proved to be neither sensitive nor specific in the diagnosis of AP. How to cite this article Roshan R, Sudhakar GD, Vijay J, Mamta M, Amirtharaj J, Priya G, et al. Aspiration during Rapid Sequence Induction: Prevalence and Risk Factors. Indian J Crit Care Med 2021;25(2):140–145.

Background:Myocardial preconditioning using volatile anesthetics such as isoflurane and sevoflurane have beneficial effects in decreasing morbidity in cardiac surgical patients. Studies in animal models have indicated that reactive oxygen and nitrogen species probably play a role in mediating these effects. However, data from human studies are scarce and the differential effect of sevoflurane vs. isoflurane on reactive oxygen species (ROS) and reactive nitrogen species (RNS) has not been studied extensively. Materials and Methods:Randomized clinical control trial comparing preconditioning effects of volatile agents isoflurane and sevoflurane when administered during coronary artery bypass surgeries on cardiopulmonary bypass (CPB). Serum samples were collected at 3 time points before induction, after cross clamp release and one hour after separation from CPB. Levels of oxidative stress markers and nitric oxide were analyzed in these samples. Results:Hemodynamic indices, cardio-pulmonary bypass duration, and ICU stay were similar between the groups. CKMB values 12 hours post-op were decreased in majority of patients in the sevoflurane group compared to isoflurane. Serum malondialdehyde and nitrate levels were lower with sevoflurane (P < 0.05) when compared to the isoflurane group, but no significant differences in protein carbonyl content or protein thiol content were evident between the 2 groups. Sevoflurane also prevented the decrease in total thiols during later stages of surgery. Conclusions:Volatile anesthetics, isoflurane and sevoflurane modulate oxidative and nitrosative stress during CABG. Between the two pre-conditioning agents, isoflurane seems to provide better protection during the pre-bypass period, while sevoflurane provides protection during both pre- as well as post-bypass period.

Objectives: The aim of this study is to assess the utility of plasma von-Willebrand factor (VWF) levels in predicting in-hospital survival for patients with severe alcoholic hepatitis. Methods: From a prospectively collected database of acute-on-chronic liver failure (ACLF) patients, we retrospectively selected all severe alcoholic hepatitis (discriminant function [DF] ≥32) patients and correlated baseline plasma VWF (antigen, Ag and collagen-binding activity [CBA]) levels with disease severity. In-hospital survival was classified as discharged alive (or) died/discharged in a terminal condition (poor outcome). Results: Of 34 consecutive severe alcoholic hepatitis patients (age: 40.5, 30–63 years; median, range, hospital stay: 6, 2–15 days) studied, 15 had a poor outcome. Plasma VWF-CBA was higher in patients with poor outcome (736 [396–1157] IU/dL) as compared to patients discharged in stable state (492 [97–986] IU/dL; P = 0.03). VWF-CBA correlated well with VWF-Ag, model for end-stage liver disease (MELD) score, sequential organ failure assessment score and ACLF grades. AUROC to predict composite poor outcome was similar for plasma VWF-CBA (0.72, 0.54–0.89) and MELD score (0.71, 0.53–0.89). Plasma VWF-CBA was higher in 23 “very severe” alcoholic hepatitis (DF >60 or MELD >30) patients. Combining plasma VWF-CBA (>750 IU/dL) and criteria for “very severe” alcoholic hepatitis had a sensitivity of 100% (81%–100%) and negative predictive value of 100% (68%–100%) for predicting poor outcome. Conclusions: Plasma VWF levels are markedly elevated, correlate with organ failure, and predict in-hospital survival in severe alcoholic hepatitis, and also in “very severe” alcoholic hepatitis, patients.

Non-cirrhotic intrahepatic portal hypertension (NCIPH) is characterized by thrombotic microangiopathy of the portal venous system, low ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs–13), and high vWF (von Willebrand factor) levels. This study aimed to screen for ADAMTS13 mutations, focusing on the CUB domain, in these patients.

Thioacetamide (TAA) administration is widely used for induction of liver cirrhosis in rats, where reactive oxygen radicals (ROS) and nitric oxide (NO) participate in development of liver damage. Cardiac dysfunction is an important complication of liver cirrhosis, but the role of ROS or NO in cardiac abnormalities during liver cirrhosis is not well understood. This was investigated in animals after TAA-induced liver cirrhosis and temporal changes in oxidative stress, NO and mitochondrial function in the heart evaluated. TAA induced elevation in cardiac levels of nitrate before development of frank liver cirrhosis, without gross histological alterations. This was accompanied by an early induction of P38 MAP kinase, which is influenced by ROS and plays an important signaling role for induction of iNOS. Increased nitrotyrosine, protein oxidation and lipid peroxidation in the heart and cardiac mitochondria, suggestive of oxidative stress, also preceded frank liver cirrhosis. However, compromised cardiac mitochondrial function with a decrease in respiratory control ratio and increased mitochondrial swelling was seen later, when cirrhosis was evident. In conclusion, TAA induces elevations in ROS and NO in the heart in parallel to early liver damage. This leads to later development of functional deficits in cardiac mitochondria after development of liver cirrhosis.

Background and Aim: ADAMTS13 (a disintegrin like and metalloproteinase with thrombospondin repeats), deficiency, which predisposes to increased platelet adhesion to endothelium, is seen in patients with decompensated cirrhosis and in NCIPH (non-cirrhotic intrahepatic portal hypertension) with preserved liver function. In this study, we compared systemic vascular complications in these patients, during follow up. Methods: From prospectively collected database of patients with portal hypertension due to unexplained liver disease, we selected patients with plasma ADAMTS13 activity <15% (estimated by in-house collagen binding assay). Vascular complications on follow up were analysed. Patients were diagnosed as NCIPH (liver biopsy showing absence of advanced fibrosis) or cryptogenic cirrhosis (CC-liver biopsy either not done or showed advanced fibrosis). Results: From 2008 to 2015, 10 NCIPH and 10 CC patients (7 did not have liver biopsy, 3—biopsy showed bridging fibrosis or cirrhosis) with <15% ADAMTS13 activity were selected for the study. NCIPH patients (age: 29, 21–42 years; median, range; Child's score: 6, 5–7) were younger; well compensated compared to CC patients (age: 54, 26–73 years; P-vaue:0.001; Child's score: 9, 5–13; P-value:0.01). On follow up (65 months, 6–225 months); 5 (50%) CC patients compared to none with NCIPH died. One patient in each group developed hepatocellular carcinoma. On follow up over 67 (15–225) months, of NCIPH patients, 4 (40%) developed new onset portal vein thrombosis; 3 (30%) developed microvascular complications—IgA nephropathy (after splenorenal shunt surgery) (1), avascular necrosis of hip (1), pulmonary hypertension (1). In contrast, only 1 CC patient developed portal vein thrombosis, other vascular complications were not seen on follow up over 62 (6–192) months. Conclusion: Unlike patients with decompensated cirrhosis, ADAMTS13 deficiency is noted in NCIPH patients despite preserved liver function. ADAMTS13 deficiency may predispose to macro and micro vascular complications in NCIPH patients. The authors have none to declare.

Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH), a chronic microangiopathy of the liver caused by arsenicosis from use of contaminated groundwater, was reported from Asia. This study aimed to see, if in the twenty-first century, arsenicosis was present in NCIPH patients at our hospital and, if present, to look for groundwater contamination by arsenic in their residential locality.

Background and Aims Circulating levels of von Willebrand factor (vWF) predict mortality in patients with cirrhosis. We hypothesized that systemic inflammation in acute-on-chronic liver failure (ACLF) will stimulate endothelium, increase vWF levels, and promote platelet microthrombi causing organ failure. Methods In this prospective study, we correlated plasma vWF levels with organ failure, liver disease severity, sepsis, and systemic inflammatory response syndrome (SIRS) and also analyzed if vWF levels predicted in-hospital composite poor outcome (i.e. death/discharged in terminal condition/liver transplantation) in consecutive ACLF patients. Results Twenty-one of the 50 ACLF patients studied had composite poor outcome. ACLF patients had markedly elevated vWF antigen and activity (sevenfold and fivefold median increase, respectively) on days 1 and 3. Median ratio of vWF to a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) activity on day 1 was significantly higher in ACLF patients (11.2) compared to 20 compensated cirrhosis patients (3.3) and healthy volunteers (0.9). On day 1, area under ROC curve (AUROC) to predict composite poor outcome of hospital stay for ACLF patients for vWF antigen, vWF activity, and model for end-stage liver disease (MELD) score were 0.63, 0.68, and 0.74, respectively. vWF activity correlated better with liver disease severity (MELD score, ACLF grade) and organ failure (Sequential Organ Failure Assessment [SOFA] score) than vWF antigen; in contrast, neither vWF antigen nor activity correlated with platelet count, sepsis, or SIRS. Conclusions vWF levels are markedly elevated, correlate with organ failure, and predict in-hospital survival in ACLF patients. This data provides a mechanistic basis for postulating that vWF-reducing treatments such as plasma exchange may benefit ACLF patients.

Background and Aim: Glutamine is an important energy source for the intestinal epithelium, and its supplementation protects intestinal epithelial cells by induction of glutathione. However, mechanisms of glutathione induction in cells at various stages of differentiation along the crypt to villus axis are not well understood. This study examined induction of glutathione in response to glutamine along the intestinal villus-crypt axis and evaluated regulatory mediators involved in the process.Methods: Animals were administered 4% glutamine in feed for 7 days, following which enterocytes at various stages of differentiation were isolated and glutathione levels and signaling mediators involved in its regulation were studied.Results: In control animals, glutathione levels were higher in the intestinal crypt than in the villus or middle region. This was accompanied by elevated expression of the modifier subunit of glutathione synthetase (GCLM) and the transcription factor Nrf2 when compared with cells from the villus and middle regions. These levels were further enhanced by glutamine throughout the intestine, although the effects were more dramatic in the crypt. In parallel to glutathione induction, glutamine supplementation also altered actin dynamics and proliferation in cells of the crypt.Conclusions: These results suggest that the variation of glutathione levels along the villus-crypt axis in the intestine is due to gradients in expression of mediators such as glutamate cysteine ligase modifier subunit and Nrf2. The protective effects of glutamine supplementation seem to be most pronounced in the crypt, where it upregulates proliferation, glutathione levels and alters actin dynamics.

Background: Oxidative and nitrosative stress caused by drug metabolism may be a trigger for keratinocyte apoptosis in the epidermis seen in toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS). Aims: To estimate oxidative damage in the serum and to examine the role of nitric oxide in mediating epidermal damage in patients with TEN and SJS. Materials and Methods: A prospective study was conducted among TEN and SJS patients and controls in a tertiary care center between January 2006 and February 2010. Patients with a maculopapular drug rash without detachment of skin constituted the control group 1 (drug exposed). Patients without a drug rash constituted the control group 2 (drug unexposed). The serum values of protein carbonyls, malondialdehyde, conjugated diene and nitrates were measured. Two-group comparison with the non-parametric Mann-Whitney U test was used. Significance of differences if any was established using Pearson's Chi-square test. Results: Ten patients in the SJS-TEN group (study group), 8 patients in control group 1 and 7 patients in control group 2 were included. More than one drug was implicated in 4/10 patients in group 1 and 3/8 patients in group 2. SCORTEN of 0, 1 and 3 at admission were seen in 2, 6 and 2 patients, respectively. The serum values of protein carbonyls, malondialdehyde, conjugated diene and nitrates were not significantly increased in the study group when compared to the controls. Conclusions: There was no elevation of oxidative stress markers in patients with TEN and SJS as compared to the control population.

Alterations in liver vascular tone play an important role in chronic liver disease. The hepatic stellate cell (HSC) and mediators such as nitric oxide (NO) and hydrogen sulfide (H2S) have been implicated in regulation of vascular tone and intra-hepatic pressure. Though these have been studied in chronic liver damage, changes in response to acute liver injury induced by hepatotoxins such as dimethyl nitrosamine are not well understood. Liver injury was induced in mice by a single intra-peritoneal injection of dimethylnitrosamine (DMN), following which animals were sacrificed at 24, 48 and 72 h. Changes in vascular mediators such as NO and H2S as well as stellate cell activation was then examined. It was found that a single low dose of DMN in mice is sufficient to induce activation of hepatic stellate cells within 24 h, accompanied by oxidative stress, compromised metabolism of H2S and decreased levels of the von Willebrand factor (vWF) cleaving protease; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), which functions in intravascular thrombosis. A suppression of hepatic NO levels is also initiated at this time point, which progresses further and is sustained up to 72 h, at which point the HSC activation is still present. Compromised levels of ADAMTS13 and H2S metabolism however, begin to recover by 48 h and are almost similar to control by 72 h. In conclusion, these data suggest that even moderate acute insults in the liver can have far reaching consequences on a number of mediators of vascular flow in the liver.

BACKGROUND:Ulcerative colitis (UC) is characterized by an energy deficiency state of the colonic epithelium. This study evaluated mitochondrial electron transport chain (ETC) complex activity in normal and disease mucosa in patients with UC. Alterations in ETC complexes were also investigated in experimental colitis in mice.METHODS:Biopsies were obtained from macroscopically normal and diseased colonic mucosa of 43 patients with UC and 35 controls undergoing screening colonoscopy and ETC complex activity was assayed biochemically. ETC complex activities were also assayed in colonic epithelial cells isolated from Swiss albino mice with dextran sodium sulfate (DSS)-induced colitis at various stages of induction of colitis. Mucosal nitrite levels and protein carbonyl content were determined.RESULTS:The activity of Complex II was significantly decreased in colonic biopsies from UC patients compared with controls, while activities of other mitochondrial complex were normal. Complex II activity was equally decreased in diseased and normal mucosa in UC; the degree of reduction did not correlate with clinical, endoscopic, or histological grading of disease activity. In DSS-fed mice, a reduction in activity of Complex IV and Complex II was observed. Activity of other complex was not affected. Administration of aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, attenuated all parameters of colitis as well as the reductions in Complex IV and Complex II activity.CONCLUSIONS:Reduction in Complex II activity appears to be a specific change in UC, present in quiescent and active disease. Mitochondrial complex dysfunction occurs in DSS colitis in mice and appears to be mediated by nitric oxide.

Background: Investigations of molecular mechanisms behind the progression of neoplastic changes in the esophagus have uncovered the role of the COX & 5-Lox pathways. Human squamous esophageal mucosa produces relatively large amounts of eicosanoids in the presence of inflammation. Laboratory and epidemiological data suggest that aspirin and non-steroidal anti-inflammatory drugs may be chemo preventive through their inhibitory effect on COX25, 10. Cell culture studies have shown that the members of the mitogen activated protein (MAP) kinase family plays an important role in the development of bile acid-induced carcinogenesis. Differences in MAPK pathways activated by bile exposure were also noted in esophageal squamous cell lines and biopsies from patients with GERD. The protective role of aspirin and its molecular mechanism is not well understood.Aims:1. The effect of duodenal reflux on esophageal mucosa.2. The role of aspirin in preventing duodenal reflux induced esophageal mucosa changes.3. If it is proven to be preventive, the mechanism of its action. A duodenal reflux rat animal model was used by an end-to-side esophago duodenostomy.Methods: Total of 56 rats was included. 3 were "Naive control" animals which did not undergo the surgical procedure. The remaining animals were divided into two groups: Surgery alone (experimental) and Surgery + aspirin [therapy group], esophagoduodenostomy. At 40 weeks, the rats were euthanized and appropriate esophageal samples were analysed for histopathology and p38 & ERK MAP kinases, VEGF, protease activity and caspase 3 activities.Results: The presence of gross mucosal nodularity was seen in 21 and 10 rats of the experimental and therapy group respectively (p = 0.03; Table 1). Reflux-associated changes such as basal cell hyperplasia were more common in the experimental group, however this association did not reach statistical significance (p = 0.15; Table 1). Epithelial hyperplasia was seen more in the experimental group, which was prevented by aspirin [p < 0.01]. Papillomatosis, as shown in Fig. 4 was more common in the experimental group (p = 0.02). Activation of p38 & ERK MAP kinases was prevented in aspirin group (p < 0.05, CI -1.796- -0.014). Examination of protease activity by zymographic analysis of the esophageal samples revealed a number of gelatinolytic bands in 50% rats of the experimental group, not observed in the therapy group. No significant changes were seen in Caspase 3 [Normal areas -99.74 & nodular areas - 100.34 percent of controls] or VEGF [mean 0.64, sd +/- 0.76 Vs 0.69 +/- 0.96] activity.Conclusions: Our data demonstrated that low dose aspirin reduced the incidence of duodenoesophageal reflux induced histological changes in the esophagus by preventing activation of proliferative & antiapoptotic MAP kinases such as p38 & ER as well as protease activity. Though Barretts' changes and adenocarcinoma have not developed, it could explain the role of duodenoesophageal reflux in the development of different histological but potential premalignant lesions and molecular level changes which are prevented by low dose aspirin. (C) 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Human serum albumin binds ligands such as fatty acids and metals in circulation. Oxidative stress can modify albumin and affect ligand binding. This study examines the role of oxidative stress and fatty acids in modulating cobalt binding to albumin in patients with fatty liver. Elevated levels of malondialdehyde and protein carbonyls, indicative of oxidative stress were evident in serum of patients with fatty liver. A significant decrease in albumin–cobalt binding was also observed. Albumin isolated from patient serum also showed an increase in bound fatty acids. In vitro experiments indicated that while oxidant exposure or removal of fatty acids independently decreased cobalt binding to albumin, removal of fatty acids from the protein prior to oxidant exposure did not influence the oxidant effect on albumin–cobalt binding. These results suggest that oxidative stress and fatty acids on albumin can influence albumin–cobalt binding in patients with fatty liver by independent mechanisms.