Functional insight into multi-omics-based interventions for climatic resilience in sorghum (Sorghum bicolor): a nutritionally rich cereal crop.

MAIN CONCLUSION: The article highlights omics-based interventions in sorghum to combat food and nutritional scarcity in the future. Sorghum with its unique ability to thrive in adverse conditions, has become a tremendous highly nutritive, and multipurpose cereal crop. It is resistant to various types of climatic stressors which will pave its way to a future food crop. Multi-omics refers to the comprehensive study of an organism at multiple molecular levels, including genomics, transcriptomics, proteomics, and metabolomics. Genomic studies have provided insights into the genetic diversity of sorghum and led to the development of genetically improved sorghum. Transcriptomics involves analysing the gene expression patterns in sorghum under various conditions. This knowledge is vital for developing crop varieties with enhanced stress tolerance. Proteomics enables the identification and quantification of the proteins present in sorghum. This approach helps in understanding the functional roles of specific proteins in response to stress and provides insights into metabolic pathways that contribute to resilience and grain production. Metabolomics studies the small molecules, or metabolites, produced by sorghum, provides information about the metabolic pathways that are activated or modified in response to environmental stress. This knowledge can be used to engineer sorghum varieties with improved metabolic efficiency, ultimately leading to better crop yields. In this review, we have focused on various multi-omics approaches, gene expression analysis, and different pathways for the improvement of Sorghum. Applying omics approaches to sorghum research allows for a holistic understanding of its genome function. This knowledge is invaluable for addressing challenges such as climate change, resource limitations, and the need for sustainable agriculture.

Incidence of Cardiovascular Instability in Patients With Guillain-Barré Syndrome: A Retrospective Study.

Introduction Guillain-Barré syndrome (GBS) is an autoimmune disease affecting radicles and peripheral nerves resulting in acute flaccid paralysis. Respiratory failure, autonomic dysfunction, and secondary complications such as pneumonia, and venous thromboembolism are the major causes of death and disability in GBS. Cardiovascular complications play a major role in the prognosis of GBS patients. The aim is to determine the incidence of cardiovascular instability in GBS patients and to see if there are any specific risk groups associated with the development of cardiovascular instability. Methodology This is a retrospective descriptive study conducted in a tertiary care center in South India. Data on 50 consecutive GBS patients were collected from hospital records including case sheets, death summaries, and discharge summaries. Patients with evidence of sepsis, blood loss, heavy alcohol consumption, and chronic liver disease were excluded from the study. Baseline demographic data, symptom onset to admission time, baseline Erasmus Guillain-Barré Syndrome Respiratory Insufficiency Score (EGRIS), and baseline liver function tests were documented. The presence of heart rate and blood pressure fluctuations was noted from the records. Frequency data were calculated from the categorical variables. Analysis of non-parametric variables by chi-square test was done using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, New York, United States). Results Cardiovascular instability was present in 15 (30%) patients in the study population. It was present in all patients (100%) who require mechanical ventilation. The incidence of cardiovascular instability was higher in patients who had lesser onset to admission times (41.9% vs 10.5%; p=0.019), EGRIS≥4 (40.6% vs 11.1%; p=0.029), and lower cranial nerve involvement (40% vs 6.7%; p=0.018). Conclusion Of patients with GBS, 30% developed cardiovascular instability during their disease course. Patients with lesser onset to admission times, EGRIS ≥4, and those with lower cranial nerve involvement had a greater incidence of cardiovascular instability.

Comparing U.S. and Canadian treatment patterns on venous thromboembolism outcomes in the GARFIELD-VTE registry.

BACKGROUND: Economically developed countries continue to find that venous thromboembolism (VTE) is a major cause of morbidity and mortality. OBJECTIVE: To compare baseline risk profiles and patient workflow patterns between the United States (U.S.) and Canadian management of VTE patients from 2014 to 2017. METHODS: The Global Anticoagulant Registry in the FIELD (GARFIELD-VTE) is a prospective, observational study of 10,679 patients with objectively confirmed VTE, followed for 3 years. In total 1101 patients enrolled in the U.S. and Canada were included in this analysis. RESULTS: Median age and body mass index were comparable between the U.S. (60.5; 30.2) and Canadian (59.7; 29) patients. A higher percentage of U.S. patients were black (n = 128, 24.1 %; n = 22, 3.9 %) and had a higher VTE-associated risk profile, including immobilization, hospitalization, and recent surgery. U.S. patients had a higher combined DVT and PE primary diagnoses (20.3 %) and were more likely to be treated in hospitals (77.2 %) than Canadians (13.3 %; 48.1 %). Direct oral anticoagulant therapy (DOAC) was nearly two-fold more frequent in Canadian patients (n = 218, 39.2 %) at the end of 3 years in comparison to the U.S. (n = 118, 23.0 %). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, the risk of all-cause mortality was 51.9 % higher in patients from the U.S. compared to those in Canada after 3 years. Patients from the U.S. also had a higher likelihood of hospitalization, major bleeding, and recurrent VTE after controlling for prior history and comorbid conditions. CONCLUSION: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies. TYPE OF RESEARCH: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). KEY FINDINGS: 531 U.S. and 557 Canadians patients included in study. DOAC use more frequent in Canadian patients after 3 years than U.S. (39.2 % vs. 23.0 %, respectively). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, all-cause mortality risk remained higher in U.S. patients vs. Canadian patients after 3 years. U.S. patients had higher likelihood of hospitalization, major bleeding, and recurrent VTE. TAKE-HOME MESSAGE: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and composition of specialists and their subsequent treatment strategies. TABLE OF CONTENTS SUMMARY: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). Higher rates of adverse VTE-associated outcomes were observed in U.S. patients vs Canadian patients, which may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies.

Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.

Approximately 50%-55% of high-grade serous ovarian carcinoma (HGSOC) patients have MYC oncogenic pathway activation. Because MYC is not directly targetable, we have analyzed molecular pathways enriched in MYC-high HGSOC tumors to identify potential therapeutic targets. Here, we report that MYC-high HGSOC tumors show enrichment in genes controlled by NRF2, an antioxidant signaling pathway, along with increased thioredoxin redox activity. Treatment of MYC-high HGSOC tumors cells with US Food and Drug Administration (FDA)-approved thioredoxin reductase 1 (TrxR1) inhibitor auranofin resulted in significant growth suppression and apoptosis in MYC-high HGSOC cells in vitro and also significantly reduced tumor growth in an MYC-high HGSOC patient-derived tumor xenograft. We found that auranofin treatment inhibited glycolysis in MYC-high cells via oxidation-induced GAPDH inhibition. Interestingly, in response to auranofin-induced glycolysis inhibition, MYC-high HGSOC cells switched to glutamine metabolism for survival. Depletion of glutamine with either glutamine starvation or glutaminase (GLS1) inhibitor CB-839 exerted synergistic anti-tumor activity with auranofin in HGSOC cells and OVCAR-8 cell line xenograft. These findings suggest that applying a combined therapy of GLS1 inhibitor and TrxR1 inhibitor could effectively treat MYC-high HGSOC patients.

36-month clinical outcomes of patients with venous thromboembolism: GARFIELD-VTE.

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population.

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

Color stability of aligner materials on exposure to indigenous food products: An in-vitro study.

Background: In the recent day, there has been an exponential growth in the usage of clear aligners for orthodontic treatment. As with any removable appliance, the compliance of patients to remove it during ingestion of food is, at times, poor. Thus, the stability of the clear aligner to be "clear" becomes questionable. This in-vitro study examined how the clear aligners changed colour on exposure to various indigenous food products used in everyday life. Methods: Aligners from 5 different companies (K Line, Clearbite Aligners, The Aligner Company, iAligners and MaxDent CA Digital) were exposed for 12 hours and 24 hours to various indigenous substances (tea, green tea, coffee, turmeric, saffron and Kashmiri red chili powder) and a control solution (distilled water) in-vitro. The color change was assessed with the help of VITA Easyshade compact colorimeter based on Commission Internationale de I'Eclairage L*a*b* color system. Values were then modified to NBS units for clinical relevance. Results: The hue of the transparent aligners was noticed to change in a statistically meaningful way when exposed to turmeric, saffron, Kashmiri red chili powder and coffee in decreasing order and mild color change in tea and green tea at both 12 hours and 24 hours intervals. Conclusion: Aligners are prone to color change when exposed to indigenous foods that contain staining properties.

Myricetin: versatile plant based flavonoid for cancer treatment by inducing cell cycle arrest and ROS-reliant mitochondria-facilitated apoptosis in A549 lung cancer cells and in silico prediction.

Myricetin is categorized under the secondary metabolite flavonoid which includes a diverse range of consumable plant parts, and it has a potential against several classes of cancer including cancers and tumors. In the present study, the anticancer potential of the unique flavonoid-myricetin in A549 lung cancer cells was evaluated. Among different doses of myricetin, 73 µg/ml was more effective to prevent the cancer cell growth. It also promoted sub-G1 phase aggregation of cells and a equivalent decrease in the fraction of cells entering the S and subsequent phase which indicates apoptotic cell death. Myricetin generated enormous free radicals and, altered the potential of mitochondrial membrane in A549 cells as paralleled to untreated cells. In addition, myricetin treatment intensified the expression of P53 and relegated the expression of EGFR in A549 cells. These results suggested that myricetin exhibits cytotoxic potential by arresting the progression of cell cycle and ROS-dependent mitochondria-mediated mortality in cancer A549 lung cancer cells and it would be useful to develop as a drug candidate for lung cancer therapeutics. In silico experiments were carried out against human EGFR and P53 tumor suppressor protein to gain more insights into the binding mode of the myricetin may act as significant potential for anticancer therapy.

An Interdisciplinary Management of Severe Facial Asymmetry Due to Hemifacial Microsomia.

This case report outlines the importance of an interdisciplinary approach and a patient centric outcome for the treatment of facial asymmetry resulting from hemifacial microsomia. Different treatment modalities are available to treat asymmetries. However, the best treatment outcome can be achieved only when the treatment plan is individualized for every patient. This report portrays an adult patient with hemifacial microsomia, who had facial asymmetry from the level of supraorbital region with a Class II skeletal base. Orthodontic treatment, along with surgical management, was required to transform the patient into a symmetrical profile, which is esthetically pleasing. A sound knowledge of the various technologies and resources that are available to us and making the best use of it to bring out a drastic change in the patient's life. Combined effort of the orthodontists and oral surgeons are required to manage patient's with hemifacial microsomia that has caused the severe facial asymmetry. Moreover, special attention has to be given to a patient-centric outcome.

Exposures to fine particulate matter (PM2.5) and birthweight in a rural-urban, mother-child cohort in Tamil Nadu, India.

BACKGROUND: Exposure to PM2.5 (fine particulate matter

Recognition of wake-sleep stage 1 multichannel eeg patterns using spectral entropy features for drowsiness detection.

Electroencephalographic (EEG) activity recorded during the entire sleep cycle reflects various complex processes associated with brain and exhibits a high degree of irregularity through various stages of sleep. The identification of transition from wakefulness to stage1 sleep is a challenging area of research for the biomedical community. In this paper, spectral entropy (SE) is used as a complexity measure to quantify irregularities in awake and stage1 sleep of 8-channel sleep EEG data from the polysomnographic recordings of ten healthy subjects. The SE measures of awake and stage1 sleep EEG data are estimated for each second and applied to a multilayer perceptron feed forward neural network (MLP-FF). The network is trained using back propagation algorithm for recognizing these two patterns. Initially, the MLP network is trained and tested for randomly chosen subject-wise combined datasets I and II and then for the combined large dataset III. In all cases, 60 % of the entire dataset is used for training while 20 % is used for testing and 20 % for validation. Results indicate that the MLP neural network learns with maximum testing accuracy of 95.9 % for dataset II. In the case of combined large dataset, the network performs with a maximum accuracy of 99.2 % with 100 hidden neurons. Results show that in channels O1, O2, F3 and F4 (A1, A2 as reference), the mean of the spectral entropy value is higher in awake state than in stage1 sleep indicating that the EEG becomes more regular and rhythmic as the subject attains stage1 sleep from wakefulness. However, in C3 and C4 the mean values of SE values are not very much discriminative of both groups. This may prove to be a very effective indicator for scoring the first two stages of sleep EEG and may be used to detect the transition from wakefulness to stage1 sleep.

Evaluation and Comparison of Intermaxillary Tooth Size Discrepancy among Class I, Class II Division 1, and Class III Subjects Using Bolton's Analysis: An in vitro Study.

AIM: The aim of the present study was to evaluation and comparison of intermaxillary tooth size discrepancy among Class I, Class II division 1, and Class III subjects using Bolton's analysis. MATERIALS AND METHODS: The pre-treatment casts were selected from the records of patients attending the Department of Orthodontics of Meenakshi Ammal Dental College, Chennai. The sample consists of 180 pre-treatment casts with both sexes evenly distributed with 60 casts in each type of malocclusion, i.e., Class I, Class II div 1, and Class III malocclusion. The sample was selected according to angles classification. All patients were Indian nationals, between the age group of 12 to 20 years and Bolton's analysis done on all the casts. RESULTS: Statistically no significant difference in all types of malocclusion except anterior Bolton's discrepancy in Class III. CONCLUSION: Mean Bolton's anterior ratio for angles Class III subjects was significantly greater than for Class I and Class II subjects. When Bolton's overall ratio was compared there was no statistically significant difference among Class I, Class II div 1, and Class III malocclusions.

CARM1 regulates astroglial lineage through transcriptional regulation of Nanog and posttranscriptional regulation by miR92a.

Coactivator-associated arginine methyltransferase (CARM1/PRMT4)-mediated transcriptional coactivation and arginine methylation is known to regulate various tissue-specific differentiation events. Although CARM1 is expressed in the neural crest region in early development, coinciding with early neuronal progenitor specification, the role of CARM1 in any neuronal developmental pathways has been unexplored. Using a specific small-molecule inhibitor of CARM1-mediated H3R17 methylation in human embryonic stem cell line, we find that H3R17 methylation contributes to the maintenance of the astroglial cell population. A network of regulation was observed on the miR92a promoter by which H3R17-responsive Nanog bound to the miR92a promoter decreased upon inhibition, resulting in an abnormal gene expression program influencing the glial lineage. This was also true in zebrafish, in which, with the help of CARM1 inhibitor and CARM1 morpholinos, we show that inhibition of H3R17 methylation results in defective glial cell morphology and a sensory defect in a subpopulation. A gain-of-function strategy in which mCARM1 was introduced in the morpholino-treated embryos exhibited recovery of the sensory defect phenotype. This study thus establishes the functional cooperation between arginine methylation and microRNA expression in the neuronal developmental process, with potential implications in sensory development pathways.

Antioxidant Potential of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Higher Basidiomycetes) Cultivated on Artocarpus heterophyllus Sawdust Substrate in India.

The artificial cultivation of Ganoderma lucidum (MTCC1039) using Artocarpus heterophyllus as sawdust substrate was optimized and free radical scavenging activities of the generated fruiting bodies were investigated. The choice of A. heterophyllus as substrate was due to its easy availability in South India. Sawdust supplemented with dextrose medium yielded better spawn hyphae and early fruiting body initiation (15 days). The biological yield obtained was 42.06 ± 2.14 g/packet and the biological efficiency was 8.41 ± 0.48%. Both aqueous and methanolic extracts of fruiting body were analyzed for radical scavenging activity. Methanolic extract showed maximum scavenging activity for 1,1-diphenyl-2-picrylhydrazyl (IC50 = 290 µg/ml) and 2,2'-azino-bis(3-ethylbenzothiazoline- 6-sulphonic acid (IC50 = 580 µg/ml), whereas aqueous extract had better scavenging for ferric reducing antioxidant power (IC50 = 5 µg/ml). Total phenolic content and total antioxidant capacity were significantly higher in methanolic extract (p < 0.01). A positive correlation existed between the phenolic content and antioxidant activity. Our results indicated that fruiting bodies of G. lucidum cultivated in sawdust medium possess antioxidant property, which can be exploited for therapeutic application.

Everolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo, while demonstrating anti-angiogenic activities.

Progression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex process which involves several pathological phenomena, including hepatic stellate cell activation, inflammation, fibrosis and angiogenesis. Therefore inhibiting multiple pathological processes using a single drug can be an effective choice to curb the progression of HCC. In the present study, we used the mTOR inhibitor everolimus to observe its effect on the in vitro activation of hepatic stellate cells and angiogenesis. The results of the present study demonstrated that everolimus treatment blocked the functions of the immortalized human activated hepatic stellate cell line LX-2 without affecting the viability and migration of primary human stellate cells. We also observed that treatment with everolimus (20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment was also able to attenuate the activation of primary stellate cells to their activated form. Angiogenesis studies showed that everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube formation and migration of liver sinusoidal endothelial cells. Finally, everolimus treatment reduced the load of tumoral myofibroblasts in a rat model of HCC. These data suggest that everolimus targets multiple mechanisms, making it a potent blocker of the progression of HCC from liver fibrosis.

Properties and mutation studies of a bacteriophage-derived chimeric recombinant staphylolytic protein P128: Comparison to recombinant lysostaphin.

P128 is a chimeric anti-staphylococcal protein having a catalytic domain from a Staphylococcus bacteriophage K tail associated structural protein and a cell wall targeting domain from the Staphylococcus bacteriocin-lysostaphin. In this study, we disclose additional properties of P128 and compared the same with lysostaphin. While lysostaphin was found to get inactivated by heat and was inactive on its parent strain S. simulans biovar staphylolyticus, P128 was thermostable and was lytic towards S. simulans biovar staphylolyticus demonstrating a difference in their mechanism of action. Selected mutation studies of the catalytic domain of P128 showed that arginine and cysteine, at 40th and 76th positions respectively, are critical for the staphylolytic activity of P128, although these amino acids are not conserved residues. In comparison to native P128, only the R40S mutant (P301) was catalytically active on zymogram gel and had a similar secondary structure, as assessed by circular dichroism analysis and in silico modeling with similar cell binding properties. Mutation of the arginine residue at 40th position of the P128 molecule caused dramatic reduction in the Vmax (∆OD600 [mg/min]) value (nearly 270 fold) and the recombinant lysostaphin also showed lesser Vmax value (nearly 1.5 fold) in comparison to the unmodified P128 protein. The kinetic parameters such as apparent Km (KmAPP) and apparent Kcat (KcatAPP) of the native P128 protein also showed significant differences in comparison to the values observed for P301 and lysostaphin.

Fahr's disease and psychiatric syndromes: A case series.

Fahr's disease is characterized by basal ganglia calcification with clinical manifestations in the form of neuropsychiatric disorders, neurological symptoms, and cognitive symptoms. In this case series, we describe two cases of basal ganglia calcification, one of whom presented with psychotic symptoms and the other with mood symptoms, and discuss the literature with regard to psychiatric manifestations of basal ganglia calcification.

Acute akathisia with quetiapine: A case report and review of literature.

Quetiapine is an atypical antipsychotic which has been shown to have greater relative affinity for 5-HT(2A) receptors than for D(2) receptors, due to which it is thought to lead to lower incidence of extrapyramidal symptoms (EPS). However, over the years literature in the form of case reports have accumulated which shows that quetiapine can lead to akathisia, especially in subjects prone to develop EPS. In this study, we report the case of a 22-year-old female who developed akathisia with quetiapine 150 mg/day, which subsided with reduction in dose. We have also reviewed the existing literature with respect to akathisia with quetiapine.

Early indicators of prognosis in fulminant hepatic failure: an assessment of the Model for End-Stage Liver Disease (MELD) and King's College Hospital criteria.

While King's Hospital Criteria (KCH) criteria are used worldwide, the Model for End-Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 +/- 14.7 yr; range 12-82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice-encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age >or=50 yr, JEI >7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time >or=35 seconds, and creatinine >or=1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of >or=33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. Any 3 CPI were superior to MELD and KCH criteria in predicting the outcome (c-statistic [95% confidence interval]: CPI 0.802 [0.726-0.878], MELD 0.717 [0.636-0.789], and KCH criteria 0.676 (0.588-0.764); P values: CPI vs. MELD 0.045, CPI vs. KCH criteria 0.019, and MELD vs. KCH criteria 0.472). In conclusion, MELD and KCH criteria are not as useful as a combination of other early CPI in predicting adverse outcome in patients with FHF due to acute viral hepatitis.