Role of direct antiglobulin test in anemia under evaluation: Its prevalence, laboratory workup, and significance in further patient management-a study from eastern India.

INTRODUCTION AND AIMS: The direct antiglobulin test (DAT) is an important diagnostic tool for immune hemolytic anemia (IHA). The present study was primarily aimed to identify the prevalence of DAT positivity in anemia patients along with its specificity . A three months follow up of the DAT positive patients were performed for the response during course of illness in terms of transfusion requirement, hemoglobin level, persistence of DAT. MATERIALS AND METHODS: This cross sectional study was performed at a government medical college on symptomatic anemia patients. At initial evaluation, complete blood count (CBC), blood grouping and DAT were performed in the EDTA blood. DAT positive blood samples were analyzed for their immunoglobulin specificity, auto or alloantibody type. Acid elution and red cell phenotyping were performed wherever applicable. Their clinical presentation, hematological and biochemical parameters of hemolysis were evaluated. Statistical analysis was performed on the results on SPSS (Version 23.0;.USA) and Graph pad Prism version 9. P value <0.05 was considered significant. RESULTS: DAT was present in 64 out of 501 patients with male female ratio 1: 4. Warm AIHA (WAIHA) was 93.7% with secondary WAIHA 60%. IgG was associated in 86% DAT positive samples, Only C3d was 14%. All the 4 cold AIHA (6.3%) had a higher antibody titre and thermal amplitude.DAT strength was directly proportional to the degree of hemolysis. During 3 months follow up, persistence of DAT and blood transfusion requirement was more in secondary WAIHA . Hemoglobin increment was more in primary WAIHA (75%). CONCLUSION: DAT played a significant role in the diagnosis as well as evaluation of AIHA.

Post COVID sequelae among COVID-19 survivors: insights from the Indian National Clinical Registry for COVID-19.

INTRODUCTION: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities. METHODS: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting. RESULTS: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03). CONCLUSION: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Clinical performance validation of the STANDARD G6PD test: A multi-country pooled analysis.

INTRODUCTION: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. METHODS AND FINDINGS: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%-85.4%) for females with intermediate activity between 30%-70%. Specificity was 98.1% (95% CI 97.6%-98.5%) and 92.8% (95% CI 91.6%-93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. CONCLUSIONS: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Determinants of post discharge mortality among hospitalized COVID-19 patients.

Background & objectives: The post-acute effects of COVID-19 are continually being updated. This investigation was conducted to evaluate the determinants of post discharge mortality in hospitalized COVID-19 patients, especially 18-45 yr of age. Methods: A series of three nested case-control analyses was conducted on follow up data collected in the National Clinical Registry for COVID-19 between September 2020 and February 2023 from 31 hospitals. Matching (1:4) was done by the date of hospital admission ±14 days for the following comparisons: (i) case-patients reported as dead vs. controls alive at any contact within one year follow up; (ii) the same in the 18-45 yr age group and (iii) case-patients reported as dead between the first and one year of follow up vs. controls alive at one year post discharge. Results: The one year post discharge mortality was 6.5 per cent (n=942). Age [≤18 yr: adjusted odds ratio (aOR) (95% confidence interval [CI]): 1.7 (1.04, 2.9); 40-59 yr: aOR (95% CI): 2.6 (1.9, 3.6); ≥60 yr: aOR (95% CI): 4.2 (3.1, 5.7)], male gender [aOR (95% CI): 1.3 (1.1, 1.5)], moderate-to-severe COVID-19 [aOR (95% CI): 1.4 (1.2, 1.8)] and comorbidities [aOR (95%CI): 1.8 (1.4, 2.2)] were associated with higher odds of post-discharge one-year mortality, whereas 60 per cent protection was conferred by vaccination before the COVID-19 infection. The history of moderate-to-severe COVID-19 disease [aOR (95% CI): 2.3 (1.4, 3.8)] and any comorbidities [aOR (95% CI): 3 (1.9, 4.8)] were associated with post-discharge mortality in the 18-45-yr age bracket as well. Post COVID condition (PCC) was reported in 17.1 per cent of the participants. Death beyond the first follow up was associated with comorbidities [aOR (95%CI): 9.4 (3.4, 26.1)] and reported PCC [aOR (95% CI): 2.7 (1.2, 6)]. Interpretation & conclusions: Prior vaccination protects against post discharge mortality till one year in hospitalized COVID-19 patients. PCC may have long term deleterious effects, including mortality, for which further research is warranted.

Deep phenotyping and genomic data from a nationally representative study on dementia in India.

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.

CardioSim: a PC-based cardiac signal simulator using segmental modeling of electrocardiogram.

Background: ECG modeling has wide application in signal representation, compression and synthetic ECG generation. Method: CardioSim generates synthetic ECG waveform in real-time using PC-based system. It provides dual facility of interface-based visualization with hardware-based waveform generation. It has two stages viz., development of reference model parameter database using Fourier model and generation of synthetic ECG waveform based on user defined parameters using normal and abnormal records (H, APC, PVC, LBBB, RBBB, P) from mitdb under PhysioNet. Result: It generates ten various ECG waveforms including one healthy and nine diseased rhythms from a single dynamic model with flexible user defined parameters. It gives higher reconstruction performance in terms of SNR and MSE. The mean SNR for different beat morphology is 89.2(H), 88.37(V), 86.32(A), 85.35(L), 97.22(P) and 83.3(R) and mean MSE is 2.45 × 10-6(H), 3.14 × 10-6(V), 8.98 × 10-6(A), 5.82 × 10-6(L), 0.43 × 10-6(P) and 0.25 × 10-6(R). Conclusion: It improves the performance parameters over published research work on ECG modeling and simulation. It can be used as a self-learning tool for entry level medical students.

Evaluation of indirect sequence-specific magneto-extraction-aided LAMP for fluorescence and electrochemical SARS-CoV-2 nucleic acid detection.

Nucleic acid amplification tests (NAATs) such as quantitative real-time reverse transcriptase PCR (qRT-PCR) or isothermal NAATs (iNAATs) such as loop-mediated isothermal amplification (LAMP) require pure nucleic acid free of any polymerase inhibitors as its substrate. This in turn, warrants the use of spin-column mediated extraction with centralized high-speed centrifuges. Additionally, the utilization of centralized real-time fluorescence readout and TaqMan-like molecular probes in qRT-PCR and real-time LAMP add cost and restrict their deployment. To circumvent these disadvantages, we report a novel sample-to-answer workflow comprising an indirect sequence-specific magneto-extraction (also referred to as magnetocapture, magneto-preconcentration, or magneto-enrichment) for detecting SARS-CoV-2 nucleic acid. It was followed by in situ fluorescence or electrochemical LAMP. After in silico validation of the approach's sequence selectivity against SARS-CoV-2 variants of concern, the comparative performance of indirect and direct magnetocapture in detecting SARS-CoV-2 nucleic acid in the presence of excess host nucleic acid or serum was probed. After proven superior, the sensitivity of the indirect sequence-specific magnetocapture in conjunction with electrochemical LAMP was investigated. In each case, its sensitivity was assessed through the detection of clinically relevant 102 and 103 copies of target nucleic acid. Overall, a highly specific nucleic acid detection method was established that can be accommodated for either centralized real-time SYBR-based fluorescence LAMP or portable electrochemical LAMP.

Characterizing the third wave of COVID-19: An analysis from the National Clinical Registry of COVID-19.

Background & objectives: Data from the National Clinical Registry for COVID-19 (NCRC) were analyzed with an aim to describe the clinical characteristics, course and outcomes of patients hospitalized with COVID-19 in the third wave of the pandemic and compare them with patients admitted earlier. Methods: The NCRC, launched in September 2020, is a multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized COVID-19 patients were captured in an electronic data portal from 38 hospitals across India. Patients enrolled during December 16, 2021 to January 17, 2022 were considered representative of the third wave of COVID-19 and compared with those registered during November 15 to December 15, 2021, representative of the tail end of the second wave. Results: Between November 15, 2021 and January 17, 2022, 3230 patients were recruited in NCRC. Patients admitted in the third wave were significantly younger than those admitted earlier (46.7±20.5 vs. 54.6±18 yr). The patients admitted in the third wave had a lower requirement of drugs including steroids, interleukin (IL)-6 inhibitors and remdesivir as well as lower oxygen supplementation and mechanical ventilation. They had improved hospital outcomes with significantly lower in-hospital mortality (11.2 vs. 15.1%). The outcomes were better among the fully vaccinated when compared to the unvaccinated or partially vaccinated. Interpretation & conclusions: The pattern of illness and outcomes were observed to be different in the third wave compared to the last wave. Hospitalized patients were younger with fewer comorbidities, decreased symptoms and improved outcomes, with fully vaccinated patients faring better than the unvaccinated and partially vaccinated ones.

Limited-resource preparable chitosan magnetic particles for extracting amplification-ready nucleic acid from complex biofluids.

Extraction and concentration of pure nucleic acid from complex biofluids are the prerequisite for nucleic acid amplification test (NAAT) applications in pathogen detection, biowarfare prevention, and genetic diseases. However, conventional spin-column mediated nucleic acid extraction is constricted by the requirement for costly power-intensive centralized lab infrastructure, making it unsuitable for limited-resource settings. Significant progress in lab-on-a-chip devices or cartridges (e.g., Cepheid GeneXpert®) that integrate nucleic acid extraction and amplification has been made, but these approaches either require additional equipment or are costly. Similarly, their complexities make them difficult to fabricate in low-resource settings by the end-user themselves. The application of magnetic particles such as silica-coated iron oxide beads for nucleic acid extraction is relatively instrument-free, rapid, user-friendly, and amenable to automation. But, they rely on hazardous chaotropic salt chemistry and ethanol desalting that could limit their efficacy for downstream NAATs. Recent advances in several types of novel material (e.g., polyamine) coated magnetic bead-based chaotropic salt-free extraction methods offer a possible solution to this problem. However, these materials also involve multistep synthesis impermissible in limited-resource settings. To offer a possible instrument-free magnetic particle-based nucleic acid extraction doable at limited-resource settings, we investigated the nucleic acid capture ability of two chitosan-coated magnetic particles that are preparable by minimally trained personnel using only a water bath and a magnetic stirrer within 6-8 h. We quantitatively probed the efficiency of the passive (without any electrical shaking or vortex-aided) DNA magnetocapture (i.e., binding to chitosan magnetic particles, physical separation from its sample of origin, and release from the particles) using UV260. To explore their suitability towards clinically relevant sensitive downstream NAATs, 100-1000 copies (i.e., in the order of zeptomole) of Escherichia coli (E. coli) or human genomic DNA from aqueous solution, crude cell lysate, and fetal bovine serum were extracted by them and then successfully detected using quantitative real-time loop-mediated isothermal amplification (LAMP) or real-time polymerase chain reaction (PCR). Alongside, their suitability with gel-based LAMP, colorimetric LAMP, and in situ (on beads) LAMP was also probed. The required optimization of the amplification methods has been discussed. Overall, the turnaround time for the magnetocapture combined with NAAT was 1.5-2 h and is thus expected to aid in rapid clinical decision making. With the ease of preparation, reproducibility, and compatibility with downstream NAATs, we anticipate that these magnetic particles would facilitate the expansion and decentralization of nucleic acid-based diagnosis for limited-resource settings.

Usability of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency: a multi-country assessment of test label comprehension and results interpretation.

BACKGROUND: Point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing has the potential to make the use of radical treatment for vivax malaria safer and more effective. Widespread use of G6PD tests as part of malaria case management has been limited, in part due to due concerns regarding product usability, user training, and supervision. This study seeks to assess how well end users can understand the Standard™ G6PD Test (SD Biosensor, Suwon, South Korea) workflow, result output, and label after training. This will ultimately help inform test registration and introduction. METHODS: Potential G6PD test users who provide malaria case management at three sites in Brazil, Ethiopia, and India were trained on the use of the SD Biosensor Standard G6PD Test and assessed based on their ability to understand the test workflow and interpret results. The assessment was done through a questionnaire, designed to assess product usability against key technical product specifications and fulfill regulatory evidence requirements. Any participant who obtained 85% or above correct responses to the questionnaire was considered to adequately comprehend how to use and interpret the test. RESULTS: Forty-five participants, including malaria microscopists, laboratory staff, nurses, and community health workers took part in the study. Seventy-eight percent of all participants in the study (35/45) obtained passing scores on the assessment with minimal training. Responses to the multiple-choice questions indicate that most participants understood well the test intended use, safety claims, and warnings. The greatest source of error regarding the test was around the correct operating temperature. Most test results were also read and interpreted correctly, with the haemoglobin measurement being a more problematic output to interpret than the G6PD measurement. CONCLUSIONS: These data results show how a standardized tool can be used to assess a user's ability to run a point-of-care diagnostic and interpret results. When applied to the SD Biosensor Standard G6PD Test, this tool demonstrates that a range of users across multiple contexts can use the test and suggests improvements to the test instructions and training that can improve product usability, increase user comprehension, and ultimately contribute to more widespread effective use of point-of-care G6PD tests. TRIAL REGISTRATION: NCT04033640.

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity.

Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity.

A Proteogenomic Analysis of Haptoglobin in Malaria.

SCOPE: Haptoglobin (Hp), an acute phase inflammatory protein is associated with malaria pathogenesis in several proteomics and genomics studies. The Hp gene has two co-dominant alleles: Hp1 and Hp2 that produce three genotypes: Hp1/Hp1, Hp1/Hp2 and Hp2/Hp2. EXPERIMENTAL DESIGN: In this study, validation of the proteomics data with Multiple Reaction Monitoring Mass Spectroscopy (MRM-MS) is performed and the association of the Hp gene variants with severe, non-severe malaria and community (healthy) controls using genotyping PCRs and DNA sequencing is analysed. RESULTS: Highly significant values of Hp is observed in the MRM assay that show a correlation with severity of malaria and is clearly distinguished from another febrile disease, dengue. Moreover, the Hp2/Hp2 genotype is seen in high percentages in non-severe malaria patients (74%) and community controls (72%) whereas patients diagnosed with severe malaria show only (31%) of this genotype. Sequencing of the Hp promoter region reveals three SNPs along with 10 unique haplotypes, out of which five are associated with non-severe and three with severe malaria populations (χ2  = 130; df = 18; p < 0.0001). CONCLUSION AND CLINICAL RELEVANCE: This proteo-genomic study focuses on the correlation of the Hp protein and gene with malaria, thus highlighting the pivotal role of this acute phase immune gene in malaria pathogenesis.

Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers.

Dengue fever (DF) is a major global health burden with a pathophysiology that is still incompletely understood. Biomarkers that predict and explain susceptibility to DF and its progression to its more severe hemorrhagic form are much needed. DF is endemic in tropical and subtropical regions of the world, with a rapidly increasing incidence of disease severity. We conducted a clinical biomarker discovery study using both a case-control and longitudinal study design. Plasma proteome alterations in patients with DF (n = 12) and dengue hemorrhagic fever (DHF, n = 24) were analyzed in comparison to healthy controls (HCs, n = 16), using the isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics methodology (false discovery rate of 1%, ≥2 peptides). Several proteins such as the alpha-2 macroglobulin, angiotensinogen, apolipoprotein B-100, serotransferrin, and ceruloplasmin were upregulated (fold change >1.2) in all DHF cases, and downregulated in DF (fold change <0.83), compared with HCs. Plasma cytokine profiling (8 DF, 8 DHF, and 8 HC) on two consecutive time points, at day 0 (day of admission) and days 5-7, found significant elevation in IL-1RA, IL-7, TNF-α, MCP1-MCAF, and MIP-1ß levels, but only in the DHF cases, which is the severe disease, and not in DF, compared with HCs (p < 0.05). These new observations on changes in the plasma proteome and cytokine profiles in patients with dengue infection identify several putative molecular leads for future biomarker development and precision medicine in relation to forecasting DF disease severity.

Enteric Parasitic Infection Among Antiretroviral Therapy Naïve HIV-Seropositive People: Infection Begets Infection-Experience from Eastern India.

CONTEXT: Parasitic opportunistic infections (POIs) frequently occur in HIV/AIDS patients and affect the quality of life. AIMS: This study assessing the standard organisms in the stool of HIV-positive patients, their comparison with HIV-negative controls, their relation with various factors, is the first of its kind in the eastern part of India. SETTINGS AND DESIGN: hospital-based case-control study. MATERIALS AND METHODS: A total of 194 antiretroviral therapy naïve HIV-positive patients (18-60 years) were taken as cases and 98 age- and sex-matched HIV-negative family members as controls. Demographical, clinical, biochemical, and microbiological parameters were studied. STATISTICAL ANALYSIS USED: Odds ratio, 95% confidence interval, and P (< 0.05 is to be significant) were calculated using Epi Info 7 software. RESULTS: POI was significantly higher among HIV-seropositive cases (61.86%) (P < 0.001). Cryptosporidium was the most common POI in HIV-seropositive patients overall and without diarrhea; Entameba was the most common POI in patients with acute diarrhea, and Isospora was the most common POI in the patients having chronic diarrhea. Entameba was the most common POI in CD4 count <350 cells/µl while for CD4 count >350 cells/µl Cryptosporidium was the most common POI. Mean CD4 count was significantly (P < 0.001) lower among people having multiple infections. Male sex, hemoglobin <10 g/dl, WHO Clinical Stage 3 or 4, tuberculosis, absolute eosinophil count of more than 540/dl, CD4 count <350 cells/µl, and seroconcordance of spouses were significantly associated with HIV-seropositive cases having POI (P < 0.05). CONCLUSIONS: Physicians should advise HIV-infected patients to undergo routine evaluation for POI, and provision of chemoprophylaxis should be made in appropriate settings.

Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

Filarial hydropneumothorax: a strange journey.

Filarial infection can have varied manifestations, but hydropneumothorax at presentation has not yet been reported. A 28-year-old man presented to our hospital with heaviness of the left chest for the past 10 days, which was preceded by a sudden, short stabbing pain in the left chest after straining. Chest X-ray revealed left-sided hydropneumothorax. A peripheral blood picture revealed significant eosinophilia. A pleural fluid report also showed eosinophilia and a few motile microfilaria of Wuchereria bancrofti. Microfilaria was also documented in peripheral blood. There was no evidence of other organ system involvement. The patient was diagnosed with 'Filarial Hydropneumothorax'. After treatment with a temporary chest drain and oral diethylcarbamazine citrate, there was dramatic relief of symptoms and radiological improvement. The patient has been symptom free with no features of recurrence through 8 months of follow-up.

Cobb syndrome: A rare cause of paraplegia.

Cobb syndrome is an exceedingly rare clinical condition defined by the presence of a vascular skin nevus and an angioma in the spinal canal at the same metamere. We report the case of a 14-year-old boy who presented with sudden onset paraplegia. Physical examination showed port-wine stains over buttock and thigh. Magnetic resonance (MR) angiogram of the dorso-lumbar spine revealed a large arteriovenous malformation (AVM) at D11-D12 to L2-L3 levels. These concurrent findings led to the diagnosis of Cobb's syndrome. The patient received orally administered prednisolone therapy and underwent endovascular embolization of spinal angioma. Cobb's syndrome is a rare disease entity and literature search revealed only a few case reports and series mentioning this condition to date. The importance lies in the recognition that cutaneous vascular lesions may clue to an associated spinal cord angioma or AVM that may lead to weakness or paralysis.

Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity.

India significantly contributes to the global malaria burden and has the largest population in the world at risk of malaria. This study aims to analyze alterations in the human serum proteome as a consequence of non-severe and severe infections by the malaria parasite Plasmodium falciparum to identify markers related to disease severity and to obtain mechanistic insights about disease pathogenesis and host immune responses. In discovery phase of the study, a comprehensive quantitative proteomic analysis was performed using gel-based (2D-DIGE) and gel-free (iTRAQ) techniques on two independent mass spectrometry platforms (ESI-Q-TOF and Q-Exactive mass spectrometry), and selected targets were validated by ELISA. Proteins showing altered serum abundance in falciparum malaria patients revealed the modulation of different physiological pathways including chemokine and cytokine signaling, IL-12 signaling and production in macrophages, complement cascades, blood coagulation, and protein ubiquitination pathways. Some muscle related and cytoskeletal proteins such as titin and galectin-3-binding protein were found to be up-regulated in severe malaria patients. Hemoglobin levels and platelet counts were also found to be drastically lower in severe malaria patients. Identified proteins including serum amyloid A, C-reactive protein, apolipoprotein E and haptoglobin, which exhibited sequential alterations in their serum abundance in different severity levels of malaria, could serve as potential predictive markers for disease severity. To the best of our information, we report here the first comprehensive analysis describing the serum proteomic alterations observed in severe P. falciparum infected patients from different malaria endemic regions of India. This article is part of a Special Issue entitled: Proteomics in India.

Clinico-biochemical correlation to histological findings in alcoholic liver disease: a single centre study from eastern India.

BACKGROUND: Alcoholism is a health problem not only in developed countries but also in developing countries. Cirrhosis due to alcohol is a common cause of death among individuals abusing alcohol. A better knowledge of the spectrum of alcoholic liver diseases, its clinical, biochemical and histopathological features could result in early detection and prevention of alcoholic liver diseases before it's catastrophic and life threatening effects. MATERIALS AND METHODS: A total of 200 patients with alcoholic liver diseases were studied with respect to alcohol consumption, clinical features, biochemical and histopathological changes. The clinical features, biochemical parameters, and histopathology of liver including Ishak's modified histological activity index (HAI) were correlated with the amount and duration of alcohol consumed. RESULT: Majority of the patients were in the age group of 40-49 years and all the cases were males. Majority consumed alcohol of about 75-90 grams per day for a duration of 10-12 years. Anorexia and jaundice were the most common symptom and clinical finding respectively. Hyperbilirubinemia and hypoalbuminemia were the most common abnormalities observed in liver function tests. Advanced HAI stages with features of cirrhosis were most frequent histo-pathological finding noted in this study. Clinico-biochemical profile was significantly correlated with degree of alcohol ingestion as well as with liver histopathology. CONCLUSION: The wide prevalence of alcoholic liver disease including cirrhosis among Indian males was noted with significantly lower quantity and duration of alcohol ingestion. The severity of liver damage is directly proportional to the quantity and duration of alcohol consumed. Clinical features and biochemical changes may forecast the liver histopathology among the patients of alcoholic liver disease.