DeepFocus: fast focus and astigmatism correction for electron microscopy.

High-throughput 2D and 3D scanning electron microscopy, which relies on automation and dependable control algorithms, requires high image quality with minimal human intervention. Classical focus and astigmatism correction algorithms attempt to explicitly model image formation and subsequently aberration correction. Such models often require parameter adjustments by experts when deployed to new microscopes, challenging samples, or imaging conditions to prevent unstable convergence, making them hard to use in practice or unreliable. Here, we introduce DeepFocus, a purely data-driven method for aberration correction in scanning electron microscopy. DeepFocus works under very low signal-to-noise ratio conditions, reduces processing times by more than an order of magnitude compared to the state-of-the-art method, rapidly converges within a large aberration range, and is easily recalibrated to different microscopes or challenging samples.

Comparison of the diagnostic yield of transbronchial lung biopsies by forceps and cryoprobe in diffuse parenchymal lung disease.

Background: Transbronchial lung cryobiopsy (TBLC) in the diagnosis of diffuse parenchymal lung disease (DPLD) has shown a promising yield in recent times, with low post-procedural mortality and morbidity. Objectives: To compare the yield of TBLC and conventional transbronchial forceps lung biopsy (TBLB). Methods: A prospective study was carried out in patients with DPLD over a period of 1 year in a tertiary respiratory care institute in New Delhi, India. All 87 patients enrolled underwent both TBLB and TBLC. The procedures were performed in the bronchoscopy suite under conscious sedation and local anaesthesia, with an attempt to take a minimum of three biopsy specimens by conventional TBLB followed by TBLC. A 1.9 mm cryoprobe with a freezing time of 4 - 5 seconds was used. An Arndt endobronchial blocker was used to control bleeding along with locally administered medications. Results: TBLB and TBLC led to a definitive diagnosis in 27 (31.0%) and 69 (79.3%) cases, respectively. The commonest diagnoses were hypersensitivity pneumonitis, sarcoidosis and pulmonary tuberculosis. TBLC led to additional diagnoses in 42 cases (48.3%). Pneumothorax was observed in 12 cases (13.8%), and moderate bleeding occurred in 63 (72.4%). There were no procedure-related deaths. Conclusion: TBLC had a better diagnostic yield than conventional TBLB in DPLD. It has the potential to become a safe day-care procedure in a resource-limited setting, if certain precautions are taken. Study synopsis: What the study adds. Compared with transbronchial forceps lung biopsy, transbronchial lung cryobiopsy (TBLC) led to additional diagnoses in 42 (48.3%) of 87 patients with clinicoradiological features of diffuse parenchymal lung disease. Pneumothorax was observed in 12 cases (13.8%) and moderate bleeding in 63 (72.4%). TBLC without rigid bronchoscopy or advanced airway devices under conscious sedation had a good diagnostic yield with an acceptable adverse events profile.Implications of the findings. TBLC under conscious sedation is not resource intensive and can be carried out in settings with limited resources.

Multi-ancestry genome-wide analysis identifies shared genetic effects and common genetic variants for self-reported sleep duration.

Both short (≤6 h per night) and long sleep duration (≥9 h per night) are associated with increased risk of chronic diseases. Despite evidence linking habitual sleep duration and risk of disease, the genetic determinants of sleep duration in the general population are poorly understood, especially outside of European (EUR) populations. Here, we report that a polygenic score of 78 European ancestry sleep duration single-nucleotide polymorphisms (SNPs) is associated with sleep duration in an African (n = 7288; P = 0.003), an East Asian (n = 13 618; P = 6 × 10-4) and a South Asian (n = 7485; P = 0.025) genetic ancestry cohort, but not in a Hispanic/Latino cohort (n = 8726; P = 0.71). Furthermore, in a pan-ancestry (N = 483 235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 73 loci are associated with genome-wide statistical significance. Follow-up of five loci (near HACD2, COG5, PRR12, SH3RF1 and KCNQ5) identified expression-quantitative trait loci for PRR12 and COG5 in brain tissues and pleiotropic associations with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.

[Pharmacological importance of novel spiro derivatives against human pathogenic fungi]. / Farmakologicheskoe znachenie novykh spiro 1,4-digidropiridinov protiv patogennykh dlia cheloveka gribov.

Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. In the present study, antifungal activity of earlier synthesized spiro-1,4-dihydropyridines (1,4-DHPs) was investigated. The antifungal activity of spiro-1,4-DHPs compounds were screened against Aspergillus flavus, A. fumigatus, and Candida albicans by using Disc Diffusion and Modified Microdilution method. Among six spiro-1,4-DHPs compounds tested all of them showed stronger antifungal activity possibly through inhibiting the synthesis of chitin in cell wall against A. flavus, A. fumigatus, and C. albicans as compared to fluconazole, a standard antifungal drug. The combination of compounds showed that the synthesized compounds had synergistic, additive effects as compared to currently used drugs as an antifungal agent. These results indicated that these designed compounds were potential chitin synthase inhibitors and had excellent antimycotic activity for the treatment of fungal infections.

Faculty-or senior resident-led SNAPPS for postgraduate teaching in pediatrics.

This was an educational intervention on postgraduates using SNAPPS (Summarize narrow, analyze, probe, plan, self-directed learning) showing comparable median (interquartile range) satisfaction scores with faculty or senior residents as 4 (3,5) and 4 (4, 4.25); respectively, P = 0.79. Further training of senior residents in medical education will enable them to participate efficiently and actively in postgraduate teaching.

Experiences with information provision and preferences for decision making of patients with acute stroke.

OBJECTIVE: The aim of this study was to gain insight into experiences of patients with acute stroke regarding information provision and their preferred involvement in decision-making processes during the initial period of hospitalisation. METHODS: A sequential explanatory design was used in two independent cohorts of patients with stroke, starting with a survey after discharge from hospital (cohort 1) followed by observations and structured interviews during hospitalisation (cohort 2). Quantitative data were analysed descriptively. RESULTS: In total, 72 patients participated in this study (52 in cohort 1 and 20 in cohort 2). During hospitalisation, the majority of the patients were educated about acute stroke and their treatment. Approximately half of the patients preferred to have an active role in the decision-making process, whereas only 21% reported to be actively involved. In cohort 2, 60% of the patients considered themselves capable to carefully consider treatment options. CONCLUSIONS: Active involvement in the acute decision-making process is preferred by approximately half of the patients with acute stroke and most of them consider themselves capable of doing so. However, they experience a limited degree of actual involvement. PRACTICE IMPLICATIONS: Physicians can facilitate patient engagement by explicitly emphasising when a decision has to be made in which the patient's opinion is important.

Risk of pre-eclampsia in patients with a maternal genetic predisposition to common medical conditions: a case-control study.

OBJECTIVE: To assess whether women with a genetic predisposition to medical conditions known to increase pre-eclampsia risk have an increased risk of pre-eclampsia in pregnancy. DESIGN: Case-control study. SETTING AND POPULATION: Pre-eclampsia cases (n = 498) and controls (n = 1864) in women of European ancestry from five US sites genotyped on a cardiovascular gene-centric array. METHODS: Significant single-nucleotide polymorphisms (SNPs) from 21 traits in seven disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal and thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous scaled genetic instrument with pre-eclampsia. Odds of pre-eclampsia were compared across quartiles of the genetic instrument and evaluated for significance. MAIN OUTCOME MEASURES: Genetic predisposition to medical conditions and relationship with pre-eclampsia. RESULTS: An increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of pre-eclampsia (DBP, overall OR 1.11, 95% CI 1.01-1.21, P = 0.025; BMI, OR 1.10, 95% CI 1.00-1.20, P = 0.042), whereas alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89, 95% CI 0.82-0.97, P = 0.008), driven primarily by pleiotropic effects of variants in the FADS gene region. The effect of DBP genetic loci was even greater in early-onset pre-eclampsia cases (at <34 weeks of gestation, OR 1.30, 95% CI 1.08-1.56, P = 0.005). For other traits, there was no evidence of an association. CONCLUSIONS: These results suggest that the underlying genetic architecture of pre-eclampsia may be shared with other disorders, specifically hypertension and obesity. TWEETABLE ABSTRACT: A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre-eclampsia.

Association between fibrinogen and fibrinogen γ' and atherosclerotic plaque morphology and composition in symptomatic carotid artery stenosis: Plaque-At-RISK study.

INTRODUCTION: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. MATERIALS AND METHODS: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen γ'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. RESULTS: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen γ' and IPH volume (B = -23.40 mm3/g/L, p = 0.01 and B = -161.73 mm3/g/L, p = 0.01) and between fibrinogen and fibrinogen γ' and LRNC volume (B = -38.89 mm3 g/L, p < 0.01 and B = -227.06 mm3 g/L, p = 0.01). Additional adjustments for C-reactive protein (CRP) did not change the results. CONCLUSIONS: Fibrinogen and fibrinogen γ' are inversely associated with IPH volume and LRNC volume, independent of inflammation. CLINICAL TRIAL REGISTRATION: clinicaltrials.govNCT01208025.

The unique composition of Indian gut microbiome, gene catalogue, and associated fecal metabolome deciphered using multi-omics approaches.

BACKGROUND: Metagenomic studies carried out in the past decade have led to an enhanced understanding of the gut microbiome in human health; however, the Indian gut microbiome has not been well explored. We analyzed the gut microbiome of 110 healthy individuals from two distinct locations (North-Central and Southern) in India using multi-omics approaches, including 16S rRNA gene amplicon sequencing, whole-genome shotgun metagenomic sequencing, and metabolomic profiling of fecal and serum samples. RESULTS: The gene catalogue established in this study emphasizes the uniqueness of the Indian gut microbiome in comparison to other populations. The gut microbiome of the cohort from North-Central India, which was primarily consuming a plant-based diet, was found to be associated with Prevotella and also showed an enrichment of branched chain amino acid (BCAA) and lipopolysaccharide biosynthesis pathways. In contrast, the gut microbiome of the cohort from Southern India, which was consuming an omnivorous diet, showed associations with Bacteroides, Ruminococcus, and Faecalibacterium and had an enrichment of short chain fatty acid biosynthesis pathway and BCAA transporters. This corroborated well with the metabolomics results, which showed higher concentration of BCAAs in the serum metabolome of the North-Central cohort and an association with Prevotella. In contrast, the concentration of BCAAs was found to be higher in the fecal metabolome of the Southern-India cohort and showed a positive correlation with the higher abundance of BCAA transporters. CONCLUSIONS: The study reveals the unique composition of the Indian gut microbiome, establishes the Indian gut microbial gene catalogue, and compares it with the gut microbiome of other populations. The functional associations revealed using metagenomic and metabolomic approaches provide novel insights on the gut-microbe-metabolic axis, which will be useful for future epidemiological and translational researches.

Spectrum of hemostatic disorders in Indian females presenting with bleeding manifestations.

INTRODUCTION: Hemostatic disorders are often missed in women with bleeding particularly menorrhagia. Preexisting hemostatic disorders are now known as common risk factor for postpartum hemorrhage and prolonged bleeding in puerperium. Females with bleeding complaints constitute an important population referred to hematology clinic. Hence, we aim to evaluate the type and frequency of hemostatic disorders among females presenting with bleeding in a tertiary care hospital and a basic hemostatic laboratory. METHODS: Three-year data were retrospectively analyzed for 200 females with various bleeding complaints. Due to resource constraints, a hemostatic workup was done with prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen assay, clot solubility test, mixing studies, specific factor assays, platelet function test, and von Willebrand factor antigen level. RESULTS: A total of 200 females were investigated to identify the cause of their bleeding. Thirty-five of 200 (17.5%) females were found with an underlying bleeding disorder. Of these 35 females, 65.7% presented with bleeding from more than 1 site. Most common bleeding manifestation was spontaneous bruising in 18 of 35 (51.4%) patients followed by petechiae (48.6%). Inherited bleeding disorders were noted in majority. The most common inherited bleeding disorder identified was von Willebrand disease (VWD) in 34.3% females. Second most common disorder was Glanzmann's thrombasthenia accounting for 22.8%. Rare coagulation factor deficiency, such as factors VII, X, and XIII deficiencies, was noted. Three cases revealed acquired causes of coagulation defects. CONCLUSION: Underlying hemostatic defects should be searched for in women with unexplained bleeding complaints. This will not only help in diagnosis but also in proper management for future hemostatic challenges.

Application of thin layer activation technique for monitoring corrosion of carbon steel in hydrocarbon processing environment.

Acidic crude oil transportation and processing in petroleum refining and petrochemical operations cause corrosion in the pipelines and associated components. Corrosion monitoring is invariably required to test and prove operational reliability. Thin Layer Activation (TLA) technique is a nuclear technique used for measurement of corrosion and erosion of materials. The technique involves irradiation of material with high energy ion beam from an accelerator and measurement of loss of radioactivity after the material is subjected to corrosive environment. In the present study, TLA technique has been used to monitor corrosion of carbon steel (CS) in crude oil environment at high temperature. Different CS coupons were irradiated with a 13 MeV proton beam to produce Cobalt-56 radioisotope on the surface of the coupons. The corrosion studies were carried out by subjecting the irradiated coupons to a corrosive environment, i.e, uninhibited straight run gas oil (SRGO) containing known amount of naphthenic acid (NA) at high temperature. The effects of different parameters, such as, concentration of NA, temperature and fluid velocity (rpm) on corrosion behaviour of CS were studied.

Autosomal Dominant Polycystic Kidney Disease: Presence of Hypomorphic Alleles in PKD1 Gene.

Autosomal dominant polycystic kidney disease is characterized by multiple cysts in both kidneys manifesting in adult life. In general, the disorder is caused by a pathogenic variant in one allele of PKD1 or PKD2 genes, while the other allele is normal. Pathogenic variants in both the alleles are rare and have variable phenotypes, from lethal or perinatal presentation to a mild form in later adulthood, depending on the type of variant. Here, we describe a proband with two variants (p.Thr1773Ile and p.Ala1871Thr in trans) in PKD1 gene, who presented with disease at age 24 years. Both the parents and one brother had a variant in one allele, the other being wild type only and had normal ultrasound findings. Segregation studies suggest that both the variants may act as "hypomorphic" or "incompletely penetrant" alleles and acting together resulted in haploinsufficiency of protein PC1 in renal cells, leading to cystogenesis in the proband. The consequences of the presence of two hypomorphic variants have been poorly documented in literature. We reviewed the few published cases having two hypomorphic variants and the data conform to the conclusions that we reached by study of the family described. It is emphasized that to resolve the significance of suspected hypomorphic variants, segregation studies in the parents and siblings are essential.

Distillery effluent as a potential medium for bacterial cellulose production: A biopolymer of great commercial importance.

In the present study, an attempt was made to utilize the distillery effluent for the production of bacterial cellulose by a novel bacterial species, Gluconacetobacter oboediens. Maximum bacterial cellulose production of 0.85g/100ml was achieved in crude distillery effluent. The production was successfully scaled up to 1.0L size producing 8.1g of bacterial cellulose. Morphological, structural and thermal characterization of purified bacterial cellulose by SEM, FT-IR and TGA analysis showed that it is pure cellulose having good properties. Henceforth, the present study proved a concept that distillery effluent could be utilized for the production of bacterial cellulose, a biopolymer of immense importance, which in turn may be used for producing different value added products.

Molecular Response to Imatinib and Its Correlation with mRNA Expression Levels of Imatinib Influx Transporter (OCT1) in Indian Chronic Myeloid Leukemia Patients

Background and objectives: Imatinib mesylate is approved for the treatment of Chronic Myeloid Leukemia (CML). About 20% of patients with CML do not respond to treatment with Imatinib either initially or because of acquired resistance. In addition to mutated BCR-ABL1 kinase, the organic cation transporter1 (OCT1, encoded by SLC22A1) has been considered to contribute to Imatinib resistance in patients with chronic myeloid leukemia (CML). OCT1 has been reported to be the main influx transporter involved in Imatinib uptake into CML cells. To date, only a few studies have been reported on involvement of influx transporters in development of Imatinib resistance. Therefore this study was aimed to determine the expression level of Imatinib uptake transporter (OCT1) in CML patients and to correlate this level with molecular response. Methods: One hundred fifty eight patients on Imatinib were considered for gene expression analysis study for OCT1 gene. Total RNA was extracted from peripheral blood mononuclear cells. Complementary DNAs (cDNAs) were synthesized and Real Time Polymerase Chain Reaction (RQ-PCR) was performed. Results: High OCT1 expression was present in 81 (51.8%) patients and low OCT1 expression was in 77 (48.7%) patients. Low Sokal risk score group have a significantly high OCT1 expression (p=0.048). The rate of molecular response was higher in those with high OCT1 expression than in those with low OCT1 expression (p=0.05). Both event-free survival and median overall survival were significantly shorter in patients with low OCT1 expressions when compared to the patients with high OCT1 expression (p=0.03 and p=0.05). Conclusions: Our findings demonstrated that the mRNA expression level of OCT1 was significantly correlated with molecular response in CML patients. Based on these findings, present study believes that the pre-therapeutic higher expression of OCT1 may help to predict response to imatinib therapy in CML patients.

Higher rate of central nervous system involvement by flow cytometry than morphology in acute lymphoblastic leukemia.

INTRODUCTION: Central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) is diagnosed traditionally by cytopathology (CP) of the cerebrospinal fluid (CSF). Role of flow cytometry (FC) to diagnose CNS involvement has not been extensively investigated. METHODS: We aimed to detect CNS involvement in 42 ALL patients (33 B-ALL, nine T-ALL) at diagnosis by FC and comparing it with CP and to correlate it with known risk factors for CNS disease like Lactate dehydrogenase (LDH). A receiver operating characteristic curve was used to determine the cutoff of LDH to predict CSF involvement. For the analysis of categorical/quantitative variables, Fisher's exact test was used. For the analysis of continuous variables, Mann-Whitney test was used. A P value of <.05 was taken as significant. RESULTS: CP and FC were positive in five (11.9%) and 11 patients (26.14%) respectively with FC detecting a significantly higher level of involvement (P=.001). All CP-positive cases were FC positive. A LDH value of >472 U/L had a sensitivity of 61% and specificity of 62.5% for diagnosis of CSF involvement by FC. CONCLUSIONS: CSF FC detects CNS disease in ALL patients at diagnosis at a rate double than CP alone and is statistically associated with an elevated LDH level. It should be incorporated in the evaluation of CSF to detect CNS involvement.

Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource.

Sleep spindles are characteristic electroencephalogram (EEG) signatures of stage 2 non-rapid eye movement sleep. Implicated in sleep regulation and cognitive functioning, spindles may represent heritable biomarkers of neuropsychiatric disease. Here we characterize spindles in 11,630 individuals aged 4 to 97 years, as a prelude to future genetic studies. Spindle properties are highly reliable but exhibit distinct developmental trajectories. Across the night, we observe complex patterns of age- and frequency-dependent dynamics, including signatures of circadian modulation. We identify previously unappreciated correlates of spindle activity, including confounding by body mass index mediated by cardiac interference in the EEG. After taking account of these confounds, genetic factors significantly contribute to spindle and spectral sleep traits. Finally, we consider topographical differences and critical measurement issues. Taken together, our findings will lead to an increased understanding of the genetic architecture of sleep spindles and their relation to behavioural and health outcomes, including neuropsychiatric disorders.

Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth.

Mutations in the p53 tumor-suppressor gene are prevalent in human cancers. The majority of p53 mutations are missense, which can be classified into contact mutations (that directly disrupts the DNA-binding activity of p53) and structural mutations (that disrupts the conformation of p53). Both of the mutations can disable the normal wild-type (WT) p53 activities. Nevertheless, it has been amply documented that small molecules can rescue activity from mutant p53 by restoring WT tumor-suppressive functions. These compounds hold promise for cancer therapy and have now entered clinical trials. In this study, we show that cruciferous-vegetable-derived phenethyl isothiocyanate (PEITC) can reactivate p53 mutant under in vitro and in vivo conditions, revealing a new mechanism of action for a dietary-related compound. PEITC exhibits growth-inhibitory activity in cells expressing p53 mutants with preferential activity toward p53(R175), one of the most frequent 'hotspot' mutations within the p53 sequence. Mechanistic studies revealed that PEITC induces apoptosis in a p53(R175) mutant-dependent manner by restoring p53 WT conformation and transactivation functions. Accordingly, in PEITC-treated cells the reactivated p53(R175) mutant induces apoptosis by activating canonical WT p53 targets, inducing a delay in S and G2/M phase, and by phosphorylating ATM/CHK2. Interestingly, the growth-inhibitory effects of PEITC depend on the redox state of the cell. Further, PEITC treatments render the p53(R175) mutant sensitive to degradation by the proteasome and autophagy in a concentration-dependent manner. PEITC-induced reactivation of p53(R175) and its subsequent sensitivity to the degradation pathways likely contribute to its anticancer activities. We further show that dietary supplementation of PEITC is able to reactivate WT activity in vivo as well, inhibiting tumor growth in xenograft mouse model. These findings provide the first example of mutant p53 reactivation by a dietary compound and have important implications for cancer prevention and therapy.

Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis.

Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Invasive renal biopsy remains the gold standard for the diagnosis and management of LN. The objective of this study is to validate serum insulin-like growth factor binding protein-2 (IGFBP-2) as a novel biomarker for clinical disease and renal pathology in LN. Eighty-five biopsy-proven lupus nephritis patients, 18 chronic kidney disease (CKD) patients and 20 healthy controls were recruited for enzyme-linked immunosorbent assay (ELISA) testing of serum IGFBP-2 levels. Compared to CKD patients of origins other than lupus or healthy controls, serum IGFBP-2 levels were elevated significantly in LN patients. Serum IGFBP-2 was able to discriminate LN patients from the other two groups of patients [area under the curve (AUC) = 0·65, 95% confidence interval (CI) = 0·52-0·78; P = 0·043 for LN versus CKD; 0·97, 95% CI = 0·93-1·00; P < 0·0001 for LN versus healthy controls]. Serum IGFBP-2 was a potential indicator of both global disease activity and renal disease activity in LN patients, correlated with serum creatinine levels (r = 0·658, P < 0·001, n = 85) and urine protein-to-creatinine levels (r = 0·397, P < 0·001, n = 85). More importantly, in 19 concurrent patient samples, serum IGFBP-2 correlated with the chronicity index of renal pathology (r = 0·576, P = 0·01, n = 19) but not renal pathological classification. In conclusion, serum IGFBP-2 is a promising biomarker for lupus nephritis, reflective of disease activity and chronicity changes in renal pathology.

Epidemiology, Clinico-Haematological Profile and Management of Aplastic Anaemia: AIIMS Experience.

BACKGROUND: The incidence of aplastic anaemia (AA) is higher in Asia than in the West. The precise incidence of AA in India is not known due to lack of epidemiological study. 20-40% of pancytopenic patients in referral centres are of aplastic anaemia. PATIENTS AND METHODS: This was an analysis of 1501 patients diagnosed with aplastic anaemia over a period of seven and half years (January 2007- June 2014) attending the Aplastic clinic of department of haematology of All India Institute of Medical Sciences, New Delhi. The details regarding medical history, physical examination, complete blood count, bone marrow aspirate and biopsy, treatment received, were retrieved. Inherited bone marrow failure was screened in patients below 35 years. Treatment response was analysed for various treatment modalities. RESULTS: 1501 patients of AA from 20 different states of India were analysed. The bulk of patients were from Uttar Pradesh (28.7%), Bihar (23.6%), Delhi/NCR (20%) and Haryana (7%).The average number of new aplastic anaemia patients enrolled per year 214 (range: 101 -263). The median age at presentation was 25 years (range 2-83),with M;F - 2.3:1. Severity of AA revealed: severe (SAA): 75%, very severe (VSAA): 15%, non-severe (NSAA): 10%. Inherited bone marrow failure syndromes constituted 5% (75 patients) of all aplastic anaemia patients. The most common clinical presentations were pallor (97%), bleeding manifestations (69.6%) and fever (54%). The haematological parameters showed: median level of haemoglobin level: 5.9 gm/dL, WBC: 2700/mm3, ANC: 380/mm3, platelet: 1 0000/mm3. PNH clone was present in 13.5% of patients. 107 patients (7%) were lost to follow up or expired before any treatment was initiated. Only 69 patients (4.5%) received treatment with HLA-matched sibling stem cell transplantation and another 232 (15.5%) patients received ATG plus cyclosporine as immunosuppressive therapy. Seven hundred thirteenpatients (47.5%) received cyclosporine. The overall response to various treatment modalities was: HLA matched sibling haematopoietic stem cell transplant: 75.3%, Anti-thymocyte globulin plus cyclosporine: 58.7%, cyclosporine plus androgen: 45.6%, cyclosporine alone: 32.2%. CONCLUSION: Management of AA is a real challenge in developing countries.This is one of the largest case series from a single centre from India. It is our endeavour to reduce the detrimental outcome by increasing awareness among patients and referring physicians to reduce the delay between diagnosis and treatment.