Assessment of early morning serum cortisol levels in adult male patients with alcohol-related disorders.

BACKGROUND: Alcohol-related disorders are a major health problem among Indian male professionals because of the unique nature of socioeconomic and demographic conditions. Various studies have highlighted the association between alcohol-related disorders and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, but the evidence accrued so far is inconclusive. In our study, we have assessed early morning serum total cortisol concentration among Indian adult male population affected with alcohol-related disorder. METHODS: A case-based cross-sectional study in which all consecutive patients admitted in the psychiatry ward of a tertiary care hospital with diagnosis of 'alcohol-related disorders', who were meeting all the inclusion criteria, and who had none of the exclusion criteria were part of the study. Diseased controls and healthy controls were chosen by applying strict inclusion and exclusion criteria. Serum early morning (0400 h) total cortisol levels were estimated using automated quantitative enzyme-linked fluorescent assay technique. RESULTS: 98 psychiatric patients and 50 healthy controls were evaluated. Out of these 98 patients 66 patients were diagnosed cases of alcohol-related disorder. Morning serum total cortisol levels in patients with alcohol-related disorders was found to be significantly different from healthy controls. CONCLUSION: Our study suggests that alcohol-related disorders are associated with chronic changes in HPA axis and significant alteration of early morning serum total cortisol levels were demonstrated in this group of patients.

Performance characteristics of an artificial intelligence based on convolutional neural network for screening conventional Papanicolaou-stained cervical smears.

BACKGROUND: The conventional Papanicolaou-stained cervical smear is the most common screening test for cervical cancer. The sensitivity of the test in detecting abnormal cells is 67-75% in various studies. Owing to the volume of smears at cancer screening centres, significant man-hours are expended in the test. We have developed a software program for identification of foci of abnormal cells from conventional smears. We have chosen the convolutional neural network (CNN) model for its efficacy in image classification. METHODS: A total of 1838 microphotographs from cervical smears, containing 1301 'normal' foci and 537 'abnormal' foci were included in the study. The data set was split into training, testing and validation sets. A CNN was developed in the Python programming language. The CNN was trained with the training and testing set. At the end of training, 94.64% accuracy was achieved in the testing set. The CNN was then run on the validation set (441 images). RESULTS: The CNN showed 94.28% sensitivity, 96.01% specificity, 91.66% positive predictive value and 97.30% negative predictive value. The CNN could recognise normal squamous cells, overlapping cells, neutrophils and debris and classify the focus appropriately. False positives were reported when the CNN failed to recognise overlapping cells (2.7% microphotographs). It could correctly label cell clusters with high nuclear cytoplasmic ratio and hyperchromasia. In 1.8% of microphotographs, a false negative was reported. CONCLUSION: The CNN showed 95.46% diagnostic accuracy, suggesting potential use in screening.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Post-mortem findings in Staphylococcus aureus acute infective endocarditis.

Infective endocarditis (IE) is a microbial infection of the heart valves or the mural endocardium that leads to the formation of vegetations composed of thrombotic debris and microorganisms often associated with the destruction of the cardiac tissues. Most of the infections are bacterial (bacterial endocarditis), although fungi and other microorganisms can be etiological agents. Causative organisms differ among the major high-risk groups. Virulent microorganisms like Staphylococcus aureus, commonly found on the skin, can infect normal or deformed valves and are responsible for 20-30% of all IE cases. Staphylococcus aureus is the major offender in IE among intravenous drug abusers. Acute infective endocarditis is typically caused by infection of a previously normal heart valve by a highly virulent organism (e.g., Staphylococcus aureus) that rapidly produces necrotizing and destructive lesions. These infections may be difficult to cure with antibiotics, and despite appropriate treatment, death can ensue within days to weeks. Here we present autopsy findings of a 31-year-old male patient who died of acute infective endocarditis caused by Staphylococcus aureus as the causative organism.

Multimodality imaging features of primary breast lymphoma - A rare entity.

Primary lymphoma of breast is very rare which has no tell-tale imaging characteristics. Multimodality imaging helps not only in suggesting the possibility of lymphoma but also in its management. We present here one such case which was extensively worked up with various imaging modalities and was histologically proven as primary breast lymphoma.

Pilot Study of an Open-source Image Analysis Software for Automated Screening of Conventional Cervical Smears.

INTRODUCTION: The Pap stained cervical smear is a screening tool for cervical cancer. Commercial systems are used for automated screening of liquid based cervical smears. However, there is no image analysis software used for conventional cervical smears. The aim of this study was to develop and test the diagnostic accuracy of a software for analysis of conventional smears. MATERIALS AND METHODS: The software was developed using Python programming language and open source libraries. It was standardized with images from Bethesda Interobserver Reproducibility Project. One hundred and thirty images from smears which were reported Negative for Intraepithelial Lesion or Malignancy (NILM), and 45 images where some abnormality has been reported, were collected from the archives of the hospital. The software was then tested on the images. RESULTS: The software was able to segregate images based on overall nuclear: cytoplasmic ratio, coefficient of variation (CV) in nuclear size, nuclear membrane irregularity, and clustering. 68.88% of abnormal images were flagged by the software, as well as 19.23% of NILM images. The major difficulties faced were segmentation of overlapping cell clusters and separation of neutrophils. CONCLUSION: The software shows potential as a screening tool for conventional cervical smears; however, further refinement in technique is required.

Mixed Phenotypic Acute Leukemia Presenting as Mediastinal Mass-2 Cases.

Mixed phenotype acute leukemia symbolizes a very small subset of acute leukemia that simply cannot be allocated as lymphoid or myeloid lineage. The 2008 World Health Organisation classification established stringent standard for diagnosis of mixed phenotype acute leukemia, accentuating myeloperoxidase for myeloid lineage, cytoplasmic CD3 for T lineage and CD19 with other B markers for B lineage obligation. Mixed phenotype leukemia is rare and 3-5 % of acute leukmias of all age groups, is associated with poor outcome with overall survival of 18 months. We wish to present two cases of mixed phenotypic acute leukemia who presented with mediastinal masses, were suspected to be T cell lymphoma/leukemia clinically and radiologically. In one case, tissue diagnosis was given as lymphoma for which treatment was given. These cases show that patients diagnosed as lymphoma on histopathology can be cases of mixed phenotype acute leukemia and varying specific treatment protocols and follow up are required. Awareness of these entities will help in proper diagnosis and treatment.

Post-mortem findings in Staphylococcus aureus acute infective endocarditis

Infective endocarditis (IE) is a microbial infection of the heart valves or the mural endocardium that leads to the formation of vegetations composed of thrombotic debris and microorganisms often associated with the destruction of the cardiac tissues. Most of the infections are bacterial (bacterial endocarditis), although fungi and other microorganisms can be etiological agents. Causative organisms differ among the major high-risk groups. Virulent microorganisms like Staphylococcus aureus, commonly found on the skin, can infect normal or deformed valves and are responsible for 20-30% of all IE cases. Staphylococcus aureus is the major offender in IE among intravenous drug abusers. Acute infective endocarditis is typically caused by infection of a previously normal heart valve by a highly virulent organism (e.g., Staphylococcus aureus) that rapidly produces necrotizing and destructive lesions. These infections may be difficult to cure with antibiotics, and despite appropriate treatment, death can ensue within days to weeks. Here we present autopsy findings of a 31-year-old male patient who died of acute infective endocarditis caused by Staphylococcus aureus as the causative organism.

Distribution of Different PML/RARα bcr Isoforms in Indian Acute Promyelocytic Leukemia (APL) Patients and Clinicohematological Correlation.

CONTEXT: Acute promyelocytic leukemia (APL), an AML subtype, is characterized morphologically by abnormal promyelocytes. Molecular studies show three possible bcr isoforms of PML-RARα fusion gene. This study undertakes analysis of PML-RARα bcr isoforms and their correlation with haematological parameters and response to treatment in Indian patients. AIMS: To study different PML-RARα bcr isoforms in Indian patients and to find any correlation with various haematological parameters and response to treatment. SETTINGS AND DESIGN: Patients diagnosed as APL on morphology or flowcytometry and confirmed by RQ PCR were included in the study. Treated APL patients or patients with relapse and on follow-up were excluded from the study. METHODS AND MATERIAL: Twenty patients over thirty one months period were included. The clinical, haematological & morphological features were analysed, the latter using routine & special cytochemical stains on blood and bone marrow. Flow cytometric evaluation using 4-color Beckman Coulter FC 500 and molecular studies using RT PCR Fusion Quant® kits for bcr-1, bcr-2 and bcr-3 of PML-RARα bcr isoforms on the instrument Rotor Gene™ 3000 were performed. STATISTICAL ANALYSIS USED: Student t test was applied to correlate different bcr isoforms with various haematological parameters and response to treatment. RESULTS: In our study, M:F ratio was 1.5:1 with median age 42 years, Hb - 8.0 g/dl, TLC-7900/µl, and platelet - 35000/µl and varied clinical presentation. Four patients were microgranular variants, and the rest were hypergranular. MPO and CAE positivity were100% and for NSE it was 33.33%. Molecular analysis revealed PML-RARα isoforms of bcr1 in 42.85%, bcr2 in 14.28% and bcr3 in 38.09% patients. No correlation was found between PML-RARα bcr isoforms, different haematological parameters and response to treatment. CONCLUSIONS: Higher incidence of PML-RARα bcr-1 isoform was found in Indian APL patients with no significant correlation between different haematological parameters and response to treatment.

Rare case of acquired haemophilia and lupus anticoagulant.

Acquired haemophilia or factor VIII (FVIII) deficiency, caused by FVIII inhibitor antibodies, is a very rare condition that commonly results in severe haemorrhagic complications. We report a case of acquired haemophilia presenting with multiple bluish patches affecting face, neck, upper & lower limbs, history of gum bleeding and left knee haemarthrosis. The patient was found to have acquired FVIII inhibitor and lupus anticoagulant (LAC). The simultaneous presence of LAC and FVIII inhibitor is exceedingly rare. The differentiation between these two conditions is crucial, because both result in a prolongation of the activated partial thromboplastin time test, which does not correct when mixed with the plasma of a normal control; however, the clinical manifestations range from thrombosis in the presence of LAC to massive haemorrhage with FVIII inhibitors.