Cardiac biomarkers are of great importance in the timely, accurate diagnosis and management of acute coronary syndrome as well as the prognosis. Diagnosis in the golden period is of utmost importance to institute therapy at the earliest and possibly reverse the myocardial damage. Cardiac biomarkers are also a powerful tool for triaging. Among the many biomarkers, the earliest examined were the myocardial enzymes, several myocardial proteins, peptides, and many other molecules. The latest addition to the repertoire is the microRNAs, which are stable molecules detectable in circulation. About four groups are found to be involved in regulation of circulatory system, and some show promise as specific and early markers of acute coronary syndrome and cardiac dysfunction. As in other fields of medicine, personalized precise treatment may be possible with the use of microRNAs. However, as of now, a multipronged approach, involving different markers of which troponins are necessary, seems to be the best way forward.

Imatinib Mesylate, a Tyrosine Kinase inhibitor, is presently the drug of choice for Chronic myeloid leukemia (CML). During therapy, a few patients develop myelosuppression and present with cytopenias. To study the bone marrow morphology in imatinib treated CML patients presenting with persistent cytopenias. The cases were retrieved from the Hematopathology record files, Department of Pathology; the study period being January 2008-June 2009. Cases of CML on Imatinib presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenias with bone marrow studies, were included in the study. The morphology of all cases was reviewed with cytogenetic studies. Follow-up details were obtained from the Medical Oncology records. During the study period, 683 Imatinib treated CML patients had bone marrow studies as part of their follow-up investigations. Of these, 60 patients (9%) had some form of persistent cytopenia. The patients ranged from 21 to 75 years of age with a median age of 38 years. The male:female ratio was 1:1. There were 46 patients with ≥grade 2 anemia, 25 patients with ≥grade 2 neutropenia and 37 patients with ≥grade 2 thrombocytopenia. Of these, 18 patients had bicytopenia and 13 cases had pancytopenia. The marrow evaluation revealed morphologic response in 30 patients, persistent marrow disease in five patients, marrow hypoplasia in six patients, extensive stromal changes including fibrosis in five patients, megaloblastic erythropoiesis in 11 patients and disease progression to accelerated or blast crisis in three patients. Various degrees of cytopenias may occur in few patients of CML on imatinib therapy. Regular hematologic follow-up is required so that the drug may be stopped or dose modified as per the individual's needs.

The use of intravenous FishLEs in premature infants appears to be safe and reverses PNALD despite significant liver disease and intestinal failure. This therapy should be used in preterm infants with PNALD and followed long term to evaluate development.

There are few publications on responses of patients with chronic phase chronic myeloid leukemia (CP-CML) from the Indian sub continent to imatinib mesylate (IM). This study analyses the response rates, progression free survival (PFS), overall survival and adverse events of early CP-CML patients on IM. Analysis of patients with untreated early CP-CML on IM from 2003 to 2006 was done. Standard criteria for hematological and cytogenetic responses were used. There were 201 patients with a median follow-up of 29.5 months. Thirty three percentage, 40% and 27% belonged to the low, intermediate and high-risk Hasford groups, respectively. Ninety seven percentage achieved complete hematological response. Fifty six percentage achieved complete cytogenetic response (CCR), 23% partial cytogenetic response, 17% minor response and 4% no response. The estimated PFS and OS at 29 months for the whole group was 77 and 94%, respectively. Hasford risk groups were predictive of CCR (p = 0.0018). None required permanent drug discontinuations due to adverse events. This study shows sub optimal outcomes to IM in early CP-CML. Late presentation may be one of the reasons for these outcomes. IM was well tolerated.

Imatinib has shown unprecendeted success in the treatment of chronic myeloid leukemia (CML). However, over few years there have been reports regarding the primary and secondary resistance to Imatinib dampening the overall outcome in CML patients. In this study we have tried to assess the effect of dose escalation in patients resistant to standard dose of Imatinib and correlate it with presence of ABL kinase domain (KD) mutations. There were 90 patients resistant to imatinib, out which 29 patients were identified with KD mutations. The most common mutation was T315I , 9 out of 29 patients had it. 35 (38%) responded to dose escalation and had 67% event free survival (EFS) at estimated 2 years. Our results showed that dose escalation can over come resistance in some patients especially those in cytogenetic failure.

Systemic Lupus Erythematosus is an autoimmune disease with female preponderance. Anemia is found in 50% of Systemic Lupus Erythematosus patients. This is a cross sectional case control study with 30 female Systemic Lupus Erythematosus patients having inflammation associated anemia (Hemoglobin \ 10.0 gm/dl) and 30 age matched controls with the aim to measure serum hepcidin and ferritin levels, correlate and study their role as homeostatic regulators of iron metabolism and utility as markers. Serum transferrin, ferritin, iron, total iron binding capacity, hsCRP, liver enzymes and renal parameters were analyzed by using automated analyser. Hepcidin levels were estimated by Sandwich-ELISA method. There was significant decrease in Iron (p \ 0.0001), Iron Binding capacity (p \ 0.0001), Transferrin (p \ 0.0001) in patients, and a significant increase in inflammatory markers: hs-CRP (p \ 0.0001), ESR (p \ 0.0001) compared to controls. Significant increase in both Hepcidin (p \ 0.0001) and Ferritin (p \ 0.0001) was observed in patients with significant positive correlation (r = 0.711) with each other. Additionally, ferritin and hepcidin significantly positively correlated with hs-CRP and ESR (r = 0.526, 0.735); (r = 0.427, 0.742) respectively. Negative correlation with hemoglobin, iron, total iron binding capacity and transferrin with hepcidin (r =-0.80,-0.307,-0.553,-0.584) and ferritin (r =-0.722,-0.22,-0.654,-0.728) was observed respectively. On ROC analysis both hepcidin and ferritin has sensitivity of 96.7%, specificity of 100% at cutoff values of 110 and 49 respectively. AUC of hepcidin was 0.993 and ferritin was 0.978. We have established a positive linear correlation between Hepcidin and Ferritin levels in disease activity and the changes correlated with the inflammatory state and anemia in patients, making them important mediators and potential markers of inflammation associated anemia.

We studied kinase domain (KD) mutations, response to dose escalation, event free survival (EFS), and overall survival (OS) of 90 patients with chronic phase CML who were resistant to imatinib mesylate (IM) 400 mg. IM was escalated to 800 mg daily. There were 65 patients with hematologic failure and 25 with cytogenetic failure. Median duration on IM at resistance detection was 18 months (range, 3-48). Twenty nine (32.2%) patients had KD mutations. Of the 29, the most common were T315I in nine (31.2%) and G250E in eight (27.6%). No clinical or laboratory factor predicted for mutation detection. Of 90 patients, 50 (55.5%) achieved a complete hematologic response and 35 (39%) a major cytogenetic response. At a median of 18 months (range 3-40), 35 patients (39%) are event free and 84 (93%) are alive. The 2 year EFS and OS were 34% and 93%, respectively. The projected 2 year EFS was superior for patients with cytogenetic failure compared to those with hematologic failures (73 vs. 22%, p = 0.0001). Dose decreases were necessary in 16 (18%) and interruptions in 31 (34%). KD mutations were detected in a third of patients with T315I being the most common. IM dose escalation can induce sustained responses in patients with cytogenetic failures.

Imatinib mesylate (Gleevec) is an effective treatment for chronic myeloid leukemia (CML). Though cytogenetic and molecular analyses are essential disease monitoring parameters in CML bone marrow morphological response is not well defined. We examined marrow samples from 40 patients with CML which have at least 2 or more follow-up marrow. A significant positive correlation with complete cytogenetic response shown for normalization of cellularity (P = 0.0097), absence of dry tap (P = 0.0368) and abnormal megakaryocytes (P = 0.005), reduction of blasts (P = 0.019), basophils (P = 0.031), M:E index (P = 0.018) and fibrosis (P = 0.018). Morphological criteria for complete cytogenetic response in CML patients treated with Imatinib can be defined.Morphologic response is also of potential clinical value in addition to cytogenetic and molecular response in patients of CML treated with Imatinib.