Role of FAB classification of acute leukemias in era of immunophenotyping

French-American-British classification for leukemias had been widely accepted due to its objectiveness and good reproducibility. WHO classification of leukemias was formulated in 1997 with a purpose of further enhancing the objectivity. However, the requirement of cytogenetics and immunophenotyping makes it difficult for many countries like India to put WHO classification in routine use. This study was carried to know the effectiveness of FAB classification in an era of technical advancement. A retrospective analysis of all acute leukemias over a period of 2 years was done. Out of total of 469 cases of acute leukemias, 193 were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically undifferentiated. Hence, only 16% of all leukemias remained unclassifiable. Subclassification of AML cases revealed a much higher percentage of AML-M3, as compared to western literature. In conclusion, FAB classification, based on morphology and simple cytochemical stains, remains effective enough, although cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.     

New angiotensins

Accumulation of a large body of evidence during the past two decades testifies to the complexity of the renin–angiotensin system (RAS). The incorporation of novel enzymatic pathways, resulting peptides, and their corresponding receptors into the biochemical cascade of the RAS provides a better understanding of its role in the regulation of cardiovascular and renal function. Hence, in recent years, it became apparent that the balance between the two opposing effector peptides, angiotensin II and angiotensin-(1-7), may have a pivotal role in determining different cardiovascular pathophysiologies. Furthermore, our recent studies provide evidence for the functional relevance of a newly discovered rat peptide, containing two additional amino acid residues compared to angiotensin I, first defined as proangiotensin-12 [angiotensin-(1-12)]. This review focuses on angiotensin-(1-7) and its important contribution to cardiovascular function and growth, while introducing angiotensin-(1-12) as a potential novel angiotensin precursor.     

Examining gender differences in emerging tobacco use using the Adolescents' Need For Smoking Scale

Aims To investigate the influence of gender on emerging tobacco use by testing for gender‐based measurement invariance of the Adolescents' Need for Smoking Scale (ANSS) and examining gender differences on each dimension across increasing levels of amount smoked. Design Cross‐sectional survey. Setting Thirteen secondary schools located in British Columbia, Canada. Participants Data from 1425 youth who reported smoking at least once in the past month. Measurements Survey questions about demographic characteristics, tobacco smoking history and need for smoking. Findings The multi‐dimensional structure of the ANSS is equivalent in boys and girls and the ANSS questions are not gender‐biased. There were no significant gender differences in the levels of physical dependence across increasing levels of amount smoked. Girls scored higher than boys on levels of emotional dependence across increasing levels of life‐time cigarette exposure. Girls also had higher scores on the social dimension of the ANSS compared to boys among those who smoked 100 or more cigarettes. Conclusions Canadian girls score higher than boys on measures of emotional dependence and social attitudes associated with tobacco smoking.     

Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

Vemurafenib and cobimetinib‐induced toxic epidermal necrolysis in a patient with metastatic melanoma

Combination therapy in the treatment of metastatic melanoma has been associated with more durable response rate compared to monotherapy. However, previous studies have shown that combined target therapy commonly causes a wide spectrum of adverse events. These adverse reactions are usually manageable, however, it is always necessary to compare drug efficacy with its potential adverse effects. Toxic epidermal necrolysis represents severe mucocutaneous reaction, usually triggered by medications and characterized by extensive necrosis and detachment of the epidermis. Here we present a first case of toxic epidermal necrolysis induced by combined target therapy (vemurafenib plus cobimetinib). The case was observed in a young patient with BRAF mutant melanoma who was started on first‐line metastatic immunotherapy with pembrolisumab.     

The Landscape of microRNA Targeting in Prostate Cancer Defined by AGO-PAR-CLIP

MicroRNA (miRNA) deregulation in prostate cancer (PCa) contributes to PCa initiation and metastatic progression. To comprehensively define the cancer-associated changes in miRNA targeting and function in commonly studied models of PCa, we performed photoactivatable ribonucleoside-enhanced cross-linking immunoprecipitation of the Argonaute protein in a panel of PCa cell lines modeling different stages of PCa progression. Using this comprehensive catalogue of miRNA targets, we analyzed miRNA targeting on known drivers of PCa and examined tissue-specific and stage-specific pathway targeting by miRNAs. We found that androgen receptor is the most frequently targeted PCa oncogene and that miR-148a targets the largest number of known PCa drivers. Globally, tissue-specific and stage-specific changes in miRNA targeting are driven by homeostatic response to active oncogenic pathways. Our findings indicate that, even in advanced PCa, the miRNA pool adapts to regulate continuing alterations in the cancer genome to balance oncogenic molecular changes. These findings are important because they are the first to globally characterize miRNA changes in PCa and demonstrate how the miRNA target spectrum responds to staged tumorigenesis.     

Total bilirubin in young men and women: Association with risk markers for cardiovascular diseases

Objective

The aim of this study was to investigate whether high bilirubin concentration is a protective factor in cardiovascular disease (CAD) and how it correlates with parameters of oxidative stress in young males and females.

Methods

The study comprised 628 healthy subjects of both genders, 18–22 years of age. In fasting sera the concentration of total bilirubin (Tbil), parameters of cardiovascular risk and oxidative stress were determined. The results were analyzed by appropriate statistical methods.

Results

We found no gender differences in body mass index (BMI), blood pressure and lipid profile between subjects with low and high Tbil level. Men with high Tbil had higher concentrations of albumin and uric acid (p < 0.001) and lower of oxLDL (< 0.05), while women had higher albumin (p < 0.05) and lower TBARS (p < 0.05). Significant positive correlation in men was found between Tbil, uric acid and albumin, while for glucose and TBARS this association was negative. In female significant positive correlation was between Tbil, HDL-C, fibrinogen, albumin and uric acid and negative between Tbil and TBARS. The high concentration of Tbil in men was independently associated with uric acid (p < 0.05) and oxLDL (p < 0.001), while in women it was independently associated with TBARS (p < 0.05). After adjustment for traditional lipid parameters the predictive power of high bilirubin in men remained for uric acid (p < 0.001) and TBARS in women (p < 0.05).

Conclusion

These findings jointly support the concept that bilirubin via its antioxidant potential has a protective effect against cardiovascular disease in young male and female.