Diagnosis of Paroxysmal Nocturnal Hemoglobinuria: Recent Advances

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder with its protean clinical manifestations. This is due to partial or complete absence of ‘glycophosphatidyl-inositol-anchor proteins’ (GPI-AP). The main aim of this review is to highlight various diagnostic modalities available, basic principle of each test and recent advances in the diagnosis of PNH. Recently among various tests available, the flow cytometry has become ‘the gold standard’ for PNH testing. In order to overcome the difficulties encountered by the testing and research laboratories throughout the world, International Clinical Cytometry Society has come up with guidelines regarding the indications for testing, protocol for sample collection, processing, panel of antibodies as well as gating strategies to be used, how to interpret the test and reporting format to be used. It is essential to test at least two GPI-linked markers on at least two different lineages particularly on red cells and granulocytes/monocytes. The fluorescent aerolysin combined with other monoclonal antibodies in multicolour flow cytometry offered an improved assay not only for diagnosis but also for monitoring of PNH clones. It is equally important to diagnose this rare entity with high index of suspicion.     

NADPH oxidases and cardiac remodelling

A heart under chronic stress undergoes cardiac remodelling, a process that comprises structural and functional changes including cardiomyocyte hypertrophy, interstitial fibrosis, contractile dysfunction, cell death and ventricular dilatation. Reactive oxygen species (ROS)-dependent modulation of intracellular signalling is implicated in the development of cardiac remodelling. Among the different ROS sources that are present in the heart, NADPH oxidases (NOXs) are particularly important in redox signalling. NOX isoforms are expressed in multiple cell types including cardiomyocytes, fibroblasts, endothelial cells and inflammatory cells—with the two main isoforms expressed in the heart being NOX2 and NOX4. Recent studies indicate that NOX-dependent signalling is involved in the development of cardiomyocyte hypertrophy, interstitial fibrosis and post-MI remodelling. NOXs may also be involved in the genesis of contractile dysfunction and myocyte apoptosis. Here, we review the main effects of NOXs in the pathogenesis of cardiac remodelling and the redox-sensitive signalling pathways that underlie these effects. The elucidation of mechanisms involved in NOX-dependent regulation of cardiac remodelling may lead to new therapeutic targets for heart failure.     

Probiotic E.faecalis — adjuvant therapy in children with recurrent rhinosinusitis

Sinusitis is a frequent complication of respiratory tract infections. Probiotics are perceived to be useful in infections, allergies, and inflammations. Our prospective trial stratified 204 children with recurrent rhinosinusitis by age (2–11 years, 54m:64f; 12–18 years, 39m:47f) and assigned them to standard treatment (antibiotics, anticongestants) or additional 60 days Symbioflor-1 (SF1; Enterococcus faecalis 1.5–4.5x10⁷ CFU). The number of sinusitis episodes was lower in SF1-treated patients (2.52±0.91) than among controls (3.27±1.36; p=0.01). Mean duration of the first sinusitis episode was 11.9±8.6 days with SF1, whereas it was 16.1±12.9 days in the younger controls (p=0.023) and 9.86±5.05 days in the elder controls (n.s.). Duration of subsequent sinusitis episodes was also shorter in SF1 patients (15.2±13.6 days) compared with controls (22.7±14.8 days; p=0.030). No adverse events were observed. Probiotic Enterococcus faecalis adjuvant to conventional therapy can reduce the number and duration of rhinosinusitis episodes in children and adolescents.     

Findings from the Adjuvant Colon Cancer End Points (ACCENT) Collaborative Group: the Power of Pooled Individual Patient Data from Multiple Clinical Trials

Randomized clinical trials (RCTs) are relied upon for determining the standard of care and changes to the standard of care in oncology. Through data sharing, the pooled individual patient data (IPD) from these trials can provide high-quality sources and enriched power for analyses beyond the original goals of each trial. To address important scientific questions in early-stage colon cancer, the Adjuvant Colon Cancer End Points (ACCENT) Collaborative Group has continuously integrated IPD from large adjuvant colon cancer RCTs conducted worldwide. Through June 2016, IPD from over 40,000 patients from 27 major trials (1977 to 2009) have been assembled. Over the past 20 years, a variety of clinical questions have been investigated and addressed by ACCENT collaborations. Many of the findings have provided additional understanding of treatment mechanisms, suggested changes or reinforced quality patient care, and informed and improved the design for the current and next generation of RCTs. We review these significant contributions from the ACCENT collaboration.     

Internal patterned injuries in trauma

Patterned bruising of the internal organs is unusual. In these cases a cutaneous pattern of bruising is not observed but the underlying tissue may show unusual injuries that may even be recognizable as a tramline pattern. We report the suicide of a 23-year-old man by jumping off a bridge. At autopsy, an unusual finding was “tramline” bruising of the right liver lobe. The “blunt objects” that inflicted the bruising were determined to be the right ribs which were pushed against the liver capsule as a consequence of the extensive thoracic and vertebral trauma after a fall from a height with intermediate impact.