Chronic myelogenous leukemia occurring in two brothers: The opposite sides of the same coin?

Herein we present a rare case of two brothers diagnosed with CML four years apart. Importantly, our case of CML occurrence among siblings is the fifth one reported and the second one investigated by both, conventional cytogenetics and RT-PCR analysis. Moreover, although Ph chromosome was detected in both our patients, RT-PCR revealed the presence of two different BCR-ABL transcripts. Finally, both our patients have been followed for a long period of time offering thus the opportunity to observe the differences in the clinical course.

Molecular Profiling of Malignant Pleural Effusions with Next Generation Sequencing (NGS): Evidence that Supports Its Role in Cancer Management.

Malignant pleural effusions (MPEs) often develop in advanced cancer patients and confer significant morbidity and mortality. In this review, we evaluated whether molecular profiling of MPEs with next generation sequencing (NGS) could have a role in cancer management, focusing on lung cancer. We reviewed and compared the diagnostic performance of pleural fluid liquid biopsy with other types of samples. When applied in MPEs, NGS may have comparable performance with corresponding tissue biopsies, yield higher DNA amount, and detect more genetic aberrations than blood-derived liquid biopsies. NGS in MPEs may also be preferable to plasma liquid biopsy in advanced cancer patients with a MPE and a paucicellular or it could be difficult to obtain tissue/fine-needle aspiration biopsy. Of interest, post-centrifuge supernatant NGS may exhibit superior results compared to cell pellet, cell block or other materials. NGS in MPEs can also guide clinicians in tailoring established therapies and identifying therapy resistance. Evidence is still premature regarding the role of NGS in MPEs from patients with cancers other than lung. We concluded that MPE processing could provide useful prognostic and theranostic information, besides its diagnostic role.

Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review.

PURPOSE: To explore whether targeted next generation sequencing (NGS) of liquid biopsy in advanced non-small cell lung cancer (NSCLC) could potentially overcome the innate problems that arise with standard tissue biopsy, like intratumoral heterogeneity and the inability to obtain adequate samples for analysis. METHODS: The Scopus, Cochrane Library, and MEDLINE (via PubMed) databases were searched for studies with matched tissue and liquid biopsies from advanced NSCLC patients, analyzed with targeted NGS. The number of mutations detected in tissue biopsy only, liquid biopsy only, or both was assessed and the positive percent agreement (PPA) of the two methods was calculated for every clinically relevant gene. RESULTS: A total of 644 unique relevant articles were retrieved and data were extracted from 38 studies fulfilling the inclusion criteria. The sample size was composed of 2000 mutations tested in matched tissue and liquid biopsies derived from 1141 patients. No studies analyzed circulating tumor cells. The calculated PPA rates were 53.6% (45/84) for ALK, 53.9% (14/26) for BRAF, 56.5% (13/23) for ERBB2, 67.8% (428/631) for EGFR, 64.2% (122/190) for KRAS, 58.6% (17/29) for MET, 54.6% (12/22) for RET, and 53.3% (8/15) for ROS1. We additionally recorded data for 65 genes that are not recommended by current guidelines for mutational testing. An extra category containing results of unspecified genes was added, with a PPA rate of 55.7% (122/219). CONCLUSION: Despite many advantages, liquid biopsy might be unable to fully substitute its tissue counterpart in detecting clinically relevant mutations in advanced NSCLC patients. However, it may serve as a helpful tool when making therapeutic decisions. More studies are needed to evaluate its role in everyday clinical practice.

Cerebral hemorrhagic infarction as the initial manifestation of deep venous thrombosis in a child with patent foramen ovale.

Arterial ischemic stroke (AIS), with an estimated incidence of 1.1-4.3 per 100,000, is an important cause of morbidity and mortality in children and the risk of recurrence is high. We present the case of an 11-year-old child who presented with a symptomatology of acute ischemic stroke of unknown etiology. The radiological investigation did not reveal any underlying brain abnormality that could cause the event. The diagnostic work up included an echocardiogram, which revealed a thrombus in the right atrium, in conjunction with a patent foramen ovale. The patient was initiated immediately on anticoagulation therapy with low molecular weight heparin and warfarin, but two days later she suffered pulmonary emboli, diagnosed with spiral thorax computed tomography (CT) scan. An ultrasound study of the vessels of the lower extremitiesgcsp201817-main-client.xml revealed deep venous thrombosis (DVT), which was considered to be the underlying causative mechanism.

Plasma Urotensin II levels in children and adolescents with chronic kidney disease: a single-centre study.

BACKGROUND: Increased plasma Urotensin II (UII) levels have been found in adults with renal diseases. Studies in children are scarce. The objective of the study is to estimate plasma UII levels in subjects with chronic kidney disease (CKD) stages 3 to 5 and renal transplant recipients (RTR). In addition, the correlation of UII with anthropometric features and biochemical parameters was assessed. METHODS: Fifty-four subjects, aged 3 to 20 years old, 23 with CKD, 13 with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) and 18 RTR were enrolled. A detailed clinical evaluation was performed. Biochemical parameters of renal and liver function were measured. Plasma UII levels were measured in all patients and in 117 healthy controls, using a high sensitive enzyme immunoassay (EIA) kit. All data were analyzed using STATA™ (Version 10.1). RESULTS: Median UII and mean log-transformed UII levels were significantly higher in CKD and RTR patients compared to healthy subjects (p < 0.001). HD patients had higher but not statistically significant UII and log-UII levels than controls. UII levels increased significantly at the end of the HD session and were higher than controls and in line to those of other patients. The geometric scores of UII in HD (before dialysis), CKD and RTR patients increased respectively by 42, 136 and 164% in comparison with controls. Metabolic acidosis was associated with statistical significant change in log-UII levels (p = 0.001). Patients with metabolic acidosis had an increase in UII concentration by 76% compared to those without acidosis. CONCLUSIONS: Children and adolescents with CKD, particularly those who are not on HD and RTR, have significantly higher levels of UII than healthy subjects. UII levels increase significantly at the end of the HD session. The presence of metabolic acidosis affects significantly plasma UII levels.

Cardiovascular involvement in pediatric systemic autoimmune diseases: the emerging role of noninvasive cardiovascular imaging.

Cardiac involvement in pediatric systemic autoimmune diseases has a wide spectrum of presentation ranging from asymptomatic to severe clinically overt involvement. Coronary artery disease, pericardial, myocardial, valvular and rythm disturbances are the most common causes of heart lesion in pediatric systemic autoimmune diseases and cannot be explained only by the traditional cardiovascular risk factors. Therefore, chronic inflammation has been considered as an additive causative factor of cardiac disease in these patients. Rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis/spondyloarthritides, juvenile scleroderma, juvenile dermatomyositis/polymyositis, Kawasaki disease and other autoimmune vasculitides are the commonest pediatric systemic autoimmune diseases with heart involvement. Noninvasive cardiovascular imaging is an absolutely necessary adjunct to the clinical evaluation of these patients. Echocardiography is the cornerstone of this assessment, due to excellent acoustic window in children, lack of radiation, low cost and high availability. However, it can not detect disease acuity and pathophysiologic background of cardiac lesions. Recently, the development of cardiovascular magnetic resonance imaging holds the promise for early detection of subclinical heart disease and detailed serial evaluation of myocardium (function, inflammation, stress perfusion-fibrosis) and coronary arteries (assessment of ectasia and aneurysms).