Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta‐analysis

Schwannomatosis is a genetic disorder characterized by the occurrence of multiple peripheral schwannomas. Segmental schwannomatosis is diagnosed when schwannomas are restricted to 1 extremity and is thought to be caused by genetic mosaicism. We studied 5 patients with segmental schwannomatosis through microstructural magnetic resonance neurography and mutation analysis of NF2, SMARCB1, and LZTR1. In 4 of 5 patients, subtle fascicular nerve lesions were detected in clinically unaffected extremities. Two patients exhibited LZTR1 germline mutations. This appears contrary to a simple concept of genetic mosaicism and suggests more complex and heterogeneous mechanisms underlying the phenotype of segmental schwannomatosis than previously thought. Ann Neurol 2016;80:625–628     

Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are characterized by genetic instability which is associated with abnormal DNA repair mechanisms. The most lethal type of DNA damage are double strand DNA breaks (DSBs), which are mainly repaired by Non Homologous End Joining Mechanism (NHEJ), whose core enzyme components include the Ku70/Ku80 heterodimer, DNA–PKcs, XRCC4 and DNA Ligase IV. The aim of the present study was the analysis of expression of proteins required for NHEJ in bone marrow cells of adult de novo MDS and their association with clinical characteristics and prognosis. Our analysis included 48 cases of MDS; 19 RA, 5 RARS, 19 RAEB, 3 RAEB-T, 1 CMML, 1 transformation to AML according to FAB classification. The expression of the enzymes Ku70, Ku80, XRCC4, DNA-PKcs and Ligase IV was determined by Western Blotting. The mean Ligase IV expression value was significantly lower in MDS patients compared to normal controls (0.53 vs. 0.78, p?=?0.03). A negative correlation was found between karyotype risk group and Ligase IV values. (p?=?0.05). Moreover, Ku70 expression levels were significantly lower in patients with a good prognosis karyotype (p?=?0.04). Furthermore, a negative correlation between Ku70 expression values and Hb levels was observed (p?=?0.04). Finally, a positive correlation was observed between enzyme Ku70 expression values and level of blasts (p?=?0.04). Our findings suppor-t a potential role of NHEJ enzyme Ligase IV in the pathogenesis of MDS. Larger numbers of cases need to be screened in order to draw definite conclusion.     

Novel oral anticoagulants in the treatment of acute coronary syndromes: is there any room for new anticoagulants?

Thrombosis plays a key role in the pathophysiology of acute coronary syndromes (ACS). The management of patients with ACS includes interventional procedures and use of antithrombotic agents acutely, and dual antiplatelet therapy (aspirin and a P2Y12 receptor antagonist) for secondary prevention. However, patients with recent ACS remain at a substantial residual risk for recurrent ischemic events or death. The idea of follow-up treatment with an oral anticoagulant on top of standard therapy seems promising. Warfarin was the first oral anticoagulant thoroughly investigated in this direction, but the widespread long-term use of warfarin in ACS has been limited by challenges associated with pharmacodynamic/pharmacokinetic deficiencies of the drug and the risk of bleeding. Novel oral anticoagulants, such as direct thrombin inhibitors (DTIs) and FXa inhibitors overcome the downsides of VKAs. Ximelagatran was the first DTI, investigated and proven to be effective in prevention of recurrent ischemic events in ACS patients, but the drug association with hepatotoxicity prompted its withdrawal. Dabigatran etexilate, apixaban, darexaban (YM150) and TAK-442 were studied in phase II dose-escalation trials in order to determine the balance between clinical effectiveness and bleeding risk in daily use with dual antiplatelet therapy, with both positive and negative results. Rivaroxaban is the only agent that completed a phase III trial, showing reduction in recurrent ischemic events rate and death from cardiovascular causes as well as all-cause death. This review summarizes the data from completed and ongoing clinical trials of the new oral anticoagulants in patients with ACS.     

A simple and sensitive GC/MS method for the determination of atropine during therapy of anticholinesterase poisoning in serum samples

Atropine is used in the daily clinical practice for the treatment of poisonings caused by anticholinesterase pesticides, due to its sympathomimetic action. The investigation of the cause of the adverse effects that appear during atropine administration showed the necessity for the development and validation of a simple, rapid, sensitive, and specific method for the determination of atropine levels in serum samples. The developed method includes liquid-liquid extraction with ethyl acetate: dichloromethane (3:1, v/v) and derivatization using N,O-bis(trimethylsilyl)-trifluoracetamide (BSTFA) with 1% trimethylchlorsilane (TMCS) in acetonitrile environment. The method was found to be selective, linear, accurate, and precise according to international guidelines. The recovery was higher than 85.9%, the limit of quantification was 2.00?ng/ml, and the calibration curve was linear within the range of 2.00-500?ng/ml (R(2) ≥?0.992). Accuracy and precision were also calculated and were found to be less than 5.2 and 8.7%, respectively. The developed method was applied in a real case of accidental poisoning with chlorpyrifos in order to determine the atropine serum levels of the patient. The proposed method proved to be useful for the investigation of adverse effects that appear during atropine treatment of patients poisoned by anticholinesterase pesticides and it can also be used for the investigation of poisonings caused after consumption of atropine containing plants.     

Phoenix 100 versus Vitek 2 in the identification of gram-positive and gram-negative bacteria: a comprehensive meta-analysis

Phoenix 100 and Vitek 2 (operating with the current colorimetric cards) are commonly used in hospital laboratories for rapid identification of microorganisms. The present meta-analysis aims to evaluate and compare their performance on Gram-positive and Gram-negative bacteria. The MEDLINE database was searched up to October 2010 for the retrieval of relevant articles. Pooled correct identification rates were derived from random-effects models, using the arcsine transformation. Separate analyses were conducted at the genus and species levels; subanalyses and meta-regression were undertaken to reveal meaningful system- and study-related modifiers. A total of 29 (6,635 isolates) and 19 (4,363 isolates) articles were eligible for Phoenix and colorimetric Vitek 2, respectively. No significant differences were observed between Phoenix and Vitek 2 either at the genus (97.70% versus 97.59%, P = 0.919) or the species (92.51% versus 88.77%, P = 0.149) level. Studies conducted with conventional comparator methods tended to report significantly better results compared to those using molecular reference techniques. Speciation of Staphylococcus aureus was significantly more accurate in comparison to coagulase-negative staphylococci by both Phoenix (99.78% versus 88.42%, P < 0.00001) and Vitek 2 (98.22% versus 91.89%, P = 0.043). Vitek 2 also reached higher correct identification rates for Gram-negative fermenters versus nonfermenters at the genus (99.60% versus 95.90%, P = 0.004) and the species (97.42% versus 84.85%, P = 0.003) level. In conclusion, the accuracy of both systems seems modified by underlying sample- and comparator method-related parameters. Future simultaneous assessment of the instruments against molecular comparator procedures may facilitate interpretation of the current observations.     

New insights into the role of lipoprotein(a)-associated lipoprotein-associated phospholipase A2 in atherosclerosis and cardiovascular disease

Lipoprotein(a) [Lp(a)] plays an important role in atherosclerosis. The biological effects of Lp(a) have been attributed either to apolipoprotein(a) or to its low-density lipoprotein-like particle. Lp(a) contains platelet-activating factor acetylhydrolase, an enzyme that exhibits a Ca2+-independent phospholipase A2 activity and is complexed to lipoproteins in plasma; thus, it is also referred to as lipoprotein-associated phospholipase A2. Substrates for lipoprotein-associated phospholipase A2 include phospholipids containing oxidatively fragmented residues at the sn-2 position (oxidized phospholipids; OxPLs). OxPLs may play important roles in vascular inflammation and atherosclerosis. Plasma levels of OxPLs present on apolipoprotein B-100 particles (OxPL/apolipoprotein B) are correlated with coronary artery, carotid, and peripheral arterial disease. Furthermore, OxPL/apolipoprotein B levels in plasma are strongly correlated with Lp(a) levels, are preferentially sequestered on Lp(a), and thus are potentially subjected to degradation by the Lp(a)-associated lipoprotein-associated phospholipase A2. The present review article focuses specifically on the characteristics of the lipoprotein-associated phospholipase A2 associated with Lp(a) and discusses the possible role of this enzyme in view of emerging data showing that OxPLs in plasma are preferentially sequestered on Lp(a) and may significantly contribute to the increased atherogenicity of this lipoprotein.     

Poorly differentiated carcinoma of the rectum with aberrant immunophenotype： A case report

We report a case of a poorly differentiated epithelial tumour of the rectum with a highly pleomorphic morphology and an aberrant immunophenotype, including the expression of epithelial markers, the focal parameter of neuroendocrine differentiation, and the unexpected detection of CD-117 overexpression. A 69-year-old man was admitted to our clinic complaining of rectal bleeding and weight loss. Colonoscopy showed an ulcerative bleeding mass located about 8 cm from the anal verge. Abdominal and pelvis CT scans demonstrated a large low-density lesion with extracanalicular growth from the middle rectum, with local lymph-node spread, and without tumour infiltration of other pelvic organs, or evidence of distant intraabdominal spread. The patient underwent a low anterior resection for rectal cancer together with wide resection of lymph nodes. In immunohistochemical analysis, pankeratin and Epithelial Membrane Antigen （EMA） immunolabeling proved the epithelial nature of the tumor cells. Chromogranin A and Leukocyte Common Antigen （LCA） were negative, whereas CD-56 expression was scanty and Neuron Specific Enolase （NSA） was heavily and diffusely expressed. Ki67 immunoexpression was particularly increased. Interestingly, the intense c-kit immunoreactivity （100%） was a common feature. The above phenotypic and immunohistochemical profile was consistent with an anaplastic carcinoma of the large intestine, with focal neuroendocrine differentiation and diffuse immunoreactivity to c-kit protein. Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor （STI571） similar to that which has been proposed in GISTs.