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Emmanuel J Favaloro, Soma Mohammed, Jennifer Curnow, Leonardo Pasalic
We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs...
January 18, 2019: Pathology
Stephen J Nicholls, Adam J Nelson
High-density lipoprotein (HDL) has received increasing interest due to observations of an inverse relationship between its systemic levels and cardiovascular risk and targeted interventions in animal models that have had favourable effects on atherosclerotic plaque. In addition to its pivotal role in reverse cholesterol transport, HDL has been reported to possess a range of functional properties, which may exert a protective influence on inflammation, oxidation, angiogenesis and glucose homeostasis. This has led to the development of a range of HDL targeted therapeutics, which have undergone evaluation in clinical trials...
January 3, 2019: Pathology
Elisa Waldmann, Klaus G Parhofer
Low-density lipoprotein (LDL)-cholesterol (LDL-c) and lipoprotein(a) [Lp(a)] are independent cardiovascular risk factors. Reduction of LDL-c leads to reduction in cardiovascular events, regardless of the method of reducing LDL-c levels. Lifestyle modification and drugs are first line treatment options. However, many patients do not reach treatment goals, as defined in guidelines worldwide, through standard medication. So far, drugs are not efficient in lowering Lp(a) levels, or the reduction of plasma levels does not result in clinical benefit...
January 2, 2019: Pathology
Réka Mózes, Ambrus Gángó, Adrienn Sulák, Livia Vida, Lilla Reiniger, Botond Timár, Tibor Krenács, Hussain Alizadeh, Tamás Masszi, Júlia Gaál-Weisinger, Judit Demeter, Judit Csomor, András Matolcsy, Béla Kajtár, Csaba Bödör
Mutations of the multifunctional protein calreticulin (CALR) are recognised as one of the main driver alterations involved in the pathogenesis of Philadelphia negative myeloproliferative neoplasms (Ph- MPN) and also represent a major diagnostic criterion in the most recent World Health Organization classification of myeloid neoplasms. Nowadays, quantitative assessment of the driver mutations is gaining importance, as recent studies demonstrated the clinical relevance of the mutation load reflecting the size of the mutant clone...
December 31, 2018: Pathology
David M Ng, John R Burnett, Damon A Bell, Robert A Hegele, Amanda J Hooper
Rare genetic lipid disorders affect the levels of cholesterol and/or triglyceride in the circulation and, if untreated, can often lead to severe multisystem complications. The field of rare lipid disorders is evolving and increasing awareness of these conditions, along with the systematic integration of recent advances or knowledge into clinical practice, is crucial to improve patient outcomes. The aim of this review is to provide an overview of selected rare genetic lipid disorders, focusing on the recommended diagnostic strategies and contemporary treatment and management options...
December 28, 2018: Pathology
Iram Hussain, Nivedita Patni, Abhimanyu Garg
Lipodystrophies are rare, heterogeneous, genetic or acquired, disorders characterised by varying degrees of body fat loss and associated metabolic complications, including insulin resistance, dyslipidaemias, hepatic steatosis and predisposition to atherosclerotic cardiovascular disease (ASCVD). The four main types of lipodystrophy, excluding antiretroviral therapy-induced lipodystrophy in HIV-infected patients, are congenital generalised lipodystrophy (CGL), familial partial lipodystrophy (FPLD), acquired generalised lipodystrophy (AGL) and acquired partial lipodystrophy (APL)...
December 27, 2018: Pathology
Sally P A McCormick, Wolfgang J Schneider
Lipoprotein(a) [Lp(a)] is an apolipoprotein B (apoB)-containing plasma lipoprotein similar in structure to low-density lipoprotein (LDL). Lp(a) is more complex than LDL due to the presence of apolipoprotein(a) [apo(a)], a large glycoprotein sharing extensive homology with plasminogen, which confers some unique properties onto Lp(a) particles. ApoB and apo(a) are essential for the assembly and catabolism of Lp(a); however, other proteins associated with the particle may modify its metabolism. Lp(a) specifically carries a cargo of oxidised phospholipids (OxPL) bound to apo(a) which stimulates many proinflammatory pathways in cells of the arterial wall, a key property underlying its pathogenicity and association with cardiovascular disease (CVD)...
December 27, 2018: Pathology
Stuart S Carr, Amanda J Hooper, David R Sullivan, John R Burnett
Low density lipoprotein (LDL) is the predominant atherogenic lipoprotein particle in the circulation. Conventionally, a fasting lipid profile has been used for atherosclerotic cardiovascular disease (ASCVD) risk assessment. A non-fasting sample is now regarded as a suitable alternative to a fasting sample. In routine clinical practice, the Friedewald equation is used to estimate LDL-cholesterol, but it has limitations. Commercially available direct measures of LDL-cholesterol are not standardised. LDL-cholesterol is a well-established risk factor for ASCVD, being the primary therapeutic target in both primary and secondary prevention...
December 27, 2018: Pathology
John R Burnett, Amanda J Hooper, Robert A Hegele
No abstract text is available yet for this article.
December 27, 2018: Pathology
Nick S R Lan, Andrew C Martin, Tom Brett, Gerald F Watts, Damon A Bell
Familial hypercholesterolaemia (FH) is a dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, which if untreated causes lifelong elevated LDL-cholesterol (LDL-c), accelerated atherosclerosis and premature cardiovascular disease. Recent evidence suggests the prevalence of heterozygous FH is ∼1:220, making FH the most common autosomal dominant condition. Lowering LDL-c with statin and lifestyle therapy reduces the risk of cardiovascular events. Furthermore, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-c in addition to statin therapy, and early outcome data suggest improved vascular outcomes with these agents in FH patients in addition to statins...
December 19, 2018: Pathology
Amanda J Berberich, Robert A Hegele
Dyslipidaemias encompass about two dozen relatively rare monogenic disorders and syndromes for which the genetic basis has largely been defined. In addition, the complex polygenic basis of disturbed lipids and lipoproteins has been characterised in many patients, and has been shown to result from accumulation of many common polymorphisms with small effects on lipids. Genetic technologies, including dedicated genotyping and sequencing methods can detect both rare and common DNA variants underlying dyslipidaemias...
December 14, 2018: Pathology
Peter M Clifton
There is a large amount of controversy relating dietary fat intake and coronary artery disease. It has been strongly suggested that saturated fat is not harmful and that polyunsaturated fat is either not beneficial or even harmful. Given that dietary lipids and fibre can influence serum lipids which are strongly linked to the risk of coronary artery disease I have reviewed recent evidence linking diet and serum lipids to confirm a diet-heart disease link. Over 84 studies have been included in a recent meta-analysis and meta-regression which examined the effects of changes in fat type on lipid levels...
December 7, 2018: Pathology
Valentin Blanchard, Ilya Khantalin, Stéphane Ramin-Mangata, Kévin Chémello, Brice Nativel, Gilles Lambert
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein governing the circulating levels of low density lipoprotein-cholesterol (LDL-C), by virtue of its pivotal role in the degradation of the LDL receptor (LDLR). In the last 15 years, in vitro and in vivo studies have allowed our understanding of the physiological role of PCSK9. In the current report, we review the key studies that have established the mode of action of PCSK9, leading to the development of PCSK9 inhibitors for clinical use...
December 3, 2018: Pathology
Simon Smith, Darren Russell, Peter Horne, Josh Hanson
Human T-lymphotropic virus type 1 (HTLV-1) is hyperendemic amongst Indigenous Australians living in Central Australia. The epidemiology of the disease is poorly defined in other parts of Australia, despite a high prevalence of classically associated conditions. All HTLV-1 serology tests requested through public health facilities in Far North Queensland (FNQ) from January 1999 to December 2016 were reviewed. The person's age, sex, ethnicity, location, rationale for testing and result were recorded. There were 444 tests performed in 409 people; 217 (53%) were male; 171 (42%) identified as Indigenous Australians...
November 28, 2018: Pathology
Alvin Ho-Kwan Cheung, Chit Chow, Mei-Yung Yu, Wendy Wai-Tak Law, Peggy Pui-Ying Law, Paul Cheung-Lung Choi, Wei Kang, Ka-Fai To
Malignant transformation of benign mature ovarian teratoma can result in a wide spectrum of cancer, including a variety of carcinoma, sarcoma, or melanoma. The role of mismatch repair defects in such malignant transformation is still elusive. In view of current immunotherapy, the role of mismatch repair deficiency can have significant implications on therapeutic strategy. Thus, we aimed to investigate the possible involvement of mismatch repair deficiency in somatic-type carcinoma arising from teratoma. We examined seven cases of malignant transformation of ovarian teratoma to carcinoma from the years 2000-2017...
November 27, 2018: Pathology
Jelena Roncevic, Ilona Djoric, Sonja Selemetjev, Jelena Jankovic, Tijana Isic Dencic, Vesna Bozic, Dubravka Cvejic
Papillary thyroid carcinoma (PTC), a common form of thyroid malignancy, displays significant variations in clinical features and outcome. The malignant transformation of the thyroid is driven by altered expression of many matrix-modulating enzymes, including matrix metalloproteinase-9 (MMP-9). A single nucleotide polymorphism in its promotor (-1562 C/T) is suspected to cause overexpression of MMP-9, which in turn contributes to development of a tumour unfavourable phenotype. The aim of this study was to investigate the impact of MMP-9 promotor genotype on MMP-9 expression in PTC samples, and to assess its value as a possible risk factor for developing PTC or its aggressive phenotype...
November 26, 2018: Pathology
Darrell Green, Archana Singh, Jasmine Sanghera, Lee Jeys, Vaiyapuri Sumathi, Tamas Dalmay, William D Fraser
No abstract text is available yet for this article.
November 26, 2018: Pathology
Junhun Cho, So Young Kang, Kyoung-Mee Kim
No abstract text is available yet for this article.
November 26, 2018: Pathology
Jen-Pi Tsai, Kuo-Chih Tseng, Ming-Nan Lin, Cheng-Chuan Su
A high seroprevalence of human herpesvirus type 8 (HHV-8) in mild cirrhotics is significantly associated with hepatitis activity. Cirrhosis is always derived from chronic hepatitis. We aimed to evaluate the prevalence of HHV-8 infection in patients with chronic hepatitis. Blood samples collected from 129 patients with chronic hepatitis and 129 age- and sex-matched healthy controls were analysed for monocyte and platelet counts, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), HHV-8 antibody and DNA, and alanine aminotransferase (ALT)...
November 26, 2018: Pathology
Tristan J Dodds, James S Wilmott, Louise A Jackett, Serigne N Lo, Georgina V Long, John F Thompson, Richard A Scolyer
Primary melanoma involving the anorectal region is rare, accounting for <1% of all melanomas in most Western countries. It characteristically presents at an advanced clinical stage and is associated with poor clinical outcomes. Preliminary reports suggest that response rates to immunotherapies in patients with advanced stage mucosal melanoma are much lower than in cutaneous (or acral) melanoma patients but reasons for this are unclear. Comprehensive characterisation of the immune microenvironment in anorectal melanoma has not previously been performed...
November 26, 2018: Pathology
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