bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of high intensity focused ultrasound and radioiodine for treating toxic thyroid nodules
Authors: Giovanella Luca , Piccardo Arnoldo , Pezzoli Cinzia , Bini Fabiano , Ricci Riccardo , Ruberto Teresa , Trimboli Pierpaolo 
Published: May 2018

SummaryPurposeWe compared the effectiveness of high intensity focused ultrasound (HIFU) and radioiodine (RAI) to treat patients carrying toxic thyroid nodule (TTN). Normalization of serum thyrotropin (TSH) 1 year after treatment was the primary end‐point; concurrent changes in nodules' volume and scintigraphic pattern were also evaluated as secondary end‐points.Materials and MethodsAmong patients ≥18 years old with TTN observed at our centre between January 1st, 2016 and December 31th, 2016 we prospectively enrolled 17 and 15 age and sex‐matched patients treated with RAI and HIFU, respectively. Biochemical thyroid tests and nodules' volume were assessed before and 3, 6 and 12 months after treatments. A thyroid scintigraphy was performed before and 1 year after treatment, respectively.ResultsThe final series included 17 patients treated with RAI and 15 patients treated with HIFU, respectively. Neither demographic nor clinical differences were found at baseline. One year after treatment 14 of 17 RAI‐treated and 4 of 15 HIFU‐treated patients fulfilled criteria for response to treatment (P = .0008). Indeed, the median TSH value was 1.5 IU/mL and 0.2 IU/mL in HIFU and RAI groups, respectively (P < .0001). Finally, despite a similar decrease in nodules' volume in both groups, a scintigraphic response was achieved in 16 of 17 (94%) RAI‐treated compared to 8 of 15 (53%) HIFU‐treated patients (P = .024), respectively.ConclusionsIn our series, RAI clearly outperforms HIFU in treating patients carrying TTN and remains the first‐line noninvasive treatment in such cases.
Eversion endarterectomy of the deceased donor renal artery to prevent kidney discard
Authors: Khan Muhammad A. , El‐Hennawy Hany , Jones Korie C. , Harriman David , Farney Alan C. , Rogers Jeffrey , Orlando Giuseppe , Stratta Robert J. 
Published: May 2018

AbstractIntroductionDeceased donor (DD) kidneys exhibiting severe atherosclerosis involving the renal artery (RA) may represent a contraindication to kidney transplantation (KT).MethodsEversion endarterectomy (EE) was performed as a salvage procedure to permit KT.ResultsWe identified 17 cases (1.2% of all DD KTs during the study period) involving EE of the DD RA. Thirteen (76.5%) kidneys were imported, and mean Kidney Donor Profile Index (KDPI) was 81%. Mean DD age was 59 years, mean RA plaque length was 1.7 cm, and mean glomerulosclerosis on biopsy was 10%. Mean recipient age was 64 years, and dialysis vintage was 32 months. With a mean follow‐up of 36 months, actual patient and graft survival rates were both 76.5%. One patient died early without a technical problem. Of the remaining 16 patients, 2‐year patient and graft survival rates were both 100%. There were no early or late vascular complications. The incidence of delayed graft function was 35%. Mean serum creatinine and GFR levels in patients with functioning grafts at latest follow‐up were 1.8 mg/dL and 40 mL/min, respectively.ConclusionsEE appears to be a safe and under‐utilized procedure that may prevent discard of marginal donor kidneys and is associated with acceptable short‐term outcomes.
Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site
Authors: Nagata Gabriela , Santana Thalita , Queiroz Aline , Caramez Renata H. , Trierveiler Marília 
Published: May 2018

BackgroundWe analyzed the different grades of dysplasia in the epithelium adjacent to lip squamous cell carcinoma (LSCC), as a parallel to actinic cheilitis (AC) that suffered malignant transformation.MethodsForty samples of epithelium adjacent to LSCC were histologically graded according to the World Health Organization (WHO) and the binary systems. The expression of mutated p53 was evaluated through immunohistochemistry.ResultsAccording to WHO system, 37.5% of the cases were graded as mild, 45% as moderate and 17.5% as severe dysplasia (P = 0.09). Considering the binary system, 90% of the cases were classified as low‐risk and 10% as high‐risk lesions. Mutated p53 was present in 73.3% of mild, 88.8% of moderate and 71.4% of severe dysplasia cases. Considering the binary system, 80.5% of the low‐risk and 75% of high‐risk lesions were immunopositive; 62.5% expressed the protein in both tumor cells and adjacent epithelium; 17.5% in adjacent epithelium only, and 7.5% in LSCC islands only (P = 0.03).ConclusionsWe observed heterogeneous grades of epithelial dysplasia in the epithelium adjacent to LSCC, which indicates that the analysis of AC morphological features is insufficient to predict patient's prognosis and to determine a treatment decision. Positive expression of mutant p53 in mild dysplasia reinforces this idea.
Forced loans in the Spanish Empire: the first requisition of American treasures in 1523
Authors: Sardone Sergio 
Published: May 2018

AbstractThis article describes the policy of forced loans, employed in Spain by Charles V to solve the principal financial crises of the Royal Treasury and to fund the main military campaigns of the Habsburg Empire. Specifically, this study is focused on the first requisition of private American treasures—the earliest case of this in European history—which were expropriated in 1523 by the Casa de la Contratación (House of Trade) of Seville to finance the campaign of Fuenterrabía against the French army. The analysis of exceptional archival sources provides details of all the forced loans imposed on the holders of remittances (primarily gold) and the conditions for extinguishing the debts without causing harmful consequences to Atlantic traders. The article challenges the widespread view of the confiscations as an attack on property rights and overly simplistic ideas about the supposedly ‘highly absolutistic’ or predatory policies attributed to the Crown of Castile in some of the economic historiography.
The contribution of infrastructure investment to Britain's urban mortality decline, 1861–1900
Authors: Chapman Jonathan 
Published: May 2018

AbstractIt is well‐recognized that both improved nutrition and sanitation infrastructure are important contributors to mortality decline. However, the relative importance of the two factors is difficult to quantify since most studies are limited to testing the effects of specific sanitary improvements. This article uses new historical data regarding total investment in urban infrastructure, measured using the outstanding loan stock, to estimate the extent to which the mortality decline in England and Wales between 1861 and 1900 can be attributed to government expenditure. Fixed effects regressions indicate that infrastructure investment explains approximately 30 per cent of the decline in mortality between 1861 and 1900. Since these specifications may not fully account for the endogeneity between investment and mortality, additional specifications are estimated using lagged investment as an instrument for current investment. These estimates suggest that government investment was the major contributor to mortality decline, explaining up to 60 per cent of the reduction in total urban mortality between 1861 and 1900. Additional results indicate that investment in urban infrastructure led to declines in mortality from both waterborne and airborne diseases.
Recent violence and legal involvement among young adults with early psychosis enrolled in Coordinated Specialty Care
Authors: Rolin Stephanie A. , Marino Leslie A. , Pope Leah G. , Compton Michael T. , Lee Rufina J. , Rosenfeld Barry , Rotter Merrill , Nossel Ilana , Dixon Lisa 
Published: May 2018

AimIndividuals with serious mental illnesses have a small increased risk of engaging in violence or legal involvement compared to the general population. This seems to be particularly true for young adults experiencing early stages of psychosis. This study analysed the prevalence of and risk factors for reports of violence and legal involvement in a sample of young adults receiving Coordinated Specialty Care for early non‐affective psychosis.MethodsA total of 373 young adults (ages 16‐30) within 2 years of the onset of non‐affective psychosis were enrolled in 10 Coordinated Specialty Care sites in New York State from October 2013 to August 2016. Baseline violent ideation or behaviour and legal involvement was described and predictors identified.ResultsApproximately one‐quarter of individuals had either recent violent ideation or behaviour at baseline (n = 90, 24.6%); nearly one‐tenth of the sample reported recent legal involvement (n = 33, 9.0%). Individuals with violent ideation or behaviour had lower levels of education and were less likely to be working. Those with recent legal involvement were more likely to be male and more likely to have substance use (alcohol, cannabis and other drugs).ConclusionsThe overall rate of recent violent ideation or behaviour is similar to other studies; up to one‐third of individuals experiencing a first‐episode of psychosis (FEP) report violence. Recent legal involvement was strongly associated with substance use. This study presents insight into violence and legal involvement among individuals with FEP and indicates the need for further research.
Genetic generalized epilepsies
Authors: Mullen Saul A. , Berkovic Samuel F. ,   the ILAE Genetics Commission
Published: May 2018

SummaryThe genetic generalized epilepsies (GGEs) are mainly genetically determined disorders. Although inheritance in most cases appears to be complex, involving multiple genes, variants of a number of genes are known to contribute. Pathogenic variants of SLC2A1 leading to autosomal‐dominant GLUT1 deficiency account for up to 1% of cases, increasing to 10% of those with absence seizures starting before age 4 years. Copy number variants are found in around 3% of cases, acting as risk alleles. Copy number variation is much more common in those with comorbid learning disability. Common variant associations are starting to emerge from genome‐wide association studies but do not yet explain a large proportion of GGEs. Although currently genetic testing is not likely to yield a diagnosis for most patients with GGEs, it can be of great importance in specific clinical situations. Providers should consider the individual patient's history in determining the utility of genetic testing.
Genetic literacy series: Primer part 2—Paradigm shifts in epilepsy genetics
Authors: Helbig Ingo , Heinzen Erin L. , Mefford Heather C. ,   the International League Against Epilepsy Genetics Commission
Published: May 2018

SummaryThis is the second of a 2‐part primer on the genetics of the epilepsies within the Genetic Literacy Series of the Genetics Commission of the International League Against Epilepsy. In Part 1, we covered types of genetic variation, inheritance patterns, and their relationship to disease. In Part 2, we apply these basic principles to the case of a young boy with epileptic encephalopathy and ask 3 important questions: (1) Is the gene in question an established genetic etiology for epilepsy? (2) Is the variant in this particular gene pathogenic by established variant interpretation criteria? (3) Is the variant considered causative in the clinical context? These questions are considered and then answered for the clinical case in question.
Methodologies for data collection in congenital haemophilia with inhibitors (CHwI): critical assessment of the literature and lessons learned from recombinant factor VIIa
Authors: Kessler C. M. , Benchikh el Fegoun S. , Worster A. 
Published: May 2018

AimsTo systematically review the effectiveness of on‐demand treatment with recombinant coagulation factor VIIa (rFVIIa) in congenital haemophilia with inhibitors and, if feasible, perform a meta‐analysis of the data.Materials and methodsPublications from Embase®, MEDLINE®, MEDLINE® In‐Process and the Cochrane Central Register of Controlled Trials were searched. Selected publications were reviewed for inclusion by two independent expert reviewers. Discrepancies were reconciled by a third independent reviewer. Data from selected studies were extracted using a predefined grid to ensure uniform and comparable results were captured.ResultsA systematic search (cut‐off date of 2 May 2016) identified 20 studies (13 observational; seven randomized controlled trials). All studies were of sufficient quality to include in this analysis and comprised 1221 participants, with 5981 bleeds in 746 individuals treated with rFVIIa. Haemostatic overall effectiveness of the individual studies identified ranged from 68% to 100% at ≤12 hours, 86% to 96% at 13‐24 hours and 76% to 99% at 24‐48 hours with rFVIIa <100 μg/kg, with similar rates reported for the ≥250 μg/kg dose. However, heterogeneity between the studies precluded pooling of results.ConclusionsData from the individual studies confirmed that rFVIIa is an effective therapy for the on‐demand treatment of bleeds in congenital haemophilia with inhibitors. However, the high levels of heterogeneity between studies precluded pooling of results for a valid, reliable or precise summary measure. There remains a need to implement standardized clinical definitions and measurements for the effectiveness and safety of haemophilia therapies in future clinical trials.
PD‐1 and PD‐L1 expression in HNSCC primary cancer and related lymph node metastasis – impact on clinical outcome
Authors: Schneider Sven , Kadletz Lorenz , Wiebringhaus Robert , Kenner Lukas , Selzer Edgar , Füreder Thorsten , Rajky Orsolya , Berghoff Anna S , Preusser Matthias , Heiduschka Gregor 
Published: May 2018

AimsExpression profiles and clinical impact of programmed cell death ligand 1 (PD‐L1) and programmed cell death 1 (PD‐1) expressing tumour infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) are not elucidated fully. This study evaluates expression patterns in primary HNSCC and related lymph node metastasis and the impact on patients’ clinical outcome.Methods and resultsImmunohistochemical staining patterns of PD‐L1 and PD‐1 were evaluated in 129 specimens of primary HNSCC and 77 lymph node metastases. Results were correlated with patients’ clinical data. PD‐L1 expression was observed in 36% of primary carcinoma and 33% of lymph node metastasis, and correlates significantly with decreased overall survival (OS) (P = 0.01) and disease‐free survival (DFS) (P = 0.001) in oral cavity squamous cell carcinoma patients. PD‐L1 expression was associated with presence of lymph node metastasis (P = 0.0223). Infiltration of PD‐1‐expressing lymphocytes correlates significantly with favourable OS (P = 0.001) and DFS (P = 0.001) in oropharyngeal cancer and hypopharyngeal cancer patients OS (P = 0.007) and DFS (P = 0.001). Presence of PD‐1 TILs also correlates significantly with better OS (P = 0.005) and DFS (P = 0) in the human papilloma virus (HPV)‐negative cohort. Cox regression multivariate analysis revealed PD‐1 TIL expression as an independent prognostic marker for OS (P = 0.004) and DFS (P = 0.001) and T stage was validated as negative prognostic marker for OS (P = 0.011). PD‐1‐expressing lymphocytes (P = 0.0412) and PD‐L1 expression (P = 0.0022) patterns correlate significantly in primary cancers and matched lymph node metastases.ConclusionsOur results characterise the expression profiles of PD‐1 axis proteins in HNSCC which might serve as possible clinical prognostic markers.
Laboratory diagnosis of clinically relevant platelet function disorders
Authors: Gresele P. , Falcinelli E. , Bury L. 
Published: May 2018

AbstractInherited platelet function disorders (IPFDs) represent a significant fraction of congenital hemorrhagic disorders, and may be associated with bleeding of considerable severity. IPFDs may be difficult to diagnose and a preliminary accurate clinical examination and an objective evaluation of the severity of the bleeding history are mandatory. The laboratory investigation of IPFDs should follow a rational algorithm based on a streamlined panel of laboratory tests with subsequent steps of increasing levels of complexity. First screening tests include platelet count, peripheral blood smear, light transmission aggregometry, measurement of platelet granule content and release, and the expression of glycoproteins by flow cytometry. Several of these tests have been largely employed, and a few validated, for the diagnosis of IPFDs and some recent developments are discussed. Point‐of‐care tests may provide the advantage of rapidity and the possibility to study platelet function in whole blood, but further studies are required to clarify their potential diagnostic application. Genotyping is recommended for some conditions (genotype/phenotype correlations, forms associated with a high risk of developing hematologic malignancies) but, especially when carried out by next‐generation sequencing (NGS) techniques, needs to be critically evaluated taking into account clinical and laboratory phenotypes.
How I investigate for bleeding disorders
Authors: Hayward C. P. M. 
Published: May 2018

AbstractIntroductionLaboratory investigations for bleeding disorders are warranted when an individual has a personal and/or family history of bleeding, and/or laboratory findings that suggest the possibility of an inherited or acquired bleeding disorder.MethodsThis review summarizes author's experience with ordering and reporting on diagnostic investigations for common and rare bleeding disorders, with consideration of recent articles on diagnosing bleeding disorders. An updated strategy is presented for investigating common and rare, congenital and acquired bleeding disorders.ResultsAn investigation of a suspected bleeding disorder requires a practical strategy that considers the clinical problem to be investigated, the pretest probability of true‐positive and false‐positive findings, the investigations can be performed locally or in a reference laboratory and limit the number of blood samples required to establish a diagnosis. It is often advantageous to simultaneously test for von Willebrand disease and platelet function disorders, and for coagulation defects, including fibrinogen disorders. An investigation for rarer bleeding disorders, including those affecting factor XIII, α2 antiplasmin, and plasminogen activator inhibitor‐1, is appropriate when faced with a severe congenital or acquired bleeding problem that cannot be explained by the initial diagnostic investigations.ConclusionAn organized strategy for investigating bleeding disorders that consider important issues, confirms abnormal findings, encourages proper interpretation of the results, and provides a helpful framework for assessing both common and rare causes of bleeding.
Genetic basis of congenital erythrocytosis
Authors: Bento C. 
Published: May 2018

AbstractIntroductionCongenital Erythrocytosis (CE) represents a rare and heterogeneous clinical entity. It is caused by deregulated erythropoiesis where red blood cell overproduction results in elevated hemoglobin and hematocrit levels. CE may either be primary or secondary to elevated erythropoietin concentrations. The only known form of primary CE is caused by mutations in the EPOR gene. Secondary CE can be a consequence of tissue hypoxia, being caused by congenital defects such as hemoglobin variants with increased oxygen affinity, due to mutations in the α‐ or β‐globin genes (HBB, HBA2, HBA1), or due to mutations in the BPGM gene. Secondary CE can also result from defects in the components of the oxygen‐sensing pathway (PHD2, HIF2α and VHL).MethodologyThe family history and the quantification of serum EPO are mandatory to define the best diagnostic strategy regarding molecular studies. Based upon the serum EPO level, P50 and familial data, it is possible to establish a diagnostic algorithm.ResultsDespite recent important discoveries in the molecular pathogenesis of CE, in about 70% of the patients the genetic causes remain to be identified. Clinical data on patients suffering from CE are sparse. This fact is conditional upon the effective way to predict the disease evolution, the establishment of the best management and the genetic counselling.ConclusionThe number and phenotypic variability of patients that remain without an identified etiology suggest that other genes have to be implicated. Studies by next generation sequencing methodologies are already being performed and it is expected the identification of other genes involved in the pathophysiology of the CE.
Vitamin B12 deficiency and clinical laboratory: Lessons revisited and clarified in seven questions
Authors: Salinas M. , Flores E. , López‐Garrigós M. , Leiva‐Salinas C. 
Published: May 2018

AbstractThe objective of this review article is to address the most frequently asked questions that pathologists and primary care physicians might face when dealing with a patient with suspicion of vitamin B12 deficiency. More specifically, the article mainly discusses the importance and prevalence of the deficit, how to recognize it, and the important role of a prompt diagnosis confirmation based on laboratory biomarkers for efficient replacement therapy.
Epidemiology of prostate cancer in Asian countries
Authors: Kimura Takahiro , Egawa Shin 
Published: May 2018

AbstractThe incidence of prostate cancer has been increasing worldwide in recent years. The GLOBOCAN project showed that prostate cancer was the second most frequently diagnosed cancer and the fifth leading cause of cancer mortality among men worldwide in 2012. This trend has been growing even in Asian countries, where the incidence had previously been low. However, the accuracy of data about incidence and mortality as a result of prostate cancer in some Asian countries is limited. The cause of this increasing trend is multifactorial. One possible explanation is changes in lifestyles due to more Westernized diets. The incidence is also statistically biased by the wide implementation of early detection systems and the accuracy of national cancer registration systems, which are still immature in most Asian countries. Mortality rate decreases in Australia, New Zealand and Japan since the 1990s are possibly due to the improvements in treatment and/or early detection efforts employed. However, this rate is increasing in the majority of other Asian countries. Studies of latent and incidental prostate cancer provide less biased information. The prevalence of latent and incidental prostate cancer in contemporary Japan and Korea is similar to those in Western countries, suggesting the influence of lifestyle changes on carcinogenesis. Many studies reported evidence of both congenital and acquired risk factors for carcinogenesis of prostate cancer. Recent changes in the acquired risk factors might be associated with the increasing occurrence of prostate cancer in Asian countries. This trend could continue, especially in developing Asian countries.