bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Application of Transoral Robotic Surgery in Failures of Traditional Transoral Laser Microsurgery: Critical Considerations
Authors: Vicini Claudio , Leone Carlo Antonio , Montevecchi Filippo , Dinelli Elisa , Seccia Veronica , Dallan Iacopo
Published: June 2014

Aims: To assess the role of transoral robotic surgery (TORS) in managing failures of conventional transoral laser microsurgery (TLM) in cases with difficult laryngeal exposure. Methods: Retrospective analysis of 3 patients with difficult laryngeal exposure treated with TORS. All 3 cases failed to be managed by conventional TLM after repeated attempts by experienced surgeons. In 2 cases, the initial disease was laryngeal cancer treated by a cricohyoidoepiglottopexy, with an obstructing residual epiglottis. The last case was a bilateral Reinke disease submitted to repeated TLM procedures, producing multiple supraglottic and glottic scars. In all cases, the difficult exposure was produced by a combination of concurrent elements including insufficient mouth opening, short and stiff neck, macroglossia and high-positioned larynx. Results: Two patients were exposed by means of a Davis Meyer mouth gag. The other patient was managed by a Feyh-Kastenbauer device. The key of the success was the possibility to work ‘around the corner' (30° angle view) where straight alignment of the larynx was impossible. Conclusions: Where possible, a TORS approach should be considered complementary to TLM in cases of very difficult or even impossible conventional transoral laryngoscopic approach.
Central Serous Chorioretinopathy
Authors: Liegl Raffael , Ulbig Michael W.
Published: June 2014

The pathogenesis of central serous chorioretinopathy (CSC) is still not fully understood. The involvement of corticosteroids is undisputed, although their exact role has not been clarified; other parts of the underlying mechanism of CSC have been mainly elucidated by imaging techniques such as fluorescein and indocyanine green angiography. Even though most cases of CSC are self-limiting, severe as well as recurrent courses exist, and for these patients only a limited number of treatment options are available: laser photocoagulation, with a risk of scotoma and choroidal neovascularization, and photodynamic therapy. In this review article, we give an overview of its epidemiology, the current understanding of its pathogenesis as well as systemic and ocular risk factors. We illuminate modern diagnostic tools as well as current treatment options in the context of CSC, particularly in the light of a better understanding of corticosteroids and their receptors involved in its pathogenesis.
Treatment Algorithm for Metastatic Renal Cell Carcinoma - Recommendations Based on Evidence and Clinical Practice
Authors: Bergmann Lothar , Beck Jochaim , Bothe Kathrin , Brinkmann Olaf A. , Buse Stephan , Goebell Peter J. , Grünwald Viktor , Holzapfel Konstantin , Kübler Hubert , Marschner Norbert W. , Mickisch Gerald , Schultze-Seemann Wolfgang , Siebels Michael , Siemer Stephan , Störkel Stephan , Gschwend Jürgen E.
Published: June 2014

Until a few years ago, the treatment options for metastatic renal cell cancer (mRCC) were very limited. The growing understanding of the molecular pathomechanisms underlying RCC allowed the development of new treatment approaches. Meanwhile, several approved target-oriented substances from different drug classes are available for mRCC. The mechanism of action of vascular endothelial growth factor (VEGF) and VEGF receptor or mTOR inhibition is well documented by phase III trials and reflected in the current guidelines. However, no predictive biomarkers have been identified in mRCC so far to demonstrate a benefit by a specific compound in an individual patient. Meanwhile, the sequential use of ‘targeted therapies' in mRCC has been established as standard treatment. The optimal sequence of available agents is still unclear. A German RCC expert panel discussed and developed an algorithm for the choices of first- and second-line treatment in mRCC based on established clinical criteria.
Preventing Catheter-Related Bacteremia with Taurolidine-Citrate Catheter Locks: A Systematic Review and Meta-Analysis
Authors: Liu Hongbo , Liu Hongmei , Deng Jing , Chen Lihua , Yuan Lu , Wu Yong
Published: June 2014

Background: Preliminary evidence from some studies suggests that taurolidine-citrate locks decrease catheter-related bacteremia (CRB), which is a major cause of morbidity and mortality in patients using intravascular catheters. No previous study has sought to summarize existing evidence on the use of taurolidine-citrate locks. A systematic review and meta-analysis were undertaken to determine whether taurolidine-citrate was more effective than heparin in the prevention of CRB. Methods: The major English (PubMed, EBSCO, Web of Science and OVID) and Chinese (CBM, CNKI, VIP and Wanfang Data) healthcare databases were searched for randomized controlled trials comparing the efficacy and safety of taurolidine-citrate lock solution (TCLS) and heparin lock solution in the prevention of CRB. Results: Three studies involving 236 patients with a total of 34,984 catheter days were included. The use of TCLS significantly decreased the risk of CRB (relative risk = 0.47, 95% CI: 0.25-0.89) and Gram-negative bacterial infection. There was no significant difference in Gram-positive infections and exit-site infections. Conclusions: Catheter locking with TCLS reduced the risk of CRB and Gram-negative bacterial infection. Adverse events include thrombotic events.
Hemangiopericytoma of the Parapharyngeal Space: A Diagnostic Challenge
Authors: Villarreal Ithzel Maria , Garcia Berrocal Jose , Brea Beatriz , Tejerina Eva , Castello Jose , Ramirez-Camacho Rafael
Published: June 2014

Parapharyngeal space tumors are known for having a difficult approach, misleading diagnosis and for representing a treatment challenge. Hemangiopericytomas account for less than 1% of all vascular neoplasms and 3% of all soft tissue sarcomas. Only 14 cases have been reported in the worldwide literature in this location. We present a case of a 44-year-old male who was referred for evaluation. A CT scan and MRI showed a large parapharyngeal mass of a possible salivary gland origin. The patient underwent a lateral cervicotomy associated with a transparotid-transmandibular approach, obtaining a vimentin-positive immunostaining tumor defining the diagnosis. The accurate management and prognosis of this type of neoplasm are provided by the definite diagnosis obtained by a correct histopathologic assessment. A high clinical suspicion is essential.
Effects of Allopurinol on Endothelial Dysfunction: A Meta-Analysis
Authors: Kanbay Mehmet , Siriopol Dimitrie , Nistor Ionut , Elcioglu Omer C. , Telci Ozge , Takir Mumtaz , Johnson Richard J. , Covic Adrian
Published: June 2014

Objective: Several studies have assessed the effect of allopurinol on endothelial function, but these studies were relatively small in size and used different methods of evaluating endothelial function. We conducted a meta-analysis to investigate the effect of allopurinol on both endothelial-dependent and -independent vasodilatation. Methods: Electronic databases, Medline, PubMed, EMBASE, SCOPUS, EBSCO and the Cochrane Library Central Register of Clinical Trials were searched from January 1985 to July 2013 on clinical trials (randomized and non-randomized) which assessed the effect of allopurinol on endothelial function. We conducted a sensitivity analysis to assess the contribution of each study to the pooled treatment effect by excluding each study one at a time and recalculating the pooled treatment effect for the remaining studies. Treatment effect was significant if p < 0.05. We assessed for heterogeneity in treatment estimates using the Cochran Q test and the χ2 statistic (with substantial heterogeneity defined as values >50%). Results: The final analysis consisted of 11 studies (2 observational and 9 randomized). For the endothelial-dependent vasodilatation there were 6 studies, including 257 patients, that evaluated flow-mediated dilatation and 5 studies with 87 patients that reported data on forearm blood flow response to acetylcholine or flow-dependent vasodilatation. Overall, there was a significant increase in the endothelium-dependent vasodilatation with allopurinol treatment (MD 2.69%, 95% CI 2.49, 2.89%, p < 0.001; heterogeneity χ2 = 319.1, I2 = 96%, p < 0.001). There was only 1 study (100 patients) assessing nitrate-mediated dilatation and 4 studies (73 patients) evaluating forearm blood flow response to sodium nitroprusside as measures of endothelial-independent vasodilatation. The overall analysis (MD -0.08, 95% CI -0.50, 0.34, p = 0.70; heterogeneity χ2 = 9.0, I2 = 44%, p = 0.11) showed no effect of allopurinol treatment on endothelium-independent vasodilatation. Conclusions: We found that treatment of hyperuricemia with allopurinol is associated with an improvement in the endothelial-dependent, but not with the endothelial-independent vasodilatation.
Meta-Analysis of Anxiety Disorders and Temperament
Authors: Kampman Olli , Viikki Merja , Järventausta Kaija , Leinonen Esa
Published: June 2014

Background: The aims of the present study were to explore whether symptoms in different anxiety disorders are associated with Cloninger's model temperament dimensions novelty seeking (NS), harm avoidance (HA), reward dependence and persistence compared with control subjects in clinical samples of adults or late adolescents. Method: Literature search in the following databases: Cochrane Library, PubMed (Medline), Web of Science, Psycinfo and PsycArticles. Systematic review, grading the level of evidence and meta-analysis for each disorder by comparing the temperament dimension scores between patient and control samples in single studies. Results: A total of 40 papers fulfilled the inclusion criteria. Meta-analyses were conducted on a total of 24 studies focusing on panic disorder (PD), social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD). The primary finding was a constant and clinically marked positive association between the HA temperament dimension and symptoms of PD, SAD and OCD, with a most marked effect in SAD, and a moderate effect in OCD and PD. Second, less marked and clinically marginal associations between NS score and SAD and OCD (negative associations), but no associations with PD were observed. The meta-analyses revealed heterogeneity between the results of individual studies, especially in the analyses including SAD and OCD. Conclusions: PD, SAD and OCD share a marked and state-dependent avoidant behavioral pattern, which is common for all anxiety disorders. However, PD showed a different pattern of arousal to novel stimuli from that of SAD and OCD. The findings are state dependent and based on cross-sectional studies.
Determination of the Optimal Echocardiographic Scoring System to Quantify Carcinoid Heart Disease
Authors: Dobson Rebecca , Cuthbertson Daniel J. , Jones Julia , Valle Juan W. , Keevil Brian , Chadwick Carrie , Poston Graeme P. , Burgess Malcolm I.
Published: June 2014

Background: Carcinoid heart disease (CHD) is an important complication of metastatic neuroendocrine disease, requiring regular monitoring to enable intervention prior to right heart failure. We aimed to identify the most appropriate echocardiographic scoring systems for the quantitative assessment of CHD. Methods: In this prospective study conducted between April and October 2012 in two European Neuroendocrine Tumor Society (ENETS) Centres of Excellence, patients with neuroendocrine tumours with liver metastases and/or carcinoid syndrome underwent transthoracic echocardiography and blood sampling for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA). Each patient was assessed according to six echocardiographic scoring systems. The individual scoring systems' feasibility, observer variability, sensitivity, specificity and correlation with the concentration biomarkers were determined. Results: 100 patients were included; 21% had echocardiographic evidence of CHD. All scores discriminated highly between those with/without CHD, with no single score performing significantly better than another. The severity, determined using all of the scoring systems, correlated with the concentration of both biomarkers, but the strongest correlations were seen between the Bhattacharyya score and serum NT-proBNP. Conclusion: All scoring systems are comparable in terms of sensitivity and specificity for the detection of CHD. There is a variation in the feasibility of the scoring systems due to varying complexity of the score components. All scores correlate with NT-proBNP and plasma 5-HIAA. The Westberg score appears to be the most optimal scoring system for use in screening of CHD whereas the more complex scoring systems are more suited to the patient with established disease who may require surgical intervention.
Current Diagnostic and Management Options in Perihilar Cholangiocarcinoma
Authors: Rizvi Sumera , Gores Gregory J.
Published: June 2014

Cholangiocarcinomas (CCAs) are heterogeneous biliary tract tumors with dismal prognosis. Perihilar CCA (pCCA) involves the large bile ducts of the hepatic hilum, and is the most common type of CCA. Primary sclerosing cholangitis (PSC) is an established risk factor for pCCA. Although the diagnosis of pCCA is challenging, recent advances have been made including cytologic techniques such as fluorescence in situ hybridization. Endoscopic ultrasound with sampling of regional lymph nodes is emerging as a valuable diagnostic modality in the diagnosis and staging of pCCA. Curative treatment options are limited to early stage disease, and include surgical resection and liver transplantation after neoadjuvant therapy. This underscores the importance of early detection, and the need for development of innovative diagnostic tools such as biomarkers. A dense desmoplastic tumor stroma plays an integral role in pCCA progression. The tumor stroma represents an additional target for development of new therapies. Herein, we discuss these advances in the diagnosis and treatment of pCCA.
Pulmonary Hypertension and Cardiopulmonary Exercise in Heart Failure
Authors: Kim Chul-Ho , Jae Sae Young , Johnson Bruce D.
Published: June 2014

In heart failure (HF), pulmonary hypertension (PH) is initially associated with a rise in the left ventricular filling pressure. PH is defined by pulmonary hemodynamic measurements including pulmonary capillary wedge pressure, mean pulmonary arterial pressure and pulmonary vascular resistance. Eventually, PH in HF may become more of a reactive process. Although the mechanism of the reactive PH development is not clearly understood, vascular dysfunction induced by remodeling, vasoactive substances and genetic variation appear to contribute significantly to this form of PH. Noninvasive cardiopulmonary exercise testing has been extensively utilized to assess disease severity in HF patients. It provides integrated information that is dependent on cardiopulmonary hemodynamics, lung mechanics, breathing pattern and strategy. In this review, we will discuss the mechanisms of PH development in HF and how noninvasive gas exchange measures obtained with submaximal exercise are influenced by PH in this population.
Exercise Hypertension
Authors: Schultz Martin G. , Sharman James E.
Published: June 2014

Irrespective of apparent ‘normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a ‘hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory ‘masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE.
Adherence to Enhanced Recovery after Surgery Protocols across a High-Volume Gastrointestinal Surgical Service
Authors: Hammond John S. , Humphries Sarah , Simson Nick , Scrimshaw Helen , Catton James , Gornall Christopher , Maxwell-Armstrong Charles
Published: June 2014

Background and Aims: Enhanced recovery after surgery (ERAS) has been shown to improve outcomes for patients following gastrointestinal surgery. Data on protocol adherence and how this impacts on outcome are limited. This study examines how protocol adherence changes over time and determines how this impacts on outcome across a large-volume gastrointestinal surgical service. Materials and Methods: A prospective review of patients eligible for colorectal, liver and oesophagogastric ERAS over two 3-month periods in 2010 and 2011 was performed. End points included: length of stay (LOS), overall protocol adherence, individual modality adherence, reason for pathway deviation and patient outcomes. Results: 172 patients (110 colorectal, 31 liver and 31 oesophagogastric) were evaluated. For each sub-speciality, the introduction of ERAS led to significant reductions in LOS that were sustained for the duration of the study. Adherence was achieved across 60% (colorectal), 75% (liver) and 88% (oesophagogastric) of individual pathway modalities. The major causes of pathway deviation were: post-operative nausea and vomiting (colorectal), pain (liver) and pulmonary complications (oesophagogastric). Conclusions: Large-scale implementation of ERAS at a high-volume centre is feasible and offers many of the benefits demonstrated in controlled trials, but adherence may diminish over time.
Treatment Policy rather than Patient Characteristics Determines Convection Volume in Online Post-Dilution Hemodiafiltration
Authors: Chapdelaine Isabelle , Mostovaya Ira M. , Blankestijn Peter J. , Bots Michiel L. , van den Dorpel Marinus A. , Lévesque Renée , Nubé Menso J. , ter Wee Piet M. , Grooteman Muriel P.C. ,   for the CONTRAST investigators
Published: June 2014

Background/Aims: Sub-analyses of three large trials showed that hemodiafiltration (HDF) patients who achieved the highest convection volumes had the lowest mortality risk. The aims of this study were (1) to identify determinants of convection volume and (2) to assess whether differences exist between patients achieving high and low volumes. Methods: HDF patients from the CONvective TRAnsport STudy (CONTRAST) with a complete dataset at 6 months (314 out of a total of 358) were included in this post hoc analysis. Determinants of convection volume were identified by regression analysis. Results: Treatment time, blood flow rate, dialysis vintage, serum albumin and hematocrit were independently related. Neither vascular access nor dialyzer characteristics showed any relation with convection volume. Except for some variation in body size, patient characteristics did not differ across tertiles of convection volume. Conclusion: Treatment time and blood flow rate are major determinants of convection volume. Hence, its magnitude depends on center policy rather than individualized patient prescription.
Predictors of Metabolic Risk in Childhood Obesity
Authors: Morandi Anita , Maffeis Claudio
Published: June 2014

Most of the complications of juvenile obesity are due to metabolic disturbances induced by an excessive accumulation of fat which leads to chronic diseases like type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Finding effective ways of identifying obese paediatric patients who are at increased risk of developing cardiovascular and metabolic complications has been recognised to be a promising strategy to improve prevention of complications of early obesity. Moreover, correctly identifying obese children who are already affected by metabolic co-morbidities should be a clinical priority. According to the state of the art summarised in this review, traditional metabolic variables included in the definitions of metabolic syndrome (MS), pre-diabetes, non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steato-hepatitis and, in obese girls, the presence of polycystic ovary syndrome are the best available longitudinal predictors of CVD and T2DM among obese children and adolescents. In clinical practice, traditional metabolic variables included in the definitions of MS should be assessed in all obese children and adolescents; fasting metabolic variables have been proposed to identify obese patients likely to be affected by impaired glucose tolerance or T2DM, and ultrasound has proved to be a valid surrogate for biopsy in the diagnosis of NAFLD. Further large longitudinal and cross-sectional studies are needed to improve our chances of identifying obese youth at the highest metabolic risk.
Salivary Neoplasms Presenting with Radiologic Venous Invasion: An Imaging Pearl to Diagnosing Metastatic Renal Cell Carcinoma
Authors: Maralani Pejman , Mohan Suyash , Rassekh Christopher H. , Loevner Laurie A.
Published: June 2014

We report the case of a 64-year-old otherwise healthy woman who presented with left facial swelling. Imaging of the neck revealed multiple masses in the salivary and thyroid glands. The mass in the left parotid gland was associated with an intravenous extension into the retromandibular, facial and internal jugular veins in the left neck. Based on multiplicity of these masses and the presence of radiologic venous invasion, the diagnosis of metastatic renal cell carcinoma (RCC) was suggested on imaging, which was subsequently confirmed on systemic workup and pathology findings. Although RCC metastasizes to the salivary glands, the primary presentation of RCC with both salivary and thyroid gland masses is extremely rare, with only a few reports. The above feature and its imaging diagnosis based on local venous invasion are the highlights of this report.
Hypoxia-Induced Gene Expression of Aquaporin-4, Cyclooxygenase-2 and Hypoxia-Inducible Factor 1α in Rat Cortical Astroglia Is Inhibited by 17β-Estradiol and Progesterone
Authors: Habib Pardes , Dang Jon , Slowik Alexander , Victor Marion , Beyer Cordian
Published: June 2014

17β-Estradiol (E2) and progesterone (P) are neuroprotective in acute brain injury by attenuating neuropathophysiological processes and regulating local glial function. Besides controlling brain-intrinsic immune responses, astrocytes are cellular targets for sex steroids in health and disease and typically resist to hypoxic damage. In this in vitro study, we aimed at uncovering astroglia-specific reactions to sublethal hypoxic conditions and astroglia-specific effects of both sex steroid hormones on these parameters. Short-term hypoxia for 3 h increased reactive oxygen species production, but had no influence on cell viability of cerebral cortical rat astroglia. Astrocytes expressed classical estrogen receptors (ER), progesterone receptor (PR), and a set of nonclassical steroid hormone receptors. Hypoxia specifically induced ERα and PR isoform A gene expression. Oxygen deprivation increased gene expression of aquaporin-4 (AQP4), hypoxia-inducible factor 1α (Hif1α), and cyclooxygenase-2 (COX2). The application of E2 and P selectively prevented this induction. Effects on protein levels of these genes appeared to be delayed. These data show that astrocytes change their receptivity for sex steroid hormones by switching steroid hormone receptor expression and that E2 and P modify or antagonize proinflammatory COX2 synthesis, edema-promoting AQP4 expression, and the Hif1α increase. In vivo studies have to address whether these cell responses contribute to steroid-mediated neuroprotection in stroke.
Late Recurrences in Early Breast Cancer: For Whom and How Long Is Endocrine Therapy Beneficial?
Authors: Knauer Michael , Filipits Martin , Dubsky Peter
Published: June 2014

During the last decade, besides the well-established clinical-pathological predictors for the risk of late recurrence in breast cancer, such as estrogen receptor status, and T and N stage, a variety of multigene assays have been shown to improve prognostication and prediction in this setting. Several clinical trials have evaluated the role of extended endocrine therapy with tamoxifen (ATLAS) or aromatase inhibitors (MA.17, NSABP-B33 and ABCSG 6a), and other randomized studies are still ongoing. However, among this patient population, it is still not clear who could benefit from extended therapy and what the optimal treatment duration should be. New multigene assays such as EndoPredict, PAM50 ROR-score, HOXB13/IL17BR ratio and Breast Cancer Index provide significant and relevant prognostic information concerning the likelihood of recurrence beyond 5 years after surgery. The identified low-risk subgroups not only show a very favorable prognosis, they also seem to have only little benefit from extended aromatase inhibitor therapy. Many of these reverse transcriptase/polymerase chain reaction-based techniques have been validated in archived tumor material from large phase III trials, and will soon be available to routine pathology laboratories as an aid in clinical decision-making for patients.
Epigenetics: A New Player in the Regulation of Mammalian Puberty
Authors: Rzeczkowska Paulina A. , Hou Huayan , Wilson Michael D. , Palmert Mark R.
Published: June 2014

All reproductively competent adults have gone through puberty. While key genes and signaling pathways that lead to the onset of sexual maturation are known, the molecular mechanisms that determine when an individual enters puberty are only beginning to be understood. Both genetic and environmental factors determine the timing of puberty. New advances in understanding how environmentally sensitive, yet highly heritable developmental processes are regulated have come from the field of epigenetics. Of note, studies investigating the epigenetic control of the onset of puberty suggest that epigenetic repression of key inhibitory loci may play a fundamental role in the initiation of puberty. Current technologies that not only read out the DNA sequence, but also determine how the DNA is modified in response to the environment, promise new insight into how puberty is regulated, including the identification and understanding of gene regulatory networks that control the biological pathways affecting pubertal timing. Here we review the findings to date and discuss how epigenetic investigation can further our understanding of this fundamental aspect of human development.
Hepatocellular Carcinoma: Current Concepts in Diagnosis, Staging and Treatment
Authors: Schütte Kerstin , Schulz Christian , Malfertheiner Peter
Published: June 2014

Background: Hepatocellular carcinoma (HCC) significantly contributes to the global burden of cancer. Liver cancer is the third most frequent cause of cancer-related death, with HCC representing more than 90% of primary liver cancers. During the last decade, much progress has been made with respect to the definition of patient populations at risk who may benefit from surveillance strategies, as well as in the diagnosis and treatment of the disease. Summary: New locoregional and systemic therapies have significantly increased the survival of patients with HCC. A multitude of clinical trials addressing patients with HCC have led to advancements in the allocation of subgroups of patients to their optimal individual treatment strategy. This review provides an overview on recent developments in diagnostic and therapeutic modalities and an outlook on future directions in the management of HCC. Key Message: New locoregional and systemic therapies in patients with HCC have significantly improved clinical outlook and patient survival. This review provides an overview of recent developments in diagnostics and therapeutics, as well as an outlook on future directions in the management of HCC. Practical Implications: Transabdominal ultrasound is the method of choice for the surveillance of patients at risk of developing HCC, and any suspicious focal lesion in the liver should be characterized. Contrast-enhanced ultrasound with application of second-generation contrast agents enables visualization of tumor vascularity. The Barcelona Clinic Liver Cancer (BCLC) system is the most widely used classification system to guide the clinical management of HCC. Liver resection should be considered for patients with well-preserved liver function and without portal hypertension or elevated bilirubin. Patients not suitable for resection should undergo local tumor ablation. Candidates who are eligible for liver transplantation may benefit from bridging therapy during their waiting period. Patients in the BCLC B category benefit from locoregional transarterial therapy; transarterial chemoembolization is the treatment of choice. Sorafenib is the only systemic therapy that has been shown to prolong overall survival in patients with advanced disease, and is therefore recommended in patients with well-preserved liver function.
Soft Tissue Sarcoma: An Update on Systemic Treatment Options for Patients with Advanced Disease
Authors: Schöffski Patrick , Cornillie Jasmien , Wozniak Agnieszka , Li Haifu , Hompes Daphne
Published: June 2014

Sarcomas are a group of rare solid tumours arising from mesenchymal or connective tissue. This review focuses on soft tissue sarcoma and covers general topics such as the epidemiology, age distribution, site of disease, histogenesis, histological subtypes, prognosis and outcome of treatment. In more detail, the article reviews current systemic treatment standards and selected adverse events of agents such as doxorubicin, ifosfamide, trabectedin and pazopanib, and briefly highlights some drugs that are used off-label in specific subtypes of sarcoma.
The Hemodynamic and Nonhemodynamic Crosstalk in Cardiorenal Syndrome Type 1
Authors: Virzì Grazia Maria , Clementi Anna , Brocca Alessandra , de Cal Massimo , Vescovo Giorgio , Granata Antonio , Ronco Claudio
Published: June 2014

The organ crosstalk can be defined as the complex biological communication and feedback between distant organs mediated via cellular, molecular, neural, endocrine and paracrine factors. In the normal state, this crosstalk helps to maintain homeostasis and optimal functioning of the human body. However, during disease states this very crosstalk can carry over the influence of the diseased organ to initiate and perpetuate structural and functional dysfunction in the other organs. Heart performance and kidney function are intimately interconnected, and the communication between these organs occurs through a variety of bidirectional pathways. The cardiorenal syndrome (CRS) is defined as a complex pathophysiological disorder of the heart and the kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. In particular, CRS type 1 is characterized by a rapid worsening of the cardiac function leading to acute kidney injury. This clinical condition requires a more complex management given its more complicated hospital course and higher mortality. A lot of research has emerged in the last years trying to explain the pathophysiology of CRS type 1 which remains in part poorly understood. This review primarily focuses on the hemodynamic and nonhemodynamic mechanisms involved in this syndrome.
Esophageal Cancer: Current Options for Therapeutic Management
Authors: Sun Li , Zhang Hongwei , Wu Kaichun
Published: June 2014

Background: Esophageal cancer (EC) is the eighth most common cancer worldwide. A worldwide-established consensus on therapeutic pathways for EC is still missing. Debate exists on whether neoadjuvant and adjuvant treatment regimens improve the prognosis and which surgical approach reaches objective benefits. Summary: This article discusses the appropriate option of the current different curative treatments in patients with EC, including surgical treatment and adjuvant therapy. Key Message: To maximize survival and quality of life and also decrease postoperative complications, the present recommended therapeutic management of EC should be individualized multidisciplinary team approaches according to patients' staging and physiologic reserve. Practical Implications: The aim of this article is to provide a decision support and also a discussion based on clinical therapeutic strategy in order to characterize the beneficial approach which reaches an optimal balance between radical resection, postoperative outcome and long-term survival of EC.
From Swill Milk to Certified Milk: Progress in Cow's Milk Quality in the 19th Century
Authors: Obladen Michael
Published: June 2014

Background: Industrialization and urbanization jeopardized infant nutrition during the 19th century. Cow's milk was produced in the cities or transported long distances under suspect conditions. Milk was contaminated with bacteria or adulterated with water, flour, chalk and other substances. When distilleries proliferated in the metropoles, their waste slop was fed to cows which then produced thin and contaminated swill milk. Summary: Following a press campaign in the USA, the sale of swill milk was prohibited by law in 1861. Bacterial counts became available in 1881 and helped to improve the quality of milk. Debates on pasteurization remained controversial; legislation varied from country to country. Disposal of the wastewater of millions of inhabitants and the manure of thousands of cows was environmentally hazardous. It was not until 1860 and after several pandemics of Asiatic cholera that effective sewage systems were built in the metropoles. Milk depots were established in the USA by Koplik for sterilized and by Coit for certified milk. In France, Budin and Dufour created consultation services named goutte de lait, which distributed sterilized milk and educated mothers in infant care. Message: Multiple efforts to improve milk quality culminated in the International gouttes de lait Congresses for the Study and Prevention of Infantile Mortality.
Differences in Cardiovascular and Hypothalamic-Pituitary-Adrenal Axis Functions between High-Altitude Visitors and Natives during a Trek on the Annapurna Circuit
Authors: Park Jai Y. , Hwang Tae K. , Park Hyun K. , Ahn Ryun S.
Published: June 2014

Objective: Differences in the cardiovascular and hypothalamic-pituitary-adrenal (HPA) axis functions at high altitudes (HAs) between visitors to and natives of HA were examined. Methods: The cardiovascular functions and peripheral oxygen saturation (SPO2) were monitored, and the cortisol awakening response (CAR) and nighttime cortisol concentration (NCC), as indices of the HPA axis function, were determined in 25 trekkers and 21 Sherpas during an Annapurna circuit trek. Results: SPO2 decreased less in the Sherpas than in the trekkers at HAs (3,540, 3,800, and 4,800 m). Blood pressure and heart rate in the Sherpas changed concurrently during the trek; however, a tachycardic response occurred without changes in blood pressure in the trekkers at HAs. The CAR and NCC at HAs in the trekkers differed from those observed at 1,100 m and those observed at HAs in the Sherpas. The trekkers exhibited an elevated morning cortisol level at 3,540 and 3,800 m, a heightened CAR at 4,800 m, and an elevated NCC at 3,800 m. Alteration of the CAR resulted in an increase in the integrated volume of cortisol released within the first hour after awakening (CARauc) in the trekkers. The changes in SPO2 occurred concurrently with the changes in the CARauc and the heart rate in the trekkers. Conclusions: The alterations of CAR occurred at HAs where blood pressure levels reached a peak plateau, which is associated with an increase in heart rate at HAs in the trekkers. The CAR was unaltered in the Sherpas during the trek.
Autoria em questão na era da cibercultura
Authors: Murakami Raquel Yukie , Nakagome Patrícia Trindade
Published: June 2014

Analisaremos neste artigo alguns desdobramentos da noção de autoria no debate contemporâneo. Para isso, optamos por dois objetos representativos de nosso tempo, marcados pela dinamicidade da cibercultura: o Facebook e o fandom. O primeiro, uma rede social de ampla utilização no Brasil, dispensa maiores apresentações. Já o fandom, o domínio do fã, como indica o nome em inglês, é menos conhecido do público geral, pois é um espaço utilizado pelos fãs para discutirem o objeto cultural de sua estima. Através da análise desses dois ambientes virtuais, veremos como a autoria é colocada em questão hoje. Apontaremos algumas tentativas de os autores demarcarem seu espaço simbólico e alguns movimentos dos leitores para se integrar no campo da autoria.
Validade em interpretação
Authors: Hirsch E. D. , Murad Samira
Published: June 2014

Tradução do capítulo do livro Validade em Interpretação de E.D Hirsch
Ubiquitous Myocardial Extensions Into the Pulmonary Artery Demonstrated by Integrated Intracardiac Echocardiography and Electroanatomic Mapping
Authors: Liu Christopher F. , Cheung Jim W. , Thomas George , Ip James E. , Markowitz Steven M. , Lerman Bruce B.
Published: June 2014

Background—

Idiopathic ventricular arrhythmias of left bundle branch block inferior axis morphology are usually localized to the right ventricular outflow tract (RVOT), presumably below the pulmonic valve (PV). However, the PV location is usually not confirmed by direct visualization.

Methods and Results—

Intracardiac echocardiography was used to visualize and tag the PV annulus, which was then integrated with 3-dimensional voltage maps of the RVOT. Distances were measured from the furthest extent of myocardial signal (bipolar voltage ≥1.5 mV) to the PV annulus. This was performed in 24 control patients and 24 prospective patients with RVOT arrhythmias. Myocardial signal beyond the PV was found in 92% of controls and 88% of RVOT arrhythmia patients (
P
=1.000). Average myocardial extension was further on the septal side than on the free wall side for control patients (5.6 mm; interquartile range [IQR], 3.6–7.7, versus 1.7 mm; IQR (−)0.1 to (+)4.0;
P
=0.002) and RVOT arrhythmia patients (5.7 mm; IQR, 2.7–7.7, versus 1.4 mm; IQR, (−)0.8 to (+)4.8;
P
=0.004). Eleven (46%) RVOT arrhythmia foci were localized beyond the valve in the pulmonary artery (median 8.2 mm above PV; IQR, 6.6–10.3 mm); these locations were confirmed as supravalvular by direct intracardiac echocardiography visualization.

Conclusions—

Myocardial voltage extension into the pulmonary artery in humans is ubiquitous and can be demonstrated in vivo using 3-dimensional integrated intracardiac echocardiography to localize the PV. These extensions frequently serve as origins of presumed RVOT arrhythmias; intracardiac echocardiography localization of the PV allows reclassification of these as pulmonary arterial arrhythmias.
Development of a Clinical Registry-Based 30-Day Readmission Measure for Coronary Artery Bypass Grafting Surgery
Authors: Shahian David M. , He Xia , O’Brien Sean M. , Grover Frederick L. , Jacobs Jeffrey P. , Edwards Fred H. , Welke Karl F. , Suter Lisa G. , Drye Elizabeth , Shewan Cynthia M. , Han Lein , Peterson Eric
Published: June 2014

Background—

Reducing readmissions is a major healthcare reform goal, and reimbursement penalties are imposed for higher-than-expected readmission rates. Most readmission risk models and performance measures are based on administrative rather than clinical data.

Methods and Results—

We examined rates and predictors of 30-day all-cause readmission following coronary artery bypass grafting surgery by using nationally representative clinical data (2008–2010) from the Society of Thoracic Surgeons National Database linked to Medicare claims records. Among 265 434 eligible Medicare records, 226 960 (86%) were successfully linked to Society of Thoracic Surgeons records; 162 572 (61%) isolated coronary artery bypass grafting admissions constituted the study cohort. Logistic regression was used to identify readmission risk factors; hierarchical regression models were then estimated. Risk-standardized readmission rates ranged from 12.6% to 23.6% (median, 16.8%) among 846 US hospitals with ≥30 eligible cases and ≥90% of eligible Centers for Medicare and Medicaid Services records linked to the Society of Thoracic Surgeons database. Readmission predictors (odds ratios [95% confidence interval]) included dialysis (2.02 [1.87–2.19]), severe chronic lung disease (1.58 [1.49–1.68]), creatinine (2.5 versus 1.0 or lower:1.49 [1.41–1.57]; 2.0 versus 1.0 or lower: 1.37 [1.32–1.43]), insulin-dependent diabetes mellitus (1.45 [1.39–1.51]), obesity in women (body surface area 2.2 versus 1.8: 1.44 [1.35–1.53]), female sex (1.38 [1.33–1.43]), immunosuppression (1.38 [1.28–1.49]), preoperative atrial fibrillation (1.36 [1.30–1.42]), age per 10-year increase (1.36 [1.33–1.39]), recent myocardial infarction (1.24 [1.08–1.42]), and low body surface area in men (1.22 [1.14–1.30]). C-statistic was 0.648. Fifty-two hospitals (6.1%) had readmission rates statistically better or worse than expected.

Conclusions—

A coronary artery bypass grafting surgery readmission measure suitable for public reporting was developed by using the national Society of Thoracic Surgeons clinical data linked to Medicare readmission claims.
B‐Type Natriuretic Peptide Predicts 30‐Day Readmission for Heart Failure but not Readmission for Other Causes
Authors: Flint Kelsey M. , Allen Larry A. , Pham Michael , Heidenreich Paul A.
Published: June 2014

Background

B‐type natriuretic peptide (
BNP
) is a marker for heart failure (HF) severity, but its association with hospital readmission is not well defined.

Methods and Results

We identified all hospital discharges (n=109 875) with a primary diagnosis of HF in the Veterans Affairs Health Care System from 2006 to 2009. We examined the association between admission (n=53 585), discharge (n=24 326), and change in
BNP
(n=7187) and 30‐day readmission for HF or other causes. Thirty‐day HF readmission was associated with elevated admission
BNP
, elevated discharge
BNP
, and smaller percent change in
BNP
from admission to discharge. Patients with a discharge
BNP
≥1000 ng/L had an unadjusted 30‐day HF readmission rate over 3 times as high as patients whose discharge
BNP
was ≤200 ng/L (15% vs. 4.1%).
BNP
improved discrimination and risk classification for 30‐day HF readmission when added to a base clinical model, with discharge
BNP
having the greatest effect (C‐statistic, 0.639 to 0.664 [
P
<0.0001]; net reclassification improvement, 9% [
P
<0.0001]). In contrast, 30‐day readmission for non‐HF causes was not associated with
BNP
levels during index HF hospitalization.

Conclusions

In this study of over 50 000 veterans hospitalized with a primary diagnosis of HF,
BNP
levels measured during hospitalization were associated with 30‐day HF readmission, but not readmissions for other causes. These data may help guide future study aimed at identifying the optimal timing for hospital discharge and help allocate high‐intensity, HF‐specific transitional care interventions to the patients most likely to benefit.
Fibroblast Growth Factor‐23 and Incident Coronary Heart Disease, Heart Failure, and Cardiovascular Mortality: The Atherosclerosis Risk In Communities Study
Authors: Lutsey Pamela L. , Alonso Alvaro , Selvin Elizabeth , Pankow James S. , Michos Erin D. , Agarwal Sunil K. , Loehr Laura R. , Eckfeldt John H. , Coresh Josef
Published: June 2014

Background

Fibroblast growth factor‐23 (
FGF
‐23) is a hormone involved in phosphorous regulation and vitamin D metabolism that may be associated with cardiovascular risk, and it is a potential target for intervention. We tested whether elevated
FGF
‐23 is associated with incident coronary heart disease, heart failure, and cardiovascular mortality, even at normal kidney function.

Methods and Results

A total of 11 638 Atherosclerosis Risk In Communities study participants, median age 57 at baseline (1990–1992), were followed through 2010. Cox regression was used to evaluate the independent association of baseline serum active FGF‐23 with incident outcomes. Models were adjusted for traditional cardiovascular risk factors and estimated glomerular filtration rate. During a median follow‐up of 18.6 years, 1125 participants developed coronary heart disease, 1515 developed heart failure, and 802 died of cardiovascular causes. For all 3 outcomes, there was a threshold, whereby FGF‐23 was not associated with risk at <40 pg/mL but was positively associated with risk at >40 pg/mL. Compared with those with FGF‐23 <40 pg/mL, those in the highest FGF‐23 category (≥58.8 pg/mL) had a higher risk of incident coronary heart disease (adjusted hazard ratio, 95% CIs: 1.65, 1.40 to 1.94), heart failure (1.75, 1.52 to 2.01), and cardiovascular mortality (1.65, 1.36 to 2.01). Associations were modestly attenuated but remained statistically significant after further adjustment for estimated glomerular filtration rate. In stratified analyses, similar results were observed in African Americans and among persons with normal kidney function.

Conclusions

High levels of serum
FGF
‐23 were associated with increased risk of coronary heart disease, heart failure, and cardiovascular mortality in this large, biracial, population‐based cohort. This association was independent of traditional cardiovascular risk factors and kidney function.
Can Response-Adaptive Randomization Increase Participation in Acute Stroke Trials?
Authors: Tehranisa Jason S. , Meurer William J.
Published: June 2014

Background and Purpose—

A response-adaptive randomization (RAR) trial design actively adjusts the ratio of participants assigned to each trial arm, favoring the better performing treatment by using outcome data from participants already in the trial. Compared with a standard clinical trial, an RAR study design has the potential to improve patient participation in acute stroke trials.

Methods—

This cross-sectional randomized survey included adult emergency department patients, age ≥18, without symptoms of stroke or other critical illness. A standardized protocol was used, and subjects were randomized to either an RAR or standard hypothetical acute stroke trial. After viewing the video describing the hypothetical trial (
http://youtu.be/cKIWduCaPZc
), reviewing the consent form, and having questions answered, subjects indicated whether they would consent to the trial. A multivariable logistic regression model was fitted to estimate the impact of RAR while controlling for demographic factors and patient understanding of the design.

Results—

A total of 418 subjects (210 standard and 208 RAR) were enrolled. All baseline characteristics were balanced between groups. There was significantly higher participation in the RAR trial (67.3%) versus the standard trial (54.5%), absolute increase: 12.8% (95% confidence interval, 3.7–22.2). The RAR group had a higher odds ratio of agreeing to research (odds ratio, 1.89; 95% confidence interval, 1.2–2.9) while adjusting for patient level factors. Trial designs were generally well understood by the participants.

Conclusions—

The hypothetical RAR trial attracted more research participation than standard randomization. RAR has the potential to increase recruitment and offer benefit to future trial participants.