bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Arthroscopic, Radioactive and Combined Synovectomy in the Treatment of Chronic Non-Specific Knee Synovitis
Authors: Karaman Ibrahim , Guney Ahmet , Dogar Fatih , Kafadar Ibrahim Halil , Bilal Okkes , Oner Mithat , Kula Mustafa
Published: September 2014

Objective: To compare the outcomes of arthroscopic, radioactive and combined synovectomies in patients with chronic non-specific recurrent synovitis who did not respond to conservative therapy. Subjects and Methods: Twenty-nine patients enrolled between 2007 and 2011 were divided into 3 groups: group 1 was treated with arthroscopy, group 2 received a radioactive drug and group 3 received a combined (radioactive and arthroscopic) synovectomy. Treatment efficacy was evaluated by comparing pre- and post-operative Lysholm knee scores (LKS), night pain, resting pain, activity pain and effusions using visual analogue scales (VAS). Patient satisfaction was assessed using the visual analogue patient satisfaction scale (VAPSS). Results: The mean age of the study participants was 41.5 ± 5.2 years (range 14-76), and the mean follow-up period was 33.6 ± 3.2 months (range 17-78). Before treatment, the mean LKS was 41.4 ± 3.4 in group 1, 39.6 ± 3.3 in group 2 and 37.1 ± 4.6 in group 3. After treatment, the corresponding mean LKS were 77.7 ± 2.1, 81.6 ± 2.8 and 91.3 ± 2.7 in groups 1, 2 and 3, respectively; the increase was statistically significant (p < 0.05). The VAS scores before and after treatment decreased significantly (p < 0.05). The mean VAPSS score, a measure of patient satisfaction, was 5.1 ± 1.7, 5.8 ± 1.5 and 7.4 ± 1.8 in groups 1, 2 and 3, respectively, and the difference between groups 1 and 2 was not statistically significant, while that between group 3 and the other two groups was significant (p < 0.05). Conclusion: This study showed that the three methods used in individuals with chronic non-specific recurrent synovitis were effective; however, arthroscopic synovectomy in combination with radioactive synovectomy was more effective than the other methods and superior in terms of patient satisfaction.
Potential Mechanisms Involved in the Anticonvulsant Effect of Walnut Extract on Pentylenetetrazole-Induced Seizure
Authors: Asadi-Shekaari Majid , Eslami Azam , Kalantaripour Tajpari , Joukar Siyavash
Published: September 2014

Objective: It was the aim of this study to determine the potential effect of walnut kernel extract (WKE) on experimentally induced seizures in rats and to evaluate the role of benzodiazepines and ethosuximide (ESM) within these pathways. Materials and Methods: Male Wistar rats were selected and divided into eight groups. Seizures were evoked by intravenous infusion of pentylenetetrazole (PTZ; 2 mg/ml/min). In combination with PTZ, animals were treated with vehicle or WKE (100 mg/kg i.p.), with or without cotreatment with either flumazenil (FMZ; 5 mg/kg i.p.), ESM (150 mg/kg i.p.) or diazepam (DPZ; 0.5 mg/kg i.p.). Results: WKE administration significantly increased the PTZ dose needed to induce the first myoclonic jerk (13.09 ± 1.29 vs. 49.71 ± 12.03 mg/kg; p < 0.001), decreased the severity of seizure grades and reduced the mortality rate to 0%. FMZ did not significantly reduce the anticonvulsant effect of WKE. The combination of DPZ and WKE showed a synergic anticonvulsant effect, whereas ESM had no significant influence (p > 0.05) on the WKE effects. Conclusion: These findings indicated that WKE was effective at reducing seizure severity, at increasing the dose to the first myoclonic jerk and highly efficacious at preventing mortality, because 100% of animals were protected. It seems that this positive effect could apply through signaling pathways other than benzodiazepine-mediated γ-aminobutyric acid receptors and may at least in part be similar to ESM.
Multiple Micronutrient Supplementation during Pregnancy and Lactation in Low-to-Middle-Income Developing Country Settings: Impact on Pregnancy Outcomes
Authors: Salam Rehana A. , Das Jai K. , Bhutta Zulfiqar A.
Published: September 2014

Background: Malnutrition, including micronutrient deficiencies, remains one of the major public health challenges, particularly in low-to-middle-income countries. Micronutrient deficiencies affect people of all ages, but its effects appear more devastating in pregnant women and children. Poor maternal nutrition contributes to at least 20% of maternal deaths and increases the probability of poor pregnancy outcomes including intrauterine growth restriction, resulting in low birth weight, stunting, wasting and mortality. Key Messages: Several strategies have been employed to provide pregnant women with micronutrients. These strategies include education, dietary modification, food provision, agricultural interventions, supplementation and fortification either alone or in combination. Micronutrient supplementation is the most widely practiced intervention to prevent and manage single or multiple micronutrient deficiencies. Micronutrient supplementation either alone or in combination has shown to be effective in improving maternal, birth and child outcomes. Conclusions: There is a need to focus on maternal micronutrient status as a continuum from the periconceptional period throughout pregnancy to lactation. Given the wide prevalence of multiple micronutrient deficiencies in low-to-middle-income countries, the challenge is to implement intervention strategies that combine appropriate maternal and child health interventions with micronutrient interventions.
Multiple Micronutrient Needs in Pregnancy in Industrialized Countries
Authors: Parisi Francesca , Laoreti Arianna , Cetin Irene
Published: September 2014

Background: As nutritional deficiencies are known to lead to adverse pregnancy outcomes, a woman's nutritional status should be assessed preconceptionally with the goal of optimizing maternal, fetal and infant health. Worldwide micronutrient intakes do not fit pregnancy requirements, so that their supplementation is recommended from the beginning of pregnancy in most of the low- and middle-income countries. Conversely, data on multiple supplementation in developed countries appear few and controversial. Key Message: Although a balanced diet is generally accessible in industrialized countries, a switch to a high-fat and low-quality diet has led to an inadequate vitamin and mineral intake during pregnancy, so that recent data show the micronutrient intake and supplementation to be lower than recommended even in high-income countries, particularly for iron, folic acid, calcium and vitamin D. Conclusions: Currently, even if there is insufficient evidence to support routine supplementation at the population level, except for periconceptional folate supplementation, these results need to be evaluated at an individual level in order to avoid nutritional deficiencies and to encourage women to establish healthful dietary practices prior to conception. The new goal in industrialized countries needs to be an individualized approach that takes account of the phenotypic, genotypic and metabolic differences among individuals of the same population.
Quality and Safety Aspects of Food Products Addressing the Needs of Pregnant Women and Infants
Authors: Hoeft Birgit , Eggersdorfer Manfred , Heck Stephan
Published: September 2014

Food safety is a primary concern for pregnant women and infants as the immune system is weakened during pregnancy and not developed enough in infants, which makes them especially vulnerable to suffering from the negative effects of nonquality food products. However, food contaminations not only affect an individual's health but also a country's economic development, social harmony, food trade and even politics, as seen during the Chinese infant formula crisis in 2008. Thus, quality control is crucial in the production processes in order to have safe food products on the market. But quality control alone is not enough: manufacturers must embrace quality beyond classic in-process parameters and perform a final microbiological analysis at the end of the production process. This requires a clear and trustworthy approach to quality and safety and the involvement of all stakeholders from industry, government and academia over policy makers to consumers. This paper provides an introductory context for current quality management systems and gives real-life examples of challenges that manufacturers face during quality management and control throughout the production process.
Diagnosis of Pulmonary Embolism: Conventional Ventilation/Perfusion SPECT Is Superior to the Combination of Perfusion SPECT and Nonenhanced CT
Authors: Palmowski Karin , Oltmanns Ute , Kreuter Michael , Mottaghy Felix M. , Palmowski Moritz , Behrendt Florian F.
Published: September 2014

Background: Ventilation/perfusion single-emission photon CT (V/P-SPECT) is widely used to detect pulmonary embolism (PE). Any pathological deficit on P-SPECT with a corresponding unremarkable V-SPECT is considered an embolism. This means that a deficit on P-SPECT with a corresponding deficit on the ventilation scan correlates with other lung pathologies such as pneumonia, bullous emphysema or tumor. In principle, it is possible to identify any of these lung pathologies on nonenhanced chest CT and so this technique has the potential to replace V-SPECT in the diagnosis of PE. Today, SPECT/CT hybrid imaging systems are increasingly applied in clinical routines. Objectives: We investigated whether embolism can be diagnosed using a combined P-SPECT/CT hybrid imaging approach without V-SPECT. Methods: Ninety-three patients with clinically suspected embolism were investigated with standard V/P-SPECT and a nonenhanced CT scan on a combined SPECT/CT system. A diagnosis of embolism was based on V/P-SPECT (gold standard). P-SPECT/CT datasets were blinded and analyzed without any knowledge of the V-SPECT data. The accuracy of P-SPECT/CT was compared to the gold standard. Results: Embolism was diagnosed in 24/93 patients using V/P-SPECT. In total, 57 lung lobes were affected. P-SPECT/CT significantly (p < 0.01) overdiagnosed embolism in nonaffected patients. In total, 36 cases with 88 affected lung lobes were shown. The sensitivity was 95.8%, the specificity 82.6%, the false-negative rate 4.2% and the false-positive rate 17.3%. Conclusions: Our results demonstrate that a nonenhanced CT scan in a novel hybrid imaging system cannot replace V-SPECT in the scintigraphy-based diagnosis of PE. V-SPECT increases specificity and reduces the number of false-positive results when compared to ‘perfusion-only' SPECT/CT.
Manual Liquid-Based Cytology: A Clinical Pilot Study of the VitroPrep™ Cytology Processing Kit
Authors: Rahangdale Lisa , Budwit Debra , Asgari Davoud , Ohadugha Anayo L.
Published: September 2014

Objective: It was the aim of this study to assess the utility of the manual liquid-based cytology (LBC) product VitroPrep™ Cytology Processing Kit (ChemQ Bioscience LLC, Research Triangle Park, N.C., USA). Study Design: This is a descriptive pilot study. Women underwent cervical sampling processed by the ThinPrep™ automated LBC system followed by cervical sampling for the VitroPrep manual system. The following criteria were assessed on a scale of 1-5 (1 = unsatisfactory, 2 = borderline, 3 = acceptable, 4 = good, 5 = excellent): monolayer cell adhesion, overall cellularity, background clarity, preservation of cellular morphology, red cell lysis, and elimination of mucus/debris. Cytological diagnosis was compared to results from ThinPrep samples. In addition, VitroPrep samples were taken prior to conization procedures and compared to pathology results. Descriptive statistics were performed. Results: Forty-two of 47 women who underwent dual cytologic sampling had satisfactory samples. All scores were 3-5, with >90% graded 4-5. The VitroPrep diagnosis correlated with the ThinPrep diagnosis in 90% (38/42) of cases. All specimens obtained from 15 women prior to conization were satisfactory and correlated abnormal cytologic findings with cervical intraepithelial neoplasia 1-3 pathology. Conclusions: The VitroPrep Cytology Processing Kit was able to provide adequate specimens for evaluation and diagnosis. This low-cost processing kit may provide a useful alternative in settings where automated LBC systems may not be feasible.
DruGeVar: An Online Resource Triangulating Drugs with Genes and Genomic Biomarkers for Clinical Pharmacogenomics
Authors: Dalabira Eleni , Viennas Emmanouil , Daki Elisavet , Komianou Angeliki , Bartsakoulia Marina , Poulas Konstantinos , Katsila Theodora , Tzimas Giannis , Patrinos George P.
Published: September 2014

Background/Aims: Pharmacogenomics aims to rationalize drug use by minimizing drug toxicity and/or by increasing drug efficacy. A large number of genomic markers have been correlated with variable drug responses and severity of adverse drug reactions. Although a number of these drugs bear pharmacogenomic information in their labels - approved by regulatory agencies - and comprehensive drug/gene lists exist online, information related to the respective pharmacogenomic biomarkers is currently missing from such lists. Methods: We extracted information from the published literature and online resources and developed DruGeVar (http://drugevar.genomicmedicinealliance.org), an online resource triangulating drugs with genes and pharmacogenomic biomarkers in an effort to build a comprehensive database that could serve clinical pharmacogenomics. Results and Conclusions: A user-friendly data querying and visualization interface allows users to formulate simple and complex queries. Such a database would be readily applicable as a stand-alone resource or a plug-in module for other databases.
Stakeholder Analysis in Pharmacogenomics and Genomic Medicine in Greece
Authors: Mitropoulou Christina , Mai Yuan , van Schaik Ron H. , Vozikis Athanassios , Patrinos George P.
Published: September 2014

Background: The pace of discoveries and advances in genomic research is not reflected in the pace of their translation and incorporation into day-to-day clinical medicine to individualize healthcare decision-making processes. One of the main obstacles is the poor understanding of the policies and the key stakeholders involved in these translation processes. Methods: We used the computerized version of the PolicyMaker political mapping tool to collect and organize important information about the pharmacogenomics and genomic medicine policy environment, serving as a database for assessments of the policy's content, the major players, their power and policy positions, their interests, and networks and coalitions that interconnect them. Results and Conclusions: Our findings indicate that the genomic medicine policy environment in Greece seems to be rather positive, as the vast majority of the stakeholders express their medium to high support in the initially set goals of genomic medicine policy environment. The Ministry of Health and public healthcare insurance funds seem to oppose it, most likely due to financial constrains. These findings would contribute in selecting and implementing policy measures that will expedite the adoption of genomics into conventional medical interventions.
Metastatic Male Breast Cancer: A Retrospective Cohort Analysis
Authors: Foerster Robert , Schroeder Lars , Foerster Frank , Wulff Volker , Schubotz Birgit , Baaske Dieter , Rudlowski Christian
Published: September 2014

Background: Metastasized male breast cancer (MMBC) is a rare disease. Given its low incidence, data regarding tumor biology, current treatment options, and survival rates are scarce. Patients and Methods: A chart review was performed of MMBC patients consecutively registered in regional cancer registries in Germany between 1995 and 2011. Tumor characteristics, treatment, and survival rates were documented and statistically evaluated. Results: 41 men with MMBC represented 25.6% of a total of 160 patients with MBC. 16 (39%) patients showed primary metastases, and 25 (61%) had recurrent metastases. Median survival from occurrence of metastasis was 32 months. Median overall survival (OS) was 68 months. 68.3% (n = 28) of the cohort received systemic therapy favoring endocrine therapy (n = 25, 61.9%). Prolonged metastatic OS (p = 0.02) was observed in patients having had a systemic treatment. Metastatic patients having received endocrine treatment showed significantly prolonged survival rates. Furthermore, patients receiving palliative chemotherapy had a significant survival benefit compared to those in whom chemotherapy was omitted. Conclusion: Our results suggest that systemic treatment in the form of both palliative chemotherapy and endocrine therapy improves outcome of MMBC. Therefore, it seems reasonable that treatment of MMBC should be based on the guidelines for female breast cancer.
Vacuum Sealing Drainage in the Treatment of Migrated Polyacrylamide Hydrogel after Breast Augmentation: A Case Report
Authors: Wu Jinfang , Zhang Xudong , Zhao Qiming , Mao Dongsheng , Lu Xin
Published: September 2014

Background: Polyacrylamide hydrogel (PAAG) injection for breast augmentation can result in a variety of complications, including implant migration. The migrated PAAG can become colonized by pathogens, resulting in secondary infections which can be extremely difficult to treat. Case Report: We report the case of a 43-year-old female patient who underwent PAAG injection for breast augmentation. Implant migration was diagnosed 8 years after the initial injection. Conclusion: Here, we report the first use of vacuum sealing drainage as a convenient and effective alternative to manage the complications of extensive PAAG migration after breast augmentation.
The Epidermal Growth Factor Receptor Inhibitor-Related Skin Toxicity Index (EGFRISTI): A New Tool for Grading and Managing Skin Adverse Reactions to Epidermal Growth Factor Receptor Inhibitors
Authors: Lisi Paolo , Bellini Veronica , Bianchi Leonardo
Published: September 2014

Background: Skin toxicity is frequent and debilitating in oncologic patients treated with epidermal growth factor receptor inhibitors (EGFRIs). Grading and management of skin adverse events (AEs) are poorly standardized. Materials and Methods: We developed a new score (EGFRISTI: Epidermal Growth Factor Receptor Inhibitor-Related Skin Toxicity Index) which is able to quantify and monitor all EGFRI-related dermatologic AEs over time. The utility of this tool was validated in 130 patients treated with 5 different EGFRIs including both monoclonal antibodies and tyrosine kinase inhibitors. Results: The mean baseline EGFRISTI score was 26.9 (range: 6.0-64.5). Mild toxicity was found in 55 patients (42.3%), moderate toxicity in 43 (33.1%), and severe toxicity in 32 patients (24.6%). After the first-line toxicity treatment, an EGFRISTI score reduction of >75% was obtained in 31 patients (34.1%) and one of 50% in 40 patients (43.9%), while an improvement of <50% was observed in the remaining 20 subjects (22.0%). Conclusions: The EGFRISTI is a simple and reliable tool to quantify and express the severity of all clinical signs and symptoms of EGFRI skin toxicity with a single numerical value, to choose the most suitable therapy, and to measure its efficacy.
Cardiopulmonary and Gas-Exchange Responses during the Six-Minute Walk Test in Patients with Chronic Obstructive Pulmonary Disease
Authors: van Gestel Arnoldus J.R. , Baty Florent , Rausch-Osthof Anne-Kathrin , Brutsche Martin H.
Published: September 2014

Background: The 6-min walk test (6MWT) is representative of daily life activities and reflects the functional capacity of patients with chronic obstructive pulmonary disease (COPD). Information on the cardiopulmonary and gas exchange responses to the 6MWT is limited. Objectives: We aimed to analyze the breath-by-breath cardiopulmonary and gas exchange responses of patients with COPD during the 6MWT. We also investigated the extent to which parameters reflecting cardiopulmonary and gas exchange function are associated with exercise capacity. Methods: The oxygen uptake (VO2) kinetics of patients were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT. A new mean response time (MRT) index was developed to quantify VO2 on-kinetics by correcting MRT for work rate (wMRT). Multiple linear regression analysis was performed to assess the association between variables reflecting cardiopulmonary and gas exchange function and exercise capacity [6-min walking distance (6MWD) and VO2 at steady state (VO2SS)]. Results: In 72 COPD patients (29 females) with a mean (SD) age of 65 (10) years, FEV1 44 (14) % predicted exercise capacity as assessed by VO2SS (p = 0.003) was significantly reduced across the stages of COPD. The criteria for maximal effort during the 6MWT were fulfilled by 82% of the patients. After adjustment for covariates, wMRT was independently associated with 6MWD (p = 9.7 × 10-5) and VO2SS (p = 5.5 × 10-10). Conclusions: As wMRT mostly depends on the rate of increase of pulmonary blood flow, our results underline the fact that cardiocirculatory function may play a significant role in exercise tolerance in patients with COPD. Our findings imply that modification of cardiocirculatory function may be beneficial in the treatment of COPD patients and improve their outcome more than anticipated previously.
Sniff Nasal Inspiratory Pressure in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: Learning Effect and Short-Term Between-Session Repeatability
Authors: Nikoletou Dimitra , Rafferty Gerrard , Man William D.-C. , Mustfa Naveed , Donaldson Nora , Grant Robert L. , Johnson Lorna , Moxham John
Published: September 2014

Background: Sniff nasal inspiratory pressure (SNIP) is a non-invasive measure of inspiratory muscle function often used as an outcome measure in clinical studies. An initial period of familiarisation with the test is recommended to minimise the learning effect. The repeatability of SNIP in patients with chronic obstructive pulmonary disease (COPD) is currently unknown. Objectives: The aim of this study was to assess the between-session repeatability of SNIP over a 3-week period in moderate-to-severe COPD patients and compare it with that of maximal inspiratory (PImax) and expiratory pressure (PEmax). Methods: Twenty-one patients (13 males) with a mean forced expiratory volume in 1 s (FEV1) of 38% of predicted (SD: 15) and FEV1/forced vital capacity of 34.3% (SD: 10.4) performed SNIP and PImax and PEmax manoeuvres on 3 different sessions (S1, S2 and S3) 3-7 days apart. SNIP was performed at functional residual capacity (FRC), and PImax was performed at FRC and at residual volume (RV) to explore volume-dependent differences in the learning effect between sessions and PEmax from total lung capacity. Results: The intra-class correlation coefficient (ICC) for SNIP was the highest of the three measures: S1-S3 ICC (95% CI) SNIP: 0.96 (0.88-0.94); PImax at FRC 0.82 (0.63-0.92); PImax at RV: 0.89 (0.78-0.95), and PEmax: 0.96 (0.92-0.98), and had the lowest mean change between sessions [mean S2 - S1: 2.1(p = 0.4) and S3 - S2: -0.3 (p = 0.9)]. Conclusions: SNIP is repeatable over a period of 3 weeks in medically stable, moderate-to-severe COPD patients. In our study, 2 sessions were adequate to learn how to perform the test.
FISH Mapping for Physical Map Improvement in the Large Genome of Barley: A Case Study on Chromosome 2H
Authors: Poursarebani Naser , Ma Lu , Schmutzer Thomas , Houben Andreas , Stein Nils
Published: September 2014

Fluorescence in situ hybridization (FISH) has been an efficient way for integrating physical and genetic maps of various small genomes like rice, sorghum and Brachypodium; whereas in the large genomes like barley, the repetitive nature of the genome complicates the generation and detection of single-copy FISH probes. Here, we used exemplarily physical map contigs of a defined interval of the long arm of barley chromosome 2H to evaluate the potential of FISH-based mapping as a supportive means for genetic anchoring of the physical map and to resolve the linear order of contigs along the respective chromosome. Repeat-free FISH probes corresponding to 8 previously anchored BAC contigs were specifically allocated to chromosome 2H. This represented an almost 90% success rate in single-copy FISH probe development. FISH mapping of contigs located in the subtelomeric region revealed an over-performance of genetic mapping over FISH for physical map anchoring.
Study Methods in Evidence-Based Surgery: Methodological Impediments and Suggested Approaches for the Creation and Transfer of Knowledge in Surgery
Authors: Hüttner Felix Jakob , Doerr-Harim Colette , Probst Pascal , Tenckhoff Solveig , Knebel Phillip , Diener Markus Konrad
Published: September 2014

Background: Since its introduction more than 20 years ago, evidence-based medicine has become an important principle in the daily routine of clinicians around the globe. Nevertheless, many surgical interventions are still not based on high-quality evidence from clinical trials. This is partially due to the fact that surgical trials pose some specific obstacles, which have to be overcome during the planning and conduct of such a trial. Objective: In this study, we will highlight specific challenges and discuss explicit obstacles of surgical clinical research. Moreover, potential solutions will be substantiated by the experience of the Study Centre of the German Surgical Society (SDGC) in surgical clinical research. Conclusions: Surgical researchers should be equipped with a basic knowledge of research methodology to be able to overcome the common impediments posed by surgical trials. Collaborations between surgeons and methodologists as well as trial networks have proven to be useful in accomplishing high-quality surgical research in various randomized controlled trials. By maintaining and refining this work and with sufficient and prompt translation of investigational knowledge into daily practice, the treatment of surgical patients should result in an improved outcome in the future.
Risk Factors in Fatal Cases of Anaphylaxis due to Contrast Media: A Forensic Evaluation
Authors: Palmiere Cristian , Reggiani Bonetti Luca
Published: September 2014

Background: Fatalities following contrast medium exposure are extremely rare in clinical routine, though they may occur as an exception. Some may fall under the purview of the inquiring authorities and forensic pathologists due to their in-hospital occurrence. The purpose of this study was to assess the risk factors for anaphylaxis due to contrast medium administration that can be identified in fatal cases. Methods: Fatalities occurred during the course of clinical investigations with contrast media described in the literature and fatal reactions to contrast agents that had undergone forensic investigations in our medicolegal center were reviewed with respect to patient characteristics, administered contrast medium, performed biochemical investigations and potential risk factors identified based on clinical history and medical records. Results: Biochemical investigations into the fatal cases examined in our facility revealed increased mast cell tryptase, total IgE and activated mast cells in all subjects. Data obtained from the literature and our own investigations indicated that in only a minority of the fatal cases had there been previous exposure to contrast compounds, while most cases of severe anaphylaxis involved patients who apparently reacted on initial exposure. Conclusions: Most fatal cases failed to present any identifiable predisposing conditions out of those traditionally considered as risk factors for an anaphylactic reaction to contrast compounds in the medical histories of the patients. Comprehensive clinical histories and thorough reviews of medical data, along with exhaustive forensic investigations, provide information that is relevant in order to better appreciate the interwoven relationships linking all factors potentially involved in the pathogenesis of fatal anaphylaxis to contrast media.
An Open-Label Extension Study to Evaluate Safety and Efficacy of Pazopanib in Patients with Advanced Renal Cell Carcinoma
Authors: Sternberg Cora N. , Davis Ian D. , Deen Keith C. , Sigal Entisar , Hawkins Robert E.
Published: September 2014

Objectives: Evaluation of the safety and efficacy of pazopanib, a multikinase angiogenesis inhibitor, in a single-arm, open-label, extension study (VEG107769/NCT00387764) for placebo-treated patients with advanced renal cell carcinoma (RCC) from a randomized, double-blind, placebo-controlled phase III study (VEG105192/NCT00334282). Methods: Patients received pazopanib 800 mg/day. The primary endpoint was the safety and tolerability of pazopanib treatment. Secondary endpoints included response rate per Response Evaluation Criteria in Solid Tumors, progression-free survival (PFS), and overall survival (OS). Results: Seventy-nine placebo-treated patients from VEG105192/NCT00334282 who experienced disease progression and one pazopanib-treated patient (an exemption) were enrolled. Forty-one patients (51%) were treatment-naive; 39 (49%) were cytokine-pretreated. Median exposure to pazopanib was 9.7 months. All patients had discontinued pazopanib at the time of analysis. The most common reason for discontinuation was disease progression (61%). The most common adverse events were hypertension (45%), diarrhea (45%), hair color changes (44%), anorexia (30%), and nausea (25%). The response rate was 37.5% [95% confidence interval (CI): 26.9-48.1]; median PFS was 9.2 months (95% CI: 7.3-12.0); median OS was 23.5 months (95% CI: 16.3-28.0). Conclusions: Efficacy and safety profiles for pazopanib in this extension study of patients with RCC previously treated with placebo were very similar to those observed for pazopanib-treated patients in the pivotal phase III study.
Neuropharmacology and Management of Chemotherapy-Induced Nausea and Vomiting in Patients with Breast Cancer
Authors: Jordan Karin , Schaffrath Judith , Jahn Franziska , Mueller-Tidow Carsten , Jordan Berit
Published: September 2014

Advances in our understanding of the pathophysiology of chemotherapy-induced nausea and vomiting (CINV), the identification of patient risk factors, and the development of new antiemetics have led to significant improvements in CINV prevention. With the correct use of antiemetic drugs, CINV can be prevented in the majority of patients. Extensive clinical data have been considered in the development of antiemetic treatment recommendations by reliable institutions such as the Multinational Association of Supportive Care in Cancer, the European Society of Medical Oncology and the American Society for Clinical Oncology. These guidelines are intended to enable physicians to incorporate the latest clinical research into their daily practice, considering CINV prevention as part of an optimal patient-centered approach to cancer management. Yet despite the availability of these guidelines, there is emerging evidence that implementation of treatment recommendations is suboptimal. Recently, guideline committees gave special consideration to patient-related risk factors (young, females) contributing to the emetogenic potential for patients receiving anthracycline and cyclophosphamide-based chemotherapy. As women with breast cancer represent a particularly challenging population regarding emesis control, it is especially important that treatment recommendations are followed. This review focuses on the content of the current antiemetic guidelines, addressing the importance of how these are intended to be implemented in routine clinical practice.
Subretinal Bone Formation in a Patient with Giant Cell Tumor of the Sphenoid
Authors: Hwang Christopher K. , Baker Hubbard III George , Rapkin Louis , Grossniklaus Hans E.
Published: September 2014

Background/Aims: To report a case of subretinal bone formation after the treatment with denosumab for a giant cell tumor of the sphenoid, which had recurred after surgical resection. Methods: The clinical history and fundus findings including imaging, histologic and immunohistochemical features of the primary tumor and subretinal lesion were reviewed. Results: A 14-year-old boy was evaluated for a suprasellar mass. Resection of the lesion showed giant cell tumor of bone (GCT). An MRI study at the 1-month follow-up appointment showed tumor progression, and denosumab was initiated. Two months after the initial presentation, the patient developed a worsening scotoma of the right eye. Dilated fundus examination showed a yellow-tan-colored subretinal mass temporal to the fovea. The subretinal lesion was removed and showed lamellar bone with associated fibrocellular tissue. Conclusion: Denosumab therapy for GCT of the sphenoid may be associated with subretinal bone formation.
A Case of a Gastrointestinal Stromal Tumor with Skeinoid Fibers of the Sigmoid Colon
Authors: Sumi Tetsuo , Katsumata Kenji , Shibuya Makoto , Katayanagi Sou , Iwasaki Kenichi , Kasuya Kazuhiko , Serizawa Hiromi , Shimazu Motohide , Tsuchida Akihiko
Published: September 2014

An 80-year-old man was diagnosed with rectal cancer and underwent Hartmann's procedure. Although no tumors were identified during the preoperative examination, gross examination of the resected specimen incidentally revealed a submucosal tumor that was 9 mm in diameter at the oral side and located in the proximal stump of the specimen from the sigmoid colon. We suspected a concurrent gastrointestinal stromal tumor (GIST) and performed a histopathological examination. An L-shaped nodular lesion measuring 9 × 6 mm was histologically composed of a patternless proliferation of spindle cells intermingled with eosinophilic globules. Cellular atypia, prominent mitotic figures and necrotic foci were not observed in the nodule. The spindle cells were positive for CD34, CD117 and vimentin, but negative for CD56, smooth muscle actin and S-100 protein. MIB-1 positivity was estimated to be as low as approximately 1-2%. Electron microscopy showed a bundle of wool-like fibers with a periodicity of approximately 40 nm. We therefore considered the lesion to be a low-risk GIST with skeinoid fibers in the large intestine. Although numerous previous reports have reported skeinoid fibers in the stomach and small intestines, there have been only 9 cases (including the present case) of skeinoid fibers in the large intestine.
A Patient with Localized Scleroderma Successfully Treated with Etretinate
Authors: Shima Tomoko , Yamamoto Yuki , Ikeda Takaharu , Furukawa Fukumi
Published: September 2014

There are several treatment methods for localized scleroderma, but treatment is difficult when the lesion is widely distributed. We encountered a case who was treated successfully with etretinate, a vitamin A derivative. The usefulness of this agent is discussed.
Localized Epidermal Cysts as a Radiation Recall Phenomenon in a Melanoma Patient Treated with Radiotherapy and the BRAF Inhibitor Vemurafenib
Authors: Houriet Carine , Klass Natalie D. , Beltraminelli Helmut , Borradori Luca , Oberholzer Patrick A.
Published: September 2014

BRAF inhibitors are broadly used for metastatic melanoma with BRAF mutations. Their use results in various cutaneous side effects, such as the development of keratoacanthomas and squamous cell carcinomas. We report a patient with metastatic melanoma treated with vemurafenib who developed dozens of histologically confirmed epidermal cysts within 2 months after initiation of vemurafenib administration. The cystic lesions were observed only in the localized area where a large exophytic melanoma tumor mass had been previously irradiated. Localized epidermal cysts may constitute an unusual radiation recall reaction in patients treated with BRAF inhibitors.
Successful Treatment of Two Cases of Squamous Cell Carcinoma on the Ear with Intra-Arterial Administration of Peplomycin through a Superficial Temporal Artery
Authors: Haga Takahiro , Fujimura Taku , Takeuchi Izuho , Deguchi Masatoshi , Aiba Setsuya
Published: September 2014

Cutaneous squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer and tends to develop in sun-exposed cosmetic areas, including the ear. In this report, we describe two cases of SCC on the ear successfully treated with intra-arterial administration of peplomycin through a superficial temporal artery. In addition to this selective chemotherapy, we administered oral tegafur, which achieved complete remission of the tumor. These findings suggest that intra-arterial administration of peplomycin with tegafur is one of the optimal therapies for the treatment of SCC developing on the ear.
Impaired In Vivo Mitochondrial Krebs Cycle Activity After Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy
Authors: Dodd Michael S. , Atherton Helen J. , Carr Carolyn A. , Stuckey Daniel J. , West James A. , Griffin Julian L. , Radda George K. , Clarke Kieran , Heather Lisa C. , Tyler Damian J.
Published: September 2014

Background—

Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities.

Methods and Results—

Using hyperpolarized carbon-13 (
13
C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased
13
C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates.

Conclusions—

The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment.
Rethinking Composite End Points in Clinical Trials
Authors: Stolker Joshua M. , Spertus John A. , Cohen David J. , Jones Philip G. , Jain Kaushik K. , Bamberger Emily , Lonergan Brady B. , Chan Paul S.
Published: September 2014

Background—

Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers.

Methods and Results—

We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 “spending weights” across 5 common adverse events comprising composite end points in cardiovascular trials: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant’s ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (
P
<0.001 for all comparisons).

Conclusions—

Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.
Blood Pressure Differences Associated With Optimal Macronutrient Intake Trial for Heart Health (OMNIHEART)–Like Diet Compared With a Typical American Diet
Authors: Molitor John , Brown Ian J. , Chan Queenie , Papathomas Michail , Liverani Silvia , Molitor NuooTing , Richardson Sylvia , Van Horn Linda , Daviglus Martha L. , Dyer Alan , Stamler Jeremiah , Elliott Paul
Published: September 2014

The Dietary Approaches to Stop Hypertension-Sodium (DASH-Sodium) trial demonstrated beneficial effects on blood pressure (BP) of the DASH diet with lower sodium intake when compared with typical American diet. The subsequent Optimal Macronutrient Intake Trial for Heart Health (OMNIHEART) trial reported additional BP benefits from replacing carbohydrate in the DASH diet with either protein or monounsaturated fats. The primary aim of this study is to assess possible BP benefits of an OMNIHEART-like diet in free-living Americans using cross-sectional US population data of the International Study of Macronutrients, Micronutrients and Blood Pressure (INTERMAP) study. The INTERMAP data include four 24-hour dietary recalls, 2 timed 24-hour urine collections, 8 BP readings for 2195 individuals aged 40 to 59 years from 8 US INTERMAP population samples. Analyses are conducted using 2 approaches: (1) regression of BP on a linear OMNIHEART nutrient score calculated for each individual and (2) a Bayesian approach comparing estimated BP levels of an OMNIHEART-like nutrient profile with a typical American nutrient profile. After adjustment for potential confounders, an OMNIHEART score higher by 1 point was associated with systolic/diastolic BP differences of −1.0/−0.5 mm Hg (both
P
<0.001). Mean systolic/diastolic BPs were 111.3/68.4 and 115.2/70.6 mm Hg for Bayesian OMNIHEART and Control profiles, respectively, after controlling for possible confounders, with BP differences of −3.9/−2.2 mm Hg,
P
(difference ≤0)=0.98/0.96. Findings were comparable for men and women, for nonhypertensive participants, and with adjustment for antihypertensive treatment. Our findings from data on US population samples indicate broad generalizability of OMNIHEART results beyond the trial setting and support recommendations for an OMNIHEART-style diet for prevention/control of population-wide adverse BP levels.
“But Me No Buts”: The Theological Debate Between the Hasidim and the Mitnagdim in Light of the Discourse-Markers Theory
Authors: Brown Benjamin
Published: September 2014

The linguistic theory of discourse markers may often help us to decipher the roots of theological controversies in traditional cultures, where both of the parties declare loyalty to the same doctrines. According to this theory, if two sentences are coupled by “but,” the conjunction bears the implicature that the statement that comes after the “but” is the one that the speaker wishes to emphasize, or grant salience over the statement that comes before it. Examined on the theological texts of the Hasidim and the Mitnagdim, the theory is proved useful: for the Hasidim, statements on the Simple Unity of God are placed after “but,” while the Mitnagdim place statements on the multiplicity in which it appears in our world.
God’s Rage: Muslim Representations of hiv/aids as a Divine Punishment from the Perspective of the Cognitive Science of Religion
Authors: Svensson Jonas
Published: September 2014

Research from a number of disciplines indicates that the interpretation ofhiv/aidsas a divine punishment for illicit sexual practices dominates both a contemporary intra-Muslim public religious discourse and perceptions of the disease among Muslims. This dominance persists despite the existence of alternative theological interpretations, and despite seemingly contradictory empirical evidence. The present article develops a hypothesis on why this is the case and poses it against existing attempts at explanations. The theoretical basis for this hypothesis is elaborated with the help of findings from within the cognitive science of religion, and particularly the notion of an “epidemiology of representations.” According to the hypothesis, a combination of general psychological and cognitive factors and specific contextual factors provide the notion ofhiv/aidsas a divine punishment, with a selective advantage in certain social contexts over both theological alternatives and non-religious understandings of the disease. The article finally puts forward some predictions that may be tested empirically in further research.
The Sacralization of Randomness: The Theological Imagination and the Logic of Digital Divination Rituals
Authors: Ruah-Midbar Marianna
Published: September 2014

An abundance of divination rituals, primarily Tarot card reading, are widespread in cyberspace. These new phenomena are accompanied by a new rationale that is described in the article under the title “the sacralization of randomness.” The shift of religion and magic to the virtual realm brings about changes in theology, cosmology, ethics, practice, and religious/spiritual values, and these are demonstrated and discussed via the test case of digital divinations. Further implications of these innovations on the spiritual-cultural scene outside the Internet are also examined.
A review of the Entocytheridae (Ostracoda) of the world: updated bibliographic and species checklists and global georeferenced database, with insights into host specificity and latitudinal patterns of species richness
Authors: Mestre Alexandre , Monrós Juan S. , Mesquita-Joanes Francesc
Published: September 2014

The creation of biodiversity datasets freely available for the scientific community is a valuable task to stimulate global research on biodiversity. Among others, the Global Biodiversity Information Facility (GBIF) is a remarkable resource providing free online access to biodiversity data on many diverse taxonomic groups (including Ostracoda) from both terrestrial and marine ecosystems. More specific databases for Ostracoda georeferenced data have been built (e.g., NACODe and OMEGA), some with freely available data. However, the Entocytheridae, a family of ostracods living commensal on other crustaceans, with 220 living species, representing the third non-marine ostracod family in number of species, has been remarkably under-represented in the currently available biodiversity databases. To cover this gap, we present here a free-access world database of Entocytheridae published in GBIF and review the current knowledge of the group by updating a bibliographic and species checklists of the Entocytheridae. We also analyse the host specificity of the group and the latitudinal species richness pattern in North and Central America (including 186 spp.). The current database includes 3509 georeferenced records from 220 species, in contrast to just 44 entocytherid georeferenced records previously published in GBIF. In addition, the updated species list accounts for 43 species and 2 genera that were not included in the previous compendium on Entocytheridae published by Hart & Hart in 1974, so as 40 species not included in the 2013 Checklist provided by the Catalogue of Life. We show that the specialisation in one unique host species is not the rule in Entocytheridae, and evidence an unusual latitudinal pattern of species richness in North and Central American entocytherids, most probably related to the biogeographic history of their hosts.