bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Postoperative Pain: An Atypical Presentation of Dropped Gallstones after Laparoscopic Cholecystectomy
Authors: Binagi Samba , Keune Jason , Awad Michael
Published: January 2015

Cholecystectomy is one of the most commonly performed surgical procedures in the United States. A common complication is dropped gallstones, and the diversity of their presentation poses a substantial diagnostic challenge. We report the case of a 58-year-old man presenting with chronic right upper quadrant hours status post cholecystectomy. Imaging demonstrated retained gallstones in the perihepatic space and symptoms remitted following their removal via laparoscopic operation. Gallstones are lost in roughly 1 in 40 cholecystectomies and are usually asymptomatic. The most common presentations are months or years status post cholecystectomy due to fistula, abscess, or sinus tract formation. We report this case hoping to bring light to a rare presentation for dropped gallstones and provide advice on the management of this common complication of cholecystectomy.
Acute and Chronic Local Inflammatory Reaction after Implantation of Different Extracellular Porcine Dermis Collagen Matrices in Rats
Authors: Lucke Silke , Hoene Andreas , Walschus Uwe , Kob Anette , Pissarek Jens-Wolfgang , Schlosser Michael
Published: January 2015

Two cross-linked acellular porcine dermal collagen matrices (Permacol and NRX) were implanted into rats and the acute and chronic local inflammatory tissue reactions were investigated after 7, 14, 28, and 112 days. Both membranes were stable in vivo for up to 112 days. All investigated immune cell populations (CD68+ macrophages, CD163+ macrophages, T lymphocytes, MHC class II positive cells, mast cells, and NK cells) were present. Their amount decreased significantly over time compared to day 7 after implantation. A change from an acute to a chronic inflammation and an associated shift from proinflammatory M1-like to anti-inflammatory M2-like macrophages were observed. In the early phase there was a significant correlation of T cells to CD68+ (M1-like) macrophages, whereas in the chronic phase T lymphocytes were positively correlated with CD163+ (M2-like) macrophages. The material NRX showed an enhanced inflammatory reaction in comparison to Permacol possibly caused by material characteristics such as a twofold higher thickness of the membrane, roughness, and water absorption capacity. Nevertheless, a more pronounced regenerative process as, for example, indicated by nestin expression demonstrated its possible suitability for applications as wound repair material.
Blade Crack Detection of Centrifugal Fan Using Adaptive Stochastic Resonance
Authors: Hu Bingbing , Li Bing
Published: January 2015

Centrifugal fans are widely used in various industries as a kind of turbo machinery. Among the components of the centrifugal fan, the impeller is a key part because it is used to transform kinetic energy into pressure energy. Crack in impeller’s blades is one of the serious hidden dangers. It is important to detect the cracks in the blades as early as possible. Based on blade vibration signals, this research applies an adaptive stochastic resonance (ASR) method to diagnose crack fault in centrifugal fan. The ASR method, which can utilize the optimization ability of the grid search method and adaptively realize the optimal stochastic resonance system matching input signals, may weaken the noise and highlight weak characteristic and thus can diagnose the fault accurately. A centrifugal fan test rig is established and experiments with three cases of blades are conducted. In comparison with the ensemble empirical mode decomposition (EEMD) analysis and the traditional Fourier transform method, the experiment verified the effectiveness of the current method in blade crack detection.
The Increase of Intra-Abdominal Pressure Can Affect Intraocular Pressure
Authors: Ece Ilhan , Vatansev Celalettin , Kucukkartallar Tevfik , Tekin Ahmet , Kartal Adil , Okka Mehmet
Published: January 2015

Objective. This study aims to explore the usage of intraocular pressure measurements as the early indicator of the increase in intra-abdominal pressure.Methods. In this prospective study, 40 patients undergoing elective surgery were included. Patients were divided into four groups of 10 patients. The control group (Group C) was not subjected to laparoscopic intervention. Laparoscopic surgery was, respectively, performed with an intra-abdominal pressure of 9, 12, and 15 mmHg in Groups L (low), M (medium), and H (high pressure). Intraocular pressure was measured binocularly in each patient at three different times (before, during, and end of surgery) using a contact tonometer.Results. Patients’ gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) class, and operative times were not different among the groups. No complications occurred with either the surgery or measurement of intraocular pressure. Intubation was associated with a severe rise in IOP(P<0.05). An increase in intraocular pressure was seen in groups M and H(P<0.05).Conclusion. Intraocular pressure was increased in the groups with an intra-abdominal pressure of 12 mmHg or more. Measuring the intraocular pressure might be a useful method to estimate the intra-abdominal pressure. This trial is registered withNCT02319213.
Salpingectomy as a Means to Reduce Ovarian Cancer Risk
Authors: Daly Mary B. , Dresher Charles W. , Yates Melinda S. , Jeter Joanne M. , Karlan Beth Y. , Alberts David S. , Lu Karen H.
Published: January 2015

Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk reduction in women at hereditary risk of ovarian cancer. Although this procedure significantly decreases both the incidence of and mortality from ovarian cancer, it affects quality of life, and the premature cessation of ovarian function may have long-term health hazards. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high-grade serous cancers (HGSC). This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. In this review, we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy. Cancer Prev Res; 8(5); 342–8. ©2015 AACR.

See related commentary by Mark H. Greene, p. 339
Odor Cues Released by Ehrlich Tumor-Bearing Mice Are Aversive and Induce Psychological Stress
Authors: Alves Glaucie Jussilane , Palermo-Neto João
Published: January 2015

Background/Aims: This study aimed to verify if odor cues released by Ehrlich tumor-bearing mice are aversive and stressful. Methods: Female mice were divided into a control group and an experimental group. One animal of each experimental pair of mice was inoculated with 5 × 106 Ehrlich tumor cells intraperitoneally; the other animal was kept undisturbed and was referred to as a CSP (companion of sick partner). One mouse of each control pair was treated intraperitoneally with 0.9% NaCl (1 mg/kg); the other animal (CHP, companion of healthy partner) was kept undisturbed. Results: It was shown that, in relation to CHP, CSP mice (1) spent less time within the companion zone in a T-maze place preference test, (2) had increased levels of social interaction, (3) had increased levels of plasmatic adrenaline and noradrenaline and (4) displayed no changes in serum corticosterone levels before and after an immobilization stress challenge. It was also shown that (5) cohabitation with 2 tumor-bearing mice was more effective in decreasing neutrophil oxidative burst than cohabitation with 1 sick partner and (6) the presence of a healthy conspecific within the cage of the tumor-injected/CSP pair abrogated the effects of cohabitation on neutrophil activity. These results show that odor cues released by Ehrlich tumor-injected mice are aversive and induce psychological stress. Conclusion: We postulate that the aversive response induced by the chemosignals released by Ehrlich tumor-injected animals activates the sympathetic nervous system and causes the neuroimmunal changes that occur in the mice cohabiting with the sick mice.
Calcitonin Gene-Related Peptide Modulates the Production of Pro-Inflammatory Cytokines Associated with Periprosthetic Osteolysis by THP-1 Macrophage-Like Cells
Authors: Jablonski Heidrun , Kauther Max Daniel , Bachmann Hagen Sjard , Jäger Marcus , Wedemeyer Christian
Published: January 2015

Objective: An anti-resorptive impact of the neuropeptide calcitonin gene-related peptide (CGRP) on periprosthetic osteolysis, the leading cause of early prosthesis loosening, has been shown previously. In this study, the impact of CGRP on pro-inflammatory cytokine production associated with periprosthetic osteolysis was analysed using THP-1 macrophage-like cells. Methods: Cells were stimulated with ultra-high-molecular-weight polyethylene (UHMWPE) particles (cell-to-particle ratios of 1:100 and 1:500) and lipopolysaccharides (LPS; 1 µg/ml) to establish osteolytic conditions, and simultaneously treated with CGRP (10-8M). Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and tumour necrosis factor (TNF)-a mRNA expression were measured by quantitative RT-PCR. RANK protein was detected by Western blot. Secreted protein levels of TNF-a as well as interleukin (IL)-1ß and IL-6 were quantified in cell culture supernatants by ELISA and Bio-Plex cytokine assay, respectively. Results: Activation of macrophage-like cells failed to enhance the production of RANK but led to a dose- and time-dependent increase of TNF-a mRNA and secreted protein levels of TNF-a, IL-1ß and IL-6. Application of CGRP time-dependently suppressed TNF-a mRNA expression induced by low-particle concentrations and LPS, while both particle- and LPS-induced secretion of TNF-a was inhibited. A pronounced inhibitory effect of CGRP on LPS-induced cytokine production at 24 h of incubation was also observed with IL-1ß and IL-6. Conclusions: CGRP shows a time-dependent inhibitory effect on the secretion of osteolysis-associated pro-inflammatory cytokines, indicating an indirect anti-resorptive influence of the neuropeptide on both aseptic prosthesis loosening and bacterially induced bone resorption which might enhance the life time of total joint replacements.
Cell-Based Modulation of Autoimmune Responses in Multiple Sclerosis and Experimental Autoimmmune Encephalomyelitis: Therapeutic Implications
Authors: Mastorodemos Vasileios , Ioannou Marianna , Verginis Panayotis
Published: January 2015

Multiple sclerosis (MS) is a prototypic autoimmune inflammatory disorder of the central nervous system (CNS). MS pathogenesis is a complex phenomenon that is influenced by genetic and environmental factors that lead to the dysregulation of immune homeostasis and tolerance. It has been shown that pathogenic T lymphocyte subsets, such as T helper 1 (Th1) and Th17 cells, play a crucial role in the autoimmune cascade influencing disease initiation, progression and subsequent tissue damage during MS. On the other hand, several mechanisms have been described in both patients and animal models of MS with the potential to modulate myelin-specific autoimmune responses and to facilitate amelioration of disease pathology. To this end, regulatory T cells (Tregs) are considered to be a powerful cell subset not only in the maintenance of homeostasis but also in the re-establishment of tolerance. Along these lines, other cell subsets such as dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), γδ T cells and natural killer (NK) cells have been shown to regulate the autoimmune response in the CNS under certain circumstances. This review will attempt to summarize the relevant knowledge of the regulatory mechanisms exerted by immune cells in MS that could hold the promise for the design of novel therapeutic strategies.
The Interaction between Rejection Sensitivity and Emotional Maltreatment in Borderline Personality Disorder
Authors: Chesin Megan , Fertuck Eric , Goodman Jeanne , Lichenstein Sarah , Stanley Barbara
Published: January 2015

Background: Borderline personality disorder (BPD) is a prevalent psychiatric disorder associated with significant distress, dysfunction, and treatment utilization. Though, theoretically, BPD is posited to arise from a combination of trait and environmental risk factors, few studies have tested trait-by-environment interactions in BPD. We investigated the roles of rejection sensitivity (RS) and childhood emotional neglect and abuse (ENA) as well as their interaction in BPD. Sampling and Methods: Eighty-five adults with a lifetime mood disorder who were recruited for outpatient studies in a psychiatric clinic were assessed for ENA using the Childhood Trauma Questionnaire and for RS with the Adult Rejection Sensitivity Questionnaire. BPD diagnoses were made by consensus using data collected on the Structured Clinical Interview for DSM-IV. Hierarchical logistic regression was used to test associations between RS, ENA, their interaction and BPD. Results: RS and ENA interacted to predict co-occurring BPD in our sample of mood-disordered patients, with the strength of the relationship between RS and BPD depending on the severity of ENA. In the context of little or no ENA, RS and BPD were more strongly related than when ENA was more severe. Conclusions: Our results extend previous findings suggesting RS and ENA are risk factors for BPD. They also provide preliminary support for contemporary theories of BPD positing trait-by-environment interactions in the development of BPD. Prospective studies are needed to confirm these findings.
Autoimmune Disease-Associated Variants of Extracellular Endoplasmic Reticulum Aminopeptidase 1 Induce Altered Innate Immune Responses by Human Immune Cells
Authors: Aldhamen Yasser A. , Pepelyayeva Yuliya , Rastall David P.W. , Seregin Sergey S. , Zervoudi Efthalia , Koumantou Despoina , Aylsworth Charles F. , Quiroga Dionisia , Godbehere Sarah , Georgiadis Dimitris , Stratikos Efstratios , Amalfitano Andrea
Published: January 2015

Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of the innate immune response. Previous studies show ERAP1 to be endoplasmic reticulum-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating the innate immune responses of human peripheral blood mononuclear cells (hPBMCs) using two experimental methods: extracellular exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression. We found that exposure of hPBMCs to ERAP1 variant proteins as well as ERAP1 overexpression by Ad5 vectors increased inflammatory cytokine and chemokine production, and enhanced immune cell activation. Investigating the molecular mechanisms behind these responses revealed that ERAP1 is able to activate innate immunity via multiple pathways, including the NLRP3 (NOD-like receptor, pyrin domain-containing 3) inflammasome. Importantly, these responses varied if autoimmune disease-associated variants of ERAP1 were examined in the assay systems. Unexpectedly, blocking ERAP1 cellular internalization augmented IL-1β production. To our knowledge, this is the first report identifying ERAP1 as being involved in modulating innate responses of human immune cells, a finding that may explain why ERAP1 has been genetically associated with several autoimmune diseases.
Assessment of Competence in Simulated Flexible Bronchoscopy Using Motion Analysis
Authors: Colella Sara , Søndergaard Svendsen Morten Bo , Konge Lars , Svendsen Lars Bo , Sivapalan Pradeesh , Clementsen Paul
Published: January 2015

Background: Flexible bronchoscopy should be performed with a correct posture and a straight scope to optimize bronchoscopy performance and at the same time minimize the risk of work-related injuries and endoscope damage. Objectives: We aimed to test whether an automatic motion analysis system could be used to explore if there is a correlation in scope movements and the operator's level of experience. Our hypothesis was that experienced bronchoscopists move less and keep the flexible scope straighter than less-experienced bronchoscopists while performing procedures. Methods: Eleven novices, 9 intermediates and 9 experienced bronchoscopy operators performed 3 procedures each on a bronchoscopy simulator. The Microsoft Kinect system was used to automatically measure the total deviation of the scope from a perfectly straight, vertical line. Results: The low-cost motion analysis system could measure the accumulated deviation of the scope precisely during the procedure. The deviations were greatest for the novices and smallest for the most experienced operators for all 3 procedures (p = 0.01, p = 0.01 and p = 0.04, respectively). The total deviation from the straight scope correlated negatively with the performance on the simulator (virtual-reality simulator score; p < 0.001). Conclusion: The motion analysis system could discriminate between different levels of experience. Automatic feedback on correct movements during self-directed training on simulators might help new bronchoscopists learn how to handle the bronchoscope like an expert.
Prospective Evaluation of the Added Value of Imaging within the Dutch National Diagnostic Appendicitis Guideline - Do we Forget our Clinical Eye?
Authors: Schok Thomas , Simons Petra C.G. , Janssen-Heijnen Maryska L.G. , Peters Nathalie A.L.R. , Konsten Joop L.M.
Published: January 2015

Background: Annually 16,000 appendectomies are performed in the Netherlands, of which 15-20% are negative. In 2010, to reduce this unacceptable percentage of superfluous appendectomies, the Dutch Association for Surgery introduced the ‘Appendicitis Guideline'. This guideline recommends the use of imaging. In this observational prospective study the added value of imaging in everyday clinical practice is evaluated. Methods: All patients with suspected appendicitis were included at the emergency department of a Dutch teaching hospital during the period from September 2011 to May 2012 (n = 350; 237 adults and 113 children under 18 years). Adherence to the guideline was evaluated. Results: 75 Patients (21%) were not referred for imaging because of a low suspicion or alternative diagnosis. In 16 patients (5%) the guideline was not followed. Of the 259 patients (74%) who underwent ultrasonography, 105 (30%) also underwent computed tomography (CT). 127 appendectomies were performed, showing appendicitis in 112 patients (88%); 15 appendectomies (12%) were negative. In the latter group, 12 were performed after false positive imaging results, and 3 following inconclusive imaging results. Conclusion: When using imaging in the diagnosis of appendicitis, the percentage of negative appendectomies remains close to the percentage declared as unacceptable by the publishers of the guideline.
APRIL Induces Cisplatin Resistance in Gastric Cancer Cells via Activation of the NF-κB Pathway
Authors: Zhi Xiaofei , Tao Jinqiu , Xiang Guoliang , Cao Hongyong , Liu Zijun , Yang Kunxing , Lv Chengyu , Ni Shaozhong
Published: January 2015

Background: A proliferation-inducing ligand (APRIL) is a tumor-necrosis factor (TNF) family member and is a novel cytokine crucial in sustaining lymphocytic leukemia B cell survival and proliferation. However, its role in gastric cancer (GC) remains unclear. In this study, we investigated the expression pattern and prognostic role of APRIL in GC. Methods: Expression of APRIL was assessed by immunohistochemistry and real-time PCR. Prognostic role of APRIL expression was evaluated. We also discovered the effect of APRIL on chemo-resistance in GC cells and the underlying mechanisms. Results: APRIL mRNA levels were significantly increased in GC tissues compared with adjacent tissues and high expression levels of APRIL in tumor cells significantly correlated with poor overall survival in patients receiving cisplatin adjuvant treatment. Overexpression of APRIL in AGS cells significantly attenuated the therapeutic efficacy of cisplatin in vitro and in vivo. In contrast, silence of APRIL in SGC7901 cells enhanced cisplatin-induced tumor suppression. Our data further revealed that the canonical NF-κB pathway was involved in APRIL-mediated chemo-resistance. In addition, expression of APRIL was regulated by miR-145 in GC cells. Conclusion: APRIL is a novel clinical chemo-resistance biomarker for gastric cancer and might be a promising therapeutic target for GC patients.
Biochanin A Promotes Proliferation that Involves a Feedback Loop of MicroRNA-375 and Estrogen Receptor Alpha in Breast Cancer Cells
Authors: Chen Jian , Ge Bo , Wang Yong , Ye Yu , Zeng Sien , Huang Zhaoquan
Published: January 2015

Background: Biochanin A and formononetin are O-methylated isoflavones that are isolated from the root of Astragalus membranaceus, and have antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and in vitro studies to further investigate the potential effect of biochanin A in promoting cell proliferation in estrogen receptor (ER)-positive cells, and to elucidate underlying mechanisms. Methods: ERα-positive breast cancer cells (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. Compared with the control, low biochanin A concentrations (2-6 μM) stimulated ERα-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells were used to study the relevant signaling pathway. Results: After treatment with biochanin A, ERα, miR-375, and Bcl-2 expression was significantly upregulated. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with biochanin A increased significantly. Conclusion: This study demonstrated that biochanin A promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.
WT1 Enhances Proliferation and Impedes Apoptosis in KRAS Mutant NSCLC via Targeting cMyc
Authors: Wu Chen , Wang Sihan , Xu Caihua , Tyler Andreas , Li Xingru , Andersson Charlotta , Oji Yusuke , Sugiyama Haruo , Chen Yijiang , Li Aihong
Published: January 2015

Background: A novel link between oncogenic KRAS signalling and WT1 was recently identified. We sought to investigate the role of WT1 and KRAS in proliferation and apoptosis. Methods: KRAS mutations and WT1 (cMyc) expression were detected using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid and siRNA via transient transfection technology in H1299 and H1568 cells. MTT assay for detection of cell proliferation, and TUNEL assay and proteomic profiler assay for apoptosis evaluation were carried out. Dual luciferase reporter assay and ChIP-PCR were performed to validate the effect of WT1 on the cMyc promoter. Results: KRAS mutations showed a negative impact on overall survival (OS). High expressions of WT1 and cMyc were associated with poor OS in KRAS mutant subgroup. The potential mechanisms that WT1 promotes proliferation and impedes apoptosis through affecting multiple apoptosis-related regulators in KRAS mutant NSCLC cells were identified. WT1 could activate cMyc promoter directly in KRAS mutant cells. Conclusion: The results suggest that WT1 and c-MYC expression is important for survival in KRAS mutant tumors as opposed to KRAS wild-type tumors. For treatment of KRAS mutant NSCLC, targeting WT1 and cMyc may provide alternative therapeutic strategies.
Angiotensin II-Induced Egr-1 Expression is Suppressed by Peroxisome Proliferator- Activated Receptor-γ Ligand 15d-PGJ2 in Macrophages
Authors: Meng Yan , Chen Chen , Tian Cui , Du Jie , Li Hui-Hua
Published: January 2015

Background/Aims: Angiotensin II (Ang II) plays a critical role in regulating vascular inflammatory diseases, such as atherosclerosis and hypertension. Early growth response-1 (Egr-1) is an immediate early gene that acts as a master switch for the inflammatory response. However, the role of Ang II in regulating Egr-1 expression in macrophages, and the effect of peroxisome proliferators-activated receptor-γ (PPAR-γ) ligand 15d-PGJ2 in this process remain to be investigated. Methods and Results: We showed that Ang II significantly up-regulated the expression of Egr-1 in RAW264.7 macrophages, and this effect was markedly attenuated by Eprosartan (an AT1R blocker), SP600125 (a JNK-specific inhibitor) and PD98059 (an ERK-specific inhibitor). Moreover, treatment of macrophages with 15d-PGJ2, a natural PPAR-γ ligand, significantly reduced Ang II-induced expression of Egr-1 and its inflammatory gene targets (IL-1β, TNF-α, TGF-β, MCP-1 and ICAM-1) through PPAR-γ activation and ROS formation. In addition, 15d-PGJ2 treatment markedly inhibited Ang II-induced macrophage migration and proliferation. Conclusions: This study for the first time demonstrates that Ang II can induce the expression of Egr-1 via AT1R/JNK and ERK signaling pathways. Activation of PPAR-γ by 15d-PGJ2 suppresses Egr-1-mediated proinflammatory response, and may be a novel therapeutic strategy for treatment of vascular inflammatory diseases.
A Simple Method for Comparing Enzymatic Capecitabine Activation in Various Mono- and Combination Chemotherapies
Authors: Buchner Philipp , Sahmanovic Azra , Schreiber Veronika , Baroian Nairi , Dittrich Christian , Czejka Martin
Published: January 2015

Before being able to develop a pharmacodynamic effect, a number of drugs have to be activated by enzymes, which are known to be potentially influenced by manifold factors, leading to a possible alteration of their activity behaviour. Based on capecitabine, we report a simple and rapid method for the estimation and comparison of the so-called ‘apparent enzyme activity' (R), not only intra- (different dose levels) but also inter-schedule, to contribute to therapeutic success. Dividing the area under the curve (AUC) of the product by the AUC of the precursor generates a factor which indicates the apparent activity of the enzyme involved in the biotransformation of a compound. Our own data as well as data from the literature was used to calculate those R levels revealing that the formation of 5′-DFUR - the immediate precursor of 5-fluorouracil - was not affected by concomitant medication within the dosing range investigated. Calculated hypothetical means of R for carboxylesterase (1.49 ± 0.66) and for cytidine deaminase (1.17 ± 0.65) were obtained. Additionally, it is important to note that the method described in this report is of general use and not limited to chemotherapeutic agents, as soon as enzymes are involved in drug activation.
A Meta-Analysis Examining the Use of Fibrin Glue Mesh Fixation versus Suture Mesh Fixation in Open Inguinal Hernia Repair
Authors: Liu Huihui , Zheng Xiao , Gu Yan , Guo Shanyu
Published: January 2015

Background: The aim of this study was to systematically analyze the randomized trials comparing fibrin glue mesh fixation with suture mesh fixation in open inguinal hernia repair. Methods: Information was collected from a literature search using PubMed, Springer, Cochrane Library database and reference lists. The methodological quality of included publications was evaluated. Statistical analysis was performed using Review Manager Version 5.2.5 software. Results: Nine articles were identified for inclusion: four randomized controlled trials (RCTs) and five prospective observational clinical studies. All the trials were considered to be of fair quality. The results showed that there was a lower incidence of chronic pain (RR 0.42, 95% CI 0.22-0.79, I2 11%; p < 0.01), and hematoma/seroma (RR 0.43, 95% CI 0.21-0.87, I2 0%; p < 0.05) in the fibrin glue mesh fixation group. However, the results of meta-analysis revealed that the incidence of recurrence or urinary problems between the two procedures were similar. Conclusions: During the 6-15 months follow-up, fibrin glue mesh fixation is a feasible alternative for mesh fixation with sutures in open inguinal hernia repair. However, the poor quality of the included trials limits the evidence; rigorously designed trials are warranted to confirm this conclusion.
Transfusion Management and Immunohematologic Complications in Liver Transplantation: Experience of a Single Institution
Authors: Solves Pilar , Carpio Nelly , Moscardo Federico , Lancharro Aima , Cano Isabel , Moya Angel , López-Andujar Rafael , Ángel Sanz Miguel
Published: January 2015

Objective: Liver transplantation (LT) has traditionally been associated with major blood loss and consequently high blood transfusion requirements. Our objective was to analyze transfusion management and incidence of immunohematologic complications in patients undergoing LT at our institution. Methods: A retrospective analysis of immunohematologic events and transfusion outcomes was carried out at La Fe University Hospital in Valencia. Data from 654 patients were reviewed: 654 underwent only one LT while 36 underwent second LT. Results: Patients received a median of 3 red blood cell (RBC) concentrates, 2 platelets concentrates (PCs) and 2 fresh frozen plasma units (FFPs). Variables significantly influencing RBC transfusions were: the MELD score, hemoglobin levels, and the platelet counts before LT. 27 patients (4.1%) had a positive antibody screening before transplant. Immunohematologic events occurred in 8% of the patients, mostly in the first month after LT, and involved hemolysis in 13 cases. Mortality was significantly higher in patients developing immunohematologic disorders (42.8 vs. 18.3%; p < 0.001). In the multivariable analysis, only ABO minor incompatibility between donor and recipient significantly increased the appearance of immunohematologic incidences (OR 4.92, 95% CI 2.31-10.50; p < 0.001). Conclusion: Transfusion management of patients that underwent LT can be complicated by immunohematologic problems. Blood banks should implement the DAT test in each transfusion to detect them.
External Beam Radiotherapy for Focal Lymphoepithelioma-Like Carcinoma in the Urinary Bladder: A Case Report and Literature Review
Authors: Kushida Nobuhiro , Kushakabe Takashi , Kataoka Masao , Kumagai Shin , Aikawa Ken , Kojima Yoshiyuki
Published: January 2015

Lymphoepithelioma is a malignant epithelial tumor in the nasopharynx characterized by prominent lymphoid infiltration. Carcinomas that resemble lymphoepitheliomas have been called lymphoepithelioma-like carcinomas and have been reported in other organs. A tumor in the bladder is categorized by the percentage of the total area occupied by the lymphoepithelioma-like carcinoma pattern, with the prognosis dependent on the percentage. We present an 81-year-old man with stage 3 chronic obstructive pulmonary disease and a history of aortic aneurysm repair. The computed tomography scans indicated thickening and irregularity of the bladder wall, with left external iliac lymph node metastasis. His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0. Transurethral resection of the bladder tumor was performed, and the pathological specimen showed that the tumor was composed of undifferentiated malignant cells with sheets and nests arranged in a syncytial pattern, as well as an urothelial carcinoma lesion. A prominent lymphoid reaction accompanied the tumor. The pathological diagnosis was focal-type lymphoepithelioma-like carcinoma containing a component of urothelial carcinoma G3>G2. His general condition was such that he could not tolerate radical cystectomy or systemic chemotherapy. External beam radiotherapy (total 60 Gy) was given to the bladder, including the lymph node metastatic lesion. No cancer recurrence was detected by regular follow-up computed tomography and cystoscopy. He eventually died of other causes 48 months later. Although treatment for focal lymphoepithelioma-like carcinoma generally requires multifocal therapies, in the present case, the bladder became tumor free. We also summarize previously reported lymphoepithelioma-like carcinoma cases treated with radiotherapy.
Cigarette Smoking and Cardiovascular Events
Authors: McEvoy John W. , Blaha Michael J. , DeFilippis Andrew P. , Lima Joao A.C. , Bluemke David A. , Hundley W. Gregory , Min James K. , Shaw Leslee J. , Lloyd-Jones Donald M. , Barr R. Graham , Budoff Matthew J. , Blumenthal Roger S. , Nasir Khurram
Published: January 2015

Objectives—

To examine the contemporary effect of smoking in a multiethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking.

Approach and Results—

We studied 6814 participants free of cardiovascular disease and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox regression was used to estimate the association between smoking parameters and all-cause cardiovascular disease, all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C-reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard ratios in current smokers were 1.7 (95% confidence interval, 1.3–2.2) for all-cause cardiovascular disease, 1.6 (1.1–2.1) for all-cause CHD, and 1.7 (1.2–2.4) for hard CHD. Similarly, among current smokers, hazard ratios were higher in the 4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1–6.6]). Both CAC>100 and high-sensitivity C-reactive protein ≥3 mg/L identified higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0 [1.5–6.0, compared with CAC=0] and 2.6 [1.4–4.8, compared with high-sensitivity C-reactive protein <2 mg/L], respectively). However, CAC was a stronger mediator of events and adversely modified the effect of smoking on events (eg,
P
-interaction=0.02 for hard CHD). Compared with never smokers, former smokers (median cessation interval=22 years) had similar adjusted hazard for events.

Conclusions—

In this multiethnic cohort, current smoking and cumulative exposure remain important modifiable determinants of cardiovascular disease. Both high-sensitivity C-reactive protein ≥3 mg/L and, particularly, CAC>100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.
Cellular Postconditioning
Authors: Kanazawa Hideaki , Tseliou Eleni , Malliaras Konstantinos , Yee Kristine , Dawkins James F. , De Couto Geoffrey , Smith Rachel R. , Kreke Michelle , Seinfeld Jeffrey , Middleton Ryan C. , Gallet Romain , Cheng Ke , Luthringer Daniel , Valle Ileana , Chowdhury Supurna , Fukuda Keiichi , Makkar Raj R. , Marbán Linda , Marbán Eduardo
Published: January 2015

Background—

Intracoronary delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human chronic myocardial infarction. However, intracoronary delivery of CDCs after reperfusion in acute myocardial infarction has never been assessed in a clinically-relevant large animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine model of myocardial infarction.

Methods and Results—

First, escalating doses (5, 7.5, and 10 million cells) of allogeneic CDCs were administered intracoronary 30 minutes after reperfusion. Forty-eight hours later, left ventriculography was performed and animals euthanized to measure area at risk, infarct size (IS), and microvascular obstruction. Second, identical end points were measured in a pivotal study of minipigs (n=14) that received 8.5 to 9 million allogeneic CDCs, placebo solution, or sham. Multiple indicators of cardioprotection were observed with 7.5 and 10 million allogeneic CDCs, but not 5 million CDCs, relative to control. In the pivotal study, IS, microvascular obstruction, cardiomyocyte apoptosis, and adverse left ventricular remodeling were all smaller in the CDC group than in sham or placebo groups. In addition, serum troponin I level at 24 hours was lower after CDC infusion than that in the placebo or sham groups, consistent with the histologically-demonstrated reduction in IS.

Conclusions—

Intracoronary delivery of allogeneic CDCs is safe, feasible, and effective in cardioprotection, reducing IS, preventing microvascular obstruction, and attenuating adverse acute remodeling. This novel cardioprotective effect, which we call cellular postconditioning, differs from previous strategies to reduce IS in that it works even when initiated with significant delay after reflow.
Validity of
International Classification of Disease
Codes to Identify Ischemic Stroke and Intracranial Hemorrhage Among Individuals With Associated Diagnosis of Atrial Fibrillation
Authors: Thigpen Jonathan L. , Dillon Chrisly , Forster Kristen B. , Henault Lori , Quinn Emily K. , Tripodis Yorghos , Berger Peter B. , Hylek Elaine M. , Limdi Nita A.
Published: January 2015

Background—

Because of its association with death and disability, stroke is a focus of outcomes in atrial fibrillation (AF) research.
International Classification of Disease-Ninth Revision
(
ICD-9
) edition codes are commonly used to identify stroke in research, particularly in large administrative data. We sought to assess the validity of
ICD-9
codes in stroke case ascertainment and for AF across 3 institutions.

Methods and Results—

Participating centers included Boston Medical Center (safety net hospital), Geisinger Health System (rural Pennsylvania), and the University of Alabama (academic center in the southeastern stroke belt).
ICD-9
codes for ischemic stroke (433–434, 436) and intracranial hemorrhage (430–432) identified 1812 stroke cases with an associated code for AF (427.31) from 2006 to 2010. Cases were vetted through chart review with final adjudication by a stroke neurologist. Review considered 94.2% of
ICD-9
identified stroke cases valid with decreased accuracy for concurrent AF diagnosis (82.28%) and stroke attributable to AF (72.8%). Among events with “without infarction” modifiers, 7.2% were valid strokes.
ICD-9
stroke code accuracy did not differ by stroke type or site. Stroke code 434 displayed higher accuracy than 433 (94.4% versus 85.2%;
P
<0.01), and primary stroke codes were more accurate than nonprimary codes (97.2% versus 83.7%;
P
<0.0001).

Conclusions—

Using
ICD-9
stroke and AF codes to identify patients with stroke plus AF resulted in inaccuracies. Given the expanded financial and policy implications of patient-oriented research, conclusions derived solely from administrative data without validation of outcome events should be interpreted with caution.
Hospital Variation in Quality of Discharge Summaries for Patients Hospitalized With Heart Failure Exacerbation
Authors: Al-Damluji Mohammed Salim , Dzara Kristina , Hodshon Beth , Punnanithinont Natdanai , Krumholz Harlan M. , Chaudhry Sarwat I. , Horwitz Leora I.
Published: January 2015

Background—

Single-site studies have demonstrated inadequate quality of discharge summaries in timeliness, transmission, and content, potentially contributing to adverse outcomes. However, degree of hospital-level variation in discharge summary quality for patients hospitalized with heart failure (HF) is uncertain.

Methods and Results—

We analyzed discharge summaries of patients enrolled in the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) study. We assessed hospital-level performance on timeliness (fraction of summaries completed on the day of discharge), documented transmission to the follow-up physician, and content (presence of components suggested by the Transitions of Care Consensus Conference). We obtained 1501 discharge summaries from 1640 (91.5%) patients discharged alive from 46 hospitals. Among hospitals contributing ≥10 summaries, the median hospital dictated 69.2% of discharge summaries on the day of discharge (range, 0.0%–98.0%;
P
<0.001); documented transmission of 33.3% of summaries to the follow-up physician (range, 0.0%–75.7%;
P
<0.001); and included 3.6 of 7 Transitions of Care Consensus Conference elements (range, 2.9–4.5;
P
<0.001). Hospital course was typically included (97.2%), but summaries were less likely to include discharge condition (30.7%), discharge volume status (16.0%), or discharge weight (15.7%). No discharge summary included all 7 Transitions of Care Consensus Conference–endorsed content elements, was dictated on the day of discharge, and was sent to a follow-up physician.

Conclusions—

Even at the highest performing hospital, discharge summary quality is insufficient in terms of timeliness, transmission, and content. Improvements in all aspects of discharge summary quality are necessary to enable the discharge summary to serve as an effective transitional care tool.
Predicting Graft Loss by 1 Year in Pediatric Heart Transplantation Candidates
Authors: Schumacher Kurt R. , Almond Christopher , Singh Tajinder P. , Kirk Richard , Spicer Robert , Hoffman Timothy M. , Hsu Daphne , Naftel David C. , Pruitt Elizabeth , Zamberlan Mary , Canter Charles E. , Gajarski Robert J.
Published: January 2015

Background—

Pediatric data on the impact of pre–heart transplantation (HTx) risk factors on early post-HTx outcomes remain inconclusive. Thus, among patients with previous congenital heart disease or cardiomyopathy, disease-specific risk models for graft loss were developed with the use pre-HTx recipient and donor characteristics.

Methods and Results—

Patients enrolled in the Pediatric Heart Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis into cardiomyopathy and congenital heart disease cohorts. Logistic regression identified independent, pre-HTx risk factors. Risk models were constructed for 1-year post-HTx graft loss. Donor factors were added for model refinement. The models were validated with the use of patients transplanted from 2007 to 2009. Risk factors for graft loss were identified in patients with cardiomyopathy (n=896) and congenital heart disease (n=965). For cardiomyopathy, independent risk factors were earlier year of transplantation, nonwhite race, female sex, diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and panel reactive antibody >10%. The recipient characteristic risk model had good accuracy in the validation cohort, with predicted versus actual survival of 97.5% versus 95.3% (C statistic, 0.73). For patients with congenital heart disease, independent risk factors were nonwhite race, history of Fontan, ventilator dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower body surface area. The risk model was less accurate, with 86.6% predicted versus 92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor characteristics did not enhance model precision.

Conclusions—

Risk factors for 1-year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis. Modeling effectively stratifies the risk of graft loss in patients with cardiomyopathy and may be an adjunctive tool in allocation policies and center performance metrics.
Genes From a Translational Analysis Support a Multifactorial Nature of White Matter Hyperintensities
Authors: Lopez Lorna M. , Hill W. David , Harris Sarah E. , Valdes Hernandez Maria , Munoz Maniega Susana , Bastin Mark E. , Bailey Emma , Smith Colin , McBride Martin , McClure John , Graham Delyth , Dominiczak Anna , Yang Qiong , Fornage Myriam , Ikram M. Arfan , Debette Stephanie , Launer Lenore , Bis Joshua C. , Schmidt Reinhold , Seshadri Sudha , Porteous David J. , Starr John , Deary Ian J. , Wardlaw Joanna M.
Published: January 2015

Background and Purpose—

White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.

Methods—

We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke–prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE.

Results—

Of 126 spontaneously hypertensive stroke–prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (
AFP
,
ALB
,
GNAI1
,
RBM8a
, and
MRPL18
) were associated with both WMH volume and score (
P
<0.05); 2 of the 10 (
XPNPEP1
,
P
=6.7×10
−5
;
FARP1
,
P
=0.024) plus another spontaneously hypertensive stroke–prone rat gene (
USMG5
,
P
=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke–prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE’s genome-wide WMH associations on chromosomes 17 (
TRIM65
and
TRIM47
) and, for the first time, 1 (
PMF1
).

Conclusions—

Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia.
Curcuma arida and C. sahuynhensis, two new species from subgenus Ecomata (Zingiberaceae) from Vietnam
Authors: LEONG-ŠKORNIČKOVÁ JANA , LÝ NGỌC-SÂM , NGUYỄN QUỐC BÌNH
Published: January 2015

Two new Curcuma species are described and illustrated from Vietnam. They are compared to their closest allies from subgenus Ecomata. Curcuma arida from Núi Chúa National Park, Ninh Thuận Province, is compared to Curcuma pambrosima and C. vitellina, while Curcuma sahuynhensis from Quảng Ngãi Province is compared to Curcuma xanthella.
New synonyms and lectotypes in Aspicilia (Megasporaceae, Ascomycota)
Authors: Nordin Anders
Published: January 2015

The genus Aspicilia A.Massal. s.l. (Megasporaceae Pertusariales Ascomycota) has a worldwide distribution and the species are common components in the lichen vegetation on exposed rocks in a wide variety of biomes from hot deserts to Arctic tundras. The genus has a reputation of being taxonomically extremely complicated, which is partly caused by the extreme morphological variation and phenotypic plasticity of the species (Nordin 2013; Nordin et al. 2007, 2008, 2010; Owe-Larsson et al. 2008, 2011; Roux et al. 2011). The only existing taxonomic treatment of the genus with a wide scope was published by Magnusson (1939), who applied very narrow species circumscriptions in most cases. Here a number of new synonyms are presented and discussed, most of which are names introduced by Magnusson (loc. cit.), and lectotypes of Lecanora griseopallida and Sagedia laevata are designated.