bluuebunny/crossref_metadata_2025 huggingface dataset:
Squash Cytology of a Dural-Based High-Grade Chondrosarcoma May Mimic That of Glioblastoma in the Central Nervous System
Authors: Lee Sangho , Kim Na Rae , Chung Dong Hae , Yee Gi-Taek , Cho Hyun Yee
Published: June 2015

Background: Intracranial chondrosarcoma is rare, and most cases occur in the skull base. Intradural chondrosarcoma is even rarer. Case: Here, we describe a case of dural chondrosarcoma with a radiation history for nasopharyngeal carcinoma and a radical prostatectomy for prostatic cancer 15 and 8 years earlier, respectively. A 67-year-old man presented with a 3-week memory disturbance and dysarthria. Computed tomography and magnetic resonance images of the brain revealed a dural-based mass in the left temporal area. Under the impression of a glioblastoma, a resection and an intraoperative squash cytology were done. A necrotic dirty background as well as bluish-to-pinkish myxoid stroma were characteristic; the nuclei of highly pleomorphic tumor cells were hyperchromatic to vesicular with an occasional ground-glass appearance. The cytoplasm was of an eosinophilic hyalinized condensed morphology with an occasional granular appearance. Histologically, the lobulated mass was composed of hypercellular lobules of well-differentiated chondrocytes intermixed with anaplastic pleomorphic cells and diagnosed as a conventional grade III chondrosarcoma. These cells were immunoreactive for D2-40, S-100 protein and vimentin. Brain invasion was also found. Conclusion: Albeit rare, dural-based chondrosarcomas should be considered in the differential diagnosis for meningeal tumors, especially in the case of previous radiation therapy.
Haemodialysis Impairs the Human Microcirculation Independent from Macrohemodynamic Parameters
Authors: Meinders Arend-Jan , Nieuwenhuis Laurens , Ince Can , Bos Willem-Jan , Elbers Paul W.G.
Published: June 2015

Hemodynamic changes during haemodialysis are common. Often these changes are associated with symptoms that are thought to be the result of reduced microcirculatory blood flow and oxygen delivery. The microcirculatory effect of hemodialysis is scarcely researched, though of possible influence on patient outcome. New techniques have become available to visualise and analyse microvascular blood flow. We performed an observational study using Sidestream Dark Field imaging, a microscopic technique using polarised light to visualise erythrocytes passing through sublingual capillaries, to analyse the effect of haemodyalisis on central microvascular blood flow. We showed that there is a substantial impairment of microvascular blood flow and a discrepancy between micro- and macro-vascular parameters.
Congenital Middle Ear Anomalies: Anatomical and Functional Results of Surgery
Authors: Quesnel Stéphanie , Benchaa Tarik , Bernard Sophie , Martine François , Viala Paul , Van Den Abbeele Thierry , Teissier Natacha
Published: June 2015

The aim of this study was to describe the audiometric results following surgery in a consecutive series of pediatric patients with a congenital middle ear disorder. Retrospective chart review was performed for 29 consecutive children who underwent 33 middle ear surgeries for congenital ossicular chain anomaly between 1990 and 2012. Anomalies were classified into four groups according to the Teunissen and Cremers classification. Audiological parameters using four frequency averages (0.5, 1, 2 and 4 kHz) were assessed pre- and postoperatively. Clinical and audiometric follow-up times were, respectively, 49 ± 8 and 35 ± 5 months (mean ± SEM). Fifty-eight percent of all patients achieved an air-bone gap (ABG) ≤20 dB, 62.5% in class I, 50% in class II and 57.9% in class III. The improvement of the mean ABG was 13.6 dB, 19.2 dB for class I, 0.2 dB in class II and 15.4 dB in class III. Overall mean pure-tone averages improved 14.8 dB with 13.9 dB for class I; there was no improvement for class II and 20.2 dB for class III. The sensorineural hearing loss rate was 9%. This pediatric series showed that hearing results depend on type of anomaly. Class I and class III showed better hearing improvement than class II.
Effects of Hemoadsorption with a Novel Adsorbent on Sepsis: In vivo and in vitro Study
Authors: Zhang Jicheng , Peng Zhiyong , Maberry Donald , Volpe Jacob , Kimmel Jeremy D. , Federspiel William J. , Kellum John A.
Published: June 2015

Background/Aims: Hemoadsorption may improve outcomes for sepsis by removing circulating cytokines. We tested a new sorbent used for hemoadsorption. Methods: CTR sorbent beads were filled into columns of three sizes: CTR0.5 (0.5 ml), CTR1 (1.0 ml) and CTR2 (2.0 ml) and tested using IL-6 capture in vitro. Next, rats were subjected to cecal ligation and puncture and randomly assigned to hemoadsorption with CTR0.5, CTR1, CTR2 or sham treatment. Plasma biomarkers were measured. Results: In vitro, IL-6 removal was accelerated with increasing bead mass. In vivo, TNF, IL-6, IL-10, high mobility group box1, and cystatin C were significantly lower 24 h after CTR2 treatment. Seven-day survival rate was 50, 64, 63, and 73% for the sham, CTR0.5, CTR1, CTR2, respectively. Conclusion: CTR appeared to have a favorable effect on kidney function despite no immediate effects on cytokine removal. However, CTR2 beads did result in a late decrease of cytokines.
Adenoma of the Nonpigmented Ciliary Body and Iris Epithelium in Mexican Mestizo Patients
Authors: Serna-Ojeda Juan Carlos , Ariza-Camacho Enrique , Collado-Solórzano Alberto , Flores-Sánchez Blanca C. , Rodríguez-Reyes Abelardo A. , Fulda-Graue Emiliano
Published: June 2015

The adenoma of the nonpigmented ciliary epithelium is a benign rare tumor, which may present with different clinical characteristics and requires resection along with histopathologic analysis and the identification of specific immunohistochemical markers for an accurate diagnosis. Here, we report a case series of 4 patients in a Mexican mestizo population with this diagnosis, their clinical features, the ultrasound imaging characteristics and the histopathological and immunohistochemical findings.
Protein SYCP2 Is an Ancient Component of the Metazoan Synaptonemal Complex
Authors: Fraune Johanna , Alsheimer Manfred , Redolfi Josef , Brochier-Armanet Céline , Benavente Ricardo
Published: June 2015

During the first meiotic prophase, chromosome synapsis is mediated by the synaptonemal complex (SC), an evolutionarily conserved meiosis-specific structure. In mammals, 7 SC protein components have been identified so far. Despite some controversy in the past, we have shown that SC proteins are ancient in metazoans and very likely formed an ancestral SC structure in the ancestor of metazoans. Protein components SYCP1, SYCP3, SYCE2, and TEX12 were identified in basal-branching metazoans, while other components (SYCE1 and SYCE3) are more recent elements. However, the evolutionary history of mammalian SYCP2 is not known. Here, we investigated this aspect with the aid of bioinformatic tools as well as with RNA and protein expression analysis. We conclude that SYCP2 belongs to the group of ancient SC proteins that was already present in the common ancestor of metazoans more than 500 million years ago.
Remodeling of Cerebral Microcirculation after Ischemia-Reperfusion
Authors: Lapi Dominga , Colantuoni Antonio
Published: June 2015

Clinical and experimental studies have been focused on the pathophysiological mechanisms induced by brain ischemia-reperfusion injury. Recovery events, such as neurogenesis, angiogenesis and the growth of new blood vessels from the preexisting vascular tree, have been intensively studied in the last decades to clarify the vascular remodeling crucial for stroke outcome. This review aims to discuss the cerebral microcirculation remodeling induced by ischemia-reperfusion and the mechanisms involved in angiogenesis and vasculogenesis. The first in vivo observations were focused on anastomotic shunting of cerebral blood flow (CBF) in experimental and clinical models. Thereafter, vascular remodeling induced by cerebral ischemia-reperfusion was reported in mice and rats. Successively, other studies have assessed that within 30 days of middle cerebral artery (MCA) occlusion in rats, there is an increase in CBF and recovery from stroke. Recently, rats submitted to transient MCA occlusion showed pial microcirculation remodeling with the formation of new arterioles sprouting from penumbra vessels and overlapping the ischemic core. This review focuses on the production and/or activation of vasculotrophic factors able to trigger and facilitate microvascular remodeling. Vascular endothelial growth factor and endothelium-released nitric oxide appear to be the main factors involved in the formation of new vessels during microvascular remodeling. These studies are fundamental for consequent interventions on molecular targets, useful for fostering vascular remodeling and the recovery of functions.
Surfactant and Noninvasive Ventilation
Authors: Blennow Mats , Bohlin Kajsa
Published: June 2015

There is mounting evidence that early continuous positive airway pressure (CPAP) from birth is feasible and safe even in very preterm infants. However, many infants will develop respiratory distress syndrome (RDS) and require surfactant treatment. Combining a noninvasive ventilation approach with a strategy for surfactant administration is important to ensure optimal outcome, but questions remain about the optimal timing, mode of delivery and value of predictive tests for surfactant deficiency. Key findings in this review include the following: (1) a noninvasive ventilation strategy with CPAP from birth has a similar outcome to routine intubation in the delivery room; (2) prophylactic surfactant treatment has no advantage over early CPAP with selective surfactant administration; (3) surfactant during CPAP can be safely administered by rapid intubation-extubation (the INSURE method or via tracheal placement of a thin catheter), and (4) predictive tests for surfactant deficiency are being developed and might in future aid in directing surfactant treatment to infants at risk of developing severe RDS. A strategy for surfactant administration should be part of a noninvasive ventilation approach for preterm infants at risk of developing significant RDS. The different methods for surfactant administration during CPAP are reviewed here.
Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia
Authors: Baker Christopher D. , Abman Steven H.
Published: June 2015

Bronchopulmonary dysplasia (BPD), the chronic lung disease associated with preterm birth, results from the disruption of normal pulmonary vascular and alveolar growth. Though BPD was once described as primarily due to postnatal injury from mechanical ventilation and oxygen therapy after preterm birth, it is increasingly appreciated that BPD results from antenatal and perinatal factors that interrupt lung development in infants born at the extremes of prematurity. The lung in BPD consists of a simplified parenchymal architecture that limits gas exchange and leads to increased cardiopulmonary morbidity and mortality. This review outlines recent advances in the understanding of pulmonary vascular development and describes how the disruption of these mechanisms results in BPD. We point to future therapies that may augment postnatal vascular growth to prevent and treat this severe chronic lung disease.
The Story of Antenatal Steroid Therapy before Preterm Birth
Authors: Hallman Mikko
Published: June 2015

Antenatal glucocorticoid has proven to be one of the most successful single therapeutic approaches for preventing serious consequences after preterm birth. The fetal compartment is protected against endogenous corticosteroid by the high endogenous 11β-hydroxysteroid dehydrogenase type 2 that converts cortisol to cortisone and by the poor responsiveness of the fetal hypothalamus to corticotropin-releasing hormone. High corticosteroid activity acutely enhances the functional maturity of the fetus. Persistently high fetal glucocorticoid activity has adverse effects on the growth and differentiation of the fetal brain and other organs. Intrauterine growth restriction may be associated with high fetal glucocorticoid activity. Antenatal glucocorticoid therapy which is aimed to be given within 1-10 days before preterm birth is likely to increase the success of postnatal noninvasive treatments of very preterm infants.
Stem Cells for the Prevention of Neonatal Lung Disease
Authors: O'Reilly Megan , Thébaud Bernard
Published: June 2015

Preterm birth affects approximately 11% of all newborns worldwide and is a major risk factor for infant mortality and morbidity. A common complication of preterm birth is the chronic lung disease of prematurity called bronchopulmonary dysplasia (BPD). Due to the lack of a specific treatment for BPD, preterm infants surviving with BPD face a lifelong risk of poor lung health. The therapeutic potential of stem cells in regenerative medicine is being harnessed for many diseases, including BPD. Compelling preclinical data using stem cells to prevent/repair lung damage in animal models of experimental BPD has built the basis for its translation into the clinic in preterm infants. This review highlights the exciting translation from bench to bedside that will hopefully lead in the near future to improved pulmonary outcomes in preterm infants.
Hippocampal Subfield Atrophy in Multi-Domain but Not Amnestic Mild Cognitive Impairment
Authors: Eliassen Carl Fredrik , Selnes Per , Selseth Almdahl Ina , Reinvang Ivar , Fladby Tormod , Hessen Erik
Published: June 2015

Background/Aims: To investigate differences in hippocampal (HP) subfields and the adjoining perirhinal and entorhinal cortices (PRC and ERC) between amnestic mild cognitive impairment (aMCI) and multi-domain amnestic MCI (mdMCI) patients, and controls. Methods: Nineteen patients characterized as aMCI were compared with 24 mdMCI patients and 31 controls by means of an automatic HP segmentation procedure. Results: We found significant atrophy of the PRC and ERC in aMCI relative to controls, whereas a more pronounced pattern of atrophy in most subfields, including total HP volume, was found in the mdMCI group. The mdMCI group also had a significant cornu ammonis sector 4 region with dentate gyrus, subiculum and total HP atrophy relative to aMCI. Conclusion: The aMCI group showed atrophy in the PRC and ERC, whereas significantly more affection of the HP subfields was evident in mdMCI. The mdMCI group may thus represent clinical progression relative to aMCI coupled with HP subfield affection.
Hyperglycaemic Preterm Babies Have Sex Differences in Insulin Secretion
Authors: Dickson Jennifer L. , Chase J. Geoffrey , Pretty Christopher G. , Gunn Cameron A. , Alsweiler Jane M.
Published: June 2015

Background: Hyperglycaemia is a common complication of prematurity and is associated with neonatal mortality and morbidity, yet the aetiology is incompletely understood. C-peptide has been used in adults to estimate endogenous insulin secretion due to its simple clearance kinetics. Objective: To determine insulin secretion calculated from plasma C-peptide concentrations in hyperglycaemic preterm babies. Methods: This is a retrospective analysis of a cohort of 41 very preterm babies with a median gestational age of 27.2 weeks (26.2-28.7) enrolled in a randomised controlled trial of tight glycaemic control when they developed hyperglycaemia (2 consecutive blood glucose concentrations, BGC, > 8.5 mmol·l-1). Insulin secretion was determined using a steady state analysis of a 2-compartment C-peptide kinetic model. Results: BGC, plasma insulin concentration, plasma C-peptide concentrations, and insulin secretion were higher at randomisation than 1-2 weeks following randomisation (p ≤ 0.02). Insulin secretion was higher in girls at 11.7 mU·l-1·kg-1·min-1 (5.3-18.7) vs. 4.7 mU·l-1·kg-1·min-1 (2.1-8.3; p < 0.005), with no difference in clinical characteristics, BGC, plasma insulin concentration, or nutrition between the sexes (p > 0.25). Insulin secretion was lower in samples taken during exogenous insulin delivery at 3.7 mU·l-1·kg-1·min-1 (1.8-6.9) vs. 9.8 mU·l-1·kg-1·min-1 (4.7-17.8; p = 0.02). Conclusions: Insulin secretion was higher when babies had higher BGC, indicating that endogenous insulin secretion is sensitive to BGC. Girls had higher insulin secretion, at similar blood glucose and plasma insulin concentrations, than boys.
Increasing Water Intake in Chronic Kidney Disease: Why? Safe? Possible?
Authors: Clark William F. , Sontrop Jessica M. , Moist Louise , Huang S.-H.
Published: June 2015

Increased water intake may slow the progression of chronic kidney disease by lowering vasopressin levels. Prior to initiating a large randomized controlled trial on the effect of increased water intake on renal decline, we conducted a six-week pilot study to examine the safety and feasibility of asking adults with chronic kidney disease to increase their water intake. We randomly assigned 29 patients to either a hydration or a control group. The hydration group was asked to increase water intake by 1 to 1.5 l/day relative to their weight, gender, and 24 h urine osmolality, in addition to usual consumed beverages; the control group was asked to continue with usual fluid intake. After six weeks, the change in urine volume was significantly different between groups (0.9 l/day; p = 0.002) with no change in serum sodium and no serious adverse effects. Similarly, preliminary results of our large clinical trial of the same intervention (489 patients enrolled to date) demonstrated a significant separation between groups on 24 h urine volume (at 12 months the mean difference between groups was 1.2 l/day; p < 0.001) with no serious adverse effects. Serum sodium has remained stable in both groups over follow-up. To our knowledge, this trial is currently the largest of its kind to date; the significant separation between groups with respect to urine volume indicates that we will have scientifically reliable data on the effect of increased fluid intake on renal decline. The analysis of primary and secondary outcomes will be conducted at the conclusion of follow-up in July 2016.
Impact of a Water Intervention on Sugar-Sweetened Beverage Intake Substitution by Water: A Clinical Trial in Overweight and Obese Mexican Women
Authors: Hernández-Cordero Sonia , Popkin Barry M.
Published: June 2015

Background/Aims: Intense marketing for sugar-sweetened beverages (SSB) along with the human innate preference for sweet taste contributes to the increase in consumption of SSB. It is important to understand the intricacies of dietary intake and global changes to the food supply to understand the complexities facing any intervention promoting water intake. We describe challenges to promote and achieve an increase in water intake and present key findings from a clinical trial examining the effects of substituting water for SSB on triglyceride levels, weight and other cardiometabolic factors in overweight/obese Mexican women. Methods: A randomized trial was conducted in Cuernavaca, Mexico selecting overweight/obese (BMI ≥25 and <39 kg/m2) women (18-45 years old), reporting an intake of SSB of at least 250 kcal/day. Women were randomly allocated to the water and education provision (WEP) group (n = 120) or to the education provision (EP) group (n = 120). Repeated 24 h dietary recall questionnaires, anthropometry, and fasting blood levels were collected at baseline and 3, 6, and 9 months following the intervention. Results: There was no effect of the intervention on triglyceride concentration or on any of the studied outcomes. Post-hoc analyses according to weight at baseline show that triglyceride concentration decreased in obese women. Prevalence of metabolic syndrome after the intervention was lower in obese women from the WEP group. Conclusion: Water intake was increased but insufficient to achieve complete substitution of SSB, without effects on triglyceride concentration. Post-hoc analyses suggested that interventions lowered triglyceride concentration. Further studies are needed.
Acute Kidney Injury in Poor Countries Should No Longer Be a Death Sentence: The ISN ‘0 by 25' Project
Authors: Perico Norberto , Remuzzi Giuseppe
Published: June 2015

Acute kidney injury (AKI) is a common disorder throughout the world that is associated with severe morbidity, mortality and cost. Although deaths due to AKI occur in both high- and low- and middle-income countries (LMIC), the majority of avoidable deaths occur in LMIC nations. If managed adequately and in a timely fashion, the majority of these cases of AKI are preventable, treatable and often reversible with simple measures. AKI also has a major economic impact on healthcare expenditure. This is particularly true in poor countries where AKI especially impacts young productive people, imposing severe penury on their families. The International Society of Nephrology (ISN) has launched a long-term program, the ‘0 by 25' project, which advocates that zero people should die of untreated AKI in the poorest part of Africa, Asia and Latin America by 2025. The mission is to eventually lessen the high burden in terms of deaths consequent to this disorder in resource-poor regions worldwide. This is a challenging but potentially feasible and productive initiative that requires a broad vision about how the public and private sectors can work in partnership with the governments of the LMIC countries and leading nongovernmental organizations operating locally, to ensure sustainability of the 0 by 25 program and save many lives.
Factors Associated with Adverse Events during Tracheal Intubation in the NICU
Authors: Foglia Elizabeth E. , Ades Anne , Napolitano Natalie , Leffelman Jessica , Nadkarni Vinay , Nishisaki Akira
Published: June 2015

Background: The incidence of adverse tracheal intubation-associated events (TIAEs) and associated patient, practice, and intubator characteristics in the neonatal intensive care unit (NICU) setting are unknown. Objectives: To determine the incidence of adverse TIAEs and to identify factors associated with TIAEs in the NICU. Methods: Single-site prospective observational cohort study of infants who were intubated in a level 4 referral NICU between September 1, 2011 and November 30, 2013. A standardized pediatric airway registry was implemented to document patient, practice, and intubator characteristics and outcomes of intubation encounters. The primary outcome was adverse TIAEs. Results: Adverse TIAEs occurred in 153 of 701 (22%) tracheal intubation encounters. Factors that were independently associated with lower incidence of TIAEs in logistic regression included attending physician (vs. resident; odds ratio (OR) 0.4, 95% CI: 0.16, 0.98) and use of paralytic medication (OR 0.45, 95% CI: 0.25, 0.81). Severe oxygen desaturations (≥20% decrease in oxygen saturation) occurred in 51.1% of encounters and were more common in tracheal intubations performed by residents (62.8%), compared to fellows (43.2%) or attendings (47.5%; p = 0.008). Conclusions: Adverse TIAEs and severe oxygen desaturation events are common in the NICU setting. Modifiable risk factors associated with TIAEs identified include intubator training level and use of paralytic medications.
Two Cases of Acute Abdomen after an Intravitreal Injection of Bevacizumab
Authors: Onoda Yasutaka , Shiba Tomoaki , Hori Yuichi , Maeno Takatoshi , Takahashi Mao
Published: June 2015

We report on a patient with ischemic colitis and another with paralytic ileus, both of whom experienced an acute abdomen after intravitreal injection of bevacizumab (IVB). Case 1 was a 78-year-old woman. Her medical history included surgery for colon carcinoma 10 years earlier. The patient developed acute severe abdominal pain and nausea the day after IVB for retinal vein occlusion with macular edema, and massive lower gastrointestinal bleeding occurred. Ischemic colitis was diagnosed. Case 2 was a 64-year-old man who presented with neovascular glaucoma with proliferative diabetic retinopathy. We performed vitreous surgery on the 9th day after IVB, and we reperformed IVB at the end of the vitreous surgery. On the first postoperative day, severe abdominal distension, vomiting and abdominal pain were observed, and paralytic ileus was diagnosed. It is possible that gastrointestinal disorders are induced after IVB, depending on the patient's background, including for example severe diabetes or a history of surgery for gastrointestinal cancer. Thus, ophthalmologists should apply alternative therapies instead of IVB to patients with severe diabetes mellitus or a history of gastrointestinal cancer.
Pericardial Biopsy Revealed Gastric Signet-Ring Cell Cancer
Authors: Hashimoto Yu , Iwata Yoshifumi , Sangen Ryusho , Usuda Daisuke , Kanda Tsugiyasu , Sakamoto Daisuke , Takagi Shou , Sakamoto Shigeru
Published: June 2015

We describe the case of an 85-year-old man who presented with a large pericardial effusion. The patient was admitted because of anorexia and general malaise. Chest X-ray revealed an increased cardiothoracic ratio and a small amount of bilateral pleural effusion. Two-dimensional ultrasonographic echocardiography showed pericardial effusions with atrial and right ventricular early diastolic collapse, establishing the diagnosis of cardiac tamponade. Signet-ring cell cancer with pericardial involvement was diagnosed by subxiphoid pericardiostomy. The clear fluid was removed through pericardial drainage. The signet-ring cell carcinoma of the stomach was revealed by gastric fiberscope examination after pericardial biopsy proved malignancy. Virchow lymph node metastasis was also found. We diagnosed the patient with gastric cancer stage IV and suggested him the best supportive therapy. He died of cardiac arrest 1 month after best supportive care.
Effect of Preterm Birth on Postnatal Apolipoprotein and Adipocytokine Profiles
Authors: Hellgren Gunnel , Engström Eva , Smith Lois E. , Löfqvist Chatarina , Hellström Ann
Published: June 2015

Background: Critical metabolic changes preparing for ex utero life may occur at the fetal age of approximately 28-32 weeks, and preterm birth <28 weeks postmenstrual age (PMA) may affect these pathways. Children born <28 weeks often have poorer outcomes possibly due to a major shift in metabolism, including nutritional supply and a shift in lipid-transporting particles and lipid profile. This shift may occur in apolipoprotein and adipocytokine levels, which may influence metabolism. Objective: To determine whether there is a shift in apolipoprotein and adipocytokine levels in neonates born at a gestational age (GA) of 28 and 32 weeks, respectively. Methods: Blood samples from 47 infants (GA 32 weeks, n = 30 and GA 28 weeks, n = 17) were collected at birth and, in the GA28 group, also at PMA 32 weeks. Apolipoproteins A-1, A-2, B, C-2, C-3, and E were analyzed, as well as adiponectin and leptin levels. Results: Serum levels of apolipoproteins A-1, C-2, C-3, and E were lower at birth in the GA28 group compared to the GA32 group. Adiponectin and leptin levels were low at birth in the GA28 group. In the GA28 group 4 weeks after birth, leptin levels were still low, whereas adiponectin levels had increased to levels similar to those found at birth in the GA32 group. Apolipoprotein A-1, C-2, C-3, and E levels were negatively correlated with days receiving total parenteral nutrition. Conclusion: There are significant differences in apolipoprotein and adipocytokine levels, which can be associated with GA and birth weight. The impact of these changes on neonatal and future morbidity remains to be determined.
Comprehensive Analysis of Serum microRNAs in Autoimmune Pancreatitis
Authors: Hamada Shin , Masamune Atsushi , Kanno Atsushi , Shimosegawa Tooru
Published: June 2015

Background/Aims: Autoimmune pancreatitis (AIP) is a rare disease that has recently emerged as a unique type of pancreatitis with a presumed autoimmune etiology. MicroRNA (miRNA) is a small non-coding RNA that targets multiple mRNAs. miRNAs might exist in serum in a stabilized form, suggesting its potential application as a biomarker. We here examined the miRNA expression profile in the serum of patients with AIP. Methods: miRNAs were prepared from serum samples of patients with various pancreatic diseases (AIP (n = 3, each before and after the steroid therapy), chronic pancreatitis (n = 5), pancreatic cancer (n = 5)) or healthy controls (n = 5). A human miRNA Oligo chip containing approximately 2,000 miRNAs was used to identify differentially expressed miRNAs. Ingenuity Pathway Analysis (IPA) was used for the integrated analysis of altered miRNAs. Results: Microarray analysis identified miRNAs highly expressed in the serum of patients with AIP: 13 miRNAs vs. CP, 204 miRNAs vs. pancreatic cancer, and 19 miRNAs vs. healthy controls. miR-150-5p was commonly upregulated in AIP compared to the other samples. IPA revealed the most biological processes affected by the steroid therapy including cellular development, cellular growth, and cell movement. Conclusion: Our results identified that miRNAs were differentially expressed in the serum of AIP patients.
Radiological Position and Clinical Outcome of Preoperative Self-Expanding Metal Stents for Obstructing Colonic Cancer: A Single-Centre Cohort Study
Authors: van den Berg Eline H. , Bergmann Jilling F. , Ledeboer Michiel , van Dijk Rob A.J.M. , Bosker Robbert J.I. , ter Borg Frank
Published: June 2015

Background: Preoperative placement of self-expanding metal stents is used in patients with obstructing colon carcinoma to prevent an emergency operation. The perceived benefits remain the subject of discussion. The data-evaluating function and complications of stents in relation to radiological position are limited. Methods: Patients receiving a preoperative stent between 2003 and 2013 were retrospectively analysed in this single-centre study. We analysed radiological deployment, eccentricity and angulation of the stent directly after placement. Endpoints were clinical success (resolution of ileus), complications needing non-elective surgery (blow-out, perforation, persistent ileus, dislocation) and other complications (bleeding, infiltrate). Associations were corrected for other potential influences. Results: Eighty-two patients were included. In 22 patients (26.8%), the stent was placed proximal to the splenic flexure. Clinical success was present in 85.4%. Twenty-two patients (26.8%) had a complication of which 16 (19.5%) underwent urgent surgery for insufficient functioning of the stent; there were two blow-outs (2.4%). A more symmetrically placed stent was associated with clinical success (p = 0.042), with large overlap between groups. However, no association was found with non-elective surgery or complications. Also, angulation and deployment were unassociated with these outcomes. Conclusions: We could not establish an association between symmetry, angulation or deployment of self-expandable colonic stents with clinical success and complications.
Esophageal Ulcer as a Cause of Death: A Population-Based Study
Authors: Rantanen Tuomo K. , Sihvo Eero I.T. , Räsänen Jari V. , Hynninen Marja , Salo Jarmo A.
Published: June 2015

Background: This study aimed at defining the mortality and the nature of fatal complications that arise out of esophageal ulcer for one clearly defined geographical area. Methods: In this national, population-based study, the occurrence of fatal esophageal ulcer or ulcer requiring hospital treatment between January 1987 and December 2000 was assessed by the use of Finland's administrative databases. Medical records provided etiology of fatal ulcer and agonal symptoms. Results: Due to an esophageal ulcer, 2,242 patients received treatment in Finnish hospitals, at an annual frequency of 3.2/100,000. Ulcer with hemorrhage (53.5%), perforation (38.4%), or aspiration pneumonia (2.3%) was the cause of death in 86 patients for an annual mortality of 0.12/100,000. Based on the number of ulcers treated, 3.8% cases ended fatally. Gastroesophageal reflux disease (GERD) seemed to be the etiologic factor for ulcer in 68 (79.0%) patients. The most common agonal symptoms were hematemesis (41.8%), abdominal pain (25.6%), melaena (22.1%), and dyspnea (17.4%). Twenty (23.3%) patients were found dead at home. Conclusion: The rarity of the disease, related disorders, and the diversity of symptoms make the complicated esophageal ulcer a diagnostic challenge. Effective monitored treatment for severe GERD may be an important step to prevent fatal outcome.
Prevention and Treatment of Chemotherapy-Induced Neutropenia with the Biosimilar Filgrastim: A Non-Interventional Observational Study of Clinical Practice Patterns
Authors: Tesch Hans , Ulshöfer Thomas , Vehling-Kaiser Ursula , Ottillinger Bertram , Bulenda Dietmar , Turner Matthew
Published: June 2015

Background: Biosimilars are similar but non-identical versions of existing biological drugs. The HEXAFIL study was an observational study that assessed the clinical usage, safety and efficacy of the biosimilar filgrastim in routine clinical practice in Germany. Patients and Methods: A total of 1,337 cancer patients received the biosimilar filgrastim for primary prophylaxis (PP), secondary prophylaxis (SP) or interventional treatment (TX) plus chemotherapy. Data including neutropenic complications and adverse events (AEs) were documented for up to 3 consecutive cycles. Results: In cycle 1, 44.9% of the patients received the biosimilar filgrastim as PP, 31.0% as SP, and 23.6% as TX. Approximately 90% of the patients required no modifications to their chemotherapy regimen, with lower rates among the PP/SP versus the TX patients. Neutropenic complications occurred in 7.9%, 6.9%, and 3.9% of the patients (cycles 1, 2, and 3, respectively). Only 1.8% of the patients experienced febrile neutropenia during cycle 1. Earlier and longer filgrastim treatment reduced grade 3/4 leukopenia and neutropenic complications. The observed safety/tolerability profile was as expected; the most common AE (4.3%) was musculoskeletal back/bone pain. Conclusion: In this observational real-life study of clinical practice, the biosimilar filgrastim was effective and well tolerated, with results consistent with those reported in phase II and phase III trials.
Reference Intervals of Serum Procalcitonin Are Affected by Postnatal Age in Very Low Birth Weight Infants during the First 60 Days after Birth
Authors: Hahn Won-Ho , Song Joon-Hwan , Park Il-Sung , Kim Ho , Park Suyeon , Oh Myung-Ho
Published: June 2015

Background: Procalcitonin (PCT) may be a more sensitive marker for neonatal bacterial infections than C-reactive protein (CRP). However, the reference intervals of serum PCT were not sufficiently studied in neonates older than 1 week of age, especially for very low birth weight infants. Objectives: This study investigated the reference level of serum PCT for neonates according to gestational age (GA) and postnatal age (PNA). Methods: Serum PCT was measured in 914 blood samples from 7-60 days after birth in 415 neonates including 184 premature infants. Infants with sepsis, congenital anomaly, or clinically evident intra-amniotic infections were excluded. Multivariate analysis of covariance was used to detect the interaction between GA and PNA. To compare subgroups dichotomized by GA and PNA, analysis of covariance was performed with clinical parameters as covariates to obtain an adjusted p value. Results: Serum PCT levels were negatively correlated with GA, PNA, birth weight, birth height, and platelet count, and positively correlated with white blood cell count, absolute neutrophil count, hematocrit, and serum CRP after logarithmic transformation. Reference intervals of serum PCT were established according to GA and PNA. High PCT levels were found in infants with GA ≤32 weeks and PNA 7-30 days. Conclusion: The reference levels of serum PCT were determined according to GA and PNA. As the reference PCT levels of infants with GA ≤32 weeks were affected by PNA, cautious interpretation of PCT levels in these infants is warranted.
Regulation of B-Cell-Activating Factor Expression on the Basophil Membrane of Allergic Patients
Authors: Boita Monica , Heffler Enrico , Pizzimenti Stefano , Raie Alberto , Saraci Elona , Omedè Paola , Bussolino Claudia , Bucca Caterina , Rolla Giovanni
Published: June 2015

Background: To investigate the modulation of B-cell-activating factor (BAFF) expression on the basophil membrane of allergic patients. BAFF is an important regulator of B-cell activation, proliferation and immunoglobulin production, which may play a role in respiratory allergic diseases in promoting the production of IgE by B cells. Methods: Peripheral blood samples of 10 patients with allergic rhinitis, 3 with severe asthma and fungal sensitization (SAFS), 3 with allergic bronchopulmonary aspergillosis (ABPA) and 11 healthy controls were assessed regarding BAFF (CD257) expression using the basophil activation test before and after stimulation with IgE and allergens, as well IgE-independent stimuli, like fMLP, lipotheichoic acid from Staphylococcus aureus (LTA-SA) and lipopolysaccharide (LPS). Results: BAFF membrane expression did not change after IgE and allergen stimulation both in patients and controls, while it was upregulated by Aspergillus stimulation, both in sensitized patients and controls. In both patients and controls, BAFF expression was significantly upregulated following LTA-SA and β-1,3-glucan exposure (toll-like receptor-2 ligands), but not following LPS stimulation. Conclusions: Basophils from allergic and healthy subjects constitutively express membrane BAFF, which is not upregulated by IgE or specific allergens but by TLR-2 ligands (LTA-SA and β-1,3-glucan). Aspergillus fumigatus stimulation was able to upregulate BAFF expression on the basophils of sensitized asthmatic patients, but not via IgE-dependent mechanisms, since results did not differ between the patient and control groups. These findings suggest that basophils may contribute to the polyclonal production of IgE commonly observed in patients with SAFS and ABPA.
A Novel Multipeptide Microarray for the Specific and Sensitive Mapping of Linear IgE-Binding Epitopes of Food Allergens
Authors: Kühne Yvonne , Reese Gerald , Ballmer-Weber Barbara K. , Niggemann Bodo , Hanschmann Kay-Martin , Vieths Stefan , Holzhauser Thomas
Published: June 2015

Background: The identification of B-cell epitopes of food allergens can possibly lead to novel diagnostic tools and therapeutic reagents for food allergy. We sought to develop a flexible, low-tech, cost-effective and reproducible multipeptide microarray for the research environment to enable large-scale screening of IgE epitopes of food allergens. Methods: Overlapping peptides (15-mer, 4 amino acid offset) covering the primary sequence of either peanut allergen Ara h 1 or all 3 subunits of the soybean allergen Gly m 5 were simultaneously synthesized in-house on a porous cellulose matrix. Identical peptide microarrays created with up to 384 duplicate peptide-cellulose microspots each were investigated for specificity and sensitivity in IgE immunodetection and in direct experimental comparison to the formerly established SPOT™ membrane technique. Results: The in-house microarray identified with 98% reproducibility the same IgE-binding peptides as the SPOT™ membrane technique. Additional IgE-binding peptides were identified using the microarray. While the sensitivity was increased between 2- and 20-fold, the amount of human serum required was reduced by at least two thirds over the SPOT™ membrane technique using the microarray. After subtraction of the potential background, we did not observe non-specific binding to the presented peptides on microarray. Conclusions: The novel peptide microarray allows simple and cost-effective screening for potential epitopes of large allergenic legume seed storage proteins, and it could be adapted for other food allergens as well, to study allergenic epitopes at the individual subject level in large paediatric and adult study groups of food allergic subjects.
Modulation of the Association between the PEPD Variant and the Risk of Type 2 Diabetes by n-3 Fatty Acids in Chinese Hans
Authors: Zheng Ju-Sheng , Huang Tao , Li Kelei , Chen Yanqiu , Xie Hua , Xu Danfeng , Sun Jianqin , Li Duo
Published: June 2015

Background/Aims: Type 2 diabetes (T2D) is modulated by the interactions between genetic and dietary factors. This study sought to examine whether the associations of genome-wide association study (GWAS)-identified genetic variants with T2D risk were modulated by n-3 fatty acids in Chinese Hans. Methods: Six hundred and twenty-two T2D patients and 293 healthy controls were recruited. Erythrocyte phospholipid fatty acids were measured by standard methods. Nine GWAS-identified T2D-related single-nucleotide polymorphisms (SNPs) were genotyped. These SNPs were all identified in GWAS of Asian populations with a high minor allele frequency (>0.2). Results: Among the 9 SNPs, only rs3786897 at PEPD (peptidase D) showed a significant interaction with n-3 fatty acids (pinteraction after Bonferroni correction = 0.027). The rs3786897 A allele was associated with a higher risk of T2D [GA+AA vs. GG: odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.32-3.55] when n-3 fatty acids were lower than the population median, but no significant association (GA+AA vs. GG: OR = 0.63, 95% CI 0.35-1.12) was observed when n-3 fatty acids were higher than the median. Conclusions: The association between the PEPD genetic variant and the risk of T2D was modulated by n-3 fatty acids. Higher n-3 fatty acids may abolish the adverse effect of the risk allele at PEPD for T2D.
Pure Laparoscopic Hepatectomy Combined with a Pure Laparoscopic Pringle Maneuver in Patients with Severe Cirrhosis
Authors: Miyagi Shigehito , Nakanishi Chikashi , Kawagishi Naoki , Kamei Takashi , Satomi Susumu , Ohuchi Noriaki
Published: June 2015

Laparoscopic hepatectomy is a standard surgical procedure. However, it is difficult to perform in patients with severe cirrhosis because of fibrosis and a high risk of hemorrhage. We report our recent experience in five cases of pure laparoscopic hepatectomy combined with a pure laparoscopic Pringle maneuver in patients with severe cirrhosis. From 2012 to 2014, we performed pure laparoscopic partial hepatectomy in five patients with severe liver cirrhosis (indocyanine green retention rate at 15 min [ICG R15] >30% and fibrosis stage f4). A pure laparoscopic Pringle maneuver was employed in all patients. We investigated operative time, blood loss, duration of hospitalization and the days when discharge was possible, and compared these findings with those of patients with a normal liver (ICG R15 <10%, f0) who underwent pure laparoscopic partial hepatectomy during the same period (n = 7). As a result, operative time, blood loss, duration of hospitalization and the days when discharge was possible were similar in patients with cirrhosis undergoing pure laparoscopic hepatectomy combined with a pure laparoscopic Pringle maneuver to those in patients with a normal liver undergoing pure laparoscopic partial hepatectomy. In conclusion, pure laparoscopic hepatectomy combined with a pure laparoscopic Pringle maneuver appears to be safe in patients with severe cirrhosis.
Behavioural Repertoires and Time Budgets of Semi-Free-Ranging and Captive Groups of Wedge-Capped Capuchin Monkeys, Cebus olivaceus, in Zoo Exhibits in Venezuela
Authors: Tárano Zaida , López Marie Charlotte
Published: June 2015

The behavioural repertoires and time budgets of 2 captive groups and 1 semi-free-ranging group of Cebus olivaceus were determined with the aim to assess the impact of the zoo environment on behaviour. The repertoires were qualitatively similar between groups and to those reported for wild troops, but the captive groups showed self-directed and stereotyped behaviours not reported in the wild. The differences in repertoires between groups were easily associated with the opportunity to interact directly with the visitors, with particularities of the enclosure and with the severity of confinement. Overall, females spent more time foraging than males in the 2 captive groups, and adults rested and watched more than subadults in all the groups. Time budgets were dominated by foraging, resting, movement and affiliative interactions, but their relative importance varied between groups, with foraging being especially prominent in the most confined group. The time budgets also varied qualitatively from those reported for wild troops. We conclude the species is behaviourally able to adjust to captivity, but the slight differences along the continuum from wild to semi-free to captive are suggestive of mild stress or social tension probably due to unstimulating environmental conditions, high visitor pressure and deviations from typical sex-age group composition.
Numbers of CD8+PD-1+ and CD4+PD-1+ Cells in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Are Independent of Binet Stage and Are Significantly Higher Compared to Healthy Volunteers
Authors: Novák Martin , Procházka Vit , Turcsányi Peter , Papajík Tomáš
Published: June 2015

The programmed cell death pathway is involved in functional impairment of cytotoxic CD8+ T cells in chronic viral infection and in tumor immune evasion. The interaction of programmed cell death-1 (PD-1) with its ligand suppresses antitumor T cell function and stimulates the regulatory T cell population. The objectives were to investigate whether examining PD-1 expression in peripheral T cells of patients with chronic lymphocytic leukemia (CLL) reflected the disease phase and Binet stage and to compare the results with those in healthy volunteers. The study analyzed peripheral blood from previously untreated patients with CLL, patients with relapsed or refractory disease under treatment and healthy blood donors using flow cytometry. PD-1 expression in peripheral blood CD4+ and CD8+ cells was markedly different between disease stages and in comparison with healthy subjects. The highest numbers of both CD8+PD-1+ and CD4+PD-1+ cells were present in patients with relapsed/refractory disease. No distinct difference according to Binet stage was found. These facts support the hypothesis that tumor clones may switch effector CD8+ cells through the PD-1/PD-1L pathway into an immunotolerant state. The extent to which the mechanisms of antitumor immunity are influenced by enhanced expression of the programmed cell death depends on the disease phase but not Binet stage.
Use of Leflunomide in Renal Transplant Recipients with Ganciclovir-Resistant/Refractory Cytomegalovirus Infection: A Case Series from the University of Chicago
Authors: Chon W. James , Kadambi Pradeep V. , Xu Chang , Becker Yolanda T. , Witkowski Piotr , Pursell Kenneth , Kane Brenna , Josephson Michelle A.
Published: June 2015

Introduction: Although antiviral prophylaxis for cytomegalovirus (CMV) is widely used, CMV infection remains common in renal transplant recipients with adverse consequences. Methods: We report 5 cases of renal transplant recipients with resistant CMV infection who were successfully managed with leflunomide at the University of Chicago Medical Center. Results: Five renal transplant recipients (2 simultaneous pancreas/kidney transplants, 3 deceased donor kidney transplants) were diagnosed with GCV-resistant CMV infection from 2003 to 2011. Of the 4 patients who had resistance genotype testing, 3 showed a UL97 mutation and 1 patient had a clinically resistant CMV infection. All patients received CMV prophylaxis with valganciclovir for 3 months. The number of days from the date of transplant to viremia ranged from 38 to 458 days (median 219). All 5 patients received other antiviral agents (e.g. ganciclovir, foscarnet), and in 4 patients, viremia was cleared before leflunomide was initiated as consolidation (or maintenance) therapy. Conclusion: Leflunomide was well tolerated and successful in preventing recurrence of viremia in renal transplant recipients with resistant CMV infection. The beneficial effect of leflunomide in this setting warrants further investigation.