bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory Tract Infection: A Risk Factor for the Onset and Relapse of Adult-Onset Minimal Change Disease in Southern China
Authors: Han Huanqin , Wang Shujun , Liang Yanting , Lin Jieping , Shi Lei , Ye Lin , Song Shiting , He Minjun , Li Shihao , Chen Futong , Pan Qingjun , Liu Hua-feng
Published: August 2018

Aims/Introduction. Steroid resistance and frequent relapse are problems in the treatment of minimal change disease (MCD). However, epidemiological factors that influence steroid-resistant and relapse of MCD are rarely reported. This study evaluated potential factors that influence the onset and relapse of MCD and the epidemiological features of southern Chinese patients with adult-onset MCD.Patients and Methods. Patients with adult-onset MCD were included from the Affiliated Hospital of Guangdong Medical University, which is located in the southernmost part of China’s mainland, between 2015 and 2016. Potential influencing factors were investigated.Results. Eighty-seven patients with incipient MCD were enrolled, and 85 of these patients were followed up; 71.8% (61/85) were steroid-sensitive and 28.2% (24/85) were steroid-resistant. In terms of seasonal distribution, the highest rate of incipient cases was in spring (39.1%, 34/87), which also showed a high rate of relapse cases (29.7%, 22/74). Among patients who were followed up for more than half a year and whose proteinuria completely resolved (69.4%, 59/85), 52.5% (31/59) were without relapse and 47.5% (28/59) were with relapse. Patients without relapse were older than those with relapse (P<0.05). Before disease onset, 20.7% (18/87) of patients with incipient MCD were diagnosed with infection, including 94.5% (17/18) with respiratory tract infection. Fourteen patients in complete remission posttreatment developed an infection before relapse, including 85.7% (12/14) with respiratory tract infection.Conclusion. Steroid resistance and frequent relapse are current challenges for the treatment of adult-onset MCD in southern China, and respiratory tract infection may be a risk factor for onset and relapse. Additionally, younger patients with MCD tend to have more frequent relapse.
Beacon-Based Time-Spatial Recognition toward Automatic Daily Care Reporting for Nursing Homes
Authors: Morita Tatsuya , Taki Kenta , Fujimoto Manato , Suwa Hirohiko , Arakawa Yutaka , Yasumoto Keiichi
Published: August 2018

As the world’s population of senior citizens continues to grow, the burden on the professionals who care for them (carers) is also increasing. In nursing homes, carers often write daily reports to improve the resident’s quality of life. However, since each carer needs to simultaneously care for multiple residents, they have difficulty thoroughly recording the activities of residents. In this paper, we address this problem by proposing an automatic daily report generation system that monitors the activities of nursing home residents. The proposed system estimates the multiple locations (areas) at which residents are situated with a BLE beacon, using a variety of methods to analyze the RSSI values of BLE signals, and recognizes the activity of each resident from the estimated area information. The information of the estimated activity of residents is stored in a server with timestamps, and the server automatically generates daily reports based on them. To show the effectiveness of the proposed system, we conducted an experiment for five days with four participants in cooperation with an actual nursing home. We determined the proposed system’s effectiveness with the following four evaluations: (1) comparison of performance of different machine-learning algorithms, (2) comparison of smoothing methods, (3) comparison of time windows, and (4) evaluation of generated daily reports. Our evaluations show the most effective combination pattern among 156 patterns to accurately generate daily reports. We conclude that the proposed system has high effectiveness, high usability, and high flexibility.
Analytical Assessment of the Effect of Vertical Ground Motion on RC Frames Designed for Gravity Loads with Various Geometric Configurations
Authors: Kim Siyun , Kim Sung Jig , Chang Chunho
Published: August 2018

The paper presents an analytical investigation of the effect of vertical ground motion on the selected 13 reinforced concrete (RC) frames with different geometric configurations. For this purpose, earthquake ground motions with various vertical‐to‐horizontal peak acceleration ratios are selected to which a suitable scale factor is applied to match with seismic hazards of Korea. The methodology involves the evaluation of the structural responses of RC frames subjected to the selected records by means of nonlinear time history analyses. The results from the analysis are compared with results from studies of the case of horizontal‐only excitation. The effect of the vertical earthquake component on damage of RC frames is considered at both the global and the local levels. The effect of vertical ground motion on axial force, shear demand, and shear capacity of RC columns is investigated to assess failure on a local level. In particular, the shear capacity is evaluated by using both the conservative method of a design code and more realistic predictive approaches. The results of the extensive analyses indicate that vertical ground motion can significantly affect the response of RC members in terms of axial force variation and shear capacity. These results point to the conclusion that vertical ground motion needs to be included in analysis for assessment and design.
Characteristics of Biodegradable Polylactide/Thermoplastic Starch/Nanosilica Composites: Effects of Plasticizer and Nanosilica Functionality
Authors: Jeziorska Regina , Szadkowska Agnieszka , Spasowka Ewa , Lukomska Aneta , Chmielarek Michal
Published: August 2018

The effect of plasticizer (polydimethylsiloxanol) and neat (SiO2) or modified (having amine functional groups) silica (A‐SiO2) on morphology, thermal, mechanical, and rheological properties of PLA/TPS blends compatibilized by maleated PLA (MPLA) was investigated. Toughened PLA/MPLA/TPS (60/10/30) blend containing 3 wt.% of plasticizer and various contents (1, 3, or 5 wt.%) of silica were prepared in a corotating twin‐screw extruder. From SEM, it is clear that plasticized PLA/MPLA/TPS blend continuous porous structure is highly related to the silica content and its functionality. The results indicate that polydimethylsiloxanol enhances ductility and the initial thermal stability of the plasticized blend. DSC and DMTA analyses show that nucleation ability and reinforcing effect of A‐SiO2 on plasticized blend crystallization are much better than those of SiO2. Silica practically had no effect on the thermo‐oxidative degradation. However, the composites with A‐SiO2 had better thermal stability than those with SiO2. Moreover, silica significantly improved the elongation at break.
Metronomic Chemotherapy with Vinorelbine Produces Clinical Benefit and Low Toxicity in Frail Elderly Patients Affected by Advanced Non-Small Cell Lung Cancer
Authors: D’Ascanio Michela , Pezzuto Aldo , Fiorentino Chiara , Sposato Bruno , Bruno Pierdonato , Grieco Alessio , Mancini Rita , Ricci Alberto
Published: August 2018

Background. Lung cancer is the leading cause of death worldwide. The treatment choice for advanced stage of lung cancer may depend on histotype, performance status (PS), age, and comorbidities. In the present study, we focused on the effect of metronomic vinorelbine treatment in elderly patients with advanced unresectable non-small cell lung cancer (NSCLC).Methods. From January 2016 to December 2016, 44 patients affected by non-small cell lung cancer referred to our oncology day hospital were progressively analyzed. The patients were treated with oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off. The patients were older than 60, stage IIIB or IV, ECOG PS ≥ 1, and have at least one important comorbidity (renal, hepatic, or cardiovascular disease). The schedule was based on ECOG-PS and comorbidities. The primary endpoint was progression-free survival (PFS). PFS was used to compare patients based on different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75 years old) as exploratory analysis. We also evaluated as secondary endpoint toxicity according to Common Toxicity Criteria Version 2.0.Results. Vinorelbine showed a good safety profile at different doses taken orally and was effective in controlling cancer progression. The median overall survival (OS) was 12 months. The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A significant difference in PFS was detected comparing patients aged below with those over 75, and the HR value was 0.72 (p<0.05). Not significant was the difference between groups with different schedules.Conclusions.This study confirmed the safety profile of metronomic vinorelbine and its applicability for patients unfit for standard chemotherapies and adds the possibility of considering this type of schedule not only for very elderly patients.
Experimental and FEM Investigation of Cob Walls under Compression
Authors: Quagliarini Enrico , Maracchini Gianluca
Published: August 2018

Earth has been used as construction material since prehistoric times, and it is still utilized nowadays in both developed and developing countries. Heritage conservation purposes and its intrinsic environmental benefits have led researchers to investigate the mechanical behaviour of this material. However, while a lot of works concern with rammed earth, CEB, and adobe techniques, very few studies are directed towards cob, which is an alternative to the more diffused rammed earth and adobe in specific geographic conditions. Due to this lack, this paper presents an experimental program aimed at assessing the failure mode and the main mechanical properties of cob earth walls (compressive strength, Young’s modulus, and Poisson’s ratio) through monotonic axial compression tests. Results show that, if compared with CEB, adobe, and rammed earth, cob has the lowest compressive strength, the lowest modulus of elasticity, and Poisson’s ratio. Differences are also found by comparing results with those obtained for other cob techniques, underlining both the high regional variability of cob and the need of performing more research on this topic. A strong dependence of material properties on loading rate and water content seems to exist too. Finally, the ability of a common analytical method used for masonry structures (an FEM macromodelling with a total strain rotating crack model) to represent the mechanical behaviour of cob walls is showed.
Protective Effects of Liu Wei Di Huang Wan on the Liver, Orbitofrontal Cortex Nissl Bodies, and Neurites in MSG+PH‐Induced Liver Regeneration Rat Model
Authors: Zhao Bin-Bin , Long Qing-hua , Wang Chao-yang , Chen Lin-lin , Xie Guang-jing , Bo Wen-ji , Xu Bo , Li Ze-fei , Li Han-Min , Wang Ping
Published: August 2018

Introduction. To examine the protective effects of Liu Wei Di Huang Wan formula (LWDH) on liver and orbitofrontal cortex (OFC) injuries in monosodium glutamate (MSG) and partial hepatectomy (PH) rat model. Methods. Neonatal Wistar rats were given MSG or saline on postnatal days 2, 4, 6, 8, and 10. The rats were caged into five groups and treated accordingly at six weeks old as follows: Saline group, Saline+PH group, MSG group, MSG+PH group, and LWDH group (MSG+PH+LWDH). The PH was performed during week 8 by excision of the left and median hepatic lobes (occupying about 68% of whole liver).On day 8 after the PH, the rats were subjected to an inner OFT before being sacrificed. The liver and OFC were stained using H&E, ORO, or Nissl staining. The expression of neurotrophic factors (β‐NGF, BDNF) was examined in the OFC lysates by ELISA. Serum levels of cytokines (IL‐1β, VEGF) were examined using the Bio‐Plex suspension array. Results. LWDH increased the total distance traveled by the animals (p<0.05), and LWDH improved the integrity of the Nissl bodies in the OFC (mean area of the Nissl bodies, p<0.01; mean diameter, p<0.05; mean density, p<0.05; and IOD, p<0.01). There were less white area in the liver (p>0.05) and decreased hepatic steatosis (p<0.01) in LWDH group. LWDH administration decreased the expression of serum levels of IL‐1β (p>0.05), while it increased VEGF (p>0.05) expression. LWDH administration increased the expression of BDNF (p>0.05) and β‐NGF (p>0.05) in the OFC, all as compared to the MSG+PH group. Conclusion. LWDH partly protected the animals from depressive‐like behaviors in the MSG+PH‐induced liver regeneration neonatal rat model. LWDH alleviated hepatic injury and steatosis and, furthermore, protected the Nissl body integrity and the growth of neurites.
Targeting STAT5 or STAT5-Regulated Pathways Suppresses Leukemogenesis of Ph+ Acute Lymphoblastic Leukemia
Authors: Minieri Valentina , De Dominici Marco , Porazzi Patrizia , Mariani Samanta A. , Spinelli Orietta , Rambaldi Alessandro , Peterson Luke F. , Porcu Pierluigi , Nevalainen Marja T. , Calabretta Bruno
Published: August 2018

Combining standard cytotoxic chemotherapy with BCR-ABL1 tyrosine kinase inhibitors (TKI) has greatly improved the upfront treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, due to the development of drug resistance through both BCR-ABL1–dependent and -independent mechanisms, prognosis remains poor. The STAT5 transcription factor is activated by BCR-ABL1 and by JAK2-dependent cytokine signaling; therefore, inhibiting its activity could address both mechanisms of resistance in Ph+ ALL. We show here that genetic and pharmacologic inhibition of STAT5 activity suppresses cell growth, induces apoptosis, and inhibits leukemogenesis of Ph+ cell lines and patient-derived newly diagnosed and relapsed/TKI-resistant Ph+ ALL cells ex vivo and in mouse models. STAT5 silencing decreased expression of the growth-promoting PIM-1 kinase, the apoptosis inhibitors MCL1 and BCL2, and increased expression of proapoptotic BIM protein. The resulting apoptosis of STAT5-silenced Ph+ BV173 cells was rescued by silencing of BIM or restoration of BCL2 expression. Treatment of Ph+ ALL cells, including samples from relapsed/refractory patients, with the PIM kinase inhibitor AZD1208 and/or the BCL2 family antagonist Sabutoclax markedly suppressed cell growth and leukemogenesis ex vivo and in mice. Together, these studies indicate that targeting STAT5 or STAT5-regulated pathways may provide a new approach for therapy development in Ph+ ALL, especially the relapsed/TKI-resistant disease.

Significance:Suppression of STAT5 by BCL2 and PIM kinase inhibitors reduces leukemia burden in mice and constitutes a new potential therapeutic approach against Ph+ ALL, especially in tyrosine kinase inhibitor-resistant disease. Cancer Res; 78(20); 5793–807. ©2018 AACR.
Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma
Authors: Braekeveldt Noémie , von Stedingk Kristoffer , Fransson Susanne , Martinez-Monleon Angela , Lindgren David , Axelson Håkan , Levander Fredrik , Willforss Jakob , Hansson Karin , Øra Ingrid , Backman Torbjörn , Börjesson Anna , Beckman Siv , Esfandyari Javanshir , Berbegall Ana P. , Noguera Rosa , Karlsson Jenny , Koster Jan , Martinsson Tommy , Gisselsson David , Påhlman Sven , Bexell Daniel
Published: August 2018

Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain underexplored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX–Avatar studies into preclinical cancer research.

Significance: These findings underpin the complexity of PDX modeling as a means to advance translational applications against neuroblastoma. Cancer Res; 78(20); 5958–69. ©2018 AACR.
Spatially Resolved Transcriptomics Enables Dissection of Genetic Heterogeneity in Stage III Cutaneous Malignant Melanoma
Authors: Thrane Kim , Eriksson Hanna , Maaskola Jonas , Hansson Johan , Lundeberg Joakim
Published: August 2018

Cutaneous malignant melanoma (melanoma) is characterized by a high mutational load, extensive intertumoral and intratumoral genetic heterogeneity, and complex tumor microenvironment (TME) interactions. Further insights into the mechanisms underlying melanoma are crucial for understanding tumor progression and responses to treatment. Here we adapted the technology of spatial transcriptomics (ST) to melanoma lymph node biopsies and successfully sequenced the transcriptomes of over 2,200 tissue domains. Deconvolution combined with traditional approaches for dimensional reduction of transcriptome-wide data enabled us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Our unsupervised analysis revealed a complex spatial intratumoral composition of melanoma metastases that was not evident through morphologic annotation. Each biopsy showed distinct gene expression profiles and included examples of the coexistence of multiple melanoma signatures within a single tumor region as well as shared profiles for lymphoid tissue characterized according to their spatial location and gene expression profiles. The lymphoid area in close proximity to the tumor region displayed a specific expression pattern, which may reflect the TME, a key component to fully understanding tumor progression. In conclusion, using the ST technology to generate gene expression profiles reveals a detailed landscape of melanoma metastases. This should inspire researchers to integrate spatial information into analyses aiming to identify the factors underlying tumor progression and therapy outcome.

Significance: Applying ST technology to gene expression profiling in melanoma lymph node metastases reveals a complex transcriptional landscape in a spatial context, which is essential for understanding the multiple components of tumor progression and therapy outcome. Cancer Res; 78(20); 5970–9. ©2018 AACR.
Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients
Authors: Tallón de Lara Paulino , Cecconi Virginia , Hiltbrunner Stefanie , Yagita Hideo , Friess Martina , Bode Beata , Opitz Isabelle , Vrugt Bart , Weder Walter , Stolzmann Paul , Felley-Bosco Emanuela , Stahel Rolf A. , Tischler Verena , Britschgi Christian , Soldini Davide , van den Broek Maries , Curioni-Fontecedro Alessandra
Published: August 2018

Purpose:

Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment.

Experimental Design:

We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options.

Results:

The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Furthermore, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two patients with mesothelioma, who were resistant to gemcitabine or anti-PD-1 as monotherapy.

Conclusions:

Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared with single treatment in the absence of steroids.
Simultaneous Resection for Synchronous Double Primary Cancers of the Pancreas and the Liver
Authors: Taniai Tomohiko , Haruki Koichiro , Shiba Hiroaki , Onda Shinji , Sakamoto Taro , Yanaga Katsuhiko
Published: August 2018

Simultaneous resection of synchronous hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) is extremely rare. Case 1 is a 64-year-old woman, who had undergone anterior resection for rectal cancer 3 years earlier was pointed out to have a cystic tumor in the pancreatic tail and a solitary tumor in the liver. CT revealed a hypovascular tumor in the pancreatic tail and a liver tumor with early enhancement. With a diagnosis of simultaneous HCC and PDAC, she underwent laparotomy, in which intraoperative frozen section examination of the liver was compatible with HCC. Therefore, she underwent hepatic resection as well as distal pancreatectomy and splenectomy. The patient received adjuvant chemotherapy with S-1 and remains well with no evidence of tumor recurrence as of 28 months after resection. Case 2 is a 73-year-old man with sustained viral response to antiviral treatment for hepatitis C virus, who was pointed out to have a tumor in the pancreatic head and a solitary tumor in the liver. Gadoxetic acid-enhanced MRI exhibited enhancement compatible with HCC. With a diagnosis of concomitant HCC and PDAC, surgery was performed. Intraoperative frozen section examination was compatible with HCC, for which a pancreaticoduodenectomy was performed. The patient received adjuvant chemotherapy with S-1 and remains well with no evidence of tumor recurrence as of 16 months after resection. In conclusion, we describe 2 cases of hepato-pancreatectomy for synchronous double primary cancers of the pancreas and the liver, where exclusion of the liver tumor as a metastatic lesion from the pancreatic cancer is important.
Feasibility Trial of the Newly Introduced Optical Enhancement Technology in Patients with Gastroesophageal Reflux Disease
Authors: Thomaidis Thomas , Rahman Fareed , Thieringer Florian , Tontini Gian E. , Mönkemüller Klaus , Ishaq Sauid , Galle Peter R. , Neumann Helmut
Published: August 2018

Background: Optical Enhancement technology (OE) combines bandwidth-limited light and image enhancement processing technology to enhance subtle mucosal and vascular details. This is the first study assessing the new technology for the diagnosis of gastroesophageal reflux disease (GERD). Patients and Methods: Consecutive patients with GERD and controls were prospectively included. The distal esophagus was examined in all quadrants with high definition white-light endoscopy (HD-WLE) followed by OE and biopsies for histopathological analysis. Features observed only by OE were compared between controls and patients with GERD. Results: A total of 100 areas were evaluated. About 56% of patients had a diagnosis of GERD. The mean age of patients was 53 years (range 27–89 years), 60% were female. Compared to controls, patients with diagnosis of GERD showed significantly more often tortuosity (p = 0.042), dilation (p = 0.0003), and increased number (p = 0.001) of intrapapillary capillary loops (IPCLs). In addition, increased vascularity and mucosal breaks were significantly more often found in patients with GERD as compared to controls (p < 0.05). On multivariate analysis, increased number and dilation of IPCL were the best predictors of GERD. Conclusions: The newly introduced OE technology significantly improves the diagnosis of GERD compared to HD-WLE. The results should be confirmed in a multicenter trial.
Melatonin Acts in Synergy with Hypothermia to Reduce Oxygen-Glucose Deprivation-Induced Cell Death in Rat Hippocampus Organotypic Slice Cultures
Authors: Carloni Silvia , Facchinetti Fabrizio , Pelizzi Nicola , Buonocore Giuseppe , Balduini Walter
Published: August 2018

Background: Hypoxic-ischemic encephalopathy is a major cause of neonatal morbidity. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Thus, adjunctive therapies, such as melatonin, are needed to provide additional neuroprotection. Objectives: The aim of this study was to determine a range of melatonin concentrations that could result in neuroprotective synergy with hypothermia. Methods: Hypoxia-ischemia was simulated by transient oxygen-glucose deprivation (OGD) in organotypic hippocampal slice cultures derived from neonatal rats. Cell damage was quantified by propidium iodide (PI) labeling. Results: Melatonin reduced OGD- induced cell death in a concentration-dependent manner (1–100 μM) with an EC50 of about 25 μM. Hypothermia attenuated cell death in a time-dependent manner, with a nearly full protection upon 24-h exposure (78%) and partial protection (40%) upon 6-h exposure. When submaximal effective concentrations of melatonin (25 or 50 μM, resulting in 54 and 64% protection) were combined with 6 h of hypothermia, nearly full protection (73 and 78%, respectively; p < 0.05 and p < 0.01) was observed. Conclusion: Melatonin acts in synergy with hypothermia in attenuating OGD-induced damage in organotypic hippocampal cultures. This reductionist approach allows the determination of a range of concentrations of melatonin capable of enhancing hypothermic neuroprotection. This information, coupled with pharmacokinetic data, will help to define the therapeutic dosage of melatonin in vivo and, ultimately, in patients.
Etiologies and Characteristics of Choroidal Neovascularization in Young Chinese Patients
Authors: Liu Bing , Zhang Xiongze , Peng Yuting , Mi Lan , Wen Feng
Published: August 2018

Purpose: To investigate the etiologies and characteristics of choroidal neovascularization (CNV) in young Chinese patients. Methods: A retrospective review of young Chinese patients (< 50 years of age) with CNV from January 2010 to June 2016 was performed. Results: Of the 501 patients (537 eyes) with CNV, 58.7% were female, and 7.2% had bilateral CNV. The mean age was 35 years. The etiologies were idiopathic CNV (ICNV, 43.9%), pathologic myopia (PM, 21.9%), punctate inner choroidopathy (PIC, 17.4%), polypoidal choroidal vasculopathy (4.4%), multifocal choroiditis with panuveitis (3.6%), and other disorders (8.8%). Five hundred and six CNVs (94.2%) showed a predominantly classic CNV composition on fundus fluorescein angiography (FFA) and 316 CNVs (96.6%) were type 2 CNV on optical coherence tomography (OCT). Conclusion: The etiologies of CNV in young Chinese patients were diverse, and ICNV, PM, and PIC were the three most common etiologies. Most CNVs were classic on FFA and type 2 on OCT.
Myope choroidale Neovaskularisation - die Motivation der Patienten nutzen
Authors: Feltgen Nicolas
Published: August 2018

Zweck: Mit der vorliegenden Studie sollten die 9-Jahres-Ergebnisse der Behandlung der myopen chorioidalen Neovaskularisation (mCNV) mit Ranibizumab als Monotherapie beurteilt werden. Methoden: Es handelt sich um eine retrospektive, nicht randomisierte Multicenterstudie zur Beurteilung der Langzeitergebnisse einer mindestens 9-jährigen Behandlung der mCNV mit Ranibizumab als Monotherapie gemäß einem streng bedarfsbasierten Therapieschema. Ergebnisse: In die Studie wurden 17 Augen von 17 Patienten (12 Frauen; Durchschnittsalter 57,9 ± 7,7 Jahre) eingeschlossen. Die mittlere Nachbeobachtungsdauer betrug 112,4 ± 3,9 Monate (Spanne: 108-120). Die mittlere Differenz in der bestkorrigierten Sehschärfe (BCVA) zwischen dem Ausgangswert und der letzten Nachuntersuchung lag bei +1,2 ± 15,6 ETDRS-Buchstaben (p = 0,004, Ausgangswert vs. 12 und 24 Monate). Die mittlere Gesamtzahl intravitrealer Injektionen bei jedem Patienten betrug 1,24 ± 1,70 pro Jahr (Spanne: 2-25). Während der 9-jährigen Nachbeobachtung wurden keine systemischen Nebenwirkungen im Zusammenhang mit der Arzneimitteltherapie beobachtet. Schlussfolgerungen: Die Langzeit-Monotherapie mit Ranibizumab bewirkt nach 9-jähriger Behandlung bei fast allen Augen eine gegenüber Studienbeginn unveränderte oder verbesserte BCVA.
Incidental Findings on Brain Magnetic Resonance Imaging in Preterm Infants
Authors: Buchiboyina Ashok , Yip Chi Seong Andrew , Madhala Sirisha , Patole Sanjay
Published: August 2018

Background: In recent years, many neonatal intensive care units have adopted the practice of routinely performing brain magnetic resonance imaging (MRI) of extremely preterm (EP) infants at term-equivalent age (TEA). This practice may result in increased identification of incidental findings (IF). Objectives: To determine the prevalence and clinical significance of incidental findings on routine MRI of EP infants. Methods: We retrospectively reviewed findings on routine brain MRI on 165 EP infants at TEA (gestation < 28 weeks) admitted between June 2015 and December 2017. Results: Incidental findings were detected in 16/165 (9.7%) infants. This included 9 cases that were clinically significant: 7 (with upper spinal cord abnormalities in 3, a choroid plexus lesion in 1, a pituitary abnormality in 1, and cerebral aqueduct narrowing in 2) required diagnostic intervention, and 2 (1 with an extramedullary arachnoid cyst and 1 with endolymphatic sac dilatation with a hypoplastic cochlear nerve) required diagnostic and therapeutic interventions. The incidental findings in the other 7 cases (a venous anomaly in 2, corpus callosum dysgenesis in 1, an absent septum pellucidum in 2, a frontal scalp mass in 1, and a nasal septum cyst in 1) were not clinically significant. Conclusions: Incidental findings were not uncommon on routine brain MRI of EP infants at TEA in our cohort. While most were clinically insignificant, some did require further diagnostic and therapeutic interventions. Prospective large studies on the prevalence and clinical significance of incidental findings on routine brain MRI of EP infants at TEA are required for developing evidence-based management plans and for counselling parents.
Arterial Pseudoaneurysm within a Pancreatic Pseudocyst
Authors: Phillip Veit , Braren Rickmer , Lukas Nikolaus , Schmid Roland M. , Geisler Fabian
Published: August 2018

The formation of pancreatic pseudocysts and (pseudo-)aneurysms of intestinal vessels are rare but life-threatening complications in acute and chronic pancreatitis. Here we report the rare case of a patient suffering from chronic pancreatitis with an arterial pseudoaneurysm within a pancreatic pseudocyst and present its successful therapeutic management by angioembolization to prevent critical bleeding. A 67-year-old male with a history of chronic pancreatitis presented with severe acute abdominal pain and vomiting to the emergency department. Seven weeks prior to the present admission, a CT scan had displayed a pancreatic pseudocyst with a maximum diameter of 53 mm. A laboratory examination revealed an elevated white blood cell count (15.40 × 103/μL), as well as elevated serum lipase (191 U/L), bilirubin (1.48 mg/dL), and blood glucose (353 mg/dL) levels. Sonographically, the previously described pancreatic pseudocyst revealed a slightly increased maximum diameter of 65 mm and an inhomogeneous echo of the cystic content. A contrast-enhanced CT scan showed a further increase in maximum diameter to 70 mm of the known pseudocyst. Inside the pseudocyst, a pseudoaneurysm originating from the splenic artery with a maximum diameter of 41 mm was visualized. After interdisciplinary consultation, prophylactic coil embolization of the splenic artery was immediately performed. The pseudoaneurysm was shut off from blood supply by back-door/front-door occlusion employing 27 coils, resulting in complete exclusion of the pseudoaneurysm from the circulation. Pseudoaneurysms are a rare complication of acute and chronic pancreatitis which has been shown to be efficiently treated by coil embolization.
Gastrointestinal Manifestations in Children with Primary Immunodeficiencies: Single Center: 12 Years Experience
Authors: Akkelle Bilge S. , Tutar Engin , Volkan Burcu , Sengul Ozlem K. , Ozen Ahmet , Celikel Cigdem A. , Ertem Deniz
Published: August 2018

Background: It has been reported that 5–50% of patients with primary immune deficiencies (PID) may present with or develop gastrointestinal (GI) manifestations. Objective: This study was aimed at analyzing GI and related endoscopic, histopathological findings in children with PID. Methods: Children with PID who were evaluated by endoscopy between 2005 and 2016 were enrolled in this study. Demographic data, growth parameters, signs and symptoms at diagnosis were obtained. Results: Of 425 children with PID, 195 had GI manifestations. Forty-seven of 195 children required endoscopic investigation, 30 (63.8%) were male, and the mean age was 7.7 ± 5 years. The rate of consanguinity was 61.7%, and the most common symptom was chronic diarrhea (57.4%). Seventy-two percent of the patients were malnourished. Giardia intestinalis was detected in 4, and Helicobacter pylori was confirmed in 8/45 (17.7%) patients. Non-celiac villous flatting was discovered in 15.5% of patients. Twelve patients were diagnosed as having immunodeficiency associated inflammatory bowel disease (IBD)-like colitis. Conclusions: PID may present with GI manifestations or develop during the course of the disease. Investigating immunodeficiency in patients with atypical GI symptoms can provide an appropriate therapeutic option, and an improved quality of life, particularly in populations with a high rate of consanguinity.
A Case of Focal Choroidal Excavation Development Associated with Multiple Evanescent White Dot Syndrome
Authors: Matsubara Hisashi , Uchiyama Eriko , Suzuki Katsuya , Matsuda Yoshito , Kondo Mineo
Published: August 2018

Focal choroidal excavation (FCE) is described as an excavated lesion of the choroid that can be detected by optical coherence tomography (OCT). While the exact pathogenesis of FCE remains unclear, it has been proposed in some cases that there is an association with the inflammation in the outer retina. We present a case of FCE development that was detected by spectral domain OCT (SD-OCT) and found to be associated with multiple evanescent white dot syndrome (MEWDS). A 40-year-old Japanese woman was diagnosed with MEWDS based on multiple white dots observed from the posterior pole to the midperiphery, along with yellow granularity in the fovea. SD-OCT revealed separation between the retinal pigment epithelium (RPE) and Bruch’s membrane (BM) and discontinuations of the ellipsoid zone, RPE, and BM. At 4 weeks after onset, several of the white dots disappeared, the yellow granularity in the fovea became small, and we detected nonconforming choroidal excavation under the central fovea. The choroidal excavation gradually deepened and changed to a conforming pattern. These findings suggest that the degree of the impairment caused by inflammation and the plasticity of the BM and RPE complex may be associated with different types of acquired FCE.
Mesenchymal Stem Cells Modified with Heme Oxygenase-1 Have Enhanced Paracrine Function and Attenuate Lipopolysaccharide-Induced Inflammatory and Oxidative Damage in Pulmonary Microvascular Endothelial Cells
Authors: Chen Xuxin , Zhang Yinliang , Wang Wenjing , Liu Zhenqian , Meng Jiguang  , Han Zhihai
Published: August 2018

Background/Aims: Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has therapeutic effects on endothelial damage during acute lung injury (ALI). Heme oxygenase-1 (HO-1) can restore homeostasis and implement cytoprotective defense functions in many pathologic states. Therefore, we explored whether transduction of HO-1 into BM-MSCs (MSCs-HO-1) would have an increased beneficial effect on lipopolysaccharide (LPS)-induced inflammatory and oxidative damage in human pulmonary microvascular endothelial cells (PVECs). Methods: MSCs were isolated from rat bone marrow and transfected with the HO-1 gene by a lentivirus vector. The phenotype and multilineage differentiation of MSCs were assessed. MSCs or MSCs-HO-1 were co-cultured with PVECs using a transwell system, and LPS was added to induce PVEC injury. The production of reactive oxygen species (ROS), and the activities of lipid peroxide (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in PVECs were determined by flow cytometry and colorimetric assays, respectively. The levels of human PVEC-derived tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the supernatants of the co-culture system, and the activity of nuclear transcription factor-κB and NF-E2-related factor 2 (Nrf2) in PVECs were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of TNF-α, IL-1β and IL-6 in PVECs was detected by quantitative real-time polymerase chain reaction (qRT-PCR), HO-1 expression and enzymatic activity in PVECs and the influence of zinc protoporphyrin (ZnPP) or HO-1 small interfering RNA on the above inflammatory and oxidative stress markers were evaluated. In addition, the expression of rat MSC-derived hepatocyte growth factor (HGF) and IL-10 was determined by ELISA and qRT-PCR. Results: MSCs showed no significant changes in phenotype or multilineage differentiation after transduction. LPS strongly increased the production of inflammatory and oxidative stress indicators, as well as decreased the levels of antioxidant components and the activity of Nrf2 in PVECs. MSC co-cultivation ameliorated these detrimental effects in PVECs and MSCs-HO-1 further improved the damage to PVECs induced by LPS when compared with MSCs alone. The beneficial effects of MSCs-HO-1 were dependent on HO-1 overexpression and may be attributed to the enhanced paracrine production of HGF and IL-10. Conclusion: MSCs-HO-1 have an enhanced ability to improve LPS-induced inflammatory and oxidative damage in PVECs, and the mechanism may be partially associated with the enhanced paracrine function of the stem cells. These data encourage further testing of the beneficial effects of MSCs-HO-1 in ALI animal models.
Particulate Matter Exposure During Perinatal Life Results in Impaired Glucose Metabolism in Adult Male Rat Offspring
Authors: Miranda Rosiane Aparecida , da Silva Franco Claudinéia Conationi , Previate Carina , Alves Vander Silva , Francisco Flávio Andrade , Moreira Veridiana Mota , de Moraes Ana Maria Praxedes , Gomes Rodrigo Mello , Picinato Maria Cecília , Natali Maria Raquel Marçal , de Freitas Mathias Paulo Cezar
Published: August 2018

Background/Aims: Particulate matter (PM) is an important risk factor for immunological system imbalance due to its small size, which can reach more distal regions of the respiratory tract, independently of its chemical composition. Some studies have suggested that PM exposure is associated with an increased incidence of diabetes, especially in industrialized urban regions. However, studies regarding the effects of PM exposure during perinatal life on glucose metabolism are limited. We tested whether exposure to PM from an urban area with poor air quality during pregnancy and lactation could cause short- and long-term dysfunction in rat offspring. Methods: Samples of < 10 µm PM were collected in an urban area of Cotonou, Benin (West Africa), and reconstituted in corn oil. Pregnant Wistar rats received 50 µg PM/day by gavage until the end of lactation. After birth, we analyzed the dams’ biochemical parameters as well as those of their male offspring at 21 and 90 days of age. Results: The results showed that PM exposure did not lead to several consequences in dams; however, the male offspring of both ages presented an increase of approximately 15% in body weight. Although the blood glucose levels remained unchanged, the insulin levels were increased 2.5- and 2-fold in PM exposure groups of both ages, respectively. HOMA-IR and HOMA-β were also increased at both ages. We also demonstrated that the number, islet area and insulin immunodensity of pancreatic islets were significantly increased at both ages from PM exposure. Conclusion: Our data show that chronic PM exposure by the oral route during perinatal life in rats leads to glucose dyshomeostasis in male offspring both in early and later life. Thus, we suggest that an ambience with poor air quality, mainly where traffic is dense, can contribute to an increase in metabolic disease incidence.
Sonographic Image of Solitary Kidney in Wilms Tumour Survivors
Authors: Kosiak Mateusz , Stefanowicz Joanna , Adamkiewicz-Drożyńska Elżbieta , Balcerska Anna , Kurylak Andrzej , Demidowicz Ewa
Published: August 2018

Background/Aims: This study presents an analysis of the sonographic and laboratory parameters of solitary kidney in Wilms tumour survivors (TWs) and compares these parameters with those of healthy individuals. Methods: Fifty-three TWs who completed treatment for Wilms tumour and 44 healthy individuals were enrolled. The study protocol consisted of completing a medical history, sonographic examination of the solitary kidney, estimation of glomerular filtration rate (eGFR) by the Schwartz or MDRD formulas, albumin urine excretion and BP measurement. Results: Sonographic signs of kidney damage were observed in 22 (41,5%) TWs. The most frequently detected abnormalities are hyperechoic rings around renal pyramids (28,3% TWs). Hypertrophy of the solitary kidney occurred in 71,7% of cases. The mean volume of the solitary kidney was 77% of the sum of the two kidney volumes in the control group. The median eGFR in the TWs group was 117 with 25Q-105,5, 75Q-130 ml/min/1,73 m2 vs 131,8 with 25Q-124, 75Q-140 ml/min/1,73 m2 in the control group (p=0,000). Six TWs (11,3%) had a value of eGFR below 90 ml/min/1,73 m2. Increased urine albumin excretion (> 30 mg/g) was observed in 7 TWs (13,2%) and in 3 (6,8%) individuals in the control group. Conclusion: Ultrasonographic abnormalities in solitary kidney of TWs are frequent. The most frequently detected abnormalities are hyperechoic rings around renal pyramids. Sonographic examination of TWs ought to be performed not only to detect tumour recurrence but also to assess the signs of kidney damage and their progression.
Central Aortic Systolic Blood Pressure Exhibits Advantages Over Brachial Blood Pressure Measurements in Chronic Kidney Disease Risk Prediction in Women
Authors: Zhang Linfeng , Wang Zhengwu , Chen Zuo , Wang Xin , Tian Ye , Shao Lan , Zhu Manlu
Published: August 2018

Background/Aims: To investigate whether the invasively obtained central aortic systolic blood pressure (CSBP) predicts chronic kidney disease (CKD) better than brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP) and brachial pulse pressure (PP) in the middle-aged Chinese population. Methods: A cross-sectional study was carried out across China in 2009-2010 among the subjects aged 35-64 years. CSBP was measured non-invasively by radial artery applanation tonometry B-pro (A-PULSE CASP and corresponding software). CSBP, SBP, DBP and PP were standardized with Z-score and the odds ratios were calculated with multivariable logistic regression model. Results: Data of 10197 participants were analyzed. The multivariable logistic regression after adjusting for possible confounders showed that a 1-standard deviation increment in each blood pressure measurement was associated with greater risk of CKD in both men and women (P < 0.05). The association of CSBP with CKD was stronger than SBP, DBP and PP in women, while in men the association of CSBP with CKD was stronger only than PP. With CSBP and SBP entering into the multivariable logistic regression models jointly, the odds ratio (95% confidence interval) for CSBP and SBP was 1.57 (1.39-1.79) and 1.22 (1.07-1.38) in women and 1.20 (1.03-1.39) and 1.48 (1.28-1.72) in men, respectively. With CSBP and DBP entering into the multivariable logistic regression models jointly, the odds ratio (95% confidence interval) for CSBP and DBP was 1.68 (1.52-1.84) and 1.15 (1.04-1.27) in women and 1.30 (1.15-1.46) and 1.45 (1.29-1.63) in men, respectively. With CSBP and PP entering into the multivariable logistic regression models jointly, the odds ratio (95% confidence interval) for CSBP and PP was 1.75 (1.58-1.94) and 1.06 (0.96-1.17) in women and 1.58 (1.41-1.77) and 1.04 (0.93-1.17) in men, respectively. Conclusion: CSBP and brachial blood pressure measurements are all predictors of CKD, however the non-invasively obtained CSBP may offer advantages over brachial blood pressure measurements in CKD risk prediction in women.
Prognostic Cardiovascular Markers in Chronic Kidney Disease
Authors: Chen Szu-Chia , Huang Jiun-Chi , Su Ho-Ming , Chiu Yi-Wen , Chang Jer-Ming , Hwang Shang-Jyh , Chen Hung-Chun
Published: August 2018

Chronic kidney disease (CKD), including end-stage renal disease (ESRD), is a public health issue worldwide, and is associated with high rates of morbidity and mortality. In addition, cardiovascular disease is a major cause of mortality in these patients. Both traditional and nontraditional risk factors associated with CKD can lead to remodeling of the myocardium and blood vessels, thereby resulting in cardiomyopathy, atherosclerosis and arterial stiffness. This can subsequently lead to ischemic heart disease, heart failure, cardiovascular death, rapid renal progression and progression to ESRD. Identifying these risk factors to allow for aggressive preventive and interventional strategies is important for the management of patients with CKD. This aim of this review was to survey the clinical outcomes of CKD using cardiac and vascular markers including echocardiographic parameters, systolic time intervals, electrocardiography, heart rate variability, ankle-brachial index, pulse wave velocity, differences between interarm and interankle blood pressure, and vascular calcification.
Additional information on Meloidogyne polycephannulata and its proposal as a junior synonym of M. incognita
Authors: Monteiro Jessica M.S. , Mattos Vanessa S. , Santos Marcilene F.A. , Gomes Ana C.M.M. , Correa Valdir R. , Sousa Daniela A. , Cares Juvenil E. , Pinheiro Jadir B. , Carneiro Regina M.D.G.
Published: August 2018

The type population ofMeloidogyne polycephannulatais synonymised withM. incognitabased on morphological and morphometric characters, as well as biochemical, molecular and phylogenetic studies. Morphological variability and a wide host range were reported forM. incognitaduring its first description and later re-description.Meloidogyne polycephannulatawas described in Brazil from specimens collected in a carrot field (type population). The esterase phenotype (Est) characterised for this species was identical to the phenotype Est I2 ofM. incognita, the most ubiquitous phenotype used for diagnostics. Morphological and morphometric characters of the descriptions of the two nominal species showed major similarities, as well as variability within the range of variation detected inM. incognita. In PCR assays, three SCAR markers species-specific forM. incognita(incK14 F/R, Mi/FR and incB06 F/R) amplified the same fragments of 399 bp, 955 bp and 1200 bp, respectively, for populations in both species. In phylogenetic studies based either on concatenated sequences of ITS1-5.8S-ITS2, D2-D3 rRNA, mitochondrialCOII regions or on RAPD and AFLP data, the populations of both species grouped in the same clade with high bootstrap support. Altogether, these results provide congruent evidence that theM. polycephannulatatype isolate deposited at the Embrapa Cryopreserved National Collection of Root-knot Nematodes is not a valid species but rather a junior synonym ofM. incognita.