bluuebunny/crossref_metadata_2025 huggingface dataset:
IL10 Release upon PD-1 Blockade Sustains Immunosuppression in Ovarian Cancer
Authors: Lamichhane Purushottam , Karyampudi Lavakumar , Shreeder Barath , Krempski James , Bahr Deborah , Daum Joshua , Kalli Kimberly R. , Goode Ellen L. , Block Matthew S. , Cannon Martin J. , Knutson Keith L.
Published: October 2017

Ligation of programmed cell death-1 (PD-1) in the tumor microenvironment is known to inhibit effective adaptive antitumor immunity. Blockade of PD-1 in humans has resulted in impressive, durable regression responses in select tumor types. However, durable responses have been elusive in ovarian cancer patients. PD-1 was recently shown to be expressed on and thereby impair the functions of tumor-infiltrating murine and human myeloid dendritic cells (TIDC) in ovarian cancer. In the present work, we characterize the regulation of PD-1 expression and the effects of PD-1 blockade on TIDC. Treatment of TIDC and bone marrow–derived dendritic cells (DC) with IL10 led to increased PD-1 expression. Both groups of DCs also responded to PD-1 blockade by increasing production of IL10. Similarly, treatment of ovarian tumor–bearing mice with PD-1 blocking antibody resulted in an increase in IL10 levels in both serum and ascites. While PD-1 blockade or IL10 neutralization as monotherapies were inefficient, combination of these two led to improved survival and delayed tumor growth; this was accompanied by augmented antitumor T- and B-cell responses and decreased infiltration of immunosuppressive MDSC. Taken together, our findings implicate compensatory release of IL10 as one of the adaptive resistance mechanisms that undermine the efficacy of anti–PD-1 (or anti–PD-L1) monotherapies and prompt further studies aimed at identifying such resistance mechanisms. Cancer Res; 77(23); 6667–78. ©2017 AACR.
Genomic Gain of 16p13.3 in Prostate Cancer Predicts Poor Clinical Outcome after Surgical Intervention
Authors: Bramhecha Yogesh M. , Guérard Karl-Philippe , Rouzbeh Shaghayegh , Scarlata Eleonora , Brimo Fadi , Chevalier Simone , Hamel Lucie , Dragomir Alice , Aprikian Armen G. , Lapointe Jacques
Published: October 2017

Identifying tumors with high metastatic potential is key to improving the clinical management of prostate cancer. Recently, we characterized a chromosome 16p13.3 gain frequently observed in prostate cancer metastases and now demonstrate the prognostic value of this genomic alteration in surgically treated prostate cancer. Dual-color FISH was used to detect 16p13.3 gain on a human tissue microarray representing 304 primary radical prostatectomy (RP) cases with clinical follow-up data. The results were validated in an external dataset. The 16p13.3 gain was detected in 42% (113/267) of the specimens scorable by FISH and was significantly associated with clinicopathologic features of aggressive prostate cancer, including high preoperative PSA (P = 0.03) levels, high Gleason score (GS, P < 0.0001), advanced pathologic tumor stage (P < 0.0001), and positive surgical margins (P = 0.009). The 16p13.3 gain predicted biochemical recurrence (BCR) in the overall cohort (log-rank P = 0.0005), and in subsets of patients with PSA ≤10 or GS ≤7 (log-rank P = 0.02 and P = 0.006, respectively). Moreover, combining the 16p13.3 gain status with standard prognostic markers improved BCR risk stratification and identified a subgroup of patients with high probability of recurrence. The 16p13.3 gain status was also associated with an increased risk of developing distant metastases (log-rank P = 0.03) further substantiating its role in prostate cancer progression.

Implications: This study demonstrates the prognostic significance of the 16p13.3 genomic gain in primary prostate tumors, suggesting potential utility in the clinical management of the disease by identifying patients at high risk of recurrence who may benefit from adjuvant therapies. Mol Cancer Res; 16(1); 115–23. ©2017 AACR.
Readmissions and Emergency Department Visits after Bariatric Surgery at Saudi Arabian Hospital: The Rates, Reasons, and Risk Factors
Authors: Ahmed Anwar , AlBuraikan Doaa , ALMuqbil Bashayr , AlJohi Wijdan , Alanazi Wala , AlRasheed Budor
Published: October 2017

Background: Saudi Arabian hospital readmissions and emergency department (ED) visits following bariatric surgery and discharge have never been investigated. This study aimed to evaluate the rates and reasons of hospital readmissions and ED visits related to surgical weight loss interventions at the King Abdulaziz Medical City - Riyadh. Methods: We conducted a retrospective cohort study on 301 patients who underwent bariatric surgery between January 2011 and July 2016. We reviewed patient medical records progressively to assess hospital readmission, ED visits, and complications. Results: Of the 301 patients analyzed, 67.1% were female and 93% had class II obesity. The readmission rate, ED visit rate after discharge and the rate of either of the two was 8%, 14%,and 18.3%, respectively. The most common causes of readmission were abdominal pain (37.5%), nausea/vomiting (29.2%), and site leak (25%), while the most common causes of ED visits were abdominal pain (59.5%) and nausea/vomiting (16.9%). Readmission rates tended to be higher in older patients (age of patients readmitted 42 ± 12.1 years vs. age of patients not readmitted 34.3 ± 11.8 years; p = 0.002). The rate of readmission tends to increase in patients with overweight or class I obesity (odds ratio (OR) = 20.15), diabetes (OR = 14.82), and obstructive sleep apnea (OR = 14.29). Dyslipidemia was positively associated with ED visits (p = 0.027, OR = 2.87). The rate of readmission or ED visits increased with age, while there were decreases in readmission and ED visits for those who had received gastric sleeve surgery. Conclusions: The study reported high rates of readmission and ED visits, thus the effectiveness of different types of weight loss surgeries should be further evaluated, particularly in individuals with complicated medical issues such as diabetes, dyslipidemia, and obstructive sleep apnea.
Combined Ayurveda and Yoga Practices for Newly Diagnosed Type 2 Diabetes Mellitus: A Controlled Trial
Authors: Datey Purnima , Hankey Alex , Nagendra H.R.
Published: October 2017

Background: The increasing prevalence of type 2 diabetes in India is a cause for national concern, particularly the spiraling cost burden to the country. As one approach to stop its increase, Yoga medicine has been widely implemented, finding popularity with all social strata. Here, we report a study suggesting that treatment with fresh herbal juices and Yoga can improve the levels of blood glucose and hemoglobin A1c (HbA1c) in people with pre-diabetes. Methods: Study design: 3-arm controlled trial 3 months in duration. Participants: 157 male prisoners with newly diagnosed, high fasting blood sugar (FBS) and postprandial blood sugar (PPBS) levels. Group interventions: (1) Rasahara and Yoga, (2) Yoga, (3) no intervention. Assessments: FBS and PPBS levels were measured every 2 weeks; HbA1c and blood lipids were determined pre- and post-intervention. Results: Significant decreases occurred in the FBS (-21.13 ± 21.16 mg/dl) and PPBS levels (-15.02 ± 14.89 mg/dl) in group 1 (both p < 0.0001) and in the FBS level (20.62 ± 32.68 mg/dl) in group 2 (p = 0.0005), while the increases in group 3 attained significance only for the PPBS level (9.62 ± 21.83 mg/dl) (p = 0.0022). Observed changes in HbA1c were: group 1, -0.044 ± 0.059 mg/dl; group 2, +0.024 ± 0.456 mg/dl (not significant); and group 3, +0.365 ± 0.369 mg/dl (p < 0.0001). Conclusions: This study of Yoga for the treatment of diabetes shows that all male prisoners could benefit from the Yoga prison programs. Addition of Yoga programs to state and federal activities at all levels is now national policy in India. Follow-up studies should be carried out to obtain more robust results.
Uma Revisão Sistemática de Instrumentos sobre Qualidade de Vida em Pessoas Idosas após Implante Coclear
Authors: Brandão Maria Piedade , Rebelo Cristiana
Published: October 2017

Introdução: A deficiência auditiva é um problema particular de saúde que afeta mais de 275 milhões de pessoas em todo o mundo e é o défice sensorial mais comum nas pessoas idosas. O objetivo deste estudo foi identificar os instrumentos para avaliar a qualidade de vida em pessoas idosas com deficiência auditiva submetidas ao implante coclear e rever os estudos que incluem a avaliação da qualidade de vida na sua relação com a especificidade da deficiência auditiva pós-lingual sensorioneural severa a profunda bilateral nessa população. Métodos: Foi conduzida uma revisão sistemática da literatura entre Janeiro de 1900 e Junho de 2012. Instrumentos validados e usados em pessoas com 65 anos de idade ou mais, com deficiência auditiva pós-lingual, sensorioneural severa a profunda, que tivessem sido sujeitas a implante coclear, foram revistos. A pesquisa bibliográfica foi limitada a estudos escritos em língua inglesa. Resultados: A revisão identificou um total de sete instrumentos validados. Destes, um foi especialmente desenhado para avaliar o impacto do implante coclear e seis para as condições gerais das pessoas com deficiência auditiva. A qualidade metodológica de todos os artigos foi avaliada segundo as recomendações de STROBE e todos os artigos foram classificados na categoria B. Conclusões: Os resultados desta revisão sistemática podem ajudar os profissionais de saúde e os investigadores a selecionarem os instrumentos mais apropriados para avaliar as mudanças na qualidade de vida dos idosos com implantes cocleares.
Retrospective Analysis of CA19-9 Decrease in Patients with Metastatic Pancreatic Carcinoma Treated with FOLFIRINOX or Gemcitabine in a Randomized Phase III Study (ACCORD11/PRODIGE4)
Authors: Robert Marie , Jarlier Marta , Gourgou Sophie , Desseigne Françoise , Ychou Marc , Bouché Olivier , Juzyna Beata , Conroy Thierry , Bennouna Jaafar
Published: October 2017

Objectives: Carbohydrate antigen 19-9 (CA19-9) is a sensitive and specific serum marker in pancreatic cancer. Our retrospective analysis aims to evaluate CA19-9 decrease in patients with metastatic pancreatic cancer treated in ACCORD11/PRODIGE4 (FOLFIRINOX vs. gemcitabine). Methods: A total of 342 patients were treated. CA19-9 was measured at 8 weeks (±2) in 160 patients from a total of 282 with abnormal CA19-9 values at baseline (gemcitabine arm, n = 75; FOLFIRINOX arm, n = 85). In the present study, 8-week CA19-9 decrease or greater CA19-9 decrease according to the 20 and 90% thresholds were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated in each subgroup. Results: In the FOLFIRINOX arm, patients with an 8-week CA19-9 decrease or greater CA19-9 decrease ≥20% showed improved median OS, PFS, and objective response rate. In the overall study population, median OS and PFS were significantly improved in patients with an 8-week CA19-9 decrease ≥20% (vs. <20%). The 8-week CA19-9 decrease was predictive of PFS (interaction test significant according to treatment arm; p = 0.006). Conclusion: An 8-week CA19-9 decrease ≥20% is a prognostic factor for OS and PFS. The 8-week CA19-9 decrease (20% threshold) is predictive of PFS. It could help to evaluate the efficacy of FOLFIRINOX and gemcitabine regimens.
Changes in the Uterine Scar during the First Year after a Caesarean Section: A Prospective Longitudinal Study
Authors: van der Voet Lucy F. , Jordans Inge P.M. , Brölmann Hans A.M. , Veersema Sebastiaan , Huirne Judith A.F.
Published: October 2017

Aim: To study changes in a ceasarean section (CS) scar during the first year after a CS using gel installation sonography (GIS). Methods: Proof-of-concept study, prospective cohort study. Twenty women who delivered by their first CS were evaluated by both transvaginal sonography and GIS 2 months and 1 year after CS. A niche was defined as an anechogenic space at the uterine caesarean scar with a depth >2 mm. The primary outcome was any change in the thickness of the residual myometrium (RMT) as evaluated by GIS. Results: Mean RMT changed in time from 11.9 mm at 2 months to 6.5 mm at 12 months after the CS (p < 0.001). Niche prevalence did not change. The adjacent myometrium (AM) reduced from 15 to 12.4 mm (p = 0.04). The ratio between RMT and AM with GIS decreased from 0.80 at 2 months to 0.54 at 12 months (p = 0.002). Conclusion: RMT thickness, the adjacent myometium and the ratio between the RMT and AM reduces from 2 to 12 months after a CS. The prevalence did not change. This needs to be taken into account when deciding on the timing of niche measurement and the interpretation of the RMT.
Distinct Penetrance of Obesity-Associated Susceptibility Alleles in the Hungarian General and Roma Populations
Authors: Nagy Károly , Fiatal Szilvia , Sándor János , Ádány Róza
Published: October 2017

Aims: The aim of our study was to explore differences in genetic predisposition to obesity between the Hungarian general and Roma populations. Methods: A total of 1,152 samples from the Hungarian Roma population and 1,743 samples from the Hungarian general population were genotyped for 20 single nucleotide polymorphisms (SNPs) associated with the risk of obesity. Two types of multilocus genetic risk scores were constructed to estimate the combined effect of selected SNPs. Results: Risk allele frequencies differed significantly between the two populations for 11 SNPs, with no enrichment in any of the two study groups. Variants (rs1558902, rs1121980, rs9939609, and rs9941349) in the fat mass and obesity-associated (FTO) gene exhibited strong but ethnicity-independent association with obesity. Genetic risk scores showed stronger associations with obesity in the Roma population compared with the Hungarian general population; however, without significant gene-population interaction. Conclusion: Differences in obesity prevalence between the Hungarian general and Hungarian Roma populations could not be explained by their distinct genetic susceptibility, rather by ethnicity-related environmental and behavioral factors. Nonetheless, particular gene-environment interactions might contribute to the distinct penetrance of the obesity-associated genetic factors in populations of different ethnic backgrounds.
Silver Diamine Fluoride Has Efficacy in Controlling Caries Progression in Primary Teeth: A Systematic Review and Meta-Analysis
Authors: Chibinski Ana Cláudia , Wambier Letícia Maíra , Feltrin Juliana , Loguercio Alessandro Dourado , Wambier Denise Stadler , Reis Alessandra
Published: October 2017

A systematic review was performed to evaluate the efficacy of silver diamine fluoride (SDF) in controlling caries progression in children when compared with active treatments or placebos. A search for randomized clinical trials that evaluate the effectiveness of SDF for caries control in children compared to active treatments or placebos with follow-ups longer than 6 months was performed in PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and grey literature. The risk of bias tool from the Cochrane Collaboration was used for quality assessment of the studies. The quality of the evidence was evaluated using the GRADE approach. Meta-analysis was performed on studies considered at low risk of bias. A total of 5,980 articles were identified. Eleven remained in the qualitative synthesis. Five studies were at “low,” 2 at “unclear,” and 4 studies at “high” risk of bias in the key domains. The studies from which the information could be extracted were included for meta-analysis. The arrestment of caries at 12 months promoted by SDF was 66% higher (95% CI 41-91%; p < 0.00001) than by other active material, but it was 154% higher (95% CI 67-85%; p < 0.00001) than by placebos. Overall, the caries arrestment was 89% higher (95% CI 49-138%; p < 0.00001) than using active materials/placebo. No heterogeneity was detected. The evidence was graded as high quality. The use of SDF is 89% more effective in controlling/arresting caries than other treatments or placebos. The quality of the evidence was graded as high.
Quality of Life in Children with Disorders of Sex Development
Authors: M Selveindran Nalini , Syed Zakaria Syed Zulkifli , Jalaludin Muhammad Yazid , Rasat Rahmah
Published: October 2017

Background/Aims: Disorders of sex development (DSD) are a heterogeneous group of rare conditions. Evidence-based treatment is challenged by a lack of clinical longitudinal outcome studies. We sought to investigate the quality of life of children with DSD other than congenital adrenal hyperplasia. Methods: The participants (aged 6–18 years) were 23 patients raised as males and 7 patients raised as females. Control data were obtained from representatives of the patients’ siblings matched for age and gender. The Pediatric Quality of Life InventoryTM Version 4.0 (PedsQL) Generic Core Scales were used as the study tool. Results: In comparison with the reference data, the patient group had significantly lower overall PedsQL (p < 0.01) and school functioning (p < 0.01) scores. Also, the total PedsQL score was significantly lower in patients with DSD who were of female social sex as compared to the controls who were females. Family income, surgical procedures, degree of virilization, and mode of puberty did not influence the PedsQL scores. Conclusion: This study revealed a poorer quality of life for patients with DSD as compared to the age-matched control group. This highlights the need for a skilled multidisciplinary team to manage this group of patients.
Nonphysician Clinicians in the Follow-Up of Resected Patients with Colorectal Cancer
Authors: Coebergh van den Braak Robert R.J. , Lalmahomed Zarina S. , Büttner Stefan , Hansen Bettina E. , Ijzermans Jan N.M. ,   on behalf of the MATCH Study Group
Published: October 2017

Background/Aims: The 5-year postoperative follow-up for patients undergoing curative treatment for colorectal cancer (CRC) is labour intensive. We assessed the added value of a dedicated nonphysician clinician (NPC) in the follow-up of patients after resection for CRC. Methods: Patients were divided into 2 groups as defined by the number of follow-up visits in the first year, including intensive (≥3×) and minimal (≤2×). Involvement of an NPC, diagnosis of disease recurrence and the course of the disease were determined. Results: Of the 681 patients, 79.9% belonged to the “intensive” and 21.1% to the “minimal” group. Involvement of an NPC resulted in a higher adherence to follow-up (84.3 vs. 73.9%, p = 0.001). Overall, patients in regular follow-up less often had multifocal recurrence (47.1 vs. 73.7%, p = 0.04), and a better survival after recurrence (SAR; hazard ratio [HR] 3.604, p < 0.001). The “intensive” group had a significantly better overall survival compared to the “minimal” group (HR 1.71, p = 0.013). Conclusion: Adherence to surveillance programs after resection for CRC is better in hospitals with a dedicated NPC. Overall, patients' adherence to follow-up resulted in less multifocal disease recurrence at the time of diagnosis as compared to patients presenting with symptoms and a better 3-year SAR.
Sudden Deafness during Antepartum versus Postpartum Periods
Authors: Zhang Bang-Yan , Young Yi-Ho
Published: October 2017

Objective: This study reviewed our experience in treating sudden deafness in antepartum (pregnant) and postpartum women during the past 2 decades. Methods: From 1997 to 2016, we have recorded sudden deafness in 16 antepartum (mean age, 32 years) and 3 postpartum (mean age, 31 years) women. Sudden deafness occurred during the 1st, 2nd, and 3rd trimesters in 5, 4, and 7 antepartum women, respectively. In contrast, the mean interval between giving birth and symptom onset in the 3 postpartum women was 18 days. Each patient underwent an inner ear test battery. Results: In 8 antepartum women treated by dextran infusion, the outcome as regards hearing was improved in 7 patients (88%) and unchanged in 1 patient. In contrast, the other 8 antepartum women selected no treatment, and only 1 patient (12%) achieved hearing improvement, exhibiting a significantly better outcome when receiving dextran treatment. For the postpartum women, 2 patients had hearing improvement when treated by antioxidants, while 1 patient retained unchanged hearing without treatment. Conclusion: Medication is needed in sudden deafness in antepartum or postpartum women rather than waiting for a natural course. No adverse effects have been identified in any of the mothers or offspring 1 year after delivery.
Elevated Phosphate Levels Trigger Autophagy-Mediated Cellular Apoptosis in H9c2 Cardiomyoblasts
Authors: Liu Yao-Lung , Lin Kuan-Ho , Tamilselvi Shanmugam , Chen Wei-Kung , Shen Chia-Yao , Chen Ray-Jade , Day Cecilia Hsuan , Wu Hsi-Chin , Viswanadha Vijaya Padma , Huang Chih-Yang
Published: October 2017

Background/Aim: In chronic kidney disease (CKD), kidneys fail to maintain phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been associated with cardiovascular diseases in CKD patients and in normal individuals. In this study, we evaluated the level of autophagy- and apoptosis-related markers under different concentrations of hyperphosphate in myocardial cells. Methods: Modulation inflicted on the levels of various survival-, autophagy-, and apoptosis-related markers were determined by Western blotting analysis using total protein extract. FITC-annexin V staining was performed to quantify the apoptotic cells in all groups. Results: Hyperphosphate treatments showed to induce autophagy-related proteins beclin-1, ATG7, and LC3 II through the pAMPK-ULK1 pathway in Western blotting analysis. Further, apoptosis-associated proteins such as Bax, Bid, cytochrome c, and c-caspase-9 were also upregulated with hyperphosphate treatment. 3-Methyladenine, an autophagy inhibitor, inhibited apoptosis significantly in FITC-annexin V staining, and the inhibition of Bax, cytochrome c, and c-caspase-3 was shown by Western blotting. Conclusion: The results suggest that hyperphosphate in H9c2 cardiomyoblasts would lead to cellular apoptosis via autophagy, which is mediated by the pAMPK signaling pathway. Our findings revealed the possible mechanism responsible for the heart damage under hyperphosphatemia.
Early Rebleeding after Brain Arteriovenous Malformation Rupture, Clinical Impact and Predictive Factors: A Monocentric Retrospective Cohort Study
Authors: Shotar Eimad , Pistocchi Silvia , Haffaf Idriss , Bartolini Bruno , Jacquens Alice , Nouet Aurélien , Chiras Jacques , Degos Vincent , Sourour Nader-Antoine , Clarençon Frédéric
Published: October 2017

Background: Brain arteriovenous malformations (BAVMs) are a leading cause of intracranial hemorrhage in young adults. This study aimed to identify individual predictive factors of early rebleeding after BAVM rupture and determine its impact on prognosis. Methods: Early rebleeding was defined as a spontaneous intracranial hemorrhage within 30 days of BAVM rupture in patients with nonobliterated BAVMs. One hundred fifty one patients with 158 BAVM hemorrhagic events admitted to a tertiary care center during 14 years were included. Univariate followed by multivariate logistic regression was performed to assess the impact of early rebleeding on in-hospital mortality and modified Rankin Scale (mRS) score beyond 3 months and to identify independent predictors of early rebleeding. Results: Eight early rebleeding events were observed, 6 of which occurred during the first 7 days. Early rebleeding was independently and significantly associated with poor outcome (mRS ≥3 beyond 3 months, p = 0.004) but not with in-hospital mortality (p = 0.9). Distal flow-related aneurysms (p = 0.009) and altered consciousness with a Glasgow coma scale score of 3 (p = 0.01) were independently associated with early rebleeding. Conclusions: Early rebleeding is a severe complication that can occur after BAVM-related hemorrhage. Distal flow-related aneurysms and initial altered consciousness are associated with early rebleeding.
Advance Directives as Support of Autonomy for Persons with Dementia A Pilot Study among Persons with Dementia and Their Informal Caregivers
Authors: Schmidhuber Martina , Haeupler Sandra , Marinova-Schmidt Velislava , Frewer Andreas , Kolominsky-Rabas Peter L.
Published: October 2017

Background: Advance directives could be an important instrument to support a person’s will once he/she is not able to consent anymore – if composed competently. A survey was conducted to identify the level of knowledge concerning possibilities and limits of advance directives. Methods: The study was conducted as part of the Bavarian Dementia Survey (BayDem). Data were collected from January 2014 to December 2015 by structured face-to-face interviews. Study participants were persons with dementia and their informal caregivers (n = 74). Results: In total, 66% reported having written an advance directive. Concerning the participants’ knowledge about possibilities and limitations of advance directives, a lack of knowledge was noted about the possibility to revoke an advance directive. Furthermore, 70% of informal caregivers and 56% of persons with dementia were not aware of the possibility to include dementia-specific terms in the advance directive. Conclusion: It is necessary to optimize structures for public information and education concerning the topic of advance directives for persons with dementia.
Pharyngolaryngeal Sensory Deficits in Patients with Middle Cerebral Artery Infarction: Lateralization and Relation to Overall Dysphagia Severity
Authors: Marian Thomas , Schröder Jens Burchard , Muhle Paul , Claus Inga , Riecker Axel , Warnecke Tobias , Suntrup-Krueger Sonja , Dziewas Rainer
Published: October 2017

Background: Dysphagia is a frequent and dangerous complication of acute stroke. Apart from a well-timed oropharyngeal muscular contraction pattern, sensory feedback is of utmost importance for safe and efficient swallowing. In the present study, we therefore analyzed the relation between pharyngolaryngeal sensory deficits and post-stroke dysphagia (PSD) severity in a cohort of acute stroke patients with middle cerebral artery (MCA) infarction. Methods: Eighty-four first-ever MCA stroke patients (41 left, 43 right) were included in this trial. In all patients, fiberoptic endoscopic evaluation of swallowing (FEES) was performed according to a standardized protocol within 96 h after stroke onset. PSD was classified according to the 6-point fiberoptic endoscopic dysphagia severity scale. Pharyngolaryngeal sensation was semi-quantitatively evaluated by a FEES-based touch technique. Results: PSD severity was closely related to the pharyngolaryngeal sensory deficit. With regards to lateralization of the sensory deficit, there was a slight but significant preponderance of sensory loss contralateral to the side of stroke. Apart from that, right hemispheric stroke patients were found to present with a more severe PSD. Conclusions: This study provides evidence that an intact sensory feedback is of utmost importance to perform nonimpaired swallowing and highlights the key role of disturbed pharyngeal and laryngeal afferents in the pathophysiology of PSD.
Malpractice Litigation in Ocular Oncology
Authors: Engelhard Stephanie B. , Aronow Mary E. , Shah Christopher T. , Sim Austin J. , Reddy Ashvini K.
Published: October 2017

Aims: The aim of this study was to report and analyze the causes and outcomes of ocular oncology malpractice litigation. Methods: The WestLaw® database was reviewed for all litigation related to ophthalmology in the United States from 1930 to 2014. All ocular oncology cases were included in this analysis and compared to other ophthalmic subspecialties. Results: Sixteen ocular oncology malpractice cases were included in this study. Overall, 56.3% of the cases were resolved in favor of the defendant. A total of 62.5% of cases were resolved via jury verdict, with 30.0% resulting in plaintiff verdicts with mean adjusted awards of USD 511,244.48, comparable to ophthalmology as a whole. Three cases (18.8%) resulted in settlements with mean adjusted indemnities of USD 828,928.14. A total of 87.5% of cases alleged insufficient intervention resulting in loss of vision and/or death. The most common clinical entities were uveal melanoma (31.3%), retinoblastoma (12.5%), and sebaceous cell carcinoma (12.5%). Conclusions: Ocular oncology malpractice litigation was relatively rare and outcomes generally favored defendants; however, unlike other subspecialties in ophthalmology, blindness or premature death were common to all cases, highlighting both the importance of prompt diagnosis and treatment and the difficulty inherent in diagnosing ocular malignancies.
The Prevalence of and Factors Related to Vascular Hyperintensity on T1-Weighted Imaging in Acute Ischemic Stroke
Authors: Sakamoto Yuki , Okubo Seiji , Nito Chikako , Suda Satoshi , Matsumoto Noriko , Abe Arata , Aoki Junya , Shimoyama Takashi , Muraga Kanako , Kanamaru Takuya , Suzuki Kentaro , Go Yuki , Mishina Masahiro , Kimura Kazumi
Published: October 2017

Background: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke. Methods: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. Results: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). Conclusion: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months.
Trigger Tool na Segurança do Doente: Uma Revisão Sistemática de Literatura
Authors: Pierdevara Ludmila , Ventura Inês Margarida , Eiras Margarida , Brito Gracias Amélia Maria
Published: October 2017

Introdução: A elevada incidência de eventos adversos (EA) é uma das situações preocupantes descritas na literatura sendo relacionada diretamente com o aumento dos custos com a prestação de cuidados de saúde e com o aumento do número de dias de internamento. A metodologia Global Trigger Tool (GTT) é relativamente nova mas tem-se mostrado promissora, em contextos internacionais, em ações de rastreio dos EA. Objetivo: Obter um corpo de evidência, reunindo um conjunto de informações acerca da utilização desta metodologia em contexto hospitalar. Metodologia: Trata-se de uma revisão sistemática da literatura, baseada em estudos primários relacionados com esta temática, publicados entre o ano 2009 e 2014. Resultados: O estudo incluiu 8 estudos primários e os resultados evidenciam dados relevantes acerca da utilidade da ferramenta GTT no âmbito hospitalar. Conclusão: A evidência científica mostra que a aplicação do método GTT, como estratégia de monitorização dos EA, é uma ferramenta viável, uma vez que permite acompanhar a implementação de mudanças orientadas para a redução da ocorrência dos EA.
The Cognitive Telephone Screening Instrument (COGTEL): A Brief, Reliable, and Valid Tool for Capturing Interindividual Differences in Cognitive Functioning in Epidemiological and Aging Studies
Authors: Ihle Andreas , Gouveia Élvio R. , Gouveia Bruna R. , Kliegel Matthias
Published: October 2017

Aims: The present study set out to evaluate the psychometric properties of the Cognitive Telephone Screening Instrument (COGTEL) in 2 different samples of older adults. Methods: We assessed COGTEL in 116 older adults, with retest after 7 days to evaluate the test-retest reliability. Moreover, we assessed COGTEL in 868 older adults to evaluate convergent validity to the Mini-Mental State Examination (MMSE). Results: Test-retest reliability of the COGTEL total score was good at 0.85 (p < 0.001). Latent variable analyses revealed that COGTEL and MMSE correlated by 0.93 (p < 0.001), indicating convergent validity of the COGTEL. Conclusion: The present analyses suggest COGTEL as a brief, reliable, and valid instrument for capturing interindividual differences in cognitive functioning in epidemiological and aging studies, with the advantage of covering more cognitive domains than traditional screening tools such as the MMSE, as well as differentiating between individual performance levels, in healthy older adults.
Expression Profiling of MicroRNAs in the Inner Ear of Elderly People by Real-Time PCR Quantification
Authors: Sekine Kuwon , Matsumura Tomohiro , Takizawa Toshihiro , Kimura Yurika , Saito Shiho , Shiiba Kyoko , Shindo Susumu , Okubo Kimihiro , Ikezono Tetsuo
Published: October 2017

The molecular mechanisms underlying age-related hearing loss are unknown, and currently, there is no treatment for this condition. Recent studies have shown that microRNAs (miRNAs) and age-related diseases are intimately linked, suggesting that some miRNAs may present attractive therapeutic targets. In this study, we obtained 8 human temporal bones from 8 elderly subjects at brain autopsy in order to investigate the expression profile of miRNAs in the inner ear with miRNA arrays. A mean of 478 different miRNAs were expressed in the samples, of which 348 were commonly expressed in all 8 samples. Of these, levels of 16 miRNAs significantly differed between young elderly and old elderly subjects. miRNAs, which play important roles in inner ear development, were detected in all samples, i.e., in both young and old elderly subjects, whether with or without hearing loss. Our results suggest that these miRNAs play important roles not only in development, but also in the maintenance of inner ear homeostasis.
Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity
Authors: Whaley-Connell Adam , Sowers James R.
Published: October 2017

Insulin resistance is a central component of the metabolic dysregulation observed in obesity, which puts one at risk for the development of type 2 diabetes and complications related to diabetes such as chronic kidney disease. Insulin resistance and compensatory hyperinsulinemia place one at risk for other risk factors such as dyslipidemia, hypertension, and proteinuria, e.g., development of kidney disease. Our traditional view of insulin actions focuses on insulin-sensitive tissues such as skeletal muscle, liver, adipose tissue, and the pancreas. However, insulin also has distinct actions in kidney tissue that regulate growth, hypertrophy, as well as microcirculatory and fibrotic pathways which, in turn, impact glomerular filtration, including that governed by tubuloglomerular feedback. However, it is often difficult to discern the distinct effects of excess circulating insulin and impaired insulin actions, as exist in the insulin resistance individual, from the associated effects of obesity or elevated systolic blood pressure on the development and progression of kidney disease over time. Therefore, we review the experimental and clinical evidence for the distinct impact of insulin resistance on kidney function and disease.
Vascular Dynamics and Peripheral Oxygen Uptake in Obese Individuals during Progressive Physical Exercise
Authors: Brunani Amelia , Lanzi Stefano , Codecasa Franco , Cornacchia Mauro , Maestrini Sabrina , Soranna Davide , Zambon Antonella , Cattaldo Stefania , Fanari Paolo , Malatesta Davide , Salvadori Alberto
Published: October 2017

Background: Obese men show higher O2 consumption than lean men during physical exercise, with a trend toward higher peripheral O2 extraction; this is probably due to their larger muscle mass. Objectives: The aim of this study was to examine this phenomenon by measuring 2 vasoactive substances, endothelin-1 (ET-1) and nitric oxide (NO), during a progressive submaximal exercise. Methods: Seventeen obese (body mass index [BMI] 38.6) and 15 lean (BMI 22.5) men performed a maximal progressive cycle ergometer exercise to determine peak power output (PPO) and peak O2 consumption (V∙O2peak); thereafter, they performed a submaximal cycle ergometer incremental test (every 6 min) at the same percentage of V∙O2peak until they reached 57.5% PPO. Blood samples were collected at rest and at the end of every step to measure ET-1 and NO concentrations. Results: At rest, the ET-1 and NO concentrations in obese men and lean controls were the same. However, during exercise, the ET-1 concentration at each step was significantly lower (p < 0.05) in the obese group. There was no significant difference in NO concentration between the 2 groups, although the increase at the beginning of the exercise session was faster in obese individuals. During submaximal exercise, end-tidal O2 pressure (PETO2) was lower in the obese group, with a significant difference in the PETO2/fat-free mass ratio at each step. Conclusions: ET-1 and NO levels during physical exercise are different in obese versus lean men. This may support the notion that increased O2 consumption in obesity is due to different behaviors of the cardiorespiratory and circulatory systems.
Abbreviation of the Follow-Up NIH Stroke Scale Using Factor Analysis
Authors: Raza Syed Ali , Frankel Michael R. , Rangaraju Srikant 
Published: October 2017

Background: The NIH Stroke Scale (NIHSS) is a 15-item measure of stroke-related neurologic deficits that, when measured at 24 h, is highly predictive of long-term functional outcome. We hypothesized that a simplified 24-h scale that incorporates the most predictive components of the NIHSS can retain prognostic accuracy and have improved interrater reliability. Methods: In a post hoc analysis of the Interventional Management of Stroke-3 (IMS-3) trial, we performed principal component (PC) analysis to resolve the 24-h NIHSS into PCs. In the PCs that explained the largest proportions of variance, key variables were identified. Using these key variables, the prognostic accuracies (area under the curve [AUC]) for good outcome (3-month modified Rankin Scale [mRS] 0–2) and poor outcome (mRS 5–6) of various abbreviated NIHSS iterations were compared with the total 24-h NIHSS. The results were validated in the NINDS intravenous tissue plasminogen activator (NINDS-TPA) study cohort. Based on previously published data, interrater reliability of the abbreviated 24-h NIHSS (aNIHSS) was compared to the total 24-h NIHSS. Results: In 545 IMS-3 participants, 2 PCs explained 60.8% of variance in the 24-h NIHSS. The key variables in PC1 included neglect, arm and leg weakness; while PC2 included level-of-consciousness (LOC) questions, LOC commands, and aphasia. A 3-variable aNIHSS (aphasia, neglect, arm weakness) retained excellent prognostic accuracy for good outcome (AUC = 0.90) as compared to the total 24-h NIHSS (AUC = 0.91), and it was more predictive (p < 0.001) than the baseline NIHSS (AUC = 0.73). The prognostic accuracy of the aNIHSS for good outcome was validated in the NINDS-TPA trial cohort (aNIHSS: AUC = 0.89 vs. total 24-h NIHSS: 0.92). An aNIHSS >9 predicted very poor outcomes (mRS 0–2: 0%, mRS 4–6: 98.5%). The estimated interrater reliability of the aNIHSS was higher than that of the total 24-h NIHSS across 6 published datasets (mean weighted kappa 0.80 vs. 0.73, p < 0.001). Conclusions: At 24 h following ischemic stroke, aphasia, neglect, and arm weakness are the most prognostically relevant neurologic findings. The aNIHSS appears to have excellent prognostic accuracy with higher reliability and may be clinically useful.
New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL/6 Mouse Strain
Authors: Takeuchi Kazuhiro , Naito Shokichi , Kawashima Nagako , Ishigaki Naoko , Sano Takashi , Kamata Kouju , Takeuchi Yasuo
Published: October 2017

Background: Focal segmental glomerulosclerosis (FSGS) is considered a subset of the podocytopathies. The molecular pathogenesis of podocytopathy is still unknown. There has not been an experimental animal model of isolated podocytopathy induced by antibody in C57BL/6 strain, which is widely used as the genetic background. Nephrin is closely associated with the slit diaphragm of the glomerular podocyte, and has recently received attention as a potential therapeutic target. The function of nephrin, especially its role in FSGS development via podocytopathy, is being elucidated. We report our experience with a C57BL/6 FSGS model induced by polyclonal rabbit anti-mouse nephrin antibody (α-mNep Ab). Methods: α-mNep Ab, which was generated by genetic immunization, was administered into C57BL/6 mice at once, intravenously. Urinary protein excretion, the development of glomerulosclerosis and the number of podocyte in mouse kidney were evaluated. Results: The α-mNep Ab-induced FSGS was associated with massive proteinuria and nephrotic syndrome. In periodic acid-Schiff staining, FSGS was observed from day 7 after antibody injection. Podocyte numbers and podocyte marker (anti-Wilms tumor 1 and anti-synaptopodin)-positive areas were clearly decreased. These results suggest that this FSGS mouse model reliably reproduces the human nephrotic syndrome and FSGS. Conclusion: We succeeded in making the nephrotic syndrome model mice induced by α-mNep Ab using C57BL/6. This model may be useful for studying the mechanisms of podocytopathy.
Clinical Relevance of Patent Foramen Ovale and Atrial Septum Aneurysm in Stroke: Findings of a Single-Center Cross-Sectional Study
Authors: Schnieder Marlena , Siddiqui Tariq , Karch André , Bähr Mathias , Hasenfuss Gerd , Liman Jan , Schroeter Marco R.
Published: October 2017

Background: A significant proportion of ischemic strokes are cryptogenic. In this context, the clinical pertinence of patent foramen ovale (PFO) with and without atrial septum aneurysm (ASA) remains controversial. The aim of this study was to identify how PFO +/–ASA and cryptogenic stroke are associated in a representative sample of stroke patients. Methods: We enrolled all patients (n = 909) with ischemic stroke or transient ischemic attack admitted to the certified stroke unit or neurological intensive care unit of our university medical center who underwent transesophageal echocardiography (TEE) between 2012 and 2014. The baseline characteristics, cardio-/neurovascular risk factors, clinical parameters and TEE findings were analyzed. Results: PFO was present in 26.2%, and PFO was combined with an ASA in 9.9%. In cryptogenic stroke, the prevalence of PFO was higher compared to other etiologies (30.9 vs. 21.9%; p < 0.002). Patients with PFO had lower National Institute of Health Stroke Score (NIHSS) values at admission than those without (2 [0–5] vs. 3 [1–7]; p = 0.001; 95% CI [0.62–0.88]). No difference was found in NIHSS values of PFO patients with or without ASA (2 [0–5] vs. 2 [0–5]; p = 0.683; 95% CI 0.94 [0.68–1.28]). Conclusions: Our study indicates that a detected PFO +/–ASA could exhibit a stroke-relevant finding, if classical risk factors for the stroke were lacking.
Regulation of Intracellular Calcium by Carbon Monoxide in Human Bronchial Epithelial Cells
Authors: Zhang Rui-Gang , Yip Chung-Yin , Ko Wing-Hung
Published: October 2017

Background/Aims: Carbon monoxide (CO) is an important autocrine/paracrine messenger involved in a variety of physiological and pathological processes. This study aimed to investigate the regulatory role of CO released by CO-releasing molecule-2 (CORM-2) in a P2Y receptor-mediated calcium-signaling pathway in the human bronchial epithelial cell line, 16HBE14o-. Methods: Intracellular calcium ([Ca2+]i) was measured by fura-2 microspectrofluorimetry. D-myo-inositol-1-phosphate (IP1) levels and cGMP-dependent protein kinase activity (PKG) were also quantified. Results: The exogenous application of CORM-2 increased both intracellular Ca2+ and IP1, which are inhibited by U73122, a phospholipase C (PLC) inhibitor. In contrast, the P2Y2/P2Y4 receptor-mediated intracellular Ca2+ release and influx induced by UTP were inhibited in the presence of CORM-2. However, CORM-2 did not affect the store-operated Ca2+ entry (SOCE) induced by thapsigargin (Tg). Moreover, the inhibitory effect of CORM-2 on UTP-induced calcium increase could be attenuated by a soluble guanylyl cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), or a Protein Kinase G (PKG) inhibitor, KT5823, suggesting the involvement of sGC/PKG signaling in this process. Conclusion: CORM-2 serves a dual role in modulating [Ca2+]i in 16HBE14o- cells. Thus, CO released by CORM-2 may act as a regulator of calcium homeostasis in human airway epithelia. These findings help further elucidate the function of CO in many physiological and pathological conditions.
Intraoperative Squash and Touch Preparation Cytology of Brain Lesions Stained with H+E and Diff-Quik™: A 20-Year Retrospective Analysis and Comparative Literature Review
Authors: Hamasaki Makoto , Chang Karen H.F. , Nabeshima Kazuki , Tauchi-Nishi Pamela S.
Published: October 2017

Objective: Squash preparation (SP) is a rapid technique for the intraoperative assessment of brain lesions. Only a few studies have employed touch preparation (TP) cytology and Diff-QuikTM (DQ) staining in conjunction with SP. Our study aimed to assess the diagnostic efficacy of SP of brain lesions at our institution, ascertain the additional effect of TP and DQ staining, examine factors affecting the sensitivity and specificity of our methods, and compare our findings with those of previous investigations. Study Design: Our database was searched for all SP/TP of brain lesions examined from January 1996 to December 2016. Results: During this 20-year study period, our search revealed 400 brain lesions diagnosed by SP/TP cytology. There were 338 (84.5%) neoplasms and 62 (15.5%) nonneoplastic lesions. The most common neoplasms were glioblastoma multiforme (24.6%), metastatic cancer (18.3%), meningioma (16.9%), astrocytoma (11.5%), lymphoma (8.3%), oligoastrocytoma (3.3%), and pituitary adenoma (3.3%). There was discordance between the SP/TP and histological diagnoses in 19/338 (5.6%) cases, i.e., 12 misclassifications of tumor subtype and 7 sampling errors. No false-positive cases were detected. Conclusion: Brain SP/TP stained with H+E/DQ demonstrated high sensitivity (97.9%), specificity (100%), and overall diagnostic accuracy (95.3%). The combined methods, in particular, aided in the diagnosis of brain tumors prone to smearing artifacts and certain metastatic malignancies.