bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes Mellitus Impairs White Matter Repair and Long-Term Functional Deficits After Cerebral Ischemia
Authors: Ma Shubei , Wang Jianyi , Wang Yanling , Dai Xuejiao , Xu Fei , Gao Xuguang , Johnson Joycelyne , Xu Na , Leak Rehana K. , Hu Xiaoming , Luo Yumin , Chen Jun 
Published: September 2018

Background and Purpose—
Type 2 diabetes mellitus (T2DM) is a major comorbidity that exacerbates ischemic brain injury and worsens functional outcome after stroke. T2DM is known to aggravate white matter (WM) impairment, but the underlying mechanism is not completely understood. This study was designed to test the hypothesis that T2DM impedes poststroke WM recovery by suppressing both oligodendrogenesis and beneficial microglia/macrophage responses.

Methods—
Permanent distal middle cerebral artery occlusion was performed in wild-type, homozygous diabetic db/db, and heterozygous db/+ mice. The adhesive removal, open field, and Morris water maze tests were used to assess neurobehavioral outcomes. Neuronal tissue loss, WM damage, oligodendrogenesis, and microglia/macrophage responses were evaluated up to 35 days after stroke. The functional integrity of WM was measured by electrophysiology. Primary microglia-oligodendrocyte cocultures were used for additional mechanistic studies.

Results—
T2DM exacerbated structural damage and impaired conduction of compound action potentials in WM 35 days after stroke. The deterioration in WM integrity correlated with poor sensorimotor performance. Furthermore, T2DM impaired the proliferation of oligodendrocyte precursor cells and the generation of new myelinating oligodendrocytes. T2DM also promoted a shift of microglia/macrophage phenotype toward the proinflammatory modality. Coculture studies confirmed that microglia/macrophage polarization toward the proinflammatory phenotype under high glucose conditions suppressed oligodendrocyte precursor cell differentiation.

Conclusions—
Deterioration of WM integrity and impairments in oligodendrogenesis after stroke are associated with poor long-term functional outcomes in experimental diabetes mellitus. High glucose concentrations may shift microglia/macrophage polarization toward a proinflammatory phenotype, significantly impairing oligodendrocyte precursor cell differentiation and WM repair.
Mechanical Thrombectomy Outcomes With or Without Intravenous Thrombolysis
Authors: Gariel Florent , Lapergue Bertrand , Bourcier Romain , Berge Jérôme , Barreau Xavier , Mazighi Mikael , Kyheng Maéva , Labreuche Julien , Fahed Robert , Blanc Raphael , Gory Benjamin , Duhamel Alain , Saleme Suzana , Costalat Vincent , Bracard Serge , Desal Hubert , Detraz Lili , Consoli Arturo , Piotin Michel , Marnat Gaultier ,   for the ASTER Trial Investigators
Published: September 2018

Background and Purpose—
Intravenous thrombolysis (IVT) within 4.5 hours of symptom onset is currently recommended before mechanical thrombectomy (MT). We compared functional outcome, neurological recovery, reperfusion, and adverse events according to the use or not of IVT before MT.

Methods—
This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was favorable 90-day functional outcome defined as a modified Rankin Scale of ≤2. Secondary outcomes were successful reperfusion following all procedures and after the first-line procedure, number of device passes, and change in National Institutes of Health Stroke Scale score at 24 hours. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage.

Results—
Three hundred eighty-one patients were included, 250 of whom received IVT before MT (IVT+MT group). There were no significant differences between IVT+MT and MT-alone groups in 90-day favorable functional outcome, in successful reperfusion rate (modified Thrombolysis In Cerebral Infarction 2b or 3), in National Institutes of Health Stroke Scale score improvement at 24 hours, or in hemorrhagic complication rate. The 90-day mortality rate in the IVT+MT group was lower than after MT alone (fully-adjusted risk ratio, 0.59; 95% CI, 0.39–0.88). In a subgroup of patients without anticoagulant medication before stroke onset, we observed in the IVT+MT group a better functional outcome (fully-adjusted risk ratio, 1.38; 95% CI, 1.02–1.89), a higher successful recanalization rate after first-line strategy (fully-adjusted risk ratio, 1.26; 95% CI, 1.05–1.50), and a lower mortality rate (fully-adjusted risk ratio, 0.58; 95% CI, 0.36–0.93).

Conclusions—
Our results show that IVT+MT patients in the ASTER trial have lower 90-day mortality compared with those receiving MT alone. In a selected population of patients without prestroke anticoagulation, we demonstrated that IVT associated with MT might improve functional outcome and recanalization while reducing mortality rates.
Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes
Authors: Larsson Susanna C. , Traylor Matthew , Mishra Aniket , Howson Joanna M.M. , Michaëlsson Karl , Markus Hugh S. ,   for the MEGASTROKE Project of the International Stroke Genetics Consortium
Published: September 2018

Background and Purpose—
Observational studies have reported increased risk of ischemic stroke among individuals with low serum 25-hydroxyvitamin D (S-25OHD) concentrations but uncertainty remains about the causality of this association. We sought to determine whether S-25OHD concentrations are causally associated with ischemic stroke and its subtypes using Mendelian randomization.

Methods—
We used summary-level data for ischemic stroke (34 217 cases and 404 630 noncases) from the MEGASTROKE consortium. As instruments, we used 6 single nucleotide polymorphisms, explaining 7.5% of the variance in S-25OHD, previously identified to be associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium (n=79 366). The analyses were conducted using the inverse-variance–weighted method and complemented with the weighted median, heterogeneity-penalized, and Mendelian randomization-Egger approaches.

Results—

Genetically higher S-25OHD concentration was not associated with ischemic stroke. The odds ratios (95% CI) per genetically predicted 1-SD (≈18 nmol/L) increase in S-25OHD concentrations, based on all 6 single nucleotide polymorphisms, were 1.01 (0.94–1.08;
P
=0.84) for all ischemic stroke, 0.94 (0.80–1.11;
P
=0.49) for large artery stroke, 0.95 (0.82–1.11;
P
=0.55) for small vessel stroke, and 1.02 (0.90–1.16;
P
=0.74) for cardioembolic stroke. The results were similar in sensitivity analyses.

Conclusions—
These findings provide no support that higher S-25OHD concentrations are causally associated with any ischemic stroke subtype. Thus, vitamin D supplementation will unlikely reduce the risk of ischemic stroke in the general population.
Extracellular Vimentin/VWF (von Willebrand Factor) Interaction Contributes to VWF String Formation and Stroke Pathology
Authors: Fasipe Titilope A. , Hong Sung-Ha , Da Qi , Valladolid Christian , Lahey Matthew T. , Richards Lisa M. , Dunn Andrew K. , Cruz Miguel A. , Marrelli Sean P. 
Published: September 2018

Background and Purpose—
VWF (von Willebrand factor) strings mediate spontaneous platelet adhesion in the vascular lumen, which may lead to microthrombi formation and contribute to stroke pathology. However, the mechanism of VWF string attachment at the endothelial surface is unknown. We tested the novel hypothesis that VWF strings are tethered to the endothelial surface through an interaction between extracellular vimentin and the A2 domain of VWF. We further explored the translational value of blocking this interaction in a model of ischemic stroke.

Methods—
Human endothelial cells and pressurized cerebral arteries were stimulated with histamine to elicit VWF string formation. Recombinant proteins and antibodies were used to block VWF string formation. Mice underwent transient middle cerebral artery occlusion with reperfusion. Just before recanalization, mice were given either vehicle or A2 protein (recombinant VWF A2 domain) to disrupt the vimentin/VWF interaction. Laser speckle contrast imaging was used to monitor cortical perfusion.

Results—
Pressurized cerebral arteries produced VWF strings following histamine stimulation, which were reduced in arteries from Vim KO (vimentin knockout) mice. VWF string formation was significantly reduced in endothelial cells incubated with A2 protein or antivimentin antibodies. Lastly, A2 protein treatment significantly improved cortical reperfusion after middle cerebral artery occlusion.

Conclusions—
We provide the first direct evidence of cerebral VWF strings and demonstrate that extracellular vimentin significantly contributes to VWF string formation via A2 domain binding. Lastly, we show that pharmacologically targeting the vimentin/VWF interaction through the A2 domain can promote improved reperfusion after ischemic stroke. Together, these studies demonstrate the critical role of VWF strings in stroke pathology and offer new therapeutic targets for treatment of ischemic stroke.
Intergrating conventional MRI, texture analysis of dynamic contrast-enhanced MRI, and susceptibility weighted imaging for glioma grading
Authors: Su Chun-Qiu , Lu Shan-Shan , Han Qiu-Yue , Zhou Mao-Dong , Hong Xun-Ning 
Published: September 2018

Background The application of conventional magnetic resonance imaging (MRI) in glioma grading is limited and non-specific. Purpose To investigate the application values of MRI, texture analysis (TA) of dynamic contrast-enhanced MRI (DCE-MRI) and intratumoral susceptibility signal (ITSS) on susceptibility weighted imaging (SWI), alone and in combination, for glioma grading. Material and Methods Fifty-two patients with pathologically confirmed gliomas who underwent DCE-MRI and SWI were enrolled in this retrospective study. Conventional MRIs were evaluated by the VASARI scoring system. TA of DCE-MRI-derived parameters and the degree of ITSS were compared between low-grade gliomas (LGGs) and high-grade gliomas (HGGs). The diagnostic ability of each parameter and their combination for glioma grading were analyzed. Results Significant statistical differences in VASARI features were observed between LGGs and HGGs ( P < 0.05), of which the enhancement quality had the highest area under the curve (AUC) (0.873) with 93.3% sensitivity and 80% specificity. The TA of DCE-MRI derived parameters were significantly different between LGGs and HGGs ( P < 0.05), of which the uniformity of Ktrans had the highest AUC (0.917) with 93.3% sensitivity and 90% specificity. The degree of ITSS was significantly different between LGGs and HGGs ( P < 0.001). The AUC of the ITSS was 0.925 with 93.3% sensitivity and 90% specificity. The best discriminative power was obtained from a combination of enhancement quality, Ktrans- uniformity, and ITSS, resulting in 96.7% sensitivity, 100.0% specificity, and AUC of 0.993. Conclusion Combining conventional MRI, TA of DCE-MRI, and ITSS on SWI may help to improve the differentiation between LGGs and HGGs.
Intraosseous Sliding Plate Fixation Used in Double Osteotomy Bunionectomy
Authors: Bennett Gordon L. , Klaus Derek , Shemory Scott , Sabetta James A. 
Published: September 2018

Background: Distal chevron metatarsal osteotomy bunionectomy is a commonly performed procedure for the treatment of mild to moderate hallux valgus. We continue to use the intraosseous sliding osteotomy plate system for fixation of the distal metatarsal osteotomy. With the addition of the Akin osteotomy, we are able to obtain reliable, reproducible correction with better cosmesis and increased patient satisfaction for more advanced deformities. Methods: We prospectively evaluated 138 (145 feet) consecutive patients who underwent double osteotomy bunionectomy using the intramedullary plate system and 3.2-mm cannulated screw system. The senior author performed all operative procedures. Patients were evaluated preoperatively, postoperatively, and at the final follow-up using the American Orthopaedic Foot & Ankle Society (AOFAS) forefoot scoring system. Results: All osteotomy sites of operatively corrected feet healed. There were no hardware failures. A small number of patients complained of stiffness and pain related to the hardware. All patients dramatically improved their AOFAS scores compared with preoperative values. The hallux valgus angle was corrected by a mean of 17.3 degrees (range, 10 to 20 degrees), and the intermetatarsal angle was corrected by a mean of 6.8 degrees (range, 5 to 9 degrees). Conclusion: Chevron osteotomy paired with an Akin osteotomy (double osteotomy bunionectomy) resulted in excellent function and pain relief. We continue to recommend the use of the intramedullary plate system and 3.2-mm cannulated screw system because of its low profile, reliability of fixation, and relative ease of use. Level of Evidence: Level III, retrospective comparative series.
Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis
Authors: Shervington Leroy , Darekar Ashish , Shaikh Murassa , Mathews Roshini , Shervington Amal 
Published: September 2018

Introduction and objective: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients. Materials and methods: Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study. The HFLS-RA–untreated and MTX-treated cells were subjected to microarray analysis. Results: Microarray data identified 74 differentially expressed genes. These genes were mapped against an RA inflammatory pathway, shortlisting 10 candidate genes. Gene expression profiling of the 10 genes were studied. Fold change (FC) was calculated to determine the differential expression of the samples. Discussion: The transcription profiles of the 10 candidate genes were highly induced in HFLS-RA cells compared with HFLS cells. However, on treating the HFLS-RA cells with MTX, the transcription profiles of these genes were highly downregulated. The most significant expression FC difference between HFLS and HFLS-RA (treated and untreated) was observed with HSPA6, MMP1, MMP13, and TNFSF10 genes. Conclusions: The data from this study suggest the use of HSPA6, MMP1, MMP13, and TNFSF10 gene expression profiles as potential diagnostic biomarkers. In addition, these gene profiles can help in predicting the therapeutic efficacy of MTX.
The Benefit of Supplemental Nutrition Education for Severely Malnourished Patients Awaiting Liver Transplant
Authors: Chaney Amanda J. , Heckman Michael G. 
Published: September 2018

Introduction: Nutritional interventions improve patient outcomes and reduce mortality in patients with cirrhosis by reducing infection risk, ascites, length of stay in hospital and intensive care unit, and mortality. Follow-up phone calls have been found to be useful in improving patient adherence to therapy. Problem: The purpose of this quality improvement project was to determine whether supplemental nutrition education would improve nutrition and outcomes among patients with cirrhosis who are undergoing a liver transplant evaluation. In addition, we sought to measure patient adherence with nutritional recommendations and whether patients perceived this additional education improved their nutrition status. Methods: The Plan-Do-Study-Ask methodology was used. Processes: Addressed 8 patients were enrolled to participate in the supplemental nutrition education, after which they received 3 follow-up phone calls. A retrospective review of data from 10 patients meeting project inclusion criteria were identified by the nutrition specialist and were used as a comparison group. Data were analyzed using descriptive statistics; comparing data from before and after implementation of the supplemental nutrition education was done. Outcomes: At the end of the 8-week project period, 4 (66.7%) patients reported weight loss since the time of enrollment (nutrition education class), and the median patient-generated subjective global assessment score increased by 4 points, rather than decreasing as expected. However, all patients reported they believed the phone calls improved their nutrition status. Implications: With a multidisciplinary approach, this additional patient education may improve patient care and outcomes.
Admission Glucose Number (AGN): A Point of Admission Score Associated With Inpatient Glucose Variability, Hypoglycemia, and Mortality
Authors: McKechnie Jennifer , Maitland Rahat , Sainsbury Christopher A. R. , Jones Gregory C. 
Published: September 2018

Aims: We investigated a point of admission metric of glycemia, the Admission Glucose Number (AGN), and its relationship with both high risk inpatient glucose patterns and mortality in hospital inpatients with type 2 diabetes (T2DM). Methods: Inpatient capillary blood glucose (CBG) data for patients with T2DM in our health board were identified for a 5-year period and associated with most recent preadmission HbA1c. AGN was calculated as first CBG measured during admission (mmol/L), subtracted from most recent preadmission HbA1c (converted to estimated median glucose mmol/l) within 15 months preadmission. The association between AGN and CBG variability (interquartile range), hypoglycemia free survival (HR) and both inpatient and 100-day mortality (HR) were investigated. Results: A total of 21 045 first admissions with available HbA1c data were identified. A positive correlation between AGN and glycemic variability was described (partial correlation coefficient 0.25, P < .001), which was stronger than the correlation of either of AGNs’ individual components: adjusted CBG1 = 0.07 ( P < .001), eAG = 0.08 ( P < .001). The hazard ratio for time to first recorded CBG < 3 mmol/L for high AGN versus low AGN was 1.74 (95% CI 1.55-1.96), P < .001. A high AGN was associated with increased 100-day mortality (HR 1.26, P = .005), however not with in-hospital mortality (HR = 1.31, P = .08). Conclusion: AGN is a simple metric that combines 2 readily available measures associated with adverse outcome in T2DM. AGN may be a useful tool to stratify patients for risk of hypoglycemia and postdischarge death.
The development of multimorbidity during 16 years after diagnosis of type 2 diabetes
Authors: Pouplier Sandra , Olsen Maria Åhlander , Willadsen Tora Grauers , Sandholdt Håkon , Siersma Volkert , Andersen Christen Lykkegaard , Olivarius Niels de Fine 
Published: September 2018

Objective: The aims of this study were to (1) quantify the development and composition of multimorbidity (MM) during 16 years following the diagnosis of type 2 diabetes and (2) evaluate whether the effectiveness of structured personal diabetes care differed between patients with and without MM. Research design and methods: One thousand three hundred eighty-one patients with newly diagnosed type 2 diabetes were randomized to receive either structured personal diabetes care or routine diabetes care. Patients were followed up for 19 years in Danish nationwide registries for the occurrence of outcomes. We analyzed the prevalence and degree of MM based on 10 well-defined disease groups. The effect of structured personal care in diabetes patients with and without MM was analyzed with Cox regression models. Results: The proportion of patients with MM increased from 31.6% at diabetes diagnosis to 80.4% after 16 years. The proportion of cardiovascular and gastrointestinal diseases in surviving patients decreased, while, for example, musculoskeletal, eye, and neurological diseases increased. The effect of the intervention was not different between type 2 diabetes patients with or without coexisting chronic disease. Conclusions: In general, the proportion of patients with MM increased after diabetes diagnosis, but the composition of chronic disease changed during the 16 years. We found cardiovascular and musculoskeletal disease to be the most prevalent disease groups during all 16 years of follow-up. The post hoc analysis of the intervention showed that its effectiveness was not different among patients who developed MM compared to those who continued to have diabetes alone.
Incidence and Treatment Trends of Symptomatic Discoid Lateral Menisci: An 18-Year Population-Based Study
Authors: Sabbag Orlando D. , Hevesi Mario , Sanders Thomas L. , Camp Christopher L. , Dahm Diane L. , Levy Bruce A. , Stuart Michael J. , Krych Aaron J. 
Published: September 2018

Background: A symptomatic discoid lateral meniscus is an uncommon orthopaedic abnormality, and the majority of information in the literature is limited to small case series. Purpose/Hypothesis: The purpose of this study was to determine the incidence of symptomatic discoid menisci in a geographically determined population and to describe treatment trends over time. The hypothesis was that the incidence of symptomatic discoid menisci would be highest among adolescent patients, and thus, the rate of surgical treatment would be high compared with nonoperative treatment. Study Design: Descriptive epidemiology study. Methods: The study population included 79 patients in Olmsted County, Minnesota, identified through a geographic database, who were diagnosed with a symptomatic discoid lateral meniscus between 1998 and 2015. The complete medical records were reviewed to confirm the diagnosis and evaluate the details of injury and treatment. Age- and sex-specific incidence rates were calculated and adjusted to the 2010 United States population. Results: The overall annual incidence of symptomatic discoid lateral menisci was 3.2 (95% CI, 2.5-3.9) per 100,000 person-years; 12.6% of the patients in the cohort had bilateral symptomatic discoid lateral menisci. The overall annual incidence was similar between male (3.5 per 100,000 person-years) and female patients (2.8 per 100,000 person-years). The highest incidence of symptomatic discoid lateral menisci was noted in adolescent male patients aged 15-18 years (18.8 per 100,000 person-years). A majority (72.2%) of patients presented with a symptomatic tear of the discoid meniscus. The remaining patients presented with mechanical symptoms, including catching/locking or effusion, with no demonstrable meniscus tear on imaging or diagnostic arthroscopic surgery. Additionally, 20.0% of patients were observed to have peripheral instability of the meniscus at the time of diagnostic arthroscopic surgery. The mean age of those with peripheral instability was significantly younger than of those who did not have peripheral instability. Sixty patients (75.9%) received surgical treatment during the study period, including 49 (81.7%) patients who underwent partial lateral meniscectomy and 11 (18.3%) patients who underwent lateral meniscus repair in addition to saucerization. Conclusion: With an overall annual incidence of 3.2 per 100,000 person-years, a symptomatic discoid meniscus is an uncommonly encountered orthopaedic abnormality. However, the incidence of symptomatic discoid lateral menisci is highest in adolescent male patients. Because of the high rate of meniscus tears in patients presenting with symptoms, the majority are treated surgically.