bluuebunny/crossref_metadata_2025 huggingface dataset:
Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats
Authors: Oraby Mamdouh A. , El-Yamany Mohammed F. , Safar Marwa M. , Assaf Naglaa , Ghoneim Hamdy A.
Published: January 2019

Background: Early prediction and clinical intervention are extremely important in order to delay or hinder diabetic nephropathy (DN) progression. Objectives: This study aimed to detect early signs of DN and study the potential ameliorating effect of the dipeptidyl peptidase-4 inhibitor, linagliptin, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetic rats. Method: Fr-STZ rats were treated with either linagliptin (3 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks. Results: Fr-STZ DN rats exhibited obvious tubular renal damage and glomerular podocyte injury as confirmed by renal kidney ­injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and vanin-1 mRNA, as well as urinary N-acetyl-β-D-glucosaminidase elevation and nephrin mRNA suppression, associated with the appearance of marked renal interstitial fibrosis and glomerulosclerosis despite the absence of microalbuminuria. Initiation of oxidative, inflammatory, fibrotic, and apoptotic reactions was evident in the settings of renal hyperglycemia. Linagliptin significantly modulated the aforementioned renal tubular injury makers and restored glomerular nephrin expression as well as reversed renal histopathological alterations. Oxidative, inflammatory, fibrotic and apoptotic processes were also alleviated. Conclusions: This study suggests that linagliptin exerts renoprotection against early features of DN in rats probably by inhibition of high glucose-induced renal tubular and glomerular injury thereby hampering KIM-1 and NGAL as well as vanin-1 associated with renal inflammation, fibrosis and oxidative stress.
Interrelationships of Cadmium, Smoking, and Angina in the National Health and Nutrition Examination Survey, a Cross-Sectional Study
Authors: Hecht Eric M. , Arheart Kristopher L. , Lee David J. , Hennekens Charles H. , Hlaing WayWay M.
Published: January 2019

The interrelationships between cadmium biomarker levels, smoking, and myocardial infarction and stroke have been established. In this cross-sectional analysis, we explored the interrelationships of blood cadmium levels, smoking, and angina. We analyzed the National Health and Nutrition Examination Survey (NHANES, 2003–2014) accounting for the multi-staged complex sampling design. Participants 40–79 years of age with blood cadmium levels but without a history of myocardial infarction and/or stroke were included (n = 14,832). We examined blood cadmium levels (3 tertile groups) in relation to 3 (diagnosed, undiagnosed, and composite diagnosed and/or undiagnosed) angina outcomes. Multivariable logistic regression models adjusted for age, diabetes, smoking status, and household income were used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Of 14,832 participants, 741 (4.2%) had positive composite angina. The crude and adjusted ORs comparing those in the lowest tertile (referent group) of blood cadmium to those in the highest tertile for the composite outcome were 1.82 (95% CI 1.42–2.34) and 1.45 (95% CI 1.12–1.88), respectively. These cross-sectional data from a nationally representative sample contribute to the hypothesis that there are interrelationships between smoking, cadmium, and angina.
Ectopic Calcification of Fibrin Sheath on the Catheter
Authors: Jia Lan , Wang Lihua , Wei Fang , Jiang Aili
Published: January 2019

We describe a case of hemodialysis catheter that appeared to be encased in a sleeve-shaped fibrous sheath with calcification. Ectopic calcification is a serious complication in hemodialysis patients with calcium-phosphorus metabolism disorder. Clinical awareness and understanding of this condition is imperative to the prevention and management of ectopic calcification.
Could Dietary Glutamate Play a Role in Psychiatric Distress?
Authors: Kraal A. Zarina , Arvanitis Nicole R. , Jaeger Andrew P. , Ellingrod Vicki L.
Published: January 2019

Glutamate is an amino acid that functions as an excitatory neurotransmitter. It has also been associated with somatic and psychiatric distress and is implicated in the pathophysiology of psychiatric disorders such as schizophrenia. Ingestion of dietary glutamate, such as monosodium glutamate (MSG), has been mechanistically linked with greater distress among patients with chronic pain conditions, though findings have been equivocal. Preliminary research suggests that an MSG-restricted diet confers beneficial effects on somatic symptoms and well-being for some individuals with chronic pain conditions. In addition to associations with somatic distress, glutamate has been associated with the onset and progression of psychiatric symptoms. Thus, the role of dietary glutamate in psychiatric distress represents an underdeveloped and potentially important area for future research aimed at clarifying pathophysiological mechanisms and identifying targets for dietary intervention in psychiatric illnesses.
In-Hospital Outcomes after Radical Cystectomy for Bladder Cancer: Comparing National Trends in the United States and Germany from 2006 to 2014
Authors: Groeben Christer , Koch Rainer , Baunacke Martin , Borkowetz Angelika , Wirth Manfred P. , Huber Johannes
Published: January 2019

Background: Radical cystectomy (RC) still poses a significant risk for mortality and morbidity. Objectives: We compared in-hospital outcomes after RC in the United States and ­Germany using population-based data. Methods: We compared data from the US Nationwide Inpatient Sample to the German hospital billing database. Mortality and transfusion during hospital stay and length of stay (LOS) were evaluated. Results: In all, 17,711 (the United States) and 60,447 (­Germany) cases were included. The share of robot-assisted RC increased to 20.5% in the United States vs. 2.3% in Germany (p < 0.001). In-hospital mortality was 1.9% (the United States) vs. 4.6% (Germany), transfusion rates were 34.2% (the United States) vs. 58.7% (Germany), and LOS was 10.7 (the United States) vs. 25.1 days (Germany; all p < 0.001). On multivariate analysis, higher patient age and lower annual hospital caseload were associated with increased mortality and longer LOS. Minimal-invasive surgery was associated with less blood transfusion and shorter LOS in the United States vs. hospital caseload and choice of urinary diversion in Germany. Conclusions: Healthcare systems might exert a relevant impact on outcomes of oncologic surgery. Increased in-hospital mortality rates in Germany seem to be partly explained by much longer LOS compared to those in the United States. Annual caseload seems to be influential on in-hospital outcomes raising the question of centralization of RC.
Chronic Addiction to Tramadol and Withdrawal Effect on the Spermatogenesis and Testicular Tissues in Adult Male Albino Rats
Authors: Ibrahim Marwan Abdel-Latif , Salah-Eldin Alaa-Eldin
Published: January 2019

Aim: The present study aimed to elucidate the effects of tramadol on the testicular functions of adult male rats due to the chronic usage of tramadol and the effect of its withdrawal. Method: Adult male albino rats were classified into the following 3 groups: (I) a control administered with normal saline and (II) tramadol-treated rats (40 mg/kg b.w. orally) for 21 successive days; and (III) like the rats in the second group but kept for 4 weeks after the last tramadol dose to study the effect of tramadol withdrawal. At the end of the experimental period, blood was collected and specimens from testis were taken for histopathological, biochemical, and molecular studies. A reverse transcription-polymerized chain reaction after RNA extraction from specimens was detected for the anti-apoptotic and pro-apoptotic genes in testicular tissues. Also, malondialdehyde (MDA) was measured in tissues homogenate and antioxidant enzymes activities were evaluated. Results: The results of this study demonstrated histological changes in testicular tissues in groups II and III compared to the control group, accompanied with increased apoptotic index and proved by increased B-cell lymphoma-2 (Bcl-2) associated-X-protein and caspase-3 expression, whereas anti-apoptotic Bcl-2 markedly decreased. Moreover, in tramadol-abused and -withdrawal groups, the MDA level increased, while the antioxidant enzymes activity decreased and revealed oxidative stress, indicating that tramadol is harmful at the cellular level and can induce apoptotic changes in testicular tissues. The withdrawal effect showed signs of improvement, but it did not return to normal levels. Conclusions: It could be concluded that the administration of tramadol causes abnormalities on testicular tissues associated with oxidative stress, which confirmed the risk of increased oxidative stress on testicular tissues due to tramadol abuse.
Diagnosis and Management of Pancreatic Adenocarcinoma in the Background of Chronic Pancreatitis: Core Issues
Authors: Narkhede Rajvilas A. , Desai Gunjan S. , Prasad Pande P. , Wagle Prasad K.
Published: January 2019

Background: The incidence of pancreatic adenocarcinoma (PDAC) in patients with chronic pancreatitis (CP) is as high as 5%. It is a commonly encountered diagnostic challenge in patients with CP on long-term follow-up. Summary: This review consolidates the existing literature on assessment of PDAC in background of CP, its evaluation through the available investigations, surgical management, and prognostication. Recent change in symptomatology of an otherwise stable CP should raise a suspicion of malignancy. Endoscopic ultrasound (EUS) is more specific and sensitive in establishing the diagnosis of PDAC compared to cross-sectional imaging (computed tomography/magnetic resonance imaging). Intraoperative assessment with careful palpation coupled with careful clinical judgment helps in differentiating between an inflammatory mass and pancreatic cancer. Confirmation can be obtained with either preoperative EUS-guided fine needle cytology/core biopsy or intraoperative core biopsy under ultrasound guidance. However, despite complete evaluation with above options, 1–6% patients often show malignancy on final histopathological examination. Key Messages: Diagnosis of PDAC in CP needs a high index of suspicion. Cross-sectional imaging has poor negative predictive value. CA 19-9 with MUC5AC combination may become an ideal investigation. EUS with core biopsy/frozen section has a good sensitivity and specificity and low false negative results. Complete radical resection should be the aim to get long-term survival.
Improved Control of Secondary Hyperparathyroidism in Hemodialysis Patients Switching from Oral Cinacalcet to Intravenous Etelcalcetide, Especially in Nonadherent Patients
Authors: Xipell Marc , Montagud-Marrahi Enrique , Rubio María Victoria , Ojeda Raquel , Arias-Guillén Marta , Fontseré Néstor , Rodas Lida , Vera Manel , Broseta José Jesús , Torregrosa Vicens , Filella Xavier , Maduell Francisco
Published: January 2019

Background: Etelcalcetide is a novel second-generation calcimimetic that, because of its intravenous administration, could improve treatment adherence in secondary hyperparathyroidism (SHPT). The aim of this study was to evaluate the effectiveness of etelcalcetide compared with that of cinacalcet in controlling SHPT in patients under hemodialysis. Methods: A prospective observational study was performed in 29 patients with SHPT under hemodialysis who switched from cinacalcet to etelcalcetide with a follow-up of 6 months. A survey was conducted of adherence to the oral calcimimetic. The primary end-point of the study was to assess whether etelcalcetide was more effective than cinacalcet in controlling SHPT. Results: After the switch of treatment, none of the patients developed clinical intolerance or new adverse effects. Etelcalcetide was more effective than cinacalcet in controlling intact parathyroid hormone (iPTH), with an overall decrease in iPTH levels that was significant from the second month. Average calcium levels remained within the normal range, with a higher percentage of hypocalcemia with etelcalcetide (6.9 vs. 13.8%), which was asymptomatic in all cases. Patients who were nonadherent to cinacalcet (38%) showed a significant reduction in calcium and iPTH during follow-up with etelcalcetide. The adherent group (62%) also showed a trend to lower iPTH levels reaching statistical significance after 5 months of follow-up. The dose conversion factor for the switch from cinacalcet to etelcalcetide was etelcalcetide/session = 0.111*mg cinacalcet/day + 0.96, R2 = 0.57. Conclusions: Etelcalcetide was more effective than cinacalcet in this patient population, especially in the nonadherent subgroup, leading to better SHPT control without adverse effects.
The Tumor Microenvironment in Neuroendocrine Tumors: Biology and Therapeutic Implications
Authors: Cives Mauro , Pelle’ Eleonora , Quaresmini Davide , Rizzo Francesca Maria , Tucci Marco , Silvestris Franco
Published: January 2019

Neuroendocrine tumors (NETs) include a heterogeneous group of malignancies arising in the diffuse neuroendocrine system and characterized by indolent growth. Complex interactions take place among the cellular components of the microenvironment of these tumors, and the recognition of the molecular mediators of their interplay and cross talk is crucial to discover novel therapeutic targets. NET cells overexpress a plethora of proangiogenic molecules including vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, semaphorins, and angiopoietins that promote both recruitment and proliferation of endothelial cell precursors, thus resulting among the most vascularized cancers with a microvessel density 10-fold higher than epithelial tumors. Also, NETs operate multifaceted interactions with stromal cells, both at local and distant sites, and whether their paracrine secretion of serotonin, connective tissue growth factor, and transforming growth factor β primarily drives the fibroblast activation to enhance the tumor proliferation, on the other side NET-derived profibrotic factors accelerate the extracellular matrix remodeling and contribute to heart valves and/or mesenteric fibrosis development, namely, major complications of functioning NETs. However, at present, little is known on the immune landscape of NETs, but accumulating evidence shows that tumor-infiltrating neutrophils, mast cells, and/or macrophages concur to promote the neoangiogenic switch of these tumors by either direct or indirect mechanisms. On the other hand, immune checkpoint molecules are heterogeneously expressed in NETs’ surrounding cells, and it is unclear whether or not tumor-infiltrating lymphocytes are antitumor armed within the microenvironment, given their low mutational load. Here, we review the current knowledge on both gastroenteropancreatic and pulmonary NETs’ microenvironment as well as both established and innovative treatments aimed at targeting the tumor-host interplay.
Projected Changes in Maternal Heat Exposure During Early Pregnancy and the Associated Congenital Heart Defect Burden in the United States
Authors: Zhang Wangjian , Spero Tanya L. , Nolte Christopher G. , Garcia Valerie C. , Lin Ziqiang , Romitti Paul A. , Shaw Gary M. , Sheridan Scott C. , Feldkamp Marcia L. , Woomert Alison , Hwang Syni‐An , Fisher Sarah C. , Browne Marilyn L. , Hao Yuantao , Lin Shao ,   the National Birth Defects Prevention Study, Hobbs Charlotte , Carmichael Suzan , Reefhuis Jennita , Tinker Sarah , Anderka Marlene , Druschel Charlotte , Bell Erin , Olshan Andy , Meyer Robert , Canfield Mark , Langlois Peter , Botto Lorenzo
Published: January 2019

Background

More intense and longer‐lasting heat events are expected in the United States as a consequence of climate change. This study aimed to project the potential changes in maternal heat exposure during early pregnancy (3–8 weeks post conception) and the associated burden of congenital heart defects (
CHD
s) in the future.

Methods and Results

This study expanded on a prior nationwide case‐control study that evaluated the association between
CHD
s and maternal heat exposure during early pregnancy in summer and spring. We defined multiple indicators of heat exposure, and applied published odds ratios obtained for the matching season of the baseline (1995–2005) into the projection period (2025–2035) to estimate potential changes in
CHD
burden throughout the United States. Increases in maternal heat exposure were projected across the United States and to be larger in the summer. The Midwest will potentially have the highest increase in summer maternal exposure to excessively hot days (3.42; 95% CI, 2.99–3.88 per pregnancy), heat event frequency (0.52; 95%
CI,
0.44–0.60) and heat event duration (1.73; 95%
CI,
1.49–1.97). We also found large increases in specific
CHD
subtypes during spring, including a 34.0% (95%
CI,
4.9%–70.8%) increase in conotruncal
CHD
in the South and a 38.6% (95%
CI
, 9.9%–75.1%) increase in atrial septal defect in the Northeast.

Conclusions

Projected increases in maternal heat exposure could result in an increased
CHD
burden in certain seasons and regions of the United States.
Abstract 104: Topographic White Matter Hyperintensity Patterns Associated With Alzheimer Pathologies
Authors: Graff-Radford Jonathan , de Arenaza-Urquijo Eider , Schwarz Christopher , Brown Robert D , Ward Chadwick P , Mielke Michelle M , Przybelski Scott , Rabinstein Alejandro A , Lenick Timothy G , Gunter Jeffrey L , Petersen Ronald C , Kantarci Kejal , Knopman David S , Lowe Val , Jack Clifford , Vemuri Prashanthi
Published: January 2019

Background:
Although white matter hyperintensities (WMH) have been viewed as a marker of vascular disease, pathology studies have found an association of WMH with Alzheimer’s disease (AD) pathologies. Our objective was to investigate the topographic patterns of WMH associated with AD biomarkers.

Methods:
From the population-based Mayo Clinic Study of aging, 434 non-demented participants with FLAIR-MRI, tau-PET and PiB-PET scans were identified. A subset had microbleeds on T2* GRE scans. We ran SPM12 based voxel-wise multiple regression analyses to detect WMH regions associated with AD biomarkers (global amyloid from PiB-PET and meta-ROI tau uptake from tau-PET) adjusting for age, sex, and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa.

Results:
Topographic patterns of WMH associated with amyloid after both voxel and cluster level corrections primarily included periventricular WMH (frontal and parietal lobes). Masks with lenient threshold (greater detection sensitivity) and strict thresholds (greater detection specificity) are shown in the figure. (A) and (B) show the areas of positive associations between PIB ratio and WMHs adjusted by age, sex, education, hypertension and Tau meta ROI. The sensitive mask (A) was thresholded at FDR p<0.05 at voxel level and FWE p<0.05 at cluster level. The specific mask (B) was thresholded at FDR p<0.001 at voxel level and FDR p<0.05 at cluster level. (C) Shows the frequency of WMHs in the study sample, ranging from infrequent (dark blue) to frequent (green to red). Both the sensitive (p<0.001, Cohen’s D=0.615) and specific WMH maps (p<0.001, Cohen’s D = 0.705) were associated with microbleeds. No WMH regions were associated with tau.

Conclusion:
Amyloid but not tau load on PET was associated with WMH topographically. The WMH regions associated with amyloid were associated with CMBs suggesting that cerebral amyloid angiopathy may be contributing to the relationship between amyloid and WMH.
Abstract 113: Late Window Transfer Patients had Favorable Outcomes Following Thrombectomy in DEFUSE 3
Authors: Sarraj Amrou , Mlynash Michael , Heit Jeremy , Marks Michael , Lansberg Maarten , Albers Gregory
Published: January 2019

Background:
Although the treatment benefit of endovascular thrombectomy (EVT) was maintained in transfer patients in the early window trials, overall rates of functional independence were lower in both the EVT and control groups among transfer patients. We hypothesized that the imaging-based selection criteria employed in DEFUSE 3 would lead to comparable outcome rates and treatment efficacy in transfer vs. direct admission patients.

Methods:
DEFUSE 3 patients were stratified based on if they presented directly to the study site or were transferred from a primary center. The primary and secondary efficacy and safety outcomes of DEFUSE 3 were compared.

Results:
Of 182 patients randomized, 121 (66%) were transfers and 61 (34%) direct. The 2 groups had similar baseline characteristics, other than transfers had 30 min longer median times from last known well time to arrival at the study site. The primary efficacy outcome (mRS shift at day 90) did not differ in the direct vs. transfer groups, OR 2.9, 95% CI 1.2-7.2, P=0.014 for direct and OR=2.6, 95% CI 1.3-4.8, P=0.009 for transfer (Fig 1). The overall rate of functional independence (mRS 0-2 at day 90) in the EVT group did not differ (44% direct, 45% transfer) nor did the treatment effect: RR 2.0 (0.9-4.4) direct vs. 3.1 (1.6-6.1) for transfer. EVT reperfusion rates were identical (mTICI≥2b 76%) in both groups. The rates of death and SICH did not differ. Transfer patients had more favorable collateral profiles (based on the hypoperfusion intensity ratio) median (IQR) for transfer 0.35 (0.18-0.47) vs. 0.42 (0.25-0.56) for direct, p=0.050.

Conclusions:
In late window patients selected by penumbral mismatch criteria, both the favorable outcome rates and treatment effects did not decline in transfer patients. These results have healthcare implications indicating transferring potential candidates for late window thrombectomy to EVT centers is associated with substantial clinical benefits and should be strongly encouraged.
Abstract 119: Final Patient-Level Results From the Michigan Stroke Transitions Trial (MISTT): A Randomized Clinical Trial to Improve Stroke Transitions
Authors: Reeves Mathew J , Fritz Michele C , Woodward Amanda T , Hughes Anne K , Coursaris Constantinos K , Swierenga Sarah J , Nasiri Mojdeh , Freddolino Paul P
Published: January 2019

Background:
Navigating the transition after returning home following a stroke can be associated with substantial psychosocial and health-related challenges. The Michigan Stroke Transitions Trial (MISTT) tested the efficacy of a social work case management (SWCM) program and access to an online information and support resource (MISTT Website) to improve outcomes in acute stroke patients who returned home.

Methods:
MISTT was a randomized, pragmatic, open, 3-group parallel designed trial conducted in 3 Michigan hospitals. Eligible subjects were acute stroke patients who returned home either directly or within 4 weeks of being discharged to a rehab facility. A total of 265 patients were randomized to one of 3 groups: 1) usual care, 2) SWCM program only, or 3) SWCM plus MISTT Website access. Interventions concluded after 90-days. Primary outcomes including Quality-of-Life (PROMIS Global-10 physical- and mental-health subscales) and the Patient Activation Measure (PAM) were collected by telephone at 7- and 90-days. The change in outcomes (90-day minus 7-day) between the three treatment groups was assessed using a differences-in-differences (D-in-D) analysis.

Results:
The mean age of the 265 randomized subjects was 66 years, 49% were female, 21% non-white, 14% had hemorrhagic stroke, 56% were discharged to a rehab facility. Following the intervention there were statistically significant treatment group differences in PROMIS physical-health (p=0.003) and PAM (p=0.042), but not PROMIS mental-health (p=0.56). Mean change in physical-health scores for group-3 (SWCM+Website) was significantly higher than both group-1 (Usual Care) (difference= 3.4; 95%CI=1.41, 5.33; p<0.001) and group-2 (SWCM) (difference= 2.4; 95%CI=0.46, 4.34; p=0.02). The mean change in PAM scores for group-3 was significantly higher than group-2 (6.7; 95%CI=1.26, 12.08; p=0.02) and marginally higher than group-1 (5.0; 95%CI=-0.47, 10.52; p=0.07).

Conclusion:
An intervention that combined social worker-led case management with access to online stroke-related information produced greater gains in patient-reported physical health and activation compared to usual care or case management alone. [ClinicalTrials.gov: NCT02653170].
Abstract 148: Indications and Prognosis With Operative versus Nonoperative Management of Subdural Hematomas: A Single Site Retrospective Review
Authors: Sharma Richa , Rocha Eva A , Pasi Marco , Lee Hang , Patel Aman , Singhal Aneesh
Published: January 2019

Background:
Guidelines for management of subdural hemorrhage (SDH) are based on small studies which account for only factors of presentation. Our aim was to characterize which patients benefit from surgical evacuation as a function of demographic, baseline functional, clinical, and radiographic information.

Methods:
Patients who did and did not undergo surgery were compared. To isolate the effect of surgery on outcome, a propensity score to undergo surgery was created. A multivariable model to predict the outcome of interest, net mRS (90-day follow-up – baseline mRS), was built. The robustness of the resulting parameter estimates was assessed by bootstrapping with 1,000 iterations. The parameter estimates were utilized to create a SDH functional prediction score. A nomogram was generated to include the predicted probability of a good net mRS by age, ambulatory status, and midline shift value with and without surgery.

Results:
A cohort of 201 patients presenting to Massachusetts General Hospital with an SDH were analyzed, of whom 120 underwent surgery. A propensity score predicting the likelihood of receiving surgery was created with the Charlson comorbidity index, focal neurologic deficit, SDH diameter, and midline shift. The odds ratio (OR) of a good net mRS with surgery was 5.76 (95% CI 1.57, 21.17) when adjusting for the propensity score. A model was built predicting a good net MRS including age (OR 0.96, 0.93-0.99), surgery (4.63, 1.13-18.93), ambulation (4.41, 1.63-11.93), and midline shift (0.82, 0.72, 0.94) with a c-statistic of 0.80. Bootstrapping with 1,000 samples demonstrated the robustness of the parameter estimates. An SDH score was created with a minimum -36 and maximum 149 depicted in the figure.

Conclusion:
An SDH score predicting functional change with and without surgery as a function of age, ambulatory status, and midline shift demonstrated discriminatory ability. We are now evaluating the SDH score in an external validation cohort.
Abstract 15: Reduction in Perihematomal Edema Leads to Improved Clinical Outcomes: Results from the MISTIE III Trial
Authors: Mould W. Andrew , Muschelli John , Avadhani Radhika , McBee Nichol , Lane Karen , Thompson Richard , Ziai Wendy , Zuccarello Mario , Awad Issam , Hanley Daniel F
Published: January 2019

Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and poor functional outcome. No successful treatments or therapies exist. Secondary injury to ICH, perihematomal edema (PHE), contributes to poor outcomes and is a potential therapeutic target. We hypothesized that minimally invasive surgery (MIS) plus rt-PA would reduce ICH and PHE volumes and that this reduction would lead to improved clinical outcomes.

MISTIE III is a multi-center, prospective, randomized, phase III trial testing the efficacy of standardized hematoma evacuation after spontaneous ICH. We conducted a semi-automated, computerized, volumetric analysis on CT imaging assessing the effect of hematoma removal on PHE at baseline (BL) and end-of-treatment (EOT).

Of 500 randomized, 240 surgical and 232 medical patients were analyzed. There was no significant difference between the two cohorts in age, GCS, ICH location, BL ICH or BL PHE volumes. Surgical patients experienced a significant reduction in ICH volumes: mean EOT ICH 14.9(12.2)mL vs medical patients, 46.8(17.4)mL; p<0.001. Moreover, surgical patients had a positive reduction in PHE, 4.7(13.8)mL, compared with medical patients -11.8(15.1)mL; p<0.001. Subdividing the cohort into pre-specified subgroups of ICH removal >65%, 20-65%, and <20% clot removal, (Med 0:5:227, Surg 167:66:7) all patients achieving <20% reduction experienced a PHE increase, while reductions of 2.1mL and 6.6mL occurred in the surgical groups achieving 20-65% and >65%, respectively; p<0.001. A continuous analysis confirmed that greater ICH removal leads to greater PHE reduction (Spearman coefficient: 0.55(0.48-0.61), p<0.001). Logistic regression was used to look at effect of PHE volume on mortality and for every 10 mL increase in PHE volume, patients in both groups were 25% more likely to die [OR=1.25 (1.11-1.41)] at 30 days and 15% more likely at 180 days [OR=1.15 (1.03-1.27)]. Complete clinical and unblinded functional outcomes data will be presented at the conference.

The MISTIE procedure has demonstrated capability to substantially reduce ICH volumes while also mitigating PHE formation. This benefit has potential to establish a viable treatment option, which may significantly improve patient outcomes in this population.
Abstract 154: Non-Contrast Computed Tomography Based Patient Selection Achieves Similar Outcomes to Advanced Neuroimaging in Late Time Window Endovascular Thrombectomy
Authors: Desai Mihir , Alsahli Khalid , Cheung Andrew , Wenderoth Jason , Kohli Akshay , Cappelen-Smith Cecilia , Cordato Dennis , Tay Kevin , Hodgkinson Suzanne , McDougall Alan , Zagami Alessandro S , Manning Nathan W
Published: January 2019

Background and Aims:
Endovascular Thrombectomy (EVT) for anterior circulation large vessel occlusion(LVO) in late time windows (over 6 hours) has been validated. Studies utilised advanced neuroimaging to select patients with small ischaemic cores. We have evaluated if routine imaging with non-contrast CT (NCCT) is inferior to CT Perfusion (CTP) to select patients for EVT in late time windows.

Method:
A prospectively maintained database of all EVT patients at two tertiary referral centres was retrospectively interrogated to identify anterior circulation LVO patients, with groin puncture times over 6 hours from symptom onset or time last seen well. Subjects were divided into those that underwent CTP in addition to routine NCCT and CT angiography (CTA) and those that were selected by NCCT/CTA alone.

Results:
A total of 85 patients were included, 39 (46%) had CTP (CTP+). No significant difference between baseline characteristics of CTP+ vs CTP- groups such as age (mean 66 vs 74, p=0.26), gender (male 49% vs 59%, p=0.36), median ASPECT (8 vs 8, p=0.84) and median NIHSS (13 vs 13, p=0.42) were observed. The two groups were also well matched with respect to time metrics including onset to imaging time (mean 519 vs 477 mins, p=0.41), time to groin puncture (mean 733 vs 690 mins, p=0.90) and procedure time (mean 41 vs 38 mins, p=0.94). No significant difference between early neurological recovery (36% vs 44%, p=0.48), 90 day mean utility weighted mRS (6.2, 95% CI [5.1, 7.4] vs 6.4, 95% CI [5.2, 7.5] p=0.75), rates of functional independence at 90 days (60% vs 64%, p=0.76), and rates of symptomatic haemorrhage (8 vs 9%, p=0.41) was observed between the groups.

Conclusion:
In late time windows, anterior circulation LVO patients selected for EVT based on routine imaging had non-inferior outcomes to those who underwent CTP. Our data suggests that late time window patients who do not have access to advanced neuroimaging should not be excluded from EVT.
Abstract 159: Baseline Perfusion Imaging Collateral Scores Predict Infarct Growth in DEFUSE 3
Authors: MacLellan Adam , Heit Jeremy J , Marks Michael P , Lansberg Maarten G , Mlynash Michael , Albers Gregory W
Published: January 2019

Background:
High relative cerebral blood volume (rCBV) within the ischemic lesion and a low hypoperfusion intensity ratio (HIR) predict good collateral vessel status and correlate with infarct growth and functional outcome in early window patients with large vessel anterior circulation occlusions. Their performance in predicting clinical and radiologic outcome has not been assessed in late presenting patients. We hypothesized that favorable baseline HIR and rCBV profiles would predict less infarct growth at 24 hours in late presenting (6-16h), non-reperfused patients in DEFUSE 3.

Methods:
Non-reperfused patients in both arms of DEFUSE 3 were included. Baseline ischemic core, Tmax >6s, and Tmax >10s perfusion lesion volumes were calculated with RAPID software; 24h infarct volumes were manually determined from DWI or CT. Substantial infarct growth was defined as a >25mL increase between baseline ischemic core and 24h infarct volume. HIR was defined as the proportion of the Tmax >6s lesion with Tmax >10s delay; rCBV was calculated by RAPID from the mean CBV values within the Tmax >6s lesion compared to regions of normal CBV. Functional independence was defined as a modified Rankin score of 0-2.

Results:
Eighty-four patients with baseline perfusion imaging were included. ROC analysis showed that HIR >0.34 (AUC=0.68) and rCBV <0.74 (AUC=0.72) optimally predicted substantial infarct growth at 24h. Median growth was 23.4 versus 73.2mL with the HIR threshold of 0.34 (p=0.005), and 24.3 versus 58.7mL with the rCBV threshold of 0.74 (p=0.004). If baseline HIR and rCBV were both favorable, median growth was 21.7mL, 40.9mL if one was favorable, and 108.2mL if both were unfavorable (p=<0.001). Baseline HIR and rCBV were not associated with functional outcome at 90 days, though baseline Tmax >10s volume was significantly smaller in functionally independent patients (p=0.04).

Conclusion:
Perfusion collateral scores (HIR and rCBV) forecast infarct growth in late presenting, non-reperfused ischemic stroke patients. These parameters may be useful for guiding transfer decisions, such as need for repeat imaging on arrival to a thrombectomy center, and may help identify slow progressing patients more likely to have persistent salvageable ischemic tissue beyond 24 hours.
Abstract 161: Interfacility Transfer for Mechanical Thrombectomy - Direct to Neuroangiography or CT Angiography First?
Authors: Humbert Kelley A , Sellers Michele , Neuhaus-Booth Elizabeth , Messé Steven R , Pukenas Bryan A , Cucchiara Brett L
Published: January 2019

Objective:
Faster time to mechanical thrombectomy (MT) is associated with better outcome in acute stroke. In patients transferred from other hospitals where a routine CT has already ruled out hemorrhage, transfer direct to angiography (DTA) suite may reduce door to groin time compared to transfer to CT angiography (CTA) first. However, this may result in unnecessary catheter angiography if many patients would have been excluded based on CTA results. We sought to determine how often CTA and repeat head CT changed the decision to proceed to MT.

Methods:
An internal transfer database at a comprehensive stroke center (CSC) was used to identify patients transferred from outside facilities for consideration of mechanical thrombectomy from July 2016 to May 2017. Detailed clinical and radiographic data was extracted using a standard case report form.

Results:
Of 187 patients transferred for MT, 171 underwent CT +/- CTA on arrival, 5 went DTA, and 11 were admitted without imaging or intervention. Among those undergoing CT +/- CTA on arrival, MT was aborted in 110 (64%) patients. Of these, 87 (79%) were aborted directly based on imaging findings, with absence of proximal large vessel occlusion (LVO) amenable to MT being the most common reason (69%), followed by rapid clinical improvement or mild deficit (7%). MT was aborted based on imaging findings in 36% of patients with NIHSS≥10 on arrival at CSC, and in 29% of patients with NIHSS≥15. In patients with outside hospital CTA demonstrating proximal LVO (n=48), MT was aborted in 48% on CSC arrival, mostly based on imaging findings (48%) or dramatic clinical improvement (31%). Use of tPA did not substantively modify any of these findings. CSC arrival to groin puncture tended to be shorter in the patients going DTA compared to CTA (median 39 v 54 min, p=0.06).

Conclusions:
While transfer DTA may be associated with faster door to groin puncture times, this might result in many patients undergoing unnecessary catheter angiography who would have been excluded based on CT +/- CTA findings. Even in transferred patients with severe stroke deficits on arrival, imaging excludes about 1/3 of patients from MT.
Abstract 167: Geographic Analysis of Mobile Stroke Unit Treatment in a Densely Populated Urban Area: The New York City METRONOME Registry
Authors: Kummer Benjamin R , Lerario Michael P , Hunter Madeleine D , Efraim Elizabeth S , Wu Xian , Omran Setareh S , Diáz Iván , Lekic Tim , Sacchetti Daniel , Kulick Erin R , Pishanidar Sammy , Mir Saad A , Zhang Yi , Asaeda Glenn , Navi Babak B , Marshall Randolph S , Fink Matthew E
Published: January 2019

Background:
Mobile stroke units (MSUs) reduce time to thrombolytic treatment in acute ischemic stroke. It is unclear whether this time advantage persists in densely-populated urban areas with many readily-accessible hospitals.

Methods:
We collected clinical data, treatment times, numbers of nearby designated stroke centers (DSC), and distances traveled from suspected stroke patients transported by a single-institution MSU operating in Manhattan, New York from October 2016-September 2017. For comparison, we collected information on patients transported to our institution via conventional ambulance for acute stroke during the same hours of MSU operation (Monday-Friday, 9AM-5PM). Our exposure was MSU care, and our coprimary outcomes were dispatch-to-scene arrival and scene arrival-to-thrombolysis times. We estimated mean differences in each primary outcome between both groups, adjusting for clinical, demographic, and geographic factors.

Results:
We identified 66 patients transported by MSU, of whom 29 (44%) were treated with IV thrombolysis, and 19 patients transported by conventional ambulance, of whom 9 (48%) were treated with IV thrombolysis. Patients treated in the MSU traveled longer to accepting hospitals and were picked up closer to a greater number of DSCs in a 1 mile radius than non-MSU patients (Table). Despite longer median dispatch-to-ambulance arrival and ambulance arrival-to-hospital arrival times than non-MSU patients, MSU patients had shorter mean dispatch-to-thrombolysis and ambulance arrival-to-thrombolysis times. In multivariable analysis, MSU care was associated with a mean increase in dispatch-to-ambulance arrival time of 6.5 minutes (95% CI, 2.3-10.6) that was offset by a mean decrease in ambulance arrival-to-thrombolysis time of 42.2 minutes (95% CI, 31.1-53.4).

Conclusions:
In a densely populated urban area, MSU care was associated with substantially quicker time-to-thrombolysis when compared to conventional care.
Abstract 176: To Stay or to Go? Utilization of a Mobile Interventional Stroke Team Shortens Time to Treatment in Large Vessel Occlusion
Authors: Velickovic Ostojic Lili , Skliut Maryna , Fifi Johanna T
Published: January 2019

Objective:
To compare outcomes of mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) presenting to a single primary stroke center (PSC). MT was performed either by a mobile interventional stroke team (MIST) on site or after interhospital transfer to a comprehensive stroke center (CSC).

Background:
MT has become standard of care in acute LVO. A majority of hospitals cannot perform MT on site, requiring patient transfer to a thrombectomy-capable center. Within a metropolitan multihospital health care system, utilization of a MIST shortens time to intervention, potentially leading to better outcomes and decreased cost of care.

Methods:
We performed a retrospective chart review of all acute LVOs presenting to a PSC in Manhattan, NY, from September 2013 to February 2018. We selected patients who underwent MT on site or after transfer to a CSC. Outcomes were assessed by Thrombolysis in Cerebral Infarction (TICI), National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) scores at 90 days.

Results:
MT was performed in 48 patients by one endovascular team; 37 patients for whom all data was available were selected for analysis. 28 MTs were performed on site by a MIST (group 1), and 9 patients were transferred to a CSC for intervention (group 2). Median age was 74.5 and 73 years respectively. In group 1, median NIHSS on presentation was 18 and median Alberta Stroke Program Early CT Score (ASPECTS) was 9, compared to 17 and 10 respectively in group 2. Median door-to-puncture (DTP) time was 144.5 minutes and 233 minutes respectively (p<0.05). In group 1, 82% had baseline mRS 0-2 (functional independence), compared to 36% at 90 days. In group 2, 100% had baseline mRS 0-2, and 22% at 90 days. TICI ≥2B was achieved in 89% in both groups. In group 1, 50% had complete reperfusion (TICI 3), compared to 11% in group 2.

Conclusion:
DTP times were significantly shorter in patients treated by a MIST. This group also had better reperfusion grades and a higher rate of functional independence, although statistical significance was not reached. Even though our study is limited by a small number of cases, the data indicates that in certain geographic areas, the utilization of a MIST may be associated with better outcomes in patients with stroke due to LVO.
Abstract 181: Large Aortic Arch Plaques are Associated With CHADS
2
and CHA
2
DS
2
-VASc Scores: A Multicenter Registry Analysis
Authors: Ueno Yuji , Tateishi Yohei , Doijiri Ryosuke , Kuriki Ayako , Shimizu Takahiro , Kikuno Muneaki , Shimada Yoshiaki , Takekawa Hidehiro , Yamaguchi Eriko , Koga Masatoshi , Kamiya Yuki , Ihara Masafumi , Tsujino Akira , Hirata Koichi , Toyoda Kazunori , Hasegawa Yasuhiro , Hattori Nobutaka , Urabe Takao
Published: January 2019

Introduction:
Recently, The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial versus Aspirin to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) failed to show the efficacy of rivaroxaban for secondary prevention of ESUS. In particular, paroxysmal atrial fibrillation was detected only 3% of patients during follow up, and was not a major cause of recurrent stroke in ESUS. Thus, current trends indicate that diverse embolic etiologies are critical in the management of ESUS/cryptogenic stroke.

Methods:
The CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for ESUS/Cryptogenic Stroke) is an observational and multicenter registry of ESUS/CS patients who were admitted to the participating hospitals and underwent transesophageal echocardiography (TEE) from April 2014 to December 2016. We obtained baseline characteristics, radiological and laboratory data, and echocardiographic findings especially in embolic sources demonstrated on TEE, which were compared according to CHADS
2
and CHA
2
DS
2
-VASc scores.

Results:
A total of 694 patients (age, 68.7 ± 12.9 years; 468 males; median National Institutes of Health Stroke Scale score, 2) were enrolled. Frequency of aortic arch plaques ≥ 4mm were significantly increased in correlation with the increases in CHADS
2
score (19%, 0 points; 33%, 1; 40%, 2; 49%, 3; 59%, 4 to 6,
P
<0.001, respectively), and CHA
2
DS
2
-VASc score (12%, 0 points; 19%, 1; 35%, 2; 39%, 3; 46%, 4; 55%, 5 to 8,
P
<0.001, respectively). On multiple logistic regression analysis, aortic arch plaques ≥ 4mm were independently associated with CHADS
2
score ≥ 2 points (odds ratio, 1.79; 95% confidence interval, 1.25-2.57;
P
=0.002) and CHA
2
DS
2
-VASc score ≥ 2 points (odds ratio, 3.04; 95% confidence interval, 1.77-5.24;
P
<0.001).

Conclusions:
Aortic arch plaques ≥ 4 mm are closely related to high CHADS
2
and CHA
2
DS
2
-VASc scores in ESUS/CS. CHADS
2
and CHA
2
DS
2
-VASc scores are linked with stroke recurrence, and thus large aortic plaques are important embolic source in ESUS/CS.
Abstract 19: Immune-Response Contributes to Primary Cardiac Dysfunction After Intracerebral Hemorrhage
Authors: Li Wei , Yan Tao , Li Linlin , Venkat Poornima , Chopp Michael , Chen Zhili , Landschoot-Ward Julie , Chen Jieli
Published: January 2019

Background:
Cardiac damage may occur after stroke in the absence of primary cardiac diseases. In this study, we investigated whether intracerebral hemorrhage (ICH) induces cardiac dysfunction in the absence of primary cardiac disease, and evaluated the role of the immune-response in mediating post ICH cardiac dysfunction in mice.

Methods:
Adult male C57BL/6J mice were subjected to ICH by blood injection or sham control without blood injection. To identify whether immunoresponse mediates brain-heart interaction after ICH, splenectomy was performed immediately after ICH. The experimental groups include: 1) sham control; 2) ICH group; 3) ICH+ splenectomy (n=10-16/group). Cardiac function was measured by echocardiography at 7 and 28 days after ICH. Neurological and cognitive functional tests, flow cytometry and immunostaining were performed.

Results:
Compared to sham control mice, ICH mice exhibit significantly (p<0.05):
1)
increased neurological and cognitive deficits, and increased cardiac dysfunction identified by decreased cardiac contractile function measured by left ventricular ejection fraction (LVEF) and fractional shortening (FS) at 7 and 28 days after ICH.
2)
increased cardiomyocyte apoptosis, cardiac hypertrophy and fibrosis at 28 days after ICH;
3)
increased inflammatory factor monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-9 expression in the heart and increased inflammatory cell (macrophages:CD45
+
/CD11b
+
/F480
+
and neutrophil:CD45
+
/CD11b
+
/Ly6G
+
) infiltration into the heart at 7 days post-ICH. Compared to ICH control mice, ICH with splenectomy mice exhibited significantly (p<0.05):
1)
improved neurological and cognitive functional outcome as well as attenuated cardiac dysfunction with increased LVEF and LVFS;
2)
decreased cardiomyocyte apoptosis, cardiac fibrosis and hypertrophy in the heart;
3)
decreased infiltration of immune cells and decreased MCP-1 expression in the heart.

Conclusions:
ICH not only induces neurological and cognitive functional deficit, but also induces cardiac dysfunction and inflammatory cell infiltration into heart. Immune-response, as evidenced by the effects of splenectomy in conjunction with ICH, may contribute to brain-heart adverse interaction after ICH.