A multi-center comparison of surgical techniques for corpus Callosotomy in pediatric drug-resistant epilepsy.

OBJECTIVES: Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug-resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi-institutional epilepsy surgery database to characterize the use of CC across participating centers. METHODS: Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0-18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically. RESULTS: Eighty-three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0-9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1-20) and 10.46 (.2-20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini-craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow-up was 12.8 months (range 1-39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant. SIGNIFICANCE: CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less-invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE.

The Laparoscopy in Biliary Exploration Research and Training Initiative (LIBERTI) trial: simulator-based training for laparoscopic management of choledocholithiasis.

BACKGROUND: Laparoscopic cholecystectomy with common bile duct exploration (LCBDE) is equivalent in safety and efficacy to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) while decreasing number of procedures and length of stay (LOS). Despite these advantages LCBDE is infrequently utilized. We hypothesized that formal, simulation-based training in LCBDE would result in increased utilization and improve patient outcomes across participating institutions. METHODS: Data was obtained from an on-going multi-center study in which simulator-based transcystic LCBDE training curricula were instituted for attending surgeons and residents. A 2-year retrospective review of LCBDE utilization prior to LCBDE training was compared to utilization up to 2 years after initiation of training. Patient outcomes were analyzed between LCBDE strategy and ERCP strategy groups using χ2, t tests, and Wilcoxon rank tests. RESULTS: A total of 50 attendings and 70 residents trained in LCBDE since November 2020. Initial LCBDE utilization rate ranged from 0.74 to 4.5%, and increased among all institutions after training, ranging from 9.3 to 41.4% of cases. There were 393 choledocholithiasis patients analyzed using LCBDE (N = 129) and ERCP (N = 264) strategies. The LCBDE group had shorter median LOS (3 days vs. 4 days, p < 0.0001). No significant differences in readmission rates between LCBDE and ERCP groups (4.7% vs. 7.2%, p = 0.33), or in post-procedure pancreatitis (0.8% v 0.8%, p > 0.98). In comparison to LCBDE, the ERCP group had higher rates of bile duct injury (0% v 3.8%, p = 0.034) and fluid collections requiring intervention (0.8% v 6.8%, p < 0.009) secondary to cholecystectomy complications. Laparoscopic antegrade balloon sphincteroplasty had the highest technical success rate (87%), followed by choledochoscopic techniques (64%). CONCLUSION: Simulator-based training in LCBDE results in higher utilization rates, shorter LOS, and comparable safety to ERCP plus cholecystectomy. Therefore, implementation of LCBDE training is strongly recommended to optimize healthcare utilization and management of patients with choledocholithiasis.

Embracing fine-root system complexity in terrestrial ecosystem modeling.

Projecting the dynamics and functioning of the biosphere requires a holistic consideration of whole-ecosystem processes. However, biases toward leaf, canopy, and soil modeling since the 1970s have constantly left fine-root systems being rudimentarily treated. As accelerated empirical advances in the last two decades establish clearly functional differentiation conferred by the hierarchical structure of fine-root orders and associations with mycorrhizal fungi, a need emerges to embrace this complexity to bridge the data-model gap in still extremely uncertain models. Here, we propose a three-pool structure comprising transport and absorptive fine roots with mycorrhizal fungi (TAM) to model vertically resolved fine-root systems across organizational and spatial-temporal scales. Emerging from a conceptual shift away from arbitrary homogenization, TAM builds upon theoretical and empirical foundations as an effective and efficient approximation that balances realism and simplicity. A proof-of-concept demonstration of TAM in a big-leaf model both conservatively and radically shows robust impacts of differentiation within fine-root systems on simulating carbon cycling in temperate forests. Theoretical and quantitative support warrants exploiting its rich potentials across ecosystems and models to confront uncertainties and challenges for a predictive understanding of the biosphere. Echoing a broad trend of embracing ecological complexity in integrative ecosystem modeling, TAM may offer a consistent framework where modelers and empiricists can work together toward this grand goal.

Validation of 5 models predicting transfusion, bleeding, and mortality in liver transplantation: an observational cohort study.

BACKGROUND: Historically, orthotopic liver transplantation (OLT) has been associated with massive blood loss, blood transfusion and morbidity. In order to predict such outcomes five nomograms have been published relating to transfusions and morbidity associated with OLTs. These nomograms, developed on the basis of three cohorts of patients consisting of 406, 750, and 800 having undergone OLTs, aimed to predict a transfusion of ≥1 red blood cell unit (RBC), a transfusion of >2 RBC units, a blood loss of >900 ml, as well as one-month and one-year survival rates. The aim of this study was to validate these five nomograms in a contemporary, independent cohort of patients. METHODS: Five nomograms were previously developed based on 406, 750, and 800 OLTs. In this study we performed a temporal validation of these nomograms on contemporary patients that consisted of three cohorts of 800, 250, and 200 OLTs. Logistic regression coefficients from the historic development cohorts were applied to the three contemporary temporal validation cohorts. RESULTS: The most accurate nomogram was able to predict transfusion of ≥1 RBC units with an area under the curve (AUC) was 0.91. The second-best nomogram was able to predict bleeding of >900 ml with an AUC of 0.70. T he AUC of the third nomogram (transfusion of >2 RBC units) was 0.70. However, is temporal validation was suboptimal, due to a low prevalence of OLTs transfused with >2 RBC units. The last 2 nomograms exhibited clearly suboptimal AUC values of 0.54 and 0.61. CONCLUSION: Two of the five nomograms predict blood transfusion and blood loss with excellent accuracy. Transfusion of ≥1 RBC unit and blood loss of >900 ml can be predicted on the basis of these nomograms. However, these nomograms are not accurate to predict one-month and one-year survival rates. These results should be further cross-validated, ideally prospectively, in additional external independent cohorts.

HDQLIFE and neuro-QoL physical function measures: Responsiveness in persons with huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurological disorder that causes severe motor symptoms that adversely impact health-related quality of life. Patient-reported physical function outcome measures in HD have shown cross-sectional evidence of validity, but responsiveness has not yet been assessed. OBJECTIVES: This study evaluates the responsiveness of the Huntington Disease Health-Related Quality of Life (HDQLIFE) and the Quality of Life in Neurological Disorders (Neuro-QoL) physical function measures in persons with HD. METHODS: A total of 347 participants completed baseline and at least 1 follow-up (12-month and 24-month) measure (HDQLIFE Chorea, HDQLIFE Swallowing Difficulties, HDQLIFE Speech Difficulties, Neuro-QoL Upper Extremity Function, and/or Neuro-QoL Lower Extremity Function). Of the participants that completed the baseline assessment, 338 (90.9%) completed the 12-month assessment, and 293 (78.8%) completed the 24-month assessment. Standardized response means and general linear models evaluated whether the physical function measures were responsive to self-reported and clinician-rated change over time. RESULTS: Small to moderate effect sizes for the standardized response means supported 12-month and 24-month responsiveness of the HDQLIFE and Neuro-QoL measures for those with either self-reported or clinician-rated declines in function. General linear models supported 12-month and 24-month responsiveness for all HRQOL measures relative to self-reported declines in health, but generally only 24-month responsiveness was supported relative to clinician-rated declines in function. CONCLUSIONS: Longitudinal analyses indicate that the HDQLIFE and the Neuro-QoL physical function measures are sensitive to change over time in individuals with HD. Thus, these scales exhibit evidence of responsiveness and may be useful outcome measures in future clinical trials. © 2019 International Parkinson and Movement Disorder Society.

Photochemical Tissue Passivation of Arteriovenous Grafts Prevents Long-Term Development of Intimal Hyperplasia in a Swine Model.

BACKGROUND: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arteriovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up. METHODS: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were harvested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immunohistologically for markers of IH. RESULTS: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ± 1.0 mm2versus 1.4 ± 1.5 mm2, respectively, P = 0.045) and medial area (5.1 ± 1.9 mm2versus 2.7 ± 2.4 mm2, respectively, P = 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining. CONCLUSIONS: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure.

Psychometric properties and responsiveness of Neuro-QoL Cognitive Function in persons with Huntington disease (HD).

PURPOSE: Individuals with Huntington disease (HD) experience progressive cognitive decline that may appear years before motor manifestations of the disease. These declines have a profound effect on health-related quality of life (HRQOL) over the disease course, and thus it is important that self-report measures of cognitive function are validated for use in longitudinal studies. METHODS: 359 individuals with premanifest or manifest HD completed baseline and at least one follow-up (12- and 24-month) assessment. Neuro-QoL™ Cognitive Function was administered at each time-point. Participants completed a self-reported global rating of cognitive change, as well as performance-based cognitive changes (using the Symbol Digit Modalities Test). Standardized response means (SRMs) and general linear models evaluated whether Neuro-QoL™ Cognitive Function was responsive to change over time with respect to self-reported and performance-based anchors. Test-retest reliability and known-group validity were also examined. RESULTS: Responsiveness was supported by effect sizes that were small in magnitude, but in the expected direction relative to self-reported and performance-based change. General linear models generally supported 12- and 24-month responsiveness relative to self-reported cognitive change and 12-month responsiveness relative to performance-based change. Test-retest reliability was excellent, and the measure exhibited known-group validity. CONCLUSION: Longitudinal analyses generally indicate that the Neuro-QoL™ Cognitive Function measure is sensitive to change over time in individuals with HD. Neuro-QoL Cognitive Function changes reflect self-reported cognitive change at 12 and 24 months and performance-based change at 12 months. This measure may be useful in clinical trials or longitudinal observation studies.

Responsiveness to change over time and test-retest reliability of the PROMIS and Neuro-QoL mental health measures in persons with Huntington disease (HD).

BACKGROUND: The majority of persons with Huntington disease (HD) experience mental health symptoms. Patient-reported outcome (PRO) measures are capable of capturing unobservable behaviors and feelings relating to mental health. The current study aimed to test the reliability and responsiveness to self-reported and clinician-rated change over time of Neuro-QoL and PROMIS mental health PROs over the course of a 24-month period. METHODS: At baseline, 12-months, and 24-months, 362 participants with premanifest or manifest HD completed the Neuro-QoL Depression computer adaptive test (CAT), PROMIS Depression short form (SF), Neuro-QoL Anxiety CAT, PROMIS Anxiety SF, PROMIS Anger CAT and SF, Neuro-QoL Emotional/Behavioral Dyscontrol CAT and SF, Neuro-QoL Positive Affect and Well-Being CAT and SF, and Neuro-QoL Stigma CAT and SF. Participants completed several clinician-administered measures at each time point, as well as several global ratings of change at 12- and 24-months. Reliability (test-retest reliability and measurement error) and responsiveness (using standardized response means and general linear models) were assessed. RESULTS: Test-retest reliability and measurement error were excellent for all PROs (all ICC ≥ .90 for test-retest reliability and all SEM percentages ≤ 6.82%). In addition, 12- and 24-month responsiveness were generally supported for the Neuro-QoL and PROMIS mental health PROs; findings relative to clinician-rated anchors of change (e.g., SRMs for the group with declines ranged from .38 to .91 for 24-month change and .09 to .45, with the majority above .25 for 12-month change) were generally more robust than those relative to self-reported anchors of change (e.g., SRMs for the group with declines ranged from .02 to .75, with the majority above .39 for 24-month change and .09 to .45, with the majority above .16 for 12-month change). CONCLUSIONS: The Neuro-QoL and PROMIS mental health PROs demonstrated strong psychometric reliability, as well as responsiveness to self-reported and clinician-rated change over time in people with HD.

Global patterns in fine root decomposition: climate, chemistry, mycorrhizal association and woodiness.

Fine root decomposition constitutes a critical yet poorly understood flux of carbon and nutrients in terrestrial ecosystems. Here, we present the first large-scale synthesis of species trait effects on the early stages of fine root decomposition at both global and local scales. Based on decomposition rates for 279 plant species across 105 studies and 176 sites, we found that mycorrhizal association and woodiness are the best categorical traits for predicting rates of fine root decomposition. Consistent positive effects of nitrogen and phosphorus concentrations and negative effects of lignin concentration emerged on decomposition rates within sites. Similar relationships were present across sites, along with positive effects of temperature and moisture. Calcium was not consistently related to decomposition rate at either scale. While the chemical drivers of fine root decomposition parallel those of leaf decomposition, our results indicate that the best plant functional groups for predicting fine root decomposition differ from those predicting leaf decomposition.

How different aspects of motor dysfunction influence day-to-day function in huntington's disease.

PURPOSE: This study examined the relationships between different aspects of motor dysfunction (chorea, dystonia, rigidity, incoordination, oculomotor dysfunction, dysarthria, and gait difficulties) and functional status in persons with Huntington's disease. METHODS: A total of 527 persons with Huntington's disease completed the Unified Huntington's Disease Rating Scale motor, total functional capacity, and functional assessments. RESULTS: Confirmatory factor analysis indicated that a 4-factor model provided a better model fit than the existing 5-factor model. Exploratory factor analysis identified the following 4 factors from the motor scale: dystonia, chorea, rigidity, and a general motor factor. Regression indicated that dystonia (ß = -0.47 and -0.79) and rigidity (ß = -0.28 and -0.59) had strong associations with function, whereas chorea had modest correlations (ß = -0.16 and -0.15). CONCLUSIONS: Dystonia and rigidity have stronger relationships with functional status than chorea in persons with Huntington's disease. The findings underscore the need for further research regarding the effects of dystonia and rigidity on functioning. © 2019 International Parkinson and Movement Disorder Society.

Photochemical Tissue Passivation Prevents Contracture of Full Thickness Wounds in Mice.

BACKGROUND AND OBJECTIVES: Wound contracture formation from excessive myofibroblast activity can result in debilitating morbidities. There are currently no treatments to prevent contracture. Photochemical tissue passivation (PTP), an established, safe, and user-friendly treatment modality, crosslinks collagen by a light-activated process, thus modulating the wound healing response and scarring. We hypothesised that PTP treatment would reinforce wounds by blunting the fibrotic response thus limiting contracture. STUDY DESIGN/MATERIALS AND METHODS: Full-thickness, 1 cm × 1 cm excisional wounds were created on the dorsum of 32 C57BL/6 mice. Treated wounds were painted with photosensitizing dye and exposed to visible light. Wounds were serially photographed over 6 weeks to measure wound contracture. At 7, 14, 21, and 42 days after wound creation, mice were euthanized and wounds were harvested for histologic review by a dermatopathologist. RESULTS: By Day 7, control wounds had significantly more contracture than those treated with PTP (33.0 ± 17.1% and 19.3 ± 9.0%, respectively; P = 0.011). PTP-treated wounds maintained approximately 20% less contracture than controls from Day 14 and on (P < 0.05). By Day 42, wounds had contracted by 86.9 ± 5.5% in controls and 64.2 ± 3.2% in PTP-treated wounds (P < 0.03). Histologically, PTP wounds had earlier growth and development of dermal collagen, neovascularization, and development of skin appendages, compared with control wounds. CONCLUSIONS: PTP significantly limits contracture of full-thickness wounds and improves wound healing. PTP-treated wounds histologically demonstrate more mature structural organization than untreated wounds and closely resemble native skin. PTP treatment may be applicable not only for excisional wounds, but also for wounds with a high incidence of contracture and associated morbidity. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Photochemical Tissue Passivation Attenuates AV Fistula Intimal Hyperplasia.

OBJECTIVE: We hypothesized that decreasing vein compliance would protect the vein against stretch injury and reduce intimal hyperplasia (IH). BACKGROUND: Although arteriovenous fistulas (AVFs) are the criterion standard for vascular access, their effectiveness is limited by poor patency with 40% to 60% failing due to IH. Venous stretch injury from exposure to arterial pressure induces IH. Photochemical tissue passivation (PTP) crosslinks adventitial collagen, decreasing vein compliance to resemble that of an artery. METHODS: AVFs were created between the femoral artery and epigastric vein in rats (n = 29). PTP was performed on the vein immediately before vessel anastomosis. AVFs were harvested after four weeks. Venous diameter was measured at the initial procedure and harvest. Intimal area was measured for each segment. Ultrasound was performed at harvest to measure AVF flow. RESULTS: Following AVF construction, venous diameter increased by 10% ±â€Š18% for PTP-treated vessels and 78% ±â€Š27% for controls (P ≤ 0.0001). At one month, PTP reduced AVF dilation by 71% compared to control (69% ±â€Š29% vs 241% ±â€Š78%; P ≤ 0.0001). Both juxta-anastomotic intimal area and total intimal area were reduced in PTP-treated vessels compared to control vessels. Specifically, intimal area was 0.024 ±â€Š0.018 and 0.095 ±â€Š0.089 mm for PTP-treated juxta-anastomotic segments of AVF and control, respectively (P < 0.05). Mean total intimal area for PTP-treated and control AVF were 0.080 ±â€Š0.042 and 0.190 ±â€Š0.110 mm, respectively (P < 0.03). AVF flow was 46.9 ±â€Š35.3 and 19.1 ±â€Š10.1 mL/min for PTP-treated and control AVF, respectively (P < 0.109). CONCLUSIONS: These data demonstrate that PTP represents a promising therapy for the prevention of AVF IH, a process that might improve surgical outcomes for patients receiving hemodialysis.

Relationships Among Apathy, Health-Related Quality of Life, and Function in Huntington's Disease.

Up to 90% of individuals with Huntington's disease (HD)-a progressive, inherited neurodegenerative disorder-experience apathy. Apathy is particularly debilitating because it is marked by a reduction in goal-directed behaviors, including self-care, social interactions, and mobility. The objective of this study was to examine relationships between variables of apathy, functional status, physical function, cognitive function, behavioral status/emotional function, and health-related quality of life. Clinician-rated measures of physical, cognitive, and behavioral function, including one clinician-rated item on apathy, and self-reported measures of physical function, health-related quality of life, and emotional, cognitive, and social function were collected in a single session from 487 persons with the HD mutation (prodromal, N=193; early-stage manifest, N=186; late-stage manifest, N=108). Multiple linear regression models were used to examine which outcomes best predicted clinician-rated apathy after controlling for disease stage. Greater apathy related to less independence, increased motor impairment, and more clinician-rated behavioral problems (i.e., anger, irritability, depression). Similarly, poorer self-reported health-related quality of life; greater chorea; greater upper- and lower-extremity dysfunction; greater speech and swallowing dysfunction; worse anxiety, depression, and behavioral dyscontrol; worse cognitive function; and less satisfaction with social roles related to greater apathy. In conclusion, apathy related to physical, cognitive, and behavioral dysfunction across disease stages. Future work should explore whether clinical interventions targeting different functional domains may have the potential to reduce apathy in this patient population.

Evaluating cognition in individuals with Huntington disease: Neuro-QoL cognitive functioning measures.

PURPOSE: Cognitive functioning impacts health-related quality of life (HRQOL) for individuals with Huntington disease (HD). The Neuro-QoL includes two patient-reported outcome (PRO) measures of cognition-Executive Function (EF) and General Concerns (GC). These measures have not previously been validated for use in HD. The purpose of this analysis is to evaluate the reliability and validity of the Neuro-QoL Cognitive Function measures for use in HD. METHODS: Five hundred ten individuals with prodromal or manifest HD completed the Neuro-QoL Cognition measures, two other PRO measures of HRQOL (WHODAS 2.0 and EQ5D), and a depression measure (PROMIS Depression). Measures of functioning The Total Functional Capacity and behavior (Problem Behaviors Assessment) were completed by clinician interview. Objective measures of cognition were obtained using clinician-administered Symbol Digit Modalities Test and the Stroop Test (Word, Color, and Interference). Self-rated, clinician-rated, and objective composite scores were developed. We examined the Neuro-QoL measures for reliability, convergent validity, discriminant validity, and known-groups validity. RESULTS: Excellent reliabilities (Cronbach's alphas ≥ 0.94) were found. Convergent validity was supported, with strong relationships between self-reported measures of cognition. Discriminant validity was supported by less robust correlations between self-reported cognition and other constructs. Prodromal participants reported fewer cognitive problems than manifest groups, and early-stage HD participants reported fewer problems than late-stage HD participants. CONCLUSIONS: The Neuro-QoL Cognition measures provide reliable and valid assessments of self-reported cognitive functioning for individuals with HD. Findings support the utility of these measures for assessing self-reported cognition.

Cerebral Microbleeds are Associated with Higher Mortality Among Ischemic Stroke Patients.

BACKGROUND: Several studies have shown that cerebral microbleeds (CMBs) increase the risk of long-term stroke-related mortality. The purpose of this study was to determine if the existence and burden of CMBs are a predictor of in-hospital death among patients with acute ischemic stroke (AIS). METHODS: We studied consecutive ischemic stroke patients who admitted to our tertiary center over a 2-year period (2013-2014). Patients who underwent thrombolysis were excluded. Baseline characteristics of patients, number and topography of CMBs, white matter lesions, and spontaneous symptomatic hemorrhagic transformation were recorded. Outcome measure in our study was in-hospital death. RESULTS: Out of 1126 consecutive AIS patients evaluated in this study, 772 patients included in the study (mean age 61.9 ± 14.2years [18-95 years], 51.6% men, and 58.2% African American). CMBs were present on the magnetic resonance imaging (MRI) sequences of 124 (16.1%) patients. The overall rate of in-hospital mortality was 4.1%. The presence or absence of CMBs was not predictive of in-hospital mortality (P = .058). After adjusting for potential confounders, the presence of ≥4 CMBs on T2*-weighted MRI was independently (P = .004) associated with a higher likelihood of in-hospital death (odds ratio: 6.6, 95% confidential interval: 2.50 and 17.46) in multivariable logistic regression analyses. Older age, higher National Institute of Health stroke scale, and history of atrial fibrillation were also associated with greater chance of in-hospital death. CONCLUSIONS: The presence or absence of CMBs was not predictive of in-hospital mortality. However, the presence of multiple CMBs was associated with a higher in-hospital mortality rate among AIS patients.

Safety of Intravenous Thrombolysis in Chronic Intracranial Hemorrhage: A Five-Year Multicenter Study.

INTRODUCTION: Although the recently updated U.S. alteplase label removed "history of intracranial hemorrhage (ICH)" as a contraindication, there are very limited data on the safety of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with chronic ICH. We sought to evaluate IVT safety in AIS patients with a history of ICH. METHODS: We analyzed consecutive AIS patients treated with IVT at 3 tertiary stroke centers during a 5-year period. We identified AIS treated with IVT with clinical history and neuroimaging confirmation of prior ICH. The safety measure was symptomatic ICH (sICH) defined according to European Cooperative Acute Stroke Study-III criteria combined with the clinical deterioration of 4 points or higher in the National Institutes of Health Stroke Scale (NIHSS) or death. RESULTS: Of the 1212 AIS patients treated with IVT, 7 (.6%) (mean age 72 ± 11 years, 57% men, median NIHSS: 5 points, interquartile range: 2-8) had a history of ICH (hematoma volume: 1-21 cm3, elapsed time between previous ICH and AIS: 1.5-12 years, 5 located in basal ganglia and 2 in periventricular white matter). Patients with previous ICH did not differ in terms of demographics and admission stroke severity in comparison with the rest. The 2 groups had similar rates of sICH (0% [0/7] versus 3.6%, P = .61) and in-hospital mortality (0% [0/7] versus 6.0%, P = .50). CONCLUSION: Our study indicates that IVT might be safe among AIS patients with a history of chronic ICH. Further research with a larger sample size is required to confirm our finding and define the shortest time interval between the hemorrhagic and ischemic events that can be associated with the safe administration of IVT.

Prevention of vein graft intimal hyperplasia with photochemical tissue passivation.

OBJECTIVE: Saphenous vein is the conduit of choice for bypass grafting. Saphenous vein grafts have poor long-term patency rates because of intimal hyperplasia (IH) and subsequent accelerated atherosclerosis. One of the primary triggers of IH is endothelial injury resulting from excessive dilation of the vein after exposure to arterial pressures. Photochemical tissue passivation (PTP) is a technology that cross-links adventitial collagen by a light-activated process, which limits dilation by improving vessel compliance. The objective of this study was to investigate whether PTP limits the development of IH in a rodent venous interposition graft model. METHODS: PTP is accomplished by coating venous adventitia with a photosensitizing dye and exposing it to light. To assess the degree of collagen cross-linking after PTP treatment, a biodegradation assay was performed. Venous interposition grafts were placed in the femoral artery of Sprague-Dawley rats. Rats were euthanized after 4 weeks, and intimal thickness was measured histologically. Vein dilation at the time of the initial procedure was also measured. RESULTS: Time to digestion was 63 ± 7 minutes for controls, 101 ± 2.4 minutes for rose bengal (RB), and 300 ± 0 minutes for PTP (P < .001 PTP vs control). A total of 37 animals underwent the procedure: 12 PTP, 12 RB only, and 13 untreated controls. Dilation of the graft after clamp release was 99% for control, 65% for RB only, and 19% for PTP-treated (P < .001 PTP vs control). Intimal thickness was 77 ± 59 µm in controls, 60 ± 27 µm in RB only, and 33 ± 28 µm in PTP-treated grafts. There was a statistically significant 57% reduction in intimal thickness after treatment with PTP compared with untreated controls (P = .03). CONCLUSIONS: PTP treatment of venous interposition grafts in a rat model resulted in significant collagen cross-linking, decreased vessel compliance, and significant reduction in IH.

Racial Difference in Cerebral Microbleed Burden among Ischemic Stroke Patients.

BACKGROUND AND AIMS: Data on the epidemiology of cerebral microbleeds (CMBs) among patients with ischemic stroke are limited. This study compared the number, associated factors, and topography of CMBs between African American and Caucasian ischemic stroke patients in the Mid-South United States. METHOD: We evaluated consecutive ischemic stroke patients admitted to our tertiary stroke center, University of Tennessee Health Science Center, Memphis, Tennessee, in a two-year period. We analyzed T2*-weighted magnetic resonance images for the number, location, and topography of CMBs, as well as patients' demographic and clinical information. RESULTS: Among 760 ischemic stroke patients who were included (mean age was 62.1 ± 13.9 years, 51.4% men), 450 (59.2%) were African American. In comparison with Caucasians, African Americans were about five years younger (P = .000) and had a higher rate of hypertension (80.9% vs. 74.5%, P = .036). Similarly, African Americans had a higher prevalence of diabetes mellitus (P = .001). There was no significant difference between African-Americans and Caucasians in terms of CMBs presence and location. African Americans had a higher number of CMBs in comparison with Caucasians, but the difference was not significant. African Americans were more likely to have CMBs ≥5 (P = .047). Although African American stroke patients had a higher rate of large confluent white matter lesions, there was no significant racial difference regarding the rate and severity of deep white matter lesions. CONCLUSION: We did not observe any differences between African American and Caucasian patients with ischemic stroke patients regarding the presence, number, and location of CMBs. However, our results suggested that the prevalence of multiple CMBs (CMBs ≥5) might be higher among African American stroke patients.

Cerebral Microbleeds and Risk of Intracerebral Hemorrhage Post Intravenous Thrombolysis.

BACKGROUND: Stroke patients who have cerebral micro bleeds (CMBs) could be potentially at a greater risk for symptomatic intracerebral hemorrhage (sICH) than those patients without CMBs. The aim of our study was to investigate whether the presence and burden of CMBs are associated with post IVT sICH. METHODS: In this multicenter study, consecutive patients treated with intravenous tissue plasminogen activator were prospectively identified and analyzed. Patients without magnetic resonance imaging (MRI) within 24 hours of treatment were excluded. CMBs were defined as round or oval, hypointense lesions with associated blooming on T2*-weighted MRI up to 10 mm in diameter. Outcome measures included the occurrence of sICH or death. RESULTS: Of 672 patients with IVT (mean age 62 ± 14 years, 52% men, median admission NIHSS: 7 points), 103 patients had CMBs on T2*-MRI. Ten patients had more than 10, whereas the remaining 93 patients had 1-10 CMBs on T2*-MRI. The rates of sICH did not differ between patients with and patients without 1-10 CMBs (5.8% versus 3.5%; P = .27). However, sICH occurred more frequently (P = .0009) in patients with > 10 CMBs (30%, 95% confidence interval [CI] by the adjusted Wald method: 10%-61%). After adjusting for potential confounders, the presence of >10 CMBs on T2*-MRI was independently (P = .0004) associated with a higher likelihood for sICH (odds ratio [OR]:13.4, 95%CI:3.2-55.9). CONCLUSIONS: Our findings indicate an increased risk of sICH after IVT when more than 10 CMBs are present.

Mycorrhizal fungi and roots are complementary in foraging within nutrient patches.

The roots of the majority of tree species are associated with either arbuscular mycorrhizal (AM) or ectomycorrhizal (EM) fungi. The absorptive roots of tree species also vary widely in their diameter. The linkages between root thickness, mycorrhiza type and nutrient foraging are poorly understood. We conducted a large root ingrowth experiment in the field to investigate how absorptive roots of varying thickness and their associated fungi (AM vs. EM) exploit different nutrient patches (inorganic and organic) in a common garden. In nutrient-rich patches, thin-root tree species more effectively proliferated absorptive roots than thick-root tree species, whereas thick-root tree species proliferated more mycorrhizal fungal biomass than thin-root tree species. Moreover, nutrient patches enriched with organic materials resulted in greater root and mycorrhizal fungal proliferation compared to those enriched with inorganic nutrients. Irrespective of root morphology, AM tree species had higher root foraging precision than mycorrhizal hyphae foraging precision within organic patches, whereas EM tree species exhibited the opposite. Our findings that roots and mycorrhizal fungi are complementary in foraging within nutrient patches provide new insights into species coexistence and element cycling in terrestrial ecosystems.