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Loma Linda, CA, United States

Pandey P.,Stanford University | Marks M.P.,Stanford University | Harraher C.D.,Stanford University | Westbroek E.M.,Stanford University | And 5 more authors.
Journal of Neurosurgery | Year: 2012

Object. Grade III arteriovenous malformations (AVMs) are diverse because of their variations in size (S), location in eloquent cortex (E), and presence of central venous drainage (V). Because they may have implications for management and outcome, the authors evaluated these variations in the present study. Methods. Between 1984 and 2010, 100 patients with Grade III AVMs were treated. The AVMs were categorized by Spetzler-Martin characteristics as follows: Type 1 = S1E1V1, Type 2 = S2E1V0, Type 3 = S2E0V1, and Type 4 = S3E0V0. The occurrence of a new neurological deficit, functional status (based on modified Rankin Scale [mRS] score) at discharge and follow-up, and radiological obliteration were correlated with demographic and morphological characteristics. Results. One hundred patients (49 female and 51 male; age range 5-68 years, mean 35.8 years) were evaluated. The size of AVMs was less than 3 cm in 28 patients, 3-6 cm in 71, and greater than 6 cm in 1; 86 AVMs were located in eloquent cortex and 38 had central drainage. The AVMs were Type 1 in 28 cases, Type 2 in 60, Type 3 in 11, and Type 4 in 1. The authors performed embolization in 77 patients (175 procedures), surgery in 64 patients (74 surgeries), and radiosurgery in 49 patients (44 primary and 5 postoperative). The mortality rate following the management of these AVMs was 1%. Fourteen patients (14%) had new neurological deficits, with 5 (5%) being disabling (mRS score > 2) and 9 (9%) being nondisabling (mRS score ≤ 2) events. Patients with Type 1 AVMs (small size) had the best outcome, with 1 (3.6%) in 28 having a new neurological deficit, compared with 72 patients with larger AVMs, of whom 13 (18.1%) had a new neurological deficit (p < 0.002). Older age (> 40 years), malformation size > 3 cm, and nonhemorrhagic presentation predicted the occurrence of new deficits (p < 0.002). Sex, eloquent cortex, and venous drainage did not confer any benefit. In 89 cases follow-up was adequate for data to be included in the obliteration analysis. The AVM was obliterated in 78 patients (87.6%), 69 of them (88.5%) demonstrated on angiography and 9 on MRI /MR angiography. There was no difference between obliteration rates between different types of AVMs, size, eloquence, and drainage. Age, sex, and clinical presentation also did not predict obliteration. Conclusions. Multimodality management of Grade III AVMs results in a high rate of obliteration, which was not influenced by size, venous drainage, or eloquent location. However, the development of new neurological deficits did correlate with size, whereas eloquence and venous drainage did not affect the neurological complication rate. The authors propose subclassifying the Grade III AVMs according to their size (< 3 and ≥ 3 cm) to account for treatment risk.

Jackson C.S.,Loma Linda Medical Center | Gerson L.B.,California Pacific Medical Center
American Journal of Gastroenterology | Year: 2014

OBJECTIVES:Gastrointestinal angiodysplastic lesions (GIADs) are defined as pathologically dilated communications between veins and capillaries. The objective of this systematic review and meta-analysis was to determine the efficacy of available treatment modalities for GIADs.METHODS:We identified eligible studies by searching through PubMed, SCOPUS, and Cochrane central register of controlled trials. We searched for clinical trials examining the efficacy of endoscopic, pharmacologic, or surgical therapy for GIADs. Data were pooled using a random-effects model, and the effect of response to medical or surgical therapy was reported as odds ratios with 95% confidence intervals (CIs). Data and quality indicators were extracted by two authors from 22 studies, including 831 individuals with GIADs. The analysis included 623 patients treated with endoscopic therapy, 63 with hormonal therapy, 72 patients with octreotide, and 73 status post aortic valve replacement surgery.RESULTS:Hormonal therapy, based on two case-control studies, was not effective for bleeding cessation (odds ratio: 1.0, 95% CI: 0.5-1.96). On the basis of 14 studies including patients with gastric, colonic, and small-bowel GIADs, endoscopic therapy was effective as initial therapy, but the pooled recurrence bleeding rate was 36% (95% CI: 28-44%) over a mean (±s.d.) of 22±13 months. The event rate for re-bleeding increased to 45% (95% CI: 37-52%) when studies including only small-bowel GIADs were included (N=341). In four studies assessing the efficacy of somatostatin analogs, the pooled odds ratio was 14.5 (95% CI: 5.9-36) for bleeding cessation. In two studies assessing the role of aortic valve replacement (AVR) in 73 patients with Heyde's syndrome, the event rate for re-bleeding was 0.19 (95% CI: 0.11-0.30) over a mean follow-up period of 4 years postoperatively.CONCLUSIONS:Over one-third of patients with GIADs experienced re-bleeding after endoscopic therapy. Somatostatin analogs and AVR for Heyde's syndrome appeared to be effective therapy for GIADs. © 2014 by the American College of Gastroenterology.

Schroeder A.R.,Santa Clara Valley Medical Center | Mansbach J.M.,Harvard University | Stevenson M.,University of Louisville | Macias C.G.,Baylor College of Medicine | And 6 more authors.
Pediatrics | Year: 2013

OBJECTIVE: To identify risk factors for inpatient apnea among children hospitalized with bronchiolitis. METHODS: We enrolled 2207 children, aged ,2 years, hospitalized with bronchiolitis at 16 sites during the winters of 2007 to 2010. Nasopharyngeal aspirates (NPAs) were obtained on all subjects, and real-time polymerase chain reaction was used to test NPA samples for 16 viruses. Inpatient apnea was ascertained by daily chart review, with outcome data in 2156 children (98%). Age was corrected for birth ,37 weeks. Multivariable logistic regression was performed to identify independent risk factors for inpatient apnea. RESULTS: Inpatient apnea was identified in 108 children (5%, 95% confidence interval [CI] 4%-6%). Statistically significant, independent predictors of inpatient apnea included: corrected ages of ,2 weeks (odds ratio [OR] 9.67) and 2 to 8 weeks (OR 4.72), compared with age $6 months; birth weight ,2.3 kg (5 pounds; OR 2.15), compared with $3.2 kg (7 pounds); caretaker report of previous apnea during this bronchiolitis episode (OR 3.63); preadmission respiratory rates of ,30 (OR 4.05), 30 to 39 (OR 2.35) and .70 (OR 2.26), compared with 40 to 49; and having a preadmission room air oxygen saturation ,90% (OR 1.60). Apnea risk was similar across the major viral pathogens. CONCLUSIONS: In this prospective, multicenter study of children hospitalized with bronchiolitis, inpatient apnea was associated with younger corrected age, lower birth weight, history of apnea, and preadmission clinical factors including low or high respiratory rates and low room air oxygen saturation. Several bronchiolitis pathogens were associated with apnea, with similar apnea risk across the major viral pathogens. Pediatrics 2013;132:e1194-e1201. Copyright © 2013 by the American Academy of Pediatrics.

Hou J.,Loma Linda University | Hou J.,Loma Linda Medical Center | Manaenko A.,Loma Linda University | Hakon J.,Rigshospitalet | And 4 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2012

The inflammatory response plays a pivotal role in propagating injury of intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with antidiabetic effect and may also have antiinflammatory properties. Despite consensus that the glucoregulatory action is mediated by the GLP-1 receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation, neurobehavior, and inflammatory parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic deficit following ICH, which were partially reversed by GLP-1R inhibitor and AMPK phosphorylation inhibitor. Liraglutide-mediated AMPK phosphorylation was unaffected by GLP-1R inhibitor, and was found to be induced by GLP-1(9-36)a. GLP-1(9-36)a showed salutary effects on primary outcomes that were reversed by AMPK phosphorylation inhibitor but not by GLP-1R inhibitor. Liraglutide and DPP-4 inhibitor co-administration reversed liraglutide-mediated AMPK phosphorylation and antiinflammatory effects. Liraglutide exerted duals actions and the antiinflammatory effects are partially mediated by its metabolite in a phosphorylated AMPK-dependent manner. Therapies that inhibit GLP-1 degradation may weaken the metabolite-mediated effects. © 2012 ISCBFM.

Ma Q.,Loma Linda University | Chen S.,Loma Linda University | Chen S.,Zhejiang University | Hu Q.,Loma Linda University | And 4 more authors.
Annals of Neurology | Year: 2014

Objective The NLRP3 (NALP3, cryopyrin) inflammasome, a key component of the innate immune system, facilitates caspase-1 and interleukin (IL)-1β processing, which amplifies the inflammatory response. Here, we investigated whether NLRP3 knockdown decreases neutrophil infiltration, reduces brain edema, and improves neurological function in an intracerebral hemorrhage (ICH) mouse model. We also determined whether mitochondrial reactive oxygen species (ROS) governed by mitochondrial permeability transition pores (mPTPs) would trigger NLRP3 inflammasome activation following ICH. Methods ICH was induced by injecting autologous arterial blood (30μl) into a mouse brain. NLRP3 small interfering RNAs were administered 24 hours before ICH. A mPTP inhibitor (TRO-19622) or a specific mitochondria ROS scavenger (Mito-TEMPO) was coinjected with the blood. In naive animals, rotenone, which is a respiration chain complex I inhibitor, was applied to induce mitochondrial ROS production, and followed by TRO-19622 or Mito-TEMPO treatment. Neurological deficits, brain edema, enzyme-linked immunosorbent assay, Western blot, in vivo chemical cross-linking, ROS assay, and immunofluorescence were evaluated. Results ICH activated the NLRP3 inflammasome. NLRP3 knockdown reduced brain edema and decreased myeloperoxidase (MPO) levels at 24 hours, and improved neurological functions from 24 to 72 hours following ICH. TRO-19622 or Mito-TEMPO reduced ROS, NLRP3 inflammasome components, and MPO levels following ICH. In naive animals, rotenone administration induced mPTP formation, ROS generation, and NLRP3 inflammasome activation, which were then reduced by TRO-19622 or Mito-TEMPO. Interpretation The NLRP3 inflammasome amplified the inflammatory response by releasing IL-1β and promoting neutrophil infiltration following ICH. Mitochondria ROS may be a major trigger of NLRP3 inflammasome activation. The results of our study suggest that the inhibition of the NLRP3 inflammasome may effectively reduce the inflammatory response following ICH. © 2014 American Neurological Association.

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