OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION: Clinical Observations and Model of Pathogenesis.

PURPOSE: To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT). METHODS: We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development. RESULTS: One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1-80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1-24.2]; P = 0.041) and >1.5 DA (9.0 [1.8-44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1-8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases. CONCLUSION: Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.

CORRELATION OF VISUAL ACUITY WITH FIBROTIC SCAR LOCATION IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION EYES.

PURPOSE: To determine whether the optical coherence tomography location of a subfoveal fibrovascular scar is correlated with visual outcome in eyes successfully treated with antivascular endothelial growth factor agents for neovascular age-related macular degeneration. METHODS: Fifty-six eyes from 56 patients with a subfoveal disciform scar after antivascular endothelial growth factor treatment were included. The initial and final visual acuity, fluorescein angiography, and spectral domain optical coherence tomography scar characteristics were retrospectively reviewed. RESULTS: Thirty-five of 56 eyes (62.5%) were classified as having entirely subretinal pigment epithelial (sub-RPE) scars, and 21 eyes (37.5%) had subretinal component scars. Mean initial visual acuity was similar between sub-RPE and subretinal scars (20/100 vs. 20/125, P = 0.517); mean final visual acuity was better in the sub-RPE scar group (20/60 vs. 20/200, P = 0.001). Eyes with sub-RPE scar had better preservation of the external limiting membrane, ellipsoid layer, and retinal thickness (P < 0.001, P = 0.017, P = 0.004, respectively) than subretinal component scar eyes. There was no difference between the groups in scar thickness or scar area (P = 0.707, P = 0.186, respectively). CONCLUSION: Sub-RPE location of subfoveal scarring in eyes treated for neovascular age-related macular degeneration is associated with better preservation of outer retinal structures and better vision, when compared with a subretinal scar.

Vein Morphology in Endoscopic Vein Harvesting: 15-Year Outcomes.

OBJECTIVE: Long-term outcomes of vein morphologies in the endoscopic vein harvesting setting are lacking. We analyzed 15-year follow-up for endoscopic versus open vein harvesting and associated vein morphology outcomes in coronary artery bypass grafting at a single center. METHODS: This single-center, prospectively collected, retrospective, observational study evaluated 15-year major adverse cardiovascular events (MACE) of endoscopic versus open vein harvesting and associated vein morphologies. RESULTS: Among 729 patients, no differences were found between endoscopic and open vein harvesting in MACE hazard ratios despite increased risks with native Hawai'ian, Pacific Islander, and Filipino patients. Asian and Filipino patients had more thin-walled veins and Asian and multirace patients had more vasovasoral branches than White patients. Bifid veins were associated with increased risk of cardiac catheterization. Varicose veins were associated with myocardial infarction, congestive heart failure, and death. Thick-walled veins were associated with revascularization and dense adhesions with cardiac catheterization and revascularization. CONCLUSIONS: Fifteen-year adjusted MACE was similar between endoscopic and open vein harvesting in small coronary targets despite increased risks with native Hawai'ian, Pacific Islander, and Filipino patients. Bifid, varicose, thick-walled veins, and dense adhesions had worse MACE.

Human Amniotic Membrane Plug for Chronic or Persistent Macular Holes.

PURPOSE: To report on the use of human amniotic membrane for macular holes at 2 Canadian tertiary care centers. DESIGN: Retrospective cohort study. SUBJECTS: Twenty-two patients with persistent or chronic macular holes. METHODS: Macular hole surgery was performed by 3 vitreoretinal surgeons. MAIN OUTCOME MEASURES: Macular hole closure with complete plugging by human amniotic membrane on spectral-domain OCT. RESULTS: The closure rate was 91% (20 of 22; median follow-up, 7 months), with no statistically significant visual acuity change overall. Complications included subretinal silicone oil (5%), choroidal neovascularization (5%), atrophy (5%), and cystoid macular edema (9%). CONCLUSIONS: Anatomical success with limited visual recovery was observed.

DELAYED-ONSET STREPTOCOCCUS INTERMEDIUS ENDOPHTHALMITIS FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INTRAVITREAL INJECTION.

PURPOSE: Endophthalmitis following intravitreal anti-vascular endothelial growth factor injections is frequently caused by Streptococcus viridans organisms and tends to be aggressive. Herein, we present a case of postinjection Streptococcus viridans endophthalmitis presenting in an atypically delayed fashion with good visual outcome. METHODS: Single clinical case report. RESULTS: A 91-year-old woman treated with aflibercept for exudative age-related macular degeneration of the left eye presented to the emergency department with mild pain and visual acuity decline to counting fingers, pigmented anterior chamber cells and vitreous haze 7 weeks after her most recent intravitreal injection. She had no symptoms of systemic infection. The presumptive diagnosis initially was vitreous hemorrhage. Over 10 days of observation, she developed worsening pain and vitritis suggestive of endophthalmitis, leading us to perform vitrectomy with intravitreal vancomycin and ceftazidime. Vitreous biopsy was culture positive for Streptococcus intermedius , a type of viridans streptococcus typically associated with head and neck abscesses. The infection resolved and the patient's visual acuity returned to her baseline of 20/100, with no recurrence of infection after 4 months of follow-up. CONCLUSSION: The virulence of viridans streptococci capable of producing postinjection endophthalmitis may vary widely. Infection ought to be suspected even in cases of delayed-onset intraocular inflammation.

PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation: Part 2: Study results-prostheses, positions, and economic development.

Objectives: The Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation (PROSE) trial purpose was to investigate whether a current-generation mechanical prosthesis (On-X; On-X Life Technologies/Artivion Inc) reduced the incidence of thromboembolic-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical). This second report documents the valve-related complications by individual prostheses and by Western and Developing populations. Methods: The PROSE trial study was conducted in 28 worldwide centers and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The study protocol, and analyses of 10 demographic variables and 24 risk factors were published in detail in 2021. Results: The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality. There were several differences between Developing and Western populations. The freedom relations at 5 years for mortality favored Western over Developing populations. Valve thrombosis was differentiated by position and site: aortic < mitral (P = .007) and Western < Developing (P = .005). In the mitral position there were no cases in Western populations, whereas there were 8 in Developing populations (P = .217). Conclusions: The On-X valve and St Jude Medical valve performed equally well in the study with no differences found. The only differentiation occurred with valve thrombosis in the mitral position more than the aortic position and occurring in Developing more than Western populations. The occurrence of valve thrombosis was also related to a younger population possibly due to anticoagulation compliance based on record review.

PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation : Part 1(Patient Dynamics): Preoperative demographics and preoperative and operative risk factors.

OBJECTIVES: The PROSE trial purpose is to investigate whether the incidence of thromboembolic-related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.-On-X) compared with a previous generation mechanical prosthesis (St Jude Medical-SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. METHODS: The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. RESULTS: The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. CONCLUSIONS: The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

REOPENING OF MACULAR HOLE AFTER INTRAVITREAL AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To describe the clinical course and surgical outcome of a patient with full-thickness macular hole recurrence after aflibercept injections for wet age-related macular degeneration. METHODS: Case report with spectral domain optical coherence tomography retinal imaging. RESULTS: An 84-year-old patient, with a successfully closed full-thickness macular hole by vitrectomy and internal limiting membrane (ILM) peel 4 years ago in the right eye, developed neovascular age-related macular degeneration (AMD) of the same eye. After 6 intravitreal aflibercept injections, visual acuity was 20/50, with minimal subretinal fluid (SRF). Four days after the seventh aflibercept injection, visual acuity decreased to 20/200. Spectral domain optical coherence tomography demonstrated a reopened full-thickness macular hole of diameter 430 µm, associated with a reduction in pigment epithelial detachment height, increase in SRF, and an epiretinal membrane (ERM). A 23-gauge pars plana vitrectomy with indocyanine green-assisted removal of residual ILM and ERM, and sulfur hexafluoride (SF6) 20% tamponade was performed. At 1 month postoperatively, the full-thickness macular hole was successfully closed and visual acuity improved to 20/80. CONCLUSION: In wet AMD eyes with previously closed macular holes, hole reopening may occur as a rare complication of aflibercept therapy.

Sutureless intrascleral fixation of intraocular lens through self-sealing sclerotomy wounds using haptic externalization and reinternalization technique.

In eyes with absent or insufficient capsule support, three-piece posterior chamber intraocular lens (PC IOL) may be fixed to the sclera. Previous techniques involve the use of sutures, flaps, glue, needles, trocars, or intrascleral tunnels to fixate the distal tips of the haptics intrasclerally. Herein we describe a modified technique for the sutureless scleral fixation of a standard 3-piece PC IOL using self-sealing sclerotomies created with a crescent blade and a 20-gauge microvitreoretinal blade, and then reinserting the haptics to leave the tips inside the vitreous cavity. We believe the relative simplicity of this technique makes it widely applicable for the placement of an IOL with insufficient capsule support.

Disorganization of Retinal Inner Layers and Ellipsoid Zone Disruption Predict Visual Outcomes in Central Retinal Vein Occlusion.

PURPOSE: To assess the associations and predictive value of spectral-domain (SD) OCT inner and outer retinal structural parameters and visual acuity (VA) outcomes in macular edema (ME) secondary to central retinal vein occlusion (CRVO). DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: Eighty-four patients with ME secondary to CRVO receiving pro re nata anti-vascular endothelial growth factor (VEGF) therapy at 3 tertiary-level retina referral centers. METHODS: In all participants, VA, demographic and clinical parameters, and SD OCT images from baseline, 3 months, and 12 months were reviewed. Spectral-domain OCT-based morphologic features in the 1500-µm foveal zone were analyzed by masked graders for disorganization of the retinal inner layers (DRIL), ellipsoid zone (EZ) and external limiting membrane disruption, cone outer segment tip (COST) visibility, cysts, subretinal and intraretinal fluid, and epiretinal membranes. MAIN OUTCOME MEASURES: Spectral-domain OCT-based retinal structural parameters and VA outcomes. RESULTS: In multivariate analyses adjusting for baseline VA, worsening VA over 1 year was associated with 1-year increases in DRIL (point estimate, 0.06 per 100 µm; P < 0.001) and EZ disruption (0.07 per 100 µm; P = 0.023), but decreased COST visibility (-0.09 per 100 µm; P = 0.018). A 3-month increase in DRIL (0.05 per 100 µm; P = 0.003) and EZ disruption (0.10 per 100 µm; P < 0.001) were the only factors predicting VA worsening over 1 year, after controlling for baseline VA. A multivariate model including 3-month evolution in DRIL, EZ disruption, and VA accounted for 86.3% of variability in 1-year VA change. Absolute differences between predicted and actual 1-year VA were within 2 lines in 80.9%. When DRIL increased by 250 µm or more over 3 months, no eyes showed VA improvement of 1 line or more in 1 year. When EZ disruption decreased by 250 µm or more over 3 months, no eyes worsened by 1 line or more over 1 year. CONCLUSIONS: Early recovery over 3 months in both DRIL and EZ parameters are key drivers of 1-year VA outcomes. Predictive models incorporating 3-month changes in DRIL and EZ disruption support their usefulness as potential robust determinants of future VA.

Clinical, Radiologic, and Prognostic Features of Myelitis Associated With Myelin Oligodendrocyte Glycoprotein Autoantibody.

Importance: Recognizing the characteristics of myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG) myelitis is essential for early accurate diagnosis and treatment. Objective: To evaluate the clinical, radiologic, and prognostic features of MOG-IgG myelitis and compare with myelitis with aquaporin-4-IgG (AQP4-IgG) and multiple sclerosis (MS). Design, Setting, and Participants: We retrospectively identified 199 MOG-IgG-positive Mayo Clinic patients from January 1, 2000, through December 31, 2017, through our neuroimmunology laboratory. Fifty-four patients met inclusion criteria of (1) clinical myelitis; (2) MOG-IgG positivity; and (3) medical records available. We excluded 145 patients without documented myelitis. Myelitis of AQP4-IgG (n = 46) and MS (n = 26) were used for comparison. Main Outcomes and Measures: Outcome variables included modified Rankin score and need for gait aid. A neuroradiologist analyzed spine magnetic resonance imaging of patients with MOG-IgG and control patients blinded to diagnosis. Results: Of 54 included patients with MOG-IgG myelitis, the median age was 25 years (range, 3-73 years) and 24 were women (44%). Isolated transverse myelitis was the initial manifestation in 29 patients (54%), and 10 (19%) were initially diagnosed as having viral/postviral acute flaccid myelitis. Cerebrospinal fluid-elevated oligoclonal bands occurred in 1 of 38 (3%). At final follow-up (median, 24 months; range, 2-120 months), 32 patients (59%) had developed 1 or more relapses of optic neuritis (n = 31); transverse myelitis (n = 7); or acute disseminated encephalomyelitis (n = 1). Clinical features favoring MOG-IgG myelitis vs AQP4-IgG or MS myelitis included prodromal symptoms and concurrent acute disseminated encephalomyelitis. Magnetic resonance imaging features favoring MOG-IgG over AQP4-IgG or MS myelitis were T2-signal abnormality confined to gray matter (sagittal line and axial H sign) and lack of enhancement. Longitudinally extensive T2 lesions were of similar frequency in MOG-IgG and AQP4-IgG myelitis (37 of 47 [79%] vs 28 of 34 [82%]; P = .52) but not found in MS. Multiple spinal cord lesions and conus involvement were more frequent with MOG-IgG than AQP4-IgG but not different from MS. Wheelchair dependence at myelitis nadir occurred in one-third of patients with MOG-IgG and AQP4-IgG but never with MS, although patients with MOG-IgG myelitis recovered better than those with AQP4-IgG. Conclusions and Relevance: Myelitis is an early manifestation of MOG-IgG-related disease and may have a clinical phenotype of acute flaccid myelitis. We identified a variety of clinical and magnetic resonance imaging features that may help clinicians identify those at risk in whom MOG-IgG should be tested.

MACULAR TELANGIECTASIA TYPE 2 IN AN OTHERWISE HEALTHY TEENAGE BOY WITH CONSANGUINEOUS PARENTS.

PURPOSE: To report a case of macular telangiectasia Type 2 in a teenage boy with consanguineous parents. METHOD: Clinical case report and literature review. RESULTS: A healthy 14-year-old boy presented with mildly reduced vision in both eyes. Visual acuity was 20/30 in the right eye and 20/25 in the left eye. Fundus examination revealed intraretinal crystals in both eyes and an intraretinal pigment plaque temporal to the fovea in the left eye. Neither eye showed evidence of choroidal neovascular membrane or peripheral telangiectasia. Fluorescein angiography revealed temporal juxtafoveal leakage in both eyes. Spectral-domain optical coherence tomography showed ellipsoid layer and external limiting membrane disruption in the right eye and an inner retinal pigment plaque with shadowing in the left eye. The patient was of South Asian descent, and his parents were first cousins. His younger brother and parents were unaffected with a normal fundus examination. CONCLUSION: This is the youngest reported case of a healthy individual with MacTel Type 2, which usually manifests in the fifth or sixth decade. This is also the only reported case of MacTel Type 2 with consanguineous parents. This proband offers a unique opportunity to study possible monogenic etiologies of the condition.

Usefulness of Discarded Vitreous Samples from Routine Vitrectomy.

Purpose. To describe the histopathological features of vitreous samples obtained after vitrectomy surgery from diabetic and nondiabetic patients. Methods. Vitreous specimens from 137 patients who underwent vitrectomy for different clinical conditions were analysed. All samples were centrifuged and each resulting pellet was fixed and processed as part of routine paraffin section histopathology. The histopathological features were categorized in a semiquantitative fashion. The samples from diabetic and nondiabetic patients were compared. Results. The 125 included patients (58 diabetic, 60% males) were aged 64.2 ± 13.9 years. The presence of hemorrhage, inflammatory cells, and histiocytes was significantly higher in the diabetic group (P < 0.001, P = 0.028, and P = 0.016, resp.), showing more vessels (P < 0.001) and ghost vessels (P = 0.049). The presence of inflammatory cells was the feature with the highest sensitivity for detecting diabetes mellitus (98%) and also the highest negative predictive value (89%). In the multivariate analysis, three variables emerged as independent significant predictors of diabetes in vitrectomy samples: hemorrhage, endothelial-lined vessels, and age (P < 0.001, P < 0.001, and P = 0.019, resp.). Conclusions. Different histopathological features can be found in vitreous samples from diabetic patients. Analysis of vitrectomy samples may serve as a tool for diabetes management.

Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery.

BACKGROUND AND PURPOSE: Pharmacological modulation of complement activation recently has been postulated as a therapeutic target in the treatment of neurological injury. We hypothesized that pexelizumab, a humanized scFv monoclonal antibody directed against the C5 complement component, would limit deficits in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. METHODS: The Phase II Pexelizumab study was a 914-patient, double-blind, placebo-controlled, 65-center study of patients undergoing coronary artery bypass graft surgery. Patients were randomized to pexelizumab bolus, bolus plus infusion, or placebo. Neurological and neurocognitive functions were assessed as secondary endpoints at baseline and on postoperative days (POD) 4 and 30. Cognitive deficits were assessed with multivariable tests accounting for baseline cognition, age, diabetes, years of education, sex, elevated creatinine, history of myocardial infarction, neurological disorder or congestive heart failure, and cardiopulmonary bypass time. RESULTS: Pexelizumab had no statistically significant effect on the primary composite endpoint or on overall cognition. When domain specific effects were examined, a decline of at least 10% in the visuo-spatial domain was observed on POD 4 in 56% of patients receiving placebo compared with 40% receiving pexelizumab by bolus and infusion (P=0.003). Similarly, on POD 30, a 10% decline was present in 21% of patients in the placebo group versus only 12% of the drug bolus plus infusion group (P=0.016). No differences were seen between treatment groups in any of the other domains. CONCLUSIONS: Pexelizumab administration for 24 hours perioperatively had no effect on global measures of cognition but may reduce dysfunction in the visuo-spatial domain.

Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study.

OBJECTIVES: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk of myocardial necrosis after coronary artery bypass graft surgery. METHODS: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients > or =18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and > or =2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. RESULTS: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P =.027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P =.005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P =.033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. CONCLUSIONS: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.

Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass.

BACKGROUND: During cardiac surgery requiring cardiopulmonary bypass, pro-inflammatory complement pathways are activated by exposure of blood to bio-incompatible surfaces of the extracorporeal circuit and reperfusion of ischemic organs. Complement activation promotes the generation of additional inflammatory mediators thereby exacerbating tissue injury. We examined the safety and efficacy of a C5 complement inhibitor for attenuating inflammation-mediated cardiovascular dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. METHODS: Pexelizumab (Alexion Pharmaceuticals, Inc, Cheshire, CT), a recombinant, single-chain, anti-C5 monoclonal antibody, was evaluated in a randomized, double-blinded, placebo-controlled, multicenter trial that involved 914 patients undergoing coronary artery bypass grafting with or without valve surgery requiring cardiopulmonary bypass. RESULTS: Pexelizumab was administered intravenously as a bolus (2.0 mg/kg) or bolus plus infusion (2.0 mg/kg plus 0.05 mg/kg/h for 24 hours), and inhibited complement activation. There were no statistically significant differences between placebo-treated and pexelizumab-treated patients in the primary endpoint (composite of death, or new Q-wave, or non-Q-wave [myocardial-specific isoform of creatine kinase > 60 ng/mL] myocardial infarction, or left ventricular dysfunction, or new central nervous system deficit). However, post hoc analysis revealed a reduction in the composite of death or myocardial infarction (myocardial-specific isoform of creatine kinase >/= 100 ng/mL) for the isolated coronary artery bypass grafting, bolus plus infusion subgroup on POD 4 (p = 0.007) and on POD 30 (p = 0.004). CONCLUSIONS: Pexelizumab had no statistically significant effect on the primary endpoint. However, the reduction in death or myocardial infarction (myocardial-specific isoform of creatine kinase >/= 100 ng/mL) as revealed in the post hoc analysis in the isolated coronary artery bypass grafting bolus plus infusion subpopulation, suggests that further investigation of anti-C5 therapy for ameliorating complement-mediated inflammation and myocardial injury is warranted.

S-nitrosoglutathione preserves platelet function during in vitro ventricular assist device circulation.

Complications (severe bleeding/thromboembolism) may occur during ventricular assist device (VAD) circulation, caused mainly by platelet dysfunction from platelet activation. We hypothesized that S-nitrosoglutathione (GSNO), having platelet activity preservation properties like nitric oxide (NO), may be a titratable agent to diminish platelet activation and thus preserve platelet function. Dose-response measurement of platelet aggregation by GSNO was performed using an aggregometer. GSNO (1,000 microM) caused inhibition of collagen and ristocetin induced aggregation by approximately 50%. Next, in vitro ventricular assist device (VAD) circulation was performed (over 48 hours using human whole blood), both without (control) and with GSNO (1,000 microM), and the aggregability of perfusate was measured at 0, 0.5, 1, 3, 6, 12, 24, and 48 hours. In control VAD circuits, collagen induced platelet aggregability gradually decreased and became significantly lower after 3 hours of circulation. With GSNO, platelet function did not significantly decrease until after 12 hours. Similar results were seen for ristocetin induced aggregation; control aggregation dropped significantly after 6 hours, but not until after 24 hours with GSNO. Liquid phase measurement of total nitrogen oxides (NO(T)) confirmed added GSNO maintained high perfusate NO(T) compared with control. GSNO is effective in preserving platelet aggregation during the first 12 to 24 hours in vitro and may be effective in preserving platelet function by inhibiting platelet activation during in vivo VAD circulation.