Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives.

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Recent advances highlight the role of tumor-derived extracellular vesicles (TEV) and circulating hybrid cells (CHC) in UM tumorigenesis. Bridged with liquid biopsies, a novel technology that has shown incredible performance in detecting cancer cells or products derived from tumors in bodily fluids, it can significantly impact disease management and outcome. The aim of this comprehensive literature review is to provide a summary of current knowledge and ongoing advances in posterior UM pathophysiology, diagnosis, and treatment. The first section of the manuscript discusses the complex and intricate role of TEVs and CHCs. The second part of this review delves into the epidemiology, etiology and risk factors, clinical presentation, and prognosis of UM. Third, current diagnostic methods, ensued by novel diagnostic tools for the early detection of UM, such as liquid biopsies and artificial intelligence-based technologies, are of paramount importance in this review. The fundamental principles, limits, and challenges associated with these diagnostic tools, as well as their potential as a tracker for disease progression, are discussed. Finally, a summary of current treatment modalities is provided, followed by an overview of ongoing preclinical and clinical research studies to provide further insights on potential biomolecular pathway alterations and therapeutic targets for the management of UM. This review is thus an important resource for all healthcare professionals, clinicians, and researchers working in the field of ocular oncology.

Pars Plana Vitrectomy With Silicone Oil or Gas Tamponade for Uncomplicated Retinal Detachment: A Systematic Review and Meta-Analysis.

PURPOSE: To compare the efficacy and safety of pars plana vitrectomy (PPV) with silicone oil compared to gas tamponade for uncomplicated rhegmatogenous retinal detachment (RRD). DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was conducted on Ovid MEDLINE, Embase, and the Cochrane Library from January 2000 to September 2023 for comparative studies evaluating the efficacy and safety of PPV with either silicone oil or gas tamponade in the setting of uncomplicated RRD. Our primary outcome was best-corrected visual acuity at the last study observation. Secondary outcomes included the rates of retinal reattachment, retinal thickness, and the incidence of adverse events. We performed a meta-analysis using a random-effects model. RESULTS: Nine observational studies reporting on 491 RRD eyes were included. The mean best-corrected visual acuity at the last study observation was significantly better in the gas tamponade group than in the silicone oil group (weighted mean difference [WMD] = 0.17 logMAR, 95% confidence interval [CI] = [0.06, 0.27], P = .002). Rates of primary retinal reattachment were similar between the silicone oil and gas tamponade groups (P = .89). The ganglion cell layer was significantly thinner in the silicone oil group compared to the gas tamponade group (WMD =-3.70 µm, 95% CI = [-5.87, -1.53, P = .0008), as was the inner plexiform layer (WMD = -2.45, 95% CI = [-4.50, -0.40], P = .02) and outer nuclear layer (WMD = -11.74 µm, 95% CI = [-18.39, -5.10], P = .0005). CONCLUSIONS: PPV with gas tamponade was associated with better functional outcomes compared to PPV with silicone oil, although both tamponades yielded comparable primary reattachment rates. The absence of randomized trials and the potential for selection bias underscore the importance of further investigation in diverse patient populations.

A timely and accurate approach to nearshore oil spill monitoring using deep learning and GIS.

Oil spill accidents are a key contributor to marine pollution worldwide. Therefore, timely and effective oil spill detection is crucial for reducing marine pollution and enhancing environmental protection. Against this backdrop, this study explored two methods for performing nearshore on-site oil spill detection and segmentation, namely the U-net and Mask region-based convolutional neural network (R-CNN) methods. The U-net and Mask R-CNN models were revealed to exhibit acceptable and favorable performance, achieving overall accuracy of 77.01 % and 89.02 %, respectively. Subsequently, a verification system based on the Geographic Information System (GIS) was developed to improve the performance of the deep-learning model. With the integration of the verification system, the Mask R-CNN model achieved higher overall accuracy of 90.78 %. The feasibility of applying deep-learning methods to nearshore on-site oil spill monitoring was demonstrated through this study. In addition, the integration of the GIS not only assisted in the provision of oil spill information but also in the improvement of the deep-learning models. The timely, accurate, and effective method for nearshore on-site oil spill monitoring that this study explored can be applied to considerably improve traditional on-site oil spill monitoring, which has received limited academic attention in the last two decades.

Whole-Genome Duplication and Genome Instability in Cancer Cells: Double the Trouble.

Whole-genome duplication (WGD) is one of the most common genomic abnormalities in cancers. WGD can provide a source of redundant genes to buffer the deleterious effect of somatic alterations and facilitate clonal evolution in cancer cells. The extra DNA and centrosome burden after WGD is associated with an elevation of genome instability. Causes of genome instability are multifaceted and occur throughout the cell cycle. Among these are DNA damage caused by the abortive mitosis that initially triggers tetraploidization, replication stress and DNA damage associated with an enlarged genome, and chromosomal instability during the subsequent mitosis in the presence of extra centrosomes and altered spindle morphology. Here, we chronicle the events after WGD, from tetraploidization instigated by abortive mitosis including mitotic slippage and cytokinesis failure to the replication of the tetraploid genome, and finally, to the mitosis in the presence of supernumerary centrosomes. A recurring theme is the ability of some cancer cells to overcome the obstacles in place for preventing WGD. The underlying mechanisms range from the attenuation of the p53-dependent G1 checkpoint to enabling pseudobipolar spindle formation via the clustering of supernumerary centrosomes. These survival tactics and the resulting genome instability confer a subset of polyploid cancer cells proliferative advantage over their diploid counterparts and the development of therapeutic resistance.

Robotic Arm-Protected Microsurgical Pericallosal and Middle Cerebral Artery Aneurysm Clipping: A Technical Note and Case Series.

BACKGROUND: Managing intraoperative aneurysm rupture (IAR) during intracranial aneurysm clipping can be challenging given the excessive hemorrhage and limited field of view under the microscope for visualizing the proximal artery and safe temporary clipping. OBJECTIVE: To describe the first known use of robotic arm for safeguarding IAR in microsurgical aneurysm clipping. METHODS: A robotic arm was used to safeguard 3 microsurgical clipping cases (1 pericallosal and 2 middle cerebral artery) performed by a single surgeon. The device was installed onto the side rail of the operating table along with the clip applier attachment. After dissecting the cerebral artery segment proximal to the aneurysm, a temporary aneurysm clip was loaded and established at the appropriate segment before dissecting distally toward the aneurysm. RESULTS: Setup for the robotic arm and temporary clip was simple, quick, precise, and without any unforeseen accommodations needed in all 3 instances. The temporary clip acted as an emergency gate and could be deployed either manually or remotely through a controller. IAR occurred in case 1, and the robotic-assisted temporary clip deployment achieved immediate hemostasis without complications. This method bypassed the need for significant suctioning, packing, and further exploration for safe temporary clipping. Case 2 and 3 demonstrated the feasibility for middle cerebral artery protection and ease of intraoperative readjustment. CONCLUSION: This technical note highlights the feasibility and relative ease of using a robotic arm as a safeguard device, and it enables on-demand control of proximal blood flow and may enhance the safety of microsurgical aneurysm procedures.

Scleral-fixated and iris-fixated intraocular lens implantation or fixation:meta-analysis.

Scleral fixation and iris fixation are common intraocular lens (IOL) implantation techniques performed because of zonulopathy. There is a lack of consensus regarding their comparative efficacy and safety. This study aims to compare the efficacy and safety outcomes after scleral-fixated (SF) vs iris-fixated (IF) IOL implantation or fixation in adults. A systematic literature search was conducted on Ovid MEDLINE, Embase, and Cochrane CENTRAL from 2005 to 2020. 785 eyes from 2 randomized controlled trials and 9 nonrandomized studies were included. There was no significant difference in the mean corrected distance visual acuity at the final follow-up ( P = .52) or absolute change in spherical equivalent ( P = .88) between SF IOL and IF IOL implantation. The incidence of vitreous hemorrhage was significantly higher in the SF IOL group (risk ratio = 3.66, 95% CI, 1.16-11.55, P = .03). There were no differences in visual acuity and refractive outcomes between SF IOL and IF IOL implantation or fixation. Trade-offs in complications exist between the 2 techniques.

Fucoxanthin Is a Potential Therapeutic Agent for the Treatment of Breast Cancer.

Breast cancer (BC) is one of the most common cancers diagnosed and the leading cause of cancer-related death in women. Although there are first-line treatments for BC, drug resistances and adverse events have been reported. Given the incidence of BC keeps increasing, seeking novel therapeutics is urgently needed. Fucoxanthin (Fx) is a dietary carotenoid commonly found in seaweeds and diatoms. Both in vitro and in vivo studies show that Fx and its deacetylated metabolite fucoxanthinol (Fxol) inhibit and prevent BC growth. The NF-κB signaling pathway is considered the major pathway contributing to the anti-proliferation, anti-angiogenesis and pro-apoptotic effects of Fx and Fxol. Other signaling molecules such as MAPK, MMP2/9, CYP and ROS are also involved in the anti-cancer effects by regulating the tumor microenvironment, cancer metastasis, carcinogen metabolism and oxidation. Besides, Fx also possesses anti-obesity effects by regulating UCP1 levels and lipid metabolism, which may help to reduce BC risk. More importantly, mounting evidence demonstrates that Fx overcomes drug resistance. This review aims to give an updated summary of the anti-cancer effects of Fx and summarize the underlying mechanisms of action, which will provide novel strategies for the development of Fx as an anti-cancer therapeutic agent.

Modern Appraisal of Patency and Complications in Cerebral Bypass Surgery: A Single Institution Experience.

BACKGROUND: Cerebral bypass is a valuable surgical technique in well-selected patient populations. Updated clinical guidelines and improved surgical techniques warrant a contemporary reevaluation of the complications and patency to inform clinical practice and enhance postoperative patient care. OBJECTIVE: To assess the complication rates and postoperative graft patency for the 3 most common indications for bypass surgery: moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. METHODS: Perioperative notes of 175 consecutive bypass patients at a single institution were retrospectively identified to evaluate the clinical course and complications of surgery. RESULTS: The rate of total postoperative complications between moyamoya disease (9 of 98, 9.2%), intracranial atherosclerotic disease (7 of 57, 12.3%), and intracranial aneurysm (4 of 20, 20%) was not statistically different (P = .33). Immediate postoperative bypass patency was significantly higher in moyamoya disease (90 of 96, 93.8%) and intracranial atherosclerotic disease (48 of 51, 94.1%) than in intracranial aneurysm (13 of 18, 72.2%; P = .02). Intravenous heparin administration during bypass suturing was negatively associated with immediate postoperative patency (87% heparin patency vs 99% no heparin patency; P = .02). Double-barrel bypass trended toward an increased risk of wound healing complications (2 of 13, 15.4%) compared with the single-barrel bypass technique (4 of 156, 2.6%; P = .07). CONCLUSION: Cerebral bypass surgery remains an excellent surgical treatment for moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. This study suggests bypass is safer in moyamoya disease and intracranial atherosclerosis. Additional studies to clarify the risk of single-barrel vs double-barrel bypass and intraoperative heparin-stratified complications may be beneficial.

Sutured Scleral-Fixated Versus Anterior Chamber Intraocular Lens Implantation: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: No consensus exists on the comparative efficacy and safety of sutured scleral-fixated (SSF) and anterior chamber (AC) intraocular lens (IOL) implantation. We aim to compare outcomes of these two techniques. PATIENTS AND METHODS: A systematic literature search of MEDLINE, Embase, and Cochrane CENTRAL was conducted (2005 to 2020). Studies comparing SSFIOLs with ACIOLs were included. Outcomes included corrected distance visual acuity and complications. A meta-analysis was conducted with a random effects model. Weighted mean differences and risk ratios with 95% CIs were computed. RESULTS: Seven hundred eighty-three eyes from nine studies were included. SSFIOLs had a significantly higher absolute postoperative spherical equivalent (weighted mean difference, 0.32; 95% CI, 0.03 to 0.60; P = .03; low certainty) and incidence of IOL decentration/subluxation (risk ratio, 2.69; 95% CI, 1.03 to 7.01; P = .04; moderate certainty) than ACIOLs. There was no difference in final corrected distance visual acuity (P = .26). CONCLUSIONS: SSFIOLs have a higher absolute postoperative spherical equivalent and incidence of IOL decentration/subluxation than ACIOLs. Future prospective studies are needed to confirm these findings. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:12-21.].

Hemodynamic analysis of the recipient parasylvian cortical arteries for predicting postoperative hyperperfusion during STA-MCA bypass in adult patients with moyamoya disease.

OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass is a common approach for treating moyamoya disease (MMD); however, the selection of recipient vessels is still controversial, and its relationship with postoperative cerebral hyperperfusion (CHP) has not been revealed. The aim of the study was to investigate the relationship between the hemodynamic sources of the recipient parasylvian cortical arteries (PSCAs) and the occurrence of postoperative CHP. METHODS: The authors retrospectively analyzed the clinical data from 68 adult patients (75 hemispheres) with MMD who underwent STA-MCA bypass. Based on their hemodynamic sources from the MCA and non-MCAs, the PSCAs were classified as M-PSCAs and non-M-PSCAs, and their distributional characteristics were studied. Moreover, the patients' demographics, incidence of postoperative CHP, and post- and preoperative relative cerebral blood flow values were examined. RESULTS: The digital subtraction angiography analysis demonstrated that 40% (30/75) of the recipient PSCAs had no hemodynamic relationship with the MCA. The post- and preoperative relative cerebral blood flow values of the M-PSCA group were significantly higher than those of the non-M-PSCA group (p < 0.001). Multivariate analysis revealed that the hemodynamic source of PSCAs from the MCA was significantly associated with the development of focal (p = 0.003) and symptomatic (p = 0.021) CHP. Twelve (85.7%) of the 14 patients with symptomatic CHP and all 4 (100%) patients with postoperative hemorrhage were from the M-PSCA group. CONCLUSIONS: This study revealed that direct anastomoses of PSCAs with anterograde hemodynamic sources from the MCA had a high risk of postoperative CHP during STA-MCA bypass in adult patients with MMD.

C-shaped Incision for Far-Lateral Suboccipital Approach: Anatomical Study and Clinical Correlation.

Background The standard incision for far-lateral suboccipital approaches has been the classic "reverse hockey stick." Although that incision provides ample exposure, concern has been raised that excessive muscle dissection and skin elevation might lead to accumulation of cerebrospinal fluid (CSF) under the flap with increased risk of CSF leak. We hypothesize that the C-shaped incision can minimize the amount of muscle dissection and provide optimal exposure and surgical outcomes. Objective To describe the anatomical dissection for the C-shaped incision and clinical application of the C-shaped incision for the far-lateral approach. Methods A retrospective analysis of all the patients operated on at our center using this approach for the treatment of aneurysm of the posterior inferior cerebellar artery (PICA) from 2005 to 2011. Results of clinical and operative outcome are evaluated. Surgical techniques are described in detail. Cadaveric dissections using the C-shaped incision were performed to assess the exposure of the far-lateral suboccipital area. Results Eleven consecutive patients who had undergone this procedure were selected. All patients underwent clipping of PICA aneurysms. Nine patients (82%) presented with ruptured aneurysms and subarachnoid hemorrhage. All of them underwent suboccipital craniectomy and C1 laminectomy. The dura mater was closed in a watertight fashion in 10 patients (91%). No CSF leak or pseudomeningocele were reported. In nine SAH patients, two (22%) had postoperative dysphagia and required long-term percutaneous endoscopic gastrostomy tube placement. One patient (11%) had chronic respiratory failure and required a tracheostomy. Three patients (33%) developed hydrocephalus and required a ventriculoperitoneal shunt. Conclusions The C-shaped incision is a valid alternative to the classic reverse hockey-stick incision to gain exposure for far-lateral craniotomies. Knowing the anatomy and dissection techniques can provide an easy and safe route to address anterior lateral cranial-cervical lesions. Our results suggest the C-shaped incision is reliable in preventing CSF leak and the formation of pseudomeningocele.

Reporting success rates in the treatment of vestibular schwannomas: are we accounting for the natural history?

Stereotactic radiosurgery is generally accepted as one of the best treatment options for vestibular schwannomas. We question whether growth control is an accurate measure of success in vestibular schwannoma treatment. We aim to clarify the success rate of stereotactic radiosurgery and adjust the reported results to the benign natural history of untreated tumors. All articles were taken from a PubMed search of the English literature from the years 2000-2011. Inclusion criteria were articles containing the number of patients treated, radiation technique, average tumor size, follow-up time, and percentage of tumors growing during follow-up. Data were extracted from 19 articles. Success rates were adjusted using published data that 17% to 30% of vestibular schwannomas grow. The average reported success rate for stereotactic radiosurgery across all articles was 95.5%. When considering 17% or 30% natural growth without intervention, the adjusted success rates became 78.2% and 86.9% respectively. These rates were obtained by applying the natural history growth percentages to any tumors not reported to be growing before radiosurgical intervention. Success in the treatment of vestibular schwannomas with stereotactic radiosurgery is often defined as lack of further growth. Recent data on the natural growth history of vestibular schwannomas raise the question of whether this is the best definition of success. We have identified a lack of continuity regarding the reporting of success and emphasize the importance of the clarification of the success of radiosurgery to make informed decisions regarding the best treatment options for vestibular schwannoma.

Field of view comparison between two-dimensional and three-dimensional endoscopy.

OBJECTIVES/HYPOTHESIS: Relative to microscopic transnasal surgery, endoscopic surgery provides improved visualization with an increased field of view. Advances such as high-definition (HD) and three-dimensional (3D) endoscopy have been introduced and clearly improve visualization. However, do both technologies maintain an increased field of view? We hypothesize that the field of view of 3D endoscopy is restricted relative to two-dimensional (2D) HD endoscopy. STUDY DESIGN: Laboratory investigation, prospective case series. METHODS: Standard measurements at 6-cm and 2-cm working distances where made to determine the comparative field of view utilizing Storz 0° 2D HD and Visionsense 3D endoscopes. Relative measurements were then made to determine field of view. Five clinical patients were then utilized to confirm laboratory studies and demonstrate the relative field of view change. RESULTS: 3D endoscopy demonstrates a 52% loss of field of view compared to 2D endoscopy in a controlled lab testing. This was confirmed in a small clinical patient series where a 55% ± 3% relative field of view reduction was observed. CONCLUSIONS: When working with 3D endoscopy in a currently available commercial product, the operator should be aware that relative to HD 2D endoscopy, there is a field of view restriction of 52%. LEVEL OF EVIDENCE: N/A.

Temporal lobe surgery in medically refractory epilepsy: a comparison between populations based on MRI findings.

INTRODUCTION: High resolution MRI findings suggestive of mesial temporal sclerosis (MRI-MTS) correlate with good outcome after surgery. However, a large group of patients present with normal brain MRI (N-MRI) and temporal lobe epilepsy (TLE). We aim to compare pre-operative ictal EEG patterns in predicting surgical outcomes in the population with MRI-MTS vs. N-MRI after selective anterior-mesial temporal lobe (AMTL) resection. METHODS: 241 patients with unilateral anterior ictal EEG findings underwent selective AMTL resection. 143 MRI-MTS and 98 N-MRI patients were identified. Outcome was based on the modified Engel classification, ictal EEG pattern at seizure onset, demographics and MRI findings. RESULTS: Seizure-free outcome was seen in the MRI-MTS in 79% of patients, compared to 59.1% (p<.005) of the N-MRI group. No significant difference was identified in ictal EEG patterns at presentation between groups. Class I outcome was achieved in 78.9% of patients that had theta rhythm and MRI-MTS compared to 57.9% of patients that had theta rhythm and N-MRI (p<0.05). DISCUSSION AND CONCLUSION: Surgical treatment for mesial TLE is effective. Positive MRI suggestive of mesial temporal sclerosis (MTS) predicts better seizure control after surgery. Theta rhythm is the most common ictal pattern and seems to carry the best prognosis for TLE. However, a well-selected group of patients with N-MRI will benefit from surgical intervention, and similar outcome to MRI-MTS patients can be achieved if delta ictal EEG pattern is presented at initial onset. Early referral to an epilepsy center cannot be emphasized enough, even in situations when high-resolution brain MRI is normal.

In vivo animal stroke models: a rationale for rodent and non-human primate models.

On average, every four minutes an individual dies from a stroke, accounting for 1 out of every 18 deaths in the United States. Approximately 795,000 Americans have a new or recurrent stroke each year, with just over 600,000 of these being first attack [1]. There have been multiple animal models of stroke demonstrating that novel therapeutics can help improve the clinical outcome. However, these results have failed to show the same outcomes when tested in human clinical trials. This review will discuss the current in vivo animal models of stroke, advantages and limitations, and the rationale for employing these animal models to satisfy translational gating items for examination of neuroprotective, as well as neurorestorative strategies in stroke patients. An emphasis in the present discussion of therapeutics development is given to stem cell therapy for stroke.

Paradoxical trends in the management of vestibular schwannoma in the United States.

OBJECT: Recent natural history studies of vestibular schwannomas (VSs) suggest that most of these tumors do not grow. The impact of these new data on management trends in the US is currently unknown. The aim in the present study was to evaluate current trends in the treatment of VS in the US by analyzing a national cancer database. METHODS: The Surveillance, Epidemiology, and End Results Program is a national database maintained by the National Cancer Institute representing 26% of the US population. Data from the database were downloaded using provided software. Cases were isolated based on histology codes and the site code. Data from 2004 to 2007 were included in the analysis. The number of patients undergoing resection was compared with the number treated with beam radiation and observation, based on tumor size. RESULTS: Three thousand six hundred fifty cases were identified in the database. Over the study period, management choices for VSs showed a significant change only for tumors with a diameter < 2 cm. In this tumor category, a decrease in resection and an increase in radiation were observed, with observation showing a modest increase but remaining low at an average of 25%. CONCLUSIONS: Study data demonstrated a shift in the management of small VSs in the US between 2004 and 2007, with microsurgical removal giving way to radiation treatment and the overall rate for observation remaining low and stable. With recent literature suggesting that the majority of small tumors do not grow, the authors assert that VSs are being overtreated in the US.

Cerebral aneurysm as an exacerbating factor in stroke pathology and a therapeutic target for neuroprotection.

Stroke remains a major cause of death in the US and around the world. Despite major scientific advances in our understanding of stroke pathology, the only FDA-approved drug for ischemic stroke is tissue plasminogen activator (tPA). Moreover, the therapeutic window for tPA is confined to the acute phase of stroke, thereby greatly limiting its benefits to less than 3% of ischemic stroke patients. Many treatment strategies for stroke have targeted the subacute or chronic phase in an effort to abrogate the secondary cell death that ensues after the initial stroke insult. Here, we advance the hypothesis that blood vessel disruption, or aneurysm, in the brain is an exacerbating factor for stroke, especially in the evolution of the penumbra or peri-infarct area. A better understanding of aneurysm, specifically its dynamic onset and juxtaposition to the ischemic brain tissue should facilitate the development of novel strategies for attenuating the secondary cell death associated with stroke. To this end, we discuss the laboratory and clinical evidence implicating aneurysm formation in stroke and also provide insights on how stem cell therapy may prove efficacious in combating aneurysm and stroke.

Immediate, but not delayed, microsurgical skull reconstruction exacerbates brain damage in experimental traumatic brain injury model.

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI.

Thirty-day morbidity and mortality rates for carotid artery intervention by surgeons who perform both carotid endarterectomy and carotid artery angioplasty and stent placement.

OBJECT: There is no known standard 30-day morbidity and mortality rate for high-risk patients undergoing carotid artery (CA) angioplasty and stent (CAS) placement. The high-risk registries and the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy, Carotid Revascularization using Endarterectomy or Stenting Systems, and European Long-term Carotid Artery Stenting trials report different rates of morbidity and mortality, and each high-risk cohort has a different risk profile. The applicability of carotid endarterectomy (CEA) results from North American Symptomatic Carotid Endarterectomy Trial/Asymptomatic Carotid Atherosclerosis Study (NASCET/ACAS) remains uncertain, as most clinical CAS placement series reported to date typically included patients who would not have qualified for those studies. At the University at Buffalo, the same neurosurgeons perform triage in patients with CA disease and perform both CEA and CAS insertion. The authors review morbidity and mortality rates in this practice model. METHODS: Diagnosis-related group codes were used to search the authors' practice database for patients who had undergone a completed CA intervention solely for the indication of atherosclerotic disease. One hundred twenty patients (129 vessels) treated with CAS surgery and 95 patients (100 vessels) treated with CEA met these criteria. In the CAS placement group, 78% of the patients would not have met NASCET/ACAS inclusion criteria. Demographic and clinical data for both groups were recorded on a spreadsheet for analysis. At 30 days, one patient in the CEA group and two in the CAS group had died. Stroke occurred in one patient in the CAS group and none in the CEA group. Myocardial infarction (MI) occurred in one patient who underwent CAS surgery compared with three undergoing CEA. Composite incidence of stroke/death/MI was 3.3% in the CAS group and 3.2% in the CEA group. CONCLUSIONS: In a practice in which surgeons perform both CEA and CAS surgery, the event rates for the CAS surgery equivalent to NASCET and ACAS rates for CEA can be achieved, even in high-risk NASCET/ACAS-ineligible patients in 78% of the CAS cases.

Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs.

Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8(+)-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.