Complications Have Not Improved With Newer Generation Robots.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The purpose of this study was to see whether upgrades in newer generation robots improve safety and clinical outcomes following spine surgery. METHODS: All patients undergoing robotic-assisted spine surgery with the Mazor X Stealth EditionTM (Medtronic, Minneapolis, MN) from 2019 to 2022 at a combined orthopedic and neurosurgical spine service were retrospectively reviewed. Robot related complications were recorded. RESULTS: 264 consecutive patients (54.1% female; age at time of surgery 63.5 ± 15.3 years) operated on by 14 surgeons were analyzed. The average number of instrumented levels with robotics was 4.2 ± 2.7, while the average number of instrumented screws with robotics was 8.3 ± 5.3. There was a nearly 50/50 split between an open and minimally invasive approach. Six patients (2.2%) had robot related complications. Three patients had temporary nerve root injuries from misplaced screws that required reoperation, one patient had a permanent motor deficit from the tap damaging the L1 and L2 nerve roots, one patient had a durotomy from a misplaced screw that required laminectomy and intra-operative repair, and one patient had a temporary sensory L5 nerve root injury from a drill. Half of these complications (3/6) were due to a reference frame error. In total, four patients (1.5%) required reoperation to fix 10 misplaced screws. CONCLUSION: Despite newer generation robots, robot related complications are not decreasing. As half the robot related complications result from reference frame errors, this is an opportunity for improvement.

The association of Takotsubo cardiomyopathy and aneurysmal subarachnoid hemorrhage: A U.S. nationwide analysis.

OBJECTIVE: Takotsubo cardiomyopathy (TC) is a stress-induced cardiomyopathy that can be precipitated by aneurysmal subarachnoid hemorrhage (aSAH). Several studies have shown patients who develop TC following aSAH have an increased risk of disability and mortality. The goal of this study is to examine the incidence of TC in aSAH, identify its risk factors, and analyze its impact on patient outcomes. METHODS: Data for patients with aSAH between the years of 2009 and 2018 were extracted from the Nationwide Inpatient Sample (NIS) and stratified based on the diagnosis of TC. Univariate analysis was used to assess the incidence of TC and covariates including patient demographics, aneurysmal treatment, in-hospital mortality rate, length of stay and costs. Multivariate logistic regression models analyzed the relationship between TC and these variables RESULTS: 80,915 aSAH patient-discharges were included in this study, 673 (0.83%) of which, developed TC. Females (OR 3.49, CI [2.82-4.33], P < 0.001), white ethnicity (69% vs 63%, P = 0.003) and patients with certain comorbidities including smoking (OR 1.64, CI [1.38-1.95], P < 0.0001) and seizures (OR 1.32, CI [1.07, 1.64], P = 0.01) were most likely to develop TC. Patients who developed TC had significantly increased mortality (OR 1.36, CI [1.13-1.65], P = 0.001), hospital stays (mean days of 19.4 vs 11.5, P < 0.0001), and costs ($104,111 vs $48,734, P < 0.0001). Hypertension (OR 0.63, CI [0.54-0.74], P < 0.0001) and hyperlipidemia (OR 0.63, CI [0.51-0.77], P < 0.0001) were found to be protective against TC. Patients with TC after acute SAH were more likely to undergo endovascular coiling (OR 1.68, CI [1.327-2.127], P < 0.001) rather than surgical clipping (OR 0.66, CI [0.52-0.83], P < 0.0001). CONCLUSIONS: Female sex, white ethnicity, smoking and seizures represented significant predictors of developing TC after aSAH, while hypercholesterolemia and hypertension were protective.

Management of non-missile penetrating spinal injury.

Review of the literature with case illustration. Non-missile penetrating spinal injury (NPSI) represents a small subset of spinal cord injuries at tertiary trauma centers and is comprised mostly of knife violence. Strict guidelines for the management of penetrating spinal cord injury remain elusive given the variability of mechanisms, rarity of clinical experience, and paucity of prospective studies. A review of the literature was conducted by search of the National Library of Medicine (PubMed) in the English language through June of 2018. Additional articles were culled from the reference lists of the included series. Eleven case series totaling 1007 patients, along with 21 case reports, were identified. In summary, magnetic resonance imaging (MRI) may be beneficial in assessing incomplete or progressive spinal injuries and can be considered with retained foreign bodies in select cases. Forty-eight hours of antibiotic prophylaxis is likely sufficient to prevent infection. Puncture wounds should be debrided, washed, and closed. Retained foreign bodies should be removed in the operating room and often require laminectomy. Early intervention is preferred. Non-missile penetrating spinal injury has a higher likelihood of neurologic recovery as compared to other traumatic spinal injuries.

Primary Diffuse Large B-Cell Lymphoma in a Patient with Rubinstein-Taybi Syndrome: Case Report and Review of the Literature.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare, congenital syndrome that is known to be associated with neoplasms of various organ systems. Evaluation and treatment of such patients is challenging, given the cognitive delay and heterogeneity of pathologic presentations that define this syndrome. CASE DESCRIPTION: Presented here is a case of a patient with RSTS, diagnosed at birth, who presented with subtle symptoms of lethargy and a change in behavior. He was found to have a large (7.0-cm × 4.7-cm), right-sided brain mass that was eventually diagnosed as a primary central nervous system lymphoma. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a primary central nervous system lymphoma presenting in a patient with RSTS. This was confirmed through microscopic and histologic studies. The large size attained by this mass in our patient highlights the increased scrutiny and surveillance needed to provide the best care for these patients. A multidisciplinary team approach is ideal as successful treatment of our patient using surgical debulking, appropriate chemotherapy, and close postoperative follow-up has resulted in an excellent clinical outcome.

Endovascular treatment of blister aneurysms.

Blister aneurysms are rare cerebrovascular lesions for which the treatment methods are reviewed here, with a focus on endovascular options. The reported pathogenesis of blister aneurysms varies, and hemodynamic stress, arterial dissection, and arteriosclerotic ulceration have all been described. There is consensus on the excessive fragility of blister aneurysms and their parent vessels, which makes clipping technically difficult. Open surgical treatment is associated with high rates of complications, morbidity, and mortality; endovascular treatment is a promising alternative. Among endovascular treatment options, deconstructive treatment has been associated with higher morbidity compared with reconstructive methods such as direct embolization, stent- or balloon-assisted direct embolization, stent monotherapy, and flow diversion. Flow diversion has been associated with higher technical success rates and similar clinical outcomes compared with non-flow diverting treatment methods. However, delayed aneurysm occlusion and the need for antiplatelet therapy are potential drawbacks to flow diversion that must be considered when choosing among treatment methods for blister aneurysms.

Combining Normobaric Oxygen with Ethanol or Hypothermia Prevents Brain Damage from Thromboembolic Stroke via PKC-Akt-NOX Modulation.

In a thromboembolic stroke model after reperfusion by recombinant tissue plasminogen activator (rt-PA), we aimed to determine whether therapeutic hypothermia (TH) and ethanol (EtOH) in combination with low concentration (60 %) of normobaric oxygen (NBO) enhanced neuroprotection, as compared to using each of these agents alone. We further aimed to elucidate a potential role of the NADPH oxidase (NOX), phosphorylated protein kinase B (Akt), and protein kinase C-δ (PKC-δ) pathway in oxidative stress and neuroprotection. In Sprague-Dawley rats, a focal middle cerebral artery (MCA) occlusion was induced by an autologous embolus in the following experimental groups: rt-PA treatment alone, rt-PA + NBO treatment, rt-PA + TH at 33 °C, rt-PA + EtOH, rt-PA + NBO + EtOH, rt-PA + NBO + TH, rt-PA + NOX inhibitor, rt-PA + EtOH + NOX inhibitor, or rt-PA + EtOH + Akt inhibitor. Control groups included sham-operated without stroke or stroke without treatment. Infarct volume and neurological deficit were assessed at 24 h after rt-PA-induced reperfusion with or without treatments. ROS levels, NOX activity, and the protein expression of NOX subunits p22phox, p47phox, p67phox, gp91phox, as well as PKC-δ and phosphorylated Akt were measured at 3 and 24 h after rt-PA-induced reperfusion. Following rt-PA in thromboembolic stroke rats, NBO combined with TH or EtOH more effectively decreased infarct volume and neurological deficit, as well as reactive oxygen species (ROS) production than with any of the used monotherapies. NOX activity and subunit expressions were downregulated and temporally associated with reduced PKC-δ and increased p-Akt expression. The present study demonstrated that combining NBO with either TH or EtOH conferred similar neuroprotection via modulation of NOX activation. The results suggest a role of Akt in NOX activation and implicate an upstream PKC-δ pathway in the Akt regulation of NOX. It is possible to substitute EtOH for TH, thus circumventing the difficulties in clinical application of TH through the comparatively easier usage of EtOH as a potential stroke management.

Animal Stroke Model: Ischemia-Reperfusion and Intracerebral Hemorrhage.

Stroke is a major health issue worldwide-one with serious financial and public health implications. As a result, ongoing clinical research on novel and improved stroke therapies is not only pertinent but also paramount. Due to the complexity of a stroke-like event and its many sequelae, devising usable methods and experimental models are necessary to study and better understand the pathophysiological processes that ensue. As it stands, animal models that simulate stroke-like events have proven to be the most logical and effective options in regards to experimental studies. A number of animal stroke models exist and have been demonstrated in previous studies on ischemic as well as hemorrhagic stroke. Considering the efficiency and reproducibility of animal models, here, we introduce an ischemic stroke model induced by middle cerebral artery occlusion (MCAO) and an intracerebral hemorrhagic stroke model induced by collagenase injection. The models outlined here have been proven to demonstrate the clinical relevance desired for use in continued research on stroke pathophysiology and the study of future therapeutic options.

Reduced cerebral monocarboxylate transporters and lactate levels by ethanol and normobaric oxygen therapy in severe transient and permanent ischemic stroke.

OBJECTIVES: Neuroprotective benefits of ethanol (EtOH) and normobaric oxygenation (NBO) were previously demonstrated in transient and permanent ischemic stroke. Here we sought to identify whether the enhanced lactic acidosis and increased expression of monocarboxylate transporters (MCTs) observed after stroke might be attenuated by single and/or combined EtOH and NBO therapies. METHODS: Sprague-Dawley rats (n=96) were subjected to right middle cerebral artery occlusion (MCAO) for 2 or 4h (transient ischemia), or 28 h (permanent ischemia) followed by 3, 24h, or no reperfusion. Rats received: (1) either an intraperitoneal injection of saline (sham treatment), one dose of EtOH (1.5 g/kg), two doses of EtOH (1.5 g/kg at 2h of MCAO, followed by 1.0 g/kg 2h after 1st dose), or (2) EtOH+95% NBO (at 2h of MCAO for 6h in permanent ischemia). Lactate levels were detected at 3 and 24h of reperfusion. Gene and protein expressions of MCT-1, -2, -4 were assessed by real-time PCR and western blotting. RESULTS: A dose-dependent EtOH neuroprotection was found in transient ischemia. Following transient ischemia, a single dose of EtOH (in 2h-MCAO) or a double dose (in 4h-MCAO), significantly attenuated lactate levels, as well as the mRNAs and protein expressions of MCT-1, MCT-2, and MCT-4. However, while two doses of EtOH alone was ineffective in permanent stroke, the combined therapy (EtOH+95% NBO) resulted in a more significant attenuation in all the above levels and expressions. CONCLUSIONS: Our study demonstrates that acute EtOH administration attenuated lactic acidosis in transient or permanent ischemic stroke. This EtOH-induced beneficial effect was potentiated by NBO therapy in permanent ischemia. Because both EtOH and NBO are readily available, inexpensive and easy to administer, their combination could be implemented in the clinics shortly after stroke.

The status on non-communicable disease prevention and control in the Philippines: A systematic review

OBJECTIVE: This paper aims to provide concise background information regarding the state of noncommunicable diseases (NCDs) and their risk factors as well as the existing efforts to address them in the Philippines in the last 25 years. METHODS: A desk review of documents and literature review as well as analyses of available statistical data and several consultations with involved government agencies have been made to come up with summary figures and tables.RESULTS: NCDs as well as metabolic conditions that can potentially lead to NCDs are on the rise in the last score of years. The Philippines, through the Department of Health, has been visionary in leading various projects and activities to fight NCDs over the last two decades, and its efforts are slowly paying off: the prevalence of tobacco use and that of hypertension have decreased over the last 5 years. NCD mortality (including premature deaths) and prevalence of behavioral risk factors, however, generally remain high, and the Philippines needs to accelerate whole-of-society and whole-of-government actions to sustain the gains and attain its NCD targets in the next 10 years or so. CONCLUSION: The need to strengthen health system interventions and promote accountability of various sectors in addressing NCDs and its risk factors in the country arises. The development of a multisectoral action plan on NCD prevention and control is needed to halt the rise of NCDs in the country.

Dynamic metabolic changes after permanent cerebral ischemia in rats with/without post-stroke exercise: a positron emission tomography (PET) study.

OBJECTIVES: Recent studies have suggested that rehabilitation therapy can accelerate functional recovery after a stroke. Although often overlooked, the cortical hemisphere contralateral to an infarction plays an important role. This study investigates alterations in metabolism of both the damaged ('ipsilateral') as well as the undamaged ('contralateral') hemisphere using (18)F-fluorodeoxyglucose (FDG)-micro-positron emission tomography (PET) in a rat permanent stroke model (with or without post-injury exercise) in order to elucidate the relative importance of either hemisphere to the recovery process following stroke. METHODS: Thirty-six adult, male Sprague-Dawley rats were divided into four groups before subsequent surgery: sham controls with or without exercise, and ischemic ('stroke') groups with or without exercise. Fluorodeoxyglucose micro-PET imaging was performed at 7, 14, and 21 days after the designated procedure according to group assignment. The imaging data was analyzed by ANOVA using SPMratIHEP software. RESULTS: Both exercise and ischemia have measurable effects on the motor cortex as well as on the striatum, the effects of which notably include the contralateral hemisphere. To that end, regions of the contralateral motor cortex and striatum have been found to be in a hypermetabolic state following exercise. We further observed that exercise reversed the hypometabolism caused by ischemia back to control levels from day 7 through day 21 on the ipsilateral side. Its effect on the contralateral hemisphere, notably, bolsters an already vigorous response observed after ischemic insult. Thus, the beneficial effect of exercise, as inferred by an increase in metabolic activity, is evident in both hemispheres. DISCUSSION: These findings suggest that the contralateral hemisphere can compensate for the damaged cortex by remodeling neuronal activity. Thus, clinical treatments specifically targeted to the 'intact' hemisphere following stroke may provide a complimentary strategy for promoting recovery of functional deficits and for improving quality of life in stroke patients.

Rodent models of ischemic stroke lack translational relevance... are baboon models the answer?

Rodent models of ischemic stroke are associated with many issues and limitations, which greatly diminish the translational potential of these studies. Recent studies demonstrate that significant differences exist between rodent and human ischemic stroke. These differences include the physical characteristics of the stroke, as well as changes in the subsequent inflammatory and molecular pathways following the acute ischemic insult. Non-human primate (NHP) models of ischemic stroke, however, are much more similar to humans. In addition to evident anatomical similarities, the physiological responses that NHPs experience during ischemic stroke are much more applicable to the human condition and thus make it an attractive model for future research. The baboon ischemic stroke model, in particular, has been studied extensively in comparison to other NHP models. Here we discuss the major shortcomings associated with rodent ischemic stroke models and provide a comparative overview of baboon ischemic stroke models. Studies have shown that baboons, although more difficult to obtain and handle, are more representative of ischemic events in humans and may have greater translational potential that can offset these deficiencies. There remain critical issues within these baboon stroke studies that need to be addressed in future investigations. The most critical issue revolves around the size and the variability of baboon ischemic stroke. Compared to rodent models, however, issues such as these can be addressed in future studies. Importantly, baboon models avoid many drawbacks associated with rodent models including vascular variability and inconsistent inflammatory responses - issues that are inherent to the species and cannot be avoided.

Impact of regional white matter lesions on cognitive function in subcortical vascular cognitive impairment.

OBJECTIVES: Exact characterization and localization of white matter lesions (WMLs) as they relate and contribute to vascular cognitive impairment is highly debated. The purpose of this study was to investigate the impact of WML on cognitive function by using a new anatomy-based classification method. METHODS: We detected WML accurately by using a three-dimensional fluid-attenuated inversion recovery (3D FLAIR) imaging technique and subsequently segmented WMLs by using an anatomy-based method. Participants included 56 consecutive patients diagnosed with subcortical vascular cognitive impairment (SubVCI). The volume of WMLs in different anatomic regions was measured. The volume of the hippocampus, the corpus callosum (CC), any lacunar infarcts, total gray matter (GM), and total brain volumes were also calculated. RESULTS: Hippocampal (P  =  0.005) as well as temporal WML volumes (P  =  0.039) were both independently associated with mini-mental state examination (MMSE) score. Only the parietal WML volume (P  =  0.000) was independently associated with Montreal Cognitive Assessment (MoCA) score. Frontal WMLs were independently correlated with executive function. Occipital WMLs were independently associated with visuospatial and recall function. Language impairment was independently correlated with both parietal GM and parietal WML volume. Functions related to orientation were independently associated with parietal WML volume. DISCUSSION: The volume of WMLs in the temporal region as well as in the hippocampus were both independently associated with MMSE score. For the MoCA score, however, only parietal WML volumes were independently correlated. White matter lesions within different anatomic regions were separately correlated with different subdomains of cognitive function.

Thrombolysis and reperfusion: advanced understanding of early management strategies in acute ischemic stroke.

Currently, intravenous (IV) thrombolysis within 3 hours from stroke onset is the only approved treatment in acute ischemic stroke (AIS). Although effective, the definition of therapeutic time window and appropriate patient selection still remains controversial. Notably, early endovascular treatment strategies may serve as an adjunct therapy for time window extension in AIS. In this article, we review the safety and efficacy of IV thrombolysis in AIS as it pertains to the optimal time window, the selection of eligible patients, and in combination with endovascular treatment. Combined clinical application of IV thrombolysis and endovascular therapy may improve the therapeutic outcomes for AIS patients.

Synergetic neuroprotection of normobaric oxygenation and ethanol in ischemic stroke through improved oxidative mechanism.

BACKGROUND AND PURPOSE: Normobaric oxygenation (NBO) and ethanol both provide neuroprotection in stroke. We evaluated the enhanced neuroprotective effect of combining these 2 treatments in a rat stroke model. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Reperfusion was then established and followed by treatment with either (1) an intraperitoneal injection of ethanol (1.0 g/kg), (2) NBO treatment (2-hour duration), or (3) NBO plus ethanol. The extent of brain injury was determined by infarct volume and motor performance. Oxidative metabolism was determined by ADP/ATP ratios, reactive oxygen species levels, nicotinamide adenine dinucleotide phosphate oxidase activity, and pyruvate dehydrogenase activity. Protein expression of major nicotinamide adenine dinucleotide phosphate oxidase subunits (p47(phox), gp91(phox), and p67(phox)) and the enzyme pyruvate dehydrogenase was evaluated through Western immunoblotting. RESULTS: NBO and ethanol monotherapies each demonstrated reductions as compared to stroke without treatment in infarct volume (36.7% and 37.9% vs 48.4%) and neurological deficits (score of 6.4 and 6.5 vs 8.4); however, the greatest neuroprotection (18.8% of infarct volume and 4.4 neurological deficit) was found in animals treated with combination therapy. This neuroprotection was associated with the largest reductions in ADP/ATP ratios, reactive oxygen species levels, and nicotinamide adenine dinucleotide phosphate oxidase activity, and the largest increase in pyruvate dehydrogenase activity. CONCLUSIONS: Combination therapy with NBO and ethanol enhances the neuroprotective effect produced by each therapy alone. The mechanism behind this synergistic action is related to changes in cellular metabolism after ischemia reperfusion. NBO plus ethanol is attractive for clinical study because of its ease of use, tolerability, and tremendous neuroprotective potential in stroke.

Differential expression of Toll-like receptor pathway genes in chronic rhinosinusitis with or without nasal polyps.

CONCLUSIONS: Our results indicate that chronic rhinosinusitis without nasal polyps (CRSsNP) is characterized by the down-regulation of a Toll-like receptor (TLR)-mediated signaling pathway and such a deficiency within the innate immune system may contribute to the inflammatory process of CRSsNP. In contrast, the inflammatory process found in CRS with nasal polyps (CRSwNP) is characterized by an excessively activated TLR-mediated signaling pathway, which may contribute to the formation of nasal polyps. This study suggests that the pathophysiologic mechanism of CRSsNP and CRSwNP is different. OBJECTIVE: The nasal mucosa expresses a variety of TLRs that serve in recognizing microorganisms. We investigated the gene expression of a TLR-mediated signaling pathway within two distinctive patient subgroups: CRSwNP and CRSsNP. METHODS: Nasal mucosal tissue was obtained from 78 subjects with CRS and 23 control subjects. qRT-PCR and immunohistochemistry were used to investigate tissues for the expression of TLR2, TLR4, TLR7, their downstream signaling components, MyD88 and TRIF, and associated cytokines, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10. RESULTS: TLR2, TLR4, TLR7, and IL-4 were significantly increased in CRSwNP patients when compared with either CRSsNP patients or control subjects, whereas TLR4 and TLR7, and downstream MyD88 were significantly decreased in CRSsNP patients versus patients from CRSwNP and control subjects.

Blood-brain barrier integrity and breast cancer metastasis to the brain.

Brain metastasis, an important cause of cancer morbidity and mortality, occurs in at least 30% of patients with breast cancer. A key event of brain metastasis is the migration of cancer cells through the blood-brain barrier (BBB). Although preventing brain metastasis is immensely important for survival, very little is known about the early stage of transmigration and the molecular mechanisms of breast tumor cells penetrating the BBB. The brain endothelium plays an important role in brain metastasis, although the mechanisms are not clear. Brain Microvascular Endothelial Cells (BMECs) are the major cellular constituent of the BBB. BMECs are joined together by intercellular tight junctions (TJs) that are responsible for acquisition of highly selective permeability. Failure of the BBB is a critical event in the development and progression of several diseases that affect the CNS, including brain tumor metastasis development. Here, we have delineated the mechanisms of BBB impairment and breast cancer metastasis to the brain. Understanding the molecular mediators that cause changes in the BBB should lead to better strategies for effective treatment modalities targeted to inhibition of brain tumors.