Risk, Predictive, and Preventive Factors for Noninfectious Ventriculitis and External Ventricular Drain Infection.

BACKGROUND: External ventricular drain (EVD) is used for monitoring intracranial pressure or diverting cerebrospinal fluid. However, confirmation of an infection is not immediate and requires obtaining culture results, often leading to the excessive use of antibiotics. This study aimed to compare noninfectious ventriculitis and EVD infection in terms of the risk factors, predictors, prognosis, and effectiveness of care bundle interventions. METHODS: This retrospective study was conducted at a medical center with 1,006 beds in northern Taiwan between January 2018 and July 2022. Standard EVD insertion protocols and care bundles have been implemented since 2018, along with the initiation of chlorhexidine. RESULTS: In total, 742 EVD cases were identified. Noninfectious ventriculitis typically presents with fever approximately 8 days following EVD placement, whereas EVD infection typically manifests as fever after 20 days. Aneurysmal subarachnoid hemorrhage was strongly associated with the development of noninfectious ventriculitis (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.4). Alcoholism (adjusted OR 3.5, 95% CI 1.1-12.3) and arteriovenous malformation (adjusted OR 13.1, 95% CI 2.9-58.2) significantly increased the risk of EVD infection. The EVD infection rate significantly decreased from 3.6% (14 of 446) to 1.0% (3 of 219) (p = 0.03) after the implementation of chlorhexidine gluconate bathing. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage or fever with neuroinflammation within 2 weeks of EVD placement is indicative of a higher likelihood of noninfectious ventriculitis. Conversely, patients with arteriovenous malformation, alcoholism, or fever with neuroinflammation occurring after more than 3 weeks of EVD placement are more likely to necessitate antibiotic treatment for EVD infection. Chlorhexidine gluconate bathing decreases EVD infection.

Correction: Liu, H.W.; et al. Enhanced Hsa-miR-181d/p-STAT3 and Hsa-miR-181d/p-STAT5A Ratios Mediate the Anticancer Effect of Garcinol in STAT3/5A-Addicted Glioblastoma. Cancers 2019, 11, 1888.

The authors wish to make the following corrections to this paper [...].

Microcatheter Originating Debris during Neuroendovascular Procedures: Mechanism of Dislodgement and Its Prevention.

Embolic material dislodgement from microcatheters can potentially induce subclinical brain damage as evidenced by a delayed enhanced or other type of lesions. Some of the most frequently used microcatheters were investigated in vitro in different setups and combinations with different port insertions and rotating hemostatic valves. It was found that side port application increases injury to the catheter surface and debris dislodgement by conflicting with internal ledges in rotating hemostatic valves. This initial observation suggests the need for measures to remove the produced debris during such procedures.

[The course of delayed intrauterine infection in children with residual manifestations of retinopathy of prematurity]. / Techenie otsrochennoi vnutriutrobnoi infektsii u detei s ostatochnymi proyavleniyami retinopatii nedonoshennykh.

Retinopathy of prematurity (ROP) is a severe vascular proliferative disease. The appearance of signs of intrauterine infection in the setting of ROP may aggravate the severity of the disease course and lead to development of complications. Two children with residual ROP effects were observe to have delayed manifestations of intrauterine infection. The first child had signs of toxoplasmosis in the period of regression of stage II ROP at 48 weeks of postmenstrual age (PMA). The second child had signs of cytomegalovirus infection in the period of induced regression of III «+¼ stage ROP at 47-48 weeks of PMA. At the time of manifestation of intrauterine infection, both children were noted to have exudative phenomena, and formed fibrous bridles that caused retinal detachment, which was visually very similar to the late stages of severe forms of ROP. However, the appearance of these symptoms in 47-48 weeks of the PMA in the setting of ROP regress excludes the activation of the disease. The course of uveitis with residual manifestations of ROP went according to the most severe scenario - with retinal detachment in the short term - within 7-10 days.

[The early diagnosis of congenital neuroinfections during ophthalmologic examination in children of the first months of life]. / Rannyaya diagnostika nekotorykh vrozhdennykh neiroinfektsii pri oftal'mologicheskom osmotre u detei pervykh mesyatsev zhizni.

OBJECTIVE: To characterize the possibilities of early diagnosis of congenital neuroinfections during an ophthalmological examination in children in the first months of life. MATERIAL AND METHODS: Five children with congenital neuroinfection, including 2 children with congenital toxoplasmosis and 3 children with congenital cytomegalovirus infection (CMVI), were studied. All babies were born prematurely (25 to 31 weeks of gestation (27.2±0.94)), with birth weight from 680 to 1610 g (1120±110.1). During the examination, binocular ophthalmoscopy and examination on a wide-field retinal pediatric camera were used. A blood testing for immunoglobulins and a polymerase chain reaction of blood were performed. To assess the state of the brain, neurosonography and magnetic resonance imaging were used. RESULTS AND CONCLUSION: Ophthalmic signs of intrauterine infection appeared at the age of 4-5 months (at 47-51 weeks of postmenstrual age). In all children (in 4 in one eye, in 1 in both eyes), apparent exudative-proliferative changes in the retina and vitreous body appeared on the periphery with the formation of epiretinal membranes that exert a traction effect on the retina. In two children with CMVI, multiple preretinal hemorrhages in different parts of the retina in both eyes were revealed. Central chorioretinal foci in the fundus were detected in children with toxoplasmosis. A positive dynamics, such as a decrease of exudative phenomena, a partial fit of the retina, complete resorption of hemorrhages, was noted in children during treatment. It has been concluded that signs of intrauterine neuroinfection can appear delayed, only by the development of chorioretinitis, 4-5 months after birth and manifest with severe exudative-proliferative changes in the retina and vitreous body.

Delayed Leukoencephalopathy: A Rare Complication after Coiling of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Delayed leukoencephalopathy is a rare complication that occurs after endovascular coiling of cerebral aneurysms. We aimed to describe a clinical picture of delayed leukoencephalopathy and explore potential associations with procedural characteristics. MATERIALS AND METHODS: We considered endovascular coiling procedures for cerebral aneurysms performed between January 2006 and December 2017 in our institution with follow-up MRIs. We used logistic regression models to estimate the ORs of delayed leukoencephalopathy for each procedural characteristic. RESULTS: We reviewed 1754 endovascular coiling procedures of 1594 aneurysms. Sixteen of 1722 (0.9%) procedures demonstrated delayed leukoencephalopathy on follow-up FLAIR MR imaging examinations after a median period of 71.5 days (interquartile range, 30-101 days) in the form of high-signal changes in the white matter at locations remote from the coil mass. Seven patients had headaches or hemiparesis, and 9 patients were asymptomatic. All imaging-associated changes improved subsequently. We found indications suggesting an association between delayed leukoencephalopathy and the number of microcatheters used per procedure (P = .009), along with indications suggesting that these procedures required larger median volumes of contrast medium (225 versus 175 mL, OR = 5.5, P = .008) as well as a longer median fluoroscopy duration (123.6 versus 99.3 minutes, OR = 3.0, P = .06). Our data did not suggest that delayed leukoencephalopathy was associated with the number of coils (P = .57), microguidewires (P = .35), and guiding systems (P = .57). CONCLUSIONS: Delayed leukoencephalopathy after coiling of cerebral aneurysms may have multiple etiologies such as foreign body emboli, contrast-induced encephalopathy, or hypersensitivity reaction to foreign bodies.

Enhanced Hsa-miR-181d/p-STAT3 and Hsa-miR-181d/p-STAT5A Ratios Mediate the Anticancer Effect of Garcinol in STAT3/5A-Addicted Glioblastoma.

BACKGROUND: Glioblastoma (GBM), a malignant grade IV tumor, is the most malignant brain tumor due to its hyper-proliferative and apoptosis-evading characteristics. The signal transducer and activators of transcription (STAT) family genes, including STAT3 and STAT5A, have been indicated to play important roles in GBM progression. Increasing number of reports suggest that garcinol, a polyisoprenylated benzophenone and major bioactive component of Garcinia indica contains potent anti-cancer activities. MATERIAL AND METHODS: The present study investigated the anti-GBM effects of garcinol, focusing on the STAT3/STAT5A activation, using a combination of bioinformatics, in vitro, and ex vivo assays. RESULTS: Our bioinformatics analysis of The Cancer Genome Atlas (TCGA)-GBM cohort (n = 173) showed that STAT3 and STAT5A are preferentially elevated in primary and recurrent GBM, compared to non-tumor brain tissues, and is significantly correlated with reduced overall survival. In support, our immunohistochemical staining of a GBM cohort (n = 45) showed an estimated 5.3-fold (p < 0.001) elevation in STAT3 and STAT5A protein expression in primary and recurrent GBM versus the non-tumor group. In vitro, garcinol treatment significantly suppressed the proliferative, invasive, and migratory potential of U87MG or GBM8401 cells, dose-dependently. In addition, garcinol anticancer effect significantly attenuated the GBM stem cell-like phenotypes, as reflected by diminished ability of U87MG or GBM8401 to form colonies and tumorspheres and suppressed expression of OCT4 and SOX2. Furthermore, analysis on GBM transcriptome revealed an inverse correlation between the level of STAT3/5A and hsa-miR-181d. Garcinol-mediated anti-GBM effects were associated with an increased hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratio. The results were further verified in vivo using U87MG mouse xenograft model where administration of garcinol significantly inhibited tumor growth. CONCLUSIONS: We present evidence of anti-GBM efficacy of garcinol mediated by enhancing the hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratios in GBM cells. Our findings suggest a potential new therapeutic agent for combating aggressive GBM.

SNAP reverses temozolomide resistance in human glioblastoma multiforme cells through down-regulation of MGMT.

Glioblastoma multiforme (GBM) is the most frequently occurring and gravest primary tumor of the CNS in adults. The development of chemoresistance to temozolomide (TMZ), the first-line chemotherapy for GBM, is an important factor contributing to poor treatment outcomes. Down-regulation of O-6-methylguanine-DNA methyltransferase (MGMT) expression in GBM cells is an attractive strategy for overcoming TMZ resistance and improving outcomes. This study revealed that the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) exerts antitumorigenic effects on TMZ-sensitive and TMZ-resistant (TMZ-R) glioma cells. Pretreatment with SNAP not only induced apoptosis, mitochondrial dysfunction, and hypoxia-inducing factor 1, but also resensitized TMZ-R GBM cells to TMZ through down-regulation of MGMT expression. SNAP acted principally through post-translational modification of p53, phosphorylated N-myc downstream regulated gene 1, and MGMT protein stability in TMZ-R GBM cells. Additionally, when applied together, SNAP and TMZ enhanced the inhibition of tumor growth in vitro and in vivo. This study sheds new light on a potential strategy to overcome TMZ resistance in GBM and thus possesses the potential for prolonging survival of patients with GBM.-Tsai, C.-K., Huang, L.-C., Wu, Y.-P., Kan, I.-Y., Hueng, D.-Y. SNAP reverses temozolomide resistance in human glioblastoma multiforme cells through down-regulation of MGMT.

Designing an agricultural vegetative waste-management system under uncertain prices of treatment-technology output products.

Setting up a sustainable agricultural vegetative waste-management system is a challenging investment task, particularly when markets for output products of waste-treatment technologies are not well established. We conduct an economic analysis of possible investments in treatment technologies of agricultural vegetative waste, while accounting for fluctuating output prices. Under a risk-neutral approach, we find the range of output-product prices within which each considered technology becomes most profitable, using average final prices as the exclusive factor. Under a risk-averse perspective, we rank the treatment technologies based on their computed certainty-equivalent profits as functions of the coefficient of variation of the technologies' output prices. We find the ranking of treatment technologies based on average prices to be robust to output-price fluctuations provided that the coefficient of variation of the output prices is below about 0.4, that is, approximately twice as high as that of well-established recycled-material markets such as glass, paper and plastic. We discuss some policy implications that arise from our analysis regarding vegetative waste management and its associated risks.

High-Resolution C-Arm CT and Metal Artifact Reduction Software: A Novel Imaging Modality for Analyzing Aneurysms Treated with Stent-Assisted Coil Embolization.

BACKGROUND AND PURPOSE: Combination of high-resolution C-arm CT and novel metal artifact reduction software may contribute to the assessment of aneurysms treated with stent-assisted coil embolization. This study aimed to evaluate the efficacy of a novel Metal Artifact Reduction prototype software combined with the currently available high spatial-resolution C-arm CT prototype implementation by using an experimental aneurysm model treated with stent-assisted coil embolization. MATERIALS AND METHODS: Eight experimental aneurysms were created in 6 swine. Coil embolization of each aneurysm was performed by using a stent-assisted technique. High-resolution C-arm CT with intra-arterial contrast injection was performed immediately after the treatment. The obtained images were processed with Metal Artifact Reduction. Five neurointerventional specialists reviewed the image quality before and after Metal Artifact Reduction. Observational and quantitative analyses (via image analysis software) were performed. RESULTS: Every aneurysm was successfully created and treated with stent-assisted coil embolization. Before Metal Artifact Reduction, coil loops protruding through the stent lumen were not visualized due to the prominent metal artifacts produced by the coils. These became visible after Metal Artifact Reduction processing. Contrast filling in the residual aneurysm was also visualized after Metal Artifact Reduction in every aneurysm. Both the observational (P < .0001) and quantitative (P < .001) analyses showed significant reduction of the metal artifacts after application of the Metal Artifact Reduction prototype software. CONCLUSIONS: The combination of high-resolution C-arm CT and Metal Artifact Reduction enables differentiation of the coil mass, stent, and contrast material on the same image by significantly reducing the metal artifacts produced by the platinum coils. This novel image technique may improve the assessment of aneurysms treated with stent-assisted coil embolization.

Evaluation of the relationship between preeclampsia and seropositivity of infectious disease in maternal plasma.

PURPOSE: The aim of the present study was to investigate the association between maternal infections and preeclampsia. MATERIALS AND METHODS: Fifty-four pregnant women with preeclampsia (study group) and 54 healthy pregnant women (control group) were enrolled in this study. Chlamydia pneumoniae (CP), Mycoplasma hominis (MH), Helicobacter pylori (HP), Cytomegalovirus (CMV), Herpes simplex virus type 2 (HSV-2), and Toxoplasma gondii (TG) antibodies were analyzed in the maternal plasma of all of the participants. RESULTS: There was no difference in the demographic data between groups. Maternal plasma seropositivity for CP IgM; MH IgA and IgG; HP IgM, IgA and IgG; TG, CMV and HSV-2 IgM and IgG were not significantly different between the preeclampsia and control groups. The seropositivity for CP IgG was significantly higher in women with preeclampsia versus the control women. CONCLUSIONS: Our results suggested that preeclampsia is associated with CP IgG seropositivity.

A swine model to analyze arterial structural changes induced by mechanical thrombectomy.

We report a novel swine model that allows direct visualization of cervical arteries undergoing mechanical thrombectomy. The model also facilitates evaluation of histologic changes observed in the arteries after treatment. Swine superficial cervical arteries, which are similar in size and branching pattern to the human middle cerebral artery, were surgically exposed, occluded with experimental thrombus, and subsequently treated with the Merci clot retriever device. Angiographic and histologic assessment were performed.

The impact of thromboemboli histology on the performance of a mechanical thrombectomy device.

BACKGROUND AND PURPOSE: Recently we published a novel method of thrombus preparation for use in a swine model for evaluation of thrombectomy designs. The clot (fibrin rich clot) is characterized by its similarity in histologic characteristics to the thromboemboli recovered from stroke patients. The purpose of this latest study was to evaluate if the performance of a mechanical thrombectomy device was affected by the histologic characteristics of thromboembolus. Erythrocyte rich clot, which was created using exogenous thrombin, and the novel experimental clot with abundance of fibrin/cellular component were used for comparison. The Merci clot retriever was used for the evaluation and the angiographic outcomes were analyzed. MATERIALS AND METHODS: Two histologically different types of experimental clot, a conventionally used thrombin-induced clot (erythrocyte-rich clot) and a novel experimental clot that is similar in histologic characteristics to the thromboemboli recovered from patients with stroke (fibrin-rich clot), were prepared. Eight extracranial arteries in swine were occluded with erythrocyte-rich clot (group A), and 8 were occluded with fibrin-rich clot (group B), and MT by using the Merci clot retriever device was performed. Angiographic results in each group were evaluated. RESULTS: A total of 48 attempts at MT were made. The average number of attempts to achieve TIMI grade II or III recanalization was 2.75 times in group A and 4.5 times in group B (P < .001), respectively. The mean time to achieve recanalization was 15.5 minutes in group A and 81.5 minutes in group B (P < .01). Every vessel in group A showed recanalization (100%), whereas only 3 of 8 samples (37.5%) achieved recanalization in group B. CONCLUSIONS: In this model, arteries occluded by fibrin-rich clot demonstrated a significantly lower recanalization rate, lower final TIMI score, and a longer mean recanalization time than did arteries occluded by erythrocyte-rich clot. The angiographic outcome of MT by using the Merci clot retriever system was influenced by the histologic characteristics of the occluding thromboembolus.

A novel method of thrombus preparation for use in a swine model for evaluation of thrombectomy devices.

We report the development of a novel technique of thrombus preparation for use in a swine model for evaluation of thrombectomy devices. The experimental thrombus prepared using plain sedimentation showed mechanical stability due to its solid fibrin-rich component. The thrombus also showed histologic similarity to the typical thromboemboli recovered from patients with stroke in the course of therapeutic thrombectomy. This new technique may be beneficial for preclinical evaluation of thrombectomy devices.

Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases.

Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. This selective hallmark pathology and the lack of effective treatment modalities make these diseases appropriate candidates for cell therapy. Bone marrow-derived mesenchymal stem cells (MSCs) are self-renewing precursors that reside in the bone marrow and may further be exploited for autologous transplantation. Autologous transplantation of MSCs entirely circumvents the problem of immune rejection, does not cause the formation of teratomas, and raises very few ethical or political concerns. More than a few studies showed that transplantation of MSCs resulted in clinical improvement. However, the exact mechanisms responsible for the beneficial outcome have yet to be defined. Possible rationalizations include cell replacement, trophic factors delivery, and immunomodulation. Cell replacement theory is based on the idea that replacement of degenerated neural cells with alternative functioning cells induces long-lasting clinical improvement. It is reasoned that the transplanted cells survive, integrate into the endogenous neural network, and lead to functional improvement. Trophic factor delivery presents a more practical short-term approach. According to this approach, MSC effectiveness may be credited to the production of neurotrophic factors that support neuronal cell survival, induce endogenous cell proliferation, and promote nerve fiber regeneration at sites of injury. The third potential mechanism of action is supported by the recent reports claiming that neuroinflammatory mechanisms play an important role in the pathogenesis of neurodegenerative disorders. Thus, inhibiting chronic inflammatory stress might explain the beneficial effects induced by MSC transplantation. Here, we assemble evidence that supports each theory and review the latest studies that have placed MSC transplantation into the spotlight of biomedical research.

Idiopathic syringomyelia: case report and review of the literature.

Syringomyelia is an uncommon disease that is caused most often by type I Chiari malformation, which develops in the hindbrain, and less frequently by other factors which are not limited to the hindbrain, including trauma, infection, or scoliosis. Idiopathic syringomyelia is rare. We present in this article a patient with idiopathic syringomyelia characterized by hypoesthesia and progressive weakness in the left lower limb. Decompression was attempted by means of laminectomy and a syringoarachnoid shunt. Motor, sensory, and bladder functions were monitored by the change in Japanese Orthopedic Association scores, which increased from 10 points preoperatively to 14 points 30 days postoperatively. This case demonstrates the effectiveness of surgical decompression in a patient with remarkable neurological deficit.

Integral therapeutic potential of bone marrow mesenchymal stem cells.

Bone marrow derived mesenchymal stem cells (MSC) are adult stem cells that reside within the bone marrow compartment. In the traditional developmental model, adult stem cells are able to differentiate only to the tissue in which they reside. Recent data have challenged the committed fate of the adult stem cells, presenting evidence for their multi-lineage differentiation potential. In addition, potential therapeutic benefits of MSC administration have been the main concern of much research, including clinical trials. These studies promote adult stem cell therapy by shedding some light on the therapeutic potential of MSC and their mechanism of action. Many doubts have found their way into MSC research. They question MSC potency and beneficial contribution. However, these obstacles should not arrest but set a challenge to MSC researchers to examine their achievements under a magnifying glass. Therapeutic benefits of MSC exogenous delivery do not run counter to its possible participation in endogenous repair. Several reports imply MSC involvement in physiological repair but no explicit data support this hypothesis. This review tries to put MSC research into perspective. Possible therapeutic applications of MSC therapy for damaged tissue replacement, tissue engineering and the underlying repair mechanisms will be discussed. In addition, reported data about MSC possible involvement in physiological multiple tissue repair, their homing to injury and site-specific differentiation will be presented.

Perceptual and conceptual sources of priming on a word generation task.

Repetition of any number of cognitive processes can facilitate subsequent performance (i.e., repetition priming). In this study, we explored several candidate mechanisms that could account for repetition priming on a word generation task. In Experiment 1, we examined whether repetition of semantic processing is necessary for priming on this task. In Experiment 2, we examined whether repetition of semantic processing is sufficient for priming on this task. In both experiments, we additionally examined the effect of changing the specific nature of the semantic retrieval task (i.e., from visual to functional, and vice versa) on performance. The results from these experiments indicated that repetition of semantic processing is both necessary and sufficient to produce a facilitation effect on the word generation task. However, semantic processing of the same attribute does not need to be repeated for facilitation effects to occur. Implications of these findings for theories of the representation and retrieval of semantic knowledge are discussed.

A patient with primary biliary cirrhosis associated with autoimmune hemolytic anemia.

Primary biliary cirrhosis is often associated with autoimmune conditions, such as thyroid disease, sicca complex, and rheumatoid arthritis. However, an association with autoimmune hemolytic anemia has rarely been reported. We present a case of primary biliary cirrhosis associated with warm type autoimmune hemolytic anemia, and we review prior reports.

Effects of repetition and competition on activity in left prefrontal cortex during word generation.

Neuroimaging studies have revealed an association between word generation and activity in the left inferior frontal gyrus (IFG) that is attentuated with item repetition. The experiment reported here examined the effects of repeated word generation, under conditions in which completion was either decreased or increased, on activity measured during whole-brain echoplanar functional magnetic resonance imaging. Activity in left IFG decreased during repetition conditions that reduced competition but increased during repetition conditions that increased competition; this pattern was contrasted to repetition effects observed in other cortical areas, specifically regions of left temporal cortex. The increase in left IFG activity, which is not predicted by a simple semantic retrieval account of prefrontal function, is consistent with the hypothesis that left IFG subserves the selection of semantic knowledge among competing alternatives.