Training Cerebrovascular and Neuroendovascular Surgery Residents: A Systematic Literature Review and Recommendations.

Background: The rapid evolution of neuroendovascular intervention has resulted in the inclusion of endovascular techniques as a core competency in neurosurgical residency training. Methods: We conducted a literature review of studies involving the training of neurosurgical residents in cerebrovascular and endovascular neurosurgery. We reviewed the evolution of cerebrovascular neurosurgery and the effects of these changes on residency, and we propose interventions to supplement contemporary training. Results: A total of 48 studies were included for full review. Studies evaluated trainee education and competency (29.2%, 14/48), neuroendovascular training models (20.8%, 10/48), and open cerebrovascular training models (52.1%, 25/48), with some overlap. We used a qualitative analysis of reviewed reports to generate a series of suggested training supplements to optimize cerebrovascular education. Conclusion: Cerebrovascular neurosurgery is at a crossroads where trainees must develop disparate skill sets with inverse trends in volume. Continued longitudinal exposure to both endovascular and open cerebrovascular surgical fields should be mandated in general resident education, and blended learning tactics using adjunct simulation systems and models should be incorporated with didactics to both optimize learning and alleviate restraints placed by decreased volume and autonomy.

Assessing the clinical reasoning of ChatGPT for mechanical thrombectomy in patients with stroke.

BACKGROUND: Artificial intelligence (AI) has become a promising tool in medicine. ChatGPT, a large language model AI Chatbot, shows promise in supporting clinical practice. We assess the potential of ChatGPT as a clinical reasoning tool for mechanical thrombectomy in patients with stroke. METHODS: An internal validation of the abilities of ChatGPT was first performed using artificially created patient scenarios before assessment of real patient scenarios from the medical center's stroke database. All patients with large vessel occlusions who underwent mechanical thrombectomy at Tulane Medical Center between January 1, 2022 and December 31, 2022 were included in the study. The performance of ChatGPT in evaluating which patients should undergo mechanical thrombectomy was compared with the decisions made by board-certified stroke neurologists and neurointerventionalists. The interpretation skills, clinical reasoning, and accuracy of ChatGPT were analyzed. RESULTS: 102 patients with large vessel occlusions underwent mechanical thrombectomy. ChatGPT agreed with the physician's decision whether or not to pursue thrombectomy in 54.3% of the cases. ChatGPT had mistakes in 8.8% of the cases, consisting of mathematics, logic, and misinterpretation errors. In the internal validation phase, ChatGPT was able to provide nuanced clinical reasoning and was able to perform multi-step thinking, although with an increased rate of making mistakes. CONCLUSION: ChatGPT shows promise in clinical reasoning, including the ability to factor a patient's underlying comorbidities when considering mechanical thrombectomy. However, ChatGPT is prone to errors as well and should not be relied on as a sole decision-making tool in its present form, but it has potential to assist clinicians with more efficient work flow.

Iatrogenic Cerebrospinal Fluid Breast Augmentation: Rare Complication of Ventriculoperitoneal Shunts and Management Strategies.

BACKGROUND: Ventriculoperitoneal shunt is one of the most common neurosurgical procedures in the treatment of hydrocephalus. There are reports of migration of the distal catheter to the breast pocket where cerebrospinal fluid then collects and can develop into a pseudocyst. There exist case reports in the literature of patients with prior breast augmentation who present with distal catheter migration from the peritoneal space into the breast tissue. We present a case series of 3 patients with preexisting breast augmentation who returned with unilateral breast enlargement after ventriculoperitoneal shunt. In all 3 patients, the distal catheter migrated out of the peritoneal space and was found to be coiled around the breast prosthesis. Additionally, we offer recommendations for managing these complications and a review of the literature. METHODS: We performed a systematic review without meta-analysis of studies involving management of shunt migration in the setting of preexisting breast implants. We present a case series of 3 patients whom we treated with breast cerebrospinal pseudocyst after migration of the distal catheter into the breast tissue. RESULTS: A total of 17 studies, dating from 2002 to 2022, met our inclusion and exclusion criteria and were selected for full review. Catheter migration occurred between 2 weeks and 9 months of initial shunt placement. All patients presented with unilateral breast enlargement and cerebrospinal fluid pseudocyst formation. All patients underwent revision shunt surgery. Surgical treatment strategies used included reimplantation of the distal catheter into the pleural space or ipsilateral or contralateral peritoneal space or complete removal of the entire shunt system. CONCLUSIONS: Breast-related ventriculoperitoneal shunt complication is a rare entity that is increasingly seen as more patients receive breast augmentation. Breast-related shunt complications most commonly present with cerebrospinal fluid pseudocyst formation in the breast. It is important for neurosurgeons to be aware of an underlying breast implant before placing a ventriculoperitoneal shunt. For patients who have migration of the distal catheter into the breast, a protocol for managing these situations should be followed to ensure no shunt infection and avoidance of future catheter migration complications with subsequent shunt revisions.

Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3.

Gut bacteria provide benefits to the host and have been implicated in inflammatory bowel disease (IBD), where adherent-invasive E. coli (AIEC) pathobionts (e.g., strain LF82) are associated with Crohn's disease. E. coli-LF82 causes fragmentation of the epithelial mitochondrial network, leading to increased epithelial permeability. We hypothesized that butyrate would limit the epithelial mitochondrial disruption caused by E. coli-LF82. Human colonic organoids and the T84 epithelial cell line infected with E. coli-LF82 (MOI = 100, 4 h) showed a significant increase in mitochondrial network fission that was reduced by butyrate (10 mM) co-treatment. Butyrate reduced the loss of mitochondrial membrane potential caused by E. coli-LF82 and increased expression of PGC-1α mRNA, the master regulator of mitochondrial biogenesis. Metabolomics revealed that butyrate significantly altered E. coli-LF82 central carbon metabolism leading to diminished glucose uptake and increased succinate secretion. Correlating with preservation of mitochondrial network form/function, butyrate reduced E. coli-LF82 transcytosis across T84-cell monolayers. The use of the G-protein inhibitor, pertussis toxin, implicated GPCR signaling as critical to the effect of butyrate, and the free fatty acid receptor three (FFAR3, GPR41) agonist, AR420626, reproduced butyrate's effect in terms of ameliorating the loss of barrier function and reducing the mitochondrial fragmentation observed in E. coli-LF82 infected T84-cells and organoids. These data indicate that butyrate helps maintain epithelial mitochondrial form/function when challenged by E. coli-LF82 and that this occurs, at least in part, via FFAR3. Thus, loss of butyrate-producing bacteria in IBD in the context of pathobionts would contribute to loss of epithelial mitochondrial and barrier functions that could evoke disease and/or exaggerate a low-grade inflammation.

Dural Closure Techniques and Cerebrospinal Fluid Leak Incidence After Resection of Primary Intradural Spinal Tumors: A Systematic Review.

STUDY DESIGN: This is a systematic review of primary intradural spinal tumors (PIDSTs) and the frequency of postoperative cerebrospinal fluid (CSF) leaks. OBJECTIVE: This study aimed to compare CSF leak rates among techniques for dural watertight closure (WTC) after the resection of PIDSTs. SUMMARY OF BACKGROUND DATA: Resection of PIDSTs may result in persistent CSF leak. This complication is associated with infection, wound dehiscence, increased length of stay, and morbidity. Dural closure techniques have been developed to decrease the CSF leak rate. METHODS: A PubMed search was performed in 2022 with these inclusion criteria: written in English, describe PIDST patients, specify the method of dural closure, report rates of CSF leak, and be published between 2015 and 2020. Articles were excluded if they had <5 patients. We used standardized toolkits to assess the risk of bias. We assessed patient baseline characteristics, tumor pathology, CSF leak rate, and dural closure techniques; analysis of variance and a 1-way Fisher exact test were used. RESULTS: A total of 4 studies (201 patients) satisfied the inclusion criteria. One study utilized artificial dura (AD) and fibrin glue to perform WTC and CSF diversion, with lumbar drainage as needed. The rate of CSF leak was different among the 4 studies (P=0.017). The study using AD with dural closure adjunct (DCA) for WTC was associated with higher CSF leak rates than those using native dura (ND) with DCA. There was no difference in CSF leak rate between ND-WTC and AD-DCA, or with any of the ND-DCA studies. CONCLUSIONS: After resection of PIDSTs, the use of autologous fat grafts with ND resulted in lower rates of CSF leak, while use of fibrin glue and AD resulted in the highest rates. These characteristics suggest that a component of hydrophobic scaffolding may be required for WTC. A limitation included articles with low levels of evidence. Continued investigation to understand mechanisms for WTC is warranted. LEVEL OF EVIDENCE: Level 3.

Minimally Invasive Hematoma Evacuation Using the MindsEye Expandable Tubular Retractor: A Technical Note.

BACKGROUND: Recent advances in intraoperative neuronavigation and cranial access devices have facilitated an increasing interest in the use of minimally invasive techniques (minimally invasive surgery) to safely treat subcortical lesions via a parafascicular approach. Newly developed expandable retractors, such as the MindsEye system further optimize such approaches. In this technical report, we describe the nuances in minimally invasive surgery parenchymal hematoma evacuation using the MindsEye device. METHODS: After placement of the device, the inner stylet and inner obturator are removed, and the expandable sheath is left in place and secured into place with a Greenberg refractor. The sheath easily dilates to the surgeonss preference with a dial, and the walls of the sheath are composed of a thin, clear, membrane to allow easy visualization of the lesion. We additionally retrospectively reviewed clinical characteristics and outcomes across three patients treated at our facility with spontaneous multicompartment intracranial hematoma using the MindsEye system. RESULTS: We provide a video case demonstrating the use of the MindsEye retractor in a transfrontal parenchymal hematoma evacuation. Successful evacuation with achieved in less than 90 minutes with near total clot removal and resolution of mass effect for all reviewed cases with no patients experiencing procedure-related postoperative decline. CONCLUSIONS: Minimally invasive catheter-based and parafascicular approaches using tubular retractors are increasingly recognized as a viable option in the treatment of subcortical lesions. The MindsEye is the first expandable brain access port designed for removal of deep intracranial lesions. We believe it represents a recent addition in the armament of cranial surgeons.

Combining chemotherapy with CAR-T cell therapy in treating solid tumors.

Chemotherapy has long been a standard treatment for a wide range of malignancies, where patients typically undergo multiple rounds of chemotherapy regimens to control tumor growth. In the clinic, the chemotherapy drugs cyclophosphamide and fludarabine are commonly used prior to Chimeric Antigen Receptor T (CAR-T) cell therapy to lymphodeplete and improve CAR-T cell engraftment. In this review, we discuss the use of chemotherapy in combination with CAR-T cell therapy. We also show that chemotherapy can deplete immunosuppressive cells, promote a pro-inflammatory tumor microenvironment, disrupt tumor stroma, and improve CAR-T cell recruitment to the tumor. Although the combination of chemotherapy plus CAR-T cell therapy is promising, certain aspects of chemotherapy also pose a challenge. In addition, the combined therapeutic effect may be heavily dependent on the dose and the treatment schedule. Thus, we also discussed the obstacles to effective clinical outcomes of the combination therapy.

The Sphenoparietal Sinus Revisited: Anatomical and Histological Study With Application to Interventional Procedures and Skull Base Surgery.

Background The sphenoparietal sinus (SPS) is implicated in various clinical pathologies, specifically arteriovenous fistulas and venous sinus thrombosis. This study is aimed to better understand this venous structure of the skull base via histological examination. Methods Ten embalmed and latex-injected adult body donors' heads (20 sides) underwent microdissection of the SPS using a surgical microscope. The entire dura on the underside of the lesser wing of the sphenoid bone encompassing the region known as the groove for the SPS was harvested from each body donor and submitted for histological analysis (H&E, Periodic acid-Schiff [PAS], Masson's Trichrome). Five left and five right transverse sinuses were harvested and analyzed histologically as controls. Results A definitive SPS was identified in 14/20 (70%) of the latex-injected body donors. When present, the sinuses were classified as small, medium, or large. Tributaries included the middle meningeal veins, superficial Sylvian vein, and anterior temporal veins. All sinuses drained medially into the cavernous sinus. For the body donors analyzed histologically, 17 (85%) were consistent with a dural venous sinus and not a vein and were observed to have a rich nerve and arterial supply within their walls. The histological findings of the SPS were similar to those seen for the transverse sinus. The combined prevalence for the SPS in gross and histological body donors was 78%. Conclusions Our findings support the presence of SPS in the majority of body donors. To our knowledge, this is the first histological study of the SPS.

Characteristics and Management of Dilated Mastoid Emissary Veins: A Case Report and Literature Review.

INTRODUCTION: The mastoid emissary vein (MEV) describes a transosseous connection between the sigmoid dural venous sinus and the suboccipital venous plexus. In cases of outflow stenosis or malformation, the MEV may become dilated and a source of pulsatile tinnitus (PT) amenable to treatment. We describe a case of PT secondary to MEV treated successfully via endovascular coil embolization and conduct a systematic review of the literature. METHODS: We performed a systematic review without meta-analysis of studies involving management of dilated MEV on January 14, 2022, and describe a case of PT secondary to an enlarged MEV treated via coil embolization. RESULTS: A total of 13 studies were selected for full review. Reports identified MEV presenting as PT in 60% (12 of 20) of cases, intraoperative hemorrhage in mastoid surgery in 15% (3 of 20), a compressive scalp mass in 10% (2 of 20), and thrombophlebitis, facial swelling, or an incidental finding in 5% (1 of 20) each. Forty-five percent (9 of 20) underwent treatment, with all experiencing symptom resolution or improvement. Surgery included transvenous coil embolization in 33.3% (3 of 9), flap reconstruction in 22.2% (2 of 9), and surgical packing, ligation, and thrombectomy in 11.1% (1 of 9) each. Dilated MEV was reported concurrently with impeded drainage pathways in 35% (7 of 20) of reports. CONCLUSIONS: Dilated MEV has been reported as an etiology of pulsatile tinnitus and appears amenable to treatment via open and endovascular means. Endovascular coil embolization appears to offer effective symptom resolution, however, available literature exists only in case reports and small series. Further investigation is highly warranted.

Impact of experimental colitis on mitochondrial bioenergetics in intestinal epithelial cells.

Intestinal homeostasis is highly dependent on optimal epithelial barrier function and permeability. Intestinal epithelial cells (IEC) regulate these properties acting as cellular gatekeepers by selectively absorbing nutrients and controlling the passage of luminal bacteria. These functions are energy demanding processes that are presumably met through mitochondrial-based processes. Routine methods for examining IEC mitochondrial function remain sparse, hence, our objective is to present standardized methods for quantifying mitochondrial energetics in an immortalized IEC line. Employing the murine IEC4.1 cell line, we present adapted methods and protocols to examine mitochondrial function using two well-known platforms: the Seahorse Extracellular Flux Analyzer and Oxygraph-2 k. To demonstrate the applicability of these protocols and instruments, IEC were treated with and without the murine colitogenic agent, dextran sulfate sodium (DSS, 2% w/v). Profound impairments with DSS treatment were found with both platforms, however, the Oxygraph-2 k allowed greater resolution of affected pathways including short-chain fatty acid metabolism. Mitochondrial functional analysis is a novel tool to explore the relationship between IEC energetics and functional consequences within the contexts of health and disease. The outlined methods offer an introductory starting point for such assessment and provide the investigator with insights into platform-specific capabilities.

Stereotactic Vacuum-Assisted Minimally Invasive Aspiration of Hemorrhagic Stroke.

Intracerebral hemorrhage (ICH), accounting for 9-27% of all strokes, carries substantial rates of morbidity and mortality that have not shown much improvement in the past decades. The poor outcomes of ICH can be attributed to the primary and secondary brain injuries caused by mass effects and inflammatory mechanisms, respectively. Early ICH evacuation is a critical component of treatment, as it mitigates the effect of both the primary and secondary mechanisms of brain injury and is associated with significant improvement in patient outcomes. However, no standardized evacuation technique exists. This technical report introduces a novel stereotactic vacuum-assisted minimally invasive (MIS) aspiration of a hemorrhagic stroke with its effectiveness evidenced by excellent patient recovery.

Interleukin-4 Programmed Macrophages Suppress Colitis and Do Not Enhance Infectious-Colitis, Inflammation-Associated Colon Cancer or Airway Hypersensitivity.

The murine interleukin-4 treated macrophage (MIL4) exerts anti-inflammatory and pro-healing effects and has been shown to reduce the severity of chemical-induced colitis. Positing M(IL4) transfer as an anti-inflammatory therapy, the possibility of side-effects must be considered. Consequently, bone marrow-derived M(IL4)s were administered via intraperitoneal injection to mice concomitant with Citrobacter rodentium infection (infections colitis), azoxymethane/dextran sodium sulphate (AOM/DSS) treatment [a model of colorectal cancer (CRC)], or ovalbumin sensitization (airway inflammation). The impact of M(IL4) treatment on C. rodentium infectivity, colon histopathology, tumor number and size and tissue-specific inflammation was examined in these models. The anti-colitic effect of the M(IL4)s were confirmed in the di-nitrobenzene sulphonic acid model of colitis and the lumen-to-blood movement of 4kDa FITC-dextran and bacterial translocation to the spleen and liver was also improved by M(IL4) treatment. Analysis of the other models of disease, that represent comorbidities that can occur in human inflammatory bowel disease (IBD), revealed that M(IL4) treatment did not exaggerate the severity of any of the conditions. Rather, there was reduction in the size (but not number) of polyps in the colon of AOM/DSS-mice and reduced infectivity and inflammation in C. rodentium-infected mice in M(IL4)-treated mice. Thus, while any new therapy can have unforeseen side effects, our data confirm and extend the anti-colitic capacity of murine M(IL4)s and indicate that systemic delivery of one million M(IL4)s did not exaggerate disease in models of colonic or airways inflammation or colonic tumorigenesis.

Hydroxylation of N-acetylneuraminic Acid Influences the in vivo Tropism of N-linked Sialic Acid-Binding Adeno-Associated Viruses AAV1, AAV5, and AAV6.

Adeno-associated virus (AAV) vectors are promising candidates for gene therapy. However, a number of recent preclinical large animal studies failed to translate into the clinic. This illustrates the formidable challenge of choosing the animal models that promise the best chance of a successful translation into the clinic. Several of the most common AAV serotypes use sialic acid (SIA) as their primary receptor. However, in contrast to most mammals, humans lack the enzyme CMAH, which hydroxylates cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac) into cytidine monophosphate-N-glycolylneuraminic acid (CMP-Neu5Gc). As a result, human glycans only contain Neu5Ac and not Neu5Gc. Here, we investigate the tropism of AAV1, 5, 6 and 9 in wild-type C57BL/6J (WT) and CMAH knock-out (CMAH-/-) mice. All N-linked SIA-binding serotypes (AAV1, 5 and 6) showed significantly lower transduction of the heart in CMAH-/- when compared to WT mice (5-5.8-fold) and, strikingly, skeletal muscle transduction by AAV5 was almost 30-fold higher in CMAH-/- compared to WT mice. Importantly, the AAV tropism or distribution of expression among different organs was also affected. For AAV1, AAV5 and AAV6, expression in the heart compared to the liver was 4.6-8-fold higher in WT than in CMAH-/- mice, and for AAV5 the expression in the heart compared to the skeletal muscle was 57.3-fold higher in WT than in CMAH-/- mice. These data thus strongly suggest that the relative abundance of Neu5Ac and Neu5Gc plays a role in AAV tropism, and that results obtained in commonly used animal models might not translate into the clinic.

Crohn's Disease Pathobiont Adherent-Invasive E coli Disrupts Epithelial Mitochondrial Networks With Implications for Gut Permeability.

BACKGROUND & AIMS: Adherent-invasive Escherichia coli are implicated in inflammatory bowel disease, and mitochondrial dysfunction has been observed in biopsy specimens from patients with inflammatory bowel disease. As a novel aspect of adherent-invasive E coli-epithelial interaction, we hypothesized that E coli (strain LF82) would elicit substantial disruption of epithelial mitochondrial form and function. METHODS: Monolayers of human colon-derived epithelial cell lines were exposed to E coli-LF82 or commensal E coli and RNA sequence analysis, mitochondrial function (adenosine triphosphate synthesis) and dynamics (mitochondrial network imaging, immunoblotting for fission and fusion proteins), and epithelial permeability (transepithelial resistance, flux of fluorescein isothiocyanate-dextran and bacteria) were assessed. RESULTS: E coli-LF82 significantly affected epithelial expression of ∼8600 genes, many relating to mitochondrial function. E coli-LF82-infected epithelia showed swollen mitochondria, reduced mitochondrial membrane potential and adenosine triphosphate, and fragmentation of the mitochondrial network: events not observed with dead E coli-LF82, medium from bacterial cultures, or control E coli. Treatment with Mitochondrial Division Inhibitor 1 (Mdivi1, inhibits dynamin-related peptide 1, guanosine triphosphatase principally responsible for mitochondrial fission) or P110 (prevents dynamin-related peptide 1 binding to mitochondrial fission 1 protein) partially reduced E coli-LF82-induced mitochondrial fragmentation in the short term. E coli-LF82-infected epithelia showed loss of the long isoform of optic atrophy factor 1, which mediates mitochondrial fusion. Mitochondrial Division Inhibitor 1 reduced the magnitude of E coli-LF82-induced increased transepithelial flux of fluorescein isothiocyanate dextran. By 8 hours after infection, increased cytosolic cytochrome C and DNA fragmentation were apparent without evidence of caspase-3 or apoptosis inducing factor activation. CONCLUSIONS: Epithelial mitochondrial fragmentation caused by E coli-LF82 could be targeted to maintain cellular homeostasis and mitigate infection-induced loss of epithelial barrier function. Data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO series accession numbers GSE154121 and GSE154122 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154121).

Human interleukin-4-treated regulatory macrophages promote epithelial wound healing and reduce colitis in a mouse model.

Murine alternatively activated macrophages can exert anti-inflammatory effects. We sought to determine if IL-4-treated human macrophages [i.e., hM(IL4)] would promote epithelial wound repair and can serve as a cell transfer treatment for inflammatory bowel disease (IBD). Blood monocytes from healthy volunteers and patients with active and inactive IBD were converted to hM(IL4)s. IL-4 treatment of blood-derived macrophages from healthy volunteers and patients with inactive IBD resulted in a characteristic CD206+CCL18+CD14low/- phenotype (RNA-seq revealed IL-4 affected expression of 996 genes). Conditioned media from freshly generated or cryopreserved hM(IL4)s promoted epithelial wound healing in part by TGF, and reduced cytokine-driven loss of epithelial barrier function in vitro. Systemic delivery of hM(IL4) to dinitrobenzene sulphonic acid (DNBS)-treated Rag1-/- mice significantly reduced disease. These findings from in vitro and in vivo analyses provide proof-of-concept support for the development of autologous M(IL4) transfer as a cellular immunotherapy for IBD.

Stroke and mechanical thrombectomy in patients with COVID-19: technical observations and patient characteristics.

BACKGROUND: COVID-19 infections have been shown to be associated with a range of thromboembolic disease. OBJECTIVE: To describe our endovascular experience in a consecutive series of patients with COVID-19 who presented with large vessel occlusions, and to describe unique findings in this population. METHODS: Mechanical thrombectomy was performed on five consecutive patients with COVID-19 with large vessel occlusions. A retrospective study of these patients was performed. Patient demographics, laboratory values, mechanical thrombectomy technique, and clinical and angiographic outcomes were reviewed. RESULTS: Four patients with COVID-19 presented with anterior circulation occlusions and one patient with COVID-19 presented with both anterior and posterior circulation occlusions. All patients had coagulation abnormalities. Mean patient age was 52.8 years. Three patients presented with an intracranial internal carotid artery occlusion. Two patients presented with an intracranial occlusion and a tandem thrombus in the carotid bulb. One patient presented with an occlusion in both the internal carotid and basilar arteries. Clot fragmentation and distal emboli to a new vascular territory were seen in two of five (40%) patients, and downstream emboli were seen in all five (100%) patients. Patient clinical outcome was generally poor in this series of patients with COVID-19 large vessel occlusion. CONCLUSION: Our series of patients with COVID-19 demonstrated coagulation abnormalities, and compared with our previous experience with mechanical thrombectomy in large vessel occlusion, this group of patients were younger, had tandem or multiple territory occlusions, a large clot burden, and a propensity for clot fragmentation. These patients present unique challenges that make successful revascularization difficult.

Curative treatment for low-grade arteriovenous malformations.

BACKGROUND: Spetzler-Martin (SM) grade I-II (low-grade) arteriovenous malformations (AVMs) are often considered safe for microsurgery or radiosurgery. The adjunctive use of preoperative embolization to reduce surgical risk in these AVMs remains controversial. OBJECTIVE: To assess the safety of combined treatment of grade I-II AVMs with preoperative embolization followed by surgical resection or radiosurgery, and determine the long-term functional outcomes. METHODS: With institutional review board approval, a retrospective analysis was carried out on patients with ruptured and unruptured SM I-II AVMs between 2002 and 2017. Details of the endovascular procedures, including number of arteries supplying the AVM, number of branches embolized, embolic agent(s) used, and complications were studied. Baseline clinical and imaging characteristics were compared. Functional status using the modified Rankin Scale (mRS) before and after endovascular and microsurgical treatments was compared. RESULTS: 258 SM I-II AVMs (36% SM I, 64% SM II) were identified in patients with a mean age of 38 ± 17 years. 48% presented with hemorrhage, 21% with seizure, 16% with headache, 10% with no symptoms, and 5% with clinical deficits. 90 patients (68%) in the unruptured group and 74 patients (59%) in the ruptured group underwent presurgical embolization (p = 0.0013). The mean number of arteries supplying the AVM was 1.44 and 1.41 in the unruptured and ruptured groups, respectively (p = 0.75). The mean number of arteries embolized was 2.51 in the unruptured group and 1.82 in the ruptured group (p = 0.003). n-Butyl cyanoacrylate and Onyx were the two most commonly used embolic agents. Four complications were seen in four patients (4/164 patients embolized): two peri-/postprocedural hemorrhage, one dissection, and one infarct. All patients undergoing surgery had a complete cure on postoperative angiography. Patients were followed up for a mean of 55 months. Good long-term outcomes (mRS score ≤ 2) were seen in 92.5% of patients with unruptured AVMs and 88.0% of those with ruptured AVMs. Permanent neurological morbidity occurred in 1.2%. CONCLUSIONS: Curative treatment of SM I-II AVMs can be performed using endovascular embolization with microsurgical resection or radiosurgery in selected cases, with very low morbidity and high cure rates. Compared with other published series, these outcomes suggest that preoperative embolization is a safe and effective adjunct to definitive surgical treatment. Long-term follow-up showed that patients with low-grade AVMs undergoing surgical resection or radiosurgery have good functional outcomes.

Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25+ T cells to suppress colitis.

Macrophages play central roles in immunity as early effectors and modulating adaptive immune reponses; we implicated macrophages in the anticolitic effect of infection with the tapeworm Hymenolepis diminuta. Here, gene arrays revealed that H. diminuta antigen (HdAg) evoked a program in murine macrophages distinct from that elicited by IL-4. Further, HdAg suppressed LPS-evoked release of TNF-α and IL-1ß from macrophages via autocrine IL-10 signaling. In assessing the ability of macrophages treated in vitro with an extract of H. diminuta [M(HdAg)] to affect disease, intravenous, but not peritoneal, injection of M(HdAg) protected wild-type but not RAG1-/- mice from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Administration of splenic CD4+ T cells from in vitro cocultures with M(HdAg), but not those cocultured with M(IL-4) cells, inhibited DNBS-induced colitis; fractionation of the T-cell population indicated that the CD4+CD25+ T cells from cocultures with M(HdAg) drove the suppression of DNBS-induced colitis. Use of IL-4-/- or IL-10-/- CD4+ T cells revealed that neither cytokine alone from the donor cells was essential for the anticolitic effect. These data illustrate that HdAg evokes a unique regulatory program in macrophages, identifies HdAg-evoked IL-10 suppression of macrophage activation, and reveals the ability of HdAg-treated macrophages to educate ( i.e., condition) and mobilize CD4+CD25+ T cells, which could be deployed to treat colonic inflammation.-Reyes, J. L., Lopes, F., Leung, G., Jayme, T. S., Matisz, C. E., Shute, A., Burkhard, R., Carneiro, M., Workentine, M. L., Wang, A., Petri, B., Beck, P. L., Geuking, M. B., McKay, D. M., Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25+ T cells to suppress colitis.

Placement of Ommaya Reservoirs Using Electromagnetic Neuronavigation and Neuroendoscopy: A Retrospective Study with Cost-Benefit Analysis.

BACKGROUND: Placement of intraventricular catheters in oncology patients is associated with high complication rates. Placing Ommaya reservoirs with the zero-error precision protocol (ZEPP), a combination of neuronavigation (AxiEM stereotactic navigation) and direct verification of catheter tip placement with a flexible neuroendoscope, is associated with decreased complication rates as a result of increased catheter placement accuracy. However, the ZEPP costs more than traditional methods of catheter placement, and the question of whether this increased accuracy with the ZEPP is cost-effective is unknown. METHODS: We performed a single-center retrospective chart review of 50 consecutive ommaya reservoir patient placements between 2010 and 2017. Twenty-five ventricular catheters were placed using the ZEPP protocol, and 25 ventricular catheters were placed using only AxiEM stealth navigation. Postoperative catheter accuracy and complication rates were assessed. A cost-benefit analysis was then conducted to determine if the overall cost for placing Ommaya reservoirs with the ZEPP was effective compared with the alternative method of using neuronavigation alone. RESULTS: In the non-ZEPP cohort, 10 of 25 catheters were placed within the optimal location compared with 25 of 25 catheters placed in the ZEPP cohort. Three complications occurred in the non-ZEPP cohort: 2 malpositioned catheters required surgical revision and 1 catheter-related hemorrhage resulted in a prolonged stay in the intensive care unit. No complications occurred in the ZEPP cohort. A cost-benefit analysis showed $4784 savings per patient with ZEPP utilization because of the high complication-associated costs. CONCLUSIONS: Implementation of the ZEPP for verifying ventricular catheter placement in Ommaya reservoirs improved catheter tip accuracy, resulted in lower complication rates, and was more cost-effective when compared with the non-ZEPP cohort, which used only neuronavigation. The ZEPP can be used for ventricular shunt catheter placement to decrease complications and verify catheter tip accuracy in Ommaya or standard ventriculoperitoneal shunts.

Helminth Antigen-Conditioned Dendritic Cells Generate Anti-Inflammatory Cd4 T Cells Independent of Antigen Presentation via Major Histocompatibility Complex Class II.

A recently identified feature of the host response to infection with helminth parasites is suppression of concomitant disease. Dendritic cells (DCs) exposed to antigens from the tapeworm Hymenolepis diminuta significantly reduce the severity of dinitrobenzene sulfonic acid-induced colitis in mice. Here we elucidate mechanisms underlying this cellular immunotherapy. We show a requirement for Ccr7 expression on transferred H. diminuta antigen-treated (HD)-DCs, suggesting that homing to secondary lymphoid tissues is important for suppression of colitis. Furthermore, sodium metaperiodate-sensitive helminth-derived glycans are required to drive the anti-colitic response in recipient mice. Induction of Th2-type cytokines and Gata-3+Cd4+ cells in secondary lymphoid tissues is dependent on major histocompatibility complex class II (MHC II) protein expression on transferred DCs, although remarkably, transfer of MHC II-/- HD-DCs still attenuated dinitrobenzene sulfonic acid-induced colitis in recipient mice. Moreover, transfer of Cd4+ splenic T cells retrieved from mice administered MHC II-/- HD-DCs suppressed dinitrobenzene sulfonic acid-induced colitis in recipient mice. Our studies reveal that HD-DCs can suppress colitis via an alternative MHC II-independent pathway that involves, in part, mobilization of T-cell responses. These data support the utility of HD-DCs in blocking colitis, revealing a requirement for Ccr7 and providing for HD-DC autologous immunotherapy for disease in which MHC II expression and/or function is compromised.