Over-the-scope clip management of non-acute, full-thickness gastrointestinal defects.

BACKGROUND: Endoscopic management of full-thickness gastrointestinal tract defects (FTGID) has become an attractive management strategy, as it avoids the morbidity of surgery. We have previously described the short-term outcomes of over-the-scope clip management of 22 patients with non-acute FTGID. This study updates our prior findings with a larger sample size and longer follow-up period. METHODS: A retrospective analysis of prospectively collected data was conducted. All patients undergoing over-the-scope clip management of FTGID between 2013 and 2019 were identified. Acute perforations immediately managed and FTGID requiring endoscopic suturing were excluded. Patient demographics, endoscopic adjunct therapies, number of endoscopic interventions, and need for operative management were evaluated. Success was strictly defined as complete FTGID closure. RESULTS: We identified 92 patients with 117 FTGID (65 fistulae and 52 leaks); 27.2% had more than one FTGID managed simultaneously. The OTSC device (Ovesco Endoscopy, Tubingen, Germany) was utilized in all cases. Additional closure attempts were required in 22.2% of defects. With a median follow-up period of 5.5 months, overall defect closure success rate was 66.1% (55.0% fistulae vs. 79.6% leaks, p = 0.007). There were four mortalities from causes unrelated to the FTGID. Only 14.9% of patients with FTGID underwent operative management. There were no complications related to endoscopic intervention and no patients required urgent surgical intervention. CONCLUSIONS: Over-the-scope clip management of FTGID represents a safe alternative to potentially morbid operative intervention. When strictly defining success as complete closure of all FTGID, endoscopy was successful in 64.4% of patients with only a small minority of patients ultimately requiring surgery.

Abdominal cocoon syndrome: an obstructive adhesiolytic metamorphosis.

Abdominal cocoon syndrome (ACS), also known as idiopathic sclerosing peritonitis and primary sclerosing peritonitis, is a rare condition causing small bowel obstruction first described in 1978 by Foo et al It is characterised by total or partial encasement of the small bowel in a fibrocollagenous cocoon-like sac accompanied by extensive intrinsic small bowel adhesions. While the aetiology of this condition remains largely unknown, ACS can be divided into two subtypes: primary or idiopathic, which is often accompanied by cryptorchidism, and secondary to another cause such as congenital dysplasia or medications. Definitive diagnosis can only be achieved following laparotomy with extensive lysis of adhesions to alleviate the obstruction. However, preoperative diagnosis is possible if clinicians are aware of the condition and its radiologic signs.

Epigenetic changes in umbilical cord mesenchymal stromal cells upon stimulation and culture expansion.

BACKGROUND: Mesenchymal stromal cells (MSCs) are studied for their immunotherapeutic potential. Prior to therapeutic use, MSCs are culture expanded to obtain the required cell numbers and, to improve their efficacy, MSCs may be primed in vitro. Culture expansion and priming induce phenotypical and functional changes in MSCs and thus standardisation and quality control measurements come in need. We investigated the impact of priming and culturing on MSC DNA methylation and examined the use of epigenetic profiling as a quality control tool. METHODS: Human umbilical cord-derived MSCs (ucMSCs) were cultured for 3 days with interferon (IFN)γ, transforming growth factor (TGF)ß or a multi-factor combination (MC; IFNγ, TGFß and retinoic acid). In addition, ucMSCs were culture expanded for 14 days. Phenotypical changes and T-cell proliferation inhibition capacity were examined. Genome-wide DNA methylation was measured with Infinium MethylationEPIC Beadchip. RESULTS: Upon priming, ucMSCs exhibited a different immunophenotype and ucMSC(IFNγ) and ucMSC(MC) had an increased capacity to inhibit T-cell proliferation. DNA methylation patterns were minimally affected by priming, with only one significantly differentially methylated site (DMS) in IFNγ- and MC-primed ucMSCs associated with autophagy activity. In contrast, 14 days after culture expansion, ucMSCs displayed minor phenotypical and functional changes but showed >4000 significantly DMSs, mostly concerning genes involved in membrane composition, cell adhesion and transmembrane signalling. DISCUSSION: These data show that DNA methylation of MSCs is only marginally affected by priming, whereas culture expansion and subsequent increased cellular interactions have a large impact on methylation. On account of this study, we suggest that DNA methylation analysis is a useful quality control tool for culture expanded therapeutic MSCs.

Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered Through Phagocytosis of MSC By Monocytic Cells.

Mesenchymal stem or stromal cells (MSC) are under investigation as a potential immunotherapy. MSC are usually administered via intravenous infusion, after which they are trapped in the lungs and die and disappear within a day. The fate of MSC after their disappearance from the lungs is unknown and it is unclear how MSC realize their immunomodulatory effects in their short lifespan. We examined immunological mechanisms determining the fate of infused MSC and the immunomodulatory response associated with it. Tracking viable and dead human umbilical cord MSC (ucMSC) in mice using Qtracker beads (contained in viable cells) and Hoechst33342 (staining all cells) revealed that viable ucMSC were present in the lungs immediately after infusion. Twenty-four hours later, the majority of ucMSC were dead and found in the lungs and liver where they were contained in monocytic cells of predominantly non-classical Ly6Clow phenotype. Monocytes containing ucMSC were also detected systemically. In vitro experiments confirmed that human CD14++ /CD16- classical monocytes polarized toward a non-classical CD14++ CD16+ CD206+ phenotype after phagocytosis of ucMSC and expressed programmed death ligand-1 and IL-10, while TNF-α was reduced. ucMSC-primed monocytes induced Foxp3+ regulatory T cell formation in mixed lymphocyte reactions. These results demonstrate that infused MSC are rapidly phagocytosed by monocytes, which subsequently migrate from the lungs to other body sites. Phagocytosis of ucMSC induces phenotypical and functional changes in monocytes, which subsequently modulate cells of the adaptive immune system. It can be concluded that monocytes play a crucial role in mediating, distributing, and transferring the immunomodulatory effect of MSC. Stem Cells 2018;36:602-615.

Inflammatory Conditions Dictate the Effect of Mesenchymal Stem or Stromal Cells on B Cell Function.

The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC-IFN-γ) to simulate inflammatory conditions. Mature B cells were obtained from spleens by CD43- selection. B cells were co-cultured with MSC and stimulated with anti-IgM, anti-CD40, and IL-2; and after 7 days, B cell proliferation, phenotype, Immunoglobulin-G (IgG), and IL-10 production were analyzed. MSC did not inhibit B cell proliferation but increased the percentage of CD38high CD24high B cells (Bregs) and IL-10 production, while MSC-IFN-γ significantly reduced B cell proliferation and inhibited IgG production by B cells in a more potent fashion but did not induce Bregs or IL-10 production. Both MSC and MSC-IFN-γ required proximity to target cells and being metabolically active to exert their effects. Indoleamine 2,3 dioxygenase expression was highly induced in MSC-IFN-γ and was responsible of the anti-proliferative and Breg reduction since addition of tryptophan (TRP) restored MSC properties. Immunological conditions dictate the effect of MSC on B cell function. Under immunological quiescent conditions, MSC stimulate Breg induction; whereas, under inflammatory conditions, MSC inhibit B cell proliferation and maturation through depletion of TRP. This knowledge is useful for customizing MSC therapy for specific purposes by appropriate pretreatment of MSC.

Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease.

BACKGROUND: Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. METHODS: MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE2 secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expression on NK cells. The immunomodulatory capacity, biodistribution and survival of pre-treated ucMSC were investigated in a CCl4-induced liver disease mouse model. In addition, capacity of pre-treated MSC to ameliorate liver inflammation was examined in an ex vivo liver inflammation co-culture model. RESULTS: IFN-γ and a multiple cytokine cocktail (MC) consisting of IFN-γ, TGFß and retinoic acid upregulated the expression of immunomodulatory factor PD-L1 and IDO activity. Subsequently, both treatments enhanced the capacity of ucMSC to inhibit CD4 and CD8 T cell proliferation and IFN-γ production. The susceptibility of ucMSC for NK cell lysis was decreased by IFN-ß, TGFß and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl4-induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB6), ucMSC(Starv + VitB6) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFß) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced modulatory capacity compared to untreated ucMSC. CONCLUSIONS: The present study demonstrates the responsiveness of ucMSC to in vitro optimisation treatment. The observed improvements in immunomodulatory capacity as well as immunogenicity after MC treatment may improve the efficacy of ucMSC as immunotherapy targeted towards liver inflammation.

Aging of bone marrow- and umbilical cord-derived mesenchymal stromal cells during expansion.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are used as experimental immunotherapy. Extensive culture expansion is necessary to obtain clinically relevant cell numbers, although the impact on MSCs stability and function is unclear. This study investigated the effects of long-term in vitro expansion on the stability and function of MSCs. METHODS: Human bone marrow-derived (bmMSCs) and umbilical cord-derived (ucMSCs) MSCs were in vitro expanded. During expansion, their proliferative capacity was examined. At passages 4, 8 and 12, analyses were performed to investigate the ploidy, metabolic stability, telomere length and immunophenotype. In addition, their potential to suppress lymphocyte proliferation and susceptibility to natural killer cell lysis was examined. RESULTS: BmMSCs and ucMSCs showed decreasing proliferative capacity over time, while their telomere lengths and mitochondrial activity remained stable. Percentage of aneuploidy in cultures was unchanged after expansion. Furthermore, expression of MSC markers and markers associated with stress or aging remained unchanged. Reduced capacity to suppress CD4 and CD8 T-cell proliferation was observed for passage 8 and 12 bmMSCs and ucMSCs. Finally, susceptibility of bmMSCs and ucMSCs to NK-cell lysis remained stable. CONCLUSIONS: We showed that after long-term expansion, phenotype of bmMSCs and ucMSCs remains stable and cells exhibit similar immunogenic properties compared with lower passage cells. However, immunosuppressive properties of MSCs are reduced. These findings reveal the consequences of application of higher passage MSCs in the clinic, which will help increase the yield of therapeutic MSCs but may interfere with their efficacy.

An Expanded Retrospective Review of Trocar Site Hernias in Laparoscopic Gastric Bypass Patients.

BACKGROUND: Trocar site hernias (TSH) are reported in 0.3% to 5.4% of laparoscopic cases, depending on diameter and type. Most occur with trocars over 10 mm in diameter. Some recommend routine fascial closure, but this requires time, costs, pain, and increased infection rates. All prior series are based on clinical presentation alone. We examined the possibly underreported prevalence of asymptomatic TSH on postoperative computed tomography (CT) scans in a series of laparoscopic gastric bypass (LGBP) patients with unclosed port site fascia. MATERIALS AND METHODS: After Institutional Review Board (IRB) approval, a retrospective review of all patients undergoing LGBP at our center from 2005 to 2014 was performed. All procedures were performed using dilating optical trocars up to 12 mm diameter, placed above the arcuate line. No fascial closures were performed. Any patients undergoing abdominal CT scanning for any reason in the study period were included; patients who had undergone a separate laparoscopic operation after LGBP but before CT were excluded. RESULTS: One thousand ninety-five patients were included; of these, 244 (22.3%) met study criteria, providing 732 port sites of 11 or 12 mm diameter to study. Only two fascial defects (0.27%), one in an 11-mm site and one in a 12-mm site, each in different patients, were identified. Both were nonpalpable, asymptomatic, and plugged with fat. CONCLUSIONS: Incisional hernias in dilating or optical access trocar sites are extremely rare in LGBP patients using trocars up to 12 mm, above the arcuate line. When found, they tend to be asymptomatic and at low risk for bowel strangulation. Routine closure of such fascial sites is likely unnecessary.

Biomaterials Influence Macrophage-Mesenchymal Stem Cell Interaction In Vitro.

BACKGROUND: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. MATERIALS AND METHODS: The effect of macrophages cultured on polypropylene (PP) or polyethylene terephthalate coated with a collagen film (PET/Col) on ASCs in monolayer or on the same material was examined either through conditioned medium (CM) or in a direct coculture. ASC proliferation, collagen production, and gene expression were examined. As comparison, the effect of macrophages stimulated with lipopolysaccharide (LPS) and interferon gamma (IFNγ) [M(LPS/IFNγ)] or interleukin (IL) 4 [M(IL-4)] on ASCs was examined. RESULTS: Macrophage-CM increased collagen deposition, proliferation, and gene expression of MMP1, PLOD2, and PTGS2 in ASCs, irrespective of the material. Culturing ASCs and macrophages in coculture when only macrophages were on the materials induced the same effects on gene expression. When both ASCs and macrophages were cultured on biomaterials, PP induced COL1A1 and MMP1 more than PET/Col. M(LPS/IFNγ) CM increased PLOD2, MMP1, and PTGS2 and decreased TGFB in ASCs more than the M(IL-4) CM. CONCLUSION: Biomaterials influence wound healing by influencing the interaction between macrophages and ASCs. We provided more insight into the behavior of different cell types during wound healing. This behavior appears to be biomaterial specific depending on which cell type interacts with the biomaterial. As such, the biomaterial will influence tissue regeneration.

Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity.

Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of action and the therapeutic components of MSC. Such knowledge allows better identification of diseases that are responsive to MSC treatment, optimization of the MSC product, and development of therapy based on functional components of MSC. To close in on the components that carry the therapeutic immunomodulatory activity of MSC, we generated MSC that were unable to respond to inflammatory signals or secrete immunomodulatory factors, but preserved their cellular integrity [heat-inactivated MSC (HI-MSC)]. Secretome-deficient HI-MSC and control MSC showed the same biodistribution and persistence after infusion in mice with ischemic kidney injury. Both control and HI-MSC induced mild inflammatory responses in healthy mice and dramatic increases in interleukin-10, and reductions in interferon gamma levels in sepsis mice. In vitro experiments showed that opposite to control MSC, HI-MSC lacked the capability to suppress T-cell proliferation or induce regulatory B-cell formation. However, both HI-MSC and control MSC modulated monocyte function in response to lipopolysaccharides. The results of this study demonstrate that, in particular disease models, the immunomodulatory effect of MSC does not depend on their secretome or active cross-talk with immune cells, but on recognition of MSC by monocytic cells. These findings provide a new view on MSC-induced immunomodulation and help identify key components of the therapeutic effects of MSC.

Effects of Freeze-Thawing and Intravenous Infusion on Mesenchymal Stromal Cell Gene Expression.

Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture, and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the cells encounter a microenvironment after administration that may impact their properties. It has been demonstrated that the majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In this study, we investigated the effect of freeze-thawing and the mouse lung microenvironment on human adipose tissue-derived MSC. There were effects of freeze-thawing on the whole genome expression profile of MSC, although the effects did not exceed interdonor differences. There were no major changes in the expression of hemostatic regulators on transcriptional level, but significantly increased expression of procoagulant tissue factor on the surface of thawed adipose MSC, correlating with increased procoagulant activity of thawed cells. Exposure for 2 h to the lung microenvironment had a major effect on MSC gene expression and affected several immunological pathways. This indicates that MSC undergo functional changes shortly after infusion and this may influence the efficacy of MSC to modulate inflammatory responses. The results of this study demonstrate that MSC rapidly alter in response to the local milieu and disease-specific conditions may shape MSC after administration.

Efficacy of immunotherapy with mesenchymal stem cells in man: a systematic review.

Mesenchymal stem cells (MSC) are widely studied for their immunomodulatory properties. Data from in vitro and pre-clinical models demonstrate that MSC suppress activated immune cells and ameliorate the severity of experimental immune disease. In complex human studies, the immunomodulatory efficacy of MSC therapy is not well established. We conducted a systematic review of clinical studies which used MSC with the purpose of immunomodulation and included at least 10 patients to investigate the efficacy of MSC therapy. Sixty-two studies comprising 10 different immune disorders were included in the analysis, of which 18 studies represented controlled trials. Although several of the studies reported an amelioration of disease severity, other studies failed to observe a beneficial effect of MSC. The low number of randomized controlled trials, small number of studies per disease category and limited immunological readout parameters made it difficult to draw a definitive conclusion on the efficacy of MSC immune therapy.

Toward Development of iMesenchymal Stem Cells for Immunomodulatory Therapy.

Mesenchymal stem cells (MSC) are under development as an immunomodulatory therapy. The anticipated immunomodulatory effects of MSC are broad, from direct inhibition of lymphocyte proliferation, induction of regulatory T and B cells, to resetting the immune system via a hit-and-run principle. There are endless flavors of MSC. Differences between MSC are originating from donors variation, differences in tissue of origin, the effects of culture conditions, and expansion time. Even standard culture conditions change the properties of MSC dramatically and generate MSC that only remotely resemble their in vivo counterparts. Adjustments in culture protocols can further emphasize properties of interest in MSC, thereby generating cells fitted for specific purposes. Culture improved immunomodulatory MSC can be designed to target particular immune disorders. In this review, we describe the observed and the desired immunomodulatory effects of MSC and propose approaches how MSC with optimal immunomodulatory properties can be developed.

Pathological mechanisms underlying aneurysmal subarachnoid haemorrhage and vasospasm.

Aneurysmal subarachnoid haemorrhage is a cerebrovascular disease associated with an overall mortality as high as 50%. Delayed ischaemic neurologic deficits are a major contributor to this statistic, as well as the significant morbidity associated with the disease. Studies examining the pathophysiologic events causing these devastating changes in cerebral blood flow have identified several mechanisms which are thought to contribute to the development of delayed ischaemic neurological deficits, perhaps the most damaging of which are increased intracranial pressure and cerebral vasospasm. In addition, the presence of blood in the subarachnoid space can trigger a myriad of reactions resulting in increased capillary permeability, breakdown of the blood-brain barrier, and inflammation in surrounding neural tissue that adds to the devastating effects of haemorrhage. A detailed understanding of the post-haemorrhagic cellular and molecular changes that contribute to the development of cerebral ischaemia and vasospasm is imperative to the formulation of treatment and prevention options for subarachnoid haemorrhage patients. Despite a large body of research within this field, a complete understanding of rupture and vasospasm remains elusive. This study reviews the role of vasoactive substances, such as endothelin-1, as well as the histochemistry and molecular pathology of post-haemorrhage inflammation in the development of vasospasm and cerebral ischaemia.

Comparison of techniques for ventriculoperitoneal shunting in 523 patients with subarachnoid hemorrhage.

OBJECTIVE: It is common practice to use a new contralateral bur hole for ventriculoperitoneal shunt (VPS) placement in subarachnoid hemorrhage (SAH) patients with an existing ventriculostomy. At Thomas Jefferson University and Jefferson Hospital for Neuroscience, the authors have primarily used the ventriculostomy site for the VPS. The purpose of this study was to compare the safety of the 2 techniques in patients with SAH. METHODS: The rates of VPS-related hemorrhage, infection, and proximal revision were compared between the 2 techniques in 523 patients undergoing VPS placement (same site in 464 and contralateral site in 59 patients). RESULTS: The rate of new VPS-related hemorrhage was significantly higher in the contralateral-site group (1.7%) than in the same-site group (0%; p = 0.006). The rate of VPS infection did not differ between the 2 groups (6.4% for same site vs 5.1% for contralateral site; p = 0.7). In multivariate analysis, higher Hunt and Hess grades (p = 0.05) and open versus endovascular treatment (p = 0.04) predicted shunt infection, but the VPS technique was not a predictive factor (p = 0.9). The rate of proximal shunt revision was 6% in the same-site group versus 8.5% in the contralateralsite group (p = 0.4). In multivariate analysis, open surgery was the only factor predicting proximal VPS revision (p = 0.05). CONCLUSIONS: The results of this study suggest that the use of the ventriculostomy site for VPS placement may be feasible and safe and may not add morbidity (infection or need for revision) compared with the use of a fresh contralateral site. This rapid and simple technique also was associated with a lower risk of shunt-related hemorrhage. While both techniques appear to be feasible and safe, a definitive answer to the question of which technique is superior awaits a higher level of medical evidence.

The role of vascular remodeling and inflammation in the pathogenesis of intracranial aneurysms.

While the mechanisms triggering pathogenesis of intracranial aneurysms have not been fully elucidated, different mechanisms have been proposed ranging from hemodynamic mechanisms to genetic predispositions. One mechanism that has been thoroughly explored is the physiological and pathological vascular remodeling that occurs in conjunction with inflammatory reactions resulting in the initiation and progression of these lesions. Both hemodynamic stimuli and vascular inflammation can trigger a series of biochemical reactions resulting in vascular smooth muscle cell apoptosis and migration causing thinned, dilated areas of the cerebral vasculature. In addition, an imbalance between extracellular matrix remodeling proteins, such as matrix metalloproteinases and their inhibitors, can result in accelerated degradation of the internal elastic lamina and the adventitial layers, further weakening the vessel. While these processes occur under normal physiological conditions, situations that alter their balance such as inflammation caused by cigarette smoking or cocaine usage or hypoxia induced under chronic hypertensive conditions can alter the delicate balance of these reactions potentiating pathological remodeling and aneurysm development. The present study represents a thorough literature review of the vascular remodeling and inflammatory components to aneurysmal pathogenesis.

CT perfusion-guided versus time-guided mechanical recanalization in acute ischemic stroke patients.

OBJECTIVE: Perfusion studies are increasingly used to triage acute stroke patients for endovascular recanalization therapies. We compare the safety and efficacy of CT perfusion (CTP)-guided to time-guided mechanical recanalization in acute ischemic stroke (AIS) patients. METHODS: A review was conducted on 132 patients, 94 undergoing CTP-guided and 38 undergoing time-guided (maximum 8h from symptom onset) mechanical recanalization at our institution. RESULTS: The rate of partial-to-complete recanalization did not differ between the CTP and the non-CTP group (78.7% vs. 81.6%, respectively, p=0.71). ICH occurred respectively in 18.1% in the CTP group versus 31.6% in the non-CTP group (p=0.06). The overall in-hospital mortality rate was significantly lower in the CTP group (15.9% vs. 36.8%, p=0.04). In multivariable analysis, CTP-guided patient selection was an independent negative predictor of in-hospital mortality (OR=3.2; p=0.01). CTP-guided patient selection, however, was not a predictor of favorable outcome (Modified Rankin Scale 0-2 or 0-3). CONCLUSIONS: CTP-based patient selection was associated with lower ICH and mortality rates. Favorable outcomes, however, did not differ between the 2 groups. These results may suggest a possible benefit in terms of in-hospital mortality with CTP-guided triage of AIS patients for endovascular treatment.

Diagnostic yield of cerebral angiography in patients with computed tomography-negative, lumbar puncture-positive subarachnoid hemorrhage.

BACKGROUND: Cerebral angiography is generally recommended in patients with subarachnoid hemorrhage (SAH) by positive lumbar puncture (LP) but negative findings on computed tomography (CT). Existing data on the yield of angiography in these patients are very limited. OBJECTIVE: To retrospectively assess the diagnostic yield of cerebral angiography in patients with CT-/LP+ SAH and to determine the clinical and laboratory predictors of a vascular abnormality on angiography. METHODS: A total of 35 patients with CT-/LP+ SAH underwent cerebral angiography at our institution between 2008 and 2011. Patient clinical characteristics and LP findings were entered into a multivariate logistic regression analysis to identify predictors of vascular abnormalities. RESULTS: Twenty-five patients (71.4%) were female and 10 (28.6%) were male, with a mean age of 53 years. Twenty-six patients (74.3%) had cerebrospinal fluid xanthochromia. Sixteen patients (45.7%) were found to have an aneurysm on cerebral angiography. The median CSF red blood cell count of both the first (7790/mm(3) vs 4700/mm(3)), and last collection tubes (6800/mm(3) vs 3219/mm(3)) were higher in patients with cerebral aneurysms vs those without aneurysms (P = .3). On multivariate analysis, there were no clinical or laboratory parameters that predicted the presence of aneurysm on cerebral angiography. CONCLUSION: The diagnostic yield of cerebral angiography is high (45.7%) in patients with CT-/LP+ SAH. Higher red blood cell counts were noted in patients with cerebral aneurysms but no clinical or laboratory parameter can reliably predict the presence of a vascular anomaly. Thus, it is reasonable to perform cerebral angiography in all patients with CT-/LP+ SAH.

Endovascular treatment of proximal and distal posterior inferior cerebellar artery aneurysms.

OBJECT: Surgical clipping of posterior inferior cerebellar artery (PICA) aneurysms can be challenging and carries a potentially significant risk of morbidity and mortality. Experience with endovascular therapy has been limited to a few studies. The authors assess the feasibility, safety, and efficacy of endovascular therapy in the largest series of proximal and distal PICA aneurysms to date. METHODS: A total of 76 patients, 54 with proximal and 22 with distal PICA aneurysms, underwent endovascular treatment at Jefferson Hospital for Neuroscience between 2001 and 2011. RESULTS: Endovascular treatment was successful in 52 patients (96.3%) with proximal aneurysms and 19 patients (86.4%) with distal aneurysms. Treatment consisted of selective aneurysm coiling in 60 patients (84.5%) (including 4 with stent assistance and 4 with balloon assistance) and parent vessel trapping in 11 patients (15.5%). Specifically, a deconstructive procedure was necessary in 9.6% of proximal aneurysms (5 of 52) and 31.6% of distal aneurysms (6 of 19). There were 9 overall procedural complications (12.7%), 6 infarcts (8.5%; 4 occurring after deliberate occlusion of the PICA), and 3 intraprocedural ruptures (4.2%). The rate of procedure-related permanent morbidity was 2.8%. Complete aneurysm occlusion was achieved in 63.4% of patients (45 of 71). One patient (1.4%) treated with selective aneurysm coiling suffered a rehemorrhage on postoperative Day 15. The mean angiographic follow-up time was 17.2 months. Recurrence and re-treatment rates were, respectively, 20% and 17.1% for proximal aneurysms compared with 30.8% and 23.1% for distal aneurysms. Favorable outcomes (moderate, mild, or no disability) at follow-up were seen in 93% of patients with unruptured aneurysms and in 78.7% of those with ruptured aneurysms. CONCLUSIONS: Endovascular therapy is a feasible, safe, and effective treatment in patients with proximal and distal PICA aneurysms, providing excellent patient outcomes and adequate protection against rehemorrhage. The long-term incidence of aneurysm recanalization appears to be high, especially in distal aneurysms, and requires careful angiographic follow-up.

Multimodal endovascular management of acute ischemic stroke in patients over 75 years old is safe and effective.

INTRODUCTION: Greater attention has been directed to endovascular recanalization of acute ischemic stroke in septuagenarians and above. TECHNIQUE: A retrospective chart review was conducted to include patients treated for acute ischemic stroke from 2006 to 2012. All patients underwent initial neurological assessment and non-contrast head CT. Patients treated from 2009 to 2012 additionally received emergent CT angiogram and CT perfusion. 51 patients met the clinical and radiographic criteria and underwent multimodal endovascular revascularization for acute ischemic events. RESULTS: All patients underwent cerebral angiography and met angiographic criteria for endovascular thrombolysis. 34 patients (67%) were older than 80 years of age. 23 patients (45%) received intravenous tissue plasminogen activator prior to admission. Eight (16%) patients underwent stent placement after intra-arterial thrombolysis, 10 (20%) underwent balloon angioplasty and seven (14%) underwent both angioplasty and stent placement. 21 (41%) required only intra-arterial thrombolytics. An improvement in Thrombolysis in Myocardial Infarction score was noted in 34 patients (67%). The average modified Rankin Scale score on discharge was 3.9. Symptomatic intracranial hemorrhage occurred in three patients (6%); none required surgery. One patient (1.9%) had a postoperative retroperitoneal hematoma, which was managed conservatively. Two fatalities resulted from intraoperative vessel rupture (3.9%), with a combined morbidity and mortality of 27.5%. CONCLUSIONS: Multimodal endovascular recanalization of acute ischemic stroke is a relatively safe treatment option in patients older than 75 years of age. Careful patient selection by clinical and radiographic inclusion criteria is necessary for the successful management of stroke in this age group.