Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage.

BACKGROUND: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. METHODS: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. RESULTS: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P, 0.026). CONCLUSIONS: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

Direct Observation of the Dynamics of Ylide Solvation by Hydrogen-bond Donors Using Time-Resolved Infrared Spectroscopy.

The photoexcitation of α-diazocarbonyl compounds produces singlet carbene intermediates that react with nucleophilic solvent molecules to form ylides. The zwitterionic nature of these newly formed ylides induces rapid changes in their interactions with the surrounding solvent. Here, ultrafast time-resolved infrared absorption spectroscopy is used to study the ylide-forming reactions of singlet carbene intermediates from the 270 nm photoexcitation of ethyl diazoacetate in various solvents and the changes in the subsequent ylide-solvent interactions. The results provide direct spectroscopic observation of the competition between ylide formation and C-H insertion in reactions of the singlet carbene with nucleophilic solvent molecules. We further report the specific solvation dynamics of the tetrahydrofuran (THF)-derived ylide (with a characteristic IR absorption band at 1636 cm-1) by various hydrogen-bond donors and the coordination by lithium cations. Hydrogen-bonded ylide bands shift to a lower wavenumber by -19 cm-1 for interactions with ethanol, -14 cm-1 for chloroform, -10 cm-1 for dichloromethane, -9 cm-1 for acetonitrile or cyclohexane, and -16 cm-1 for Li+ coordination, allowing the time evolution of the ylide-solvent interactions to be tracked. The hydrogen-bonded ylide bands grow with rate coefficients that are close to the diffusional limit. We further characterize the specific interactions of ethanol with the THF-derived ylide using quantum chemical (MP2) calculations and DFT-based atom-centered density matrix propagation trajectories, which show preferential coordination to the α-carbonyl group. This coordination alters the hybridization character of the ylidic carbon atom, with the greatest change toward sp2 character found for lithium-ion coordination.

Transient absorption spectroscopy of the electron transfer step in the photochemically activated polymerizations of N-ethylcarbazole and 9-phenylcarbazole.

The polymerization of photoexcited N-ethylcarbazole (N-EC) in the presence of an electron acceptor begins with an electron transfer (ET) step to generate a radical cation of N-EC (N-EC˙+). Here, the production of N-EC˙+ is studied on picosecond to nanosecond timescales after N-EC photoexcitation at a wavelength λex = 345 nm using transient electronic and vibrational absorption spectroscopy. The kinetics and mechanisms of ET to diphenyliodonium hexafluorophosphate (Ph2I+PF6-) or para-alkylated variants are examined in dichloromethane (DCM) and acetonitrile (ACN) solutions. The generation of N-EC˙+ is well described by a diffusional kinetic model based on Smoluchowski theory: with Ph2I+PF6-, the derived bimolecular rate coefficient for ET is kET = (1.8 ± 0.5) × 1010 M-1 s-1 in DCM, which is consistent with diffusion-limited kinetics. This ET occurs from the first excited singlet (S1) state of N-EC, in competition with intersystem crossing to populate the triplet (T1) state, from which ET may also arise. A faster component of the ET reaction suggests pre-formation of a ground-state complex between N-EC and the electron acceptor. In ACN, the contribution from pre-reaction complexes is smaller, and the derived ET rate coefficient is kET = (1.0 ± 0.3) × 1010 M-1 s-1. Corresponding measurements for solutions of photoexcited 9-phenylcarbazole (9-PC) and Ph2I+PF6- give kET = (5 ± 1) × 109 M-1 s-1 in DCM. Structural modifications of the electron acceptor to increase its steric bulk reduce the magnitude of kET: methyl and t-butyl additions to the para positions of the phenyl rings (para Me2Ph2I+PF6- and t-butyl-Ph2I+PF6-) respectively give kET = (1.2 ± 0.3) × 1010 M-1 s-1 and kET = (5.4 ± 1.5) × 109 M-1 s-1 for reaction with photoexcited N-EC in DCM. These reductions in kET are attributed to slower rates of diffusion or to steric constraints in the ET reaction.

Occult Brain Arteriovenous Malformation Superimposed on a Pial Arteriovenous Fistula: Case Report.

INTRODUCTION: Pial arteriovenous fistulas are characterized by an abnormal connection between an intracranial artery and vein without an intervening nidus. Their predominant symptoms largely arise from mass effect, shunting, or hemorrhage. Most conservatively managed cases progress to death, but endovascular and/or surgical intervention is often successful. CASE PRESENTATION: We present the unique case of a 15-year-old girl with spontaneous intracranial hemorrhage from a single-vessel arteriovenous fistula. Although preoperative imaging failed to show a distinct nidus, intraoperative indocyanine green angiography performed after successful clipping of the primary fistulous site revealed residual shunting from a peri-lesional arteriovenous malformation. DISCUSSION/CONCLUSION: This case demonstrates the importance of intraoperative imaging and meticulous circumferential inspection of these lesions to detect residual vascular shunting.

Direct Observation of Ylide and Enol Intermediates Formed in Competition with Wolff Rearrangement of Photoexcited Ethyl Diazoacetoacetate.

The photoexcitation of α-diazocarbonyl compounds produces ketenes by both concerted and stepwise Wolff rearrangements. The stepwise mechanism proceeds through singlet carbene intermediates which can also participate in bimolecular reactions such as ylide formation with nucleophiles. Here, ultrafast transient infrared absorption spectroscopy is used to show competitive production of singlet carbene and ketene intermediates from the photoexcitation of ethyl diazoacetoacetate. We provide direct spectroscopic evidence for ylide formation by singlet α-carbonyl carbene capture in aprotic nucleophilic solvents (with ylide bands at 1625 cm-1 in acetonitrile and 1586 and 1635 cm-1 in tetrahydrofuran) and report an enol-mediated pathway for singlet α-carbonyl carbene reaction with alcohols (ethanol or tert-butanol) identified by an absorption band at 1694 cm-1; however, we find no evidence for a previously proposed ylide pathway. The α-carbonyl carbene is monitored by using a band with solvent-dependent wavenumber in the range 1627-1645 cm-1. A computed two-dimensional cut of the potential energy surface for the reaction of the singlet α-carbonyl carbene with methanol shows that the enol forms without a barrier and that this reaction is promoted by an intermolecular hydrogen bond from methanol to the carbonyl oxygen atom. The corresponding ylide structure lies higher in energy, with a barrierless downhill path to isomerization to the enol.

Left behind?: male clients of female sex workers in Zambia.

Male clients of female sex workers (CFSWs) are a key-affected group within the HIV epidemic. However, few studies have quantified HIV/STI burdens among CFSWs. This study used nationally representative data from the 2013-14 Zambia Demographic and Health Survey to estimate proxies for HIV and STI prevalence among sexually active men aged 15-59 paying for sex recently (past 12 months) [5%, n = 679] or in their lifetime [15%, n = 1,887]. Chi-square tests were calculated to assess differences in prevalence estimates between CFSWs and non-clients. Multivariable logistic regression models were generated to identify sociodemographic factors associated with prevention characteristics. CFSWs had higher odds of reporting HIV infection (recent: aOR 1.413, p < 0.05; lifetime: aOR 1.604, p < 0.001) and past-year STI symptomology (recent: aOR 3.342, p < 0.001; lifetime: aOR 2.266, p < 0.001) than non-clients, irrespective of transactional sex recency. Compared to non-clients, CFSWs were more likely to be <25yo (42% vs. 29%, p < 0.001), have a cohabitating partner (43% vs. 35%, p < 0.001), use condoms at last sex (31% vs. 27%, p < 0.001), and never test for HIV (36% vs. 29%, p < 0.001). When comparing CFSWs to non-clients, marital status was an effect modifier of HIV testing, medical circumcision, and condom use at last sex. Findings suggest high HIV/STI burdens and highlight the urgent need for differentiated HIV prevention programming for CFSWs in Zambia including the provision of PrEP.

National trends in cerebral bypass surgery in the United States, 2002-2014.

OBJECTIVECerebral bypass procedures are microsurgical techniques to augment or restore cerebral blood flow when treating a number of brain vascular diseases including moyamoya disease, occlusive vascular disease, and cerebral aneurysms. With advances in endovascular therapy and evolving evidence-based guidelines, it has been suggested that cerebral bypass procedures are in a state of decline. Here, the authors characterize the national trends in cerebral bypass surgery in the United States from 2002 to 2014.METHODSUsing the National (Nationwide) Inpatient Sample, the authors extracted for analysis the data on all adult patients who had undergone cerebral bypass as indicated by ICD-9-CM procedure code 34.28. Indications for bypass procedures, patient demographics, healthcare costs, and regional variations are described. Results were stratified by indication for cerebral bypass including moyamoya disease, occlusive vascular disease, and cerebral aneurysms. Predictors of inpatient complications and death were evaluated using multivariable logistic regression analysis.RESULTSFrom 2002 to 2014, there was an increase in the annual number of cerebral bypass surgeries performed in the United States. This increase reflected a growth in the number of cerebral bypass procedures performed for adult moyamoya disease, whereas cases performed for occlusive vascular disease or cerebral aneurysms declined. Inpatient complication rates for cerebral bypass performed for moyamoya disease, vascular occlusive disease, and cerebral aneurysm were 13.2%, 25.1%, and 56.3%, respectively. Rates of iatrogenic stroke ranged from 3.8% to 20.4%, and mortality rates were 0.3%, 1.4%, and 7.8% for moyamoya disease, occlusive vascular disease, and cerebral aneurysms, respectively. Multivariate logistic regression confirmed that cerebral bypass for vascular occlusive disease or cerebral aneurysm is a statistically significant predictor of inpatient complications and death. Mean healthcare costs of cerebral bypass remained unchanged from 2002 to 20014 and varied with treatment indication: moyamoya disease $38,406 ± $483, vascular occlusive disease $46,618 ± $774, and aneurysm $111,753 ± $2381.CONCLUSIONSThe number of cerebral bypass surgeries performed for adult revascularization has increased in the United States from 2002 to 2014. Rising rates of surgical bypass reflect a greater proportion of surgeries performed for moyamoya disease, whereas bypasses performed for vascular occlusive disease and aneurysms are decreasing. Despite evolving indications, cerebral bypass remains an important surgical tool in the modern endovascular era and may be increasing in use. Stagnant complication rates highlight the need for continued interest in advancing available bypass techniques or technologies to improve patient outcomes.

Tracking the conical intersection dynamics for the photoinduced Jahn-Teller switch of a Mn(iii) complex.

Octahedral Mn(iii) ions predominantly exhibit an axially elongated Jahn-Teller (JT) distortion, which is responsible for their large uniaxial magnetic anisotropy. As a result, they are often used in the synthesis of single-molecule magnets (SMMs). Modulation of the JT distortion using femtosecond laser pulses could offer a route to controlling the magnetisation direction, and therefore is promising for the development of data storage devices that work on ultrafast timescales. Photoinduced switching of the distortion from an axially elongated to an axially compressed structure has been demonstrated for various Mn(iii) complexes. However, the dynamics around the region of the conical intersection for the photoinduced JT switch remains unclear. Here, ultrafast transient absorption spectra were recorded for solutions of tris(2,2,6,6-tetramethyl-3,5-heptanedionato)manganese(iii) (Mn(dpm)3) in ethanol to further explore the dynamics of the photoinduced JT switch. We observe the generation of a vibrational wavepacket on the excited state surface, which has a frequency of approximately 155 cm-1 and encompasses a JT-active vibrational mode. This coherent motion is maintained after passage through the conical intersection back to the ground state, which launches wavepackets along the ground state potential energy surface (PES) with frequencies of approximately 180 and 110 cm-1 that we assign to the elongated and compressed state, respectively. Inspection of the relative phases of the frequencies reveals phase shifts that are consistent with a one-mode reaction coordinate, and passes through the conical intersection at 1/4 and 3/4 of the excited state vibrational period. Our results provide direct insights into the non-adiabatic dynamics of Mn(iii) complexes, which can be used to guide the synthesis of optically controlled SMMs.

Competing Nonadiabatic Relaxation Pathways for Near-UV Excited ortho-Nitrophenol in Aqueous Solution.

Nitrophenols are atmospheric pollutants found in brown carbon aerosols produced by biomass burning. Absorption of solar radiation by these nitrophenols contributes to atmospheric radiative forcing, but quantifying this climate impact requires better understanding of their photochemical pathways. Here, the photochemistry of near-UV (λ = 350 nm) excited ortho-nitrophenol in aqueous solution is investigated using transient absorption spectroscopy and time-resolved infrared spectroscopy over the fs to µs time scale to characterize the excited states, intermediates, and photoproducts. Interpretation of the transient spectroscopy data is supported by quantum chemical calculations using linear-response time-dependent density functional theory (LR-TDDFT). Our results indicate efficient nonradiative decay via an S1(ππ*)/S0 conical intersection leading to hot ground state ortho-nitrophenol which vibrationally cools in solution. A previously unreported minor pathway involves intersystem crossing near an S1(nπ*) minimum, with decay of the resulting triplet ortho-nitrophenol facilitated by deprotonation. These efficient relaxation pathways account for the low quantum yields of photodegradation.

Tracking nuclear motion in single-molecule magnets using femtosecond X-ray absorption spectroscopy.

The development of new data storage solutions is crucial for emerging digital technologies. Recently, all-optical magnetic switching has been achieved in dielectrics, proving to be faster than traditional methods. Despite this, single-molecule magnets (SMMs), which are an important class of magnetic materials due to their nanometre size, remain underexplored for ultrafast photomagnetic switching. Herein, we report femtosecond time-resolved K-edge X-ray absorption spectroscopy (TR-XAS) on a Mn(III)-based trinuclear SMM. Exploiting the elemental specificity of XAS, we directly track nuclear dynamics around the metal ions and show that the ultrafast dynamics upon excitation of a crystal-field transition are dominated by a magnetically active Jahn-Teller mode. Our results, supported by simulations, reveal minute bond length changes from 0.01 to 0.05 Å demonstrating the sensitivity of the method. These geometrical changes are discussed in terms of magneto-structural relationships and consequently our results illustrate the importance of TR-XAS for the emerging area of ultrafast molecular magnetism.

Equatorial restriction of the photoinduced Jahn-Teller switch in Mn(iii)-cyclam complexes.

Ultrafast transient absorption spectra were recorded for solutions of [MnIII(cyclam)(H2O)(OTf)][OTf]2 (cyclam = 1,4,8,11-tetraazacyclotetradecane and OTf = trifluoromethanesulfonate) in water to explore the possibility to restrict the equatorial expansion following photoexcitation of the dxy ← dz2 electronic transition, often resulting in a switch from axial to equatorial Jahn-Teller distortion in MnIII complexes. Strong oscillations were observed in the excited state absorption signal and were attributed to an excited state wavepacket. The structural rigidity of the cyclam ligand causes a complex reaction coordinate with frequencies of 333, 368, 454 and 517 cm-1, and a significantly shorter compressed-state lifetime compared to other MnIII complexes with less restricted equatorial ligands. Complementary density functional theory quantum chemistry calculations indicate a switch from an axially elongated to a compressed structure in the first excited quintet state Q1, which is accompanied by a modulation of the axial tilt angle. Computed harmonic frequencies for the axial stretching mode (∼379 cm-1) and the equatorial expansions (∼410 and 503 cm-1) of the Q1 state agree well with the observed coherences and indicate that the axial bond length contraction is significantly larger than the equatorial expansion, which implies a successful restriction of the wavepacket motion. The weak oscillation observed around 517 cm-1 is assigned to a see-saw motion of the axial tilt (predicted ∼610 cm-1). The results provide insights into the structural perturbations to the molecular evolution along excited state potential energy surfaces of MnIII octahedral complexes and can be used to guide the synthesis of optically controlled MnIII-based single-molecule magnets.

N-myc-Mediated Translation Control Is a Therapeutic Vulnerability in Medulloblastoma.

Deregulation of neuroblastoma-derived myc (N-myc) is a leading cause of malignant brain tumors in children. To target N-myc-driven medulloblastoma, most research has focused on identifying genomic alterations or on the analysis of the medulloblastoma transcriptome. Here, we have broadly characterized the translatome of medulloblastoma and shown that N-myc unexpectedly drives selective translation of transcripts that promote protein homeostasis. Cancer cells are constantly exposed to proteotoxic stress associated with alterations in protein production or folding. It remains poorly understood how cancers cope with proteotoxic stress to promote their growth. Here, our data revealed that N-myc regulates the expression of specific components (∼5%) of the protein folding machinery at the translational level through the major cap binding protein, eukaryotic initiation factor eIF4E. Reducing eIF4E levels in mouse models of medulloblastoma blocked tumorigenesis. Importantly, targeting Hsp70, a protein folding chaperone translationally regulated by N-myc, suppressed tumor growth in mouse and human medulloblastoma xenograft models. These findings reveal a previously hidden molecular program that promotes medulloblastoma formation and identify new therapies that may have impact in the clinic. SIGNIFICANCE: Translatome analysis in medulloblastoma shows that N-myc drives selective translation of transcripts that promote protein homeostasis and that represent new therapeutic vulnerabilities.

Neuroinflammatory Biomarkers for Traumatic Brain Injury Diagnosis and Prognosis: A TRACK-TBI Pilot Study.

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24 h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1-4/5-8); and incomplete versus full recovery (GOSE <8/ = 8). One-hundred sixty TBI subjects, 28 OCs, and 18 HCs were included. Markers discriminating TBI/OC: HMGB-1 (AUC = 0.835), IL-1b (0.795), IL-16 (0.784), IL-7 (0.742), and TARC (0.731). Markers discriminating GCS 3-12/13-15: IL-6 (AUC = 0.747), CRP (0.726), IL-15 (0.720), and SAA (0.716). Markers discriminating CT positive/CT negative: SAA (AUC = 0.767), IL-6 (0.757), CRP (0.733), and IL-15 (0.724). At 3 months, IL-15 (AUC = 0.738) and IL-2 (0.705) discriminated GOSE 5-8/1-4. At 6 months, IL-15 discriminated GOSE 1-4/5-8 (AUC = 0.704) and GOSE <8/ = 8 (0.711); SAA discriminated GOSE 1-4/5-8 (0.704). We identified a profile of acute circulating inflammatory proteins with potential relevance for TBI diagnosis, severity differentiation, and prognosis. IL-15 and serum amyloid A are priority markers with acceptable discrimination across multiple diagnostic and outcome categories. Validation in larger prospective cohorts is needed. ClinicalTrials.gov Registration: NCT01565551.

Natural history, angiographic presentation and outcomes of anterior cranial fossa dural arteriovenous fistulas.

BACKGROUND: Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs. METHODS: The CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990-2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed. RESULTS: 60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs. CONCLUSION: Most ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation.

Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes.

BACKGROUND AND OBJECTIVES: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs. METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed. RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09). CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

Socioeconomic factors associated with pediatric moyamoya disease hospitalizations: a nationwide cross-sectional study.

OBJECTIVE: Healthcare disparities are widely described in adults, but barriers affecting access to care for pediatric patients with moyamoya disease (MMD) are unknown. Understanding socioeconomic factors impacting hospital access and outcomes is necessary to address pediatric healthcare disparities. METHODS: In this cross-sectional observational study, the Kids' Inpatient Database was used to identify patients admitted with a primary diagnosis of MMD from 2003 to 2016. Patients ≤ 18 years with a primary diagnosis of MMD based on International Classification of Diseases (ICD) codes were included. Hospital admissions were queried for use of cerebral revascularization based on ICD procedure codes. RESULTS: Query of the KID yielded 1449 MMD hospitalizations. After multivariable regression, Hispanic ethnicity (OR 0.52 [95% CI 0.33-0.81], p = 0.004) was associated with lack of surgical revascularization. Private insurance (OR 1.56 [95% CI 1.15-2.13], p = 0.004), admissions at medium- and high-volume centers (OR 2.01 [95% CI 1.42-2.83], p < 0.001 and OR 2.84 [95% CI 1.95-4.14], p < 0.001, respectively), and elective hospitalization (OR 3.37 [95% CI 2.46-4.64], p < 0.001) were positively associated with revascularization. Compared with Caucasian race, Hispanic ethnicity was associated with increased mean (± SEM) length of stay by 2.01 ± 0.70 days (p = 0.004) and increased hospital charges by $24,333.61 ± $7918.20 (p = 0.002), despite the decreased utilization of surgical revascularization. Private insurance was associated with elective admission (OR 1.50 [95% CI 1.10-2.05], p = 0.01) and admission to high-volume centers (OR 1.90 [95% CI 1.26-2.88], p = 0.002). African American race was associated with the development of in-hospital complications (OR 2.52 [95% CI 1.38-4.59], p = 0.003). CONCLUSIONS: Among pediatric MMD hospitalizations, multiple socioeconomic factors were associated with access to care, whether surgical treatment is provided, and whether in-hospital complications occur. These results suggest that socioeconomic factors are important drivers of healthcare disparities in children with MMD and warrant further study.

Comparison of Outcomes following Primary and Repeat Resection of Craniopharyngioma.

Introduction The management of recurrent craniopharyngioma is complex with limited data to guide decision-making. Some reports suggest reoperation should be avoided due to an increased complication profile, while others have demonstrated that safe reoperation can be performed. For other types of skull base lesions, maximal safe resection followed by adjuvant therapy has replaced radical gross total resection due to the favorable morbidity profiles. Methods Seventy-one patients underwent resection over a 9-year period for craniopharyngioma and were retrospectively reviewed. Patients were separated into primary resection and reoperation cohorts and stratified by surgical approach (endonasal vs. cranial) and survival analyses were performed based on cohort and surgical approach. Results Fifty patients underwent primary resection, while 21 underwent reoperation for recurrence. Fifty endonasal transsphenoidal surgeries and 21 craniotomies were performed. Surgical approaches were similarly distributed across cohorts. Subtotal resection was achieved in 83% of all cases. There were no differences in extent of resection, visual outcomes, subsequent neuroendocrine function, and complications across cohorts and surgical approaches. The median time to recurrence was 87 months overall, and there were no differences by cohort and approach. The 5-year survival rate was 81.1% after reoperation versus 93.2% after primary resection. Conclusion Compared with primary resection, reoperation for craniopharyngioma recurrence is associated with similar functional and survival outcomes in light of individualized surgical approaches. Maximal safe resection followed by adjuvant radiotherapy for residual tumor likely preserves vision and endocrine function without sacrificing overall patient survival.

Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR): rationale, design, and initial characterization of patient cohort.

OBJECTIVE: Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort. METHODS: Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained. RESULTS: CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120-1038.5 days). CONCLUSIONS: With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.

Onyx embolization for dural arteriovenous fistulas: a multi-institutional study.

BACKGROUND: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance. OBJECTIVE: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs. METHODS: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models. RESULTS: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes. CONCLUSIONS: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.