Vascular risk profile and changes of arterial hypertension after surgical revascularization in adult Moyamoya patients.

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly more frequently in MMD patients with increasing age, whereas the vascular risk profile in terms of obesity, nicotine and alcohol consumption was similar to that of the general population. Antihypertensive medication was changed one year after surgical revascularization in 67.5% of patients with a tendency towards dose reduction in 43.2% of all patients. After revascularization, physicians need to be aware of a high likelihood of changes in arterial hypertension and should adjust all other modifiable systemic vascular risk factors to achieve the best treatment possible.

Preoperative growth dynamics of untreated glioblastoma: Description of an exponential growth type, correlating factors, and association with postoperative survival.

Background: Little is known about the growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival. Methods: We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of ≥3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1 mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined by multivariable. Results: Out of 749 patients screened, 13 had ≥3 preoperative MRI, 70 had 2 MRI and met the inclusion criteria. A curve estimation regression model showed the best fit for exponential tumor growth. Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho = -0.59, P < .001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log-rank: P = .010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox regression model for patients after tumor resection. Conclusions: Especially small lesions suggestive of glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample.

Intensity Score of Vessel Wall Contrast Enhancement in MRI Allows Prediction of Disease Progression in Moyamoya Angiopathy.

BACKGROUND AND OBJECTIVES: The underlying pathophysiological cause of moyamoya angiopathy (MMA) is still unclear. High-resolution vessel wall imaging has become a useful tool. The aim was to study vessel wall contrast-enhancement (VW-CE) as an imaging marker to predict disease progression in MMA. METHODS: Patients with MMA, who had undergone serial contrast-enhanced high-resolution MRI with concomitant and follow-up digital subtraction angiography, were analyzed retrospectively. VW-CE was semiquantified by measurement of the signal intensity of the vessel wall in in contrast-enhanced high-resolution MRI. A comparative quotient with the contrast-intensity of the pituitary stalk was calculated and graded accordingly from grade 1 to 5. VW-CE status was correlated with disease status, stroke, cerebrovascular reactivity in CO2-triggered blood-oxygen level-dependent MRI, angiographic disease progression, revascularization surgery, and follow-up imaging. RESULTS: Forty eight patients met the inclusion criteria. N = 56 MRI and digital subtraction angiography time-intervals were evaluated for 12 vessel sections per hemisphere each (N = 1344). N = 38 (79%) patients showed VW-CE and N = 10 (21%) did not. VW-CE was only observed in the terminal internal carotid artery and the proximal circle of Willis (N = 96/1344). Notably, patients with VW-CE significantly more often presented with acute infarction in the concomitant MRI. The incidence of angiographically proven disease progression was significantly associated with the incidence of VW-CE, and time to disease progression was earlier in higher grades of VW-CE compared with lower grades. CONCLUSION: VW-CE is a semiquantifiable marker for disease activity in patients with MMA and associated with disease progression and increased risk of stroke. VW-CE analysis can be routinely performed in patients with MMA to estimate the risk for disease progression and stroke.

Evaluation of the contribution of individual arteries to the cerebral blood supply in patients with Moyamoya angiopathy: comparison of vessel-encoded arterial spin labeling and digital subtraction angiography.

PURPOSE: Vessel-encoded arterial spin labeling (VE-ASL) is able to provide noninvasive information about the contribution of individual arteries to the cerebral perfusion. The aim of this study was to compare VE-ASL to the diagnostic standard digital subtraction angiography (DSA) with respect to its ability to visualize vascular territories. METHODS: In total, 20 VE-ASL and DSA data sets of 17 patients with Moyamoya angiopathy with and without revascularization surgery were retrospectively analyzed. Two neuroradiologists independently assessed the agreement between VE-ASL and DSA using a 4-point Likert scale (no- very high agreement). Additionally, grading of the vascular supply of subterritories (A1-A2, M1-M6) on the VE-ASL images and angiograms was performed. The intermodal agreement was calculated for all subterritories in total and for the subdivision into without and after revascularization (direct or indirect bypass). RESULTS: There was a very high agreement between the VE-ASL and the DSA data sets (median = 1, modus = 1) with a substantial inter-rater agreement (kw = 0.762 (95% CI 0.561-0.963)). The inter-modality agreement between VE-ASL and DSA in vascular subterritories was almost perfect for all subterritories (k = 0.899 (0.865-0.945)), in the subgroup of direct revascularized subterritories (k = 0.827 (0.738-0.915)), in the subgroup of indirect revascularized subterritories (k = 0.843 (0.683-1.003)), and in the subgroup of never revascularized subterritories (k = 0.958 (0.899-1.017)). CONCLUSION: Vessel-encoded ASL seems to be a promising non-invasive method to depict the contributions of individual arteries to the cerebral perfusion before and after revascularization surgery.

Health-Related Quality of Life and Neuropsychological Outcome After EC-IC Bypass Revascularization in Adult Patients With Moyamoya Disease.

BACKGROUND AND OBJECTIVES: Patients with Moyamoya disease (MMD) have an above-average incidence of neuropsychological impairment and psychiatric comorbidities such as depression. Prevalence and correlation with preoperative imaging findings were identified in previous studies, and a reduced health-related quality of life (HRQOL) has been shown. This study investigates changes in neuropsychological performance and HRQOL after revascularization. METHODS: Thirty-two adult patients with MMD (23 female, 9 male; mean age 39.1 year ±14.7) with revascularization were included in this retrospective cohort study, and their results of structured neuropsychological testing were analyzed preoperatively and 1 year postoperatively. Sensorimotor deficits assessed with the National Institutes of Health Stroke Scale were considered to be possible confounders. RESULTS: Patients with preoperatively poor test results showed improvement in various items such as psychological well-being (95% CI [0.55-2.25], P = .002), vitality (95% CI [0.23-1.68], P = .007), general health perception (95% CI [0.09-1.44], P = .014), psychoticism (95% CI [-12.24 to -4.85], P < .001), and psychomotor processing speed (95% CI [0.10-1.14], P = .010), whereas the intensity of depression fell by a mean of 6.9 points (95% CI [-10.14 to -3.61], P < .001). For patients without preoperative neuropsychological or HRQOL deterioration, preservation of these functions without relevant worsening after revascularization was observed. Significant improvement in vitality, psychological well-being, psychoticism, psychomotor processing speed, and depression were also seen in patients with unchanged National Institutes of Health Stroke Scale. CONCLUSION: Chronic steno-occlusive cerebral hypoperfusion in patients with MMD not only may lead to neurological deficits but is also associated with neuropsychological impairment, reduced HRQOL, and increased depression. The results of this study show that patients with preoperative neuropsychological deterioration might benefit from revascularization surgery, whereas patients without preoperative impairment continue to remain stable postoperatively. Neuropsychological assessment should be routinely evaluated and considered a relevant variable when determining treatment for patients with MMD.

Intraoperative MRI-Guided Resection Is Not Superior to 5-Aminolevulinic Acid Guidance in Newly Diagnosed Glioblastoma: A Prospective Controlled Multicenter Clinical Trial.

PURPOSE: Prospective data suggested a superiority of intraoperative MRI (iMRI) over 5-aminolevulinic acid (5-ALA) for achieving complete resections of contrast enhancement in glioblastoma surgery. We investigated this hypothesis in a prospective clinical trial and correlated residual disease volumes with clinical outcome in newly diagnosed glioblastoma. METHODS: This is a prospective controlled multicenter parallel-group trial with two center-specific treatment arms (5-ALA and iMRI) and blinded evaluation. The primary end point was complete resection of contrast enhancement on early postoperative MRI. We assessed resectability and extent of resection by an independent blinded centralized review of preoperative and postoperative MRI with 1-mm slices. Secondary end points included progression-free survival (PFS) and overall survival (OS), patient-reported quality of life, and clinical parameters. RESULTS: We recruited 314 patients with newly diagnosed glioblastomas at 11 German centers. A total of 127 patients in the 5-ALA and 150 in the iMRI arm were analyzed in the as-treated analysis. Complete resections, defined as a residual tumor ≤0.175 cm³, were achieved in 90 patients (78%) in the 5-ALA and 115 (81%) in the iMRI arm (P = .79). Incision-suture times (P < .001) were significantly longer in the iMRI arm (316 v 215 [5-ALA] minutes). Median PFS and OS were comparable in both arms. The lack of any residual contrast enhancing tumor (0 cm³) was a significant favorable prognostic factor for PFS (P < .001) and OS (P = .048), especially in methylguanine-DNA-methyltransferase unmethylated tumors (P = .006). CONCLUSION: We could not confirm superiority of iMRI over 5-ALA for achieving complete resections. Neurosurgical interventions in newly diagnosed glioblastoma shall aim for safe complete resections with 0 cm³ contrast-enhancing residual disease, as any other residual tumor volume is a negative predictor for PFS and OS.

PrImary decompressive Craniectomy in AneurySmal Subarachnoid hemOrrhage (PICASSO) trial: study protocol for a randomized controlled trial.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is associated with poor neurological outcome and high mortality. A major factor influencing morbidity and mortality is brain swelling in the acute phase. Decompressive craniectomy (DC) is currently used as an option in order to reduce intractably elevated intracranial pressure (ICP). However, execution and optimal timing of DC remain unclear. METHODS: PICASSO resembles a multicentric, prospective, 1:1 randomized standard treatment-controlled trial which analyzes whether primary DC (pDC) performed within 24 h combined with the best medical treatment in patients with poor-grade SAH reduces mortality and severe disability in comparison to best medical treatment alone and secondary craniectomy as ultima ratio therapy for elevated ICP. Consecutive patients presenting with poor-grade SAH, defined as grade 4-5 according to the World Federation of Neurosurgical Societies (WFNS), will be screened for eligibility. Two hundred sixteen patients will be randomized to receive either pDC additional to best medical treatment or best medical treatment alone. The primary outcome is the clinical outcome according to the modified Rankin Scale (mRS) at 12 months, which is dichotomized to favorable (mRS 0-4) and unfavorable (mRS 5-6). Secondary outcomes include morbidity and mortality, time to death, length of intensive care unit (ICU) stay and hospital stay, quality of life, rate of secondary DC due to intractably elevated ICP, effect of size of DC on outcome, use of duraplasty, and complications of DC. DISCUSSION: This multicenter trial aims to generate the first confirmatory data in a controlled randomized fashion that pDC improves the outcome in a clinically relevant endpoint in poor-grade SAH patients. TRIAL REGISTRATION: DRKS DRKS00017650. Registered on 09 June 2019.

Near-zero cohesion and loose packing of Bennu's near subsurface revealed by spacecraft contact.

When the OSIRIS-REx spacecraft pressed its sample collection mechanism into the surface of Bennu, it provided a direct test of the poorly understood near-subsurface physical properties of rubble-pile asteroids, which consist of rock fragments at rest in microgravity. Here, we find that the forces measured by the spacecraft are best modeled as a granular bed with near-zero cohesion that is half as dense as the bulk asteroid. The low gravity of a small rubble-pile asteroid such as Bennu effectively weakens its near subsurface by not compressing the upper layers, thereby minimizing the influence of interparticle cohesion on surface geology. The underdensity and weak near subsurface should be global properties of Bennu and not localized to the contact point.

Case Report: Posterolateral Epidural Supra-C2-Root Approach (PESCA) for Biopsy of a Retro-Odontoid Lesions in Same Sitting After Occipitocervical Fixation and Decompression in a Case of Crowned Dens Syndrome With Brainstem Compression and Displacement.

Background: 'Crowned dens syndrome' (CDS) is a special form of calcium pyrophosphate dihydrate deposition disease which is characterized radiologically by a halo-like or crown-like distribution in the periodontoid region and clinically by cervical pain. Herein, we will describe our experience of posterolateral epidural supra-C2-root approach (PESCA) for biopsy of retro-odontoid lesions in one surgical session after occipitocervical fixation and decompression in a patient with CDS and massive brainstem compression. Case Presentation: A 70-year-old woman presented to our department with a 4-week history of progressive walking impairment, neck pain, neck rigidity, fever, dizziness, slight palsy of the left hand, and multiple fall episodes. Magnetic resonance imaging (MRI) of the craniovertebral junction (CVJ) and cervical spine revealed a lesion of the odontoid process and the retro-odontoid region with mainly solid components, as well as small cystic components, and brainstem compression and displacement. In first step, fusion surgery of the CVJ C0-C4 was performed with occiptocervical decompression. After fusion and decompression the lower lateral part of the C1 arc and the lateral superior part of the left side of the C2 arc were removed. The entry point was located directly above the superior part of the C2 root. A biopsy of the lateral portions of the lesions was obtained by bioptic forceps under microscope guidance. Pathologic examination of the mass revealed deposition of birefringent crystals compatible with calcium pyrophosphate. In addition to the clinical symptoms (especially neck pain), the diagnosis of CDS was made. Non-steroidal inflammatory drugs (NSAIDs) and colchicine (and later magnesium) were started. At follow-up examination 6 months after surgery, an MRI scan of the cervical spine revealed regression of the pannus and the cyst with replacement of the brainstem, clinical improvement of walking, and increased strength of the left hand. Conclusions: This study demonstrates that PESCA can be used to obtain tissue for pathological analysis in one surgical sitting after fusion and decompression and that fusion, decompression, and PESCA (in the same session) together with subsequent conservative management could be a good alternative for the treatment of CDS.

Design and Evaluation of a Custom-Made Electromyographic Biofeedback System for Facial Rehabilitation.

Background: In the rehabilitation of postoperative facial palsy, physical therapy is of paramount importance. However, in the early rehabilitation phase, voluntary movements are often limited, and thus, the motivation of patients is impacted. In these situations, biofeedback of facial electromyographic (EMG) signals enables the visual representation of the rehabilitation progress, even without apparent facial movements. In the present study, we designed and evaluated a custom-made EMG biofeedback system enabling cost-effective facial rehabilitation. Methods: This prospective study describes a custom-made EMG system, consisting of a microcontroller board and muscle sensors, which was used to record the EMG of frontal and zygomatic facial muscles during frowning and smiling. First, the mean EMG amplitudes and movement onset detection rates (ACC) achieved with the custom-made EMG system were compared with a commercial EMG device in 12 healthy subjects. Subsequently, the custom-made device was applied to 12 patients with and without postoperative facial paresis after neurosurgical intervention. Here, the ratio [laterality index (LI)] between the mean EMG amplitude of the healthy and affected side was calculated and related to the facial function as measured by the House and Brackmann scale (H&B) ranging from 1 (normal) to 6 (total paralysis). Results: In healthy subjects, a good correlation was measured between the mean EMG amplitudes of the custom-made and commercial EMG device for both frontal (r = 0.84, p = 0.001) and zygomatic muscles (r = 0.8, p = 0.002). In patients, the LI of the frontal and zygomatic muscles correlated significantly with the H&B (r = -0.83, p = 0.001 and r = -0.65, p = 0.023). The ACC of the custom-made EMG system varied between 65 and 79% depending on the recorded muscle and cohort. Conclusion: The present study demonstrates a good application potential of our custom-made EMG biofeedback device to detect facial EMG activity in healthy subjects as well as patients with facial palsies. There is a correlation between the electrophysiological measurements and the clinical outcome. Such a device might enable cost-efficient home-based facial EMG biofeedback. However, movement detection accuracy should be improved in future studies to reach ranges of commercial devices.

Quality of life impairment in adult Moyamoya patients-preoperative neuropsychological assessment and correlation to MRI and H215O PET findings.

Moyamoya angiopathy (MMA) related cerebral perfusion deficits or infarctions might influence quality of life (QoL). This study examines preoperative QoL in adult patients with MMA and correlates these with findings obtained via diagnostic imaging. Sixty-seven adult Moyamoya patients underwent preoperative neuropsychological testing including questionnaires to determine QoL, as well as psychiatric and depressive symptoms. The results were checked for correlation with territorial hypoperfusions seen in H215O PET with acetazolamide (ACZ) challenge (cerebrovascular reserve) and infarction patterns observed in MRI. Each vascular territory was analyzed separately and correlated with QoL. Physical role function was restricted in 41.0% of cases and emotional role function in 34.4% of cases (SF-36). Obsessive-compulsive disorder (39.3%) (SCL-90-R), psychoticism (34.4%) (SCL-90-R), and depression (32.7%) (BDI-II) were also very common. Psychoticism was significantly more frequent in cases where perfusion deficits in PET CT were observed in both MCA territories (left p = 0.0124, right p = 0.0145) and infarctions in MRI were present in the right MCA territory (p = 0.0232). Depression was significantly associated with infarctions in the right MCA territory (SCL-90-R p = 0.0174, BDI-II p = 0.0246). Women were affected more frequently by depression (BDI-II, p = 0.0234). Physical role function impairment was significantly associated with perfusion deficits in the left MCA territory (p = 0.0178) and infarctions in the right MCA territory (p = 0.0428). MMA leads to impairments in different areas of QoL. Approximately one-third of all adult MMA patients suffered from depression, with women being most affected. In addition to depression, presence of executive dysfunctions and mental disorders such as psychoticism, obsessive-compulsive disorder, and impaired physical and emotional role function affected QoL. These patients showed significantly more often infarctions and perfusion deficits in the right MCA territory. Long-term studies with follow-up results are necessary to clarify a possible beneficial impact of early surgical revascularization on QoL and depression in adult MMA patients.

Early Post-operative CT-Angiography Imaging After EC-IC Bypass Surgery in Moyamoya Patients.

Objective: To evaluate the clinical value of early post-operative computed tomographic angiography (CTA) after direct extracranial-intracranial (EC-IC) bypass surgery in moyamoya patients. Methods: A retrospective analysis of all adult moyamoya patients treated at our center from 2013 to 2019 with a direct EC-IC bypass was performed. Early post-operative CTA (within 24 h after surgery) was compared with conventional digital subtraction angiography (DSA) 6-12 months after surgery. If available, magnetic resonance time-of-flight angiography (MR-TOF) was evaluated 3 months and 6-12 months post-operatively as well. Imaging results were analyzed and compared with CTA, MR-TOF and DSA, whereat DSA was used as the final and definite modality to decide on bypass patency. Results: A total of 103 direct EC-IC bypasses in 63 moyamoya patients were analyzed. All inclusion criteria were met in 32 patients (53 direct bypasses). In 84.9% the bypass appeared definitively, in 5.7% uncertainly and in 9.4% not patent according to early post-operative CTA. MR-TOF suggested definitive bypass patency in 86.8% 3 months after surgery and in 93.5% 6-12 months after surgery. DSA 6-12 months post-operatively showed a patency in 98.1% of all bypasses. The positive predictive value (to correctly detect an occluded bypass) on post-operative CTA was 12.5%, the negative predictive value (to correctly detect a patent bypass) was 100% with a sensitivity of 100% and a specificity of 86.5%. Conclusion: Early post-operative CTA has a high predictive value to confirm the patency of a bypass. On the other hand, a high false positive rate of (according to CTA) occluded bypasses after direct EC-IC bypass surgery can be seen. This must be considered critically when initiating possible therapeutic measures.

One-on-one mentoring for final year medical students during the neurosurgery rotation.

BACKGROUND: Medical students show varying clinical practical skills when entering their final year clinical clerkship, which is the final period to acquire and improve practical skills prior to their residency. We developed a one-on-one mentoring program to allow individually tailored teaching of clinical practical skills to support final year students with varying skill sets during their neurosurgical clinical clerkship. METHODS: Each participating student (n = 23) was paired with a mentor. At the beginning students were asked about their expectations, teaching preferences and surgical interest. Regular meetings and evaluations of clinical practical skills were scheduled every 2 weeks together with fixed rotations that could be individually adjusted. The one-on-one meetings and evaluations with the mentor gave each student the chance for individually tailored teaching. After completion of the program each student evaluated their experience. RESULTS: The mentoring program was well received by participating students and acquisition or improvement of clinical practical skills was achieved by most students. A varying practical skill level and interest in the field of surgery was seen. CONCLUSIONS: A neurosurgical one-on-one mentoring program is well received by final year medical students and allows for individually tailored learning of clinical practical skills.

Posterolateral epidural supra-C2-root approach (PESCA) for biopsy of lesions of the odontoid process in same sitting after occipitocervical fixation and decompression-perioperative management and how to avoid vertebral artery injury.

This study aims to describe the posterolateral epidural supra-C2-root approach (PESCA), which might be a good alternative to the transoral, anterolateral, and other posterolateral approaches for biopsy of lesions of the odontoid process (OP). The preoperative planning of PESCA included computerized tomography (CT), CT-angiography, and three-dimensional reconstruction (if possible, even with three-dimensional print) to analyze the angle of the trajectory and the anatomy of the vertebral artery (VA). For PESCA, the patient is positioned under general anesthesia in prone position. In case of an osteolytic lesion with fracture of the OP, an X-ray is performed after positioning to verify anatomic alignment. In the first step, in case of instability and compression of the spinal cord, a craniocervical fusion and decompression is performed (laminectomy of the middle part of the C1 arc and removal of the lower part of the lateral C1 arc). The trajectory is immediately above the C2 root (and under the upper rest of the lateral part of C1 arc). Even if the trajectory is narrowed, it is possible to perform PESCA without relevant traction of the spinal cord. The vertical segment of V3 of the VA at the level of C2 is protected by the vertebral foramen, and the horizontal part of V3 is protected by the remnant upper lateral part of the C1 arc (in case of normal variants). PESCA might be a good choice for biopsy of selected lesions of the OP in same sitting procedure after craniocervical stabilization and decompression.

Technical limitations and pitfalls of diffusion-weighted imaging in intraoperative high-field MRI.

OBJECTIVE: Image quality in high-field intraoperative MRI (iMRI) is often influenced negatively by susceptibility artifacts. While routine sequences are rather robust, advanced imaging such as diffusion-weighted imaging (DWI) is very sensitive to susceptibility resulting in insufficient imaging data. This study aims to analyze intraoperatively acquired DWI to identify the main factors for susceptibility, to compare results with postoperative images and to identify technical aspects for improvement of intraoperative DWI. METHODS: 100 patients with intraaxial lesions operated in a high-field iMRI were analyzed retrospectively for the quality of intraoperative DWI in comparison to the postoperative scan. General quality of the MR scan, individual diffusion restrictions, artifacts, and their causes were analyzed. RESULTS: Inclusion criteria were met in 78 patients, 124 diffusion restrictions were included in the comparative analysis. PPV and NPV for the detection of DWI changes intraoperatively were 0.94 and 0.56, respectively (SEN 0.94; SPE 0.56). Image quality was rated significantly (p < 0.0001) worse intraoperatively compared to the postoperative MRI. The main reasons for reduced image quality intraoperatively were air (64%) and artificial material (e.g., compress) (38%) in the resection cavity, as well as positioning of patient's head outside the MR's isocenter 37%. Analysis of surgical approaches showed that frontal craniotomies have the highest risk of limited image quality (40%), whereat better results (15% limited image quality) were seen for all other approaches (p = 0.059). CONCLUSION: Intraoperative DWI showed reliable results in this analysis. However, image-quality was limited severely in many cases leading to uncertainty in the interpretation. Susceptibility-causing factors might be prevented in many cases, if the surgical team is aware of them. The most important factors are good filling of the resection cavity with irrigation fluid, not placing artificial materials in the resection cavity and adequate positioning of patient's head according to the MR isocenter.

Neuropsychological impairment in adults with moyamoya angiopathy: preoperative assessment and correlation to MRI and H215O PET.

Patients with moyamoya angiopathy (MMA) are known to have an increased risk of impaired executive function (dysexecutive cognitive syndrome (DCS)). Numbers of moyamoya patients with DCS vary strongly in the literature; evidence of a correlation to affected vascular territories is low. This study aims to identify cognitive impairment in adult moyamoya patients and to correlate findings with imaging results. In addition, the predictive value of individual tests for the identification of DCS was analyzed. Neuropsychological test data of 41 adult moyamoya patients was analyzed for a possible correlation with territorial hypoperfusion on H215O PET with acetazolamide (ACZ) challenge (cerebrovascular reserve-CVR) and infarction patterns observed in MRI. Each vascular territory was analyzed separately and correlated to neuropsychological test results and to the presence of DCS. In total, 41.5% of patients presented with DCS. Significant association of DCS and affection of the right middle cerebral artery (MCA) territory was seen for insufficient CVR in PET (p = 0.030) and for patients with infarctions seen in MRI (p = 0.014). Analysis of individual neuropsychological test results confirmed the main association with the right MCA territory, as well as some association with the right anterior cerebral artery (ACA) territory. Analysis of a subgroup of patients with chronic disease on MRI (presence of large post-infarction gliosis and brain atrophy in affected territories) revealed a significantly higher risk for DCS (85% affected) than non-chronic patients (21% affected) (p < 0.001). Analysis of neuropsychological test data in this moyamoya cohort reveals DCS in 41.5% of all patients. Correlation between DCS and an impairment of CVR seen in PET and/or infarctions seen in MRI was significant for the right MCA territory. Patients with chronic disease had a significantly higher risk for DCS than non-chronic patients (p < 0.001).

Persulfide Dioxygenase From Acidithiobacillus caldus: Variable Roles of Cysteine Residues and Hydrogen Bond Networks of the Active Site.

Persulfide dioxygenases (PDOs) are abundant in Bacteria and also crucial for H2S detoxification in mitochondria. One of the two pdo-genes of the acidophilic bacterium Acidithiobacillus caldus was expressed in Escherichia coli. The protein (AcPDO) had 0.77 ± 0.1 Fe/subunit and an average specific sulfite formation activity of 111.5 U/mg protein (Vmax) at 40°C and pH 7.5 with sulfur and GSH following Michaelis-Menten kinetics. KM for GSH and Kcat were 0.5 mM and 181 s-1, respectively. Glutathione persulfide (GSSH) as substrate gave a sigmoidal curve with a Vmax of 122.3 U/mg protein, a Kcat of 198 s-1 and a Hill coefficient of 2.3 ± 0.22 suggesting positive cooperativity. Gel permeation chromatography and non-denaturing gels showed mostly tetramers. The temperature optimum was 40-45°C, the melting point 63 ± 1.3°C in thermal unfolding experiments, whereas low activity was measurable up to 95°C. Site-directed mutagenesis showed that residues located in the predicted GSH/GSSH binding site and in the central hydrogen bond networks including the iron ligands are essential for activity. Among these, the R139A, D141A, and H171A variants were inactive concomitant to a decrease of their melting points by 3-8 K. Other variants were inactivated without significant melting point change. Two out of five cysteines are likewise essential, both of which lie presumably in close proximity at the surface of the protein (C87 and C224). MalPEG labeling experiments suggests that they form a disulfide bridge. The reducing agent Tris(2-carboxyethyl)phosphine was inhibitory besides N-ethylmaleimide and iodoacetamide suggesting an involvement of cysteines and the disulfide in catalysis and/or protein stabilization. Mass spectrometry revealed modification of C87, C137, and C224 by 305 mass units equivalent to GSH after incubation with GSSH and with GSH in case of the C87A and C224A variants. The results of this study suggest that disulfide formation between the two essential surface-exposed cysteines and Cys-S-glutathionylation serve as a protective mechanism against uncontrolled thiol oxidation and the associated loss of enzyme activity.

Tracheotomy Outcomes in Super Obese Patients.

IMPORTANCE: Surgeons need to understand the expected outcomes for super obese patients undergoing tracheotomy to appropriately counsel patients and families about likely risks and benefits. OBJECTIVE: To determine the outcomes, complications, and mortality after tracheotomy in super obese patients (those with a body mass index [BMI] greater than 50). DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of billing records from a tertiary care academic medical center from November 1, 2010, through June 30, 2013, to identify patients undergoing tracheotomy. Medical records were reviewed to identify patients with a BMI (calculated as weight in kilograms divided by height in meters squared) greater than 50 and a control group with a BMI of 30 to 50. Patient characteristics, including BMI, age, race/ethnicity, primary diagnosis for hospitalization, medical comorbidities, and surgical technique, were measured. MAIN OUTCOMES AND MEASURES: The primary outcome measure was dependence on tracheostomy at discharge. Secondary outcomes included rates of ventilator dependence, mortality, postoperative complications, and discharge disposition. RESULTS: The super obese population included 31 patients and was predominantly African American (20 patients [65%]) and female (21 patients [68%]). Mean BMI of super obese patients was 64.0 (range, 50.2-95.5). The obese patient population was mainly African American (25 patients [74%]) and female (17 patients [50%]). Twenty-five of 31 super obese patients (81%) were discharged with a tracheotomy tube in place, compared with 16 of 34 obese patients (52%). Seven patients (23%) in the super obese group were ventilator dependent at discharge, compared with 4 patients (13%) in the obese group. Only 2 of the super obese patients (3%) were decannulated before discharge, compared with 15 (44%) in the obese group. In-hospital mortality was similar for the 2 groups (super obese, 4 patients [13%] and obese, 3 patients [9%]). The overall complication rate was 19% in the super obese group (6 patients) compared with 6% in the obese group (2 patients). Super obese patients were less likely to be discharged to a health care facility (17 patients [55%]) compared with patients in the obese group (22 patients [65%]). CONCLUSIONS AND RELEVANCE: Tracheotomy in super obese patients is a safe and effective strategy for airway management. Critically ill, super obese patients have a high likelihood of remaining dependent on a tracheotomy or ventilator at the time of discharge.

Relationships among measures of physical activity and hearing in African Americans: The Jackson Heart Study.

OBJECTIVES/HYPOTHESIS: To evaluate the relationships among measures of physical activity and hearing in the Jackson Heart Study. STUDY DESIGN: Prospective cohort study. METHODS: We assessed hearing on 1,221 Jackson Heart Study participants who also had validated physical activity questionnaire data on file. Hearing thresholds were measured across frequency octaves from 250 to 8,000 Hz, and various frequency pure-tone averages (PTAs) were constructed, including PTA4 (average of 500, 1,000, 2,000, and 4,000 Hz), PTA-high (average of 4,000 and 8,000 Hz), PTA-mid (average of 1,000 and 2,000 Hz), and PTA-low (average of 250 and 500 Hz). Hearing loss was defined for pure tones and pure-tone averages as >25 dB HL in either ear and averaged between the ears. Associations between physical activity and hearing were estimated using linear regression, reporting changes in decibel hearing level, and logistic regression, reporting odds ratios (OR) of hearing loss. RESULTS: Physical activity exhibited a statistically significant but small inverse relationship with PTA4, -0.20 dB HL per doubling of activity (95% confidence interval [CI]: -0.35, -0.04; P = .016), as well as with PTA-low and pure tones at 250, 2,000, and 4,000 Hz in adjusted models. Multivariable logistic regression modeling supported a decrease in the odds of high-frequency hearing loss among participants who reported at least some moderate weekly physical activity (PTA-high, OR: 0.69 [95% CI: 0.52, 0.92]; P = .011 and 4000 Hz, OR: 0.75 [95% CI: 0.57, 0.99]; P = .044). CONCLUSIONS: Our study provides further evidence that physical activity is related to better hearing; however, the clinical significance of this relationship cannot be estimated given the nature of the cross-sectional study design. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:2376-2381, 2016.

Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5.

Increased dietary fructose in rodents recapitulates many aspects of the Metabolic Syndrome with hypertension, insulin resistance and dyslipidemia. Here we show that fructose increased jejunal NaCl and water absorption which was significantly decreased in mice whose apical chloride/base exchanger Slc26a6 (PAT1, CFEX) was knocked out. Increased dietary fructose intake enhanced expression of this transporter as well as the fructose-absorbing transporter Slc2a5 (Glut5) in the small intestine of wild type mice. Fructose feeding decreased salt excretion by the kidney and resulted in hypertension, a response almost abolished in the knockout mice. In parallel studies, a chloride-free diet blocked fructose-induced hypertension in Sprague Dawley rats. Serum uric acid remained unchanged in animals on increased fructose intake with hypertension. We suggest that fructose-induced hypertension is likely caused by increased salt absorption by the intestine and kidney and the transporters Slc26a6 and Slc2a5 are essential in this process.