Bilateral Basal Ganglia Hemorrhage in a Patient with Confirmed COVID-19.

Bilateral basal ganglia hemorrhage is exceedingly rare. To our knowledge, our patient is the first reported case of a confirmed coronavirus disease 2019 (COVID-19) patient who had bilateral basal ganglia hemorrhage. In the absence of other risk factors for bilateral deep cerebral involvement, we suspect that COVID-19 may be contributing to these rare pathologies. Most published data represent a correlation between COVID-19 and neurologic complications, and more research is still needed to prove causation.

Ostium Ratio and Neck Ratio Could Predict the Outcome of Sidewall Intracranial Aneurysms Treated with Flow Diverters.

BACKGROUND AND PURPOSE: Incompletely occluded flow diverter treated aneurysms remain at risk of rupture and thromboembolic complications. Our aim was to identify the potential for incomplete occlusion of intracranial aneurysms treated by flow diverters. We investigated whether aneurysm ostium size in relation to parent artery size affects angiographic outcomes of flow diverter-treated sidewall aneurysms. MATERIALS AND METHODS: Flow diverter-treated sidewall aneurysms were divided into "occluded" and "residual" (incomplete occlusion) groups based on 6-month angiographic follow-up. We calculated the ostium ratio, a new parameter defined as the aneurysm ostium surface area versus the circumferential surface area of the parent artery. We also calculated the neck ratio, defined as clinical aneurysm neck diameter versus parent artery diameter from pretreatment 2D DSA, as a 2D surrogate. We compared the performance of these ratios with existing aneurysm morphometrics (size, neck diameter, volume, aspect ratio, size ratio, undulation index, nonsphericity index, ellipticity index, bottleneck factor, aneurysm angle, and parent vessel angle) and flow diverter-related parameters (metal coverage rate and pore density). Statistical tests and receiver operating characteristic analyses were performed to identify significantly different parameters between the 2 groups and test their predictive performances. RESULTS: We included 63 flow diverter-treated aneurysms, 46 occluded and 17 residual. The ostium ratio and neck ratio were significantly higher in the residual group than in the occluded group (P < .001 and P = .02, respectively), whereas all other parameters showed no statistical difference. As discriminating parameters for occlusion, ostium ratio and neck ratio achieved areas under the curve of 0.912 (95% CI, 0.838-0.985) and 0.707 (95% CI, 0.558-0.856), respectively. CONCLUSIONS: High ostium ratios and neck ratios could predict incomplete occlusion of flow diverter-treated sidewall aneurysms. Neck ratio can be easily calculated by interventionists to predict flow-diverter treatment outcomes.

Marginal ulcer perforation: a single center experience.

PURPOSE: Marginal ulcer (MU) is defined as ulcer on the jejunal side of the gastrojejunostomy (GJ) anastomosis. Most MUs are managed medically but those with complications like bleeding or perforation require intervention. It is recommended that GJ anastomosis be revised in patients with MU perforation (MUP). The aim of this case series is to study the clinical presentation and management of MUP. METHODS: Three hundred and thirty-two patients who underwent emergency surgery for perforated peptic ulcer at a single center were studied over a period of 5 years. RESULTS: Nine patients (2.7 %) presented with MUP. GJ was previously done for either complicated peptic ulcer (n = 4) or for suspected gastric malignancy (n = 5). Two patients had previously completed H. pylori therapy. None of the patients presented with septic shock. MU was on the jejunal side of GJ in all patients. The median MUP size was 10 mm. Four patients (44.4 %) had omental patch repair, three (33.3 %) had primary closure, and one each had revision of GJ and jejunal serosal patch repair. There were no leaks, intra-abdominal abscess or reoperation and no malignancies. CONCLUSION: MUP patients do not present with septic shock. Omental patch repair or primary closure is sufficient enough. Revision of Billroth-II-GJ into Roux-en-Y-GJ is not mandatory.

Enhanced aneurysmal flow diversion using a dynamic push-pull technique: an experimental and modeling study.

BACKGROUND AND PURPOSE: Neurovascular flow diverters are flexible, braided stent-meshes for intracranial aneurysm treatment. We applied the dynamic push-pull technique to manipulate the flow-diverter mesh density at the aneurysm orifice to maximize flow diversion. This study investigated the hemodynamic impact of the dynamic push-pull technique on patient-specific aneurysms by using the developed high-fidelity virtual-stenting computational modeling technique combined with computational fluid dynamics. MATERIALS AND METHODS: We deployed 2 Pipeline Embolization Devices into 2 identical sidewall anterior cerebral artery aneurysm phantoms by using the dynamic push-pull technique with different delivery-wire advancements. We then numerically simulated these deployment processes and validated the simulated mesh geometry. Computational fluid dynamics analysis was performed to evaluate detailed hemodynamic changes by deployed flow diverters in the sidewall aneurysm and a fusiform basilar trunk aneurysm (deployments implemented previously). Images of manipulated flow diverter mesh from sample clinical cases were also evaluated. RESULTS: The flow diverters deployed in silico accurately replicated in vitro geometries. Increased delivery wire advancement (21 versus 11 mm) by using a dynamic push-pull technique produced a higher mesh compaction at the aneurysm orifice (50% metal coverage versus 36%), which led to more effective aneurysmal inflow reduction (62% versus 50% in the sidewall aneurysm; 57% versus 36% in the fusiform aneurysm). The dynamic push-pull technique also caused relatively lower metal coverage along the parent vessel due to elongation of the flow diverter. High and low mesh compactions were also achieved for 2 real patients by using the dynamic push-pull technique. CONCLUSIONS: The described dynamic push-pull technique increases metal coverage of pure braided flow diverters over the aneurysm orifice, thereby enhancing the intended flow diversion, while reducing metal coverage along the parent vessel to prevent flow reduction in nearby perforators.

Evaluation of a second-generation self-expanding variable-porosity flow diverter in a rabbit elastase aneurysm model.

BACKGROUND AND PURPOSE: The self-expanding V-POD is a second-generation flow-diverting device with a low-porosity PTFE patch on a self-expanding microstent. The authors evaluated this device for the treatment of elastase-induced aneurysms in rabbits. MATERIALS AND METHODS: Three V-POD types (A, circumferential patch closed-cell stent [n = 9]; B, asymmetric patch closed-cell stent [n = 7]; and C, asymmetric patch open-cell stent [n = 4]) were evaluated by using angiography, conebeam micro-CT, histology, and SEM. Aneurysm flow modifications were expressed in terms of immediate poststent/prestent ratios of maximum CA volume entering the aneurysm dome tracked on procedural angiograms. Flow modifications were correlated with 4 weeks' follow-up angiographic, micro-CT, histologic, and SEM results. RESULTS: Mechanical stent-deployment difficulties in 4 aneurysms (1 type A; 3 type B) led to suboptimal results and exclusion from analysis. Of the remaining 16 aneurysms, 4-week post-treatment angiograms showed no aneurysm filling in 10 (63%), 3 (∼19%) had no filling with a small remnant neck, and 3 (∼19%) had <0.25 filling. Successfully treated aneurysms (n = 16) demonstrated an immediate poststent/prestent CA maximum volume ratio of 0.13 ± 0.18% (0.0%-0.5%). Favorable contrast-flow modification on immediate angiography after deployment correlated significantly with aneurysm occlusion on follow-up angiography, micro-CT, and histology. The occlusion percentage derived from micro-CT was 96 ± 6.8%. Histology indicated advanced healing (grade ≥3) in the aneurysm dome in 13 of 16 cases. SEM revealed 15 of 16 stents in an advanced state of endothelialization. CONCLUSIONS: This study showed the feasibility and effectiveness of V-POD for aneurysm healing in a rabbit elastase model.

The Micro-Angiographic Fluoroscope (MAF) in High Definition (HD) Mode for Improved Contrast-to-Noise Ratio and Resolution in Fluoroscopy and Roadmapping.

During image guided interventional procedures, superior resolution and image quality is critically important. Operating the MAF in the new High Definition (HD) fluoroscopy mode provides high resolution and increased contrast-to-noise ratio. The MAF has a CCD camera and a 300 micron cesium iodide x-ray convertor phosphor coupled to a light image intensifier (LII) through a fiber-optic taper. The MAF captures 1024 × 1024 pixels with an effective pixel size of 35 microns, and is capable of real-time imaging at 30 fps. The HD mode uses the advantages of higher exposure along with a small focal spot effectively improving the contrast-to-noise ratio (CNR) and the spatial resolution. The Control Acquisition Processing and Image Display System (CAPIDS) software for the MAF controls the LII gain. The interventionalist can select either fluoroscopic or angiographic modes using the two standard foot pedals. When improved image quality is needed and the angiography footpedal is used for HD mode, the x-ray machine will operate at a preset higher exposure rate using a small focal spot, while the CAPIDS will automatically adjust the LII gain to achieve proper image brightness. HD mode fluoroscopy and roadmapping are thus achieved conveniently during the interventional procedure. For CNR and resolution evaluation we used a bar phantom with images taken in HD mode with both the MAF and a Flat Panel Detector (FPD). It was seen that the FPD could not resolve more than 2.8 lp/mm whereas the MAF could resolve more than 5 lp/mm. The CNR of the MAF was better than that of the FPD by 60% at lower frequencies and by 600% at the Nyquist frequency of the FPD. The HD mode has become the preferred mode during animal model interventions because it enables detailed features of endovascular devices such as stent struts to be visualized clearly for the first time. Clinical testing of the MAF in HD mode is imminent.

Outcomes of ruptured intracranial aneurysms treated by microsurgical clipping and endovascular coiling in a high-volume center.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze the 3-month outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH) treated from January 2005 to June 2006. This paper describes the outcomes after treatment of aneurysmal SAH and comparison between patients treated by clipping or coiling in a high volume center. MATERIALS AND METHODS: A retrospective chart review was performed of records of 195 consecutive patients with SAH. The overall outcome and the pretreatment variables predicting outcomes and the difference between the clipping and coiling groups were analyzed by logistic regression analysis. RESULTS: A total of 105 (55%) patients had microsurgical clipping and 87 (45%) had endovascular coiling. At 3 months, 69% of patients recovered with no or mild disability. The predictors of a 3-month modified Rankin Scale (mRS) were Hunt and Hess (HH) grade on admission and the presence of intracerebral hemorrhage (ICH). Patients in the coiling group had worse admission grades; they had worse 3-month mRS (2.28 vs 1.73), but this was not significant when the groups were matched (P = .38). Vasospasm rate was significantly higher in the clipping group (66% vs 52%). The immediate incomplete occlusion rate of aneurysms was higher (21.7% vs 7.6%) in the coiling group. CONCLUSION: The overall results of treatment of aneurysmal SAH have improved. There is no significant difference in the outcomes between the patients in the clipping and coiling groups.

MDCT in the staging of gallbladder carcinoma.

OBJECTIVE: The purpose of our study was to determine the utility of dual-phase MDCT with 3D reconstruction in the staging and resectability of gallbladder carcinoma. SUBJECTS AND METHODS: Twenty-seven consecutive patients with suspected gallbladder carcinoma on clinical examination and routine sonography were prospectively analyzed with dual-phase MDCT. Of these patients, only 20 who underwent a laparotomy for extended cholecystectomy or a palliative surgery were included in the study. Three-dimensional volume-rendered reconstruction was used for evaluation of the vascular invasion and anatomy. The staging and resectability as determined on CT were compared with preoperative findings. RESULTS: On the basis of the CT findings, eight tumors were resectable and 12 were unresectable. On surgery, 11 tumors were found to be resectable and the remaining were unresectable. Overstaging by CT occurred in three patients due to overassessment of duodenal infiltration. CT had a sensitivity of 72.7%, a specificity of 100%, and an accuracy of 85% for determining resectability of gallbladder carcinoma. For the diagnosis of hepatic and vascular invasion by the tumor, there was 100% correlation between CT and surgery. Vascular variations were found in six of the 11 patients who underwent radical cholecystectomy. CONCLUSION: Dual-phase MDCT with 3D reconstruction is a comprehensive imaging technique for staging gallbladder carcinoma and determining the vascular road map before surgery.

Determinants of the peptide-induced conformational change in the human class II major histocompatibility complex protein HLA-DR1.

The human class II major histocompatibility complex protein HLA-DR1 has been shown previously to undergo a distinct conformational change from an open to a compact form upon binding peptide. To investigate the role of peptide in triggering the conformational change, the minimal requirements for inducing the compact conformation were determined. Peptides as short as two and four residues, which occupy only a small fraction of the peptide-binding cleft, were able to induce the conformational change. A mutant HLA-DR1 protein with a substitution in the beta subunit designed to fill the P1 pocket from within the protein (Gly(86) to Tyr) adopted to a large extent the compact, peptide-bound conformation. Interactions important in stabilizing the compact conformation are shown to be distinct from those responsible for high affinity binding or for stabilization of the complex against thermal denaturation. The results suggest that occupancy of the P1 pocket is responsible for partial conversion to the compact form but that both side chain and main chain interactions contribute to the full conformational change. The implications of the conformational change to intracellular antigen loading and presentation are discussed.

Stable peptide binding to MHC class II molecule is rapid and is determined by a receptive conformation shaped by prior association with low affinity peptides.

Formation of stable class II MHC/peptide complex involves conformational changes and proceeds via an intermediate. Although this intermediate complex forms and dissociates in minutes, its conversion to a stable complex is a very slow process, taking up to a few days to reach completion. Here, we investigate the different steps of this binding and demonstrate that the conformational changes necessary to generate a receptive molecule is the rate-determining slow step in the process, while formation of the stable MHC/peptide complex is very rapid. With HLA-DR1 as our model class II molecule, we first used low affinity variants of hemagglutinin peptide (HA306-318), which lack the principal anchor, to shape the conformation of the MHC and then studied the kinetics of stable binding of HA306-318 to such an induced conformation. We found that the apparent association rate of HA306-318 is equivalent to the dissociation rate of the low affinity peptide. A 4- to 18-fold enhancement in the binding rates of HA306-318 was observed depending on the dissociation rates of the low affinity peptides. These results establish that 1) formation of stable MHC/peptide complexes is very rapid and 2) prior binding of low affinity peptide induces a receptive conformation in MHC for efficient stable peptide binding. Furthermore, in the absence of any free peptide, this receptive molecule rapidly reverts to slow binding behavior toward the subsequently offered peptide. These results have important implications for the roles of low affinity MHC/peptide complexes in Ag presentation.

Sodium dodecyl sulfate stability of HLA-DR1 complexes correlates with burial of hydrophobic residues in pocket 1.

Certain class II MHC-peptide complexes are resistant to SDS-induced dissociation. This property, which has been used as an in vivo as well as an in vitro peptide binding assay, is not understood at the molecular level. Here we have investigated the mechanistic basis of SDS stability of HLA-DR1 complexes by using a biosensor-based assay and SDS-PAGE with a combination of wild-type and mutant HLA-DR1 and variants of hemagglutinin peptide HA306-318. Experiments with wild-type DR1 along with previously published results establish that the SDS-stable complexes are formed only when the hydrophobic pocket 1 (P1) is occupied by a bulky aromatic (Trp, Phe, Tyr) or an aliphatic residue (Met, Ile, Val, Leu). To further explore whether the SDS sensitivity is primarily due to the exposed hydrophobic regions, we mutated residue beta Gly86 at the bottom of P1 to tyrosine, presumably reducing the depth of the pocket and the exposure of hydrophobic residues and increasing the contacts between subunits. In direct contrast to wild-type DR1, the peptide-free mutant DR1 exists as an alpha/beta heterodimer in SDS. Moreover, the presence of a smaller hydrophobic residue, such as alanine, as P1 anchor with no contribution from any other anchor is sufficient to enhance the SDS stability of the mutant complexes, demonstrating that the basis of SDS resistance may be localized to P1 interactions. The good correlation between SDS sensitivity and the exposure of hydrophobic residues provides a biochemical rationale for the use of this assay to investigate the maturation of class II molecules and the longevity of the complexes.

Minimizing nonproductive substrate binding: a new look at glucoamylase subsite affinities.

A subsite model as proposed by Hiromi [Hiromi, K. (1970) Biochem. Biophys. Res. Commun. 40, 1-6] has been applied to various hydrolases including glucoamylase (GA). The model assumes a single enzyme complex, a hydrolytic rate constant which is independent of substrate length, and a ratelimiting hydrolytic step. Recent kinetic studies with GA contradict these assumptions. Here we reevaluate the substrate binding of GA studying the pre-steady-state kinetics with glucose, which is reported here for the first time, and maltose. The association equilibrium constants for glucose and maltose interactions with wild-type and Trp120-->Phe GA from Aspergillus awamori in H2O and D2O buffers were obtained. Kinetic results indicate that a single glucose molecule binds to GA weakly by a single-step mechanism, E + G1<-->EG1, under the conditions studied. Similar fluorescence intensities of the GA-glucose and GA-maltose complexes, the high tryptophan concentration around subsite 1, crystal structures of various inhibitor complexes, pre-steady-state and steady-state modeling, feasibility of condensation reactions, and other evidence strongly suggest that glucose binds at subsite 1. These results conflict with the high subsite 2 and low subsite 1 affinities obtained using Hiromi's model. Using the substrate association constants for glucose and maltose obtained by pre-steady-state kinetics, the affinity of alpha-glucose for subsite 1 is shown to be substantially higher than the apparent affinity of glucose for subsite 2. We propose a GA catalytic mechanism whereby substrate binding is initiated by subsite 1 interactions with the nonreducing end of the oligosaccharide substrate, minimizing nonproductive substrate binding. Through conformational changes, entropic contributions, and increased local concentration, subsite 2 subsequently has enhanced affinity for the second covalently linked glucosyl residue.

Identification of enzyme-substrate and enzyme-product complexes in the catalytic mechanism of glucoamylase from Aspergillus awamori.

Intermediates in the catalytic mechanism of Aspergillus awamori glucoamylase (GA) were identified by studying pre-steady-state and steady-state kinetics of the wild-type GA/maltose and Trp120 -->Phe GA/maltotriose reactions in H2O and D2O. Pre-steady-state fluorescence signal analysis was carried out to ascertain the relative intrinsic fluorescence of the enzyme intermediates. A three-step minimal pathway for oligosaccharide hydrolysis represented by E + Gx (k1) reversible (k-1) EGX (k2)reversible(k-2) EP (kcat)--> E + P is proposed. The first step, represented by the association constant K1 (k1/k-1), depicts the fast formation of enzyme-substrate complex and is the primary factor in fluorescence quenching. A 2.7-fold increase in K1 with D2O as solvent is observed with both enzymes due to the cumulative effect of deuterium on complex hydrogen bonding at the active site. The second step further quenches the enzyme fluorescence and is identified as the hydrolytic step, forming an enzyme-product complex. Both k2 and k-2 values show similar 2-fold decreases in D2O for both enzymes, consistent with the microscopic reversibility of the hydrolytic reaction. The solvent isotopic effect on the hydrolytic step is likely due to either abstraction of an exchangeable proton from the general acid Glu179 or directed addition of water to the oxocarbonium ion intermediate by the general base Glu400. No significant isotope effect was observed on the steady-state kcat value for wild-type GA with maltose, indicating a ronhydrolytic step as rate-limiting. The third step, a posthydrolytic rate-determining step, is the product release as evident from steady-state kinetics with wild-type and Trp120-->Phe GAs using alpha-D-glucosyl fluoride.