Comparative Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke Patients with ASPECTS 2-3 vs. 4-5.

BACKGROUND: The influence of Alberta Stroke Program Early CT Score (ASPECTS) on outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients with low ASPECTS remains unknown. In this study, we compared the outcomes of AIS patients treated with MT for large vessel occlusion (LVO) categorized by ASPECTS value. METHODS: We conducted a retrospective analysis involving 305 patients with AIS caused by LVO, defined as the occlusion of the internal carotid artery and/or the M1 segments of the middle cerebral artery, stratified into two groups: ASPECTS 2-3 and 4-5. The primary outcome was favorable outcome defined as a 90-day modified Rankin Scale (mRS) score of 0-3. Secondary outcomes were 90-day mRS 0-2, 90-day mortality, any intracerebral hemorrhage (ICH), and symptomatic ICH (sICH). We performed multivariable logistic regression analysis to evaluate the impact of ASPECTS 2-3 vs. 4-5 on outcomes. RESULTS: Fifty-nine patients (19.3%) had ASPECTS 2-3 and 246 (80.7%) had ASPECTS 4-5. Favorable outcomes showed no significant difference between the two groups (adjusted odds ratio [aOR]= 1.13, 95% confidence interval [CI]: 0.52-2.41, p=0.80). There were also no significant differences in 90-day mRS 0-2 (aOR= 1.65, 95% CI: 0.66-3.99, p=0.30), 90-day mortality (aOR= 1.14, 95% CI: 0.58-2.20, p=0.70), any ICH (aOR= 0.54, 95% CI: 0.28-1.00, p=0.06), and sICH (aOR= 0.70, 95% CI: 0.27-1.63, p = 0.40) between the groups. CONCLUSIONS: AIS patients with LVO undergoing MT with ASPECTS 2-3 had similar outcomes compared to ASPECTS 4-5.

Integration of conventional and digital surgical guide fabrication techniques for the partially edentulous patient: Reducing the number of surgical procedures for a complete arch implant-supported prosthesis.

Surgical procedures on partially edentulous patients for complete arch implant-supported prostheses involve remaining tooth extraction, alveolar bone reduction, and implant placement. Traditionally, partially edentulous patients undergo multiple surgeries, which extends the healing time and results in an extensively prolonged total treatment timeline. This technical article focuses on the fabrication of a more stable and predictive surgical guide to perform multiple surgical procedures in a single surgical appointment and planning a complete arch implant-supported prosthesis for the partially edentulous patient.

Internal Carotid Artery Occlusion: Management.

PURPOSE OF REVIEW: Acute internal carotid artery occlusion (ICAO) is associated with high rates of morbidity and mortality, whereas chronic ICAO can present insidiously with recurrent strokes. In this review, we discuss the medical and surgical management approaches among patients with acute, subacute, and chronic ICAO. RECENT FINDINGS: We reviewed the recent literature regarding clinical presentation of acute and chronic cases of ICAO, and discuss the current data, accepted guidelines, and prospects. Surgical, endovascular, or a combination (hybrid) revascularization has been shown to be effective in recanalization with improved functional outcomes in patients with ICAO in comparison to systemic thrombolysis or medical therapy alone. Future prospective or randomized clinical trials are warranted to elucidate the procedural superiority for revascularization of patients with ICAO.

Effect of Hispanic Status in Mechanical Thrombectomy Outcomes After Ischemic Stroke: Insights From STAR.

Background and Purpose: Epidemiological studies have shown racial and ethnic minorities to have higher stroke risk and worse outcomes than non-Hispanic Whites. In this cohort study, we analyzed the STAR (Stroke Thrombectomy and Aneurysm Registry) database, a multi-institutional database of patients who underwent mechanical thrombectomy for acute large vessel occlusion stroke to determine the relationship between mechanical thrombectomy outcomes and race. Methods: Patients who underwent mechanical thrombectomy between January 2017 and May 2020 were analyzed. Data included baseline characteristics, vascular risk factors, complications, and long-term outcomes. Functional outcomes were assessed with respect to Hispanic status delineated as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic patients. Multivariate analysis was performed to identify variables associated with unfavorable outcome or modified Rankin Scale ≥3 at 90 days. Results: Records of 2115 patients from the registry were analyzed. Median age of Hispanic patients undergoing mechanical thrombectomy was 60 years (72­84), compared with 63 years (54­74) for NHB, and 71 years (60­80) for NHW patients (P<0.001). Hispanic patients had a higher incidence of diabetes (41%; P<0.001) and hypertension (82%; P<0.001) compared with NHW and NHB patients. Median procedure time was shorter in Hispanics (36 minutes) compared to NHB (39 minutes) and NHW (44 minutes) patients (P<0.001). In multivariate analysis, Hispanic patients were less likely to have favorable outcome (odds ratio, 0.502 [95% CI, 0.263­0.959]), controlling for other significant predictors (age, admission National Institutes Health Stroke Scale, onset to groin time, number of attempts, procedure time). Conclusions: Hispanic patients are less likely to have favorable outcome at 90 days following mechanical thrombectomy compared to NHW or NHB patients. Further prospective studies are required to validate our findings.

Management of brain metastases from large cell neuroendocrine carcinoma of the lung: improved outcomes with radiosurgery.

OBJECTIVES: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare pulmonary tumor, having similar natural history and management strategy as small cell lung cancer. Therefore, the management of brain metastases in these patients has mirrored that of SCLC through the use of whole brain radiation therapy (WBRT). We used the National Cancer Database (NCDB) to look at predictors of stereotactic radiosurgery (SRS) and any potential differences in outcomes for patients with brain metastases from LCNEC. MATERIAL AND METHODS: We queried the NCDB from 2004 to 2015 for patients with LCNEC of the lung with brain metastases that received brain radiation. Univariable and multivariable analyses were performed to identify factors predictive of SRS use and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Out of 9970 patients with LCNEC of the lung we identified 348 with brain metastases. Sixty-eight patients were treated with upfront SRS and 280 were treated with WBRT. Patients that were treated at an academic facility or received chemotherapy as part of upfront treatment were more likely to receive SRS. Univariable analysis revealed improved outcomes with SRS compared to WBRT, with a median OS of 11 months compared to 6 months, respectively (p = .007). Multivariable Cox regression with propensity score confirmed SRS to have improved survival (HR: 0.68, 95%CI: 0.51-0.91, p = .0093). Multivariable Cox regression with propensity score also identified younger age, receipt of chemotherapy, absence of extracranial disease and non-rural locations as additional predictors of improved OS. CONCLUSIONS: Treatment of brain metastases from LCNEC of the lung with SRS was associated with improved survival. For the appropriate patients, upfront treatment of limited brain metastases with SRS may be appropriate.

Perineural invasion present exclusively in central tissue blocks of Mohs surgical excisions of basal cell carcinoma.

Perineural invasion (PNI) may be present in basal cell carcinomas (BCC) treated with Mohs micrographic surgery. This single-centre, non-randomised, prospective study demonstrates the potential for PNI to exist exclusively within the central tissue blocks of Mohs specimens.

'Something in the way she moves': The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI).

Protein disulfide isomerase (PDI) has diverse functions in the endoplasmic reticulum as catalyst of redox transfer, disulfide isomerization and oxidative protein folding, as molecular chaperone and in multi-subunit complexes. It interacts with an extraordinarily wide range of substrate and partner proteins, but there is only limited structural information on these interactions. Extensive evidence on the flexibility of PDI in solution is not matched by any detailed picture of the scope of its motion. A new rapid method for simulating the motion of large proteins provides detailed molecular trajectories for PDI demonstrating extensive changes in the relative orientation of its four domains, great variation in the distances between key sites and internal motion within the core ligand-binding domain. The review shows that these simulations are consistent with experimental evidence and provide insight into the functional capabilities conferred by the extensive flexible motion of PDI.

Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.

To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.

A temperature-sensitive allele of a putative mRNA splicing helicase down-regulates many cell wall genes and causes radial swelling in Arabidopsis thaliana.

The putative RNA helicase encoded by the Arabidopsis gene At1g32490 is a homolog of the yeast splicing RNA helicases Prp2 and Prp22. We isolated a temperature-sensitive allele (rsw12) of the gene in a screen for root radial swelling mutants. Plants containing this allele grown at the restrictive temperature showed weak radial swelling, were stunted with reduced root elongation, and contained reduced levels of cellulose. The role of the protein was further explored by microarray analysis. By using both fold change cutoffs and a weighted gene coexpression network analysis (WGCNA) to investigate coexpression of genes, we found that the radial swelling phenotype was not linked to genes usually associated with primary cell wall biosynthesis. Instead, the mutation has strong effects on expression of secondary cell wall related genes. Many genes potentially associated with secondary walls were present in the most significant WGCNA module, as were genes coding for arabinogalactans and proteins with GPI anchors. The proportion of up-regulated genes that possess introns in rsw12 was above that expected if splicing was unrelated to the activity of the RNA helicase, suggesting that the helicase does indeed play a role in splicing in Arabidopsis. The phenotype may be due to a change in the expression of one or more genes coding for cell wall proteins.

A review of biophysical and socio-economic effects of unconventional oil and gas extraction - Implications for South Africa.

The impacts associated with unconventional oil and gas (UOG) extraction will be cumulative in nature and will most likely occur on a regional scale, highlighting the importance of using strategic decision-making and management tools. Managing possible impacts responsibly is extremely important in a water scarce country such as South Africa, versus countries where more water may be available for UOG extraction activities. This review article explains the possible biophysical and socio-economic impacts associated with UOG extraction within the South African context and how these complex impacts interlink. Relevant policy and governance frameworks to manage these impacts are also highlighted.

Solar elastosis and cutaneous melanoma: a site-specific analysis.

Cutaneous melanomas are postulated to arise through at least two causal pathways, namely the "chronic sun exposure" and "nevus" pathways. While chronic sun exposure probably causes many head/neck melanomas, its role at other sites is unclear. In a population-based, case-case comparison study conducted in Brisbane, Australia, we determined the prevalence and epidemiologic correlates of chronic solar damage in skin adjacent to invasive, incident melanomas on the trunk (n = 418) or head/neck (n = 92) among patients aged 18-79 in 2007-2010. Participants self-reported information about environmental and phenotypic factors, and a dermatologist counted nevi and actinic keratoses. Dermatopathologists assessed solar elastosis adjacent to each melanoma using a four-point scale (nil, mild, moderate, marked), and noted the presence or absence of adjacent neval remnants. We measured associations between various factors and solar elastosis using polytomous logistic regression. Marked or moderate solar elastosis was observed in 10% and 27%, respectively, of trunk melanomas, and 60% and 17%, respectively, of head/neck melanomas. At both sites, marked elastosis was positively associated with age (p(trend) < 0.0001) and inversely associated with neval remnants (p(trend) < 0.001). For trunk melanomas, marked elastosis was associated with highest quartiles of total sun exposure [odds-ratio (OR) = 5.47, 95% confidence interval (CI) = 1.08-27.60] and facial freckling (OR = 2.98, 95% CI = 1.17-7.56), and inversely associated with deeply tanning skin (OR = 0.29, 95% CI = 0.08-1.11) and high nevus counts (OR = 0.08, 95% CI = 0.01-0.66). Mostly similar associations were observed with moderate solar elastosis. About one in three trunk melanomas in Queensland have evidence of moderate-to-marked sun damage, and they differ in risk associations from those without.

Prospective study of patterns of surgical management in adults with primary cutaneous melanoma at high risk of spread, in Queensland, Australia.

BACKGROUND: Knowledge of variation in diagnosis and surgery in high-risk primary melanoma patients is limited. We assessed frequency and determinants of diagnostic procedures, wide local excision (WLE) and sentinel lymph node biopsy (SLNB). METHODS: People in Queensland newly diagnosed with melanoma, clinical stage 1b or 2, were recruited prospectively. Patient information was collected from questionnaires and pathology records. Differences in surgical procedures in relation to host and tumor characteristics were assessed. RESULTS: In 787 participants, primary melanoma was diagnosed by surgical excision (74%), shave (14%), punch (12%) or incisional (1%) biopsy. General practitioners (GPs) diagnosed 80%. Diagnostic procedure differed by remoteness of residence, health sector, treating doctor's specialty and melanoma site and thickness. 766 patients had WLE, 86% by surgeons. Of 134 residual melanomas, 13 (10%) were ≤ 1 mm at diagnosis but > 1 mm at WLE, mostly after shave biopsy. SLNB was performed in 261 (33%) patients. SLNB was more common in those under 50, in remoter locations or treated by GP initially, and less common with head and neck melanoma. CONCLUSION: Diagnostic and surgical procedures for primary melanoma vary substantially and partial biopsy can influence initial tumor microstaging. Patient, tumor and doctor characteristics influence SLNB practice.

Q2DSTD NMR deciphers epitope-mapping variability for peptide recognition of integrin αvß6.

Integrin αvß6 is a cell surface arginine-glycine-aspartic acid (RGD)-specific heterodimeric glycoprotein that is only expressed on epithelia during processes of tissue remodelling, including cancer. The specificity and molecular nature of interactions toward this integrin are poorly understood and new insights into such processes are important to cell biologists and pharmaceutical drug discovery. This study demonstrates the application of quantitative two-dimensional saturation transfer (Q2DSTD) NMR to obtain precise details of peptide interactions with integrin αvß6 and their correlation to specificity for the integrin. This approach highlights subtle but significant differences in ligand contact by three related 21-mer peptides: FMDV2, an αvß6 specific peptide and DBD1 and LAP2T1 peptides that bind many αv integrins in addition to αvß6. FMDV2 and DBD1 differ only by the cyclisation of DBD1; a process that removes αvß6 specificity. Q2DSTD NMR demonstrates these peptides experience significantly different interactions with the integrin; FMDV contacts primarily through four residues: 6Leu, 10Leu, 12Val and 13Leu, whereas DBD1 and LAP2T1 have more widespread contacts across their sequences. Q2DSTD NMR combined two-dimensional STD with quantitation by considering the relaxation of the ligand (CRL) to provide precise ligand contact information. This study also examines the role of CRL in the Q2DSTD process and how quantitation modifies STD data and unravels epitope-mapping variability to provide precise results that differentiate interactions at the atomic level for each peptide.

Verruciform xanthoma of the penis: a rare Australian case.

We present a case of verruciform xanthoma ((VX) of the penis in an elderly man in whom an asymptomatic papule on his foreskin was noted during a routine clinical examination. VX is a rare, benign condition with a predilection for the oral cavity and clinically presents as isolated, painless mucosal lesions with a verrucoid surface. Accurate diagnosis is important in avoiding aggressive surgical management of this relatively rare condition.

19F NMR spectroscopy monitors ligand binding to recombinantly fluorine-labelled b'x from human protein disulphide isomerase (hPDI).

We report a protein-observe (19)F NMR-based ligand titration binding study of human PDI b'x with Δ-somatostatin that also emphasises the need to optimise recombinant protein fluorination when using 5- or 6-fluoroindole. This study highlights a recombinant preference for 5-fluoroindole over 6-fluoroindole; most likely due to the influence of fluorine atomic packing within the folded protein structure. Fluorination affords a single (19)F resonance probe to follow displacement of the protein x-linker as ligand is titrated and provides a dissociation constant of 23 ± 4 µM.

High-resolution NMR studies of structure and dynamics of human ERp27 indicate extensive interdomain flexibility.

ERp27 (endoplasmic reticulum protein 27.7 kDa) is a homologue of PDI (protein disulfide-isomerase) localized to the endoplasmic reticulum. ERp27 is predicted to consist of two thioredoxin-fold domains homologous with the non-catalytic b and b' domains of PDI. The structure in solution of the N-terminal b-like domain of ERp27 was solved using high-resolution NMR data. The structure confirms that it has the thioredoxin fold and that ERp27 is a member of the PDI family. (15)N-NMR relaxation data were obtained and ModelFree analysis highlighted limited exchange contributions and slow internal motions, and indicated that the domain has an average order parameter S(2) of 0.79. Comparison of the single-domain structure determined in the present study with the equivalent domain within full-length ERp27, determined independently by X-ray diffraction, indicated very close agreement. The domain interface inferred from NMR data in solution was much more extensive than that observed in the X-ray structure, suggesting that the domains flex independently and that crystallization selects one specific interdomain orientation. This led us to apply a new rapid method to simulate the flexibility of the full-length protein, establishing that the domains show considerable freedom to flex (tilt and twist) about the interdomain linker, consistent with the NMR data.

Treatment of an Intracranial Fusiform Vertebral Aneurysm Using the MVP® Micro Vascular Plug System as an Adjunct to Pipeline(TM) Embolization: Technical Case Instruction.

Fusiform and dolichoectatic aneurysms pose unique challenges in treatment, often requiring alternative approaches compared to saccular aneurysms. Microsurgical options like clipping or a bypass can be difficult, leading to the advancement of endovascular techniques. Flow-diverting stents and vessel sacrifice with detachable coils have shown efficacy in reconstruction. The MVP® Micro Vascular Plug System (Medtronic, Minneapolis, Minnesota, USA) offers a resheathable plug for vessel occlusion through electrolytic detachment. This case report illustrates the supplementary application of MVP® subsequent to flow diverter (FD) stenting, resulting in the effective endovascular management of a fusiform aneurysm affecting both vertebral arteries (VA), following unsuccessful coil vessel sacrifice treatment. A 61-year-old female presented with an unruptured fusiform aneurysm in the bilateral vertebral arteries (VAs). Treatment included a flow diverter in the right VA and vessel sacrifice in the left VA using Onyx-18 and coils. Despite initial success, left V4 segment recanalization occurred. Endovascular treatment, deploying two devices and additional coils using the MVP®, halted the flow. Follow-up showed left VA occlusion and reconstruction of the treated right VA, with the patient being discharged without deficits. This case demonstrates a unique approach using MVP® alongside a flow diverter (a PipelineTM Embolization Device (PED), Medtronic) for the treatment of a V4 segment fusiform aneurysm. This innovative technique is an alternative when conventional coil embolization for vessel sacrifice fails. The MVP®'s ease of use and precise delivery render it a feasible and efficacious alternative for treating complex aneurysms.

Surgical Posture with Microscopic Versus Exoscopic Visualization in Anterior Cervical Procedures.

BACKGROUND: Surgeons sustain deviated postures during procedures even with the use of loupes or an operative microscope. The surgical exoscope is a new intraoperative visualization technology designed to improve surgical ergonomics; however, no objective data exist to say that surgeon posture is significantly improved. This study aimed to quantify the difference in posture during standard anterior cervical spine procedures performed with the aid of an operative microscope versus an exoscope. METHODS: This was a prospective cohort study utilizing a posture-sensing device at the surgeon's cervicothoracic junction. The primary outcome was the proportion of time under scope spent in a deviated posture, defined as greater than 10 degrees of deviation from neutral in the x- and y-axes (flexion/extension and lateral bending) of the surgeon's upper torso. Average deviation from baseline for the x-, y-, and z-axes (flexion/extension, lateral bending, and axial rotation, respectively), as well as the percentage of operative time spent with the visualization aid was also analyzed. RESULTS: Overall, 37 anterior cervical procedures were recorded: 18 were performed with an exoscope and 19 with a microscope. Surgeons spent significantly more time in the deviated posture with the operative microscope than with the exoscope (32% vs. 8% with x-axis >10 deg, P <0.005; 20% vs. 6% with y-axis >10 deg, P <0.05). This is also reflected by the significant differences in the average deviation in the x- and y-axes, while under scope. CONCLUSIONS: Utilizing the exoscope for anterior cervical spine procedures allows surgeons to spend less time in a deviated posture.

Frontotemporal craniotomy with orbital osteotomy for superior hypophyseal artery aneurysm clipping.

Superior hypophyseal artery (SHA) aneurysms are rare paraclinoid aneurysms with a mortality rate as high as 3%-6%. Surgical clipping of these aneurysms is technically challenging due to the surrounding anatomy. The large size and complicated surrounding anatomy make endovascular coiling very difficult. Here we present the case of a ruptured right SHA aneurysm. The authors present technical nuances of the clipping using an exoscope rather than a traditional microscope. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23157.

Impact of Procedure Time on First Pass Effect in Mechanical Thrombectomy for Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT). METHODS: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation. RESULTS: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable. CONCLUSION: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.