Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

CONTEXT.­: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. OBJECTIVE.­: To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. DESIGN.­: Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. RESULTS.­: In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). CONCLUSIONS.­: PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Predictors of occlusion, long-term outcomes, and safety in a cohort of 674 aneurysms treated with the Pipeline embolization device.

OBJECTIVE: By providing a more physiological approach to the treatment of intracranial aneurysms, the Pipeline embolization device (PED) has revolutionized the endovascular treatment of aneurysms. Although there are many flow diverters on the market, the authors report their experience with the PED, the first flow diverter to be approved by the Food and Drug Administration. They aimed to assess the efficacy and safety of PED flow diversion for the treatment of a wide range of aneurysms, as well as to look at factors affecting occlusion. METHODS: This is a retrospective study of a prospectively maintained database of patients treated with the PED between January 2011 and December 2019. Charts were reviewed for patient, aneurysm, and procedure characteristics. The primary outcomes of interest were complication rates, occlusion outcomes (O'Kelly-Marotta grading scale), and functional outcomes (modified Rankin Scale [mRS]). Secondary outcomes included predictors of incomplete occlusion at 6 and 24 months of follow-up. RESULTS: The study cohort included 581 patients with 674 aneurysms. Most aneurysms (90.5%) were in the anterior circulation and had a saccular morphology (85.6%). Additionally, 638 aneurysms (94.7%) were unruptured, whereas 36 (5.3%) were acutely ruptured. The largest mean aneurysm diameter was 8.3 ± 6.1 mm. Complications occurred at a rate of 5.5% (n = 32). The complete occlusion rate was 89.3% at 24 months' follow-up, and 94.8% of patients had a favorable neurological outcome (mRS score 0-2) at the last follow-up. On multivariate analysis, predictors of incomplete aneurysm occlusion at 6 months were hypertension (OR 1.7, p = 0.03), previous aneurysm treatment (OR 2.4, p = 0.001), and increasing aneurysm neck diameter (OR 1.2, p = 0.02), whereas a saccular morphology was protective (OR 0.5, p = 0.05). Predictors of incomplete occlusion at 24 months were increasing aneurysm neck diameter (OR 1.2, p = 0.01) and previous aneurysm treatment (OR 2.3, p = 0.01). CONCLUSIONS: The study findings are corroborated by those of previous studies and trials. The complete occlusion rate was 89.3% at 24 months' follow-up, with 94.8% of patients having favorable functional outcomes (mRS score 0-2). Aneurysm treatment before PED deployment and an increasing aneurysm neck diameter increase the risk of incomplete occlusion at 6 and 24 months.

Comparison of PED/PED Flex and PED Shield in the treatment of unruptured intracerebral aneurysms.

OBJECTIVE: The object of this study was to compare the efficacy and safety profile of the Pipeline embolization device (PED)/Pipeline Flex embolization device (PED Flex) with that of the Pipeline Flex embolization device with Shield Technology (PED Shield). After introducing the first-generation PED and the second-generation PED Flex with its updated delivery system, the PED Shield was launched with a synthetic layer of phosphorylcholine surface modification to reduce thrombogenicity. METHODS: This is a retrospective review of unruptured aneurysms treated with PED/PED Flex versus PED Shield between 2017 and 2022 at the authors' institution. Patients with ruptured aneurysms, adjunctive treatment, failed flow diverter deployment, and prior treatment of the target aneurysm were excluded. Baseline characteristics were collected for all patients, including age, sex, past medical history (hypertension, hyperlipidemia, diabetes mellitus), smoking status, aneurysm location, and aneurysm dimensions (neck, width, height) and morphology (saccular, nonsaccular). The primary outcome was procedural and periprocedural complication rates. RESULTS: The study cohort comprised 200 patients with 200 aneurysms, including 150 aneurysms treated with the PED/PED Flex and 50 treated with the PED Shield. With respect to intraprocedural and periprocedural complications, length of stay, length of follow-up, and functional outcome at discharge, there was no significant difference between the two cohorts. At the midterm follow-up, the rate of in-stent stenosis (PED/PED Flex: 14.2% vs PED Shield: 14.6%, p = 0.927), aneurysm occlusion (complete occlusion: 79.5% vs 80.5%, respectively; neck remnant: 4.7% vs 12.2%; dome remnant: 15.7% vs 7.3%; p = 0.119), and the need for retreatment (5.3% vs 0%, p = 0.097) were comparable between the two cohorts. CONCLUSIONS: This study suggests that, as compared to first- and second-generation PED and PED Flex, the third-generation PED Shield offers similar rates of complications, aneurysm occlusion, and in-stent stenosis at the midterm follow-up.

The Rate and Predictors of 30-Day Readmission in Patients Treated for Unruptured Cerebral Aneurysms: A Large Single-Center Study.

BACKGROUND AND OBJECTIVES: Numerous studies of various populations and diseases have shown that unplanned 30-day readmission rates are positively correlated with increased morbidity and all-cause mortality. In this study, we aim to provide the rate and predictors of 30-day readmission in patients undergoing treatment for unruptured intracranial aneurysms. METHODS: This is a retrospective study of 525 patients presenting for aneurysm treatment between 2017 and 2022. All patients who were admitted and underwent a successful treatment of their unruptured intracerebral aneurysms were included in the study. The primary outcome was the rate and predictors of 30-day readmission. RESULTS: The rate of 30-day readmission was 6.3%, and the mean duration to readmission was 7.8 days ± 6.9. On univariate analysis, factors associated with 30-day readmission were antiplatelet use on admission (odds ratio [OR]: 0.4, P = .009), peri-procedural rupture (OR: 15.8, P = .007), surgical treatment of aneurysms (OR: 2.2, P = .035), disposition to rehabilitation (OR: 9.5, P < .001), and increasing length of stay (OR: 1.1, P = .0008). On multivariate analysis, antiplatelet use on admission was inversely correlated with readmission (OR: 0.4, P = .045), whereas peri-procedural rupture (OR: 9.5, P = .04) and discharge to rehabilitation (OR: 4.5, P = .029) were independent predictors of 30-day readmission. CONCLUSION: In our study, risk factors for 30-day readmission were aneurysm rupture during the hospital stay and disposition to rehabilitation, whereas the use of antiplatelet on admission was inversely correlated with 30-day readmission. Although aneurysm rupture is a nonmodifiable risk factor, more studies are encouraged to focus on the correlation of antiplatelet use and rehabilitation disposition with 30-day readmission rates.

Predictors of Transfemoral Access Site Complications in Neuroendovascular Procedures: A large Single-Center Cohort Study.

OBJECTIVE: The transfemoral (TF) route has historically been the preferred access site for endovascular procedures. However, despite its widespread use, TF procedures may confer morbidity as a result of access site complications. The aim of this study is to provide the rate and predictors of TF access site complications for neuroendovascular procedures. METHODS: This is a single center retrospective study of TF neuroendovascular procedures performed between 2017 and 2022. The incidence of complications and associated risk factors were analyzed across a large cohort of patients. RESULTS: The study comprised of 2043 patients undergoing transfemoral neuroendovascular procedures. The composite rate of access site complications was 8.6 % (n = 176). These complications were divided into groin hematoma formation (n = 118, 5.78 %), retroperitoneal hematoma (n = 14, 0.69 %), pseudoaneurysm formation (n = 40, 1.96 %), and femoral artery occlusion (n = 4, 0.19 %). The cross-over to trans radial access rate was 1.1 % (n = 22). On univariate analysis, increasing age (OR=1.0, p = 0.06) coronary artery disease (OR=1.7, p = 0.05) peripheral vascular disease (OR=1.9, p = 0.07), emergent mechanical thrombectomy procedures (OR=2.1, p < 0.001) and increasing sheath size (OR=1.3, p < 0.001) were associated with higher TF access site complications. On multivariate analysis, larger sheath size was an independent risk factor for TF access site complications (OR=1.8, p = 0.02). CONCLUSION: Several pertinent factors contribute towards the incidence of TF access site complications. Factors associated with TF access site complications include patient demographics (older age) and clinical risk factors (vascular disease), as well as periprocedural factors (sheath size).

Minimally invasive intracerebral hemorrhage evacuation: A bibliometric analysis of current research trends.

OBJECTIVE: Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Randomized clinical trials focusing on minimally invasive surgery (MIS) for ICH evacuation have suggested a potential benefit regarding mortality but results remain unclear regarding impact on functional outcome. This study presents a bibliometric analysis investigating the current trends in the literature on MIS for ICH. METHODS: Using the Scopus collection database, a search was performed to identify literature that discussed MIS for ICH from 2000 to 2021. Primary research articles were included in this study. Reviews and book chapters were excluded. Analysis and visualization of the included literature were completed with VOSviewer. RESULTS: A total of 278 articles were identified. An upward trend in publications began in 2008, with the most publications in 2021 (36) followed by 2020 (25). The most citations occurred in 2013 (1192). The h-index, i-10 and i-100 were 37, 79 and 6 respectively. For the top 100 most cited studies, the mean citation count was 45.55 with a range of 6-760. The highest-producing institutions of MIS for ICH literature were Johns Hopkins University (31, 15 %), University of Chicago with (21, 10 %), Guiyang Medical College (17, 8 %), and Icahn School of Medicine at Mount Sinai (15, 7 %). Keyword analysis revealed four major avenues: 1) medication enhancement of clot removal, 2) minimally invasive devices such as endoscopes, 3) craniotomy approach, and 4) physiology of clot removal. CONCLUSIONS: The literature on MIS for ICH has been expanding since 2008. Key topics include thrombolysis, device innovation, and surgical approach.

Social Media and Neurosurgery: Insights from the Top 100 Neurosurgery Influencers on Twitter.

BACKGROUND: The rise in popularity of social media (SoMe) in medicine has created a powerful tool for the professional development and continued education of clinicians. Numerous benefits of SoMe exist; however, significant challenges concerning professionalism, confidentiality, and spread of misinformation may limit its usefulness. To understand the ways the top 100 Twitter influencers interact with SoMe, their views on SoMe, and its future in the medical field. METHODS: Literature was reviewed to obtain common concerns about SoMe in the medical field. A survey with 30 questions was sent to the top 100 Twitter influencers in the Neurosurgical field identified by Riccio et al. The survey assessed participant demographics, SoMe activity, stance toward SoMe, and views on the future of SoMe. RESULTS: Most participants were in the age group of 35-44 years (n = 23, 44.2%), resided in the United States (n = 39, 73.6%), have been in practice for 6-10 years (n = 14, 26.4%), and ranked Twitter as the mostly used platform (n = 37,72.6%). Per participant Reponses, 35 (66%) participants have taken a political stance on SoMe, 0 (0%) have gotten into any legal issues regarding a post shared on SoMe, 45 (84.9%) agreed/strongly agreed that SoMe is essential for networking and mentorship, and 49 (92.3%) agreed/strongly agreed that that SoMe will continue to play a major role in the medical field. CONCLUSIONS: Although SoMe has its advantages, several disadvantages render it a double-edged sword. Maximizing SoMe's benefits and minimizing its misuse will further strengthen its role in the medical field.

The Effect of COVID-19 Vaccines on Stroke Outcomes: A Single-Center Study.

BACKGROUND: One of the defining narratives of the COVID-19 pandemic has been the acceptance and distribution of vaccine. To compare the outcomes of COVID-19 positive vaccinated and unvaccinated stroke patients. METHODS: This is a single-center retrospective study of COVID-19-vaccinated and unvaccinated stroke patients between April 2020 and March 2022. All patients presenting with stroke regardless of treatment modalities were included. National Institutes of Health Stroke Scale was used to assess stroke severity. The primary outcome was functional capacity of the patients at discharge. RESULTS: The study cohort comprised 203 COVID-19 positive stroke patients divided into 139 unvaccinated and 64 fully vaccinated patients. At discharge, the modified Rankin scale score was significantly lower in the vaccinated cohort (3[1-4] vs. 4[2-5], odds ratio = 0.508, P = 0.011). At 3 months of follow-up, the median modified Rankin scale score was comparable between both cohorts. CONCLUSIONS: Although vaccination did not show any significant difference in stroke patient outcomes on follow-up, vaccines were associated with lower rates of morbidity and mortality at discharge among stroke patients during the pandemic.

Comparison of Flow-Redirection Endoluminal Device and Pipeline Embolization Device in the Treatment of Intracerebral Aneurysms.

BACKGROUND: The use of flow diverters for treating intracranial aneurysms has been widely used in the past decade; however, data comparing pipeline embolization device (PED; Medtronic Inc) and flow-redirection endoluminal device (FRED; MicroVention) in the treatment of intracranial aneurysms remain scarce. OBJECTIVE: To compare the outcomes of PED and FRED in the treatment of intracranial aneurysms. METHODS: This is a single-center retrospective review of aneurysms treated with PED and FRED devices. Patients treated with PED or FRED were included. Cases requiring multiple or adjunctive devices were excluded. Primary outcome was complete aneurysm occlusion at 6 months. Secondary outcomes included good functional outcome, need for retreatment, and any complication. RESULTS: The study cohort comprised 150 patients, including 35 aneurysms treated with FRED and 115 treated with PED. Aneurysm characteristics including location and size were comparable between the 2 cohorts. 6-month complete occlusion rate was significantly higher in the PED cohort (74.7% vs 51.5%; P = .017) but lost significance after inverse probability weights. Patients in the PED cohort were associated with higher rates of periprocedural complications (3.5% vs 0%; P = .573), and the rate of in-stent stenosis was approximately double in the FRED cohort (15.2% vs 6.9%; P = .172). CONCLUSION: Compared with PED, FRED offers modest 6-month occlusion rates, which may be due to aneurysmal and baseline patient characteristics differences between both cohorts. Although not significant, FRED was associated with a higher complication rate mostly because of in-stent stenosis. Additional studies with longer follow-up durations should be conducted to further evaluate FRED thrombogenicity.

Amelioration of Alpha-1 Antitrypsin Deficiency Diseases with Genome Editing in Transgenic Mice.

Alpha-1 antitrypsin deficiency (AATD) is a hereditary liver disease caused by mutations in the SERPINA1 serine protease inhibitor gene. Most severe patients are homozygous for PiZ alleles (PiZZ; amino acid E324K), which lead to protein aggregates in hepatocytes and reduced circulating levels of AAT. The liver aggregates typically lead to fibrosis, cirrhosis, and hepatocellular carcinoma, and the reduced circulating AAT levels can lead to emphysema and chronic obstructive pulmonary diseases. In this study, two CRISPR/Cas9 gene editing approaches were used to decrease liver aggregates and increase systemic AAT-M levels in the PiZ transgenic mouse. In the first approach, AAT expression in hepatocytes was reduced more than 98% following the systemic delivery of AAV8-CRISPR targeting exon 2 of hSERPINA1, leading to reduced aggregates in hepatocytes. In the second approach, a second adeno-associated virus, which provided the donor template to correct the Z mutation, was also administered. These treated mice had reduced AAT expression (> 98%) and a low level (5%) of wildtype AAT-M mRNA. Taken together, this study shows that CRISPR gene editing can efficiently reduce liver expression of AAT-Z and restore modest levels of wildtype AAT-M in a mouse model of AATD, raising the possibility of CRISPR gene editing therapeutic for AATD.