Bivalirudin as a substitute for heparin in neurointervention for patients with heparin-induced thrombocytopenia.

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.

Background Subtraction Angiography with Deep Learning Using Multi-frame Spatiotemporal Angiographic Input.

Catheter Digital Subtraction Angiography (DSA) is markedly degraded by all voluntary, respiratory, or cardiac motion artifact that occurs during the exam acquisition. Prior efforts directed toward improving DSA images with machine learning have focused on extracting vessels from individual, isolated 2D angiographic frames. In this work, we introduce improved 2D + t deep learning models that leverage the rich temporal information in angiographic timeseries. A total of 516 cerebral angiograms were collected with 8784 individual series. We utilized feature-based computer vision algorithms to separate the database into "motionless" and "motion-degraded" subsets. Motion measured from the "motion degraded" category was then used to create a realistic, but synthetic, motion-augmented dataset suitable for training 2D U-Net, 3D U-Net, SegResNet, and UNETR models. Quantitative results on a hold-out test set demonstrate that the 3D U-Net outperforms competing 2D U-Net architectures, with substantially reduced motion artifacts when compared to DSA. In comparison to single-frame 2D U-Net, the 3D U-Net utilizing 16 input frames achieves a reduced RMSE (35.77 ± 15.02 vs 23.14 ± 9.56, p < 0.0001; mean ± std dev) and an improved Multi-Scale SSIM (0.86 ± 0.08 vs 0.93 ± 0.05, p < 0.0001). The 3D U-Net also performs favorably in comparison to alternative convolutional and transformer-based architectures (U-Net RMSE 23.20 ± 7.55 vs SegResNet 23.99 ± 7.81, p < 0.0001, and UNETR 25.42 ± 7.79, p < 0.0001, mean ± std dev). These results demonstrate that multi-frame temporal information can boost performance of motion-resistant Background Subtraction Deep Learning algorithms, and we have presented a neuroangiography domain-specific synthetic affine motion augmentation pipeline that can be utilized to generate suitable datasets for supervised training of 3D (2d + t) architectures.

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

OBJECTIVES: Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. DATA SOURCES: A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. STUDY SELECTION: Abstracts and full texts were assessed independently and in duplicate by two reviewers. DATA EXTRACTION: Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. DATA SYNTHESIS: The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. CONCLUSIONS: A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.

Charlson Comorbidity Index and Frailty as Predictors of Resolution Following Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.

BACKGROUND: Research on variables associated with chronic subdural hematoma (cSDH) resolution following middle meningeal artery embolization (MMAE) is limited. This study investigated the clinical utility of age-adjusted Charlson Comorbidity Index (ACCI) and modified 5-item Frailty Index (mFI - 5) for predicting cSDH resolution following MMAE. METHODS: We identified patients who underwent MMAE at our institution between January 2018 and December 2022, with at least 20 days of follow-up and one radiographic follow-up study. Patient demographics, characteristics, and outcomes were collected. Complete resolution was defined as absence of subdural collections on CT-scan at last follow-up. Nonage adjusted CCI (CCI), ACCI, and mFI - 5 scores were calculated. Univariate and multivariable logistic regression analyzed the relationship between cSDH resolution and variables. A receiver operating characteristic (ROC) curve established the utility of ACCI and mFI - 5 in predicting hematoma resolution. RESULTS: The study included 85 MMAE procedures. In univariate analysis, patients without resolution were older, had higher CCI, higher ACCI, higher mFI - 5, and were more likely to have diabetes mellitus. In multivarible analysis, CCI (OR: 0.66, 95% CI: 0.48, 0.91) was independently associated with resolution controlling for age and antithrombotic resumption. The area under the ROC (AUROC) curve was 0.75 (95% CI: 0.65-0.85) for ACCI and 0.64 (95% CI: 0.52-0.76) for mFI - 5. The optimal cutoffs for predicting resolution were ACCI ≥5 (sensitivity = 0.63, specificity = 0.77), and mFI - 5 > 0 (sensitivity = 0.84, specificity = 0.43). CONCLUSIONS: ACCI and mFI - 5 moderately predict MMAE resolution and may aid in medical decision-making.

Radionuclide shuntography for cerebrospinal fluid shunt flow evaluation in adults.

OBJECTIVE: Radionuclide shuntography (RS) performed using 99mTc-DTPA injected into the reservoir of CSF shunts enables evaluation of CSF flow for suspected shunt malfunctions. The goal of this study was to report the authors' institutional experience with RS and evaluate its utility and associated complications. METHODS: The authors retrospectively reviewed all RS studies performed between November 2003 and June 2022. Patients with shunted hydrocephalus who were ≥ 18 years of age were included. Patients undergoing RS for evaluation of Ommaya reservoirs were excluded. Demographics, hydrocephalus etiology, presenting symptoms, study results, subsequent management, complications, and intraoperative diagnoses were recorded. Chi-square tests were reported for categorical variables and standard 2 × 2 contingency methods were used for sensitivity/specificity analysis. RESULTS: The authors identified 211 RS procedures performed in 142 patients. The mean age at procedure was 55.6 ± 20.9 years (mean ± SD). Normal pressure hydrocephalus was the most common hydrocephalus etiology (37.0%), followed by congenital malformations (26.1%) and idiopathic intracranial hypertension (15.6%). Successful radionuclide injection was achieved in 207 studies (98.1%). Shunt patency was confirmed in 63.8% of successful injections, whereas malfunction was demonstrated in 27.1% and abnormally slow flow was seen in 9.2%. RS studies demonstrating shunt malfunction were more likely to result in subsequent revisions than were studies showing patency (86.6% vs 2.9%; p < 0.0001). The overall sensitivity and specificity of RS for detecting shunt malfunction was 92.3% and 96.2%, respectively. The median follow-up time was 29 months, with 151 cases having ≥ 6 months of follow-up. There were no complications or infections attributable to RS in this cohort. CONCLUSIONS: RS is a useful and safe tool in the workup of shunt malfunction.

Deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial sections.

Tumors may contain billions of cells including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that is consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.

Quantifying the Effect Size of Management Actions on Aboveground Carbon Stocks in Forest Plantations.

Purpose of the Review: Improved forest management is a promising avenue for climate change mitigation. However, we lack synthetic understanding of how different management actions impact aboveground carbon stocks, particularly at scales relevant for designing and implementing forest-based climate solutions. Here, we quantitatively assess and review the impacts of three common practices-application of inorganic NPK fertilizer, interplanting with N-fixing species, and thinning-on aboveground carbon stocks in plantation forests. Recent Findings: Site-level empirical studies show both positive and negative effects of inorganic fertilization, interplanting, and thinning on aboveground carbon stocks in plantation forests. Recent findings and the results of our analysis suggest that these effects are heavily moderated by factors such as species selection, precipitation, time since practice, soil moisture regime, and previous land use. Interplanting of N-fixing crops initially has no effect on carbon storage in main tree crops, but the effect becomes positive in older stands. Conversely, the application of NPK fertilizers increases aboveground carbon stocks, though the effect lessens with time. Moreover, increases in aboveground carbon stocks may be partially or completely offset by emissions from the application of inorganic fertilizer. Thinning results in a strong reduction of aboveground carbon stocks, though the effect lessens with time. Summary: Management practices tend to have strong directional effects on aboveground carbon stocks in plantation forests but are moderated by site-specific management, climatic, and edaphic factors. The effect sizes quantified in our meta-analysis can serve as benchmarks for the design and scoping of improved forest management projects as forest-based climate solutions. Overall, management actions can enhance the climate mitigation potential of plantation forests, if performed with sufficient attention to the nuances of local conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40725-023-00182-5.

Outpatient telemedicine in neurosurgery: 15,677 consecutive encounters in a comparative analysis of its effectiveness and impact on the surgical conversion rate.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has necessitated the use of telehealth visits (THVs). The effects on neurosurgical practice have not been well characterized, especially concerning new-patient THVs. Therefore, the authors of this study reviewed their institution's experience with outpatient clinic visits and THVs from before the COVID-19 pandemic to the present to focus on clinical metrics, rates of surgery, and the effects of implementing THVs in order to better understand their implications for clinical practice as more data emerge over time. METHODS: The authors reviewed 15,677 consecutive new outpatient in-person visits (IPVs), THVs, and neurosurgical procedures/cases proceeding from their institution between 2018 and 2022 for trends and associations related to THVs. RESULTS: Among spine patients, there was no difference in the proportion of encounters that led to surgery (surgical conversion rate) between THVs and IPVs (p = 0.49). Among cranial patients, THVs were negatively associated with conversion (OR 0.73, p = 0.03). On average, patients using THVs lived further from the hospital (p < 0.001); however, the patient catchment area appeared unchanged. The median distance to the hospital among THV patients was counterbalanced by a decreased distance for spine patients pursing IPVs (p < 0.001), with no significant change to case volume. There was no change in distance to the hospital among cranial patients. For both cranial and spine patients, surgical conversion was more likely among those who lived a great distance from the hospital if their initial encounter was an IPV (p = 0.007 and < 0.001, respectively). However, there was no relationship between distance from the hospital and surgical conversion among THV patients (p = 0.565). The availability of THVs did not significantly affect follow-up time (p = 0.837). For new patients at IPVs, there was no difference in time to the operating room between cranial and spine cases; for new patients at THVs, however, time to the operating room was significantly faster for cranial cases than for spine cases (p = 0.0018). CONCLUSIONS: Compared to IPVs, THVs lead to decreased surgical conversion for cranial patients but not spine patients. THVs do not appear to increase the catchment area. For patients who live far from the hospital, an IPV is associated with surgical conversion. Surgical conversion is faster following cranial THVs than after spine THVs. THVs did not increase the duration of follow-up.

Fabrication of a positional brain shift phantom through the utilization of the frozen intermediate hydrogel state.

Synthetic models (phantoms) of the brain-skull system are useful tools for the study of surgical events that are otherwise difficult to study directly in humans. To date, very few studies can be found which replicate the full anatomical brain-skull system. Such models are required to study the more global mechanical events that can occur in neurosurgery, such as positional brain shift. Presented in this work is a novel workflow for the fabrication of a biofidelic brain-skull phantom which features a full hydrogel brain with fluid-filled ventricle/fissure spaces, elastomer dural septa and fluid-filled skull. Central to this workflow is the utilization of the frozen intermediate curing state of an established brain tissue surrogate, which allows for a novel moulding and skull installation approach that permits a much fuller recreation of the anatomy. The mechanical realism of the phantom was validated through indentation testing of the phantom's brain and simulation of the supine to prone brain shift event, while the geometric realism was validated through magnetic resonance imaging. The developed phantom captured a novel measurement of the supine to prone brain shift event with a magnitude that accurately reproduces that seen in the literature.

An analysis of the relationship between microneedle spacing, needle force and skin strain during the indentation phase prior to skin penetration.

Microneedle (MN) array patches present a promising new approach for the minimally invasive delivery of therapeutics and vaccines. However, ensuring reproducible insertion of MNs into the skin is challenging. The spacing and arrangement of MNs in an array are critical determinants of skin penetration and the mechanical integrity of the MNs. In this work, the finite element method was used to model the effect of MN spacing on needle reaction force and skin strain during the indentation phase prior to skin penetration. Spacings smaller than 2-3 mm (depending on variables, e.g., skin stretch) were found to significantly increase these parameters.

Unplanned readmission after carotid stenting versus endarterectomy: analysis of the United States Nationwide Readmissions Database.

BACKGROUND: Hospital readmissions are costly and reflect negatively on care delivered. OBJECTIVE: To have a better understanding of unplanned readmissions after carotid revascularization, which might help to prevent them. METHODS: The Nationwide Readmissions Database was used to determine rates and reasons for unplanned readmission following carotid endarterectomy (CEA) and carotid artery stenting (CAS). Trends were assessed by annual percent change, modified Poisson regression was used to estimate risk ratios (RR) for readmission, and propensity scores were used to match cohorts. RESULTS: Analysis yielded 522 040 asymptomatic and 55 485 symptomatic admissions for carotid revascularization between 2010 and 2015. Higher 30-day readmission rates were noted after CAS versus CEA in both symptomatic (9.1% vs 7.7%, p<0.001) and asymptomatic (6.8% vs 5.7%, p<0.001) patients. Readmission rates trended lower over time, significantly so for 90-day readmissions in symptomatic patients undergoing CEA. The most common cause for 30-day readmission was stroke in both symptomatic (5.5%) and asymptomatic (3.9%) patients. Factors associated with a higher risk of readmission included age over 80; male gender; Medicaid health insurance; and increases in severity of illness, mortality risk, and comorbidity indices. Analysis of matched cohorts showed that CAS had higher readmission than CEA (RR=1.14 (95% CI 1.06 to 1.22); p<0.001) only in asymptomatic patients. Adverse events during initial admission which predicted 30-day readmission included acute renal failure and acute respiratory failure in asymptomatic patients; hematoma and cardiac events were additional predictive adverse events in symptomatic patients. CONCLUSIONS: Readmission is not uncommon after carotid revascularization, occurs more often after CAS, and is predicted by baseline factors and by preventable adverse events at initial admission.

In vivo measurement of human brain material properties under quasi-static loading.

Computational modelling of the brain requires accurate representation of the tissues concerned. Mechanical testing has numerous challenges, in particular for low strain rates, like neurosurgery, where redistribution of fluid is biomechanically important. A finite-element (FE) model was generated in FEBio, incorporating a spring element/fluid-structure interaction representation of the pia-arachnoid complex (PAC). The model was loaded to represent gravity in prone and supine positions. Material parameter identification and sensitivity analysis were performed using statistical software, comparing the FE results to human in vivo measurements. Results for the brain Ogden parameters µ, α and k yielded values of 670 Pa, -19 and 148 kPa, supporting values reported in the literature. Values of the order of 1.2 MPa and 7.7 kPa were obtained for stiffness of the pia mater and out-of-plane tensile stiffness of the PAC, respectively. Positional brain shift was found to be non-rigid and largely driven by redistribution of fluid within the tissue. To the best of our knowledge, this is the first study using in vivo human data and gravitational loading in order to estimate the material properties of intracranial tissues. This model could now be applied to reduce the impact of positional brain shift in stereotactic neurosurgery.

Low-molecular-weight Heparin (enoxaparin) versus unfractionated heparin for venous thromboembolism prophylaxis in patients undergoing craniotomy.

OBJECTIVE: To explore the difference in post-operative DVT, PE, and ICH complications following administration of prophylactic UFH or enoxaparin in patients undergoing craniotomy. METHODS: A retrospective chart review was conducted for 542 patients at our institution receiving either 5000units/0.5 mL UFH (BID or TID; 180 patients) or single daily 40 mg/0.4 mL enoxaparin (362 patients) following craniotomy. Multivariate linear regression models were developed comparing rates of postoperative DVT, PE, and reoperation for bleeding in patients given enoxaparin versus UFH prophylaxis while controlling for age at surgery, history of VTE, surgery duration, number of post-operative hospital days, reoperation, post-operative infections, and reason for surgery (tumor type, genetics, etc.). Mann Whitney U tests were subsequently performed comparing rates of postoperative DVT, PE, and ICH for each group. RESULTS: Patients receiving prophylactic enoxaparin, when compared to UFH, exhibited similar rates of postoperative DVT (22 % vs 20.6 %, p = 0.86), PE (9.7 % vs 8.9 %, p = 0.86), and reoperation for bleeding (0.4 % vs 0.2 %, p = 0.58), while controlling for the factors described above. CONCLUSION: In patients undergoing craniotomy, rates for DVT, PE, and ICH were similar between patients treated with either prophylactic enoxaparin or UFH. Further studies are needed to understand whether a certain subset of patients demonstrate improved benefit from either prophylactic anticoagulant.

Rates and drivers of aboveground carbon accumulation in global monoculture plantation forests.

Restoring forest cover is a key action for mitigating climate change. Although monoculture plantations dominate existing commitments to restore forest cover, we lack a synthetic view of how carbon accumulates in these systems. Here, we assemble a global database of 4756 field-plot measurements from monoculture plantations across all forested continents. With these data, we model carbon accumulation in aboveground live tree biomass and examine the biological, environmental, and human drivers that influence this growth. Our results identify four-fold variation in carbon accumulation rates across tree genera, plant functional types, and biomes, as well as the key mediators (e.g., genus of tree, endemism of species, prior land use) of variation in these rates. Our nonlinear growth models advance our understanding of carbon accumulation in forests relative to mean annual rates, particularly during the next few decades that are critical for mitigating climate change.

Ethical Considerations in Surgical Decompression for Stroke.

Stroke is a major cause of morbidity and mortality. Neurosurgical decompression is often considered for the treatment of malignant infarcts and intraparenchymal hemorrhages, but this treatment can be frought with ethical dilemmas. In this article, the authors outline the primary principles of bioethics and their application to stroke care, provide an overview of key ethical issues and special situations in the neurosurgical management of stroke, and highlight methods to improve ethical decision-making for patients with stroke. Understanding these ethical principles is essential for stroke care teams to deliver appropriate, timely, and ethical care to patients with stroke.

Continued Dominance of Carotid Endarterectomy over Stenting in the United States: Volumes, Outcomes, and Complications from the National Inpatient Sample (1997-2015).

BACKGROUND: The introduction of carotid stenting (CAS) has led to numerous comparative trials with carotid endarterectomy (CEA). OBJECTIVE: The objective of the study was to review real-world volumes, outcomes, and complications following CEA versus CAS over an extended period to identify durable changes in practice. METHODS: Data were extracted from the National Inpatient Sample. Trends were assessed by annual percent change (APC), and adjusted risk ratios were calculated across the last 5 years of the study period. RESULTS: During 1997-2015, 199,330 symptomatic and 1,995,637 asymptomatic patients underwent carotid revascularization. In symptomatic patients, CEA declined (1997-2004; APC = -7.68%, P < 0.001) and CAS rose (1997-2008; APC = 15.48%, P < 0.001) during the first decade, subsequently becoming more muted. In asymptomatic patients, CEA decreased, whereas CAS initially increased (1997-2006; APC = 20.27%, P < 0.001) and then decreased (2007-2015; APC = -4.52%, P < 0.001). Routine discharge after symptomatic revascularization declined in CEA after 2003 and in CAS after 2006 (APC = -1.72% and -3.11%, respectively, P < 0.001 for both), corresponding to increasing patient comorbidity; similar trends were seen in asymptomatic patients. Death decreased after CEA (symptomatic and asymptomatic; APC = -4.85% and -3.53%, respectively, P < 0.001 for both) and CAS (asymptomatic only, APC = -2.53%, P = 0.04). CAS remained associated with a higher adjusted risk ratio for death, venous thromboembolism, and seizures in all patients and stroke and nonroutine discharge in symptomatic patients, during the last 5 years of the study period. CONCLUSIONS: Mortality has improved, but routine discharge has decreased following both CEA and CAS, congruent with increasing patient comorbidity. Trends in volumes, outcomes, and complication rates continue to favor CEA in real-world practice.

Land management explains major trends in forest structure and composition over the last millennium in California's Klamath Mountains.

SignificanceWe provide the first assessment of aboveground live tree biomass in a mixed conifer forest over the late Holocene. The biomass record, coupled with local Native oral history and fire scar records, shows that Native burning practices, along with a natural lightning-based fire regime, promoted long-term stability of the forest structure and composition for at least 1 millennium in a California forest. This record demonstrates that climate alone cannot account for observed forest conditions. Instead, forests were also shaped by a regime of frequent fire, including intentional ignitions by Native people. This work suggests a large-scale intervention could be required to achieve the historical conditions that supported forest resiliency and reflected Indigenous influence.

Holohemispheric Prostate Carcinoma Dural Metastasis Mimicking Subdural Hematoma: Case Report and Review of the Literature.

Prostate carcinomas are the most common malignancy to metastasize to the dura. These metastases can commonly mimic subdural hematomas and may similarly present with brain compression. The optimal management and outcomes after surgical management are not well characterized. We present a case of prostate carcinoma metastatic to the dura that was initially thought to be a large isodense subdural hematoma and was treated with surgical decompression. We also review the literature regarding prostate dural metastases mimicking subdural hematomas and discuss the relevant imaging findings, treatments, and outcomes. Dural metastasis should be considered when a patient with known metastatic prostate cancer presents with imaging evidence of a subdural mass.