Future Hemorrhage Research Articles

Laser interstitial thermal therapy for cavernous malformations: a meta-analysis of individual patient-level data.

Several case series have investigated the use of laser interstitial thermal therapy (LITT) to treat cavernous malformations (CMs), for either seizure control or reduction of neurological symptoms and future hemorrhage risk. However, pooled outcomes are largely unknown. The authors aimed to quantify posttreatment seizure freedom, symptomatic progression or hemorrhage, perioperative complications, and imaging outcomes from the available literature. This study was a PRISMA-compliant systematic review and individual patient-level data meta-analysis of studies reporting LITT ablation of CMs. For patients with epilepsy, the pooled Engel seizure freedom rate was calculated. The rate of symptomatic progression or hemorrhage was calculated for all patients. Fixed-effects logistic regression models were used to test for predictors of seizure freedom and postoperative complications. Linear regression models were used to obtain pooled estimates of the percent CM volume ablated. A total of 39 patients (28 with epilepsy) underwent LITT for the treatment of 45 CMs (37 cortical, 8 subcortical) at six centers. Among patients with epilepsy, 88.0% (95% CI 68.7%-96.1%) were seizure free at the last follow-up (median 30.0 months, range 12.0-49.0 months). Six patients (15.4%) experienced immediate postoperative neurological deficits. No perioperative hemorrhage was reported, and no patients experienced subsequent hemorrhage or symptomatic progression during follow-up (median 26.0 months, range 2.0-53.0 months). There was no difference in the odds of seizure freedom or adverse events based on preoperative characteristics. Nonepileptogenic CMs (mean volume 2.5 cm3) were significantly larger than epileptogenic CMs (mean volume 0.8 cm3; p = 0.002). LITT was associated with a mean CM volume reduction of 73.7% (95% CI 64.1%-83.2%, p < 0.0001) for epileptogenic CMs and 53.8% (95% CI 14.2%-93.3%, p < 0.023) for nonepileptogenic CMs (p = 0.14). LITT is a promising therapy for CMs with the goal of seizure control or prevention of symptomatic progression or hemorrhage. While there is a notable risk of immediate postablation neurological deficit, most were transient and nondisabling, and this risk must be weighed against that of continued observation or open resection. Considering the limited number of studies, small number of patients, and limited follow-up time available, additional experience and research with larger patient cohorts and longer-term follow-up will be necessary to validate these findings.

Angiographic features and progression risk factors in children with asymptomatic moyamoya disease.

This study aims to explore the potential contribution of angiographic characteristics in the increased stroke risk among pediatric patients. This study retrospectively enrolled pediatric patients with ischemic, hemorrhagic, and asymptomatic moyamoya disease. Their hemispheres were categorized into five groups for the analysis of angiographic characteristics, which included Suzuki's stage, moyamoya vessels, lenticulostriate artery, thalamotuberal artery, thalamoperforating artery, anterior choroidal arteries, posterior choroidal arteries, and posterior cerebral artery involvement. Two hundred and nineteen pediatric patients with four hundred and thirty-eight hemispheres were enrolled. There was no significant difference in collateral dilatation between asymptomatic and hemorrhagic hemispheres. However, asymptomatic hemispheres had significantly lower incidence of posterior cerebral artery involvement and Suzuki's stage compared to hemorrhagic (p = 0.008, p = 0.004) and ischemic hemispheres (p = 0.026, p < 0.001). Multivariate analysis revealed that Suzuki's stage (p = 0.002, 95% CI 1.261-2.867) is a risk factor for ischemia, while age (p < 0.001, 95% CI 0.712-2.014) and posterior cerebral artery involvement (p = 0.037, 95% CI 0.087-13.377) are risk factors for hemorrhage. Angiographic features in children with asymptomatic moyamoya disease resemble those observed in the hemorrhagic pediatric patients, indicating that greater attention should be focused on the risk of future hemorrhage in these patients, rather than on ischemia. Additionally, studies have demonstrated a correlation between posterior cerebral artery involvement and age with the incidence of hemorrhage. Monitoring angiographic characteristics may assist in tracking the transition from asymptomatic to symptomatic hemispheres.

Heart failure and major haemorrhage in people with atrial fibrillation

BackgroundHeart failure (HF) is not included in atrial fibrillation (AF) bleeding risk prediction scores, reflecting uncertainty regarding its importance as a risk factor for major haemorrhage. We aimed to report...

Rotational thromboelastometry predicts future bleeding events in patients with cirrhosis

Background and aims Patients with cirrhosis of the liver are in a delicate state of rebalanced haemostasis and are at risk of developing both bleeding and thrombotic complications. Conventional haemostatic tests are unable to predict bleeding and thrombosis in these patients. We aimed to explore the role of Rotational Thromboelastometry (ROTEM) in predicting bleeding and thrombotic events in patients with cirrhosis. Methods We conducted a prospective cohort study of patients with cirrhosis at two metropolitan hospitals. All patients underwent ROTEM analysis and were then followed to record any bleeding and thrombotic events. Univariate and multivariate logistic regression analyses were performed to explore associations with bleeding and thrombotic events. Results Nineteen of the 162 patients recruited experienced a bleeding event within one year of ROTEM analysis. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in patients who had a bleeding event, compared to those who did not (50 mm vs. 57 mm, p < 0.01 and 48 mm vs. 54 mm, p < 0.01, respectively). In addition, on univariate analysis, clotting time (CT) in the INTEM test was prolonged in the bleeding group (214 s vs. 198 s, p = 0.01). On multivariate analysis, only MCFEX was a significant predictor of bleeding events. In contrast, there was no association found between ROTEM parameters and development of thrombosis within a one-year period. Conclusions ROTEM may provide a useful tool in predicting future bleeding events in patients with cirrhosis. Larger studies are required to further validate this finding and explore its application in clinical practice.

Early Postoperative Changes in Von Willebrand Factor Activity Are Associated With Future Bleeding and Stroke in HeartMate 3 Patients.

Hemocompatibility-related adverse events (HRAEs), particularly gastrointestinal bleeding, remain a frequent complication after left ventricular assist device (LVAD) implantation. The current study sought to describe and analyze whether early (<60 days) postoperative von Willebrand factor (VWF) activity assays predict the risk of gastrointestinal bleeding and stroke. A prospective single-center study including 74 HeartMate 3 device recipients between 2016 and 2023 was undertaken. The postoperative trajectory of the VWF profile was analyzed using linear mixed-effect models and Cox models were used to quantify associations between an early postoperative dip (≤0.7) in VWF activity assay measurements and late outcomes. Preoperatively, the mean VWF:Activity (Act)/Antigen (Ag) and VWF:Collagen Binding (CB)/Ag ratios were 0.94 (95% confidence interval [CI] = 0.81-1.02) and 0.95 (95% CI = 0.80-1.03), respectively, decreasing to 0.66 (95% CI = 0.57-0.73) and 0.67 (95% CI = 0.58-0.74) within 40 days (p < 0.05). In patients with VWF:CB/Ag and VWF:Act/Ag ratios ≤0.7 significantly more gastrointestinal bleeding (hazard ratio [HR]: 2.53; 95% CI = 1.1-5.8, and HR: 3.7; 95% CI = 1.5-9.2, respectively) and hemorrhagic stroke events (HR: 3.5; 95% CI = 1.6-7.6 and HR: 4.9; 95% CI = 2.1-11.7, respectively) were observed throughout the entire late (>60 days) postoperative period. In patients with VWF:Act/Ag ratio ≤0.7 less ischemic stroke events were observed (HR: 0.11; 95% CI = 0.01-0.85). In conclusion, VWF:Act/Ag and VWF:CB/Ag ratios ≤0.7 in the early postoperative phase can be used as biomarkers to predict HRAEs during long-term LVAD support.

Self-healing, antioxidant, and antibacterial Bletilla striata polysaccharide-tannic acid dual dynamic crosslinked hydrogels for tissue adhesion and rapid hemostasis

Biomaterials capable of achieving effective sealing and hemostasis at moist wounds are in high demand in the clinical management of acute hemorrhage. Bletilla striata polysaccharide (BSP), a natural polysaccharide renowned for its hemostatic properties, holds promising applications in biomedical fields. In this study, a dual-dynamic-bonds crosslinked hydrogel was synthesized via a facile one-pot method utilizing poly(vinyl alcohol) (PVA)-borax as a matrix system, followed by the incorporation of BSP and tannic acid (TA). Chemical borate ester bonds formed around borax, coupled with multiple physical hydrogen bonds between BSP and other components, enhanced the mechanical properties and rapid self-healing capabilities. The catechol moieties in TA endowed the hydrogel with excellent adhesive strength of 30.2 kPa on the surface of wet tissues and facilitated easy removal without residue. Benefiting from the synergistic effect of TA and the preservation of the intrinsic properties of BSP, the hydrogel exhibited outstanding biocompatibility, antibacterial, and antioxidant properties. Moreover, it effectively halted acute bleeding within 31.3 s, resulting in blood loss of 15.6 % of that of the untreated group. As a superior hemostatic adhesive, the hydrogel in this study is poised to offer a novel solution for addressing future acute hemorrhage, wound healing, and other biomedical applications.

691 Correlation of Cerebral Arteriovenous Malformation Flow Measured by Quantitative Magnetic Resonance Angiography and MR-detected Arteriovenous Malformation Microhemorrhage

INTRODUCTION: Intracranial hemorrhage (ICH) significantly contributes to morbidity and mortality in cerebral arteriovenous malformations (AVM) patients, with a history of prior hemorrhage being the most significant predictor of a future hemorrhage. Recently, silent microhemorrhage as detected on magnetic resonance imaging (MRI) has been proposed as a potential risk factor for future hemorrhage in AVM patients. Recent data suggests that silent microhemorrhage is associated with higher nidal velocity measured through color-coded DSA, raising the question of correlation between flow and microhemorrhage. METHODS: All unruptured AVM patients with a baseline QMRA with noninvasive optimal vessel analysis (NOVA) and gradient echo or susceptibility-weighted MRI were retrospectively reviewed (2004-2022). AVM flow was calculated from the aggregate flow within primary arterial feeders relative to their contralateral counterparts. A review of the MRI determined the presence of microhemorrhages. Descriptive statistics, the X2 test, and a binomial logistic regression were performed to test the association of demographics, clinical, and AVM features with microhemorrhage. RESULTS: The study consisted of ninety patients, with fifty microhemorrhage-positive and forty microhemorrhage-negative patients. The presence of venous anomaly (varix, ectasia, aneurysm) is independently predictive of microhemorrhage (OR = 2.444, p = 0.050), and a compact AVM nidus trended towards independent negative predictability of microhemorrhage (OR =.462, p = 0.081). Calculated AVM flow trends higher in the microhemorrhage-positive group with the median flow 407 mL/min vs. 238 mL/min, and a trend towards predicting presence of microhemorrhage (OR = 1.375, p = 0.106). CONCLUSIONS: Patients with AVM-associated venous anomalies have an increased likelihood of AVM microhemorrhage. Higher AVM flow and a diffuse AVM nidus trend towards a higher likelihood of AVM microhemorrhage. These findings demonstrate the possible relationship between higher AVM flow and risk of future bleeding.

397 Rehemorrhage of Brainstem Cavernous Malformations: A Benchmark Approach to Individualized Risk and Severity Assessment

INTRODUCTION: Brainstem cavernous malformations (BSCMs) represent a unique subgroup of cavernous malformations with more hemorrhagic presentation and technical challenges. METHODS: A total of 123 consecutive BSCM patients with symptomatic hemorrhage were identified between 2015 and 2022, with untreated follow-up &gt; 12 months or subsequent hemorrhage during the untreated follow-up. Nomograms were proposed to individualize the assessment of subsequent hemorrhage risk and neurological status (determined by the modified Rankin Scale [mRS] score) after future hemorrhage. The least absolute shrinkage and selector operation (LASSO) regression was used for feature screening. The calibration curve and concordance index (C-index) were used to assess the internal calibration and discrimination performance of the nomograms. Cross-validation was further performed to validate the accuracy of the nomograms. RESULTS: Prior hemorrhage times (adjusted OR [aOR] 6.78 per ictus increase) and Zabramski type I or V (OR 11.04) were associated with rehemorrhage within 1 year. A lower mRS score after previous hemorrhage (aOR 0.38 for a shift to a higher mRS score), Zabramski type I or V (OR 3.41), medulla or midbrain location (aOR 2.77), and multiple cerebral cavernous malformations (aOR 11.76) were associated with worsened neurological status at subsequent hemorrhage. The nomograms showed good accuracy and discrimination, with a C-index of 0.80 for predicting subsequent hemorrhage within 1 year and 0.71 for predicting neurological status after subsequent hemorrhage, which were maintained in cross-validation. CONCLUSIONS: An individualized approach to risk and severity assessment of BSCM rehemorrhage was feasible with clinical and imaging features.

An MRI radiomics approach to discriminate hemorrhage prone intracranial tumors before stereotactic biopsy.

To explore imaging biomarkers predictive of intratumoral hemorrhage for lesions intended for elective stereotactic biopsy. This study included a retrospective cohort of 143 patients with 175 intracranial lesions intended for stereotactic biopsy. All the lesions were randomly split into a training dataset (n=121) and a test dataset (n=54) at a ratio of 7:3. 34 lesions were defined as "hemorrhage-prone tumors" as hemorrhage occurred between initial diagnostic MRI acquisition and the scheduled biopsy procedure. Radiomics features were extracted from the contrast-enhanced T1WI and T2WI images. Features informative of hemorrhage were then selected by the LASSO algorithm and an SVM model was built with selected features. The SVM model was further simplified by discarding features with low importance calculated using a "permutation importance" method. The model's performance was evaluated with confusion matrix-derived metrics and AUC value on the independent test dataset. Nine radiomics features were selected as hemorrhage related features of intracranial tumors by the LASSO algorithm. The simplified model's sensitivity, specificity, accuracy, and AUC reached 0.909, 0.930, 0.926, and 0.949 (95%CI: 0.865-1.000) on the test dataset in the discrimination of "hemorrhage-prone tumors". The permutation method rated feature "T2_gradient_firstorder_10Percentile" as the most important, the absence of which decreased the model's accuracy by 10.9%. Radiomics features extracted on contrast-enhanced T1WI and T2WI sequences were predictive of future hemorrhage of intracranial tumors with favorable accuracy. This model may assist in the arrangement of biopsy procedures and the selection of target lesions in patients with multiple lesions.

Three-year progression-free survival of a patient with concomitant mucinous adenocarcinoma of the colon with peritoneal dissemination and multiple myeloma who received lenalidomide: a case report

BackgroundConcomitant multiple myeloma (MM) and other primary malignancies is rare. Therefore, the treatment outcomes of patients with these conditions have not been well discussed. Lenalidomide is an oral thalidomide analog drug used for MM. Recently, the antitumor effect of lenalidomide has been gaining attention, and lenalidomide has been applied for managing solid tumors. The current case showed the treatment course of a patient treated with lenalidomide for concomitant MM and colon cancer with peritoneal dissemination.Case presentationA 74-year-old female patient receiving treatment for MM was diagnosed with mucinous adenocarcinoma of the transverse colon. The patient was clinically diagnosed with stage IIIC T4aN2M0 disease. Subsequently, laparoscopic colectomy with lymph node dissection was planned. However, intraperitoneal observation revealed peritoneal dissemination that had sporadically and widely spread. Therefore, palliative partial colectomy was performed to prevent future hemorrhage or obstruction. The patient was discharged on the 10th postoperative day without postoperative complication. Based on the patient’s preference, lenalidomide was continually administered for MM without systemic chemotherapy. The patient survived for > 36 months without any signs of tumor progression.ConclusionThe current case first showed the treatment course of concomitant MM and colon cancer. The antitumor effect of lenalidomide can possibly contribute to 3-year progression-free survival in patients with mucinous adenocarcinoma of the colon with peritoneal dissemination.

Morphologic differences between ruptured and unruptured choroidal anastomosis in adult moyamoya disease: a high-resolution vessel wall imaging study.

Choroidal anastomosis (ChA) has been implicated as the main indicator of an increased hemorrhagic risk in adult moyamoya disease. In this retrospective study, the authors aimed to identify the potential risk factors that can influence the rupture of ChA. The authors evaluated the clinical and radiological data on brain hemispheres positive for ChA from September 2019 to March 2023. The rupture status of the ChA was determined using previously described methods. Two independent raters quantitatively investigated the lumen diameter (LD) and lumen area (LA) of the ChA using high-resolution vessel wall imaging (VWI). Multivariate logistic regression analysis was conducted to identify the risk factors for ruptured ChA. Ruptured and unruptured ChAs were identified in 16 and 60 hemispheres, respectively. Univariate analysis showed that the mean values of the LD (1.251 ± 0.241 vs 0.967 ± 0.214 mm, p < 0.001) and LA (1.607 ± 0.445 vs 0.945 ± 0.372 mm2, p < 0.001) of ChAs were significantly greater in the ruptured group than in the unruptured group. A periventricular anastomosis (PA) score of 1, indicating the angiographic presence of ChA alone, was more prevalent in the ruptured group than in the unruptured group (43.8% vs 11.7%, p = 0.003). Multivariate analysis demonstrated that a larger LA of the ChA (OR 37.01, 95% CI 5.787-236.7, p < 0.001) and PA score 1 (OR 6.661, 95% CI 1.260-35.21, p = 0.026) were independently associated with ruptured ChA hemispheres. Receiver operating characteristic curve analysis revealed that the optimal cutoff point for the LA was 1.285 mm2 (sensitivity 81.3%, specificity 86.7%). A larger LA (> 1.285 mm2) of the ChA and the angiographic presence of ChA alone are independent risk factors for a ruptured ChA. Revascularization surgery for the prevention of future hemorrhage may be indicated for hemispheres with a high-risk unruptured ChA. These characteristics may help to determine treatment strategies for patients with an unruptured ChA.

Abstract WP158: Cortical Superficial Siderosis is Associated With Ischemia After Intracerebral Hemorrhage

Background: Ischemia on diffusion weighted imaging (DWI) after intracerebral hemorrhage (ICH) increases the risk of future ischemic stroke. Radiographic markers of small vessel disease, including cerebral microbleeds (CMB), are associated with DWI lesions. Though cortical superficial siderosis (cSS) is also a hemorrhagic small vessel disease subtype, it is unclear if cSS similarly relates to DWI lesions. We hypothesized that cSS would represent a more severe phenotype of small vessel disease and would associate with DWI lesions after ICH independent to other small vessel disease markers. Methods: Using the Intracerebral Hemorrhage Outcomes Project (ICHOP), we included all cases of spontaneous ICH who underwent DWI and susceptibility imaging/gradient echo. DWI hyperintensities were identified if &gt;10mm from the hematoma with decreased ADC signal. cSS were identified as subarachnoid hemosiderin deposition without acute subarachnoid hemorrhage. The relationship of cSS with DWI lesion presence as the outcome was assessed with logistic regression adjusted for ICH score, blood pressure change within 24 hours, and small vessel disease markers (CMB and white matter hyperintensity). Sensitivity analyses were performed to adjust for demographics and ICH location. A secondary analysis using linear regression assessed the association with the number of DWI lesions adjusted for similar covariates. Results: Of 198 patients analyzed, DWI lesions were observed in 31.3% and cSS in 10.6%. The presence of cSS was associated with DWI lesions (adjusted OR 3.72, CI: 1.29-10.72), independent of other small vessel disease markers. Separate sensitivity analyses adjusting for sex, race, and ICH location did not change the association of cSS with DWI lesions. In secondary analyses, cSS was not associated with greater number of DWI lesions counts (b 0.213, CI -0.53-0.63). Discussion: cSS is associated with the presence of DWI lesions, independent to other small vessel disease markers. cSS may represent a severe phenotype of small vessel disease with a risk of ICH recurrence and ischemia. Further work is required to investigate underlying mechanisms and optimal strategies to mitigate competing risks of future hemorrhage and ischemic events in these patients.

Association Between Vertebral Arterial Tortuosity and Aneurysm Growth in Intracranial Vertebral Artery Dissection.

An intracranial vertebral artery dissecting aneurysm (iVADA) increases the risk of future subarachnoid hemorrhage, which is a severe complication with high rebleeding rates and poor outcomes. Identifying potential risk factors associated with iVADA growth is crucial for their effective management. This observational study was carried out at a single center and included patients who had been diagnosed with iVADA based on neuroimaging findings. We divided the patients into two groups: with and without iVADA growth. Growth was defined as any enlargement of a dilated region or a morphological change in follow-up imaging. We measured the vertebral artery tortuosity index (VTI) in the contralateral vertebral artery (VA), defined as its actual length divided by its straight length. We investigated the factors associated with iVADA growth. This study included 124 patients. The median follow-up period was 7 months. We observed iVADA growth in 54 patients (43.5%), who were more likely to be current smokers (33.3% vs. 14.3%, p=0.012) and have a higher VTI (1.14±0.11 [mean±standard deviation] vs. 1.06±0.12, p=0.035) compared with those without iVADA growth. A multivariate analysis revealed that the VTI (adjusted odds ratio=28.490, 95% confidence interval=1.025-792.046, p=0.048) was independently associated with iVADA growth. This study has identified an independent association between VA tortuosity and iVADA growth.

Biological Abnormalities of Hemostasis in Patients with Epistaxis or Menorrhagia in Yaoundé, Cameroon.

In Cameroon, screening and diagnosis of minor hemorrhagic syndromes remain difficult and few research studies have been done to assess the magnitude of future bleeding risk and the burden of these disorders on quality of life. Epistaxis and menorrhagia are the two leading causes of bleeding disorders in the world population. The aim of this study was to investigate the biological abnormalities of hemostasis in patients with epistaxis and menorrhagia. From January to December 2021, we conducted a cross-sectional study in six hospitals with a gynecology and ENT department. We selected patients who presented epistasis or menorrhagia through clinical file and made them pass an interview and biological exams. Venous blood collected on EDTA tube allowed us to measure full blood count, thin blood smear, and blood grouping. PT, APPT, and fibrinogen assay were measured from citrate platelet-poor plasma. This plasma stored at -20°C for a maximum of 3 months allowed us to measure vWF : Ag and vWF : CBA ELISA. The bleeding time was measured at the time of sampling. In total, our study population consisted of 60 patients aged 01-45 years. Epistaxis (40%) and menorrhagia (29%) were the two main causes of bleeding complaints in our study, in addition to gingivorrhagia (15%) and prolonged bleeding after injury (03%). Almost 60% of the population had at least one abnormal hemostasis parameter. The main abnormalities found were low von Willebrand factor (30.19%), presence of macroplatelets (16.98%), prolonged bleeding time (15.09%), prolonged PT (15.09%), and low platelet count (¬07.55%). In Cameroon, bleeding disorders manifested by epistaxis and menorrhagia are mainly caused by abnormalities of primary hemostasis.

Risk of endometrial polyp and surgical intervention in postmenopausal women with proliferative endometrium.

To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and requiring future gynecological interventions, and to compare them with women with atrophic endometrium. Retrospective cohort study of all women aged 55 or over who underwent endometrial biopsy between 1/1997 and 12/2008. Outcome data were available through to 2/2018. Women with proliferative endometrium were compared with those with atrophic endometrium for the presence of endometrial polyps, uterine fibroids, future endometrial biopsy for recurrent vaginal bleeding, and future hysteroscopy or hysterectomy. Logistic regression models were used to evaluate the association of endometrial histology and other covariates with the risk of morbidities. Postmenopausal women with proliferative endometrium are at higher risk of developing endometrial polyps, uterine fibroids and need for surgical intervention. Of 1808 women who underwent endometrial biopsy during the study period, 962 met inclusion criteria: 278 had proliferative and 684 had atrophic endometrium. Length of surveillance was similar in the two groups (11.9 vs. 11.5years, p=0.2). Compared with women with atrophic endometrium, women with proliferative endometrium had significantly higher rates of endometrial polyps (17.3% vs 9.7% p=0.001). Multivariable logistic regression confirmed that women with proliferative endometrium had more fibroids on ultrasound (62.1% vs 50.3% 3=0.02), and had increased risks of developing endometrial polyps (aOR 1.9, 95% CI 1.28-3.07, p=0.002), repeat endometrial biopsy (34.9% vs. 16.8%p<0.001) and future hysterectomy or hysteroscopy (26.6% vs 16.2% p<0.001). In addition to the long-term increased risk of cancer, postmenopausal women with proliferative endometrium are more likely to have future bleeding, surgical interventions and diagnosis of endometrial polyps. Medical management to reduce estrogenic activity and associated risks may be considered in these cases.

BNP level predicts bleeding event in patients with heart failure after percutaneous coronary intervention

ObjectiveThis study aimed to investigate the association between heart failure (HF) severity measured based on brain natriuretic peptide (BNP) levels and future bleeding events after percutaneous coronary intervention (PCI).BackgroundThe Academic...

Natural History of Isolated Splanchnic Vein Thrombosis in Cancer Patients

Introduction : Venous thromboembolism (VTE), especially pulmonary embolism (PE) and deep vein thrombosis (DVT), is associated with increased morbidity in cancer patients. However, the clinical course and optimal management of unusual and isolated splanchnic vein thrombosis (iSpVT) remain unclear. Past studies often excluded cancer patients or combined them in heterogeneous cohorts. We aimed to describe the natural history of cancer associated iSpVT. Methods : We queried a cancer registry linked database from a large safety-net hospital system from 2011-2020. Patients with incident cancer diagnosis and intra-abdominal venous thrombosis were identified by a combination of International Classification of Diseases (ICD) code and natural language processing (NLP) algorithm (Figure 1). iSpVT was defined as symptomatic or incidental portal, hepatic, splenic, mesenteric vein thrombosis without concurrent PE/DVT. Patients were excluded for remote SpVT &amp;gt;6 months (mo) before or &amp;gt;36 mo after cancer diagnosis, concurrent PE/DVT, existing anticoagulation (AC), or inadequate follow-up &amp;lt;3 mo (unless death). Thrombus type was classified as bland vs. tumor/mixed based on radiology impression. AC was defined by intention for extended therapeutic AC. Venous recanalization was defined as resolution or reduction in thrombus size in a subset of patients with repeat contrast radiology scans in 3-12 mo. VTE was defined as PE or DVT. Bleeding was defined as ISTH major (MB) or clinically relevant non-major (CRNMB). Cumulative incidence of VTE at 180 days (d) was estimated using competing risk method and overall mortality was assessed by Kaplan Meier estimator. Results : Figure 1 highlights the cohort selection where 298 of 15,342 patients (1.9%) met inclusion criteria for iSpVT. Median time from cancer diagnosis to iSpVT was 19d (IQR 0-138). Most occurred in upper gastrointestinal cancers; 54% were bland and 46% were tumor/mixed. Tumor (n=99) and bland (n-44) thrombi in hepatocellular carcinoma (HCC), along with bland thrombi in pancreatic ductal adenocarcinoma (PDCA) (n=24) comprised over half of iSpVT. AC rate differed by cancer and thrombus type. Most tumor thrombi regardless of cancer type did not receive AC (97%). Most HCC and PDCA regardless of thrombus type did not receive AC (96%). Among those with bland thrombi in other cancers, 39% received AC. Due to strong selection bias for AC, we analyzed future VTE, bleeding, recanalization, and mortality in different subgroups: 1) untreated iSpVT in HCC/PDCA (compare to similar patients without SpVT); 2) all other cancers with bland iSpVT (compare AC vs. no AC) (Table 2). Among 143 HCC patients with untreated iSpVT, 44 had bland thrombi. The 180d VTE incidence was 2.4% (95% CI 0.2-10.7), which was non-significantly lower than HCC patients without iSpVT at 4.7% (95% CI 3.2-6.7). In contrast, 99 HCC patients with tumor thrombi had twice the risk of VTE and mortality compared to bland thrombi. Among 32 PDCA patients with untreated iSpVT, 24 had bland splenic vein thrombi due to tumor encasement. The 180d VTE incidence was 13.5% (3.3-30.7), similar to PDCA patients without SpVT at 17.2% (13.2-21.7). Among 87 mixed cancer type patients with bland iSpVT, the overall 180d VTE incidence was 4.6% (1.5-10.6). Thirty-four received AC with a median duration of 81d (IQR 31-181). AC was associated with increased recanalization rate (46.7% vs. 21.7%); however, it was not associated with decreased VTE (12.1% vs. 0%) or mortality (42% vs. 42%) due to confounding by treatment indication. Notably, 3 of 4 VTE occurred &amp;lt; 2 weeks after stopping AC. Bleeding occurred in 26% (n=9) of patients on AC with 15% MB (n=5) and 12% CRNMB (n=4), at a median of 28d (IQR 7.5-115) after starting AC. Conclusion: iSpVT in cancer patients is not a singular entity but rather a heterogeneous disease based on cancer and thrombus type. Tumor thrombi are associated with higher risk of future VTE and mortality. Untreated iSpVT in HCC and PDCA appear to have similar risk of VTE as those without SpVT, which supports current practice of not anticoagulating these patients. Beyond these cancers, AC varies by perceived risk of thrombosis vs bleeding. Despite strong selection bias, AC is associated with higher recanalization rate but at a cost of high bleeding risk. Prospective studies in a cancer-specific context are needed to determine if iSpVT should be treated similarly as PE/DVT among cancer patients.

Regression of periventricular anastomosis after indirect revascularization in pediatric patients with moyamoya disease.

The aim of this study was to evaluate whether indirect revascularization in pediatric patients with moyamoya disease leads to periventricular anastomosis (PVA) regression, which is markedly developed in moyamoya vessels and is regarded as a risk factor for hemorrhage. Pediatric patients with moyamoya disease treated with indirect revascularization from 2011 to 2021 were included in this study. Magnetic resonance angiography and arterial spin labeling images acquired before and 1 year after surgery were assessed to obtain a visual scale of postoperative collateral artery formation, moyamoya vessels, PVA, and quantitative values of cerebral blood flow (CBF). The relationship between background information (age, sex, RNF213 p.R4810K variant status, and preoperative CBF) and postoperative collateral artery formation, as well as postoperative CBF improvement and regression of moyamoya vessels and PVA, was evaluated. Of 89 hemispheres in 58 patients (34 females; mean [SD] patient age 8.0 [3.4] years), 74.2% showed good postoperative collateral artery formation and a significant increase in CBF (p < 0.001). Postoperative PVA showed significant regression (postoperative score 1.46 [1.06] vs 2.02 [1.69], p = 0.001), especially in those arising from choroidal arteries (postoperative score 0.28 [0.50] vs 0.72 [0.67], p < 0.001). Compared with hemispheres without good collateral artery formation, those with good collateral artery formation were more likely to show a higher increase in CBF (9.74 [12.44] ml/min/100 g vs -4.86 [9.68] ml/min/100 g, p < 0.001) and regression of PVA (54.5% [36/66] vs 30.4% [7/23], p = 0.015). Although not statistically significant, patients with postoperative PVA progression were younger than those with regression (6.75 [3.03] years vs 8.18 [3.17] years, p = 0.188), and patients with the RNF213 p.R4810K variant were more likely to show regression (28/57 [49.1%] hemispheres vs 5/13 [38.5%] hemispheres, p = 0.069). Indirect revascularization in pediatric patients with moyamoya disease resulted in good collateral extracranial artery formation and an increase in CBF and PVA regression, especially of vessels arising from choroidal arteries. With good postoperative collateral artery development, patients were more likely to show improved CBF and regression of moyamoya vessels, including PVA. Whether postoperative PVA changes reduce future hemorrhage risk requires further investigation.

Technical evolution of pediatric neurosurgery: moyamoya disease.

Moyamoya disease (MMD) is a rare steno-occlusive disease of the bilateral internal carotid arteries that predominantly occurs in East Asia. Since the first description of the MMD by Suzuki and Takaku in 1969, significant advances have been made in both basic and clinical understanding of the disease. The incidence and prevalence of pediatric MMD have increased, potentially due to improved detection rates. The advancement of neuroimaging techniques has enabled MRI-based diagnostics and detailed visualization of the vessel wall. Various methods of surgical treatments are successful in pediatric MMD patients, and recent studies emphasize the importance of reducing postoperative complications since the goal of MMD surgery is to prevent future cerebral infarction and hemorrhage. Long-term outcomes following appropriate surgical treatment in pediatric MMD patients have shown promising results, including favorable outcomes in very young patients. Further studies with a large patient cohort are needed to establish individualized risk group stratification for determining the optimal timing of surgical treatment and to conduct multidisciplinary outcome assessments.

Clinical characteristics of familial and sporadic pediatric cerebral cavernous malformations and outcomes.

Cerebral cavernous malformation (CCM) is a subtype of the vascular malformations found within the cerebral cortex. Although rare and usually discovered incidentally, these vascular abnormalities can predispose patients to spontaneous cerebral hemorrhage and subsequently lead to a myriad of neurological symptoms at presentation such as seizures and other focal neurological deficits. Although the symptoms and presentations of CCM have been adequately described in the adult population, disease characteristics and outcomes have not been extensively described in the pediatric population. Furthermore, the etiology of CCM-e.g., familial versus sporadic disease, as well as the risk factors for hemorrhage and neurological deficits and predictors of clinical and surgical outcomes-has not been adequately explored in the pediatric population. The current study attempts to classify and characterize differences in the clinical presentation, characteristics, and outcomes of CCMs between familial and sporadic cases within the pediatric population. A retrospective review identified 131 pediatric patients with radiographically confirmed diagnosis of CCM. All pertinent demographic and clinical variables were collected. CCM lesions were characterized using T2-weighted and susceptibility-weighted angiography (SWAN) MRI. Statistical analysis was conducted using the t-test for continuous variables, whereas categorical variables were analyzed with the Fisher exact test or chi-square test. Multivariate analysis was performed using a Cox proportional hazards model with R version 4.2.0. This retrospective study identified 131 pediatric CCM patients with a mean age of 8.4 years, and 54% (n = 71) were male. Twenty-seven percent (n = 35) were identified as cases with familial CCM, with the remainder classified as sporadic. The most common symptoms at presentation included generalized symptoms (headaches, nausea, and vomiting) or seizures, with a large proportion of patients also presenting as asymptomatic. No significant differences were observed in severity of symptoms between patients harboring different forms of the disease. Patients with familial CCM were noted to have a larger lesion size on average (5.26 cm3 vs 1.6 cm3, p = 0.047). These patients also had a shorter progression-free follow-up interval, with 50% of patients showing progression by 888 days, compared with only 15% of sporadic CCM patients during the same period (p = 0.0019). Familial etiology of the disease and larger average lesion volume were independent, significant predictors of disease progression (p = 0.001, HR 3.29, 95% CI 1.65-6.54) and future hemorrhage (p = 0.023, HR 1.1, 95% CI 1.01-1.10), respectively. Familial and sporadic CCMs tend to present with similar characteristics within the pediatric population. Patients with the familial form of the disease have an increased risk of progressive disease in terms of further hemorrhagic events.