Sex differences in long-term outcomes of patients with deep vein thrombosis.

OBJECTIVE: Sex differences in short-term outcomes of patients with deep vein thrombosis (DVT) have been reported, but differences in long-term outcomes remain poorly characterized. This study aimed to evaluate sex differences in long-term mortality, venous thromboembolism (VTE)-related mortality, and bleeding-related mortality in patients with DVT at a tertiary care center. METHODS: A retrospective chart review from 2012 to 2018 of all consecutive patients diagnosed with DVT was performed. Patients were grouped by sex, and baseline characteristics and treatment modalities were compared. Long-term outcomes of recurrent VTE, bleeding, and related mortalities were analyzed. Multivariable regression analysis was performed to determine factors associated with overall mortality. RESULTS: A total of 1043 (female = 521 and male = 522) patients with DVT were captured in this study period. Female patients were older (64.7 vs 61.6 years old, p = 0.01) and less likely to be obese (68.2% vs. 71.1%, p = 0.04),but had a higher average Caprini score (6.73 vs 6.35, p = 0.04). There was no difference in anatomic extent of DVT, association with PE, and severity of PE between sexes. Most patients (80.5%) were treated with anticoagulation, with no differences in choice of anticoagulant or duration of anticoagulation between females and males. Male patients were more likely to undergo catheter-directed thrombolysis (CDT) for DVT (4.2% vs 1.7%, p = 0.02) and PE (2.7% vs 0.9%, p = 0.04). Female patients were more likely to receive systemic thrombolysis for PE (2.9% vs 1.1%, p = 0.05). After an average 2.3 years follow-up, there was significantly higher bleeding complications among females (22.2% vs 16.7%, p = 0.027). The overall mortality rate was 33.5% and not different between males and females. Females were more likely to experience VTE-related mortality compared to males (3.3% vs 0.6%, p = 0.002). On regression analysis, older age (OR = 1.04 [1.03-1.06]), cancer (OR = 7.64 [5.45-10.7]), and congestive heart failure (OR = 3.84 [2.15-6.86]) were independently associated with overall mortality. CONCLUSIONS: In this study, there was no difference in overall long-term mortality between sexes for patients presenting with DVT. However, females had increased risk of long-term bleeding and VTE-related mortality compared to males.

Neuronal rhythmicity and cortical arousal in a mouse model of absence epilepsy.

OBJECTIVES: Absence seizures impair psychosocial function, yet their detailed neuronal basis remains unknown. Recent work in a rat model suggests that cortical arousal state changes prior to seizures and that single neurons show diverse firing patterns during seizures. Our aim was to extend these investigations to a mouse model with studies of neuronal activity and arousal state to facilitate future fundamental investigations of absence epilepsy. METHODS: We performed in vivo extracellular single unit recordings on awake head-fixed C3H/HeJ mice. Mice were implanted with tripolar electrodes for cortical electroencephalography (EEG). Extracellular single unit recordings were obtained with glass micropipettes in the somatosensory barrel cortex, while animals ambulated freely on a running wheel. Signals were digitized and analyzed during seizures and at baseline. RESULTS: Neuronal activity was recorded from 36 cortical neurons in 19 mice while EEG showed characteristic 7-8 Hz spike-wave discharges. Different single neurons showed distinct firing patterns during seizures, but the overall mean population neuronal firing rate during seizures was no different from pre-seizure baseline. However, the rhythmicity of neuronal firing during seizures was significantly increased (p < 0.001). In addition, beginning 10s prior to seizure initiation, we observed a progressive decrease in cortical high frequency (>40 Hz) EEG and an increase in lower frequency (1-39 Hz) activity suggesting decreased arousal state. SIGNIFICANCE: We found that the awake head-fixed C3H/HeJ mouse model demonstrated rhythmic neuronal firing during seizures, and a decreased cortical arousal state prior to seizure onset. Unlike the rat model we did not observe an overall decrease in neuronal firing during seizures. Similarities and differences across species strengthen the ability to investigate fundamental key mechanisms. Future work in the mouse model will identify the molecular basis of neurons with different firing patterns, their role in seizure initiation and behavioral deficits, with ultimate translation to human absence epilepsy.

Isolated unilateral alar ligamentous injury: illustrative cases.

BACKGROUND: Isolated unilateral alar ligament injury (IUALI) is a rare and likely underreported occurrence after upper cervical trauma, with only 16 cases documented in the literature to date. Patients generally present with neck pain, and definitive diagnosis is typically made by magnetic resonance imaging (MRI). Unfortunately, likely due in part to its rarity, there are no formal guidelines for the treatment of an IUALI. Furthermore, there is a limited understanding of the long-term consequences associated with its inadequate treatment. OBSERVATIONS: Here, the authors report on three pediatric patients, each found to have an IUALI after significant trauma. All patients presented with neck tenderness, and two of the three had associated pain-limited range of neck motion. Imaging revealed either a laterally deviated odontoid process on cervical radiographs and/or MRI evidence of ligamentous strain or discontinuity. Each patient was placed in a hard cervical collar for 1 to 2 months with excellent resolution of symptoms. A comprehensive review of the literature showed that all patients with IUALI who had undergone external immobilization with either rigid cervical collar or halo fixation had favorable outcomes at follow-up. LESSONS: For patients with IUALI, a moderate course of nonsurgical management with rigid external immobilization appears to be an adequate first-line treatment.

Leptomeningeal dissemination in pediatric brain tumors.

Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies. LMD may be diagnosed simultaneously with the primary tumor, at time of recurrence, or as primary LMD without a primary intraparenchymal lesion. Dissemination and seeding of the cerebrospinal fluid (CSF) involves a modified invasion-metastasis cascade and is often the result of direct deposition of tumor cells into the CSF. Cells develop select environmental advantages to survive the harsh, nutrient poor and turbulent environment of the CSF and leptomeninges. Improved understanding of the molecular mechanisms that underlie LMD, along with improved diagnostic and treatment approaches, will help the prognosis of children affected by primary brain tumors.