The implications of antithrombotic agents on subdural hematoma evacuation: what does "reversal" truly entail?

OBJECTIVE: The optimal perioperative management of antithrombotic therapy (ATT) in patients requiring urgent neurosurgical intervention for subdural hematoma (SDH) is poorly understood. The delicate equilibrium of effective hemostasis while preventing thrombosis is complex and relies on numerous factors such as indication for and type of ATT, medical comorbidities, and extent of neurological injury. This study aimed to analyze the impact of ATT and reversal strategies on surgical outcomes to highlight current challenges in the management of these high-risk patients. METHODS: The authors performed a retrospective surgical cohort analysis of 100 patients undergoing urgent SDH evacuation at a level I trauma center between March 2020 and May 2021. The patients were first stratified into two cohorts based on preoperative ATT use and then further segregated by receipt of reversal agents. Statistical analysis included the chi-square test, Welch two-sample t-test, and multivariate logistic regression. The primary outcome was mortality. Secondary endpoints included radiographic SDH reexpansion, revision surgery, improvement in preoperative neurological deficits, and incidence of thromboembolism. A crossover cohort was secondarily analyzed in patients for whom ATT was interrupted for a minimum duration equal to effective drug metabolism. Finally, ATT reinitiation patterns were examined. RESULTS: Of 100 patients, 48% received ATT, 54.2% of whom were given reversal agents. ATT use was significantly associated with decreased rates of postoperative neurological improvement (p = 0.023) with trends toward increased mortality (p = 0.078), SDH reexpansion (p = 0.12), and need for revision surgery (p = 0.10). Patient crossover revealed a 4 times greater likelihood of death in patients without ATT interruption prior to surgery (p = 0.040) without an observable impact on secondary outcomes. ATT reversal contributed no improvement in outcomes other than a decreased intensive care unit length of stay when adjusted for in-hospital mortality (p = 0.014). The rate of postoperative thromboembolism following ATT reversal was 11.5%. ATT reinitiation was highly variable, occurring in 59.5% of patients, with median times of 17 and 15 days for antiplatelets and anticoagulants, respectively. CONCLUSIONS: Use of preoperative ATT portends poor clinical outcomes following nonelective SDH evacuation regardless of attempts to reverse these medications with replacement blood products. This study further reinforces the critical need for judicious use of ATT and optimization of reversal strategies in high-risk patient populations as best guided by multidisciplinary teams and evolving clinical practice guidelines.

Predictive factors for operative intervention and ideal length of non-operative trial in adhesive small bowel obstruction.

BACKGROUND: Small bowel obstruction (SBO) is responsible for 350,000 U.S. hospitalizations and costs ~ $2.3 billion annually. The current standard of care for SBO is to trial 3 to 5 days of non-operative management. This study evaluated the factors associated with operative management. METHODS: This retrospective cohort study included adult patients admitted with adhesive SBO. Exclusions were for operative intervention within 24 h or death. RESULTS: At baseline (N = 360), mean age was 65.9 years, 57.8% female, 72.3% white, mean BMI 26.1, 38.7% with history of SBO and 98.1% had history of abdominal surgery. Symptom onset prior to hospitalization was 1-2 days. 55.6% had successful non-operative management at discharge (median length of stay 3 days) vs. 44.4% operative conversion. In univariate analyses, BMI, SBO history, surgical history, days symptom onset, vitals, abdominal pain, obstipation, acute kidney injury, and lack of small bowel feces sign on CT scan were significantly associated with operative management. In a multivariable logistic regression, after controlling all other variables, a lack of small bowel feces sign (adjusted odds ratio, aOR = 2.25, 95% CI 1.06-4.77, p = 0.04) and history of exploratory laparotomy (aOR = 0.44, 95% CI 0.21-0.90, p = 0.03) were significantly associated with operative management. Time from admission to surgery averaged 3.89 days: small bowel resection (55/160) was 4.9 days (median = 4), compared to patients without resection (3.4 days, median = 2; p = 0.00; OR = 1.2, 95% CI 1.07-1.35). CONCLUSIONS: A lack of small bowel feces sign can be a potential indicator for operative management and should be further explored. Since the median resolution of symptoms in the non-operative management group was ~ 2 days and a 20% higher odds for bowel resection each day surgery is delayed, the conservative trial period for adhesive SBO should not exceed 3 days.

Directional Deep Brain Stimulation-A Step in the Right Direction? A Systematic Review of the Clinical and Therapeutic Efficacy of Directional Deep Brain Stimulation in Parkinson Disease.

BACKGROUND: The use of directional deep brain stimulation (dDBS) electrodes for the treatment of movement disorders such as Parkinson disease (PD) has become relatively widespread. However, the efficacy of dDBS relative to its omnidirectional deep brain stimulation (oDBS) counterpart is not well characterized. This systematic review aims to synthesize the literature comparing clinical and therapeutic outcomes of dDBS relative to oDBS in patients with PD. METHODS: A systematic literature search for studies with comparative clinical outcome data between dDBS and oDBS was performed across the PubMed, Ovid MEDLINE, and Web of Science databases. Data including therapeutic window (TW) and surrogate measures and the Unified Parkinson's Disease Rating Scale score were collected and summarized across multiple time periods. RESULTS: Ten studies met the eligibility criteria. Three of these studies evaluated motor performance in the form of Unified Parkinson's Disease Rating Scale III, with none finding differences between dDBS and oDBS. Two studies assessed quality-of-life measures with neither finding differences between dDBS and oDBS. TW or a surrogate measure was assessed in 6 studies; 5 studies found an increase or strong trend toward increase in dDBS relative to oDBS. CONCLUSIONS: The current evidence, although limited by bias, does suggest that dDBS in the treatment of PD yields improvements in motor symptoms and quality of life that are comparable to oDBS; TW and surrogate measures are consistently improved in patients with PD under a directional configuration relative to omnidirectional.

Repeat stereotactic radiosurgery for cerebral arteriovenous malformations.

OBJECTIVE: The purpose of this retrospective, single-institution study was to evaluate radiological and clinical outcomes of patients managed with repeat stereotactic radiosurgery (SRS) for residual cerebral arteriovenous malformation (AVM) after prior SRS. METHODS: The authors evaluated the clinical and radiological outcomes of consecutive patients treated with repeat single-session SRS for a residual brain AVM from 1989 to 2021. RESULTS: In total, 170 patients underwent repeat SRS for AVM (90 [52.9%] females; median [interquartile range] age at the first SRS procedure 28 [21.5] years; median [interquartile range] age at the second SRS procedure 32 [22.5] years). After repeat SRS, the actuarial 3-, 5-, and 10-year AVM obliteration rates were 37.6%, 57.3%, and 80.9%, respectively. Higher obliteration rates were associated with margin dose ≥ 19 Gy (p = 0.001). After the second SRS procedure, hemorrhage occurred in 8.2% of patients and was lethal in 1 patient. The risk factors of intracranial hemorrhage were age < 18 years (p = 0.03) and residual AVM diameter > 20 mm (p = 0.004). Lower obliteration rates were noted in patients with residual AVM diameter > 20 mm (p = 0.04) and those < 18 years of age (p = 0.04). Asymptomatic, symptomatic, and permanent radiation-induced changes (RICs) after the second SRS procedure occurred in 25.9%, 8.8%, and 5.3% of patients, respectively, and were associated with RIC after the first SRS procedure (p = 0.006). There was 1 case of a radiation-induced meningioma 12 years after SRS. CONCLUSIONS: Repeat SRS is a reasonable therapeutic option, in particular for patients with residual AVM. Repeat SRS was associated with more favorable outcomes in adult patients and those with residual AVM smaller than 20 mm in maximum diameter. To increase the rate of residual AVM obliteration, a prescription dose ≥ 19 Gy should ideally be used for repeat SRS.

Cyanocobalamin prevents cardiomyopathy in type 1 diabetes by modulating oxidative stress and DNMT-SOCS1/3-IGF-1 signaling.

Patients with long-standing diabetes have a high risk for cardiac complications that is exacerbated by increased reactive oxygen species (ROS) production. We found that feeding cyanocobalamin (B12), a scavenger of superoxide, not only prevented but reversed signs of cardiomyopathy in type 1 diabetic Elmo1H/H Ins2Akita/+ mice. ROS reductions in plasma and hearts were comparable to those in mice treated with other antioxidants, N-acetyl-L-cysteine or tempol, but B12 produced better cardioprotective effects. Diabetes markedly decreased plasma insulin-like growth factor (IGF)-1 levels, while B12, but not N-acetyl-L-cysteine nor tempol, restored them. B12 activated hepatic IGF-1 production via normalization of S-adenosylmethionine levels, DNA methyltransferase (DNMT)-1/3a/3b mRNA, and DNA methylation of promoters for suppressor of cytokine signaling (SOCS)-1/3. Reductions of cardiac IGF-1 mRNA and phosphorylated IGF-1 receptors were also restored. Thus, B12 is a promising option for preventing diabetic cardiomyopathy via ROS reduction and IGF-1 retrieval through DNMT-SOCS1/3 signaling.