Safety and timing of early therapeutic anticoagulation therapy after craniotomy.

Background: To date, there are few guidelines and studies to guide the timing of initiation of therapeutic anticoagulation (AC) after craniotomy. The goal of this study was to assess the timing, safety, and outcomes of patients following the administration of therapeutic AC after craniotomy. Methods: A retrospective case-control study was performed evaluating all craniotomy patients from August 2017 to July 2021. Cases were selected if they received therapeutic AC within ten days of craniotomy. Nineteen out of 1013 craniotomy patients met the inclusion criteria. Indications for therapeutic AC were diverse, including deep venous thrombosis, pulmonary embolism, dural venous sinus thrombosis, mechanical heart valve, and left ventricular thrombus. Results: The mean and median time to therapeutic AC were 5.35 and 5 days, respectively. Three patients developed intracerebral hemorrhage (ICH) that was stable on repeat imaging and did not require any surgical intervention or result in new neurologic deficits. There was no significant association between therapeutic AC and postoperative ICH (P = 0.067). Conclusion: This study demonstrated that the initiation of therapeutic AC in postoperative craniotomy patients from postoperative days 2 to 10 did not result in any major complications. A prospective study is warranted to clarify the indications and safety of therapeutic AC after craniotomy.

Decompression and Interlaminar Stabilization for Lumbar Spinal Stenosis: A Cohort Study and Two-Dimensional Operative Video.

Background and Objectives: Lumbar spinal stenosis is one of the most common causes of disability in the elderly and often necessitates surgical intervention in patients over the age of 65. Our study aimed to evaluate the clinical efficacy of interlaminar stabilization following decompressive laminectomy in patients with lumbar stenosis without instability. Materials and Methods: Twenty patients with lumbar stenosis underwent decompressive laminectomy and interlaminar stabilization at our academic institution. Clinical outcomes were measured using the visual analog scale (VAS) and Oswestry disability index (ODI) at the 2-month, 6-month, and 1-year postoperative visits, and these outcomes were compared to the preoperative scores. Results: The average VAS scores for low back pain significantly improved from 8.8 preoperatively to 4.0, 3.7, and 3.9 at 2 months, 6 months, and 1 year postoperatively, respectively (p < 0.001). The average VAS scores for lower extremity pain significantly improved from 9.0 preoperatively to 2.7, 2.5, and 2.5 at 2 months, 6 months, and 1 year postoperatively, respectively (p < 0.001). The average ODI scores significantly improved from 66.6 preoperatively to 23.8, 23.3, and 24.5 at 2 months, 6 months, and 1 year postoperatively, respectively (p < 0.001). There was no statistical significance for difference in VAS or ODI scores between 2 months, 6 months, and 1 year. One patient had an intraoperative durotomy that was successfully treated with local repair and lumbar drainage. Another patient had progression of stenosis and had to undergo bilateral facetectomy and fusion. Conclusions: Decompressive laminectomy and interlaminar stabilization in patients with spinal claudication and low back pain is a good surgical option in the absence of instability and may provide significant clinical improvement of pain and functional disability.

Long noncoding RNA MALAT1 suppresses breast cancer metastasis.

MALAT1 has previously been described as a metastasis-promoting long noncoding RNA (lncRNA). We show here, however, that targeted inactivation of the Malat1 gene in a transgenic mouse model of breast cancer, without altering the expression of its adjacent genes, promotes lung metastasis, and that this phenotype can be reversed by genetic add-back of Malat1. Similarly, knockout of MALAT1 in human breast cancer cells induces their metastatic ability, which is reversed by re-expression of Malat1. Conversely, overexpression of Malat1 suppresses breast cancer metastasis in transgenic, xenograft, and syngeneic models. Mechanistically, the MALAT1 lncRNA binds and inactivates the prometastatic transcription factor TEAD, preventing TEAD from associating with its co-activator YAP and target gene promoters. Moreover, MALAT1 levels inversely correlate with breast cancer progression and metastatic ability. These findings demonstrate that MALAT1 is a metastasis-suppressing lncRNA rather than a metastasis promoter in breast cancer, calling for rectification of the model for this highly abundant and conserved lncRNA.

ZRANB1 Is an EZH2 Deubiquitinase and a Potential Therapeutic Target in Breast Cancer.

Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC). Intriguingly, a small-molecule inhibitor of ZRANB1 destabilizes EZH2 and inhibits the viability of TNBC cells. In patients with breast cancer, ZRANB1 levels correlate with EZH2 levels and poor survival. These findings suggest the therapeutic potential for targeting the EZH2 deubiquitinase ZRANB1.