Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs

BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P \u3c .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients

Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair

Background: Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective: This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods: A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results: Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion: Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity

Rapidly Injecting 10 MG of Intrathecal Fluorescein Caused No Neurologic Complications

Background: Intrathecal fluorescein (ITF) is often effective in localizing nasal cerebrospinal fluid (CSF) leaks along the skull base under nasal endoscopy. Previous reports of seizures and paralysis have led to administration practices aimed at minimizing the risk of these potentially catastrophic neurologic complications. Since these early reports, surgeons have often reported injecting ITF slowly over a variable number of minutes, and that it should be diluted either in saline or patients\u27 CSF. However, no study has assessed whether ITF administration duration or dilution alters the risks of these neurologic complications. Methods: From September 2015 through August 2022, all patients undergoing ITF injection through lumbar drains for localization of possible or confirmed nasal CSF leaks were included. All patients had ITF administered by mixing 0.1 mL of 10% fluorescein (10 mg) with 3 to 5 mL of CSF, with no additional fluorescein dilution. The solutions were then injected through lumbar drains rapidly over 1 to 2 seconds. Patient demographics, CSF leak etiologies, and histories of seizures or cerebrovascular accidents were recorded. Results: Sixty-one patients were included, mean age was 56.3 ± 15.6 years, and 82% were female. Fifty patients had CSF leaks repaired successfully, and 11 patients had negative explorations. CSF leaks were due to the following etiologies: idiopathic intracranial hypertension (76%), skull base tumors (10%), accidental trauma (8%), and surgical trauma (6%). Four patients had histories of seizure disorders, and five patients had remote histories of prior cerebrovascular accidents. There were no intraoperative or postoperative episodes of seizure, paralysis, or other neurologic complications. Conclusion: Injecting 10 mg of ITF through lumbar drains rapidly and without true dilution resulted in no seizures, paralysis, or other neurologic complications in patients undergoing endoscopic exploration with or without nasal CSF leak repair

Traumatic Brain Injury in Myanmar: Preliminary Results and Development of an Adjunct Electronic Medical Record

BACKGROUND: The treatment of traumatic brain injury (TBI) in Myanmar is a major health issue. Comprehensive appreciation of the pathology is limited given the lack of granular metadata available. In this proof-of-concept study, we analyzed demographic data on TBI generated from a novel prospective, online database in a low-to-middle income country (LMIC). METHODS: Neurosurgery residents were given an electronic tablet for data entry onto an online database. Metadata-driven data capture was carried prospectively by the trained residents and the information was reviewed weekly by the supervising team in the United States. RESULTS: Complete data was available on 242/253 (96%) patients. Age at admission was 37 years (range 16-85) and length of stay was 3.53 days (1-21). Etiologies included motorcycle accidents, falls, assaults, pedestrian vehicular injuries and industrial accidents. Dispositions were primarily to home (211). Average Glasgow Coma Score (GCS) at admission was 12.97. There was a 68% mortality rate of patients directly admitted to NOGH with GCS75% for patients transferred in from other facilities. Surgery was performed on 30 patients (12.4%). CONCLUSIONS: Despite a lack of formal training in electronic medical records or research, the resident team was able to capture the majority of admissions with granular-level data. This helped shed light on the etiology and severity of TBI in Myanmar. As a result, more effective transport systems and access to trauma care must be achieved. Accessible regional trauma centers with investment in intensive care units, operative care, anesthesia, and imaging resources is necessary

DNA Methylation-based Signatures Classify Sporadic Pituitary Tumors According to Clinicopathological Features

BACKGROUND: Distinct genome-wide methylation patterns cluster pituitary neuroendocrine tumors (PitNETs) into molecular groups associated with specific clinicopathological features. Here we aim to identify, characterize and validate methylation signatures that objectively classify PitNET into clinicopathological groups. METHODS: Combining in-house and publicly available data, we conducted an analysis of the methylome profile of a comprehensive cohort of 177 tumors (Panpit cohort) and 20 nontumor specimens from the pituitary gland. We also retrieved methylome data from an independent PitNET cohort (N=86) to validate our findings. RESULTS: We identified three methylation clusters associated with adenohypophyseal cell lineages and functional status using an unsupervised approach. Differentially methylated CpG probes (DMP) significantly distinguished the Panpit clusters and accurately assigned the samples of the validation cohort to their corresponding lineage and functional subtypes memberships. The DMPs were annotated in regulatory regions enriched of enhancer elements, associated with pathways and genes involved in pituitary cell identity, function, tumorigenesis, invasiveness. Some DMPs correlated with genes with prognostic and therapeutic values in other intra or extracranial tumors. CONCLUSIONS: We identified and validated methylation signatures, mainly annotated in enhancer regions that distinguished PitNETs by distinct adenohypophyseal cell lineages and functional status. These signatures provide the groundwork to develop an unbiased approach to classifying PitNETs according to the most recent classification recommended by the 2017 WHO and to explore their biological and clinical relevance in these tumors

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors.

BACKGROUND: DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. METHODS: We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET. RESULTS: Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. CONCLUSIONS: Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas.

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas

Abstract Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients

Acute Care Neurosurgery by Case Management : Pearls and Pitfalls

Acute Care Neurosurgery by Case Managemen