Disparities in Primary Spinal Osseous Malignant Bone Tumor Survival by Medicaid Status: A National Population-Based Risk Analysis.

BACKGROUND: The impact of Medicaid status on survival outcomes of patients with spinal primary malignant bone tumors (sPMBT) has not been investigated. METHODS: Using the SEER-Medicaid database, adults diagnosed between 2006 and 2013 with sPMBT including chordoma, osteosarcoma, chondrosarcoma, Ewing sarcoma, or malignant giant cell tumor (GCT) were studied. Five-year survival analysis was performed using the Kaplan-Meier method. Adjusted survival analysis was performed using Cox proportional-hazards regression controlling for age, sex, marital status, cancer stage, poverty level, vertebral versus sacral location, geography, rurality, tumor diameter, tumor grade, tumor histology, and therapy. RESULTS: A total of 572 patients with sPMBT (Medicaid: 59, non-Medicaid: 513) were identified. Medicaid patients were more likely to be younger (P < 0.001), Black (P < 0.001), live in high poverty neighborhoods (P = 0.006), have distant metastases at diagnosis (P < 0.001), and less likely to receive surgery (P = 0.006). The 5-year survival rate was 65.7% (chondrosarcoma: 70.0%, chordoma: 91.5%, Ewing sarcoma: 44.6%, GCT: 90.0%, osteosarcoma: 34.2%). Medicaid patients had significantly worse 5-year survival than non-Medicaid patients (52.0% vs. 67.2%, P = 0.02). Minority individuals on Medicaid were associated with an increased risk of cancer-specific mortality compared with White non-Medicaid patients (adjusted hazard ratio [aHR] = 2.51, [95% CI 1.18-5.35], P = 0.017). Among Medicaid patients, those who received surgery had significantly better survival than those who did not (64.5% vs. 30.6%, P = 0.001). For all patients, not receiving surgery (aHR = 1.90 [1.23-2.95], P = 0.004) and tumor diameter >50 mm (aHR=1.89 [1.10-3.25], P = 0.023) were associated with an increased risk of mortality. CONCLUSIONS: Medicaid patients may be less likely to receive surgery and suffer from poorer survival. These disparities may be especially prominent among minorities.

Patterns in Decompression and Fusion Procedures for Patients With Lumbar Stenosis After Major Clinical Trial Results, 2016 to 2019.

Importance: Use of lumbar fusion has increased substantially over the last 2 decades. For patients with lumbar stenosis and degenerative spondylolisthesis, 2 landmark prospective randomized clinical trials (RCTs) published in the New England Journal of Medicine in 2016 did not find clear evidence in favor of decompression with fusion over decompression alone in this population. Objective: To assess the national use of decompression with fusion vs decompression alone for the surgical treatment of lumbar stenosis and degenerative spondylolisthesis from 2016 to 2019. Design, Setting, and Participants: This retrospective cohort study included 121 745 hospitalized adult patients (aged ≥18 years) undergoing 1-level decompression alone or decompression with fusion for the management of lumbar stenosis and degenerative spondylolisthesis from January 1, 2016, to December 31, 2019. All data were obtained from the National Inpatient Sample (NIS). Analyses were conducted, reviewed, or updated on June 9, 2023. Main Outcome and Measure: The primary outcome of this study was the use of decompression with fusion vs decompression alone. For the secondary outcome, multivariable logistic regression analysis was used to evaluate factors associated with the decision to perform decompression with fusion vs decompression alone. Results: Among 121 745 eligible hospitalized patients (mean age, 65.2 years [95% CI, 65.0-65.4 years]; 96 645 of 117 640 [82.2%] non-Hispanic White) with lumbar stenosis and degenerative spondylolisthesis, 21 230 (17.4%) underwent decompression alone, and 100 515 (82.6%) underwent decompression with fusion. The proportion of patients undergoing decompression alone decreased from 2016 (7625 of 23 405 [32.6%]) to 2019 (3560 of 37 215 [9.6%]), whereas the proportion of patients undergoing decompression with fusion increased over the same period (from 15 780 of 23 405 [67.4%] in 2016 to 33 655 of 37 215 [90.4%] in 2019). In univariable analysis, patients undergoing decompression alone differed significantly from those undergoing decompression with fusion with regard to age (mean, 68.6 years [95% CI, 68.2-68.9 years] vs 64.5 years [95% CI, 64.3-64.7 years]; P < .001), insurance status (eg, Medicare: 13 725 of 21 205 [64.7%] vs 53 320 of 100 420 [53.1%]; P < .001), All Patient Refined Diagnosis Related Group risk of death (eg, minor risk: 16 900 [79.6%] vs 83 730 [83.3%]; P < .001), and hospital region of the country (eg, South: 7030 [33.1%] vs 38 905 [38.7%]; Midwest: 4470 [21.1%] vs 23 360 [23.2%]; P < .001 for both comparisons). In multivariable logistic regression analysis, older age (adjusted odds ratio [AOR], 0.96 per year; 95% CI, 0.95-0.96 per year), year after 2016 (AOR, 1.76 per year; 95% CI, 1.69-1.85 per year), self-pay insurance status (AOR, 0.59; 95% CI, 0.36-0.95), medium hospital size (AOR, 0.77; 95% CI, 0.67-0.89), large hospital size (AOR, 0.76; 95% CI, 0.67-0.86), and highest median income quartile by patient residence zip code (AOR, 0.79; 95% CI, 0.70-0.89) were associated with lower odds of undergoing decompression with fusion. Conversely, hospital region in the Midwest (AOR, 1.34; 95% CI, 1.14-1.57) or South (AOR, 1.32; 95% CI, 1.14-1.54) was associated with higher odds of undergoing decompression with fusion. Decompression with fusion vs decompression alone was associated with longer length of stay (mean, 2.96 days [95% CI, 2.92-3.01 days] vs 2.55 days [95% CI, 2.49-2.62 days]; P < .001), higher total admission costs (mean, $30 288 [95% CI, $29 386-$31 189] vs $16 190 [95% CI, $15 189-$17 191]; P < .001), and higher total admission charges (mean, $121 892 [95% CI, $119 566-$124 219] vs $82 197 [95% CI, $79 745-$84 648]; P < .001). Conclusions and Relevance: In this cohort study, despite 2 prospective RCTs that demonstrated the noninferiority of decompression alone compared with decompression with fusion, use of decompression with fusion relative to decompression alone increased from 2016 to 2019. A variety of patient- and hospital-level factors were associated with surgical procedure choice. These results suggest the findings of 2 major RCTs have not yet produced changes in surgical practice patterns and deserve renewed focus.

The incidence of failed back surgery syndrome varies between clinical setting and procedure type.

BACKGROUND: Failed back surgery syndrome (FBSS) is a significant cause of lumbar disability and is associated with severe patient morbidity. As the etiology of FBSS is not completely elucidated, the risk factors and evaluation of patients with FBSS remains challenging. Our analysis of a wide variety of operation types, clinical setting, and their correlation to FBSS seeks to allow fellow clinicians to be aware of the potential risk factors that leads to this devastating diagnosis. METHODS: Data were obtained for patients undergoing anterior lumbar fusion, posterior lumbar fusion, or decompression procedures from January 2010 to December 2017 from the Mariner insurance database. Rates of FBSS at six- and twelve-months post-surgery were determined for patients undergoing single/multilevel procedures according to place of service, and approach/procedure type. RESULTS: From 2010 to 2017, 102,047 patients underwent lumbar fusion or decompression surgery (54% decompression procedures, 36% posterior fusions, and 8.9% anterior fusions).5.4% of patients were diagnosed with FBSS within six months of the index procedure, and 8.4% were diagnosed with FBSS within twelve months. FBSS was higher in the inpatient (6.0%) vs. outpatient (4.3%) cohort. Among the surgical techniques, multi-level procedures had significantly higher rates of FBSS than single-level procedures, the highest being 10% in multi-level inpatient decompression procedures (p < 0.05). CONCLUSION: The highest rates of FBSS occurred in in the elderly (age group 70-74), for those patients whose index procedure was received in an inpatient setting, as well as for those receiving a multi-level surgery.

Use of graft materials and biologics in spine deformity surgery: a state-of-the-art review.

PURPOSE: The aim of the current review is to summarize the current evidence on graft materials used in fusion procedures for spinal deformity corrections. METHODS: PubMed, Embase, and Cochrane Library were searched for relevant published observational studies and clinical trials using osteobiologics and biomaterials in spinal deformity surgery. RESULTS: The use of autograft in deformity correction surgeries has been reported in a limited number of studies, with the harvest sites including iliac crest, ribs, and local bone. Various allografts and biologics have been used in the treatment of spinal deformities including idiopathic and degenerative scoliosis, either as stand alone or in combination with autograft. Limited number of studies reported no differences in fusion rates or outcomes. Use of rh-BMP2 in anterior, posterior or front/back approaches showed higher fusion rates than other graft materials in patients with spinal deformities. Due to the limited number of quality studies included in the review, as well as alternative factors, such as costs, availability, and surgeon expertise/preference, no definitive conclusion or recommendations can be made as to the ideal graft choice in spinal deformity surgery. CONCLUSIONS: Most commonly used grafts included autograft, allograft and rh-BMP2, with new biologics and biomaterials constantly emerging in the market. Limited number of high-quality comparative studies and heterogeneity in study design prevented direct comparisons that can lead to meaningful recommendations. Further studies are needed to prove superiority of any single graft material and/or biologic that is also cost-effective and safe.

Lumbar surgical drains do not increase the risk of infections in patients undergoing spine surgery.

PURPOSE: The aim of this study was to characterize if the use of surgical drains or length of drain placement following spine surgery increases the risk of post-operative infection. METHODS: Records of patients undergoing elective spinal surgery at a tertiary care center were collected between May 5, 2016 and August 16, 2018. Pre-operative baseline characteristics were recorded including patient's demographics and comorbidities. Intraoperative procedure information was documented related to procedure type, blood loss, and antibiotics used. Following surgery, patients were then further subdivided into two groups: patients who were discharged with a spinal surgical site drain and patients who did not receive a drain. Post-operative surgical variables included length of stay (LOS), drain length, number of antibiotics given, and type of post-operative infection. Univariate and multivariate statistical analysis was conducted. RESULTS: A total of 671 patients were included in the current study, 386 (57.5%) with and 285 (42.5%) without the drain. The overall infection rate was 5.7% with 6.22% among patients with the drain compared to 4.91% in patients without drain. The univariate analysis identified the following variables to be significantly associated with the infection: total number of surgical levels, spinal region, blood loss, redosing of antibiotics, length of stay, length of drain placement, and number of antibiotics (P < 0.05). However, the multivariate analysis none of the predictors was significant. CONCLUSIONS: The current study shows that the placement of drain does not increase rate of infection, irrespective of levels, length of surgery, or approach.

Surviving Over a Decade With Glioblastoma: A Clinical Course Characterized by Multiple Recurrences, Numerous Salvage Treatments, and Novel Use of Cesium-131 Tiles.

The prognosis for patients diagnosed with recurrent glioblastoma (GBM) remains poor, with no clear standard of care regarding salvage therapy. Common approaches include chemotherapy, re-resection, tumor treating fields, and reirradiation. However, most studies have shown these to have limited benefits. Reirradiation is particularly difficult due to concern for increased risk of toxicity to surrounding normal brain tissue. A novel intracranial brachytherapy system called GammaTile® (GT Medical Technologies, Tempe, Arizona) involves the placement of Cesium-131 radioactive tiles in the tumor cavity following maximal safe resection. This allows for a highly conformal dose distribution with rapid fall-off to minimize overlap with prior radiation fields and for the application of radiation directly to the high-risk tumor bed. This case report highlights a patient with GBM who survived 11.5 years through multiple recurrences and discusses the many salvage treatments he received, including bevacizumab, irinotecan, and stereotactic radiosurgery (SRS). This case exemplifies that aggressive systemic and local therapies can work well in select patients allowing for long-term survival with a good quality of life. Further efforts should be made to identify which patients may benefit from these therapies. The case study additionally reports on the use of GammaTile therapy. Due to prior external beam radiation therapy and SRS to the treatment site, further external beam radiation options were limited, and the patient was offered GammaTile as local therapy. Although it did not provide a survival benefit in this case due to progressive disease outside of the field of treatment, GammaTile serves as a valuable option in providing local therapy to patients who can no longer receive further radiation. It should be used with careful consideration in lesions characterized by aggressive local invasion.

Comparison of Postoperative Complications and Reoperation Rates Following Surgical Management of Cervical Spondylotic Myelopathy in the Privately Insured Patient Population.

STUDY DESIGN: This was a large database study. OBJECTIVE: The objective of this study was to compare the incidence of complications and reoperation rates between the most common surgical treatments for cervical spondylotic myelopathy (CSM): anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and posterior laminectomy and fusion (Lamifusion). SUMMARY OF BACKGROUND DATA: CSM is a major contributor to disability and reduced quality of life worldwide. METHODS: Humana insurance database was queried for CSM diagnoses between 2007 and 2016. The initial population was divided based on the surgical treatment and matched for age, sex, and Charlson Comorbidity index. Specific postoperative complications or revisions were analyzed at individual time points. Pearson χ2 analysis with Yate continuity correction was used. RESULTS: Lamifusion had significantly higher rates of wound infection/disruption than ACDF or ACCF (5.03%, 2.19%, 2.29%; P=0.0008, 0.002, respectively) as well as iatrogenic deformity (4.75%, 2.19%, 2.10%; P=0.0036, 0.0013). Lamifusion also had a significantly higher rate of shock and same-day transfusion than ACDF (4.75%, 2.01%, P=0.0005), circulatory complications (2.01%, <1%, P=0.0183), and C5 palsy (4.84%, 1.74%, P≤0.0001). Compared with ACDF, Lamifusion had higher rates of hardware complication (3.29%, 2.01%, P=0.0468), and revision surgery (8.23% 5.85%, P=0.0395). Lamifusion had significantly lower rates of dysphagia than either ACDF (3.93% vs. 6.58%, P=0.0089) or ACCF (3.93% vs. 8.59%, P<0.0001). When comparing ACCF to ACDF, ACCF had significantly higher rates of circulatory complications (2.38%, <1%, P=0.0053), shock/same-day transfusion (3.2%, 2.0%, P=0.59), C5 palsy (3.47%, 1.74%, P=0.0108), and revision surgery (9.51%, 5.85%, P=0.0086). CONCLUSIONS: The data shows that posterior Lamifusion has higher overall rate of complications compared with ACDF or ACCF. Furthermore, when comparing the anterior approaches, ACDF was associated with lower rate of complication and revision. ACCF had the highest overall rate of revision surgery.

Development and clinical validation of a grading system for pituitary adenoma consistency.

OBJECTIVE: Pituitary adenoma (PA) consistency, or texture, is an important intraoperative characteristic that may dictate operative dissection techniques and/or instruments used for tumor removal during endoscopic endonasal approaches (EEAs). The impact of PA consistency on surgical outcomes has yet to be elucidated. METHODS: The authors developed an objective 5-point grading scale for PA consistency based on intraoperative characteristics, including ease of tumor debulking, manipulation, and instrument selection, ranging from cystic/hemorrhagic tumors (grade 1) to calcified tumors (grade 5). The proposed grading system was prospectively assessed in 306 consecutive patients who underwent an EEA for PAs, and who were subsequently analyzed for associations with surgical outcomes, including extent of resection (EOR) and complication profiles. RESULTS: Institutional database review identified 306 patients who underwent intraoperative assessment of PA consistency, of which 96% were macroadenomas, 70% had suprasellar extension, and 44% had cavernous sinus invasion (CSI). There were 214 (69.9%) nonfunctional PAs and 92 functional PAs (31.1%). Distribution of scores included 15 grade 1 tumors (4.9%), 112 grade 2 tumors (36.6%), 125 grade 3 tumors (40.8%), 52 grade 4 tumors (17%), and 2 grade 5 tumors (0.7%). Compared to grade 1/2 and grade 3 PAs, grade 4/5 PAs were significantly larger (22.5 vs 26.6 vs 27.4 mm, p < 0.01), more likely to exhibit CSI (39% vs 42% vs 59%, p < 0.05), and trended toward nonfunctionality (67% vs 68% vs 82%, p = 0.086). Although there was no association between PA consistency and preoperative headaches or visual dysfunction, grade 4/5 PAs trended toward preoperative (p = 0.058) and postoperative panhypopituitarism (p = 0.066). Patients with preoperative visual dysfunction experienced greater improvement if they had a grade 1/2 PA (p < 0.05). Intraoperative CSF leaks were noted in 32% of cases and were more common with higher-consistency-grade tumors (p = 0.048), although this difference did not translate to postoperative CSF leaks. Gross-total resection (%) was more likely with lower PA consistency score as follows: grade 1/2 (60%), grade 3 (50%), grade 4/5 (44%; p = 0.045). Extracapsular techniques were almost exclusively performed in grade 4/5 PAs. Assignment of scores showed low variance and high reproducibility, with an intraclass correlation coefficient of 0.905 (95% CI 0.815-0.958), indicating excellent interrater reliability. CONCLUSIONS: These findings demonstrate clinical validity of the proposed intraoperative grading scale with respect to PA subtype, neuroimaging features, EOR, and endocrine complications. Future studies will assess the relation of PA consistency to preoperative MRI findings to accurately predict consistency, thereby allowing the surgeon to tailor the exposure and prepare for varying resection strategies.

Prospective clinical validation of a meningioma consistency grading scheme: association with surgical outcomes and extent of tumor resection.

OBJECTIVEThe present study aims to assess the clinical utility of a previously validated intraoperative meningioma consistency grading scale and its association with extent of resection (EOR) and various surgical outcomes.METHODSThe previously validated grading system was prospectively assessed in 127 consecutive patients undergoing open craniotomy for meningioma by multiple neurosurgeons at two high-volume academic hospitals from 2013 to 2016. Consistency grading scores ranging from 1 (soft) to 5 (firm/calcified) were retrospectively analyzed to test for association with surgical outcomes and EOR, categorized as gross-total resection (GTR) or subtotal resection, defined by postoperative MRI.RESULTSOne hundred twenty-seven patients were included in the analysis with a tumor consistency distribution as follows: grade 1, 3.1%; grade 2, 14.2%; grade 3, 44.1%; grade 4, 32.3%; and grade 5, 6.3%. The mean tumor diameter was 3.6 ± 1.7 cm. Tumor consistency grades were grouped into soft (grades 1 and 2), average (grade 3), and firm (grades 4 and 5) groups for statistical analysis with distributions of 17.3%, 44.1%, and 38.6%, respectively. There was no association between meningioma consistency and maximal tumor diameter, or location. Mean duration of surgery was longer for tumors with higher consistency: grades 1 and 2, 186 minutes; grade 3, 219 minutes; and grades 4 and 5, 299 minutes (p = 0.000028). There was a trend toward higher perioperative complication rates for tumors of increased consistency: grades 1 and 2, 4.5%; grade 3, 7.0%; and grades 4 and 5, 20.8% (p = 0.047). The proportion of GTR for each consistency group was as follows: grades 1 and 2, 77%; grade 3, 68%; and grades 4 and 5, 43% (p = 0.0062).CONCLUSIONSIn addition to other important meningioma characteristics such as invasiveness, tumor consistency is a key determinant of surgical outcomes, including operative duration and EOR. Future studies predicting tumor consistency based on preoperative neuroimaging will help considerably with preoperative planning for meningiomas.

Feasibility of a Fourth Ventriculopleural Shunt for Diversion of an Isolated Fourth Ventricle: A Technical Note.

Isolated fourth ventricle syndrome is an uncommon entity due to obstruction of both inlet and outflow foramina. The resulting mass effect from the progressively expanding fourth ventricle may cause symptoms from both cerebellar and brainstem compression. Although a variety of treatment modalities have been advocated for this condition, an in-depth description of placement of a fourth ventriculopleural (VPL) shunt from a single-stage prone approach has not yet been published in the literature. We describe here a case of successful placement of a fourth VPL shunt in a 22-year-old female with a history of a prior posterior fossa pilocytic astrocytoma resection who presented with symptomatic isolated fourth ventricular hydrocephalus.

Adjacent segment disease requiring reoperation in cervical total disc arthroplasty: A literature review and update.

OBJECTIVE: To evaluate the difference in rate of reoperation for adjacent segment disease (ASD) between anterior cervical decompression and fusion (ACDF) and total disc replacement (TDR). METHOD: A systematic review of literature was performed using PubMed, clinicaltrials.gov, and various other search engines. Nine studies met the inclusion criteria and were used to report an estimated overall rate of reoperation secondary to ASD for both ACDF and TDR. RESULTS: Forty-six clinical trials were identified after the initial search, and 9 studies met our inclusion criteria. Although the data was not pooled due to significant variation in level of evidence and length of follow-up, the overall rate of reoperation for ASD in the TDR cohort of patients analyzed in our review was 3.1% (range: 0-7.1%) with a follow-up between 24 and 80months. In contrast, the reoperation rate for ASD in the ACDF control was 6.0% (range: 1.0-11.9%). CONCLUSION: The average reoperation rate for ASD was 3.1% for the TDR across all studies, which was lower than the reoperation rate of 6.0% in the ACDF group. Further studies and follow-up data are still needed to determine if cervical TDR preserves adjacent segment motion more efficiently than the natural history of the disease, and if it will be a durable option when compared to the already excellent results of ACDF.

Risk factors associated with the surgical management of craniopharyngiomas in pediatric patients: analysis of 1961 patients from a national registry database.

OBJECTIVE Patient demographic characteristics, hospital volume, and admission status have been shown to impact surgical outcomes of sellar region tumors in adults; however, the data available following the resection of craniopharyngiomas in the pediatric population remain limited. The authors sought to identify potential risk factors associated with outcomes following surgical management of pediatric craniopharyngiomas. METHODS The Nationwide Inpatient Sample database and Kids' Inpatient Database were analyzed to include admissions for pediatric patients (≤ 18 years) who underwent a transcranial or transsphenoidal craniotomy for resection of a craniopharyngioma. Patient-level factors, including age, race, comorbidities, and insurance type, as well as hospital factors were collected. Outcomes analyzed included mortality rate, endocrine and nonendocrine complications, hospital charges, and length of stay. A multivariate model controlling for variables analyzed was constructed to examine significant independent risk factors. RESULTS Between 2000 and 2011, 1961 pediatric patients were identified who underwent a transcranial (71.2%) or a transsphenoidal (28.8%) craniotomy for resection of a craniopharyngioma. A major predilection for age was observed with the selection of a transcranial (23.4% in < 7-year-olds, 28.1% in 7- to 12-year-olds, and 19.7% in 13- to 18-year-olds) versus transphenoidal (2.9% in < 7-year-olds, 7.4% in 7- to 12-year-olds, and 18.4% in 13- to 18-year-olds) approach. No significant outcomes were associated with a particular surgical approach, except that 7- to 12-year-old patients had a higher risk of nonendocrine complications (relative risk [RR] 2.42, 95% CI 1.04-5.65, p = 0.04) with the transsphenoidal approach when compared with 13- to 18-year-old patients. The overall inpatient mortality rate was 0.5% and the most common postoperative complication was diabetes insipidus (64.2%). There were no independent factors associated with inpatient mortality rates and no significant differences in outcomes among groups based on sex and race. The average length of stay was 11.8 days, and the mean hospital charge was $116,5 22. Hospitals with medium and large bed capacity were protective against nonendocrine complications (RR 0.53, 95% CI 0.3-0.93, p = 0.03 [medium]; RR 0.45, 95% CI 0.25-0.8, p < 0.01 [large]) and total complications (RR 0.73, 95% CI 0.55-0.97, p = 0.03 [medium]; RR 0.68, 95% CI 0.51-0.9, p < 0.01 [large]) when compared with hospitals with small bed capacity (< 200 beds). Patients admitted to rural hospitals had an increased risk for nonendocrine complications (RR 2.56, 95% CI 1.11-5.9, p = 0.03). The presence of one or more medical comorbidities increased the risk of higher total complications (RR 1.38, 95% CI 1.14-1.68), p < 0.01 [1 comorbidity]; RR 2.37, 95% CI 1.98-2.84, p < 0.01 [≥ 2 comorbidities]) and higher total hospital charges (RR 2.9, 95% CI 1.08-7.81, p = 0.04 [1 comorbidity]; RR 9.1, 95% CI 3.74-22.12, p < 0.01 [≥ 2 comorbidities]). CONCLUSIONS This analysis identified patient age, comorbidities, insurance type, hospital bed capacity, and rural or nonteaching hospital status as independent risk factors for postoperative complications and/or increased hospital charges in pediatric patients with craniopharyngioma. Transsphenoidal surgery in younger patients with craniopharyngioma was a risk factor for nonendocrine complications.

Infection rate correlated with time to repair of open neural tube defects (myelomeningoceles): an institutional and national study.

BACKGROUND: The optimal time to closure of a newborn with an open neural tube defect (NTD-myelomeningocele) has been the subject of a number of investigations. One aspect of timing that has received attention is its relationship to repair site and central nervous system (CNS) infection that can lead to irreversible deficits and prolonged hospital stays. No studies have evaluated infection as a function of surgical timing at a national level. We hypothesized an increase in wound infection in those patients with delays in myelomeningocele repair when evaluated in both a single-center and national database. METHODS: Treatment outcomes following documented times to transfer and closure were evaluated at Children's Hospital of Los Angeles (CHLA) for the years 2004 to 2014. Data of newborns with a myelomeningocele with varying time to repair were also obtained from non-overlapping abstracts of the 2000-2010 Kids' Inpatient Database (KID) and Nationwide Inpatient Sample (NIS). Poisson multivariable regression analyses were used to assess the effect of time to repair on infection and time to discharge. RESULTS: At CHLA, 95 neonates who underwent myelomeningocele repair were identified, with a median time from birth to treatment of 1 day. Six (6 %) patients were noted to have postrepair complications. CHLA data was not sufficiently powered to detect a difference in infection following delay in closure. In the NIS, we identified 3775 neonates with repaired myelomeningocele of whom infection was reported in 681 (18 %) patients. There was no significant difference in rates of infection between same-day and 1-day wait times (p = 0.22). Wait times of two (RR = 1.65 [1.23, 2.22], p < 0.01) or more days (RR = 1.88 [1.39, 2.54], p < 0.01), respectively, experienced a 65 % and 88 increase in rates of infection compared to same-day procedures. Prolonged wait time was 32 % less likely at facilities with increased myelomeningocele repair volume (RR = 0.68 [0.56 0.83], p < 0.01). The presence of infection was associated with a 54 % (RR = 1.54 [1.36, 1.74], p < 0.01) increase in the length of stay when compared to neonates without infection. CONCLUSION: Myelomeningocele closure, when delayed more than 1 day after birth, is associated with an increased rate of infection and length of stay in the national cohort. High-volume centers are associated with fewer delays to repair. Though constrained by limitations of a national coded database, these results suggest that early myelomeningocele repair decreases the rate of infection.

Versatile utilization of real-time intraoperative contrast-enhanced ultrasound in cranial neurosurgery: technical note and retrospective case series.

OBJECTIVE: Intraoperative contrast-enhanced ultrasound (iCEUS) offers dynamic imaging and provides functional data in real time. However, no standardized protocols or validated quantitative data exist to guide its routine use in neurosurgery. The authors aimed to provide further clinical data on the versatile application of iCEUS through a technical note and illustrative case series. METHODS: Five patients undergoing craniotomies for suspected tumors were included. iCEUS was performed using a contrast agent composed of lipid shell microspheres enclosing perflutren (octafluoropropane) gas. Perfusion data were acquired through a time-intensity curve analysis protocol obtained using iCEUS prior to biopsy and/or resection of all lesions. RESULTS: Three primary tumors (gemistocytic astrocytoma, glioblastoma multiforme, and meningioma), 1 metastatic lesion (melanoma), and 1 tumefactive demyelinating lesion (multiple sclerosis) were assessed using real-time iCEUS. No intraoperative complications occurred following multiple administrations of contrast agent in all cases. In all neoplastic cases, iCEUS replicated enhancement patterns observed on preoperative Gd-enhanced MRI, facilitated safe tumor debulking by differentiating neoplastic tissue from normal brain parenchyma, and helped identify arterial feeders and draining veins in and around the surgical cavity. Intraoperative CEUS was also useful in guiding a successful intraoperative needle biopsy of a cerebellar tumefactive demyelinating lesion obtained during real-time perfusion analysis. CONCLUSIONS: Intraoperative CEUS has potential for safe, real-time, dynamic contrast-based imaging for routine use in neurooncological surgery and image-guided biopsy. Intraoperative CEUS eliminates the effect of anatomical distortions associated with standard neuronavigation and provides quantitative perfusion data in real time, which may hold major implications for intraoperative diagnosis, tissue differentiation, and quantification of extent of resection. Further prospective studies will help standardize the role of iCEUS in neurosurgery.

The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity.

Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies have shown that LB100, a small-molecule inhibitor of PP2A, sensitizes cancer cells to radiation-mediated DNA damage. We hypothesized that LB100 could sensitize ovarian cancer cells to cisplatin treatment. We performed in vitro studies in SKOV-3, OVCAR-8, and PEO1, -4, and -6 ovarian cancer lines to assess cytotoxicity potentiation, cell-death mechanism(s), cell-cycle regulation, and DDR signaling. In vivo studies were conducted in an intraperitoneal metastatic mouse model using SKOV-3/f-Luc cells. LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and γH2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites. In vivo, cisplatin sensitization via LB100 significantly enhanced tumor growth inhibition and prevented disease progression after treatment cessation. Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation.

Say no to DMSO: dimethylsulfoxide inactivates cisplatin, carboplatin, and other platinum complexes.

The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence are extensively studied in the laboratory setting. In this study, we examined the literature and found a significant number of studies (11%-34%) in prominent cancer journals utilizing cisplatin dissolved in DMSO. However, dissolving cisplatin in DMSO for laboratory-based studies results in ligand displacement and changes to the structure of the complex. We examined the effect of DMSO on platinum complexes, including cisplatin, carboplatin, and oxaliplatin, finding that DMSO reacted with the complexes, inhibited their cytotoxicity and their ability to initiate cell death. These results render a substantial portion of the literature on cisplatin uninterpretable. Raising awareness of this significant issue in the cancer biology community is critical, and we make recommendations on appropriate solvation of platinum drugs for research.

AVM Management Equipoise Survey: physician opinions regarding the management of brain arteriovenous malformations.

INTRODUCTION: Management of unruptured brain arteriovenous malformations (AVMs) is controversial, and conducting clinical trials in this area has been a challenge. We sought to determine which, if any, patient/AVM characteristics were most likely to influence clinicians' decisions regarding management and clinical trial enrollment. METHODS: We performed an online survey (Survey Monkey) of members of the American Association of Neurological Surgeons (AANS) (n=4836) and Society of NeuroInterventional Surgeons (SNIS) (n=512). Physicians were asked to rate the likelihood that various patient/AVM characteristics would influence their treatment decisions and recommendations for clinical trial enrollment. 10 hypothetical case vignettes were also provided, and respondents were asked to select a management recommendation. RESULTS: 277 (5.2%) responses were received. Characteristics that the majority (>50%) of respondents felt should lead to treatment included size <3 cm, superficial or cerebellar location, single draining vein, age <30 years, venous aneurysm, prior AVM hemorrhage, poorly controlled seizures, intranidal aneurysm, and patient's desire for treatment. However, a significant minority (>30%) felt that six of these same characteristics should lead to observation or should not influence treatment decisions. Characteristics that the majority (>50%) of respondents felt should lead to clinical trial enrollment included size > 6 cm, deep or eloquent location, and age 51-70 years. The only characteristic that the majority felt should not lead to enrollment was the presence of an intranidal aneurysm. For the 10 vignettes, the majority of respondents (>50%) favored a specific course of management in only five cases. CONCLUSIONS: Clinicians' opinions on which patient/AVM characteristics are important for decisions regarding treatment or trial enrollment vary widely. These results suggest that there is no uniform opinion of clinical equipoise with regard to the management of brain AVMs.