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Intramedullary spinal cord tumors (IMSCTs) are rare tumors associated with significant morbidity and mortality. Surgical resection is often indicated for symptomatic lesions but may result in new neurological deficits and decrease quality of life. Identifying predictors of these adverse outcomes may help target interventions designed to reduce their occurrence. Nonetheless, most prior studies have employed population-level datasets with limited granularity.To determine independent predictors of nonroutine discharge, prolonged length of stay (LOS), and 30 day readmission and reoperation, and to deploy these results as a web-based calculator.Retrospective cohort study PATIENT SAMPLE: A total of 235 patients who underwent resection of IMSCTs at a single comprehensive cancer center.Nonroutine discharge, prolonged LOS, 30 day readmission, and 30 day reoperation METHODS: Patients who underwent surgery from June 2002 to May 2020 at a single tertiary center were included. Data was collected on patient demographics, clinical presentation, tumor histology, surgical procedures, and 30 day readmission and reoperation. Functional status was assessed using the Modified McCormick Scale (MMS) and queried preoperative neurological symptoms included weakness, urinary and bowel dysfunction, numbness, and back and radicular pain. Variables significant on univariable analysis at the α≤0.15 level were entered into a stepwise multivariable logistic regression model.Of 235 included cases, 131 (56%) experienced a nonhome discharge and 68 (29%) experienced a prolonged LOS. Of 178 patients with ≥ 30 days of follow-up, 17 (9.6%) were readmitted within 30 days and 13 (7.4%) underwent reoperation. Wound dehiscence (29%) was the most common reason for readmission. Nonhome discharge was independently predicted by older age (OR=1.03/year; p.01), thoracic location of the tumor (OR=2.36; p=.01), presenting with bowel dysfunction (OR=4.09; p=.03), and longer incision length (OR=1.44 per level; p=.03). Independent predictors of prolonged LOS included presenting with urinary incontinence (OR=2.65; p=.05) or a higher preoperative white blood cell count (OR=1.08 per 10We found that neurological presentation, patient demographics, and incision length were important predictors of adverse perioperative outcomes in patients with IMSCTs. The calculators can be used by clinicians for risk stratification, preoperative counseling, and targeted interventions.

In the present study, we identified the risk factors for wound complications, wound infection, and reoperation for wound complications after spine metastasis surgery and deployed the resultant model as a web-based calculator.Patients treated at a single comprehensive cancer center during a 7-year period were included. The demographics, pathology, comorbidities, laboratory values, and operative details were collected. Factors with P0.15 on univariable regression were entered into multivariable logistic regression to generate predictive models internally validated using 1000 bootstrapped samples.Of the 330 patients included, 29 (7.6%) had experienced a surgical site infection. The independent predictive factors for wound-related complications were a higher Charlson comorbidity index (CCI; odds ratio [OR], 1.41 per point; P0.01), Karnofsky performance scale score ≤70 (OR, 2.14; P = 0.04), lower platelet count (OR, 0.49 per 10Low platelet counts, poorer health status, more invasive surgery, and revision surgery all independently predicted the risk of wound complications, including infection and unplanned reoperation for infection. Validation of the calculators in a prospective study is merited.

To determine those clinical, demographic, and operative factors that predict 30-day unplanned reoperation and readmission within a population of adults who underwent spinal metastasis surgery at a comprehensive cancer center.Adults who underwent spinal metastasis surgery at a comprehensive cancer center were analyzed. Data included baseline laboratory values, cancer history, demographics, operative characteristics and medical comorbidities. Medical comorbidities were quantified using the modified Charlson Comorbidity Index (CCI). Values associated with the outcomes of interest were then subjected to multivariable logistic regression to identify independent predictors of readmission and reoperation.A total of 345 cases were identified. Mean age was 59.4 ± 11.7 years, 56% were male, and the racial makeup was 64% white, 29% black, and 7.3% other. Forty-two patients (12.2%) had unplanned readmissions, most commonly for wound infection with dehiscence (14.2%), venous thromboembolism (14.2%), and bowel obstruction/complication (11.9%). Thirteen patients required reoperation (4%), most commonly for wound infection with dehiscence (39%) or local recurrence (23%). Multivariable analysis showed that the modified CCI (odds ratio [OR], 1.25; 95% confidence interval [CI] 1.03-1.52; P = 0.03) was an independent predictor of 30-day readmission. Independent predictors of 30-day unplanned reoperation were: black (vs. white) race (OR, 0.08; 95% CI, 0.01-0.41; P0.01), length of stay (OR, 1.05 per day; 95% CI, 1.00-1.09; P = 0.04), and CCI (OR, 1.72 per point; 95% CI, 1.29-2.28; P 0.01).Increasing medical comorbidities is independently predictive of both 30-day unplanned readmission and reoperation after spinal metastasis surgery. Unplanned reoperation is also positively predicted by a longer index admission. Neither tumor pathology nor age predicted outcome, suggesting that poor wound-healing factors and increased surgical morbidity may best predict these adverse outcomes.

The objective of the study was to determine home program matching percentage (staying in a program affiliated with one's medical school) for each neurosurgical residency program in the United States. Secondarily, it was to elucidate both program-level and resident characteristics associated with home program matching.Demographic and bibliometric characteristics were collected for 1572 residents in U.S.-based and Accreditation Council for Graduate Medical Education-accredited neurosurgery programs over the 2014-2020 match period using publicly available websites. Program characteristics were collected, including number of clinical faculty, top 20 Doximity research ranking, top 10 Doximity reputation ranking, top 10 U.S. News department ranking, affiliation with a U.S. News top 10 medical school, and geographic region. Programs were ranked according to home program matching percentage, and associations were statistically evaluated.The average home program matching percentage per residency was 18.6%. NewYork-Presbyterian/Columbia retained the largest percentage of its own medical students with a home program matching percentage of 57.14%. From the resident frame of reference, only a higher preresidency H-index (3.7 ± 4.0 vs. 3.2 ± 3.7, P = 0.033) was significantly associated with home program matching. From a program perspective, program size (standardized β = 0.234, P = 0.006), Doximity research (standardized β = 0.206, P = 0.031), Doximity reputation (standardized β = 0.196, P = 0.040), and U.S. News program rankings (standardized β = 0.200, P = 0.036) were all significantly associated with home program matching. Overall home program matching percentage remained relatively constant over the 2014-2020 time period.The results of this study delineate home program matching patterns on a program-by-program level for U.S. neurosurgical residency programs.

OBJECTIVE The authors aimed to characterize which US medical schools have the most female neurosurgery residents and to identify potential associations between medical school characteristics and successful recruitment of women pursuing a neurosurgery career. METHODS The authors evaluated a total of 1572 residents in US neurosurgery programs accredited by the Accreditation Council for Graduate Medical Education as of February 2021, representing match cohorts from 2014 to 2020. The authors extracted US medical school characteristics and ranked schools based on the percentages of women graduates entering neurosurgery. They additionally studied yearly trends of the percentage of women constituting incoming neurosurgery resident cohorts as well as associations between female recruitment percentage and medical school characteristics using univariable and stepwise multivariable linear regression (including significant univariable factors). RESULTS The cohort consisted of 1255 male and 317 (20%) female residents. Yearly trends indicated a significant drop in incoming female residents in 2016, followed by significant increases in 2017 and 2019. On multivariable analysis, the following factors were associated with a higher average percentage of female graduates entering neurosurgery: total affiliated neurosurgery clinical faculty (β = 0.006, 95% CI 0.001–0.011, p = 0.01), allopathic versus osteopathic schools (β = 0.231, 95% CI 0.053–0.409, p = 0.01), and top 10 U.S. News & World Report ranking (β = 0.380, 95% CI 0.129–0.589, p < 0.01). When the number of female clinical faculty was added to the model, the variable was not statistically significant. Multivariable bibliometric analyses indicated a higher mean preresidency H-index for men, with an even greater gender difference identified in the 2021 H-index. CONCLUSIONS This study characterizes which medical schools are most successful at recruiting female students who constituted the total neurosurgery resident workforce of the 2020–2021 academic year. The overall number of clinical neurosurgery faculty rather than faculty gender was independently associated with female recruitment. Gender differences in research productivity persisted with control for confounders and increased between preresidency and 2021 time points. Such understanding of factors that influence the recruitment of women can help improve female representation in neurosurgery residency training moving forward.

OBJECTIVE Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms whose treatment is often technically challenging. Given the low volume seen at most centers, perioperative outcomes have been reported infrequently. Here, the authors present the largest single-institution series of IMSCTs, focusing on the clinical presentation, histological makeup, perioperative outcomes, and long-term survival of surgically treated patients. METHODS A cohort of patients operated on for primary IMSCTs at a comprehensive cancer center between June 2002 and May 2020 was retrospectively identified. Data on patient demographics, tumor histology, neuraxial location, baseline neurological status, functional deficits, and operative characteristics were collected. Perioperative outcomes of interest included length of stay, postoperative complications, readmission, reoperation, and discharge disposition. Data were compared across tumor histologies using the Kruskal-Wallis H test, chi-square test, and Fisher exact test. Pairwise comparisons were conducted using Tukey’s honest significant difference test, chi-square test, and Fisher exact test. Long-term survival was assessed across tumor categories and histological subtype using the log-rank test. RESULTS Three hundred two patients were included in the study (mean age 34.9 ± 19 years, 77% white, 57% male). The most common tumors were ependymomas (47%), astrocytomas (31%), and hemangioblastomas (11%). Ependymomas and hemangioblastomas disproportionately localized to the cervical cord (54% and 59%, respectively), whereas astrocytomas were distributed almost equally between the cervical cord (36%) and thoracic cord (38%). Clinical presentation, extent of functional dependence, and postoperative 30-day outcomes were largely independent of underlying tumor pathology, although tumors of the thoracic cord had worse American Spinal Injury Association (ASIA) grades than cervical tumors. Rates of gross-total resection were lower for astrocytomas than for ependymomas (54% vs 84%, p < 0.01) and hemangioblastomas (54% vs 100%, p < 0.01). Additionally, 30-day readmission rates were significantly higher for astrocytomas than ependymomas (14% vs 6%, p = 0.02). Overall survival was significantly affected by the underlying pathology, with astrocytomas having poorer associated prognoses (40% at 15 years) than ependymomas (81%) and hemangioblastomas (66%; p < 0.01) and patients with high-grade ependymomas and astrocytomas having poorer long-term survival than those with low-grade lesions (p < 0.01). CONCLUSIONS The neuraxial location of IMSCTs, extent of resection, and postoperative survival differed significantly across tumor pathologies. However, perioperative outcomes did not vary significantly across tumor cohorts, suggesting that operative details, rather than pathology, may have a stronger influence on the short-term clinical course, whereas pathology appears to have a stronger impact on long-term survival.

OBJECTIVE In this study, the authors sought to determine which US medical schools have produced the most neurosurgery residents and to evaluate potential associations between recruitment and medical school characteristics. METHODS Demographic and bibliometric characteristics were collected for 1572 residents in US-based and Accreditation Council for Graduate Medical Education (ACGME)–accredited neurosurgery programs over the 2014 to 2020 match period using publicly available websites. US medical school characteristics were collected, including class size, presence of a home neurosurgery program, number of clinical neurosurgery faculty, research funding, presence of a neurosurgery interest group, and a top 10 ranking via U.S. News & World Report or Doximity. Correlations and associations were then evaluated using Pearson’s correlation coefficient (PCC), independent-samples t-test, and univariable or stepwise multivariable linear regression, as appropriate. RESULTS Vanderbilt University produced the most neurosurgery residents as a percentage of medical graduates at 3.799%. Case Western Reserve University produced the greatest absolute number of neurosurgery residents (n = 40). The following factors were shown to be associated with a higher mean percentage of graduates entering neurosurgery: number of clinical neurosurgery faculty (PCC 0.509, p < 0.001), presence of a neurosurgery interest group (1.022% ± 0.737% vs 0.351% ± 0.327%, p < 0.001) or home neurosurgery program (1.169% ± 0.766% vs 0.428% ± 0.327%, p < 0.001), allopathic compared with osteopathic school (0.976% ± 0.719% vs 0.232% ± 0.272%, p < 0.001), U.S. News top 10 ranking for neurology and neurosurgery (1.923% ± 0.924% vs 0.757% ± 0.607%, p < 0.001), Doximity top 10 residency program ranking (1.715% ± 0.803% vs 0.814% ± 0.688%, p < 0.001), and amount of NIH funding (PCC 0.528, p < 0.001). CONCLUSIONS The results of this study have delineated which medical schools produced the most neurosurgery residents currently in training, and the most important independent factors predicting the percentage of graduates entering neurosurgery and the preresidency h-index.

Objective Surgical site infection and dehiscence are devastating complications of surgery for spinal metastases. Wound closure involving plastic surgeons has been proposed as a strategy to lower post-operative complications. Here we investigated whether plastic surgery closure is associated with lower rates of wound complications, wound infection, and wound reoperation compared to simple closure by spine surgeons. Methods Patients surgically treated for metastatic tumors at a single comprehensive cancer center between April 2013–2020 were retrospectively identified. Primary pathology, demographic information, clinical characteristics, pre-operative laboratory values, tumor location, operative characteristics, and post-operative outcomes were collected. Univariable analyses used student t-tests for continuous variables and χ2 tests for categorical variables. Multivariable regressions were performed to control for confounders. Results We included 317 patients, of which 56 underwent closure by plastic surgeons and 291 by neurosurgeons. Patients in the plastic surgery cohort were more likely to have received prior radiation to the surgical site, more often on long-term corticosteroid therapy, and more likely to have sacrococcygeal tumors. Operations involving plastic surgeons were more likely to be revision surgeries, corpectomies, and to involve a staged approach. Additionally, patients in the plastic surgery cohort had longer incision lengths, longer surgeries, greater intraoperative blood loss (IOBL), were more likely to receive transfusions, and had longer hospitalizations. Local paraspinous advancement flaps were the most common complex wound closure technique. Plastic surgery closure was not significantly associated with a difference in rates of post-operative wound complications, wound infection, or wound-related reoperations compared to simple wound closure. Conclusion We identified that patients undergoing plastic surgery wound closure had worse baseline risk, longer surgeries, greater IOBL, and longer hospitalizations compared to patients receiving simple closure. Despite their increased risk, complex wound closure did not significantly alter the rates of post-operative wound complications, wound infection, or wound-related reoperations. Consideration may be given to plastic surgery closure in patients at high risk of wound complications or with extensive wound defects.

OBJECTIVE Frailty—the state defined by decreased physiological reserve and increased vulnerability to physiological stress—is exceedingly common in oncology patients. Given the palliative nature of spine metastasis surgery, it is imperative that patients be healthy enough to tolerate the physical insult of surgery. In the present study, the authors compared the association of two frailty metrics and the widely used Charlson Comorbidity Index (CCI) with postoperative morbidity in spine metastasis patients. METHODS A retrospective cohort of patients who underwent operations for spinal metastases at a comprehensive cancer center were identified. Data on patient demographic characteristics, disease state, medical comorbidities, operative details, and postoperative outcomes were collected. Frailty was measured with the modified 5-item frailty index (mFI-5) and metastatic spinal tumor frailty index (MSTFI). Outcomes of interest were length of stay (LOS) greater than the 75th percentile of the cohort, nonroutine discharge, and the occurrence of ≥ 1 postoperative complication. RESULTS In total, 322 patients were included (mean age 59.5 ± 12 years; 56.9% of patients were male). The mean ± SD LOS was 11.2 ± 9.9 days, 44.5% of patients had nonroutine discharge, and 24.0% experienced ≥ 1 postoperative complication. On multivariable analysis, increased frailty on mFI-5 and MSTFI was independently predictive of all three outcomes: prolonged LOS (OR 1.67 per point, 95% CI 1.06–2.63, p = 0.03; and OR 1.63 per point, 95% CI 1.29–2.05, p < 0.01, respectively), nonroutine discharge (OR 2.65 per point, 95% CI 1.74–4.04, p < 0.01; and OR 1.69 per point, 95% CI 1.36–2.11, p < 0.01), and ≥ 1 complication (OR 1.95 per point, 95% CI 1.23–3.09, p = 0.01; and OR 1.41 per point, 95% CI 1.12–1.77, p < 0.01). CCI was found to be independently predictive of only the occurrence of ≥ 1 postoperative complication (OR 1.45 per point, 95% CI 1.22–1.72, p < 0.01). CONCLUSIONS Frailty measured with either mFI-5 or MSTFI scores was a more robust independent predictor of adverse postoperative outcomes than the more widely used CCI. Both mFI-5 and MSTFI were significantly associated with prolonged LOS, higher complication rates, and nonroutine discharge. Further investigation in a prospective multicenter cohort is merited.

OBJECTIVE Previous studies have suggested the possibility of racial disparities in surgical outcomes for patients undergoing spine surgery, although this has not been thoroughly investigated in those with spinal metastases. Given the increasing prevalence of spinal metastases requiring intervention, knowledge about potential discrepancies in outcomes would benefit overall patient care. The objective in the present study was to investigate whether race was an independent predictor of postoperative complications, nonroutine discharge, and prolonged length of stay (LOS) after surgery for spinal metastasis. METHODS The authors retrospectively examined patients at a single comprehensive cancer center who had undergone surgery for spinal metastasis between April 2013 and April 2020. Demographic information, primary pathology, preoperative clinical characteristics, and operative outcomes were collected. Factors achieving p values < 0.15 on univariate regression were entered into a stepwise multivariable logistic regression to generate predictive models. Nonroutine discharge was defined as a nonhome discharge destination and prolonged LOS was defined as LOS greater than the 75th percentile for the entire cohort. RESULTS Three hundred twenty-eight patients who had undergone 348 operations were included: 240 (69.0%) White and 108 (31.0%) Black. On univariable analysis, cohorts significantly differed in age (p = 0.02), marital status (p < 0.001), insurance status (p = 0.03), income quartile (p = 0.02), primary tumor type (p = 0.04), and preoperative Karnofsky Performance Scale (KPS) score (p < 0.001). On multivariable analysis, race was an independent predictor for nonroutine discharge: Black patients had significantly higher odds of nonroutine discharge than White patients (adjusted odds ratio [AOR] 2.24, 95% confidence interval [CI] 1.28–3.92, p = 0.005). Older age (AOR 1.06 per year, 95% CI 1.03–1.09, p < 0.001), preoperative KPS score ≤ 70 (AOR 3.30, 95% CI 1.93–5.65, p < 0.001), preoperative Frankel grade A–C (AOR 3.48, 95% CI 1.17–10.3, p = 0.02), insurance status (p = 0.005), being unmarried (AOR 0.58, 95% CI 0.35–0.97, p = 0.04), number of levels (AOR 1.17 per level, 95% CI 1.05–1.31, p = 0.004), and thoracic involvement (AOR 1.71, 95% CI 1.02–2.88, p = 0.04) were also predictive of nonroutine discharge. However, race was not independently predictive of postoperative complications or prolonged LOS. Higher Charlson Comorbidity Index (AOR 1.22 per point, 95% CI 1.04–1.43, p = 0.01), low preoperative KPS score (AOR 1.84, 95% CI 1.16–2.92, p = 0.01), and number of levels (AOR 1.15 per level, 95% CI 1.05–1.27, p = 0.004) were predictive of complications, while insurance status (p = 0.05), income quartile (p = 0.01), low preoperative KPS score (AOR 1.64, 95% CI 1.03–2.72, p = 0.05), and number of levels (AOR 1.16 per level, 95% CI 1.05–1.30, p = 0.004) were predictive of prolonged LOS. CONCLUSIONS Race, insurance status, age, baseline functional status, and marital status were all independently associated with nonroutine discharge. This suggests that a combination of socioeconomic factors and functional status, rather than medical comorbidities, may best predict postdischarge disposition in patients treated for spinal metastases. Further investigation in a prospective cohort is merited.

Significance Progress in studying the androgen receptor (AR), the primary drug target in prostate cancer, has been hampered by challenges in expressing and purifying active multidomain AR for use in cell-free biochemical reconstitution assays. Here we successfully express full-length and truncated AR variants and demonstrate that the oncogenic ETS protein ERG, responsible for half of all prostate cancers, enhances the ability of AR to bind DNA through direct interaction with AR. In addition to providing a biochemical system to evaluate AR activity on different DNA templates, our findings provide insight into why ERG-positive prostate cancers have an expanded AR cistrome., The androgen receptor (AR) is a type I nuclear hormone receptor and the primary drug target in prostate cancer due to its role as a lineage survival factor in prostate luminal epithelium. In prostate cancer, the AR cistrome is reprogrammed relative to normal prostate epithelium and particularly in cancers driven by oncogenic ETS fusion genes. The molecular basis for this change has remained elusive. Using purified proteins, we report a minimal cell-free system that demonstrates interdomain cooperativity between the ligand (LBD) and DNA binding domains (DBD) of AR, and its autoinhibition by the N terminus of AR. Furthermore, we identify ERG as a cofactor that activates AR’s ability to bind DNA in both high and lower affinity contexts through direct interaction within a newly identified AR-interacting motif (AIM) in the ETS domain, independent of ERG’s own DNA binding ability. Finally, we present evidence that this interaction is conserved among ETS factors whose expression is altered in prostate cancer. Our work highlights, at a biochemical level, how tumor-initiating ETS translocations result in reprogramming of the AR cistrome.

β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, to initiate signaling on their own, and to mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR-βarr complexes: the "tail" conformation, with βarr primarily coupled to the phosphorylated GPCR C-terminal tail, and the "core" conformation, where, in addition to the phosphorylated C-terminal tail, βarr is further engaged with the receptor transmembrane core. However, the relationship of these distinct conformations to the various functions of βarrs is unknown. Here, we created a mutant form of βarr lacking the "finger-loop" region, which is unable to form the core conformation but retains the ability to form the tail conformation. We find that the tail conformation preserves the ability to mediate receptor internalization and βarr signaling but not desensitization of G protein signaling. Thus, the two GPCR-βarr conformations can carry out distinct functions.