Antiretroviral Drug Repositioning for Glioblastoma.

Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in multiple cancers; however, its efficacy in GBM remains unclear. To better understand the pleiotropic anticancer effects of ART on GBM, we conducted a comprehensive drug repurposing analysis of ART in GBM to highlight its utility in translational neuro-oncology. To uncover the anticancer role of ART in GBM, we conducted a comprehensive bioinformatic and in vitro screen of antiretrovirals against glioblastoma. Using the DepMap repository and reversal of gene expression score, we conducted an unbiased screen of 16 antiretrovirals in 40 glioma cell lines to identify promising candidates for GBM drug repositioning. We utilized patient-derived neurospheres and glioma cell lines to assess neurosphere viability, proliferation, and stemness. Our in silico screen revealed that several ART drugs including reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) demonstrated marked anti-glioma activity with the capability of reversing the GBM disease signature. RTIs effectively decreased cell viability, GBM stem cell markers, and proliferation. Our study provides mechanistic and functional insight into the utility of ART repurposing for malignant gliomas, which supports the current literature. Given their safety profile, preclinical efficacy, and neuropenetrance, ARTs may be a promising adjuvant treatment for GBM.

The Effect of the Coronavirus Disease 2019 Pandemic on Pituitary Surgery.

OBJECTIVE: As the coronavirus disease 2019 (COVID-19) pandemic spread to the United States in 2020, there was an impetus toward postponing or ceasing nonurgent transsphenoidal pituitary surgeries to prevent the spread of the virus. Some centers encouraged transcranial approaches for patients with declining neurologic function. However, no large-scale data exist evaluating the effects that this situation had on national pituitary practice patterns. METHODS: Pituitary surgeries in the National Inpatient Sample were identified from 2017 to 2020. Surgeries in 2020 were compared with the 3 years previously to determine any differences in demographics, surgical trends/approaches, and perioperative outcomes. RESULTS: In 2020, there was a decline in overall pituitary surgeries (34.2 vs. 36.3%; odds ratio (OR), 0.88; P < 0.001) yet transsphenoidal approaches represented a higher proportion of interventions (69.0 vs. 64.9%; P < 0.001). Neurosurgical complications were higher (51.9 vs. 47.4%; OR, 1.13; P < 0.001) and patients were less likely to be discharged home (86.4 vs. 88.5%; OR, 0.84; P < 0.001). This finding was especially true in April 2020 during the first peak in COVID-19 cases, when transcranial approaches and odds of mortality/complications were highest. CONCLUSIONS: In 2020, transsphenoidal surgery remained the preferred approach for pituitary tumor resection despite initial recommendations against the approach to prevent COVID-19 spread. Pituitary surgeries had a higher risk of periprocedural complications despite accounting for preoperative comorbidities, COVID-19 infection status, and surgical approach, suggesting that an overwhelmed hospital system can negatively influence surgical outcomes in noninfected patients.

Outcomes in patients with large vessel occlusion strokes undergoing mechanical thrombectomy with concurrent COVID-19: a nationwide retrospective analysis.

BACKGROUND: Preliminary studies show that patients with large vessel occlusion (LVO) acute ischemic strokes have worse outcomes with concurrent COVID-19 infection. We investigated the outcomes for patients with LVO strokes undergoing mechanical thrombectomy (MT) with concurrent COVID-19 infection. METHODS: The National Inpatient Database (NIS) was used for our analysis. Patients in the year 2020 with an ICD-10 diagnosis code for acute ischemic stroke and procedural code for MT were included with and without COVID-19. Odds ratios (OR) were calculated using a logistic regression model with age, sex, stroke location, Elixhauser comorbidity score, and other patient variables deemed clinically relevant as covariates. RESULTS: Patients in the COVID-19 group were younger (64.3±14.4 vs 69.4±14.5 years, P<0.001), had a higher rate of inpatient mortality (22.4% vs 10.1%, P<0.001), and a longer length of stay (10 vs 6 days, P<0.001). Patients with COVID-19 had higher odds of death (OR 2.78, 95% CI 2.11 to 3.65) and lower odds of a routine discharge (OR 0.65, 95% CI 0.48 to 0.89). There was no difference in the odds of subsequent stroke and cerebral hemorrhage, but patients with COVID-19 had statistically significantly higher odds of respiratory failure, pulmonary embolism, deep vein thrombosis, myocardial infarction, acute kidney injury, and sepsis. CONCLUSIONS: Patients with LVOs undergoing MT within the 2020 NIS database had worse outcomes when co-diagnosed with COVID-19, likely due to non-neurological manifestations of COVID-19.

Impact of COVID-19 pandemic on treatment and outcomes of cerebral arteriovenous malformations.

BACKGROUND: There has been a recent decrease in interventional management of cerebral arteriovenous malformations (AVMs). The objective of our study was to evaluate the changing patterns in management of AVMs in the first year of the COVID-19 pandemic. METHODS: The National Inpatient Sample (NIS) database was used. From 2016 to 2020, patients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis code for a cerebral AVM were included. An intervention was defined as ICD-10 code for surgical, endovascular, or stereotactic radiosurgery treatment. Odds ratios (ORs) were calculated using a logistic regression model with covariates deemed to be clinically relevant. RESULTS: 63 610 patients with AVMs were identified between 2016 and 2020, 14 340 of which were ruptured. In 2020, patients had an OR of 0.69 for intervention of an unruptured AVM (P<0.0001) compared with 2016-19. The rate of intervention for unruptured AVMs decreased to 13.5% in 2020 from 17.6% in 2016-19 (P<0.0001). The rate of AVM rupture in 2020 increased to 23.9% from 22.2% in 2016-19 (P<0.0001). In 2020, patients with ruptured AVMs had an OR for inpatient mortality of 1.72 compared with 2016-19. Linear regression analysis from 2016 to 2020 showed an inverse relationship between intervention rate and rupture rate (slope -0.499, R2=0.88, P=0.019). CONCLUSION: In 2020, the rate of intervention for unruptured cerebral AVMs decreased compared with past years, with an associated increase in the rate of rupture. Patients with ruptured AVMs also had a higher odds of mortality.

Laser Interstitial Thermal Therapy Induces Robust Local Immune Response for Newly Diagnosed Glioblastoma With Long-term Survival and Disease Control.

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique used to ablate intra-axial brain tumors. The impact of LITT on the tumor microenvironment is scarcely reported. Nonablative LITT-induced hyperthermia (33-43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting immunogenic cell death. To understand the local immune response post-LITT, we performed longitudinal molecular profiling in a newly diagnosed glioblastoma and conducted a systematic review of anti-tumoral immune responses after LITT. A 51-year-old male presented after a fall with progressive dizziness, ataxia, and worsening headaches with a small, frontal ring-enhancing lesion. After clinical and radiographic progression, the patient underwent stereotactic needle biopsy, confirming an IDH-WT World Health Organization Grade IV Glioblastoma, followed by LITT. The patient was subsequently started on adjuvant temozolomide, and 60 Gy fractionated radiotherapy to the post-LITT tumor volume. After 3 months, surgical debulking was conducted due to perilesional vasogenic edema and cognitive decline, with H&E staining demonstrating perivascular lymphocytic infiltration. Postoperative serial imaging over 3 years showed no evidence of tumor recurrence. The patient is currently alive 9 years after diagnosis. Multiplex immunofluorescence imaging of pre-LITT and post-LITT biopsies showed increased CD8 and activated macrophage infiltration and programmed death ligand 1 expression. This is the first depiction of the in-situ immune response to LITT and the first human clinical presentation of increased CD8 infiltration and programmed death ligand 1 expression in post-LITT tissue. Our findings point to LITT as a treatment approach with the potential for long-term delay of recurrence and improving response to immunotherapy.

Concurrent bacterial endocarditis is associated with worse inpatient outcomes for large vessel occlusions.

BACKGROUND: Neurological complications of bacterial endocarditis (BE) are common, including acute ischemic stroke (AIS). Although mechanical thrombectomy (MT) is effective for large vessel occlusion (LVO) stroke, data are limited on MT for LVOs in patients with endocarditis. We assess outcomes in patients treated with thrombectomy for LVOs with concurrent BE. METHODS: The National Inpatient Sample (NIS) was used. The NIS was queried from October 2015-2019 for patients receiving MT for LVO of the middle cerebral artery. Odds ratios (OR) were calculated using a multivariate logistic regression model. RESULTS: A total of 635 AIS with BE patients and 57 420 AIS only patients were identified undergoing MT. AIS with BE patients had a death rate of 26.8% versus 10.2% in the stroke alone cohort, and were also less likely to have a routine discharge (10.2% vs 20.9%, both P<0.0001). AIS with BE patients had higher odds of death (OR 3.94) and lower odds of routine discharge (OR 0.23). AIS with BE patients also had higher rates of post-treatment cerebral hemorrhage, 39.4% vs 23.7%, with an OR of 2.20 (P<0.0001 for both analyses). These patients also had higher odds of other complications, including hydrocephalus, respiratory failure, acute kidney injury, and sepsis. CONCLUSION: While MT can be used to treat endocarditis patients with LVOs, these patients have worse outcomes. Additional investigations should be undertaken to better understand their clinical course, and further develop treatments for endocarditis patients with stroke.

Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma.

Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2-specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target.

Chiari I malformation management in patients with heritable connective tissue disorders.

Background: Chiari malformation type I (CMI) is relatively common neurosurgical condition typically treated with posterior fossa decompression. However, the management of CMI in patients with heritable connective tissue disorders (CTDs), such as Ehlers-Danlos Syndrome, Marfan Syndrome, or Osteogenesis Imperfecta, involves a unique set of perioperative challenges. Objective: This study aims to define the demographic information, comorbidities, and perioperative course of patients with concomitant CMI and CTD. Methods: Patients with CMI admitted for surgical decompression from 2008 to 2015 were captured using the National Inpatient Sample (NIS). Information was collected based on ICD-9 codes. Descriptive and regression analyses were performed in SPSS (version 26). Results: 38,169 CMI patients, 353 of whom had CTD (0.92%), were identified. CMI patients with CTD were more likely to be female (p < 0.001) and present during teenage (p = 0.033) or young adult years (p < 0.001). They had more chronic issues (p < 0.001): systemic comorbidities include postural orthostatic tachycardia syndrome, cardiac dysrhythmias, and gastroparesis (all p < 0.001). CNS comorbidities include migraine, tethered spinal cord, and epilepsy (all p < 0.001). They have increased joint instability (both p < 0.001), as well as craniocervical instability (CCI). More posterior cervical fusion surgeries and application of cervical halo devices were seen during the same inpatient stay (both p < 0.001). Conclusions: Patients with concurrent CTD and CMI were more likely to present with complex Chiari and associated CCI. They were also younger, more often female, and had more systemic, CNS, and joint abnormalities. As such, preoperative recognition of an underlying CTD is imperative to achieve optimal outcomes in this patient population.

Transradial Access Failures During Neuroangiography for Patients With Moyamoya.

BACKGROUND: Despite studies continuing to demonstrate the utility of transradial access (TRA) in neuroangiography, minimal data exist regarding predictors of TRA failure. Furthermore, although many patients with moyamoya disease/syndrome will require life-long angiographic evaluation, even less has been reported on the usage of TRA in this population. OBJECTIVE: To perform a matched analysis at our high-volume moyamoya center to determine predictors of TRA failure in these patients. METHODS: A total of 636 patients undergoing TRA for neuroangiography were identified from 2018 to 2020. Demographic and angiographic characteristics including radial artery spasm (RAS), radial anomalies, and access site conversion were compared between patients with moyamoya and the rest of the cohort. A 4:1 matched analysis, based on age and sex, was also performed to eliminate confounding variables. RESULTS: Patients with moyamoya were younger (40 vs 57 years, P < .0001), had smaller radial diameters (1.9 vs 2.6 mm, P < .0001), more commonly had a high brachial bifurcation (25.9% vs 8.5%, P = .008), more frequently experienced clinically significant RAS (40% vs 8.4%, P < .0001), and more often required access site conversion (26.7% vs 7.8%, P = .002). Increasing age was associated with less TRA failures in patients with moyamoya (odds ratio = 0.918) but more failures in the rest of the cohort (odds ratio = 1.034). In the matched analysis, patients with moyamoya continued to experience more radial anomalies, RAS, and access site conversions. CONCLUSION: Patients with moyamoya, when controlling for age and sex, have higher rates of TRA failure during neuroangiography. Increasing age in Moyamoya is inversely correlated with TRA failures suggesting that younger patients with moyamoya are at higher risk of extracranial arteriopathy.

Predicting Academic Career Placement via Development of Novel Intra-residency Metrics.

OBJECTIVE: Increasing centralization of high-level neurosurgical practice at academic centers has increased the need for academic neurosurgeons. The lack of systematic metrics-based analyses among neurosurgery trainees and the recent pass/fail U.S. Medical Licensing Examination system necessitates a multiparametric approach to assess academic success among trainees. METHODS: We conducted a comprehensive analysis of the University of Miami residency program using 2 data sets, one containing applicants' pre-residency metrics and a second containing trainees' intra-residency metrics. Intra-residency metrics were subjectively and anonymously assessed by faculty. Univariate and multivariate logistic regression analyses were performed to determine differences among academic and non-academic neurosurgeons and identify predictors of academic careers. RESULTS: Academic neurosurgeons had a significantly higher median Step 1 percentile relative to non-academic neurosurgeons (P = 0.015), and medical school ranking had no significant impact on career (P > 0.05). Among intra-residency metrics, academic neurosurgeons demonstrated higher mean rating of leadership skills (mean difference [MD] 0.46, P = 0.0011), technical skill (MD 0.42, P = 0.006), and other intra-residency metrics. Higher administrative and leadership skills were significantly associated with increased likelihood of pursuing an academic career (odds ratio [OR] 9.03, 95% CI [2.296 to 49.88], P = 0.0044). Clinical judgment and clinical knowledge were strongly associated with pursuit of an academic career (OR 9.33 and OR 9.32, respectively, with P = 0.0060 and P = 0.0010, respectively). CONCLUSIONS: Pre-residency metrics had little predictive value in determining academic careers. Furthermore, medical school ranking does not play a significant role in determining a career in academic neurosurgery. Intra-residency judgment appears to play a significant role in career placement, as academic neurosurgeons were rated consistently higher than their non-academic peers in multiple key parameters by their attending physicians.

Transdural Approach for Resection of Craniovertebral Junction Cysts: Case Series.

BACKGROUND: Craniovertebral junction (CVJ) cysts, including retro-odontoid pseudotumors, are challenging pathologies to treat and manage effectively. Surgical intervention is indicated when these lesions result in progressive myelopathy, intractable pain, or instability. OBJECTIVE: To present a case series of older patients who underwent successful resection retro-odontoid lesions using transdural approach. METHODS: A single-center, retrospective observation study of older patients who underwent transdural resection of CVJ cysts at a single institution was performed. Summary demographic information, clinical presentation, perioperative and intraoperative imaging, and Nurick scores were collected and analyzed. RESULTS: Eight patients were included (mean age [±SD] 75.88 ± 9.09 years). All patients presented with retro-odontoid lesions resulting in severe cervical stenosis, cord compression, and myelopathy. The mean duration of surgery was 226 ± 83.7 minutes. The average intraoperative blood loss was 181.2 cc. The average hospital stay was 4.5 days ± 1.3 (range, 3-7 days). The average follow-up time was 12.5 ± 9.5 months. No intraoperative complications were encountered. The Nurick classification score for myelopathy improved at the final postoperative examination (2.38 ± 1.06 vs 1 ± 1.07). Three patients demonstrated a pre-existing deformity prompting an instrumented fusion. Both computed tomography and MRI evidence of complete regression of retro-odontoid cyst were noted in all patients on the final follow-up. CONCLUSION: Posterior cervical transdural approach for ventral lesions at the CVJ is a safe and effective means of treating older patients with progressive myelopathy. This technique provides immediate spinal cord decompression while limiting neurological complications commonly associated with open or endoscopic anterior transpharyngeal approaches.

National reduction in cerebral arteriovenous malformation treatment correlated with increased rupture incidence.

BACKGROUND: Recently, there has been a shift in management of unruptured cerebral arteriovenous malformations (AVMs) following studies suggesting that medical management alone was superior to interventional therapy. OBJECTIVE: To evaluate the influence of contemporary AVM management on AVM rupture patterns in the United States. METHODS: 154 297 AVM admissions were identified between 2003 and 2017 in the National Inpatient Sample. Annual AVM intervention and rupture rates were computed and multivariable logistic regression assessed the likelihood of AVM intervention pre- and post-2014. Segmented regression identified significant change points and fitted segmented linear models for annual intervention and rupture rates. Correlation coefficients assessed the relationship between annual AVM intervention and rupture rates. RESULTS: For unruptured AVMs, intervention likelihood and proportion decreased after 2014 (28.1% to 22.3%, p<0.0001; adjusted OR=0.857, 95% CI 0.751 to 0.977, p=0.02). Ruptured AVM admissions increased from 14.7% to 18.6% after 2014 (p<0.0001). Between 2003 and 2017, segmented linear regression identified one significant change point in intervention rate between 2014 and 2015. Average annual percent change for rupture incidence and intervention rate increased by 0.49% (p=0.0001) and decreased by 1.17% (p=0.0001), respectively. Annual AVM intervention rates were inversely correlated with annual AVM rupture incidence (Pearson coefficient=-0.82, p=0.0002). In 2017, the annual AVM rupture rate (20.6%) surpassed the annual AVM intervention rate (19.7%). CONCLUSIONS: After 2014, the likelihood of intervention for unruptured AVMs decreased while the incidence of ruptured AVMs increased. These findings suggest that fewer unruptured AVM treatments may lead to increases in AVM rupture incidence.

Effects of Obesity on Cervical Disc Arthroplasty Complications.

OBJECTIVE: High body mass index is a well-established modifiable comorbidity that is known to increase postoperative complications in all types of surgery, including spine surgery. Obesity is increasing in prevalence amongst the general population. As this growing population of obese patients ages, understanding how they faire undergoing cervical disc arthroplasty (CDA) is important for providing safe and effective evidence-based care for cervical degenerative pathology. METHODS: Our study used the Healthcare Cost and Utilization Project's National Inpatient Sample to assess patients undergoing CDA comparing patient characteristics and outcomes in nonobese patients to obese patients from 2004 to 2014. RESULTS: Our study found a significant increase in the overall utilization of CDA as a treatment modality (p = 0.012) and a statistically significant increase in obese patients undergoing CDA (p < 0.0001) from 2004 to 2014. Obesity was identified as an independent risk factor associated with increased rates of inpatient neurologic complications (odds ratio [OR], 6.99; p = 0.03), pulmonary embolus (OR, 5.41; p = 0.05), and wound infection (OR, 6.97; p < 0.001) in patients undergoing CDA from 2004 to 2014. CONCLUSION: In patients undergoing CDA, from 2004 to 2014, obesity was identified as an independent risk factor with significantly increased rates of inpatient neurologic complications, pulmonary embolus and wound infection. Large prospective trials are needed to validate these findings.

Brain Arteriovenous Malformations: Status of Open Surgery after A Randomized Trial of Unruptured Brain Arteriovenous Malformations.

The results of "A Randomized Trial of Unruptured Brain Arteriovenous Malformations" (ARUBA) suggested that observation alone resulted in less morbidity and mortality than intervention for these lesions. These findings generated significant controversy throughout the cerebrovascular community and resulted in several subsequent studies investigating the role of microsurgical resection on ARUBA-eligible patients. Herein, we provide a brief overview of the ARUBA trial, its subsequent criticisms, the resultant publications challenging the findings in ARUBA, and discuss the available data regarding the effect ARUBA has had on arteriovenous malformation (AVM) treatments.

The Role of HERV-K in Cancer Stemness.

Human endogenous retrovirus-K (HERV-K) is the most recently integrated retrovirus in the human genome, with implications for multiple disorders, including cancer. Although typically transcriptionally silenced in normal adult cells, dysregulation of HERV-K (HML-2) elements has been observed in cancer, including breast, germ cell tumors, pancreatic, melanoma, and brain cancer. While multiple methods of carcinogenesis have been proposed, here we discuss the role of HERV-K (HML-2) in the promotion and maintenance of the stem-cell in cancer. Aberrant expression of HERV-K has been shown to promote expression of stem cell markers and promote dedifferentiation. In this review, we discuss HERV-K (HML-2) as a potential therapeutic target based on evidence that some tumors depend on the expression of its proteins for survival.

Positive predictive value and trends of inferior petrosal sinus sampling (IPSS) in diagnosing cushing disease and ectopic ACTH secretion: A systematic review and meta-analysis.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) offers a means of differentiating between Cushing disease and Cushing syndrome with lower false-positive and false-negative rates relative to traditional techniques. However, consolidated data on efficiency reflecting contemporary use is lacking. We present a comprehensive meta-analysis of IPSS as a means of diagnosing ACTH-cortisol axis derangements via both CRH and desmopressin-stimulated techniques. METHODS: Searches of 7 electronic databases from inception to December 2020 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were pooled by random-effects meta-analyses of proportions where possible. We performed a meta-analysis of sixty-eight unique publications, assessing each technique for positive predictive value (PPV), false positive rates, and overall changes in practice patterns over time. RESULTS: A total of 68 studies satisfied all criteria, with 3685 (3471, 94.2% confirmed) and 332 (285, 85.8% confirmed) patients tested for Cushing's disease and syndrome, respectively. Pooled analyses demonstrated an overall PPV of 89.3% (95%CI[83.6%, 94.0%]) in CRH stimulation diagnosis of Cushing disease. In desmopressin stimulation, our analyses demonstrated an overall PPV of 96.5% (95%CI[94.5%, 98.1%]) in diagnosis of Cushing disease. There was a significant decline in the use of CRH-stimulation IPSS in diagnosis of both Cushing disease (p = 0.0055) and Cushing syndrome (p = 0.013). Concurrently, there was a significant increase in the use of desmopressin-stimulation IPSS in diagnosis of both pathologies (p < 0.0001). CONCLUSION: Our findings demonstrate significant changes in practice patterns with respect to IPSS stimulation technique. Our pooled analyses demonstrate improved diagnostic performance in desmopressin stimulation procedures relative to CRH stimulation procedures. Further multi-institutional studies with special attention to acquiring quality data for sensitivity, specificity, and other critical analyses are necessary to truly evaluate this promising technique.

Glioblastoma multiforme in patients with human immunodeficiency virus: an integrated review and analysis.

INTRODUCTION: As lifespans for persons living with HIV (PLWH) have improved over the last decade, there has been a simultaneous increase in non-AIDS-related cancer in that group. However, there is a paucity of data regarding the incidence of glioblastoma multiforme (GBM) in PLWH. Better understanding of the oncogenesis, natural history, and treatment outcomes of GBM in PLWH should lead to improved treatment strategies. METHODS: We performed a comprehensive literature search of six electronic databases to identify eligible cases of GBM among PLWH. Kaplan-Meier estimates, Fisher's exact test, and logistic regression were used to interrogate the data. Epidemiologic data on global HIV prevalence was obtained from the 2016 UNAIDS incidence report, and CNS cancer incidence was obtained from the GDB 2016 Brain and Other CNS Cancer Collaborators. RESULTS: There is an inverse relationship between the incidence of HIV and CNS cancer globally. Median overall survival (OS) from GBM diagnosis was 8 months. Estimates for survival at 1 and 2 years were 28 and 5%, respectively. There were no statistically significant predictors of OS in this setting. There was a significant difference (p < 0.01) in OS in PLWH and GBM when compared to TCGA age matched cohorts. CONCLUSION: The diagnosis of GBM in PLWH is severely underreported in the literature. Despite maximal treatment, OS in this patient population is significantly less than in HIV-negative people. There was a poor prognosis of GBM in PLWH, which is inconsistent with previous reports. Further investigation is required for PLWH and concomitant GBM. Analyses must consider if HAART is maintained in PLWH during GBM treatment.

The declining incidence of cervical spine surgery in patients with rheumatoid arthritis: a single-surgeon series and literature review.

OBJECTIVE: With an increasing number of disease-modifying drugs available to manage rheumatoid arthritis (RA), spine surgeons have anecdotally noted decreased rates of cervical spine surgical procedures in this population. Although these medications have been shown to mitigate RA progression and its systemic effects on joint destruction, there are currently no large-scale studies of RA patients that suggest the use of these disease-modifying drugs has truly coincided with a decline in cervical spine surgery. METHODS: Patients with RA who underwent cervical spinal fusion from 1998 to 2021 performed by the senior author were retrospectively reviewed. The cohort was stratified into 3 categories based on procedure level: 1) occipitocervical, 2) atlantoaxial, and 3) subaxial. The number of surgical procedures per year in each subgroup was evaluated to determine treatment trends over time. National (Nationwide) Inpatient Sample (NIS) data on both RA and non-RA patients who underwent cervical fusion were analyzed to assess for surgical trends over time and for differences in likelihood of surgical intervention between RA and non-RA patients over the epoch. RESULTS: From 1998 to 2021, the number of overall cervical fusions performed in RA patients significantly declined (-0.13 procedures/year, p = 0.01) in this cohort, despite an overall significant increase in cervical fusions in non-RA patients over the same period. NIS analysis of cervical fusions across all patients similarly demonstrated a significant increase in cervical fusions over the same epoch (19,278 cases/year, p < 0.0001). When normalized for changes in population size, the incidence of new surgical procedures was lower in patients with RA regardless of surgical technique. Anterior cervical fusion was the most common approach used over the epoch in both RA and non-RA patients; correspondingly, RA patients were significantly less likely to undergo anterior cervical fusion (OR 0.655, 95% CI -0.4504 to -0.3972, p < 0.0001). CONCLUSIONS: At the authors' institution, there was a clear decline in the number of cervical fusions performed to treat the 3 most common forms of cervical spine pathology in RA patients (basilar impression, atlantoaxial instability, and subaxial cervical deformity). Although national trends suggest an increase in total cervical fusions in both RA and non-RA patients, the incidence of new procedures in patients with RA was significantly lower than in patients without RA, which supports the anecdotal results of spine surgeons nationally.