Intramedullary spinal cord abscess as postoperative complication: A case report.

Background: Intramedullary spinal cord abscesses (ISCA) can result in high morbidity and mortality if not treated in a timely manner. The incidence and outcomes of postsurgical ISCA are unknown. We present a case of a 52-year-old male patient with neurofibromatosis type 1 who developed an intramedullary spinal cord abscess after a previous resection of a cervical intradural, extramedullary neurofibroma. Case Description: A 52-year-old male with a history of neurofibromatosis type 1 had previously undergone multiple resections of cervical intradural, extramedullary neurofibromas with internal stabilization. Sixteen months after his initial surgery, he developed acute-onset interscapular pain with bilateral lower extremity pain and left hemi-body weakness. Magnetic resonance imaging (MRI) of the cervical spine demonstrated an enlarging contrast-enhancing intramedullary lesion. Surgical exploration and evacuation of the lesion were completed. Intramedullary cultures confirmed a Serratia marcescens abscess. After abscess evacuation and intravenous antibiotics, the patient's symptoms resolved. Conclusion: Given the potential for permanent neurologic damage and loss of independence with intramedullary spinal cord abscess, we advocate that clinicians maintain a high index of suspicion in the postsurgical patient. Diagnostic imaging through contrasted MRI or computed tomography myelogram should be obtained, and prompt intervention, including evacuation and/or antibiotics, should be implemented for the best chance of a favorable outcome.

Development of a "Geo-Tagged" tumor sample registry: intra-operative linkage of sample location to imaging.

PURPOSE: There is a growing body of literature documenting glioma heterogeneity in terms of radiographic, histologic, molecular, and genetic characteristics. Incomplete spatial specification of intraoperative tumor samples may contribute to variability in the results of pathological and biological investigations. We have developed a system, termed geo-tagging, for routine intraoperative linkage of each tumor sample to its location via neuronavigation. METHODS: This is a single-institution, IRB approved, prospective database of undergoing clinically indicated surgery. We evaluated relevant factors affecting data collection by this registry, including tumor and surgical factors (e.g. tumor volume, location, grade and surgeon). RESULTS: Over a 2-year period, 487 patients underwent craniotomy for an intra-axial tumor. Of those, 214 underwent surgery for a newly diagnosed or recurrent glioma. There was significant variation in the average number of samples collected per registered case, with a range of samples from 2.53 to 4.75 per tumor type. Histology and grade impacted on sampling with a range of 2.0 samples per tumor in Grade four, IDH-WT gliomas to 4.5 samples in grade four, IDH-mutant gliomas. The range of cases with sampling per surgeon was 6 to 99 with a mean of 47.6 cases and there was a statistically significant differences between surgeons. Tumor grade did not have a statistically significant impact on number of samples per case. No significant correlation was found between the number of samples collected and enhancing tumor volume, EOR, or volume of tumor resected. CONCLUSION: We are using the results of this analysis to develop a prospective sample collection protocol.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

STUDY QUESTION: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)? SUMMARY ANSWER: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro. STUDY DESIGN, SIZE, DURATION: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility. WIDER IMPLICATIONS OF THE FINDINGS: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes. STUDY FUNDING/COMPETING INTEREST(S): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare.

Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases.

BACKGROUND: Immunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and various systemic therapies. METHODS: Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1+CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. Comparisons between groups were made for overall survival (OS), distant MBM control, local MBM, systemic progression-free survival (sPFS), and neurotoxicity. RESULTS: In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 and 2020 were identified. On MVA, treatment with anti-PD1+anti-CTLA-4, anti-PD-1, and BRAF/MEK-i improved distant intracranial control over conventional chemotherapy. No significant differences were noted in local control (LC) between groups (p = 0.78). Kaplan-Meier OS at 12 months for anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, and conventional chemotherapy was 68%, 59%, 45%, 62%, 21%, and 15%, respectively (p = <0.0001). The sPFS rates at 12 months were 57%, 53%, 42%, 45%, 14%, and 6% (p = <0.0001). No significant differences were noted in rates of radiation necrosis (p = 0.93). CONCLUSIONS: This is among the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in OS, distant MBM control, and sPFS by systemic therapy. No differences in LC or radiation necrosis risk were noted.

Radiofrequency Ablation Provides Rapid and Durable Pain Relief for the Palliative Treatment of Lytic Bone Metastases Independent of Radiation Therapy: Final Results from the OsteoCool Tumor Ablation Post-Market Study.

PURPOSE: The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. MATERIALS AND METHODS: Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. RESULTS: 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. CONCLUSION: RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. LEVEL OF EVIDENCE: 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma.

Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.

Kyphoplasty of C2 Pathological Fractures Using an Anterior Midline Approach and Steerable Osteotome: Technical Note and Case Series.

BACKGROUND: Malignant lesions involving the C2 vertebral body (axis) may be challenging to treat, and not all patients with cancer are good candidates for posterior cervical or occipitocervical instrumentation. OBJECTIVE: To describe a modified technique of the direct anterolateral C2 kyphoplasty using a steerable osteotome, commonly used for the treatment of thoracolumbar spinal lesions. We also report a case series of 11 patients treated with this technique at our institution. METHODS: The authors performed a retrospective review of all patients who underwent a C2 kyphoplasty using the anterior midline approach from 2010 to 2020. Patient demographics, tumor characteristics, pain severity (visual analog scale), Karnofsky performance status , perioperative complications, and postoperative spinal stability were assessed. RESULTS: The main indication for a C2 kyphoplasty was refractory neck pain. All patients tolerated the procedure well. There were no intraoperative complications. One patient developed transient dysphagia. Visual analog scale scores were 9.00 ± 1.10 preoperative and 3.73 ± 1.85 at 2 weeks and 1.67 ± 1.66 at 3 months after the procedure and continued to stay low during the remainder of the follow-up (4-60 months). The Karnofsky performance status improved from 72.73 ± 11.04 preoperatively to 82.22 ± 8.33 at 2 weeks and 86.67 ± 5.00 at 3 months after the procedure. There was no evidence of new occurrence or progression of C2 fractures. CONCLUSION: The anterior kyphoplasty using a steerable osteotome for tumors of the axis can result in lasting pain reduction and improved cervical stability while demonstrating a low complication rate.

Molecular determinants of outcomes in meningiomas.

Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.

Use of virtual magnetic resonance imaging to compensate for brain shift during image-guided surgery: illustrative case.

BACKGROUND: Maximal safe resection is the paramount objective in the surgical management of malignant brain tumors. It is facilitated through use of image-guided neuronavigation. Intraoperative image guidance systems use preoperative magnetic resonance imaging (MRI) as the navigational map. The accuracy of neuronavigation is limited by intraoperative brain shift and can become less accurate over the course of the procedure. Intraoperative MRI can compensate for dynamic brain shift but requires significant space and capital investment, often unavailable at many centers. OBSERVATIONS: The authors described a case in which an image fusion algorithm was used in conjunction with an intraoperative computed tomography (CT) system to compensate for brain shift during resection of a brainstem hemorrhagic melanoma metastasis. Following initial debulking of the hemorrhagic metastasis, intraoperative CT was performed to ascertain extent of resection. An elastic image fusion (EIF) algorithm was used to create virtual MRI relative to both the intraoperative CT scan and preoperative MRI, which facilitated complete resection of the tumor while preserving critical brainstem anatomy. LESSONS: EIF algorithms can be used with multimodal images (preoperative MRI and intraoperative CT) and create an updated virtual MRI data set to compensate for brain shift in neurosurgery and aid in maximum safe resection of malignant brain tumors.

Whole-genome risk prediction of common diseases in human preimplantation embryos.

Preimplantation genetic testing (PGT) of in-vitro-fertilized embryos has been proposed as a method to reduce transmission of common disease; however, more comprehensive embryo genetic assessment, combining the effects of common variants and rare variants, remains unavailable. Here, we used a combination of molecular and statistical techniques to reliably infer inherited genome sequence in 110 embryos and model susceptibility across 12 common conditions. We observed a genotype accuracy of 99.0-99.4% at sites relevant to polygenic risk scoring in cases from day-5 embryo biopsies and 97.2-99.1% in cases from day-3 embryo biopsies. Combining rare variants with polygenic risk score (PRS) magnifies predicted differences across sibling embryos. For example, in a couple with a pathogenic BRCA1 variant, we predicted a 15-fold difference in odds ratio (OR) across siblings when combining versus a 4.5-fold or 3-fold difference with BRCA1 or PRS alone. Our findings may inform the discussion of utility and implementation of genome-based PGT in clinical practice.

Topical vancomycin reduces surgical site infections in patients subjected to craniotomy for primary brain tumor resection: A comprehensive cancer center experience.

BACKGROUND: Craniotomies for resection of neoplastic lesions are at increased risk for surgical site infections (SSIs) as compared to non-neoplastic pathologies. SSIs can be detrimental due to delay in pivotal adjuvant therapies. OBJECTIVE: The purpose of this study was to determine the rate of SSI in primary brain tumors, to analyze risk factors, and to evaluate effectiveness of topical vancomycin in reducing SSIs. METHODS: A retrospective cohort study was conducted at a National Cancer Institutedesignated Comprehensive Cancer Center. Patients with primary brain tumors (n = 799) who were subjected to craniotomy from 2004 to 2014 were included. Patient demographics, tumor characteristics, use of topical vancomycin and clinical outcomes were analyzed. RESULTS: Topical vancomycin was associated with a significantly lower rate of SSI (0.8%) compared to standard care (5%), ( p = 0.00071; OR = 0.15; 95% CI = 0.02 - 0.5). Narcotic use ( p = 0.043; OR = 2.24; 95% CI = 0.96 - 4.81), previous brain radiation ( p = 0.043; OR = 2.08; 95% CI = 1.02 - 4.29), length of hospitalization ( p = 0.01; OR= 1.04; 95% CI = 1.01 - 1.08), and 30 day re-operation ( p = 1.58 ×10 -10; OR = 15.23; 95% CI = 7.06 - 32.71) were associated with increased risk for SSI. CONCLUSION: Topical vancomycin effectively reduced the rate of SSI in patients subjected to craniotomy for primary brain tumor resection. Furthermore, preoperative narcotic use, previous head/brain radiation, length of hospitalization, and 30-day reoperation were associated with increased risk of SSI.

Improving Brain Metastases Outcomes Through Therapeutic Synergy Between Stereotactic Radiosurgery and Targeted Cancer Therapies.

Brain metastases are the most common form of brain cancer. Increasing knowledge of primary tumor biology, actionable molecular targets and continued improvements in systemic and radiotherapy regimens have helped improve survival but necessitate multidisciplinary collaboration between neurosurgical, medical and radiation oncologists. In this review, we will discuss the advances of targeted therapies to date and discuss findings of studies investigating the synergy between these therapies and stereotactic radiosurgery for non-small cell lung cancer, breast cancer, melanoma, and renal cell carcinoma brain metastases.

Nivolumab and Stereotactic Radiosurgery for Patients With Breast Cancer Brain Metastases: A Nonrandomized, Open-Label Phase 1b Study.

PURPOSE: We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone. METHODS AND MATERIALS: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT03807765. RESULTS: Between February 2019 and July 2020, a total of 12 patients were treated to 17 lesions. No dose limiting toxicities were noted in our patient population. The most common neurologic adverse events included grade 1 to 2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% confidence interval, 3-14 months) with 6- and 12-month control rates of 55% and 22%, respectively. A total of 4 patients had systemic progression during the study. Median time to systemic progression free survival has not been reached with 6- and-12 month rates of 63% and 51%, respectively. CONCLUSIONS: Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary data reveals activity in certain breast cancer patients to study therapy.

Acute motor axonal neuropathy after ipilimumab and nivolumab treatment in melanoma brain metastases: A case report and review of the literature.

The use of immune checkpoint inhibitors including ipilimumab and nivolumab has expanded for several tumors including melanoma brain metastasis. These have resulted in a growing spectrum of neurologic immune-related adverse events, including ones that are rare and difficult to diagnose and treat. Here, we present a patient with melanoma brain metastasis who was treated with immune checkpoint inhibitors and developed an Acute Motor Axonal Neuropathy. To our knowledge, this is the first case of Acute Motor Axonal Neuropathy as an immune-related adverse event associated with combination treatment of ipilimumab and nivolumab, who was successfully treated. A 28-year-old woman with metastatic BRAF V600E melanoma developed melanoma brain metastasis and was enrolled on Checkmate 204, a Phase 2 clinical trial using ipilimumab (3 mg/kg intravenous) and nivolumab (1 mg/kg intravenous) every 3 weeks for four cycles, followed by monotherapy with nivolumab (240 mg intravenous) every 2 weeks. A few days after Cycle 2 of ipilimumab and nivolumab, she developed a pure motor axonal neuropathy consistent with Acute Motor Axonal Neuropathy. She was treated with several immunosuppressive treatments including high dose methylprednisolone, immune globulin, and infliximab, and her motor neuropathy eventually improved several months after onset of symptoms. Unfortunately, she had progression of her systemic disease and died several months later. This is the first case reported of Acute Motor Axonal Neuropathy associated with ipilimumab and nivolumab, successfully treated with immune-suppressive therapy. As the field of immunotherapy expands with the increasing use of the immune checkpoint inhibitors, it is critical to increase our knowledge and understanding of the neurologic immune-related adverse events associated with immune checkpoint inhibitors. This includes the spectrum of rare neurologic immune-related adverse events, which can be quite difficult to recognize and treat. Early consultations with neurology may expedite a diagnosis and treatment plan in patients with unexplained weakness receiving immune checkpoint inhibitor therapy.

Sacroiliac joint arthropathy in adult spinal deformity patients with long constructs to the pelvis.

OBJECTIVE: Sacroiliac joint (SIJ) arthropathy is an increasingly recognized problem in adult spinal deformity patients undergoing long construct surgery. S2-alar-iliac (S2AI) screw instrumentation is thought to reduce morbidity from pelvic fixation in these patients. The goal of this study is to assess the overall incidence of SIJ arthropathy in patients with long constructs to the pelvis as well as compare SIJ outcomes of partially threaded (PT) versus fully threaded (FT) S2AI screws. METHODS: Data of eligible patients were collected from a prospectively maintained database with retrospective review of electronic records at an academic institution between 2016 and 2019. RESULTS: 65 consecutive patients who underwent S2AI screw instrumentation (40 in PT group, 25 in FT group) were enrolled. The rate of postoperative SIJ pain was higher in the PT (52.5 %) compared to FT (32 %) group. There was a significantly shorter time-to-pain development in the PT compared to FT group (11.8 versus 20.1 months, respectively). Of those who developed SIJ pain in the PT group, the pain worsened in 80.9 % versus only 25 % of those in the FT group despite conservative treatment. Cox regression found the PT group more likely to develop SIJ pain at any point during follow-up compared to the FT group (Hazard Ratio = 7.308). SIJ fusion was not detected on imaging of any patient during follow-up. CONCLUSION: FT S2AI screws are associated with better SIJ outcomes compared to PT screws. However, our data suggest that S2AI screw instrumentation is not sufficient to achieve fusion or prevent development of SIJ pain. Concurrent SIJ fusion may be necessary in patients with long constructs to prevent SIJ arthropathy.

Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.

BACKGROUND: Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs). METHODS: Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. RESULTS: Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%. CONCLUSIONS: The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.

Radiofrequency Ablation for the Palliative Treatment of Bone Metastases: Outcomes from the Multicenter OsteoCool Tumor Ablation Post-Market Study (OPuS One Study) in 100 Patients.

PURPOSE: To evaluate the effectiveness of radiofrequency (RF) ablation as measured by change in worst pain score from baseline to 3 mo after RF ablation for the palliative treatment of painful bone metastases. MATERIALS AND METHODS: One hundred patients (mean age, 64.6 y) underwent RF ablation for metastatic bone disease and were followed up to 6 mo. Subjects' pain and quality of life were measured before RF ablation and postoperatively by using the Brief Pain Index and European Quality of Life questionnaires. Opioid agent use and device-, procedure-, and/or therapy-related adverse events (AEs) were collected. RESULTS: Eighty-seven patients were treated for tumors involving the thoracolumbar spine and 13 for tumors located in the pelvis and/or sacrum. All ablations were technically successful, and 97% were followed by cementoplasty. Mean worst pain score decreased from 8.2 ± 1.7 at baseline to 3.5 ± 3.2 at 6 mo (n = 22; P < 0.0001 for all visits). Subjects experienced significant improvement for all visits in average pain (P < .0001), pain interference (P < .0001), and quality of life (P < .003). Four AEs were reported, of which 2 resulted in hospitalization for pneumonia and respiratory failure. All 30 deaths reported during the study were attributed to the underlying malignancy and not related to the study procedure. CONCLUSIONS: Results from this study show rapid (within 3 d) and statistically significant pain improvement with sustained long-term relief through 6 mo in patients treated with RF ablation for metastatic bone disease.

Multiple myeloma presenting as an intramedullary spinal cord tumor: a case report and review of the literature.

BACKGROUND: Extramedullary disease in multiple myeloma often portends a worse diagnosis. In approximately 1% of cases, multiple myeloma may metastasize to the central nervous system as either leptomeningeal involvement or an intracranial, intraparenchymal lesion. Spinal cord metastases, however, are exceedingly rare. We present a case of spinal cord multiple myeloma as well as a literature review of reported cases. CASE PRESENTATION: A 66-year-old African American man with multiple myeloma presented with acute midthoracic pain and lower extremity paresis and paresthesia. Magnetic resonance imaging of the spine revealed two contrast-enhancing intramedullary enhancing lesions in the T1-T2 and T6-T7 cord. Resection with biopsy yielded a diagnosis of metastatic multiple myeloma. CONCLUSION: To date, only six cases of extramedullary disease to the spinal cord in patients with multiple myeloma have been reported, including our patient's case. In all cases, neurologic deficit was observed at presentation, and magnetic resonance imaging of the spine revealed an intramedullary, homogeneously enhancing lesion. Current evidence suggests worse prognosis in patients with extramedullary disease to the central nervous system, and treatment paradigms remain debatable.

Management of Thoracic Disc Herniation Using the Mini-Open Retropleural Approach: Technique Illustration and Clinical Outcomes of 33 Patients From a Single Academic Center.

BACKGROUND: Conventional surgical approaches used in the management of thoracic disc herniation (TDH) are associated with high morbidity. The development of minimally invasive and mini-open approaches has consistently improved patient outcomes. OBJECTIVE: To report our experience and outcomes of patients with symptomatic TDHs who underwent discectomy and partial corpectomy using the mini-open retropleural (MORP) approach as well as provide a detailed and illustrated technical description of the approach. METHODS: Retrospective chart review was performed on all patients with symptomatic TDHs who underwent a MORP approach at a tertiary academic center between 2011 and 2019. Patient demographic, clinical, and imaging data were examined (n = 33). The surgical technique is illustrated and described in detail. RESULTS: Discectomy of the herniated thoracic discs was successfully achieved in all patients using the MORP approach. Calcified discs were present in 63.6% (n = 21) of patients. Immediate instrumentation and fusion were performed in 30.3% (n = 10) of patients, which were among the earlier cases in this series. Symptomatic pleural effusions and cerebrospinal fluid leakage occurred in 6.1% (n = 2) and 9.1% (n = 3), respectively. No patient required chest tube placement. CONCLUSION: The MORP approach described in this manuscript is feasible and safe in achieving discectomy in patients with symptomatic TDHs. Compared to conventional open and other minimally invasive approaches, patients undergoing the MORP approach may have better outcomes with lower complication rates.

CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases.

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors are becoming increasingly utilized in the setting of advanced, hormone receptor (HR+) positive breast cancer. Pre-clinical data suggests a potential synergy between radiation therapy (RT) and CDK4/6 inhibitors. We assessed clinical outcomes of patients treated at our institution with the use of CDK4/6 inhibitors and stereotactic radiation in the management of HR+ breast brain metastases. METHODS: A retrospective analysis of patients who received stereotactic radiotherapy for HR+ brain metastases within 6 months of CDK4/6 inhibitor administration was performed. The primary endpoint was neurotoxicity during or after stereotactic radiation. Secondary endpoints were local brain control, distant brain control, and overall survival (OS). RESULTS: A total of 42 lesions treated with stereotactic radiation in 15 patients were identified. Patients received either palbociclib (n = 10; 67%) or abemaciclib (n = 5; 33%). RT was delivered concurrently, before, or after CDK4/6 inhibitors in 18 (43%), 9 (21%), and 15 (36%) lesions, respectively. Median follow-up following stereotactic radiation was 9 months. Two lesions (5%) developed radionecrosis, both of which received four prior RT courses to the affected lesion prior to onset of radionecrosis and subsequently managed with steroids and bevacizumab. Six- and 12-month local control of treated lesions was 88% and 88%, while 6- and 12-month distant brain control was 61% and 39%, respectively. Median OS was 36.7 months from the date of brain metastases diagnosis. CONCLUSIONS: Stereotactic radiation to breast brain metastases was well tolerated alongside CDK4/6 inhibitors. Compared to historical data, brain metastases control rates are similar whereas survival appears prolonged.