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Simple Summary: There is an unmet need for novel anticancer therapeutics that work differently to current standard-of-care therapies. BOLD-100 is a unique clinical-stage anticancer compound that is based on the rare metal, ruthenium. Understanding the bioactivity of BOLD-100 can accelerate its development towards approval and into clinical practice. The aim of this study was to use a large panel of cancer cell lines to formulate a sensitivity profile of BOLD-100 across various cancer types. BOLD-100 demonstrated increased activity in cell lines from esophageal cancer, blood cancers, and bladder cancer. These indications are in addition to the gastrointestinal cancers currently in clinical development, thus opening new opportunities. Using the sensitivity profile for downstream bioinformatics and pathway analysis revealed associations between cancer cell lines' sensitivity to BOLD-100 and ribosomal gene expression, including several genes coding for large- and small-ribosomal subunits. These findings provide evidence that ribosomal processes may be a critical component of BOLD-100's mechanism. BOLD-100 (sodium trans-[tetrachlorobis(1H indazole)ruthenate(III)]) is a ruthenium-based anticancer compound currently in clinical development. The identification of cancer types that show increased sensitivity towards BOLD-100 can lead to improved developmental strategies. Sensitivity profiling can also identify mechanisms of action that are pertinent for the bioactivity of complex therapeutics. Sensitivity to BOLD-100 was measured in a 319-cancer-cell line panel spanning 24 tissues. BOLD-100's sensitivity profile showed variation across the tissue lineages, including increased response in esophageal, bladder, and hematologic cancers. Multiple cancers, including esophageal, bile duct and colon cancer, had higher relative response to BOLD-100 than to cisplatin. Response to BOLD-100 showed only moderate correlation to anticancer compounds in the Genomics of Drug Sensitivity in Cancer (GDSC) database, as well as no clear theme in bioactivity of correlated hits, suggesting that BOLD-100 may have a differentiated therapeutic profile. The genomic modalities of cancer cell lines were modeled against the BOLD-100 sensitivity profile, which revealed that genes related to ribosomal processes were associated with sensitivity to BOLD-100. Machine learning modeling of the sensitivity profile to BOLD-100 and gene expression data provided moderative predictive value. These findings provide further mechanistic understanding around BOLD-100 and support its development for additional cancer types. [ABSTRACT FROM AUTHOR]

Background: The healing process after C1-C2 posterior screw fixation (C1-C2 PSF) for odontoid fractures is not well understood. Here, we evaluated such processes and identified factors potentially contributing to pseudoarthroses following fusions for Type II odontoid fractures. Methods: Pre- and post-operative cervical radiographs and computed tomography (CT) images from 15 patients with preoperative Type II odontoid fractures who underwent C1-C2 PSF were retrospectively reviewed. Results: CT images identified three areas of bone fusion: The primary fracture site in the dens (9/15 patients, 60%), the atlanto-dental interspace (ADI) (10/15, 67%), and C1-C2 interlaminar space after onlay bone grafting (4/15, 27%). All patients showed bone fusion in at least one of three areas, while only one patient (6.7%) achieved bone fusion in all three areas. With these overall criteria, nine of 15 patients (60%) were considered fused, while six patients (40%) were determined to exhibit pseudoarthroses. Univariate analyzes showed that the preoperative C2-C7 SVA for the nonunion group was significantly larger versus the union group, and bone fusion at the level of the ADI was significantly more common in the nonunion versus the union group. Conclusion: CT studies identified three anatomical areas where bone fusion likely occurs after C1-C2 PSF. Increased sagittal balance in the cervical spine may negatively impact the fusion of odontoid fractures. Further, bone fusion occurring at other sites, not the primary fracture location, through stress shielding may contribute to delayed or failed fusions. [ABSTRACT FROM AUTHOR]

Posterior cervical decompression and instrumentation (PCDI) often is associated with increase in sagittal balance and loss of lordosis. Here, we propose a simple method of surgical positioning using a readily available smartphone application to optimize cervical thoracic alignment in PCDI. The intent of this optimization is to minimize losses in lordosis and increases in sagittal balance. For patients since 2019, the position of the head was adjusted so that the occiput to thoracic spine was aligned and the chin brow angle was parallel to the rails of the surgical table using a leveling smart application (RIDGID level). Patients before 2019 who were not optimized were compared. There were 13 patients in the nonoptimized cohort (NOC) and 20 in the optimized cohort (OC). In the NOC, the change in lordosis was –7° (P = 0.016) and change in C2–sagittal vertical axis was 7 mm (P < 0.001) from preoperative to postoperative values. In the OC, the change in lordosis was 2° (P = 0.104) and change in C2-SVA was 2 mm (P = 0.592) from preoperative to postoperative values. Between the NOC and OC cohorts, the changes in lordosis and sagittal balance between cohorts were significant (P = 0.002 and P = 0.001, respectively). There was no significant difference in clinical outcomes as measured by Japanese Orthopaedic Association or complication rates. Positioning of the patient in preparation for PCDI can influence postoperative lordosis and sagittal balance. Using the leveling application on the smartphone (RIDGID level), is a rapid and free alternative for the maintenance of lordosis and sagittal balance during instrumentation in the operating room. [ABSTRACT FROM AUTHOR]

Isolated spinal cord neurosarcoidosis is extremely rare. The potential implications of long-term immunosuppressant therapy make correct diagnosis imperative. However, there are challenges inherent in isolated spinal cord involvement that require a multidisciplinary approach. Here we present the largest series of definite and possible isolated spinal neurosarcoidosis and discuss our institutional experience in managing this rare but morbid condition. A retrospective review was performed to identify all neurosarcoidosis cases starting from 2002 to 2020 at our institution. Patients were screened for cases of isolated spinal neurosarcoidosis. A descriptive analysis was performed for each case. A total of 64 cases of neurosarcoidosis were identified. The spine was involved in 26 (40.6%) patients. Only 4 (6.3%) cases had isolated spinal cord involvement. A full medical and imaging workup was performed in determining isolated spinal cord involvement. Three patients subsequently underwent surgical biopsy, and 1 did not undergo biopsy because of patient preference. One of the patients who underwent biopsy had an initial nondiagnostic biopsy and had a repeat biopsy. Corticosteroids were employed in all cases with additional immunosuppressive agents for maintenance therapy and refractory cases. All showed radiographic improvement and were clinically stable to improved. Isolated spinal cord involvement of neurosarcoidosis is rare and can present challenges in diagnosis. A biopsy can be performed when necessary. However, a biopsy of the spinal cord carries inherent risks and may not always be possible or result in a nondiagnostic sample. In the setting of high clinical suspicion, maximal medical therapy is still employed. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma with metastases to the spine (RCCMS) requires a multidisciplinary approach. We reviewed our institutional experience with RCCMS patients undergoing spinal surgery in order to identify factors that may affect clinical outcomes, survival, and complications. Patients with RCCMS who underwent operative intervention from 2007 to 2020 were reviewed retrospectively. Forty-four patients with the diagnosis of RCCMS were identified. Pain was the most common symptom, and neurologic dysfunction was present in one third of cases. Thoracic spine was the most common location (N = 27), followed by the lumbar (N = 12) and cervical (N = 5) regions. The overall survival from diagnosis of renal cell carcinoma was 25 (2 − 194) months and 8 (0.3 − 92) months after spinal surgery. Gender, age, spinal level, postoperative radiation, and nephrectomy had no bearing on survival. Survival for patients with a Tokuhashi score of 0 − 8, 9 − 11, and 12 − 15 was 6.5 (1.5 − 23.5), 8.9 (0.3 − 91.6), and 23.4 (2.5 − 66) months, respectively (P = 0.03). The postoperative American Spinal Cord Injury Association score of E (hazard ratio 0.109 [95% confidence interval 0.022 − 0.534, P = 0.006) also bore a significant influence on survival. There was a total of 10 complications in 7 of 44 (16%) patients. Median postoperative survival of patients with RCCMS was 8 (0.3 − 92) months. Higher Tokuhashi score and ASIA E score at follow-up correlated with improved overall survival. Complication rate was 16%. Spinal surgery in RCCMS is indicated for the preservation of function and prevention of neurologic deterioration. Multimodality therapy with improved chemotherapy and stereotactic spinal radiation is expected to impact quality and length of survival positively. [ABSTRACT FROM AUTHOR]

Objective. Holographic mixed reality (HMR) allows for the superimposition of computer-generated virtual objects onto the operator's view of the world. Innovative solutions can be developed to enable the use of this technology during surgery. The authors developed and iteratively optimized a pipeline to construct, visualize, and register intraoperative holographic models of patient landmarks during spinal fusion surgery. Methods. The study was carried out in two phases. In phase 1, the custom intraoperative pipeline to generate patient-specific holographic models was developed over 7 patients. In phase 2, registration accuracy was optimized iteratively for 6 patients in a real-time operative setting. Results. In phase 1, an intraoperative pipeline was successfully employed to generate and deploy patient-specific holographic models. In phase 2, the registration error with the native hand-gesture registration was 20.2 ± 10.8 mm (n = 7 test points). Custom controller-based registration significantly reduced the mean registration error to 4.18 ± 2.83 mm (n = 24 test points, P <.01). Accuracy improved over time (B = −.69, P <.0001) with the final patient achieving a registration error of 2.30 ±.58 mm. Across both phases, the average model generation time was 18.0 ± 6.1 minutes (n = 6) for isolated spinal hardware and 33.8 ± 8.6 minutes (n = 6) for spinal anatomy. Conclusions. A custom pipeline is described for the generation of intraoperative 3D holographic models during spine surgery. Registration accuracy dramatically improved with iterative optimization of the pipeline and technique. While significant improvements and advancements need to be made to enable clinical utility, HMR demonstrates significant potential as the next frontier of intraoperative visualization. [ABSTRACT FROM AUTHOR]

The majority of the abnormalities and diseases that affect the craniovertebral junction (CVJ) have already been reported, and therefore it is exceedingly rare to identify new pathology that affects the CVJ. Immunoglobulin G4–related disease (IgG4-RD) is an immune mediated process treated with immunosuppressive medications. To our knowledge, this is the first reported case of IgG4-RD affecting the CVJ. The authors report the case of a woman aged 71 years with IgG4-RD of the CVJ. She presented with intractable left occipital pain and limited flexion, extension, and rotation of the neck. Computed tomography and magnetic resonance imaging revealed a lytic enhancing lesion of the left occipital condyle, left C1 lateral mass, and left C1 anterior arch resulting in cranial settling, basilar invagination, and CVJ instability. An open biopsy, subtotal resection, and occiput to C2 fusion was performed. Pathology revealed IgG4-RD. The patient was subsequently placed on rituximab immunotherapy with complete resolution of enhancement on magnetic resonance imaging and bone growth at the previous site of the lytic IgG4-RD lesion. To our knowledge, this case describes the first case of IgG4-RD affecting the CVJ, which mimicked a tumor-like process. When IgG4-RD affects the CVJ, stability must be accounted for, especially in the cases of osteolytic destruction. The combination of medical therapy to target the underlying inflammatory process and surgery to provide structural stability was successful. [ABSTRACT FROM AUTHOR]

Introduction: The aging of the western population and the increased use of oral anticoagulation (OAC) and antiplatelet drugs (APD) will result in a clinical dilemma on how to balance the recurrence risk of chronic subdural hematoma (cSDH) with the risk of withholding blood thinners. Objective: To identify features that predicts recurrence, thromboembolism (TEE), hospital stay and mortality. To identify the optimal window for resuming APD or OAC. Methods: We performed a retrospective multivariate analysis of a prospectively collected database. We then build machine learning models for outcomes prediction. Results: We identified 596 patients. The rate of recurrence was 22.17%, that of thromboembolism was 0.9% and that of mortality was 14.78%. Smoking, platelet dysfunction, CKD, and alcohol use were independent predictors of higher recurrence, while resolution of the SDH was protective. OAC use had higher odds of developing TEEs. CKD, developing a new neurological deficit or a TEEs were independent predictors of higher mortality. We find the optimal time of resuming OAC to be after 2 days but before 21 days as these patients had the lowest recurrence of bleeding associated with a low risk of stroke. The ML model achieved an accuracy of 93, precision of 0.84 and recall of 0.80 for recurrence prediction. ML models for hospital stay performed poorly (R 2 = 0.33). ML model for stroke was overfitted given the low number of events. Conclusion: ML modeling is feasible. However, large well-designed prospective multicenter studies are needed for accurate ML so that clinicians can balance the risks of recurrence with the risk of TEEs, especially for high-risk anticoagulated patients. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinomas (SCCHN) arise in the mucosa of the upper aerodigestive tract at multiple anatomic sites. While tobacco and alcohol exposure remain the primary risk factors for this malignancy, infection with the human papilloma virus is emerging as a major contributing factor to cancers that arise primarily in the oropharynx. Despite therapeutic advances, survival has remained relatively unchanged over the past few decades. Increased understand of the cellular and molecular biology of these cancers will improve our understanding of this malignancy and facilitate the development of more effective therapeutic strategies. Alterations that have been studied to date include genetic and epigenetic changes. While the epidermal growth factor receptor (EGFR) is the only established molecular therapeutic target, other proteins and pathways are under active investigation to determine their contribution to SCCHN carcinogenesis and progression. [ABSTRACT FROM AUTHOR]

Objective/Hypothesis: To describe our institution's experience with the management of cervical metastasis in papillary thyroid carcinoma (PTC) and suggest a treatment strategy based on the incidence of pathologic nodes and cervical recurrence in patients undergoing varied surgical approaches to address lymphadenopathy over the study dates. Materials and Methods: Between December 1, 1972 and September 1, 2007, 183 total patients diagnosed with PTC at the University of Pittsburgh Medical Center were treated with lymphadenectomy. Pathologic parameters, including number of pathologic nodes and extent of lymphadenectomy were correlated to disease recurrence. Study Design: Retrospective chart review. Results: The incidence of pathologic nodes in lymphadenectomy specimens (57.9%) and the recurrence rate (33.7%) were high, in our study population. In comparing techniques with address lymphadenopathy, the highest recurrence rate was observed in patients with pathologic nodes treated with 'lymph node plucking' procedures at the time of thyroidectomy and those patients with multiple nodes involved. Few patients with no pathologic nodes, regardless of lymphadenectomy extent recurred. Conclusions: Our data show that limited neck dissection and disease burden are associated with the highest rates of cervical recurrence in regional metastatic PTC. Comprehensive functional neck dissection would seem to offer the patient the best opportunity for control of cervical metastasis. The American Thyroid Association recommends thyroglobulin monitoring and ultrasound evaluation of the neck in all postoperative patients. Therefore patients with the diagnosis of papillary thyroid cancer need preoperative ultrasound of the lateral neck and fine needle aspiration of suspicious nodes to avoid undertreating patients scheduled for total thyroidectomy. Neck dissection of the compartments in which pathologic nodes were detected (central, lateral, or both) should then be undertaken at the time of initial thyroidectomy. Eliminating all disease remains elusive and the prognosticsignificance of cervical disease persistence and recurrence is still unknown. Patients with cervical metastasis are at substantial risk of regional recurrence, necessitating repeat surgery. Parathyroid implantation should be considered at the time of the initial surgery to reduce the risk of hypoparathyroidism should subsequent procedures be required. More information will be necessary to better understand the prognostic significance of these regional metastases. In the interim, many patients may be overtreated, whereas some remain at risk of death because of disease. [ABSTRACT FROM AUTHOR]

Mesenrhombencephalitis is a rare inflammatory process involving the midbrain, pons, and medulla. The diagnosis is difficult as clinical and laboratory findings may be nonspecific. Magnetic resonance (MR) imaging demonstrates abnormal T2 signal in the brainstem, which can suggest the diagnosis. The clinical, laboratory and MR imaging findings are described in five patients with this serious, life-threatening disease. MR imaging can be of value in the early diagnosis of this rare disorder. [Copyright &y& Elsevier]