Object Patient age at presentation with congenital atlantoaxial dislocation (CAAD) is variable. In addition, the factors determining irreducibility or reducibility in these patients remain unclear. The facets appear to contribute to the stability of the joint, albeit to an unknown extent. The objective of this paper was to study the characteristics of C1–2 facets in these patients and their bearing on the clinicoradiological presentation and management. Methods Twenty-four patients with CAAD were studied. Fifteen patients had irreducible CAAD (IrAAD); 3 of these patients experienced incomplete reduction after traction, and 9 had reducible CAAD (RAAD). The images (CT scans of the craniovertebral junction in a neutral position) obtained in the parasagittal, axial, and coronal planes were studied with respect to the C1–2 facets and were compared with 32 control scans. The inferior sagittal and coronal C-1 facet angles were measured. The lordosis of the cervical spine (cervical spine angle calculated on radiographs of the cervical spine, neutral view) in these patients was compared with normal. The management of these patients is described. Results The inferior sagittal C-1 facet angle and at least one coronal angle in patients with IrAAD were significantly acute compared with those in patients with RAAD and the control population. A significant correlation was found between age and the acuteness of the inferior sagittal C-1 facet angle (that is, the more acute the angle, the earlier the presentation). The lordosis of the cervical spine was exaggerated in patients with IrAAD. Three patients with IrAAD who had smaller acute angles experienced a partial reduction after traction and a complete reduction after intraoperative distraction of the facets, thereby avoiding a transoral procedure. An inferior sagittal C-1 facet angle of more than 150° in the sagittal plane predicted reducibility. Drilling a wedge off the facet in the sagittal plane to make the inferior sagittal C-1 facet angle 150° can reduce the C1–2 joint intraoperatively by posterior approach alone. Conclusions The acuteness of the inferior C-1 sagittal facet angles possibly determines the age at presentation and reducibility. The coronal angles determine the telescoping of C-2 within C-1. Patients with IrAAD can be treated using a posterior approach alone with the exception of those with extremely acute angles or a retroflexed dens. The exaggerated lordosis of the cervical spine in these patients is a compensatory phenomenon.

The novel coronavirus, or COVID-19, has rapidly become a global pandemic. A major cause of morbidity and mortality due to COVID-19 has been the worsening hypoxia that, if untreated, can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. Past work has found that intubated patients with ARDS experience physiological benefits to the prone position, because it promotes better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs. We created a systemwide multi-institutional (New York-Presbyterian Hospital enterprise) protocol for placing awake, nonintubated, emergency department patients with suspected or confirmed COVID-19 in the prone position. In this piece, we describe the background literature and the approach we have taken at our institution as we care for a high burden of COVID-19 cases with respiratory symptoms.

GKS is an effective modality of treatment for central AVMs, though relatively lower obliteration rates and higher complication rates are seen compared to AVMs at other locations.

Background Multiple myeloma (MM) is characterized by expression of the cell surface protein B-cell maturation antigen (BCMA), a validated target for therapeutic intervention. REGN5458 is a BCMA x CD3 bispecific antibody (Ab) that binds to both BCMA and CD3, thereby targeting MM cells with T-cell effector function via BCMA. Previously, we presented data showing REGN5458 has an acceptable safety profile with evidence of clinical efficacy in heavily pre-treated patients with RRMM. Here we describe the updated safety and response durability in a Phase 1 trial of REGN5458 monotherapy in patients with RRMM (NCT03761108). Methods The primary objectives of the Phase 1 portion of the study are to determine the safety, tolerability, and occurrence of dose-limiting toxicities (DLTs) of REGN5458. Key secondary objectives include assessment of objective response rate (ORR), duration of response (DOR), minimum residual disease (MRD) status, pharmacokinetics (PK), and pharmacodynamics. Enrollment into the Phase 1 portion follows a standard 4+3 dose escalation design. Enrolled patients must have progressive MM after ≥3 prior lines of systemic therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 Ab. Treatment consists of weekly doses of REGN5458, followed by a maintenance phase administered every 2 weeks. Response assessments are according to modified International Myeloma Working Group criteria. MRD is assessed by flow cytometry. Results As of the June 15, 2020 data cut-off, 45 patients were treated with REGN5458. The median age at enrollment was 64.0 years (range, 41−81), of which 14 (31.1%) patients were >70 years. As per Revised International Staging System, 60.0% and 22.2% of patients were stage 2 and 3, respectively. Patients had a median of 5.0 (range, 2−17) prior lines of systemic therapy; 32 patients (71.1%) received a prior autologous stem cell transplant. All patients were refractory to an anti-CD38 Ab; 6.7% were triple-refractory, 33.3% were quad-refractory, and 53.3% were penta-refractory. REGN5458 was escalated in cohorts from 3−96 mg over six dose levels. The median duration of follow-up was 2.37 months (range, 0.7−12.3). The most common treatment-related adverse events (TRAEs) include cytokine release syndrome (CRS; 37.8%), fatigue (17.8%), nausea (17.8%), and myalgias (13.3%). CRS occurred primarily during the initial doses and was Grade (Gr) 1 in 88.2% of patients. No patients had Gr >3 CRS. Infusion-related reactions occurred in 6.7% of patients. Infection-related adverse events (AEs) occurred in 46.7% of patients (Gr ≥3 20%). Gr >3 treatment-related neurological events occurred in one patient (Gr 3 syncope 130 days after first infusion). Four patients discontinued due to AE with one patient having a TRAE (also DLT) of Gr 4 acute kidney injury. One patient had a DLT due to transient Gr 3 liver transaminases associated with CRS. Upon recovery, the patient continued study drug and has achieved ongoing partial remission. Gr >3 TRAEs occurred in 28.9% of patients, with the most common being anemia (8.9%) and lymphopenia (6.7%). Serious TRAEs occurred in 22.2% of patients, with the most common due to CRS (11.1%). Gr 5 AEs (all unrelated to study drug) occurred in three patients: two sepsis and one COVID-19. ORR was 35.6% across all dose levels (60% in highest dose level), with 81.3% of responders achieving at least a very good partial response; 31.3% had a complete response (CR) or stringent CR. A total of 43.8% of responders had a DOR >4 months and 18.8% had a DOR >8 months. The ORR in patients with extramedullary plasmacytomas was 16.7%. Additional efficacy, PK, and biomarker data will be available at the time of presentation. Conclusions In this updated analysis of the first-in-human study, REGN5458 continues to show an acceptable safety profile and durable efficacy in heavily pre-treated patients with RRMM. Enrollment in the Phase 1 dose escalation portion is ongoing, and the Phase 2 portion of the study is recruiting. Disclosures Madduri: Janssen: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; AbbVie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Brayer:Janssen: Consultancy; Bristol-Myers Squibb, WindMIL Therapeutics: Research Funding; Bristol-Myers Squibb, Janssen, Amgen: Speakers Bureau. Zonder:Prothena: Consultancy; BMS: Consultancy, Research Funding; Caelum: Consultancy; Oncopeptide: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Other: Personal fees; Alnylam: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Intellia: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Research Funding. Bensinger:Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau. Li:Regeneron Pharmaceuticals, Inc: Current Employment, Current equity holder in publicly-traded company. Xu:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Adriaens:Regeneron Pharmaceuticals, Inc: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: Dosing regime that mitigates cytokine release syndrome for therapeutic antibodies (status: pending). Chokshi:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Zhang:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Boyapati:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Sharma:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Seebach:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Sirulnik:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Weinreich:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Yancopoulos:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Dhodapkar:Amgen: Membership on an entity's Board of Directors or advisory committees, Other; Kite: Membership on an entity's Board of Directors or advisory committees, Other; Janssen: Membership on an entity's Board of Directors or advisory committees, Other; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Other; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other. Lentzsch:Mesoblast: Divested equity in a private or publicly-traded company in the past 24 months; Caelum Biosciences: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Celularity: Consultancy, Other; Janssen: Consultancy; Karyopharm: Research Funding; Magenta: Current equity holder in private company. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. OffLabel Disclosure: The data described in the abstract will report on use of REGN5458 in a first-in-human trial in patients with multiple myeloma.

To analyze the effect of Gamma Knife radiosurgery (GKS) on tumor control and hearing preservation rates in patients with vestibular schwannomas (VS) in a setting of neurofibromatosis type 2 (NF 2), a retrospective study was carried out at a tertiary-level referral Gamma Knife unit. Dose plans, pre- and postoperative radiology, and follow-up clinical records of patients with NF 2 who had undergone GKS for VS using a Leksell Gamma Knife (Elekta Instruments AB, Stockholm, Sweden) model B unit from 1997 to 2008 were reviewed. Thirty patients with 54 VS underwent GKS. The average age of the cohort was 29 years (range 10-56 years). Twenty-four patients had bilateral VS. The commonest clinical presentation was hearing loss and tinnitus. Primary GKS was given to 36 tumors, while 18 tumors received it as an adjunct to surgery. Average tumor size was 3.7 cc (range 0.1-13.3 cc). A median 12 Gy prescription dose (range 10-15 Gy) was administered at the 50% isodose (range 42-50%) to cover on average 91.5% of the tumor. Eighteen patients were available for clinical, 14 patients for radiological, and 5 patients (with useful hearing) for audiometric follow-up at an average of 26.6 months. The tumor control rate was 87.5% in this series (33.3% tumor regression), while hearing preservation was noted in 66.7% of cases. One patient developed worsening of facial function. GKS for VS provides satisfactory tumor control and hearing preservation in patients with NF 2. Long-term follow-up will determine future recommendations.