LILRB3 Modulates Acute Myeloid Leukemia Progression and Acts as an Effective Target for CAR T-cell Therapy.

Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. In addition, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, whereas phosphorylation of proliferation regulators, for example, AKT, cyclin D1, and retinoblastoma protein, was decreased. Conversely, transcriptomic analysis showed LILRB3 activation by agonist antibodies may enhance leukemia survival through upregulation of cholesterol metabolism, which has been shown to promote leukemia cell survival. Moreover, LILRB3-targeted CAR T cells exhibited potent antitumor effects both in vitro and in vivo. Taken together, our results suggest that LILRB3 is a potentially potent target for multiple treatment modalities in AML. SIGNIFICANCE: LILRB3 regulates differentiation and proliferation in acute myeloid leukemia and can be targeted with monoclonal antibodies and CAR T cells to suppress leukemia growth.

Feasibility and Efficacy of Low-profile Visual Intraluminal Support Device: A Single Center Five-year Experience.

INTRODUCTION: The Low-Profile Visualized Intraluminal Support (LVIS) devices are a new generation of self-expandable, high-porosity stents approved for the treatment of large to giant wide-necked intracranial aneurysms via stent-assisted coiling. Here we report the radiographic and clinical outcomes seen with LVIS, LVIS Jr. and LVIS Blue from a single institution over a fiveyear period. METHODS: Patients with intracranial aneurysms treated by LVIS, LVIS Jr. and LVIS Blue technology over a five-year period (2012 - 2017) at our institution were retrospectively reviewed. RESULTS: Seventy-four patients (55 females and 19 males; average age = 59.2) with 74 aneurysms underwent embolization of intracranial aneurysms using LVIS (N = 10), LVIS Jr. (N = 47) or LVIS Blue (N = 12) devices at our institution over the study period. The most common location of treated aneurysms was the anterior communicating artery (31%), followed by the basilar artery (19%), and the middle cerebral artery (13%). The mean neck and dome sizes were 3.9±1.5mm and 6.6±3.2mm, respectively. The median follow-up time was 6 months. At the last radiographic follow- up, 93.1% of patients had complete occlusion (RR-I or OKM-D). In 5 cases (7%), the LVIS stent failed to open, requiring balloon angioplasty (N = 3) or stent recapture and use of a non-LVIS branded device (N = 2). Five patients had post-embolization infarcts, and 1 patient had an intra-operative dome rupture. CONCLUSION: LVIS brand of stents is a safe, effective, and technically feasible treatment strategy for wide-neck intracranial aneurysms, with high deployment success and aneurysm obliteration rates.

The utility of routine post-hospitalization CT imaging in patients with non-operative mild to moderate traumatic brain injury.

Primary Objective: The purpose of this study was to determine the utility of CT imaging in patients with non-operative mild-moderate TBI with respect to changes in management.Methods: We conducted a retrospective analysis for 191 patients over a 5-year interval to examine whether follow-up CT initiated a change in management. We created a logistic regression model to incorporate different variables contributing to change in management.Results: Of 191 patients, 31 (16.2%) underwent a change in management. Change in management was associated with older age (65 yo vs. 55 yo, p = .011), diagnosis of subdural hematoma (p = .041), antiplatelet/anticoagulant therapy (p = .009), imaging performed (p = .16), and increased blood products on CT (p = <0.0001). For patients on antiplatelet/anticoagulant therapy, only those with worsening findings on CT required a change in management (p = .0002, 0.039). Surgical intervention was indicated in two patients.Conclusions: Limited clinical value exists in repeat CT scans for patients with mild TBI. Most patients with traumatic SAH, contusions, or asymptomatic patients should not have repeat imaging, as our study revealed only 2% of patients with positive CT finding and 0.6% requiring surgical intervention.

Hybrid Anterior Column Realignment-Pedicle Subtraction Osteotomy for Severe Rigid Sagittal Deformity.

OBJECTIVE: Recently, a hybrid anterior column realignment-pedicle subtraction osteotomy (ACR-PSO) approach has been conceived for patients with severe rigid sagittal deformity, the clinical and radiographic outcomes of which require further investigation compared with ACR only. METHODS: A single-center, retrospective chart review identified patients undergoing a combination of hyperlordotic lateral lumbar interbody grafting (ACR) and concurrent Schwab grade 3 three-column osteotomy and propensity-matched patients undergoing ACR only in the same time frame. Anterior longitudinal ligament was directly released or partially sectioned in all patients. Chart data included demographics, Oswestry Disability Index scores, ACR and osteotomy locations, cage dimensions, fusion length, and complications. Radiographic measurements included lumbar lordosis, sagittal vertical axis, pelvic tilt (PT), and proximal junctional kyphosis. RESULTS: Fourteen patients were enrolled in the ACR + PSO group and 36 in the ACR-only group. Mean ages were 68.5 and 63.9 years, 64% and 67% were female, average body mass index was 27.9 and 29.2, and cardiopulmonary comorbidities were 21% and 17%, respectively. There was no difference in complications (P = 0.347). The average follow-up for the ACR + PSO and ACR-only groups were 22 and 18 months, respectively. Excluding 2 mortalities, fusion occurred in all patients. Average change in lumbar lordosis measured -40.8 ± 9.2 degrees and -19.1 ± 15.7 degrees (P = 0.0006), and PT correction measured 10.5 ± 3.4 degrees and 27.3 ± 1.6 degrees (P < 0.0001), respectively. CONCLUSIONS: For patients with severe rigid sagittal deformity, the hybrid ACR-PSO approach offers significant restoration of lumbar lordosis compared with ACR only, with similar complications but reduced PT correction.

Complications associated with L4-5 anterior retroperitoneal trans-psoas interbody fusion: a single institution series.

BACKGROUND: Lateral lumbar interbody fusion (LLIF), first described in the literature in 2006 by Ozgur et al., involves direct access to the lateral disc space via a retroperitoneal trans-psoas tubular approach. Neuromonitoring is vital during this approach since the surgical corridor traverses the psoas muscle where the lumbar plexus lies, risking injury to the lumbosacral plexus that could result in sensory or motor deficits. The risk of neurologic injury is especially higher at L4-5 due to the anatomy of the plexus at this level. Here we report our single-center clinical experience with L4-5 LLIF. METHODS: A retrospective chart review of all patients who underwent an L4-5 LLIF between May 2016 and March 2019 was performed. Baseline demographics and clinical characteristics, such as body mass index (BMI), medical comorbidities, surgical history, tobacco status, operative time and blood loss, length of stay (LOS), and post-op complications were recorded. RESULTS: A total of 220 (58% female and 42% male) cases were reviewed. The most common presenting pathology was spondylolisthesis. The average age, BMI, operative time, blood loss, and LOS were 64.6 years, 29 kg/m2, 214 min, 75 cc, and 2.5 days respectively. A review of post-operative neurologic deficits revealed 31.4% transient hip flexor weakness and 4.5% quadricep weakness on the approach side. At 3-week follow-up, 9.1% of patients experienced mild hip flexor weakness (4 or 4+/5), 0.9% reported mild quadricep weakness, and 9.5% reported anterior thigh dysesthesias; 93.2% of patients were discharged home and 2.3% were readmitted within the first 30 days post discharge. Female sex, higher BMI and longer operative time were associated with hip flexor weakness. CONCLUSIONS: LLIF at L4-5 is a safe, feasible, and versatile approach to the lumbar spine with an acceptable approach-related sensory and motor neurologic complication rates.

Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment.

Tumor-mediated regulation of the host immune system involves an intricate signaling network that results in the tumor's inherent survival benefit. Myeloid cells are central in orchestrating the mechanisms by which tumors escape immune detection and continue their proliferative programming. Myeloid cell activation has historically been classified using a dichotomous system of classical (M1-like) and alternative (M2-like) states, defining general pro- and anti-inflammatory functions, respectively. Explosions in bioinformatics analyses have rapidly expanded the definitions of myeloid cell pro- and anti-inflammatory states with different combinations of tissue- and disease-specific phenotypic and functional markers. These new definitions have allowed researchers to target specific subsets of disease-propagating myeloid cells in order to modify or arrest the natural progression of the associated disease, especially in the context of tumor-immune interactions. Here, we discuss the myeloid cell contribution to solid tumor initiation and maintenance, and strategies to reprogram their phenotypic and functional fate, thereby disabling the network that benefits tumor survival.

Corrigendum: Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment.

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