Anterior cervical hybrid constructs reduce superior adjacent segment burden compared to multilevel anterior cervical discectomy and fusion.

Background: Traditional surgical treatment for symptomatic cervical degenerative disc disease is anterior cervical discectomy and fusion (ACDF), yet the increased risk of adjacent segment degeneration (ASD) requiring additional surgery exists and may result in limiting long-term surgical success when it occurs. Disc arthroplasty can preserve or restore physiologic range of motion (ROM), decreasing adjacent level stress and subsequent surgery. For patients with multilevel pathology requiring at least a 1-level fusion, interest is growing in anterior cervical hybrid (ACH) surgery as a partial motion-preserving procedure to decrease the adjacent level burden. This radiographic study compares postoperative superior adjacent segment motion between ACH and ACDF. Secondarily, total global motion, construct motion, inferior adjacent segment motion, and sagittal alignment parameters were compared. Methods: This is a single-center, multi-surgeon, retrospective cohort study of 2- and 3-level ACH and ACDF cases between 2013 and 2021. Degrees of motion were analyzed on flexion/extension views using Cobb angles to measure global (C2-C7) construct and adjacent segment lordosis. Neutral lateral X-rays were analyzed for alignment parameters, including global lordosis, cervical sagittal vertical axis (cSVA), and T1 slope (T1S). Differences were determined by independent t-test and Fisher's exact test. Results: Of 100 patients, 38% were 2-level cases (47% ACH, 53% ACDF) and 62% were 3-level cases: (52% ACH, 48% ACDF). Postoperatively, superior adjacent segment motion increased with ACDF and decreased with ACH (-1.3°±5.3° ACH, 1.6°±4.6° ACDF, P=0.005). Postoperatively, the ACH group had greater ROM across the construct (16.3°±8.7° ACH, 4.7°±3.3° ACDF, P<0.001) and total global ROM (38.0°±12.8° ACH, 28.0°±11.1° ACDF, P<0.001). ACH resulted in a significant reduction of motion loss across the construct (-10.0°±11.7° ACH, -18.1°±10.8° ACDF, P<0.001). Postoperative alignment restoration was similar between both cohorts (-2.61°±8.36° ACH, 0.04°±12.24° ACDF, P=0.21). Conclusions: Compared to ACDF, hybrid constructs partially preserved motion across operative levels and had greater postoperative global ROM without increasing superior adjacent segment mobility or sacrificing alignment restoration. This supports the consideration of ACH in patients with multilevel degenerative cervical pathology requiring at least a 1-level fusion and suggests a propensity for long-term success by reducing the superior adjacent segment burden.

The IL-7R antagonist lusvertikimab reduces leukemic burden in xenograft ALL via antibody-dependent cellular phagocytosis.

ABSTRACT: Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of B-cell precursors (BCP-ALL) or T cells (T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (R/R) disease, high-risk (HR) leukemias and T-ALL, in which immunotherapy approaches remain scarce. Although the interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R-targeting immunotherapy has yet reached clinical application in ALL. The IL-7Rα chain (CD127)-targeting IgG4 antibody lusvertikimab (LUSV; formerly OSE-127) is a full antagonist of the IL-7R pathway, showing a good safety profile in healthy volunteers. Here, we show that ∼85% of ALL cases express surface CD127. We demonstrate significant in vivo efficacy of LUSV immunotherapy in a heterogeneous cohort of BCP- and T-ALL patient-derived xenografts (PDX) in minimal residual disease (MRD) and overt leukemia models, including R/R and HR leukemias. Importantly, LUSV was particularly effective when combined with polychemotherapy in a phase 2-like PDX study with CD127high samples leading to MRD-negativity in >50% of mice treated with combination therapy. Mechanistically, LUSV targeted ALL cells via a dual mode of action comprising direct IL-7R antagonistic activity and induction of macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). LUSV-mediated in vitro ADCP levels significantly correlated with CD127 expression levels and the reduction of leukemia burden upon treatment of PDX animals in vivo. Altogether, through its dual mode of action and good safety profile, LUSV may represent a novel immunotherapy option for any CD127+ ALL, particularly in combination with standard-of-care polychemotherapy.

Semi-supervised generative approach to chemical disorder: application to point-defect formation in uranium-plutonium mixed oxides.

Chemical disorder has a major impact on the characterization of the atomic-scale properties of highly complex chemical compounds, such as the properties of point defects. Due to the vast amount of possible atomic configurations, the study of such properties becomes intractable if treated with direct sampling. In this work, we propose an alternative approach, in which samples are selected based on the local atomic composition around the defect, and the defect formation energy is obtained as a function of this local composition with a reduced computational cost. We apply this approach to (U, Pu)O2 nuclear fuels. The formation-energy distribution is computed using machine-learning generative methods, and used to investigate the impact of chemical disorder and the range of influence of local composition on the defect properties. The predicted distributions are then used to calculate the concentration of thermal defects. This approach allows for the first time for the computation of the latter property with a physically meaningful exploration of the configuration space, and opens the way to a more efficient determination of physico-chemical properties in other chemically-disordered compounds such as high-entropy alloys.

Action affordance affects proximal and distal goal-oriented planning.

Visual attention is mainly goal directed and allocated based on the upcoming action. However, it is unclear how far this feature of gaze behaviour generalizes in more naturalistic settings. The present study investigates the influence of action affordances on active inference processes revealed by eye movements during interaction with familiar and novel tools. In a between-subject design, a cohort of participants interacted with a virtual reality controller in a low-realism environment; another performed the task with an interaction setup that allowed differentiated hand and finger movements in a high-realism environment. We investigated the differences in odds of fixations and their eccentricity towards the tool parts before action initiation. The results show that participants fixate more on the tool's effector part before action initiation when asked to produce tool-specific movements, especially with unfamiliar tools. These findings suggest that fixations are made in a task-oriented way to plan the distal goals of producing the task- and tool-specific actions well before action initiation. Moreover, with more realistic action affordance, fixations were biased towards the tool handle when it was oriented incongruent with the subjects' handedness. We hypothesize that these fixations are made towards the proximal goal of planning the grasp even though the perceived action on the tools is identical for both experimental setups. Taken together, proximal and distal goal-oriented planning is contextualized to the realism of action/interaction afforded by an environment.

Augmented Reality-Assisted Spine Surgery: An Early Experience Demonstrating Safety and Accuracy with 218 Screws.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: In spine surgery, accurate screw guidance is critical to achieving satisfactory fixation. Augmented reality (AR) is a novel technology to assist in screw placement and has shown promising results in early studies. This study aims to provide our early experience evaluating safety and efficacy with an Food and Drug Administration-approved head-mounted (head-mounted device augmented reality (HMD-AR)) device. METHODS: Consecutive adult patients undergoing AR-assisted thoracolumbar fusion between October 2020 and August 2021 with 2 -week follow-up were included. Preoperative, intraoperative, and postoperative data were collected to include demographics, complications, revision surgeries, and AR performance. Intraoperative 3D imaging was used to assess screw accuracy using the Gertzbein-Robbins (G-R) grading scale. RESULTS: Thirty-two patients (40.6% male) were included with a total of 222 screws executed using HMD-AR. Intraoperatively, 4 (1.8%) were deemed misplaced and revised using AR or freehand. The remaining 218 (98.2%) screws were placed accurately. There were no intraoperative adverse events or complications, and AR was not abandoned in any case. Of the 208 AR-placed screws with 3D imaging confirmation, 97.1% were considered clinically accurate (91.8% Grade A, 5.3% Grade B). There were no early postoperative surgical complications or revision surgeries during the 2 -week follow-up. CONCLUSIONS: This early experience study reports an overall G-R accuracy of 97.1% across 218 AR-guided screws with no intra or early postoperative complications. This shows that HMD-AR-assisted spine surgery is a safe and accurate tool for pedicle, cortical, and pelvic fixation. Larger studies are needed to continue to support this compelling evolution in spine surgery.

Adoption of Enhanced Surgical Recovery (ESR) Protocol for Lumbar Fusion Decreases In-Hospital Postoperative Opioid Consumption.

STUDY DESIGN: Retrospective observational cohort. OBJECTIVES: We sought to evaluate the impact of ESR on in-hospital and 90-day postoperative opioid consumption, length of stay, urinary catheter removal and postoperative ambulation after lumbar fusion for degenerative conditions. METHODS: We evaluated patients undergoing lumbar fusion surgery at a single, multi-surgeon center in the transition period prior to (N = 174) and after (N = 116) adoption of ESR, comparing in-hospital and 90-day postoperative opioid consumption. Regression analysis was used to control for confounders. Secondary analysis was preformed to evaluate the association between ESR and length of stay, urinary catheter removal and ambulation after surgery. RESULTS: Mean age study participants was 52.6 years with 62 (47%) females. Demographic characteristics were similar between the Pre-ESR and ESR groups. ESR patients had better 3-month pain scores, ambulated earlier, had urinary catheters removed earlier and decreased in-hospital opioid consumption compared to Pre-ESR patients. There was no difference in 90-day opioid consumption between the 2 groups. Regression analysis showed that ESR was strongly associated with in-hospital opioid consumption, accounting for 30% of the variability in Morphine Milligram Equivalents (MME). In-hospital opioid consumption was also associated with preoperative pain scores, number of surgical levels, and insurance type (private vs government). Pre-op pain sores were associated with 90-day opioid consumption. Secondary analysis showed that ESR was associated with a shorter length of stay and earlier ambulation. CONCLUSIONS: This study showed ESR has the potential to improve recovery after lumbar fusion for degenerative conditions with reduced in-hospital opioid consumption and improved postoperative pain scores.

Opioid use after elective spine surgery: Do spine surgery patients consume less than prescribed today?

Background: The opioid epidemic in the US has led prescribers to reevaluate postoperative pain control particularly in the field of spine surgery, where postoperative analgesia requirements and consumption have historically been high. There is a need to mitigate the quantity of unused pills after surgery by adjusting prescribing practices. Achieving the balance of pain control after surgery without overprescribing opioids may be accomplished by developing a modified approach to prescribing practices; however, there is a need to first understand the opioid requirements of the modern spine surgery patient with respect to their elective spine surgery. Therefore, the primary aim of this study was to determine the percentage of opioids not utilized at 90-days after elective spine surgery. Secondary aims were to identify differences in the percentage of unused opioids between surgical subgroups and preoperative opioid status, to determine factors associated with opioid utilization, and to estimate the distribution of opioids consumed to control pain up to the 90th percentile in each surgical subgroup. Methods: In this prospective, observational cohort study, adults undergoing elective spine surgery at a multi-surgeon, single center were prospectively enrolled and divided into subgroups: anterior cervical, lumbar decompression, and short-segment lumbar fusion. Prescribed MMEs were identified from prescriptions, consumed MMEs were obtained from pill counts, and the percent leftover was calculated. Distributions of MMEs consumed were analyzed to compare utilization between preoperative opioid users or non-users within each surgical subgroup. Results: Of 117 patients, 41.9% were preoperative opioid users. The percentage of unused opioids by surgical subgroup was: 45.4% cervical, 57.3% lumbar decompression, and 37.4% lumbar fusion (p=0.066). The percentage of unused opioids by preoperative opioid exposure was greater in the opioid non-users (58.0%) than users (28.4%, p<0.001)). Regression analysis showed that surgical subgroup and preoperative opioid exposure were associated with leftover opioids. Conclusions: At 90-days, the percentage of unused opioids was over 45% in this cohort of elective spine surgery patients and was nearly double in the group without preoperative opioid exposure. These results suggest the modern elective spine surgery patient is using less opioids than prescribed, supporting the conclusion that the number of MMEs prescribed can be reduced to minimize quantities of leftover pills available for diversion, without sacrificing the priority of appropriate postoperative pain control.

Low Back Pain, Disability, and Quality of Life One Year following Intradiscal Injection of Autologous Bone Marrow Aspirate Concentrate.

Introduction: Degenerative disc disease is a common cause of chronic low back pain. Surgical intervention is an invasive treatment associated with high costs. There is growing interest in regenerative medicine as a less invasive but direct disc treatment for chronic discogenic low back pain. Objective: To evaluate clinical improvement of primary discogenic low back pain with intradiscal injection of autologous bone marrow aspirate concentrate (BMAC). Study Design. Prospective cohort study. Setting. Single, multiphysician center. Patients. 32 adult patients undergoing intradiscal injection of autologous BMAC for the treatment of primary discogenic low back pain. Interventions. Intradiscal injection of autologous BMAC. Main Outcome Measures. Primary outcome measure is visual analog back pain scale (VAS back pain). Secondary outcome measures include ODI, VAS leg pain, and EQ-5D-5L scores. Outcomes were compared from baseline to 1 year. Results: Thirty-two patients (56.3% male) with a mean age of 45.9 years were enrolled, giving 92 treated levels. Mean VAS back and leg pain scores improved from 5.4 to 3.0 (p < 0.001) and 2.8 to 1.3 (p = 0.005), respectively. Mean ODI scores decreased from 33.5 to 21.1 (p < 0.001), and EQ-5D-5L scores improved from 0.69 to 0.78 (p = 0.001). Using established MCID values, 59.4% had clinically significant improvement in VAS back pain, 43.8% in VAS leg pain, and 56.3% in ODI scores. Conclusion: Intradiscal injection of autologous BMAC significantly improved low back pain, disability, and quality of life at one year. This study suggests that intradiscal BMAC has the potential to be an effective nonsurgical treatment for chronic discogenic low back pain.

A Consistent Framework for Coupling Basal Friction With Subglacial Hydrology on Hard-Bedded Glaciers.

Below hard-bedded glaciers, both basal friction and distributed subglacial drainage are thought to be controlled by a network of cavities. Previous coupled hydro-mechanical models, however, describe cavity-driven friction and hydraulic transmissivity independently, resulting in a physically inconsistent cavity evolution between the two components of the models. Here, we overcome this issue by describing the hydro-mechanical system using a common cavity-evolution description, that governs both transient friction and hydraulic transmissivity. We show that our coupling approach is superior to previous formulations in explaining a unique observation record of glacier sliding speed from the French Alps. We find that, at multi-day to multi-decadal timescales, sliding speed can be expressed as a direct function of basal shear stress and water discharge, without accounting for water pressure, which simply adjusts to maintain the cavitation ratio needed to accommodate the water supply.

T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.

Upon antigen recognition by the T cell receptor (TCR), a complex signaling network orchestrated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) regulates the transmission of the extracellular signal to the nucleus. The role of the PTPs Src-homology 2 (SH2) domain-containing phosphatase 1 (SHP1, Ptpn6) and Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2, Ptpn11) have been studied in various cell types including T cells. Whereas SHP1 acts as an essential negative regulator of the proximal steps in T cell signalling, the role of SHP2 in T cell activation is still a matter of debate. Here, we analyzed the role of the constitutively active SHP2-D61Y-mutant in T cell activation using knock-in mice expressing the mutant form Ptpn11D61Y in T cells. We observed reduced numbers of CD8+ and increased numbers of CD4+ T cells in the bone marrow and spleen of young and aged SHP2-D61Y-mutant mice as well as in Influenza A Virus (IAV)-infected mice compared to controls. In addition, we found elevated frequencies of effector memory CD8+ T cells and an upregulation of the programmed cell death protein 1 (PD-1)-receptor on both CD4+ and CD8+ T cells. Functional analysis of SHP2-D61Y-mutated T cells revealed an induction of late apoptosis/necrosis, a reduced proliferation and altered signaling upon TCR stimulation. However, the ability of D61Y-mutant mice to clear viral infection was not affected. In conclusion, our data indicate an important regulatory role of SHP2 in T cell function, where the effect is determined by the kinetics of SHP2 phosphatase activity and differs in the presence of the permanently active and the temporally regulated phosphatase. Due to interaction of SHP2 with the PD-1-receptor targeting the protein-tyrosine phosphatase might be a valuable tool to enhance T cell activities in immunotherapy.

Characterization of Maladaptive Processes in Acute, Chronic and Remission Phases of Experimental Colitis in C57BL/6 Mice.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease with unknown etiology. Dextran sulfate sodium (DSS) induced colitis is a widely used mouse model in IBD research. DSS colitis involves activation of the submucosal immune system and can be used to study IBD-like disease characteristics in acute, chronic, remission and transition phases. Insight into colon inflammatory parameters is needed to understand potentially irreversible adaptations to the chronification of colitis, determining the baseline and impact of further inflammatory episodes. We performed analyses of non-invasive and invasive colitis parameters in acute, chronic and remission phases of the DSS colitis in C57BL/6 mice. Non-invasive colitis parameters poorly reflected inflammatory aspects of colitis in chronic remission phase. We found invasive inflammatory parameters, positively linked to repeated DSS-episodes, such as specific colon weight, inflamed colon area, spleen weight, absolute cell numbers of CD4+ and CD8+ T cells as well as B cells, blood IFN-γ level, colonic chemokines BLC and MDC as well as the prevalence of Turicibacter species in feces. Moreover, microbial Lactobacillus species decreased with chronification of disease. Our data point out indicative parameters of recurrent gut inflammation in context of DSS colitis.

Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route.

Toxoplasma gondii is a highly successful parasite capable of infecting all warm-blooded animals. The natural way of infection in intermediate hosts is the oral ingestion of parasite-contaminated water or food. In murine experimental models, oral infection (p.o.) of mice with T. gondii is applied to investigate mucosal and peripheral immune cell dynamics, whereas intraperitoneal infection (i.p.) is frequently used to study peripheral inflammation as well as immune cell - neuronal interaction in the central nervous system (CNS). However, the two infection routes have not yet been systematically compared along the course of infection. Here, C57BL/6 mice were infected p.o. or i.p. with a low dose of T. gondii cysts, and the acute and chronic stages of infection were compared. A more severe course of infection was detected following i.p. challenge, characterized by an increased weight loss and marked expression of proinflammatory cytokines particularly in the CNS during the chronic stage. The elevated proinflammatory cytokine expression in the ileum was more prominent after p.o. challenge that continued following the acute phase in both i.p. or p.o. infected mice. This resulted in sustained microbial dysbiosis, especially after p.o. challenge, highlighted by increased abundance of pathobionts from the phyla proteobacteria and a reduction of beneficial commensal species. Further, we revealed that in the CNS of i.p. infected mice CD4 and CD8 T cells displayed higher IFNγ production in the chronic stage. This corresponded with an increased expression of C1q and CD68 in the CNS and reduced expression of genes involved in neuronal signal transmission. Neuroinflammation-associated synaptic alterations, especially PSD-95, VGLUT, and EAAT2 expression, were more pronounced in the cortex upon i.p. infection highlighting the profound interplay between peripheral inflammation and CNS homeostasis.

Novel artificial intelligence algorithm: an accurate and independent measure of spinopelvic parameters.

OBJECTIVE: The analysis of sagittal alignment by measuring spinopelvic parameters has been widely adopted among spine surgeons globally, and sagittal imbalance is a well-documented cause of poor quality of life. These measurements are time-consuming but necessary to make, which creates a growing need for an automated analysis tool that measures spinopelvic parameters with speed, precision, and reproducibility without relying on user input. This study introduces and evaluates an algorithm based on artificial intelligence (AI) that fully automatically measures spinopelvic parameters. METHODS: Two hundred lateral lumbar radiographs (pre- and postoperative images from 100 patients undergoing lumbar fusion) were retrospectively analyzed by board-certified spine surgeons who digitally measured lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope. The novel AI algorithm was also used to measure the same parameters. To evaluate the agreement between human and AI-automated measurements, the mean error (95% CI, SD) was calculated and interrater reliability was assessed using the 2-way random single-measure intraclass correlation coefficient (ICC). ICC values larger than 0.75 were considered excellent. RESULTS: The AI algorithm determined all parameters in 98% of preoperative and in 95% of postoperative images with excellent ICC values (preoperative range 0.85-0.92, postoperative range 0.81-0.87). The mean errors were smallest for pelvic incidence both pre- and postoperatively (preoperatively -0.5° [95% CI -1.5° to 0.6°] and postoperatively 0.0° [95% CI -1.1° to 1.2°]) and largest preoperatively for sacral slope (-2.2° [95% CI -3.0° to -1.5°]) and postoperatively for lumbar lordosis (3.8° [95% CI 2.5° to 5.0°]). CONCLUSIONS: Advancements in AI translate to the arena of medical imaging analysis. This method of measuring spinopelvic parameters on spine radiographs has excellent reliability comparable to expert human raters. This application allows users to accurately obtain critical spinopelvic measurements automatically, which can be applied to clinical practice. This solution can assist physicians by saving time in routine work and by avoiding error-prone manual measurements.

A multicenter study of the 5-year trends in robot-assisted spine surgery outcomes and complications.

Background: Although a growing amount of literature that suggests robots are safe and can achieve comparable outcomes to conventional techniques, much of this literature is limited by small sample sizes and single-surgeon or single center series. Furthermore, it is unclear what the impact of robotic technology has made on operative and clinical outcomes over time. This is the first and largest multicenter study to examine the trends in outcomes and complications after robot-assisted spine surgery over a 5-year period. Methods: Adult (≥18 years old) patients who underwent spine surgery with robot-assistance between 2015 and 2019 at four unique spine centers. The robotic systems used included the Mazor Renaissance, Mazor X, and Mazor Stealth Edition. Patients with incomplete data were excluded from this study. The minimum follow-up was 90 days. Results: A total of 722 adult patients were included (117 Renaissance, 477 X, 128 Stealth). Most patient and operative factors (e.g., sex, tobacco status, total instrumented levels, and pelvic fixation,) were similar across the years. Mean ± standard deviation Charlson comorbidity index (CCI) was 1.5±1.5. The most commonly reported diagnoses included high grade spondylolisthesis (40.6%), degenerative disc disease (18.4%), and degenerative scoliosis (17.6%). Mean (standard deviation) number of instrumented levels was 3.8±3.4. From 2015 to 2019, average robot time per screw improved from 7.2 to 5.5 minutes (P=0.004, R2=0.649). Average fluoroscopy time per screw improved from 15.2 to 9.4 seconds (P=0.002). Rates of both intraoperative screw exchange for misplaced screw (2015-2016: 2.7%, 2019: 0.8%, P=0.0115, R2=0.1316) and robot abandonment (2015-2016: 7.1%, 2019: 1.1%, P=0.011, R2=0.215) improved significantly over time. The incidence of other intraoperative complications (e.g., dural tear, loss of motor/sensory function, blood transfusion) remained consistently low, but similar throughout the years. The length of stay (LOS) decreased by nearly 1 day from 2015 to 2019 (P=0.007, R2=0.779). 90-day reoperation rates did not change significantly. Conclusions: At four institutions among seven surgeons, we demonstrate robot screw accuracy, reliability, operative efficiency, and radiation exposure improved significantly from 2015 to 2019. 90-day complication rates remained low and LOS decreased significantly with time. These findings further validate continued usage of robot-assisted spine surgery and the path toward improved value-based care.

IFNAR signaling in fibroblastic reticular cells can modulate CD8+ memory fate decision.

CD8+ memory T cells (TM ) are crucial for long-term protection from infections and cancer. Multiple cell types and cytokines are involved in the regulation of CD8+ T cell responses and subsequent TM formation. Besides their direct antiviral effects, type I interferons (IFN-I) modulate CD8+ T cell immunity via their action on several immune cell subsets. However, it is largely unclear how nonimmune cells are involved in this multicellular network modulating CD8+ TM formation. Fibroblastic reticular cells (FRCs) form the 3D scaffold of secondary lymphoid organs, express the IFN-I receptor (IFNAR), and modulate adaptive immune responses. However, it is unclear whether and how early IFNAR signals in lymph node (LN) FRCs affect CD8+ TM differentiation. Using peptide vaccination and viral infection, we studied CD8+ TM differentiation in mice with an FRC-specific IFNAR deletion (FRCΔIFNAR ). We show here that the differentiation of CD8+ TCR-transgenic T cells into central memory cells (TCM ) is enhanced in peptide-vaccinated FRCΔIFNAR mice. Conversely, vesicular stomatitis virus infection of FRCΔIFNAR mice is associated with impaired TCM formation and the accumulation of vesicular stomatitis virus specific double-positive CD127hi KLRG-1hi effector memory T cells. In summary, we provide evidence for a context-dependent contribution of FRC-specific IFNAR signaling to CD8+ TM differentiation.

Type 1 innate lymphoid cells regulate the onset of Toxoplasma gondii-induced neuroinflammation.

Cerebral infections are restrained by a complex interplay of tissue-resident and recruited peripheral immune cells. Whether innate lymphoid cells (ILCs) are involved in the orchestration of the neuroinflammatory dynamics is not fully understood. Here, we demonstrate that ILCs accumulate in the cerebral parenchyma, the choroid plexus, and the meninges in the onset of cerebral Toxoplasma gondii infection. Antibody-mediated depletion of conventional natural killer (cNK) cells and ILC1s in the early stage of infection results in diminished cytokine and chemokine expression and increased cerebral parasite burden. Using cNK- and ILC1-deficient murine models, we demonstrate that exclusively the lack of ILC1s affects cerebral immune responses. In summary, our results provide evidence that ILC1s are an early source of IFN-γ and TNF in response to cerebral T. gondii infection, thereby inducing host defense factors and initiating the development of a neuroinflammatory response.

Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis.

BACKGROUND: Toxoplasma gondii (T. gondii) is a highly successful parasite being able to cross all biological barriers of the body, finally reaching the central nervous system (CNS). Previous studies have highlighted the critical involvement of the blood-brain barrier (BBB) during T. gondii invasion and development of subsequent neuroinflammation. Still, the potential contribution of the choroid plexus (CP), the main structure forming the blood-cerebrospinal fluid (CSF) barrier (BCSFB) have not been addressed. METHODS: To investigate T. gondii invasion at the onset of neuroinflammation, the CP and brain microvessels (BMV) were isolated and analyzed for parasite burden. Additionally, immuno-stained brain sections and three-dimensional whole mount preparations were evaluated for parasite localization and morphological alterations. Activation of choroidal and brain endothelial cells were characterized by flow cytometry. To evaluate the impact of early immune responses on CP and BMV, expression levels of inflammatory mediators, tight junctions (TJ) and matrix metalloproteinases (MMPs) were quantified. Additionally, FITC-dextran was applied to determine infection-related changes in BCSFB permeability. Finally, the response of primary CP epithelial cells to T. gondii parasites was tested in vitro. RESULTS: Here we revealed that endothelial cells in the CP are initially infected by T. gondii, and become activated prior to BBB endothelial cells indicated by MHCII upregulation. Additionally, CP elicited early local immune response with upregulation of IFN-γ, TNF, IL-6, host-defence factors as well as swift expression of CXCL9 chemokine, when compared to the BMV. Consequently, we uncovered distinct TJ disturbances of claudins, associated with upregulation of MMP-8 and MMP-13 expression in infected CP in vivo, which was confirmed by in vitro infection of primary CP epithelial cells. Notably, we detected early barrier damage and functional loss by increased BCSFB permeability to FITC-dextran in vivo, which was extended over the infection course. CONCLUSIONS: Altogether, our data reveal a close interaction between T. gondii infection at the CP and the impairment of the BCSFB function indicating that infection-related neuroinflammation is initiated in the CP.

Robotic-guidance allows for accurate S2AI screw placement without complications.

The study design is retrospective, multi-surgeon, single-center review. The objective is to evaluate complication rates, revision rates, and accuracy grading for robotic-guided S2 alar-iliac (S2AI) screws. Sixty-five consecutive patients underwent S2AI fixation (118 screws) as part of a posterior spine fusion using robotic-guidance. Screws were placed percutaneously in 14 cases and 51 were placed in an open fashion by three board-certified spine surgeons using the Mazor core technology robotic systems (Mazor X, n = 42; Mazor XSE, n = 23). Medical charts were retrospectively reviewed for revisions and complications. All patients were followed for 90 days or greater. Postoperative CT scans were obtained in 22 of the 51 patients, allowing for 46 screws to be reviewed by an independent neuroradiologist who graded the screws for accuracy. There were no intraoperative or postoperative complications associated with S2AI screw placement. There were no revisions found to be related to the S2AI screw placement. All 46 screws evaluated with postoperative CT scans were reported as being at the highest level of accuracy, grade A, with a breach distance of 0 mm (no breach). The robotic-guided technique for S2AI screw placement is a reliable method to achieving pelvic fixation with low complication and revision rates. In addition, a high degree of accuracy can be achieved without relying on visible and tactile landmarks needed for the freehand technique or the additional radiation associated with fluoroscopic-guidance.

Adoption of enhanced surgical recovery (ESR) protocol for adult spinal deformity (ASD) surgery decreases in-hospital and 90-day post-operative opioid consumption.

PURPOSE: Retrospective observational cohort study of primary adult spinal deformity (ASD) surgery during the transitional period prior to and after the implementation of Enhanced Surgical Recovery (ESR) at a single center. We sought to determine if ESR reduces in-hospital and 90-day post-operative opioid consumption for ASD surgery. METHODS: We evaluated patients undergoing primary ASD surgery in the transition period prior to (N = 29) and after (N = 56) adoption of ESR, comparing in-hospital and 90-day post-operative opioid consumption. Regression analysis was used to control for confounders including age, number of surgical levels, surgical approach, staged vs same-day surgery, insurance type and pre-op opioid use. RESULTS: Mean age of the cohort was 53 years with 57 (60%) females. Regression analysis showed that pre-operative opioid use and number of levels fused were associated with higher in-hospital and 90-day post-operative opioid consumption, while use of ESR was associated with lower in-hospital and 90-day post-operative opioid consumption. Secondary analysis showed that patients on ESR ambulated earlier (0.6 days vs 1.1, p = 0.028) and had their urinary catheter removed earlier (2.7 days vs 3.9, p = 0.006) compared to non-ESR patients. CONCLUSIONS: ESR was associated with a significantly decreased in-hospital and 90-day post-operative opioid consumption and earlier mobilization with earlier urinary catheter removal in patients undergoing primary ASD surgery. These results demonstrate ESR's potential to improve outcomes in ASD perioperative care. LEVEL OF EVIDENCE: 3.