Citations

Background: Vertebral body defects pose a significant challenge in spinal reconstructive surgery. Compression fractures of the vertebral corpus are typically treated with vertebral augmentation procedures. There are significant risks associated with the introduction of foreign material in the spine, including infection and pseudarthrosis. Vascularized bone grafts (VBGs) have become a popular alternative for spinal reconstruction in the last decade thanks to their robust blood supply and autologous nature. VBGs have been described predominantly for the reconstruction of posterior vertebral defects. The objective of this study is to describe a novel procedure for the reconstruction of vertebral corpus defects in the lumbar and distal thoracic spine. Methods: This is a cadaveric anatomy study. The authors performed the novel surgical technique on an anonymized cadaveric donor in the prone position and recorded the procedure through clinical photography. Consent for the procedure and photography was obtained from the Center for Procedural Innovation. Results: A 5-cm-long posterior iliac crest VBG (IC-VBG) was successfully harvested on a pedicle of the quadratus lumborum muscle. The VBG was rotated and mobilized anteromedially to the vertebral corpus. In this donor, the IC-VBG could be inset with minimal tension anywhere along the vertebral bodies of the spine from the L5 to the T9 level. Conclusions: A rotated, anteromedially mobilized IC-VBG represents a novel technique for reconstruction of the anterior vertebral corpus of the lumbar and distal thoracic spine with a lower risk of infection and pseudarthrosis than reconstruction with foreign materials.

Abstract The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate ‘pro-aging’ or ‘pro-youthful’ effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear. We examined five previously identified brain rejuvenation factors in cerebrospinal fluid of adults with autosomal dominant forms of frontotemporal dementia and sporadic Alzheimer’s disease. Our frontotemporal dementia cohort included 100 observationally followed adults carrying autosomal dominant frontotemporal dementia mutations (Mage = 49.6; 50% female; 43% C9orf72, 24% GRN, 33% MAPT) and 62 non-carriers (Mage = 52.6; 45% female) with cerebrospinal fluid analysed on Somascan, and longitudinal (Mvisits = 3 years, range 1–7 years) neuropsychological and functional assessments and plasma neurofilament light chain. Our Alzheimer’s disease cohort included 35 adults with sporadic Alzheimer’s disease (Mage = 69.4; 60% female) and 56 controls (Mage = 68.8, 50% female) who completed the same cerebrospinal fluid and clinical outcome measures cross-sectionally. Levels of C-C motif chemokine ligand 11, C-C motif chemokine ligand 2, beta-2-micorglobulin, bone gamma-carboxyglutamate protein (aka Osteocalcin) and colony stimulating factor 2 in cerebrospinal fluid were linearly combined into a composite score, with higher values reflecting ‘pro-youthful’ levels. In genetic frontotemporal dementia, higher baseline cerebrospinal fluid rejuvenation proteins predicted slower decline across cognitive, functional, and neurofilament light chain trajectories; estimates were similar across genotypes. In transdiagnostic analyses, higher cerebrospinal fluid rejuvenation proteins associated with better functional, cognitive, and neurofilament light chain outcomes in adults with sporadic Alzheimer’s disease. Proteins with pre-clinical evidence for brain rejuvenation show translational clinical relevance in adults with Alzheimer’s disease and related dementias and warrant further investigation.

Introduction/Purpose The multicenter, prospective, single‐arm, controlled, non‐randomized SCENT trial on flow diverter (FD) treatment for intracranial aneurysms (IA) was analyzed for patients’ age and IA characteristics impacting stroke and occlusion rates over 5 years. Materials and Methods Impact on major ipsilateral stroke and IA occlusion was studied by stratifying age as </= 65 years versus >65 years. Twice as many subjects treated were </= 65 years old (n=119/180). Product‐limit (Kaplan‐Meier) estimates of time to both endpoints, stratified by age group, were created. Univariate predictors of time to stroke were identified by including candidate variables in univariable proportional hazards regression models. Those variables found to be significant (p<0.10) at the univariate level were entered into a multivariable survival model to identify independent predictors. The stepwise selection produced a final reduced model with a significance level to both enter and stay set at 0.05. Results When parent artery stenosis and IA size were entered into a multiple‐stepwise survival model, only stenosis remained as an independently significant predictor of time to stroke. At 3‐year follow‐up, there were a total of 23 strokes (12.8%), with 11 (47.8%) occurring in subjects </= 65 years; there was a greater risk for seniors (HR1.96, 95% CI 0.83‐4.78, p=.122). Four patients (4/180; 2.2%) experienced aneurysm ruptured within the first week post‐treatment, with 3 being </= 65 and the fourth aged 66 years. No new strokes were reported between 3 and 5 years. Complete IA occlusion rates for seniors were 60.0% (33/55), 67.6% (25/37), and 85.7% (18/21) at 12, 36, and 60 months, respectively, as compared to 79.1% (87/110), 82.5% (66/80), and 91.8% (56/61) for younger subjects. The time to complete IA occlusion was shorter in younger patients (HR1.53, 95% CI 1.07‐2.19, p=.020). Five subjects (2.8%) underwent retreatment, 2 in 60‐year‐old patients, and one each aged 64, 70, and 75. Conclusion Stroke, early rupture risk, and aneurysm occlusion in patients treated with FD are related to age and pre‐existing parent artery stenosis, IA size, and location. With demographic shifts, future treatments need to focus on expedited and improved healing.

Abstract Although social determinants of health (SDoH) investigations have shown limited analyses of socioeconomic and race-ethnic status on certain hematologic malignancies, the impact of factors beyond those across a fuller scope of hematologic cancers remains unknown. The Social Vulnerability Index (SVI), a tool for assessing varied US census–derived sociodemographic factors, allows for the specific quantification of SDoH in dynamic, regional contexts for their associations with hematologic malignancy inequities. To assess the summative influence of varied SDoH factors on hematologic malignancy outcomes and discern which SDoH factors contributed the largest associations toward disparities, 796 005 adults with hematologic malignancies between 1975 to 2017 were identified for this retrospective cohort study. Vulnerability in 15 SDoH factors was measured using composite and subcategory SVI scores geographically matched to patients. Regressions between SVI factors and follow-up time after diagnosis and survival period were performed. Increasing overall SVI correlated with significantly decreased surveillance period in 11 of 14 hematologic malignancies, with decreases upward of 33.4% (39.0-26.0 months for acute lymphocytic leukemia). Increasing SVI significantly associated with decreased survival period across 11 of 14 hematologic malignancies, with decreases upward of 47.2% (89.5-47.3 months for Hodgkin lymphoma). Socioeconomic status and housing and transportation vulnerabilities showed the largest magnitude of contributions, followed by minority language and household composition. Significant decreases in hematologic malignancy prognosis associate with increasing overall SDoH vulnerability in varied sociodemographic contexts in the United States. Furthermore, there are quantifiable differences in which types of SDoH contribute more to trends per malignancy type. These findings demonstrate specific SDoH targets for further research and policy initiatives to combat hematologic malignancy disparity more effectively.

Abstract Autoimmunity affects 10% of the population. Within this umbrella, autoantibody-mediated diseases targeting one autoantigen provide a unique opportunity to comprehensively understand the developmental pathway of disease-causing B cells and autoantibodies. While such autoreactivities are believed to be generated during germinal centre reactions, the roles of earlier immune checkpoints in autoantigen-specific B cell tolerance are poorly understood. We address this concept in patients with CASPR2-autoantibody encephalitis and healthy controls. In both groups, comparable and high (∼0.5%) frequencies of unmutated CASPR2-reactive naïve B cells were identified. By contrast, CASPR2-reactive memory B cells were exclusive to patients, and their B cell receptors demonstrated affinity-enhancing somatic mutations with heterogenous binding kinetics. These effector molecules possessed epitope-dependent pathogenic effects in vitro neuronal cultures and in vivo. The unmutated common ancestors of these memory B cells showed a distinctive balance between strong CASPR2 reactivity and very limited binding across the remaining human proteome. Our results are the first to propose mechanisms underlying autoantigen-specific tolerance in humans. We identify permissive central tolerance, defective peripheral tolerance and heterogenous autoantibody binding properties as sequential pathogenic steps which licence CASPR2-directed pathology. By leveraging the basic immunobiology, we rationally direct tolerance-restoring approaches in CASPR2-antibody diseases. This paradigm is applicable across autoimmune conditions.

BACKGROUND: During orthotopic liver transplantation, allograft reperfusion is a dynamic point in the operation and often requires vasoactive medications and blood transfusions. Normothermic machine perfusion (NMP) of liver allografts has emerged to increase the number of transplantable organs and may have utility during donation after circulatory death (DCD) liver transplantation in reducing transfusion burden and vasoactive medication requirements. METHODS: This is a single-center retrospective study involving 226 DCD liver transplant recipients who received an allograft transported with NMP (DCD-NMP group) or with static cold storage (DCD-SCS group). Veno-venous bypass was not used in any patients. Infusion doses of norepinephrine, epinephrine, and vasopressin as well as bolus doses of vasoactive medications during reperfusion were recorded. Blood component therapy was recorded according to phase of liver transplantation and during the first 24 hours postprocedure. RESULTS: A total of 103 recipients in the DCD-NMP group and 123 patients in the DCD-SCS group were included. Post-reperfusion syndrome (PRS) incidence was reduced in the DCD-NMP group compared to the DCD-SCS group (10.7% [95% confidence interval, CI, 5.5%–18.3%] vs 42.3% [95% CI, 33.4%–51.5%]; P < .001). During the reperfusion period, patients in the DCD-SCS group required increased bolus doses of epinephrine and vasopressin compared to the DCD-NMP group (24.6 vs 7.5 µg; P < .001) and (5.4 vs 2.4 units; P < .001), respectively. The DCD-SCS group received a higher infusion dose of epinephrine during anhepatic phase, at reperfusion, and up to 90 minutes after reperfusion. In the postreperfusion period, there were significant increases in the transfusion of red blood cells (RBCs; 5.3 vs 3.7 units; P = .006), fresh frozen plasma (FFP; 3.4 vs 1.9 units; P < .001), cryoprecipitate (2.7 vs 1.8 pooled units; P = .015) and platelets (0.9 vs 0.4 units; P = .008) in the DCD-SCS group compared to the DCD-NMP group. During the first 24 hours postprocedure, transfusion of RBCs, FFP, and cryoprecipitate in the DCD-SCS group was increased compared to the DCD-NMP group ([2.6 vs 1.7 units; P = .028], [1.6 vs 0.8 units; P < .001], [1.5 vs 0.9 pooled units; P = .031]) respectively. Administration of tranexamic acid was more frequent in the DCD-SCS group during the post-reperfusion period compared to the DCD-NMP group (13% [95% CI, 5.7%–17.4%] vs 3.9% [95% CI, 1.1%–9.6% 95%]; P = .018). CONCLUSIONS: In DCD liver transplantation, use of NMP was associated with reduced incidence of PRS and decreased vasopressor and inotrope requirements at the time of allograft reperfusion compared to using SCS. Additionally, NMP was associated with reduced transfusion of all blood product components as well as antifibrinolytic agent administration in the post-reperfusion period. Reduced transfusion burden in the DCD-NMP group also occurred during the first 24 hours posttransplant.

BACKGROUND AND OBJECTIVES: Vertebral artery injury (VAI) because of traumatic subaxial cervical spine injury is a rare but potentially devastating condition as it could lead to stroke. The aim of this study was to examine the incidence, risk factors, outcomes, and radiographic predictors of VAI in patients surgically treated for subaxial cervical spine injuries at a tertiary care trauma center. METHODS: This is a retrospective population-based cohort study, including all patients surgically treated for traumatic subaxial cervical spine injuries at the study center between 2006 and 2018. Primary outcomes included mortality and morbidity after the injury. Propensity score matching, survival, univariable, and multivariable analyses were used to study the outcomes of interest. RESULTS: Traumatic VAI primarily occurred after high-energy traumas such as motor vehicle accidents and falls from heights. The median age was 64.4 years (47.4-69.1), and 69% were male. In the cohort of patients with subaxial cervical injury, 54% had a spinal cord injury (SCI). In the subgroup with VAI, the frequency of SCI was 66% and a concomitant SCI and VAI were associated with a more severe American Spinal Cord Injury Association Impairment Scale grade ( P = .015). However, after accounting for age, sex, and associated injuries, VAI did not affect postoperative complications, short- or long-term outcomes, or mortality rates. Facet joint dislocation was a unique radiographic predictor of VAI (odds ratio 3.8 [CI 1.42-10.7], P = .009). CONCLUSION: The findings suggest that clinical outcomes of patients with traumatic cervical spine injuries were not negatively affected by the presence of a VAI. Several radiographic factors were associated with VAI; however, only facet joint dislocation remained as an independent predictor of this injury.

AbstractEUS-guided gallbladder drainage (EUS-GBD) using lumen apposing metal stents (LAMS) has excellent technical and short-term clinical success for acute cholecystitis (AC). The goals of this study were to determine the long-term clinical outcomes and adverse events (AEs) of EUS-GBD with LAMS.A multicenter, retrospective study was conducted at 18 US tertiary care institutions. Inclusion criteria: any AC patient with attempted EUS-GBD with LAMS and minimum 30-day post-procedure follow-up. Long-term clinical success was defined as absence of recurrent acute cholecystitis (RAC) > 30 days and long-term AE was defined as occurring > 30 days from the index procedure.A total of 109 patients were included. Technical success was achieved in 108 of 109 (99.1%) and initial clinical success in 106 of 109 (97.2%). Long-term clinical success was achieved in 98 of 109 (89.9%) over a median follow-up of 140 days (range 30–1188). On multivariable analysis (MVA), acalculous cholecystitis (odds ratio [OR] 15.93, 95% confidence interval [CI] 1.22–208.52, P = 0.04) and the occurrence of a LAMS-specific AE (OR 63.60, 95% CI 5.08–799.29, P <0.01) were associated with RAC. AEs occurred in 38 of 109 patients (34.9%) at any time, and in 10 of 109 (9.17%) > 30 days from the index procedure. Most long-term AEs (7 of 109; 6.42%) were LAMS-specific. No technical or clinical factors were associated with occurrence of AEs. LAMS were removed in 24 of 109 patients (22%). There was no difference in RAC or AEs whether LAMS was removed or not.EUS-GBD with LAMS has a high rate of long-term clinical success and modest AE rates in patients with AC and is a reasonable destination therapy for high-risk surgical candidates.

ABSTRACTBackground and AimsChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is difficult to distinguish from mimicking disorders, with misdiagnosis resulting in IVIG overutilization. We evaluate a clinical‐electrophysiological model to facilitate CIDP versus mimic neuropathy prediction.MethodsUsing the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 CIDP guidelines we derived 26 clinical and 144 nerve conduction variables. The model was generated and validated utilizing total CIDP (n = 129) and mimics (n = 309); including (1) IgG4‐nodopathies; (2) POEMS (polyneuropathy–organomegaly–endocrinopathy–monoclonal protein‐skin changes); (3) anti‐myelin‐associated‐glycoprotein; (4) paraneoplastic; (5) Waldenström B‐cell lymphoma; (6) diabetic neuropathies; (7) amyloidosis; (8) Charcot–Marie–Tooth; (9) motor neuropathies/neuronopathies; and (10) idiopathic‐inflammatory‐myopathies.ResultsWe analyzed 9282 clinical and 51 408 electrophysiological data points. Univariate analysis identified 11 of 26 clinical variables with significant odds ratios. A multivariate regression model using four clinical and two electrophysiologic variables achieved 93% area‐under‐curve (95% CI 91–95): progression over 8 weeks (OR 40.66, 95% CI 5.31–311.36), absent autonomic involvement (OR 17.82, 95% CI 2.93–108.24), absent muscle atrophy (OR 16.65, 95% CI 3.27–84.73), proximal weakness (OR 3.63, 95% CI 1.58–8.33), ulnar motor conduction velocity slowing < 35.7 m/s (OR 5.21, 95% CI 2.13–12.76), and ulnar motor conduction block (OR 13.37, 95% CI 2.47–72.40). A web‐based probability calculator (https://news.mayocliniclabs.com/cidp‐calculator/) was developed, with 100% sensitivity and 68% specificity at a 92% probability threshold. Specificity improved to 93% when considering “red flags,” electrophysiologic criteria, and laboratory testing.InterpretationA probability calculator using clinical electrophysiological variables assists CIDP differentiation from mimics, with scores below 92% unlikely to have CIDP. The highest specificity is achieved by considering clinical “red flags,” electrophysiologic demyelination, and laboratory testing.

Study Design Narrative Review. Objective The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability. Carbon fiber reinforced pedicle screws (CFRP) are increasingly used in the oncologic setting due to reductions in both imaging artifacts and radiotherapy perturbations compared to titanium implants. We performed a review of the literature and highlight advantages and future areas of study for CFRP. Methods We performed a systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 10 articles including 573 patients. Across all studies we reviewed patient demographics, tumor types treated, hardware-related features, complication rates, recurrence, survival, and follow-up. Results Across 10 studies, a total of 1371 screws placed. Surgical and non-surgical complications were reported in 18.3% of patients. Disease progression at the surgical site was detected in 7.3% of patients. There was no significant difference in clinical or hardware complications between CFRP or titanium implants. The most frequent complication attributable to implanted CFRP hardware included screw breakage in 2.4% and loosening in 1.7% of patients, respectively. Conclusion CFRP provide a unique tool in the setting of spinal oncology. With a safety profile comparable to titanium, we review the documented advantages of CFRP posterior implants compared to titanium, while also addressing their current limitations. Additionally, we highlight several areas of future research to identify the optimal patients who will achieve the greatest benefit of CFRP.