Morvan Fibrillary Chorea Associated with Monoclonal B Cell Lymphocytosis.

BACKGROUND Morvan fibrillary chorea (Morvan syndrome) is a rare disorder marked by a collection of neurological symptoms such as myokymia, peripheral nerve excitability, neuromyotonia, autonomic instability, memory impairment, and delirium. Morvan syndrome is suspected to occur through antibodies directed against voltage gated potassium channels (VGKC), and has been linked with several autoimmune conditions and hematologic malignancies. We present a case of Morvan syndrome in association with monoclonal B cell lymphocytosis. Upon our literature review, we believe this to be the first documented case of Morvan syndrome associated with monoclonal B cell lymphocytosis. CASE REPORT The present case report describes a 75-year-old man with Morvan's syndrome. The patient had a diverse neurologic presentation with encephalopathy, progressive neuropathic pain, muscle fasciculations, myokymia, sensory deficits, and Bell's palsy. Ultimately, a paraneoplastic antibody panel revealed a positive titer of contactin-associated protein-like IgG (CASPR) and VGKC antibody. Flow cytometry showed a small population of abnormal lambda-restricted B cells. Given his symptoms, positive CASPR antibody, and flow cytometry findings, he was diagnosed with Morvan syndrome associated with monoclonal B cell lymphocytosis. He was treated with IV methylprednisolone and IVIG, with immediate improvement in neurologic symptoms. CONCLUSIONS Morvan syndrome presents with a spectrum of neurologic symptoms and is associated with autoantibodies against VGKC through anti-CASPR2 antibodies. Classically, Morvan syndrome presents as a paraneoplastic disease secondary to thymomas. Our case demonstrates that there is an association between B cell lymphoproliferative disorders and Morvan syndrome.

Genomic epidemiology uncovers the timing and origin of the emergence of mpox in humans.

Five years before the 2022-2023 global mpox outbreak Nigeria reported its first cases in nearly 40 years, with the ongoing epidemic since driven by sustained human-to-human transmission. However, limited genomic data has left questions about the timing and origin of the mpox virus' (MPXV) emergence. Here we generated 112 MPXV genomes from Nigeria from 2021-2023. We identify the closest zoonotic outgroup to the human epidemic in southern Nigeria, and estimate that the lineage transmitting from human-to-human emerged around July 2014, circulating cryptically until detected in September 2017. The epidemic originated in Southern Nigeria, particularly Rivers State, which also acted as a persistent and dominant source of viral dissemination to other states. We show that APOBEC3 activity increased MPXV's evolutionary rate twenty-fold during human-to-human transmission. We also show how Delphy, a tool for near-real-time Bayesian phylogenetics, can aid rapid outbreak analytics. Our study sheds light on MPXV's establishment in West Africa before the 2022-2023 global outbreak and highlights the need for improved pathogen surveillance and response.

Molecular epidemiology of recurrent zoonotic transmission of mpox virus in West Africa.

Nigeria and Cameroon reported their first mpox cases in over three decades in 2017 and 2018 respectively. The outbreak in Nigeria is recognised as an ongoing human epidemic. However, owing to sparse surveillance and genomic data, it is not known whether the increase in cases in Cameroon is driven by zoonotic or sustained human transmission. Notably, the frequency of zoonotic transmission remains unknown in both Cameroon and Nigeria. To address these uncertainties, we investigated the zoonotic transmission dynamics of the mpox virus (MPXV) in Cameroon and Nigeria, with a particular focus on the border regions. We show that in these regions mpox cases are still driven by zoonotic transmission of a newly identified Clade IIb.1. We identify two distinct zoonotic lineages that circulate across the Nigeria-Cameroon border, with evidence of recent and historic cross border dissemination. Our findings support that the complex cross-border forest ecosystems likely hosts shared animal populations that drive cross-border viral spread, which is likely where extant Clade IIb originated. We identify that the closest zoonotic outgroup to the human epidemic circulated in southern Nigeria in October 2013. We also show that the zoonotic precursor lineage circulated in an animal population in southern Nigeria for more than 45 years. This supports findings that southern Nigeria was the origin of the human epidemic. Our study highlights the ongoing MPXV zoonotic transmission in Cameroon and Nigeria, underscoring the continuous risk of MPXV (re)emergence.

The effect of classical optimizers and Ansatz depth on QAOA performance in noisy devices.

The Quantum Approximate Optimization Algorithm (QAOA) is a variational quantum algorithm for Near-term Intermediate-Scale Quantum computers (NISQ) providing approximate solutions for combinatorial optimization problems. The QAOA utilizes a quantum-classical loop, consisting of a quantum ansatz and a classical optimizer, to minimize some cost function, computed on the quantum device. This paper presents an investigation into the impact of realistic noise on the classical optimizer and the determination of optimal circuit depth for the Quantum Approximate Optimization Algorithm (QAOA) in the presence of noise. We find that, while there is no significant difference in the performance of classical optimizers in a state vector simulation, the Adam and AMSGrad optimizers perform best in the presence of shot noise. Under the conditions of real noise, the SPSA optimizer, along with ADAM and AMSGrad, emerge as the top performers. The study also reveals that the quality of solutions to some 5 qubit minimum vertex cover problems increases for up to around six layers in the QAOA circuit, after which it begins to decline. This analysis shows that increasing the number of layers in the QAOA in an attempt to increase accuracy may not work well in a noisy device.

Deadlift-Induced Paraspinal Compartment Syndrome: A Case Report.

Paraspinal compartment syndrome is a rare and potentially life-threatening condition. Diagnosis and treatment are often delayed due to a broad differential for back pain, from musculoskeletal to abdominal etiologies. Diagnosis is made with difficulty through clinical picture, laboratory values representative of rhabdomyolysis, advanced imaging, and compartment pressure measurements. Unfortunately, this diagnosis is late; therefore, risks of significant morbidity increase. The mainstay of treatment is emergent fasciotomy of the paraspinal muscles and medical management of rhabdomyolysis. The majority of patients return to baseline functional strength and full range of motion after early treatment. We present a case of severe bilateral paraspinal compartment syndrome that resulted in excisional debridement of necrotic muscle, acute kidney injury, and ileus.

High Lumbar Spinal Fusion Rates Using Cellular Bone Allograft Irrespective of Surgical Approach.

BACKGROUND: Mounting evidence demonstrates a promising safety and efficacy profile for spinal fusion procedures using cellular bone allograft (CBA). However, limited data exists on fusion outcomes stratified by surgical approach. The current study investigates the effectiveness of CBA in lumbar spinal fusion by surgical approach (ie, anterior, lateral, and posterior approaches). METHODS: Patients undergoing lumbar spinal fusion with CBA (Trinity Elite) were enrolled into a prospective, multi-center, open-label clinical study (NCT02969616). Fusion status was assessed by an independent review of dynamic radiographs and computed tomography images. Clinical outcome measures included quality of life (QoL; EQ5D), disability (Oswestry Disability Index [ODI]), and pain (visual analog scale [VAS]) for back pain and leg pain). Patient data extending to 24 months were analyzed in a post-hoc analysis. RESULTS: A total of 252 patients underwent interbody fusion (159 women; 93 men). Patients had a mean age of 58.3 years (SD 12.5), height of 168.3 cm (SD 10.2), and weight of 87.3 kg (SD 20.0) with a body mass index of 30.8 kg/m2 (SD 6.5). At 12 months, the overall fusion success rate for bridging bone was 98.5%; fusion success was 98.1%, 100.0%, and 97.9% for anterior, lateral, and posterior approaches, respectively. At 24 months, the overall fusion success rate for bridging bone was 98.9%; fusion success was 97.9%, 100.0%, and 98.8% for anterior, lateral, and posterior approaches, respectively. The surgical approach did not significantly impact fusion success. A significant (P < 0.0001) improvement in QoL, pain, and disability scores was also observed. Significant differences in the ODI, VAS, and EQ5D were observed between the treatment groups (P < 0.05). CONCLUSIONS: CBA represents an attractive alternative to autograft alone, reporting a high rate of successful fusion and clinical outcomes across various surgical approaches. CLINICAL RELEVANCE: The use of CBA for spinal fusion procedures, regardless of surgical approach, provides high rates of fusion with a favorable safety profile and improved patient outcomes. TRIAL REGISTRATION: NCT02969616.

Examining the structure of plant-lemur interactions in the face of imperfect knowledge.

Biotic interactions, such as plant-animal seed dispersal mutualisms, are essential for ecosystem function. Such interactions are threatened by the possible extinction of the animal partners. Using a data set that includes plant-lemur interactions across Madagascar, we studied the current state of knowledge of these interactions and their structure to determine which plant species are most at risk of losing dispersal services due to the loss of lemurs. We found substantial gaps in understanding of plant-lemur interactions; data were substantially skewed toward a few lemur species and locations. There was also a large gap in knowledge on the interactions of plants and small-bodied or nocturnal lemurs and lemurs outside a few highly studied locations. Of the recorded interactions, a significant portion occurred between lemurs and endemic plants, rather than native or introduced plants. We also found that lemur species tended to primarily consume closely related plant species. Such interaction patterns may indicate the threats to Malagasy endemic plants and highlight how lemur population loss or reductions could affect plant phylogenetic diversity. When examining the impacts of lemur extinction, losing critically endangered species left 164 plant species with no known lemur frugivore partners. Despite phylogenetic patterns in lemur diet, plants for which the only known lemur frugivore is critically endangered were not closely related. These results emphasize the need for further studies to complete our knowledge on these essential interactions and to inform conservation priorities.

Análisis de la estructura de las interacciones entre lémures y plantas de cara al conocimiento incompleto Resumen Las interacciones bióticas, como el mutualismo entre plantas y animales para la dispersión de semillas, son esenciales para que el ecosistema funcione. Dichas interacciones se encuentran amenazadas por la posible extinción del animal que participa en ellas. Usamos un conjunto de datos que incluye las interacciones entre lémures y plantas en Madagascar para estudiar el estado actual del conocimiento de estas interacciones y su estructura. Con lo anterior determinamos cuáles especies botánicas tienen mayor riesgo de perder la dispersión de semillas debido a la extinción de los lémures. Encontramos vacíos sustanciales en el entendimiento de las interacciones entre lémures y plantas; los datos estaban sesgados para unas cuantas especies de lémures y localidades. Hubo un gran vacío de conocimiento para las interacciones entre las plantas y los lémures pequeños o nocturnos y aquellos fuera de unas cuantas localidades estudiadas. De las interacciones registradas, una porción importante ocurrió entre los lémures y plantas endémicas, en lugar de plantas nativas o introducidas. También encontramos que las especies de lémures tienden a consumir especies botánicas con filogenia cercana. Dichos patrones de interacción podrían indicar las amenazas para las plantas endémicas de Madagascar y enfatizar cómo la pérdida o reducción de las poblaciones de lémures podrían afectar la diversidad filogenética de las plantas. Cuando examinamos el impacto de la extinción de los lémures, la pérdida de especies en peligro crítico dejó a 164 especies de plantas sin un lémur frugívoro mutualista. A pesar de los patrones filogenéticos en la dieta de los lémures, las plantas cuyo único lémur frugívoro se encuentra en peligro crítico no tienen una filogenia cercana. Estos resultados resaltan la necesidad de más estudios para completar nuestro conocimiento sobre estas interacciones esenciales y para guiar las prioridades de conservación.

Equivalence in osteoporosis workup and management after femoral neck fracture fixation and vertebral compression fracture cement augmentation: A single-center retrospective study highlighting persistent Underdiagnosis and Undertreatment.

Background: The purpose of this study was to evaluate pre- and post-fracture medical management of osteoporosis among patients who underwent surgical fixation of femoral neck fractures (FNF) and vertebral compression fractures (VCF), and to investigate if there is a difference in treatment, management, and subsequent fractures between FNF and VCF patients. Methods: Patients who underwent surgical fixation of FNF or VCF were retrospectively reviewed at a minimum 1 year follow up. Patients were excluded if their fracture was caused by high energy trauma or malignancy, <50 years-old, deceased, or lost to follow up. Patient demographics such as age, sex, BMI, American Society of Anesthesiology Physical Status Classification System and Charleston Comorbidity index were recorded. Management of osteoporosis, including medication regimen and dual-energy X-ray absorptiometry (DEXA) scans were assessed preoperatively and at minimum one year follow up. Subsequent fractures were also recorded. Results: In the analysis of 370 patients (74.7% FNF, 25.2% VCF), demographics showed a predominantly female population (mean age 78.1). Preoperatively, 21.6% were diagnosed with osteoporosis, consistent between FNF and VCF. Postoperatively, there were no significant differences in new osteoporosis diagnoses, bisphosphonate use, or subsequent fractures. VCF patients, however, were more likely to receive denosumab and post-operative DEXA scans (p < 0.05). Within a year, 6.2% experienced subsequent fractures, with no significant FNF-VCF difference. Only 12.7% received appropriate post-operative osteoporosis treatment, 27.1% had DEXA scans, and 25% had a recorded osteoporosis diagnosis. Multivariable analysis highlighted pre-fracture osteoporosis diagnosis as the sole predictor for post-operative DEXA scans and anti-osteoporotic medication (p < 0.001). Conclusions: This study suggests that factors beyond the type of fragility fracture may influence subsequent fracture risk and anti-osteoporotic medication administration in elderly patients. These findings underscore the importance of a comprehensive approach to fracture risk assessment and treatment decisions in this population. Level of evidence: III.

Comparison of the penile microbiome in infant male circumcision: Mogen clamp versus Shangring.

BACKGROUND: This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). METHODS: We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. FINDINGS: Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: -15.0%, (SD = 19.1); Mogen clamp Prevotella: -3.6% (11.2); ShangRing Veillonella: -11.3% (17.2); Mogen clamp Veillonella: -2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. INTERPRETATION: Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. FUNDING: Bill and Melinda Gates Foundation.

Format-tuning of in vivo-launched bispecific T cell engager enhances efficacy against renal cell carcinoma.

BACKGROUND: Advanced clear cell renal cell carcinoma (ccRCC) is a prevalent kidney cancer for which long-term survival rates are abysmal, though immunotherapies are showing potential. Not yet clinically vetted are bispecific T cell engagers (BTEs) that activate T cell-mediated cancer killing through intercellular synapsing. Multiple BTE formats exist, however, with limited cross-characterizations to help optimize new drug design. Here, we developed BTEs to treat ccRCC by targeting carbonic anhydrase 9 (CA9) while characterizing the persistent BTE (PBTE) format and comparing it to a new format, the persistent multivalent T cell engager (PMTE). These antibody therapies against ccRCC are developed as both recombinant and synthetic DNA (synDNA) medicines. METHODS: Antibody formatting effects on binding kinetics were assessed by flow cytometry and intercellular synaptic strength assays while potency was tested using T-cell activation and cytotoxicity assays. Mouse models were used to study antibody plasma and tumor pharmacokinetics, as well as antitumor efficacy as both recombinant and synDNA medicines. Specifically, three models using ccRCC cell line xenografts and human donor T cells in immunodeficient mice were used to support this study. RESULTS: Compared with a first-generation BTE, we show that the PBTE reduced avidity, intercellular synaptic strength, cytotoxic potency by as much as 33-fold, and ultimately efficacy against ccRCC tumors in vivo. However, compared with the PBTE, we demonstrate that the PMTE improved cell avidity, restored intercellular synapses, augmented cytotoxic potency by 40-fold, improved tumor distribution pharmacokinetics by 2-fold, and recovered synDNA efficacy in mouse tumor models by 20-fold. All the while, the PMTE displayed a desirable half-life of 4 days in mice compared with the conventional BTE's 2 hours. CONCLUSIONS: With impressive efficacy, the CA9-targeted PMTE is a promising new therapy for advanced ccRCC, which can be effectively delivered through synDNA. The highly potent PMTE format itself is a promising new tool for future applications in the multispecific antibody space.

Pediatric urinary tract infections caused by poultry-associated Escherichia coli.

Escherichia coli is the leading cause of urinary tract infections (UTIs) in children and adults. The gastrointestinal tract is the primary reservoir of uropathogenic E. coli, which can be acquired from a variety of environmental exposures, including retail meat. In the current study, we used a novel statistical-genomic approach to estimate the proportion of pediatric UTIs caused by foodborne zoonotic E. coli strains. E. coli urine isolates were collected from DC residents aged 2 months to 17 years from the Children's National Medical Center Laboratory, 2013-2014. During the same period, E. coli isolates were collected from retail poultry products purchased from 15 sites throughout DC. A total of 52 urine and 56 poultry isolates underwent whole-genome sequencing, core genome phylogenetic analysis, and host-origin prediction by a Bayesian latent class model that incorporated data on the presence of mobile genetic elements (MGEs) among E. coli isolates from multiple vertebrate hosts. A total of 56 multilocus sequence types were identified among the isolates. Five sequence types-ST10, ST38, ST69, ST117, and ST131-were observed among both urine and poultry isolates. Using the Bayesian latent class model, we estimated that 19% (10/52) of the clinical E. coli isolates in our population were foodborne zoonotic strains. These data suggest that a substantial portion of pediatric UTIs in the Washington DC region may be caused by E. coli strains originating in food animals and likely transmitted via contaminated poultry meat.IMPORTANCEEscherichia coli UTIs are a heavy public health burden and can have long-term negative health consequences for pediatric patients. E. coli has an extremely broad host range, including humans, chickens, turkeys, pigs, and cattle. E. coli derived from food animals is a frequent contaminant of retail meat products, but little is known about the risk these strains pose to pediatric populations. Quantifying the proportion of pediatric UTIs caused by food-animal-derived E. coli, characterizing the highest-risk strains, and identifying their primary reservoir species could inform novel intervention strategies to reduce UTI burden in this vulnerable population. Our results suggest that retail poultry meat may be an important vehicle for pediatric exposure to zoonotic E. coli strains capable of causing UTIs. Vaccinating poultry against the highest-risk strains could potentially reduce poultry colonization, poultry meat contamination, and downstream pediatric infections.

Meta-analysis of the efficacy and adverse effects of acalabrutinib in the management of relapsed/refractory chronic lymphocytic leukemia.

The advent of Bruton tyrosine kinase inhibitor (BTKi) therapy with ibrutinib introduced a highly effective targeted therapy in the management of chronic lymphocytic leukemia (CLL). However, due to the adverse effect profile some patients cannot tolerate this novel therapy. Newer, more potent and targeted BTK inhibitors such as acalabrutinib have been developed. Acalabrutinib is an irreversible and second generation BTKi that covalently inhibits BTK with greater selectivity than ibrutinib. As novel BTKis are developed, a greater understanding of their efficacy and adverse effect rates can assist clinicians and patients in the shared clinical decision-making process. A search was conducted using the PICOS model and PRISMA guidelines. PubMeb, Embase, and Cochrane Library databases were searched using the keywords: Acalabrutinib, Acalabrutinib Monotherapy, Tyrosine Kinase Inhibitor, and Relapsed/Refractory (R/R) CLL. After initial literature review 12 studies were chosen for evaluation in this meta-analysis. Meta-analysis and follow up meta-regression models were completed. The results were as follows: ORR 82% (95% CI 74%-90%, I2 = 84.14%, p < 0.01), CR 4% (95% CI 2%-6%, I2 = 0.00%, p = 0.99), mortality rate 12% (95% CI 6%-19%, I2 = 87.23%, p < 0.01), mortality rate due to adverse effect 7% (95% CI 3%-10%, I2 = 67.67%, p = 0.01), mortality due to pneumonia 2% (95% CI 1%-3%, I2 = 0.00%, p = 0.43), mortality due to CLL progression 4% (95% CI 2%-6%, I2 = 61.03%, p = 0.04), neutropenia (≥ grade 3) 18% (95% CI 15%-20%, I2 = 0.00%, p = 0.70), thrombocytopenia (≥ grade 3) 7% (95% CI 4%-11%, I2 = 54%, p = 0.09), anemia (≥ grade 3) 9% (95% CI 6%-12%, I2 = 36.93%, p = 0.18), pneumonia (≥ grade 3) 10% (95% CI 6%-14%, I2 = 66.37%, p = 0.02) and atrial fibrillation 7% (95% CI 3%-11%, I2 = 80.13%, p = 0.00). The results demonstrate that acalabrutinib shows efficacy in the treatment of R/R CLL with tolerable adverse reaction rates.

Impact of surgical risk factors for non-union on lumbar spinal fusion outcomes using cellular bone allograft at 24-months follow-up.

BACKGROUND: The current report investigates fusion rates and patient-reported outcomes following lumbar spinal surgery using cellular bone allograft (CBA) in patients with risk factors for non-union. METHODS: A prospective, open label study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT02969616) to assess fusion success rates and patient-reported outcomes in subjects with risk factors for non-union. Subjects were categorized into low-risk (≤ 1 risk factors) and high-risk (> 1 risk factors) groups. Radiographic fusion status was evaluated by an independent review of dynamic radiographs and CT scans. Patient-reported outcome measures included quality of life (EQ-5D), Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain. Adverse event reporting was conducted throughout 24-months of follow-up. RESULTS: A total of 274 subjects were enrolled: 140 subjects (51.1%) were categorized into the high-risk group (> 1 risk factor) and 134 subjects (48.9%) into the low-risk group (≤ 1 risk factors). The overall mean age at screening was 58.8 years (SD 12.5) with a higher distribution of females (63.1%) than males (36.9%). No statistical difference in fusion rates were observed between the low-risk (90.0%) and high-risk (93.9%) groups (p > 0.05). A statistically significant improvement in patient-reported outcomes (EQ-5D, ODI and VAS) was observed at all time points (p < 0.05) in both low and high-risk groups. The low-risk group showed enhanced improvement at multiple timepoints in EQ-5D, ODI, VAS-Back pain and VAS-Leg pain scores compared to the high-risk group (p < 0.05). The number of AEs were similar among risk groups. CONCLUSIONS: This study demonstrates high fusion rates following lumbar spinal surgery using CBA, regardless of associated risk factors. Patient reported outcomes and fusion rates were not adversely affected by risk factor profiles. TRIAL REGISTRATION: NCT02969616 (21/11/2016).

Glymphatic inhibition exacerbates tau propagation in an Alzheimer's disease model.

BACKGROUND: The aggregation and spread of misfolded amyloid structured proteins, such as tau and α-synuclein, are key pathological features associated with neurodegenerative disorders, including Alzheimer's and Parkinson's disease. These proteins possess a prion-like property, enabling their transmission from cell to cell leading to propagation throughout the central and peripheral nervous systems. While the mechanisms underlying their intracellular spread are still being elucidated, targeting the extracellular space has emerged as a potential therapeutic approach. The glymphatic system, a brain-wide pathway responsible for clearing extracellular metabolic waste from the central nervous system, has gained attention as a promising target for removing these toxic proteins. METHODS: In this study, we investigated the impact of long-term modulation of glymphatic function on tau aggregation and spread by chronically treating a mouse model of tau propagation with a pharmacological inhibitor of AQP4, TGN-020. Thy1-hTau.P301S mice were intracerebrally inoculated with tau into the hippocampus and overlying cortex, and subsequently treated with TGN-020 (3 doses/week, 50 mg/kg TGN-020, i.p.) for 10-weeks. During this time, animal memory was studied using cognitive behavioural tasks, and structural MR images were acquired of the brain in vivo prior to brain extraction for immunohistochemical characterisation. RESULTS: Our findings demonstrate increased tau aggregation in the brain and transhemispheric propagation in the hippocampus following the inhibition of glymphatic clearance. Moreover, disruption of the glymphatic system aggravated recognition memory in tau inoculated mice and exacerbated regional changes in brain volume detected in the model. When initiation of drug treatment was delayed for several weeks post-inoculation, the alterations were attenuated. CONCLUSIONS: These results indicate that by modulating AQP4 function and, consequently, glymphatic clearance, it is possible to modify the propagation and pathological impact of tau in the brain, particularly during the initial stages of the disease. These findings highlight the critical role of the glymphatic system in preserving healthy brain homeostasis and offer valuable insights into the therapeutic implications of targeting this system for managing neurodegenerative diseases characterized by protein aggregation and spread.

A Comparison of 2 Cage Sizes in Biportal Endoscopic Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: This study compared the fusion and subsidence rate and clinical outcomes when using different-sized static PEEK cages in BE-TLIF. SUMMARY OF BACKGROUND DATA: Biportal endoscopic techniques for transforaminal lumbar interbody fusion (BE-TLIF) have been shown to have similar clinical and fusion outcomes with faster clinical recovery in comparison to tubular surgery. Subsidence of the interbody, however, could be a complication. METHODS: Patients who underwent 1 or 2 level BE-TLIF for degenerative and isthmic spondylolisthesis between January 2019 and January 2022 were included. A 32×10 mm cage (group A) and a 40×15 mm cage (group B) were compared. The visual analog scale (VAS) for back and leg symptoms, and Oswestry disability index (ODI) were collected. Plain radiographs and computed tomography assessed fusion and subsidence at a minimum of 12 months. RESULTS: Of the 69 enrolled patients, 39 group A patients (51 levels) and 30 group B patients (32 levels) were compared. The operation time per level was 123 ± 15.8 and 138 ± 10.5 minutes per fusion level in groups A and B, respectively (P < 0.05). ODI improved from 64.8 ± 6.2 to 15.7 ± 7.1 in group A and from 65.3 ± 5.6 to 15.1 ± 6.3 in group B at the final follow-up (P < 0.05). VAS leg and back score improvement between the groups did not differ; however, the 3-month postoperative VAS back improvement was significantly higher in group B. The final fusion rate at the final follow-up did not significantly differ; however, the fusion ratio at 1 year was higher in group B (P < 0.05). Subsidence occurred in 5 cases (9.8%) in group A and none in group B (P < 0.05). CONCLUSION: BE-TLIF using a larger cage can be performed safely with similar patient-reported outcome measures with a faster fusion rate with less subsidence risk. LEVEL OF STUDY: III.

Functional implication of the homotrimeric multidomain vacuolar sorting receptor 1 (VSR1) from Arabidopsis thaliana.

The vacuolar sorting receptors (VSRs) are specific to plants and are responsible for sorting and transporting particular proteins from the trans-Golgi network to the vacuole. This process is critically important for various cellular functions, including storing nutrients during seed development. Despite many years of intense studies on VSRs, a complete relation between function and structure has not yet been revealed. Here, we present the crystal structure of the entire luminal region of glycosylated VSR1 from Arabidopsis thaliana (AtVSR1) for the first time. The structure provides insights into the tertiary and quaternary structures of VSR1, which are composed of an N-terminal protease-associated (PA) domain, a unique central region, and one epidermal growth factor (EGF)-like domain followed by two disordered EGF-like domains. The structure of VSR1 exhibits unique characteristics, the significance of which is yet to be fully understood.

Radiographic Fusion Outcomes for Trinity Cellular Based Allograft versus Local Bone in Posterolateral Lumbar Fusion.

INTRODUCTION: Cellular-based autograft (CBA) is being used in posterolateral lumbar arthrodesis as a fusion supplementation alternative. OBJECTIVE: To assess radiographic fusion in patients undergoing posterolateral lumbar fusion with unilateral Trinity CBA compared with contralateral local bone autograft as an internal control. METHODS: A single surgeon's practice database was interrogated for consecutive patients undergoing primary posterolateral lumbar fusion with Trinity from 2018 to 2021. Patients had Trinity applied unilaterally, with local bone autograft applied contralaterally. Fusion was assessed postoperatively by using CT after 9 months. Demographics and patient-reported outcome measures were collected preoperatively and up to 12 months postoperatively. RESULTS: Thirty-nine patients were included. There were 81 attempted fusion levels. Overall fusion rate, defined as bony bridging on at least one side of a given level for all levels fused, was 85.2% of patients. No statistically significant difference was observed in fusion rates between CBA versus local bone (79.0% versus 76.54% of levels attempted, respectively, P = 0.3527). Oswestry Disability Index improved by 3 months (P = 0.0152) and was maintained. Two patients required revision for symptomatic nonunion. CONCLUSIONS: Similar radiographic fusion rates were achieved with Trinity and local bone. Trinity is a viable alternative to local bone in posterolateral lumbar fusion.

Growing utilization of ambulatory spine surgery in Medicare patients from 2010-2021.

Background: There is growing interest in transitioning various surgical procedures to the outpatient care setting. However, for Medicare patients, the site of service for surgical procedures is influenced by regulations within the Inpatient and Outpatient Prospective Payment Systems. The purpose of this study is to quantify changes in utilization of outpatient spine surgery within the Medicare population, as well as to determine changes in outpatient volume after removal of a procedure from the "inpatient-only" list. Methods: This is a cross-sectional study of Medicare billing database information for selected spine procedures included in the Medicare Physician/Supplier Procedure Summary (PSPS) public use files from 2010-2021. These files include aggregated data from Medicare Part B fee-for-service claims, published yearly. Procedures from Healthcare Common Procedural Coding System (HCPCS) code ranges 22010-22899 and 62380-63103 were selected for analysis, limited to surgical services delivered in the inpatient, hospital outpatient department (HOPD), and ambulatory surgical center (ASC) settings. For each HCPCS code included, estimates of the total number of services and corresponding changes in volume were calculated. Results: Within the range of codes included in the study, the total number of outpatient spine procedures rose approximately 193% from 2010 to 2021, with compound annual growth rate (CAGR) for outpatient procedures per year of 9.9% for HOPDs and 15.7% for ASCs (-2.2% for inpatient procedures). Within this period, the ASC list grew from 12 procedures to 58 procedures. In 2021, the highest volume ASC procedure was HCPCS 63047, at approximately 4970 procedures. Conclusions: This study demonstrates a trend of increasing utilization of HOPDs and ASCs for spine procedures among Medicare beneficiaries from 2010 to 2021. Though HOPDs are currently more widely utilized, the ongoing additions of spine procedures to the ASC covered procedures list may shift this balance.

A Family-Based Study of Inherited Genetic Risk in Lipedema.

Background: Lipedema is a progressive condition involving excessive deposition of subcutaneous adipose tissue, predominantly in the lower limbs, which severely compromises quality of life. Despite the impact of lipedema, its molecular and genetic bases are poorly understood, making diagnosis and treatment difficult. Historical evaluation of individuals with lipedema indicates a positive family history in 60%-80% of cases; however, genetic investigation of larger family cohorts is required. Here, we report the largest family-based sequencing study to date, aimed at identifying genetic changes that contribute to lipedema. Methods and Results: DNA samples from 31 individuals from 9 lipedema families were analyzed to reveal genetic variants predicted to alter protein function, yielding candidate variants in 469 genes. We did not identify any individual genes that contained likely disease-causing variants across all participating families. However, gene ontology analysis highlighted vasopressin receptor activity, microfibril binding, and patched binding as statistically significantly overrepresented categories for the set of candidate variants. Conclusions: Our study suggests that lipedema is not caused by a single exomic genetic factor, providing support for the hypothesis of genetic heterogeneity in the etiology of lipedema. As the largest study of its kind in the lipedema field, the results advance our understanding of the disease and provide a roadmap for future research aimed at improving the lives of those affected by lipedema.

The Effect of Marijuana on Postoperative Spine Patients' Emergency Department Visits, Readmission Rates, and Opioid Consumption.

OBJECTIVE: To compare postoperative opioid consumption with patients who tested negative for tetrahydrocannabinol (THC) preoperatively with those who were THC-positive and patients who were positive for THC and any other drug and to compare 90-day rates of postoperative emergency department (ED) visits and 90-day readmission rates, using morphine milligram equivalents (MMEs), for those three patient populations. METHODS: Three patient groups were confirmed with preoperative urine drug screens. Chart reviews were conducted to determine whether there was an ED visit or hospital readmission 90 days from the index procedure. MMEs were calculated for all patients. RESULTS: There were a total of 252 patients in the THC-negative control group, 54 in the THC-positive group, and 47 in the THC-and-opioid-positive group. The 90-day ED visit and 90-day readmission rates were not statistically significant among the groups. Both the multidrug and THC-only-positive patients showed a higher 90-day MME compared with the control patients. DISCUSSION: Our study demonstrates that THC used may increase opioid consumption. The THC patients to be cautious toward are the multidrug user. Although not statistically significant, multidrug patients were noted for a trend toward increased ED visits and readmissions.