Psoas Muscle Health is Correlated with Time to Achieve MCID in Patients with Predominant Axial Back Pain Following Decompression Surgery: Early Results.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the impact of psoas muscle health (cross-sectional area, CSA) on achieving minimal clinically important differences (MCID) in patient-reported outcome measures (PROMs) following laminectomy for patients with predominant back pain (PBP) and leg pain (PLP). SUMMARY OF BACKGROUND DATA: Psoas muscle health is linked to postoperative outcomes in decompression patients, with MRI-based grading of psoas CSA correlating with these outcomes. However, evidence on its impact on symptomatic recovery, measured by PROMs, is lacking. METHODS: 106 patients with PBP (VAS back >VAS leg) and 139 patients with PLP (VAS leg >VAS back) who underwent laminectomy from 2017-2021 were included. Axial T2 MRI images were analyzed for psoas CSA using a validated method. Based on the lowest-quartile normalized total psoas area (NTPA) thresholds, patients were divided into "Good" and "Poor" muscle health groups. The correlation analyses were performed between the psoas CSA and changes in PROMs. Kaplan-Meier survival analysis was conducted to determine the probability of achieving MCID as a function of time. RESULTS: Of 106 PBP patients, 83 (78.3%) had good muscle health, 23 (21.6%) had poor muscle health. Of 139 PLP patients, 54 (38.8%) had good muscle health, 85 (61.1%) had poor muscle health. In the PBP group, older age was associated with poor muscle health (69.70±9.26 vs. 59.92±15.01, P=0.0002). For both cohorts, there were no differences in the rate of MCID achievement for any PROMs between the good and poor muscle health groups. In the PBP group, Kaplan-Meier analysis showed patients with good psoas health achieved MCID-VAS back and Oswestry Disability Index (ODI) in median times of 14 and 42 days (P=0.045 and 0.015), respectively. CONCLUSION: Good psoas muscle health is linked to faster attainment of MCID, especially in patients with PBP compared to PLP after decompression surgery. LEVEL OF EVIDENCE: 3.

Impact of Metabolic Syndrome on Early Postoperative Outcomes After Cervical Disk Replacement: A Propensity-matched Analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the demographics, perioperative variables, and complication rates following cervical disk replacement (CDR) among patients with and without metabolic syndrome (MetS). SUMMARY OF BACKGROUND DATA: The prevalence of MetS-involving concurrent obesity, insulin resistance, hypertension, and hyperlipidemia-has increased in the United States over the last 2 decades. Little is known about the impact of MetS on early postoperative outcomes and complications following CDR. METHODS: The 2005-2020 National Surgical Quality Improvement Program was queried for patients who underwent primary 1- or 2-level CDR. Patients with and without MetS were divided into 2 cohorts. MetS was defined, according to other National Surgical Quality Improvement Program studies, as concurrent diabetes mellitus, hypertension requiring medication, and body mass index ≥30 kg/m2. Rates of 30-day readmission, reoperation, complications, length of hospital stay, and discharge disposition were compared using χ2 and Fisher exact tests. One to 2 propensity-matching was performed, matching for demographics, comorbidities, and number of operative levels. RESULTS: A total of 5395 patients were included for unmatched analysis. Two hundred thirty-six had MetS, and 5159 did not. The MetS cohort had greater rates of 30-day readmission (2.5% vs. 0.9%; P=0.023), morbidity (2.5% vs. 0.9%; P=0.032), nonhome discharges (3% vs. 0.6%; P=0.002), and longer hospital stays (1.35±4.04 vs. 1±1.48 days; P=0.029). After propensity-matching, 699 patients were included. All differences reported above lost significance (P>0.05) except for 30-day morbidity (superficial wound infections), which remained higher for the MetS cohort (2.5% vs. 0.4%, P=0.02). CONCLUSIONS: We identified MetS as an independent predictor of 30-day morbidity in the form of superficial wound infections following single-level CDR. Although MetS patients experienced greater rates of 30-day readmission, nonhome discharge, and longer lengths of stay, MetS did not independently predict these outcomes after controlling for baseline differences in patient characteristics. LEVEL OF EVIDENCE: Level III.

Early changes in tumor-naive cell-free methylomes and fragmentomes predict outcomes in pembrolizumab-treated solid tumors.

Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab, but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify a cancer-specific methylation (CSM) and fragment length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab.

The Impact of Posterior Intervertebral Osteophytes on Patient-Reported Outcome Measures After L5-S1 Anterior Lumbar Interbody Fusion and Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: (1) To develop a reliable grading system to assess the severity of posterior intervertebral osteophytes and (2) to investigate the impact of posterior intervertebral osteophytes on clinical outcomes after L5-S1 decompression and fusion through anterior lumbar interbody fusion (ALIF) and minimally-invasive transforaminal lumbar interbody fusion (MIS-TLIF). BACKGROUND: There is limited evidence regarding the clinical implications of posterior lumbar vertebral body osteophytes for ALIF and MIS-TLIF surgeries and there are no established grading systems that define the severity of these posterior lumbar intervertebral osteophytes. PATIENTS AND METHODS: A retrospective analysis of patients undergoing L5-S1 ALIF or MIS-TLIF was performed. Preoperative and postoperative patient-reported outcome measures of the Oswestry Disability Index (ODI) and leg Visual Analog Scale (VAS) at 2-week, 6-week, 12-week, and 6-month follow-up time points were assessed. Minimal clinically important difference (MCID) for ODI of 14.9 and VAS leg of 2.8 were utilized. Osteophyte grade was based on the ratio of osteophyte length to foraminal width. "High-grade" osteophytes were defined as a maximal osteophyte length >50% of the total foraminal width. RESULTS: A total of 70 consecutive patients (32 ALIF and 38 MIS-TLIF) were included in the study. There were no significant differences between the two cohorts in patient-reported outcome measures or achievement of MCID for Leg VAS or ODI preoperatively or at any follow-ups. On multivariate analysis, neither the surgical approach nor the presence of high-grade foraminal osteophytes was associated with leg VAS or ODI scores at any follow-up time point. In addition, neither the surgical approach nor the presence of high-grade foraminal osteophytes was associated with the achievement of MCID for leg VAS or ODI at 6 months. CONCLUSION: ALIF and MIS-TLIF are both valid options for treating degenerative spine conditions and lumbar radiculopathy, even in the presence of high-grade osteophytes that significantly occupy the intervertebral foramen. LEVEL OF EVIDENCE: 3.

Early Cancer Detection in Li-Fraumeni Syndrome with Cell-Free DNA.

People with Li-Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face a near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multimodal liquid biopsy assay that integrates a targeted gene panel, shallow whole-genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 LFS patients. Multimodal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis and was able to detect cancer-associated signal(s) in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%). Although adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with LFS. SIGNIFICANCE: By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients. See related commentary by Latham et al., p. 23. This article is featured in Selected Articles from This Issue, p. 5.

Direct Experimental Observations of Ion Distributions during Overcharging at the Muscovite-Water Interface by Adsorption of Rb+ and Halides (Cl- , Br- , I- ) at High Salinity.

The front cover artwork is provided by Argonne National Laboratory. The image shows the arrangement of correlated cations and anions at a charged solid surface in contact with highly concentrated electrolyte solutions. Read the full text of the Research Article at 10.1002/cphc.202300545.

Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation.

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, ‶spiral transformation″, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

Severe Obesity Is an Independent Risk Factor of Early Readmission and Nonhome Discharge After Cervical Disc Replacement.

OBJECTIVE: Despite growing interest in cervical disc replacement (CDR) for conditions such as cervical radiculopathy, limited data exists describing the impact of obesity on early postoperative outcomes and complications. These data are especially important as nearly half of the adult population in the United States is expected to become obese (body mass index [BMI] ≥ 30 kg/m2) by 2030. The goal of this study was to compare the demographics, perioperative variables, and complication rates following CDR. METHODS: The 2005-2020 American College of Surgeons National Surgical Quality Improvement Program datasets were queried for patients who underwent primary 1- or 2-level CDR. Patients were divided into 3 cohorts: Nonobese (BMI: 18.5-29.9 kg/m2), Obese class-I (BMI: 30-34.9 kg/m2), Obese class-II/III (BMI ≥ 35 kg/m2). Morbidity was defined as the presence of any complication within 30 days postoperatively. Rates of 30-day readmission, reoperation, morbidity, individual complications, length of stay, frequency of nonhome discharge disposition were collected. RESULTS: A total of 5,397 patients were included for analysis: 3,130 were nonobese, 1,348 were obese class I, and 919 were obese class II/III. There were more 2-level CDRs performed in the class II/III cohort compared to the nonobese group (25.7% vs. 21.5%, respectively; p < 0.05). Class-II/III had more nonhome discharges than class I and nonobese (2.1% vs. 0.5% vs. 0.7%, respectively; p < 0.001). Readmission rates differed as well (nonobese: 0.5%, class I: 1.1%, class II/III: 2.1%; p < 0.001) with pairwise significance between class II/II and nonobese. Class II/III obesity was an independent risk factor for both readmission (odds ratio [OR], 3.32; p = 0.002) and nonhome discharge (OR, 2.51; p = 0.02). Neither 30-day reoperation nor morbidity rates demonstrated significance. No mortalities were reported. CONCLUSION: Although obese class-II/III were risk factors for 30-day readmission and nonhome discharge, there was no significant difference in reoperation rates or morbidity. CDR procedures can continue to be safely preformed independent of obesity status.

Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.

Direct Experimental Observations of Ion Distributions during Overcharging at the Muscovite-Water Interface by Adsorption of Rb+ and Halides (Cl- , Br- , I- ) at High Salinity.

Classical electric double layer (EDL) models have been widely used to describe ion distributions at charged solid-water interfaces in dilute electrolytes. However, the chemistry of EDLs remains poorly constrained at high ionic strength where ion-ion correlations control non-classical behavior such as overcharging, i. e., the accumulation of counter-ions in amounts exceeding the substrate's surface charge. Here, we provide direct experimental observations of correlated cation and anion distributions adsorbed at the muscovite (001)-aqueous electrolyte interface as a function of dissolved RbBr concentration ([RbBr]=0.01-5.8 M) using resonant anomalous X-ray reflectivity. Our results show alternating cation-anion layers in the EDL when [RbBr]≳100 mM, whose spatial extension (i. e., ~20 Šfrom the surface) far exceeds the dimension of the classical Stern layer. Comparison to RbCl and RbI electrolytes indicates that these behaviors are sensitive to the choice of co-ion. This new in-depth molecular-scale understanding of the EDL structure during transition from classical to non-classical regimes supports the development of realistic EDL models for technologies operating at high salinity such as water purification applications or modern electrochemical storage.

Direct-print three-dimensional electrodes for large- scale, high-density, and customizable neural inter- faces.

Silicon-based planar microelectronics is a powerful tool for scalably recording and modulating neural activity at high spatiotemporal resolution, but it remains challenging to target neural structures in three dimensions (3D). We present a method for directly fabricating 3D arrays of tissue-penetrating microelectrodes onto silicon microelectronics. Leveraging a high-resolution 3D printing technology based on 2-photon polymerization and scalable microfabrication processes, we fabricated arrays of 6,600 microelectrodes 10-130 µm tall and at 35-µm pitch onto a planar silicon-based microelectrode array. The process enables customizable electrode shape, height and positioning for precise targeting of neuron populations distributed in 3D. As a proof of concept, we addressed the challenge of specifically targeting retinal ganglion cell (RGC) somas when interfacing with the retina. The array was customized for insertion into the retina and recording from somas while avoiding the axon layer. We verified locations of the microelectrodes with confocal microscopy and recorded high-resolution spontaneous RGC activity at cellular resolution. This revealed strong somatic and dendritic components with little axon contribution, unlike recordings with planar microelectrode arrays. The technology could be a versatile solution for interfacing silicon microelectronics with neural structures and modulating neural activity at large scale with single-cell resolution.

MEDIPIPE: an automated and comprehensive pipeline for cfMeDIP-seq data quality control and analysis.

SUMMARY: Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) has emerged as a promising liquid biopsy technology to detect cancers and monitor treatments. While several bioinformatics tools for DNA methylation analysis have been adapted for cfMeDIP-seq data, an end-to-end pipeline and quality control framework specifically for this data type is still lacking. Here, we present the MEDIPIPE, which provides a one-stop solution for cfMeDIP-seq data quality control, methylation quantification, and sample aggregation. The major advantages of MEDIPIPE are: (i) ease of implementation and reproducibility with Snakemake containerized execution environments that will be automatically deployed via Conda; (ii) flexibility to handle different experimental settings with a single configuration file; and (iii) computationally efficiency for large-scale cfMeDIP-seq profiling data analysis and aggregation. AVAILABILITY AND IMPLEMENTATION: This pipeline is an open-source software under the MIT license and it is freely available at https://github.com/pughlab/MEDIPIPE.

A CMOS-based highly scalable flexible neural electrode interface.

Perception, thoughts, and actions are encoded by the coordinated activity of large neuronal populations spread over large areas. However, existing electrophysiological devices are limited by their scalability in capturing this cortex-wide activity. Here, we developed an electrode connector based on an ultra-conformable thin-film electrode array that self-assembles onto silicon microelectrode arrays enabling multithousand channel counts at a millimeter scale. The interconnects are formed using microfabricated electrode pads suspended by thin support arms, termed Flex2Chip. Capillary-assisted assembly drives the pads to deform toward the chip surface, and van der Waals forces maintain this deformation, establishing Ohmic contact. Flex2Chip arrays successfully measured extracellular action potentials ex vivo and resolved micrometer scale seizure propagation trajectories in epileptic mice. We find that seizure dynamics in absence epilepsy in the Scn8a+/- model do not have constant propagation trajectories.

Postoperative Radiculitis After L5-S1 Anterior Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective chart review. OBJECTIVE: This study aimed to examine postoperative radiculitis after isolated L5-S1 anterior lumbar interbody fusion (ALIF), determine which factors contribute to its development, and investigate the comparative outcomes of patients with versus without postoperative radiculitis. SUMMARY OF BACKGROUND DATA: Both standalone and traditionalALIF are common and safe lumbar spine fusion techniques. Although optimal safety and effectiveness are achieved through appropriate patient selection, postoperative radiculitis after L5-S1 ALIF is a potential complication that seems to be the least predictable in the absence of iatrogenic injury. PATIENTS AND METHODS: All adult patients (18-80 yr) with preoperative radiculopathies who underwent L5-S1 ALIF by 9 board-certified spine surgeons at a single academic institution from January 2016 to December 2021 with a minimum of 3 months follow-up were included. Patient records were assessed for data on clinical characteristics and patient-reported outcome scores (patient-reported outcome measures). All patient records were evaluated to determine whether postoperative radiculitis developed. Radiographic measurements using x-rays were completed using all available pre and postoperative imaging. Multivariable logistic regressions were performed utilizing radiculitis as the dependent variable and various independent predictor variables. RESULTS: One hundred forty patients were included, 48 (34%) patients developed postoperative radiculitis, with symptom onset and resolution occurring at 14.5 and 83 days, respectively. The two groups had no differences in preoperative or postoperative radiographic parameters. Multivariable regression showed 3 independent predictors of postoperative radiculitis: methylprednisolone use [OR: 6.032; (95% CI: 1.670-25.568)], increased implant height [OR: 1.509; (95% CI: 1.189-1.960)], and no posterior fixation [OR: 2.973; (95% CI: 1.353-0.806)]. CONCLUSIONS: Of the 34% of patients who developed postoperative radiculitis after L5-S1 ALIF, it resolved on average within 3 months of surgery. These findings may help reduce the risk of undue short-term morbidity after isolated L5-S1 ALIF by informing preoperative counseling and intraoperative decision-making.

Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.

BACKGROUND: The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients. METHODS: In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated. RESULTS: The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup "SHH_3" (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively). CONCLUSIONS: LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.

Endoscopic ultrasound-directed transgastric ERCP (EDGE): A multicenter US study on long-term follow-up and fistula closure.

Background and study aims Endoscopic ultrasound-directed transgastric ERCP (EDGE) is a safe and efficacious procedure to treat pancreaticobiliary diseases in Roux-en-Y gastric bypass (RYGB). This multicenter study aimed to determine the long-term outcomes of EDGE focusing on fistula persistence rates and post-procedure weight change. Patients and methods Information about patients with Roux-en-Y gastric bypass anatomy who underwent EDGE between 2015 and 2021 from 10 institutions was captured in a registry. Patient demographics, procedural details, and clinical outcomes were analyzed. Results One hundred seventy-two patients were included in the study (mean age 60, 25 % male). Technical success of lumen-apposing metal stent (LAMS) placement was 171 of 172 (99.4 %) while clinical success of intervention was 95%. The mean procedure time was 65 minutes. The most commonly reported complication was stent dislodgement/migration (n = 29, 17). Mean length of time of LAMS duration was 69 days. Mean follow-up time was 6 months. Endoscopic fistula closure was performed in 40 % of patients (69/172) at the time of LAMS removal. Persistence of fistula was observed in 19 of 62 patients (31 %) assessed. Length of LAMS indwell time (days) was a predictor of persistent fistula. The average weight gain while the LAMS was in place was 12 lb in 63 patients (36.6 %); 59.4 % of patients gained < 5 lb. Conclusions EDGE is a safe and efficacious procedure for RYGB patients requiring ERCP. Post-procedure evaluation and management of the enteral fistula varies widely among centers currently and would benefit from further standardization. Fistula persistence appears to be uncommon and can be managed endoscopically but may be related to length of indwell times of the LAMS.

Poor muscle health and low preoperative ODI are independent predictors for slower achievement of MCID after minimally invasive decompression.

BACKGROUND CONTEXT: Although some previous studies have analyzed predictors of nonimprovement, most of these have focused on demographic and clinical variables and have not accounted for radiological predictors. In addition, while several studies have examined the degree of improvement after decompression, there is less data on the rate of improvement. PURPOSE: To identify the risk factors and predictors (both radiological and nonradiological) for slower as well as nonachievement of minimal clinically important difference (MCID) after minimally invasive decompression. DESIGN: Retrospective cohort. PATIENT SAMPLE: Patients who underwent minimally invasive decompression for degenerative lumbar spine conditions and had a minimum of 1-year follow up were included. Patients with preoperative Oswestry Disability Index (ODI) <20 were excluded. OUTCOME MEASURE: MCID achievement in ODI (cut off 12.8). METHODS: Patients were stratified into two groups (achieved MCID, did not achieve MCID) at two timepoints (early ≤3 months, late ≥6 months). Nonradiological (age, gender, BMI, comorbidities, anxiety, depression, number of levels operated, preoperative ODI, preoperative back pain) and radiological (MRI - Schizas grading for stenosis, dural sac cross-sectional area, Pfirrmann grading for disc degeneration, psoas cross-sectional area and Goutallier grading, facet cyst/effusion; X-ray - spondylolisthesis, lumbar lordosis, spinopelvic parameters) variables were assessed with comparative analysis to identify risk factors and with multiple regression models to identify predictors for slower achievement of MCID (MCID not achieved by ≤3 months) and nonachievement of MCID (MCID not achieved at ≥6 months). RESULTS: A total of 338 patients were included. At ≤3 months, patients who did not achieve MCID had significantly lower preoperative ODI (40.1 vs 48.1, p<0.001) and worse psoas Goutallier grading (p=.048). At ≥6 months, patients who did not achieve MCID had significantly lower preoperative ODI (38 vs 47.5, p<.001), higher age (68 vs 63 years, p=.007), worse average L1-S1 Pfirrmann grading (3.5 vs 3.2, p=.035), and higher rate of pre-existing spondylolisthesis at the operated level (p=.047). When these and other probable risk factors were put into a regression model, low preoperative ODI (p=.002) and poor Goutallier grading (p=.042) at the early timepoint and low preoperative ODI (p<.001) at the late timepoint came out as independent predictors for MCID nonachievement. CONCLUSION: After minimally invasive decompression, low preoperative ODI and poor muscle health are risk factors and predictors for slower achievement of MCID. For nonachievement of MCID, low preoperative ODI, higher age, greater disc degeneration, and spondylolisthesis are risk factors and low preoperative ODI is the only independent predictor.

Integrated, Longitudinal Analysis of Cell-free DNA in Uveal Melanoma.

Uveal melanomas are rare tumors arising from melanocytes that reside in the eye. Despite surgical or radiation treatment, approximately 50% of patients with uveal melanoma will progress to metastatic disease, most often to the liver. Cell-free DNA (cfDNA) sequencing is a promising technology due to the minimally invasive sample collection and ability to infer multiple aspects of tumor response. We analyzed 46 serial cfDNA samples from 11 patients with uveal melanoma over a 1-year period following enucleation or brachytherapy (n = ∼4/patient) using targeted panel, shallow whole genome, and cell-free methylated DNA immunoprecipitation sequencing. We found detection of relapse was highly variable using independent analyses (P = 0.06-0.46), whereas a logistic regression model integrating all cfDNA profiles significantly improved relapse detection (P = 0.02), with greatest power derived from fragmentomic profiles. This work provides support for the use of integrated analyses to improve the sensitivity of circulating tumor DNA detection using multi-modal cfDNA sequencing. Significance: Here, we demonstrate integrated, longitudinal cfDNA sequencing using multi-omic approaches is more effective than unimodal analysis. This approach supports the use of frequent blood testing using comprehensive genomic, fragmentomic, and epigenomic techniques.

On-Demand, Reversible, Ultrasensitive Polymer Membrane Based on Molecular Imprinting Polymer.

The development of in vivo, longitudinal, real-time monitoring devices is an essential step toward continuous, precision health monitoring. Molecularly imprinted polymers (MIPs) are popular sensor capture agents that are more robust than antibodies and have been used for sensors, drug delivery, affinity separations, assays, and solid-phase extraction. However, MIP sensors are typically limited to one-time use due to their high binding affinity (>107 M-1) and slow-release kinetics (<10-4 µM/sec). To overcome this challenge, current research has focused on stimuli-responsive MIPs (SR-MIPs), which undergo a conformational change induced by external stimuli to reverse molecular binding, requiring additional chemicals or outside stimuli. Here, we demonstrate fully reversible MIP sensors based on electrostatic repulsion. Once the target analyte is bound within a thin film MIP on an electrode, a small electrical potential successfully releases the bound molecules, enabling repeated, accurate measurements. We demonstrate an electrostatically refreshed dopamine sensor with a 760 pM limit of detection, linear response profile, and accuracy even after 30 sensing-release cycles. These sensors could repeatedly detect <1 nM dopamine released from PC-12 cells in vitro, demonstrating they can longitudinally measure low concentrations in complex biological environments without clogging. Our work provides a simple and effective strategy for enhancing the use of MIPs-based biosensors for all charged molecules in continuous, real-time health monitoring and other sensing applications.