Kumar, Rahul

Abstract Cerebrospinal fluid (CSF) is the biofluid most proximal to the central nervous system (CNS), yet its proteomic organization across neurological disease remains unresolved. We assembled a meta-atlas of 35 CSF proteomic datasets (2016–2026) comprising 10,560 quality-controlled samples spanning neurodegenerative, neuroinflammatory, neuro-oncological, infectious and structural-injury contexts. Meta-analysis of cross-cohort detection defined a 747-protein core mass-spectrometry-accessible CSF proteome that generalizes to held-out cohorts. We derived thirteen consensus meta-programs that transfer across independent cohorts and span the major neural, barrier, immune and plasma compartments. Unexpectedly, these programs are dominated by a single axis of variation opposing complement- and plasma-associated inflammation against neuronal-synaptic homeostasis. This injury–homeostasis axis is diagnosis-spanning and tracks clinical severity and disease activity across diverse neurological conditions. We show that a two-protein C5–NRCAM model can approximate the injury–homeostasis axis, bridging deep proteomic profiling toward bedside assessment.

BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) placement is a common treatment for idiopathic normal pressure hydrocephalus (iNPH), but patients may require VPS revision. This study aims to evaluate the effectiveness of a standardized VPS placement protocol by comparing indications and rates of shunt revision compared with a historical institutional cohort. METHODS: All patients treated with VPS for “suspected” iNPH at a tertiary care center between January 2000 and January 2023 were retrospectively reviewed and divided into temporally distinct historical (before 2017) and standardized (after 2017) cohorts. Cumulative incidence and timing of VPS revision were compared using competing risks analyses. RESULTS: A total of 561 patients (median age 75.0 years) were identified with 324 (57.8%) in the historical and 237 (42.2%) in the standardized cohorts. Significant variations in surgical technique and shunt hardware were noted between the cohorts. With a median follow-up of 11.4 months for historical and 12.4 months for standardized cohort, shunt revisions occurred in 19.4% and 8.4% of patients in the historical and standardized cohorts, respectively ( P < .001). Revision indications also varied significantly with lower rates of overdrainage ( P < .001), infection ( P < .001), and proximal malfunction ( P = .042) but higher rate of distal malfunction ( P = .03) in the standardized cohort. Notably, no infections were noted in the standardized cohort. CONCLUSION: Risk of shunt revision among iNPH patients may be associated with modifiable factors related to surgical technique and shunt hardware selection. Importantly, no short-term complications such as hemorrhage, infection, or catheter malposition were observed with the standardized protocol. Development and refinement of standardized shunt protocols for iNPH patients should be commonplace to facilitate tracking, identification, and modification of modifiable technical risk factors.

BACKGROUND AND OBJECTIVES: Anterior lumbar interbody fusion (ALIF) is a powerful procedure for sagittal correction and indirect decompression in the lumbar spine, though aggressive correction can cause stretch neuropraxia and implant subsidence. The aim of this study was to identify radiographic and clinical predictors of segmental correction, as well as to evaluate the degree to which segmental correction on supine intraoperative radiographs translates to postoperative upright alignment changes. METHODS: We identified patients treated with 1- or 2-level ALIF at a tertiary care center and extracted data on demographics, spinopelvic parameters, and surgical details. Patients treated with isolated ALIF and ALIF with supplementary posterior instrumentation were compared on pre- and postoperative intradiscal lordosis (IDL) and change in IDL. Multivariable linear regression was performed to identify independent predictors of postoperative IDL. RESULTS: We included 204 patients (median age 57 years, 55.4% male) treated at 258 levels, of whom 114 (55.9%) underwent supplementary posterior fixation and 150 (73.5%) underwent single-level implantation. Across all patients, postoperative IDL was significantly greater than preoperative segmental lordosis (25.4° vs 15.3°; P < .001). Standalone ALIF achieved less ΔIDL than circumferential fusion for L5/S1 procedures (7.4° vs 11.6°; P < .001), though ΔIDL for L3/4 and L4/5 was similar between the standalone and circumferential groups. Multivariable analysis showed postoperative IDL to be predicted by greater preoperative IDL (β = 0.26° per degree; [0.15, 0.36]; P < .001), L5/S1 [vs L4/5] implantation (β = 3.97°; [2.72, 5.21]; P < .001), use of supplementary posterior fixation (β = 1.80°; [0.70, 2.89]; P < .001), and greater implant lordosis (β = 0.62° per degree; [0.44, 0.79]; P < .001). CONCLUSION: Postoperative IDL after 1- or 2-level ALIF is best predicted by placement of larger interbody sizes, L5/S1 implantation, greater baseline IDL, and use of adjunct posterior fixation. Patients with higher preoperative lordosis experienced smaller postoperative increases in IDL, though this was likely influenced by a treatment bias.

Background For large vessel occlusion (LVO) ischemic strokes, three major techniques of mechanical thrombectomy (MT) have demonstrated efficacy. Here we compare the safety and efficacy of stent retrievers (SR), contact aspiration (Asp), and a combined mechanical thrombectomy (cMT) for LVO ischemic stroke. Methods Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, EMBASE, Scopus, and Web of Science databases for studies published prior to December 2024 describing patients with ischemic stroke who underwent MT using SR, Asp, or cMT. Results Twnety-four studies comprising a total of 12 845 patients were included in the analysis. Compared with cMT, Asp was associated with a lower rate of first pass effect (FPE) (risk ratio (RR) 0.67; 95% CI 0.46 to 0.96), shorter procedure duration (mean difference (MD) −13.35 min; 95% CI −20.83 to –5.87), and lower risk of arterial dissection (RR 0.50; 95% CI 0.29 to 0.87). Additionally, SR use was linked to a higher procedure duration compared with Asp (MD 13.39 min; 95% CI 5.55 to 21.22) and a lower symptomatic intracranial hemorrhage rate (RR 0.75; 95% CI 0.59 to 0.96). No significant differences were observed between groups in terms of number of passes, successful recanalization, 90-day functional outcomes, mortality, arterial perforation, or embolization to new territory. Conclusions All three techniques demonstrated similar recanalization rates and functional outcomes. However, Asp was associated with shorter procedure times and fewer arterial dissection complications, while cMT showed a higher FPE. Given the comparable overall efficacy, the choice of technique should be guided by the physician’s preference, expertise, and confidence, tailored to the individual patient’s profile.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is increasingly used as a primary treatment modality for intracranial meningiomas. We aim to describe clinical outcomes after single-fraction SRS for sporadic intracranial meningiomas. METHODS: A prospectively maintained database was reviewed for patients with sporadic meningiomas who underwent SRS (Gamma Knife) as primary treatment modality from April 1997 to February 2022. Primary outcomes included progression-free survival (PFS) and treatment-related complications. RESULTS: Six hundred sixteen patients (653 tumors) underwent SRS with median follow-up of 6.3 years (interquartile range [IQR] 3.1-10.5 years). The median tumor volume was 4.5 cm 3 (IQR 2.0-8.0 cm 3 ). The median margin dose was 15.0 Gy (IQR 14.0-16.0). In-field progression was noted in 7 tumors (1.1%) and marginal progression in 2 tumors (0.3%) for a raw failure rate of 1.4%. PFS estimates at 5, 10, and 15 years were 99.8%, 99.0%, and 93.2%, respectively. Factors associated with reduced PFS on univariable analysis included older age (hazards ratio [HR] 1.14, 95% CI, 1.05-1.22, P < .001), male sex (HR 5.44, 95% CI, 1.45-20.4, P = .010), increasing tumor volume (HR 1.06, 95% CI, 0.99-1.13, P = .028), and lower tumor margin dose (HR 0.65, 95% CI, 0.43-0.97, P = .006). Treatment-related complications were noted in 56 patients (9.1%), of which 45 (7.3%) were temporary, 5 (0.8%) were minor, and 6 (1.0%) were permanent and/or required intervention. Radiosurgical parameters associated with treatment-related complications included increased number of isocenters (odds ratio [OR] 1.09, 95% CI, 1.04-1.14, P < .001), higher 12-Gy volume (OR 1.06, 95% CI, 1.03-1.09, P < .001), larger tumor volume (OR 1.06, 95% CI, 1.02-1.10, P < .001), and lower maximal dose (OR 0.90, 95% CI, 0.82-0.98, P = .11). CONCLUSION: SRS is effective as a primary treatment modality for sporadic, small-volume to medium-volume intracranial meningiomas. Pre-emptive SRS should be discussed as a safe management strategy compared with observation alone for incidentally discovered meningiomas.

Introduction: Bone health optimization is a key component of the preoperative management of spine surgery patients, as poor bone quality increases the odds of mechanical complications. The present study aimed to achieve the following: (1) compare the relative efficacy of current osteoporosis medications in improving bone quality; (2) identify factors influencing treatment response in preoperative spine surgery patients. Methods: Patients treated at a single, multisite institution who received osteoporosis treatment were identified. Data were gathered on pre- and post-treatment lumbar spine Hounsfield Unit (HU) measurements, patient demographics, frailty scores (modified Frailty Index/mFI, risk analysis index/RAI), and pharmacologic treatment details. The primary outcome was a ≥7 point improvement in lumbar HU, and baseline and logistic regression models were utilized to identify factors associated with this improvement. Medications were grouped as anabolic (teriparatide, romosozumab) and antiresorptive (denosumab, alendronate) therapies. Results: A total of 267 patients were included (median age: 74 years; IQR [66–81]; 67.3% female), with 127 (47.6%) improving by ≥7 HU. The treatment agents used were alendronate (95), denosumab (113), romosozumab (31), and teriparatide (28). Univariable comparisons revealed significant differences across medication groups in age (p < 0.001), sex (p < 0.001), mFI (p < 0.001), RAI (p = 0.004), BMI (p < 0.001), pre-treatment HU (p = 0.022), and treatment duration (p < 0.001). The highest HU improvement rates (ΔHU ≥ 7) were observed in patients receiving the anabolic medications romosozumab (67.7%) and teriparatide (60.7%). Univariable logistic regression identified male sex (OR 0.54, p = 0.019), higher pre-treatment HU (OR 0.99, p = 0.006), and longer treatment duration (OR 0.97, p = 0.003) as factors associated with lower odds of HU improvement. Only romosozumab was associated with significantly higher odds of HU improvement relative to alendronate (OR 3.02, p = 0.012). In our multivariable analysis, male sex (OR 0.53, p = 0.028) and higher pre-treatment HU (OR 0.99, p = 0.002) remained significant predictors of HU improvement. However, medication type was not significant in the multivariable analysis. Conclusions: Our study highlights that male sex and higher pre-treatment HU were independently associated with lower odds of HU improvement, while medication type was not a significant predictor. Additionally, anabolic agents offered superior improvement relative to antiresorptive therapies.

BACKGROUND AND OBJECTIVES: Transforaminal lumbar interbody fusion (TLIF) allows for direct and indirect decompression and segmental lordosis in sagittal plane correction. This study compares the effectiveness of “Bullet” type and “Banana” type devices for sagittal plane correction. METHODS: Patients who underwent 1-level or 2-level TLIF for degenerative pathology at a single tertiary care center were identified. Details were extracted on demographics, interbody dimensions, and preoperative and postoperative lumbopelvic parameters from upright radiographs. Cages were categorized as “Bullet” or “Banana” type based on morphology and manufacturer description of optimal position. Univariable comparisons between levels treated with “Bullet” and “Banana” type interbodies were performed. Multivariable linear regression was performed to identify independent predictors of postoperative segmental lordosis and change in segmental lordosis. RESULTS: One hundred and ninety eight unique patients (median 66.6 years; [IQR 59.5, 73.7]; 56.6% female) were included with 241 levels treated, of which 114 (52.7%) were treated with “Banana” type interbodies and 127 (47.3%) with “Bullet” type. “Banana” type interbodies afforded both greater postoperative segmental lordosis (8.1 [6.2, 10.7] vs 7.5 [5.2, 9.6]; P = .048) and greater increase in segmental lordosis (3.3 [0.7, 7.0] vs 2.3 [0.1, 4.2]; P = .015). On multivariable linear regression, only preoperative segmental lordosis (β = 0.322 per degree; [0.244, 0.399]; P < .001), implant listed lordosis (β = 0.146 per degree; 95% CI [0.048, 0.244]; P = .004), preoperative pelvic incidence (0.072 per degree; [0.034, 0.111]; P < .001), and use of bilateral TLIF windows (β = 3.133; [1.213, 5.053]; P = .001) were predictive of postoperative segmental lordosis. CONCLUSION: The present analysis suggests that baseline lumbopelvic anatomy, interbody lordosis, and the use of bilateral TLIF windows are the most important predictors of postoperative segmental lordosis. Use of “Banana” vs “Bullet” type interbodies was not predictive of segmental lordosis achieved on immediate postoperative upright radiographs. Further work is merited to determine whether the 2 interbody types demonstrate differences regarding subsidence risk or maintenance of correction.

Abstract Purpose: Current methods for glioma response assessment are limited. This study aimed to assess the technical and clinical feasibility of molecular profiling using longitudinal intracranial cerebrospinal fluid (CSF) from patients with gliomas. Experimental Design: Adults with gliomas underwent longitudinal intracranial CSF collection via Ommaya reservoirs or ventriculoperitoneal shunts. Cell-free DNA (cfDNA) was extracted and analyzed using PredicineCARE for cancer variant profiling and/or PredicineSCORE for low-pass whole-genome sequencing. Results: Five patients (two females and three males; median age, 40 years; range, 32–64 years) underwent longitudinal intracranial CSF collection via Ommaya reservoirs (n = 4) or ventriculoperitoneal shunts (n = 1). In total, 47 CSF samples were obtained (median volume, 4.00 mL; 0.5–5 mL). Forty-one samples (87.2%) yielded sufficient cfDNA for testing. Patient-specific tumor-associated variant allelic frequencies (VAF), and thus tumor fraction, decreased in pre- versus postchemoradiation samples, including through pseudoprogression. These also increased with radiographic progression in three patients, although identifying the time of definitive disease progression from MRIs was a significant limitation. In two patients with isocitrate dehydrogenase (IDH)–mutant gliomas, decreasing IDH1 VAF after resection and chemoradiation correlated with decreased CSF D-2-hydroxyglutarate levels (0.64× and 0.62×, respectively, for the first patient and 0.01× and 0.07× for the other patient), although D-2-hydroxyglutarate and IDH1 VAF were not concordant in one patient thereafter. Moreover, the copy-number burden decreased below the limit of quantification during treatment and increased above the limit at progression. Conclusions: Longitudinal intracranial CSF cfDNA can be obtained in patients with gliomas during their disease course. However, before deploying this technique, numerous questions and challenges should be answered.