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Outcomes of Radiosurgery for WHO Grade 2 Meningiomas: The Role of Ki-67 Index in Guiding the Tumor Margin Dose

Meng, Ying; Bernstein, Kenneth; Mashiach, Elad; Santhumayor, Brandon; Kannapadi, Nivedha; Gurewitz, Jason; Snuderl, Matija; Pacione, Donato; Sen, Chandra; Donahue, Bernadine; Silverman, Joshua S; Sulman, Erik; Golfinos, John; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:The management of World Health Organization (WHO) grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited but suggests that a higher dose is better for tumor control. We characterize the predictors of post-SRS outcomes that can help guide planning and management. METHODS:We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. RESULTS:Ninety-nine patients (median age 62 years) underwent SRS, 11 of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received previous irradiation. The median follow-up was 49 months. The median overall survival was 119 months (95% CI 92-NA) with estimated 5- and 10-year survival of 83% and 27%, respectively. The median progression-free survival (PFS) was 40 months (95% CI 32-62), with 3- and 5-year rates at 54% and 35%, respectively. The median locomarginal PFS was 63 months (95% CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 Common Terminology Criteria for Adverse Events grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session cohort, Ki-67 significantly predicted both overall survival and intracranial PFS. Tumors with Ki-67 >10% had 2.17 times the risk of locomarginal progression compared with Ki-67 ≤10% (P = .018) adjusting for covariates. Sex, prescription dose, tumor volume, and location also predicted tumor control. In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control but not for tumors with Ki-67 ≤10%. CONCLUSION/CONCLUSIONS:The management of WHO grade 2 meningiomas requires a multimodality approach. This study demonstrates the value of a targeted SRS approach in patients with limited disease and further establishes predictive biomarkers that can guide planning through a personalized approach.
PMID: 39526756
ISSN: 1524-4040
CID: 5752612

Digital Preoperative Huddle Platform Use Leads to Decreased Surgical Cost

Eremiev, Alexander; London, Dennis; Ber, Roee; Kurland, David B; Sheerin, Kathleen; Dennett, Haleigh; Pacione, Donato; Laufer, Ilya
BACKGROUND AND OBJECTIVES/OBJECTIVE:Communication has a well-established effect on improving outcomes. The current study evaluated the effect of multidisciplinary preoperative team communication using a digital huddle software platform on operating room costs. METHODS:A digital huddle software platform was implemented in March 2022 for neurosurgical procedures performed at a single tertiary care center. Surgeons were encouraged, but not required, to participate. General linear models were used to test the association between participation and the difference in supply-related cost and case length, using intergroup comparison and historical controls. RESULTS:A total of 29626 cases (performed by 97 surgeons), conducted between March 2021 and June 2023, were included in our analysis. Cases from participating neurosurgeons (12 surgeons, 4064 cases) were compared with cases from nonparticipating neurosurgeons (6 surgeons, 2452 cases), non-neurosurgery cases carried out by the same operating room staff (20 orthopedic spine surgeons, 6073 cases), and non-neurosurgery cases performed in a different operating room unit (59 surgeons, 21 996 cases). In aggregate, operating room (OR) costs increased by 7.3% (95% CI: 0.9-14.1, P = .025) in the postintervention period. In the same period, participation in the digital huddle platform was associated with an OR utilization and supply-related cost decrease of 16.3% (95% CI: 8.3%-23.6%, P < .001). Among neurosurgeons specifically, participation was associated with a supply-related cost decrease of 17.5% (95% CI: 6.0%-27.5%, P = .0037). There was no change in case length (median case length 171 minutes, change: +2.7% increase, 95% CI:-2.2%-7.9%, P = .28). CONCLUSION/CONCLUSIONS:The implementation of a digital huddle software platform resulted in an OR utilization and supply cost decrease among participants during a period when the overall nonparticipating control cohort experienced an increase in cost.
PMID: 38842337
ISSN: 1524-4040
CID: 5665602

Prognostic value of DNA methylation subclassification, aneuploidy, and CDKN2A/B homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas

Galbraith, Kristyn; Garcia, Mekka; Wei, Siyu; Chen, Anna; Schroff, Chanel; Serrano, Jonathan; Pacione, Donato; Placantonakis, Dimitris G; William, Christopher M; Faustin, Arline; Zagzag, David; Barbaro, Marissa; Eibl, Maria Del Pilar Guillermo Prieto; Shirahata, Mitsuaki; Reuss, David; Tran, Quynh T; Alom, Zahangir; von Deimling, Andreas; Orr, Brent A; Sulman, Erik P; Golfinos, John G; Orringer, Daniel A; Jain, Rajan; Lieberman, Evan; Feng, Yang; Snuderl, Matija
BACKGROUND:Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma. METHODS:We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts. RESULTS:There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534). CONCLUSIONS:The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.
PMCID:11145445
PMID: 38243818
ISSN: 1523-5866
CID: 5664582

Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy

Nasir-Moin, Mustafa; Wadiura, Lisa Irina; Sacalean, Vlad; Juros, Devin; Movahed-Ezazi, Misha; Lock, Emily K; Smith, Andrew; Lee, Matthew; Weiss, Hannah; Müther, Michael; Alber, Daniel; Ratna, Sujay; Fang, Camila; Suero-Molina, Eric; Hellwig, Sönke; Stummer, Walter; Rössler, Karl; Hainfellner, Johannes A; Widhalm, Georg; Kiesel, Barbara; Reichert, David; Mischkulnig, Mario; Jain, Rajan; Straehle, Jakob; Neidert, Nicolas; Schnell, Oliver; Beck, Jürgen; Trautman, Jay; Pastore, Steve; Pacione, Donato; Placantonakis, Dimitris; Oermann, Eric Karl; Golfinos, John G; Hollon, Todd C; Snuderl, Matija; Freudiger, Christian W; Heiland, Dieter Henrik; Orringer, Daniel A
The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.
PMID: 38987630
ISSN: 2157-846x
CID: 5699002

Endoscopic Endonasal Approach for Direct Puncture Embolization of Cavernous Dural Arteriovenous Fistula: 2-Dimensional Operative Video

Sangwon, Karl L; Esparza, Rogelio; Sharashidze, Vera; Dastagirzada, Yosef; Shapiro, Maksim; Riina, Howard A; Lieberman, Seth; Pacione, Donato; Raz, Eytan; Nossek, Erez
PMID: 37831980
ISSN: 2332-4260
CID: 5604252

Percutaneous Juxtapedicular Cement Salvage of Failed Spinal Instrumentation? Institutional Experience and Cadaveric Biomechanical Study

Kurland, David B; Lendhey, Matin; Delavari, Nader; Winfield, Jalen; Mahoney, Jonathan M; Becske, Tibor; Shapiro, Maksim; Raz, Eytan; Pacione, Donato; Bucklen, Brandon S; Frempong-Boadu, Anthony K
BACKGROUND AND OBJECTIVES/OBJECTIVE:Instrumented spinal fusion constructs sometimes fail because of fatigue loading, frequently necessitating open revision surgery. Favorable outcomes after percutaneous juxtapedicular cement salvage (perc-cement salvage) of failing instrumentation have been described; however, this approach is not widely known among spine surgeons , and its biomechanical properties have not been evaluated. We report our institutional experience with perc-cement salvage and investigate the relative biomechanical strength of this technique as compared with 3 other common open revision techniques. METHODS:A retrospective chart review of patients who underwent perc-cement salvage was conducted. Biomechanical characterization of revision techniques was performed in a cadaveric model of critical pedicle screw failure. Three revision cohorts involved removal and replacement of hardware: (1) screw upsizing, (2) vertebroplasty, and (3) fenestrated screw with cement augmentation. These were compared with a cohort with perc-cement salvage performed using a juxtapedicular trajectory with the failed primary screw remaining engaged in the vertebral body. RESULTS:Ten patients underwent perc-cement salvage from 2018 to 2022 to address screw haloing and/or endplate fracture threatening construct integrity. Pain palliation was reported by 8/10 patients. Open revision surgery was required in 4/10 patients, an average of 8.9 months after the salvage procedure (range 6.2-14.7 months). Only one revision was due to progressive hardware dislodgement. The remainder avoided open revision surgery through an average of 1.9 years of follow-up. In the cadaveric study, there were no significant differences in pedicle screw pullout strength among any of the revision cohorts. CONCLUSION/CONCLUSIONS:Perc-cement salvage of failing instrumentation is reasonably efficacious. The technique is biomechanically noninferior to other revision strategies that require open surgery for removal and replacement of hardware. Open revision surgery may be avoided by perc-cement salvage in select cases.
PMID: 37747337
ISSN: 2332-4260
CID: 5613042

Characterizing Hearing Outcomes Following Treatment of Cerebellopontine Angle Meningiomas

Papazian, Michael; Cottrell, Justin; Pan, Lydia; Kay-Rivest, Emily; Friedmann, David R.; Jethanamest, Daniel; Kondziolka, Douglas; Pacione, Donato; Sen, Chandranath; Golfinos, John G.; Roland, J. Thomas; McMenomey, Sean O.
Objectives To characterize treatment and hearing outcomes for cerebellopontine angle (CPA) meningiomas with inherent risks of hearing loss and identify predictors of hearing loss for surgically treated lesions. Design Retrospective chart review. Setting Tertiary care medical center. Participants Adult patients with CPA meningiomas impinging upon cranial nerve VIII and/or pretreatment hearing loss managed with microsurgery or stereotactic radiosurgery (SRS) with Gamma Knife at our center between 2012 and 2023. Main Outcome Measures Hearing preservation rate was determined from analysis of patients with pretreatment serviceable hearing for whom hearing-preserving treatment was attempted. Surgical patients were further analyzed using multivariable Cox proportional hazards regression models to identify factors predictive of postoperative hearing loss. Results We identified 80 patients with CPA meningiomas meeting inclusion criteria who were managed with either microsurgery (43, 54%) or radiosurgery (37, 46%). Following SRS, hearing was preserved in 88% of cases. Following microsurgery, hearing was preserved in 71% of patients-all patients who lost hearing had tumors involving the internal auditory canal (IAC). Among surgical patients only, multivariable analysis accounting for preoperative hearing, recurrence status, lesion size, and patient age, the preoperative imaging finding that the CPA meningioma surrounded the vestibulocochlear nerve was significantly associated with hearing loss (hazard ratio: 10.3, 95% confidence interval: 1.3-81.4, p = 0.02). Conclusion Most patients with meningiomas of the CPA can experience preservation of hearing, even when there is risk of hearing loss based on pretreatment evaluation. IAC invasion and surrounding of eighth nerve by tumor may portend poorer hearing outcomes in surgically managed patients.
SCOPUS:85204132363
ISSN: 2193-6331
CID: 5716162

Risk of intracranial meningioma in patients with acromegaly: a systematic review

Guo, Amy X; Job, Asha; Pacione, Donato; Agrawal, Nidhi
UNLABELLED:Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of insulin-like growth factor 1 (IGF-1) which leads to the insidious onset of clinical manifestations. The most common primary central nervous system (CNS) tumors, meningiomas originate from the arachnoid layer of the meninges and are typically benign and slow-growing. Meningiomas are over twice as common in women as in men, with age-adjusted incidence (per 100,000 individuals) of 10.66 and 4.75, respectively. Several reports describe co-occurrence of meningiomas and acromegaly. We aimed to determine whether patients with acromegaly are at elevated risk for meningioma. Investigation of the literature showed that co-occurrence of a pituitary adenoma and a meningioma is a rare phenomenon, and the majority of cases involve GH-secreting adenomas. To the best of our knowledge, a systematic review examining the association between meningiomas and elevated GH levels (due to GH-secreting adenomas in acromegaly or exposure to exogenous GH) has never been conducted. The nature of the observed coexistence between acromegaly and meningioma -whether it reflects causation or mere co-association -is unclear, as is the pathophysiologic etiology. SYSTEMATIC REVIEW REGISTRATION/UNASSIGNED:https://www.crd.york.ac.uk/prospero/, identifier CRD42022376998.
PMCID:11196394
PMID: 38919490
ISSN: 1664-2392
CID: 5702672

Developing an Automated Registry (Autoregistry) of Spine Surgery Using Natural Language Processing and Health System Scale Databases

Cheung, Alexander T M; Kurland, David B; Neifert, Sean; Mandelberg, Nataniel; Nasir-Moin, Mustafa; Laufer, Ilya; Pacione, Donato; Lau, Darryl; Frempong-Boadu, Anthony K; Kondziolka, Douglas; Golfinos, John G; Oermann, Eric Karl
BACKGROUND AND OBJECTIVES/OBJECTIVE:Clinical registries are critical for modern surgery and underpin outcomes research, device monitoring, and trial development. However, existing approaches to registry construction are labor-intensive, costly, and prone to manual error. Natural language processing techniques combined with electronic health record (EHR) data sets can theoretically automate the construction and maintenance of registries. Our aim was to automate the generation of a spine surgery registry at an academic medical center using regular expression (regex) classifiers developed by neurosurgeons to combine domain expertise with interpretable algorithms. METHODS:We used a Hadoop data lake consisting of all the information generated by an academic medical center. Using this database and structured query language queries, we retrieved every operative note written in the department of neurosurgery since our transition to EHR. Notes were parsed using regex classifiers and compared with a random subset of 100 manually reviewed notes. RESULTS:A total of 31 502 operative cases were downloaded and processed using regex classifiers. The codebase required 5 days of development, 3 weeks of validation, and less than 1 hour for the software to generate the autoregistry. Regex classifiers had an average accuracy of 98.86% at identifying both spinal procedures and the relevant vertebral levels, and it correctly identified the entire list of defined surgical procedures in 89% of patients. We were able to identify patients who required additional operations within 30 days to monitor outcomes and quality metrics. CONCLUSION/CONCLUSIONS:This study demonstrates the feasibility of automatically generating a spine registry using the EHR and an interpretable, customizable natural language processing algorithm which may reduce pitfalls associated with manual registry development and facilitate rapid clinical research.
PMID: 37345933
ISSN: 1524-4040
CID: 5542832

Development and implementation of an Enhanced Recovery After Cranial Surgery pathway following supratentorial tumor resection at a tertiary care center

Khan, Hammad A; Hill, Travis C; Suryadevara, Carter M; Carter, Camiren C; Eremiev, Alexander N; Save, Akshay V; Golfinos, John G; Pacione, Donato
OBJECTIVE:Controlling length of stay (LOS) reduces rates of nosocomial infections and falls, facilitates earlier return to daily activities, and decreases strain on the healthcare system. Complications following supratentorial tumor resection present early in the postoperative period, thereby enhancing the prospect of safe, early discharge. Here, the authors describe their initial experience with the development and implementation of an Enhanced Recovery After Cranial Surgery (ERACS) pathway following resection of supratentorial tumors in select patients. METHODS:This was a nonrandomized, ambispective quality improvement study of patients undergoing elective craniotomy for supratentorial tumor resection at New York University Langone Health between November 17, 2020, and May 19, 2022. Eligible patients were prospectively enrolled in either the ERACS pathway or the standard pathway. These prospective cohorts were compared to a retrospective cohort of patients who met eligibility criteria for the pathway. Patients in the ERACS pathway cohort were targeted for discharge on postoperative day 2. The primary outcome metric was hospital LOS. Secondary outcome metrics included duration of intensive care unit (ICU) care and rates of 30-day emergency department visits, readmissions, and complications. RESULTS:Over the study period, 188 of 317 patients (59.3%) who underwent supratentorial tumor resection met inclusion criteria for ERACS pathway enrollment. Sixty-three patients were enrolled in the ERACS pathway, and 125 patients completed the standard pathway. The historical cohort consisted of 332 patients who would have been eligible for ERACS enrollment. Patients in the ERACS pathway cohort had a median LOS of 1.93 days compared with 2.92 and 2.88 days for patients in the standard pathway and historical cohort, respectively (p < 0.001). There was a significant reduction in ICU utilization in ERACS pathway patients (16.0 ± 6.53 vs 29.5 ± 53.0 vs 21.8 ± 18.2 hours, p = 0.005). There were no differences in the rates of 30-day emergency department visits (12.7% vs 9.6% vs 10.9%, p = 0.809) and readmissions (4.8% vs 4.0% vs 7.8%, p = 0.279) between groups. CONCLUSIONS:Patients in the ERACS pathway cohort experienced reduced LOS and ICU utilization, with similar rates of adverse outcomes compared to standard pathway patients. The authors' initial experience suggests that an accelerated recovery pathway can be safely implemented following supratentorial tumor resection in select patients.
PMID: 38039535
ISSN: 1092-0684
CID: 5590472