Clinical Predictors of Overall Survival in Very Elderly Patients With Glioblastoma: A National Cancer Database Multivariable Analysis.

BACKGROUND AND OBJECTIVES: Surgery for the very elderly is a progressively important paradigm as life expectancy continues to rise. Patients with glioblastoma multiforme often undergo surgery, radiotherapy (RT), and chemotherapy (CT) to prolong overall survival (OS). However, the efficacy of these treatment modalities in patients aged 80 years and older has yet to be fully assessed in the literature. METHODS: The National Cancer Database was used to retrospectively identify patients aged 65 years and older with glioblastoma multiforme (1989-2016). All available patient demographic characteristics, disease characteristics, and clinical outcomes were collected. To study OS, bivariable survival models were created using Kaplan-Meier estimates. A Cox proportional-hazards model was used for final adjusted analyses. RESULTS: A total of 578 very elderly patients (aged 80 years and older) and 2836 elderly patients (aged 65-79 years) were identified. Compared with elderly patients, very elderly patients were more likely to have Medicare (odds ratio [OR] 1.899 [95% CI: 1.417-2.544], P < .001) while less likely to have private insurance status (OR 0.544 [95% CI: 0.401-0.739], P < .001). In addition, very elderly patients were more likely to travel the least distance for treatment and have multiple tumors (P < .001). When controlling for demographic and disease characteristics, very elderly patients were less likely to receive gross total resection (GTR) (OR 0.822 [95% CI: 0.681-0.991], P < .041), RT (OR 0.385 [95% CI: 0.319-0.466], P < .001), or postoperative CT (OR 0.298 [95% CI: 0.219-0.359], P < .001) relative to elderly counterparts. Within very elderly patients, GTR, RT, and CT all independently and significantly predicted improved OS (P < .001 for all). These predictive models were deployed in an online calculator (https://spine.shinyapps.io/GBM_elderly). CONCLUSION: Very elderly patients are less likely to receive GTR, RT, or CT when compared with elderly counterparts despite use of these therapies conferring improved OS. Selected very elderly patients may benefit from more aggressive attempts at surgical and adjuvant treatment.

Fractionated radiotherapy after gross-total resection of spinal chordoma: a systematic review of survival outcomes using individualized patient data.

OBJECTIVE: Spinal chordoma treatment guidelines recommend resection. However, in patients in whom gross-total resection (GTR) is achieved, the benefits of radiation therapy (RT) are unclear. Therefore, the authors performed a systematic review to determine if RT is associated with postoperative progression-free survival (PFS) or overall survival (OS) after achieving GTR of spinal chordoma. METHODS: The PubMed database was searched for studies including individualized data of patients undergoing GTR with or without RT for spinal chordoma. Patients < 18 years of age or those who underwent stereotactic body RT were excluded. Qualitative assessment was performed using Newcastle-Ottawa Scale guidelines. Log-rank tests for time-to-event data and a Cox proportional-hazards model were generated for a multivariable statistical model. RESULTS: Complete data of 132 patients were retrieved, with 37 (28%) patients receiving adjuvant RT and 95 (72%) not receiving adjuvant RT. The mean follow-up was not statistically significantly different between those undergoing RT and not undergoing RT (54.02 months and 65.43 months, respectively). Patients were more likely not to undergo RT if their disease was located in the sacrum versus the mobile spine (p < 0.001). When controlling for age ≥ 65 years, male sex, disease location, and treatment year ≥ 2010, patients undergoing RT had similar PFS and OS when compared with those not undergoing RT on multivariable survival analysis (HR 0.935 [95% CI 0.703-2.340], p = 0.844 and HR 2.078 [95% CI 0.848-5.090], p = 0.110, respectively). However, age ≥ 65 years was associated with poorer OS in adjusted analyses (HR 2.761 [95% CI 1.185-6.432], p = 0.018) relative to patients < 65 years of age. CONCLUSIONS: After achieving GTR of spinal chordoma, the utility of RT on PFS and OS remains unclear. Age ≥ 65 years appears to be associated with OS in spinal chordoma patients. Additional multicenter prospective studies are needed to determine the utility of RT in this patient population.

Synthesis of 6H-Chromeno[4,3-b]quinolin-7-ylphosphonates through Three Component Phosphonylation of Coumarin Carbaldehyde and Their Antimicrobial and Photophysical Properties.

Organophosphorylated coumarin derivatives were synthesized by a three-component reaction of 4-chloro-3-formylcoumarin, aromatic amines, and dialkyl phosphite in the presence of ZnCl2. This process includes the formation of C(sp3)-P and C(sp2)-N bonds in one pot. The modular scope of the reaction allowed rapid access to a variety of 6H-chromeno[4,3-b]quinolin-7-ylphosphonate derivatives in good yields. Furthermore, photophysical studies of the products revealed their stimulating fluorescence properties.

Exploring the impact of primary care utilization and health information exchange upon treatment patterns and clinical outcomes of glioblastoma patients.

PURPOSE: There is limited literature describing care coordination for patients with glioblastoma (GBM). We aimed to investigate the impact of primary care and electronic health information exchange (HIE) between neurosurgeons, oncologists, and primary care providers (PCP) on GBM treatment patterns, postoperative outcomes, and survival. METHODS: We identified adult GBM patients undergoing primary resection at our institution (2007-2020). HIE was defined as shared electronic medical information between PCPs, oncologists, and neurosurgeons. Multivariate logistic regression analyses were used to determine the effect of PCPs and HIE upon initiation and completion of adjuvant therapy. Kaplan-Meier and multivariate Cox regression models were used to evaluate overall survival (OS). RESULTS: Among 374 patients (mean age ± SD: 57.7 ± 13.5, 39.0% female), 81.0% had a PCP and 62.4% had electronic HIE. In multivariate analyses, having a PCP was associated with initiation (OR: 7.9, P < 0.001) and completion (OR: 4.4, P < 0.001) of 6 weeks of concomitant chemoradiation, as well as initiation (OR: 4.0, P < 0.001) and completion (OR: 3.0, P = 0.007) of 6 cycles of maintenance temozolomide thereafter. Having a PCP (median OS [95%CI]: 14.6[13.1-16.1] vs. 10.8[8.2-13.3] months, P = 0.005) and HIE (15.40[12.82-17.98] vs. 13.80[12.51-15.09] months, P = 0.029) were associated with improved OS relative to counterparts in Kaplan-Meier analysis and in multivariate Cox regression analysis (hazard ratio [HR] = 0.7, [95% CI] 0.5-1.0, P = 0.048). In multivariate analyses, chemoradiation (HR = 0.34, [95% CI] 0.2-0.7, P = 0.002) and maintenance temozolomide (HR = 0.5, 95%CI 0.3-0.8, P = 0.002) were associated with improved OS relative to counterparts. CONCLUSION: Effective care coordination between neurosurgeons, oncologists, and PCPs may offer a modifiable avenue to improve GBM outcomes.

Availability and utilization of molecular testing for primary central nervous system tumors among US hospitals.

Advanced molecular testing has increasingly become an integral component for accurate diagnosis of central nervous system (CNS) tumors. We sought to establish the current state of molecular testing availability and approaches for the diagnosis of CNS tumors in US hospitals that conduct high volumes of CNS tumor resections. We distributed a 16-item survey inquiring about molecular testing approaches for CNS tumors to 115 neuropathologists at US hospitals with neurosurgery residency programs. Thirty-five neuropathologists (30.4%) responded to the survey, all of whom indicated their institutions perform molecular testing on CNS tumor tissue. The most commonly offered tests were MGMT methylation profiling and next-generation sequencing. Fourteen respondents (40%) indicated that their institution is able to test for and report all of the molecular alterations included in our survey. Nine (25.7%) respondents indicated that molecular testing is performed as standard of care for all patients with resected CNS tumors. Our results suggest that even in academic hospitals with a high volume of CNS tumor resections, molecular testing for these tumors is limited. Continued initiatives are necessary to expand the availability of molecular testing for CNS tumors to ensure diagnostic accuracy and guide targeted therapy.

Clinical and socioeconomic predictors of shunt malfunction in the pediatric emergency department.

OBJECTIVE: The aim of this study was to delineate the clinical and socioeconomic variables associated with shunt revision in pediatric patients presenting to the emergency department (ED) with concerns of ventricular shunt malfunction. METHODS: A retrospective analysis of pediatric ED consultations for shunt malfunction over a 1-year period was conducted, examining clinical symptoms, radiographic findings, and socioeconomic variables. Sensitivities, specificities, and positive and negative predictive values were calculated for each presenting symptom collected. Logistic regression models were used to estimate the odds ratios for shunt revision based on these variables, and multivariate analyses were used to adjust for potential confounders. RESULTS: Of the 271 ED visits from 137 patients, 19.2% resulted in shunt revision. Increased ventricle size on imaging (OR 11.38, p < 0.001), shunt site swelling (OR 9.04, p = 0.01), bradycardia (OR 7.08, p < 0.001), and lethargy (OR 5.77, p < 0.001) were significantly associated with shunt revision. Seizure-like activity was inversely related to revision needs (OR 0.24, p < 0.001). Patients with private or self-pay insurance were more likely to undergo revision compared with those with public insurance (p = 0.028). Multivariate analysis further confirmed the significant associations of increased ventricle size, lethargy, and bradycardia with shunt revision, while also revealing that seizure-like activity inversely affected the likelihood of revision. Patients with severe cognitive and language disabilities were more likely to be admitted to the hospital from the ED but were not more likely to undergo revision. CONCLUSIONS: Clinical signs such as increased ventricle size, shunt site swelling, bradycardia, and lethargy may be strong predictors of the need for shunt revision in pediatric patients presenting to the ED with concerns of shunt malfunction. Socioeconomic factors play a less clear role in predicting shunt revision and admission from the ED; however, the nature of their influence is unclear. These findings can help inform clinical decision-making and optimize resource utilization in the ED.

The Socioeconomic Distressed Communities Index Predicts 90-Day Mortality Among Intracranial Tumor Patients.

BACKGROUND: Socioeconomic status (SES) is a major determinant of quality of life and outcomes. However, SES remains difficult to measure comprehensively. Distress communities index (DCI), a composite of 7 socioeconomic factors, has been increasingly recognized for its correlation with poor outcomes. As a result, the objective of the present study is to determine the predictive value of the DCI on outcomes following intracranial tumor surgery. METHODS: A single institution, retrospective review was conducted to identify adult intracranial tumor patients undergoing resection (2016-2021). Patient ZIP codes were matched to DCI and stratified by DCI quartiles (low:0-24.9, low-intermediate:25-49.9, intermediate-high:50-74.9, high:75-100). Univariate followed by multivariate regressions assessed the effects of DCI on postoperative outcomes. Receiver operating curves were generated for significant outcomes. RESULTS: A total of 2389 patients were included: 1015 patients (42.5%) resided in low distress communities, 689 (28.8%) in low-intermediate distress communities, 445 (18.6%) in intermediate-high distress communities, and 240 (10.0%) in high distress communities. On multivariate analysis, risk of fracture (adjusted odds ratio = 1.60, 95% confidence interval 1.26-2.05, P < 0.001) and 90-day mortality (adjusted odds ratio = 1.58, 95% confidence interval 1.21-2.06, P < 0.001) increased with increasing DCI quartile. Good predictive accuracy was observed for both models, with receiver operating curves of 0.746 (95% CI 0.720-0.766) for fracture and 0.743 (95% CI 0.714-0.772) for 90-day mortality. CONCLUSIONS: Intracranial tumor patients from distressed communities are at increased risk for adverse events and death in the postoperative period. DCI may be a useful, holistic measure of SES that can help risk stratifying patients and should be considered when building healthcare pathways.

The hospital frailty risk score independently predicts postoperative outcomes in meningioma patients.

OBJECTIVE: The Hospital Frailty Risk Score (HFRS) is a recently developed tool that uses ICD-10 codes to measure patient frailty. However, the effectiveness of HFRS has not yet been assessed in meningioma patients specifically. The present study aimed to evaluate the effectiveness of HFRS in predicting surgical outcomes for patients with meningiomas. METHODS: This retrospective study utilized data from patients undergoing meningioma resection at a single institution (2017-2019). Data were obtained through a combination of automated data retrieval and manual chart review. Bivariate logistic regression was used to assess the prognostic ability of several frailty indices for predicting postoperative outcomes. Further, discrimination for each model was assessed using the area under the receiver operating characteristic curve (AUROC). Generalized linear models with gamma error distributions and a log-link function were used to model hospital length of stay (LOS), total charges, complications, and disposition. RESULTS: A total of 464 meningioma patients (mean age 58.20 years, 72.8 % female, 66.4 % white) were included. HFRS had a significantly greater AUROC when compared to ASA (p = 0.0074) for postoperative complications, and HFRS significantly outperformed ASA (p = 0.0021) and mFI-5 (p = 0.018) when predicting nonroutine discharge. On multivariate analysis, increasing HFRS scores were significantly and independently associated with greater LOS (p < 0.0001), higher hospital charges (p < 0.0001), higher odds of postoperative complications (OR = 1.05, p = 0.019), and nonroutine discharge (OR = 1.12, p < 0.0001). The HFRS was non-inferior compared to the mFI-5, CCI, ASA and mFI-11 in terms of model discrimination. CONCLUSION: HFRS effectively predicts postoperative outcomes for meningiomas and outperforms other indices in predicting complications and nonroutine discharge. This novel index may be used to improve clinical decision-making and reduce adverse postoperative outcomes among meningioma patients.

Preoperative patient-reported physical health-related quality of life predicts short-term postoperative outcomes in brain tumor patients.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly used to assess patients' perioperative health. The PROM Information System 29 (PROMIS-29) is a well-validated global health assessment instrument for patient physical health, though its utility in cranial neurosurgery is unclear. OBJECTIVE: To investigate the utility of preoperative PROMIS-29 physical health (PH) summary scores in predicting postoperative outcomes in brain tumor patients. METHODS: Adult brain tumor patients undergoing resection at a single institution (January 2018-December 2021) were identified and prospectively received PROMIS-29 surveys during pre-operative visits. PH summary scores were constructed and optimum prediction thresholds for length of stay (LOS), discharge disposition (DD), and 30-day readmission were approximated by finding the Youden index of the associated receiver operating characteristic curves. Bivariate analyses were used to study the distribution of low (z-score≤-1) versus high (z-score>-1) PH scores according to baseline characteristics. Logistic regression models quantified the association between preoperative PH summary scores and post-operative outcomes. RESULTS: A total of 157 brain tumor patients were identified (mean age 55.4±15.4 years; 58.0% female; mean PH score 45.5+10.5). Outcomes included prolonged LOS (24.8%), non-routine discharge disposition (37.6%), and 30-day readmission (19.1%). On bivariate analysis, patients with low PH scores were significantly more likely to be diagnosed with a high-grade tumor (69.6% vs 38.85%, p=0.010) and less likely to have elective surgery (34.8% vs 70.9%, p=0.002). Low PH score was associated with prolonged LOS (26.1% vs 22%, p<0.001), nonroutine discharge (73.9% vs 31.3%, p<0.001) and 30-day readmission (43.5% vs 14.9%, p=0.003). In multivariate analysis, low PH scores predicted greater LOS (odds ratio [OR]=6.09, p=0.003), nonroutine discharge (OR=4.25, p=0.020), and 30-day readmission (OR=3.93, p=0.020). CONCLUSION: The PROMIS-29 PH summary score predicts short-term postoperative outcomes in brain tumor patients and may be incorporated into prospective clinical workflows.

The Hospital Frailty Risk Score Independently Predicts Postoperative Outcomes in Glioblastoma Patients.

OBJECTIVE: The Hospital Frailty Risk Score (HFRS) is a tool for quantifying patient frailty using International Classification of Diseases, Tenth Revision codes. This study aimed to determine the utility of the HFRS in predicting surgical outcomes after resection of glioblastoma (GBM) and compare its prognostic ability with other validated indices such as American Society of Anesthesiologists score and Charlson Comorbidity Index. METHODS: A retrospective analysis was conducted using a GBM patient database (2017-2019) at a single institution. HFRS was calculated using International Classification of Diseases, Tenth Revision codes. Bivariate logistic regression was used to model prognostic ability of each frailty index, and model discrimination was assessed using area under the receiver operating characteristic curve. Multivariate linear and logistic regression models were used to assess for significant associations between HFRS and continuous and binary postoperative outcomes, respectively. RESULTS: The study included 263 patients with GBM. The HFRS had a significantly greater area under the receiver operating characteristic curve compared with American Society of Anesthesiologists score (P = 0.016) and Charlson Comorbidity Index (P = 0.037) for predicting 30-day readmission. On multivariate analysis, the HFRS was significantly and independently associated with hospital length of stay (P = 0.0038), nonroutine discharge (P = 0.018), and 30-day readmission (P = 0.0051). CONCLUSIONS: The HFRS has utility in predicting postoperative outcomes for patients with GBM and more effectively predicts 30-day readmission than other frailty indices. The HFRS may be used as a tool for optimizing clinical decision making to reduce adverse postoperative outcomes in patients with GBM.

Practical photocatalytic and sonophotocatalytic reduction of nitroarenes in water under blue LED irradiation using ß-CD modified TiO2 as a green nest photocatalyst.

Photocatalysis using natural photosynthesis is a green technology that is gaining popularity in a number of industries due to its potential for environmental applications and the use of solar energy. Focus is being placed on using inexpensive materials and light-emitting diodes (LEDs) of various wavelengths in photocatalytic reactions in order to improve the performance of solar-driven photocatalysts at a lower cost. In this study, a scalable, highly efficient photocatalytic and sonophotocatalytic method was investigated for the reduction of nitro-compounds by a water/titania/ß-cyclodextrin system under sunlight and blue LED irradiation, using sodium sulfide as a sacrificial electron donor. ß-Cyclodextrin, chemically bound to TiO2 nanoparticles as an encapsulating agent, hosted nitro compounds in aqueous media and formed an inclusion complex. In addition, this method was used to successfully carry out one-pot reduction-amidation of nitroarene compounds in the presence of acetic anhydride. Interestingly, it was found that ultrasound has a synergistic effect on photocatalytic reduction and considerably reduces the duration time. In this regard, a fast, practical sonophotocatalytic reduction of nitroarenes was carried out in an ultrasound bath.

ZnCl2-mediated stereo- and chemoselective synthesis of vinylphosphonates.

A highly chemo- and stereoselective synthesis of diethyl (E)-2-(alkylidene)-2-phosphonoacetonitriles via the Knoevenagel condensation reaction of carbonyl compounds with diethyl cyanomethylphosphonate in the presence of zinc chloride has been achieved. By the presented method, various E-isomers of arylmethylidene phosphonates rather than Horner-Wadsworth-Emmons olefination products were obtained in good to excellent yields. Their E configurations were determined by X-ray diffraction and NMR analyses. In addition, DFT calculations provided insights into the chemo- and stereoselectivity of the reaction.

Clinical Presentation of Foramen Magnum Meningioma Masqueraded by Carpal Tunnel Syndrome: A Report of 2 Cases.

CASE: Meningioma is the second most common intracranial tumor. We present 2 cases of foramen magnum meningioma (FMM) that was first operated on with the diagnosis of carpal tunnel syndrome (CTS). CONCLUSION: During the diagnostic assessment of CTS and recalcitrant CTS, a more proximal etiology of nerve compression should be considered, including FMM. If a more proximal cause of nerve dysfunction is suspected, cervical spine magnetic resonance imaging may be beneficial to evaluate a patient for spinal etiology.

The effect of fractionated gamma knife radiosurgery on visual acuity in patients with optic nerve tumor.

BACKGROUND: Stereotactic radiosurgery (SRS) method has been considered the first-line treatment option to treat patients involved with pre-optic nerve tumors. However, studies have shown that using fractionated SRS, normal tissue sparing and tumor dose can be strongly increased simultaneously. Our main goal was to illustrate the effects of fractionated SRS approach in optic nerve tumor treatment and its adjacent sensitive structures. MATERIALS AND METHODS: 19 patients involved in optic nerve tumor with clinical symptoms of vision loss were treated with Gamma Knife radiosurgery in three sessions with 12 hours intervals between them. The prescribed dose was about 6.0 ± 1.2 Gy. Patient-related parameters including pre-treatment and after-treatment tumor size, visual acuity and visual field were evaluated using the Snell chart and MRI imaging. Patients were followed for about 14 months. RESULT: The overall result showed vision improvement for patients with low and moderate visual loss. However, there was no significant improvement in patients with severe visual loss. Relative improvement was observed in blind patients, although poorly. There was no evidence of growth, recurrence, or new tumor after treatment in patients. CONCLUSION: Fractionated gamma knife radiosurgery offers a safe and effective alternative for benign lesions adjacent to the optic nerve.

Synthesis, characterization, and in vitro evaluation of the starch-based α-amylase responsive hydrogels.

Controlled-release drug delivery systems are promising platforms in medicine. Among various types of material in drug delivery, hydrogels are interesting ones. They are water-soluble and tissue compatible polymers with a high capacity to carry and release drugs in a controllable manner. In this study, we introduce the synthesis, characterization, and application of an α-amylase responsive hydrogel in controlled drug delivery. The newly synthesized starch-based hydrogels structurally characterized by means of Fourier-transform infrared spectroscopy and scanning electron microscopy. A proapoptotic drug, doxorubicin, was loaded into the hydrogels and the controlled release of the drug was assessed in the presence of α-amylase and ultimately it was evaluated to controlled-drug release in vitro and subsequently in killing cancer cells. Our results highlight the effectiveness of temporal drug delivery using α-amylase responsive hydrogels in killing cancer cells.

Electrochemical Synthesis of Sulfinate Esters: Nickel(II)-Catalyzed Oxidative Esterification of Thiols with Alcohols in an Undivided Cell.

In this study, nickel-catalyzed electrochemical oxidative esterification of thiols with alcohols for the synthesis of sulfinate esters has been reported. The electrochemical oxidative esterification proceeded through a nickel-catalyzed oxidation of thiols using an undivided cell of graphite/nickel electrodes, where the nickel oxidation was studied by cyclic voltammetry. The method was conveniently and directly used for the one-pot synthesis of sulfinate esters of thiols.

Chemoselective photocatalytic oxidation of alcohols to aldehydes and ketones by nitromethane on titanium dioxide under violet 400 nm LED light irradiation.

In this study, for the first time, nitroalkanes, especially nitromethane, have been used as electron acceptors for the highly chemoselective oxidation of alcohols in the presence of a TiO2 photocatalyst under 400 nm LED irradiation. The reactions showed excellent selectivity for the production of aldehydes. Interestingly, aldehydes such as benzaldehyde and p-methoxybenzaldehyde are stable under the reaction conditions. In the case of the use of 2-nitropropane and 2-methyl-2-nitropropane, the product imine, which is the result of the reaction of the aldehyde with aliphatic amine, is also obtained.

Spinal Cord Tethering, a Very Rare Cause of Cauda Equina Syndrome after Lumbar Disk Surgery: A Case Report.

Tethered cord syndrome (TCS) may rarely remain asymptomatic until degenerative or nondegenerative lumbar diseases superimpose in adulthood and expose the hidden anomaly. In such cases, different treatment options can be selected and simultaneous detethering might be considered too. We are reporting an undiscovered TCS in a young lady who underwent lumbar diskectomy due to symptomatic disk extrusion and suffered complete cauda equina syndrome (CES), postoperatively.