Multiplicative effect of frailty and obesity on postoperative mortality following spine surgery: a deep dive into the frailty, obesity, and Clavien-Dindo dynamic.

BACKGROUND/OBJECTIVES: Obesity is a global health challenge that affects a large proportion of adults worldwide. Obesity and frailty pose considerable health risks due to their potential to interact and amplify one another's negative effects. Therefore, we sought to compare the discriminatory thresholds of the risk analysis index (RAI), 5-factor modified frailty index (m-FI-5) and patient age for the primary endpoint of postoperative mortality. SUBJECTS/METHODS: We included spine surgery patients ≥18 years old, from the American College of Surgeons National Quality Improvement program database from 2012-2020, that were classified as obese. We performed receiver operating characteristic curve analysis to compare the discrimination threshold of RAI, mFI-5, and patient age for postoperative mortality. Proportional hazards risk-adjusted regressions were performed, and Hazard ratios and corresponding 95% Confidence intervals (CI) are reported. RESULTS: Overall, there were 149 163 patients evaluated, and in the ROC analysis for postoperative mortality, RAI showed superior discrimination C-statistic 0.793 (95%CI: 0.773-0.813), compared to mFI-5 C-statistic 0.671 (95%CI 0.650-0.691), and patient age C-statistic 0.686 (95%CI 0.666-0.707). Risk-adjusted analyses were performed, and the RAI had a stepwise increasing effect size across frailty strata: typical patients HR 2.55 (95%CI 2.03-3.19), frail patients HR 3.48 (95%CI 2.49-4.86), and very frail patients HR 4.90 (95%CI 2.87-8.37). We found increasing postoperative mortality effect sizes within Clavein-Dindo complication strata, consistent across obesity categories, exponentially increasing with frailty, and multiplicatively enhanced within CD, frailty and obesity strata. CONCLUSION: In this study of 149 163 patients classified as obese and undergoing spine procedures in an international prospective surgical database, the RAI demonstrated superior discrimination compared to the mFI-5 and patient age in predicting postoperative mortality risk. The deleterious effects of frailty and obesity were synergistic as their combined effect predicted worse outcomes.

Catastrophic delayed cervical arthroplasty failure: illustrative case.

BACKGROUND: Cervical disc replacement (CDR) is an increasingly used alternative to fusion for symptomatic cervical disc disease. While more studies have suggested favorability of CDR over fusion procedures, limited data exist regarding implant fatigability. Here, the authors present a unique and previously unreported failure of the M6-C prosthesis causing spinal cord injury. OBSERVATIONS: A 49-year-old female with history of cervical degenerative disease and prior C4-7 M6-C arthroplasty presented 9 years later after a minor fall from standing. She endorsed bilateral hand numbness ascending to forearms and shoulders, with dysesthesias and weakness. Imaging showed fractured arthroplasty penetrating the spinal cord. Revision surgery found a ruptured arthroplasty annulus with metal piece piercing the spinal cord. Partial C4 and C5 corpectomy was performed to remove the integrated fins of the arthroplasty and inspect the cord and dura. This was reconstructed with a corpectomy cage and plate. The patient made an excellent recovery, with improvement in her weakness and resolution of her sensory symptoms. LESSONS: Possibility of fatigue-related failures presenting years after implantation have only been infrequently reported but can be catastrophic for patients. The authors encourage further discussions in this area, increased counseling with patients, and recommend a patient registry to better document adverse events.

Frailty Status Is a More Robust Predictor Than Age of Spinal Tumor Surgery Outcomes: A NSQIP Analysis of 4,662 Patients.

OBJECTIVE: The present study aimed to evaluate the effect of baseline frailty status (as measured by modified frailty index-5 [mFI-5]) versus age on postoperative outcomes of patients undergoing surgery for spinal tumors using data from a large national registry. METHODS: The National Surgical Quality Improvement Program database was used to collect spinal tumor resection patients' data from 2015 to 2019 (n = 4,662). Univariate and multivariate analyses for age and mFI-5 were performed for the following outcomes: 30-day mortality, major complications, unplanned reoperation, unplanned readmission, hospital length of stay (LOS), and discharge to a nonhome destination. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative performance of age versus mFI-5. RESULTS: Both univariate and multivariate analyses demonstrated that mFI-5 was a more robust predictor of worse postoperative outcomes as compared to age. Furthermore, based on categorical analysis of frailty tiers, increasing frailty was significantly associated with increased risk of adverse outcomes. 'Severely frail' patients were found to have the highest risk, with odds ratio 16.4 (95% confidence interval [CI],11.21-35.44) for 30-day mortality, 3.02 (95% CI, 1.97-4.56) for major complications, and 2.94 (95% CI, 2.32-4.21) for LOS. In ROC curve analysis, mFI-5 score (area under the curve [AUC] = 0.743) achieved superior discrimination compared to age (AUC = 0.594) for mortality. CONCLUSION: Increasing frailty, as measured by mFI-5, is a more robust predictor as compared to age, for poor postoperative outcomes in spinal tumor surgery patients. The mFI-5 may be clinically used for preoperative risk stratification of spinal tumor patients.

Delineation of a 1.65 Mb critical region for hemihyperplasia and digital anomalies on Xq25.

Duplications involving portions of the long arm of the X-chromosome can be associated with mental retardation, short stature, microcephaly, panhypopituitarism, and a wide range of physical findings. Less common are duplications in distal Xq associated with hemihyperplasia and digital anomalies. We report on a 4-year-old female with hemihyperplasia, syndactyly of fingers and toes, bilateral 5th finger clinodactyly, short stature, developmental delay, and microcephaly associated with an 11.2 Mb duplication of Xq25-Xq27.1. The boundaries of this duplication were mapped using high resolution array comparative genome hybridization and follow-up studies revealed that the same duplication was carried by the patient's mother who has short stature and cognitive disabilities. Using the duplication boundaries from this case, and data from previously published reports, we have delineated a 1.65 Mb critical region for hemihyperplasia and digital anomalies on chromosome Xq25. Based on these findings physicians should consider obtaining array comparative genome hybridization studies on individuals with hemihyperplasia especially when accompanied by digital findings since identification of an Xq25 duplication can dramatically change recurrence risk estimations and may also provide insight into the possible comorbidities.

Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C.

We present four patients, in whom we identified overlapping deletions in 5q14.3 involving MEF2C using a clinical oligonucleotide array comparative genomic hybridization (CGH) chromosomal microarray analysis (CMA). In case 1, CMA revealed an approximately 140 kb deletion encompassing the first three exons of MEF2C in a 3-year-old patient with severe psychomotor retardation, periodic tremor, and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features. MRI of the brain showed mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes. In case 2, an approximately 1.8 Mb deletion of TMEM161B and MEF2C was found in a child with severe developmental delay, hypotonia, and seizures. Patient 3 had epilepsy, hypotonia, thinning of the corpus callosum, and developmental delay associated with a de novo approximately 2.4 Mb deletion in 5q14.3 including MEF2C and five other genes. In case 4, a de novo approximately 5.7 Mb deletion of MEF2C and five other genes was found in a child with truncal hypotonia, intractable seizures, profound developmental delay, and shortening of the corpus callosum on brain MRI. These deletions further support that haploinsufficiency of MEF2C is responsible for severe mental retardation, seizures, and hypotonia. Our results, in combination with previous reports, imply that exon-targeted oligo array CGH, which is more efficient in identifying exonic copy number variants, should improve the detection of clinically significant deletions and duplications over arrays with probes spaced evenly throughout the genome.

ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts.

BACKGROUND: Temozolomide (TMZ) is active against glioblastomas (GBM) in which the O6-methylguanine-DNA methyltransferase (MGMT) gene is silenced. However, even in responsive cases, its beneficial effect is undermined by the emergence of drug resistance. Here, we tested whether inhibition of poly (ADP-ribose) polymerase-1 and -2 (PARP) enhanced the effectiveness of TMZ. METHODS: Using patient derived brain tumor initiating cells (BTICs) and orthotopic xenografts as models of newly diagnosed and recurrent high-grade glioma, we assessed the effects of TMZ, ABT-888, and the combination of TMZ and ABT-888 on the viability of BTICs and survival of tumor-bearing mice. We also studied DNA damage repair, checkpoint protein phosphorylation, and DNA replication in mismatch repair (MMR) deficient cells treated with TMZ and TMZ plus ABT-888. RESULTS: Cells and xenografts derived from newly diagnosed MGMT methylated high-grade gliomas were sensitive to TMZ while those derived from unmethylated and recurrent gliomas were typically resistant. ABT-888 had no effect on the viability of BTICs or tumor bearing mice, but co-treatment with TMZ restored sensitivity in resistant cells and xenografts from newly diagnosed unmethylated gliomas and recurrent gliomas with MSH6 mutations. In contrast, the addition of ABT-888 to TMZ had little sensitizing effect on cells and xenografts derived from newly diagnosed methylated gliomas. In a model of acquired TMZ resistance mediated by loss of MMR gene MSH6, re-sensitization to TMZ by ABT-888 was accompanied by persistent DNA strand breaks, re-engagement of checkpoint kinase signaling, and interruption of DNA synthesis. CONCLUSION: In laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ.

Minimally Invasive Treatment of Spine Trauma.

The role for minimally invasive surgery (MIS) continues to expand in the management of spinal pathology. In the setting of trauma, operative techniques that can minimize morbidity without compromising clinical efficacy have significant value. MIS techniques are associated with decreased intraoperative blood loss, operative time, and morbidity, while providing patients with comparable outcomes when compared with conventional open procedures. MIS interventions further enable earlier mobilization, decreased hospital stay, decreased pain, and an earlier return to baseline function when compared with traditional techniques. This article reviews patient selection and select MIS techniques for those who have suffered traumatic spinal injury.

Educational Resources "Over the Head" of Neurosurgical Patients: The Economic Impact of Inadequate Health Literacy.

BACKGROUND: Health literacy is the ability with which individuals can obtain, understand, and apply basic health information. Approximately 36% of Americans have basic or below basic health literacy skills. This low health literacy is particularly prevalent in neurosurgery, a growing field of medicine with considerable complexity and a patient population commonly affected with disease-related cognitive impairment. Consequences of poor patient understanding range from increased emergency department admissions rates to reduced adherence to preoperative medication instructions. Economic implications include increasing health care expenditures, decreasing access to health care, and decreasing quality of care. Health literacy costs the United States $106-236 billion per year. METHODS: Consequences of inadequate patient understanding vary widely. This article reviews and addresses the economic impact of the failure to address low health literacy in neurosurgery. RESULTS: Various groups have proposed techniques and devised outlines to improve health literacy, such as detailing principles targeting the underlying issues of health care illiteracy. The government, through legislation including the Affordable Care Act and the National Action Plan to Improve Health Literacy, has also shown its desire to remedy the effects of insufficient health literacy. CONCLUSIONS: Despite current efforts, further action is still needed. Health literacy is a key determinant in ensuring longevity and quality of life.

Extracellular matrices, artificial neural scaffolds and the promise of neural regeneration.

Over last 20 years, extracellular matrices have been shown to be useful in promoting tissue regeneration. Recently, they have been used and have had success in achieving neurogenesis. Recent developments in extracellular matrix design have allowed their successful in vivo incorporation to engender an environment favorable for neural regeneration in animal models. Promising treatments under investigation include manipulation of the intrinsic extracellular matrix and incorporation of engineered naometer-sized scaffolds through which inhibition of molecules serving as barriers to neuroregeneration and delivery of neurotrophic factors and/or cells for successful tissue regeneration can be achieved. Further understanding of the changes incurred within the extracellular matrix following central nervous system injury will undoubtedly help design a clinically efficacious extracellular matrix scaffold that can mitigate or reverse neural degeneration in the clinical setting.