Matching-adjusted indirect comparisons of axicabtagene ciloleucel to mosunetuzumab for the treatment of relapsed/refractory follicular lymphoma.

BACKGROUND: Axicabtagene ciloleucel (axi-cel) was the first chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL) patients, while mosunetuzumab was the first bispecific monoclonal antibody approved in this population. In the absence of head-to-head evidence, this study sought to conduct a matching-adjusted indirect comparison (MAIC) to estimate the comparative efficacy and safety of these treatments in 3rd line or higher (3L+) FL. METHODS: The evidence base consisted of individual patient data (IPD) of all enrolled patients, regardless of infusion status, from the single-arm axi-cel trial, ZUMA-5 (NCT03105336), and aggregate data from the mosunetuzumab FL trial (NCT02500407) from publications identified through a systematic review. Efficacy outcomes were progression-free survival (PFS), duration of response (DoR), objective response rate (ORR), complete response rate (CRR). Analyses used independent central review for both trials, where possible. Safety outcomes were cytokine release syndrome (CRS), neurological events (NE), and treatment-related adverse events (TRAEs). Unanchored MAICs were conducted to align ZUMA-5 to the patient characteristics of the mosunetuzumab trial. For each outcome, prognostic factors were identified a priori through quantitative analysis and clinical experts. For time-to-event outcomes, hazard ratios (HRs) were estimated using Cox regression using IPD from ZUMA-5 and pseudo-IPD extracted from Kaplan-Meier plots for mosunetuzumab. RESULTS: Patient characteristics were well-aligned between trials leading to large effective-sample sizes after matching, ranging from 93.4 to 115.5, for ZUMA-5 (n=127). In comparisons to mosunetuzumab (n=90), axi-cel was associated with improved PFS (HR: 0.39; 95% confidence interval [CI]: 0.24-0.62) and DoR (HR: 0.45; 95% CI: 0.27-0.76). Similarly, axi-cel led to higher ORR (OR: 3.87; 95% CI: 1.53-9.76) and CRR (OR: 2.80; 95% CI: 1.50-5.26). Although axi-cel was associated with a higher rate of all-grade CRS (OR: 5.54; 95% CI: 2.63-8.94) and NEs (OR: 3.54; 95% CI: 1.28-9.83), differences in grade ≥3 CRS and TRAEs were not statistically significant. CONCLUSIONS: Findings from this study show improved efficacy and more durable response for the treatment of 3L+ R/R FL with axi-cel relative to mosunetuzumab, with increased odds of all-grade CRS and NE, but not G3+ CRS and TRAEs.

A Comparison of 3-Year Follow-up of ZUMA-5 (Axicabtagene Ciloleucel) With SCHOLAR-5 in Relapsed/Refractory Follicular Lymphoma.

In the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory follicular lymphoma patients. SCHOLAR-5 is an external control cohort designed to act as a comparator to ZUMA-5. Here, we present an updated comparative analysis of ZUMA-5 and SCHOLAR-5, using the 36-month follow-up data and the intent-to-treat population of ZUMA-5. Using propensity-score methods, 127 patients in ZUMA-5 were compared to 129 patients in SCHOLAR-5. At this extended follow-up, axi-cel continues to demonstrate clinically meaningful benefits in survival compared to historically available treatments in this population.

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5).

ABSTRACT: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.

A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed/refractory follicular lymphoma.

BACKGROUND: In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data. RESEARCH DESIGN AND METHODS: The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response rate was compared using a weighted logistic regression. Time-to-event outcomes were evaluated using a Cox regression. RESULTS: For SCHOLAR-5, the sum of weights for the 143 patients was 85 after SMR weighting, versus 86 patients in ZUMA-5. The median follow-up was 29.4 months and 25.4 months for ZUMA-5 and SCHOLAR-5, respectively. The hazard ratios for overall survival and progression-free survival were 0.52 (95% confidence interval (CI): 0.28-0.95) and 0.28 (95% CI: 0.17-0.45), favoring axi-cel. CONCLUSION: This updated analysis, using a longer minimum follow-up than a previously published analysis, shows that the improved efficacy of axi-cel, relative to available therapies, in r/r FL is durable. .

Determinants of resistance to engineered T cell therapies targeting CD19 in large B cell lymphomas.

Most relapsed/refractory large B cell lymphoma (r/rLBCL) patients receiving anti-CD19 chimeric antigen receptor (CAR19) T cells relapse. To characterize determinants of resistance, we profiled over 700 longitudinal specimens from two independent cohorts (n = 65 and n = 73) of r/rLBCL patients treated with axicabtagene ciloleucel. A method for simultaneous profiling of circulating tumor DNA (ctDNA), cell-free CAR19 (cfCAR19) retroviral fragments, and cell-free T cell receptor rearrangements (cfTCR) enabled integration of tumor and both engineered and non-engineered T cell effector-mediated factors for assessing treatment failure and predicting outcomes. Alterations in multiple classes of genes are associated with resistance, including B cell identity (PAX5 and IRF8), immune checkpoints (CD274), and those affecting the microenvironment (TMEM30A). Somatic tumor alterations affect CAR19 therapy at multiple levels, including CAR19 T cell expansion, persistence, and tumor microenvironment. Further, CAR19 T cells play a reciprocal role in shaping tumor genotype and phenotype. We envision these findings will facilitate improved chimeric antigen receptor (CAR) T cells and personalized therapeutic approaches.

Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study.

The SCHOLAR-5 study examines treatment patterns and outcomes of real-world follicular lymphoma (FL) patients on 3rd line of treatment (LoT) or higher, for whom existing data are limited. SCHOLAR-5 is a retrospective cohort study using data from adults (≥ 18 years) with grade 1-3a FL, initiating ≥3rd LoT after June 2014 at major lymphoma centers in the US and Europe. Objective response rate (ORR), complete response (CR), progression-free survival (PFS) and overall survival (OS) were analyzed by LoT. Time-to-event outcomes were assessed using Kaplan-Meier methods. Of 128 patients, 87 initiated 3rd LoT, 63 initiated 4th LoT, and 47 initiated 5th LoT. At 1st eligible LoT, 31% progressed within 24-months of 1st LoT anti-CD20 combination therapy, 28% had prior autologous stem cell transplantation, and 31% were refractory to the previous LoT. The most common regimen in each LoT was chemoimmunotherapy; however, experimental drugs were increasingly used at later LoT. In the US, anti-CD20 monotherapy was more common at ≥3rd LoT compared to Europe, where stem cell transplants were more common. ORR at 3rd LoT was 68% (CR 44%), but decreased after each LoT to 37% (CR 22%) in ≥5 LoT. Median OS and PFS at 3rd LoT were 68 and 11 months, respectively, and reduced to 43 and 4 months at ≥5 LoT. Treatments were heterogenous at each LoT in both the US and Europe. Few FL patients achieved CR in later LoT, and duration of response and survival diminished with each subsequent line.

Resistance to mogamulizumab is associated with loss of CCR4 in cutaneous T-cell lymphoma.

Mogamulizumab is a humanized anti-CC chemokine receptor 4 (CCR4) antibody approved for the treatment of mycosis fungoides and Sézary syndrome. Despite almost universal expression of CCR4 in these diseases, most patients eventually develop resistance to mogamulizumab. We tested whether resistance to mogamulizumab is associated with loss of CCR4 expression. We identified 17 patients with mycosis fungoides or Sézary syndrome who either were intrinsically resistant or acquired resistance to mogamulizumab. Low expression of CCR4 by immunohistochemistry or flow cytometry was found in 65% of patients. Novel emergent CCR4 mutations targeting the N-terminal and transmembrane domains were found in 3 patients after disease progression. Emerging CCR4 copy number loss was detected in 2 patients with CCR4 mutations. Acquisition of CCR4 genomic alterations corresponded with loss of CCR4 antigen expression. We also report on outcomes of 3 cutaneous T-cell lymphoma (CTCL) patients with gain-of-function CCR4 mutations treated with mogamulizumab. Our study indicates that resistance to mogamulizumab in CTCL frequently involves loss of CCR4 expression and emergence of CCR4 genomic alterations. This finding has implications for management and monitoring of CTCL patients on mogamulizumab and development of future CCR4-directed therapies.

CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity.

To obtain a deeper understanding of poor responses to COVID-19 vaccination in patients with lymphoma, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls 1 and 4 months after COVID-19 vaccination. Fifty-five percent of patients developed blocking antibodies postvaccination, compared with 100% of controls. When evaluating patients last treated from days to nearly 18 years prior to vaccination, time since last anti-CD20 was a significant independent predictor of vaccine response. None of 31 patients who had received anti-CD20 treatment within 6 months prior to vaccination developed blocking antibodies. In contrast, patients who initiated anti-CD20 treatment shortly after achieving a vaccine-induced antibody response tended to retain that response during treatment, suggesting a policy of immunizing prior to treatment whenever possible. SIGNIFICANCE: In a large cohort of patients with B-cell lymphoma, time since anti-CD20 treatment was an independent predictor of neutralizing antibody response to COVID-19 vaccination. Comparing patients who received anti-CD20 treatment before or after vaccination, we demonstrate that vaccinating first can generate an antibody response that endures through anti-CD20-containing treatment. This article is highlighted in the In This Issue feature, p. 85.

Impact of initial biopsy type on the time to final diagnostic biopsy in patients with follicular lymphoma and suspected histologic transformation.

Diagnosis of histologic transformation (HT) of follicular lymphoma (FL) requires tissue biopsy. While surgical biopsy represents the gold standard, less invasive procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are frequently performed. In this retrospective multi-institutional study including 269 patients with FL and suspected HT, the median time from initial clinical suspicion to final diagnostic biopsy was similar whether the workup began with FNAB, CNB, or surgical biopsy (4, 9, and 6 days, respectively; p=.27), despite more subsequent biopsies performed following initial FNAB. Periprocedural complications were uniformly minimal. Biopsy-proven HT was more common in the initial surgery group and in workups including positron emission tomography/computed tomography (PET/CT). Our findings, derived from US academic centers with specialized procedural and pathology expertise, suggest that FNAB, CNB, and surgical biopsy are all viable initial diagnostic procedures that can inform clinical decision-making in select FL patients with suspected HT.

Frontline treatment of diffuse large B-cell lymphoma in elderly: a systematic review of clinical trials in post-rituximab era.

Treatment of diffuse large B cell lymphoma (DLBCL) remains challenging in elderly population and systematic reviews are lacking in this area. Medline and Cochrane Register of Controlled Trials in addition to conference proceedings were searched for therapeutic clinical trials on frontline treatment of DLBCL in adults ≥60 in post-rituximab era. Forty-one out of 713 reviewed papers met our inclusion criteria. Six cycles of rituximab, cyclophosphamide, vincristine, prednisone (R-CHOP) administered every 21 d remain the standard treatment for fit elderly, with no role for maintenance rituximab. For individuals ≥80, the strongest evidence favors rituximab/ofatumumab-miniCHOP. Numerous alternative approaches including the use of liposomal anthracyclines, dose and regimen adjustment to frailty/comorbidity score, brief duration regimens, and consolidative radioimmunotherapy have produced promising outcomes and could be considered for R-CHOP inappropriate elderly. Phase III randomized trials studying the efficacy of liposomal vincristine, extended-exposure rituximab, and lenalidomide plus R-CHOP are ongoing.

The Foot That Broke Both Hips: A Case Report and Literature Review of Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia and clinical symptoms of osteomalacia. Only discussed as case reports, there is still limited knowledge of this condition as a potentially curable cause of osteomalacia among clinicians and pathologists. In this article, we present a case of tumor-induced osteomalacia in a 59-year-old gentleman followed by an up-to-date review of the existing literature on TIO.

Suture Choice in Lumbar Dural Closure Contributes to Variation in Leak Pressures: Experimental Model.

STUDY DESIGN: Open-label laboratory investigational study; non-animal surgical simulation. OBJECTIVE: The authors perform a comparison of dural closure strength in a durotomy simulator across 2 different suture materials. SUMMARY OF BACKGROUND DATA: Incidental durotomy leading to persistent cerebrospinal fluid leak adds considerable morbidity to spinal procedures, often complicating routine elective lumbar spinal procedures. Using an experimental durotomy simulation, the authors compare the strength of closure using Gore-Tex with other suture types and sizes, using various closure techniques. METHODS: A comparison of dural closures was performed through an analysis of the peak pressure at which leakage occurred from a standardized durotomy closure in an established cerebrospinal fluid repair model with a premade L3 laminectomy. Nurolon was compared with Gore-Tex sutures sizes (for Gore-Tex, CV-6/5-0 and CV-5/4-0 was compared with Nurolon 4-0, 5-0, and 6-0). RESULTS: Thirty-six trials were performed with Nurolon 4-0, 5-0, and 6-0, whereas 21 trials were performed for 4-0 and 5-0 Gore-Tex. The mean peak pressure at which fluid leakage was observed was 21 cm H2O for Nurolon and 34 cm H2O for Gore-Tex. Irrespective of suture choice, all trials were grouped by closure technique: running suture, locked continuous, and interrupted suture. No significant difference was noted between the groups. For each of the 3 trials groups by closure technique, running, locked continuous, and interrupted, Gore-Tex closures had a significantly higher peak pressure to failure. Interrupted Gore-Tex was significantly higher than Interrupted Nurolon (P=0.007), running Gore-Tex was significantly higher than running Nurolon (P=0.034), and locked Gore-Tex was significantly higher than locked Nurolon (P=0.014). CONCLUSIONS: Durotomy closure in the lumbar spine with Gore-Tex suture may be a reasonable option for providing a watertight closure. In this laboratory study, Gore-Tex suture provided watertight dural closures that withstood higher peak pressures.

Improved patient quality of life following intradural extramedullary spinal tumor resection.

OBJECTIVE Resection significantly improves the clinical symptoms and functional outcomes of patients with intradural extramedullary tumors. However, patient quality of life following resection has not been adequately investigated. The aim in this retrospective analysis of prospectively collected quality of life outcomes is to analyze the efficacy of resection of intradural extramedullary spinal tumors in terms of quality of life markers. METHODS A retrospective review of a single institutional neurosurgical administrative database was conducted to analyze clinical data. The Oswestry Disability Index (ODI), visual analog scale (VAS) for pain, and the EQ-5D-3 L descriptive system were used to analyze quality of life preoperatively, less than 1 month postoperatively, 1-3 months postoperatively, 3-12 months postoperatively, and more than 12 months postoperatively. RESULTS The ODI scores increased perioperatively at the < 1-month follow-up from 36 preoperatively to 47. Relative to preoperative values, the ODI score decreased significantly at 1-3, 3-12, and > 12 months to 23, 17, and 20, respectively. VAS scores significantly decreased from 6.1 to 3.5, 2.4, 2.0, and 2.9 at the < 1-month, 1- to 3-, 3- to 12-, and > 12-month follow-ups, respectively. EQ-5D mobility significantly worsened at the < 1-month follow-up but improved at the 3- to 12-and > 12-month follow-ups. EQ-5D self-care significantly worsened at the < 1-month follow-up but significantly improved by the 3- to 12-month follow-up. EQ-5D usual activities improved at the 1- to 3-, 3- to 12-, and > 12-month follow-ups. EQ-5D pain and discomfort significantly improved at all follow-up points. EQ-5D anxiety and depression significantly improved at 1- to 3-month and 3- to 12-month follow-ups. CONCLUSIONS Resection of intradural extramedullary spine tumors appears to significantly improve patient quality of life by decreasing patient disability and pain and by improving each of the EQ-5D domains.

Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes.

Surgical management in 40 consecutive patients with cervical spinal epidural abscesses: shifting toward circumferential treatment.

STUDY DESIGN: Retrospective database review of a prospectively maintained neurosurgical database. OBJECTIVE: The surgical management of cervical spinal epidural abscesses (CSEA) is reviewed examining the shift from single to staged anteroposterior decompression and stabilization. SUMMARY OF BACKGROUND DATA: CSEA management is guided by small case series. METHODS: A retrospective review from 1997 to 2011 was conducted for patients with the diagnostic headings: cervical epidural abscess, infection, osteomyelitis, osteodiscitis, spondylodiscitis, and abscess. Comorbidities, risk factors, surgical approach, neurologic grade, and outcomes were recorded. RESULTS: Forty consecutive patients (mean age 53 years, age range 23-74, SD ±14, 10 female) were identified with CSEA in the operative database from 1997 to 2010. Twenty one patients had a body mass index more than 25 (53%), 6 (15%) had diabetes mellitus, 6 (15%) had a prior malignancy with 2 having prior neck irradiation, and 9 (23%) used tobacco products. The most common risk factor associated with CSEA was intravenous drug abuse, found in 10 patients (25%). The most common level of discitis involvement was C6-C7 in 12 (30%) followed by C5-C6 disc in 11 (28%) and least often at C1-C2 level in 2(5%) and C7-T1 in 2(5%). The most common neurologic grades at presentation were AIS D in 20 (50%) followed by AIS E in 9 (28%). All patients received magnetic resonance imaging identifying 17 (43%) with dorsal, 12 ventral (30%), and 11 circumferential epidural abscesses (28%). The majority of patients underwent anterior followed by posterior decompression and stabilization (n = 26, 65%); 8 (20%) underwent a ventral approach and six underwent a dorsal approach (15%). Fusion was achieved in 39 of 40 (97.5%) and not significantly influenced halo use in 10 patients. CONCLUSIONS: In this series, patients underwent acute evacuation and spinal cord decompression, and the shift toward staged treatment did not lead to an increased periprocedural complication rate. LEVEL OF EVIDENCE: 3.

Comparison of systemic mycophenolate mofetil with topical clobetasol in lichen planopilaris: a parallel-group, assessor- and analyst-blinded, randomized controlled trial.

INTRODUCTION: Lichen planopilaris (LPP) is the most common cause of inflammatory immune-mediated cicatricial alopecia. If not diagnosed and treated properly, it may lead to irreversible hair loss with a devastating impact on quality of life. However, treatment can be a challenge. In an area lacking these sorts of studies, we conducted a randomized controlled trial (RCT) to study the tolerability and therapeutic effects of topical clobetasol versus systemic mycophenolate mofetil (MMF). METHODS: A randomized, assessor- and analyst-blinded controlled trial was conducted in 60 patients with LPP in Razi Dermatology Hospital, Tehran, Iran, between February and December 2013. Patients were treated with clobetasol lotion 0.05 % applied at night or oral MMF 2 g/day and were followed for 6 months. The Lichen Planopilaris Activity Index (LPPAI) was the primary measure of response to treatment. RESULTS: Systemic MMF and topical clobetasol were equally effective in reducing the LPPAI over 6 months of treatment. Treatment tolerability was excellent in both groups and no serious irreversible adverse effects were detected. Satisfaction with treatment rose in the MMF group over time; however, it declined in the clobetasol group. CONCLUSION: Given the similar efficacy profiles, topical clobetasol seems to be a more suitable and reasonable choice for treatment of LPP than MMF.

C-5 palsy after cerebrospinal fluid diversion in posttraumatic syringomyelia: case report.

Syringomyelia is a potentially debilitating disease that involves abnormal CSF flow mechanics; its incidence after traumatic spinal cord injury (SCI) is approximately 15%. Treatment consists of restoration of CSF flow, typically via arachnoidolysis and syrinx decompression. The authors present a case of pronounced syringomyelia in a patient with concomitant severe cervical myelomalacia to demonstrate unilateral C-5 palsy as a potential complication of aggressive syrinx decompression at a remote level. A 56-year-old man with a remote history of SCI at T-11 (ASIA [American Spinal Injury Association] Grade A) presented with complaints of ascending motor and sensory weakness into the bilateral upper extremities that had progressed over 1 year. MRI demonstrated severe distortion of the spinal cord at the prior injury level of T10-11, where an old anterior column injury and prior hook-rod construct was visualized. Of note, the patient had a holocord syrinx with demonstrable myelomalacia. To restore CSF flow and decompress the spinal cord, T-2 and T-3 laminectomies, followed by arachnoidolysis and syringopleural shunt placement, were performed. Postoperatively on Day 1, with the exception of a unilateral deltoid palsy, the patient had immediate improvement in upper-extremity strength and myelopathy. He was discharged from the hospital on postoperative Day 5; however, at his 2-week follow-up visit, a persistent unilateral deltoid palsy was noted. MRI demonstrated a significant reduction in the holocord syrinx, no neural foraminal stenosis, and a significant positional shift of the ventral spinal cord. Further motor recovery was noted at the 8-month follow-up. Syringomyelia is a debilitating disease arising most often as a result of traumatic SCI. In the setting of myelomalacia with a pronounced syrinx, C-5 palsy is a potential complication of syrinx decompression.

Incidence of traumatic spinal cord injury worldwide: a systematic review.

PURPOSE: Traumatic spinal cord injuries (TSCI) are among the most devastating conditions in developed and developing countries, which can be prevented. The situation of TSCI around the world is not well understood which complicates the preventive policy decision making in fight against TSCI. This study was aimed to gather the available information about incidence of TSCI around the world. METHODS: A systematic search strategy was designed and run in Medline and EMBASE, along with extensive grey literature search, personal communications, website searching, and reference checking of related papers. RESULTS: Overall, 133 resources including 101 papers, 17 trauma registries, 6 conference proceedings, 5 books, 2 theses and 2 personal communication data were retrieved. Data were found for 41 individual countries. The incidence of TSCI ranges from 3.6 to 195.4 patients per million around the world. Australia, Canada, US, and high-income European countries have various valuable reports of TSCI, while African and Asian countries lack the appropriate epidemiologic data on TSCI. CONCLUSION: Data of epidemiologic information in TSCI are available for 41 countries of the world, which are mostly European and high-income countries. Researches and efforts should be made to gather information in developing and low-income countries to plan appropriate cost-effective preventive strategies in fight against TSCI.

Timing in the surgical evacuation of spinal epidural abscesses.

OBJECT: One often overlooked aspect of spinal epidural abscesses (SEAs) is the timing of surgical management. Limited evidence is available correlating earlier intervention with outcomes. Spinal epidural abscesses, once a rare diagnosis carrying a poor prognosis, are steadily becoming more common, with one recent inpatient meta-analysis citing an approximate incidence of 1 in 10,000 admissions with a mortality approaching 16%. One key issue of contention is the benefit of rapid surgical management of SEA to maximize outcomes. Timing of surgical management is definitely one overlooked aspect of care in spinal infections. Therefore, the authors performed a retrospective analysis in which they evaluated patients who underwent early (evacuation within 24 hours) versus delayed surgical intervention (> 24 hours) from the point of diagnosis, in an attempt to test the hypothesis that earlier surgery results in improved outcomes. METHODS: A retrospective review of a prospectively maintained adult neurosurgical database from 2009 to 2011 was conducted for patients with the diagnostic heading: epidural abscess, infection, osteomyelitis, osteodiscitis, spondylodiscitis, and abscess. The primary end point for each patient was neurological grade, measured as an American Spinal Injury Association Impairment Scale grade using hospital inpatient records on admission and discharge. Patients were divided into early surgical (< 24 hours) and delayed surgical cohorts. RESULTS: Eighty-seven consecutive patients were identified (25 females; mean age 55.5 years, age range 18-87 years). Fifty-four patients received surgery within 24 hours of admission (mean time from admission to incision, 11.2 hours), and 33 underwent surgery longer than 24 hours (mean 59 hours) after admission. Of the 54 patients undergoing early surgery 45 (85%) had a neurological deficit, whereas in the delayed surgical group 21 (64%) of 33 patients presented with a neurological deficit (p = 0.09). Patients in the delayed surgery cohort were significantly older by 10 years (59.6 vs 51.8 years, p = 0.01). With regard to history of prior revision, body mass index, intravenous drug abuse, tobacco use, prior radiation therapy, diabetes, chronic systemic infection, and prior osteomyelitis, there were no significant differences. There was no significant difference between early and delayed surgery groups in neurological grade on presentation, discharge, or location of epidural abscess. The most common organism isolated was Staphylococcus aureus (n = 51, 59.3%). The incidence of methicillin-resistant S. aureus was 21% (18 of 87). CONCLUSIONS: Evacuation within 24 hours appeared to have a relative advantage over delayed surgery with regard to discharge neurological grade. However, due to a limited, variable sample size, a significant benefit could not be shown. Further subgroup analyses with larger populations are required.