Comparative efficacy and safety of subcutaneous infliximab and vedolizumab in patients with Crohn's disease and ulcerative colitis included in randomised controlled trials.

BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.

Comparative Complications Associated With BMP Use In Patients Undergoing ACDF for Degenerative Spinal Conditions: Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic Review and Meta-Analysis. OBJECTIVES: To compare complication incidence in patients with or without the use of recombinant human Bone Morphogenic Protein-2 (BMP2) undergoing anterior cervical discectomy and fusion (ACDF) for degenerative conditions. METHODS: A systematic search of eight online databases was conducted using PRISMA guidelines. Inclusion criteria included English language studies with a minimum of 10 adult patients undergoing instrumented ACDF surgery for a degenerative spinal condition in which BMP2 was used in all patients or one of the treatment arms. Studies with patients undergoing circumferential fusions, with non-degenerative indications, or which did not report post-operative complication data were excluded. Patients with and without BMP2 were compared in terms of the incidence of dysphagia/dysphonia, anterior soft tissue complications (hematoma, seroma, infection, dysphagia/dysphonia), nonunion, medical complications, and new neurologic deficits. RESULTS: Of 1832 preliminary search results, 27 manuscripts were included. Meta-analysis revealed the relative risk of dysphagia or dysphonia (RR = 1.39, CI 95% 1.18 - 1.64, P = <.001), anterior soft tissue complications (RR = 1.43, CI 95% 1.25-1.64, P = <.001), and medical complications (RR = 1.32, CI 95% 1.06-1.66, P = .013) were statistically significant in the BMP2 group while the relative risk of non-union (RR = .5, CI 95% .23 - 1.13, P = .09) trended lower in the BMP2 group. Neurological deficit (RR = 1.06, CI 95% .82-1.37, P = .66), and additional medical complications (RR = 1.53, CI 95% .98-2.38, P = .06) were not found to be statistically different between the groups. CONCLUSIONS: This meta-analysis identified a high rate of arthrodesis when BMP2 was used in ACDF, but confirmed increased rates of dysphagia and anterior soft tissue complications. Surgeons may consider reserving BMP2 implementation for cases with a high risk of non-union, and should be aware of the risk of airway compromise.

Improving Surgical Triage in Spine Clinic: Predicting Likelihood of Surgery Using Machine Learning.

BACKGROUND: Correctly triaging patients to a surgeon or a nonoperative provider is an important part of the referral process. Clinics typically triage new patients based on simple intake questions. This is time-consuming and does not incorporate objective data. Our goal was to use machine learning to more accurately screen surgical candidates seen in a spine clinic. METHODS: Using questionnaire data and magnetic resonance imaging reports, a set of artificial neural networks was trained to predict whether a patient would be recommended for spine surgery. Questionnaire responses included demographics, chief complaint, and pain characteristics. The primary end point was the surgeon's determination of whether a patient was an operative candidate. Model accuracy in predicting this end point was assessed using a separate subset of patients. RESULTS: The retrospective dataset included 1663 patients in cervical and lumbar cohorts. Questionnaire data were available for all participants, and magnetic resonance imaging reports were available for 242 patients. Within 6 months of initial evaluation, 717 (43.1%) patients were deemed surgical candidates by the surgeon. Our models predicted surgeons' recommendations with area under the curve scores of 0.686 for lumbar (positive predictive value 66%, negative predictive value 80%) and 0.821 for cervical (positive predictive value 83%, negative predictive value 85%) patients. CONCLUSIONS: Our models used patient data to accurately predict whether patients will receive a surgical recommendation. The high negative predictive value demonstrates that this approach can reduce the burden of nonsurgical patients in surgery clinic without losing many surgical candidates. This could reduce unnecessary visits for patients, increase the proportion of operative candidates seen by surgeons, and improve quality of patient care.

A Developer's Perspective on Clinical Evidence and Benefits for Rituximab Biosimilar Uptake, with a Focus on CT-P10.

To date, four rituximab biosimilars have received regulatory approval from the European Medicines Agency and/or US Food and Drug Administration. CT-P10 was the first rituximab biosimilar to be approved by each agency, in 2017 and 2018, respectively. Regulatory approval of CT-P10 followed demonstration of pharmacokinetic equivalence to the reference product in a phase I study in patients with rheumatoid arthritis. Phase III pivotal studies of CT-P10 subsequently demonstrated equivalence or non-inferiority of pharmacokinetics and efficacy between CT-P10 and reference rituximab in patients with rheumatoid arthritis, advanced-stage follicular lymphoma, and low-tumour-burden follicular lymphoma. Almost 5 years after its initial regulatory approval, significant real-world experience has accumulated with CT-P10 use, particularly in diffuse large B-cell lymphoma, one of the indications approved by extrapolation. This article summarises the pivotal data underlying regulatory approval for the four licensed rituximab biosimilars, before focusing on real-world data gathered with CT-P10. These data provide further support for the safety and effectiveness of CT-P10 and should boost healthcare professional and patient confidence in its use. Pharmacoeconomic analyses support the potential healthcare system cost savings offered by rituximab biosimilar uptake, which could lead to improved patient access to biologic treatments. Opportunities arising from biosimilar uptake extend further, potentially enabling innovative investigator-led research and therapeutic advances.

Comparison of Minimally Invasive Versus Open Transforaminal Interbody Lumbar Fusion.

STUDY DESIGN: Narrative review. OBJECTIVES: In this review, we address the question of whether the literature supports the notion that minimally invasive transforaminal interbody fusion (MIS-TLIF) improves outcome as compared with open TLIF (open-TLIF). Short and long-term outcomes, fusion rate, and cost-effectiveness were reviewed. METHODS: This is a narrative review using various databases. Open-TLIF and MIS-TLIF studies were included and posterior lumbar interbody fusion studies were excluded. A description of paramedian incision in surgical technique was essential to the definition of MIS-TLIF. The present review included 14 prospective observational studies and 6 randomized controlled trials. RESULTS: With short-term outcomes, some studies indicate a better outcome with MIS-TLIF regarding intraoperative bleeding, hospital stay, time to ambulation, postoperative narcotic use, and time to resume work. Both MIS-TLIF and open-TLIF surgeries improved Oswestry Disability Index, back pain, and leg pain. Some studies show that MIS-TLIF resulted in lower back pain than open-TLIF. Radiation exposure was higher with MIS-TLIF. In the longer term, clinical outcomes were improved in both MIS and open TLIF groups. Fusion rates were more than 90% in both MIS-TLIF and open-TLIF. Cost-effectiveness and length of surgery had mixed results. CONCLUSIONS: The potential benefits of MIS-TLIF might be present in the early recovery period after surgery. Long-term outcomes were similar with both MIS-TLIF and open-TLIF.

Trends and Costs of External Electrical Bone Stimulators and Grafting Materials in Anterior Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review. PURPOSE: To identify the trends in stimulator use, pair those trends with various grafting materials, and determine the influence of stimulators on the risk of revision surgery. OVERVIEW OF LITERATURE: A large number of studies has reported beneficial effects of electromagnetic energy in healing long bone fractures. However, there are few clinical studies regarding the use of electrical stimulators in spinal fusion. METHODS: We used insurance billing codes to identify patients with lumbar disc degeneration who underwent anterior lumbar interbody fusion (ALIF). Comparisons between patients who did and did not receive electrical stimulators following surgery were performed using logistic regression analysis, chi-square test, and odds ratio (OR) analysis. RESULTS: Approximately 19% of the patients (495/2,613) received external stimulators following ALIF surgery. There was a slight increase in stimulator use from 2008 to 2014 (multi-level R2=0.08, single-level R2=0.05). Patients who underwent multi-level procedures were more likely to receive stimulators than patients who underwent single-level procedures (p<0.05; OR, 3.72; 95% confidence interval, 3.02-4.57). Grafting options associated with most frequent stimulator use were bone marrow aspirates (BMA) plus autograft or allograft for single-level and allograft alone for multi-level procedures. In both cohorts, patients treated with bone morphogenetic proteins were least likely to receive electrical stimulators (p<0.05). Patients who received stimulation generally had higher reimbursements. Concurrent posterior lumbar fusion (PLF) (ALIF+PLF) increased the likelihood of receiving stimulators (p<0.05). Patients who received electrical stimulators had similar revision rates as those who did not receive stimulation (p>0.05), except those in the multilevel ALIF+PLF cohort, wherein the patients who underwent stimulation had higher rates of revision surgery. CONCLUSIONS: Concurrent PLF or multi-level procedures increased patients' likelihood of receiving stimulators, however, the presence of comorbidities did not. Patients who received BMA plus autograft or allograft were more likely to receive stimulation. Patients with and without bone stimulators had similar rates of revision surgery.

Scaled Signal Intensity of Uterine Fibroids on T2-Weighted MR Imaging as a Predictor of the Potential Response to Uterine Fibroid Embolization.

PURPOSE: To determine feasibility of scaled signal intensity (SSI) of uterine fibroids on T2-weighted magnetic resonance (MR) images to predict volume reduction rate (VRR) after uterine fibroid embolization (UFE). MATERIALS AND METHODS: In this retrospective study, 66 premenopausal women underwent UFE. Patients underwent follow-up MR imaging 3 months after UFE. SSI of predominant fibroids was measured on T2-weighted MR images obtained before the procedure by standardizing the mean signal intensity to a 0-to-100 scale, with 0 representing rectus abdominis muscle and 100 representing subcutaneous fat (100) for reference values. RESULTS: VRR of predominant fibroids was 12.3%-99.0% (mean 53.7%). SSI of predominant fibroids was 0.9-73.6 (mean 24.6). SSI was significantly related to VRR of fibroids (P < .01). The optimal SSI cutoff value to predict VRR > 50% was 18.16 with sensitivity of 78.8% and specificity of 66.7%. The optimal SSI cutoff value to predict VRR < 30% was 14.38 with sensitivity of 75% and specificity of 70.7%. CONCLUSIONS: SSI of fibroids was significantly related to fibroid VRR after UFE. SSI may be useful in the quantified prediction of volume reduction.

New organ-based tube current modulation method to reduce the radiation dose during computed tomography of the head: evaluation of image quality and radiation dose to the eyes in the phantom study.

A new organ-based tube current modulation (NOB-TCM) method was designed with the intent to decrease tube current by 30% over a prescribed 90° radial arc across the anterior aspect of the radiosensitive organ, without increasing tube current in the remaining radial arc. We compared a reference scan and five other dose-reducing methods with regard to effects on dose, practicality, and image quality to determine the most effective method for the reduction of the radiation dose to the eyes during CT examinations of the head. We compared the radiation doses to the eyes and physical image quality in different regions of interest for TCM and shielding scans. Three types of TCM scans were performed: longitudinal TCM, angular TCM, and NOB-TCM. A bismuth sheet and lead goggles were each applied for the shielding scan. Relative to the reference scan, the dose to the eye was reduced to 25.88% with NOB-TCM, 44.53% with lead goggles, and 36.91% with a bismuth shield. Relative to the reference scan, the mean signal-to-noise ratio (SNR) was decreased to 8.02% with NOB-TCM, 28.36% with lead goggles, and 32.95% with the bismuth shield. The SNR of the anterior region of interest was decreased to 11.89% with NOB-TCM and 87.89% with the bismuth shield. The average figure of merit was increased by 11.7% with longitudinal TCM and 13.39% with NOB-TCM, compared with the reference scan. NOB-TCM is a superior solution for head CT, including the orbital area, due to the reduction in radiation exposure without significant loss in image quality.

Activation of JNK and IRE1 is critically involved in tanshinone I-induced p62 dependent autophagy in malignant pleural mesothelioma cells: implication of p62 UBA domain.

The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells. Furthermore, autophagy flux was enhanced in Tan I-treated H28 cells transfected by RFP-GFP-LC3 constructs, with colocalization of GFP-LC3 punctae with LAMP1 or Lysotracker. Interestingly, C-terminal UBA domain is required for Tan 1 induced aggregation of p62 in H28 cells. Notably, Tan I upregulated CCAAT-enhancer-binding protein homologous protein (CHOP), inositol-requiring protein-1 (IRE1) and p-c-Jun N-terminal kinase (p-JNK), but silencing of IRE1 or p62 and JNK inhibitor SP600125 blocked the LC3II accumulation in Tan I-treated H28 cells. Overall, these findings demonstrate that Tan I exerts antitumor activity through a compromise between apoptosis and p62/SQSTM1-dependent autophagy via activation of JNK and IRE 1 in malignant mesothelioma cells.

Novel Method Using Baseline Normalization and Area Under the Curve to Evaluate Differences in Outcome Between Treatment Groups and Application to Patients With Cervical Spondylotic Myelopathy Undergoing Anterior Versus Posterior Surgery.

STUDY DESIGN: Retrospective review of a prospective database. OBJECTIVE: To describe a novel method that uses baseline normalization and area under the curve (AUC) to compare surgical outcomes between patients surgically treated anteriorly versus posteriorly for cervical spondylotic myelopathy (CSM). SUMMARY AND BACKGROUND DATA: It is important to control for baseline characteristics, especially disease severity, when evaluating differences in outcomes between 2 treatment groups. However, current methods of reporting outcomes are limited perhaps diminish the health impact of the entire postoperative recovery experience. METHODS: In the prospective, multicenter AO Spine North America CSM database, 147 patients had complete modified Japanese Orthopaedic Association (mJOA) data at baseline and at 6-, 12-, and 24-months postoperatively and were either treated anteriorly (n = 94) or posteriorly (n = 53). Each patient's follow-up mJOA scores were normalized by dividing them by the patient's baseline value. A graph was then plotted with the time point on the x-axis and the normalized score or "recovery index" on the y-axis. The AUC was calculated and then compared between the anterior and posterior surgical approach groups. RESULTS: The non-normalized recovery profile of the anterior group was better than that of the posterior group, as the patients treated anteriorly had less functional impairment at baseline. After normalization, patients in the anterior and posterior group had similar recovery indices and AUCs at 6-months following surgery. At 24-months, patients treated posteriorly had a significantly higher recovery index (1.32) and a larger AUC (16.3) than those treated anteriorly (1.11, 14.5, P = 0.004 and P = 0.006, respectively). CONCLUSION: This is the first study to apply AUC analysis to patients with CSM. In surgical patients with CSM, those treated anteriorly achieved a higher mJOA score at all time points than those treated posteriorly. The recovery indices, however, were not significantly different between approach groups at 6 months. LEVEL OF EVIDENCE: 3.

Scaled signal intensity of uterine fibroids based on T2-weighted MR images: a potential objective method to determine the suitability for magnetic resonance-guided focused ultrasound surgery of uterine fibroids.

OBJECTIVES: Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive method to treat uterine fibroids. To help determine the patient suitability for MRgFUS, we propose a new objective measure: the scaled signal intensity (SSI) of uterine fibroids in T2 weighted MR images (T2WI). METHODS: Forty three uterine fibroids in 40 premenopausal women were included in this retrospective study. SSI of each fibroid was measured from the screening T2WI by standardizing its mean signal intensity to a 0-100 scale, using reference intensities of rectus abdominis muscle (0) and subcutaneous fat (100). Correlation between the SSI and the non-perfused volume (NPV) ratio (a measure for treatment success) was calculated. RESULTS: Pre-treatment SSI showed a significant inverse-correlation with post treatment NPV ratio (p < 0.05). When dichotomizing NPV ratio at 45 %, the optimal cut off value of the SSI was found to be 16.0. CONCLUSIONS: A fibroid with SSI value 16.0 or less can be expected to have optimal responses. The SSI of uterine fibroids in T2WI can be suggested as an objective parameter to help in patient selection for MRgFUS. KEY POINTS: • Signal intensity of fibroid in MR images predicts treatment response to MRgFUS. • Signal intensity is standardized into scaled form using adjacent tissues as references. • Fibroids with SSI less than 16.0 are expected to have optimal responses.

Upregulation of death receptor 5 and activation of caspase 8/3 play a critical role in ergosterol peroxide induced apoptosis in DU 145 prostate cancer cells.

BACKGROUND: Though ergosterol peroxide (EP) derived from Neungyi mushrooms (Sarcodon aspratus) was known to have cytotoxic, apoptotic, anti-inflammatory and antimycobacterial effects, the underlying molecular mechanism of EP still remains unclear. Thus, in the present study, the apoptotic mechanism of EP was elucidated in DU 145 prostate cancer cells. METHODS: Cell viability of prostate cancer cells was measured by MTT assay. To see whether EP induces the apoptosis, FACS, western blot and TUNEL assay were performed. To determine the role of Death receptor (DR) 5 molecules in EP-induced apoptosis in DU 145 prostate cancer cells, the silencing of DR 5 was performed by using siRNAs. RESULTS: EP showed significant cytotoxicity against DU 145, PC 3, M2182 prostate cancer cells. Also, EP effectively increased the sub G1 population and terminal deoxynucleotidyl transferase DUTP nick end labeling (TUNEL) positive cells in DU 145 prostate cancer cells. Furthermore, western blotting revealed that EP cleaved poly (ADP-ribose) polymerase (PARP) and caspase 8/3, attenuated the expression of fluorescence loss in photobleaching (FLIP), Bcl-XL and Bcl-2 as well as activated Bax, Fas-associated death domain (FADD) and DR 5 in a concentration dependent manner in DU 145 prostate cancer cells. Conversely, caspase 8 inhibitor Z-IETD-FMK blocked the apoptotic ability of EP to cleave PARP and an increase of sub G1 population in DU 145 prostate cancer cells. Likewise, the silencing of DR 5 suppressed the cleavages of PARP induced by EP in DU 145 prostate cancer cells. CONCLUSION: Overall, our findings suggest that ergosterol peroxide induces apoptosis via activation of death receptor 5 and caspase 8/3 in DU 145 prostate cancer cells as a cancer chemopreventive agent or dietary factor.

Mild diabetes is not a contraindication for surgical decompression in cervical spondylotic myelopathy: results of the AOSpine North America multicenter prospective study (CSM).

BACKGROUND CONTEXT: Cervical spondylotic myelopathy (CSM) is a chronic spinal cord disease and can lead to progressive or stepwise neurologic decline. Several factors may influence this process, including extent of spinal cord compression, duration of symptoms, and medical comorbidities. Diabetes is a systemic disease that can impact multiple organ systems, including the central and peripheral nervous systems. There has been little information regarding the effect of diabetes on patients with coexistent CSM. PURPOSE: To provide empirical data regarding the effect of diabetes on treatment outcomes in patients who underwent surgical decompression for coexistent CSM. STUDY DESIGN/SETTING: Large prospective multicenter cohort study of patients with and without diabetes who underwent decompressive surgery for CSM. PATIENT SAMPLE: Two hundred thirty-six patients without and 42 patients with diabetes were enrolled. Of these, 37 were mild cases and five were moderate cases. Four required insulin. There were no severe cases associated with end-organ damage. OUTCOME MEASURES: Self-report measures include Neck Disability Index and version 2 of 36-Item Short Form Health Survey (SF-36v2), and functional measures include modified Japanese Orthopedic Association (mJOA) score and Nurick grade. METHODS: We compared presurgery symptoms and treatment outcomes between patients with and without diabetes using univariate and multivariate models, adjusting for demographics and comorbidities. RESULTS: Diabetic patients were older, less likely to smoke, and more likely to be on social security disability insurance. Patients with diabetes presented with a worse Nurick grade, but there were no differences in mJOA and SF-36v2 at presentation. Overall, there was a significant improvement in all outcome parameters at 12 and 24 months. There was no difference in the level of improvement between the patients with and without diabetes, except in the SF-36v2 Physical Functioning, in which diabetic patients experienced significantly less improvement. There were no differences in surgical complication rates between diabetic patients and nondiabetic patients. CONCLUSIONS: Except for a worse Nurick grade, diabetes does not seem to affect severity of symptoms at presentation for surgery. More importantly, with the exception of the SF-36v2 Physical Functioning scores, outcomes of surgical treatment are similar in patients with diabetes and without diabetes. Surgical decompression is effective and should be offered to patients with diabetes who have symptomatic CSM and are appropriate surgical candidates.

Anterior versus posterior surgical approaches to treat cervical spondylotic myelopathy: outcomes of the prospective multicenter AOSpine North America CSM study in 264 patients.

STUDY DESIGN: A prospective observational multicenter study. OBJECTIVE: To help solve the debate regarding whether the anterior or posterior surgical approach is optimal for patients with cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: The optimal surgical approach to treat CSM remains debated with varying opinions favoring anterior versus posterior surgical approaches. We present an analysis of a prospective observational multicenter study examining outcomes of surgical treatment for CSM. METHODS: A total of 278 subjects from 12 sites in North America received anterior/posterior or combined surgery at the discretion of the surgeon. This study focused on subjects who had either anterior or posterior surgery (n = 264, follow-up rate, 87%). Outcome measures included the modified Japanese Orthopedic Assessment scale, the Nurick scale, the Neck Disability Index, and the Short-Form 36 (SF-36) Health Survey version 2 Physical and Mental Component Scores. RESULTS: One hundred and sixty-nine patients were treated anteriorly and 95 underwent posterior surgery. Anterior surgical cases were younger and had less severe myelopathy as assessed by mJOA and Nurick scores. There were no baseline differences in Neck Disability Index or SF-36 between the anterior and posterior cases. Improvement in the mJOA was significantly lower in the anterior group than posterior group (2.47 vs. 3.62, respectively, P < 0.01), although the groups started at different levels of baseline impairment. The extent of improvement in the Nurick Scale, Neck Disability Index, SF-36 version 2 Physical Component Score, and SF-36 version 2 Mental Component Score did not differ between the groups. CONCLUSION: Patients with CSM show significant improvements in several health-related outcome measures with either anterior or posterior surgery. Importantly, patients treated with anterior techniques were younger, with less severe impairment and more focal pathology. We demonstrate for the first time that, when patient and disease factors are controlled for, anterior and posterior surgical techniques have equivalent efficacy in the treatment of CSM. LEVEL OF EVIDENCE: 3.

Efficacy and safety of surgical decompression in patients with cervical spondylotic myelopathy: results of the AOSpine North America prospective multi-center study.

BACKGROUND: Cervical spondylotic myelopathy is the leading cause of spinal cord dysfunction worldwide. The objective of this study was to evaluate the impact of surgical decompression on functional, quality-of-life, and disability outcomes at one year after surgery in a large cohort of patients with this condition. METHODS: Adult patients with symptomatic cervical spondylotic myelopathy and magnetic resonance imaging evidence of spinal cord compression were enrolled at twelve North American centers from 2005 to 2007. At enrollment, the myelopathy was categorized as mild (modified Japanese Orthopaedic Association [mJOA] score ≥ 15), moderate (mJOA = 12 to 14), or severe (mJOA < 12). Patients were followed prospectively for one year, at which point the outcomes of interest included the mJOA score, Nurick grade, Neck Disability Index (NDI), and Short Form-36 version 2 (SF-36v2). All outcomes at one year were compared with the preoperative values with use of univariate paired statistics. Outcomes were also compared among the severity classes with use of one-way analysis of variance. Finally, a multivariate analysis that adjusted for baseline differences among the severity groups was performed. Treatment-related complication data were collected and the overall complication rate was calculated. RESULTS: Eighty-five (30.6%) of the 278 enrolled patients had mild cervical spondylotic myelopathy, 110 (39.6%) had moderate disease, and 83 (29.9%) had severe disease preoperatively. One-year follow-up data were available for 222 (85.4%) of 260 patients. There was a significant improvement from baseline to one year postoperatively (p < 0.05) in the mJOA score, Nurick grade, NDI score, and all SF-36v2 health dimensions (including the mental and physical health composite scores) except general health. With the exception of the change in the mJOA, the degree of improvement did not depend on the severity of the preoperative symptoms. These results remained unchanged after adjusting for relevant confounders in the multivariate analysis. Fifty-two patients experienced complications (prevalence, 18.7%), with no significant differences among the severity groups. CONCLUSIONS: Surgical decompression for the treatment of cervical spondylotic myelopathy was associated with improvement in functional, disability-related, and quality-of-life outcomes at one year of follow-up for all disease severity categories. Furthermore, complication rates observed in the study were commensurate with those in previously reported cervical spondylotic myelopathy series.

A clinical prediction model to determine outcomes in patients with cervical spondylotic myelopathy undergoing surgical treatment: data from the prospective, multi-center AOSpine North America study.

BACKGROUND: Cervical spondylotic myelopathy is a progressive spine disease and the most common cause of spinal cord dysfunction worldwide. The objective of this study was to develop a prediction model, based on data from a prospective multi-center study, relating a combination of clinical and imaging variables to surgical outcome in patients with cervical spondylotic myelopathy. METHODS: Two hundred and seventy-eight patients diagnosed with cervical spondylotic myelopathy treated surgically were enrolled at twelve different sites in the multi-center AOSpine North America study. Univariate analyses were performed to evaluate the relationship between outcome, assessed with the modified Japanese Orthopaedic Association (mJOA) score, and various clinical and imaging predictors. A set of important candidate variables for the final model was selected on the basis of author consensus, literature support, and statistical findings. Logistic regression was used to formulate the final model. RESULTS: Univariate analyses demonstrated that the odds of a successful outcome decreased with a longer duration of symptoms (odds ratio [OR] = 0.80, 95% confidence interval [CI] = 0.65 to 0.98, p = 0.030); a lower baseline mJOA score (OR = 0.74, 95% CI = 0.65 to 0.84, p < 0.0001); the presence of psychological comorbidities (OR = 0.51, 95% CI = 0.29 to 0.92, p = 0.024); the presence of broad-based, unstable gait (OR = 2.72, 95% CI = 1.47 to 5.06, p = 0.0018) or other gait impairment (OR = 3.56, 95% CI = 1.75 to 7.22, p = 0.0005); and older age (OR = 0.96, 95% CI = 0.93 to 0.98, p = 0.0004). The dependent variable, the mJOA score at one year, was dichotomized for logistic regression: a "successful" outcome was defined as a final score of ≥16 and a "failed" outcome was a score of <16. The final model included age (OR = 0.97, 95% CI = 0.94 to 0.99, p = 0.0017), duration of symptoms (OR = 0.78, 95% CI = 0.61 to 0.997, p = 0.048), smoking status (OR = 0.46, 95% CI = 0.21 to 0.98, p = 0.043), impairment of gait (OR = 2.66, 95% CI = 1.17 to 6.06, p = 0.020), psychological comorbidities (OR = 0.33, 95% CI = 0.15 to 0.69, p = 0.0035), baseline mJOA score (OR = 1.22, 95% CI = 1.05 to 1.41, p = 0.0084), and baseline transverse area of the cord on magnetic resonance imaging (OR = 1.02, 95% CI = 0.99 to 1.05, p = 0.19). The area under the receiver operator characteristic curve was 0.79, indicating good model prediction. CONCLUSIONS: On the basis of the results of the AOSpine North America study, we identified a list of the most important predictors of surgical outcome for cervical spondylotic myelopathy.

Magnetic resonance imaging-guided focused ultrasound surgery for symptomatic uterine fibroids: estimation of treatment efficacy using thermal dose calculations.

OBJECTIVE: To study the correlation between the predicted thermal dose volume (TDV) and the actual ablation volumes in MR-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine fibroids, and to follow up the outcome for 12 months post-treatment. STUDY DESIGN: Phase-difference fast spoiled gradient-echo MR images were used to analyze thermal change during the energy deliveries of MRgFUS in 60 consecutive patients treated for symptomatic uterine fibroids. The TDV obtained through analysis of these MR images was compared with the non-perfused volume (NPV) measured on post-treatment contrast enhanced T1-weighted images. Final values of TDV ratio and NPV ratio were obtained by dividing these values by original fibroid volume. Patients were followed for 12 months post-treatment to assess symptomatic relief using the symptom severity score (SSS). RESULTS: Treatments in which we managed to reach a TDV ratio larger than 27% of the treated fibroid yielded a ratio of NPV to TDV of 1.1±0.5, indicating accurate control of the non-invasive procedure. Patient symptoms, as measured by the SSS, continuously decreased from a mean baseline score of 50±22 to 19±12 (P<0.0001) 12 months post-treatment. CONCLUSIONS: At large treatment volumes (exceeding 27% TDV ratio), thermal dose estimates correspond very closely to non-perfused volumes measured immediately post treatment. These large treatment volumes result in continuous clinical improvement throughout the first 12 months after MRgFUS.

Magnetic resonance imaging-guided focused ultrasound treatment of pedunculated subserosal uterine fibroids: a preliminary report.

PURPOSE: To evaluate magnetic resonance (MR) imaging-guided focused ultrasound (US) as a treatment for pedunculated subserosal fibroids. MATERIALS AND METHODS: Over a 2-year period (March 2007 to March 2009), 135 women with symptomatic uterine fibroids were treated in the authors' institution using MR imaging-guided focused US. Of these women, nine (mean age, 39 years; range, 25-47 y) had a single pedunculated subserosal fibroid. During treatment, these pedunculated fibroids were targeted, while sparing the stalk connection between the fibroid and the uterus. Contrast-enhanced T1-weighted MR images were obtained immediately after the treatment to measure the nonperfused volume (NPV) ratio and to check stalk viability. Changes in tumor volume, diameter of the stalk, patient symptoms and adverse events were evaluated 6 months after treatment. RESULTS: The volume of the treated fibroids (n=9) ranged from 79-380cm(3) (mean, 198cm(3)), and NPV ratio ranged from 45%-80% (mean, 67%). MR imaging follow-up at 6 months showed a 14%-48% (mean, 30%) reduction in the volume of the treated fibroids (P =.008). In all cases, the pedunculated subserosal fibroids remained connected to the uterus with a 13% average decrease in the mean diameter of the stalks (from 3.5 to 3.0cm; P=.008). Eight of nine patients (89%) reported improvement in bulk-related fibroid symptoms after treatment. CONCLUSIONS: The results of this preliminary study suggest that MR imaging-guided focused US may be a safe and effective treatment for pedunculated subserosal fibroids. Larger prospective studies with longer follow-up are needed to confirm the suitability of MR imaging-guided focused US to treat this type of fibroid.

Comparison of image quality and radiation dose between combined automatic tube current modulation and fixed tube current technique in CT of abdomen and pelvis.

BACKGROUND: Tube current is an important determinant of radiation dose and image quality in X-ray-based examination. The combined automatic tube current modulation technique (ATCM) enables automatic adjustment of the tube current in various planes (x-y and z) based on the size and attenuation of the body area scanned. PURPOSE: To compare image quality and radiation dose of the ATCM with those of a fixed tube current technique (FTC) in CT of the abdomen and pelvis performed with a 16-slice multidetector row CT. MATERIAL AND METHODS: We reviewed 100 patients in whom initial and follow-up CT of the abdomen and pelvis were performed with FTC and ATCM. All acquisition parameters were identical in both techniques except for tube current. We recorded objective image noise in liver parenchyma, subjective image noise and diagnostic acceptability by using a five-point scale, radiation dose, and body mass index (BMI, kg/m(2)). Data were analyzed with parametric and non-parametric statistical tests. RESULTS: There was no significant difference in image noise and diagnostic acceptability between two techniques. All subjects had acceptable subjective image noise in both techniques. The significant reduction in radiation dose (45.25% reduction) was noted with combined ATCM (P < 0.001). There was a significant linear statistical correlation between BMI and dose reduction (r = -0.78, P < 0.05). CONCLUSION: The ATCM for CT of the abdomen and pelvis substantially reduced radiation dose while maintaining diagnostic image quality. Patients with lower BMI showed more reduction in radiation dose.