Background Context The North American Spine Society's (NASS ) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis features evidence-based ...recommendations for diagnosing and treating degenerative lumbar spondylolisthesis. The guideline updates the 2008 guideline on this topic and is intended to reflect contemporary treatment concepts for symptomatic degenerative lumbar spondylolisthesis as reflected in the highest quality clinical literature available on this subject as of May 2013. NASS' guideline on this topic is the only guideline on degenerative lumbar spondylolisthesis included in the Agency for Healthcare Research and Quality's National Guideline Clearinghouse (NGC). Purpose The purpose of this guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for patients with degenerative lumbar spondylolisthesis. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. Study Design Guideline summary review Methods This guideline is the product of the Degenerative Lumbar Spondylolisthesis Work Group of NASS' Evidence-Based Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multi-disciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members utilized NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guidelines were submitted to an internal peer review process and ultimately approved by the NASS Board of Directors. Upon publication, the Degenerative Lumbar Spondylolisthesis guideline was accepted into the NGC and will be updated approximately every 5 years. Results Twenty-seven clinical questions were addressed in this guideline update, including 15 clinical questions from the original guideline and 12 new clinical questions. The respective recommendations were graded by strength of the supporting literature, which was stratified by levels of evidence. Twenty-one new or updated recommendations or consensus statements were issued and 13 recommendations or consensus statements were maintained from the original guideline. Conclusions The clinical guideline was created using the techniques of evidence-based medicine and best available evidence to aid practitioners in the care of patients with degenerative lumbar spondylolisthesis. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flow chart, suggestions for future research and all of the references, is available electronically on the NASS website at https://www.spine.org/Pages/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx and will remain updated on a timely schedule.
Summary Background Tuberous sclerosis complex is a genetic disorder leading to constitutive activation of mammalian target of rapamycin (mTOR) and growth of benign tumours in several organs. In the ...brain, growth of subependymal giant cell astrocytomas can cause life-threatening symptoms—eg, hydrocephalus, requiring surgery. In an open-label, phase 1/2 study, the mTOR inhibitor everolimus substantially and significantly reduced the volume of subependymal giant cell astrocytomas. We assessed the efficacy and safety of everolimus in patients with subependymal giant cell astrocytomas associated with tuberous sclerosis complex. Methods In this double-blind, placebo-controlled, phase 3 trial, patients (aged 0–65 years) in 24 centres in Australia, Belgium, Canada, Germany, the UK, Italy, the Netherlands, Poland, Russian Federation, and the USA were randomly assigned, with an interactive internet-response system, in a 2:1 ratio to oral everolimus 4·5 mg/m2 per day (titrated to achieve blood trough concentrations of 5–15 ng/mL) or placebo. Eligible patients had a definite diagnosis of tuberous sclerosis complex and at least one lesion with a diameter of 1 cm or greater, and either serial growth of a subependymal giant cell astrocytoma, a new lesion of 1 cm or greater, or new or worsening hydrocephalus. The primary endpoint was the proportion of patients with confirmed response—ie, reduction in target volume of 50% or greater relative to baseline in subependymal giant cell astrocytomas. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00789828. Findings 117 patients were randomly assigned to everolimus (n=78) or placebo (n=39). 27 (35%) patients in the everolimus group had at least 50% reduction in the volume of subependymal giant cell astrocytomas versus none in the placebo group (difference 35%, 95% CI 15–52; one-sided exact Cochran-Mantel-Haenszel test, p<0·0001). Adverse events were mostly grade 1 or 2; no patients discontinued treatment because of adverse events. The most common adverse events were mouth ulceration (25 32% in the everolimus group vs two 5% in the placebo group), stomatitis (24 31% vs eight 21%), convulsion (18 23% vs ten 26%), and pyrexia (17 22% vs six 15%). Interpretation These results support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis. Additionally, everolimus might represent a disease-modifying treatment for other aspects of tuberous sclerosis. Funding Novartis Pharmaceuticals.
Abstract Background Previous studies indicate that remote ischemic conditioning performed before percutaneous coronary intervention (PCI) reduces infarct size in patients with STEMI. It remains ...unclear whether remote conditioning affords protection when performed in adjunct to primary PCI. We aimed to study whether remote ischemic per-postconditioning (RIperpostC) initiated after admission to the catheterization laboratory attenuates myocardial infarct size in patients with anterior ST-elevation myocardial infarction (STEMI). Methods In this prospective multicenter trial 93 patients with anterior STEMI were randomized to RIperpostC or sham procedure as adjunct to primary PCI. RIperpostC was started on arrival in the catheterization laboratory by 5 min cycles of inflation and deflation of a blood pressure cuff around the left thigh and continued throughout the PCI procedure. Infarct size and myocardium at risk were determined by cardiac magnetic resonance at day four to seven. The primary outcome was myocardial salvage index (MSI). Results There was no significant difference in MSI between the RIperpostC and control group (median 48.5% and interquartile range 30.9%–60.8% vs. 49.2% (42.1%–58.8%)). Neither did absolute infarct size in relation to left ventricular myocardial volume differ significantly (RIperpostC 20.6% (14.1%–31.7%) vs. control 17.9% (13.4%–25.0%)). The RIperpostC group had larger myocardial area at risk than the control group (43.1% (35.4%–49.7%) vs. 37.0% (30.8%–44.1%) of the left ventricle, P = .03). Peak value and area under the curve for troponin T did not differ significantly between the study groups. Conclusions RIperpostC initiated after admission to the catheterization laboratory in patients with anterior STEMI did not confer protection against reperfusion injury.
Objectives This study sought to compare fractional flow reserve (FFR) with the instantaneous wave-free ratio (iFR) in patients with coronary artery disease and also to determine whether the iFR is ...independent of hyperemia. Background FFR is a validated index of coronary stenosis severity. FFR-guided percutaneous coronary intervention (PCI) improves clinical outcomes compared to angiographic guidance alone. iFR has been proposed as a new index of stenosis severity that can be measured without adenosine. Methods We conducted a prospective, multicenter, international study of 206 consecutive patients referred for PCI and a retrospective analysis of 500 archived pressure recordings. Aortic and distal coronary pressures were measured in duplicate in patients under resting conditions and during intravenous adenosine infusion at 140 μg/kg/min. Results Compared to the FFR cut-off value of ≤0.80, the diagnostic accuracy of the iFR value of ≤0.80 was 60% (95% confidence interval CI: 53% to 67%) for all vessels studied and 51% (95% CI: 43% to 59%) for those patients with FFR in the range of 0.60 to 0.90. iFR was significantly influenced by the induction of hyperemia: mean ± SD iFR at rest was 0.82 ± 0.16 versus 0.64 ± 0.18 with hyperemia (p < 0.001). Receiver operating characteristics confirmed that the diagnostic accuracy of iFR was similar to resting Pd/Pa and trans-stenotic pressure gradient and significantly inferior to hyperemic iFR. Analysis of our retrospectively acquired dataset showed similar results. Conclusions iFR correlates weakly with FFR and is not independent of hyperemia. iFR cannot be recommended for clinical decision making in patients with coronary artery disease. (Comparison of Fractional Flow Reserve Versus Instant Wave-Free Ratio for Assessment of Coronary Artery Stenosis Severity in Routine Practice; NCT01559493 )
Abstract Objectives This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure ...(Pa), and the instantaneous wave-free ratio (iFR). Background FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. Methods We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. Results A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. Conclusions cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement.
Antibody-mediated rejection (AMR) after lung transplantation remains enigmatic, and there is no consensus on the characteristic clinical, immunologic and histologic features.
We performed a ...retrospective, single-center cohort study and identified cases of acute AMR based on the presence of circulating donor-specific human leukocyte antigen (HLA) antibodies (DSA), histologic evidence of acute lung injury, C4d deposition and clinical allograft dysfunction.
We identified 21 recipients with acute AMR based on the aforementioned criteria. AMR occurred a median 258 days after transplantation; 7 recipients developed AMR within 45 days of transplantation. All patients had clinical allograft dysfunction, DSA, histology of acute lung injury and capillary endothelial C4d deposition. Fifteen recipients improved clinically and survived to hospital discharge, but 6 died of refractory AMR. One survivor had bronchiolitis obliterans syndrome at the time of AMR diagnosis; 13 of the 14 remaining survivors developed chronic lung allograft dysfunction (CLAD) during follow-up. Overall, 15 recipients died during the study period, and the median survival after the diagnosis of AMR was 593 days.
Acute AMR can be a fulminant form of lung rejection, and survivors are at increased risk of developing CLAD. The constellation of acute lung injury, DSA and capillary endothelial C4d deposition is compelling for acute AMR in recipients with allograft dysfunction. This clinicopathologic definition requires validation in a multicenter cohort, but may serve as a foundation for future studies to further characterize AMR.
Lung volume reduction of emphysematous lobes results in clinical improvement for patients with severe emphysema. However, some segments within a lobe are often substantially more diseased than ...others, thereby warranting a more targeted approach of the emphysematous parts of a lobe. We therefore did a study to assess whether or not selective sequential treatment of the more diseased upper lobe segments with bronchoscopic vapour ablation led to clinical improvement.
For the multicentre, parallel-group, randomised, controlled, open-label Sequential Staged Treatment of Emphysema with Upper Lobe Predominance (STEP-UP) trial, adult patients aged 45-75 years with severe, upper lobe-predominant emphysema with a forced expiratory volume in 1 s (FEV1) between 20% and 45%, substantial hyperinflation, and post-rehabilitation 6-min walk test (6MWT) greater than 140 m were enrolled from 13 hospital sites in Europe (ten sites) and Australia (three sites). A computer-generated blocked randomisation scheme (block size three per site based on a random table from an independent biostatistician) stratified by site was used to randomly assign enrolled patients 2:1 to segmental vapour ablation (treatment group) or standard medical management (control group). Patients and investigators were not masked to group assignment. The primary efficacy endpoints were statistically significant changes in FEV1 and St George's Respiratory Questionnaire (SGRQ-C) scores between trial groups at 6 months, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01719263.
Between June 30, 2013, and Oct 1, 2014, 134 patients were screened and 70 were enrolled and randomly assigned: 46 to the treatment group and 24 to the control group. One patient in the treatment group did not receive treatment because of physician decision post-randomisation; this patient is excluded from all analyses. The mean relative improvement in FEV1 between the treatment group versus the control group was 14·7% (95% CI 7·8-21·5%; p<0·0001) and in SGRQ-C was -9·7 points (95% CI -15·7 to -3·7; p=0·0021). COPD exacerbation was the most common serious adverse event, occurring in 11 (24%) of 45 patients in the treatment group and one (4%) of 24 in the control group. One exacerbation resulted in a patient death 84 days after treatment; this was judged by the data and safety monitoring board to be possibly related to treatment. No pneumothorax occurred within 30 days of treatment.
Compared with standard medical management, targeted thermal vapour ablation of more diseased segments and preservation of less diseased segments resulted in clinically meaningful and statistically significant improvements in lung function and quality of life at 6 months, with an acceptable safety profile.
Uptake Medical.
Oral anticoagulation (OAC) is permanently discontinued in up to 50% of patients following a gastrointestinal (GI) bleed. A previous meta-analysis showed a reduced risk of thromboembolism and death, ...and a non-statistically significant increased risk of re-bleeding associated with resumption. We conducted an updated meta-analysis to determine the risks of recurrent GI bleeding, thromboembolism, and death in patients who resumed OAC compared to those who did not.
We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for new references from January 2014 to September 2017. Randomized controlled trials and observational studies involving adults with OAC-related GI bleeding were included. Risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooled relative risk (RR) ratios were calculated using a random-effects model.
We identified 12 observational studies involving 3098 patients. There was an increased risk of recurrent GI bleeding (RR 1.91, 95% CI 1.47–2.48, I2 = 0%, 11 studies), and a reduced risk of thromboembolism (RR 0.30, 95% CI 0.13–0.68, I2 = 59.8%, 9 studies) and death (RR 0.51, 95% CI 0.38–0.70, I2 = 71.8%, 8 studies) in patients who resumed OAC compared to those who did not. Eleven studies were judged to be at serious risk of bias due to confounding.
Resuming OAC after OAC-related GI bleeding appears to be associated with an increase in recurrent GI bleeding, but a reduction in thromboembolism and death. Further prospective data are needed to identify patients for whom the net clinical benefit favours OAC resumption and the optimal timing of resumption.
•40% of oral anticoagulant (OAC)-related bleeds are gastrointestinal (GI) bleeds.•OAC is discontinued in 41–51% of patients after a GI bleed.•Resuming OAC is associated with an increased risk of recurrent GI bleeding.•Resuming OAC is associated with a reduced risk of thromboembolism and mortality.
The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition ...of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation.
Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%.
110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients.
The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.
Background
Recent studies have created awareness that facial features can be reconstructed from high-resolution MRI. Therefore, data sharing in neuroimaging requires special attention to protect ...participants’ privacy. Facial features removal (FFR) could alleviate these concerns. We assessed the impact of three FFR methods on subsequent automated image analysis to obtain clinically relevant outcome measurements in three clinical groups.
Methods
FFR was performed using QuickShear, FaceMasking, and Defacing. In 110 subjects of Alzheimer’s Disease Neuroimaging Initiative, normalized brain volumes (NBV) were measured by SIENAX. In 70 multiple sclerosis patients of the MAGNIMS Study Group, lesion volumes (WMLV) were measured by lesion prediction algorithm in lesion segmentation toolbox. In 84 glioblastoma patients of the PICTURE Study Group, tumor volumes (GBV) were measured by BraTumIA. Failed analyses on FFR-processed images were recorded. Only cases in which all image analyses completed successfully were analyzed. Differences between outcomes obtained from FFR-processed and full images were assessed, by quantifying the intra-class correlation coefficient (ICC) for absolute agreement and by testing for systematic differences using paired
t
tests.
Results
Automated analysis methods failed in 0–19% of cases in FFR-processed images versus 0–2% of cases in full images. ICC for absolute agreement ranged from 0.312 (GBV after FaceMasking) to 0.998 (WMLV after Defacing). FaceMasking yielded higher NBV (
p
= 0.003) and WMLV (
p
≤ 0.001). GBV was lower after QuickShear and Defacing (both
p
< 0.001).
Conclusions
All three outcome measures were affected differently by FFR, including failure of analysis methods and both “random” variation and systematic differences. Further study is warranted to ensure high-quality neuroimaging research while protecting participants’ privacy.
Key Points
•
Protecting participants’ privacy when sharing MRI data is important
.
•
Impact of three facial features removal methods on subsequent analysis was assessed in three clinical groups
.
•
Removing facial features degrades performance of image analysis methods
.
PDF
