Cost-Effectiveness Analysis of Pertuzumab With Trastuzumab and Chemotherapy Compared to Trastuzumab and Chemotherapy in the Adjuvant Treatment of HER2-Positive Breast Cancer in the United States.

OBJECTIVE: The APHINITY trial assessed the effectiveness and the safety of adding pertuzumab to trastuzumab and chemotherapy (THP) compared to trastuzumab and chemotherapy (TH) in the adjuvant management of human epidermal growth factor 2-positive (HER2+) breast cancer. We performed a study to project the potential cost-effectiveness of THP vs. TH. STUDY DESIGN: Trial-based cost-utility modeling analysis. METHODS: We performed an economic evaluation from a payer perspective using a Markov model with six health states: invasive disease-free survival, non-metastatic recurrence, remission, first-line metastatic, subsequent line metastatic, and death. We parameterized the model using data from both arms in APHINITY extrapolated to a patient's lifetime horizon. Estimates of health state utilities were based on EQ-5D trial data and the literature, and costs were estimated from government sources and the published literature. The primary outcomes of the model were life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed via univariate and probabilistic sensitivity analyses. RESULTS: For the intention-to-treat population, the model projected improved outcomes (by 0.50 LYs and 0.45 QALYs) and increased costs (by $74 420) for ICERs of $147 774/LY gained and $167 185/QALY gained for PHT vs. HT patients. In the node-positive patient population, the model projected improved outcomes (by 0.86 LYs and 0.76 QALYs) and increased costs (by $66 647) for ICERs of $77 684/LY gained and $87 929/QALY gained. For the hormone-receptor-negative patient population, the model projected health gains, increased costs, and ICERs of $147 022/LY gained and $166 518/QALY gained. The results were sensitive to changes in the model time horizon. CONCLUSION: The addition of pertuzumab to the available regimens for HER2+ early breast cancer is likely to be cost-effective for patients in the U.S. at high risk of recurrence.

Post-trauma scoliosis after conservative treatment of thoracolumbar spinal fracture in children and adolescents: results in 48 patients.

PURPOSE: Authors examined a case series of patients younger than 18 years old who had sustained a traumatic thoracolumbar spine fracture to evaluate radiological and clinical findings of coronal spinal balance, after conservative treatment. METHODS: From 1996 to 2014, a tricentric cohort of 48 patients with an average age of 12 years was radiographically reviewed at 50 months. Cobb angle of fractured vertebra and regional Cobb angle were measured both at baseline and follow-up. Analyses were done according to initial Risser grade, number of fractures and level of injury. RESULTS: There was a total of 11 scoliosis. In group with Risser grade 3 or above, with a single vertebral fracture and lumbar fracture, final regional Cobb angle was statistically higher than initial regional Cobb angle. CONCLUSIONS: The prevalence of scoliosis in our population is higher than those of idiopathic scoliosis; Risser grade 3 or above, lumbar fracture and a single fracture seem to account for more severe coronal deformation.

Bone morphogenetic protein use in spine surgery-complications and outcomes: a systematic review.

PURPOSE: Because of significant complications related to the use of autologous bone grafts in spinal fusion surgery, bone substitutes and growth factors such as bone morphogenetic protein (BMP) have been developed. One of them, recombinant human (rh) BMP-2, has been approved by the Food and Drug Administration (FDA) for use under precise conditions. However, rhBMP-2-related side effects have been reported, used in FDA-approved procedures, but also in off-label use.A systematic review of clinical data was conducted to analyse the rhBMP-2-related adverse events (AEs), in order to assess their prevalence and the associated surgery practices. METHODS: Medline search with keywords "bone morphogenetic protein 2", "lumbar spine", "anterolateral interbody fusion" (ALIF) and the filter "clinical trial". FDA published reports were also included. Study assessment was made by authors (experienced spine surgeons), based on quality of study designs and level of evidence. RESULTS: Extensive review of randomised controlled trials (RCTs) and controlled series published up to the present point, reveal no evidence of a significant increase of AEs related to rhBMP-2 use during ALIF surgeries, provided that it is used following FDA guidelines. Two additional RCTs performed with rhBMP-2 in combination with allogenic bone dowels reported increased bone remodelling in BMP-treated patients. This AE was transient and had no consequence on the clinical outcome of the patients. No other BMP-related AEs were reported in these studies. CONCLUSIONS: This literature review confirms that the use of rhBMP-2 following FDA-approved recommendations (i.e. one-level ALIF surgery with an LT-cage) is safe. The rate of complications is low and the AEs had been identified by the FDA during the pre-marketing clinical trials. The clinical efficiency of rhBMP-2 is equal or superior to that of allogenic or autologous bone graft in respect to fusion rate, low back pain disability, patient satisfaction and rate of re-operations. For all other off-label use, the safety and effectiveness of rhBMP-2 have not been established, and further RCTs with high level of evidence are required.

Clinical and radiological outcome after arthroscopic rotator cuff repair using PEEK-CF anchors.

PURPOSE: The goal of this study was to evaluate the clinical and radiological outcome after arthroscopic rotator cuff repair using new carbonfiber reinforced polyetheretherketone (CF-PEEK) suture anchors. METHODS: One hundred (n=100) patients with rotator cuff tears were enrolled at seven French hospitals between July 2019 and June 2020. Pain levels, Constant score and Subjective Shoulder Value (SSV) were taken preoperatively and 6months postoperatively. Ultrasonography (US) was performed at 6months postoperatively to evaluate tendon healing using the Sugaya classification. Statistical analysis was done with the Student t-test with 95% confidence intervals. RESULTS: One hundred patients of the 100 patients were followed at 6months. The mean SSV and Constant score improved from 40.1% preoperatively to 78% at 6months (p<0.0001) and from 43 points preoperatively to 65 points at 6months (p<0.0001), respectively. The mean level of pain, as measured with the visual analogue scale, decreased from 5.9 to 1.6 (p<0.001). There were no postoperative complications that resulted in revision surgery. CONCLUSION: The study showed good results at 6months follow-up using carbonfiber reinforced PEEK anchors with improved Constant and SSV scores as well as a high ultrasonographic tendon healing rate, making PEEK-CF anchors safe to use, comparable to commonly used anchors. LEVEL OF EVIDENCE: IV.

Conservative treatment of pediatric thoracic and lumbar spinal fractures: outcomes in the sagittal plane.

To assess sagittal plane spinopelvic balance and functional outcomes in a pediatric cohort of patients with a thoracic and/or a lumbar fracture treated conservatively. A multicentric study retrospectively reviewed radiological and functional outcomes (mean follow-up 49 months) of 48 patients (mean age 12 years) with thoracic and/or lumbar spinal fractures that occurred between 1996 and 2014. Demographic data and radiological spinopelvic parameters were analyzed. Functional outcome was evaluated by a telephone interview. First, a comparison between the initial and the last follow-up full-spine radiographs was performed for the assessment of bone remodeling and sagittal plane balance. Then, patients were classified into two groups (group 1: Risser≤2 and group 2, Risser>2) to assess the influence of skeletal maturity on the restoration of a correct sagittal balance. A total of 62% of the patients were at skeletal maturity at the final follow-up (Risser 4 and 5). Patients with a Risser grade of 2 or less had a higher remodeling potential. The mean residual local kyphosis in thoracic and lumbar fractures was, respectively, 8.2° and 8.7°. The mean thoracic global kyphosis remains stable at the last follow-up, in contrast to lumbar lordosis, which increased significantly. Sagittal plane global measurements on the basis of the C7-plumbline remained unchanged at the last follow-up. There was no change in the pelvic parameters, except for the sacral slope in the group 1 for patients with a lumbar fracture. The current study confirms a greater correction in younger patients (Risser≤2) in spinal fractures and reported that thoracic fractures have a higher remodeling potential than lumbar fracture. A local kyphosis of almost 10° remained at the last follow-up. However, no deterioration in the sagittal plane balance was found. This suggests compensatory mechanisms in adjacent structures for children and adolescents and excludes the only hypothesis of bone remodeling.

3D anatomical and perfusion MRI for longitudinal evaluation of biomaterials for bone regeneration of femoral bone defect in rats.

Magnetic Resonance Imaging (MRI) appears as a good surrogate to Computed Tomography (CT) scan as it does not involve radiation. In this context, a 3D anatomical and perfusion MR imaging protocol was developed to follow the evolution of bone regeneration and the neo-vascularization in femoral bone defects in rats. For this, three different biomaterials based on Pullulan-Dextran and containing either Fucoidan or HydroxyApatite or both were implanted. In vivo MRI, ex vivo micro-CT and histology were performed 1, 3 and 5 weeks after implantation. The high spatially resolved (156 × 182 × 195 µm) anatomical images showed a high contrast from the defects filled with biomaterials that decreased over time due to bone formation. The 3D Dynamic Contrast Enhanced (DCE) imaging with high temporal resolution (1 image/19 s) enabled to detect a modification in the Area-Under-The-Gadolinium-Curve over the weeks post implantation. The high sensitivity of MRI enabled to distinguish which biomaterial was the least efficient for bone regeneration, which was confirmed by micro-CT images and by a lower vessel density observed by histology. In conclusion, the methodology developed here highlights the efficiency of longitudinal MRI for tissue engineering as a routine small animal exam.

Morphological changes of the multifidus muscle in patients with symptomatic lumbar disc herniation.

OBJECT: Lumbar disc herniations are associated with segmental muscle alterations of the ipsilateral segmental multifidus muscle. The aim of the present study was a histopathological analysis of the myopathological changes of the multifidus muscle and correlation with the duration of radicular symptoms. METHODS: Multifidus muscle biopsies were performed in 20 patients during discectomy. Specimens were obtained from the area of the multifidus muscle innervated by the nerve from the level of the affected disc. Histopathological findings were classified according as neurogenic tissue syndrome and nonspecific myopathological syndrome, and these results were correlated with the duration of radicular symptoms. RESULTS: Results of multifidus muscle biopsies were classified as neurogenic tissue syndrome in 12 patients and as nonspecific myopathological syndrome in 8. The mean (+/- SD) duration of radicular symptoms was 10.75 +/- 7.9 months in patients with neurogenic tissue syndrome and 4.37 +/- 3.9 months in patients with a nonspecific myopathological syndrome. There was a positive correlation between group assignment and symptom duration (correlation coefficient 0.457, p = 0.043). CONCLUSIONS: A long duration of radicular symptoms is associated with a neurogenic tissue syndrome, whereas a nonspecific myopathological tissue syndrome is seen in patients with shorter duration of symptoms. This suggests that patients with long duration of radicular symptoms originating from a lumbar disc herniation have an increased risk for neurogenic muscular changes, and that consideration should be given to an earlier surgical intervention.

Lumbar decompression and fusion in elderly osteoporotic patients: a prospective study using less rigid titanium rod fixation.

TYPE OF STUDY: A 2 to 4-year clinical and radiologic prospective study was conducted for 39 patients over the age of 65 treated by lumbar arthrodesis. OBJECTIVES: Evaluate the quality of lumbar arthrodesis results in elderly patients, in which the bone osteoporosis (poor quality of the spine's anatomic components) and general factors (frequent comorbidity) are likely to make this surgery difficult if not dangerous and evaluate a dedicated instrumentation for osteoporotic bone. MATERIALS AND METHODS: Thirty-nine patients over 65 years of age (average 73 y) underwent arthrodesis surgery in 2001 and 2002 and were followed for at least 2 years. The instrumentation used (Equation, Medtronic, Memphis, USA) was selected for its mechanical properties adapted for bone of poor mechanical quality. The clinical analysis was based on Oswestry, Visual Analog Scale, and Japanese Orthopaedic Association scores. Radiologic results were evaluated on standard anteroposterior, lateral, and 3/4 radiographs, and computed tomography scans if necessary. RESULTS: All the patients were followed for 2 to 4 years. Clinical analysis confirmed a very satisfactory progression of the clinical parameters such as lumbar and radicular pain, and the results were maintained between the first and second years and at last follow-up. No serious general complication or need for reoperation was seen in this series. On x-rays, 35 grafts appear to have fused. The anchors did not come out nor did the instrumentation come apart. On the other hand, 2-year radiographs revealed that 2 screws and 2 rods had failed, but this did not affect correction in the 4 completely asymptomatic patients. These 4 cases are considered stable at last follow-up. CONCLUSIONS: Arthrodesis for elderly patients will undoubtedly increase in the coming years. The conditions for this surgery are different than those for younger patients and it is desirable to try to provide reliable surgical techniques and solutions regarding options for instrumentation and overall perioperative care for these fragile patients. Dedicated instrumentation for osteoporotic bone seems to allow good clinical outcomes.