The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multiomics analyses of bone marrow–confined intramedullary disease and paired breakout lesions that disrupt the cortical bone. These analyses revealed a distinct cellular microenvironment and architectural features of breakout lesions, characterized by extensive areas of malignant plasma cells interspersed with lesion-specific solitary natural killer and macrophage populations, as well as focal accumulations of immune cell agglomerates. Within these agglomerates, spatially confined T cell clones expanded alongside various immune cells, coinciding with the local genomic evolution of tumor cells. These analyses identify breakout lesions as a hotspot for tumor-immune cell interactions and diversification, representing a key event in myeloma pathogenesis.
Chêneau-brace (C-Brace) is a potential tool for the treatment of adolescent idiopathic scoliosis (AIS) with a Cobb angle between 20° and 45° for the primary curve. The aim of the present study was (1) to estimate study cohorts with C-brace therapy success and therapy failure and (2) to analyze possible factors that influence the therapy outcome. Seventy-eight patients with AIS were assessed before the initiation of C-brace treatment. Each patient underwent radiography examinations before the brace, in-brace, and at the therapy end. Cobb angle was considered as increased when the value at the end of therapy was increased more than 5° (Δ > 5°), unchanged—when the value was unchanged within ± 5° and decreased- when the value was decreased more than 5° (Δ < −5°). The study cohort was stratified due to curve topography in the thoracic, thoracolumbar, and lumbar scoliosis groups. Global analysis revealed no statistically significant modification of the Cobb angle (Cobb angle pre-brace vs. Cobb angle post-brace: 30.8° ± 8.2 vs. 29.3° ± 15.2, p = 0.26). However, at the end of C-brace therapy, the primary Cobb angle was decreased by more than 5° in 27 patients (35%), unchanged (Δ within the range of ±5°) in 36 patients (46%), and increased more than 5° in 15 patients (19%). Sub-group analysis due to curve topography and skeletal maturity has shown higher rates of brace therapy failure in thoracic curves and in younger patients (Risser grade 0). Patients with higher Cobb angle correction with C-brace had lower rates of therapy failure. The C-brace can be useful for the prevention of scoliotic curve progression in patients with AIS. However, many factors influence the therapy effect.
Sports are relevant to younger populations in society. Adolescent idiopathic scoliosis (AIS) patients who undergo surgical correction of the spine are often intensively involved in sports. For that, returning to the sport is often an important concern for the patients and their families. To the best of our knowledge, there is still a lack of scientific data indicating established recommendations about the time of returning to sport activities after surgical spinal correction. The aim of this study was to investigate (1) when AIS patients return to athletic activities after a posterior fusion, and (2) if they change their activities postoperatively. Furthermore, another question was (3) if the length of the performed posterior fusion or (4) fusion to the lower lumbar spine could have an influence on the rates or time of returning to sport activities postoperatively. Data collection was performed using questionnaires assessing patients’ contentment and athletic activity. Athletic activities were categorized into three categories: (1) contact, (2) contact/non-contact and (3) non-contact sports. The intensity of exercised sports, the time of returning to the sport and changes in sport habits were documented. Radiographs were evaluated pre- and postoperatively to determine the Cobb angle and the length of the posterior fusion via the identification of the upper (UIV) and lower instrumented vertebra (LIV). Stratification analysis due to the fusion length was performed to answer a hypothetical question. This retrospective survery of 113 AIS patients treated with a posterior fusion revealed that, on average, returning to sport activities required 8 months of postoperative rest. The preoperative to postoperative rate of patients participating in sport activities increased from 88 (78%) to 94 (89%). Furthermore, postoperatively, a relevant shift of exercised activities from contact to non-contact sports was noted. Further subanalysis revealed that only 33 subjects were able to return to exactly the same athletic activities as before surgery (10 months postoperatively). The assessment of radiographs revealed that in this study group, the length of the performed posterior fusion and fusions to the lower lumbar spine had no influence on the time of return to athletic activities. The results of this study might shed some light on postoperative recommendations for sport activities after AIS treatment with a posterior fusion and may be beneficial for surgeons treating patients.
Chêneau-brace is an effective therapy tool for treatment in adolescent idiopathic scoliosis (AIS). Data on potential interdependent changes of the sagittal profile including the cervical spine are still sparse. The purpose of this study was to evaluate in-brace changes of the thoracic and lumbar spine and their influence on the pelvis and the cervical spine and apical vertebral rotation was reported. Ninety-three patients with AIS undergoing Chêneau-bracing were included. Patients were stratified by lumbar, thoracic and global spine alignment into normolordotic vs. hyperlordotic or normokyphotic vs. hypokyphotic or anteriorly aligned vs. posteriorly aligned groups. The coronal Cobb angle was significantly decreased in all groups indicating good correction while in-brace therapy. Sagittally, in-brace treatment led to significant flattening of lumbar lordosis (LL) in all stratified groups. Thoracic kyphosis (TK) was significantly flattened in the normokyphotic group, but no TK changes were noticed in the hypokyphotic group. Pelvic tilt (PT) stayed unchanged during the in-brace therapy. Chêneau-brace showed marginal changes in the lower cervical spine but had no influence on the upper cervical spine. The apical vertebral axis in primary and secondary curves was unchanged during the first radiological follow-up. Results from this study contribute to better understanding of initial spine behavior in sagittal and axial plane in the context of bracing.
Background: Spinal infections represent a therapeutic challenge. The often protracted course of the disease is accompanied by pain, which can lead to a chronic pain experience even after the infectious disease has been treated successfully. The aim of this study was to investigate possible risk factors of pain chronification. Methods: In a prospective study, 14 patients with spinal infections were examined at admission (T1), at discharge from inpatient therapy (T2), and three to eight months postoperatively (T3) byquestionnaires on risk factors for pain chronification and by quantitative sensory testing (QST). Results: In-patient treatment lasted on average 45.3 days (±33.13). The patients complained of pain for 3.43 months (±2.77) prior to inpatient treatment. The visual analogue scale (VAS) for pain (0–10) and the Oswestry Disability Index detected significant improvement in the course of the study. However, patients also reported catastrophic thinking, as well as fear of movement and (re)-injury. Conclusion: In summary, our results demonstrate that patients with spinal infections did not suffer from pain chronification, but might benefit from an interdisciplinary therapeutic approach, which emphasizes promoting active pain-coping strategies, as well as addressing fear of movement and catastrophic thinking.