The indication of fusion to the pelvis in neuromuscular scoliosis is based on the underlying disease rather than on pelvic obliquity.

INTRODUCTION: The decision to instrument to L5 or ilium, in NMS, is usually based on radiologic factors, including pelvic obliquity (PO) > 15°, apex of curvature < L3, and Cobb angle > 60°. Since scoliosis in these patients is caused by a neurologic disease, we based our decision to stop at L5 on the presence of spasticity or flaccidity. PATIENTS & METHODS: The senior author did 109 primary fusions in NMS. Of those with DMD or SMA only 16% were instrumented to the ilium. The main factor for our decision was the correction potential of the truncal shift and PO in the supine traction radiographs and the absence of severe spasticity. RESULTS: The 57 patients with DMD/SMA had a mean preoperative curvature of 68°, PO of 17°, and truncal shift of 20°. 74% should have been instrumented to the pelvis, but only 16% were. Those instrumented shorter as the rule, were corrected from 74° to 26° and had a postoperative PO of 8°. There was no significant difference in postoperative correction and PO compared to those instrumented to L5 on standard protocol. Subsequent extension to the pelvis was needed in 1 CP patient. There were no significant changes after 2 years. Of the 20 patients instrumented to the pelvis 11 had cerebral palsy and a preop curvature of 89°, a PO of 21° and a truncal shift of 25°. DISCUSSION: The decision on instrumentation length should take flexibility and disease into consideration. If the trunk is centred over the pelvis, deterioration will not occur in absence of spasticity.

Derotation screws provide no advantage over polyaxial screws regarding coronal & sagittal correction in thoracic curves of AIS patients.

PURPOSE: We compared two techniques for thoracic apical derotation; one using conventional reduction screws (Single-Innie-SI) and one requiring special derotation screws that can be converted to monoaxial screws to enhance dorotation (Dual-Innie-DI) for coronal and sagittal correction and. METHODS: A total of 200 patients with thoracic AIS have been included. In the SI-Group (n = 127) the convex rod was applied first. Vertebral derotation was done by translation to the concave rod with the convex rod being in place and center of rotation (COR). In the DI-Group (n = 73) correction started with translation on the concave side as well but now followed by derotation around the concave rod using the DI-mechanism. RESULTS: The mean rotation according to Raimondi and coronal correction was not sig. affected (72 (± 12) % in the SI-Group versus 68 (± 15) % in the DI-Group), even when flexibility was respected (Cincinnati Correction Index CCI was 2.9 (± 4.9) versus 3.5 (± 4.4). (p < 0.01). The gain of kyphosis was sig greater (2.7°) in the SI-group, but not clinical relevant. CONCLUSION: The use of DI screws for apical derotation did not provide an advantage for coronal correction or derotation in thoracic curves. Presumably after translation is performed in the DI-group, there was too much tension and friction in the construct impeding further derotation. Simultaneous translation and derotation in the SI-group, with the convex rod being the COR, yielded similar correction with better kyphosis and was faster and more economic.

Artificial intelligence facilitates decision-making in the treatment of lumbar disc herniations.

PURPOSE: Apart from patients with severe neurological deficits, it is not clear whether surgical or conservative treatment of lumbar disc herniations is superior for the individual patient. We investigated whether deep learning techniques can predict the outcome of patients with lumbar disc herniation after 6 months of treatment. METHODS: The data of 60 patients were used to train and test a deep learning algorithm with the aim to achieve an accurate prediction of the ODI 6 months after surgery or the start of conservative therapy. We developed an algorithm that predicts the ODI of 6 randomly selected test patients in tenfold cross-validation. RESULTS: A 100% accurate prediction of an ODI range could be achieved by dividing the ODI scale into 12% sections. A maximum absolute difference of only 3.4% between individually predicted and actual ODI after 6 months of a given therapy was achieved with our most powerful model. The application of artificial intelligence as shown in this work also allowed to compare the actual patient values after 6 months with the prediction for the alternative therapy, showing deviations up to 18.8%. CONCLUSION: Deep learning in the supervised form applied here can identify patients at an early stage who would benefit from conservative therapy, and on the contrary avoid painful and unnecessary delays for patients who would profit from surgical therapy. In addition, this approach can be used in many other areas of medicine as an effective tool for decision-making when choosing between opposing treatment options, despite small patient groups.

Mucosal layers and related nerve fibres in non-chagasic and chagasic human colon--a quantitative immunohistochemical study.

Chagasic megacolon is accompanied by extensive myenteric and, simultaneously, moderate submucosal neuron loss. Here, we examined changes of the innervation pattern of the lamina propria (LP) and muscularis mucosae (MM). Two alternating sets of cryosections were taken from seven non-chagasic colonic and seven chagasic megacolonic specimens (the latter included both the dilated megacolonic and the non-dilated transitional oral and anal zones) and were immunohistochemically triple-stained for smooth-muscle actin (SMA), synaptophysin (SYN) and glial acid protein S100 and, alternatively, for SMA, vasoactive intestinal peptide (VIP) and somatostatin (SOM). Subsequent image analysis and statistical evaluation of nervous tissue profile areas revealed that, in LP, the most extreme differences (i.e. increase in thickness or decrease in nerve, glia and muscle tissue profile area, respectively) compared with control values occurred in the dilated megacolonic zone itself. In contrast, the most extreme differences in the MM were in the anal-to-megacolonic zone (except the profile area of muscle tissue, which was lowest in the megacolonic zone). This parallels our previous results in the external muscle coat. A partial and selective survival of VIP-immunoreactive in contrast to SOM-immunoreactive nerve fibres was observed in both mucosal layers investigated. Thus, VIPergic nerve elements might be crucial for the maintenance of the mucosal barrier. The differential changes of neural tissue parameters in LP and MM might reflect a multifactorial rather than a pure neurogenic development of megacolon in chronic Chagas' disease.

Is the anterior approach still superior to posterior correction in AIS regarding correction, fusion levels and kyphosis when modern posterior systems are used?

PURPOSE: The aim of our study is to compare anterior and posterior corrections of thoracic (Lenke I) and lumbar (Lenke V) curves when modern posterior pedicle screw systems with vertebral derotation techniques are used. Curves that could not be corrected with both systems were excluded. METHODS: A thoracic group (N = 56) of Lenke I AIS patients (18 anterior and 38 posterior) and a lumbar group (N = 42) of Lenke V patients (14 anterior and 28 posterior) with similar curves < 65° were identified. RESULTS: Thoracic group The mean postoperative correction (POC) was 68 ± 13.4% in the anterior and 72 ± 10.5% in the posterior group. The postoperative change in thoracic kyphosis was +4° and +5° respectively. The median length of fusion was eight segments in the posterior and seven segments in the anterior groups. In 89% the LIV was EV or shorter in the anterior, and in 71% of the posterior corrections. Lumbar group The mean POC was 75 ± 18.3% (anterior) and 72 ± 8.5% (posterior). The postoperative gain in lumbar lordosis was 0.8° (anterior) and 4° (posterior). The median length of fusion was five segments in both groups and there was no difference in relation of the LIV to the EV. CONCLUSION: With modern implants and derotation techniques, the posterior approach can achieve similar coronal correction, apical derotation and thoracic kyphosis with similar length of fusion and better lumbar lordosis restoration.

An Evolution Gaining Momentum-The Growing Role of Artificial Intelligence in the Diagnosis and Treatment of Spinal Diseases.

In recent years, applications using artificial intelligence have been gaining importance in the diagnosis and treatment of spinal diseases. In our review, we describe the basic features of artificial intelligence which are currently applied in the field of spine diagnosis and treatment, and we provide an orientation of the recent technical developments and their applications. Furthermore, we point out the possible limitations and challenges in dealing with such technological advances. Despite the momentary limitations in practical application, artificial intelligence is gaining ground in the field of spine treatment. As an applying physician, it is therefore necessary to engage with it in order to benefit from those advances in the interest of the patient and to prevent these applications being misused by non-medical partners.

AI Prediction of Neuropathic Pain after Lumbar Disc Herniation-Machine Learning Reveals Influencing Factors.

The treatment options for neuropathic pain caused by lumbar disc herniation have been debated controversially in the literature. Whether surgical or conservative therapy makes more sense in individual cases can hardly be answered. We have investigated whether a machine learning-based prediction of outcome, regarding neuropathic pain development, after lumbar disc herniation treatment is possible. The extensive datasets of 123 consecutive patients were used to predict the development of neuropathic pain, measured by a visual analogue scale (VAS) for leg pain and the Oswestry Disability Index (ODI), at 6 weeks, 6 months and 1 year after treatment of lumbar disc herniation in a machine learning approach. Using a decision tree regressor algorithm, a prediction quality within the limits of the minimum clinically important difference for the VAS and ODI value could be achieved. An analysis of the influencing factors of the algorithm reveals the important role of psychological factors as well as body weight and age with pre-existing conditions for an accurate prediction of neuropathic pain. The machine learning algorithm developed here can enable an assessment of the course of treatment after lumbar disc herniation. The early, comparative individual prediction of a therapy outcome is important to avoid unnecessary surgical therapies as well as insufficient conservative therapies and prevent the chronification of neuropathic pain.

Combined Artificial Intelligence Approaches Analyzing 1000 Conservative Patients with Back Pain-A Methodological Pathway to Predicting Treatment Efficacy and Diagnostic Groups.

Patients with back pain are common and present a challenge in everyday medical practice due to the multitude of possible causes and the individual effects of treatments. Predicting causes and therapy efficien cy with the help of artificial intelligence could improve and simplify the treatment. In an exemplary collective of 1000 conservatively treated back pain patients, it was investigated whether the prediction of therapy efficiency and the underlying diagnosis is possible by combining different artificial intelligence approaches. For this purpose, supervised and unsupervised artificial intelligence methods were analyzed and a methodology for combining the predictions was developed. Supervised AI is suitable for predicting therapy efficiency at the borderline of minimal clinical difference. Non-supervised AI can show patterns in the dataset. We can show that the identification of the underlying diagnostic groups only becomes possible through a combination of different AI approaches and the baseline data. The presented methodology for the combined application of artificial intelligence algorithms shows a transferable path to establish correlations in heterogeneous data sets when individual AI approaches only provide weak results.

Open versus minimally invasive TLIF: literature review and meta-analysis.

STUDY DESIGN: This study is a comparative, literature review. OBJECTIVE: The aim of this study is to provide a comparative analysis of open vs. minimally invasive TLIF using a literature review and a meta-analysis. Lumbar interbody fusion is a well-established surgical procedure for treating several spinal disorders. Transforaminal lumbar interbody fusion (TLIF) was initially introduced in the early 1980s. To reduce approach-related morbidity associated with traditional open TLIF (OTLIF), minimally invasive TLIF (MITLIF) was developed. We aimed to provide a comparative analysis of open vs. minimally invasive TLIF using a literature review. METHODS: We searched the online database PubMed (2005-2017), which yielded an initial 194 studies. We first searched the articles' abstracts. Based on our inclusion criteria, we excluded 162 studies and included 32 studies: 18 prospective, 13 retrospective, and a single randomized controlled trial. Operative time, blood loss, length of hospital stay, radiation exposure time, complication rate, and pain scores (visual analogue scale, Oswestry Disability Index) for both techniques were recorded and presented as means. We then performed a meta-analysis. RESULTS: The meta-analysis for all outcomes showed reduced blood loss (P < 0.00001) and length of hospital stay (P < 0.00001) for MITLIF compared with OTLIF, but with increased radiation exposure time with MITLIF (P < 0.00001). There was no significant difference in operative time between techniques (P = 0.78). The complication rate was lower with MITLIF (11.3%) vs. OTLIF (14.2%), but not statistically significantly different (P = 0.05). No significant differences were found in visual analogue scores (back and leg) and Oswestry Disability Index scores between techniques, at the final follow-up. CONCLUSION: MITLIF and OTLIF provide equivalent long-term clinical outcomes. MITLIF had less tissue injury, blood loss, and length of hospital stay. MITLIF is also a safe alternative in obese patients and, in experienced hands, can also be used safely in select cases of spondylodiscitis even with epidural abscess. MITLIF is also a cost-saving procedure associated with reduced hospital and social costs. Long-term studies are required to better evaluate controversial items such as operative time.

Panobinostat mediated cell death: a novel therapeutic approach for osteosarcoma.

Osteosarcoma is an aggressive cancer with a poor long term prognosis. Neo-adjuvant poly-chemotherapy followed by surgical resection remains the standard treatment, which is restricted by multi-drug resistance. If first-line therapy fails, disease control and patient survival rate drop dramatically. We aimed to identify alternative apoptotic mechanisms induced by the histone deacetylase inhibitor panobinostat in osteosarcoma cells. Saos-2, MG63 and U2-OS osteosarcoma cell lines, the immortalized human osteoblast line hFOB and the mouse embryo osteoblasts (MC3T3-E1) were treated with panobinostat. Real time viability and FACS confirmed the cytotoxicity of panobinostat. Cell stress/death related factors were analysed by RT-qPCR and western blot. Cell morphology was assessed by electron microscopy. 10 nM panobinostat caused cell viability arrest and death in all osteosarcoma and osteoblast cells. P21 up-regulation was observed in osteosarcoma cells, while over-expression of p73 was restricted to Saos-2 (TP53-/-). Survivin and Bcl-2 were suppressed by panobinostat. Endoplasmic reticulum (ER) stress markers BiP, CHOP, ATF4 and ATF6 were induced in osteosarcoma cells. The un-spliced Xbp was no further detectable after treatment. Autophagy players Beclin1, Map1LC3B and UVRAG transcripts over-expressed after 6 hours. Protein levels of Beclin1, Map1LC3B and p62 were up-regulated at 72 hours. DRAM1 was stable. Electron micrographs revealed the fragmentation and the disappearance of the ER and the statistically significant increase of autophagosome vesiculation after treatment. Panobinostat showed a synergistic suppression of survival and promotion of cell death in osteosarcoma cells. Panobinostat offers new perspectives for the treatment of osteosarcoma and other malignant bone tumours.

The distal radius fracture: concomitant fractures and their relevancy.

BACKGROUND: The distal radius keeps heading the list of commonly fractured bones. Although little is known about the frequency and localization of accompanying fractures as well as their influence on the total course of in-patient treatment. OBJECTIVE: This study is supposed to show the influence of concomitant fractures. These fractures should be identified as risk factors for a prolonged stay to improve the in hospital treatment. METHODS: We retrospectively reviewed 721 patients with distal radius fracture. Frequency and localization of concomitant fractures, AO-type, patient age as well as duration of in-hospital treatment were analyzed. RESULTS: Out of 721 patients 124 (17.2%) had one or more concomitant fractures (CF). The most common CF were proximal femur fractures, pelvic ring fractures and humerus fractures. Compared to patients without CF, these patients showed a significant increase in duration of post operative hospital stay (5.2 vs. 12.5 days, p=0.0001). CONCLUSIONS: Patients presenting a concomitant fracture should be thoroughly cared for by their physicians and therapists. Especially an early and focused mobilization and a well-timed relocation for further medical treatment are important to reduce avoidable treatment days in the acute care hospital.

Early magnetic resonance imaging in spinal cord injury without radiological abnormality in adults: a retrospective study.

BACKGROUND: The purpose of this study was to describe the clinical and imaging characteristics of patients experiencing blunt spinal trauma without radiological abnormalities but transient or persistent neurological deficits. METHODS: This retrospective study analyzed plain radiographs, computed tomographic scans, and magnetic resonance images of patients with spinal cord injury without radiological abnormality (SCIWORA) who were admitted to a Level I trauma center. Neurologic status, Frankel grade, and short-term patient outcome were assessed. RESULTS: Of 1,604 patients experiencing blunt spinal trauma, 21 (12 men and 9 women) with a mean age of 35.5 years (range, 16.2-70.9 years) presented with a clinicoradiographic mismatch. Magnetic resonance imaging (MRI) was available in 15 patients. In seven patients (46.6%), MRI revealed either neural (n = 2, 13.3%) or extraneural (n = 5, 33.3%) spinal abnormalities. Importantly, in eight patients (53.3%), no spinal abnormalities were visible on MRI. Furthermore, subgroup analysis revealed no prognostic value regarding the presence or absence of detectable spinal injuries. CONCLUSION: Spinal abnormalities were not detected on MRI in a substantial proportion of patients presenting with SCIWORA. The prognostic value of MRI findings in SCIWORA needs to be validated by future studies. LEVEL OF EVIDENCE: Epidemiological study, level V.

Thymoquinone accelerates osteoblast differentiation and activates bone morphogenetic protein-2 and ERK pathway.

Thymoquinone (TQ), the active component of Nigella sativa L. is well known for its various beneficial effects against several diseases. However, its detailed effect on bone metabolism has not been studied before. Therefore, the aim of the present study is to evaluate the effect of TQ on the proliferation, differentiation, and mineralization of MC3T3-E1 osteoblast cells. Our data shows that TQ induced the proliferation of MC3T3-E1 cells and proved to be non-toxic for up to 72 h of incubation. TQ induced the mineralization of MC3T3-E1 cells as evidenced by an increase in bone nodule formation 14 days post TQ treatment. qRT-PCR analysis shows that TQ induced the expression levels of differentiation related genes including alkaline phosphatase, osteocalcin, and osteopontin, while no effect was seen on collagen 1a1. TQ also induced the expression levels of bone morphogenetic protein-2 (BMP-2) and upregulated the phosphorylation of ERK signaling pathway. In summary, the present study shows for the first time that TQ has anabolic effects on MC3T3-E1 cells and that this effect is mediated by an increase in the expression of BMP-2 along with the involvement of the ERK signaling pathway. This study also reveals that TQ may be beneficial in inducing osteogenesis.

Anterior cruciate ligament reconstruction using quadriceps tendon autograft for adolescents with open physes- a technical note.

BACKGROUND: One major concern in the treatment of ACL lesions in children and adolescents with open physes is the risk of iatrogenic damage to the physes and a possibly resulting growth disturbance. PURPOSE: The primary purpose of this article is to describe our technique of a transphyseal ACL reconstruction using quadriceps tendon-bone autograft in children and adolescents with open growth plates. The secondary aim is to report our early results in terms of postoperative growth disturbances which are considered to be a major concern in this challenging group of patients. It was our hypothesis that with our proposed technique no significant growth disturbances would occur. METHODS: From January 1997 to December 2007 49 consecutive children and adolescents with open growth plates were treated for a torn ACL using the aforementioned surgical technique. The patients (28 males and 21 females) with a median age at surgery of 13 (range 8-15) years were retrospectively evaluated. Outcome measures were follow-up radiographs (weight-bearing long leg radiographs of the injured and uninjured knee, anteroposterior and lateral views, a tangential view of the patella and a tunnel view of the injured knee) and follow-up notes (6 weeks, 3, 6, 12 months and until closing of physes) for occurrence of any tibial and/or femoral growth changes. RESULTS: All of the 49 patients had a sufficient clinical and radiological follow-up (minimum 5 years, rate 100%). 48 cases did not show any clinical and radiological growth disturbance. One case of growth disturbance in a 10.5 years old girl was observed. She developed a progressive valgus-flexion deformity which was attributed to a malplacement of the autograft bone block within the femoral posterolateral epiphyseal plate leading to an early localized growth stop. None of the patients were reoperated due to ACL graft failure. Five of the patients underwent revision ACL surgery due to another adequate sports trauma after the growth-stop. The tibial fixation screw had to be removed under local anaesthesia in 10 patients. CONCLUSIONS: The described ACL reconstruction technique represents a promising alternative to previously described procedures in the treatment of children and adolescents with open growth plates. Using quadriceps tendon future graft availability is not compromised, as the most frequently used autograft-source, ipsilateral hamstring tendons, remains untouched.

Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent colorectal cancer cells.

Thymoquinone (TQ), the major compound of black seed oil, has been shown to induce pro-apoptotic signaling pathways in various human cancer models. Although TQ is commonly used in traditional medicine, its use in humans is limited due to its chemical properties and poor membrane penetration capacity. We therefore attached saturated and unsaturated fatty acid residues to TQ and evaluated the effect on cell proliferation, apoptosis and underlying signaling pathways in HCT116 and HCT116(p53-/-) colon cancer and HepG2 hepatoma cells in vitro. Treatment with thymoquinone-4-α-linolenoylhydrazone (TQ-H-10) or thymoquinone-4-palmitoylhydrazone (TQ-H-11) induced a cytostatic effect, particularly in p53-competent HCT116 cells, mediated by an up-regulation of p21(cip1/waf1) and a down-regulation of cyclin E, and associated with an S/G(2) arrest of the cell cycle. Cells lacking p53 (HCT116(p53-/-)) or HepG2 liver cancer cells showed only a minor response to TQ-H-10. These findings demonstrate that derivatives of TQ inhibit cell proliferation dependent on p53 status by activating the cell cycle inhibitor p21(cip1/waf1) at lower concentrations than unmodified TQ. Structural modifications can therefore contribute to the further clinical development of TQ.