Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study.

Introduction: Allogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population. Methods: We report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells. Results: Thirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation. Discussion: Our study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease. Clinical trial registration: https://clinicaltrials.gov, identifier NCT02227641.

The Lipid Raft-Associated Protein Stomatin Is Required for Accumulation of Dectin-1 in the Phagosomal Membrane and for Full Activity of Macrophages against Aspergillus fumigatus.

Alveolar macrophages belong to the first line of defense against inhaled conidia of the human-pathogenic fungus Aspergillus fumigatus. In lung alveoli, they contribute to phagocytosis and elimination of conidia. As a counterdefense, conidia have a gray-green pigment that enables them to survive in phagosomes of macrophages for some time. Previously, we showed that this conidial pigment interferes with the formation of flotillin-dependent lipid raft microdomains in the phagosomal membrane, thereby preventing the formation of functional phagolysosomes. Besides flotillins, stomatin is a major component of lipid rafts and can be targeted to the membrane. However, only limited information on stomatin is available, in particular on its role in defense against pathogens. To determine the function of this integral membrane protein, a stomatin-deficient macrophage line was generated by CRISPR/Cas9 gene editing. Immunofluorescence microscopy and flow cytometry revealed that stomatin contributes to the phagocytosis of conidia and is important for recruitment of the ß-glucan receptor dectin-1 to both the cytoplasmic membrane and phagosomal membrane. In stomatin knockout cells, fusion of phagosomes and lysosomes, recruitment of the vATPase to phagosomes, and tumor necrosis factor alpha (TNF-α) levels were reduced when cells were infected with pigmentless conidia. Thus, our data suggest that stomatin is involved in maturation of phagosomes via fostering fusion of phagosomes with lysosomes. IMPORTANCE Stomatin is an integral membrane protein that contributes to the uptake of microbes, e.g., spores of the human-pathogenic fungus Aspergillus fumigatus. By generation of a stomatin-deficient macrophage line by advanced genetic engineering, we found that stomatin is involved in the recruitment of the ß-glucan receptor dectin-1 to the phagosomal membrane of macrophages. Furthermore, stomatin is involved in maturation of phagosomes via fostering fusion of phagosomes with lysosomes. The data provide new insights on the important role of stomatin in the immune response against human-pathogenic fungi.

Leukoreductive response to the combination of sorafenib and chemotherapy in hyperleukocytosis of FLT3-ITD mutated pediatric AML.

Twelve to 22% of pediatric acute myeloid leukemia (AML) patients present with hyperleukocytosis, which is one of the main risk factors of early death due to its clinical complications: leukostasis, causing pulmonary or central nervous system injuries, tumor lysis syndrome, and disseminated intravascular coagulation. Sorafenib is a multi-kinase inhibitor that blocks the Fms-Related Tyrosine Kinase 3 receptor (FLT3) in AML patients with a FLT3-internal tandem duplication (FLT3-ITD), leading to a reduction of proliferation. Here we report four de novo diagnosed or relapsed pediatric FLT3-ITD-positive AML patients with hyperleukocytosis, which were treated with sorafenib in combination with cytoreductive chemotherapy prior to the start of the induction phase. We observed a fast reduction of white blood cells in peripheral blood and bone marrow. This resulted in a rapid clinical stabilization of the patients. Adverse side effects-such as dermatologic toxicity, elevation of transaminases and hypertension-occurred but were mild and inductive chemotherapy could be started in parallel or subsequently. This implies sorafenib as a safe and effective treatment option in combination with chemotherapy during cytoreductive prephase for children with this life-threatening condition.

Safety and Feasibility of Augmented Reality Assistance in Minimally Invasive and Open Resection of Benign Intradural Extramedullary Tumors.

OBJECTIVE: Surgical resection of benign intradural extramedullary tumors (BIETs) is effective for appropriately selected patients. Minimally invasive surgical (MIS) techniques have been described for successful resection of BIET while minimizing soft tissue injury. Augmented reality (AR) is a promising new technology that can accurately allow for intraoperative localization from skin through the intradural compartment. We present a case series evaluating the timing, steps, and accuracy at which this technology is able to enhance BIET resection. METHODS: A protocol for MIS and open AR-guided BIET resection was developed and applied to determine the feasibility. The tumor is marked on diagnostic magnetic resonance imaging (MRI) using AR software. Intraoperatively, the planning MRI is fused with the intraoperative computed tomography. The position and size of the tumor is projected into the surgical microscope and directly into the surgeon's field of view. Intraoperative orientation is performed exclusively via navigation and AR projection. Demographic and perioperative factors were collected. RESULTS: Eight patients were enrolled. The average operative time for MIS cases was 128 ± 8 minutes and for open cases 206 ± 55 minutes. The estimated intraoperative blood loss was 97 ± 77 mL in MIS and 240 ± 206 mL in open procedures. AR tumor location and margins were considered sufficiently precise by the surgeon in every case. Neither correction of the approach trajectory nor ultrasound assistance to localize the tumor were necessary in any case. No intraoperative complications were observed. CONCLUSION: Current findings suggest that AR may be a feasible technique for tumor localization in the MIS and open resection of benign spinal extramedullary tumors.

Augmented Reality to Improve Surgical Workflow in Minimally Invasive Transforaminal Lumbar Interbody Fusion - A Feasibility Study With Case Series.

OBJECTIVE: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a highly reproducible procedure for the fusion of spinal segments. We recently introduced the concept of "total navigation" to improve workflow and eliminate fluoroscopy. Imageguided surgery incorporating augmented reality (AR) may further facilitate workflow. In this study, we developed and evaluated a protocol to integrate AR into the workflow of MISTLIF. METHODS: A case series of 10 patients was the basis for the evaluation of a protocol to facilitate tubular MIS-TLIF by the application of AR. Surgical TLIF landmarks were marked on a preoperative computed tomography (CT)-scan using dedicated software. This marked CT scan was fused intraoperatively with the low-dose navigation CT scan using elastic image fusion, and the markers were transferred to the intraoperative scan. Our experience with this workflow and the surgical outcomes were collected. RESULTS: Our AR protocol was safely implemented in all cases. The TLIF landmarks could be preoperatively planned and transferred to the intraoperative imaging. Of the 10 cases, 1 case had additionally a synovial cyst resection and in 2 cases an additional bony decompression was performed due to central stenosis. The average procedure time was 160.6 ± 31.9 minutes. The AR implementation added 1.72 ± 0.37 minutes to the overall procedure time. No complications occurred. CONCLUSION: Our findings support the idea that total navigation with AR may further facilitate the workflow, especially in cases with more complex anatomy and for teaching and training purposes. More work is needed to simplify the software and make AR integration more user-friendly.

Lumbar Giant Disk Herniations Treated With a Unilateral Approach for Bilateral Decompression.

BACKGROUND: Disk herniations that obstruct the spinal canal by more than 50% are named "giant disk herniations" (GDHs). GDHs are challenging to treat from a surgical perspective because of their size and the risk of iatrogenic manipulation during resection resulting in additional neurological compromise. As a result, the appropriateness of minimally invasive tubular approaches for the treatment of lumbar GDHs remains controversial. OBJECTIVE: To report our experience in treating lumbar GDHs using tubular minimally invasive surgery. METHODS: A total number of 228 disk herniations were evaluated for the criteria of GDH. In addition, the presence of neurological deficits such as cauda equina syndrome, pain as measured by a visual analog scale, operating time, complications, estimated intraoperative blood loss, and number of surgical revisions were assessed. The standard tubular diskectomy technique was modified to include unilateral laminectomy for bilateral decompression before the diskectomy to create a sufficient working space for removal of the disk fragments. RESULTS: Twenty-three (10%) patients met the criteria for GDH. Clinically significant motor weakness was present in 21 patients (91.3%) before surgery, and 3 patients (13%) presented with cauda equina syndrome. The average mean visual analog scale (±SD) for the preoperative pain score was 8.3 and decreased to 2.4 at follow-up after surgery. All cases of cauda equina syndrome resolved postoperatively. CONCLUSION: Unilateral tubular minimally invasive surgery diskectomy seems to be a safe and effective treatment alternative for lumbar GDHs, combined with the "over-the-top" decompression, which provides bilateral decompression and working space.

[Evaluation of a user habit-based ophthalmologic e-learning platform]. / Evaluation eines nutzerorientierten eLearning-Angebots für die Augenheilkunde.

BACKGROUND: In medical studies digital learning is often achieved by the use of learning management platforms, such as Ilias. Lecture presentations and organizational documents are typical contents. Students use multiple, mostly external learning options for acquisition of knowledge and competences. We present our updated ophthalmology e­learning environment for medical students and its evaluation. OBJECTIVE: Evaluation of an ophthalmology e­learning platform for medical students, which considers prevalent learning habits. MATERIAL AND METHODS: The platform should provide and link a selection of internal and external learning resources following anatomical structures of the eye. For every subject area the platform provides a text with essential matters, clinical cases, lecture presentations, multiple choice questions for practice, links to corresponding chapters of a textbook and the appropriate AMBOSS learning cards (Amboss GmbH, Berlin, Germany). At the end of the semester an evaluation of the platform was carried out. Different statements were rated by the students on ordinal scales and analyzed. RESULTS: The platform was rated with 1.47 ± 0.54 (mean ± standard deviation; n = 107) on a German school grade scale (1 = best, 6 = worst). It was perceived as helpful for the individual learning with 1.62 ± 0.77 (1 = very helpful, 7 = not helpful at all). The structuring of the internal and external learning resources was rated as very good 1.44 ± 0.66 (1 = very good, 7 = very bad). The median for subjective amount of usage was 1-5 h (ordinal scale <1, 1-5, 6-10, 15-20, >20 h). CONCLUSION: It appears to be meaningful to specifically link external learning resources corresponding to the own curricular structure in order to provide medical students with a modern basis for learning in ophthalmology.

[Ophthalmic emergencies: training via interactive key feature cases for medical students]. / Notfälle in der Augenheilkunde: Vermittlung anhand interaktiver Key-feature-Fälle für Medizinstudierende.

BACKGROUND: Autonomous diagnosis and assessment of medical emergencies are important skills to acquire for medical students. Ophthalmology features certain specialty-specific "red flag" signs and symptoms, which pose a challenge for educators in ophthalmology. To support medical students in identifying those "red flags" we developed and implemented interactive cases for our e­learning platform. MATERIAL AND METHODS: A total of seven interactive cases with key feature problems regarding potentially dangerous signs and symptoms, such as painless loss of vision or red eye were developed. Medical students were guided through a case and performed formative assessments. The interactive cases were created with e­learning authoring software and were available on the learning management system presence of the department of ophthalmology. They were mandatory for medical students in the ophthalmology course. Students evaluated the cases after the course. RESULTS: The interactive cases were rated on average at 1.51 ± 0.68 (mean ± standard deviation; n = 163) on a grade scale (1 = best, 6 = worst). On a Likert scale they were perceived as helpful for individual learning at 1.60 ± 0.81 (1 = very helpful, 7 = not helpful at all; n = 164). The information provided on the cases and selection of scenarios was positively evaluated. CONCLUSION: To support students in identifying and managing ophthalmic emergencies in the context of limited time in tightly packed curricula, interactive key feature cases can be part of corresponding e­learning resources. An integration of such cases was evaluated as desirable.

Novel MIS 3D NAV Single Step Pedicle Screw System (SSPSS): Workflow, Accuracy and Initial Clinical Experience.

STUDY DESIGN: Prospective case series. OBJECTIVE: SSPSS (single step pedicle screw system) was developed for minimally invasive spine surgery. We performed this study to report on safety, workflow, and our initial clinical experience with this novel technique. METHODS: The prospective study was conducted on patients who underwent pedicle screw fixation between October 2017 and April 2018 using a novel single step 3D navigated pedicle screw system for MIS. Outcome measurements were obtained from intraoperative computerized tomography. The images were evaluated to determine pedicle wall penetration. We used a grading system to assess the severity of the pedicle wall penetration. Breaches were classified as grade 1 (<2 mm), grade 2 (2-4 mm), or grade 3 (<4 mm),1 and as cranial, caudal, medial, and lateral. RESULTS: Our study includes 135 screws in 24 patients. SSPSS eliminated K-wires and multiple steps traditionally necessary for MIS pedicle screw insertion. The median time per screw was 2.45 minutes. 3 screws were corrected intraoperatively. Pedicle wall penetration occurred in 14 screws (10%). Grade 1 breaches occurred in 4 screws (3%) and grade 2 breaches occurred in 10 screws (7%). Lateral breaches were observed more often than medial breaches. The accuracy rate in our study was 90% (Grade 0 breach). No revision surgeries were needed and no complications occurred. CONCLUSIONS: Our study suggests that SSPSS could be a safe, accurate, and efficient tool. Our accuracy rate is comparable to that found in the literature.

Combined Endothelialization Promoting and Surface Binding Chimeric Conjugate with Low Thrombogenicity.

Endothelialization of blood contacting implants, e.g., vascular stents, is regarded as a prerequisite for an improved performance in terms of minimizing thrombogenicity and the inhibition of restenosis. Commonly used materials, such as Ti-based alloys, can be surface-modified in order to improve endothelial cell (EC) colonization as well as to reduce platelet adhesion. Standard modification techniques involve silanization and are laborious and time-consuming. We propose a novel single-step procedure based on a surface-recognizing peptide generated by phage display methodology. Combining this with a polyethylene glycol (PEG) spacer and an EC-specific sequence yielded a conjugate applicable for the modification of Ti surfaces.

Elastic Image Fusion Software to Coregister Preoperatively Planned Pedicle Screws With Intraoperative Computed Tomography Data for Image-Guided Spinal Surgery.

BACKGROUND: For complex spinal cases, especially when robotic guidance is used, preoperative planning of pedicle screws can be helpful. Transfer of these preoperatively planned pedicle screws to intraoperative 3-dimensional imaging is challenging because of changes in anatomic alignment between preoperative supine and intraoperative prone imaging, especially when multiple levels are involved. In the spine, where each individual vertebra is subject to independent movement from adjacent level, rigid image fusion is confined to a single vertebra and can display fusion inaccuracies on adjacent levels. A novel elastic fusion algorithm is introduced to overcome these disadvantages. This study aimed to investigate image registration accuracy of preoperatively planned pedicle screws with an elastic fusion algorithm vs. rigid fusion for intraoperative placement with image-guided surgery. METHODS: A total of 12 patients, were selected depending on the availability of a preoperative spinal computed tomography (CT) and an intraoperative AIRO CT scan (BrainLAB AG, Munich, Germany) of the same spinal region. To verify accuracy differences between rigid fusion and elastic fusion 76 bilateral screw trajectories were virtually defined in the preoperative CT image, and they were transferred via either rigid fusion or elastic fusion to the intraoperative CT scan. Accuracy of the transferred screws in the rigid and elastic fusion group was determined by measuring pedicle breaches on the intraoperative CT. RESULTS: In the rigid fusion group 1.3% of screws showed a breach of less than 2 mm, 9.2% showed breaches between 2 and 4 mm, and 18.4% of the screws showed an error above 4 mm. The elastic fusion group showed no breaches and provided high accuracy between preoperative and intraoperative screw placement. CONCLUSION: Elastic fusion provides high registration accuracy and represents a considerable step towards efficiency and safety in CT-based image-guided surgery. LEVEL OF EVIDENCE: 3.

Intraoperative image guidance for cervical spine surgery.

Intraoperative image-guidance in spinal surgery has been influenced by various technological developments in imaging science since the early 1990s. The technology has evolved from simple fluoroscopic-based guidance to state-of-art intraoperative computed tomography (iCT)-based navigation systems. Although the intraoperative navigation is more commonly used in thoracolumbar spine surgery, this newer imaging platform has rapidly gained popularity in cervical approaches. The purpose of this manuscript is to address the applications of advanced image-guidance in cervical spine surgery and to describe the use of intraoperative neuro-navigation in surgical planning and execution. In this review, we aim to cover the following surgical techniques: anterior cervical approaches, atlanto-axial fixation, subaxial instrumentation, percutaneous interfacet cage implantation as well as minimally invasive posterior cervical foraminotomy (PCF) and unilateral laminotomy for bilateral decompression. The currently available data suggested that the use of 3D navigation significantly reduces the screw malposition, operative time, mean blood loss, radiation exposure, and complication rates in comparison to the conventional fluoroscopic-guidance. With the advancements in technology and surgical techniques, 3D navigation has potential to replace conventional fluoroscopy completely.

Isolation and immunofluorescence staining of Aspergillus fumigatus conidia-containing phagolysosomes.

The analysis of phagolysosomes within professional phagocytic cells is facilitated by their isolation. Here, we optimized a protocol for the isolation of intact phagolysosomes from macrophages infected with the spores of Aspergillus fumigatus. Purified phagolysosomes allow improved immunostaining, e.g., of phagolysosomal membrane proteins, or proteome analysis. For complete details on the use and execution of this protocol, please refer to Schmidt et al. (2020).

[Implementation of a digital semester for ophthalmology during the COVID-19 pandemic]. / Umsetzung eines digitalen Semesters Augenheilkunde während der COVID-19-Pandemie.

BACKGROUND: The first wave of the COVID-19 pandemic posed great challenges for teachers and students, as teaching had to take place despite the restriction of classroom teaching. For attendance lessons and events with patient contact alternatives had to be arranged at short notice between mid-March and the beginning of the semester in mid-April. OBJECTIVE: Description of the concept and implementation in the student teaching at the Department of Ophthalmology of the University Medical Center Mainz in complete digital form in spring 2020. PRESENTATION OF CONCEPT: Lectures, examination course and practical training in ophthalmology take place in the 5th and 6th semester of the study of human medicine. The basis of the new concept were the former course curricula. Implemented concepts included a complete revision and implementation of lectures as video podcasts, examination videos, online examination conferences, interactive patient cases, narrated videos of surgery, anamnesis videos of patients and the design of the virtual patient room, a live online practice with presentation and examination of patients including transmission of the slit-lamp image to reproduce anterior and posterior segment examination. An evaluation showed a very positive reception of the new concept by students. DISCUSSION: Within a tight timeframe of 4 weeks a complete revision of the ophthalmology course was achieved. The implementation was time-consuming, with the largest share in the media production of examination videos, interactive patient cases and video podcasts of the lectures. We consider a reduction of classroom teaching for parts of the learning objectives that can be represented by such videos to be possibly useful. An independent digital appropriation of such content may enable a more productive learning environment in face-to-face teaching.

Minimally Invasive Posterior Cervical Foraminotomy Using 3-Dimensional Total Navigation: 2-Dimensional Operative Video.

Minimally invasive posterior cervical foraminotomy (MPCF) has shown comparable outcomes to those of an open approach, with shorter operation times and length of hospital stays, as well as decreased blood loss and inpatient analgesic use. This surgical technique is mainly used to treat unilateral radiculopathy due to foraminal soft disc fragments or bone spurs. Three-dimensional (3D) navigation-guidance facilitates the surgical workflow, and it is utilized in planning the incision, determining the extent of the medial facetectomy, and confirming sufficient decompression, especially in the lower cervical spine and cervicothoracic junction, where the shoulders make localization with fluoroscopy difficult. In this video, we present the case of a 49-yr-old male patient with mechanical neck pain and C8 radiculopathy due to multilevel cervical spinal stenosis with disc herniations and C7-T1 right-sided foraminal stenosis. There was loss of cervical lordosis at the upper levels. The patient underwent anterior cervical discectomy and fusion (ACDF) at the C4-5, C5-6, and C6-7 levels to treat mechanical neck pain and restore lordosis. In order to avoid an extra-level fusion and preserve motion, we performed a right-sided C7-T1 MPCF using a portable intraoperative computed tomography (iCT) scanner (Airo®; Brainlab AG, Feldkirchen, Germany), combined with 3D computer navigation to address the patient's radicular symptoms. Patient consent was obtained prior to performing the procedure.

Level of Tumor Necrosis Factor Production by Stimulated Blood Mononuclear Cells Can Be Used to Predict Response of Patients With Inflammatory Bowel Diseases to Infliximab.

BACKGROUND & AIMS: A substantial proportion patients with inflammatory bowel disease (IBD) have a primary non-response to infliximab; markers are needed to identify patients most likely to respond to treatment. We investigated whether production of tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMCs) can be used as a marker to predict response. METHODS: We performed a prospective study of 41 adults with IBD (mean age, 38 years; 21 male; 21 with Crohn's disease and 20 with ulcerative colitis) not treated with a biologic agent within the past 6 months; patients were given their first infusion of infliximab at a hospital or clinic in Berlin, Germany. We collected data on clinical scores, levels of C-reactive protein, and ultrasound results (Limberg scores) at baseline (before the first infusion) and after 6 weeks (3rd infliximab infusion). PMBCs were obtained from patients at baseline and 10 healthy individuals (controls) and incubated with lipopolysaccharide. We measured production of cytokines (TNF, interleukin 1 [IL1], IL6, IL8, IL10, IL12p70, and IL22) by ELISA and performed cytometric bead array and flow cytometry analyses. The primary endpoint was clinical response (decrease in Harvey Bradshaw Index scores of 2 or more or decrease in partial Mayo scores of 3 or more at week 6) in patients with PBMCs that produced high vs low levels of TNF. RESULTS: Responders had a shorter median disease duration (P = .018) and higher median Limberg score (P = .021), than nonresponders. Baseline PBMCs from responders produced significantly more TNF (P = .049) and IL6 (P = .028) than from nonresponders; a level of 500 pg/ml TNF identified responders with 82% sensitivity and 78% specificity. In patients with Crohn's disease, this cutoff value (500 pg/ml TNF) identified responders with 100% sensitivity and 82% specificity; TNF levels above this level were independently associated with response to infliximab in multivariate analysis (odds ratio, 16.2; 95% CI, 1.8-148.7; P = .014). The percentage of TNF-positive cells was higher among CD14+ monocytes than lymphocytes after stimulation. CONCLUSIONS: Production of a high level of TNF by PBMCs (specifically CD14+ cells) from patients with IBD can identify those most likely to have a clinical response to infliximab therapy. In patients with Crohn's disease, a cutoff value of 500 pg/ml TNF identified responders with 100% sensitivity and 82% specificity.

Flotillin-Dependent Membrane Microdomains Are Required for Functional Phagolysosomes against Fungal Infections.

Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the assembly of both major defense complexes vATPase and NADPH oxidase requires membrane microdomains. Furthermore, we describe a virulence mechanism leading to dysregulation of membrane microdomains by melanized wild-type conidia of the important human-pathogenic fungus Aspergillus fumigatus resulting in reduced phagolysosomal acidification. We show that phagolysosomes with ingested melanized conidia contain a reduced amount of free Ca2+ ions and that inhibition of Ca2+-dependent calmodulin activity led to reduced lipid-raft formation. We identify a single-nucleotide polymorphism in the human FLOT1 gene resulting in heightened susceptibility for invasive aspergillosis in hematopoietic stem cell transplant recipients. Collectively, flotillin-dependent microdomains on the phagolysosomal membrane play an essential role in protective antifungal immunity.

Development of a Curriculum for Minimally Invasive Spine Surgery (MISS).

The purpose of this review is to describe how a curriculum for minimally invasive spine surgery (MISS) was developed and implemented. The authors discuss the curriculum roadmap, its target audience, and the educational process for teaching general skills and specific procedures in MISS. Initiated by AOSpine, a panel of experts within spinal surgery from multiple centers formed the minimally invasive spine surgery task force. Together, task force members redefined the standards and milestones of the MISS education and training. Therefore, we conclude that the MISS task force created a structured curriculum which will have a positive influence on daily practice for surgeons and patients worldwide.

Soft Tissue: A Possible Source of Pain Pre and Post Minimally Invasive Spine Surgery.

STUDY DESIGN: Case studies. OBJECTIVES: To demonstrate that muscle generated pain (MGP) may be a cause of pain in patients who have undergone minimally invasive spine surgery (MISS). METHODS: A physical examination including electrical stimulation of putative pain generating muscles to identify the presence of lowered thresholds for depolarization of muscle nociceptors, and an examination of strength and flexibility of key muscles in the upper and lower body, may identify multiple etiologies of MGP. Treatment of identified muscles consisted of muscle/tendon injections to identified sensitized muscles followed by exercises incorporating relaxation limbering and stretching. RESULTS: Postsurgical pain was eliminated and mobility restored in both presented cases replicating success in prior published studies. CONCLUSIONS: Understanding the pathophysiological mechanisms of muscle pain may facilitate the evaluation and treatment of MGP in MISS patients diagnosed with failed back surgery syndrome.

Evolving Navigation, Robotics, and Augmented Reality in Minimally Invasive Spine Surgery.

Innovative technology and techniques have revolutionized minimally invasive spine surgery (MIS) within the past decade. The introduction of navigation and image-guided surgery has greatly affected spinal surgery and will continue to make surgery safer and more efficient. Eventually, it is conceivable that fluoroscopy will be completely replaced with image guidance. These advancements, among others such as robotics and virtual and augmented reality technology, will continue to drive the value of 3-dimensional navigation in MIS. In this review, we cover pertinent features of navigation in MIS and explore their evolution over time. Moreover, we aim to discuss the key features germane to surgical advancement, including technique and technology development, accuracy, overall health care costs, operating room time efficiency, and radiation exposure.