The Brainstem Cavernoma Case Series: A Formula for Surgery and Surgical Technique.

Background and Objectives: Cavernous malformations (CM) are vascular malformations with low blood flow. The removal of brainstem CMs (BS) is associated with high surgical morbidity, and there is no general consensus on when to treat deep-seated BS CMs. The aim of this study is to compare the surgical outcomes of a series of deep-seated BS CMs with the surgical outcomes of a series of superficially located BS CMs operated on at the Department of Neurosurgery, College of Tuebingen, Germany. Materials and Methods: A retrospective evaluation was performed using patient charts, surgical video recordings, and outpatient examinations. Factors were identified in which surgical intervention was performed in cases of BS CMs. Preoperative radiological examinations included MRI and diffusion tensor imaging (DTI). For deep-seated BS CMs, a voxel-based 3D neuronavigation system and electrophysiological mapping of the brainstem surface were used. Results: A total of 34 consecutive patients with primary superficial (n = 20/58.8%) and deep-seated (n = 14/41.2%) brainstem cavernomas (BS CM) were enrolled in this comparative study. Complete removal was achieved in 31 patients (91.2%). Deep-seated BS CMs: The mean diameter was 14.7 mm (range: 8.3 to 27.7 mm). All but one of these lesions were completely removed. The median follow-up time was 5.8 years. Two patients (5.9%) developed new neurologic deficits after surgery. Superficial BS CMs: The median diameter was 14.9 mm (range: 7.2 to 27.3 mm). All but two of the superficial BS CMs could be completely removed. New permanent neurologic deficits were observed in two patients (5.9%) after surgery. The median follow-up time in this group was 3.6 years. Conclusions: The treatment of BS CMs remains complex. However, the results of this study demonstrate that with less invasive posterior fossa approaches, brainstem mapping, and neuronavigation combined with the use of a blunt "spinal cord" dissection technique, deep-seated BS CMs can be completely removed in selected cases, with good functional outcomes comparable to those of superficial BS CM.

Tropical peatlands and their contribution to the global carbon cycle and climate change.

Peatlands are carbon-rich ecosystems that cover 185-423 million hectares (Mha) of the earth's surface. The majority of the world's peatlands are in temperate and boreal zones, whereas tropical ones cover only a total area of 90-170 Mha. However, there are still considerable uncertainties in C stock estimates as well as a lack of information about depth, bulk density and carbon accumulation rates. The incomplete data are notable especially in tropical peatlands located in South America, which are estimated to have the largest area of peatlands in the tropical zone. This paper displays the current state of knowledge surrounding tropical peatlands and their biophysical characteristics, distribution and carbon stock, role in the global climate, the impacts of direct human disturbances on carbon accumulation rates and greenhouse gas (GHG) emissions. Based on the new peat extension and depth data, we estimate that tropical peatlands store 152-288 Gt C, or about half of the global peatland emitted carbon. We discuss the knowledge gaps in research on distribution, depth, C stock and fluxes in these ecosystems which play an important role in the global carbon cycle and risk releasing large quantities of GHGs into the atmosphere (CO2 and CH4 ) when subjected to anthropogenic interferences (e.g., drainage and deforestation). Recent studies show that although climate change has an impact on the carbon fluxes of these ecosystems, the direct anthropogenic disturbance may play a greater role. The future of these systems as carbon sinks will depend on advancing current scientific knowledge and incorporating local understanding to support policies geared toward managing and conserving peatlands in vulnerable regions, such as the Amazon where recent records show increased forest fires and deforestation.

Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV).

BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. OBJECTIVES: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. RESULTS: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.

Patient response to awake craniotomy - a summary overview.

BACKGROUND: Awake craniotomy is a valuable procedure since it allows brain mapping and live monitoring of eloquent brain functions. The advantage of minimizing resource utilization is also emphasized by some physicians in North America. Data on how well an awake craniotomy is tolerated by patients and how much stress it creates is available from different studies, but this topic has not consequently been summarized in a review of the available literature. Therefore, it is the purpose of this review to shed more light on the still controversially discussed aspect of an awake craniotomy. METHODS: We reviewed the available English literature published until December 2013 searching for studies that investigated patients' responses to awake craniotomies. RESULTS: Twelve studies, published between 1998 and 2013, including 396 patients with awake surgery were identified. Eleven of these 12 studies set the focus on the perioperative time, one study focused on the later postoperative time. The vast majority of patients felt well prepared and overall satisfaction with the procedure was high. In the majority of studies up to 30 % of the patients recalled considerable pain and 10-14 % experienced strong anxiety during the procedure. The majority of patients reported that they would undergo an awake craniotomy again. A post traumatic stress disorder was present neither shortly nor years after surgery. However, a normal human response to such an exceptional situation can for instance be the delayed appearance of unintentional distressing recollections of the event despite the patients' satisfaction concerning the procedure. CONCLUSIONS: For selected patients, an awake craniotomy presents the best possible way to reduce the risk of surgery related neurological deficits. However, benefits and burdens of this type of procedure should be carefully considered when planning an awake craniotomy and the decision should serve the interests of the patient.

Surgical corridor formation by minimally invasive lateral occipital infracortical supra-/transtentorial (OICST) approach in pineal region tumor surgery: A review of 11 cases.

INTRODUCTION: The pineal region is a hard-to-reach part of the brain. There is no unequivocal opinion on the choice of a surgical approach to the pineal region. The surgical approaches described differ in both trajectory (infra- and supratentorial, interhemispheric) and size of craniotomy. They have advantages and disadvantages. The minimally invasive lateral occipital infracortical supra-/transtentorial (OICST) approach we have described has all the advantages of the standard supratentorial approach and minimizes its disadvantages, namely, compression and contusion of the occipital lobe. The minimally invasive craniotomy and small surgical corridor facilitate that. METHODS: We describe 11 consecutive patients with various pineal region tumors (7 cases of pineal cysts, 2 cases of pinealocytoma, 1 case of medulloblastoma, and 1 case of meningioma) who were operated on in our hospital using the lateral OICST approach. Preoperative planning was performed using Surgical Theater®. The surgical corridor was formed using a retractor made from half of a syringe shortened according to the length of the surgical corridor. Preoperative lumbar drain was used. RESULTS: The pineal region tumors were completely resected in all cases. The mean craniotomy size was 2.22 × 1.79 cm. No long-term neurological deficits were reported. CONCLUSIONS: The use of semicircular retractors and intraoperative CSF drainage via a lumbar drain allows to form a small surgical corridor to the pineal region via minimally invasive craniotomy. This reduces traction and traumatization of the occipital lobe, as well as minimizes intra- and postoperative risks.

Minimally Invasive Approaches in the Surgical Treatment of Intracranial Meningiomas: An Analysis of 54 Cases.

BACKGROUND: Intracranial meningiomas, being a fairly common disease in the population, often require surgical treatment, which, in turn, can completely heal the patient. The localization of meningiomas often influences treatment even if they are asymptomatic. By modernizing approaches to surgical treatment, it is possible to minimize intra- and postoperative risks, while achieving complete removal of the tumor. One of these methods is minimally invasive neurosurgery, the development of which in recent years allows it to compete with standard surgical methods. The purpose of this study was the objectification of minimally invasive approaches, such as the calculation of the craniotomy area and the ratio of craniotomy area to the resected tumor volume. METHODS: The retrospective study consisted of a group of 54 consecutive patients who were operated on in our neurosurgery clinic specialized on minimally invasive neurosurgery. Preoperative planning was carried out using the Surgical Theater visualization platform. Using this system, the tumor volume and craniotomy surface area were calculated. During the analysis, the symptoms before and after the surgery, classification of tumors, postoperative complications, further treatment and follow-up results were assessed. RESULTS: Twelve (22.2%) patients were men and 42 (77.8%) were women. The mean age of the group was 64.2 years (median 67.5). The craniotomy area ranged from 202 to 2,108 mm² (mean 631 mm²). Tumor volume ranged from 0.85 to 110.1 cm3 (mean 21.6 cm3). The craniotomy size of minimally invasive approaches to the skull base was 3-5 times smaller than standard approaches. Skull base meningiomas accounted for 19 cases (35.2%), convexity meningiomas for 26 cases (48.1%), and falx and tentorium meningiomas for 9 cases (16.7%). Three complications were reported: postoperative hemorrhage, CSF leakage, and ophthalmoplegia. Relapse was detected in 2 patients with a mean follow-up of 26.3 months (median 20). CONCLUSION: Minimally invasive approaches in the surgical treatment of intracranial meningiomas reduce the possibility of operating trauma by several times; they are safe and sufficient for complete removal of the tumor.

Minimally Invasive Approaches in Reoperations after Conventional Craniotomies : Case Series.

Objective: Reoperations are part of neurosurgical practice. In these cases, an already formed craniotomy seems the most logical and appropriate. However, reoperations via large approaches can be quite traumatic for the patient. Then minimally invasive approaches, being less traumatic, can be a good alternative. Methods: We describe 7 consecutive patients who underwent reoperations using minimally invasive approaches in the areas of conventional craniotomies. Surgical Theater® visualization platform was used for preoperative planning. The study evaluated the size of surgical approach, surgical efficacy, and the presence of complications. Results: The size of a minimally invasive craniotomy was significantly smaller than that of a conventional approach. The preoperative goals were achieved in all described cases. There were no complications in the early postoperative period. Although the anatomy of the operated brain region in reoperations is altered, keyhole approaches can be successfully used with the support of preoperative planning and intraoperative neuronavigation. Given that the goals of reoperations may differ from those of the primary surgery, and a large approach is more traumatic for the patient, minimally invasive craniotomy can be considered as a good alternative. The successful use of minimally invasive approaches in areas of conventional craniotomies reinforces the philosophy of keyhole neurosurgery. In cases where goals can be achieved using small approaches, it makes no sense to use large conventional ones. Conclusion: Minimally invasive approaches can be successfully used during reoperations in patients after conventional craniotomies.

Multiple Intracranial Schwannomas of the Vestibular and Trigeminal Nerves: A Technical Note.

BACKGROUND: A schwannoma is a nerve sheath tumor that is formed by Schwann cells. Vestibular schwannomas are thought to account for the majority of intracranial schwannomas. Nonvestibular schwannomas account for about 10%, about half of which are trigeminal schwannomas. Multiple intracranial schwannomas originating from different cranial nerves are extremely rare. METHODS: We describe the clinical case of a 42-year-old female patient with vestibular schwannoma and multiple trigeminal schwannomas. RESULTS: That case shows how multiple trigeminal schwannomas were identified intraoperatively during elective surgery for vestibular schwannoma removal, most of which were resected. No new neurological deficits were observed in the patient. CONCLUSIONS: The presence of multiple intracranial schwannomas is extremely rare in neurosurgical practice and can change the intraoperative strategy and the course of the surgery.

Primary cerebral low-grade B-cell lymphoma, monoclonal immunoglobulin deposition disease, cerebral light chain deposition disease and "aggregoma": an update on classification and diagnosis.

BACKGROUND: This work aims to add evidence and provide an update on the classification and diagnosis of monoclonal immunoglobulin deposition disease (MIDD) and primary central nervous system low-grade lymphomas. MIDD is characterized by the deposition of light and heavy chain proteins. Depending on the spatial arrangement of the secreted proteins, light chain-derived amyloidosis (AL) can be distinguished from non-amyloid light chain deposition disease (LCDD). We present a case of an extremely rare tumoral presentation of LCDD (aggregoma) and review the 3 previously published LCDD cases and discuss their presentation with respect to AL. CASE PRESENTATION: A 61-year-old woman presented with a 3½-year history of neurologic symptoms due to a progressive white matter lesion of the left subcortical parieto-insular lobe and basal ganglia. 2 former stereotactic biopsies conducted at different hospitals revealed no evidence of malignancy or inflammation; thus, no therapy had been initiated. After performing physiological and functional magnetic resonance imaging (MRI), the tumor was removed under intraoperative monitoring at our department. Histological analysis revealed large amorphous deposits and small islands of lymphoid cells. CONCLUSION: LCCD is a very rare and obscure manifestation of primary central nervous system low-grade lymphomas that can be easily misdiagnosed by stereotactic biopsy sampling. If stereotactic biopsy does not reveal a definite result, a "wait-and-see" strategy can delay possible therapy for this disease. The impact of surgical removal, radiotherapy and chemotherapy in LCDD obviously remains controversial because of the low number of relevant cases.

Propionibacterium acnes: A Difficult-to-Diagnose Ventriculoperitoneal Shunt Infection. Case Report.

BACKGROUND: Ventriculoperitoneal (VP) shunt infections are a fairly common complication in both the early and late postoperative periods. Sometimes diagnosis is difficult despite the fact that infection is often accompanied by clinical symptoms. Furthermore, pathogenic bacteria can be detected in the cerebrospinal fluid. METHOD: We describe a case of chronic VP shunt infection in a 24-year-old female patient who was operated on for posterior fossa pilocytic astrocytoma and needed a VP shunt. The infection revealed itself 5 years after shunt implantation with nonspecific symptoms, and it took approximately 2 years to make a correct diagnosis. Meanwhile, the patient's condition became critical. The infection was caused by Propionibacterium acnes, which is capable of forming biofilms on implants, and which is difficult to identify due to the peculiarity of its cultivation. RESULT: When the bacterium was identified, the shunt was replaced and antimicrobial therapy was performed, after which the patient's condition improved dramatically and she got back to her normal life. CONCLUSIONS: This case shows how difficult the diagnosis of VP shunt infection can be and what clinical significance it can have for the patient.

Fully endoscopic posterior fossa decompression for Chiari malformation type I: illustrative case.

BACKGROUND: Surgery for symptomatic Arnold-Chiari malformation type I involves posterior fossa decompression. There are various approaches, including endoscope-assisted ones. New possibilities and fields of application of fully endoscopic techniques are currently being developed since new and advanced endoscopic equipment and instrumentation are available. OBSERVATIONS: The authors describe the case of a fully endoscopic microsurgical procedure in a 30-year-old female patient with progressive vertigo who was diagnosed with Chiari malformation type I. Neuronavigation and neuromonitoring were used during the surgery. LESSONS: Fully endoscopic surgery can be successfully performed in patients with Chiari malformation I. Intraoperative neuromonitoring and neuronavigation increase safety during this procedure.

The Minimally Invasive Lateral Occipital Infracortical Supra-/Transtentorial Approach in Surgery of Lesions of the Pineal Region: A Possible Alternative to the Standard Approaches.

OBJECTIVE: The pineal region is an anatomical region that is difficult to access surgically, especially when it comes to removing neoplasms. Four main surgical approaches to this region are used as standards nowadays: infratentorial supracerebellar, occipital supra-/transtentorial, interhemispheric, and transventricular approaches. All methods have both advantages and disadvantages and are associated to any extent with intra- and postoperative risks. We have developed a lateral minimally invasive occipital infracortical supra-/transtentorial (OICST) approach, which retains the advantages of the standard occipital transtentorial approach while improving tumor exposure and minimizing its disadvantages. METHODS: We describe 7 consecutive cases of successful complete removals of pineal tumor formations of various quality and size (3 pineal cysts, 2 pineocytomas, 1 meningioma, 1 medulloblastoma) using the OICST approach developed by us. Preoperative 3-dimensional and virtual reality-modeling and the use of a special retractor also contributed to reducing the size of the surgical approach. RESULTS: All patients underwent surgery for removal of a lesion in the pineal region and suffered from no new and permanent neurological deficits postoperatively. The mean size of the craniotomies was 2.3 × 1.85 cm. The minimally invasive approach developed by us carries the advantages of the standard occipital transtentorial approach, but minimizes its disadvantages. The main disadvantage of the standard occipital approach is excessive retraction of the occipital lobe, which is frequently associated with visual neurological deficits. Also, with occipital approach, the Rosenthal vein lying along the surgical corridor is frequently not good visible since the tumor is approached from its tip rather than side which limits the overview of the surgical field and can pose a risk. Damage to this vein can cause infarction of the basal ganglia. By approaching the pineal region from more laterally the size of the craniotomy can significantly be reduced, excessive retraction of the occipital lobe can be avoided and the risk of damage to large deep veins can be minimized. The cosmetic outcome with a small skin incision of only about 3 cm is also a very good side effect of this minimally invasive technique. CONCLUSIONS: The minimally invasive lateral OICST approach described by us can be successfully used in the surgery of pineal neoplasms. Reducing the size of the craniotomy does not limit the possibility of complete removal of tumors of various sizes and tissue consistency, and also minimizes the risks of both intra- and postoperative complications.

Minimally Invasive Dorsal Approach for the Treatment of Giant Presacral Schwannomas.

BACKGROUND: The treatment of giant presacral schwannomas is currently a grand challenge for neurosurgeons. Although these tumors are benign and do not infiltrate the surrounding tissues, it is difficult to choose the best surgical approach because they are surrounded by the pelvic organs and great vessels. There is no universally accepted approach to the surgical treatment because giant presacral schwannomas are rare in the population. The anterior approach through laparotomy is more often recommended in the literature. A dorsal approach that involves laminotomy and stabilization is also described in the literature. However, these approaches are rather traumatic for the patient and have both intraoperative and postoperative risks. OBJECTIVE: To report a minimally invasive dorsal approach for the treatment of giant presacral schwannomas. METHODS: We present a fundamentally new approach to the treatment of these tumors using a minimally invasive dorsal approach, based on the specific anatomy and growth of giant presacral schwannomas. This approach is using the potential of modern neurosurgery. RESULTS: We describe 2 cases of successful total tumor resection using this novel surgical approach. No complications have been registered after the surgery. CONCLUSION: A minimally invasive dorsal approach for the treatment of giant presacral schwannomas is sufficient for complete tumor removal, minimizes intraoperative and postoperative risks, is associated with good cosmetic effect, and can be successfully applied in surgical practice.

Minimally Invasive Dorsal Approach in the Surgery of Giant Thoracic Disk Herniation: Technical Note and Clinical Case Report.

BACKGROUND: Giant thoracic disk herniations are calcified hernias that fill >40% of the spinal canal and result in myelopathy with associated neurologic symptoms. This is a fairly rare abnormality that requires surgical treatment. Currently, there is no unambiguous opinion about the surgical approach to the treatment for this pathology. It is believed that the most effective method is the anterior approach (minithoracotomy or thoracoscopic approach), which reduces the risks of spinal cord injury but is associated with the risks of damage to the lungs, pleura, and major vessels. A giant thoracic disk herniation is also quite large. METHODS: We describe the case of a 60-year-old female patient with a giant thoracic disk herniation. Complete removal of the hernia through a minimally invasive dorsal approach was performed, followed by stabilization. In this case, we used 3-dimensional planning with the help of Surgical Theater, as well as intraoperative neuromonitoring. We also used the ZEISS QEVO, a microinspection tool to aid in resection. RESULTS: No complications have been registered after the surgery. In this case, surgery resulted in a curative treatment outcome for the patient. CONCLUSIONS: The minimally invasive dorsal approach in the surgery of giant thoracic herniated disks can be successfully used in neurosurgical practice. With this approach, it may be possible to avoid dorsal stabilization, but this requires additional research.

The progressive ankylosis protein regulates cementum apposition and extracellular matrix composition.

BACKGROUND/AIMS: Tooth root cementum is sensitive to modulation of inorganic pyrophosphate (PP(i)), an inhibitor of hydroxyapatite precipitation. Factors increasing PP(i) include progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) while tissue nonspecific alkaline phosphatase hydrolyzes PP(i). Studies here aimed to define the role of ANK in root and cementum by analyzing tooth development in Ank knock-out (KO) mice versus wild type. MATERIALS AND METHODS: Periodontal development in KO versus control mice was analyzed by histology, histomorphometry, immunohistochemistry, in situ hybridization, electron microscopy, and nanoindentation. Cementoblast cultures were used in vitro to provide mechanistic underpinnings for PP(i) modulation of cell function. RESULTS: Over the course of root development, Ank KO cervical cementum became 8- to 12-fold thicker than control cervical cementum. Periodontal ligament width was maintained and other dentoalveolar tissues, including apical cementum, were unaltered. Cervical cementum uncharacteristically included numerous cells, from rapid cementogenesis. Ank KO increased osteopontin and dentin matrix protein 1 gene and protein expression, and markedly increased NPP1 protein expression in cementoblasts but not in other cell types. Conditional ablation of Ank in joints and periodontia confirmed a local role for ANK in cementogenesis. In vitro studies employing cementoblasts indicated that Ank and Enpp1 mRNA levels increased in step with mineral nodule formation, supporting a role for these factors in regulation of cementum matrix mineralization. CONCLUSION: ANK, by modulating local PP(i), controls cervical cementum apposition and extracellular matrix. Loss of ANK created a local environment conducive to rapid cementogenesis; therefore, approaches modulating PP(i) in periodontal tissues have potential to promote cementum regeneration.

Total resection of presacral giant schwannoma via minimally invasive dorsal approach: illustrative case.

BACKGROUND: Giant presacral schwannomas are extremely rare in neurosurgery. There are various approaches to the surgical treatment of symptomatic giant presacral schwannomas. The least traumatic is the one-stage surgery with a dorsal approach. OBSERVATIONS: The authors describe a case of a 52-year-old male with pain in the sacral region and partial urinary dysfunction. A total tumor resection through a minimally invasive dorsal approach was performed, and anatomical and functional preservation of all sacral nerves with no postoperative complications was achieved. LESSONS: The authors have shown the possibility of total tumor resection with a minimally invasive dorsal approach without the development of intra- and postoperative complications. Operative corridors that have been created by a tumor can be used and expanded for a minimally invasive dorsal approach to facilitate resection and minimize tissue disruption.

Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice.

There is increasing evidence that the extent of tumor removal in low-grade glioma surgery is related to patient survival time. Thus, the goal of resecting the largest amount of tumor possible without leading to permanent neurological sequelae is a challenge for the neurosurgeon. Electrical stimulation of the brain to detect cortical and axonal areas involved in motor, language, and cognitive function and located within the tumor or along its boundaries has become an essential tool in combination with awake craniotomy. Based on a literature review, discussions within the European Low-Grade Glioma Group, and illustrative clinical experience, the authors of this paper provide an overview for neurosurgeons, neurophysiologists, linguists, and anesthesiologists as well as those new to the field about the stimulation techniques currently being used for mapping sensorimotor, language, and cognitive function in awake surgery for low-grade glioma. The paper is intended to help the understanding of these techniques and facilitate a comparison of results between users.

Large Variability of Frequency and Type of Physical Therapy in Patients in the German Network for Systemic Sclerosis.

OBJECTIVE: To determine the type and frequency of physical therapy (PT) prescribed by physicians for patients in the registry of the German Network for Systemic Sclerosis. METHODS: The data for 4,252 patients were analyzed using descriptive statistics, chi-square tests, and odds ratios (ORs). RESULTS: Overall, 37.4% of patients (1,590 of 4,252) received PT at the end of a yearly follow-up. The most frequently used type of PT was lymphatic drainage (n = 1,061, 36.8%), followed by exercise therapy (n = 1,047, 36.3%) and heat therapy (n = 689, 23.9%). More than three-fourths of treated patients (82%) received 1 or 2 different forms of PT simultaneously. The prescription of PT was associated with the extent of skin fibrosis as measured by the modified Rodnan skin thickness score (<10 [41.8% of patients], 11-20 [55.8% of patients], and >21 [63.9% of patients]; P < 0.001). Patients with musculoskeletal involvement (e.g., arthritis, muscle weakness, joint contractures, tendon friction rubs) had a higher chance of receiving PT than patients without these symptoms, with corresponding ORs ranging from 1.96 (95% confidence interval [95% CI] 1.69-2.28) for joint contractures to 3.83 (95% CI 2.89-5.08) for arthritis. When comparing the type of PT prescription across the initial and all follow-up visits from 2003 to 2017, significant alterations with a decreasing frequency of patients receiving PT could be observed (P = 0.001). CONCLUSION: To our knowledge, this is the first study reporting the use of PT in patients with systemic sclerosis (SSc) in a large cohort. Although SSc is characterized by considerable disability and restriction of motion, <40% of patients received PT.

Reducing off target viral delivery in ovarian cancer gene therapy using a protease-activated AAV2 vector platform.

Gene therapy is a promising strategy for treating metastatic epithelial ovarian cancer (EOC). However, efficient vector targeting to tumors is difficult and off-target effects can be severely detrimental. Most vector targeting approaches rely on surface receptors overexpressed on some subpopulation of cancer cells. Unfortunately, there is no universally expressed cell surface biomarker for tumor cells. As an alternative, we developed an adeno-associated virus (AAV) based "Provector" whose cellular transduction can be activated by extracellular proteases, such as matrix metalloproteinases (MMP) that are overexpressed in the tumor microenvironments of the most aggressive forms of EOC. In a non-tumor bearing mouse model, the Provector demonstrates efficient de-targeting of healthy tissues, especially the liver, where viral delivery is <1% of AAV2. In an orthotopic HeyA8 tumor model of EOC, the Provector maintains decreased off-target delivery in the liver and other tissues but with no loss in tumor delivery. Notably, approximately 10% of the injected Provector is still detected in the blood at 24 h while >99% of injected AAV2 has been cleared from the blood by 1 h. Furthermore, mouse serum raised against the Provector is 16-fold less able to neutralize Provector transduction compared to AAV2 serum neutralizing AAV2 transduction (1:200 vs 1:3200 serum dilution, respectively). Thus, the Provector appears to generate less neutralizing antibodies than AAV2. Importantly, serum against AAV2 does not neutralize the Provector as well as AAV2, suggesting that pre-existing antibodies against AAV2 would not negate the clinical application of Provectors. Taken together, we present an EOC gene delivery vector platform based on AAV with decreased off-target delivery without loss of on-target specificity, and greater immunological stealth over the traditional AAV2 gene delivery vector.

Feasibility and accuracy of a voxel-based neuronavigation system with 3D image rendering in preoperative planning and as a learning tool for young neurosurgeons, exemplified by the anatomical localization of the superior sagittal sinus.

It is essential for a neurosurgeon to know individual anatomy and the corresponding anatomical landmarks before starting a surgery. Continuous training, especially of young neurosurgeons, is crucial for understanding complex neuroanatomy. In this study, we used a neuronavigation system with 3D volumetric image rendering to determine the anatomical relationship between the sagittal suture and the superior sagittal sinus (SSS) in patients with intracranial lesions. Furthermore, we discussed the applicability of such system in preoperative planning, residency training, and research. The study included 30 adult patients (18 female/12 male) who underwent a cranial computed tomography (CT) scan combined with venous angiography, for preoperative planning. The position of the sagittal suture in relation to the SSS was assessed in 3D CT images using an image guidance system (IGS) with 3D volumetric image rendering. Measurements were performed along the course of the sagittal sinus at the bregma, lambda, and in the middle between these two points. The SSS deviated to the right side of the sagittal suture in 50% of cases at the bregma, and in 46.7% at the midpoint and lambda. The SSS was displaced to the left of the sagittal suture in 10% of cases at the bregma and lambda and in 13% at the midpoint. IGSs with 3D volumetric image rendering enable simultaneous visualization of bony surfaces, soft tissue and vascular structures and interactive modulation of tissue transparency. They can be used in preoperative planning and intraoperative guidance to validate external landmarks and to determine anatomical relationships. In addition, 3D IGSs can be utilized for training of surgical residents and for research in anatomy.