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Hearing restoration using a cochlear implant requires a surgical access to the inner ear. In order to enhance patient safety, reduce trauma, and shorten the patient’s time under anaesthesia current research focusses on minimally invasive cochlear implantation surgery by drilling only a single bore hole. This demands a highly accurate surgical assistance device to guide the drill along a predetermined trajectory planned in patient’s image data. In this study a recently developed surgical targeting system was evaluated for the first time in a human cadaver trial. After screwing a reference frame on a temporal bone specimen and imaging of both, a trajectory through the facial recess was planned in order to reach the middle ear. Based on this plan a patient specific surgical template including a linear guide for the surgical drill was composed utilizing bone cement. After the hardening of the bone cement the surgical template was mounted on top of the reference frame. The drilling could be performed as previously planned without harming facial nerve and chorda tympani. The deviation of the actual drill hole to the planned trajectory was 0.17 mm at the level of the facial recess. The minimal distance of the drill hole to the facial nerve was 0.59 mm. This proof-of-concept study demonstrates the feasibility of performing the access to the middle ear in a minimally invasive manner using the mouldable surgical targeting system. The presented process allows the patient specific individualization of a drill guide under sterile conditions. This might facilitate its integration into clinical routine.

Introduction: The essential aspect of the CI surgery is the placement of the CI electrode into the cochlea. However, the main part of the conventional surgical procedure is dealing with the approach to the cochlea. Reducing the approach to a slim tunnel, drilled by high accurate surgical instruments based on temporal bone imaging would reduce the vast extent of the conventional surgical approach. We develop currently a mini-stereotactic frame to hit the cochlea by drilling a tunnel in the mastoid through the facial recess, called RoboJig. The success of the system is mainly dependent its accuracy. We investigated how accurate the target point needs to be reached and how accurate the RoboJig system may be under lab conditions. Methods: Relevant anatomical structures for the CI surgery approach were segmented in eight 3D histological data sets of human temporal bone specimens. Different straight trajectories from the surface of the mastoid passing through the facial recess and entering the cochlea were planned in this virtual environment. A circular region was defined indicating proper places for Cochleostomy To determine the technical accuracy of the system, 20 RoboJig guiding platforms with different trajectories were fabricated and the position and orientation of an inserted drill guide were measured in lab, using a portable coordinate measuring machine. Results: On average the suitable target region was 1.56mm ± 0.11 mm in diameter leading to a mean safety margin of 0.28 mm if the cochleostomy has a diameter of 1.0 mm. On the other side, positioning accuracy was 0.11 mm ± 0.04 mm. Conclusions: Based on planning the surgical root for the straight approach to the cochlea in virtual histological dataset, the RoboJig system seems to be accurate enough for minimally invasive cochlear implantation surgery. However, additional error sources are expected if the drilling is performed in the inhomogeneous bone of the mastoid. [ABSTRACT FROM AUTHOR]

We established rapid local viral sequencing to document the genomic diversity of severe acute respiratory syndrome coronavirus 2 entering Uganda. Virus lineages closely followed the travel origins of infected persons. Our sequence data provide an important baseline for tracking any further transmission of the virus throughout the country and region.

Surgical treatment with a cochlear implant (CI) for hearing rehabilitation requires a highly accurate and personalized opening of the inner ear (cochlea) to protect the delicate intra-cochlear fine structures, whose functional integrity needs to be maintained to preserve residual hearing. Spatial orientation within the complex anatomy of the lateral skull base during the procedure is a highly demanding task for the surgeon. In order to reduce risk of facial nerve palsy and loss of residual hearing as well as to establish minimally invasive CI surgery (minCIS), image-guided procedures incorporating surgical assistance systems are under development. However, there is a lack of an accuracy threshold value or range that such a system needs to fulfill to be considered sufficiently accurate for atraumatic opening of the inner ear. In this study, high resolution three-dimensional (3D) morphological images of eight human temporal bone specimens were manually segmented to build anatomical models of the human inner ear including all surgically relevant intra-cochlear structures as well as the facial recess. These 3D models were used to plan the surgical access path to the basal turn of the cochlea using the mastoidectomy posterior tympanotomy approach (MPTA). Therefore, custom-made image-processing software was developed to perform both path planning and identification of the valid target region- i.e., the largest possible region for atraumatic opening of the scala tympani. The developed 3D models provide visualization of the complex and variable anatomy of the basal portion of the human cochlear duct (also known as cochlear "hook region") as well as its spatial relationship to the facial recess. Their spatial arrangement directly impacts the accessibility of the hook region and limits the entry direction into scala tympani. The average diameter of the target region was found to be 1.56 mm ± 0.10 mm (range: 1.43 to 1.72 mm). The anatomic variability and the need for a high safety level of at least 95% for hearing preservation CI surgery lead to a remaining safety margin of approximately 0.3 mm. In the future, this accuracy threshold value can serve as benchmark during the pre-clinical evaluation of image-guidance technologies to allow for highly accurate CI surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Different approaches have been developed to find the position of the internal auditory canal (IAC) in middle cranial fossa approach. A feasibility study was performed to investigate the combination of cone beam computed tomography (CBCT), optical coherence tomography (OCT), and laser ablation to assist a surgeon in a middle cranial fossa approach by outlining the internal auditory canal (IAC)., Materials and Methods: A combined OCT laser setup was used to outline the position of IAC on the surface of the petrous bone in cadaveric semi-heads. The position of the hidden structures, such as IAC, was determined in MATLAB software using an intraoperative CBCT scan. Four titanium spheres attached to the edge of the craniotomy served as reference markers visible in both CBCT and OCT images in order to transfer the plan to the patient. The integrated erbium-doped yttrium aluminum garnet laser was used to mark the surface of the bone by shallow ablation under OCT-based navigation before the surgeon continued the operation., Result: The technical setup was feasible, and the laser marking of the border of the IAC was performed with an overall accuracy of 300 μm. The depth of each ablation phase was 300 μm. The marks indicating a safe path supported the surgeon in the surgery., Conclusion: The technique investigated in the present study could decrease the surgical risks for the mentioned structures and improve the pace and precision of operation.

Serum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after myocardial ischemia. To this end, we employed a viable SGK1 knockout mouse model generated in a 129/SvJ background. Ablation of SGK1 in these mice caused a significant decrease in phosphorylation of SGK1 target protein NDRG1, which correlated with alterations in NF-κB signalling and expression of its downstream target protein, VEGF-A. Disruption of these signalling pathways was accompanied by smaller heart and body size. Moreover, the lack of SGK1 led to defective endothelial cell (ECs) migration and tube formation in vitro, and increased scarring with decreased angiogenesis in vivo after myocardial infarct. This study underscores the importance of SGK1 signalling in cardiac neo-angiogenesis and wound healing after an ischemic insult in vivo.

Tamoxifen-inducible Cre-mediated manipulation of animal genomes has achieved wide acceptance over the last decade, with numerous important studies heavily relying on this technique. Recently, a number of groups have reported transient complications of using this protocol in the heart. In the present study we observed a previously unreported focal fibrosis and depressed left-ventricular function in tamoxifen-treated αMHC-MerCreMer-positive animals in a Tβ4shRNAflox × αMHC-MerCreMer cross at 6-7 weeks following standard tamoxifen treatment, regardless of the presence of the floxed transgene. The phenotype was reproduced by treating mice from the original αMHC-MerCreMer strain with tamoxifen. In the acute phase after tamoxifen treatment, cell infiltration into the myocardium was accompanied by increased expression of pro-inflammatory cytokines (IL-1β, IL-6, TNFα, IFNγ, Ccl2) and markers of hypertrophy (ANF, BNP, Col3a1). These observations highlight the requirement for including tamoxifen-treated MerCreMer littermate controls to avert misinterpretation of conditional mutant phenotypes. A survey of the field as well as the protocols presented here suggests that controlling the parameters of tamoxifen delivery is important in avoiding the chronic MerCreMer-mediated cardiac phenotype reported here.

The aim of this study was to investigate whether supplemental IGF-1Ea transgene expression induces activation of local cardiac and bone marrow stem cell population to mediate mammalian heart repair. In physiologic conditions, cardiac overexpression of the IGF-1Ea propeptide is associated with an enrichment of c-Kit/Sca-1 positive side population cells in the bone marrow and the occurrence of an endothelial-primed CD34 positive side population in the heart. This cellular profile is shown here to correlate with the expression of cytokines involved in stem cell mobilization and vessel formation. This molecular and cellular interplay favored IGF-1Ea-mediated vessel formation in injured hearts. The physiologic and pathologic connection between cytokines and stem cells in response to IGF-1Ea may represent an important model to understand how to elicit endogenous reparative signaling., (Copyright © 2011 Elsevier Inc. All rights reserved.)