Rac1 , a subunit of NADPH oxidase , plays an important role in directed endothelial cell motility. We reported previously that Rac1 activation was necessary for choroidal endothelial cell migration across the retinal pigment epithelium , a critical step in the development of vision-threatening neovascular age-related macular degeneration. Here we explored the roles of Rac1 and NADPH oxidase activation in response to vascular endothelial growth factor treatment in vitro and in a model of laser-induced choroidal neovascularization. We found that vascular endothelial growth factor induced the activation of Rac1 and of NADPH oxidase in cultured human choroidal endothelial cells. Further , vascular endothelial growth factor led to heightened generation of reactive oxygen species from cultured human choroidal endothelial cells, which was prevented by the NADPH oxidase inhibitors , apocynin and diphenyleneiodonium , or the antioxidant , N-acetyl-L-cysteine.

BackgroundAdvances in digital imaging, screen technology, and optics have led to the development of extracorporeal telescopes, also known as exoscopes, as alternatives to surgical loupes (SLs) and traditional operating microscopes (OMs) for surgical magnification. Theoretical advantages of the exoscope over conventional devices include improved surgeon ergonomics; superior three‐dimensional, high‐definition optics; and greater ease‐of‐use. The ORBEYE exoscope, in particular, has demonstrated early efficacy in the surgical arena. The purpose of this study was to compare the ORBEYE with conventional microscopy.MethodsIn this case–control pilot study, we compared the ORBEYE (n = 22) with conventional microscopy (n = 27) across 49 consecutive microsurgical cases during a 6‐week period. Both visualization methods consisted of breast, and head and neck cases, while the ORBEYE was also used for extremity and lymphedema microsurgical cases. The ORBEYE was utilized during flap dissection and microvascular anastomosis. Baseline demographics, operative time, ischemia time, and intra‐ and postoperative microvascular complications were examined and compared. Attending surgeons completed an ergonomics and performance survey postoperatively comparing the ORBEYE with their previous use of SL/OM using a 5‐point Likert scale.ResultsThere was no difference in operative time (507 ± 132 min vs. 522 ± 139, p = .714), ischemia time (77.9 ± 31.4 min vs. 77.5 ± 36.0, p = .972), or microsurgical complications (0% vs. 4%, p = 1) between the ORBEYE and conventional microscopy groups. In a survey administered immediately postoperatively, surgeons reported favorable ergonomics, excellent image quality, and ease of equipment manipulation using the exoscope.ConclusionsThe ORBEYE is an effective microsurgical tool and may be considered as an alternative to conventional optical magnification technology.

Hypothesis Cochlear trauma due to electrode insertion can be detected in acoustic responses to low frequencies in an animal model with a hearing condition similar to patients using electroacoustic stimulation. Background Clinical evidence suggests that intracochlear damage during cochlear implantation negatively affects residual hearing. Recently, we demonstrated the utility of acoustically evoked potentials to detect cochlear trauma in normal hearing gerbils. Here, gerbils with noise-induced hearing loss were used to investigate the effects of remote trauma on residual hearing. Methods Gerbils underwent high-pass (4 kHz cutoff) noise exposure to produce sloping hearing loss. After one-month recovery, each animal’s hearing loss was determined from ABRs and baseline intracochlear recording of the cochlear microphonic (CM) and compound action potential (CAP) obtained at the round window. Subsequently, electrode insertions were performed to produce basal trauma while the acoustically generated potentials to a 1 kHz tone burst were recorded after each step of electrode advancement. Hair cell counts were made to characterize the noise damage and cochlear whole mounts were used to identify cochlear trauma due to the electrode. Results The noise exposure paradigm produced a pattern of hair cell, ABR and intracochlear potential losses that closely mimicked that of EAS patients. Trauma in the basal turn, in the 15 – 30 kHz portion of the deafened region, remote from preserved hair cells, induced a decline in intracochlear acoustic responses to the hearing preserved frequency of 1 kHz. Conclusions The results indicate that a recording algorithm based on physiological markers to low frequency acoustic stimuli can identify cochlear trauma during implantation. Future work will focus on translating these results for use with current cochlear implant technology in humans.

Objectives Cochlear implants (CI) perform especially well if residual acoustic hearing is retained and combined with the CI in the same ear (also termed hybrid or electric-acoustic stimulation). However, in most CI patients, residual hearing is at least partially compromised during surgery, and in some it is lost completely. At present, clinicians have no feedback on the functional status of the cochlea during electrode insertion. Development of an intraoperative physiological recording algorithm during electrode insertion could serve to detect reversible cochlear trauma and optimal placement relative to surviving hair cells. In this report, an animal model was used to assist in determining physiological markers for these conditions using a flexible electrode similar to human surgery. Design The animal model was the normal-hearing gerbil. The flexible electrodes had 1 to 2 platinum-iridium contacts embedded in a 200 µm diameter silastic carrier. As control experiments some insertions were also made with much smaller (50 µm diameter) rigid electrodes. In either case, the electrode was positioned at or just inside the round window membrane and subsequently advanced into the scala tympani longitudinally in 50 to 100 µm increments. After each advancement, acoustic stimulation was used to elicit a cochlear microphonic (CM) and compound action potential (CAP). Stimuli were suprathreshold tone bursts of 1 to 16 kHz in octave steps with 2 msec rise and fall times and a 10 msec plateau. Anatomical integrity of the cochlea was subsequently assessed using a whole-mount preparation. Results In contrast with the CAP, which was relatively stable during insertion, the CM showed a variety of changes related to electrode movement. To tone bursts of 1 to 8 kHz the CM typically remained stable or increased during the insertion before contact with cochlear structures. After contact, the potentials often dropped dramatically. The CM to 16 kHz was the most variable; in some cases it increased but in other cases it decreased early in the insertion and later showed large and abrupt increases. In some instances, this pattern was seen to progressively lower frequencies as well. Histological analysis and the gerbil frequency map indicate that electrode travel was limited to the basal turn (~4 mm from the hook) and did not intrude into the characteristic frequency regions of most frequencies used. Conclusions First, the CM provides a more sensitive indication of cochlear trauma than does the CAP. Second, stable or steady increases in the CM are a physiological marker for unimpeded travel through the scala tympani as the electrode approaches responding hair cells. Third, abrupt reductions in the CM across frequency are a physiological marker of contact with cochlear structures. Fourth, abrupt increases after a decline, which occurred primarily to 16 kHz but to a lesser degree to other frequencies as well, are a physiological marker for a release from contact. The interpretation is that as the tip of the electrode bends the shaft can ...

No abstract

4

The central compartment is a common site for nodal spread from differentiated thyroid carcinoma, often occurring in patients without clinical or ultrasonographic (US) evidence of neck lymph node metastasis (cN0). However, the role of elective central compartment neck dissection (CND) among patients with DTC remains controversial. We performed a systematic literature review, also including review of international guidelines, with discussion of anatomic and technical aspects, as well as risks and benefits of performing elective CND. The recent literature does not uniformly support or refute elective CND in patients with DTC, and therefore an individualized approach is warranted which considers individual surgeon experience, including individual recurrence and complication rates. Patients (especially older males) with large tumors (>4 cm) and extrathyroidal extension are more likely to benefit from elective CND, but elective CND also increases risk for hypoparathyroidism and recurrent nerve injury, especially when operated by low-volume surgeons. Individual surgeons who perform elective CND must ensure the number of central compartment dissections needed to prevent one recurrence (number needed to treat) is not disproportionate to their individual number of central compartment dissections per related complication (number needed to harm).

Background Advancements in three-dimensional (3D) printing have enabled production of patient-specific guides to aid perforator mapping and pedicle dissection during abdominal flap harvest. We present our early experience using this tool to navigate deep inferior epigastric artery (DIEA) topography and evaluate its impact on operative efficiency and clinical outcomes. Patients and Methods Between January 2013 and December 2018, a total of 50 women underwent computed tomographic angiography (CTA)-guided perforator mapping prior to abdominal flap breast reconstruction, with (n = 9) and without (n = 41) 3D-printed vascular modeling (3DVM). Models were assessed for their accuracy in identifying perforator location and source-vessel anatomy, as determined by operative findings from 18 hemi-abdomens. The margin of error (MOE) for perforator localization using 3DVM was calculated and compared with CTA-derived measurements for the same patients. Flap harvest times, outcomes, and complications for patients who were preoperatively mapped using 3DVM versus CTA alone were analyzed. Results Overall, complete concordance was observed between 3DVM and operative findings with regards to perforator number, source-vessel origin, and DIEA branching pattern. By comparison, CTA interpretation of these parameters inaccurately identified branching pattern and perforator source-vessel origin in 28 and 33% of hemi-abdomens, respectively (p = 0.045 and p = 0.02). Compared with operative measurements, the average MOE for perforator localization using 3DVM was significantly lower than that obtained from CTA alone (0.81 vs. 8.71 mm, p < 0.0001). Reference of 3D-printed models, intraoperatively, was associated with a mean reduction in flap harvest time by 21 minutes (60.7 vs. 81.7 minutes, p < 0.001). Although not statistically significant, rates of perforator-level injury, microvascular insufficiency, and fat necrosis were lower among patients mapped using 3DVM. Conclusion The results of this study support the accuracy of 3DVM for identifying DIEA topography and perforator location. Application of this technology may translate to enhanced operative efficiency and fewer perfusion-related complications for patients undergoing abdominal free flap breast reconstruction.