Dissociated Representation of Binaural Cues in Single-Sided Deafness: Implications for Cochlear Implantation.

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in the auditory system. Cochlear implantation (CI) of the deaf ear is an effective treatment for SSD. However, the newly introduced auditory input in congenital SSD often does not reach expectations in late-implanted CI recipients with respect to binaural hearing and speech perception. In a previous study, a reduction of the interaural time difference (ITD) sensitivity has been shown in unilaterally congenitally deaf cats (uCDCs). In the present study, we focused on the interaural level difference (ILD) processing in the primary auditory cortex. The uCDC group was compared with hearing cats (HCs) and bilaterally congenitally deaf cats (CDCs). The ILD representation was reorganized, replacing the preference for the contralateral ear with a preference for the hearing ear, regardless of the cortical hemisphere. In accordance with the previous study, uCDCs were less sensitive to interaural time differences than HCs, resulting in unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs and ILDs cannot be integrated for binaural sound source localization. In normal hearing, the predominant effect of each ear is excitation of the auditory cortex in the contralateral cortical hemisphere and inhibition in the ipsilateral hemisphere. In SSD, however, auditory pathways reorganized such that the hearing ear produced greater excitation in both cortical hemispheres and the deaf ear produced weaker excitation and preserved inhibition in both cortical hemispheres.

Indocyanine green videoangiography-assisted prediction of flap necrosis in the rat epigastric flap using the flow® 800 tool.

BACKGROUND: The decision to re-operate on a potentially ischemic free flap remains challenging. Indocyanine green videoangiography (ICG) with the FLOW® 800 tool is a method which allows an immediate qualitative conclusion about the patency of an anastomosis. Is it also able to predict the outcome of potentially compromised vascular free flaps? MATERIALS AND METHODS: An epigastric flap was raised and repositioned in 79 rats. Intraoperative fluorescence angiography was performed using ICG videoangiography and the FLOW® 800 tool was applied. Six regions of interest were positioned systematically over the flap, changes of the ICG fluorescence were color coded with respect to time and 474 measurements were performed. The flap was clinically monitored for one week and the resulting necrotic areas were correlated with the ICG/FLOW® 800 results. RESULTS: Mean intensity of clinically vital areas was 83.39 ± 50.96 arbitrary units (AU) and 37.33 ± 15.14 AU in necrotic areas. The receiver operating characteristic curve and Youden-Index analysis revealed that the optimal cutoff for the maximal intensity of ICG after FLOW® 800 analysis was ≤ 61.733 for the prediction of flap necrosis and > 61.733 for the prediction of flap survival (P < 0.0001; 95% CI = 0.85-0.91; Youden-Index: 0.67). The maximal intensity of ICG angiography had a specificity of 96.1% and sensitivity of 71.4%. The positive predictive value was 97.46% and the corresponding negative predictive value was 61.34%. CONCLUSION: This demonstrates the potential additional value of ICG videoangiography including FLOW® 800 analyses in the postoperative monitoring of transplanted flaps. © 2016 Wiley Periodicals, Inc. Microsurgery 37:235-242, 2017.

Objective Perfusion Assessment in Gracilis Muscle Interposition-A Novel Software-Based Approach to Indocyanine Green Derived Near-Infrared Fluorescence in Reconstructive Surgery.

BACKGROUND: Gracilis muscle interposition (GMI) is an established treatment option for complex perineal fistulas and reconstruction. The outcome is limited by complications such as necrosis, impaired wound healing and fistula persistence or recurrence. Quantifiable methods of assessing muscle flap perfusion intraoperatively are lacking. This study evaluates a novel and objective software-based assessment of indocyanine green near-infrared fluorescence (ICG-NIRF) in GMI. METHODS: Intraoperative ICG-NIRF visualization data of five patients with inflammatory bowel disease (IBD) undergoing GMI for perineal fistula and reconstruction were analyzed retrospectively. A new software was utilized to generate perfusion curves for the specific regions of interest (ROIs) of each GMI by depicting the fluorescence intensity over time. Additionally, a pixel-to-pixel and perfusion zone analysis were performed. The findings were correlated with the clinical outcome. RESULTS: Four patients underwent GMI without postoperative complications within 3 months. The novel perfusion indicators identified here (shape of the perfusion curve, maximum slope value, distribution and range) indicated adequate perfusion. In one patient, GMI failed. In this case, the perfusion indicators suggested impaired perfusion. CONCLUSIONS: We present a novel, software-based approach for ICG-NIRF perfusion assessment, identifying previously unknown objective indicators of muscle flap perfusion. Ready for intraoperative real-time use, this method has considerable potential to optimize GMI surgery in the future.

Perfusion Visualization during Ileal J-Pouch Formation-A Proposal for the Standardization of Intraoperative Imaging with Indocyanine Green Near-Infrared Fluorescence and a Postoperative Follow-Up in IBD Surgery.

BACKGROUND: An anastomotic leak (AL) after a restorative proctocolectomy and an ileal J-pouch increases morbidity and the risk of pouch failure. Thus, a perfusion assessment during J-pouch formation is crucial. While indocyanine green near-infrared fluorescence (ICG-NIRF) has shown potential to reduce ALs, its suitability in a restorative proctocolectomy remains unclear. We aimed to develop a standardized approach for investigating ICG-NIRF and ALs in pouch surgery. METHODS: Patients undergoing a restorative proctocolectomy with an ileal J-pouch for ulcerative colitis at an IBD-referral-center were included in a prospective study in which an AL within 30 postoperative days was the primary outcome. Intraoperatively, standardized perfusion visualization with ICG-NIRF was performed and video recorded for postoperative analysis at three time points. Quantitative clinical and technical variables (secondary outcome) were correlated with the primary outcome by descriptive analysis and logistic regression. A novel definition and grading of AL of the J-pouch was applied. A postoperative pouchoscopy was routinely performed to screen for AL. RESULTS: Intraoperative ICG-NIRF-visualization and its postoperative visual analysis in 25 patients did not indicate an AL. The anastomotic site after pouch formation appeared completely fluorescent with a strong fluorescence signal (category 2) in all cases of ALs (4 of 25). Anastomotic site was not changed. ICG-NIRF visualization was reproducible and standardized. Logistic regression identified a two-stage approach vs. a three-stage approach (Odds ratio (OR) = 20.00, 95% confidence interval [CI] = 1.37-580.18, p = 0.029) as a risk factor for ALs. CONCLUSION: We present a standardized, comparable approach of ICG-NIRF visualization in pouch surgery. Our data indicate that the visual interpretation of ICG-NIRF alone may not detect ALs of the pouch in all cases-quantifiable, objective methods of interpretation may be required in the future.

Feasibility of Novel Software-Based Perfusion Indicators for the Ileal J-Pouch-On the Path towards Objective and Quantifiable Intraoperative Perfusion Assessment with Indocyanine Green Near-Infrared Fluorescence.

BACKGROUND: In restorative proctocolectomy with ileal J-pouch, perfusion assessment is vital to prevent complications such as anastomotic leak (AL). Indocyanine green near-infrared fluorescence (ICG-NIRF) is gaining popularity, while its interpretation and relevance remain subjective. This study aimed to evaluate a standardized ICG-NIRF imaging protocol combined with a novel, software-based assessment to detect areas of impaired perfusion and a possible correlation with AL of the pouch. METHODS: In this prospective study, patients undergoing ileal J-pouch for ulcerative colitis at an inflammatory bowel disease (IBD) referral center were included. Intraoperatively, strictly standardized ICG-NIRF visualization was performed and video-recorded. Postoperatively, a specific software was utilized to determine the change in fluorescence intensity per second (i/s) for systematic regions of interest, generating perfusion-time curves and a pixel-to-pixel map. These were analysed in detail and correlated with clinical outcome (primary end point: AL within 30 days; clearly defined and screened for by pouchoscopy). RESULTS: Four out of 18 included patients developed AL of the ileal pouch-anal anastomosis (IPAA). In the AL group, the perfusion curves on the area adjacent to the IPAA (pouch apex) displayed considerably lower ingress/inflow (median = 1.7; range = 8.5; interquartile-range = 3.8 i/s) and egress/outflow (median = -0.1; range = 0.7; interquartile-range = 0.5 i/s) values than in the non-AL group (ingress: median = 4.3; range = 10.3; interquartile-range = 4.0 i/s); egress: median = (-1.1); range = 3.9; interquartile range = 1.0 i/s). This was confirmed by further novel parameters of pouch perfusion (maximum ingress; maximum egress) and pixel-to-pixel analysis. CONCLUSIONS: This study presents the feasibility of a novel methodology to precisely assess pouch perfusion with ICG-NIRF, identifying comparable, quantifiable, and objective parameters to potentially detect perfusion-associated complications in surgery in real-time.

Effects of endothelial defects and venous interposition grafts on the acute incidence of thrombus formation within microvascular procedures.

Endothelial defects (ED) and the usage of interposition vein grafts (IVG) are known risk factors for free flap failure. This experimental study aimed to compare both situations of thrombus formation and fluorescence angiographic behavior. Indocyanine green videoangiography (ICGVA) with the FLOW 800 tool was systematically performed in groups I = ED, II = IVG, and III = ED and IVG (each n = 11). ICGVA was able to detect thrombosis in five animals and safely ruled it out in 26 with two false-positive cases (sensitivity, specificity, and positive and negative predictive values were 100%, 90%, 62%, and 100%, respectively). The difference between visually and ICGVA-assisted ED measurements was significant (p = 0.04). The areas of thrombosis showed no significant difference. Moreover, ICGVA detected a decrease of all parameters at the ED area and/or within the IVG section in all groups. The presence of an endothelial defect had a higher impact on thrombus formation than the IVG usage. ICGVA is qualitatively able to detect endothelial defects and clinically evident thrombosis. However, the quantitative values are not yet attributable to one of the clinical scenarios that may jeopardize free flap transfer.

Publisher Correction: A comparative analysis using flowmeter, laser-Doppler spectrophotometry, and indocyanine green-videoangiography for detection of vascular stenosis in free flaps.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A comparative analysis using flowmeter, laser-Doppler |spectrophotometry, and indocyanine green-videoangiography for detection of vascular stenosis in free flaps.

The effects of gradual vascular occlusion on the blood supply of perfused areas are poorly described. Information relating to the comparison of flap monitoring techniques is lacking. Varying stenotic conditions (0%, 25%, 50%, 75% and 100%) were generated on purpose at the A. and V. femoralis in the rat model. Analyses included flowmeter, simultaneous laser-Doppler flowmetry and tissue spectrophotometry (O2C) and indocyanine green- (ICG-) videoangiography with integrated FLOW 800 tool. A Random Forests prediction model was used to analyse the importance of each method to diagnose the stenotic conditions. The ability to discriminate and to accurately estimate the probability of stenosis was assessed by Receiver Operating Characteristic (ROC) curves and calibration plots. Blood flow changes for all modalities were described in detail. Flowmeter displayed earliest a linear decrease as a result of increasing stenosis. A stenosis of 50% degrees was most difficult to detect correctly. The combination of flowmeter and ICG-videoangiography showed high diagnostic power for each stenotic situation (area under the ROC > 0.79). Flowmeter and ICG-videoangiography showed to be most relevant in detection of varying stenotic conditions and may change the clinical outcome. The O2C showed less effect on varying stenotic situations as the only surface monitoring device.

Multimodal analysis using flowmeter analysis, laser-Doppler spectrophotometry, and indocyanine green videoangiography for the detection of venous compromise in flaps in rats.

Venous congestion results in tissue damage and remains the most common failure of free microvascular transfer if it is not recognized early. The purpose of this experimental study was to evaluate venous congestion and describe the findings with two different monitoring tools. A standardized epigastric flap was raised, and total occlusion of the draining vein was temporarily applied for 4, 5, 6, or 7 h. Blood flow measurements, including laser-Doppler flowmetry, and tissue spectrophotometry (O2C) and indocyanine green (ICG) videoangiography using the FLOW® 800 tool, were performed systematically after each surgical step, an interval of venous occlusion, and 1 week of clinical observation. Both monitoring tools were capable of detecting acute venous occlusion. ICG videoangiography data showed a significant decrease in the first and second maximum, and the area under the curve, during venous occlusion, whereas hemoglobin levels in the O2C analysis remained stable. Changes in fluorescence values in border areas of the flap correlated significantly with the incidence of necrosis. O2C data later showed significant correlation with the area of necrosis, and more individual changes during flap monitoring. ICG videoangiography might therefore be useful in the prediction of flap necrosis in critical areas of perfusion.

Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux.

Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products without taking any damage. Therefore, effects of a sudden rise in glucose concentrations were studied in yeast cells. This revealed a feedback mechanism initiated by the reactive dicarbonyl methylglyoxal, which is formed non-enzymatically during glycolysis. Low levels of methylglyoxal activate a multi-layered defence response against toxic metabolites composed of prevention, detoxification and damage remission. The latter is mediated by the protein quality control system and requires inducible Hsp70 and Btn2, the aggregase that sequesters misfolded proteins. This glycohormetic mechanism enables cells to pre-adapt to rising energy flux and directly links metabolic to proteotoxic stress. Further data suggest the existence of a similar response in endothelial cells.

Anterior capsulotomy for treatment of refractory obsessive-compulsive disorder: results in a young and an old patient.

The objective of this case report was to assess the effect of anterior capsulotomy for obsessive-compulsive disorder (OCD) in 2 patients beyond extremes of age ranges of published radiofrequency capsulotomy. The youngest patient developed OCD at age 10 with increasing symptoms of tension and worry. The symptoms were refractory to medications and behavioral therapy. He underwent anterior capsulotomy at age 18. The older patient was 64 at the time of surgery. His OCD began about age 17 with checking and counting rituals. His obsessions extended into other areas such as fear of injuring people while driving. His work performance was greatly compromised. Despite medication trials his rituals and obsessions intensified. After 47 years of severe symptoms he underwent surgery. The youngest patient returned to high school full-time and graduated. He was able to read and comprehend without obsessing about the meaning of words. His thinking and behavior became symptom free and he married 4.5 years after surgery. His score on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after surgery on no medication is zero. The older patient improved gradually without medication. He could play with and touch his grandchildren for the first time. He could drive a car again and his Y-BOCS dropped from 30 preoperatively to 8. Twenty-four months after surgery he is essentially free of obsessions, compulsions and anxiety. We conclude that treatment-refractory OCD may be alleviated by anterior radiofrequency capsulotomy in the young and the old patient. This study expands the documented age range of response from 18 to 64.