Complete mesocolic excision for right colonic cancer: prospective multicentre study.

BACKGROUND: Complete mesocolic excision (CME) for right colonic cancer is a more complex operation than standard right hemicolectomy but evidence to support its routine use is still limited. This prospective multicentre study evaluated the effect of CME on long-term survival in colorectal cancer centres in Germany (RESECTAT trial). The primary hypothesis was that 5-year disease-free survival would be higher after CME than non-CME surgery. A secondary hypothesis was that there would be improved survival of patients with a mesenteric area greater than 15 000 mm2. METHODS: Centres were asked to continue their current surgical practices. The surgery was classified as CME if the superior mesenteric vein was dissected; otherwise it was assumed that no CME had been performed. All specimens were shipped to one institution for pathological analysis and documentation. Clinical data were recorded in an established registry for quality assurance. The primary endpoint was 5-year overall survival for stages I-III. Multivariable adjustment for group allocation was planned. Using a primary hypothesis of an increase in disease-free survival from 60 to 70 per cent, a sample size of 662 patients was calculated with a 50 per cent anticipated drop-out rate. RESULTS: A total of 1004 patients from 53 centres were recruited for the final analysis (496 CME, 508 no CME). Most operations (88.4 per cent) were done by an open approach. Anastomotic leak occurred in 3.4 per cent in the CME and 1.8 per cent in the non-CME group. There were slightly more lymph nodes found in CME than non-CME specimens (mean 55.6 and 50.4 respectively). Positive central mesenteric nodes were detected more in non-CME than CME specimens (5.9 versus 4.0 per cent). One-fifth of patients had died at the time of study with recorded recurrences (63, 6.3 per cent), too few to calculate disease-free survival (the original primary outcome), so overall survival (not disease-specific) results are presented. Short-term and overall survival were similar in the CME and non-CME groups. Adjusted Cox regression indicated a possible benefit for overall survival with CME in stage III disease (HR 0.52, 95 per cent c.i. 0.31 to 0.85; P = 0.010) but less so for disease-free survival (HR 0.66; P = 0.068). The secondary outcome (15 000 mm2 mesenteric size) did not influence survival at any stage (removal of more mesentery did not alter survival). CONCLUSION: No general benefit of CME could be established. The observation of better overall survival in stage III on unplanned exploratory analysis is of uncertain significance.

Detecting and managing partial shorts in Cochlear implants: A validation of scalp surface potential testing.

OBJECTIVE: To investigate the value of scalp surface potentials to identify and manage partial short circuits to ground in cochlear implant electrodes. DESIGN: A retrospective review of patients with suspected partial short circuits. MAIN OUTCOME MEASURE: Electrical output of individual electrodes was measured using scalp surface potentials for patients reporting a change in hearing function. Electrical output was compared to functional performance and impedance measurements to determine if devices with suspected partial short circuits were experiencing a decrease in performance as a result of reduced electrical output. Electrical output was checked in an artificial cochlea for two implants following explant surgery to confirm scalp surface potential results. RESULTS: All patients with suspected partial short circuits (n = 49) had reduced electrical output, a drop in impedances to approximately ½ of previously stable measurements or to below 2 kΩ, an atypical electrical field measurement (EFI) and a decline in hearing function. Only devices with an atypical EFI showed reduced electrical output. Results of scalp based surface potentials could be replicated in an artificial cochlea following explantation of the device. All explant reports received to date (n = 42) have confirmed partial short circuits, with an additional four devices failing integrity tests. CONCLUSION: Surface potential measurements can detect partial shorts and had 100% correlation with atypical EFI measurements, which are characteristic of a partial short to ground in this device. Surface potentials can help determine the degree to which the electrode array is affected, particularly when behavioural testing is limited or not possible.

A Surrogate Matrix-Based Approach Toward Multiplexed Quantitation of an sGC Stimulator and cGMP in Ocular Tissue and Plasma.

A liquid chromatography-tandem mass spectrometry assay was developed and qualified for the multiplexed quantitation of a small molecule stimulator of soluble guanylate cyclase (sGC) and its target engagement biomarker, 3',5'-cyclic guanosine monophosphate (cGMP), in ocular tissues and plasma from a single surrogate matrix calibration curve. A surrogate matrix approach was used in this assay due to the limited quantities of blank ocular matrices in a discovery research setting. After optimization, the assay showed high accuracy, precision, and recovery as well as parallelism between the surrogate matrix and the biological matrices (rabbit plasma, vitreous, and retina-choroid). This assay provided pharmacokinetic and target engagement data after intravitreal administration of the sGC stimulator. The nitric oxide-sGC-cGMP pathway is a potential target to address glaucoma. Increasing sGC-mediated production of cGMP could improve aqueous humor outflow and ocular blood flow. The sGC stimulator showed dose-dependent exposure in rabbit vitreous, retina-choroid, and plasma. The cGMP exhibited a delayed yet sustained increase in vitreous humor but not retina-choroid. Multiplexed measurement of both pharmacokinetic and target engagement analytes reduced animal usage and provided improved context for interpreting PK and PD relationships.

Detection of Extracochlear Electrodes in Cochlear Implants with Electric Field Imaging/Transimpedance Measurements: A Human Cadaver Study.

OBJECTIVES: Extracochlear electrodes in cochlear implants (CI), defined as individual electrodes on the electrode array located outside of the cochlea, are not a rare phenomenon. The presence of extracochlear electrodes frequently goes unnoticed and could result in them being assigned stimulation frequencies that are either not delivered to, or stimulating neurons that overlap with intracochlear electrodes, potentially reducing performance. The current gold-standard for detection of extracochlear electrodes is computed tomography (CT), which is time-intensive, costly and involves radiation. It is hypothesized that a collection of Stimulation-Current-Induced Non-Stimulating Electrode Voltage recordings (SCINSEVs), commonly referred to as "transimpedance measurements (TIMs)" or electric field imaging (EFI), could be utilized to detect extracochlear electrodes even when contact impedances are low. An automated analysis tool is introduced for detection and quantification of extracochlear electrodes. DESIGN: Eight fresh-frozen human cadaveric heads were implanted with the Advanced Bionics HiRes90K with a HiFocus 1J lateral-wall electrode. The cochlea was flushed with 1.0% saline through the lateral semicircular canal. Contact impedances and SCINSEVs were recorded for complete insertion and for 1 to 5 extracochlear electrodes. Measured conditions included: air in the middle ear (to simulate electrodes situated in the middle ear), 1.0% saline in the middle ear (to simulate intraoperative conditions with saline or blood in the middle ear), and soft tissue (temporal muscle) wrapped around the extracochlear electrodes (to simulate postoperative soft-tissue encapsulation of the electrodes). Intraoperative SCINSEVs from patients were collected, for clinical purposes during slow insertion of the electrode array, as well as from a patient postoperatively with known extracochlear electrodes. RESULTS: Full insertion of the cochlear implant in the fresh-frozen human cadaveric heads with a flushed cochlea resulted in contact impedances in the range of 6.06 ± 2.99 kΩ (mean ± 2SD). Contact impedances were high when the extracochlear electrodes were located in air, but remained similar to intracochlear contact impedances when in saline or soft tissue. SCINSEVs showed a change in shape for the extracochlear electrodes in air, saline, and soft tissue. The automated analysis tool showed a specificity and sensitivity of 100% for detection of two or more extracochlear electrodes in saline and soft tissue. The quantification of two or more extracochlear electrodes was correct for 84% and 81% of the saline and soft tissue measurements, respectively. CONCLUSIONS: Our analysis of SCINSEVs (specifically the EFIs from this manufacturer) shows good potential as a detection tool for extracochlear electrodes, even when contact impedances remain similar to intracochlear values. SCINSEVs could potentially replace CT in the initial screening for extracochlear electrodes. Detecting migration of the electrode array during the final stages of surgery could potentially prevent re-insertion surgery for some CI users. The automated detection tool could assist in detection and quantification of two or more extracochlear electrodes.

Noninvasive diagnosis of urothelial cancer in urine using DNA hypermethylation signatures-Gender matters.

Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa-associated hypermethylated sites were identified in urine of a male screening cohort (n = 24) applying Infinium-450K-methylation arrays and verified in two separate mixed-gender study groups (n = 617 in total) using mass spectrometry as an independent technique. Additionally, tissue samples (n = 56) of mixed-gender UCa and urological controls (UCt) were analyzed. The hypermethylation signature of UCa in urine was specific and sensitive across all stages and grades of UCa and independent on hematuria. Individual CpG sensitivities reached up to 81.3% at 95% specificity. Albeit similar methylation differences in tissue of both genders, differences were less pronounced in urine from women, most likely due to the frequent presence of squamous epithelial cells and leukocytes. Increased repression of methylation levels was observed at leukocyte counts ≥500/µl urine which was apparent in 30% of female and 7% of male UCa cases, further confirming the significance of the relative amounts of cancerous and noncancerous cells in urine. Our study shows that gender difference is a most relevant issue when evaluating the performance of urinary biomarkers in cancer diagnostics. In case of UCa, the clinical benefits of methylation signatures to male patients may outweigh those in females due to the general composition of women's urine. Accordingly, these markers offer a diagnostic option specifically in males to decrease the number of invasive cystoscopies.

Oligo(Lactic Acid)8-Rapamycin Prodrug-Loaded Poly(Ethylene Glycol)-block-Poly(Lactic Acid) Micelles for Injection.

PURPOSE: To prepare an oligo(lactic acid)8-rapamycin prodrug (o(LA)8-RAP)-loaded poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelle for injection and characterize its compatibility and performance versus a RAP-loaded PEG-b-PLA micelle for injection in vitro and in vivo. METHODS: Monodisperse o(LA)8 was coupled on RAP at the C-40 via DCC/DMAP chemistry, and conversion of o(LA)8-RAP prodrug into RAP was characterized in vitro. Physicochemical properties of o(LA)8-RAP- and RAP-loaded PEG-b-PLA micelles and their antitumor efficacies in a syngeneic 4 T1 breast tumor model were compared. RESULTS: Synthesis of o(LA)8-RAP prodrug was confirmed by 1H NMR and mass spectroscopy. The o(LA)8-RAP prodrug underwent conversion in PBS and rat plasma by backbiting and esterase-mediated cleavage, respectively. O(LA)8-RAP-loaded PEG-b-PLA micelles increased water solubility of RAP equivalent to 3.3 mg/ml with no signs of precipitation. Further, o(LA)8-RAP was released more slowly than RAP from PEG-b-PLA micelles. With added physical stability, o(LA)8-RAP-loaded PEG-b-PLA micelles significantly inhibited tumor growth relative to RAP-loaded PEG-b-PLA micelles in 4 T1 breast tumor-bearing mice without signs of acute toxicity. CONCLUSIONS: An o(LA)8-RAP-loaded PEG-b-PLA micelle for injection is more stable than a RAP-loaded PEG-b-PLA micelle for injection, and o(LA)8-RAP converts into RAP rapidly in rat plasma (t1/2 = 1 h), resulting in antitumor efficacy in a syngeneic 4 T1 breast tumor model.

TGFBI Protein Is Increased in the Urine of Patients with High-Grade Urothelial Carcinomas, and Promotes Cell Proliferation and Migration.

Here, we discovered TGFBI as a new urinary biomarker for muscle invasive and high-grade urothelial carcinoma (UC). After biomarker identification using antibody arrays, results were verified in urine samples from a study population consisting of 303 patients with UC, and 128 urological and 58 population controls. The analyses of possible modifying factors (age, sex, smoking status, urinary leukocytes and erythrocytes, and history of UC) were calculated by multiple logistic regression. Additionally, we performed knockdown experiments with TGFBI siRNA in bladder cancer cells and investigated the effects on proliferation and migration by wound closure assays and BrdU cell cycle analysis. TGFBI concentrations in urine are generally increased in patients with UC when compared to urological and population controls (1321.0 versus 701.3 and 475.6 pg/mg creatinine, respectively). However, significantly increased TGFBI was predominantly found in muscle invasive (14,411.7 pg/mg creatinine), high-grade (8190.7 pg/mg) and de novo UC (1856.7 pg/mg; all p < 0.0001). Knockdown experiments in vitro led to a significant decline of cell proliferation and migration. In summary, our results suggest a critical role of TGFBI in UC tumorigenesis and particularly in high-risk UC patients with poor prognosis and an elevated risk of progression on the molecular level.

Oligo(lactic acid)n-Paclitaxel Prodrugs for Poly(ethylene glycol)-block-poly(lactic acid) Micelles: Loading, Release, and Backbiting Conversion for Anticancer Activity.

Poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) micelles are nanocarriers for poorly water-soluble anticancer agents and have advanced paclitaxel (PTX) to humans due to drug solubilization, biocompatibility, and dose escalation. However, PEG-b-PLA micelles rapidly release PTX, resulting in widespread biodistribution and low tumor exposure. To improve delivery of PTX by PEG-b-PLA micelles, monodisperse oligo(l-lactic acid), o(LA)8 or o(LA)16, has been coupled onto PTX at the 7-OH position, forming ester prodrugs: o(LA)8-PTX and o(LA)16-PTX, respectively. As expected, o(LA)n-PTX was more compatible with PEG-b-PLA micelles than PTX, increasing drug loading from 11 to 54%. While in vitro release of PTX was rapid, resulting in precipitation, o(LA)n-PTX release was more gradual: t1/2 = 14 and 26 h for o(LA)8-PTX and o(LA)16-PTX, respectively. Notably, o(LA)8-PTX and o(LA)16-PTX in PEG-b-PLA micelles resisted backbiting chain end scission, based on reverse-phase HPLC analysis. By contrast, o(LA)8-PTX and o(LA)16-PTX degraded substantially in 1:1 acetonitrile:10 mM PBS, pH 7.4, at 37 °C, generating primarily o(LA)2-PTX. The IC50 value of o(LA)2-PTX was ∼2.3 nM for A549 human lung cancer cells, equipotent with PTX in vitro. After weekly IV injections at 20 mg/kg as PEG-b-PLA micelles, o(LA)8-PTX induced tumor regression in A549 tumor-bearing mice, whereas PTX delayed tumor growth. Surprisingly, o(LA)8-PTX caused less toxicity than PTX in terms of change in body weight. In conclusion, o(LA)n acts as a novel promoiety, undergoing backbiting conversion without a reliance on metabolizing enzymes, and o(LA)n-PTX improves PTX delivery by PEG-b-PLA micelles, providing a strong justification for clinical evaluation.

The uncinate process first approach: a novel technique for laparoscopic right hemicolectomy with complete mesocolic excision.

BACKGROUND: Current evidence suggests that complete mesocolic excision (CME) for right-sided colon cancer could be beneficial in terms of long-term survival. However, CME is a considerably more complex operation than standard right hemicolectomy; this is especially true for the laparoscopic approach. Consequently, we have explored a new laparoscopic approach that provides surgical radicality at the mesenteric root on the one hand and maximum safety on the other hand. METHODS: The key feature of the uncinate process first approach (UFA) is the commencement of the dissection at the fourth part of the duodenum using a medial to lateral approach, thus mobilizing the whole mesenteric root posteriorly before the central parts of the mesenteric vessels are accessed. Twenty-eight selected patients with right-sided colon cancer underwent surgery using the UFA and were compared with 51 patients who underwent an open CME procedure (CON). In 11/28 and 51/51 patients in the UFA and CON groups, respectively, a planimetric assessment of the specimen was performed. RESULTS: Surgical time was longer (144.8 vs. 202.5 min; p < 0.000) and postoperative stay shorter (8.0 vs. 10.5 days; p < 0.01) for the laparoscopic approach. The area of the resected mesentery (UFA, 15,097 mm(2); CON, 15,788 mm(2); p = 0.47) and the lymph node count (UFA, 59.0; CON, 51.0; p = 0.09) was not significantly different; additionally, no difference was observed regarding anastomotic leakage (both n = 0) and postoperative mortality (UFA, 0/28; CON, 1/51; p = 1.0). CONCLUSION: Laparoscopic right hemicolectomy with CME using the UFA provides adequate radicality according to the CME principles and seems feasible and as safe as an open technique. However, future trails will have to demonstrate whether the theoretical advantages of the UFA, with a higher degree of mobility and accessibility of the mesenteric root, translate into a significant clinical benefit, especially relative to the other laparoscopic techniques.

Itinerancy-enhanced quantum fluctuation of magnetic moments in iron-based superconductors.

We investigate the influence of itinerant carriers on the dynamics and fluctuation of local moments in Fe-based superconductors, via linear spin-wave analysis of a spin-fermion model containing both itinerant and local degrees of freedom. Surprisingly, against the common lore, instead of enhancing the (π,0) order, itinerant carriers with well-nested Fermi surfaces are found to induce a significant amount of spatial and temporal quantum fluctuation that leads to the observed small ordered moment. Interestingly, the underlying mechanism is shown to be an intrapocket nesting-associated long-range coupling rather than the previously believed ferromagnetic double-exchange effect. This challenges the validity of ferromagnetically compensated first-neighbor coupling reported from short-range fitting to the experimental dispersion, which turns out to result instead from the ferro-orbital order that is also found instrumental in stabilizing the magnetic order.

A scoping review on the clinical effectiveness of Trans-Impedance Matrix (TIM) measurements in detecting extracochlear electrodes and tip fold overs in Cochlear Ltd devices.

BACKGROUND: Extrusion of electrodes outside the cochlea and tip fold overs may lead to suboptimal outcomes in cochlear implant (CI) recipients. Intraoperative measures such as Trans-Impedance Matrix (TIM) measurements may enable clinicians to identify electrode malposition and direct surgeons to correctly place the electrode array during surgery. OBJECTIVES: To assess the current literature on the effectiveness of TIM measurements in identifying extracochlear electrodes and tip fold overs. METHODS: A scoping review of studies on TIM-based measurements were carried out using the Databases-Medline/PubMed, AMED, EMBASE, CINAHL and the Cochrane Library following PRISMA guidelines. Eleven full texts articles met the inclusion criteria. Only human studies pertaining to TIM as a tool used in CI were included in the review. Further, patient characteristics, electrode design, and TIM measurement outcomes were reported. RESULTS: TIM measurements were available for 550 implanted ears with the subjects age ranged between 9 months to 89 years. Abnormal TIM measurements were reported for 6.55% (36). Tip fold over was detected in 3.64% (20) of the cases, extracochlear electrodes in 1.45% (8), and 1.45% (8) were reported as buckling. Slim-modiolar electrode array designs were more common (54.71%) than pre-curved (23.34%) or lateral wall (21.95%) electrode array. Abnormal cochlear anatomy was reported for five ears (0.89%), with normal cochlear anatomy for all other patients. CONCLUSION: TIM measurement is a promising tool for the intraoperative detection of electrode malposition. TIM measurement has a potential to replace intraoperative imaging in future. Though, TIM measurement is in its early stages of clinical utility, intuitive normative data sets coupled with standardised criteria for detection of abnormal electrode positioning would enhance its sensitivity.

A New Approach for Preparing Stable High-Concentration Peptide Nanoparticle Formulations.

The subcutaneous administration of therapeutic peptides would provide significant benefits to patients. However, subcutaneous injections are limited in dosing volume, potentially resulting in high peptide concentrations that can incur significant challenges with solubility limitations, high viscosity, and stability liabilities. Herein, we report on the discovery that low-shear resonant acoustic mixing can be used as a general method to prepare stable nanoparticles of a number of peptides of diverse molecular weights and structures in water without the need for extensive amounts of organic solvents or lipid excipients. This approach avoids the stability issues observed with typical high-shear, high-intensity milling methods. The resultant peptide nanosuspensions exhibit low viscosity even at high concentrations of >100 mg/mL while remaining chemically and physically stable. An example nanosuspension of cyclosporine nanoparticles was dosed in rats via a subcutaneous injection and exhibited sustained release behavior. This suggests that peptide nanosuspension formulations can be one approach to overcome the challenges with high-concentration peptide formulations.

Detection of Extracochlear Electrodes Using Stimulation-Current- Induced Non-Stimulating Electrode Voltage Recordings With Different Electrode Designs.

HYPOTHESIS: Stimulation-Current-Induced Non-Stimulating Electrode Voltage Recordings (SCINSEVs) can help detect extracochlear electrodes for a variety of Cochlear Implant (CI) devices. BACKGROUND: Extracochlear electrodes (EEs) occur in 9 to 13% of cochlear implantations and commonly go unnoticed without imaging. Electrodes on the electrode array located extracochlearly are associated with non-auditory stimulation and a decrease in speech outcomes. We have previously shown that SCINSEVs, with hardware and software from one manufacturer, could detect EEs. Here, we test the generalizability to other manufacturers. METHODS: Fresh-frozen human cadaveric heads were implanted with Cochlear Ltd. CI522 (CI-A) and MED-EL's FLEX24 (CI-B) electrodes. Contact impedances and SCIN- SEVs were measured, with Cochlear Ltd. research Custom Sound software (Transimpedance Matrix) and MED-EL's clinical MAESTRO (Impedance Field Telemetry), for full insertion and EEs in air, saline and soft tissue. An automated detection tool was optimized and tested for these implants. Intra-operative SCINSEVs with EEs were collected for clinical purposes for six patients. RESULTS: The pattern of SCINSEVs changed in the transition zone from intracochlear to extracochlear electrodes, even with low contact impedances on EEs. Automated detection in the cadaveric specimens, with two or more EEs in saline or soft tissue, showed a mean 91% sensitivity and specificity for CI-A and 100% sensitivity and specificity for CI-B. Quantification of EEs showed significant correlations of r  = 0.69 between estimated and actual EEs for CI-A and r = 0.76 for CI-B. CONCLUSION: The applicability of SCINSEVs to detect extra- cochlear electrodes could be expanded to other cochlear implant companies despite differences in electrode array design and measurement software.

Management of Severe Facial Nerve Cross Stimulation by Cochlear Implant Replacement to Change Pulse Shape and Grounding Configuration: A Case-series.

OBJECTIVES: To investigate the combined effect of changing pulse shape and grounding configuration to manage facial nerve stimulation (FNS) in cochlear implant (CI) recipients. PATIENTS: Three adult CI recipients with severe FNS were offered a replacement implant when standard stimulation strategies and programming adjustments did not resolve symptoms. Our hypothesis was that the facial nerve was less likely to be activated when using anodic pulses with "mixed-mode" intra-cochlear and extra-cochlear current return. INTERVENTION: All patients were reimplanted with an implant that uses a pseudo-monophasic anodic pulse shape, with mixed-mode grounding (stimulus mixed-mode anodic)-the Neuro Zti CI (Oticon Medical). This device also allows measurements of neural function and loudness with monopolar, symmetric biphasic pulses (stimulus MB), the clinical standard used by most CIs as a comparison. MAIN OUTCOME MEASURES: The combined effect of pulse shape and grounding configuration on FNS was monitored during surgery. Following CI activation, FNS symptoms and performance with the Neuro Zti implant were compared with outcomes before reimplantation. RESULTS: FNS could only be recorded using stimulus MB for all patients. In clinical use, all patients reported reduced FNS and showed an improvement in Bamford-Kowal-Bench sentences recognition compared with immediately before reimplantation. Bamford-Kowal-Bench scores with a male speaker were lower compared with measurements taken before the onset of severe FNS for patients 1 and 2. CONCLUSIONS: In patients where CI auditory performance was severely limited by FNS, charge-balanced pseudo-monophasic stimulation mode with a mixed-mode grounding configuration limited FNS and improved loudness percept compared with standard biphasic stimulation with monopolar grounding.

An Instrumented Cochlea Model for the Evaluation of Cochlear Implant Electrical Stimulus Spread.

Cochlear implants use electrical stimulation of the auditory nerve to restore the sensation of hearing to deaf people. Unfortunately, the stimulation current spreads extensively within the cochlea, resulting in "blurring" of the signal, and hearing that is far from normal. Current spread can be indirectly measured using the implant electrodes for both stimulating and sensing, but this provides incomplete information near the stimulating electrode due to electrode-electrolyte interface effects. Here, we present a 3D-printed "unwrapped" physical cochlea model with integrated sensing wires. We integrate resistors into the walls of the model to simulate current spread through the cochlear bony wall, and "tune" these resistances by calibration with an in-vivo electrical measurement from a cochlear implant patient. We then use this model to compare electrical current spread under different stimulation modes including monopolar, bipolar and tripolar configurations. Importantly, a trade-off is observed between stimulation amplitude and current focusing among different stimulation modes. By combining different stimulation modes and changing intracochlear current sinking configurations in the model, we explore this trade-off between stimulation amplitude and focusing further. These results will inform clinical strategies for use in delivering speech signals to cochlear implant patients.

3D printed biomimetic cochleae and machine learning co-modelling provides clinical informatics for cochlear implant patients.

Cochlear implants restore hearing in patients with severe to profound deafness by delivering electrical stimuli inside the cochlea. Understanding stimulus current spread, and how it correlates to patient-dependent factors, is hampered by the poor accessibility of the inner ear and by the lack of clinically-relevant in vitro, in vivo or in silico models. Here, we present 3D printing-neural network co-modelling for interpreting electric field imaging profiles of cochlear implant patients. With tuneable electro-anatomy, the 3D printed cochleae can replicate clinical scenarios of electric field imaging profiles at the off-stimuli positions. The co-modelling framework demonstrated autonomous and robust predictions of patient profiles or cochlear geometry, unfolded the electro-anatomical factors causing current spread, assisted on-demand printing for implant testing, and inferred patients' in vivo cochlear tissue resistivity (estimated mean = 6.6 kΩcm). We anticipate our framework will facilitate physical modelling and digital twin innovations for neuromodulation implants.

Cochlear Implantation in NF2 Patients Without Intracochlear Schwannoma Removal.

OBJECTIVE: To determine if cochlear implantation without removal of inner ear schwannomas (IES) is an effective treatment option for Neurofibromatosis 2 (NF2) patients. To determine how the presence of an intracochlear schwannoma might impact cochlear implant (CI) outcomes and programming parameters. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary center for cochlear and auditory brainstem implantation. PATIENTS: Of 10 NF2 patients with IES, 8 are reported with no previous tumor removal on the implanted ear. INTERVENTIONS: Cochlear implant without tumor removal. MAIN OUTCOME MEASURES: Performance outcomes with CI at least 1-year post intervention. Programming parameters, including impedances, for patients with IES. RESULTS: All patients had full insertion of the electrode arrays with round window approaches. Performance outcomes ranged from 0 to 100% for Bamford-Kowal-Bench sentences. Impedance measurements for active electrodes for patients with IES were comparable to those measured in patients without vestibular schwannoma (VS). Only patients who had radiation treatment before receiving their implant had elevated threshold requirements for CI programming compared with CI recipients without VS. CONCLUSION: Cochlear implantation without tumor removal is an effective option for treating NF2 patients with IES. The presence of an intracochlear tumor did not have an impact on CI performance or programming requirements compared with patients without VS; however, previous treatment with radiation may be related to elevated current requirements in the CI settings.