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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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ayas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The overall incidence of skin cancer has risen over the past half a decade worldwide and is associated with significant morbidity and mortality. Recent advances in molecular testing have allowed us to better characterize microbiome alterations in skin cancer. However, literature specific to skin microbiome and skin cancer remain heterogenous and scattered. A systematic review was performed to identify the existing literature and its usefulness in providing microbiome-based biomarkers. A search of the databases (PubMed, Medline, EMBASE, GoogleScholar) was conducted from June to July 2022 in accordance with the PRISMA guidelines. A total of 1,543 articles were identified, of which 16 were selected for inclusion in the review (11 articles on cancer of the keratinocytes and 5 articles on melanoma). Increased Staphylococcus (S.) aureus prevalence with decline in commensal organisms is seen in squamous cell carcinoma (SCC) and actinic keratosis (AK), compared to healthy skin. While the microbiome of melanoma appears to be distinct from healthy skin, limited data is available to draw meaningful conclusions. Our review summarizes the current evidence on the microbiome of keratinocyte skin cancers and melanoma. The study establishes that the microbiome of these cancers is altered from healthy skin and that this dysbiosis involves both pathogenic and commensal organisms., (© 2024 Deutsche Dermatologische Gesellschaft (DDG).)

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., (© 2022 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Background: Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear., Aim: To evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients., Methods: We searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity ( I 2 ) were estimated using Review Manager version 5.3., Results: From 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I 2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I 2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I 2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients., Conclusion: Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients., Competing Interests: Conflict-of-interest statement: Dr. Wong YJ was an invited speaker for Gilead Science. Other authors have no conflict of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: The increasing number of reports on cutaneous reactions following COVID-19 vaccination has led to growing concerns among certain groups., Objective: We reviewed the published reports of cutaneous lesions after COVID-19 vaccination., Methods: We conducted a literature search for original and review articles published between January 1, 2020, and September 27, 2021., Results: Eleven cutaneous reactions associated with COVID-19 vaccines were determined; the most prevalent reactions were local injection site reactions, delayed local reactions, urticaria, angioedema, and morbilliform eruptions. There were more reports on skin reactions following the administration of messenger RNA-based vaccines than on those following the administration of adenoviral vector or inactivated whole-virus vaccines, in part, due to their higher administration rate. Most reported skin reactions occurred after the first vaccine dose., Limitations: A reporting bias could not be excluded, and skin biopsy results were not available for most included individuals. Moreover, given that the included trials focused on vaccine efficacy, there was a lack of details concerning cutaneous reactions and participant information., Conclusion: Not all cutaneous reactions observed after COVID-19 vaccination are hypersensitivity reactions. Different cutaneous reactions may reflect underlying immune responses to the vaccines. A large majority of COVID-19 vaccination reactions were mild and self-limiting, and people should be encouraged to complete their vaccination regimen., Competing Interests: None disclosed., (© 2022 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

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., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Introduction and Aim: Portal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis., Methods: We performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death., Results: From 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I 2  = 79%) and lower pooled risk of PVT progression (RR = 0.14, 95%CI: 0.03-0.57, I 2  = 0%). The pooled risk of major bleeding (RR = 0.29, 95%CI: 0.08-1.01, I 2  = 0%), variceal bleeding (RR = 1.29, 95%CI: 0.64-2.59, I 2  = 0%) and death (RR = 0.31, 95%CI: 0.01-9.578, I 2  = 80%) was similar between DOAC and VKA., Conclusion: For the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings., Competing Interests: Declaration of Competing Interest All authors declared that we had no conflict of interest related to this study titled “Efficacy and safety of direct-acting oral anticoagulants versus vitamin K antagonists for cirrhosis patients with portal vein thrombosis: a systematic review and meta-analysis”, (Copyright © 2021. Published by Elsevier Ltd.)

Background: Occupational dermatoses caused by personal protective equipment (PPE) in the ongoing COVID-19 pandemic are emerging occupational health challenges that must be promptly and effectively addressed to ease burden on our health care workers., Objective: A systematic review was conducted to determine common PPE-related dermatoses, affected body sites, and implicated occupational contactants. We further proposed solutions to mitigate this problem., Methods: Online databases were searched for articles on PPE-related dermatoses in health care workers during the COVID-19 pandemic written in English and published from January 1, 2020, to January 30, 2021., Results: Sixteen studies, including a total of 3958 participants, were included. The most common dermatoses were xerosis, pressure-related erythema, and contact dermatitis, mainly affecting the face and hands. The most widely implicated contactants were increased frequency of hand hygiene, gloves, N95 masks, and goggles. Proposed solutions were categorized as individual self-care, protection of the workforce, and long-term preventive measures., Conclusion: Through measures such as regular basic skin care education, early access to specialty clinics via telemedicine, and designing of better-fit PPE, the challenges posed by PPE-related occupational dermatoses can be significantly reduced., Competing Interests: None disclosed., (© 2021 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

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., (© 2021. The Author(s).)

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., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Background and Aims: The efficacy and safety of albumin infusion for treatment and prevention of overt hepatic encephalopathy (OHE) among cirrhosis patients remained controversial. We performed a systematic review and meta-analysis to evaluate the benefit of albumin infusion for the treatment and prevention of OHE., Methods: We performed a systematic search of 4 electronic databases up to 31st January 2021. The primary outcome was the resolution of OHE. Secondary outcomes were inpatient mortality and albumin-associated adverse events. We assessed the pooled odds' risk, pooled mean differences, 95% confidence interval and heterogeneity using Review Manager Version 5.3., Results: A total of 12 studies (2,087 subjects) were identified. Among cirrhosis patients with OHE, albumin infusion was associated with a lower pooled risk of OHE (OR=0.43, 95%CI: 0.27, 0.68; I 2 =0%). Among patients without baseline OHE, albumin infusion was associated with a lower pooled risk of developing OHE (OR=0.53, 95%CI: 0.32, 0.86; I 2 =62%). Albumin infusion was associated with a lower pooled risk of inpatient mortality (OR=0.36, 95%CI: 0.21, 0.60; I 2 =0%)., Conclusion: Well-powered randomized trials are required to confirm the benefits of albumin infusion for the prevention and treatment of overt hepatic encephalopathy among decompensated cirrhosis patients., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Because of the increasing emergence of skin manifestations of COVID-19 worldwide, we investigated the published reports of these lesions., Methods: We conducted a literature search for original and review articles published from November 11, 2019 to September 30, 2020., Results: We identified 5 skin lesions common in patients with COVID-19: pseudo-chilblains, rashes containing macules and papules, and urticarial, vesicular, and vaso-occlusive lesions. These lesions manifested at various times in relation to the COVID-19 symptoms, which may indicate whether the lesions are virus-induced or are delayed immunological responses to the infection. Skin lesions were more prevalent among Europeans and United States residents than among Asians, as was pseudo-chilblain, and the morphology of the skin lesions varied among continents. Pseudo-chilblains were the most common COVID-19 skin manifestation in Europe and the United States, but there was only 1 reported case from Asian populations. Additionally, patients with vaso-occlusive lesions were more likely than those with pseudo-chilblains to be admitted to the intensive care unit and to die., Conclusion: Different cutaneous manifestations in patients with COVID-19 could reflect a wide spectrum of viral interactions with the skin, though reporting bias may play a role as well., Competing Interests: None disclosed., (© 2020 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials INTRODUCTION: Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin., Aim: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients., Methods: We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1 st December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed., Results: A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I 2 =0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I 2 =0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I 2 =0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I 2 =0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02)., Conclusion: Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

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.

We identified DNA methylation targets specific for urothelial cancer (UC) by genome-wide methylation difference analysis of human urothelial (RT4, J82, 5637), prostate (LNCAP, DU-145, PC3) and renal (RCC-KP, CAKI-2, CAL-54) cancer cell lines with their respective primary epithelial cells. A large overlap of differentially methylated targets between all organs was observed and 40 Cytosine-phosphate-Guanine motifs (CpGs) were only specific for UC cells. Of those sites, two also showed high methylation differences (≥47%) in vivo when we further compared our data to those previously obtained in our array-based analyses of urine samples in 12 UC patients and 12 controls. Using mass spectrometry, we finally assessed seven CpG sites in this "bladder-specific" region of interest in urine samples of patients with urothelial ( n = 293), prostate ( n = 75) and renal ( n = 23) cancer, and 143 controls. DNA methylation was significantly increased in UC compared to non-UC individuals. The differences were more pronounced for males rather than females. Male UC cases could be distinguished from non-UC individuals with >30% sensitivity at 95% specificity (Area under the curve (AUC) 0.85). In summary, methylation sites highly specific in UC cell lines were also specific in urine samples of UC patients showing that in-vitro data can be successfully used to identify biomarker candidates of in-vivo relevance.

Objective: To assess the complication rate of magnetic resonance imaging (MRI) using 1.5 T scanners on cochlear implant (CI) and auditory brainstem implant (ABI) recipients over 14.5 years., Methods: Prospective study conducted in a tertiary referral center for cochlear and auditory brainstem implantation, including patients with neurofibromatosis 2. The primary outcome was complications related to MRI scanning in implant recipients, including failure to complete MRI sessions. The secondary outcome was magnet void size due to MRI scanning with magnet in situ., Results: Ninety-seven patients (21 ABI recipients, 76 CI recipients of whom 23 were bilateral) underwent a total of 428 MRI sessions consisting of 680 MRI procedures, which generated 2,601 MRI sequences (excluding localizers). Of these, 28/428 (6.5%) MRI sessions were performed with magnet removed, and the remaining 400/428 (93.4%) with the magnet in situ. The overall complication rate per session was 15/428 (3.5%). The majority of complications were accounted for by patient discomfort, in some cases requiring abandoning the scan session, but 5 magnet dislocations were also recorded. There were no cases of implant device failure or excessive demagnetization of the receiver stimulator magnet.For CI and ABI recipients, the implant caused large voids of around 110 mm × 60 mm with the magnet in situ which reduced to 60 mm × 30 mm when the magnet was removed. However, it was usually possible to visualize the internal acoustic meatus and cerebellopontine angle by positioning the implant package higher and further forward compared with conventional positioning., Conclusion: MRI scanning in ABI and CI recipients is generally safe and well tolerated without magnet removal, and carries a low rate of complications. However, patients should be fully informed of the possibility of discomfort, and precautions such as local anesthetic injection and head bandaging may reduce the likelihood of adverse events.

Hypothesis: A novel cochlea implant (CI) device magnet providing alignment to the static field of a magnetic resonance imaging (MRI) will lead to reduced torque, longitudinal forces, and demagnetization effects. The image void and distortion will be comparable to those obtained with standard CI magnets., Background: MRI investigations of CI users pose several challenges such as magnet dislocation, demagnetization, and may cause pain. The presence of a CI magnet within MRI field causes image distortions and may diminish the diagnostic value of an MRI procedure. Objective of this work is to evaluate magnetic forces and imaging properties of the novel CI magnet within 1.5 and 3T MRI., Methods: Forces and torque of the novel CI magnet were measured in both 1.5 and 3T MRI and compared with the standard magnet in 1.5T. One cadaver head was implanted with the CI devices containing the novel and standard magnets in different configurations reflecting clinical scenarios and imaging properties were assessed and compared., Results: In particular the torque has been reduced with the novel CI magnet in comparison to the standard one. Both CI magnets have not shown any signs of demagnetization. The image void and distortion was comparable between the two magnets for the main MRI clinical scanning protocols in 1.5T MRI., Conclusions: The novel CI magnet is safe to use for MRI investigations of CI users in 3T MRI without a need for bandaging and has acceptable level of image artefacts.

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.

A series of experiments investigated potential changes in temporal processing during the months following activation of a cochlear implant (CI) and as a function of stimulus level. Experiment 1 tested patients on the day of implant activation and 2 and 6 months later. All stimuli were presented using direct stimulation of a single apical electrode. The dependent variables were rate discrimination ratios (RDRs) for pulse trains with rates centred on 120 pulses per second (pps), obtained using an adaptive procedure, and a measure of the upper limit of temporal pitch, obtained using a pitch-ranking procedure. All stimuli were presented at their most comfortable level (MCL). RDRs decreased from 1.23 to 1.16 and the upper limit increased from 357 to 485 pps from 0 to 2 months post-activation, with no overall change from 2 to 6 months. Because MCLs and hence the testing level increased across sessions, two further experiments investigated whether the performance changes observed across sessions could be due to level differences. Experiment 2 re-tested a subset of subjects at 9 months post-activation, using current levels similar to those used at 0 months. Although the stimuli sounded softer, some subjects showed lower RDRs and/or higher upper limits at this re-test. Experiment 3 measured RDRs and the upper limit for a separate group of subjects at levels equal to 60 %, 80 % and 100 % of the dynamic range. RDRs decreased with increasing level. The upper limit increased with increasing level for most subjects, with two notable exceptions. Implications of the results for temporal plasticity are discussed, along with possible influences of the effects of level and of across-session learning.

Information on biomarkers of urothelial carcinomas (UC) for clinical decision-making is limited. Here, we newly identified and verified CXCL16 as a promising novel biomarker in urine for high grade and muscle invasive UC in a cross-sectional cohort of 308 UC patients, 126 urological hospital controls, and 50 population controls using antibody arrays and ELISA. Median CXCL16 levels in urine was significantly higher in UC patients (273.2 pg/mg creatinine) compared to hospital (148.1 pg/mg) and population controls (85.1 pg/mg) with a particular preference for high grade (460.8 pg/mg), muscle invasive (535.7 pg/mg) and primary UC (327.8 pg/mg) (all p<0.0001). Group differences were confirmed after adjusting or stratifying for potential clinical and individual characteristics, such as leukocyte counts, haematuria, age, gender, and smoking status. In contrast, CXCL16 showed less discriminating power in low grade (244.3 pg/mg), non-muscle invasive (≤pT1, 251.2 pg/mg) and recurrent UC (203.9 pg/mg). In agreement with its function in immune defence, expression of CXCL16 in tissue samples of primary UC patients (n=53) showed only a weak or no immunoreactivity compared to urological hospital controls (n=32). Expression of CXCR6, the G-protein-coupled receptor of CXCL16, remained unchanged. Our findings suggest that evading the immune defence by shedding cell-surface CXCL16 and its increased elimination in urine is a molecular feature of high grade and muscle invasive UC. Therefore, urinary CXCL16 may serve as a useful, simple and non-invasive tool to identify high-risk UC with increased risk of progression at the molecular level., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objective: Review of cochlear implant (CI) outcomes in patients with Neurofibromatosis Type 2 (NF2), implanted in the presence of an ipsilateral vestibular schwannoma (VS). Hearing restoration was combined in some cases with a Bevacizumab regime., Method: Retrospective review of 12 patients, managed over the period 2009-2016, at a tertiary referral multidisciplinary NF2 clinic. The patients are grouped by hearing outcomes to explore likely protective factors, and to generate a proposed decision-making tool for the selection of either CI or Auditory Brainstem Implant (ABI)., Results: Four of the 12 patients achieved speech discrimination without lip-reading. In these individuals there is reason to think that the mechanism of their hearing loss was cochlear dysfunction. A further four patients received benefit to lip-reading and awareness of environmental sound. For such patients their hearing loss may have been due to both cochlear and neural dysfunction. Two patients gained access to environmental sound only from their CI. Two patients derived no benefit from their CIs, which were subsequently explanted. Both these latter patients had had prior ipsilateral tumour surgery, one just before the CI insertion., Conclusion: Cochlear implantation can lead to open set speech discrimination in patients with NF2 in the presence of a stable VS. Use of promontory stimulation and intraoperative electrically evoked auditory brainstem response testing, along with case history, can inform the decision whether to implant an ABI or CI.

Objective: To assess differences in pitch-ranking ability across a range of speech understanding performance levels and as a function of electrode position., Study Design: An observational study of a cross-section of cochlear implantees., Setting: Tertiary referral center for cochlear implantation., Patients: A total of 22 patients were recruited. All three manufacturers' devices were included (MED-EL, Innsbruck, Austria, n = 10; Advanced Bionics, California, USA, n = 8; and Cochlear, Sydney, Australia, n = 4) and all patients were long-term users (more than 18 months). Twelve of these were poor performers (scores on BKB sentence lists <60%) and 10 were excellent performers (BKB >90%)., Intervention: After measurement of threshold and comfort levels, and loudness balancing across the array, all patients underwent thorough pitch-ranking assessments at 80% of comfort levels., Main Outcome Measure: Ability to discriminate pitch across the electrode array, measured by consistency in discrimination of adjacent pairs of electrodes, as well as an assessment of the pitch order across the array using the midpoint comparison task., Results: Within the poor performing group there was wide variability in ability to pitch rank, from no errors, to a complete inability to reliably and consistently differentiate pitch change across the electrode array. Good performers were overall significantly more accurate at pitch ranking (p = 0.026). Consistent pitch ranking was found to be a significant independent predictor of BKB score, even after adjusting for age. Users of the MED-EL implant experienced significantly more pitch confusions at the apex than at more basal parts of the electrode array., Conclusions: Many cochlear implant users struggle to discriminate pitch effectively. Accurate pitch ranking appears to be an independent predictor of overall outcome. Future work will concentrate on manipulating maps based upon pitch discrimination findings in an attempt to improve speech understanding.

Objective: To assess the impact on image quality of MRI without magnet removal in cochlear implant (CI) and auditory brainstem implant (ABI) users with neurofibromatosis type 2 (NF2)., Study Design: Prospective cohort., Setting: Tertiary center for cochlear and auditory brainstem implantation., Patients: Thirteen patients (10 ABI, 3CI) with NF2 underwent a total of 76 MRI scans., Interventions: MRI without magnet removal., Main Outcome Measure: Ability to visualize the ipsilateral and contralateral cerebellopontine angles (CPAs) and internal auditory meati (IAM) with head MRI., Results: Of the 76 scans, 40 were of the head, 28 of the spine and 8 of other regions. Scanning was performed with a tight head bandage and plastic card. There were no cases of altered implant function or demagnetization of the device magnet.A grading system was used to assess the view of the ipsilateral IAM-CPA. In 85% of head scans, the view was unimpaired (Grade 0). In 13%, there was distortion (Grade 1). In 2% (1 case), the view was entirely obscured by artifact (Grade 2). Views of the contralateral CPA and IAM were unimpaired in all cases. The best 3 sequences for the depiction of the ipsilateral IAM-CPA (percent graded as 0) were as follows: axial 3D inversion recovery prepared fast spoiled gradient echo (100%), 2 mm coronal T1W of the IAM-CPA (88.9%), and 2 mm axial T1W of the IAM-CPA (76.9%)., Conclusion: MRI scanning without magnet removal is safe and well tolerated in NF2 patients with auditory implants. With appropriate MRI sequences, the image quality is not significantly impaired.

Objective: To assess published hand hygiene behavioral interventions that employed a social marketing framework and to recommend improvements to future interventions., Methods: We performed a systematic literature review by searching the PubMed database and the Cumulative Index to Nursing and Allied Health Literature for published articles about hand hygiene behavioral interventions in healthcare facilities, schools, and community settings. Our analysis included articles that describe multifaceted interventions and evaluated them with predefined social marketing benchmark criteria., Results: Of 53 interventions analyzed in this review, 16 (30.2%) employed primary formative audience research, 5 (9.4%) incorporated social or behavioral theories, 27 (50.9%) employed segmentation and targeting of the audience, 44 (83.0%) used components of the "marketing mix," 3 (5.7%) considered the influence of competing behaviors, 7 (13.2%) cultivated relationships with the target audience, and 15 (28.3%) provided simple behavioral messages. Thirty-five (66.0%) of the interventions demonstrated a significant improvement in performance, but only 21 (39.6%) were considered to have a strong evaluative design. The median duration of the interventions was 8.0 months., Conclusions: From a social marketing perspective, the promotion of hand hygiene could be improved in several ways. The effectiveness of social marketing in hand hygiene promotion should be tested in future interventions.

Concerns about life support equipment accompanying the critically ill patient have to date made magnetic resonance imaging (MRI) studies of this patient group the exception. We present here a series of tests performed on an IVAC P3000 infusion pump to investigate its suitability for the magnetic resonance imaging environment. We investigate safety, pump performance and image quality issues. The pump was housed at the end of the patient couch to prevent motion towards the scanner. Gravimetric tests found the pump to work within acceptable parameters at a static field of 10 mT. Image interference issues were addressed.

Managing a patient with acquired profound deafness with a cochlear implant involves a lifetime commitment to rehabilitation and also to maintaining the device in a functioning condition. This paper describes the Cambridge experience of maintaining the Ineraid cochlear implant in a series of 25 patients over a 4 year period. On average, maintenance (repair of replacement) of components was required every 2.3 months of implant use, although some minor variations were noted between patients, and between component type. This rate of failure is sufficient to cause an Implant Centre to consider provision for repairs and holding of spare stock. It should be remembered that each breakdown returns the patient to a deafened state, albeit temporarily, but this can cause significant distress.

Fluctuation tests à la Luria and Delbruck were performed with mouse LMTK cells, and the results indicate that the appearance of variants resistant to cadmium is due to random spontaneous mutations and not to epigenetic events. The rate of spontaneous mutations leading to cadmium resistance was calculated to be 0.92 x 10(-6) per cell per generation. This rate increased 14-fold on treatment with ethyl methane sulfonate. Several stable mutant cell lines resistant to cadmium were selected and characterized with respect to metallothionein (MT) induction. Based on the copy number of mt+ genes and the levels of MT proteins and mRNA, the mutants could be divided into two classes, A and B. Although group A mutants have the same number of mt1+ and mt2+ genes as wild-type cells, upon induction with cadmium, the amount of MT proteins and mRNA in the mutants are greatly increased over wild-type levels. This observation strongly suggests a mutation that regulates MT gene transcription in these cells. In group B mutants, the mt+ genes are amplified about three- to fourfold, and their MT protein and mRNA basal levels are, as expected, much higher than in the wild-type cells, under uninduced and induced conditions.

A universal method of assessing the performance of infusion devices is described. An electronic balance was interfaced to a personal computer and software was written to provide a graphical display of output rate and to check for inconsistency in performance.

We have isolated a rabbit metallothionein-I gene from a lambda gt10 library. The coding sequence of this gene is interrupted by two introns occurring at amino acid positions 9 1/3 and 30 1/3. Comparison of the promoter sequence of this gene with the promoters of other metallothionein genes identified a number of oligonucleotide sequences which are recognized by trans-acting proteins involved in the regulation of these genes by heavy metals, glucocorticoids and alpha interferon.

Culture fluids from this microorganism, fibroblasts and HeLa cells contained potent factors which inhibited thymidine uptake in HeLa cells. The outcome of heating the culture fluid and fractionating it by gel filtration suggested that this was not due to bacterial hyaluronidase activity. Purified peptostreptococcal hyaluronidase and several commercially-available mucopolysaccharidases also did not inhibit thymidine uptake.

Hyaluronidase was purified to apparent homogeneity from the spent medium of Peptostreptococcus sp. strain 84H14S. The enzyme was purified 310-fold by ethanol precipitation, gel chromatography, and cation-exchange chromatography with a recovery of 42% of the original activity in the culture medium. The molecular weight of the purified enzyme was estimated to be 160,000 by gel filtration with Sephacryl S-300. Like bacterial mucopolysaccharidases of other sources, the enzyme carried out an eliminative reaction with the substrate, producing 4,5-unsaturated disaccharides as the final end products. Its optimum temperature of activity is 46 degrees C. The purified peptostreptococcal hyaluronidase was different from previously reported bacterial hyaluronidases in several respects. It degraded hyaluronic acid rapidly and also exhibited some activity against chondroitin sulfate A and chondroitin sulfate C. The KmS for hyaluronic acid, chondroitin sulfate A, and chondroitin sulfate C were 0.14, 1.4, and 2.6 mg/ml, respectively. The specific activity of hyaluronidase was much higher than that of any previously purified mucopolysaccharidases. The Vmax against hyaluronic acid reached 400 mmol of product per min per mg of protein at 22 degrees C. The peptostreptococcal hyaluronidase was also unique in that its optimum pH of activity was around neutrality, whereas other bacterial hyaluronidases were most active at acidic pHs.

Samples of subgingival plaque from patients with periodontal disease and control subjects were stained with the Fluoretec Fluorescent test kits (Pfizer Inc., New York) developed for the rapid detection of members of the Bacteroides fragilis and B. melaninogenicus groups of anaerobes. The same fluorescent fields were also examined by dark-field microscopy for the total count of bacteria. Bacteroides fragilis and B. melaninogenicus were found in plaque samples of healthy subjects and periodontally diseased patients with no significant difference in percent of total flora. Oral spirochetes also fluoresced with the antisera used. Samples from healthy sites showed virtually no spirochetes; spirochetes were present in diseased sites. Tests with other antisera also showed that fluorescein-labelled antibodies can be adsorbed nonspecifically to the surface of spirochetes. Such a phenomenon can be used to monitor an individual's periodontal disease state.

A rabbit metallothionein-2 pseudogene (MT-2 psi) has been isolated from a partial rabbit genomic library. Its unusual sequence shows evidence of complex rearrangements involving recombination and deletion events. There are no intervening sequences, 3' poly A tract or 5' regulatory DNA sequences. The pseudogene is flanked by two sets of direct repeats (CT)3 GT(CT)4 and CTGG(G)CTC. They are most probably the sites of insertion of MT-2 psi in the rabbit genome. In addition, a number of repetitive DNA sequences are observed flanking the MT-2 psi gene. These are features of a processed retrogene.

Peptostreptococci isolated from diseased periodontal pockets produced large amounts of extracellular hyaluronidase throughout their growth cycle. Phase variants, obtained by re-streaking aged colonies of the wild types, had different colonial morphology and shorter generation times. These variants produced less hyaluronidase, and enzyme production occurred only during the early stationary phase.