Checkpoint inhibition enhances cell contacts between CD4+ T cells and Hodgkin-Reed-Sternberg cells of classic Hodgkin lymphoma.

Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as Nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of Nivolumab in cHL. However, the mechanism of action of Nivolumab in cHL is not fully understood. The aim of this study was to monitor changes in cell motility and cell contacts after administration of Nivolumab to an in vitro model of cHL as well as to native hyperplastic lymphoid tissue and native human tissue from cHL. In both tissue and in vitro, CD4+, CD8+, CD30+ and CD20+ cell velocities were unchanged after Nivolumab incubation. In contrast, in primary cHL tissue, the duration of cell contacts between CD4+ T cells and HRS cells was significantly increased after 5 h Nivolumab treatment, and the number of contacts with HRS cells was also slightly increased for CD4+ T cells (not significant), suggesting that CD4+ T cells in particular contribute to the cytotoxicity observed as a result of Nivolumab therapy. There was no change in the duration of cell contacts in the hyperplastic lymphoid tissue after Nivolumab incubation. In conclusion, we show here for the first time by imaging of native lymphoma tissue an enhanced interaction of CD4+ T cells and HRS cells in cHL after Nivolumab administration.

Thematic coverage and readability of online patient information on cochlear implant care.

INTRODUCTION: The treatment of patients with a cochlear implant (CI) is usually an elective, complex and interdisciplinary process. As an important source of information, patients often access the internet prior to treatment. The quality of internet-based information regarding thematic coverage has not yet been analysed in detail. Therefore, the aim of this study was to analyse the information on CI care available on the internet regarding its thematic coverage and readability. MATERIAL METHODS: Eight search phrases related to CI care were defined as part of the study. A checklist for completeness of thematic coverage was then created for each search phrase. The current German CI clinical practice guideline and the white paper on CI care in Germany were used as a basis. As a further parameter, readability was assessed using Flesch Reading Ease Scores. The search phrases were used for an internet search with Google. The first ten results were then analysed with regard to thematic coverage, readability and the provider of the website. RESULTS: A total of 80 websites were identified, which were set up by 54 different providers (16 providers were found in multiple entries) from eight different provider groups. The average completeness of thematic coverage was 41.6 ± 28.2%. Readability according to the Flesch Reading Ease Score was categorised as "hard to read" on average (34.7 ± 14.2 points, range: 0-72). There was a negative statistically significant correlation between the thematic coverage of content and readability (Spearman's rank correlation: r = - 0.413, p = 0.00014). The completeness of thematic coverage of information on CI care available on the internet was highly heterogeneous and had a significant negative correlation with the readability. This result should be taken into account by both the providers of internet information and by patients when using internet-based information on CI care and help to further improve the quality of web-based information.

[Fluorescence confocal microscopy-complete digitization of pathology]. / Fluoreszenzbasierte Konfokalmikroskopie ­ vollständige Digitalisierung der Pathologie.

BACKGROUND: Fluorescence-based confocal microscopy (FCM) can be used to create virtual H&E sections in real time. So far, FCM has been used in dermato-, uro-, and gynecopathology. FCM allows the creation of a completely digitized frozen section, which could potentially replace conventional frozen sections in the future. OBJECTIVE: The aim of the current work is to implement FCM technology as a component of fully digitized processes in the pathological workflow. For this purpose, the current use of FCM in liver transplant pathology will be extended to other disciplines such as urology and otorhinolaryngology. MATERIALS AND METHODS: The FCM technique continues to be used prospectively on native tissue samples from potential donor livers. Conventional frozen sections are used comparatively to virtual FCM scans. RESULTS: The data show a nearly perfect agreement for the detection of cholangitis, fibrosis, and malignancy, and a high level of agreement for, e.g., macrovesicular steatosis, inflammation, steatohepatitis, and necrosis between virtual FCM scans and conventional routine diagnostic frozen sections. CONCLUSION: Since the availability of time- and cost-intensive frozen section diagnostics in the context of transplant pathology in continuous operation (24/7) is now only established at very few university centers in Germany due to an increasing shortage of specialists, the use of FCM could be an important building block in the current process leading towards a fully digitized pathology workflow and should thus be extended to various disciplines.

Cochlear implant therapy improves the quality of life and social participation in the elderly: a prospective long-term evaluation.

PURPOSE: In recent years, the number of elderly cochlear implant (CI) candidates is continuously rising. In addition to the audiological improvement, other positive effects of CI treatment can also be observed in clinical routine. The "quality of life" as a parameter of success directly experienced by the patient is increasingly becoming the focus of clinical research. Although there are already clear indications of a rapid and significant improvement in quality of life, there is still a lack of systematic, prospectively collected longitudinal long-term data in patients over the age of 65. METHODS: This prospective longitudinal observational study included 31 patients between the age of 71 and 92 years who had first been treated unilaterally with a CI 6 years ago. In addition to free-field monosyllable recognition, quality of life was assessed using the World Health Organization Quality-of-Life Scale-old (WHOQL-OLD). The results were compared with the data from our previous study, in which we focused on the short- and medium-term effects on quality of life. In both studies, the same patient population was examined. In addition, these study data were compared with an age-matched average population. RESULTS: In speech recognition, there was no significant change from the control 6 months postoperatively compared with the results 6 years postoperatively. No significant changes occurred in the total quality of life score or any of the other six facets of quality of life when comparing the results 6 months postoperatively with the results 6 years postoperatively. In "Social participation", the CI patients even exceed the values of the age-matched average population 6 years after treatment. CONCLUSION: Improvement in the quality of life and especially in social participation appears stable over many years in elderly patients after hearing rehabilitation with a CI.

The RHOA Mutation G17V Does Not Lead to Increased Migration of Human Malignant T Cells but Is Associated with Matrix Remodelling.

Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL), is characterized by constitutional symptoms, advanced-stage disease, and generalized lymphadenopathy. A genetic hallmark of this lymphoma is the frequent occurrence of the RHOA mutation G17V in neoplastic cells, which is observed in around 60% of patients. Because RHOA is involved in both T-cell receptor downstream signalling and cell migration, we hypothesized that the characteristic presentation of AITL could be the result of enhanced tumor cell migration. Therefore, this study aimed to elucidate the impact of the RHOA variant G17V on the migration of neoplastic T cells. We transfected the T-cell lymphoma cell lines HH and HuT78 to stably express the RHOA-G17V variant. RHOA-G17V-expressing T cells did not exhibit enhanced motility compared to empty-vector-transfected cells in microchannels, a 3D collagen gel, or primary human lymphatic tissue. Cells of the HH cell line expressing RHOA-G17V had an increased number of cells with cleaved collagen compared with the empty-vector-transfected cells. Therefore, we hypothesized that the early spread of AITL tumor cells may be related to remodelling of the extracellular matrix. Accordingly, we observed a significant negative correlation between the relative area of collagen in histological sections from 18 primary AITL and the allele frequency of the RHOA-G17V mutation. In conclusion, our results suggest that the characteristic presentation of AITL with early, widespread dissemination of lymphoma cells is not the result of an enhanced migration capacity due to the RHOA-G17V mutation; instead, this feature may rather be related to extracellular matrix remodelling.

[Has the SARS-CoV-2 pandemic improved teaching?-Virtual education in otorhinolaryngology from the students' perspective]. / Hat die SARS-CoV-2-Pandemie die Lehre verbessert? ­ Virtueller Unterricht im Fach HNO-Heilkunde aus Sicht der Studierenden.

BACKGROUND: The Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV­2) pandemic has significantly changed the education of medical students. Due to the contact restrictions and the associated requirement for distance learning, digital teaching formats had to be implemented within a short period of time. The aim of our work was to analyze student evaluation data for virtual teaching in otorhinolaryngology (ORL) during the SARS-CoV­2 pandemic and to compare the data with previously obtained evaluation data under face-to-face conditions. MATERIALS AND METHODS: Evaluation data for the block practical courses in winter semester 2020/21 and summer semester 2021, which were carried out in a virtual format with a short face-to-face phase as well as those for the block practical courses from summer semester 2018 to winter semester 2019/20, which had been performed completely in a conventional face-to-face format, were analyzed. The anonymous survey of the students focused on various aspects of the courses such as organization, didactics and learning atmosphere. RESULTS: Of 16 surveyed categories, 14 (87.5%) showed significantly better evaluation results for the virtual courses compared to the courses carried out previously under face-to-face conditions. This very positive assessment of the digital teaching offer showed no significant change during the course of the pandemic over the period of two semesters. CONCLUSIONS: Our data show a high acceptance of digital teaching in ORL for students. Even though essential components of the medical education such as teaching on the patient and clinical-practical skills can still only be realized in a face-to-face format, our data suggest that digital elements could also play a role in medical education after the SARS-CoV­2 pandemic.

Long-term effects on the quality of life following cochlear implant treatment in older patients.

PURPOSE: Even in older patients, hearing rehabilitation with a cochlear implant has become an established method for deafened or severely hearing-impaired patients. In addition to the hearing improvement, numerous other effects of CI treatment can be observed in clinical routine. In the literature, there is multiple evidence for a rapid and significant improvement in quality of life with CI treatment. The aim of this study was to evaluate the long-term effects of hearing rehabilitation using CI on the quality of life in older patients (≥ 65 years). METHODS: This prospective cross-sectional study examined 84 patients between the age of 65 and 101 years who received unilateral CI treatment for the first time between one and 10 years ago. The World Health Organization Quality-of-Life Scale-Old (WHOQL-OLD) was used to determine the quality of life. The study cohort was divided into three groups to compare the quality of life over time: group I (1-3 years after CI treatment), group II (4-6 years after CI treatment), and group III (7-10 years after CI treatment). In addition, the data from this study were compared with the results of our previous study (Issing et al. 2020) in which we focused on the first 6 months after CI treatment. RESULTS: In all three groups, there was a significant improvement in monosyllabic discrimination within 1 year after CI fitting (p > 0.001). No significant differences were found between the three groups. There were no significant differences between the three groups in the WHOQOL-OLD total score (p = 0.487) or any of the other six facets. Moreover, no significant differences were found compared to the study group of our previous study 6 months after CI treatment. CONCLUSION: This study demonstrates the long-term stability of the improved quality of life following unilateral CI treatment in patients aged 65 years or older.

Landscape of 4D Cell Interaction in Hodgkin and Non-Hodgkin Lymphomas.

Profound knowledge exists about the clinical, morphologic, genomic, and transcriptomic characteristics of most lymphoma entities. However, information is currently lacking on the dynamic behavior of malignant lymphomas. This pilot study aimed to gain insight into the motility of malignant lymphomas and bystander cells in 20 human lymph nodes. Generally, B cells were faster under reactive conditions compared with B cells in malignant lymphomas. In contrast, PD1-positive T cells did not show systematic differences in velocity between reactive and neoplastic conditions in general. However, lymphomas could be divided into two groups: one with fast PD1-positive T cells (e.g., Hodgkin lymphoma and mantle cell lymphoma; means 8.4 and 7.8 µm/min) and another with slower PD1-positive T cells (e.g., mediastinal grey zone lymphoma; mean 3.5 µm/min). Although the number of contacts between lymphoma cells and PD1-positive T cells was similar in different lymphoma types, important differences were observed in the duration of these contacts. Among the lymphomas with fast PD1-positive T cells, contacts were particularly short in mantle cell lymphoma (mean 54 s), whereas nodular lymphocyte-predominant Hodgkin lymphoma presented prolonged contact times (mean 6.1 min). Short contact times in mantle cell lymphoma were associated with the largest spatial displacement of PD1-positive cells (mean 12.3 µm). Although PD1-positive T cells in nodular lymphocyte-predominant Hodgkin lymphoma were fast, they remained in close contact with the lymphoma cells, in line with a dynamic immunological synapse. This pilot study shows for the first time systematic differences in the dynamic behavior of lymphoma and bystander cells between different lymphoma types.

Magnetic Resonance Imaging in Patients With Hearing Implants - Follow-up on Prevalence and Complications.

OBJECTIVE: To examine the number of magnetic resonance imaging (MRI) examinations performed in patients with hearing implants and to quantify side effects or complications related to this procedure. STUDY DESIGN: Questionnaire. SETTING: Tertiary referral center, academic hospital. PATIENTS: One thousand four hundred sixty-onepatients with an implanted hearing system. INTERVENTION: Patients were asked to complete a questionnaire either during a visit to the clinic (304) or by mail contact (1,157) between February 2018 and March 2019. MAIN OUTCOME MEASURES: Number of examinations by means of MRI per patient and number of side effects or complications. RESULTS: A total of 711 questionnaires were returned. After excluding nonvalid information on the questionnaire, 12.8% of patients were identified who had undergone an MRI after having received their hearing implant. Within this group of 91 patients, the most common precaution undertaken was a head bandage (69%). Side effects were mainly pain (37%), followed by anxiety (15%) and tinnitus (9%). The MRI had to be aborted in 14% and dislocation of the magnet occurred in 7% of examinations. CONCLUSIONS: Our data indicate that patients undergoing hearing implant surgery need better information about the limitations and requirements of MRI. The occurrence of side effects is likely as only half of the patients in our study group were completely free of symptoms. Dislocation of the implant magnet was observed in several cases, hence patients and physicians need to be educated about this potential complication.

Typical symptoms of common otorhinolaryngological diseases may mask a SARS-CoV-2 infection.

PURPOSE: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) replicates predominantly in the upper respiratory tract and is primarily transmitted by droplets and aerosols. Taking the medical history for typical COVID-19 symptoms and PCR-based SARS-CoV-2 testing have become established as screening procedures. The aim of this work was to describe the clinical appearance of SARS-CoV-2-PCR positive patients and to determine the SARS-CoV-2 contact risk for health care workers (HCW). METHODS: The retrospective study included n = 2283 SARS-CoV-2 PCR tests from n = 1725 patients with otorhinolaryngological (ORL) diseases performed from March to November 2020 prior to inpatient treatment. In addition, demographic data and medical history were assessed. RESULTS: n = 13 PCR tests (0.6%) were positive for SARS-CoV-2 RNA. The positive rate showed a significant increase during the observation period (p < 0.01). None of the patients had clinical symptoms that led to a suspected diagnosis of COVID-19 before PCR testing. The patients were either asymptomatic (n = 4) or had symptoms that were interpreted as symptoms typical of the ORL disease or secondary diagnoses (n = 9). CONCLUSION: The identification of SARS-CoV-2-positive patients is a considerable challenge in clinical practice. Our findings illustrate that taking a medical history alone is of limited value and cannot replace molecular SARS-CoV-2 testing, especially for patients with ORL diseases. Our data also demonstrate that there is a high probability of contact with SARS-CoV-2-positive patients in everyday clinical practice, so that the use of personal protective equipment, even in apparently "routine cases", is highly recommended.

Comparison of bandaging techniques to prevent cochlear implant magnet displacement following MRI.

INTRODUCTION: For cochlear implants (CI) with removable magnets, a pressure bandage usually is recommended during MR imaging to avoid magnet dislocation. Nevertheless, this complication is regularly observed despite applying a pressure bandage. The aim of this study was to compare various bandaging techniques to avoid magnet displacement. MATERIALS AND METHODS: As an experimental model a force measuring stand was developed and validated, on which the process of magnet dislocation could be simulated on a cochlear implant. In a test series with six combinations of cohesive and elastic bandages with different counter pressure elements (CPE), the forces required to induce magnet dislocation against the resistance of a compression bandage was determined. In addition, the inter- and intraindividual variability of the compression bandages was measured for ten different users. RESULTS: The cohesive bandage had the lowest average holding force of 10.70 N. The elastic bandage developed more than four times the retention force of the cohesive bandage (44.88 N, p < 0.01). By adding a CPE, these values could be increased highly significantly up to factor 3. The optimum combination in terms of fixation force against magnet dislocation was an elastic bandage plus a cylindrical CPE (76.60 N). The data showed a high interindividual variability. CONCLUSION: Even though most CI manufacturers now offer 3T-conditional implants, a pressure bandage will have to be applied to thousands of patients with previous implant generations to prevent magnet dislocation. We examined for the first time force measurements to compare different bandaging techniques by detecting the holding force of the CI magnet. We were able to identify an optimized combination of a bandage and a CPE to immobilize the CI magnet. However, our data also demonstrated a significant scatter amongst different examiners. Although our data provide valuable data for potential clinical application, future development of the dressing technique is required for human use.

Aerosol Exposure During Surgical Tracheotomy in SARS-CoV-2 Positive Patients.

INTRODUCTION: Since December 2019, the novel coronavirus SARS-CoV-2 has been spreading worldwide. Since the main route of infection with SARS-CoV-2 is probably via contact with virus-containing droplets of the exhaled air, any method of securing the airway is of extremely high risk for the health care professionals involved. We evaluated the aerosol exposure to the interventional team during a tracheotomy in a semiquantitative fashion. In addition, we present novel protective measures. PATIENTS AND METHODS: To visualize the air movements occurring during a tracheotomy, we used a breathing simulator filled with artificial fog. Normal breathing and coughing were simulated under surgery. The speed of aerosol propagation and particle density in the direct visual field of the surgeon were evaluated. RESULTS: Laminar air flow (LAF) in the OR reduced significantly the aerosol exposure during tracheostomy. Only 4.8 ±â€Š3.4% of the aerosol was in contact with the surgeon. Without LAF, however, the aerosol density in the inspiratory area of the surgeon is 10 times higher (47.9 ±â€Š10.8%, P < 0.01). Coughing through the opened trachea exposed the surgeon within 400 ms with 76.0 ±â€Š8.0% of the aerosol-independent of the function of the LAF. Only when a blocked tube was inserted into the airway, no aerosol leakage could be detected. DISCUSSION: Coughing and expiration during a surgical tracheotomy expose the surgical team considerably to airway aerosols. This is potentially associated with an increased risk for employees being infected by airborne-transmitted pathogens. Laminar airflow in an operating room leads to a significant reduction in the aerosol exposure of the surgeon and is therefore preferable to a bedside tracheotomy in terms of infection prevention. Ideal protection of medical staff is achieved when the procedure is performed under endotracheal intubation and muscle relaxation.

In vitro comparison of surgical techniques in times of the SARS-CoV-2 pandemic: electrocautery generates more droplets and aerosol than laser surgery or drilling.

INTRODUCTION: Based on current knowledge, the SARS-CoV-2 is transmitted via droplet, aerosols and smear infection. Due to a confirmed high virus load in the upper respiratory tract of COVID-19 patients, there is a potential risk of infection for health care professionals when performing surgical procedures in this area. The aim of this study was the semi-quantitative comparison of ENT-typical interventions in the head and neck area with regard to particle and aerosol generation. These data can potentially contribute to a better risk assessment of aerogenic SARS-CoV-2-transmission caused by medical procedures. MATERIALS AND METHODS: As a model, a test chamber was created to examine various typical surgical interventions on porcine soft and hard tissues. Simultaneously, particle and aerosol release were recorded and semi-quantitatively evaluated time-dependently. Five typical surgical intervention techniques (mechanical stress with a passive instrument with and without suction, CO2 laser treatment, drilling and bipolar electrocoagulation) were examined and compared regarding resulting particle release. RESULTS: Neither aerosols nor particles could be detected during mechanical manipulation with and without suction. The use of laser technique showed considerable formation of aerosol. During drilling, mainly solid tissue particles were scattered into the environment (18.2 ± 15.7 particles/cm2/min). The strongest particle release was determined during electrocoagulation (77.2 ± 30.4 particles/cm2/min). The difference in particle release between electrocoagulation and drilling was significant (p < 0.05), while particle diameter was comparable. In addition, relevant amounts of aerosol were released during electrocoagulation (79.6% of the maximum flue gas emission during laser treatment). DISCUSSION: Our results demonstrated clear differences comparing surgical model interventions. In contrast to sole mechanical stress with passive instruments, all active instruments (laser, drilling and electrocoagulation) released particles and aerosols. Assuming that particle and aerosol exposure is clinically correlated to the risk of SARS-CoV-2-transmission from the patient to the physician, a potential risk for health care professionals for infection cannot be excluded. Especially electrocautery is frequently used for emergency treatment, e.g., nose bleeding. The use of this technique may, therefore, be considered particularly critical in potentially infectious patients. Alternative methods may be given preference and personal protective equipment should be used consequently.

Landscape of T Follicular Helper Cell Dynamics in Human Germinal Centers.

T follicular helper (Tfh) cells play a very important role in mounting a humoral response. Studies conducted in mouse models have revealed with good kinetic and spatial resolution the dynamics of these cells in germinal centers (GC) and their cross-talk with B cells upon an immune response. However, whether a similar migratory behavior is performed by human Tfh cells is unclear, as technology to track them in situ has been lacking. In this study, we combined traditional immunohistochemistry and real-time fluorescent imaging approaches on fresh human adenoid slices to provide static and dynamic information on Tfh cells. Our data indicate that GC light zones are composed of two distinct areas in terms of Tfh cell distribution and migration. In the outer GC light zones, Tfh cells migrate actively and with a high ability to form dynamic clusters showing intense and rapid reorganization. In these outer regions, Tfh cells demonstrate multiple interactions between each other. Conversely, in central regions of GC light zones, Tfh cells are much more static, forming long-lasting conjugates. These findings reveal for the first time, to our knowledge, the dynamic behavior whereby Tfh cells migrate in human GC and highlight the heterogeneity of GC for Tfh cell motility.

The Effect of a Bone Groove Against Cochlear Implant Electrode Migration.

HYPOTHESIS: The risk of electrode migration in cochlear implant (CI) surgery can be reduced by securing the electrode lead in a bone groove in the chorda-facial angle. BACKGROUND: Electrode migration is an important complication in CI surgery, which affects hearing performance, may induce pain and facial nerve stimulation, and requires surgical revision. A potential method to secure the electrode is to use a bone groove created in the facial recess to fixate the electrode lead. This surgical measure is a standard procedure for lateral wall electrodes (LWE) in our clinic since 2013. METHODS: Retrospective analysis of consecutive CI cases of a tertiary referral center from 2006 to 2016 and comparison of incidence rates between group A (without bone groove, years 2006-2012) and group B (with bone groove fixation, years 2013-2016). Clinical cases were reviewed with respect to electrode type, migration length, time interval to migration, and findings during revision surgery. RESULTS: Seventeen cases of electrode migration were found in a total of 1,603 cochlear implantations. Only LWE designs were affected by migration. The cumulative incidence for LWE in group B (0.5%) was significantly lower than in group A (3.7%, p < 0.01). The two migration cases in group B revealed insufficient geometric design of the bone grooves. Only one patient experienced a remigration after revision surgery. CONCLUSION: The fixation in a bone groove in the chorda-facial angle is an effective measure against migration of LWE. Proper surgical execution is mandatory to ensure a tight and enduring fit.

Treatment of iliac artery bifurcation aneurysms with the second-generation straight iliac bifurcated device.

BACKGROUND: There are few long term studies to show the safety and efficacy of iliac artery aneurysm exclusion, especially in regards to the straight iliac branched device. The objective of our study was to add our data with a mean follow-up of 32 months to the existing data available. METHODS: Patients undergoing iliac bifurcation procedure either as standalone or in combination with abdominal aortic aneurysm exclusion at two vascular centers had data prospectively gathered between 2004 and 2014. Collected data was analyzed for baseline characteristics, procedural events, and clinical follow-up; variables included endoleaks, reinterventions, and internal iliac artery (IIA) closure. RESULTS: A total of 45 iliac vessels in 41 patients (36 male) with a mean age of 70.4 years were treated with the iliac branched device. Procedural success was achieved in 85% (35/41) of patients and 87% (39/45) vessels with no intraoperative death. Of the six technical failures, three occurred due to failure to place the straight iliac branched device or stent properly. Two occurred because of endoleaks at the end of the procedure, and one occurred because the IIA side-branch occluded and could not be reopened. The mean patient follow-up was 32.0 ± 27.3 months (range, 0-109 months). During this time period, the IIA patency rate on an intention-to-treat basis was 81%, and the freedom from endoleak rate on an intention-to-treat basis was 76% per patient. The freedom from reintervention per patient was 75%. No patient reported symptoms of pelvic ischemia and permanent buttock claudication. CONCLUSIONS: In this study with mean follow-up of 32 months, treatment with iliac bifurcated devices is a safe and durable option in a carefully selected population of patients with iliac artery bifurcation aneurysms.