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Copyright of Die Radiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Immune checkpoint inhibitors (ICI) applied in patients with melanoma in an adjuvant setting have proven safety and efficacy in several studies, but data on elderly patients aged 75 years or more is scarce. Aim of this study was to investigate efficacy and safety of adjuvant ICI in patients aged ≥ 75 years compared to patients < 75 years in a real-world setting. Methods: We retrospectively analyzed clinical data, including occurrence of immune-related adverse events (irAE) and outcome of 456 patients that had been treated with adjuvant ICI between January 1st, 2018 and December 20th, 2022. We then compared patients aged ≥ 75 years (n = 117) to patients < 75 years (n = 339) in terms of safety and disease-free survival (DFS). Results and conclusion: ICI were well tolerated in both groups, with no significant difference observed in the overall occurrence of irAE. However, within the elderly subgroup, there was a significantly higher proportion of skin or nephrological toxicity and colitis/diarrhea compared to the other group. In terms of efficacy, a significantly shorter DFS in patients aged ≥ 75 years was observed. Adjuvant ICI in patients ≥ 75 years was less effective and furthermore associated with an increased risk for skin, renal or bowel toxicity. Therefore, in elderly patients, adjuvant ICI should be used with precaution. [ABSTRACT FROM AUTHOR]

Copyright of Die Unfallchirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: After living with the COVID-19 pandemic for more than 2 years, the impact of lockdown measures on preterm birth rates is inconsistent according to data from different countries. In this study, rates of preterm-born infants during the time of COVID-19-related lockdowns were analyzed in a tertiary perinatal center at Munich University, Germany. Methods: We analyzed the number of preterm births, infants, and stillbirths before 37 weeks of gestation during the German COVID-19 lockdown period compared to the same time periods in the years 2018 and 2019 combined. Additionally, we expanded the analysis to Pre- and Post-Lockdown Periods in 2020 compared to the respective control periods in the years 2018 and 2019. Results: Our database shows a reduction in the rate of preterm infants during the COVID-19 lockdown period (18.6%) compared to the combined control periods in 2018 and 2019 (23.2%, p = 0.027). This was mainly based on a reduced rate of preterm multiples during the lockdown period (12.8% vs. 28.9%, p = 0.003) followed by a reversed effect showing a threefold rise in multiple births after the lockdown. In singletons, the rate of preterm births was not reduced during the lockdown. The rate of stillbirths was not affected by the lockdown measures as compared to the control period (0.9% vs. 0.7%, p = 0.750). Conclusion: During the COVID-19 pandemic lockdown period, we found a reduced rate of preterm-born infants compared to a combined control period in the years 2018 and 2019 in our large tertiary University Center in Germany. Due to the predominant reduction in preterm multiples, we postulate that less physical activity might have led to the protective effect by lockdown measures. [ABSTRACT FROM AUTHOR]

Purpose: Since the introduction of immune checkpoint inhibitors (ICI) and targeted therapies (TT), survival rates of metastatic melanoma patients have increased significantly and complete remissions are no longer rarities. Consequently, there is an increasing number of long-term survivors who have not yet been comprehensively characterized. Methods: We included melanoma patients who entered stage IV between 2014 and 2017 and survived at least 5 years after entering stage IV. Descriptive statistics were performed to characterize the applied systemic therapies, response rates and to report which of these patients are still alive today. Results: 640 patients entered stage IV at the University Hospital Tuebingen. Of these, 207 patients (32%) were still alive at least 5 years after entering stage IV. Details of applied therapies and response rates were available in 176 patients (85%). About 90% of patients (n = 159) were still alive at the time of analysis. Median survival since first stage IV diagnosis was 6.0 years (range 5–9 years). An impressive majority of patients (n = 146, 83%) were no longer receiving systemic therapy at the time of evaluation. Complete remission under first line systemic therapy was seen in 36% of the patients. Conclusion: This dataset comprises the largest available cohort of long-term surviving stage IV melanoma patients. Since 90% of patients in our cohort are still alive today, we expect an increasing number of long-term survivors in the future. Our data indicate the need for specific follow-up programs addressing the needs of long-term survivors. [ABSTRACT FROM AUTHOR]

This correction notice addresses the article "Encounters: East/West dialogs on existence" by Christian Ferencz-Flatz and Alex Cistelecan, originally published without Open Access. The authors have now opted for Open Choice, making the article available under the Creative Commons Attribution 4.0 International License. Readers can access the corrected version online with proper attribution to the authors and source. [Extracted from the article]

This paper discusses the phenomenological method's reliance on imaginative procedures in view of ethnomethodological research. While ethnomethodology has often been seen in continuity with Alfred Schütz' phenomenological sociology, it mainly parts ways with phenomenology by stressing that the decisive details structuring mutual understanding (gestures, bodily expressions, or the myriad trifles that regulate casual conversation) are „not imaginable, but can only be found out". This paper reflects from a phenomenological perspective on what such a claim entails by first delineating this line of criticism from other objections raised against the use of imaginative procedures in phenomenology and by showing how this line of questioning departs from the core philosophical debates concerning imaginabilitiy and unimaginability in the Kantian tradition. Further on, the paper offers an in-depth interpretation of the aforementioned ethnomethodological claim in order not only to outline its methodological implications for phenomenology, but also to show that it involves possible key insights for understanding interaction, which phenomenology needs to take into account despite its eidetic scope. [ABSTRACT FROM AUTHOR]

Takács sets out by retracing the sustained criticism of existentialism articulated by Lukács at various stages of his post-war thought (from his 1948 I Marxism and Existentialism i , to his 1954 I Destruction of Reason i , to his posthumous I Ontology of Social Being i ), in which he consistently condemned existentialism's "idealist and irrationalist" anthropological underpinnings. Keywords: Existentialism; Marxism-Leninism; Eastern Europe; Philosophy EN Existentialism Marxism-Leninism Eastern Europe Philosophy 367 372 6 08/31/23 20230901 NES 230901 The papers in this special issue address the reception, critique, and appropriation of existentialist philosophy in state-socialist Europe from complementary thematic and methodological vantage points, focusing either on specific case studies from the various socialist states or developing a more comprehensive transnational perspective. Consequently, the previous positive reception of existentialism at the hands of Marxists humanists came to be seen as a subjective idealist deviation, whereas existentialism remained ill-reputed until the late 80s. [Extracted from the article]

The article discusses the historical background and transnational context of the dialogue between East-European communist philosophy and Western existentialism. It does so by first outlining the exchanges between Lukács, Sartre and Merleau-Ponty between the late 1940s and the early 1960s. Subsequently three major forums of East–West philosophical dialogue are surveyed, that took place during the 1960s: the 'Morals and Society' colloquium, organized by Instituto Gramsci in Rome in May 1964; the Korčula summer school, organized by the Praxis group between 1964 and 1975; and the International Congress for Philosophy organized in Vienna in September 1968. This series of events and the dialogue and confrontations that they engendered prove that, contrary to the exclusively negative reception of existentialism in the socialist camp in the 1950s, but also contrary to the distorted representation, which can be found in dissidents' recollections and which became dominant after the fall of communism, which excluded any possibility of dialogue between the two sides during socialism, such a dialogue has taken place, and led to mutual appropriations on both sides. [ABSTRACT FROM AUTHOR]

Introduction: Within its 2 week period, the Oktoberfest attracts around 6 million visitors yearly to Munich, Germany. Due to alcohol intake, congested halls, and disorderly activities, numerous accidents occur. Although many hand injuries are observed, the impact of Oktoberfest on severe hand trauma injury frequency is under investigated. Materials and methods: Data from the regional emergency medical service (EMS) was analyzed over a 9 year period regarding the frequency of severe hand injuries during the world's largest fair and compared to the corresponding period in the years 2020 and 2021 where the event was cancelled due to the world-wide COVID-19 pandemic. Additionally, we compared the patient numbers during the same period in one Emergency Department of a level-1-trauma and hand trauma center located close to the venue. Results: An exploratory description is made from data collected over a 9 year period (2013–2021) with focus on hand injuries before, during and after the "Oktoberfest". A total of 4017 hand injuries were allocated to hospitals by EMS. There was an increase in severe hand injuries by 66% during the 2-weeks-Oktoberfest-period compared to years where the Oktoberfest did not take place. Pre-pandemic statistics show an increasing severe hand trauma frequency of 57.5% in September, compared to EMS-referrals during the remanding year. Conclusion: The risk of injuring relevant structures of the hand during Oktoberfest is extremely high as compared to other parts of the body due to beer stein and fall-associated injuries. These injuries can lead to lifelong impairments. Our data are the first that quantifies and pinpoints the risk of severe injury to the hand during Oktoberfest and therefore, it is of great interest for visitors, hand surgeons, paramedics and emergency department healthcare workers. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibition (ICI) has changed the melanoma treatment spectrum. Few studies have examined the characteristics and long-term outcomes of patients achieving complete response (CR) under ICI. Materials and methods: We evaluated patients with unresectable stage IV melanoma treated with first-line ICI. The characteristics of those achieving CR were compared with those not achieving CR. Progression-free survival (PFS) and overall survival (OS) were assessed. Late-onset toxicities, response to second-line treatment, the prognostic value of clinicopathologic features, and blood markers were examined. Results: A total of 265 patients were included; 41 (15.5%) achieved CR, while 224 (84.5%) had progressive disease, stable disease, or partial response. At the therapy start, those who had CR were more likely to be older than 65 years of age (p = 0.013), have a platelet-to-lymphocyte ratio below 213 (p = 0.036), and have lower lactate dehydrogenase levels (p = 0.008) than those not achieving a CR. For those who discontinued therapy after CR, the median follow-up time after CR was 56 months (interquartile range [IQR] 52–58) and the median time from CR to therapy end was 10 months (IQR 1–17). Five-year PFS after CR was 79% and 5-year OS was 83%. Most complete responders had a normalization of S100 at the time of CR (p < 0.001). In simple Cox regression analysis, age below 77 years at CR (p = 0.04) was associated with better prognosis after CR. Eight patients received second-line ICI; disease control was seen in 63%. Late immune-related toxicities occurred in 25% of patients, most being cutaneous immune-related toxicities. Conclusions: Response, according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, is, until now, the most important prognostic factor, and CR is a valid surrogate marker for long-term survival in patients treated with ICI. Our results highlight the importance of investigating the optimal therapy duration in complete responders. [ABSTRACT FROM AUTHOR]

This correction notice from Studies in East European Thought addresses a missing Acknowledgements section in the article "From fertile hostility to stale benevolence." The corrected version now includes acknowledgment of support from the Ministry of Research, Innovation and Digitization. The original article has been updated to reflect this correction. [Extracted from the article]

Purpose: Mobility patterns of western societies have been changing due to ongoing demographic change. Therefore, continuously updated epidemiological data on fracture morphology and treatment strategies are needed. Methods: This retrospective single-center study included all tibial plateau fractures (TPF) between January 2011 and December 2020 in a level-I trauma center in Central Europe. Epidemiology, trauma mechanism and fracture morphology were analyzed. Age- and sex-specific differences regarding fracture classification (Schatzker, AO/OTA, Moore) and changes during the study period are highlighted. Results: A total of 607 patients (55.2% women, 44.8% men, mean age 52.9 years (± 17.9)) were included in the study, 462 (76.1%) thereof having undergone surgical treatment. Over the decade, an increase in mean age (+ 7.4 years; p = 0.10), incidence (+ 68%; p < 0.05) and low-energy trauma was observed, with the highest peak in elderly women. Within classifications, AO/OTA 41-B3 (24.9%), Schatzker II (26.8%) and Moore V (46.6%) fractures were the most common. Conclusion: Incidence (+ 68%), mean age and fractures with signs of knee dislocation of tibial plateau fracture increased over the last decade and low-energy trauma mechanism are more frequent. As the increase in incidence is mainly seen in older women, the comorbidities and need for immediate postoperative full weight-bearing have to be considered in treatment strategies. [ABSTRACT FROM AUTHOR]

Background: High tumor mutational burden (TMB) is associated with a favorable outcome in metastatic melanoma patients treated with immune checkpoint inhibitors. However, data are limited in the adjuvant setting. As BRAF mutated patients have an alternative with targeted adjuvant therapy, it is important to identify predictive factors for relapse and recurrence-free survival (RFS) in patients receiving adjuvant anti-PD-1 antibodies. Methods: We evaluated 165 melanoma patients who started adjuvant anti-PD-1 antibody therapy at our center between March 2018 and September 2019. The initial tumor stage was assessed at the beginning of therapy according to the 8th edition of the AJCC Cancer Staging Manual. Tumor and normal tissue of the high-risk stages IIIC/D/IV were sequenced using a 700 gene NGS panel. Results: The tumor stages at the beginning of adjuvant anti-PD-1 therapy were as follows: N = 80 stage IIIA/B (48%), N = 85 stage IIIC/D/IV (52%). 72/165 patients (44%) suffered a relapse, 44/72 (61%) with only loco regional and 28/72 (39%) with distant metastases. Sequencing results were available from 83 to 85 patients with stage IIIC/D/IV. BRAF mutation status (HR 2.12, 95% CI 1.12–4.08; p = 0.022) and TMB (HR 7.11, 95% CI 2.19–23.11; p = 0.001) were significant and independent predictive factors for relapse-free survival (RFS). Conclusion: BRAF mutation status and TMB were independent predictive factors for RFS. Patients with BRAF V600E/K mutation and TMB high had the best outcome. A classification based on BRAF mutation status and TMB is proposed to predict RFS in melanoma patients with adjuvant anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Visceral organs and tissues of 89 free-living alpine marmots (Marmota marmota) shot during a population control program in Switzerland, were collected. Between emergence from hibernation in April to July, the gastrointestinal tract (stomach to colon) gained 51% of mass and the liver mass increased by 24%. At the same time, the basal metabolic rate (BMR), determined with a portable oxygen analyzer, increased by 18%. The organ masses of the digestive system (stomach, small intestine, caecum, large intestine) were all significantly correlated with BMR. Interestingly, the mass of abdominal white adipose tissue (WAT) and of the remaining carcass (mainly skin and bones) were also significantly correlated with BMR. These results indicate that the gastrointestinal tract and organs involved in digestive function are metabolically expensive. They also show that it is costly to maintain even tissues with low metabolic rate such as WAT, especially if they are large. Heart and kidneys and especially brain and lungs did not explain a large proportion of the variance in BMR. Marmots increased the uptake of fat prior to hibernation, both by selective feeding and enhanced gastrointestinal capacity. Large fat reserves enable marmots to hibernate without food intake and to reproduce in spring, but at the cost of an elevated BMR. We predict that climate changes that disturb energy accumulation in summer, increase energy expenditure in winter, or delay the emergence from hibernation in spring, such as the occurrence of storms with increasing frequency, will increase mortality in alpine marmots. [ABSTRACT FROM AUTHOR]

Ever since the 1960s, media and communication studies have abounded in heated debates concerning the psychological and social effects of fictional media violence. Massive empirical research has first tried to tie film violence to cultivating either fear or aggressive tendencies among its viewership, while later research has focused on other media as well (television, video games). The present paper does not aim to settle the factual question of whether or not medial experiences indeed engender real emotional dispositions. Instead, it brings into play the resources of genetic phenomenology in order to ask how the formation of such dispositions would be generally possible. Thus, it aims to further the discussion by overtly employing the framework of Husserl's later genetic phenomenology to the field of emotional experience. By posing questions with regard to how fictional emotional experiences contribute to the formation of apperceptions and to the specificities of emotional sedimentation, it also points out some shortcomings in Husserl's account by drawing from Freud's dynamic theory of drives and emotions. [ABSTRACT FROM AUTHOR]

Objectives: In pediatric audiology, objective techniques for hearing threshold estimation in infants and children with profound or severe hearing loss play a key role. Auditory brainstem responses (ABR) and auditory steady-state responses (ASSR) are available for frequency-dependent hearing threshold estimations and both techniques show strong correlations but sometimes with considerable differences. The aim of the study was to compare hearing threshold estimations in children with and without cochlear and cochlear nerve malformations. Methods: Two groups with profound or severe hearing loss were retrospectively compared. In 20 ears (15 children) with malformation of the inner ear and/or cochlear nerve hypoplasia and a control group of 20 ears (11 children) without malformation, ABR were measured with the Interacoustics Eclipse EP25 ABR system® (Denmark) with narrow-band CE-chirps® at 500, 1000, 2000 and 4000 Hz and compared to ASSR at the same center frequencies under similar conditions. Results: ABR and ASSR correlated significantly in both groups (r = 0.413 in malformation group, r = 0.82 in control group). The malformation group showed a significantly lower percentage of "equal" hearing threshold estimations than the control group. In detail, patients with isolated cochlear malformation did not differ significantly from the control group, whereas patients with cochlear nerve hypoplasia showed significantly greater differences. Conclusion: ABR and ASSR should be used jointly in the diagnostic approach in children with suspected profound or severe hearing loss. A great difference in hearing threshold estimation between these techniques could hint at the involvement of cochlear nerve or cochlear nerve hypoplasia itself. [ABSTRACT FROM AUTHOR]

Copyright of Medizinische Klinik: Intensivmedizin & Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper addresses the question of occasional expressions, as discussed by Husserl in his First and Sixth Logical Investigation in relation to the problem of gestures. It aims to show that gestures are intimately related to the use of occasional expressions and have an indispensible contribution to their understanding. In doing so, the paper points out an important lack in Husserl's early theory of signification, which has to do with its exclusion of all aspects related to intersubjective communication. The paper begins with a short presentation of Husserl's interpretation of occasional expressions in the Logical Investigations. Further on it identifies the main source of Husserl's difficulties in coming to terms with this issue in his problematic treatment of communication, and shows how the consideration of gestures can help overcome these difficulties. Finally, the paper considers some consequences which derive from such a treatment of the issue for Husserl's theory of fulfillment (Bedeutungserfüllung). [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients. Methods: Data from a prospective biomarker cohort comprising melanoma and non-small cell lung cancer (NSCLC) patients were used to analyze the incidence of ICI-induced hepatitis, putatively associated factors, and outcome. Results: 40 patients with melanoma and 91 patients with NSCLC received ICI between July 2016 and May 2019. 11 patients developed ICI-induced hepatitis (8.4%). Prior to treatment, 45.5% of patients in the hepatitis cohort and 43.8% of the control cohort showed elevated titers of autoantibodies commonly associated with autoimmune liver diseases (p = 0.82). We found two nominally significant associations between the occurrence of ICI-induced hepatitis and HLA alleles associated with autoimmune liver diseases among NSCLC patients. Of note, significantly more patients with ICI-induced hepatitis developed additional irAEs in other organs (p = 0.0001). Neither overall nor progression-free survival was affected in the hepatitis group. Conclusion: We found nominally significant associations of ICI-induced hepatitis with two HLA alleles. ICI-induced hepatitis showed no correlation with liver-specific autoantibodies, but frequently co-occurred with irAEs affecting other organs. Unlike other irAEs, ICI-induced hepatitis is not associated with a better prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Physical activity has been shown to improve survival and quality of life of cancer patients. Due to differences in patient populations, healthcare settings, and types of intervention, cost-effectiveness analyses of physical activity interventions in cancer survivors are difficult to compare. Available evidence from breast cancer survivor research has shown inconsistent results, and transfer of results to other types of cancer is not straightforward. This paper systematically reviewed current evidence on the cost-effectiveness of physical activity interventions in cancer survivors independent of cancer type compared to usual care or another experimental intervention. Methods: The literature search was conducted in seven databases and enhanced by a search for gray literature. Eligible studies were restricted to developed countries and assessed using the CHEERS, CHEC, and PHILIPS checklists. The study protocol was pre-published in PROSPERO. Results: Seven studies, five cost-utility, and two combined cost-utility/cost-effectiveness analyses fully met the inclusion criteria. They covered eight different types of cancer and various interventions. The cost-effectiveness analyses were of moderate to high methodological quality. A high probability of cost-effectiveness was reported in two analyses. One intervention appeared to be not cost-effective, and one to be cost-effective only from an organizational perspective. Three other analyses reported a cost-effectiveness better than US$ 101,195 (€ 80,000) per QALY gained. Conclusions: Physical activity interventions in cancer survivors of developed countries were cost-effective in some but not all clinical trials reviewed. Implications for Cancer Survivors: Cost-effectiveness of physical activity interventions appear to depend upon the intensity of the activity. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intratumoral treatment of mice with a recombinant lymphocytic choriomeningitis virus-based vaccine vector expressing a melanocyte differentiation antigen resulted in T cell-dependent long-term control of melanomas. Using single-cell RNA-seq analysis, we demonstrate that viral vector-mediated transduction reprogrammed and activated a Cxcl13-expressing FSC subset that show a pronounced immunostimulatory signature and increased expression of the inflammatory cytokine IL-33. Ablation of Il33 gene expression in Cxcl13-Cre-positive FSCs reduces the functionality of intratumoral T cells and unleashes tumor growth. Thus, reprogramming of FSCs by a self-antigen-expressing viral vector in the TME is critical for curative melanoma treatment by locally sustaining the activity of tumor-specific T cells. Lymphocytic choriomeningitis virus (LCMV)-based viral vectors have been shown to induce potent antitumor immune responses. Here the authors show that a LCMV-based vaccine vector remodels the tumor-associated fibroblastic stroma, sustaining CD8+ T cell activation and reducing tumor growth in a preclinical model of melanoma. [ABSTRACT FROM AUTHOR]

Background: Hepatic immune-related adverse events (irAE) including elevated liver function tests (transaminases) occur in 1.4–22.3% of melanoma patients receiving immune checkpoint inhibitors (ICPI) and constitute a potentially serious toxicity that is challenging to treat. In contrast to the liver transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST), only little is known about the frequency and impact of gamma-glutamyl transferase (GGT) elevations. Methods: GGT determined prior to and during therapy of metastatic melanoma patients treated with ICPI were retrospectively assessed in two independent cohorts (PD-1: n = 218, Ipi + Nivo: n = 148). Overall survival (OS) and best objective response were analyzed according to baseline and immune-related GGT (irGGT) elevations during treatment. Results: In multivariate analysis, OS was reduced in patients with elevated baseline GGT (PD-1 group: hazard ratio [HR] 1.76, p =.0073; Ipi + Nivo group: HR 1.77, p =.032). Immune-related GGT elevation was recorded in 17% (PD-1 group) and 38.5% (Ipi + Nivo group). Of these patients, the majority (81 and 68%, respectively) had normal ALT and AST and showed no clinical signs of hepatotoxicity. Patients who experienced irGGT elevation had superior response (PD-1 group: odds ratio [OR] 3.57, p =.00072; Ipi + Nivo group: OR 1.74, p =.12) and OS (PD-1 group: HR 0.37, p =.0016; Ipi + Nivo group: HR 0.33, p =.00050). Conclusions: The frequency of hepatic irAE is currently underestimated. The addition of the sensitive enzyme GGT to the laboratory panel before and during therapy with ICPI allows to detect two to three times more patients developing hepatic or hepatobiliary toxicity than known so far. Immune-related GGT elevations correlate with response and favorable survival. Precis for use in the Table of Contents The frequency of hepatotoxicity under immune checkpoint blockade is currently underestimated. We suggest the addition of gamma-glutamyl transferase to the laboratory panel in checkpoint inhibitor patients for the detection of hepatobiliary toxicity. [ABSTRACT FROM AUTHOR]

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Immune checkpoint inhibitors (ICIs) are emerging as the new standard of care for treating various metastatic cancers. It is known that effective anti-tumor immune responses are associated with a stronger presence of tumor-infiltrating lymphocytes (TILs) in solid tumor tissue. Cancer patients with relapsing–remitting multiple sclerosis (RRMS) are often under continuous treatment with fingolimod, an immune-modulating drug that inhibits lymphocyte egress from secondary lymphatic organs. Little is known about the effect of fingolimod on ICI cancer therapy, as fingolimod may limit the number of TILs. Here we present three patients with RRMS, who developed various cancers during fingolimod treatment. Histology of all tumors consistently showed low numbers of TILs. A second biopsy taken from one of the tumors, a melanoma, revealed a significant increase of TILs after stopping fingolimod and starting pembrolizumab, indicating a surge in the number and re-invigoration of T cells. Our study suggests that fingolimod limits the number of TILs in solid tumors and may, thus, inhibit anti-cancer immune responses. [ABSTRACT FROM AUTHOR]

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Keywords: Non-Hodgkin lymphoma; Intratumoral lymphography; Embolization; Chylothorax; Wasting syndrome EN Non-Hodgkin lymphoma Intratumoral lymphography Embolization Chylothorax Wasting syndrome 2002 2004 3 11/30/21 20211201 NES 211201 To the Editor, Chylous effusion is a rare and potentially fatal complication of lymphoma due to respiratory complications and nutritional wasting syndrome [[1]]. This report describes a case of CT-guided intratumoral lymph-embolization for lymphoma-associated chylothorax. In conclusion, intratumoral lipiodol lymphography and adjunctive glue embolization could serve as an effective minimal-invasive treatment option with possible long-term remission in lymphoma-associated chylothorax. [Extracted from the article]

Purpose: We assessed the static nasal valve angle with MR imaging in healthy subjects and evaluated the complex mechanism of nasal valve dynamics during physiologic and forced inspiration. Methods: In 17 healthy subjects, measurements of the static nasal valve angle were conducted on MR scans, using a TSE Axial T2-weighted sequence and a 3 mm slice thickness. The dynamic changes of nasal valve movement were detected using MR Cine-imaging techniques. Results: The static median angle of the nasal valve was found to be 28.6° with a range of 12.7°–39.3°. The median degree of nasal valve collapse during forced inspiration was 68% (range 20–99%) of the baseline (static nasal valve angle). In the moderately forced inspiration (3 s) the median nasal valve angle declined to 76% of the baseline angle (range 42–100%). In the physiologic or unforced inspiration, the median nasal valve angle was reduced to 86.3% of the baseline angle (range 52–100%). Conclusion: MRI, as a non-invasive tool, is a reliable method for evaluation of the static nasal valve angle and for the illustration of the complex nasal valve dynamics. [ABSTRACT FROM AUTHOR]

Adorno's intensive criticism of phenomenology is well known, his entire early period during the 1920s and 1930s being marked by various polemical engagements with Husserl. This engagement finds its peak during his work at his second dissertation project in Oxford, a dissertation that was supposed to systematicaly expose the antinomies of phenomenological thinking while particularly focusing on Husserl's concept of "eidetic intuition" or "intuition of essences" (Wesensschau). The present paper will take this criticism as its starting point in focusing on two highly specific aspects of Adorno's interpretation: the opposition between eidetic intuition and the traditional theories of abstraction and its relationship to genetic phenomenology. In light of this criticism I subsequently show: 1. that, in his later work, Adorno's understanding of eidetic intuition undergoes a significant revaluation; 2. that he reappropriates key elements of the eidetic method in his own procedure of physiognomic analysis, and 3. that his account of physiognomics is relevant for addressing the aforementioned incongruities of phenomenological eidetics itself. [ABSTRACT FROM AUTHOR]

Introduction: Hydropic ear disease, initially described by and named after Prosper Menière, is one of the most frequent vertigo disorders and one of the most frequent inner ear disorders. It is the syndrome of endolymphatic hydrops which until 2007 could be diagnostically confirmed only by post-mortem histology. In the past, various attempts to formulate clinical diagnostic criteria have been undertaken but were hampered by the inability to ascertain the diagnosis in living patients. With the milestone achievement of endolymphatic hydrops imaging, today the pathology can be ascertained. In this study, we have performed a detailed analysis of the clinical features of hydropic ear disease for the first time by examining a large cohort of patients with morphologically confirmed endolymphatic hydrops using a detailed physician-administered neurotologic face-to-face interview.Results: During a hydropic vertigo attack, the patients report nausea, vomiting, sweating, urge to defecate, urge to urinate, phosphenes, headache, photophobia, phonophobia and even transient loss of consciousness. A third of the patients does not experience auditory symptoms during the vertigo attacks. Vertigo attacks last less than 20 min in more than one-fourth of the patients. Audiometric hearing loss has its greatest diagnostic value at the frequencies of 1 kHz and below. Cochleovestibular symptom onset simultaneity is associated with a high frequency of drop-attacks. Migraine and autoimmune disorders are not associated with hydropic ear disease.Conclusion: This study marks the beginning of the clinical characterization of hydropic ear disease. The findings have important implications for the future formulation of clinical diagnostic criteria. [ABSTRACT FROM AUTHOR]

Background: Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites.Methods: We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR).Results: We analyzed 52 patients including 44% females, 58% adenocarcinoma and 8% never smokers. Involved organs had target-lesions in the lung (42%), liver (25%), lymph nodes (56%) and soft tissue (13%) and non-target lesions in the bones (23%). ORR and disease control rate (DCR) were 20% and 45%, respectively. Median overall survival, progression-free survival and duration of response were 11.9, 2.3 and 10.3 months. OSRR and organ-specific DCR (OSDCR) were 28% and 90% in lymph nodes, 8% and 54 in the liver, and 9% and 55% in lung metastases. Nine out of 12 patients with bone metastases had progressive lesions. The cumulative incidence probability of organ-specific progression at 6 months was 14% in lymph nodes, 42% in the liver, 36% in lung metastases and 26% in the primary tumor, 29% in soft tissue and 33% in adrenal metastases.Conclusion: In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit. [ABSTRACT FROM AUTHOR]

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Background: Superior canal dehiscence syndrome (SCDS) is a relatively rare neurotological disorder that is characterized by a heterogeneous clinical picture. Recently, vestibular evoked myogenic potential (VEMP) measurement was established for the diagnosis of SCDS. In the present study, a case series of patients with SCDS were analyzed, with a focus on VEMP.Methods: Four patients with SCDS were prospectively examined with ocular VEMP (oVEMP) and cervical VEMP (cVEMP). The clinical features and the standard audiovestibular test battery results are summarized and analyzed. The diagnostic accuracy of VEMP testing is evaluated.Results: The increased oVEMP amplitudes had a specificity of 100% in this patient population. All patients had normal caloric function and head impulse testing. The Tullio sign was observed in two patients. Three patients had autophony. The air-bone gap was not greater than 10 dB in any of the patients. Two patients had marked fremitus nystagmus. All patients had a bony dehiscence of the superior semicircular canal on computed tomography imaging.Conclusion: The subjective and clinical features in this case series of SCDS patients were heterogeneous. However, objective oVEMP testing had the highest diagnostic value. Furthermore, we describe a new diagnostic clinical sign: fremitus nystagmus. [ABSTRACT FROM AUTHOR]

Prognosis of metastatic melanoma improved with the development of checkpoint inhibitors. The role of tumor infiltrating lymphocytes (TILs) in lymph node metastases of stage III melanoma remains unclear. We retrospectively characterized TILs in primary melanomas and matched lymph node metastases (stage III melanoma) of patients treated with the checkpoint inhibitor ipilimumab. Tumor infiltrating lymphocytes were characterized for CD3, CD4, and CD8 expressions by immunohistochemistry. 4/9 patients (44%) responded to treatment with ipilimumab (1 complete and 2 partial remissions, 1 stable disease). All responders exhibited CD4 and CD8 T-cell infiltration in their lymph node metastases, whereas all non-responders did not show an infiltration of the lymph node metastasis with TILs. The correlation between the presence and absence of TILs in responders vs. non-responders was statistically significant ( p = 0.008). Median distant metastases free survival, i.e., progression from stage III to stage IV melanoma, was similar in responders and non-responders (22.1 vs. 19.3 months; p = 0.462). Median progression free and overall survival show a trend in favor of the patients having TIL rich lymph node metastases (6.8 vs. 3.3 months, p = 0.09; and all alive at last follow-up vs. 8.2 months, respectively, p = 0.08). Our data suggest a correlation between the T-cell infiltration of the lymph node metastases in stage III melanoma and the response to ipilimumab once these patients progress to stage IV disease. [ABSTRACT FROM AUTHOR]

Purpose: To establish an optimized ultralow-dose digital pulsed fluoroscopy (FP) protocol for upper gastrointestinal tract examinations and to investigate the radiation dose and image quality. Materials and methods: An Alderson-Rando-Phantom with 60 thermoluminescent dosimeters was used for dose measurements to systematically evaluate the dose-area product (DAP) and organ doses of the optimized FP protocol with the following acquisition parameters: 86.7 kV; 77 mA; 0.9 mm, automatic image noise and contrast adaption. Subjective image quality, depiction of contrast agent and image noise (5-point Likert scale; 5 = excellent) were assessed in 41 patients, who underwent contrast-enhanced FP with the aforementioned optimized protocol by two radiologists in consensus. A conventional digital radiograph (DR) acquisition protocol served as the reference standard for radiation dose and image quality analyses. Results: Phantom measurements revealed a general dose reduction of approximately 96% per image for the FP protocol as compared to the DR standard. DAP could be reduced by 97%. Significant dose reductions were also found for organ doses, both in the direct and scattered radiation beam with negligible orbital (FP 5.6 × 10 vs. DR 0.11; p = 0.02) and gonadal dose exposure (female FP 2.4 × 10 vs. DR 0.05; male FP 8 × 10 vs. DR 0.03; p ≤ 0.0004). FP provided diagnostic image quality in all patients, although reading scores were significantly lower for all evaluated parameters as compared to the DR standard ( p < 0.05). Conclusion: Ultralow-dose FP is feasible for clinical routine allowing a significant reduction of direct and scattered dose exposure while providing sufficient diagnostic image quality for reliable diagnosis. [ABSTRACT FROM AUTHOR]

Loss of neural structures (such as hair cells or neurones within the spiral ganglion) has been proposed to be involved in Menière's disease (MD) (Spoendlin et al. Acta oto-laryngologica Supplementum 499:1-21, 1; Merchant et al. Eur Arch Oto-Rhino-Laryngol Off J Eur Feder Oto-Rhino-Laryngol Soc (EUFOS) Affil German Soc Oto-Rhino-Laryngol Head Neck Surg 252(2):63-75, 2; Tsuji et al. Ann Otol Rhinol Laryngol Suppl 81:26-31, 3; Kariya, Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 28(8):1063-1068, 4; Megerian Laryngoscope 115(9):1525-1535, 5) but this has yet to be confirmed. Therefore, the aim of this study was to investigate morphometric changes of VIIth and VIIIth cranial nerve in MD. MD is characterized by episodic vertigo, tinnitus, fluctuating hearing loss, and aural fullness. The exact pathophysiological mechanisms involved such as viral infections, autoimmune processes, genetic predisposition, cellular apoptosis, and oxidative stress are still not clear. Using a T2-weighted 3D-GE 'constructive interference in steady state' (CISS) 3T magnetic resonance imaging (MRI) sequence, we evaluated the properties of the VIIth and VIIIth cranial nerves as they passed from the cerebellopontine angle to the inner ear modiolus. 21 patients with MD were examined along with 39 normal controls. Bidirectional nerve diameters and cross-sectional areas (CSA) were measured in a transverse plane. The comparison of study and control group showed statistically significant ( P < 0.000595 after Bonferroni correction) differences between the CSA measurements. The facial, cochlear, superior vestibular, and inferior vestibular nerves (FN, CN, SVN, IVN) of MD patients were significantly larger than those of the control group, both on the MD-affected side and on the healthy side. Thus for example, the cochlear nerve CSA measurements were 0.69 ± 0.14 mm ( P < 0.0001) in the affected ears of the unilateral MD group, 0.70 ± 0.12 mm ( P < 0.0001) in the affected ears of the cohort including the bilateral MD group, 0.71 ± 0.13 mm ( P < 0.0001) in the non-affected ears of the MD patients, as compared to 0.46 ± 0.14 mm in the control group. The perpendicular nerve diameters were found to vary according to site of measurement and type of measurement used. For example a statistically significant enlargement of the short diameter measurements of the SVN at the level of the meatus was found, but not of long diameter measurements at the same site. Although cellular death would theoretically be expected to lead to a decreased nerve thickness, our data showed a swelling of cranial nerves VII and VIII within the study group compared to our normal hearing control group. The similar reaction of the facial nerve supports mediator-based theories of MD pathophysiology. [ABSTRACT FROM AUTHOR]

The paper addresses the methodological tensions between Husserl's phenomenology and history by reinterpreting the Addendum III of the Krisis-work in view of genetic phenomenology. Thus, the paper starts out by retracing the traditional criticism against the unhistorical character of Husserl's phenomenology as voiced by Heidegger, Adorno and others. Afterwards, it moves on to analyse the troubled relationship between static and genetic phenomenology, on the one hand, and between genetic phenomenology and empirical genesis, on the other hand. Finally, it arrives at a step by step methodological reconstruction of Husserl's considerations on the 'origin of geometry', which are regarded to be an application of the methods of genetic phenomenology to the field of history. [ABSTRACT FROM AUTHOR]

In several of his research manuscripts from the 1930s, Edmund Husserl considers the concrete life-world to be a world essentially determined by both humans and animals, or a 'humanized' and 'animalized' world. Husserl bases this claim on two observations. First, in his view, the surrounding objects of the human world are as such marked by cultural practices. Second, he considers that there is a corresponding animal world that similarly bears the existential traces of the animal. The following paper attempts to lay bare the various forms of interplay between these two processes, as they come to the fore in several analyses, especially in Husserl's reflections on pets. Although Husserl's treatment of this issue remains rather unilateral and elliptic, the paper attempts to draw from his reflections several consequences that might also be relevant for current debates in animal ethics. [ABSTRACT FROM AUTHOR]

Alexandru Dragomir became widely known in Romania as a philosopher 2 years after his death, in 2004. He had no prior publications and only a few of his close acquaintances were even aware of his work as a thinker. The editors of the five volumes of his posthumous papers have from the onset tried to present Dragomir, a former doctoral student of Heidegger, as a phenomenologist, while this interpretation is today well-established. The following paper tries to submit this interpretation to a closer scrutiny, on the one hand, by addressing the history of Dragomir's publication and reception in Romania and abroad, and on the other hand, by analyzing several aspects of his oeuvre which do indeed hold close resemblance to aspects of the phenomenological method, even though they actually have quite different motivations. [ABSTRACT FROM AUTHOR]

Purpose: Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign neoplasm that occurs almost exclusively in the nasopharynx of adolescent male individuals. Methods: We performed a retrospective study to determine the efficacy and safety of preoperative embolization and the surgical outcome in patients with JNA in a single-center institution. Fifteen cases undergoing embolization and surgical treatment between April 2003 and February 2013 were evaluated retrospectively. The demographic data, clinical presentation, and treatment were reviewed including the kind of preoperative embolization and different surgical approaches performed. The parameters investigated were the amount of blood loss, the tumor stage, and the rates of recurrence. Subsequently, a comparison was made between patients who had undergone Onyx embolization versus those who had been embolized with the standard approach. Results: In these 15 patients (mean age, 15 years), a total of 27 surgical procedures were performed. One patient was at stage Ia, two were at stage Ib, two were at stage IIa, six were at stage IIb, one was at stage IIc, and three were at stage IIIa based on the Radkowsky classification. All patients underwent preoperative embolization and subsequent surgery. The surgical approach and the embolization technique varied and evolved during time. The embolization procedure decreased the intraoperative blood loss to a minimum of 250 ml, and with the advent of intratumoral embolization, the rate of recurrence diminished. Conclusion: Preoperative Onyx embolization facilitates the shift in the treatment to endoscopic excision in selected patients, which reduces recurrence rates and overall morbidity. [ABSTRACT FROM AUTHOR]

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Heidegger's doubts concerning the concept of 'empathy' are unequivocally proven not only by his general tendency to avoid it, but also by his sharp critique of this term, as presented in both Being and Time and the lectures from the Summer Semester 1925, History of the Concept of Time. However, the concept of empathy is used by Heidegger in a positive, albeit rather allusive fashion, in three consecutive lectures of his early Freiburg period: Basic Problems of Phenomenology (Winter Semester 1919/20), Phenomenology of Intuition and Expression (Summer Semester 1920) and The Phenomenology of Religious Life (Winter Semester 1920/21). The present paper analyzes these three passages of Heidegger's early lectures in close detail, revealing their connection to the conceptions of empathy found in the works of both Dilthey and Scheler. Thus it aims to connect Heidegger's rather idiosyncratic conception of intersubjectivity with some of the discussions on that topic in the phenomenological millieu of the early 1920s. [ABSTRACT FROM AUTHOR]

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)