Publications by authors named "Andreas Arnold"

139 Publications

Electroencephalography Findings in Older Adults Undergoing Geriatric Treatment: A Surrogate for the Outcome?

Brain Sci 2022 Jun 28;12(7). Epub 2022 Jun 28.

Department of Geriatrics and Neurology, Diakonie Hospital Jung Stilling Siegen, 57080 Siegen, Germany.

Background: Comprehensive geriatric care (CGC) is a multidisciplinary approach developed to meet the needs of older patients. Electroencephalography (EEG) provides valuable information for monitoring the cerebral function. As a surrogate, EEG findings may help to estimate the course of diseases as well as the treatment outcomes.

Objectives: Therefore, the aim of the present study is to investigate EEG findings in older patients receiving CGC.

Methods: Patients with an initial EEG in a geriatric unit between May 2019 and April 2020 and treated using the CGC approach were analyzed. EEG abnormalities were defined as generalized (diffuse) background slowing and/or intermittent/persistent focal slowing and/or epileptiform discharges. Assessment results for the Barthel index (BI), Tinetti Balance and Gait test (TBGT), and Timed Up and Go test (TUG) were analyzed in relation to the presence of EEG abnormalities.

Results: The study included 398 patients (mean age: 83.0 ± 6.57 years, 69.3% were female). Abnormal EEG patterns were found in 94 (23.6%) patients. Patients with EEG abnormalities had a mean age of 83.4 years versus a mean of 82.8 years in those without ( = 0.451). Based on all calculated scores, the majority of the patients improved after CGC, with a tendency to higher-grade improvements in those without EEG abnormalities (BI: 86.2% vs. 75.5%, = 0.024; TUG: 53.3% vs. 31.9%, < 0.001); for TBGT, only a gradual difference was detected (TBGT: 79.9% vs. 71.3%, = 0.088). The presence of EEG abnormalities was associated with the parameters dementia (36.2% vs. 22.4%, = 0.010), known epilepsy/seizure (19.1% vs. 5.9%, < 0.001), structural brain lesion (47.9% vs. 19.7%, < 0.001), and delirium (9.6% vs. 3.6%, = 0.030) during hospitalization.

Conclusions: We found EEG abnormalities in almost a quarter of the patients treated in the geriatric unit. In older patients, the presence of EEG abnormalities is associated with lower improvements after CGC.
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http://dx.doi.org/10.3390/brainsci12070839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312893PMC
June 2022

Improvement of occupational leg edema and discomforts (RCT).

Clin Hemorheol Microcirc 2022 Jul 6. Epub 2022 Jul 6.

Department of Dermatology, University medicine Greifswald, Germany.

Background: Edema and subjective leg complaints (e.g. pain, heaviness) after long standing or sitting, are defined as orthostatic leg complaints or occupational edema. Compression hosiery should help to prevent or decrease those symptoms.

Objective: Assess the effects on leg discomforts and leg volume and wearing comfort in two medical below-knee compression stocking types (A vs. B) with an interface pressure of 18 -20 mmHg and a below-knee-low-pressure support stocking (LPSS) with an interface pressure of 8-10mmHg (C).

Methods: Two different types of below-knee medical compression stockings and a LPSS were examined in this randomized, blinded, crossover trial in volunteers having leg discomforts and edema after being in an upright position during the day. Participants were divided into two cohorts, and each type of stocking was worn for three consecutive days in one week with a subsequent washout phase. The assessment of effects and wearing comfort was ascertained by questionnaires. Volume changes in the lower leg were measured with the Bodytronic 600® (Bauerfeind AG, Zeulenroda, Germany).

Results: A significant reduction of lower leg volume (mean stocking A: 204.7 ml; mean stocking B: 153.5 ml; mean stocking C: 48.2 ml) and a significant reduction of the life-quality dimension leg-complaints (p <  0.0001) was achieved by all three types of stockings. Compared to the LPSS both compression stockings decreased the lower leg volume significantly more (p <  0.001) and had a significant better fit (p <  0.001).

Conclusion: Below-knee medical compression stockings with an interface pressure 18-21mmHg and LPSS with an interface pressure of 8-10 mmHg reduce significantly occupational orthostatic edema and leg discomforts which are due to long standing and sitting activities.
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http://dx.doi.org/10.3233/CH-211366DOI Listing
July 2022

Contact force guided radiofrequency current application at developing myocardium.

J Cardiovasc Electrophysiol 2022 May 16. Epub 2022 May 16.

Department of Pediatric Cardiology and Intensive Care Medicine, Georg August University Medical Center, Göttingen, Germany.

Introduction: Catheter contact is a key determinant for lesion size in radiofrequency catheter ablation (RFA). Monitoring of contact force (CF) during RFA has been shown to improve efficacy of RFA in experimental settings as well as in adult patients. Coronary artery narrowing after RFA has been described in experimental settings as well as in children and adults and may be dependent from catheter contact. The value of CF monitoring concerning these issues has not been systematically studied yet. Value of high versus low CF during RFA in piglets was studied to assess lesion size and potential coronary artery involvement mimicking RFA in small children.

Methods: RFA with continuous CF monitoring was performed in 24 piglets (median weight 18.5 kg) using a 7 F TactiCath Quartz radiofrequency (RF) ablation catheter (Abbott). A total of 7 lesions were induced in each animal applying low (10-20 g) or high (40-60 g) CF. RF energy was delivered with a target temperature of 65°C at 30 W for 30 s. Coronary angiography was performed prior and immediately after RF application. Animals were assigned to repeat coronary angiography followed by heart removal after 48 h (n = 12) or 6 months (n = 12). Lesions with surrounding myocardium were excised, fixated, and stained. Lesion volumes were measured by microscopic planimetry.

Results: A total of 148 RF lesions were identified in the explanted hearts. Only in the subset of lesions at the AV annulus 6 month after ablation, lesion size and number of lesions exhibiting transmural extension were higher in the high CF group compared to low CF. In all other locations CF had no impact on lesion size and mural extension after 48 h as well as after 6 months. Additional parameters such as lesion size index and force time integral were also not related to lesion size. Coronary artery damage was present in two animals after 48 h and in one after 6 months and was not related to CF.

Conclusion: In our experimental setting, lesion size in piglets was not related to catheter CF. Transmural extension of the RF lesions involving the layers of the coronary arteries was frequently noted irrespective of CF. Coronary artery narrowing was present in 3/24 animals and was not related to CF. In infants and toddlers, low CF (10-20 g) may be of adequate effect. Impact of CF monitoring during conventional RF ablation in children requires further investigation.
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http://dx.doi.org/10.1111/jce.15544DOI Listing
May 2022

Validation of the psychometric properties of a "Modified Version of the Hornheider Screening Instrument" (HSI-MV) using a sample of outpatient and inpatient skin tumor patients.

J Dtsch Dermatol Ges 2022 05 15;20(5):597-609. Epub 2022 Apr 15.

Institute of Medical Psychology, Greifswald University Medical Faculty, Greifswald, Germany.

Background: The basis for adequate psycho-oncological care is the identification of patients with psychosocial support needs. The German Working Group for Psychooncology also recommends the Hornheider Screening Instrument (HSI) for this purpose. The question, "Is anyone in your family particularly burdened by the hospital stay?" is intended to capture disease-related family stress. But is this item equally suitable for outpatients and inpatients? The study objective was to examine how replacing the original item affects the test performance of this modified version of the HSI and the frequency of psychosocial stress.

Patients And Methods: 92 outpatients and 98 inpatients with skin tumors assessed their psychosocial situation using different questionnaires.

Results: Compared to inpatients, less than half as many outpatients answered the item in the affirmative. If the question was replaced by: "Is someone in your family particularly burdened by your disease or the course of the disease?" this setting-related difference did not arise. The "Alternative item" and the "Modified version of the HIS" (HSI-MV) proved to be superior to the original item and the original HSI with regard to all examined criteria.

Conclusions: The HSI-MV can be used as a reliable and valid instrument for the systematic assessment of psychosocial care needs in outpatient and inpatient settings. Depending on care capacity, a threshold of ≥ 5 or ≥ 4 is appropriate. In addition to screening, the desire for support should be enquired.
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http://dx.doi.org/10.1111/ddg.14692DOI Listing
May 2022

Preparing railway stakeholders against CBRNe threats through better cooperation with security practitioners.

Appl Ergon 2022 Jul 5;102:103752. Epub 2022 Apr 5.

Deutsche Hochschule der Polizei (DHPol), Germany.

This paper presents partial results from the Horizon2020 PROACTIVE project, following a set of literature reviews and surveys conducted with first responder organisations and rail security experts. Qualitative and quantitative data from two surveys are being presented. The results provide an overview of the CBRNe (Chemical, Biological, Radiological, Nuclear and explosive) preparedness and response capabilities of railway stakeholders and how these relate to a wider context represented by CBRNe first responders. The results highlight a set of challenges as well as five core skills that railway staff need to develop or improve: 1) understand the specific characteristics of the CBRNe threat, 2) develop basic response measures, 3) cooperate with authorities and train with specialised first responders, 4) improve public awareness about this threat, and 5) optimise crisis communication. In line with these, project PROACTIVE will further help update rail crisis management plans with practical recommendations concerning the CBRNe threat.
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http://dx.doi.org/10.1016/j.apergo.2022.103752DOI Listing
July 2022

Prevalence, atopic and psychological comorbidity of physician-diagnosed atopic dermatitis in an adult general population sample: A cross-sectional study.

Allergy 2022 06 29;77(6):1915-1917. Epub 2022 Mar 29.

Institute of Social Medicine and Health Systems Research, Medical Faculty Magdeburg, Magdeburg, Germany.

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http://dx.doi.org/10.1111/all.15288DOI Listing
June 2022

Comparison between incus short process and long process coupling of the vibrant soundbridge in human temporal bones.

Int J Audiol 2022 Feb 17:1-7. Epub 2022 Feb 17.

ENT Department, University Basel Hospital, Basel, Switzerland.

Objective: The Vibrant Soundbridge (VSB) is one of the most widely used implantable hearing devices. It consists of a vibrating floating mass transducer (FMT) that is connected to a middle ear structure. The standard coupling devices for sensorineural hearing loss are short process (SP) or long process (LP) couplers.

Design And Study Sample: This study directly compared the electro-mechanical performance of the SP- and LP-coupled FMT of the VSB in the same temporal bone specimen (= 10). We measured velocity magnitudes and total harmonic distortions (THD) of the stapes (ST) and the round window (RW) using laser Doppler Vibrometry (LDV).

Results: Comparison shows a maximally 10 dB higher magnitude for the LP coupler at ST and RW for frequencies below 600 Hz, whereas the SP coupler shows a maximally 20 dB higher magnitude at the ST and RW for frequencies above 600 Hz. THD show similar behaviour with less distortion at 500 Hz for the LP coupler and less distortions for the SP coupler in higher frequencies.

Conclusions: Our experiments showed that the SP coupling may be mechanically favourable, in terms of magnitude and distortion, for the transmission of FMT vibrations at higher frequencies.
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http://dx.doi.org/10.1080/14992027.2022.2031317DOI Listing
February 2022

Improvement of dynamic venous function after thermal ablation with steam vein occlusion - 6-weeks and 1-year follow-up after 167 treatments.

Clin Hemorheol Microcirc 2022 ;80(3):291-305

Department of Dermatology, Universitätsmedizin Greifswald, Greifswald, Germany.

Background: In this paper, the method of steam vein occlusion for the treatment of the great/small saphenous vein (GSV/SSV) was analyzed in terms of a therapeutic influence on the dynamic parameters of global vein function, its effects on subjective symptoms based on chronic venous insufficiency (CVI) and the side effects of the steam vein sclerosis (SVS). It has been questioned whether the effects of this method lead to a recommendation for routine clinical practice.

Methods: The venous drainage and the venous refilling time (T0) of the leg treated were determined by photoplethysmography (Elcat, Wolfratshausen, Germany) before, six weeks and one year after the intervention to examine the effects on global venous function. Further changes of clinical symptoms and findings were assessed by the Venous Clinical Severity Score (VCSS), preoperatively and after one year, and the complication rate at 6-week follow-up was monitored.

Results: The SVS was performed on 167 veins (GSV: 124; SSV: 43) in a total of 156 patients. Eight patients (5.1%) did not attend the 6-week follow-up, while 29 patients (18.6%) were lost in the 1-year follow-up. Patients were suffering from symptoms such as leg pain and leg edema, which resulted in a VCSS of 9.4 (cumulated mean score of all patients) preoperatively. The T0 was reduced to mean values of 20.6 s (GSV cohort) and 21 s (SSV cohort). The VCSS improved to 6.0 after one year. This correlated with the hemodynamic parameters. The T0 increased in the GSV cohort after six weeks to 31.8 s, p < 0.001, and showed a nonsignificant improvement to 32.2 s, p = 0.509, in the 1-year check. The T0 also increased in the SSV cohort significantly after 6 weeks to 30.1 s, p < 0.001, and showed a nonsignificant reduction after one year, p = 0.289. A total of 71%of the GSV and 69.8%of the SSV of the patients involved no complications following the treatment. Light complications (grade 1) occurred (reddening, hematoma, hyperpigmentation) in the majority: 24.2%of the GSV and 18.6%of the SSV. We noticed one grade 3 complication with thrombosis in the SSV cohort, which led to a pulmonary embolism. Forty-seven complete questionnaires were analyzed (responder rate: 28.1%); 40.4%of the patients had light complaints after the treatment, such as pain, warmth or local pressure sensations (Fig. 7); 63%of those patients noticed only slight pain at a maximum of 3 out of 10. The majority (91%) would recommend this procedure.

Conclusion: The SVS revealed endoluminal catheter-based intervention to abolish venous reflux of the G/SSV as safe. As one therapeutic target is to eliminate venous reflux, effectiveness of a method cannot be based on sonographic data alone; one must further assess patients' symptoms and dynamic venous function. This data shows an improvement of patients' symptoms which correlated well with the improvement of the venous function in digital photoplethysmography. The SVS can be recommended as a catheter-based treatment in the future.
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http://dx.doi.org/10.3233/CH-211239DOI Listing
March 2022

Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4.

Nat Commun 2021 11 16;12(1):6618. Epub 2021 Nov 16.

Department of Twins Research and Genetic Epidemiology, King's College London, London, UK.

Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.
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http://dx.doi.org/10.1038/s41467-021-26783-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595373PMC
November 2021

Lack of Significant Association between Sex Hormone Concentrations and Atopic Dermatitis in Adolescents and Adults in Two Population-Based Studies.

J Invest Dermatol 2022 02 24;142(2):486-489.e4. Epub 2021 Jul 24.

Clinic of Dermatology, University Medicine Greifswald, University of Greifswald, Greifswald, Germany.

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http://dx.doi.org/10.1016/j.jid.2021.07.133DOI Listing
February 2022

Micro-CT imaging of Thiel-embalmed and iodine-stained human temporal bone for 3D modeling.

J Otolaryngol Head Neck Surg 2021 Jun 2;50(1):33. Epub 2021 Jun 2.

University of Bern, Hochschulstrasse 6, CH-3012, Bern, Switzerland.

Introduction: This pilot study explores whether a human Thiel-embalmed temporal bone is suitable for generating an accurate and complete data set with micro-computed tomography (micro-CT) and whether solid iodine-staining improves visualization and facilitates segmentation of middle ear structures.

Methods: A temporal bone was used to verify the accuracy of the imaging by first digitally measuring the stapes on the tomography images and then physically under the microscope after removal from the temporal bone. All measurements were compared with literature values. The contralateral temporal bone was used to evaluate segmentation and three-dimensional (3D) modeling after iodine staining and micro-CT scanning.

Results: The digital and physical stapes measurements differed by 0.01-0.17 mm or 1-19%, respectively, but correlated well with the literature values. Soft tissue structures were visible in the unstained scan. However, iodine staining increased the contrast-to-noise ratio by a factor of 3.7 on average. The 3D model depicts all ossicles and soft tissue structures in detail, including the chorda tympani, which was not visible in the unstained scan.

Conclusions: Micro-CT imaging of a Thiel-embalmed temporal bone accurately represented the entire anatomy. Iodine staining considerably increased the contrast of soft tissues, simplified segmentation and enabled detailed 3D modeling of the middle ear.
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http://dx.doi.org/10.1186/s40463-021-00522-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173723PMC
June 2021

Improved Balance and Gait Ability and Basic Activities of Daily Living after Comprehensive Geriatric Care in Frail Older Patients with Fractures.

Healthcare (Basel) 2021 May 11;9(5). Epub 2021 May 11.

Department of Geriatrics and Neurology, Diakonie Hospital Jung Stilling, 57074 Siegen, Germany.

(1) Purpose: Comprehensive geriatric care (CGC) is a multidisciplinary treatment approach for elderly patients. We aimed to investigate outcomes in fracture patients who had been treated using this approach in a large geriatric unit. (2) Methods: This observational cohort study assessed the gait function (using the Tinetti Balance and Gait Test (TBGT)) and basic activities of daily living (ADL) (using the Barthel index (BI)) before and after CGC and compared the results. Baseline data, walking ability assessments (Timed Up and Go, TUG), and cognitive status (mini mental status examination, MMSE) were also analyzed in the subgroup of patients with versus without fractures. (3) Results: Out of 1263 hospitalized patients, 1099 received CGC (median age: 83.1 years (IQR: 79.0-87.8 years); 64.1% were female). TBGT improvement was observed in 90.7% and BI increased in 82.7% of fracture patients. A TBGT improvement of >5 was noted in 47.3% and was associated with female sex, a lower BI at admission (median: 40 versus 45; = 0.010), and poorer mobility on admission (TUG: median 5 versus 4; = 0.001). An improvement in BI of ≥15 was observed in 63.0% of the cases, and was associated with a better cognitive status (MMSE: median 25 versus 18; = 0.001) and inversely associated with diabetes mellitus and a previous stroke. (4) Conclusion: CGC in specialized geriatric units improves the balance and gait and the basic ADL in geriatric patients. After fracture, female patients are more likely to experience improvements in gait and balance, while patients with better cognitive condition are more likely to experience improvements in ADL.
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http://dx.doi.org/10.3390/healthcare9050560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151142PMC
May 2021

Effect of conservation method on ear mechanics for the same specimen.

Hear Res 2021 03 16;401:108152. Epub 2020 Dec 16.

Department of ENT, University Basel Hospital, Hebelstrasse 10, 4031 Basel, Switzerland. Electronic address:

Background And Aims: As an alternative to fresh temporal bones, Thiel conserved specimens can be used in the study of ear mechanics. Conserved temporal bones do not decay, permit long-term experiments and overcome problems with limited access to fresh (frozen) temporal bones. Air conduction motion of the tympanic membrane (TM), stapes (ST) and round window (RW) in Thiel specimens is similar to that of fresh specimens according to reports in the literature. Our study compares this motion directly before and after conservation for the same specimens.

Methods: The magnitude of motion of TM, ST and RW elicited by acoustic stimulation via the external auditory canal was measured using single point laser Doppler vibrometry (LDV) accessed through a posterior tympanotomy. For the initial measurements (10 ears), fresh frozen whole heads were thawed for at least 24 h. Afterwards, the entire whole heads were embalmed according to the Thiel embalming method and measurements were repeated 3 and 12 months later.

Results: The magnitudes of TM, ST and RW motion before and after Thiel conservation differed maximally 10 dB on average. A significant increase in TM motion was observed at low frequencies only after long term conservation (12 months). ST motions decreased significantly between 161 and 5300 Hz after 3 months of Thiel conservation. Over the same time period RW motions decreased significantly between 100 and 161 Hz and 489-788 Hz. The ST and RW motions across all measured frequencies were lower after 3 months by 5.7 dB and 7.1 dB, respectively, without further changes after 12 months of conservation. The mean phase shift between ST and RW motion was only 2.1° for frequencies below 450 Hz.

Discussion And Conclusion: Thiel embalming changes motion of TM after long term conservation. ST and RW motion changed mainly after short term conservation. The phase shifts close to 180° between ST and RW motion indicates that the cochlea was still filled with liquid without air bubbles. The results show that Thiel conserved specimens can be used as an alternative model to fresh frozen preparations with some limitations when studying mechanics of the normal human ear, for example, in implant design.
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http://dx.doi.org/10.1016/j.heares.2020.108152DOI Listing
March 2021

Dual Role of an mps-2/KCNE-Dependent Pathway in Long-Term Memory and Age-Dependent Memory Decline.

Curr Biol 2021 02 30;31(3):527-539.e7. Epub 2020 Nov 30.

Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland. Electronic address:

Activity-dependent persistent changes in neuronal intrinsic excitability and synaptic strength are underlying learning and memory. Voltage-gated potassium (K) channels are potential regulators of memory and may be linked to age-dependent neuronal disfunction. MinK-related peptides (MiRPs) are conserved transmembrane proteins modulating K channels; however, their possible role in the regulation of memory and age-dependent memory decline are unknown. Here, we show that, in C. elegans, mps-2 is the sole member of the MiRP family that controls exclusively long-term associative memory (LTAM) in AVA neuron. In addition, we demonstrate that mps-2 also plays a critical role in age-dependent memory decline. In young adult worms, mps-2 is transcriptionally upregulated by CRH-1/cyclic AMP (cAMP)-response-binding protein (CREB) during LTAM, although the mps-2 baseline expression is CREB independent and instead, during aging, relies on nhr-66, which acts as an age-dependent repressor. Deletion of nhr-66 or its binding element in the mps-2 promoter prevents age-dependent transcriptional repression of mps-2 and memory decline. Finally, MPS-2 acts through the modulation of the K2.1/KVS-3 and K2.2/KVS-4 heteromeric potassium channels. Altogether, we describe a conserved MPS-2/KVS-3/KVS-4 pathway essential for LTAM and also for a programmed control of physiological age-dependent memory decline.
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http://dx.doi.org/10.1016/j.cub.2020.10.069DOI Listing
February 2021

Skin Cancer Development in Solid Organ Transplant Recipients in Switzerland (Swiss Transplant Cohort Study).

Dermatology 2021 23;237(6):970-980. Epub 2020 Nov 23.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland,

Importance: Skin cancer, in particular squamous cell carcinoma, is the most frequent malignancy among solid organ transplant recipients with a higher incidence compared to the general population.

Objective: To determine the skin cancer incidence in organ transplant recipients in Switzerland and to assess the impact of immunosuppressants and other risk factors.

Design: Prospective cohort study of solid organ transplant recipients in Switzerland enrolled in the Swiss Transplant Cohort Study from 2008 to 2013.

Participants: 2,192 solid organ transplant recipients.

Materials And Methods: Occurrence of first and subsequent squamous cell carcinoma, basal cell carcinoma, melanoma and other skin cancers after transplantation extracted from the Swiss Transplant Cohort Study database and validated by medical record review. Incidence rates were calculated for skin cancer overall and subgroups. The effect of risk factors on the occurrence of first skin cancer and recurrent skin cancer was calculated by the Cox proportional hazard model.

Results: In 2,192 organ transplant recipients, 136 (6.2%) developed 335 cases of skin cancer during a median follow-up of 32.4 months, with squamous cell carcinoma as the most frequent one. 79.4% of skin cancer patients were male. Risk factors for first and recurrent skin cancer were age at transplantation, male sex, skin cancer before transplantation and previous transplantation. For a first skin cancer, the number of immunosuppressive drugs was a risk factor as well.

Conclusions And Relevance: Skin cancer following solid organ transplantation in Switzerland is greatly increased with risk factors: age at transplantation, male sex, skin cancer before transplantation, previous transplantation and number of immunosuppressive drugs.
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http://dx.doi.org/10.1159/000510685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619732PMC
February 2022

Psychosocial stress of dermatology inpatients and their relatives - Comparison of patients with and without cancer.

J Dtsch Dermatol Ges 2020 Oct 28;18(10):1103-1113. Epub 2020 Sep 28.

Institut für Medizinische Psychologie, Universitätsmedizin Greifswald [Institute of Medical Psychology, Greifswald University Medical Faculty.

Background: In the clinical treatment pathways of certified oncological centers, psychotherapeutic services are mandatory. Although patients with somatic, non-oncological illnesses show an equally high prevalence of psychosocial stress, these guidelines do not exist for the general hospital sector. Are these patients really less burdened and is psychological support only needed in individual cases? The example of dermatological patients will be used to show whether the need for psychosocial care and the desire for support vary between individuals with and without malignant disease.

Patients And Methods: Using the Hornheider screening instrument and distress thermometer, 216 dermatological inpatients assessed their psychosocial stress and that of a close relative. In addition, they were asked about their desire for support and preferred support provider.

Results: i) Patients without skin cancer were more frequently and more severely distressed than cancer patients. ii) Patients of both groups assessed their relatives to be approximately equally distressed. Compared with their own distress, cancer patients assessed their relatives as more frequently and on average more severely distressed. More than 50 % of all patients regarded their own disease as the cause of their relatives' distress. iii) The desire for support in both groups was about 18 %. iv) Doctors and psychologists were usually named as potential contact persons.

Conclusions: The expansion of psychosocial support services for non-tumor patients and their relatives seems necessary. The establishment of appropriate screening methods should be considered. Further studies in other clinical areas are required.
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http://dx.doi.org/10.1111/ddg.14285DOI Listing
October 2020

The course of Kaposi's sarcoma, a marker disease for the initial diagnosis of AIDS, under ongoing cART.

Clin Hemorheol Microcirc 2020 ;76(2):263-277

Klinik- und Poliklinik für Haut-und Geschlechtskrankheiten, Universitätsmedizin Greifswald, Greifswald, Germany.

While Kaposi's sarcoma (KS) was common in the 1980s and early 1990s in HIV-positive patients and one of the most common AIDS-defining diseases, its prevalence today has decreased significantly due to the early and widespread use of chimeric antigen receptor T-cell (cART) therapy. The rapid initiation of cART or, if occurring during ongoing cART, an optimization of antiretroviral therapy leads to a healing of this tumour disease in most patients. The aim of the therapy is immune reconstitution, as the immunodeficiency resulting from the HIV disease (reduced CD4+-T helper cells) promotes the development and spread of KS. This case report describes the course of KS in the first diagnosis of AIDS in a 36-year-old patient. The HIV copy count was below the detection limit and the CD3+/CD4+ T-helper cell count was only slightly below the normal value in the six-month follow-up after initial diagnosis and initiation of cART therapy. However, the clinical findings in the one-year follow-up showed only a partial response, whereby it was noted that new tumour lesions also developed focally in addition to individual progressive lesions. This was demonstrated clinically, dermatoscopically and by laser Doppler fluxmetry measurements of the lesions. Such a progression was observed in about one-third of the patients affected in various studies and is called Immune Reconstitution Inflammatory Syndrome. Other therapies in addition to cART are necessary here to suppress this immunological phenomenon (including cytostatic drugs). Promising studies are currently underway, including utilising checkpoint inhibitors. These are of great therapeutic interest due to the high immunological activity of KS itself and usually of systemic inflammatory response syndrome.
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http://dx.doi.org/10.3233/CH-209203DOI Listing
December 2020

Analysis of pigmented skin lesions and malignant melanoma by Laser Doppler flowmetry - Report of different cases and further analysis by a neuronal network.

Clin Hemorheol Microcirc 2020 ;76(4):525-533

Department of Dermatology, Universitätsmedizin Greifswald, Greifswald, Germany.

Background: Dermatoscopy is successfully used for the early diagnosis of suspicious skin lesions, however, correct diagnosis depends on training. There is evidence that wavelet analysis by Laser Doppler flowmetry (LDF) can identify malignant melanomas by their hypervascularization and changes in the capillary morphology.

Objective: To show the capability of LDF in the distinction of melanomas and benign pigmented skin lesions based on data collected over 16 years.

Methods: Evaluation of pigmented skin lesions was based on clinical information. The LDF measurements were taken. The suspect lesion was excised afterwards for histological work-up. Four case reports are presented. Data collected over 16 years was processed into a neuronal network to estimate the dignity of the lesion.

Results: A total of 517 suspicious lesions were analyzed by LDF. In the histological work-up, 114 lesions turned out to be melanomas, whereas 403 benign naevi were secured. Specificity to detect melanomas was good based on the clinical information. The LDF increases the sensitivity of melanoma detection, which is also illustrated in four case reports.

Conclusion: In addition to clinical parameters, such as color and border, information from the LDF can help in the diagnosis of malignant melanomas. The LDF provides information on the vascularization of the skin lesion.
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http://dx.doi.org/10.3233/CH-200876DOI Listing
February 2021

Evolutionary conserved role of neural cell adhesion molecule-1 in memory.

Transl Psychiatry 2020 07 6;10(1):217. Epub 2020 Jul 6.

University of Basel, Department of Psychology, Division of Molecular Neuroscience, Birmannsgasse 8, CH-4055, Basel, Switzerland.

The neural cell adhesion molecule 1 (NCAM-1) has been implicated in several brain-related biological processes, including neuronal migration, axonal branching, fasciculation, and synaptogenesis, with a pivotal role in synaptic plasticity. Here, we investigated the evolutionary conserved role of NCAM-1 in learning and memory. First, we investigated sustained changes in ncam-1 expression following aversive olfactory conditioning in C. elegans using molecular genetic methods. Furthermore, we examined the link between epigenetic signatures of the NCAM1 gene and memory in two human samples of healthy individuals (N = 568 and N = 319) and in two samples of traumatized individuals (N = 350 and N = 463). We found that olfactory conditioning in C. elegans induced ncam-1 expression and that loss of ncam-1 function selectively impaired associative long-term memory, without causing acquisition, sensory, or short-term memory deficits. Reintroduction of the C. elegans or human NCAM1 fully rescued memory impairment, suggesting a conserved role of NCAM1 for memory. In parallel, DNA methylation of the NCAM1 promoter in two independent healthy Swiss cohorts was associated with memory performance. In two independent Sub-Saharan populations of conflict zone survivors who had faced severe trauma, DNA methylation at an alternative promoter of the NCAM1 gene was associated with traumatic memories. Our results support a role of NCAM1 in associative memory in nematodes and humans, and might, ultimately, be helpful in elucidating diagnostic markers or suggest novel therapy targets for memory-related disorders, like PTSD.
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http://dx.doi.org/10.1038/s41398-020-00899-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338365PMC
July 2020

A rare case of a patient with PPP syndrome presenting pancreatic pseudocysts, panniculitis, and symptoms of polyarthritis. A radicular cyst of the upper jaw could be another manifestation of the syndrome.

Clin Case Rep 2020 Apr 14;8(4):625-629. Epub 2020 Jan 14.

Department of Dermatology University of Greifswald Greifswald Germany.

In rare cases, pancreatic enzymes can enter the bloodstream and cause fat necrosis in the bone and tissue leading to a disorder called pancreatitis, panniculitis, and polyarthritis syndrome. Clinicians should have this syndrome in mind when treating patients with pancreatitis.
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http://dx.doi.org/10.1002/ccr3.2651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141739PMC
April 2020

Verifying molecular clusters by 2-color localization microscopy and significance testing.

Sci Rep 2020 03 6;10(1):4230. Epub 2020 Mar 6.

Institute of Applied Physics, TU Wien, Getreidemarkt 9, A-1060, Vienna, Austria.

While single-molecule localization microscopy (SMLM) offers the invaluable prospect to visualize cellular structures below the diffraction limit of light microscopy, its potential has not yet been fully capitalized due to its inherent susceptibility to blinking artifacts. Particularly, overcounting of single molecule localizations has impeded a reliable and sensitive detection of biomolecular nanoclusters. Here we introduce a 2-Color Localization microscopy And Significance Testing Approach (2-CLASTA), providing a parameter-free statistical framework for the qualitative analysis of two-dimensional SMLM data via significance testing methods. 2-CLASTA yields p-values for the null hypothesis of random biomolecular distributions, independent of the blinking behavior of the chosen fluorescent labels. The method is parameter-free and does not require any additional measurements nor grouping of localizations. We validated the method both by computer simulations as well as experimentally, using protein concatemers as a mimicry of biomolecular clustering. As the new approach is not affected by overcounting artifacts, it is able to detect biomolecular clustering of various shapes at high sensitivity down to a level of dimers.
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http://dx.doi.org/10.1038/s41598-020-60976-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060173PMC
March 2020

Multimodal Imaging With Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging to Detect Extracapsular Extension in Head and Neck Cancer.

Laryngoscope 2021 01 6;131(1):E163-E169. Epub 2020 Mar 6.

Department of Otorhinolaryngology-Head and Neck Surgery, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.

Objectives/hypothesis: To assess the ability of specific positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) features to detect extracapsular extension (ECE) in head and neck squamous cell carcinoma (HNSCC) patients.

Study Design: Retrospective study in a tertiary certified university cancer institute.

Methods: We performed a review of patients with advanced HNSCC at Bern University Hospital between 2014 and 2018. Patients with pretherapeutic PET/CT and/or MRI who underwent neck dissection were included, with 212 patients fulfilling inclusion criteria. Blinded evaluation of specific PET/CT and MRI features with respect to presence of ECE was performed. Histopathological examination of neck dissection specimens was used as the gold standard to determine ECE status.

Results: Out of the 212 included patients, 184 had PET/CT, 186 MRI, and 158 both modalities. Overall clinical stage IV (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 2.25-11.74), ill-defined margins in both PET/CT and MRI (OR: 3.48, 95% CI: 1.21-9.98 and OR: 2.14, 95% CI: 0.94-4.89, respectively), and a maximum standardized uptake value ≥ 10 (OR: 5.44, 95% CI: 1.21-9.98) were all significant independent predictors of ECE. When combined, these four features led to a cumulative score able to predict ECE status with an accuracy of 91.43%.

Conclusions: The current findings indicate specific features in PET/CT and MRI are potential predictors of ECE status and may help in pretherapeutic stratification in HNSCC.

Level Of Evidence: 4 Laryngoscope, 131:E163-E169, 2021.
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http://dx.doi.org/10.1002/lary.28602DOI Listing
January 2021

Protein-coding variants contribute to the risk of atopic dermatitis and skin-specific gene expression.

J Allergy Clin Immunol 2020 04 9;145(4):1208-1218. Epub 2019 Nov 9.

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.

Background: Fifteen percent of atopic dermatitis (AD) liability-scale heritability could be attributed to 31 susceptibility loci identified by using genome-wide association studies, with only 3 of them (IL13, IL-6 receptor [IL6R], and filaggrin [FLG]) resolved to protein-coding variants.

Objective: We examined whether a significant portion of unexplained AD heritability is further explained by low-frequency and rare variants in the gene-coding sequence.

Methods: We evaluated common, low-frequency, and rare protein-coding variants using exome chip and replication genotype data of 15,574 patients and 377,839 control subjects combined with whole-transcriptome data on lesional, nonlesional, and healthy skin samples of 27 patients and 38 control subjects.

Results: An additional 12.56% (SE, 0.74%) of AD heritability is explained by rare protein-coding variation. We identified docking protein 2 (DOK2) and CD200 receptor 1 (CD200R1) as novel genome-wide significant susceptibility genes. Rare coding variants associated with AD are further enriched in 5 genes (IL-4 receptor [IL4R], IL13, Janus kinase 1 [JAK1], JAK2, and tyrosine kinase 2 [TYK2]) of the IL13 pathway, all of which are targets for novel systemic AD therapeutics. Multiomics-based network and RNA sequencing analysis revealed DOK2 as a central hub interacting with, among others, CD200R1, IL6R, and signal transducer and activator of transcription 3 (STAT3). Multitissue gene expression profile analysis for 53 tissue types from the Genotype-Tissue Expression project showed that disease-associated protein-coding variants exert their greatest effect in skin tissues.

Conclusion: Our discoveries highlight a major role of rare coding variants in AD acting independently of common variants. Further extensive functional studies are required to detect all potential causal variants and to specify the contribution of the novel susceptibility genes DOK2 and CD200R1 to overall disease susceptibility.
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http://dx.doi.org/10.1016/j.jaci.2019.10.030DOI Listing
April 2020

Positive Effect of Steroids in Posterior Reversible Encephalopathy Syndrome.

Case Rep Neurol 2019 May-Aug;11(2):173-177. Epub 2019 May 21.

Department of Geriatrics, Jung-Stilling Hospital Siegen, Siegen, Germany.

We present a case of posterior reversible encephalopathy syndrome with severe clinical manifestation. Apart from initial aphasia, hemiparesis, and a generalized seizure, the patient had a prolonged loss of consciousness. Although blood pressure was normalized, the clinical status deteriorated continuously. After adding steroids to the therapy, the patient recovered rapidly, suggesting that this could have been a useful therapeutic approach. Even the vasogenic edema in the cerebral magnetic resonance imaging disappeared shortly within 6 days.
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http://dx.doi.org/10.1159/000500410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738275PMC
May 2019

[An erythematous macule is not always a fungal infection].

Authors:
Andreas W Arnold

Ther Umsch 2019 Aug;76(2):98-104

1 Dermatologie am Rhein, Basel.

An erythematous macule is not always a fungal infection In this article we show ten cases of erythematic macules and plaques which we think are most important in the differential diagnosis to a fungal infection of the skin. The macules are mostly solitary. A few of them can be also exanthematous. It is important to know about the differential diagnosis because clinic is often doubtful and can be challenging, especially if the evolution is not clear.
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http://dx.doi.org/10.1024/0040-5930/a001062DOI Listing
August 2019

Round window and promontory movements during bone conduction with different middle ear conditions in Thiel embalmed specimens.

Acta Otolaryngol 2019 Apr 16;139(4):351-356. Epub 2019 Apr 16.

b Department of ENT , Inselspital, University Bern , Bern , Switzerland.

Background: Thiel conservation is mainly based on a watery solution of salts. We have shown that bone conduction (BC) evokes motion in normal middle ears of Thiel embalmed specimens that is comparable to the motion for other cadaveric models.

Aims/objectives: We evaluated whether promontory and round window (RW) motion identifies differences in BC transmission for different middle ear conditions.

Methods: We investigated the conditions of mobile ossicle chain, cement-fixed stapes and stapedectomy in seven ears. A retroauricular bone anchored hearing system provided BC stimulation. The motions of the promontory and the RW were measured using single point laser Doppler vibrometer (LDV, HLV1000, Polytec).

Results: The averaged differences between the conditions were small for RW motion and for promontory motion. However, for RW motion we found differences of more than one standard deviation at some frequencies. These differences in RW motion were more apparent when we limited the analysis to three selected specimens.

Conclusions And Significance: Extracochlear measurement of the RW motion with LDV allowed differentiation between BC for different middle ear conditions. These changes could be detected best in a small frequency range in selected specimens. Promontory motion could not be used to differentiate between different conditions of the middle ear.

Abbreviations: LDV: laser Doppler vibrometry; Prom: cochlear promontory; RW: round window; ST: stapes; TM: tympanic membrane; VProm: velocity of the promontory; VRW: velocity of the round window.
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http://dx.doi.org/10.1080/00016489.2019.1592226DOI Listing
April 2019

Dislocation rates of postoperative airway exchange catheters - a prospective case series of 200 patients.

BMC Anesthesiol 2019 04 11;19(1):52. Epub 2019 Apr 11.

Department of Anesthesiology and Pain Therapy, Bern University Hospital and University of Bern, CH-3010, Bern, Switzerland.

Background: The dislocation rate of oral versus nasal airway exchange catheters (AEC) in the postoperative care unit (PACU) are unknown. Our aim was to establish dislocation rates and to assess the usefulness of waveform capnography to detect dislocation.

Methods: In this non-randomized, prospective observational trial at the University Hospital Bern, Switzerland, we included 200 patients admitted to PACU after extubation via AEC, having provided written informed consent. The study was approved by the local ethical committee. AEC position was assessed by nasal fiberoptic endoscopy at beginning of PACU stay and before removal of the AEC. Capnography was continuously recorded via the AEC. Additional measurements included retching and coughing of the patient, and re-intubation, if necessary.

Results: Data from 182 patients could be evaluated regarding dislocation. Overall dislocation rate was not different between oral and nasal catheters (7.2% vs. 2.7%, p = 0.16). Retching was more often noted in oral catheters (26% vs. 8%, p < 0.01). Waveform capnography was unreliable in predicting dislocation (negative predictive value 17%). Re-intubation was successful in all five of the nine re-intubations where an AEC was still in situ. In four patients, the AEC was already removed when re-intubation became necessary, and re-intubation failed once, with a front of neck access as a rescue maneuver.

Conclusions: We found no difference in dislocation rate between nasal and oral position of an airway exchange catheter. However, nasal catheters seemed to be tolerated better. In the future, catheters like the staged extubation catheter may further increase tolerance.

Trial Registration: The study was registered in a clinical study registry ( ISRCTN 96726807 ) on 10/06/2010.
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http://dx.doi.org/10.1186/s12871-019-0723-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458602PMC
April 2019

Stereotactic radiosurgery combined with immune checkpoint inhibitors or kinase inhibitors for patients with multiple brain metastases of malignant melanoma.

Melanoma Res 2019 04;29(2):187-195

Dermatology, University Medical Center Schleswig-Holstein, Kiel.

The aim was to evaluate toxicity and oncological outcome of combined stereotactic radiosurgery (SRS) and immunotherapy or targeted therapy in patients with multiple brain metastases originating from malignant melanoma. Despite the fact that both SRS and kinase inhibitors or immune checkpoint inhibitors are considered standard treatment options for this indication, the optimal combination and sequence of these modalities remains largely unknown, especially for patients with a high number of brain metastases. For this retrospective analysis, conducted in two large SRS dedicated centers, we identified patients with brain metastases from malignant melanoma and simultaneous application of immunotherapy or targeted therapy within 30 days of SRS. Forty-eight patients with a total of 250 lesions (median: 3) were treated in 65 single fraction SRS sessions from 2012 to 2018. After a median follow-up of 8.3 months (range: 1.2-43.6 months), the 6-month and 1-year overall survival rates were 75.3 and 50.8%, respectively. The local control rate at one year was 89.5%. Immunotherapy and the application of systemic treatment directly before or concomitant to SRS were both associated with improved overall survival (P=0.037 and 0.045, respectively). We observed four grade III toxicities, of which only two can be clearly attributed to the combined treatment. Various combinations of SRS and kinase inhibitors or immune checkpoint inhibitors appear feasible and provide promising oncological results and safety profiles for treating few (n=1-4) and also multiple (n≥5) melanoma brain metastases.
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http://dx.doi.org/10.1097/CMR.0000000000000542DOI Listing
April 2019
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