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Michael Furian,1,* Deborah Flueck,1,* Tsogyal D Latshang,1 Philipp M Scheiwiller,1 Sebastian Daniel Segitz,1 Séverine Mueller-Mottet,1 Christian Murer,1 Adrian Steiner,1 Silvia Ulrich,1 Thomas Rothe,2 Malcolm Kohler,1 Konrad E Bloch1 1Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland; 2Zuercher RehaZentrum Davos, Davos Clavadel, Switzerland *These authors contributed equally to this work Objective: To evaluate the effects of altitude travel on exercise performance and symptoms in lowlanders with COPD. Design: Randomized crossover trial. Setting: University Hospital Zurich (490 m), research facility in mountain villages, Davos Clavadel (1,650 m) and Davos Jakobshorn (2,590 m). Participants: Forty COPD patients, Global Initiative for Obstructive Lung Disease (GOLD) grade 2–3, living below 800 m, median (quartiles) age 67 y (60; 69), forced expiratory volume in 1 second 57% predicted (49; 70). Intervention: Two-day sojourns at 490 m, 1,650 m, and 2,590 m in randomized order. Outcome measures: Six-minute walk distance (6MWD), cardiopulmonary exercise tests, symptoms, and other health effects. Results: At 490 m, days 1 and 2, median (quartiles) 6MWD were 558 m (477; 587) and 577 m (531; 629). At 2,590 m, days 1 and 2, mean changes in 6MWD from corresponding day at 490 m were -41 m (95% CI -51 to -31) and -40 m (-53 to -27), n=40, P

Background Narrowband ( TL-01) UVB phototherapy ( UVB nb) is effective in treating inflammatory skin disease. The addition of UVA is traditionally advocated to reduce pruritus, but lacks evidence for this recommendation. Objectives The aim of this study was to assess the effect of UVB nb and UVA phototherapy in combination compared against UVB nb monotherapy on pruritus, disease activity and quality of life. Methods In this double-blind randomized clinical trial, 53 patients suffering from inflammatory skin diseases with pronounced itching (Visual Analogue Scale ( VAS) for pruritus ≥5) were randomized into two treatment groups. One group received UVB nb (311 nm) phototherapy alone and another group received a combination of UVB nb and UVA (320-400 nm) phototherapy. UV therapy was performed three times per week over 16 weeks. Pruritus ( VAS and 5-D itch score), disease activity and quality of life (Dermatology Life Quality Index, DLQI) were assessed at baseline and weeks 4, 8, 12 and 16. Results In both treatment groups, there was a reduction in pruritus scores, disease activity and DLQI. No difference in pruritus score, disease activity and quality of life could be detected between the group receiving UVB nb alone and those receiving UVB nb combined with UVA. Conclusions Phototherapy with UVB nb alone, and UVB nb combined with UVA are equally effective in treating inflammatory skin disease and indifferent in reducing disease-associated pruritus. Given this non-inferiority for UVB nb monotherapy, the recommendation of adding UVA to UVB nb phototherapy for pruritic inflammatory skin disease should be abandoned. [ABSTRACT FROM AUTHOR]

Background: Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research., Methods: All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed., Results: The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with <5 % for almost all variables. A considerable number of missing source data occurred for CFTR variants. Availability of ICs varied largely between centers (10 centers had >5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved., Conclusions: Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kathleen Jahn, Andreas Jung, Philipp Latzin, Alexander Moeller, Christian Murer, Lutz Naehrlich, Alain Sauty and Jakob Usemann have received honoraria from Vertex Pharmaceuticals. Andreas Jung has received consulting fees and honoraria from EffRx Pharmaceuticals and Viatris. Philipp Latzin has received honoraria from CSL Vifor., (Copyright © 2023. Published by Elsevier B.V.)

Background: There is evidence that sensorimotor and executive functions are inherently intertwined, but that the relationship between these functions differ depending on an individual's stage in development (e.g., childhood, adolescence, adulthood)., Objective: In this study, sensorimotor and executive function performance was examined in a group of children ( n = 40; 8-12 years), adolescents ( n = 39; 13-17 years), and young adults ( n = 83; 18-24 years) to investigate maturation of these functions, and how the relationships between these functions differ between groups., Results: Adults and adolescents outperformed children on all sensorimotor and executive functions. Adults and adolescents exhibited similar levels of executive functioning, but adults outperformed adolescents on two sensorimotor functioning measures (eye-hand coordination spatial precision and proprioceptive variability). Regression analysis demonstrated that executive functions contribute to children's sensorimotor performance, but do not contribute to adolescent's sensorimotor performance., Conclusion: These findings highlight the key role that developmental stage plays in the relationship between sensorimotor and executive functions. Specifically, executive functions appear to contribute to more successful sensorimotor function performance in childhood, but not during adolescence. It is likely that sensorimotor functions begin to develop independently from executive functions during adolescence, and therefore do not contribute to successful sensorimotor performance. The change in the relationship between sensorimotor and executive functions is important to take into consideration when developing sensorimotor and executive function interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gordon-Murer, Stöckel, Sera and Hughes.)

Physicians' and patients' perspectives can vary significantly. For a long time, physicians considered psoriasis a non-pruritic dermatosis until a survey found pruritus to be the most bothersome symptom among psoriasis patients. In our study, we wanted to get an insight into the factors that affect patients and evaluate whether gender differences exist. A link of an anonymous online survey ( www.fightpsoriasis.ch ) with 24 questions was placed on the website of the Swiss Psoriasis and Vitiligo Patient Association ( www.spvg.ch ) from May 2016 until June 2017. 3164 persons participated in this online survey, of which 1979 were diagnosed with psoriasis. Significantly more females than males were affected by psoriatic pruritus [713 (36%) vs. 500 (25.3%), p ≤ 0.001] and 756 (39.7%) of all patients identified pruritus as the most life quality-limiting factor. Fewer women reported high satisfaction with their therapy compared to men [96 (4.9%) vs. 110 (5.6%), p ≤ 0.015]. Pruritus remains the most bothersome symptom and women were more often affected by it, leading to a lower treatment satisfaction among female patients.

Stroke is becoming one of the leading causes of adult disability and death in sub-Saharan African countries. The aim of the present study is to provide an up-to-date account of the clinical and demographic characteristics of patients with stroke admitted to the University of Gondar College of Medicine and Health Science Comprehensive Specialized Hospital (CMHS). A hospital based retrospective study design was used to analyze the medical records of all patients with stroke admitted to CMHS from June 20th 2012 and April 30th 2018. Data were cleaned and entered into SPSS for analysis. Among the 448 patients with stroke admitted to CMHS, 58.0% ( n = 260) of patients were female, and 42.0% ( n = 188) were male. In the present sample, 141 (31.5%) had an ischemic stroke confirmed by neuroimaging, 82 (18.3%) had a hemorrhagic stroke confirmed by neuroimaging, and 252 (50.2%) had a stroke with undetermined type. The mean age of stroke was 63.9 years (range = 18-100, SD : 15.1 years), with no differences observed between stroke subtypes. The most common symptoms that led to patients seeking medical intervention were hemiparesis (67.4%), communication difficulties (56.0%), facial deviation (37.3%), and globalized headache (36.4%). Hypertension was the most commonly reported risk factor (37.1%), which was more prevalent in hemorrhagic ( n = 37, 45.1%) than ischemic stroke patients ( n = 53, 37.6%), stroke with undetermined type ( n = 76, 33.8%). Stroke places a significant burden on sub-Saharan African countries. Results of the current study highlight the need to develop programs that educate the Ethiopian populace about the risk factors and symptoms of stroke, the importance of seeking medical care within the golden window, and the benefits of neuroimaging to accurately diagnose stroke subtype. In addition, the current study provides hospital administrators with empirical data that they can use to form an interdisciplinary stroke rehabilitation team capable of improving outcomes of Ethiopian patients with stroke., (Copyright © 2020 Baye, Hintze, Gordon-Murer, Mariscal, Belay, Gebremariam and Hughes.)

Background: Nurse practitioners are a common resource for victims of intimate partner violence (IPV) presenting to health care settings. However, they often have inadequate knowledge about IPV and lack self-efficacy and confidence to be able to screen for IPV and communicate effectively with patients., Objective: The aim of this study was to develop and test the usability of a blended learning system aimed at educating nurse practitioner students on topics related to IPV (ie, the mPOWERED system [Health Equity Institute])., Methods: Development of the mPOWERED system involved usability testing with 7 nurse educators (NEs) and 18 nurse practitioner students. Users were asked to complete usability testing using a speak-aloud procedure and then complete a satisfaction and usability questionnaire., Results: Overall, the mPOWERED system was deemed to have high usability and was positively evaluated by both NEs and nurse practitioner students. Respondents provided critical feedback that will be used to improve the system., Conclusions: By including target end users in the design and evaluation of the mPOWERED system, we have developed a blended IPV learning system that can easily be integrated into health care education. Larger-scale evaluation of the pedagogical impact of this system is underway., Competing Interests: Conflicts of Interest: None declared., (©Charmayne Hughes, Elaine A Musselman, Lilia Walsh, Tatiana Mariscal, Sam Warner, Amy Hintze, Neela Rashidi, Chloe Gordon-Murer, Tiana Tanha, Fahrial Licudo, Rachel Ng, Jenna Tran. Originally published in JMIR Nursing Informatics (https://nursing.jmir.org), 03.01.2020.)

Background: Patients with mastocytosis often suffer from a variety of symptoms caused by mast cell mediators where treatments remain difficult, showing various success rates. Omalizumab, a monoclonal anti-IgE antibody, has been postulated to have a positive impact on mastocytosis-associated symptoms such as flush, vertigo, gastrointestinal problems, or anaphylaxis., Objective: To investigate the efficacy and safety of omalizumab in systemic mastocytosis., Methods: Patients with histologically proven mastocytosis were investigated in a multicenter prospective double-blind placebo-controlled trial to receive either omalizumab or placebo, dosed according to IgE and body weight. The primary endpoint was change in the AFIRMM activity score after 6 months of treatment. Different laboratory parameters were analyzed., Results: Sixteen patients were analyzed: 7 to omalizumab and 9 to placebo (mean age 47.7 ± 13.8 vs. 45.4 ± 8.8 years; 66.6 vs. 85.7% were female; mean disease duration 10.0 ± 5.1 vs. 4.5 ± 2.9 years, respectively). After 6 months the median AFIRMM score decreased 50% from 52.0 to 26.0 in the omalizumab group versus 104.0-102.0 in the placebo group (p = 0.286); however, the difference was not significant (p = 0.941). Secondary endpoints, including the number of allergic reactions, changes in major complaints, wheal-and-flare reaction due to mechanical irritation (Darier's sign), and frequency of the use of mastocytosis-specific drugs improved in the omalizumab group, but not significantly. Adverse events like urticaria, bronchospasm, and anaphylactic shock showed no significant difference between the groups. No severe adverse events occurred. FcεRI (Fc-epsilon receptor) expression on basophils decreased after receiving omalizumab versus placebo., Conclusion: Omalizumab was safe and showed a tendency to improve mastocytosis-related symptoms, in particular diarrhea, dizziness, flush, and anaphylactic reactions, including the AFIRMM score and secondary endpoints; however, the difference was not significant. Due to the small study size and difference at baseline between the study groups, further studies are required to confirm our findings., (© 2020 S. Karger AG, Basel.)

Acquired brain injuries place a significant burden on sub-Saharan African rehabilitation clinicians and health care facilities. While wearable sensors have the potential to alleviate these issues, many are beyond the financial capabilities of the majority of African persons and clinics. To bridge this gap, we have developed a low-cost wrist-worn sensor (the outREACH sensor) capable of accurately measuring upper limb movement kinematics. In this study we evaluated the extent to which the outREACH sensor is sensitive to the hand performing the task (unimpaired, impaired) and level of impairment (mild, moderate) in 14 Ethiopian persons with acquired brain injury (mean age = 51.6 ± 12.2 years, 1 female, 13 male). Participants performed an object manipulation task with both the impaired and the unimpaired limb, and reaching performance was measured using standard kinematic measures (i.e., movement time, spectral arc length, peak velocity, peak acceleration, mean velocity, mean acceleration). Overall, movements were smoother and faster when performed by the patient's unimpaired limb. In contrast, maximum velocity did not differ between the two limbs. Moreover, the outREACH sensor was sensitive to differences in performance-based upper limb impairment. Fugl-Meyer assessment for upper extremity scores were significantly correlated with movement time, spectral arc length, and peak velocity. Upper limb movement kinematics can be accurately measured using the outREACH sensor. The outREACH sensor can be a valuable addition to standardized clinical measures that provides rehabilitation clinicians with information regarding initial upper limb impairment level and changes in function across the rehabilitation lifespan., (Copyright © 2019 Hughes, Baye, Gordon-Murer, Louie, Sun, Belay and Zhang.)

The development of context-appropriate sensor technologies could alleviate the significant burden of stroke in Sub-Saharan African rehabilitation clinicians and health care facilities. However, many commercially available wearable sensors are beyond the financial capabilities of the majority of African persons. In this study, we evaluated the concurrent validity of a low-cost wearable sensor (i.e., the outREACH sensor) to measure upper limb movement kinematics of 31 healthy persons, using an 8-camera Vicon motion capture system as the reference standard. The outREACH sensor showed high correlation ( r range: 0.808-0.990) and agreement (mean difference range: -1.60 to 1.10) with the reference system regardless of task or kinematic parameter. Moreover, Bland-Altman analyses indicated that there were no significant systematic errors present. This study indicates that upper limb movement kinematics can be accurately measured using the outREACH sensor, and have the potential to enhance stroke evaluation and rehabilitation in sub-Saharan Africa., (Copyright © 2019 Hughes, Louie, Sun, Gordon-Murer, Belay, Baye and Zhang.)

This study utilized a 3-degree of freedom robotic device (Wristbot) to examine wrist proprioception and eye-hand coordination in a cross-sectional sample of sixty-three young adults (19-29 years), 20 older young adults (30-49), and 17 older adults (50 years and older). Results indicated differences in the emergence of age-related declines in sensorimotor functioning depending on the tested motor skill component. While young adults exhibited smaller matching error and lower variability compared to older young adults and older adults on the proprioception task, we observed lower times-on-target and higher Linearity indices for participants older than 50 years of age compared to both young adults and older young adults. The present results provide necessary quantitative information on sensorimotor function in adulthood, and have implications for the early diagnosis and effective management of sensorimotor dysfunction in clinical settings using a commercially available robotic device.

Objectives: Potassium iodide (KI) is a medication that has been used for decades in dermatology and it is mentioned as a treatment option in all major dermatology textbooks. Yet, there is little recent information on its efficacy. In our study, we wanted to retrospectively evaluate the therapy response to KI in our patients., Methods: The hospital information system was searched for patients treated with KI at the Department of Dermatology (University Hospital Zurich) in the last 20 years (January 1, 1998 to December 31, 2017). A total of 52 patients were found and, subsequently, 35 patients were included in our study., Results: KI was prescribed for the following skin conditions: erythema nodosum, disseminated granuloma anulare, necrobiosis lipoidica, nodular vasculitis, cutaneous sarcoidosis, and granulomatous perioral dermatitis/ rosacea. The median duration of KI intake was 5 ± 7.7 weeks (range 1-26). The global assessment of efficacy by the treating physician showed an improvement of disease in about a third of all patients. No response was seen in 14 patients and 9 even had a progression of disease. An adverse event was documented in 16 cases., Conclusions: Our findings show that an improvement was reached in only about a third of all cases. High response rates with only mild side effects (in 16 out of 35 patients) were observed., (© 2018 S. Karger AG, Basel.)

Aims of the Study: Cystic fibrosis is the most common genetic disorder in Caucasians. The combination of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector lumacaftor / potentiator ivacaftor (LUM/IVA) has been shown to increase forced expiratory volume in 1 second (FEV1) moderately, but predominantly reduce acute exacerbation rate (AER) in Phe508del homozygous cystic fibrosis patients; however, patients with FEV1 <40% predicted were excluded from studies. We used LUM/IVA on a "compassionate use" basis in cystic fibrosis patients with end-stage pulmonary disease. Our aim was to evaluate if this patient cohort tolerates LUM/IVA treatment and if there is clinical stabilisation. Lung transplantation (LTX) is the ultimate treatment option for these patients despite maximal therapy. If LTX candidates stabilise clinically, conditions for LTX, when it is indicated, improve. This is particularly important in countries such as Switzerland with a low organ donation rate and long waiting times for suitable donor organs., Methods: We included all patients from the Adult Cystic Fibrosis Centre at the University Hospital Zurich with Phe508del homozygous genotype and a predicted FEV1 <40% or being evaluated or already listed for LTX. Clinical outcome data comprised AER, 6-minute walking distance (6-MWD), FEV1, forced vital capacity (FVC), mid-expiratory flow (MEF 25-75%), sweat chloride, body mass index (BMI) and quality of life. Respiratory-related adverse events (RAEs) were recorded. LUM/IVA treatment was initiated at a low dose and the dose increased stepwise., Results: Twenty patients were on trial with LUM/IVA; at the cut-off date, 6-month follow-up was complete for 10 patients. RAEs were severe and occurred early. The dropout rate due to RAE or lack of clinical success was 20%. Median AER decreased from 2.5 in the 6 months pre-treatment to 1 during the observation period. FEV1 increased from 32 to 34.5% predicted, p = 0.292. The 6-MWD increased by a median 33 m (p = 0.6086). Sweat chloride decreased significantly by a median of 25 mmol/l (p = 0.0003). Median BMI increased from 19 to 19.9 kg/m2 (p = 0.1488). At the cut-off, three previously listed patients were paused on the transplant waiting list., Conclusion: Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease tolerated LUM/IVA, although RAEs occurred early and were severe. This positive finding was probably due to the stepwise dose increases. There was clinical benefit mainly from reduction in AER and stabilisation of lung function. We propose that all suitable Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease should have a trial of LUM/IVA treatment in experienced centres.

Scedosporium species are fungal pathogens increasingly recognized in cystic fibrosis (CF). They can cause multiresistant, life-threatening infections that are of particular concern in CF patients undergoing lung transplantation, as optimal treatment remains unclear. Here, we describe our Zurich experience of CF patients with Scedosporium infection. Disseminated infection occurred in one patient after transplantation and was successfully treated. We propose a step-by-step approach to treat candidates with colonization, and discuss our cases in the context of the current literature., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Effects of hypobaric hypoxia at altitude on exercise performance of lowlanders with chronic obstructive pulmonary disease (COPD) have not been studied in detail., Objectives: To quantify changes in exercise performance and associated physiologic responses in lowlanders with COPD travelling to moderate altitude., Methods: A total of 31 COPD patients with a median age (quartiles) of 66 years (59; 69) and FEV1 of 56% predicted (49; 69) living below 800 m performed a constant-load bicycle exercise to exhaustion at 60% of the maximal work rate at 490 m (Zurich) and at an identical work rate at 2,590 m (Davos) in randomized order. Pulmonary gas exchange, pulse oximetry (SpO2), cerebral tissue oxygenation (CTO; near-infrared spectroscopy), and middle cerebral artery peak blood flow velocity (MCAv) by Doppler ultrasound during 30 s at end exercise were compared between altitudes., Results: With ascent from 490 to 2,590 m, the median endurance time (quartiles) was reduced from 500 s (256; 795) to 205 s (139; 297) by a median (95% CI) of 303 s (150-420) (p < 0.001). End exercise SpO2 decreased from 92% (89; 94) to 81% (77; 84) and CTO from 62% (56; 66) to 55% (50; 60); end exercise minute ventilation increased from 40.6 L/min (35.5; 47.8) to 47.2 L/min (39.6; 58.7) (p < 0.05; all comparisons 2,590 vs. 490 m). MCAv increased similarly from rest to end exercise at 490 m (+25% [17; 36]) and at 2,590 m (+21% [14; 30]). However, the ratio of MCAv increase to SpO2 drop during exercise decreased from +6%/% (3; 12) at 490 m to +3%/% (2; 5) at 2,590 m (p < 0.05)., Conclusions: In lowlanders with COPD travelling to 2,590 m, exercise endurance is reduced by more than half compared to 490 m in association with reductions in systemic and cerebral oxygen availability., (© 2018 S. Karger AG, Basel.)

Current-induced spin-orbit torques are one of the most effective ways to manipulate the magnetization in spintronic devices, and hold promise for fast switching applications in non-volatile memory and logic units. Here, we report the direct observation of spin-orbit-torque-driven magnetization dynamics in Pt/Co/AlO x dots during current pulse injection. Time-resolved X-ray images with 25 nm spatial and 100 ps temporal resolution reveal that switching is achieved within the duration of a subnanosecond current pulse by the fast nucleation of an inverted domain at the edge of the dot and propagation of a tilted domain wall across the dot. The nucleation point is deterministic and alternates between the four dot quadrants depending on the sign of the magnetization, current and external field. Our measurements reveal how the magnetic symmetry is broken by the concerted action of the damping-like and field-like spin-orbit torques and the Dzyaloshinskii-Moriya interaction, and show that reproducible switching events can be obtained for over 10 12 reversal cycles.

Introduction: In contrast to skin cancer and lymphoproliferative disorders, de-novo lung allograft cancer is seldom reported after lung transplantation., Case Report: A 19-year-old patient with severe pulmonary hypertension listed urgently for lung transplantation underwent successful bilateral lung transplant procedure receiving lungs from a 55-year-old donor with a smoking history of 30 pack years. After 3.5 years of lung transplantation, a locally advanced squamous cell carcinoma in the left lung allograft was diagnosed. Extended (intra-pericardial) left pneumonectomy was successfully performed, but the patient died a few weeks later due to acute respiratory distress syndrome., Conclusion: Usage of extended criteria donors seems a successful strategy to overcome shortage of donor lungs by the increasing number of lung transplant candidates. However, this approach might increase the risk of novel development of lung allograft cancer, a potential fatal complication that must be considered during follow-up of lung transplant recipients.

Treatment of melanoma remains a challenge in advanced disease. Recently, the molecular differentiation in BRAF-mutated, NRAS-mutated and c-kit-mutated melanomas led to new treatment strategies. Different trials show that imatinib or nilotinib lead to meaningful responses in c-kit-mutated melanoma patients. There are little published data on sequential inhibition using these two drugs in melanoma. We describe the sequential use of imatinib after nilotinib in a c-kit-mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine, nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor imatinib. From July 2011 to September 2011, the patient received ipilimumab (four doses with 3 mg/kg). Clinical assessment after immunotherapy showed disease progression. Therefore, a treatment change to imatinib 800 mg daily was made from February 2012 to May 2013. Under this treatment, the patient showed a partial response as per the RECIST criteria. The present lesions continued responding (computed tomography scans: May 2012-March 2013). Unfortunately, in October 2012, new brain metastases developed. Nevertheless, the use of c-kit inhibitors in c-kit-mutated melanoma patients seems to be a promising treatment option. Furthermore, a delayed response to ipilimumab after 6 months could also have led to or supported the partial response in this case. However, when two biologically similar compounds are administered in a melanoma patient and the tumour mass shows progressive disease upon administration of the first agent, an additional progression with no effect may be expected when the second one is used. This case shows, in contrast, that the use of imatinib after progression upon nilotinib can be beneficial.

A patient with tinea incognita is presented together with a review of the literature of figurate erythema. Figurate lesions are emblematic for dermatology and perhaps the most picturesque efflorescences. The differential diagnosis can be broad and sometimes challenging. Many clinical entities with resembling primary and secondary efflorescences have to be considered as differentials and can be due to anti-infectious, paraneoplastic, allergic, autoimmune or other immune reactions.

Background: Extracorporeal photopheresis (ECP) has been reported to be safe and the ultimate treatment option in lung transplant recipients with chronic lung allograft dysfunction (CLAD), the main overall cause of mortality in lung transplant recipients. However, ECP is not reimbursed in selected health jurisdictions, and reimbursement by health insurance providers is a major issue. In Switzerland, ECP is not recognised by the health authorities as a therapy option for CLAD; thus by the end of 2014, ECP had to be stopped in the majority of adult lung transplant recipients cared for at the University Hospital Zurich because of lack of continuous funding., Objective: To describe the outcome of lung transplant recipients after forced cessation of ECP treatment., Method: We retrospectively analysed outcome of 12 lung transplant recipients undergoing ECP for different phenotypes of CLAD (bronchiolitis obliterans syndrome, restrictive allograft syndrome) at our centre followed-up for 12 months after forced cessation of ECP., Results: Within the 12 months after treatment cessation, seven patients (58%) died with a median survival of 207 days (range 6-365 days). Lung function (FEV1, forced expiratory volume in 1 second) declined significantly 6 months after ECP cessation (p = 0.003)., Conclusion: Our data support the role of ECP as valuable treatment option in lung transplant recipients with CLAD.

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

Lung transplantation is an established therapy for advanced lung disease. Among the common disease indications for lung transplantation, patients with interstitial lung disease, in particular, idiopathic pulmonary fibrosis (IPF), have the worst prognosis. Thus referral to a transplant center should ideally be realised at the time of diagnosis of usual interstitial pneumonitis (UIP), regardless of lung function, in order to carry out a through initial assessment and evaluation.

Background: Treatment with selective BRAF or MEK inhibitors is frequently associated with cutaneous toxicities, including squamous cell carcinoma (SCC), papillomas and rash. These cutaneous adverse effects are typically observed at a lower incidence during combined BRAF and MEK inhibitor therapy., Patients and Methods: Two male patients with stage IV metastatic BRAF-mutated melanoma were treated with a combination of a selective BRAF inhibitor and a selective MEK inhibitor (dabrafenib and trametinib, or encorafenib (LGX818) and binimetinib (MEK162)) within two different clinical trials. Ten and 150 days after treatment start respectively, the patients developed painful nodules on the legs. In addition, one patient developed symmetrical articulation pain and intermittent fever episodes., Results: Based on the clinical and histological presentation, erythema nodosum-like panniculitis was diagnosed in both cases. No other aetiology could be found. After receiving topical or oral steroid treatment and anti-inflammatory analgesics, the painful nodular lesions disappeared several weeks later. In one case, a rebound of the painful nodules was observed when the combination treatment (dabrafenib and trametinib) was resumed after a 1-week unscheduled treatment interruption., Conclusions: Panniculitis has previously been described in association with BRAF inhibitor treatment, but not MEK inhibitor treatment. Combination treatment is usually associated with a lower incidence of cutaneous adverse events (AEs), as compared to monotherapy. Panniculitis was observed in two patients during combined BRAF and MEK inhibitor treatment. These cases illustrate the need for further research in a larger patient population to identify a possible link between combined BRAF and MEK inhibitor treatment and the incidence of panniculitis.

In this paper, we present a strategy to use interfacial strain in multilayer heterostructures to tune their resistive response and ionic transport as active component in an oxide-based multilayer microdot device on chip. For this, fabrication of strained multilayer microdot devices with sideways attached electrodes is reported with the material system Gd0.1Ce0.9O(2-δ)/Er2O3. The fast ionic conducting Gd0.1Ce0.9O(2-δ) single layers are altered in lattice strain by the electrically insulating erbia phases of a microdot. The strain activated volume of the Gd0.1Ce0.9O(2-δ) is investigated by changing the number of individual layers from 1 to 60 while keeping the microdot at a constant thickness; i.e., the proportion of strained volume was systematically varied. Electrical measurements showed that the activation energy of the devices could be altered by Δ0.31 eV by changing the compressive strain of a microdot ceria-based phase by more than 1.16%. The electrical conductivity data is analyzed and interpreted with a strain volume model and defect thermodynamics. Additionally, an equivalent circuit model is presented for sideways contacted multilayer microdots. We give a proof-of-concept for microdot contacting to capture real strain-ionic transport effects and reveal that for classic top-electrode contacting the effect is nil, highlighting the need for sideways electric contacting on a nanoscopic scale. The near order ionic transport interaction is supported by Raman spectroscopy measurements. These were conducted and analyzed together with fully relaxed single thin film samples. Strain states are described relative to the strain activated volumes of Gd0.1Ce0.9O(2-δ) in the microdot multilayer. These findings reveal that strain engineering in microfabricated devices allows altering the ionic conduction over a wide range beyond classic doping strategies for single films. The reported fabrication route and concept of strained multilayer microdots is a promising path for applying strained multilayer oxides as active new building blocks relevant for a broad range of microelectrochemical devices, e.g., resistive switching memory prototypes, resistive or electrochemical sensors, or as active catalytic solid state surface components for microfuel cells or all-solid-state batteries.