Elevated baseline soluble FcεRI may be linked to early response to omalizumab treatment in chronic spontaneous urticaria.

BACKGROUND: Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment in chronic spontaneous urticaria (CSU). Predictors of fast and good response for omalizumab treatment have not yet been identified and characterized. OBJECTIVE: To evaluate whether soluble FcεRI (sFcεRI), a marker of IgE-mediated mast cell activation, predicts the time of response to omalizumab in CSU. METHODS: Sera of 67 CSU patients were obtained before omalizumab treatment and analysed for sFcεRI levels by ELISA (2 ng/mL was used as cut-off for elevated sFcɛRI). Treatment response during the first 4 weeks was assessed with the urticaria activity score (UAS7), urticaria control test (UCT) and the rolling UAS7 (rUAS7). RESULTS: Elevated pre-treatment sFcɛRI levels were detected in more than 70% of patients with completely controlled disease (UCT = 16) and well-controlled disease (UCT = 12-15) and were significantly associated with disease control (χ2 = 4.94, p < 0.05). More than half of the patients (14/25) with low levels had poor disease control (UCT < 12). Of the patients who achieved complete and marked UAS7 response, respectively, 75% and 63% had elevated baseline sFcɛRI levels. Post-treatment UAS7 scores were lower in patients with elevated sFcɛRI levels reaching statistical significance at Week 3 (p < 0.05). Patients with elevated baseline sFcɛRI levels achieved rUAS7 ≤ 6 and = 0 earlier than those with lower levels (Days 9 vs. 13 and Days 12 vs. 14, respectively). CONCLUSION: Elevated sFcεRI serum levels predict early and good response to treatment with omalizumab, which may help to better design treatment options for CSU patients.

Clinically uninvolved but not healthy-The skin of patients with atopic dermatitis is primed for itch and inflammation.

BACKGROUND: Atopic dermatitis (AD) is a highly prevalent inflammatory skin disorder characterized by episodic exacerbations and remissions. Why the clinically healthy skin of AD patients becomes rapidly inflamed and very pruritic is poorly understood. OBJECTIVE: To investigate cowhage- and histamine-induced itch and skin expression levels of their target receptors in lesional and non-lesional skin of AD, compared to the skin of patients with psoriasis, chronic spontaneous urticaria (CSU) and healthy subjects. METHODS: Patients with AD, psoriasis and chronic spontaneous urticaria (CSU) as well as healthy control subjects (HC) (n = 20 each) were assessed for differences in itch parameters, neurogenic flare reaction and local blood flow responses to skin provocations with cowhage and histamine. Skin biopsies from 10 AD, 10 psoriasis,11 CSU and 12 HC were obtained to assess expression of protease-activated receptors 2 and 4 (PAR-2, PAR-4), histamine H1 and H4 receptors (H1R, H4R), and mast cells. RESULTS: Provocation of non-lesional skin of AD patients with cowhage resulted in prolonged itch (p = 0.020), which was not observed in psoriasis and CSU. Significantly prolonged and more intense cowhage- and histamine-induced itch (for duration, peak and overall intensity) was also observed in lesional AD skin. Diminished neurogenic flare reaction and blood flow after histamine provocation were shown in AD and psoriasis patients. Non-lesional AD skin along with lesional AD and psoriasis skin showed an increased expression of PAR-2 and PAR-4, H1R and H4R. Mast cell number was higher in lesional AD and psoriasis skin (p = 0.006 and p = 0.006, respectively). CONCLUSION: The non-lesional skin of AD patients markedly differs from healthy skin in cowhage-induced itch responses and the expression of receptors for proteases and histamine. Proactive therapeutic interventions that downregulate these receptors may prevent episodic exacerbation in AD.

Space hardware for concrete sample production on ISS "MASON concrete mixer".

Advances in space flight technology will enable the construction of Moon or even Mars bases in the not-too-distant future. Thus, materials will be needed that are suitable for building in microgravity environments. One idea is to use concrete, the most used construction material on Earth, for these challenging tasks. The hardening and the properties of concrete under the boundary conditions prevailing on Earth are well understood, but there is only limited research on concrete produced in microgravity. Hence, a research project called MASON was established, which aims to mix and harden concrete on the ISS and to investigate the properties of the specimens made in microgravity extensively. Since a defined geometry of the specimens would be favorable for these investigations, a special hardware was developed, called the MASON Concrete Mixer (MCM), which allows the production of concrete specimens fulfilling the requirements on the geometry as well as the safety requirements. Subsequently, the development, design, tests, and qualification of the MCM as well as its usage are presented.

An international Delphi study on the burden of allergic rhinoconjunctivitis and urticaria and the role of bilastine among current treatment options.

BACKGROUND: Allergic rhinoconjunctivitis and chronic urticaria are common histamine-driven diseases, exerting detrimental effects on cognitive functions, sleep, daily activities, and quality of life. Non-sedating second-generation H1-antihistamines are the first-line treatment of choice. Aim of the study was to define the role of bilastine among second-generation H1-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria in patients of different ages. METHODS: An international Delphi study was carried out to assess consensus among experts from 17 European and extra-European countries on three main topics: 1) Burden of disease; 2) Current treatment options; 3) Specific characteristics of bilastine among second-generation antihistamines. RESULTS: Here, we present the results obtained for a selection of 15 out of 27 consensus statements, focused on disease burden, role of second-generation antihistamines and bilastine profile. The rate of concordance was ≥98% for 4 statements, ≥ 96% for 6, ≥ 94% for 3, and ≥90% for 2. CONCLUSIONS: The high degree of agreement obtained suggests a wide awareness of the burden of allergic rhinoconjunctivitis and chronic urticaria among experts from all over the world and reflects a broad consensus on the role of second-generation antihistamines in general and of bilastine in particular for their management.

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

CAD/CAM and conventional reconstruction of the mandibular condyle by fibula free flap: a clinical and radiological evaluation.

The aim of this study was to analyse the radiological and clinical outcomes of condylar reconstruction by fibula free flap (FFF), comparing conventional freehand and CAD/CAM techniques. Fifteen patients (nine CAD/CAM, six freehand) who underwent condylar reconstruction with a FFF were reviewed retrospectively regarding pre- and postoperative computed tomography/cone beam computed tomography scans and clinical function. After surgery, all patients were free of temporomandibular joint pain. Mean postoperative mouth opening was 30.80 mm, with no significant difference between the freehand and CAD/CAM groups. In all patients, laterotrusion was decreased to the contralateral side (P = 0.002), with no difference between freehand and CAD/CAM, while the axis of mouth opening deviated to the side of surgery (P < 0.001). All patients showed significant radiological deviation of the fibular neocondyle in the laterocaudal direction (lateral: P = 0.015; caudal: P = 0.001), independent of the technique. In conclusion, reconstruction of the mandibular condyle by FFF provided favourable functional results in terms of mouth opening, reduction of pain, and mandibular excursions. Radiological deviation of the neocondyle and deviation of laterotrusion and mouth opening did not impair clinical function. CAD/CAM planning facilitated surgery, decreased the surgery time, and improved the fit of the neocondyle in the fossa.

A comprehensive, tri-national, cross-sectional analysis of characteristics and impact of pruritus in psoriasis.

BACKGROUND: Pruritus is prevalent in psoriasis but still many features of pruritus, its response to therapy and its burden in psoriasis remain to be better characterized. OBJECTIVE: To investigate characteristics and burden of pruritus in an international cohort of patients with psoriasis. METHODS: This cross-sectional study included a total of 634 patients and 246 controls from Germany, Poland and Russia. Physicians examined and interviewed participants, recording clinical characteristics, such as severity, therapy and localization of psoriatic lesions. Participants filled out self-reported questionnaires including questions on pruritus severity and impact, characteristics, and response to therapy, and quality of life (QoL). Localization patterns of pruritus and skin lesions were visualized using body heat maps. RESULTS: Most patients (82%) experienced pruritus throughout their disease, and 75% had current pruritus. The majority of patients (64%) perceived pure pruritus, and those who reported additional painful and/or burning sensations (36%) reported overall stronger pruritus. The scalp was the most frequently reported localization of pruritus, even in the absence of skin lesions. Body surface area (BSA) of pruritus was not linked to pruritus intensity, but to BSA of psoriatic lesions (rho = 0.278; P < 0.001). One third of patients (31%) reported impaired sex-life, and 4% had suicidal ideations due to pruritus. In up to one third of patients, psoriasis therapies had little or no effect on pruritus. The only therapeutic option offered to some of these patients were antihistamines, which appeared to be effective in most cases. CONCLUSION: Pruritus is highly prevalent in psoriasis and is linked to a significant burden. Current psoriasis therapies are frequently insufficient to control pruritus. Managing psoriasis should include the assessment and control of itch. Efficient antipruritic therapies should be developed and be made available for patients with psoriasis.

German guideline for diagnosis and treatment of multiple sclerosis - a survey focusing neurologists in daily practise.

We performed a web-based survey among German-speaking neurologists to evaluate the acceptance of the 2021 German guideline in the diagnosis and treatment of multiple sclerosis. Based on 327 replies in total, the current survey largely reproduced the findings of an earlier, smaller survey on the prefinal consultation version of the guideline and confirmed high acceptance rates. Half of the participants were practising neurologists. Neurologists from MS centers with more than 500 patients per year (n=26) were more critical of the guideline. They reiterated some of the criticisms of the previous feedback, and, in particular, felt that safety aspects are overemphasized in the guideline, thereby superseding early aggressive therapy.

Prevalence and factors associated with sleep disturbance in adult patients with psoriasis.

BACKGROUND: Sleep, which is crucial for restoring of physiological functions and health, is reportedly impaired in psoriasis. The role of different potential sleep confounding factors, including detailed pruritus characteristics, and the complex interplay between psychological variables (anxiety and depression), pruritus and sleep disturbance in psoriasis remain insufficiently investigated. OBJECTIVES: To investigate sleep characteristics and to identify clinical, demographic and psychological factors associated with sleep disturbance in psoriasis. METHODS: This cross-sectional study included 334 psoriasis patients (response rate 86%) and 126 control subjects (response rate 82%). Measures included sleep quality [Pittsburgh Sleep Quality Index (PSQI)], psoriasis severity, pruritus characteristics, including average pruritus intensity [visual analogue scale (VAS)], severity of comorbidities, anxiety and depression (Hospital Anxiety and Depression Scale - HADS) and quality of life (Dermatology Life Quality Index - DLQI, and Short Form 12 - SF12). RESULTS: Fifty-nine per cent of patients and 34% of control subjects (P < 0.001) suffered from sleep disturbance (PSQI > 5). Patients slept 1 h less than control subjects (median 6 vs. 7 h, P < 0.001). Patients without pruritus had less impaired sleep (global PSQI) than patients with strong (P < 0.001) and very strong pruritus (P < 0.001). Anxiety (HADS-A) and depression (HADS-D) levels were the strongest predictors of sleep impairment, followed by pruritus exacerbation at night, age, female sex, pruritus exacerbation in the morning, average pruritus intensity (VAS), diagnosed depression and gastroesophageal reflux disease, altogether explaining 32%-37% of the variance in global sleep quality. Both anxiety (HADS-A) and depression (HADS-D) were significant mediators explaining the association between pruritus intensity (VAS) and sleep impairment in 42% and 37% respectively. CONCLUSIONS: Sleep disturbance in patients with psoriasis is highly prevalent. Patients with psoriasis should be assessed for sleep impairment, pruritus, anxiety and depression. Reduction in pruritus should be considered as an important therapeutic goal, along with therapies aimed at reducing anxiety and depression.

Screening for hepatocellular carcinoma among adults with HIV/HBV co-infection in Zambia: a pilot study.

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). An HCC screening initiative was piloted in an established cohort of individuals co-infected with human immunodeficiency virus (HIV) and HBV on antiretroviral therapy (ART) at two outpatient clinics in Lusaka, Zambia. METHODS: All patients underwent abdominal ultrasound (AUS) and transient elastography. RESULTS: Among 279 patients co-infected with HIV/HBV, 165 (59.1%) were men, median age was 34 years [interquartile range (IQR) 28-39 years] and median CD4 count was 246 cells/µL (IQR 112-355 cells/µL) at ART initiation. While 102 (55.7%) individuals had elevated transaminases, 114 (59.7%) had HBV levels >2000 IU/mL and 59 (24.6%) had significant fibrosis. At their first AUS measurement, 75 (26.9%) participants had hepatomegaly and 69 (24.7%) had periportal fibrosis. Five patients had a liver lesion >1 cm, an indication for confirmatory imaging. CONCLUSIONS: In one of the first HCC screening initiatives in SSA, 2% of patients co-infected with HIV/HBV had significant liver lesions, and one-quarter had findings suggestive of schistosomiasis-induced liver damage.

[Digital documentation of complications in visceral surgery: possibilities and evaluation of an instrument for quality management]. / Digitale Komplikationserfassung in der Viszeralchirurgie: Möglichkeiten und Evaluation eines Instrumentes für das Qualitätsmanagement.

Against the background of the growing economization of clinical medicine, in the last decades the topics of risk and complication management have also become more important in surgical disciplines. The standardization and reproducible documentation of outcome and complication data play a key role for valid quality control. In this article a digital system implemented at the surgical clinic of the Charité University Medicine in Berlin is analyzed with respect to its practicability for perioperative and postoperative monitoring of complications within the framework of quality assurance.

Epidemiology, comorbidities, and healthcare utilization of patients with chronic urticaria in Germany.

BACKGROUND: Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary. OBJECTIVES: To investigate the epidemiology of CU, overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database. METHODS: Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin [InGef] (01 January 2015-30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD-10-GM codes). Twelve-month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthcare utilization by patients with CU were investigated. RESULTS: Of 4 693 772 individuals of all ages listed in the database, 3 538 540 were observable during 2017. Overall, 17 524 patients (˜0.5%) were diagnosed with CU; chronic spontaneous urticaria (CSU: 71.2%), chronic inducible urticaria (CIndU: 19.7%), CSU+CIndU (9.1%). Females, vs. males, had higher diagnosed prevalence (0.62% vs. 0.37%) and diagnosed incidence (0.18% vs. 0.11%) of CU among all patients. Patients most frequently visited general practitioners (41.3% of total visits). Hypertensive diseases (43.5%), lipoprotein metabolism disorders (32.1%) and affective disorders (26.0%) were the most frequently reported comorbidities of special interest. Rates of most comorbidities of special interests were similar to atopic dermatitis and psoriasis patients, and all higher vs. overall population. More than half (54.1%) of all CU patients were not prescribed any treatment. Second-generation H1 -antihistamines were the most commonly prescribed medication for adult (17.9%) and paediatric (27.9%) patients. Patients with CIndU (paediatric, 15.5%; adult, 7.8%) were more often hospitalized versus patients with CSU (paediatric, 9.9%; adult, 4.6%). CONCLUSIONS: In Germany, prevalence of CU along with multiple comorbidities may pose increased burden on the healthcare system. Awareness of adhering to treatment guidelines, and aiming for complete control of urticaria, needs to be driven and may improve outcomes.

Variability of disease activity in patients with hereditary angioedema type 1/2: longitudinal data from the Icatibant Outcome Survey.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE-1/2) is a chronic and debilitating disease. The unpredictable clinical course represents a significant patient burden. OBJECTIVE: To analyse longitudinal registry data from the Icatibant Outcome Survey (IOS) in order to characterize temporal changes in disease activity in patients with HAE-1/2. METHODS: Icatibant Outcome Survey (NCT01034969) is an international observational registry monitoring the clinical outcomes of patients eligible for icatibant treatment. The current analyses are based on data collected between July 2009 and July 2019. Retrospective data for attacks recorded in the 12 months prior to IOS enrolment and for each 12-month period up to 7 years were analysed. RESULTS: Included patients reported angioedema attacks without long-term prophylaxis (LTP; n = 315) and with LTP (n = 292) use at the time of attack onset. Androgens were the most frequently used LTP option (80.8%). At the population level, regardless of LTP use, most patients (52-80%) reporting <5 attacks in Year 1 continued experiencing this rate; similarly, many patients (25-76%) who reported high attack frequency continued reporting ≥10 attacks/year. However, year on year, 31-51% of patients experienced notable changes (increase/decrease of ≥5 attacks) in annual attack frequency. Of patients who reported an absolute change of ≥10 attacks from Year 1 to 2, 17-50% continued to experience a change of this magnitude in subsequent years. CONCLUSION: At the population level, attack frequency was generally consistent over 7 years. At the small group level, 28.8-34.5% of patients reported a change in attack frequency of ≥5 attacks from Year 1 to Year 2; up to half of these patients continued to experience this magnitude of variation in disease activity in later years, reflecting high intra-patient variability.