Epidemiology of patch tested patients with permanent tattoos-A comparative analysis of 9693 IVDK patients (2020-2022).

BACKGROUND: Permanent tattooing is the invasive introduction of tattoo ink (pigments) into the dermis. The ink and aftercare cosmetics applied on pre-damaged skin may contain skin sensitisers. OBJECTIVES: To identify patient characteristics and the pattern of sensitisation in tattooed patients patch tested within the Information Network of Departments of Dermatology (IVDK). PATIENTS AND METHODS: Comparative analysis of patient characteristics and reaction frequencies to baseline series allergens in 1648 consecutive patients with and 8045 consecutive patients without permanent tattoos. Non-overlapping 95%-confidence intervals were considered as significant. RESULTS: Having permanent tattoos was related with female sex, age <40 years, tobacco smoking, atopic dermatitis, (occupational) hand dermatitis and being employed in particular occupational groups (e.g., healthcare workers, mechanics, hairdressers). Sensitisation to nickel was increased in tattooed patients and associated with female sex (OR 4.23 [95%-CI, 3.48-5.18]), age ≥40 years (OR 1.26 [95%-CI, 1.08-1.49]), tobacco smoking (OR 1.19 [95%-CI, 1.01-1.40]) and having permanent tattoos (OR 1.27 [95%-CI, 1.05-1.53]). CONCLUSIONS: The association between nickel sensitisation and permanent tattoos is probably confounded by past reactions to pierced costume jewellery. Socio-economic factors most probably contribute to the connection between tattoos, tobacco smoking, occupational or hand dermatitis, and being employed in particular occupational groups.

The feasibility and effectiveness of a novel online mental health literacy course in supporting university student mental health: a pilot study.

BACKGROUND: There is a need for effective universal approaches to promote and support university student mental health that are scalable and sustainable. In this pilot study we assess the feasibility and acceptability of a fully-digitalized, comprehensive mental health literacy course co-created with and tailored to the needs of undergraduate students. We also explore preliminary associations with mental health and positive behaviour change. METHODS: An accredited online mental health literacy course was developed using state-of-the-art pedagogical principles and a reverse mentorship approach. The course was offered as an interdisciplinary undergraduate elective. Students completed an online survey before and after the 12-week course that collected demographic information and assessed mental health knowledge, emotional self-awareness, mental health, stigma, and health-related behaviors using validated measures. Dependent group t-tests were used to compare pre- and post-course levels of knowledge, mental health, sleep quality and substance use. Mental health outcomes of students who completed the course were compared to an age and sex-matched sample of students not enrolled in the course and who completed the same survey measures over the same academic year. Multivariable linear regression was used to examine the effect of course participation on outcomes at follow-up. RESULTS: The course had good uptake and was positively reviewed by participants. Specifically, students found the course engaging, relevant, and applicable, and agreed they would recommend it to their peers. Among course participants there was improvement in mental health knowledge (p < 0.001) and emotional self-awareness (p = 0.02) at course completion. Compared to the matched comparison group, taking the course was associated with reduced alcohol (ß = - 0.41, p = 0.01) and cannabis use (ß = - 0.35, p = 0.03), and improved sleep quality (ß = 1.56, p = 0.09) at the end of the term. CONCLUSIONS: Findings suggest that delivering mental health literacy as an online accredited course may be an acceptable and effective way of promoting university student mental health through improved knowledge, emotional self-awareness, and healthy lifestyle choices. As the course is expanded to larger and more diverse student cohorts we will be able to further examine the short and long-term effectiveness of the course in supporting student mental health and the underlying mechanisms.

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.

Patch test informed consent form: position statement by European Academy of Dermatology and Venereology Task Force on Contact Dermatitis.

BACKGROUND: To our knowledge, an international consensus is lacking regarding the development of an adequate informed consent form for a patch test (PT) and the information that should be included in such document. OBJECTIVES: The aim of the study was to reach a consensus on the specific points that need to be addressed in a PT consent form. METHODS: A Delphi survey, comprising 2 rounds and 1 final discussion, was used to gather and analyse data, which was conducted over the Internet. Each statement that reached a consensus with the respondents (9 expert dermatologists from Europe) was defined as a median consensus score (MED) of ≥7 and agreement among panelists as an interquartile range (IQR) of ≤3. All study participants were members of the EADV task force on contact dermatitis. RESULTS: The expert panel addressed several topics that should be included in an informed consent form for a PT: introduction, preparation for PT, testing procedure, allowed activities, adverse events and additional authorizations. CONCLUSIONS: Our results assess recommendations regarding points to be contained in an informed consent form for a PR. Future actions towards standardization and harmonization of this specific consent form are needed.

[Contact allergy due to insulin pumps and glucose sensor systems]. / Kontaktallergie auf Glukosemesssysteme und Insulinpumpen.

The design and development of insulin pumps and various glucose sensor systems has an enormous impact on life quality of diabetic patients. Surveillance and therapy of diabetes has improved due to the new diabetic devices, which are affixed to the patients' skin for several days. Since their introduction, irritant and allergic contact dermatitis have been frequently reported. Patients often acquire contact sensitization to isobornyl acrylate, N,N-dimethylacrylamide or formerly to 2­ethyl-cyanoacrylate. These contact allergens were found in the patch, in the glue to affix the box on the patch or in the casing of the system itself. Development of contact allergy to substances of these systems may result in the need to abandon modern diabetic devices.

[Increasing overhead ressources of the trauma room]. / Steigender Vorhalteaufwand für den Schockraum.

BACKGROUND: Every year up to 35,000 people in Germany are severely injured in accidents in traffic, during work or leisure activities. The 24-h availability of the trauma room as well as surgical and intensive care unit capacities are essential to provide optimal acute care. This study analyzed the frequency of utilization of the resource trauma room in a level I trauma center in the past. METHODS: Data of a level I trauma center from 2005 to 2016 including trauma room alerts deployed by the rescue coordination center and the number of patients found to be severely injured (ISS ≥ 16) during trauma room diagnostics were analyzed retrospectively. Additionally, alerts due to trauma mechanism, accompanying by the emergency physician, ventilation and resuscitation were evaluated via a web-based interdisciplinary care capacity system (IVENA) from 2012 to 2016. Therefore, a comparison between the number of trauma room alerts and the number of severely injured patients was performed for the time after 2012. RESULTS: For the time from 2012 to 2016, data obtained by IVENA showed a continuous increase in the number of trauma room alerts (n = 367 to n = 623). At the same time, the number of patients admitted under resuscitation (n = 15 to n = 45) as well as ventilated patients (n = 78 to n = 139) increased significantly; however, there was also an increase in the number of trauma alerts due to trauma mechanisms (n = 84 to n = 194) as well as the number of patients admitted to the trauma room not accompanied by an emergency physician (n = 38 to n = 132). The ratio between the number of trauma room alerts and severely injured patients (ISS ≥ 16) increased from 3.1 in 2012 to 5.4 in 2015 and 4.6 in 2016. CONCLUSION: The data at hand showed a constant number of severely injured trauma patients admitted to a level I trauma center over the past few years. At the same time, there was a significant increase in utilization of the trauma room; however, in a considerable number of patients admitted to the trauma room the diagnostic process resulted in non-traumatic diagnostic findings. In the analyzed cohort, especially patients admitted to the trauma room due to trauma mechanism or without an accompanying emergency physician contributed to this development, necessitating an increased operational readiness of the trauma room team.

Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling.

BACKGROUND: Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different α-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal. METHODS: Three serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected MA, and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated α-Gal. RESULTS: Singleplex allergy diagnostics using the α-Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-α-Gal) was identified, which is associated with MA. CONCLUSIONS: Detection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal-sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.

Dynamic properties of different liquid states in systems with competing interactions studied with lysozyme solutions.

Recent studies of colloidal systems with a short-range attraction and long-range repulsion (SALR) have been demonstrated to have a generalized phase diagram with multiple liquid states defined by their structures. In this paper, we identify the different liquid states of previous experimentally studied lysozyme samples within this proposed generalized state diagram and explore the dynamic properties of each liquid state. We show that most lysozyme samples studied here and previously at low and intermediate concentrations are dispersed fluids while a few high concentration samples are randomly percolated liquids. In the dispersed fluid region, the short-time diffusion coefficient measured by neutron spin echo agrees well with the long time diffusion coefficient estimated with the solution viscosity. This dynamic feature is maintained even for some samples in the random percolated region. However, the short-time and long-time diffusion coefficients of random percolated fluids deviate at larger concentration and attraction strength. At high enough concentrations, the mean square displacement can be as slow as those of many glassy colloidal systems at time scales near the characteristic diffusion time even though these lysozyme samples remain in liquid states at the long-time limit. We thus identify the region in the generalized phase diagram where these equilibrium states with extremely slow local dynamics exist relative to bulk percolation and kinetic arrest (gel and glassy) transitions.

High volume of polysorbate-containing (Tween® 80) solutions induces false-positive results in intradermal test.

BACKGROUND: Intradermal test is used to detect causative allergens in IgE-mediated hypersensitivity. The surfactant polysorbate 80 can be added to intradermal test solutions to more reliably dissolve the allergen and ensure a constant bioavailability of the injected allergen. Polysorbate 80 has, however, some histamine-releasing properties which could blur the difference to the histamine-induced wheal. Routinely serving as a control. OBJECTIVE: Allergen-free polysorbate 80 containing (0.005%) test solutions were therefore systematically tested at different injection volumes to see whether polysorbate can falsify skin reactions and if yes whether conditions can be identified to avoid this. METHODS: In a partly blinded study, 30 patients were tested intracutaneously at the back: each received at three separate sites 0.05 mL of polysorbate-containing solvent, 0.02 mL polysorbate-containing solvent as well as 0.02 mL polysorbate-free solvent. After 15 min, wheal and erythema were documented and planimetrically quantified. RESULTS: Unexpectedly 23 of 30 (77%) patients showed false-positive test reactions to the volume of 0.05 mL of the polysorbate-containing solvent whereas the polysorbate-containing solvent with 0.02 mL and the polysorbate-free solvent with 0.02 mL injection volume had no reinforcing effect on skin test reaction. CONCLUSIONS: Different volumes of polysorbate-containing solutions, all recommended by manufacturers for intradermal tests, may significantly influence test results. The study shows that a polysorbate 80 used at 0.005% in solvents for intradermal test to provide a better bioavailability of allergens produces false-positive reactivity in a surprising and a hitherto unknown 77% if the 0.05 mL volume is injected. It is, therefore, mandatory to strictly adhere to an intradermal test volume of 0.02 mL as only then falsifying effects of the polysorbate additive are avoided, and comparable test results are ensured.

H1-antihistamine-refractory chronic spontaneous urticaria: it's worse than we thought - first results of the multicenter real-life AWARE study.

BACKGROUND: Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real-life setting. OBJECTIVE: To describe the baseline characteristics of the first 1539 German AWARE patients with H1-antihistamine-refractory CSU. METHODS: This prospective non-interventional study included patients (18-75 years) with a diagnosis of H1-antihistamine-refractory CSU for > 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU-Q2 oL), and angioedema QoL questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. RESULTS: Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m2 , respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second-generation H1-antihistamines (46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU-Q2 oL, and total AE-QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or dermatologists (50.7%). CONCLUSIONS AND CLINICAL RELEVANCE: This study reveals that German H1-antihistamine-refractory CSU patients have high rates of uncontrolled disease, angioedema, and comorbid CIndU, are undertreated, have impaired QoL, and rely heavily on healthcare resources.

Observation of partial relaxation mechanisms via anisotropic strain relief on epitaxial islands using semiconductor nanomembranes.

In this work we attempt to directly observe anisotropic partial relaxation of epitaxial InAs islands using transmission electron microscopy (TEM) and synchrotron x-ray diffraction on a 15 nm thick InAs:GaAs nanomembrane. We show that under such conditions TEM provides improved real-space statistics, allowing the observation of partial relaxation processes that were not previously detected by other techniques or by usual TEM cross section images. Besides the fully coherent and fully relaxed islands that are known to exist above previously established critical thickness, we prove the existence of partially relaxed islands, where incomplete 60° half-loop misfit dislocations lead to a lattice relaxation along one of the 〈110〉 directions, keeping a strained lattice in the perpendicular direction. Although individual defects cannot be directly observed, their implications to the resulting island registry are identified and discussed within the frame of half-loops propagations.

The lung microbiome in patients with pneumocystosis.

BACKROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection that is associated with a high morbidity and mortality in immunocompromised individuals. In this study, we analysed the microbiome of the lower respiratory tract from critically ill intensive care unit patients with and without pneumocystosis. METHODS: Broncho-alveolar fluids from 65 intubated and mechanically ventilated intensive care unit patients (34 PCP+ and 31 PCP- patients) were collected. Sequence analysis of bacterial 16S rRNA gene V3/V4 regions was performed to study the composition of the respiratory microbiome using the Illumina MiSeq platform. RESULTS: Differences in the microbial composition detected between PCP+ and PCP- patients were not statistically significant on class, order, family and genus level. In addition, alpha and beta diversity metrics did not reveal significant differences between PCP+ and PCP- patients. The composition of the lung microbiota was highly variable between PCP+ patients and comparable in its variety with the microbiota composition of the heterogeneous collective of PCP- patients. CONCLUSIONS: The lower respiratory tract microbiome in patients with pneumocystosis does not appear to be determined by a specific microbial composition or to be dominated by a single bacterial species.

A Popular myth - low-histamine diet improves chronic spontaneous urticaria - fact or fiction?

BACKGROUND: Chronic spontaneous urticaria (CsU) is a frequent dermatological disease that might last for months or years with high impact on quality of life. Known causes are autoreactive phenomena, infections or intolerances, rarely IgE-mediated allergies. One-third of CsU patients benefit from a low-pseudoallergen diet. Additionally, it is often discussed, that reducing histamine ingestion alone might improve clinical symptoms and quality of life in CsU patients despite the uncertain role of the histamine-degrading enzyme diamine oxidase (DAO). OBJECTIVE: Aim of this study was to investigate the impact of low-histamine diet on symptoms and quality of life in patients with CsU. METHODS: Patients suffering from CsU accompanied by gastrointestinal symptoms were included in the study. They underwent low-histamine diet for at least 3 weeks. During the whole study, urticaria activity score (UAS) was recorded daily in a patient's diary. Quality of life was assessed during screening, baseline and post diet visits by completing questionnaires (DLQI and Cu-Q(2)oL). DAO activity was measured before and after elimination diet. RESULTS: A total of 75% of the patients had a benefit from the low-histamine diet. Thirty-four of 56 patients (61%) reached the primary endpoint of the study, an improvement of UAS 4 of ≥3. Overall, a significant reduction from 9.05 to 4.23 points (P = 0.004) was achieved; the average reduction in a strongly affected subgroup was 8.59 points (P < 0.001). DAO activity remained stable. CONCLUSION: Low-histamine diet is a therapeutically useful, simple and cost-free tool to decrease symptoms and increase quality of life in CsU patients with gastrointestinal involvement. Further research is needed to understand the role of diamine oxidase.

The role of infants' mother-directed gaze, maternal sensitivity, and emotion recognition in childhood callous unemotional behaviours.

While some children with callous unemotional (CU) behaviours show difficulty recognizing emotional expressions, the underlying developmental pathways are not well understood. Reduced infant attention to the caregiver's face and a lack of sensitive parenting have previously been associated with emerging CU features. The current study examined whether facial emotion recognition mediates the association between infants' mother-directed gaze, maternal sensitivity, and later CU behaviours. Participants were 206 full-term infants and their families from a prospective longitudinal study, the Durham Child Health and Development Study (DCHDS). Measures of infants' mother-directed gaze, and maternal sensitivity were collected at 6 months, facial emotion recognition performance at 6 years, and CU behaviours at 7 years. A path analysis showed a significant effect of emotion recognition predicting CU behaviours (ß = -0.275, S.E. = 0.084, p = 0.001). While the main effects of infants' mother-directed gaze and maternal sensitivity were not significant, their interaction significantly predicted CU behaviours (ß = 0.194, S.E. = 0.081, p = 0.016) with region of significance analysis showing a significant negative relationship between infant gaze and later CU behaviours only for those with low maternal sensitivity. There were no indirect effects of infants' mother-directed gaze, maternal sensitivity or the mother-directed gaze by maternal sensitivity interaction via emotion recognition. Emotion recognition appears to act as an independent predictor of CU behaviours, rather than mediating the relationship between infants' mother-directed gaze and maternal sensitivity with later CU behaviours. This supports the idea of multiple risk factors for CU behaviours.

Otolaryngology residency education: a scoping review on the shift towards competency-based medical education.

BACKGROUND: Residency training programmes worldwide are experiencing a shift from the traditional time-based curriculum to competency-based medical education (CBME), due to changes in the healthcare system that have impacted clinical learning opportunities. Otolaryngology-Head and Neck Surgery (OTL-HNS) programmes are one of the first North American surgical specialties to adopt the new CBME curriculum. OBJECTIVE OF REVIEW: The purpose of this scoping review is to examine the literature pertaining to CBME in OTL-HNS programmes worldwide, to identify the tools that have been developed and identify potential barriers to the implementation of CBME. SEARCH STRATEGY: Four online databases, OVID MEDLINE (R) from 1946 to 5 August 2015, EMBASE 1974 to 5 August 2015, Cochrane and CINAHL databases up to 5 August 2015, were searched using key words related to OTL-HNS and CBME. EVALUATION METHOD: Two researchers independently reviewed the literature in a systematic manner and met to discuss and address any discrepancies at each step of the review process. RESULTS: Of the 207 publications identified in the initial search, 31 were included in this scoping review. Two key themes emerged from the literature: first, OTL-HNS programmes reported a need for new assessment tools that assess competency and also provide the learner with formative feedback. Second, although varieties of tools assessing both technical and non-technical skills have been developed, implementation of such tools has been met with some challenges. These challenges include a lack of faculty support, inadequate administrative support and a lack of knowledge on how to start the transition to CBME. CONCLUSIONS: This scoping review suggests that task-specific checklists, entrustment scales, evaluation portfolios from multiple assessments and faculty training sessions are key aspects to incorporate as OTL-HNS training programmes shift towards a CBME curriculum.

CXCR5 is critically involved in progression of lupus through regulation of B cell and double-negative T cell trafficking.

The recruitment of immune cells to sites of tissue inflammation is orchestrated by chemokine/chemokine receptor networks. Among these, the CXCL13/CXCR5 axis is thought to be involved critically in systemic lupus erythematosus (SLE) and lupus nephritis pathogenesis. Beyond B cell abnormalities, another hallmark of SLE disease is the occurrence of aberrant T cell responses. In particular, double-negative (DN) T cells are expanded in the peripheral blood of patients with SLE and in lupus-prone mice. DN T cells induce immunoglobulin production, secrete proinflammatory cytokines and infiltrate inflamed tissue, including kidneys. We aimed to investigate how CXCR5 deficiency changes immune cell trafficking in murine lupus. We therefore crossed CXCR5(-/-) mice with B6/lpr mice, a well-established murine lupus model. B cell numbers and B cellular immune responses were diminished in CXCR5-deficient B6/lpr mice. In addition, we observed reduced accumulation of DN T cells in spleen and lymph nodes, paralleled by reduced splenomegaly and lymphadenopathy. In-vivo migration assays revealed reduced migration of CXCR5-deficient DN T cells into lymph nodes, and ex-vivo-activated CXCR5-deficient DN T cells failed to infiltrate kidneys of recipients. Moreover, DN T cells and B cells of CXCR5-deficient B6/lpr mice failed to migrate towards CXCL13 in vitro. We propose that CXCR5 is involved critically in B cell trafficking and germinal cell (GC) formation in murine lupus and in guiding pathogenic DN T cells into lymphoid organs and kidneys, and we therefore describe new pathomechanisms for the CXCL13/CXCR5 axis in SLE.

Development and validation of the mastocytosis quality of life questionnaire: MC-QoL.

BACKGROUND: Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients affected suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific instrument to measure health-related quality of life (HRQoL) impairment in patients with mastocytosis. OBJECTIVE: The aim of this study was to develop and validate a disease-specific tool to assess HRQoL impairment in patients with cutaneous and indolent systemic mastocytosis, the Mastocytosis Quality of Life Questionnaire (MC-QoL). METHODS: Sixty-two potential MC-QoL items were developed in a combined approach consisting of semi-structured patient interviews, expert input and literature research. Item selection was performed by impact analysis with 76 patients and a final review for face validity. The resulting MC-QoL was tested for validity, reliability and influence factors. In parallel, an US American-English version of the MC-QoL was developed. RESULTS: A total of 158 patients (41 CM, 41 MIS and 76 ISM) took part in the MC-QoL validation study. The final 27-item questionnaire was found to have a four-domain structure ('symptoms', 'emotions', 'social life/functioning' and 'skin'), a valid total score and an excellent test-retest reliability. Multiple regression analysis revealed disease duration, but not age, gender or skin involvement to be a significant determinant of HRQoL impairment in mastocytosis. CONCLUSIONS: The MC-QoL is the first disease-specific HRQoL questionnaire for adult patients with cutaneous and indolent systemic mastocytosis. This short, validated and reliable instrument will serve as a valuable tool in future clinical studies and in routine patient care.

Sera from severe trauma patients with pneumonia and without infectious complications have differential effects on neutrophil biology.

BACKGROUND: Major trauma patients (TP) developing imbalanced immune response are at high risk for infectious post-injury complications including pneumonia. Neutrophils play a central role in the host defense against bacteria and thereby pathogenesis of infections. While there are numerous studies about neutrophil function after trauma, data about their biology in patients who suffer from pneumonia following trauma are sparse. Here, we studied the effect of serum isolated from patients who do and do not develop infection (inf.) on the biology of neutrophils from healthy volunteers. METHODS: Sera samples from eighteen TP with an injury severity score above 16 were obtained. Nine patients were grouped to no inf. group (TP without pneumonia), and nine to inf. group (TP with pneumonia). Samples were obtained at admission to emergency department (ED), a day prior pneumonia diagnosis (1 d prior inf) or at the day of diagnosis (1 d prior inf). Samples from the equal post-injury days in the corresponding no inf. group were used. Neutrophils from nine healthy volunteers were isolated. Effects for sera isolated from infected and non-infected patients on neutrophil biology were analyzed. Migratory capacity of neutrophils towards TP's serum, their CD11b and CD62L membrane receptor expression and oxidative burst activity after stimulation with TP's serum were determined and compared between groups. RESULTS: Migratory capacity of neutrophils was significantly increased after trauma and persisted during the study period. CD11b expression in all groups was significantly increased. CD62L expression decreased generally in samples from ED and recovered later to baseline. Stratifying no inf. and inf. groups showed significantly decreased migratory capacity, increased CD11b and significantly decreased CD62L expression in the no inf. group. These differences persisted during the complete observational period. ROS production was strongly reduced in the no inf. group compared to the inf. group at later experimental time points. CONCLUSIONS: This data indicate that patients at risk for pneumonia development have differentially and early activated neutrophils following trauma compared to patients who are not at risk for post-injury complication. Studies about the differential biology of neutrophils and their immediately after trauma modified activity depending on the post-injury clinical course are warranted, and may deliver predictive or even therapeutic strategies to control inflammation.

Anti-Toxoplasma activity and impact evaluation of lyophilization, hot molding process, and gamma-irradiation techniques on CLH-PLGA intravitreal implants.

Intraocular delivery systems have been developed to treat many eye diseases, especially those affecting the posterior segment of the eye. However, ocular toxoplasmosis, the leading cause of infectious posterior uveitis in the world, still lacks an effective treatment. Therefore, our group developed an intravitreal polymeric implant to release clindamycin, a potent anti-Toxoplasma antibiotic. In this work, we used different techniques such as differential scanning calorimetry, thermogravimetry, X-ray diffraction, scanning electron microscopy, and fourier-transform infrared spectroscopy to investigate drug/polymer properties while manufacturing the delivery system. We showed that the lyophilization, hot molding process, and sterilization by gamma irradiation did not change drug/polymer physical-chemistry properties. The drug was found to be homogeneously dispersed into the poly lactic-co-glycolic acid (PLGA) chains and the profile release was characterized by an initial burst followed by prolonged release. The drug profile release was not modified after gamma irradiation and non-covalent interaction was found between the drug and the PLGA. We also observed the preservation of the drug activity by showing the potent anti-Toxoplasma effect of the implant, after 24-72 h in contact with cells infected by the parasite, which highlights this system as an alternative to treat toxoplasmic retinochoroiditis.

Interleukin-2 treatment reverses effects of cAMP-responsive element modulator α-over-expressing T cells in autoimmune-prone mice.

Systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), are often characterized by a failure of self-tolerance and result in an uncontrolled activation of B cells and effector T cells. Interleukin (IL)-2 critically maintains homeostasis of regulatory T cells (T(reg)) and effector T cells in the periphery. Previously, we identified the cAMP-responsive element modulator α (CREMα) as a major factor responsible for decreased IL-2 production in T cells from SLE patients. Additionally, using a transgenic mouse that specifically over-expresses CREMα in T cells (CD2CREMαtg), we provided in-vivo evidence that CREMα indeed suppresses IL-2 production. To analyse the effects of CREMα in an autoimmune prone mouse model we introduced a Fas mutation in the CD2CREMαtg mice (FVB/Fas(-/-) CD2CREMαtg). Overexpression of CREMα strongly accelerated the lymphadenopathy and splenomegaly in the FVB/Fas(-/-) mice. This was accompanied by a massive expansion of double-negative (DN) T cells, enhanced numbers of interferon (IFN)-γ-producing T cells and reduced percentages of T(regs). Treatment of FVB/Fas(-/-) CD2CREMαtg mice with IL-2 restored the percentage of T(regs) and reversed increased IFN-γ production, but did not affect the number of DNTs. Our data indicate that CREMα contributes to the failure of tolerance in SLE by favouring effector T cells and decreasing regulatory T cells, partially mediated by repression of IL-2 in vivo.