Trends in survival of epithelial ovarian/tubal cancer by histology and socioeconomic status in Denmark 1996-2017.

OBJECTIVES: To examine time trends in ovarian/tubal cancer relative survival, excess mortality, and all-cause mortality for different histological types and levels of socioeconomic position. METHODS: Women with ovarian/tubal cancer diagnosed 1996-2017 were identified in the Danish Cancer Registry (n = 11,755). Age-standardized 5-year relative survival over time was estimated by histology, socioeconomic status, and stage. Furthermore, 5-year excess mortality rate ratios (EMRR) according to calendar time for all categories of histology and socioeconomic status were calculated using a Poisson regression model. Finally, all-cause mortality by histology and socioeconomic status was estimated in multivariate Cox proportional hazards regression models. RESULTS: Statistically significant improvements in 5-year relative survival occurred for all histological types over time except mucinous tumors (5-year EMRR, localized: 0.92 (95% CI: 0.71-1.16); advanced: 0.96 (95% CI: 0.85-1.08). Increase in relative survival over time and corresponding decrease in excess mortality was observed for all categories of socioeconomic status except for women with localized disease in the lowest income group (5-year EMRR = 0.91 (95% CI:0.76-1.10)). The impact of histology and socioeconomic status on all-cause mortality depended on time since diagnosis. Among the socioeconomic factors, especially low educational level and living alone were associated with increased all-cause mortality, particularly in the first year after diagnosis. CONCLUSIONS: Ovarian/tubal cancer survival generally increased over time across histological types and socioeconomic factors. However, the lack of improvement for mucinous tumors needs further research. Additionally, the results for women with low income and education shows that continued focus on social equality in survival is necessary.

Predicting the need of aortic valve surgery in patients with chronic aortic regurgitation: a comparison between cardiovascular magnetic resonance imaging and transthoracic echocardiography.

To compare the ability of cardiac magnetic resonance tomography (CMR) and transthoracic echocardiography (TTE) to predict the need for valve surgery in patients with chronic aortic regurgitation on a mid-term basis. 66 individuals underwent assessment of aortic regurgitation (AR) both in CMR and TTE between August 2012 and April 2017. The follow-up rate was 76% with a median of 5.1 years. Cox proportional hazards method was used to assess the association of the time-to-aortic-valve-surgery, including valve replacement and reconstruction, and imaging parameters. A direct comparison of most predictive CMR and echocardiographic parameters was performed by using nested-factor-models. Sixteen patients (32%) were treated with aortic valve surgery during follow-up. Aortic valve insufficiency parameters, both of echocardiography and CMR, showed good discriminative and predictive power regarding the need of valve surgery. Within all examined parameters AR gradation derived by CMR correlated best with outcome [χ2 = 27.1; HR 12.2 (95% CI: 4.56, 36.8); (p < 0.0001)]. In direct comparison of both modalities, CMR assessment provided additive prognostic power beyond echocardiographic assessment of AR but not vice versa (improvement of χ2 from 21.4 to 28.4; p = 0.008). Nested model analysis demonstrated an overall better correlation with outcome by using both modalities compared with using echo alone with the best improvement in the moderate to severe AR range with an echo grade II out of III and a regurgitation fraction of 32% in CMR. This study corroborates the capability of CMR in direct quantification of AR and its role for guiding further treatment decisions particularly in patients with moderate AR in echocardiography.

A Danish nationwide study of risk factors associated with Type I and Type II endometrial cancer.

OBJECTIVE: To examine risk factors for Type I and Type II endometrial cancer (EC) and to directly compare the influence of risk factors for Type II with Type I tumors. Furthermore, to examine whether risk factors for high-grade Type I and Type II tumors differed from low-grade Type I tumors. METHODS: Women with EC diagnosed during 2000-2016 were identified in the Danish Cancer Registry. A case-control analysis was conducted with 1:15 random population controls matched on age and gender. Using conditional logistic regression, odds ratios and 95% confidence intervals on risk factors for Type I and II tumors were estimated. In case-case analyses, risk factors were evaluated in a direct comparison of cases grouped by tumor type and grade. RESULTS: We identified 6958 women with Type I EC and 1206 women with Type II EC. In the case-control analysis, nulliparity and diabetes were associated with increased risk of both tumor types, whereas hormone replacement therapy only increased the risk of Type I EC. When directly comparing Type I and II tumors, the influence of BMI ≥ 30, current smoking, and parity ≥ 3 was strongest for Type I EC. The associations for the majority of risk factors were similar for Type II and high-grade Type I tumors compared with low-grade Type II tumors. CONCLUSIONS: Risk factors for Type I and II tumors were overlapping suggesting that Type II tumors may be less estrogen-independent than previously anticipated. High-grade Type I tumors seemed to resemble Type II tumors more than low-grade Type I tumors.

MRGPRX2 and Immediate Drug Hypersensitivity: Insights From Cultured Human Mast Cells.

BACKGROUND AND OBJECTIVES: Mast cell (MC) degranulation via activation of the Mas-related G protein-coupled receptor X2 (MRGPRX2) plays a key role in immediate drug hypersensitivity (IDH). However, data in humans are limited to observations in specific cell lines. Objective: To study the usefulness of silencing MRGPRX2 in human MCs with the aim of further unveiling the MRGPRX2 pathway in IDH. METHODS: MCs were cultured from CD34+ progenitor cells obtained from peripheral blood (PBCMCs) and incubated with substance P (as a positive control), rocuronium, moxifloxacin, morphine, or amoxicillin. Immunophenotyping of the cells included flow cytometry and microscopy analyses of the expression of CD117, CD203c, and MRGPRX2. Intracellular calcium was measured using Fluo-4. Degranulation was analyzed by quantifying CD63 expression. For MRGPRX2 silencing, MCs were electroporated with Dicer small interference RNAs. RESULTS: Incubation of MCs with substance P, morphine, and moxifloxacin increased intracellular calcium levels and triggered MC degranulation, which, for the drugs, is almost completely abolished by selective MRGPRX2 silencing. Despite an increase in intracellular calcium in MRGPRX2+ cells, incubation with nontoxic concentrations of rocuronium does not result in degranulation of PBCMCs. Amoxicillin has no effect on PBCMCs. CONCLUSION: The use of MRGPRX2 silencing in human MCs can provide important insights into the role of MRGPRX2 in the pathogenesis of IDH. As induction of calcium signals does not necessarily translate into a secretory response, measurement of the degranulation reaction seems more meaningful in the context of drug testing.

MRGPRX2 and Immediate Drug Hypersensitivity: Insights From Cultured Human Mast Cells

Background: Mast cell (MC) degranulation via activation of the Mas-related G protein–coupled receptor X2 (MRGPRX2) plays a key role in immediate drug hypersensitivity (IDH). However, data in humans are limited to observations in specific cell lines. Objective: To study the usefulness of silencing MRGPRX2 in human MCs with the aim of further unveiling the MRGPRX2 pathway in IDH. Methods: MCs were cultured from CD34+ progenitor cells obtained from peripheral blood (PBCMCs) and incubated with substance P (as a positive control), rocuronium, moxifloxacin, morphine, or amoxicillin. Immunophenotyping of the cells included flow cytometry and microscopy analyses of the expression of CD117, CD203c, and MRGPRX2. Intracellular calcium was measured using Fluo-4. Degranulation was analyzed by quantifying CD63 expression. For MRGPRX2 silencing, MCs were electroporated with Dicer small interference RNAs. Results: Incubation of MCs with substance P, morphine, and moxifloxacin increased intracellular calcium levels and triggered MC degranulation, which, for the drugs, is almost completely abolished by selective MRGPRX2 silencing. Despite an increase in intracellular calcium in MRGPRX2+ cells, incubation with nontoxic concentrations of rocuronium does not result in degranulation of PBCMCs. Amoxicillin has no effect on PBCMCs. Conclusion: The use of MRGPRX2 silencing in human MCs can provide important insights into the role of MRGPRX2 in the pathogenesis of IDH. As induction of calcium signals does not necessarily translate into a secretory response, measurement of the degranulation reaction seems more meaningful in the context of drug testing (AU)

Antecedentes: La desgranulación de los mastocitos (MC) a través de la activación del receptor X2 acoplado a proteína G relacionada con Mas (MRGPRX2) se considera clave para la hipersensibilidad inmediata a fármacos. Sin embargo, los datos en humanos se limitan a observaciones en líneas celulares específicas. Objetivo: Estudiar la utilidad del silenciamiento de MRGPRX2 en MC humanos para conocer mejor la vía MRGPRX2 en la hipersensibilidad inmediata a fármacos. Métodos Los MC se cultivaron a partir de células progenitoras CD34+ obtenidas de sangre periférica (PBCMC) y se incubaron con la sustancia P como control positivo, rocuronio, moxifloxacina, morfina o amoxicilina. El inmunofenotipaje de las células incluyó análisis por citometría de flujo y microscopia de la expresión de CD117, CD203c y MRGPRX2. El calcio intracelular se midió usando Fluo-4. La desgranulación se analizó por cuantificación de la expresión de CD63. Para el silenciamiento de MRGPRX2, los MC se electroporaron con ARN silente del sustrato Dicer. Resultados: La incubación de MC con sustancia P, morfina y moxifloxacina provocó el aumento de los niveles de calcio intracelular y desencadenó la desgranulación de MC. En el caso de la desgranulación provocada por los fármacos, ésta se eliminó casi por completo mediante el silenciamiento selectivo de MRGPRX2. A pesar del aumento del calcio intracelular en las células MRGPRX2+, la incubación con concentraciones no tóxicas de rocuronio no produce la desgranulación de los PBCMC, mientras que la amoxicilina no tiene efecto sobre los PBCMC. Conclusión: El uso del silenciamiento de MRGPRX2 en MC humanos puede proporcionar información importante sobre el papel de MRGPRX2 en la patogénesis de la hipersensibilidad inmediata a fármacos. Como la inducción de señales de calcio no se traduce necesariamente en una respuesta secretora, parece más significativa la medición de la reacción de desgranulación en el contexto de las pruebas a fármacos (AU)

A randomized controlled efficacy study of the Medido medication dispenser in Parkinson's disease.

BACKGROUND: Complex medication schedules in Parkinson's disease (PD) result in lower therapy adherence, which contributes to suboptimal therapy and clinical deterioration. Medication reminder systems might improve therapy adherence and subsequently improve symptoms of PD. This randomized controlled study assessed the effect of the electronic medication dispenser Medido on physical disability in PD, as a proxy for changes in therapy adherence.x METHODS: Eighty-seven patients were randomized into the Medido group or control group. The primary outcome of physical disability was measured by the AMC Linear Disability Scale (ALDS). Secondary outcomes were quality of life (QoL) (PDQ-39), health status (EQ5D-5L, VAS), non-motor symptoms (NMS-Quest), and QoL of the caregiver (PDQ-carer). Measurements were performed at baseline, and after 3 and 6 months follow-up. RESULTS: When using the Medido, a non-significant improvement of 3.0 points (95% CI -5.6;11.6) was seen in ALDS. The exploratory subgroup Hoehn & Yahr classification (H&Y) > 2.5 improved significantly on ALDS with 14.7 points (95% CI -28.5;-0.9, p = 0.029 for group x time interaction). QoL deteriorated with 1.0 point in PDQ-39 (p = 0.01 for group x time interaction) in favor of the control group. Non-significant differences were observed for VAS (0.4 points, p = 0.057) and NMS-Quest (1.3 points, p = 0.095) in favor of the Medido group. No changes over time were observed in EQ5D-5L and PDQ-carer. CONCLUSIONS: Based on these data, no firm conclusion can be drawn, but use of the Medido medication dispenser may result in a clinical improvement of physical disability and seems particularly appropriate for more severe patients. TRIAL REGISTRATION: NTR3917 . Registered 19 March 2013.

Oral & Maxillofacial surgery is ready for patient-centred eHealth interventions - the outcomes of a scoping review.

Within the field of oral and maxillofacial (OMF) surgery, eHealth is expected to be a tool to improve quality of care. The aim of this study is to map the research of patient-centred eHealth interventions within OMF surgery by means of a scoping review. After a systematic literature search, relevant studies on patient-centred eHealth interventions for OMF-surgery patients were selected. The interventions were mapped based on their key components, target population and outcome measures. To gain insight in the research phase of evaluation, the framework of the Medical Research Council (MRC) was used. Forty-one papers were included, comprising 34 unique interventions. Nineteen interventions were designed for head and neck cancer patients, 11 interventions concernd video-teleconsultation. According to the MRC framework, 26 papers fitted into the feasibility and piloting phase of research, 8 into the evaluation phase, 7 were in the development phase. No implementation studies were found. This scoping review can be a starting point for those who are interested in applying and evaluating eHealth in their practice. Since many feasibility and pilot studies were found on similar interventions, a more extensive collaboration with and connecting to each other is recommended to catalyze the implementation of eHealth in daily practice. Profound involvement of patients in developing and evaluating eHealth interventions is essential to achieve true patient-centred OMF surgery.

Design and effects of outcome-based payment models in healthcare: a systematic review.

INTRODUCTION: Outcome-based payment models (OBPMs) might solve the shortcomings of fee-for-service or diagnostic-related group (DRG) models using financial incentives based on outcome indicators of the provided care. This review provides an analysis of the characteristics and effectiveness of OBPMs, to determine which models lead to favourable effects. METHODS: We first developed a definition for OBPMs. Next, we searched four data sources to identify the models: (1) scientific literature databases; (2) websites of relevant governmental and scientific agencies; (3) the reference lists of included articles; (4) experts in the field. We only selected studies that examined the impact of the payment model on quality and/or costs. A narrative evidence synthesis was used to link specific design features to effects on quality of care or healthcare costs. RESULTS: We included 88 articles, describing 12 OBPMs. We identified two groups of models based on differences in design features: narrow OBPMs (financial incentives based on quality indicators) and broad OBPMs (combination of global budgets, risk sharing, and financial incentives based on quality indicators). Most (5 out of 9) of the narrow OBPMs showed positive effects on quality; the others had mixed (2) or negative (2) effects. The effects of narrow OBPMs on healthcare utilization or costs, however, were unfavourable (3) or unknown (6). All broad OBPMs (3) showed positive effects on quality of care, while reducing healthcare cost growth. DISCUSSION: Although strong empirical evidence on the effects of OBPMs on healthcare quality, utilization, and costs is limited, our findings suggest that broad OBPMs may be preferred over narrow OBPMs.

Waist circumference percentiles of black South African children aged 10 - 14 years from different study sites

Background. Waist circumference (WC) is a useful predictor of cardiometabolic risk in children. Published data on WC percentiles of children from African countries are limited.Objectives. To describe age- and sex-specific Wpercentiles in black South African (SA) children from different study sites, and compare these percentiles with median WCpercentiles of African-American (AA) children.Methods. Secondary data on WC for 10 - 14-year-old black SA children (N=4 954; 2 406 boys and 2 548 girls) were extracted from the data sets of six studies. Smoothed WC percentile curves for boys and girls were constructed using the LMS method. The 50th percentile for age- and sex-specific WC measurements was compared across study sites and with AA counterparts.Results. Girls had higher WC values than boys from the 50th to 95th percentiles at all ages. The 50th WC percentiles of all groups of SA children combined were lower than those of AA children. When SA groups were considered separately, Western Cape children had median WC values similar to AA children, while rural Limpopo children had the lowest WC values. The 95th percentiles for Western Cape girls exceeded the adult cutoff point for metabolic syndrome (WC ≥80 cm) from age 11years.Conclusions. The differences in WC values for 10 - 14-year-old children across the six study sites highlight the need for nationally representative data to develop age-, sex- and ethnic-specific WC percentiles for black SA children. The results raise concerns about high WC among Western Cape girls

Professional occupation and the risk of Parkinson's disease.

BACKGROUND AND PURPOSE: Creativity in Parkinson's disease (PD) is strongly related to dopaminergic activity and medication. We hypothesized that patients with PD, including those who are in the pre-diagnostic phase of PD, are prone to choose highly structured 'conventional' professional occupations and avoid highly creative 'artistic' occupations. METHODS: At baseline of the population-based Rotterdam Study, we asked 12 147 individuals aged ≥45 years about their latest occupation and categorized occupations according to the RIASEC model. Participants underwent baseline and follow-up (median 11 years) examinations for PD. We determined associations of artistic (versus any other occupation) and conventional (versus any other occupation) occupations with PD. Additionally, we pooled our results with a recently published case-control study (Radboud Study). RESULTS: At baseline, conventional occupations were common [n = 4356 (36%)], whereas artistic occupations were rare [n = 137 (1%)]. There were 217 patients with PD, including 91 with prevalent PD and 126 with incident PD. The risk of PD varied substantially across occupational categories (chi-square, 14.61; P = 0.01). The penalized odds ratio (OR) of artistic occupations for PD was 0.19 [95% confidence interval (CI), 0.00-1.31; P = 0.11], whereas the OR of conventional occupations for PD was 1.23 (95% CI, 0.95-1.66; P = 0.10). The direction and magnitude of ORs were similar in cross-sectional and longitudinal subsamples. Pooled ORs across the Rotterdam and Radboud Studies were 0.20 (95% CI, 0.08-0.52; P < 0.001) for artistic and 1.23 (95% CI, 0.92-1.67; P = 0.08) for conventional occupations. CONCLUSIONS: The risk of PD varies substantially by choice of professional occupation. Our findings suggest that dopaminergic degeneration affects choice of occupation, which may start in the pre-diagnostic phase of PD.

Hepatitis E virus seroprevalence, seroincidence and seroreversion in the German adult population.

A steep rise in Hepatitis E diagnoses is currently being observed in Germany and other European countries. The objective of this study was (i) to assess whether this trend mirrors an increase in infection pressure or is caused by increased attention and testing and (ii) estimate individual and population-based Hepatitis E Virus (HEV) seroconversion and seroreversion rates for Germany. We measured anti-HEV IgG prevalence in 10 407 adults participating in two linked, population-representative serosurveys (total n = 12 971) conducted in 1998 and 2010. In this period, we found a moderate but statistically significant decline of overall anti-HEV IgG prevalence from 18.6% to 15.3%. At both time points, seroprevalence increased with age and peaked in persons born between 1935 and 1959 suggesting a past period of increased infection pressure. Paired samples of individuals participating in 1998 and 2010 (n = 2564) revealed respective seroconversion and seroreversion rates of 6.2% and 22.6% among seronegative and seropositive individuals during 12 years, or 5.2 and 2.9 per 1000 inhabitants per year. This corresponds to a total of 417 242 [95%CI: 344 363-495 971] new seroconversions per year in the German population. While anti-HEV seroprevalence has decreased in the last decade, infection pressure and seroincidence remains high in Germany. Continuously rising numbers of Hepatitis E diagnoses in Europe are likely due to an increased awareness of clinicians and indicate that still there is a gap between incident and diagnosed cases. Studies on the true burden of the disease, specific risk factors and sources of autochthonous infections as well as targeted prevention measures are urgently needed.

Dutch surgeons' views on the volume-outcome mechanism in surgery: A qualitative interview study.

OBJECTIVE: To contribute to a better understanding of volume-outcome relationships in surgery by exploring Dutch surgeons' views on the underlying mechanism. DESIGN: A qualitative study based on face-to-face semi structured interviews and an inductive content analysis approach. SETTING: Interviews were conducted in eight hospitals in the Netherlands (2 university, 4 teaching and 2 general). PARTICIPANTS: Twenty surgeons (gastrointestinal, vascular and trauma). MAIN OUTCOME MEASURE(S): Dutch surgeons' views on volume-outcome relationships in surgery and the underlying mechanism. RESULTS: The majority of surgeons believed volume is related to outcomes after surgery. Interviewees highlighted the importance of both focus and skills when describing the underlying mechanism. Focus was visible on three levels: hospital, surgeon and team. Focus on a hospital level referred to investing in specific infrastructure and dedicated personnel. Surgeons described both the benefits and downsides of surgeons' increased focus to a certain surgical subspeciality. And their experiences on the importance of working with fixed, procedure-specific teams. The positive influence of caseload on technical and nontechnical skills was acknowledged, as well as the benefits of combining skills by operating together. Although a basic skill set should be maintained, this does not necessarily require high volume. CONCLUSIONS: Focus and skills are important explanatory factors in volume-outcome relationships according to Dutch surgeons. This suggests that both high- and low-volume providers should enable specialized, fixed teams for complex surgeries and focus on maintenance of both their technical and nontechnical skills. By uncovering the underlying mechanism, imperfect quality indicators such as volume can be supplemented or replaced.

Immediate moxifloxacin hypersensitivity: Is there more than currently meets the eye?

Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and nine moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c, and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in seven of 15 patients. Only two of these seven patients demonstrated appearance of CD63 and release of histamine. In the remainder eight patients, no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63-/CD203c-based BAT. Deciphering the complexity of quinolone IDHR seems mandatory.

[Shared decision-making: dilemmas in daily practice]. / Samen beslissen: dilemma's in de praktijk.

Shared decision-making is an essential - but often neglected - component of evidence-based medicine. In practice, doctors, nurses and patients encounter dilemmas which are understandable, but not insurmountable. We illustrate this by means of a complex decision concerning therapy in the advanced stage of Parkinson's disease. Evidence of effectiveness differs with each individual therapy, and, in practice, the experiences of neurologists also vary widely. In addition, the various treatment strategies all require a different sort of daily care, and have differing impacts on people's lives. It is time that we worked towards a realistic view of shared decision-making. Shared decision-making cannot be generalised to a 'one size fits all' strategy that we can choose to apply or not to apply at will. It should be a flexible instrument which, depending on the individual and the specific situation, can be put to use to deliver the best tailored care.

In Vitro Diagnosis of Immediate Drug Hypersensitivity Anno 2017: Potentials and Limitations.

BACKGROUND: For most physicians, quantification of drug-specific immunoglobulin E (drug-sIgE) antibodies constitutes the primary in vitro measure to document immediate drug hypersensitivity reactions (IDHR). Unfortunately, this is often insufficient to correctly identify patients with IgE-mediated IDHR and impossible for non-IgE-mediated IDHR that result from alternative routes of basophil and mast cell activation. In these difficult cases, diagnosis might benefit from cellular tests such as basophil activation tests (BAT). AIM: The aim was to review the potential and limitations of quantification of sIgE and BAT in diagnosing IDHR. The utility of quantification of serum tryptase is discussed. METHODS: A literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, specific IgE antibodies; this was complemented by the authors' own experience. RESULTS: The drugs that have been most studied with both techniques are ß-lactam antibiotics and curarizing neuromuscular blocking agents (NMBA). For sIgE morphine, data are available on the value of this test as a biomarker for sensitization to substituted ammonium structures that constitute the major epitope of NMBA, especially rocuronium and suxamethonium. For the BAT, there are also data on non-steroidal anti-inflammatory drugs (NSAIDs) and iodinated radiocontrast media. For ß-lactam antibiotics, sensitivity and specificity of sIgE varies between 0 and 85% and 52 and 100%, respectively. For NMBA, sensitivity and specificity varies between 38.5 and 92% and 85.7 and 100%, respectively. Specific IgE to morphine should not be used in isolation to diagnose IDHR to NMBA nor opiates. For the BAT, sensitivity generally varies between 50 and 60%, whereas specificity attains 80%, except for quinolones and NSAIDs. CONCLUSIONS: Although drug-sIgE assays and BAT can provide useful information in the diagnosis of IDHR, their predictive value is not absolute. Large-scale collaborative studies are mandatory to harmonize and optimize test protocols and to establish drug-specific decision thresholds.

Steep rise in norovirus cases and emergence of a new recombinant strain GII.P16-GII.2, Germany, 2016.

Since early November 2016, the number of laboratory-confirmed norovirus infections reported in Germany has been increasing steeply. Here, we report the detection and genetic characterisation of an emerging norovirus recombinant, GII.P16-GII.2. This strain was frequently identified as the cause of sporadic cases as well as outbreaks in nine federal states of Germany. Our findings suggest that the emergence of GII.P16-GII.2 contributed to rising case numbers of norovirus gastroenteritis in Germany.

Phenotypic and functional characterization of in vitro cultured human mast cells.

BACKGROUND: Mast cell progenitor cells, derived from CD34+ hematopoietic stem cells, enter the circulation and subsequently mucosal or connective tissues where they mature to mast cells. Upon activation, mast cells increase the expression of activation markers, e.g. CD63, and release histamine amongst other mediators. Traditionally, release of these mediators is quantified using assays measuring their extracellular concentration in the supernatant of stimulated cells. METHODS: Human mast cells (HuMC) were cultured from peripheral blood, phenotypically characterized, passively sensitized with allogenic IgE antibodies and finally stimulated by anti-IgE that crosslinks IgE/FcεRI complexes. Alterations in the number of cells positive for CD63 and release of histamine were quantified simultaneously by flow cytometry. RESULTS: In culture, two distinct CD45+ cell populations were identified: CD117+ CD203c+hi and CD117- CD203c+low cells. Both populations showed positivity for FcεRI, tryptase and chymase, and contained histamine. Activation resulted in a significant increase of cells positive for CD63+ up to 21% (range: 11-39) for CD117+ CD203c+hi cells (P = 0.005), and 27% (18-55) CD63+ for CD117- CD203c+low cells (P = 0.02). Baseline histamine content was higher for CD117+ CD203c+hi cells than for CD117- CD203c+low cells, respectively 994 (695-6815) Molecules of Equivalent Specific Fluorochrome V500 per cell (MESF-V500/cell) and 797 (629-4978) MESF-V500/cell (P = 0.02). After activation, CD117+ CD203c+hi cells showed significant histamine release of 578 (366-1521) MESF-V500/cell, whilst CD117- CD203c+low cells resulted in 310 (217-366) MESF-V500/cell histamine release. CONCLUSION: This study discloses that culturing HuMC from CD34+ progenitors yields 2 phenotypically distinct cell populations that display a greatly similar response upon cross-linking of IgE/FcεRI complexes. © 2016 International Clinical Cytometry Society.

Shellfish allergens: tropomyosin and beyond.

IgE-mediated shellfish allergy constitutes an important cause of food-related adverse reactions. Shellfish are classified into mollusks and crustaceans, the latter belonging to the class of arthropoda. Among crustaceans, shrimps are the most predominant cause of allergic reactions and thus more extensively studied. Several major and minor allergens have been identified and cloned. Among them, invertebrate tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, and hemocyanin are the most relevant. This review summarizes our current knowledge about these allergens.

Cannabis sativa allergy: looking through the fog.

IgE-mediated Cannabis (C. sativa, marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may trigger a C. sativa sensitization and/or allergy. The clinical presentation of a C. sativa allergy varies from mild to life-threatening reactions and often seems to depend on the route of exposure. In addition, sensitization to cannabis allergens can result in various cross-allergies, mostly for plant foods. This clinical entity, designated as the 'cannabis-fruit/vegetable syndrome', might also imply cross-reactivity with tobacco, natural latex and plant-food-derived alcoholic beverages. Hitherto, these cross-allergies are predominantly reported in Europe and appear mainly to rely upon cross-reactivity between nonspecific lipid transfer proteins or thaumatin-like proteins present in C. sativa and their homologues, ubiquitously distributed throughout plant kingdom. At present, diagnosis of cannabis-related allergies predominantly rests upon a thorough history completed with skin testing using native extracts from crushed buds and leaves. However, quantification of specific IgE antibodies and basophil activation tests can also be helpful to establish correct diagnosis. In the absence of a cure, treatment comprises absolute avoidance measures. Whether avoidance of further use will halt the extension of related cross-allergies remains uncertain.