Association between allergen component sensitisation and clinical allergic disease in children

Background: Allergen component sensitisation testing is becoming increasingly important in the diagnosis of peanut allergy. The aim of the present study was to evaluate the relationship between sensitisation and symptoms of allergic disease in children by testing a large panel of inhalants, food allergens, and allergen components. Methods: For 287 children visiting our laboratory for allergy testing, symptoms of allergic disease were recorded by standardised validated questionnaires. Specific IgE to 11 whole allergens was assessed by ImmunoCAP, and to 112 allergen components by ISAC ImmunoCAP assay. We used latent class analysis (LCA) to distinguish clinical phenotypes. Results: Inhalant and food allergen sensitisation was common, irrespective of the children's allergic symptom type. Less than 10% of the variance in symptom scores was explained by variations in the number of allergens (components) that the child was sensitised to. In LCA, 135 children (50.2%) had mild allergy, with few symptoms and sensitisation to no or few allergens, 74 children (27.5%) had more symptoms and sensitisation to inhalant allergens (respiratory allergy) and 60 children (22.3%) showed polysensitisation to a median of six allergens and had more severe symptoms of different organ systems. Adding allergen component test results to LCA failed to result in identifiable classes of allergic disease in children. Conclusions: In this group of children with allergic symptoms, referred for allergy testing by their physician, broad screening for allergen component sensitisation did not contribute to distinguishing phenotypes of allergic disease. (C) 2022 Codon Publications. Published by Codon Publications

Timing of restoration of bowel continuity after decompressing stoma, in left-sided obstructive colon cancer:a nationwide retrospective cohort

BACKGROUND: With the increasing use of decompressing stoma as a bridge to surgery for left-sided obstructive colon cancer (LSOCC), the timing of restoration of bowel continuity (ROBC) is a subject of debate. There is a lack of data on immediate ROBC during elective resection as an alternative for a 3-stage procedure. This study analysed if immediate ROBC during tumour resection is safe and of any benefit for patients who underwent decompressing stoma for LSOCC. METHODS: In a Dutch nationwide collaborative research project, 3153 patients who underwent resection for LSOCC in 75 hospitals (2009-2016) were identified. Extensive data on disease and procedural characteristics, and outcomes was collected by local collaborators. For this analysis, 332 patients who underwent decompressing stoma followed by curative resection were selected. Immediate ROBC during tumour resection was compared to two no immediate ROBC groups, (1) tumour resection with primary anastomosis (PA) with leaving the decompressing stoma in situ, and (2) tumour resection without PA. RESULTS: Immediate ROBC was performed in 113 patients (34.0%) and no immediate ROBC in 219 patients [168 with PA (50.6%) and 51 patients without PA (15.4%)]. No differences at baseline between the groups were found for age, ASA score, cT, and cM. Major surgical complications (8.8% immediate ROBC vs. 4.8% PA with decompressing stoma and 7.8% no PA; P =0.37) and mortality (2.7% vs. 2.4% and 0%, respectively; P =0.52) were similar. Immediate ROBC resulted in a shorter time with a stoma (mean 41 vs. 240 and 314 days, respectively; P &lt;0.001), and fewer permanent stomas (7% vs. 21% and 80%, respectively; P &lt;0.001) as compared to PA with a decompressing stoma or no PA. CONCLUSION: After a decompressing stoma for LSOCC, immediate ROBC during elective resection appears safe, reduces the total time with a stoma and the risk of a permanent stoma.</p

Alteration of the Exhaled Volatile Organic Compound Pattern in Colorectal Cancer Patients after Intentional Curative Surgery—A Prospective Pilot Study

As current follow-up modalities for colorectal carcinoma (CRC) have restricted sensitivity, novel diagnostic tools are needed. The presence of CRC changes the endogenous metabolism, resulting in the release of a specific volatile organic compounds (VOC) pattern that can be detected with an electronic nose or AeonoseTM. To evaluate the use of an electronic nose in the follow-up of CRC, we studied the effect of curative surgery on the VOC pattern recognition using AeonoseTM. A prospective cohort study was performed, in which 47 patients diagnosed with CRC were included, all of whom underwent curative surgical resection. Breath testing was performed before and after surgery using the AeonoseTM. A machine learning model was developed by discerning between the 94 pre-and postoperative breath samples. The training model differentiated between the pre-and postoperative CRC breath samples with a sensitivity and specificity of 0.78 (95%CI 0.61–0.90) and 0.73 (95%CI 0.56–0.86), respectively, with an accuracy of 0.76 (95%CI 0.66–0.85), and an area under the curve of 0.79 (95%CI 0.68–0.89). The internal validation of the test set resulted in an accuracy of 0.75 (95%CI 0.51–0.91) and AUC of 0.82 (95%CI 0.61–1). In conclusion, our results suggest that the VOC pattern of CRC patients is altered by curative surgery in a short period, indicating that the exhaled VOCs might be closely related to the presence of CRC. However, to use AeonoseTM as a potential diagnostic tool in the clinical follow-up of CRC patients, the performance of the models needs to be improved through further large-scale prospective research.</p

Quantification of human complement C2 protein using an automated turbidimetric immunoassay

Background: The measurement of complement components is clinically useful where a deficiency is suspected, or where excessive activation and consumption are present in disease. C2 deficiency carries an increased risk of developing systemic lupus erythematosus, recurrent infections and atherosclerosis. In this study, we have evaluated The Binding Site’s Human Complement C2 SPAPLUS® assay. Methods: Linearity was tested using 13 sample dilutions covering the standard measuring range. Within- and between-assay variabilities were calculated using five samples with different C2 concentrations. The correlation between C2 concentrations in EDTA-plasma and serum was assessed, as was the correlation between C2 measurements by the automated assay and radial immunodiffusion. C2 concentrations were compared with CH50 activity, and quantified in individuals with homozygous or heterozygous C2 deficiency, acquired angioedema and patients with chronic inflammatory conditions. Results: The assay was linear across the measuring range (3.8–42.3 mg/L). Intra- and interassay variability were 2.3%–3.8% and 0%–3.3%, respectively. Comparison between C2 measurements in EDTA-plasma and serum provided a strong correlation (p<0.0001, R2=0.82, slope 0.92), as did the correlation between the automated and radial immunodiffusion methods (p<0.0001, R2=0.89, slope 1.07). A positive correlation between C2 concentration and CH50 activity was demonstrated (p<0.0001, R2=0.48). Significant differences were observed between the median C2 concentrations obtained in healthy controls and the patient clinical samples, with homozygous C2-deficient patients giving below detectable results. Conclusions: This C2 SPAPLUS® assay allows the automated, rapid and precice quantification of complement C2 protein and could therefore be considered as a replacement for older, more time-consuming methods

The validity of Dutch health claims data for identifying patients with chronic kidney disease:a hospital-based study in the Netherlands

Background. Health claims data may be an efficient and easily accessible source to study chronic kidney disease (CKD) prevalence in a nationwide population. Our aim was to study Dutch claims data for their ability to identify CKD patients in different subgroups. Methods. From a laboratory database, we selected 24 895 adults with at least one creatinine measurement in 2014 ordered at an outpatient clinic. Of these, 15 805 had >= 2 creatinine measurements at least 3 months apart and could be assessed for the chronicity criterion. We estimated the validity of a claim-based diagnosis of CKD and advanced CKD. The estimated glomerular filtration rate (eGFR)-based definitions for CKD (eGFR = 75 years. The specificity of CKD and advanced CKD was >= 99%. Positive predictive values ranged from 72% to 99% and negative predictive values ranged from 40% to 100%. Conclusion. When using health claims data for the estimation of CKD prevalence, it is important to take into account the characteristics of the population at hand. The younger the subjects and the more advanced the stage of CKD the higher the sensitivity of such data. Understanding which patients are selected using health claims data is crucial for a correct interpretation of study results

Personal Genomes in Practice:Exploring Citizen and Healthcare Professionals’ Perspectives on Personalized Genomic Medicine and Personal Health Data Spaces Using a Mixed-Methods Design

Ongoing health challenges, such as the increased global burden of chronic disease, are increasingly answered by calls for personalized approaches to healthcare. Genomic medicine, a vital component of these personalization strategies, is applied in risk assessment, prevention, prognostication, and therapeutic targeting. However, several practical, ethical, and technological challenges remain. Across Europe, Personal Health Data Space (PHDS) projects are under development aiming to establish patient-centered, interoperable data ecosystems balancing data access, control, and use for individual citizens to complement the research and commercial focus of the European Health Data Space provisions. The current study explores healthcare users’ and health care professionals’ perspectives on personalized genomic medicine and PHDS solutions, in casu the Personal Genetic Locker (PGL). A mixed-methods design was used, including surveys, interviews, and focus groups. Several meta-themes were generated from the data: (i) participants were interested in genomic information; (ii) participants valued data control, robust infrastructure, and sharing data with non-commercial stakeholders; (iii) autonomy was a central concern for all participants; (iv) institutional and interpersonal trust were highly significant for genomic medicine; and (v) participants encouraged the implementation of PHDSs since PHDSs were thought to promote the use of genomic data and enhance patients’ control over their data. To conclude, we formulated several facilitators to implement genomic medicine in healthcare based on the perspectives of a diverse set of stakeholders.</p

Possible Value of Faecal Immunochemical Test (FIT) When Added in Symptomatic Patients Referred for Colonoscopy: A Systematic Review

UNLABELLED: If Colorectal cancer (CRC) is detected and treated early, the survival rate is high. This is one of the reasons that population-based screening programs for the early detection of CRC using the faecal immunochemical test (FIT) started worldwide. These programs compete with regular colonoscopy programs and increase the waiting time for symptomatic patients. However, the literature has shown that the correlation between intestinal complaints and the gain of colonoscopy is poor. The aim of this study is to assess the diagnostic utility of symptoms for the yield (CRC) of colonoscopy and to compare this with the diagnostic utility of FIT when offered to symptomatic patients. METHODS: We performed a systematic review search for CRC as an outcome of colonoscopy in referred symptomatic patients and separately for CRC as an outcome in symptomatic patients with a positive FIT. We searched systematically for clinical trials or observational studies in databases, followed by hand-searching of reference lists. We used random Meta-Disc to evaluate the diagnostic performance, using the exploration of heterogeneity with a variety of test statistics and by computing the pooled estimates. RESULTS: We included 35 studies, with almost 5 million symptomatic patients. In addition, we included nine prospective studies with a positive FIT in symptomatic patients, with more than 5000 patients. Significant heterogeneity was found for every symptom and the outcome of colonoscopy in the effect size of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio. In a random effect model, the pooled sensitivity of colonoscopy in symptomatic patients was very low (25%). However, the pooled sensitivity in symptomatic patients with a positive FIT was 83% and the pooled specificity 77%. A total of 75 symptomatic patients (1.4%) had a false-negative FIT. CONCLUSION: Adding FIT in symptomatic patients seems useful for predicting CRC as an outcome of colonoscopy. FIT seems a potential tool for an improved triage of colonoscopy in symptomatic patients

Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers

Contains fulltext : 89737.pdf (publisher's version ) (Closed access)BRCA1/2 mutation carriers have a high lifetime risk of developing breast cancer. Differences in penetrance indicate that this risk may be influenced by lifestyle factors. Because physical activity is one of the few modifiable risk factors, it may provide a target to add to breast cancer prevention in this high-risk population. We examined the association between self-reported lifetime sports activity and breast cancer risk in a nationwide retrospective cohort study, including 725 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. We found a nonsignificantly decreased risk for ever engaging in sports activity (HR = 0.84, 95%CI = 0.57-1.24). Among women who had participated in sports, a medium versus low level of intensity and duration (i.e., between 11.0 and 22.7 mean MET hours/week averaged over a lifetime) reduced the risk of breast cancer (HR = 0.59, 95%CI = 0.36-0.95); no dose-response trend was observed. For mean hours/week of sports activity, a nonsignificant trend was observed (HR(low versus never) = 0.93, 95%CI = 0.60-1.43; HR(medium versus never) = 0.81, 95%CI = 0.51-1.29; HR(high versus never) = 0.78, 95%CI = 0.48-1.29; p (trend overall) = 0.272; p (trend active women) = 0.487). For number of years of sports activity no significant associations were found. Among women active in sports before age 30, mean MET hours/week showed the strongest inverse association of all activity measures (HR(medium versus low) = 0.60, 95%CI = 0.38-0.96; HR(high versus low) = 0.58, 95%CI = 0.35-0.94; p (trend) = 0.053). Engaging in sports activity after age 30 was also inversely associated with breast cancer risk (HR = 0.63, 95%CI = 0.44-0.91). Our results indicate that sports activity may reduce the risk of breast cancer in BRCA1/2 mutation carriers.1 februari 201

Body weight and risk of breast cancer in BRCA1/2 mutation carriers

Contains fulltext : 95679.pdf (publisher's version ) (Closed access)Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI (HR(22.50-24.99 vs. 18.50-22.49) = 0.83, 95% CI = 0.47-1.44 and HR(>/= 25.00 vs. 18.50-22.49) = 0.41, 95% CI = 0.13-1.27). For postmenopausal breast cancer, being 1.67 m and taller increased the risk 1.7-fold (HR = 1.67, 95% CI = 1.01-2.74) when compared to a height /= 72 kg increased the risk of postmenopausal breast cancer 2.1-fold (95% CI = 1.23-3.59). A current BMI of >/= 25.0 kg/m(2), an adult weight gain of 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50-60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86-2.51), HR = 1.56 (95% CI = 0.85-2.87), and HR = 1.60 (95% CI = 0.97-2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life

Reference values for interleukin-6 and interleukin-8 in cord blood of healthy term neonates and their association with stress-related perinatal factors.

BACKGROUND: Automated interleukin assays are promising diagnostic aids for early-onset neonatal sepsis, however, reference values for healthy term neonates are incompletely known. The goal of this study is to determine reference values for interleukin-6 (IL-6) and interleukin-8 (IL-8) in cord blood of healthy term neonates. METHODS AND FINDINGS: Women were recruited from April 2012 to August 2012. IL-6 and IL-8 levels were measured using an automated immunometric assay (Immulite) in cord blood of 93 healthy term newborns, 60 of them were born via vaginal delivery and 33 by elective caesarean section (ECS). A mean value for IL-8 of 8.1 ± 3.0 pg/mL was found in cord blood of healthy term neonates, which apply to both vaginal delivery and ECS. Regarding IL-6, two values apply. For vaginal delivery, a median value of 3.3 pg/mL (range, <2 to 9.53 pg/mL) was found, while for ECS, a median value of <2 pg/mL (range, <2 to 48 pg/mL) applies. CONCLUSIONS: We propose a reference value of <14.1 pg/mL for IL-8 (mean + 2SD), applying to vaginally delivered and ECS-delivered healthy term newborns. From a clinical point of view, we also propose one reference value for IL-6 to be applied to vaginally delivered and ECS-delivered healthy term newborns, which is <10.2 pg/mL (97.5th percentile total group). These values have to be validated in larger cohorts of neonates, inclusive of those with and without early-onset neonatal sepsis