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Objective The pathogenesis of attention‐deficit/hyperactivity disorder (ADHD) is currently unclear. We hypothesized that chronic immune activation, as indexed by T and B cells, plays a role in the pathophysiology of attention problems. Therefore, we examined T and B cell subsets in a general pediatric population with information on attention problems. Methods We included 756 10‐year‐old children from the Generation R population‐based cohort. Eleven‐color flow cytometry was performed on peripheral blood samples to determine T and B cell subsets. The Child Behavior Checklist rated by parents was used to measure attention problems. Data were analyzed using linear regression analyses, adjusting for maternal and child covariates and co‐occurring childhood psychopathology. Results For T helper 1 (Th1) cells, one standard deviation (SD) increase was associated with 5.3% (95%CI 0.3; 10.5) higher attention problem scores. Furthermore, 1SD increase in CD8+ T cells was associated with 7.5% (95%CI 2.4; 12.7) higher attention problem scores. Within total CD8+ T cells, 1SD increase in naive or central memory cells was associated with 6.9% (95%CI 2.0; 12.1) and 6.4% (95%CI 1.5; 11.6) higher attention problem scores, respectively. No associations between Th2, Treg or B memory cells and attention problem scores were observed. Conclusion Higher Th1 and cytotoxic T cell numbers are associated with higher attention problem scores independent of co‐occurring psychopathology. This might indicate a possible role of a pro‐inflammatory immune profile in childhood attention problems. Attention problems have been associated with inflammatory diseases previously, however the exact underlying pathophysiology of ADHD is unclear. This study shows increased T helper 1 and CD8+ total, CD8+ naive, CD8+ central memory numbers in children from a general pediatric population with higher attention problem scores independent of other childhood neurodevelopmental problems.

Abstract Context Adult obesity is associated with chronic low-grade inflammation and may give rise to future chronic disease. However, it is unclear whether adiposity-related inflammation is already apparent in childhood. Objective To study associations between child adiposity measures with circulating monocytes and naive and memory subsets in CD4, CD8, and γδ T cell lineages. Methods Ten-year-old children (n = 890) from the Generation R Cohort underwent dual-energy x-ray absorptiometry and magnetic resonance imaging for body composition (body mass index [BMI], fat mass index [FMI], android-to-gynoid fat mass ratio, visceral fat index, liver fat fraction). Blood samples were taken for detailed immunophenotyping of leukocytes by 11-color flow cytometry. Results Several statistically significant associations were observed. A 1-SD increase in total FMI was associated with +8.4% (95% CI 2.0, 15.2) Vδ2+Vγ9+ and +7.4% (95% CI 2.4, 12.5) CD8+TEMRO cell numbers. A 1-SD increase in visceral fat index was associated with +10.7% (95% CI 3.3, 18.7) Vδ2+Vγ9+ and +8.3% (95% CI 2.6, 14.4) CD8+TEMRO cell numbers. Higher android-to-gynoid fat mass ratio was only associated with higher Vδ2+Vγ9+ T cells. Liver fat was associated with higher CD8+TEMRO cells but not with Vδ2+Vγ9+ T cells. Only liver fat was associated with lower Th17 cell numbers: a 1-SD increase was associated with −8.9% (95% CI −13.7, −3.7) Th17 cells. No associations for total CD8+, CD4+ T cells, or monocytes were observed. BMI was not associated with immune cells. Conclusion Higher Vδ2+Vγ9+ and CD8+TEMRO cell numbers in children with higher visceral fat index could reflect presence of adiposity-related inflammation in children with adiposity of a general population.

Context: Adult obesity is associated with chronic low-grade inflammation and may give rise to future chronic disease. However, it is unclear whether adiposity-related inflammation is already apparent in childhood. Objective: To study associations between child adiposity measures with circulating monocytes and naive and memory subsets in CD4, CD8, and [gamma][delta] T cell lineages. Methods: Ten-year-old children (n = 890) from the Generation R Cohort underwent dual-energy x-ray absorptiometry and magnetic resonance imaging for body composition (body mass index [BMI], fat mass index [FMI], android-to-gynoid fat mass ratio, visceral fat index, liver fat fraction). Blood samples were taken for detailed immunophenotyping of leukocytes by 11-color flow cytometry. Results: Several statistically significant associations were observed. A 1-SD increase in total FMI was associated with +8.4% (95% CI 2.0, 15.2) V[delta][2.sup.+]V[gamma][9.sup.+] and +7.4% (95% CI 2.4, 12.5) CD[8.sup.+.sup.TEMRO] cell numbers. A 1-SD increase in visceral fat index was associated with +10.7% (95% CI 3.3, 18.7) V[delta][2.sup.+]V[gamma][9.sup.+] and +8.3% (95% CI 2.6, 14.4) CD[8.sup.+.sup.TEMRO] cell numbers. Higher android-to-gynoid fat mass ratio was only associated with higher V[delta][2.sup.+]V[gamma][9.sup.+] T cells. Liver fat was associated with higher CD[8.sup.+.sup.TEMRO] cells but not with V[delta][2.sup.+]V[gamma][9.sup.+] T cells. Only liver fat was associated with lower Th17 cell numbers: a 1-SD increase was associated with -8.9% (95% CI -13.7, -3.7) Th17 cells. No associations for total CD[8.sup.+], CD[4.sup.+] T cells, or monocytes were observed. BMI was not associated with immune cells. Conclusion: Higher V[delta][2.sup.+]V[gamma][9.sup.+] and CD[8.sup.+.sup.EMRO] cell numbers in children with higher visceral fat index could reflect presence of adiposity-related inflammation in children with adiposity of a general population. Key Words: child, effector memory T cell, gamma delta T cell, fat mass, inflammation, monocyte

A previously healthy 40-year-old man was referred to our emergency department with pruritic skin lesions and dyspnoea. Laboratory investigation revealed hypereosinophilia. Further diagnostic work-up confirmed the diagnosis of idiopathic hypereosinophilic syndrome (iHES), a rare myeloproliferative disease with a heterogeneous clinical presentation. We describe a unique case with cardiac, pulmonary, hepatic and cutaneous involvement at time of presentation. This case accentuates the importance of an extensive multidisciplinary diagnostic work-up, since iHES is a condition with potential rapid progressive multiorgan failure which requires prompt analysis and treatment. In addition, this case emphasises the importance of being aware of tunnel vision, especially during the COVID-19 pandemic, which might give rise to an increased risk of missing rare diagnoses. Our patient was treated with prednisolone, after which both his clinical condition and eosinophil concentrations markedly improved.

Objective To compare the cumulative incidence of cervical cancer diagnosed within 72 months after a normal screening sample between conventional cytology and liquid based cytology tests SurePath and ThinPrep.Design Retrospective population based cohort study.Setting Nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), January 2000 to March 2013.Population Women with 5 924 474 normal screening samples (23 833 123 person years).Exposure Use of SurePath or ThinPrep versus conventional cytology as screening test.Main outcome measure 72 month cumulative incidence of invasive cervical cancer after a normal screening sample for each screening test. Cox regression analyses assessed the hazard ratios, adjusted for calendar time, age, screening history, and socioeconomic status and including laboratories as random effects.Results The 72 month cumulative cancer incidence was 58.5 (95% confidence interval 54.6 to 62.7) per 100 000 normal conventional cytology samples, compared with 66.8 (56.7 to 78.7) for ThinPrep and 44.6 (37.8 to 52.6) for SurePath. Compared with conventional cytology, the hazard of invasive cancer was 19% lower (hazard ratio 0.81, 95% confidence interval 0.66 to 0.99) for SurePath, mainly caused by a 27% lower hazard (0.73, 0.57 to 0.93) of a clinically detected cancer. For ThinPrep, the hazard was on average 15% higher (hazard ratio 1.15, 0.95 to 1.38), mainly caused by a 56% higher hazard of a screen detected cancer (1.56, 1.17 to 2.08).Conclusions These findings should provoke reconsideration of the assumed similarity in sensitivity to detect progressive cervical intraepithelial neoplasia between different types of liquid based cytology and conventional cytology.

IntroductionInformed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence.Methods and analysisThe PRINCE (Process of Informed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardised format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is disclosed, in which format, etc) and correlation of donor knowledge with surgeons' estimation thereof.Ethics and disseminationApproval for this study was obtained from the medical ethical committee of the Erasmus MC, University Medical Center, Rotterdam, on 18 February 2015. Secondary approval has been obtained from the local ethics committees in six participating centres. Approval in the last centre has been sought.ResultsOutcome will be published in a scientific journal.Trial registration numberNTR5374; Pre-results.