Islet cell cytoplasmic antibody reactivity in midgestational human fetal pancreas

The reactivity of islet cell cytoplasmic antibodies (ICA)-positive and ICA-negative sera of recent onset type 1 diabetic patients was studied in human fetal pancreata of 12-18 weeks' gestation and compared with the reactivity of these sera in adult human control pancreata. The aims of the study were: (1) to observe the presence of ICA staining in human fetal islet cells; (2) to compare endpoint titres (in Juvenile Diabetes Foundation units) of ICA-positive patient sera in fetal pancreata and adult human control pancreata. Ten ICA-positive sera and eight ICA-negative sera from newly diagnosed diabetic patients and four sera from healthy controls were tested on three human adult and eight human fetal pancreata. As in the adult control pancreata. ICA-positive sera reacted to insulin-, glucagon-, and somatostatin-positive cells of fetal pancreata of all gestational ages. This was observed both in single cells and in cells in islet-like cell clusters. Dilution of a reference serum gave similar results in both adult and fetal pancreata. In contrast, the ICA-positive patient sera yielded a striking heterogeneity in fetal as well as in adult pancreata. However, end-point titres between adult and fetal pancreata did not differ significantly (P>0.05). In conclusion, ICA-positive sera from recent onset diabetic patients show that the expression of molecules to which ICA react is present in all islet cells and starts before week 12 of gestation

Optimized Preoperative Planning of Double Outlet Right Ventricle Patients by 3D Printing and Virtual Reality:A Pilot Study

OBJECTIVES: In complex double outlet right ventricle (DORV) patients, the optimal surgical approach may be difficult to assess based on conventional two-dimensional (2D) ultrasound (US) and computed tomography (CT) imaging. The aim of this study is to assess the added value of 3D printed and 3D Virtual Reality (VR) models of the heart used for surgical planning in DORV patients, supplementary to the gold standard 2D imaging modalities.METHODS: Five patients with different DORV-subtypes and high-quality CT scans were selected retrospectively. 3D prints and 3D-VR models were created. Twelve congenital cardiac surgeons and paediatric cardiologists, from three different hospitals, were shown 2D-CT first, after which they assessed the 3D print and 3D-VR models in random order. After each imaging method, a questionnaire was filled in on the visibility of essential structures and the surgical plan.RESULTS: Spatial relationships were generally better visualized using 3D methods (3D printing/3D-VR) than in 2D. The feasibility of VSD patch closure could be determined best using 3D-VR reconstructions (3D-VR 92%, 3D print 66%, and US/CT 46%, P &lt; 0.01). The percentage of proposed surgical plans corresponding to the performed surgical approach was 66% for plans based on US/CT, 78% for plans based on 3D printing, and 80% for plans based on 3D-VR visualization.CONCLUSIONS: This study shows that both 3D printing and 3D-VR have additional value for cardiac surgeons and cardiologists over 2D imaging, because of better visualization of spatial relationships. As a result, the proposed surgical plans based on the 3D visualizations matched the actual performed surgery to a greater extent.</p

Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM

Weight Gain in Early Life Predicts Risk of Islet Autoimmunity in Children With a First-Degree Relative With Type 1 Diabetes

OBJECTIVE—In a prospective birth cohort study, we followed infants who had a first-degree relative with type 1 diabetes to investigate the relationship between early growth and infant feeding and the risk of islet autoimmunity

Referral rates for diagnostic testing support an incidence of permanent neonatal diabetes in three European countries of at least 1 in 260,000 live births

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Impact of analyzing fewer image frames per segment during offline volumetric radiofrequency-based intravascular ultrasound measurements of target lesions prior to percutaneous coronary interventions

In the present study, we evaluated the impact of a 50% reduction in number of image frames (every second frame) on the analysis time and variability of offline volumetric radiofrequency-based intravascular ultrasound (RF-IVUS) measurements in target lesions prior to percutaneous coronary interventions (PCI). Volumetric RF-IVUS data of vessel geometry and plaque composition are generally obtained by a semi-automated analysis process that includes time-consuming manual contour editing. A reduction in the number of frames used for volumetric analysis may speed up the analysis, but could increase measurement variability. We repeatedly performed offline volumetric analyses in RF-IVUS image sets of 20 mm-long coronary segments that contained 30 de novo lesions prior to PCI. A 50% reduction in frames decreased the analysis time significantly (from 57.5 ± 7.3 to 35.7 ± 3.7 min; P < 0.0001) while geometric and compositional RF-IVUS measurements did not differ significantly from measurements obtained from all frames. The variability between measurements on the reduced number of frames versus all frames was comparable to the intra-observer measurement variability. In target lesions prior to PCI, offline volumetric RF-IVUS analyses can be performed using a reduced number of image frames (every second frame). This reduces the time of analysis without substantially increasing measurement variability

Quantitative multi-modality imaging analysis of a fully bioresorbable stent: a head-to-head comparison between QCA, IVUS and OCT

The bioresorbable vascular stent (BVS) is totally translucent and radiolucent, leading to challenges when using conventional invasive imaging modalities. Agreement between quantitative coronary angiography (QCA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in the BVS is unknown. Forty five patients enrolled in the ABSORB cohort B1 study underwent coronary angiography, IVUS and OCT immediately post BVS implantation, and at 6 months. OCT estimated stent length accurately compared to nominal length (95% CI of the difference: −0.19; 0.37 and −0.15; 0.47 mm2 for baseline and 6 months, respectively), whereas QCA incurred consistent underestimation of the same magnitude at both time points (Pearson correlation = 0.806). IVUS yielded low accuracy (95% CI of the difference: 0.77; 3.74 and −1.15; 3.27 mm2 for baseline and 6 months, respectively), with several outliers and random variability test–retest. Minimal lumen area (MLA) decreased substantially between baseline and 6 months on QCA and OCT and only minimally on IVUS (95% CI: 0.11; 0.42). Agreement between the different imaging modalities is poor: worst agreement Videodensitometry-IVUS post-implantation (ICCa 0.289); best agreement IVUS-OCT at baseline (ICCa 0.767). All pairs deviated significantly from linearity (P < 0.01). Passing-Bablok non-parametric orthogonal regression showed constant and proportional bias between IVUS and OCT. OCT is the most accurate technique for measuring stent length, whilst QCA incurs systematic underestimation (foreshortening) and solid state IVUS incurs random error. Volumetric calculations using solid state IVUS are therefore not reliable. There is poor agreement for MLA estimation between all the imaging modalities studied, including IVUS-OCT, hence their values are not interchangeable

Interstudy reproducibility of the second generation, Fourier domain optical coherence tomography in patients with coronary artery disease and comparison with intravascular ultrasound: a study applying automated contour detection

Recently, Fourier domain OCT (FD-OCT) has been introduced for clinical use. This approach allows in vivo, high resolution (15 micron) imaging with very fast data acquisition, however, it requires brief flushing of the lumen during imaging. The reproducibility of such fast data acquisition under intracoronary flush application is poorly understood. To assess the inter-study variability of FD-OCT and to compare lumen morphometry to the established invasive imaging method, IVUS. 18 consecutive patients with coronary artery disease scheduled for PCI were included. In each target vessel a FD-OCT pullback (MGH system, light source 1,310 nm, 105 fps, pullback speed 20 mm/s) was acquired during brief (3 s) injection of X-ray contrast (flow 3 ml/s) through the guiding catheter. A second pullback was repeated under the same conditions after re-introduction of the FD OCT catheter into the coronary artery. IVUS and OCT imaging was performed in random order. FD-OCT and IVUS pullback data were analyzed using a recently developed software employing semi automated lumen contour and stent strut detection algorithms. Corresponding ROI were matched based on anatomical landmarks such as side branches and/or stent edges. Inter-study variability is presented as the absolute difference between the two pullbacks. FD-OCT showed remarkably good reproducibility. Inter-study variability in native vessels (cohort A) was very low for mean and minimal luminal area (0.10 ± 0.38, 0.19 ± 0.57 mm[superscript 2], respectively). Likewise inter-study variability was very low in stented coronary segments (cohort B) for mean lumen, mean stent, minimal luminal and minimal stent area (0.06 ± 0.08, 0.07 ± 0.10, 0.04 ± 0.09, 0.04 ± 0.10 mm[superscript 2], respectively). Comparison to IVUS morphometry revealed no significant differences. The differences between both imaging methods, OCT and IVUS, were very low for mean lumen, mean stent, minimal luminal and minimal stent area (0.10 ± 0.45, 0.10 ± 0.36, 0.26 ± 0.54, 0.05 ± 0.47 mm[superscript 2], respectively). FD-OCT shows excellent reproducibility and very low inter-study variability in both, native and stented coronary segments. No significant differences in quantitative lumen morphometry were observed between FD-OCT and IVUS. Evaluating these results suggest that FD-OCT is a reliable imaging tool to apply in longitudinal coronary artery disease studie

The effects of COVID-19 on child mental health:Biannual assessments up to April 2022 in a clinical and two general population samples

BACKGROUND: The COVID-19 pandemic has had an acute impact on child mental and social health, but long-term effects are still unclear. We examined how child mental health has developed since the start of the COVID-19 pandemic up to 2 years into the pandemic (April 2022).METHODS: We included children (age 8-18) from two general population samples (N = 222-1333 per measurement and N = 2401-13,362 for pre-covid data) and one clinical sample receiving psychiatric care (N = 334-748). Behavioral questionnaire data were assessed five times from April 2020 till April 2022 and pre-pandemic data were available for both general population samples. We collected parent-reported data on internalizing and externalizing problems with the Brief Problem Monitor and self-reported data on Anxiety, Depressive symptoms, Sleep-related impairments, Anger, Global health, and Peer relations with the Patient-Reported Outcomes Measurement Information System (PROMIS®).RESULTS: In all samples, parents reported overall increased internalizing problems, but no increases in externalizing problems, in their children. Children from the general population self-reported increased mental health problems from before to during the pandemic on all six PROMIS domains, with generally worst scores in April 2021, and scores improving toward April 2022 but not to pre-pandemic norms. Children from the clinical sample reported increased mental health problems throughout the pandemic, with generally worst scores in April 2021 or April 2022 and no improvement. We found evidence of minor age effects and no sex effects.CONCLUSIONS: Child mental health in the general population has deteriorated during the first phase of the COVID-19 pandemic, has improved since April 2021, but has not yet returned to pre-pandemic levels. Children in psychiatric care show worsening of mental health problems during the pandemic, which has not improved since. Changes in child mental health should be monitored comprehensively to inform health care and policy.</p