A COVID-19 vaccination program for high-risk children aged 12-17 years in Curacao.

Objective: This study aimed to describe and critically evaluate the COVID-19 vaccination program for high-risk children in Curacao and provide information about important factors such as parents' vaccination hesitancy and effective strategies for communicating and delivering information about vaccination. Methods: This was a cross-sectional study. It was important to identify children aged 12-17 years who were at high risk of severe COVID-19 infection because of the limited medical facilities on the island; children considered to be at high risk were those with diseases such as obesity, hypertension or diabetes mellitus type 2. These children or their caregivers were invited by their pediatricians to be vaccinated as part of a program run by the Public Health Department of Curacao. These high-risk patients were vaccinated between 30 May 2021 and 25 February 2022 in designated child-friendly spaces, with a pediatrician present for guidance and reassurance. Children received the Pfizer-BioNTech COVID-19 vaccine at the recommended dose for their age. The primary outcome was a description and evaluation of the attendance for vaccination. The secondary outcomes were side effects after vaccination for the age groups 12-15 years and 16-17 years. Reasons for refusal or nonadherence were also registered. Results: Altogether 51% (24/47) of those aged 16-17 years who were invited were vaccinated compared with 42% (26/69) of those aged 12-15 years who were invited. Altogether, 46% of these high-risk children were vaccinated compared with 48% of children aged 12-17 years without risk factors. In our population, most patients did not experience any side effects and if they did, the side effects were mild. No cases of myocarditis or pericarditis were observed. A lack of trust in the vaccine and a lack of prioritization of vaccination when scheduling daily activities were important factors in refusal and nonadherence. Conclusions: To organize a successful vaccination program in a small community with limited resources for treating high-risk children it is crucial for medical professionals to provide reliable information. Public health initiatives should focus on assuaging parents' fears about vaccines. In addition, ensuring there is good cooperation between doctors and the Public Health Department can help to make implementation successful. Finally, involving pediatricians and using dedicated areas for vaccinating children can help build trust with parents and caregivers.

Genetic care in geographically isolated small island communities: 8 years of experience in the Dutch Caribbean.

Worldwide, there are large inequalities in genetic service delivery. In 2011, we established a bi-annual joint pediatric-genetics clinic with a visiting clinical geneticist in the Dutch Caribbean. This retrospective study evaluates the yield of diagnostic testing and the clinical utility of a diagnosis for patients with rare diseases on these relatively isolated, resource-limited islands. A total of 331 patients that were referred to the clinical geneticist between November 2011 and November 2019 and had genetic testing were included in this study. A total of 508 genetic tests were performed on these patients. Microarray, next-generation sequencing gene panels, and single-gene analyses were the most frequently performed genetic tests. A molecularly confirmed diagnosis was established in 33% of patients (n = 108). Most diagnosed patients had single nucleotide variants or small insertions and/or deletions (48%) or copy number variants (34%). Molecular diagnostic yield was highest in patients referred for seizures and developmental delay/intellectual disability. The genetic diagnosis had an impact on clinical management in 52% of patients. Referrals to other health professionals and changes in therapy were the most frequently reported clinical consequences. In conclusion, despite limited financial resources, our genetics service resulted in a reasonably high molecular diagnostic yield. Even in this resource-limited setting, a genetic diagnosis had an impact on clinical management for the majority of patients. Our approach with a visiting clinical geneticist may be an example for others who are developing genetic services in similar settings.

Clinical validation of 2D perfusion angiography using Syngo iFlow software during peripheral arterial interventions.

OBJECTIVE: Endovascular surgery is an important treatment modality in peripheral arterial disease. Digital subtraction angiography is the standard post revascularisation diagnostic tool to locate lesions and to evaluate the effect of an intervention. However, interpretation of digital subtraction angiography images is subjective and it is difficult to determine whether revascularisation has been sufficient for clinical improvement. A new technique is 2D perfusion angiography, which creates a 2D colour map and time density curve from the digital subtraction angiography scan for an objective evaluation of the results. However, its clinical relevance is unknown. The aim is to evaluate the association between 2D perfusion angiography parameters and clinical outcome after peripheral arterial interventions. METHODS: In this retrospective study, post revascularisation angiographic data and clinical data were reviewed of patients who underwent treatment of femoral-popliteal or femoral-tibial arteries. The outcome was assessed at three time points using three classification systems for peripheral arterial disease: Fontaine classification, American Medical Association whole person impairment classification (AMA) and average wound, ischemia, foot infection score. Post revascularisation angiographic data consisted of time density curves of the foot and lower leg which were extracted from the Syngo iFlow system (Siemens Healthineers). For each time density curve, five descriptive parameters were calculated: time of arrival, time to peak, mean transit time, wash-in rate and area under the curve. The association between the time density curve parameters and peripheral arterial disease classification systems was assessed using a regression analysis. RESULTS: Between July 2016 and December 2018, 103 patients underwent peripheral endovascular interventions in the hybrid operating room; 39 patients were suitable for analysis, of which 28 patients underwent digital subtraction angiography of the lower leg, 3 patients underwent digital subtraction angiography of the foot and 8 patients underwent digital subtraction angiography of both regions. Limited significant relations were found for time of arrival with Fontainde classification (B = 0.806, p = 0.043) and area under the curve with AMA classification (B = -0.027, p = 0.047). CONCLUSION: In this retrospective study, time density curve parameters (time of arrival and area under the curve), measured in the lower leg, showed a limited significant association with two classification systems for peripheral arterial disease. Future prospective studies to determine the clinical relevance of this 2D perfusion angiography method should focus on standardisation of angiography protocols and comparison of pre- and post-intervention parameters.

Characterization of anti-EBA175RIII-V in asymptomatic adults and children living in communities in the Greater Accra Region of Ghana with varying malaria transmission intensities.

BACKGROUND: Antibodies against Region III-V of the erythrocyte binding antigen (EBA) 175 (EBA175RIII-V) have been suggested to provide protection from malaria in a natural infection. However, the quality and quantity of naturally induced antibodies to EBA175RIII-V has not been fully characterized in different cohorts of Ghanaians. This study sought to determine the characteristics of antibodies against EBA175RIII-V in asymptomatic adults and children living in two communities of varying P. falciparum parasite prevalence in southern Ghana. METHODS: Microscopic evaluation of thick and thin blood smears was used to identify asymptomatic Plasmodium falciparum carriage and indirect enzyme linked immunosorbent (ELISA) used to assess antibody concentrations and avidity. RESULTS: Parasite carriage estimated by microscopy in Obom was 35.6% as opposed to 3.5% in Asutsuare. Levels of IgG, IgG1, IgG2, IgG3 and IgG4 against EBA175RIII-V in the participants from Obom were significantly higher (P < 0.05, Dunn's Multiple Comparison test) than those in Asutsuare. However the relative avidity of IgG antibodies against EBA175RIII-V was significantly higher (P < 0.0001, Mann Whitney test) in Asutsuare than in Obom. CONCLUSIONS: People living in communities with limited exposure to P. falciparum parasites have low quantities of high avidity antibodies against EBA175RIII-V whilst people living in communities with high exposure to the parasites have high quantities of age-dependent but low avidity antibodies against EBA175RIII-V.

FDG-PET/CT in the management of lymphomas: current status and future directions.

FDG-PET/CT is the current state-of-the-art imaging in lymphoma and plays a central role in treatment decisions. At diagnosis, accurate staging is crucial for appropriate therapy selection: FDG-PET/CT can identify areas of lymphoma missed by CT alone and avoid under-treatment of patients with advanced disease stage who would have been misclassified as having limited stage disease by CT. Particularly in Hodgkin lymphoma, positive interim FDG-PET/CT scans are adversely prognostic for clinical outcomes and can inform PET-adapted treatment strategies, but such data are less consistent in diffuse large B-cell lymphoma. The use of quantitative FDG-PET/CT metrics using metabolic tumour volume, possibly in combination with other biomarkers, may better define prognostic subgroups and thus facilitate better treatment selection. After chemotherapy, FDG-PET/CT response is predictive of outcome and may identify a subgroup who benefit from consolidative radiotherapy. Novel therapies, in particular immunotherapies, exhibit different response patterns than conventional chemotherapy, which has led to modified response criteria that take into account the risk of transient pseudo-progression. In relapsed lymphoma, FDG-PET/CT after second-line therapy and prior to high-dose therapy is also strongly associated with outcome and may be used to guide intensity of salvage therapy in relapsed Hodgkin lymphoma. Currently, FDG-PET/CT has no role in the routine follow-up after complete metabolic response to therapy, but it remains a powerful tool for excluding relapse if patients develop clinical features suggestive of disease relapse. In conclusion, FDG-PET/CT plays major roles in the various phases of management of lymphoma and constitutes a step towards the pursuit of personalized treatment.

Late Radiological and Clinical Outcomes of Traumatic Thoracic Aortic Injury Managed with Thoracic Endovascular Aortic Repair.

PURPOSE: Patients treated with thoracic endovascular aortic repair (TEVAR) for traumatic thoracic aortic injury (TTAI) are often young and data on long-term durability of this treatment is not widely documented. The aims of this study were to report the New Zealand (NZ) national experience of TEVAR and to assess the durability of late outcomes and radiological follow-up of patients treated for TTAI. METHODS: Consecutive patients treated with TEVAR during a 12-year period from all tertiary centers in NZ were included. Early (30-day), late survival and radiological imaging data were recorded to document late graft-related complications and re-interventions. RESULTS: 88 patients with a median (range) age of 35 (15-87) year and 63 (71.6 %) males were included. Eleven patients (12.5 %) died within 30 days, of which three were aortic related deaths. The median (range) follow-up was 76.3 (0.3-164.6) months. Six (7.8 %) patients died during the follow-up period due to non-aortic-related causes. Nine (11.5 %) patients were lost to follow-up of which three emigrated overseas. Of those on surveillance, two patients required TEVAR re-intervention to previously treated aortic segments; one for a type 1b endoleak and the other for a symptomatic pseudo-coarctation. Both were treated successfully with a TEVAR. CONCLUSIONS: This multicenter study suggests that TEVAR is a durable option for treatment of traumatic thoracic aortic injury. Although, stent graft complications were uncommon, but when it occurred, it leads to re-intervention. Further radiological follow-up is required particularly in young patient to document late aortic/stent complications.

Population-based analysis of the impact and generalizability of the NSABP-B24 study on endocrine therapy for patients with ductal carcinoma in situ of the breast.

BACKGROUND: In 1999, the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B24 trial demonstrated that tamoxifen reduced relapse risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and radiotherapy (RT). In 2002, Allred's subgroup analysis showed that tamoxifen mainly benefitted estrogen receptor (ER)-positive disease. This study evaluates the impact and generalizability of these trial findings at the population level. PATIENTS AND METHODS: From 1989 to 2009, 2061 women with DCIS underwent BCS + RT in British Columbia. The following cohorts were analyzed: (1) pre-NSABP-B24 era (1989-1998, N = 417); (2) post-NSABP-B24 era (2000-2009, N = 1548). Cohort 2 was further divided into pre- and post-Allred eras. RESULTS: Endocrine therapy (ET) was used in 404/2061 (20%) patients. Median age of patients treated with compared with without ET, was 53 versus 57 years, (P < 0.0005). One of 417 (0.2%) versus 399/1548 (26%) patients took ET before versus after NSABP-B24. Among the post-Allred era cohort treated with ET (N = 227), tumors were ER-positive in 65%, ER-negative in 1%, and ER-unknown in 33%; whereas of those treated without ET (N = 801), ER was positive in 43%, negative in 15%, and unknown in 42% (P < 0.0005). On multivariable analysis of the post-NSABP-B24 era, ET was associated with improved event-free survival (EFS) (hazard ratio 0.6; P = 0.02); 5-year EFS were 96.9% with ET versus 94.5% without ET. CONCLUSIONS: ET use in DCIS patients treated with BCS + RT increased significantly after the NSABP-B24 study. ER+ disease and younger age were associated with increased ET use. ET was associated with improved EFS, confirming the generalizability of trial data at a population level.

Opacification of the middle ear and mastoid: imaging findings and clues to differential diagnosis.

Opacification of the middle ear and mastoid represents a spectrum of inflammatory, neoplastic, vascular, fibro-osseous, and traumatic changes. This article reviews the most important clinical and pathological characteristics, emphasizing CT and MRI findings. Knowledge of subtle patterns of middle ear and mastoid opacification at CT and MRI provide guidance towards the correct diagnosis.

A Deep Learning System to Predict Epithelial Dysplasia in Oral Leukoplakia.

Oral leukoplakia (OL) has an inherent disposition to develop oral cancer. OL with epithelial dysplasia (OED) is significantly likely to undergo malignant transformation; however, routine OED assessment is invasive and challenging. This study investigated whether a deep learning (DL) model can predict dysplasia probability among patients with leukoplakia using oral photographs. In addition, we assessed the performance of the DL model in comparison with clinicians' ratings and in providing decision support on dysplasia assessment. Retrospective images of leukoplakia taken before biopsy/histopathology were obtained to construct the DL model (n = 2,073). OED status following histopathology was used as the gold standard for all images. We first developed, fine-tuned, and internally validated a DL architecture with an EfficientNet-B2 backbone that outputs the predicted probability of OED, OED status, and regions-of-interest heat maps. Then, we tested the performance of the DL model on a temporal cohort before geographical validation. We also assessed the model's performance at external validation with opinions provided by human raters on OED status. Performance evaluation included discrimination, calibration, and potential net benefit. The DL model achieved good Brier scores, areas under the curve, and balanced accuracies of 0.124 (0.079-0.169), 0.882 (0.838-0.926), and 81.8% (76.5-87.1) at testing and 0.146 (0.112-0.18), 0.828 (0.792-0.864), and 76.4% (72.3-80.5) at external validation, respectively. In addition, the model had a higher potential net benefit in selecting patients with OL for biopsy/histopathology during OED assessment than when biopsies were performed for all patients. External validation also showed that the DL model had better accuracy than 92.3% (24/26) of human raters in classifying the OED status of leukoplakia from oral images (balanced accuracy: 54.8%-79.7%). Overall, the photograph-based intelligent model can predict OED probability and status in leukoplakia with good calibration and discrimination, which shows potential for decision support to select patients for biopsy/histopathology, obviate unnecessary biopsy, and assist in patient self-monitoring.

COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

Alterations in basement membrane immunoreactivity of the diabetic retina in three diabetic mouse models.

BACKGROUND: The mouse retina contains three kinds of basement membrane (BM) structures; the inner limiting membrane (ILM), Bruch's membrane (BrM), and the BM surrounding the capillaries. We aimed to investigate possible variations of individual BM components and to detect effects caused by diabetes in three different diabetic mouse models. METHODS: After 4 and 6 months of diabetes (defined by blood glucose > 250 mg/dl), we analyzed by immunohistochemistry the laminin, collagen IV, and nidogen-1 and nidogen-2 protein composition of the BMs obtained from diabetic and non-diabetic Leptin-receptor deficient (db/db) mice and insulin receptor (IR)/insulin receptor substrate-1 (IRS-1) double heterozygous knockout mice. In addition, C57BL/6 J mice were rendered diabetic by intraperitoneal injections of streptozotocin (STZ). RESULTS: All analyzed BM proteins were detected in all of the three BMs with the exception of collagen IV, which was not detectable in the ILM of db/db mice and IR/IRS-1 mice. We present the first analysis of nidogen expression in diabetic BM. The staining patterns did not differ between the type-1 diabetic model (STZ) or the type-2 diabetic models (db/db and IR/IRS-1) and the wild-type controls, with only one exception: both the db/db mice and the IR/IRS-1 mice but not the STZ mice showed a decreased nidogen-1 immunoreactivity in the BrM after 4 months of diabetes, but not after 6 months. CONCLUSIONS: The BMs in the three mouse strains differ with regard to protein immunoreactivity in the inner limiting membrane. Changes in BM composition may affect both the assembly and the function of the retinal BM. However, there are no marked differences in the BM composition between type-1 and type-2 diabetes. These results provide evidence for BM remodelling during diabetic retinopathy.