Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19.

Background: The impact of COVID-19 on gastrointestinal (GI) outcomes in children during the post-acute and chronic phases of the disease is not well understood. Methods: We conducted a retrospective cohort study across twenty-nine healthcare institutions from March 2020 to September 2023, including 413,455 pediatric patients with confirmed SARS-CoV-2 infection and 1,163,478 controls without infection. Infection was confirmed via polymerase chain reaction (PCR), serology, antigen tests, or clinical diagnosis of COVID-19 and related conditions. We examined the incidence of predefined GI symptoms and disorders during the post-acute (28 to 179 days post-infection) and chronic (180 to 729 days post-infection) phases. The adjusted risk ratios (aRRs) were calculated using stratified Poisson regression, with stratification based on propensity scores. Results: Our cohort comprised 1,576,933 patients, with females representing 48.0% of the sample. The analysis revealed that children with SARS-CoV-2 infection had an increased risk of developing at least one GI symptom or disorder in both the post-acute (8.64% vs. 6.85%; aRR 1.25, 95% CI 1.24-1.27) and chronic phases (12.60% vs. 9.47%; aRR 1.28, 95% CI 1.26-1.30) compared to uninfected peers. Specifically, the risk of abdominal pain was higher in COVID-19 positive patients during the post-acute phase (2.54% vs. 2.06%; aRR 1.14, 95% CI 1.11-1.17) and chronic phase (4.57% vs. 3.40%; aRR 1.24, 95% CI 1.22-1.27). Interpretation: Children with a history of SARS-CoV-2 infection are at an increased risk of GI symptoms and disorders during the post-acute and chronic phases of COVID-19. This highlights the need for ongoing monitoring and management of GI outcomes in this population.

Corrigendum: Comparison of indocyanine green angiography and swept-source wide-field optical coherence tomography angiography in posterior uveitis.

[This corrects the article DOI: 10.3389/fmed.2022.853315.].

Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

Post-Acute Cardiovascular Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Project.

Background: The risk of cardiovascular outcomes in the post-acute phase of SARS-CoV-2 infection has been quantified among adults and children. This paper aimed to assess a multitude of cardiac signs, symptoms, and conditions, as well as focused on patients with and without congenital heart defects (CHDs), to provide a more comprehensive assessment of the post-acute cardiovascular outcomes among children and adolescents after COVID-19. Methods: This retrospective cohort study used data from the RECOVER consortium comprising 19 US children's hospitals and health institutions between March 2020 and September 2023. Every participant had at least a six-month follow-up after cohort entry. Absolute risks of incident post-acute COVID-19 sequelae were reported. Relative risks (RRs) were calculated by contrasting COVID-19-positive with COVID-19-negative groups using a Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through propensity scoring stratification. Results: A total of 1,213,322 individuals under 21 years old (mean[SD] age, 7.75[6.11] years; 623,806 male [51.4%]) were included. The absolute rate of any post-acute cardiovascular outcome in this study was 2.32% in COVID-19 positive and 1.38% in negative groups. Patients with CHD post-SARS-CoV-2 infection showed increased risks of any cardiovascular outcome (RR, 1.63; 95% confidence interval (CI), 1.47-1.80), including increased risks of 11 of 18 post-acute sequelae in hypertension, arrhythmias (atrial fibrillation and ventricular arrhythmias), myocarditis, other cardiac disorders (heart failure, cardiomyopathy, and cardiac arrest), thrombotic disorders (thrombophlebitis and thromboembolism), and cardiovascular-related symptoms (chest pain and palpitations). Those without CHDs also experienced heightened cardiovascular risks after SARS-CoV-2 infection (RR, 1.63; 95% CI, 1.57-1.69), covering 14 of 18 conditions in hypertension, arrhythmias (ventricular arrhythmias and premature atrial or ventricular contractions), inflammatory heart disease (pericarditis and myocarditis), other cardiac disorders (heart failure, cardiomyopathy, cardiac arrest, and cardiogenic shock), thrombotic disorders (pulmonary embolism and thromboembolism), and cardiovascular-related symptoms (chest pain, palpitations, and syncope). Conclusions: Both children with and without CHDs showed increased risks for a variety of cardiovascular outcomes after SARS-CoV-2 infection, underscoring the need for targeted monitoring and management in the post-acute phase.

Gender differences in retinal diseases: A review.

Gender medicine is a medical specialty that addresses gender differences in health and disease. Traditionally, medical research and clinical practice have often been focused on male subjects and patients. As a result, gender differences in medicine have been overlooked. Gender medicine considers the biological, psychological, and social differences between the genders and how these differences affect the development, diagnosis, treatment, and prevention of disease. For ophthalmological diseases epidemiological differences are known. However, there are not yet any gender-based ophthalmic treatment approaches for women and men. This review provides an overview of gender differences in retinal diseases. It is intended to make ophthalmologists, especially retinologists, more sensitive to the topic of gender medicine. The goal is to enhance comprehension of these aspects by highlighting fundamental gender differences. Integrating gender medicine into ophthalmological practice helps promote personalized and gender-responsive health care and makes medical research more accurate and relevant to the entire population.

Racial and ethnic disparities in diagnostic imaging for child physical abuse.

IMPORTANCE: Racial bias may affect occult injury testing decisions for children with concern for abuse. OBJECTIVES: To determine the association of race on occult injury testing decisions at children's hospitals. DESIGN: In this retrospective study, we measured disparities in: (1) the proportion of visits for which indicated diagnostic imaging studies for child abuse were obtained; (2) the proportion of positive tests. SETTING: The Pediatric Health Information System (PHIS) administrative database encompassing 49 tertiary children's hospitals during 2017-2019. PARTICIPANTS: We built three cohorts based on guidelines for diagnostic testing for child abuse: infants with traumatic brain injury (TBI; n = 1952), children <2 years old with extremity fracture (n = 20,842), and children <2 years old who received a skeletal survey (SS; n = 13,081). MAIN OUTCOMES AND MEASURES: For each group we measured: (1) the odds of receiving a specific guideline-recommended diagnostic imaging study; (2) among those with the indicated imaging study, the odds of an abuse-related injury diagnosis. We calculated both unadjusted and adjusted odds ratios (AOR) by race and ethnicity, adjusting for sex, age in months, payor, and hospital. RESULTS: In infants with TBI, the odds of receiving a SS did not differ by racial group. Among those with a SS, the odds of rib fracture were higher for non-Hispanic Black than Hispanic (AOR 2.05 (CI 1.31, 3.2)) and non-Hispanic White (AOR 1.57 (CI 1.11, 2.32)) patients. In children with extremity fractures, the odds of receiving a SS were higher for non-Hispanic Black than Hispanic and non-Hispanic White patients (AOR 1.97 (CI 1.74, 2.23)); (AOR 1.17 (CI 1.05, 1.31)), respectively, and lower for Hispanic than non-Hispanic White patients (AOR 0.59 (CI 0.53, 0.67)). Among those receiving a SS, the rate of rib fractures did not differ by race. In children with skeletal surveys, the odds of receiving neuroimaging did not differ by race. Among those with neuroimaging, the odds of a non-fracture, non-concussion TBI were lower in non-Hispanic Black than Hispanic patients (AOR 0.7 (CI 0.57, 0.86)) and were higher among Hispanic than non-Hispanic White patients (AOR 1.23 (CI 1.02, 1.47)). CONCLUSIONS AND RELEVANCE: We did not identify a consistent pattern of race-based disparities in occult injury testing when considering the concurrent yield for abuse-related injuries.

Unwinding of Continuous Medicaid Coverage Among Patients at Community Health Centers.

This retrospective cohort study uses data from the Accelerating Data Value Across a National Community Health Center Network to assess patterns of Medicaid disenrollment during the first 6 months after the end of continuous enrollment.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling.

Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.

Assessment of choriocapillaris and choroidal vascular changes in posterior uveitis using swept-source wide-field optical coherence tomography angiography.

PURPOSE: To evaluate choriocapillaris (CC) and choroidal vascular changes in patients with posterior uveitis using swept-source (SS) wide-field optical coherence tomography angiography (OCTA). METHOD: Consecutive patients with posterior uveitis were evaluated using 3×3 mm and 12×12 mm OCTA scan patterns and montage images of 5×12×12 mm or 2×15×9 mm, covering approximately 70°-90° of the retina. The images were quantitatively and qualitatively analysed and compared with healthy controls. RESULTS: Eighty-six eyes of 56 patients with posterior uveitis (mean age 45.2±19.9 years; 58.9% female), and 38 eyes of 19 age-matched healthy controls (57.9% female) were included. The mean perfusion density (PD) in 3×3 mm and 12×12 mm CC scans was significantly lower in eyes with posterior uveitis compared with those of healthy controls. However, no significant difference in the mean PD of choroidal scans was found comparing eyes with posterior uveitis and healthy controls. The mean PD in eyes with active disease was significantly higher compared with the inactive eyes on 12×12 mm choroidal scans (55.61% vs 51.25%, p=0.02), while no difference was found in the CC slabs. CONCLUSION: CC and choroidal assessment using OCTA provides useful information in patients with posterior uveitis. SS-OCTA metrics of the CC and choroidal slabs are promising tools in uveitis patients in the future. TRIAL REGISTRATION NUMBER: NCT02811536.

RETINAL TECTONICS AFTER MACULAR PUCKER SURGERY: Thickness Changes and En Face Displacement Recovery.

PURPOSE: To study visual function, retinal layer thickness changes, and tangential displacement after pars plana vitrectomy for epiretinal membrane. METHODS: Retrospective series of patients undergoing pars plana vitrectomy for epiretinal membrane, with 6-month follow-up including best-corrected visual acuity, optical coherence tomography, M-charts, epiretinal membrane grading, and infrared fundus photograph at time 0 (T0, preop) at months 1 (T1), 3 (T3), and 6 (T6) postop (±1 week). Retinal layer thickness and tangential ( en face ) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En face displacement was calculated as optical flow of consecutive images. RESULTS: Average best-corrected visual acuity improved from 0.28 ± 0.08 logarithm of Minimum Angle of Resolution at T0 to 0.16 ± 0.25 at T6 ( P = 0.05), best-corrected visual acuity improvement correlated with best corrected visual acuity (BCVA) at T0 ( P < 0.001). Vertical metamorphopsia decreased from 1.33° ± 0.70° at T0 to 0.82° ± 0.69° at T6 ( P < 0.05). Foveal thickness reduced from 453 ± 53 µ m at T0 to 359 ± 31 µ m at T6 ( P < 0.05) and reduction correlated with best-corrected visual acuity improvement ( P < 0.05). Foveal layers decreased ( P < 0.05) in all cases. The mean en face deformation was 155.82 ± 50.17 µ m and mostly occurred in the first month: T0-T1 displacement was 83.59 ± 30.28 µ m, T1-T3 was 36.28 ± 14.45 µ m, while T3-T6 was 39.11 ± 22.79 µ m ( P < 0.001) on average. Perifoveal and parafoveal deformation correlated with optical coherence tomography foveal thickness reduction at all time intervals (1, 3, and 6 months: P < 0.01). CONCLUSION: Epiretinal membrane peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en face and in-depth changes correlate with visual function.

Agents of Socialization, Anxiety, College Women, and Fear of Rape.

This paper examines the impact of messages about sexual danger women receive from parents, peers, media, school officials, and past victimization on fear of stranger and acquaintance rape. Analyzing survey data for 630 undergraduate women, we find that parental warnings, internalized mean world view, university crime alerts, and being more prone to anxiety are significant predictors of fear of rape across models, while effects of media and victimization are limited. When high and low proneness to anxiety subgroups are considered separately, numerous differences emerge. Results suggest the need to include formal measures of anxiety in future fear of crime research.

LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

MULTIPLE EVANESCENT WHITE DOT SYNDROME FROM A PATIENT'S PERSPECTIVE.

PURPOSE: Multiple evanescent white dot syndrome is a self-limiting inflammatory condition of the outer retina. Only little information is available how patients experience their symptoms. METHOD: We report a case of a 28-year-old male graphic designer with multiple evanescent white dot syndrome, who precisely illustrated the development and course of the characteristic symptoms while looking at the ceiling, at a face and on his phone. RESULT: At onset, the scotoma was sparking/shiny and appeared on the temporal field of view, consistent with an enlarged blind spot. Over the course of the disease, the scotoma decreased in intensity and moved superiorly and nasally until it completely faded. CONCLUSION: Illustrations from a patient's perspective over the course of the disease can be beneficial for physicians and other multiple evanescent white dot syndrome patients for a better understanding and monitoring of their disease.

Behavioral Development of Pediatric Exotic Pets and Practical Applications.

The discovery of epigenetics and the interaction between genes and the environment have moved our understanding of how animal behavior develops from gestation to adulthood, and even throughout generations, to a new level. Studying the natural biology of exotic pets is key to providing them with a rich social and physical environment that will encourage species-specific behaviors. Combining parent-raising with appropriately timed human handling is likely to result in individuals with more resilience to stress. Using operant conditioning techniques early in life to train the animals' basic behaviors gives them control over their environment, empowering them through their social interactions.

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents.

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.

Testing the Effectiveness of the "Smelly" Elephant Repellent in Controlled Experiments in Semi-Captive Asian and African Savanna Elephants.

Crop-raiding by elephants is one of the most prevalent forms of human-elephant conflict and is increasing with the spread of agriculture into wildlife range areas. As the magnitude of conflicts between people and elephants increases across Africa and Asia, mitigating and reducing the impacts of elephant crop-raiding has become a major focus of conservation intervention. In this study, we tested the responses of semi-captive elephants to the "smelly" elephant repellent, a novel olfactory crop-raiding mitigation method. At two trial sites, in Zambia and Thailand, African elephants (Loxodonta africana) and Asian elephants (Elephas maximus) were exposed to the repellent, in order to test whether or not they entered an area protected by the repellent and whether they ate the food provided. The repellent elicited clear reactions from both study groups of elephants compared to control conditions. Generalised linear models revealed that the elephants were more alert, sniffed more, and vocalised more when they encountered the repellent. Although the repellent triggered a response, it did not prevent elephants from entering plots protected by the repellent or from eating crops, unlike in trials conducted with wild elephants. Personality played a role in responses towards the repellent, as the elephants that entered the experimental plots were bolder and more curious individuals. We conclude that, although captive environments provide controlled settings for experimental testing, the ecological validity of testing human-elephant conflict mitigation methods with captive wildlife should be strongly considered. This study also shows that understanding animal behaviour is essential for improving human-elephant coexistence and for designing deterrence mechanisms. Appreciating personality traits in elephants, especially amongst "problem" elephants who have a greater propensity to crop raid, could lead to the design of new mitigation methods designed to target these individuals.