Factors associated with elevated SARS-CoV-2 immune response in children and adolescents.

Background: Understanding the distinct immunologic responses to SARS-CoV-2 infection among pediatric populations is pivotal in navigating the COVID-19 pandemic and informing future public health strategies. This study aimed to identify factors associated with heightened antibody responses in children and adolescents to identify potential unique immune dynamics in this population. Methods: Data collected between July and December 2023 from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a statewide prospective population-based antibody survey among 1-to-19-year-old participants, were analyzed. Each participant had the following data available for analysis: (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for Nucleocapsid protein antibodies (Roche N-test), (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test), and (3) self-reported antigen/PCR COVID-19 test results, vaccination, and health status. Statistical analysis identified associations between participant characteristics and spike antibody quartile group. Results: The analytical sample consisted of 411 participants (mean age 12.2 years, 50.6% female). Spike antibody values ranged from a low of 6.3 U/ml in the lowest quartile to a maximum of 203,132.0 U/ml in the highest quartile in the aggregate sample. Older age at test date (OR = 1.22, 95% CI: 1.12, 1.35, p < .001) and vaccination status (primary series/partially vaccinated, one or multiple boosters) showed significantly higher odds of being in the highest spike antibody quartile compared to younger age and unvaccinated status. Conversely, fewer days since the last immunity challenge showed decreased odds (OR = 0.98, 95% CI: 0.96, 0.99, p = 0.002) of being in the highest spike antibody quartile vs. more days since last immunity challenge. Additionally, one out of every three COVID-19 infections were asymptomatic. Conclusions: Older age, duration since the last immunity challenge (vaccine or infection), and vaccination status were associated with heightened spike antibody responses, highlighting the nuanced immune dynamics in the pediatric population. A significant proportion of children/adolescents continue to have asymptomatic infection, which has important public health implications.

Machine learning progressive CKD risk prediction model is associated with CKD-mineral bone disorder.

Background: Recently, we developed the machine learning (ML)-based Progressive CKD Risk Classifier (PCRC), which accurately predicts CKD progression within 5 years. While its performance is robust, it is unknown whether PCRC categorization is associated with CKD-mineral bone disorder (CKD-MBD), a critical, yet under-recognized, downstream consequence. Therefore, we aimed to 1) survey real-world testing utilization data for CKD-MBD and 2) evaluate ML-based PCRC categorization with CKD-MBD. Methods: The cohort study utilized deidentified data from a US laboratory outpatient network, composed of 330,238 outpatients, over 5 years. The main outcomes were: 1) Laboratory testing utilization of eGFR, urine albumin creatinine ratio (UACR), parathyroid hormone (PTH), calcium, phosphate; and 2) PCRC categorization and biochemical abnormalities associated with CKD-MBD over 5 years. Results: We identified significant under-utilization of laboratory testing for UACR, phosphate and PTH, which ranged from -40 % to -100 % against the minimum standard-of-care. At five years, the CKD progression group, as predicted by the PCRC, was associated with 15.5 % increase in phosphate (P value <<0.01) and 94.9 % increase in PTH (P value <<0.01), consistent with CKD-MBD. Conclusions: We identified significant under-utilization of laboratory testing for CKD-MBD. Moreover, we demonstrated that CKD progression, as predicted by the PCRC, is associated with CKD-MBD, several years in advance of disease. To our knowledge, this investigation is the first to examine the role of predictive analytics for CKD progression on mineral bone disorder. While further studies are required, these findings have the potential to advance AI/ML-based risk stratification and treatment of CKD and CKD-MBD.

Prozone masks elevated SARS-CoV-2 antibody level measurements.

We report a prozone effect in measurement of SARS-CoV-2 spike protein antibody levels from an antibody surveillance program. Briefly, the prozone effect occurs in immunoassays when excessively high antibody concentration disrupts the immune complex formation, resulting in a spuriously low reported result. Following participant inquiries, we observed anomalously low measurement of SARS-CoV-2 spike protein antibody levels using the Roche Elecsys® Anti-SARS-CoV-2 S immunoassay from participants in the Texas Coronavirus Antibody Research survey (Texas CARES), an ongoing prospective, longitudinal antibody surveillance program. In July, 2022, samples were collected from ten participants with anomalously low results for serial dilution studies, and a prozone effect was confirmed. From October, 2022 to March, 2023, serial dilution of samples detected 74 additional cases of prozone out of 1,720 participants' samples. Prozone effect may affect clinical management of at-risk populations repeatedly exposed to SARS-CoV-2 spike protein through multiple immunizations or serial infections, making awareness and mitigation of this issue paramount.

CKD Progression Prediction in a Diverse US Population: A Machine-Learning Model.

Rationale & Objective: Chronic kidney disease (CKD) is a major cause of morbidity and mortality. To date, there are no widely used machine-learning models that can predict progressive CKD across the entire disease spectrum, including the earliest stages. The objective of this study was to use readily available demographic and laboratory data from Sonic Healthcare USA laboratories to train and test the performance of machine learning-based predictive risk models for CKD progression. Study Design: Retrospective observational study. Setting & Participants: The study population was composed of deidentified laboratory information services data procured from a large US outpatient laboratory network. The retrospective data set included 110,264 adult patients over a 5-year period with initial estimated glomerular filtration rate (eGFR) values between 15-89 mL/min/1.73 m2. Predictors: Patient demographic and laboratory characteristics. Outcomes: Accelerated (ie, >30%) eGFR decline associated with CKD progression within 5 years. Analytical Approach: Machine-learning models were developed using random forest survival methods, with laboratory-based risk factors analyzed as potential predictors of significant eGFR decline. Results: The 7-variable risk classifier model accurately predicted an eGFR decline of >30% within 5 years and achieved an area under the curve receiver-operator characteristic of 0.85. The most important predictor of progressive decline in kidney function was the eGFR slope. Other key contributors to the model included initial eGFR, urine albumin-creatinine ratio, serum albumin (initial and slope), age, and sex. Limitations: The cohort study did not evaluate the role of clinical variables (eg, blood pressure) on the performance of the model. Conclusions: Our progressive CKD classifier accurately predicts significant eGFR decline in patients with early, mid, and advanced disease using readily obtainable laboratory data. Although prospective studies are warranted, our results support the clinical utility of the model to improve timely recognition and optimal management for patients at risk for CKD progression. Plain-Language Summary: Defined by a significant decrease in estimated glomerular filtration rate (eGFR), chronic kidney disease (CKD) progression is strongly associated with kidney failure. However, to date, there are no broadly used resources that can predict this clinically significant event. Using machine-learning techniques on a diverse US population, this cohort study aimed to address this deficiency and found that a 5-year risk prediction model for CKD progression was accurate. The most important predictor of progressive decline in kidney function was the eGFR slope, followed by the urine albumin-creatinine ratio and serum albumin slope. Although further study is warranted, the results showed that a machine-learning model using readily obtainable laboratory information accurately predicts CKD progression, which may inform clinical diagnosis and management for this at-risk population.

Incidence and Predictors of Breakthrough and Severe Breakthrough Infections of SARS-CoV-2 After Primary Series Vaccination in Adults: A Population-Based Survey of 22 575 Participants.

BACKGROUND: Breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well documented. The current study estimates breakthrough incidence across pandemic waves, and evaluates predictors of breakthrough and severe breakthrough infections (defined as those requiring hospitalization). METHODS: In total, 89 762 participants underwent longitudinal antibody surveillance. Incidence rates were calculated using total person-days contributed. Bias-corrected and age-adjusted logistic regression determined multivariable predictors of breakthrough and severe breakthrough infection, respectively. RESULTS: The incidence was 0.45 (95% confidence interval [CI], .38-.50) during pre-Delta, 2.80 (95% CI, 2.25-3.14) during Delta, and 11.2 (95% CI, 8.80-12.95) during Omicron, per 10 000 person-days. Factors associated with elevated odds of breakthrough included Hispanic ethnicity (vs non-Hispanic white, OR = 1.243; 95% CI, 1.073-1.441), larger household size (OR = 1.251 [95% CI, 1.048-1.494] for 3-5 vs 1 and OR = 1.726 [95% CI, 1.317-2.262] for more than 5 vs 1 person), rural versus urban living (OR = 1.383; 95% CI, 1.122-1.704), receiving Pfizer or Johnson & Johnson versus Moderna, and multiple comorbidities. Of the 1700 breakthrough infections, 1665 reported on severity; 112 (6.73%) were severe. Higher body mass index, Hispanic ethnicity, vaccine type, asthma, and hypertension predicted severe breakthroughs. CONCLUSIONS: Breakthrough infection was 4-25 times more common during the Omicron-dominant wave versus earlier waves. Higher burden of severe breakthrough infections was identified in subgroups.

Antibody Duration After Infection From SARS-CoV-2 in the Texas Coronavirus Antibody Response Survey.

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not).

Case Report of Conjunctival Melanoacanthoma.

PURPOSE: The purpose of this study was to describe a case of conjunctival melanoacanthoma, an exceedingly rare condition that has yet to be fully described in the literature. METHODS: Melanoacanthomas are most commonly seen on the skin or oral mucosa and are believed to result from local irritation or trauma. A 34-year-old Hispanic man presented with a painless, solitary, pigmented conjunctival lesion, in addition to bilateral pterygia suggesting chronic solar damage. The lesion was excised and sent for analysis. RESULTS: Histopathologic analysis of tissue samples demonstrated melanocyte proliferation and epithelial dysplasia, yielding a final pathologic diagnosis of conjunctival melanoacanthoma with dysplastic and acantholytic-type features. The patient is being closely followed and has not had recurrence of the lesion. CONCLUSIONS: Only 1 prior case of conjunctival melanoacanthoma has been documented. As such, there is no standard of care regarding appropriate management.

Epstein-Barr-virus-positive large B-cell lymphoma associated with breast implants: an analysis of eight patients suggesting a possible pathogenetic relationship.

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report eight cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were noninvasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the noninvasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe that this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting.

M-health: the union of technology and healthcare regulations.

As healthcare continues to become technology-based, so too does the potential for increased governmental regulation of mobile health (m-health). "M-health" is a broad term that applies to hardware or software that is mobile and delivers healthcare wirelessly. M-health includes consumer- and provider-oriented medical applications (apps), such as weight monitoring apps, and medical devices, such as glucose meters, that send health information back to the provider. It is important for anyone entering the field of mobile healthcare, whether developing apps, providing remote medical care, or simply investing in the future of healthcare technology, to understand the impact governmental oversight can have on this industry. Understanding the different roles to be played by the federal and state governments can be the difference between success and frustration.

Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer.

BACKGROUND: This study assessed BRCA1 and BRCA2 mutation prevalence in an unselected cohort of patients with triple-negative breast cancer (BC). METHODS: One hundred ninety-nine patients were enrolled. Triple negativity was defined as <1% estrogen and progesterone staining by immunohistochemistry and HER-2/neu not overexpressed by fluorescence in situ hybridization. Having given consent, patients had BRCA1 and BRCA2 full sequencing and large rearrangement analysis. Mutation prevalence was assessed among the triple-negative BC patients and the subset of patients without a family history of breast/ovarian cancer. Independent pathological review was completed on 50 patients. RESULTS: Twenty-one deleterious BRCA mutations were identified--13 in BRCA1 and 8 in BRCA2 (prevalence, 10.6%). In 153 patients (76.9%) without significant family history (first-degree or second-degree relatives with BC aged <50 years or ovarian cancer at any age), 8 (5.2%) mutations were found. By using prior National Comprehensive Cancer Network (NCCN) guidelines recommending testing for triple-negative BC patients aged <45 years, 4 of 21 mutations (19%) would have been missed. Two of 21 mutations (10%) would have been missed using updated NCCN guidelines recommending testing for triple-negative BC patients aged <60 years. CONCLUSIONS: The observed mutation rate was significantly higher (P = .0005) than expected based on previously established prevalence tables among patients unselected for pathology. BRCA1 mutation prevalence was lower, and BRCA2 mutation prevalence was higher, than previously described. Additional mutation carriers would have met new NCCN testing guidelines, underscoring the value of the updated criteria. Study data suggest that by increasing the age limit to 65 years, all carriers would have been identified.