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Modifications of the Effect of Juvenile Idiopathic Arthritis (JIA) on Anxiety and Depression in Children and Adolescents: A Pseudo-longitudinal Study of 192,019 Children in the United States
No full textIntroduction: Juvenile Idiopathic Arthritis (JIA), among children and adolescents, is a heterogeneous condition and is a prevalent chronic rheumatological disease. Non-medical (e.g., self-efficacy, social support, parental distress, and coping with pain), medical factors (e.g., permanent damage to joints), and psychological factors (e.g., depression and anxiety) can significantly impact the quality of life for individuals with JIA.
Methods: This study aimed to investigate the effect modifiers of the associations of anxiety and depression in children with JIA. The National Survey of Children's Health database (2016-2021) was used for the current study. A total of 192,019 children were included in the analyses. An augmented backward elimination model selection method was used to identify predictors for depression and anxiety.
Results: The period prevalence of JIA was 2.723 per 1,000. Sex was an effect modifier. Among boys, those who had JIA were 2.96 times (p<0.0001) more likely to have depression compared to non-JIA boys. On the other hand, the effects of JIA on anxiety were different across the insurance types. Among children with public insurance, children with JIA were 6.28 times (p <0.0001) more likely to have anxiety than those without JIA. Among children with JIA, those with public insurance were 5.23 times (p = 0.0005) more likely to have anxiety than those with private insurance.
Discussion: This population-based study found that typical sex differences in depression were not observed in the JIA group and that children with JIA had higher rates of anxiety, particularly those with public insurance. These findings highlight the need for integrated care that addresses both physical and mental health.Collaborative models involving rheumatologists and mental health professionals may aid in early intervention. Limitations include the study's cross-sectional design, which did not establish a causal association, and a lack of analysis by the JIA subtype, which could have varying impacts on mental health outcomes.
Conclusion: The findings highlight the importance of conducting comprehensive mental health assessments and developing personalized interventions tailored to the needs of JIA patients. The observed sex differences and the impact of insurance type on anxiety further emphasize the necessity of individualized care approaches
Sensitivity and specificity of the Cobas Liat CT/NG/MG nucleic acid test in a clinical laboratory setting and point-of-care location
No full textSexually transmitted infections, e.g., Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG), present with similar signs/symptoms and are often treated empirically due to delays in receiving diagnostic test results. This study evaluated the clinical performance of the Cobas Liat CT/NG/MG nucleic acid amplification test (NAAT) in detecting these pathogens in a point-of-care (POC) setting. This non-interventional, multicenter study recruited symptomatic/asymptomatic participants from 13 geographically diverse POC sites across the USA. Prospective clinician- and self-collected specimens (urine/vaginal swabs) were used to determine the sensitivity and specificity of the Cobas Liat CT/NG/MG test relative to the composite reference standard (CRS), determined using a combination of results from three FDA-approved NAATs and one laboratory-developed test. Among 4,800 evaluable participants, 40.4% (n = 1,941) were symptomatic, and 51.9% (n = 2,489) were female at birth. The Cobas Liat CT/NG/MG test demonstrated good clinical performance across all specimen types regardless of symptom status, with specificity >97% for each analyte, and sensitivity ≥92%, except female urine (≥CT 87%, NG ≥ 83%, MG ≥ 77%). The test was considered easy to use, and no statistically significant difference in performance results was observed between trained/untrained users. The Cobas Liat CT/NG/MG test demonstrated good clinical performance, with high sensitivity and specificity for CT/NG/MG detection, regardless of symptom status. The assay provides a short turn-around time (approximately 20 min) with centralized testing laboratory accuracy at the POC for self- and clinician-collected samples. POC testing can facilitate rapid pathogen identification and accurate treatment, thereby mitigating the need for empiric treatment.IMPORTANCENucleic acid amplification tests are the preferred method for diagnosing CT and NG infections and are the only reliable tests for MG; however, delays in receiving results can lead to empiric treatment, potentially causing misdiagnosis and overtreatment of STIs. Point-of-care testing could mitigate these issues by enabling rapid pathogen identification and treatment, but no rapid POC tests are currently available for the detection of CT, NG, and MG despite the similarity of symptoms, and these three pathogens being responsible for the majority of symptomatic STIs in some settings. Our findings suggest that the Cobas Liat CT/NG/MG assay may help to reduce reliance on empiric treatment of symptoms and minimize resulting return visits for unresolved infections. Use of the Cobas Liat CT/NG/MG assay may also result in improved patient outcomes, help realize population benefits by reducing the duration of infection and potentially transmission, and reduce healthcare costs
Epigenetic Modulation, Intratumoral Microbiome, and Immunity in Early-Onset Colorectal Cancer
No full textThe incidence of colorectal cancer in young adults (age of diagnosis <50 years) has been rapidly increasing. Although ∼20% of early-onset colorectal cancer (EOCRC) cases are due to germline mutations, the etiology of the majority of EOCRC cases remains poorly understood. Nongenetic factors such as environmental exposure and lifestyle changes are likely to have a direct link to the increased incidence of sporadic EOCRC. We hypothesize that such factors may be observable as alterations in the epigenome, microbiome, and immunome. We characterized the DNA methylation (DNAm) signature and measured DNAm age in EOCRC by using The Cancer Genome Atlas (TCGA). Furthermore, we carefully identified intratumoral microbes from TCGA and the Oncology Research Information Exchange Network datasets and then related the microbes to deconvolved immune cell abundances in EOCRC. We observed that the DNAm age in the EOCRC cohort was 12 years older when compared with the average-onset colorectal cancer (AOCRC) cohort, using three different epigenetic clocks. Differentially methylated sites associated with gene expression include cAMP-responsive element binding protein signaling in neurons, G protein-coupled receptor signaling, phagosome formation, and S100 family signaling. These differences were validated in the gene expression data from TCGA and the Oncology Research Information Exchange Network. When comparing the intratumoral microbes between EOCRC and AOCRC, no consistent differences were observed. Interestingly, the most abundant microbes interacted with the immune systems differently between the EOCRC and AOCRC tumors, characterized by more and larger positive correlations in EOCRC. These data suggest that epigenetic modulation and accelerated aging may play a key role in the development of EOCRC.
Significance: We investigated whether environmentally driven factors contribute to EOCRC. We observed accelerated epigenetic aging in EOCRC and epigenetic changes associated with chronic inflammation. Tumor immune cell abundances correlated more strongly with microbes in EOCRC than in AOCRC. These data suggest a dysregulation of the immune response in EOCRC, driving chronic inflammation and tissue aging
Possible role of anastrozole-induced hormonal alterations in pathogenesis of mammary apocrine carcinoma and follicular lymphoma: a case report and review of the literature
No full textBackground: In postmenopausal women, aromatase inhibitors decrease estrogen levels and increase local dihydrotestosterone concentrations. In this case report, we describe interesting associations between aromatase-inhibitor-induced hormonal changes and the development of apocrine mammary carcinoma and follicular lymphoma.
Case presentation: Here we report an 83-year-old Caucasian female patient who initially presented with Paget's disease of the right nipple and associated small focus of invasive ductal carcinoma (ERα + PR + HER2-). The patient did not pursue surgical resection and was treated only with anastrozole, and 5 years later, she was diagnosed with a 1.1 cm ipsilateral periareolar apocrine mammary carcinoma (ERα-ERβ + PR - AR + HER2-) that was detected during surveillance mammography. In addition to this tumor, the subsequent mastectomy specimen revealed an adjacent residual focus of the original invasive ductal carcinoma (ERα + ERβ + PR + AR + HER2-) within the nipple and a focus of follicular lymphoma (ERα-ERβ + ARlow) in the retroareolar area. Sentinel lymph nodes and imaging studies were negative for malignancy. The patient was continued on observation. Anastrozole was stopped after 10 months, and 2 months later, during a routine screening, a 1.8 cm invasive apocrine carcinoma (ERα-ERβ + PR-AR + HER2-) was detected in the patient's contralateral breast and she underwent simple mastectomy with sentinel lymph node biopsy. The sentinel lymph node was negative. No chemotherapy or radiation therapy was recommended. All carcinomas exposed to anastrozole expressed androgen-responsive molecules (GCDFP-15, NKX3.1). Germline genetic testing for 19 genes associated with hereditary breast cancer syndromes was negative, and 3 years later, the patient is still alive with no recurrences.
Conclusion: Our case suggests that unopposed local androgen exposure and loss of ERβ-mediated suppressive effect of estrogens may be involved in development of apocrine mammary tumors and lymphomas, respectively. However, further studies are necessary to clarify the roles of steroid hormones in pathogenesis of apocrine carcinoma and follicular lymphoma. This case also illustrates the importance of patient follow-up during and after aromatase inhibitor therapy. Appropriate surveillance for lymphoma may also be considered for those patients. Finally, when lymphoid aggregates are encountered in specimens from patients with breast cancer, a clinical history of hormonal therapy should alert the pathologist for a possibility of lymphoma
Evaluating first-line genetic testing strategies for inpatients with congenital heart defects
No full textGenetic testing strategies used to determine the etiology of congenital heart disease/defects (CHD/CHDs) vary between and within institutions, leading to potentially missed diagnostic opportunities. There has been little investigation comparing the diagnostic utility of gene panels among more comprehensive strategies used in the genetic evaluation of patients with CHD. In this descriptive study, we investigated the diagnostic yields of different genetic testing strategies in a real-world cohort of 263 patients with CHDs with genetic diagnoses. We counterfactually determined the diagnostic yield of a virtual gene panel designed for this study. We compared the diagnostic yield of the gene panel to other testing strategies, including chromosomal microarray (CMA), CMA + the gene panel, and genome sequencing. We assessed diagnostic yield differences according to clinical presentations to determine if phenotypes can inform optimal testing strategies. The virtual gene panel would have identified 51.3% of genetic disorders in this cohort, and 25.9% of genetic disorders would have remained undetected; another 22.8% may have needed additional testing to fully characterize the diagnoses. A combined approach of the virtual gene panel and CMA increased the diagnostic yield compared with panel-only testing or CMA alone (87.8% vs. 51.3% and 63.1%, respectively). The gene panel plus CMA would have increased the diagnostic yield by 24%-35% compared with CMA or panel testing alone in patients with extracardiac anomalies, 19%-41% in syndromic patients, and 0%-70% across CHD classifications. This combined approach also eliminated the potential need for follow-up testing; however, genome sequencing had a higher diagnostic yield across all clinical presentations (99.6%). CHD gene panels and CMA used individually or in combination are suboptimal first-line testing strategies, missing up to 36.5% of genetic disorders in our sample. Given the wide spectrum of phenotypes and genetic etiologies, our results support consideration of standardized genome sequencing for patients with CHDs
Low Body Trust Predicts Lower Interoceptive-Based Regulation in Maltreated Youth.
No full textBackground
Early maltreatment negatively impacts interoceptive awareness (IA), the attention to internal states and bodily sensations in daily life. Body trust, the belief that one can rely on internal bodily sensations as safe and accurate cues for needs, emotions, and states of arousal, is especially compromised. In the absence of body-based awareness youth struggle to develop a coherent sense of self because they lack reliable internal feedback about their own experiences. Prolonged and early experiences of abuse and neglect are associated with a pervading lack of trust in the bodily self and body sensations which persistently alters the ways in which maltreated youth relate to their bodies.
Objectives
Assess the extent to which interoceptive-based Body Trust is uniquely associated with attention regulation, emotional awareness, self-regulation and body listening in a clinical sample of maltreated youth.
Method
Participants: A clinical sample of 132 youth (ages 7–17) receiving mental health services for early abuse and neglect. Mean age of 12 years, with 54% female and 80% in adoptive or guardian care.
Design & Analysis: Secondary analysis of Multidimensional Assessment of Interoceptive Awareness-Youth (MAIA-Y)8 cross-sectional data. Body Trust scores were dichotomized at the sample grand mean (M=3.45): Lower Trust Group (n=59) and Higher Trust Group (n=73). Four dependent variables: Attention Regulation, Emotional Awareness, Self-Regulation, and Body-Listening were analyzed in separate SPSS v31 GLM Univariate Regressions (α = .05).
Results:
A majority of youth (80%) reported Low Body Trust (LBT). Across all four MAIA-Y dimensions, LBT uniquely predicted lower interoceptive-based regulation (|β| = .72–1.18, all p < .001; R² = .12 -.25). LBT had the largest negative effect on Self -Regulation, accounting for 25% of the difference in Self-Regulation scores across the study sample.
In comparison with the higher Body Trust group, youth with LBT scored:
• 0.72 points lower on Attention Regulation;
• 0.88 points lower on Emotional Awareness;
• 1.18 points lower on Self-Regulation;
• 0.81 points lower on Body-Listening
Conclusion
Youth with LBT have difficulty initiating and completing body-based strategies that shift states into functionally adaptive zones
Tunneling nanotube–like structures regulate distant cellular interactions during heart formation
No full textIn the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube-like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and initiated myocardial growth toward the heart lumen to form ventricular trabeculae-like structures. Loss of TNTLs disturbed signaling interactions and, subsequently, ventricular patterning
Real-world effectiveness of burosumab vs oral phosphate and active vitamin D in adults with X-linked hypophosphatemia
No full textIn X-linked hypophosphatemia (XLH), PHEX gene variants lead to elevated FGF23 production, resulting in hypophosphatemia, osteomalacia, osteomalacia-related fractures, osteoarthritis, enthesopathy, spinal stenosis, and symptoms of pain, stiffness, and decreased physical function. Burosumab is an anti-FGF23 monoclonal Ab approved for XLH treatment. Randomized studies comparing oral phosphate/active vitamin D (Pi/D) to burosumab in adults are lacking. This analysis, which utilized real-world data from the prospective, Americas-based XLH Disease Monitoring Program (NCT03651505), evaluated the effectiveness of burosumab vs Pi/D, based on changes from baseline to the year 1 visit in serum phosphate, 1,25(OH)2D, PTH, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF), and Timed Up and Go performance outcome. Two cohorts of adults with XLH who either began burosumab between baseline and the year 1 visit (n = 65) or were on Pi/D (n = 74) at study entry and did not receive burosumab were included. Inverse probability of treatment weighting was employed to adjust for potential confounding due to baseline cohort differences. At the year 1 visit, mean (SE) change from baseline was significant for burosumab vs Pi/D in serum phosphate (0.78 [0.08] vs 0.15 [0.14] mg/dL; p < .001), 1,25(OH)2D (19.41 [3.39] vs 5.49 [3.43] pg/mL; p = .011), PTH (-13.82 [5.00] vs 11.79 [8.10] pg/mL; p = .006), WOMAC pain (-7.50 [2.34] vs 4.47 [3.23]; p = .004), WOMAC physical function (-5.68 [1.96] vs 6.77 [4.85]; p = .006), and WOMAC total (-7.78 [2.06] vs 3.15 [3.37]; p = .005) scores, PROMIS PF (1.51 [0.73] vs -1.64 [1.11], p = .018), and TUG (-1.19 [0.42] vs 0.55 [0.43] s, p = .011). A trend towards improved WOMAC stiffness was observed for burosumab (-10.16 [2.85] vs -1.79 [3.68]; p = .086). In this real-world analysis of adults with XLH, burosumab treatment was associated with improved biochemical parameters, pain, physical function, and mobility compared with Pi/D
Espinoza technique leads to excessive retroversion in piriformis fossa entry nailing: computed tomographic analysis
No full textObjectives: To evaluate whether aligning femoral rotation utilizing the intramedullary nail's inherent anteversion during antegrade femoral intramedullary nailing (Espinoza technique) is equally reliable through piriformis fossa (PF) and greater trochanter (GT) entry portals.
Design: Retrospective computed tomography analysis.
Setting: Level I Trauma Center.
Patients/participants: Adult patients without prior femur fractures or congenital femoral abnormalities and with prior computed tomography scans of the entire femur for indications unrelated to fractures.
Intervention: Ideal femoral head screw trajectory was mapped by aligning the PF and GT entry points with the center of the femoral head. The angle between these lines and the distal femur posterior condylar tangent line was measured to demonstrate resultant femoral anteversion.
Main outcome measure: The difference between these angles was compared to show the difference in femoral version between PF and GT entry nailing using the Espinoza technique to assess rotational fracture alignment.
Results: Thirty femurs from 15 uninjured patients were evaluated. Mean rotational difference between GT and PF entry points was 15.8° ± 5.6° of additional retroversion with the PF entry point (P < 0.001).
Conclusions: During PF entry nailing, application of the Espinoza technique can lead to an additional unplanned average of 16° of postoperative femoral retroversion due to the relatively posterior and medial location of the PF entry point. Use of the Espinoza technique may need to be restricted to GT entry nailing to prevent fracture malrotation