The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

Pseudohyperkalemia in pediatric patients with newly diagnosed hematological malignancies.

Patients with newly diagnosed hematological malignancies often present with a considerable cellular burden, leading to complications including hyperkalemia. However, pseudohyperkalemia, arising from in vitro cell lysis, can pose challenges in clinical practice. Although pseudohyperkalemia is frequently reported in adult hematological malignancies, its occurrence in pediatric patients is underreported, and its incidence in this demographic remains unclear. We retrospectively reviewed the medical records of pediatric patients who received a new diagnosis of hematological malignancies from 2011 to 2022 at Taichung Veterans General Hospital. Hyperkalemia was defined by a serum or plasma potassium level exceeding 5.5 mEq/L. Pseudohyperkalemia was defined by 1) a potassium decrease of over 1 mEq/L in within 4 h without intervention or 2) the absence of electrocardiography changes indicative of hyperkalemia. Cases with apparent red blood cell hemolysis were excluded. A total of 157 pediatric patients with a new diagnosis of hematological malignancies were included, 14 of whom exhibited hyperkalemia. Among these 14 cases, 7 cases (4.5%) were of pseudohyperkalemia. This rate increased to 21.2% in patients with initial hyperleukocytosis. Pseudohyperkalemia was associated with a higher initial white blood cell count and lower serum sodium level. All episodes of pseudohyperkalemia occurred in the pediatric emergency department, where samples were obtained as plasma, whereas all true hyperkalemia cases were observed in the ordinary ward or intensive care unit, where samples were obtained as serum. Timely recognition of pseudohyperkalemia is crucial to avoiding unnecessary potassium-lowering interventions in pediatric patients with newly diagnosed hematological malignancies.

The Role of New 3D Pathology and Lymphocyte Expression of Interstitial Inflammation in Pediatric-Onset Lupus Nephritis.

Lupus nephritis (LN) is a common and severe manifestation of pediatric-onset systemic lupus erythematosus (pSLE). It is one of the major causes of long-term glucocorticoid/immune suppressants use in pSLE. It causes long-term glucocorticoid/immune suppressants use and even end-stage renal disease (ESRD) in pSLE. It is now well known that high chronicity, especially the tubulointerstitial components in the renal biopsy, predicts a poor renal outcome. Interstitial inflammation (II), a component of activity in LN pathology, can be an early predictor for the renal outcome. With the advent of 3D pathology and CD19-targeted CAR-T cell therapy in the 2020s, the present study focuses on detailed pathology and B cell expression in II. We recruited 48 pSLE patients with class III/IV LN to analyze the risk of ESRD based on different II scores. We also studied 3D renal pathology and immunofluorescence (IF) staining of CD3, 19, 20, and 138 in patients with a high II score but low chronicity. Those pSLE LN patients with II scores of 2 or 3 showed a higher risk for ESRD (p = 0.003) than those with II scores of 0 or 1. Excluding patients with chronicity >3, high II scores still carried a higher risk for ESRD (p = 0.005). Checking the average scores from the renal specimens from different depths, the II, and chronicity showed good consistency between 3D and 2D pathology (interclass correlation coefficient [ICC], II = 0.91, p = 0.0015; chronicity = 0.86, p = 0.024). However, the sum of tubular atrophy plus interstitial fibrosis showed no good consistency (ICC = 0.79, p = 0.071). The selected LN patients with negative CD19/20 IF stains showed scattered CD3 infiltration and a different IF pattern of Syndecan-1 expression. Our study provides unique data in LN, including 3D pathology and different in situ Syndecan-1 patterns in LN patients.

Incidence and survival of cancers among 1,054 hemophilia patients: A nationwide and 14-year cohort study.

As life expectancy increases in persons with hemophilia (PWH), more age-related diseases such as cancer emerge among this patient group. The aim of this study was to investigate incidence and survival of cancers among PWH in Taiwan. We analyzed data of 1,054 PWH retrieved from Taiwan's National Health Insurance Research Database between 1997 and 2010, by comparing variables to 10540 age- and gender-matched healthy individuals from the general population. There were 43 PWH and 178 individuals of general population with newly diagnosed cancer (RR 2.42, 95% CI 1.74-3.35). The cumulative incidences of cancer in PWH and the general population were 4.7 and 1.9%, respectively. Hepatocellular carcinoma (HCC) was the major type of cancer (17 cases) in PWH; cancer rate was still increased when HCC and HIV-related cancers were excluded (RR 1.66, 95% CI 1.06-2.59). There was no significant difference observed in lung, colorectal, or prostate cancer occurrence. Compared to the general population, PWH were younger at the time of cancer diagnosis (45.1 vs. 57.2 years old, P value < 0.001), and had fewer co-morbidities. Nineteen PWH with cancers died during the study period, and no bleeding-related death was recorded among these patients. The survival rate was not different between PWH and the general population, P = 0.86. In conclusion, the cumulative incidence of cancer among PWH was higher than the general population. PWH with cancer were younger and had fewer comorbidities, but the survival rates were similar in the two groups.

Modeling and assessment of long afterglow decay curves.

Multiple exponential equations have been successfully fitted to experimental long afterglow decay curve data for some phosphor materials by previous researchers. The calculated decay constants in such equations are used to assess the phosphorescence characteristics of an object. This study generates decay constants from experimental test data and from existing literature for comparison. It shows that the decay constants of an object may not be invariant and that they are dependent on phosphor material, temperature, irradiation intensity, sample thickness, and phosphor density for samples. In addition, the use of different numbers of exponential components in interpretation leads to different numerical results for decay constants. The relationship between the calculated decay constants and the afterglow characteristics of an object is studied and discussed in this paper. The appearance of the luminescence intensity is less correlated to the decay constants than to the time-invariant constants in an equation.

Effects of the offset term in experimental simulation on afterglow decay curve.

This study examines the effect of the offset term in a multiple single exponential equation that fits into experimental afterglow decay curve data for material applications. For afterglow materials applied and attached to structures, the inclusion of this offset term may reduce the values of the calculated decay times, τ i , and enlarge the time invariant constants, A i , in the associated equation compared to theoretically perfect test conditions. Using a set of experimental data obtained from a lab under dim light, adjustments can be made to calculate the required parameters for an equation without the offset term. This study uses mathematical simulations and lab tests to support our thesis and crosslink test results generated from different ambient light conditions. This paper defines the offset ratio as the ratio of the offset value, I 0, versus the initial light intensity in an equation. This ratio can be used to evaluate possible effects on the calculated parameters of an equation in an associated numerical simulation. The most reliable parameters will have consistent results from the use of multiple single exponential equations, with and without the offset term, in simulations to obtain them in an equation to model a set of data.

The correlation between trajectories of serum C3 variability and clinical course in Pediatric-onset systemic lupus erythematosus.

OBJECTIVE: The aim of this study is to investigate the usefulness which 2-year trajectories of C3 variability have in predicting clinical remission and systemic corticosteroids (SCS) use in pediatric patients with systemic lupus erythematosus (pSLE). METHODS: We recruited 189 confirmed pSLE patients from the electronic database of our hospital, all had undergone SCS treatment. The follow up period was 4.17-14.83 years. We used Group-Based Trajectory modeling to divide the patients into four different trajectory groups by their initial 2-year C3 variability. We divided the patients into groups A, B or C by their clinical course and SCS use. Statistical methods included Kruskal-Wallis and Chi-square tests and logic regression test. RESULTS: There were 4 separate trajectories. The distribution of groups A, B and C in these 4 trajectories showed a significant difference (p = 0.005). Initial C3 and C4 levels in these 4 revealed significant differences (p â‰¦ 0.001, p â‰¦ 0.016). When compared to other trajectories, trajectory1 showed a higher risk for persistent SCS use (p < 0.05). The distributions of severe clinical manifestations, including proteinuria, hematuria, CNS involvement and thrombocytopenia were different in these 4 trajectories (p = 0.003). Nevertheless, none of the above manifestations contributed to the risk of persistent SCS use. CONCLUSIONS: We have found 4 distinct C3 trajectories in pSLE patients. Distributions of clinical outcome groups were different in these 4 trajectories. Patients with trajectory1 displayed a higher risk for persistent SCS use, thus an earlier institution of immunosuppressant(s) and biological agents can be considered for these children.

Remission and long-term remission of pediatric-onset systemic lupus erythematosus.

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse clinical presentations and prognoses. Remission can be achieved with or without glucocorticoid (GC) use, and several recent studies have suggested that long-term remission can be achieved in a small portion of patients. Nevertheless, few studies have investigated remission or long-term remission in the pediatric-onset SLE subgroup. This study analyzed the characteristics and factors associated with long-term remission and GC use in pediatric-onset SLE. Methods: We enrolled 226 patients aged <18 years who received a diagnosis of SLE between January 2006 and December 2016. Three remission condition groups were defined: (A) complete remission, (B) clinical remission off GCs, and (C) clinical remission on GCs. Long-term remission was defined as remission for more than 5 years. We analyzed the treatment durations before remission, durations of remission, and risk factors for non-remission with persistent GC use. Results: During follow-up, 8 patients (3.5%) achieved complete remission, 35 patients (15.5%) achieved clinical remission off GCs, and 93 patients (41.2%) achieved clinical remission on GCs. In groups A, B, and C, 12.5%, 68.6%, and 65.6% of patients, respectively, remained in remission for >1 year. Conclusion: This study assessed remission of pediatric-onset SLE. Up to 60.2% of patients had clinical remission after treatment, and 19% of patients achieved remission off GCs. Long-term remission is rarer in pediatric-onset SLE than in adult-onset SLE.

Automatic Screening of Pediatric Renal Ultrasound Abnormalities: Deep Learning and Transfer Learning Approach.

BACKGROUND: In recent years, the progress and generalization surrounding portable ultrasonic probes has made ultrasound (US) a useful tool for physicians when making a diagnosis. With the advent of machine learning and deep learning, the development of a computer-aided diagnostic system for screening renal US abnormalities can assist general practitioners in the early detection of pediatric kidney diseases. OBJECTIVE: In this paper, we sought to evaluate the diagnostic performance of deep learning techniques to classify kidney images as normal and abnormal. METHODS: We chose 330 normal and 1269 abnormal pediatric renal US images for establishing a model for artificial intelligence. The abnormal images involved stones, cysts, hyperechogenicity, space-occupying lesions, and hydronephrosis. We performed preprocessing of the original images for subsequent deep learning. We redefined the final connecting layers for classification of the extracted features as abnormal or normal from the ResNet-50 pretrained model. The performances of the model were tested by a validation data set using area under the receiver operating characteristic curve, accuracy, specificity, and sensitivity. RESULTS: The deep learning model, 94 MB parameters in size, based on ResNet-50, was built for classifying normal and abnormal images. The accuracy, (%)/area under curve, of the validated images of stone, cyst, hyperechogenicity, space-occupying lesions, and hydronephrosis were 93.2/0.973, 91.6/0.940, 89.9/0.940, 91.3/0.934, and 94.1/0.996, respectively. The accuracy of normal image classification in the validation data set was 90.1%. Overall accuracy of (%)/area under curve was 92.9/0.959.. CONCLUSIONS: We established a useful, computer-aided model for automatic classification of pediatric renal US images in terms of normal and abnormal categories.

Pseudohyperkalemia accompanying actual hyperphosphatemia and hypocalcemia in an adolescent with T-lymphoblastic lymphoma.

Tumor lysis syndrome (TLS) is a life-threatening condition that may occur in patients with lymphoma, leukemia, or cancers with high cellular burdens. Without appropriate treatment, electrolyte imbalances, namely hyperkalemia, hyperphosphatemia, and hypocalcemia, can be fatal in patients with TLS. In pseudohyperkalemia, concurrent hyperphosphatemia and hypocalcemia can render devising a treatment strategy challenging. We report an adolescent with T-lymphoblastic lymphoma who presented with pseudohyperkalemia but actual hyperphosphatemia and hypocalcemia, to highlight the importance of accurate clinical interpretations of laboratory data in patients with TLS.