Case Report: Intravesical and extravesical urachal cyst in children with lower abdominal pain and hematuria.

Bladder urachal cysts in children are a rare form of urachal abnormality. In this paper, we present a case of atypical imaging that presented with lower abdominal pain accompanied by hematuria, resulting in the formation of both internal and external urachal cysts in a child. A 6-year-old male child presented with repeated abdominal pain over a span of 4 days. Color ultrasound and pelvic CT scans revealed a soft tissue lesion on the right anterior wall of the bladder with an unclear boundary from the bladder wall. Voiding Cystourethrography (VCUG) showed no significant abnormalities in the bladder, while routine urine testing was positive for hematuria. A cystoscopy was simultaneously performed with a laparoscopic resection of the urachal cyst. Intraoperative cystoscopy identified the intravesical lesion, which was precisely removed using a cystoscope-assisted laparoscopy. Postoperative pathology confirmed that both extravesical and intravesical lesions were consistent with a urachal cyst. No complications were observed after the operation, and no recurrence was noted during a six-month follow-up. Therefore, for urachal cysts at the bladder's end, the possibility of intravesical urachal cysts should not be excluded, especially in patients with microscopic hematuria. We recommend performing cystoscopy simultaneously with laparoscopic urachal cyst removal to avoid missing intravesical lesions.

Application of clitoris exposure + episioplasty + dermabrasion + platelet-rich plasma injection + chemexfoliation in vulvar lichen sclerosus.

Introduction: To investigate the therapeutic effect of clitoris exposure + episioplasty + dermabrasion + platelet-rich plasma (PRP) injection + chemexfoliation on vulvar lichen sclerosus (VLS). Methods: Twenty children with VLS (under 14 years old) at our hospital from July 2020 to November 2022 were enrolled and treated with clitoris exposure + episioplasty + dermabrasion + PRP injection + chemexfoliation. Additionally, symptomatic changes and improvements in signs were recorded. Results: Significant therapeutic effects were achieved in all children enrolled in this study. The Cattanco score was 8.02 ± 1.22 points before surgery, 2.21 ± 0.70 points 3 months after surgery, and 2.61 ± 0.59 points 6 months after surgery, demonstrating that the score after surgery was significantly lower than that before surgery (p < 0.05). Mild complications (one case of mild vulvar swelling, one case of minor bleeding, and one case of superficial ulcer) were observed in three children after surgery, with an overall complication incidence of 15%; all complications were improved after the intervention, and no severe adverse reactions were observed. Recurrence was observed in one child (5%) 6 months after surgery. Conclusion: Clitoris exposure + episioplasty + dermabrasion + PRP injection + chemexfoliation is an effective approach for the treatment of VLS. Systematic Review Registration: https://www.chictr.org.cn/searchproj.html, identifier: ChiCTR2100054787.

Single-site laparoscopic ligation of the hernia sac in infants with congenital Morgagni hernia.

Background: Congenital Morgagni hernia (CMH) is a rare midline defect involving herniation of abdominal viscera into the thoracic cavity through triangular parasternal gaps in the diaphragm. Methods: The medical records of three patients with CMH admitted to the Department of Pediatric Surgery at the Affiliated Hospital of Zunyi Medical University between 2018 and 2022 were retrospectively reviewed. Pre-operative diagnosis was based on chest x-ray, chest computerized tomography, and barium enema. All patients were treated with single-site laparoscopic ligation of the hernia sac. Results: Hernia repair was successful in all patients (males; age: 14 months, 30 months, 48 months). The average operative time for repair of a unilateral hernia was 20 ± 5 min. Volume of surgical blood loss was 2-3 ml. There was no damage to organs such as the liver or intestines, or to tissues such as the pericardium or the phrenic nerve. Patients were allowed a fluid diet 6-8 h after surgery, and remained on bed rest until 16 h after surgery. No postoperative complications occurred, and patients were discharged on postoperative Day 2 or 3. No symptoms or complications were noted during the 1-48 months of follow-up. Aesthetic outcomes were satisfactory. Conclusions: Single-site laparoscopic ligation of the hernia sac provides pediatric surgeons a safe and effective technique for repair of CMH in infants and children. The procedure is straightforward, operative time and surgical blood loss are minimal, recurrence is unlikely, and aesthetic outcomes are satisfactory.

Comparative study of different surgical approaches for treatment of UPJ obstruction according to the degree/severity of hydronephrosis factor.

Objective: To compare the efficacy of two different surgical approaches during and after pyeloplasty according to the degree/severity of hydronephrosis factor. Materials and methods: Sixty child patients with UPJ obstruction admitted to our hospital from August 2019 to October 2021 were collected. Patients who underwent retroperitoneal laparoscopic pyeloplasty (RPLP) were enrolled into Group A (n = 20), while those who received transperitoneal laparoscopic pyeloplasty (TLP) were selected as Group B (n = 40). Clinical parameters, including gender, age, laterality of UPJ obstruction, degree/severity of hydronephrosis, body weight, operation time, drainage tube indwelling time, complete oral feeding time, and length of hospital stay, were compared between the two groups. Results: All 60 child patients were operated upon successfully without conversion to open surgery. There were no statistically significant differences in gender, age, laterality of UPJ obstruction, and body weight between the two groups, while the operation time of TLP was shorter than that of RPLP, indicating a statistically significant difference (P < 0.001). The differences in complete oral feeding time, drainage tube indwelling time, and length of hospital stay were statistically significant between the two groups, and RPLP was superior to TLP in terms of postoperative recovery time (P < 0.001). A stratified comparison showed that there were no statistically significant differences in anteroposterior diameter ≤ 20 mm, while there were statistically significant differences in anteroposterior diameter >20 mm. Hydronephrosis is reviewed after 3 months of the operation, degree/severity of hydronephrosis have been reduced. Conclusion: Both RPLP and TLP are safe and feasible in the treatment of UPJ obstruction, and their overall surgical effects are equivalent. For child patients with anteroposterior diameter ≤ 20 mm, RPLP is available, while patients with anteroposterior diameter >20 mm, TLP is recommended.

Study of pharmacogenomic information in FDA-approved drug labeling to facilitate application of precision medicine.

Pharmacogenomics (PGx), studying the relationship between drug response and genetic makeup of an individual, is accelerating advances in precision medicine. The FDA includes PGx information in the labeling of approved drugs to better inform on their safety and effectiveness. We herein present a summary of PGx information found in 261 prescription drug labeling documents by querying the publicly available FDALabel database. A total of 362 drug-biomarker pairs (DBPs) were identified. We profiled DBPs using frequency of the biomarkers and their therapeutic classes. Four categories of applications (indication, safety, dosing and information) were discussed according to information in labeling. This analysis facilitates better understanding, utilization and translation of PGx information in drug labeling among researchers, healthcare professionals and the public.

Study of serious adverse drug reactions using FDA-approved drug labeling and MedDRA.

BACKGROUND: Adverse Drug Reactions (ADRs) are of great public health concern. FDA-approved drug labeling summarizes ADRs of a drug product mainly in three sections, i.e., Boxed Warning (BW), Warnings and Precautions (WP), and Adverse Reactions (AR), where the severity of ADRs are intended to decrease in the order of BW > WP > AR. Several reported studies have extracted ADRs from labeling documents, but most, if not all, did not discriminate the severity of the ADRs by the different labeling sections. Such a practice could overstate or underestimate the impact of certain ADRs to the public health. In this study, we applied the Medical Dictionary for Regulatory Activities (MedDRA) to drug labeling and systematically analyzed and compared the ADRs from the three labeling sections with a specific emphasis on analyzing serious ADRs presented in BW, which is of most drug safety concern. RESULTS: This study investigated New Drug Application (NDA) labeling documents for 1164 single-ingredient drugs using Oracle Text search to extract MedDRA terms. We found that only a small portion of MedDRA Preferred Terms (PTs), 3819 out of 21,920 or 17.42%, were observed in a whole set of documents. In detail, 466/3819 (12.0%) PTs were in BW, 2023/3819 (53.0%) were in WP, and 2961/3819 (77.5%) were in AR sections. We also found a higher overlap of top 20 occurring BW PTs with WP sections compared to AR sections. Within the MedDRA System Organ Class levels, serious ADRs (sADRs) from BW were prevalent in Nervous System disorders and Vascular disorders. A Hierarchical Cluster Analysis (HCA) revealed that drugs within the same therapeutic category shared the same ADR patterns in BW (e.g., nervous system drug class is highly associated with drug abuse terms such as dependence, substance abuse, and respiratory depression). CONCLUSIONS: This study demonstrated that combining MedDRA standard terminologies with data mining techniques facilitated computer-aided ADR analysis of drug labeling. We also highlighted the importance of labeling sections that differ in seriousness and application in drug safety. Using sADRs primarily related to BW sections, we illustrated a prototype approach for computer-aided ADR monitoring and studies which can be applied to other public health documents.

FDA drug labeling: rich resources to facilitate precision medicine, drug safety, and regulatory science.

Here, we provide a concise overview of US Food and Drug Administration (FDA) drug labeling, which details drug products, drug-drug interactions, adverse drug reactions (ADRs), and more. Labeling data have been collected over several decades by the FDA and are an important resource for regulatory research and decision making. However, navigating through this data is challenging. To aid such navigation, the FDALabel database was developed, which contains a set of approximately 80000 labeling data. The full-text searching capability of FDALabel and querying based on any combination of specific sections, document types, market categories, market date, and other labeling information makes it a powerful and attractive tool for a variety of applications. Here, we illustrate the utility of FDALabel using case scenarios in pharmacogenomics biomarkers and ADR studies.

Quantitative structure-activity relationship models for predicting drug-induced liver injury based on FDA-approved drug labeling annotation and using a large collection of drugs.

Drug-induced liver injury (DILI) is one of the leading causes of the termination of drug development programs. Consequently, identifying the risk of DILI in humans for drug candidates during the early stages of the development process would greatly reduce the drug attrition rate in the pharmaceutical industry but would require the implementation of new research and development strategies. In this regard, several in silico models have been proposed as alternative means in prioritizing drug candidates. Because the accuracy and utility of a predictive model rests largely on how to annotate the potential of a drug to cause DILI in a reliable and consistent way, the Food and Drug Administration-approved drug labeling was given prominence. Out of 387 drugs annotated, 197 drugs were used to develop a quantitative structure-activity relationship (QSAR) model and the model was subsequently challenged by the left of drugs serving as an external validation set with an overall prediction accuracy of 68.9%. The performance of the model was further assessed by the use of 2 additional independent validation sets, and the 3 validation data sets have a total of 483 unique drugs. We observed that the QSAR model's performance varied for drugs with different therapeutic uses; however, it achieved a better estimated accuracy (73.6%) as well as negative predictive value (77.0%) when focusing only on these therapeutic categories with high prediction confidence. Thus, the model's applicability domain was defined. Taken collectively, the developed QSAR model has the potential utility to prioritize compound's risk for DILI in humans, particularly for the high-confidence therapeutic subgroups like analgesics, antibacterial agents, and antihistamines.

EADB: an estrogenic activity database for assessing potential endocrine activity.

Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body's endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.

SNPTrack™ : an integrated bioinformatics system for genetic association studies.

A genetic association study is a complicated process that involves collecting phenotypic data, generating genotypic data, analyzing associations between genotypic and phenotypic data, and interpreting genetic biomarkers identified. SNPTrack is an integrated bioinformatics system developed by the US Food and Drug Administration (FDA) to support the review and analysis of pharmacogenetics data resulting from FDA research or submitted by sponsors. The system integrates data management, analysis, and interpretation in a single platform for genetic association studies. Specifically, it stores genotyping data and single-nucleotide polymorphism (SNP) annotations along with study design data in an Oracle database. It also integrates popular genetic analysis tools, such as PLINK and Haploview. SNPTrack provides genetic analysis capabilities and captures analysis results in its database as SNP lists that can be cross-linked for biological interpretation to gene/protein annotations, Gene Ontology, and pathway analysis data. With SNPTrack, users can do the entire stream of bioinformatics jobs for genetic association studies. SNPTrack is freely available to the public at http://www.fda.gov/ScienceResearch/BioinformaticsTools/SNPTrack/default.htm.

An FDA bioinformatics tool for microbial genomics research on molecular characterization of bacterial foodborne pathogens using microarrays.

BACKGROUND: Advances in microbial genomics and bioinformatics are offering greater insights into the emergence and spread of foodborne pathogens in outbreak scenarios. The Food and Drug Administration (FDA) has developed a genomics tool, ArrayTrack™, which provides extensive functionalities to manage, analyze, and interpret genomic data for mammalian species. ArrayTrack™ has been widely adopted by the research community and used for pharmacogenomics data review in the FDA's Voluntary Genomics Data Submission program. RESULTS: ArrayTrack™ has been extended to manage and analyze genomics data from bacterial pathogens of human, animal, and food origin. It was populated with bioinformatics data from public databases such as NCBI, Swiss-Prot, KEGG Pathway, and Gene Ontology to facilitate pathogen detection and characterization. ArrayTrack™'s data processing and visualization tools were enhanced with analysis capabilities designed specifically for microbial genomics including flag-based hierarchical clustering analysis (HCA), flag concordance heat maps, and mixed scatter plots. These specific functionalities were evaluated on data generated from a custom Affymetrix array (FDA-ECSG) previously developed within the FDA. The FDA-ECSG array represents 32 complete genomes of Escherichia coli and Shigella. The new functions were also used to analyze microarray data focusing on antimicrobial resistance genes from Salmonella isolates in a poultry production environment using a universal antimicrobial resistance microarray developed by the United States Department of Agriculture (USDA). CONCLUSION: The application of ArrayTrack™ to different microarray platforms demonstrates its utility in microbial genomics research, and thus will improve the capabilities of the FDA to rapidly identify foodborne bacteria and their genetic traits (e.g., antimicrobial resistance, virulence, etc.) during outbreak investigations. ArrayTrack™ is free to use and available to public, private, and academic researchers at http://www.fda.gov/ArrayTrack.