Renal bleeding: imaging and interventions in patients with tumors.

In patients with cancer, spontaneous renal bleeding can stem from a range of underlying factors, necessitating precise diagnostic tools for effective patient management. Benign and malignant renal tumors are among the primary culprits, with angiomyolipomas and renal cell carcinomas being the most common among them. Vascular anomalies, infections, ureteral obstructions, and coagulation disorders can also contribute to renal-related bleeding. Cross-sectional imaging techniques, particularly ultrasound and computed tomography (CT), play pivotal roles in the initial detection of renal bleeding. Magnetic resonance imaging and CT are preferred for follow-up evaluations and aid in detecting underlying enhancing masses. IV contrast-enhanced ultrasound can provide additional information for active bleeding detection and differentiation. This review article explores specific disorders associated with or resembling spontaneous acute renal bleeding in patients with renal tumors; it focuses on the significance of advanced imaging techniques in accurately identifying and characterizing renal bleeding in these individuals. It also provides insights into the clinical presentations, imaging findings, and treatment options for various causes of renal bleeding, aiming to enhance the understanding, diagnosis, and management of the issue.

Corrigendum: Glioblastoma survival is associated with distinct proteomic alteration signatures post chemoirradiation in a large-scale proteomic panel.

[This corrects the article DOI: 10.3389/fonc.2023.1127645.].

Oxygen saturation thresholds in managing sickle cell disease at US children's hospitals.

BACKGROUND: Adequate oxygen saturation (SpO2 ) is crucial for managing sickle cell disease (SCD). Children with SCD are at increased risk for occult hypoxemia; therefore, understanding SpO2 threshold practices would help identify barriers to oxygen optimization in a population sensitive to oxyhemoglobin imbalances. We investigated SpO2 cutoff levels used in clinical algorithms for management of acute SCD events at children's hospitals across the United States, and determined their consistency with recommended national guidelines (SpO2  > 95%). METHODS: Clinical pathways and algorithms used for the management of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) in SCD were obtained and reviewed from large children's hospitals in the United States. RESULTS: Responses were obtained from 94% (140/149) of eligible children's hospitals. Of these, 63 (45%) had available clinical algorithms to manage VOC and ACS. SpO2 cutoff was provided in 71.4% (45/63) of clinical algorithms. Substantial variation in SpO2 cutoff levels was noted, ranging from ≥90% to more than 95%. Only seven hospitals (5% of total hospitals and 15.6% of hospitals with clinical algorithms available) specified oxygen cutoffs that were consistent with national guidelines. Hospitals geographically located in the South (46.8%; n = 29/62) and Midwest (54.8%; n = 17/31) were more likely to have VOC and ACS clinical algorithms, compared to the Northeast (26.5%; n = 9/34) and West (36.4%; n = 8/22). CONCLUSION: There is inconsistency in the use of clinical algorithms and oxygen thresholds for VOC and ACS across US children's hospitals. Children with SCD could be at risk for insufficient oxygen therapy during adverse acute events.

Glioblastoma survival is associated with distinct proteomic alteration signatures post chemoirradiation in a large-scale proteomic panel.

Background: Glioblastomas (GBM) are rapidly progressive, nearly uniformly fatal brain tumors. Proteomic analysis represents an opportunity for noninvasive GBM classification and biological understanding of treatment response. Purpose: We analyzed differential proteomic expression pre vs. post completion of concurrent chemoirradiation (CRT) in patient serum samples to explore proteomic alterations and classify GBM by integrating clinical and proteomic parameters. Materials and methods: 82 patients with GBM were clinically annotated and serum samples obtained pre- and post-CRT. Serum samples were then screened using the aptamer-based SOMAScan® proteomic assay. Significant traits from uni- and multivariate Cox models for overall survival (OS) were designated independent prognostic factors and principal component analysis (PCA) was carried out. Differential expression of protein signals was calculated using paired t-tests, with KOBAS used to identify associated KEGG pathways. GSEA pre-ranked analysis was employed on the overall list of differentially expressed proteins (DEPs) against the MSigDB Hallmark, GO Biological Process, and Reactome databases with weighted gene correlation network analysis (WGCNA) and Enrichr used to validate pathway hits internally. Results: 3 clinical clusters of patients with differential survival were identified. 389 significantly DEPs pre vs. post-treatment were identified, including 284 upregulated and 105 downregulated, representing several pathways relevant to cancer metabolism and progression. The lowest survival group (median OS 13.2 months) was associated with DEPs affiliated with proliferative pathways and exhibiting distinct oppositional response including with respect to radiation therapy related pathways, as compared to better-performing groups (intermediate, median OS 22.4 months; highest, median OS 28.7 months). Opposite signaling patterns across multiple analyses in several pathways (notably fatty acid metabolism, NOTCH, TNFα via NF-κB, Myc target V1 signaling, UV response, unfolded protein response, peroxisome, and interferon response) were distinct between clinical survival groups and supported by WGCNA. 23 proteins were statistically signficant for OS with 5 (NETO2, CST7, SEMA6D, CBLN4, NPS) supported by KM. Conclusion: Distinct proteomic alterations with hallmarks of cancer, including progression, resistance, stemness, and invasion, were identified in serum samples obtained from GBM patients pre vs. post CRT and corresponded with clinical survival. The proteome can potentially be employed for glioma classification and biological interrogation of cancer pathways.

Compound K Production: Achievements and Perspectives.

Compound K (CK) is one of the major metabolites found in mammalian blood and organs following oral administration of Panax plants. CK, also known as minor ginsenoside, can be absorbed in the systemic circulation. It has garnered significant attention in healthcare and medical products due to its pharmacological activities, such as antioxidation, anticancer, antiproliferation, antidiabetics, neuroprotection, and anti-atherogenic activities. However, CK is not found in natural ginseng plants but in traditional chemical synthesis, which uses toxic solvents and leads to environmental pollution during the harvest process. Moreover, enzymatic reactions are impractical for industrial CK production due to low yield and high costs. Although CK could be generated from major ginsenosides, most ginsenosides, including protopanaxatriol-oleanane and ocotillol-type, are not converted into CK by catalyzing ß-glucosidase. Therefore, microbial cell systems have been used as a promising solution, providing a safe and efficient approach to CK production. This review provides a summary of various approaches for the production of CK, including chemical and enzymatic reactions, biotransformation by the human intestinal bacteria and endophytes as well as engineered microbes. Moreover, the approaches for CK production have been discussed to improve the productivity of target compounds.

Multi-omics Pathways Workflow (MOPAW): An Automated Multi-omics Workflow on the Cancer Genomics Cloud.

Introduction: In the era of big data, gene-set pathway analyses derived from multi-omics are exceptionally powerful. When preparing and analyzing high-dimensional multi-omics data, the installation process and programing skills required to use existing tools can be challenging. This is especially the case for those who are not familiar with coding. In addition, implementation with high performance computing solutions is required to run these tools efficiently. Methods: We introduce an automatic multi-omics pathway workflow, a point and click graphical user interface to Multivariate Single Sample Gene Set Analysis (MOGSA), hosted on the Cancer Genomics Cloud by Seven Bridges Genomics. This workflow leverages the combination of different tools to perform data preparation for each given data types, dimensionality reduction, and MOGSA pathway analysis. The Omics data includes copy number alteration, transcriptomics data, proteomics and phosphoproteomics data. We have also provided an additional workflow to help with downloading data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium and preprocessing these data to be used for this multi-omics pathway workflow. Results: The main outputs of this workflow are the distinct pathways for subgroups of interest provided by users, which are displayed in heatmaps if identified. In addition to this, graphs and tables are provided to users for reviewing. Conclusion: Multi-omics Pathway Workflow requires no coding experience. Users can bring their own data or download and preprocess public datasets from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium using our additional workflow based on the samples of interest. Distinct overactivated or deactivated pathways for groups of interest can be found. This useful information is important in effective therapeutic targeting.

Colorectal Arteriovenous Malformations causing Prolonged Bleeding were Managed Successfully by Laparoscopic Low Anterior Resection with Sphincter Preservation: A Case Report.

Gastrointestinal arteriovenous malformations (AVMs) are a rare disease. Sigmoid-anorectal AVM has only been reported in a few cases. The condition is usually detected when patients have gastrointestinal bleeding complications. The diagnosis and treatment of colorectal AVMs are still challenging. This paper presents a case of an Asian 32-year-old female patient admitted to hospital because of lower gastrointestinal bleeding lasting 17 years. The patient was diagnosed with sigmoid-rectal arteriovenous malformation and failed with other medical treatments. The damaged gastrointestinal tract was removed by a laparoscopic low anterior resection. The results were positive after a three-month follow-up; the bleeding was resolved, and the anal sphincter function was intact. Laparoscopic low anterior resection is a safe, less invasive, and effective approach for managing patients with digestive tract bleeding due to extensive colorectal AVM and preservation of the anal sphincter.

Cervical cancer in the pregnant population.

Cervical cancer is the second most encountered cancer in pregnant patients. The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer updated the staging of primary cervical carcinoma and disease process, with formal incorporation of imaging as a vital source of information in the management process to improve accuracy. Diagnosis and treatment of the pregnant population is a complex interplay of achieving adequate diagnostic information and optimal treatment while minimizing toxicity and risks to the mother and fetus. While novel imaging techniques and anticancer therapies are rapidly developed, much information on the safety and feasibility of different therapies is not yet available in the pregnant population. Therefore, managing pregnant patients with cervical cancer is complex and requires a multidisciplinary approach.

Screening for asthma in preschool children with sickle cell disease.

BACKGROUND: Asthma in preschool children is poorly defined, proving to be a challenge for early detection. The Breathmobile Case Identification Survey (BCIS) has been shown to be a feasible screening tool in older SCD children and could be effective in younger children. We attempted to validate the BCIS as an asthma screening tool in preschool children with SCD. METHODS: This is a prospective, single-center study of 50 children aged 2-5 years with SCD. BCIS was administered to all patients and a pulmonologist blinded to the results evaluated patients for asthma. Demographic, clinical, and laboratory data were obtained to assess risk factors for asthma and acute chest syndrome in this population. RESULTS: Asthma prevalence (n = 3/50; 6%) was lower than atopic dermatitis (20%) and allergic rhinitis (32%). Sensitivity (100%), specificity (85%), positive predictive value (30%), and negative predictive value (100%) of the BCIS were high. Clinical demographics, atopic dermatitis, allergic rhinitis, asthma, viral respiratory infection, hematology parameters, sickle hemoglobin subtype, tobacco smoke exposure, and hydroxyurea were not different between patients with or without history of ACS, although eosinophil was significantly lower in the ACS group (p = 0.0093). All those with asthma had ACS, known viral respiratory infection resulting in hospitalization (3 RSV and 1 influenza), and HbSS (homozygous Hemoglobin SS) subtype. CONCLUSION: The BCIS is an effective asthma screening tool in preschool children with SCD. Asthma prevalence in young children with SCD is low. Previously known ACS risk factors were not seen, possibly from the beneficial effects of early life initiation of hydroxyurea.

Malignancy in pregnancy: Multimodality imaging and treatment.

The diagnosis of cancer is increasingly made in the pregnant population, thought to be from the increasing average age of pregnancy and the use of prenatal fetal noninvasive screening techniques, leading to incidental detection of cancer in the mother. Complex challenges are associated with imaging, diagnosis, staging, and treatment of cancers in this patient population, which require highly specialized interdisciplinary management. This report discusses the use of multimodality imaging and safety considerations in pregnant patients, reviews the current guidelines for ionizing radiation imaging techniques, and presents a series of commonly and uncommonly encountered cancers in pregnancy with current diagnostic imaging guidelines. The authors also discuss the role of multidisciplinary management and treatment options and provide an overview of therapy-related considerations in the age of novel anticancer therapies. PLAIN LANGUAGE SUMMARY: The diagnosis and management of pregnant patients who have cancer are actively evolving as novel imaging techniques and anticancer therapies are being developed. Radiologically, there are inherent difficulties in balancing the minimization of fetal ionization while acquiring diagnostic quality imaging necessary for the diagnosis, staging, and treatment of maternal disease. Standardized imaging protocols are still being developed, with evolving imaging guidelines coupled with rapidly expanding research and development of novel anticancer therapies, which come with their side effects and complications. Caring for this patient population is especially challenging and requires specialized multidisciplinary attention.

Discovery of a cytochrome P450 enzyme catalyzing the formation of spirooxindole alkaloid scaffold.

Spirooxindole alkaloids feature a unique scaffold of an oxindole ring sharing an atom with a heterocyclic moiety. These compounds display an extensive range of biological activities such as anticancer, antibiotics, and anti-hypertension. Despite their structural and functional significance, the establishment and rationale of the spirooxindole scaffold biosynthesis are yet to be elucidated. Herein, we report the discovery and characterization of a cytochrome P450 enzyme from kratom (Mitragyna speciosa) responsible for the formation of the spirooxindole alkaloids 3-epi-corynoxeine (3R, 7R) and isocorynoxeine (3S, 7S) from the corynanthe-type (3R)-secoyohimbane precursors. Expression of the newly discovered enzyme in Saccharomyces cerevisiae yeast allows for the efficient in vivo and in vitro production of spirooxindoles. This discovery highlights the versatility of plant cytochrome P450 enzymes in building unusual alkaloid scaffolds and opens a gateway to access the prestigious spirooxindole pharmacophore and its derivatives.

Leveraging synthetic biology and metabolic engineering to overcome obstacles in plant pathway elucidation.

Major hurdles in plant biosynthetic pathway elucidation and engineering include the need for rapid testing of enzyme candidates and the lack of complex substrates that are often not accumulated in the plant, amenable to synthesis, or commercially available. Linking metabolic engineering with gene discovery in both yeast and plant holds great promise to expedite the elucidation process and, at the same time, provide a platform for the sustainable production of plant metabolites. In this review, we highlight how synthetic biology and metabolic engineering alleviated longstanding obstacles in plant pathway elucidation. Recent advances in developing these chassis that showcase established and emerging strategies in accelerating biosynthetic gene discovery will also be discussed.

Pulmonary hypertension screening in children with sickle cell disease.

BACKGROUND: Screening for pulmonary hypertension (PHT) is recommended in children with sickle cell disease (SCD). However, best approaches are poorly described. We examined the utility of PHT symptoms, echocardiogram (ECHO), N-terminal-pro hormone brain natriuretic peptide (NT-proBNP), and BNP to screen for PHT in the SCD pediatric population. METHODS: Children (8-18 years old) with SCD-HbSS and HbSthal° were prospectively included and underwent PHT screening. The screening consisted of a comprehensive PHT symptoms evaluation, ECHO measurement, and NT-proBNP and BNP levels. RESULTS: A total of 73 patients were included (mean age 12 ± 5.7 years; >80% on hydroxyurea), of which 37% had a symptom consistent with PHT, including exertional dyspnea (26.5%), fatigue (17.6%), palpitation (14.7%), and chest pain (10.3%). ECHO was obtained in 53 (72.6%) patients, with only ECHO of 48 patients included in the final analysis. Elevated ECHO peak tricuspid regurgitant jet velocity (TRV) >2.5 m/s or indirect findings to suggest PHT were seen in only two of 48 (4.2%). No significant differences were seen between those with and without PHT symptoms when compared for NT-proBNP, BNP, hemoglobin, pulmonary function testing, fractional exhaled nitric oxide, asthma, oxygen saturation, and sleep apnea. CONCLUSION: PHT symptoms are not consistent with ECHO, NT-proBNP nor BNP findings in children with SCD. PHT prevalence based on TRV was low in children on hydroxyurea, therefore screening may not be warranted for this group.

18 F-Fluciclovine PET Detected Early Tumor Recurrence in Prostatectomy Bed With Low PSA of 0.3 ng/mL But Negative on 18 F-PSMA PET Scan.

ABSTRACT: A 58-year-old man with metastatic prostate cancer was treated with prostatectomy, radiation therapy to bone metastasis, and androgen deprivation therapy plus abiraterone. He had posttreatment nadir PSA of 0.1 ng/mL. A follow-up 18 F-fluciclovine PET performed with PSA of 0.3 ng/mL showed a focal tracer-avid lesion in the left prostatectomy bed. This lesion was negative on 18 F-DCFPyL PET/CT, but with typical MRI features for disease recurrence. Minimal urinary activity of fluciclovine helped detection of local disease recurrence in the prostatectomy bed.

A population-based cohort study on the risk of obstructive lung disease after bilateral oophorectomy.

There is increasing evidence that sex hormones may impact the development of obstructive lung disease (OLD). Therefore, we studied the effect of bilateral oophorectomy (oophorectomy) on the development of OLD. Women were identified from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Data were collected using the Rochester Epidemiology Project records-linkage system. A total of 1653 women who underwent oophorectomy and 1653 referent women of similar age were assessed for OLD using diagnostic codes and medical record abstraction. Women who underwent oophorectomy had an overall higher risk of all OLD, all chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis but not of all asthma, confirmed asthma, or confirmed COPD. The association with all OLD was stronger in women who were age ≤45 years at oophorectomy, never smokers, non-obese, and in women with benign indications; however, the interactions were not statistically significant. There was an increased risk of all asthma in women age ≤45 years at oophorectomy who took estrogen therapy. Never smokers of all ages had a stronger association of oophorectomy with all asthma and all COPD, whereas smokers had a stronger association of oophorectomy with emphysema and chronic bronchitis. Non-obese women of all ages had a stronger association of oophorectomy with all COPD, emphysema, and chronic bronchitis. The results of this study combined with the increased risk of several chronic diseases reported in previous studies suggest that oophorectomy in premenopausal women should be avoided unless there is clear evidence of a high genetic risk of ovarian cancer.

Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants, and therapeutically relevant pathways.

We present a deep proteogenomic profiling study of 87 lung adenocarcinoma (LUAD) tumors from the United States, integrating whole-genome sequencing, transcriptome sequencing, proteomics and phosphoproteomics by mass spectrometry, and reverse-phase protein arrays. We identify three subtypes from somatic genome signature analysis, including a transition-high subtype enriched with never smokers, a transversion-high subtype enriched with current smokers, and a structurally altered subtype enriched with former smokers, TP53 alterations, and genome-wide structural alterations. We show that within-tumor correlations of RNA and protein expression associate with tumor purity and immune cell profiles. We detect and independently validate expression signatures of RNA and protein that predict patient survival. Additionally, among co-measured genes, we found that protein expression is more often associated with patient survival than RNA. Finally, integrative analysis characterizes three expression subtypes with divergent mutations, proteomic regulatory networks, and therapeutic vulnerabilities. This proteogenomic characterization provides a foundation for molecularly informed medicine in LUAD.

Columnar Metaplasia of the Esophagus Presenting as Iron Deficiency Anemia in Children with Neurologic Impairment or Congenital Esophageal Atresia.

BACKGROUND Columnar metaplasia of the lower esophagus includes both gastric and intestinal metaplasia. Children with severe neurologic impairment and congenital esophageal atresia often have gastroesophageal reflux disease, which can lead to Barrett's esophagus, a form of lower esophageal columnar metaplasia and precursor to esophageal adenocarcinoma, with some, but not all, guidelines specifically requiring the presence of intestinal metaplasia for diagnosis. This case series illustrates how iron deficiency anemia may be the primary symptom of esophageal columnar metaplasia in such children and how upper endoscopy is essential in their initial and ongoing evaluation. CASE REPORT We review 5 cases of columnar metaplasia of the lower esophagus in children, 3 with severe neurologic impairment and 2 with esophageal atresia. Each child presented with marked iron deficiency anemia and minimal-to-no gastrointestinal symptoms. CONCLUSIONS We conclude that columnar metaplasia of the esophagus may present with iron deficiency anemia in children with neurologic impairment or congenital esophageal atresia, even if without overt gastrointestinal symptoms. Accordingly, we propose that early endoscopic evaluation should be considered in this specific patient population. Based on our literature review, we also emphasize the need for guidelines on the endoscopic surveillance of such children with any type of columnar metaplasia of the lower esophagus, given the associated risk of malignant transformation.

Does financial literacy influence preventive health check-up behavior in Japan? a cross-sectional study.

BACKGROUND: General health check-ups are an important element of healthcare, as they are designed to detect diseases, thereby reducing morbidity and mortality. Recent studies have found that financial literacy promotes preventive healthcare usage and reduces risky health behaviors such as smoking, lack of exercise, and gambling. Based on this evidence, we hypothesize that financial literacy, as a rational decision-making tool, is positively associated with health check-up behavior in Japan. METHODS: We extracted data on financial literacy, the main explanatory variable of this study, from the 2010 wave of the Preference Parameter Study (PPS) of Osaka University. Data on health check-up behavior as a dependent variable, along with control variables, were obtained from the 2011 PPS wave. Our sample focused on Japan's middle-aged working population (40-64 years), and we applied probit regressions to test our hypothesis. RESULTS: Our final sample size was 2,208 participants after merging the two datasets. Descriptive statistics show that respondents had moderate financial literacy (mean = 0.62, SD = 0.33), low financial education (mean = 0.17, SD = 0.38), and low participation (mean = 31.75%, SD = 46.56%) in the health check-up. The probit regression analysis showed that financial literacy is insignificantly associated with health check-up behavior in Japan (coefficient = -0.0229; 95% CI: -0.2011-0.1551; p-value = 0.801). However, demographic factors such as being male (coefficient = -0.2299; 95% CI: -0.3649--0.0950; p-value = 0.001), older (coefficient = 0.0280; 95% CI: 0.0188 - 0.0371; p-value = 0.000), and married (coefficient = 0.3217; 95% CI: 0.0728 - 0.5705; p-value = 0.011), as well as risky health behavior such as smoking (coefficient = -0.2784; 95% CI: -0.4262--0.1305; p-value = 0.000) are significantly related to health check-up behavior. CONCLUSIONS: Our results suggest that financial literacy insignificantly motivates people to behave rationally and understand the value of health check-ups as a tool for sustainable health.

Multimodality imaging of renal lymphoma and its mimics.

Lymphomatous involvement of the genitourinary system, particularly the kidneys, is commonly detected on autopsies; yet on conventional diagnostic imaging renal lymphoma is significantly underestimated and underreported, in part due to its variable imaging appearance and overlapping features with other conditions. We present a spectrum of typical and atypical appearances of renal lymphoma using multimodality imaging, while reviewing the roles of imaging in the detection, diagnosis, staging, and surveillance of patients with lymphoma. We also illustrate a breadth of benign and malignant entities with similar imaging features confounding the diagnosis of renal lymphoma, emphasizing the role of percutaneous image-guided biopsy. Understanding the spectrum of appearances of renal lymphoma and recognizing the overlapping entities will help radiologists improve diagnostic confidence and accuracy.

Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles.

Lung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor targeting nanoparticles that can provide cancer specific therapies. In this research, we have developed novel dual-stimuli nanoparticles (E-DSNPs), comprised of two parts; (1) Core: responsive to glutathione as stimuli and encapsulating Cisplatin (a chemo-drug), and (2) Shell: responsive to irradiation as stimuli and containing NU7441 (a radiation sensitizer). The targeting moieties on these nanoparticles are Ephrin transmembrane receptors A2 (EphA2) that are highly expressed on the surfaces of lung cancer cells. These nanoparticles were then evaluated for their enhanced targeting and therapeutic efficiency against lung cancer cell lines. E-DSNPs displayed very high uptake by lung cancer cells compared to healthy lung epithelial cells. These nanoparticles also demonstrated a triggered release of both drugs against respective stimuli and a subsequent reduction in in vitro cancer cell survival fraction compared to free drugs of equivalent concentration (survival fraction of about 0.019 and 0.19, respectively). Thus, these nanoparticles could potentially pave the path to targeted cancer therapy, while overcoming the side effects of conventional clinical therapies.