Effects of Short-Term Episodes of Atrial Fibrillation after Coronary Artery Bypass Grafting on the Long-term Incidence of Atrial Fibrillation and Ischemic Stroke.

BACKGROUND: To explore whether postoperative atrial fibrillation (POAF) has an impact on the incidence of late atrial fibrillation (AF) and late ischemic stroke after isolated coronary artery bypass grafting (CABG) compared to non-POAF patients. METHODS: A total of 243 eligible patients were followed for five years, and divided into a POAF group (n = 69) and a non-POAF group (n = 174). The primary end point was the incidence of late AF, and late ischemic stroke. Kaplan-Meier analyses and Cox proportional hazards models were used to examine whether POAF is an independent risk factor for the occurrence of late AF and late ischemic stroke. RESULTS: POAF patients were older than non-POAF patients. During the 5-year follow-up, the late occurrence of AF was significantly higher in POAF patients than in non-POAF (15.9% vs. 7.9% p = 0.006). There was no significant difference in the incidence of late ischemic stroke between POAF and non-POAF groups (p = 0.406). COX proportional regression analysis showed that POAF was independently associated with the late occurrence of AF (hazard ratio (HR) 3.27; 95% confidence interval (CI): 1.33-8.03, p = 0.01). CONCLUSION: POAF is an independent risk factor for the occurrence of late AF but not stroke after isolated CABG.

A senescence-related lncRNA signature predicts prognosis and reflects immune landscape in HNSCC.

OBJECTIVE: Long noncoding RNAs (lncRNAs) regulate cancer cell senescence in many cancers. However, their specific involvement in head and neck squamous cell carcinoma (HNSCC) remains unclear. We are looking for an ingenious prognostic signature that utilizes senescence-related lncRNAs (SRlncRNAs) to predict prognosis and provide insights into the immune landscape in HNSCC. MATERIALS AND METHODS: HNSCC clinical and Cellular senescence genes information were collected from The Cancer Genome Atlas and Human Aging Genomic Resources. Then we performed Cox and Lasso regression to locate SRlncRNAs related to the prognosis of HNSCC and built a predictive signature. Further, prognosis assessment, potential mechanisms, and immune status were assessed by Kaplan-Meier analysis, Gene Set Enrichment Analysis (GSEA), and CIBERSORT, respectively. RESULTS: A prognosis prediction model based on sixteen SRlncRNAs was identified and internally validated. Then, patients with high-risk scores suffered an unfavorable overall survival (All p < 0.05). The risk score, age, and stage were independent prognostic parameters (all p < 0.001). Our model has good predictive ability (The AUC (area under the curves) 1-year = 0.707, AUC3-year = 0.748 and AUC5-year = 0.779). Subsequently, GESA revealed SRlncRNAs regulated immune responses. Patients in the high-risk group had higher tumor mutation burden and Tumor Immune Dysfunction and Exclusion but lower levels of 37 immune checkpoint genes, immune scores, and immune cells like CD8 + T cells, follicular helper T cells, and regulatory T cells. CONCLUSIONS: A prognostic model based on SRlncRNAs is the potential target for improving immunotherapy outcomes for HNSCC.

Development and validation of a model based on immunogenic cell death related genes to predict the prognosis and immune response to bladder urothelial carcinoma.

Background: Immunogenic cell death (ICD) has been categorized as a variant of regulated cell death that is capable of inducing an adaptive immune response. A growing body of evidence has indicated that ICD can modify the tumor immune microenvironment by releasing danger signals or damage-associated molecular patterns (DAMPs), potentially enhancing the efficacy of immunotherapy. Consequently, the identification of biomarkers associated with ICD that can classify patients based on their potential response to ICD immunotherapy would be highly advantageous. Therefore the goal of the study is to better understand and identify what patients with bladder urothelial carcinoma (BLCA) will respond to immunotherapy by analyzing ICD signatures and investigate ICD-related prognostic factors in the context of BLCA. Methods: The data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases regarding BLCA and normal samples was categorized based on ICD-related genes (IRGs). Specifically, we conducted an immunohistochemical (IHC) experiment to validate the expression levels of Calreticulin (CALR) in both tumor and adjacent tissues, and evaluated its prognostic significance using the Kaplan-Meier (KM) curve. Subsequently, the samples from TCGA were divided into two subtypes using consensus clustering. To obtain a more comprehensive comprehension of the biological functions, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The calculation of immune landscape between two subtypes was performed through ESTIMATE and CIBERSORT. Risk models were constructed using Cox and Lasso regression and their prognosis predictive ability was evaluated using nomogram, receiver operating characteristic (ROC), and calibration curves. Finally, Tumor Immune Dysfunction and Exclusion (TIDE) algorithms was utilized to predict the response to immunotherapy. Results: A total of 34 IRGs were identified, with most of them exhibiting upregulation in BLCA samples. The expression of CALR was notably higher in BLCA compared to the adjacent tissue, and this increase was associated with an unfavorable prognosis. The differentially expressed genes (DEGs) associated with ICD were linked to various immune-related pathways. The ICD-high subtypes exhibited an immune-activated tumor microenvironment (TME) compared to the ICD-low subtypes. Utilizing three IRGs including CALR, IFNB1, and IFNG, a risk model was developed to categorize BLCA patients into high- and low-risk groups. The overall survival (OS) was considerably greater in the low-risk group compared to the high-risk group, as evidenced by both the TCGA and GEO cohorts. The risk score was identified as an independent prognostic parameter (all p < 0.001). Our model demonstrated good predictive ability (The area under the ROC curve (AUC), AUC1-year= 0.632, AUC3-year= 0.637, and AUC5-year =0.653). Ultimately, the lower risk score was associated with a more responsive immunotherapy group. Conclusion: The potential of the ICD-based risk signature to function as a marker for evaluating the prognosis and immune landscape in BLCA suggests its usefulness in identifying the suitable population for effective immunotherapy against BLCA.

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy.

BACKGROUND: SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. METHODS: This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types. RESULTS: A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H (p < 0.01) and had a lower death hazard than TMB-H in pancancer patients (0.511 vs 0.757). Significantly higher MSI and lower homologous recombination deficiency were observed in the SETD2 deleterious mutation group. Improved survival rate was found in the MSKCC-IO cohort (P < 0.0001) and was further confirmed in our Chinese cohort. CONCLUSION: We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.

Prognostic values of regulatory T cells (Tregs) and Treg-related genes in gastric cancer.

Introduction: This study attempted to investigate the potential of a risk model constructed for regulatory T cells (Tregs) and their related genes in predicting gastric cancer (GC) prognosis. Material and methods: We used flow cytometry to detect the content of CD4+CD25+ Tregs. After detecting expression of five Treg-related genes by quantitative real-time polymerase chain reaction (qRT-PCR), Pearson analysis was employed to analyze the correlation between Tregs and related gene expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation and transwell assays were used to detect the effects of a disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12) on cell functions. A prognostic risk model was built after Cox regression analysis. The Kaplan-Meier method was employed to assess how Tregs, 5-gene risk scores and expression of 5 genes were correlated with the survival time. Results: A significantly increased content of Tregs was found in GC tissues (p < 0.05). 5 Treg- related genes were significantly up-regulated in GC with a positive correlation with the content of Tregs (p < 0.05). Overexpression of ADAMTS12 significantly enhanced the viability, proliferation, migration and invasion of tumor cells. Kaplan-Meier analysis demonstrated poor overall survival and disease-free survival in the high-risk group. The results of survival analysis of Treg content and related gene expression were consistent with those of Cox analysis. Conclusions: The risk model constructed based on five Treg-related genes can enable effective prediction in the prognosis of GC patients.

Prenatal ultrasound diagnosis of congenital vertical talus.

OBJECTIVE: This study aimed to analyze the ultrasound characteristics of fetal congenital vertical talus (CVT) to provide a detailed basis for the prenatal diagnosis of CVT. METHODS: We retrospectively analyzed the ultrasonographic findings of fetuses with CVT confirmed by X-ray, surgery, or autopsy from 2010 to 2020. Clinical characteristics and ultrasonographic findings of CVT, including foot morphology, ossification center of the calcaneus and talus, associated deformities, and chromosomal test results, were recorded. RESULTS: Thirteen patients diagnosed with CVT by prenatal ultrasound were confirmed postpartum. Nine cases were bilateral, and four were unilateral. Under two-dimensional ultrasound, 13/13 cases had abnormal foot morphology, and 10 of 13 cases (76.9%) showed that the ossification center of the talus moved downward, and the calcaneus moved laterally. Under three-dimensional ultrasound, 11 cases (84.6%) presented a "rocking chair" appearance, and two cases did not obtain satisfactory three-dimensional image due to oligohydramnios and fetal position. In this group of cases, two cases (15.4%) were isolated CVT, and the other 11 cases (84.6%) were complicated with other abnormalities. Eleven cases of non-isolated CVT and 1 case of isolated CVT were induced, and another patient with isolated CVT had undergone postnatal surgery, which had been followed up for 8 years and recovered well. CONCLUSIONS: The combination of fetal foot morphology, ossification center position of the calcaneus and talus, and three-dimensional ultrasound can provide a reliable diagnosis of CVT. Furthermore, we should pay more attention to the evaluation of other systemic and chromosomal abnormalities in CVT cases.

An Immunogenic Cell Death-Related Gene Signature Reflects Immune Landscape and Predicts Prognosis in Melanoma Independently of BRAF V600E Status.

Immunogenic cell death (ICD) is a type of regulated cell death that can activate adaptive immune response, and its ability to reshape the tumor microenvironment via multiple mechanisms may contribute to immunotherapy. The treatment options for patients with skin cutaneous melanoma (SKCM) vary based on BRAF V600E statuses. However, all standard treatments include immunotherapy. Therefore, it is critical to identify ICD-associated signatures that can help classify patients according to benefits from ICD immunotherapy. In this study, data on melanoma samples with BRAF V600E mutation (BRAF V600E-mutant melanoma) and melanoma samples with wild-type BRAF V600E alleles (BRAF V600E WT melanoma) were collected from The Cancer Genome Atlas (TCGA) database. The ICD-related (ICD-high and ICD-low) subgroups of patients with BRAF V600E WT melanoma were established via consensus clustering. The analyses of survival, differentially expressed genes (DEGs), functional annotation, and immune landscape were performed in these two subgroups. Results showed that ICD-high subgroup was correlated with a positive overall survival (OS) and active tumor immune landscape. A model comprising seven prognosis ICD-related gene biomarkers was developed. Survival analysis and receiver operating characteristic (ROC) curve evaluation in both cohorts with BRAF V600E WT and BRAF V600E-mutant melanoma showed an accurate prognostic estimation of ICD-related risk signature. There was a correlation between immune cell infiltration and immunotherapy response and risk score. Thus, the ICD risk signature was closely associated with the tumor's immune microenvironment. Our results may provide insights to further individualize and improve precision therapeutic decision-making in BRAF V600E-mutant and WT melanoma.

Prediction of Fetal Biliary Atresia Based on Second and Third-Trimester Ultrasound Characteristics.

OBJECTIVE: To explore the diagnostic performance of prenatal ultrasound in the prediction of biliary atresia (BA). METHODS: We prospectively collected cases of suspected biliary abnormalities in the 2nd trimester of pregnancy and performed a series (at least 3) of prenatal ultrasound examinations in the 2nd and 3rd trimester. The presence of the gallbladder was examined each time, and its size and shape were assessed if the gallbladder was visible. The existence of other abnormalities was carefully evaluated. Neonatal ultrasound examination was conducted within 1 month after birth, and clinical data were followed-up for 6 months after birth. RESULTS: Among the 41 895 patients, 298 were suspected to have biliary abnormalities, while 82 patients were excluded due to loss to follow-up or induced labor caused by other abnormalities. A total of 216 patients were included in this study, and 15 were diagnosed with BA. We summarized the ultrasound findings of the gallbladders and defined a high-risk gallbladder for the prenatal diagnosis of BA. This was demonstrated to have the best diagnostic performance as a single parameter, with an area under the curve of 0.914 (95 %CI: 0.869-0.948). In addition, higher incidences of biliary cysts, right hepatic artery dilation, echogenic bowel, and ascites were observed in BA fetuses. Logistic regression analysis showed that the combination of 5 parameters had better diagnostic performance, with an area under the curve of 0.995 (95 %CI: 0.973-0.999). CONCLUSION: The fetal gallbladder was found to be a critical feature for the identification of BA. Concomitant abnormalities could be helpful to improve the accuracy of the diagnosis.

FAM3D as a Prognostic Indicator of Head and Neck Squamous Cell Carcinoma Is Associated with Immune Infiltration.

Background: Globally, head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor with high morbidity and mortality. Hence, it is important to find effective biomarkers for the diagnosis and prediction of the prognosis of patients with HNSCC. FAM3D had been proven to be vital in other cancers. However, its predictive and therapeutic value in HNSCC is unclear. Therefore, it is valuable to explore the association between the expression level of FAM3D and its impacts on the prognosis and tumor microenvironment in HNSCC. Methods: The Cancer Genome Atlas (TCGA) dataset, Genotype-Tissue Expression (GTEx) dataset, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset, and The Human Protein Atlas (THPA) website were used to assess HNSCC expressions in tumor and nontumor tissues. Then, we further conducted immunohistochemistry experiment as internal cohort to validate the same results. The Cox regression analysis, Kaplan-Meier analysis, and nomograms were performed to find the predictive prognostic value of FAM3D in HNSCC patients and its relationship with the clinicopathological features in HNSCC. The Gene Expression Omnibus (GEO) dataset was utilized to externally verify the prognosis value of FAM3D in HNSCC. Gene Set Enrichment Analysis (GESA) was applied to search the molecular and biological functions of FAM3D. The association between FAM3D and immune cell infiltration was investigated with the Tumor Immune Estimating Resource, version 2 (TIMER2). The relationships between FAM3D expression and tumor microenvironment (TME) scores, immune checkpoints, and antitumor compound half-maximal inhibitory concentration predictions were also explored. Results: In different datasets, FAM3D mRNA and protein levels were all significantly lower in HNSCC tissues than in normal tissues, and they were strongly inversely associated with tumor grade, stage, lymph node metastasis, and T stage. Patients with high-FAM3D-expression displayed better prognosis than those with low-FAM3D-expression. FAM3D was also determined to be a suitable biomarker for predicting the prognosis of patients with HNSCC. This was externally validated in the GEO dataset. As for gene and protein level, the functional and pathway research results of FAM3D indicated that it was enriched in alteration of immune-related pathways in HNSCC. The low-expression group had higher stromal and ESTIMATE scores by convention than the high-expression group. FAM3D expression were found to be positively correlated with immune infiltrating cells, such as cancer-associated fibroblasts, myeloid-derived suppressor cells, macrophage cells, T cell CD8+ cells, regulatory T cells, and T cell follicular helper cells. FAM3D's relationships with immune checkpoints and sensitivity to antitumor drugs were also investigated. Conclusion: Our study explored the impact of FAM3D as a favorable prognostic marker for HNSCC on the tumor immune microenvironment from multiple perspectives. The results may provide new insights into HNSCC-targeted immunotherapy.

Characteristic and antibacterial effect of a histone H2A and its preliminary roles in extracellular traps in manila clam Ruditapes philippinarum.

In the present study, a histone H2A (designed as RpH2A) was identified and characterized from clam Ruditapes philippinarum, and its open reading frame (ORF) was of 387 bp encoding a polypeptide of 128 amino acids. The deduced amino acid sequence of RpH2A shared high identities ranging from 57.1% to 96.1% with that of other identified H2A. The mRNA expression of RpH2A was up-regulated significantly after Vibrio anguillarum challenge. The recombinant RpH2A protein (rRpH2A) displayed significantly binding affinity to lipopolysaccharide (LPS) and peptidoglycan (PGN) in vitro, and also exhibited antimicrobial properties against Escherichia coli. In addition, the antimicrobial RpH2A was shown to co-localize with extracellular traps (ETs) released from hemocytes induced by E. coli, suggesting that RpH2A might contribute to eliminate invading bacteria in clam ETs. Altogether, our data revealed that RpH2A could function as antimicrobial peptides, which might play a crucial role in the immune responses of hemocytes ETs in clams.

Prognostic impact of Breslow thickness in acral melanoma: A retrospective analysis.

BACKGROUND: Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited. OBJECTIVE: The objective of the study was to determine the prognostic impact of Breslow thickness in AM. METHODS: This multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression. RESULTS: A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The median follow-up time was 60.1 months. The median MSS in patients with T1-T4 disease was not reached, 111.0, 92.8, and 67.1 months, respectively. MSS differed significantly among cN0 patients with T1-T3 AM (log-rank P = .004, .012, <0.001 for T1 vs T2, T2 vs T3, and T1 vs T3, respectively); however, there was no significant difference between T3 and T4 AM (hazard ratio = 0.82, 95% CI, 0.62-1.09). Six-subgroup analyses confirmed that survival outcomes were similar between different subgroups with tumor thickness >2 mm. LIMITATIONS: The limitations were retrospective design and some missing variables. CONCLUSIONS: There was no association between tumor thickness and survival in AM patients with a Breslow thickness >2 mm.

Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta.

BACKGROUND: Spina bifida aperta (SBA) is a relatively common clinical type of neural tube defect. Although prenatal fetal surgery has been proven to be an effective treatment for SBA, the recovery of neurological function remains unsatisfactory due to neuron deficiencies. Our previous results demonstrated that intra-amniotic transplanted bone marrow mesenchymal stem cells (BMSCs) could preserve neural function through lesion-specific engraftment and regeneration. To further optimize the role of BMSCs and improve the environment of defective spinal cords so as to make it more conducive to nerve repair, the intra-amniotic transplanted BMSCs were modified with brain-derived neurotrophic factor (BDNF-BMSCs), and the therapeutic potential of BDNF-BMSCs was verified in this study. METHODS: BMSCs were modified by adenovirus encoding a green fluorescent protein and brain-derived neurotrophic factor (Ad-GFP-BDNF) in vitro and then transplanted into the amniotic cavity of rat fetuses with spina bifida aperta which were induced by all-trans-retinoic acid on embryonic day 15. Immunofluorescence, western blot and real-time quantitative PCR were used to detect the expression of different neuron markers and apoptosis-related genes in the defective spinal cords. Lesion areas of the rat fetuses with spina bifida aperta were measured on embryonic day 20. The microenvironment changes after intra-amniotic BDNF-BMSCs transplantation were investigated by a protein array with 90 cytokines. RESULTS: We found that BDNF-BMSCs sustained the characteristic of directional migration, engrafted at the SBA lesion area, increased the expression of BDNF in the defective spinal cords, alleviated the apoptosis of spinal cord cells, differentiated into neurons and skin-like cells, reduced the area of skin lesions, and improved the amniotic fluid microenvironment. Moreover, the BDNF-modified BMSCs showed a better effect than pure BMSCs on the inhibition of apoptosis and promotion of neural differentiation. CONCLUSION: These findings collectively indicate that intra-amniotic transplanted BDNF-BMSCs have an advantage of promoting the recovery of defective neural tissue of SBA fetuses.

Potential Diagnostic and Prognostic Values of CBX8 Expression in Liver Hepatocellular Carcinoma, Kidney Renal Clear Cell Carcinoma, and Ovarian Cancer: A Study Based on TCGA Data Mining.

Background: Chromobox protein homolog 8 (CBX8), a transcriptional repressor, participates in many biological processes in various carcinomas. Cell differentiation, aging, and cell cycle progression are examples of such processes. It is critical to investigate CBX8 expression and its relationship with clinicopathological characteristics in liver hepatocellular carcinoma (LIHC), kidney renal clear cell carcinoma (KIRC), and ovarian cancer (OV) to investigate CBX8's potential diagnostic and prognostic values. Methods: TCGA and CPTAC databases were used to compare the data between cancer and matched normal tissues on RNA and protein expression profiles and their relevant clinical information to determine the relationship between CBX8 and clinicopathological features. Kaplan-Meier analyses were used to assess CBX8 relationship's with disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). The multivariate Cox regression analysis was used to identify independent risk factors which affect prognosis. DNA methylation and genetic changes and their impact on prognoses were evaluated by cBioPortal and MethSurv websites. Spearman's correlation was used to determine the relationship of CBX8 expression with somatic mutation. Tumor immune estimation resource (TIMER) was adopted to investigate the relationship between CBX8 and immune cell infiltration (ICI). CBX8-relevant genes and proteins are analyzed by EnhancedVolcano and STRING databases. The gene set enrichment analysis (GSEA) was performed to investigate the potential functions of CBX8. Results: CBX8 RNA and protein overexpression were confirmed in LIHC, KIRC, and OV (p < 0.05). High CBX8 was significantly related to the clinical features and poor prognoses. The CBX8 genetic alteration rate was 3%. DNA methylation was also associated with prognoses. CBX8 closely interacted with ICI, TMB, MSI, purity, and ploidy. GO analyses revealed that CBX8-associated genes were enriched in biological processes, cell cycle regulation, and molecular functions. KEGG analyses exhibited that CBX8 was gathered in signaling pathway regulation. GSEA revealed that cell cycle, DNA replication, and Wnt signaling pathways were differentially enriched in the high CBX8 expression group. Conclusions: CBX8 could be a potential diagnostic and prognostic biomarker for LIHC, KIRC, and OV cancers.

Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer.

ABSRACT: Neoantigens are ideal targets for dendritic cell (DC) vaccines. So far, only a few neoantigen-based DC vaccines have been investigated in clinical trials. Here, we reported a case of a patient with metastatic gastric cancer who received personalized neoantigen-loaded monocyte-derived dendritic cell (Neo-MoDC) vaccines followed by combination therapy of the Neo-MoDC and immune checkpoint inhibitor (ICI). The patient developed T cell responses against neoantigens after receiving the Neo-MoDC vaccine alone. The following combination therapy triggered a stronger immune response and mediated complete regression of all tumors for over 25 months till October, 2021. Peripheral blood mononuclear cells recognized seven of the eight vaccine neoantigens. And the frequency of neoantigen-specific T cell clones increased obviously after vaccination. Overall, this report describing a complete tumor regression in a gastric cancer patient mediated by Neo-MoDC vaccine in combination with ICI, and suggesting a promising treatment for patients with metastatic gastric cancer.

Characteristics of fetal physiological and pathological uterine effusion observed on prenatal ultrasonography: a case report.

BACKGROUND: The prenatal detection rate of fetal uterine effusion is very low, and current case reports mainly focus on pathological hydrometrocolpos. We presented two cases of fetal physiological uterine effusion with different ultrasonic characteristics and compared them with one case of hydrometrocolpos with the hope of identifying strategies to reduce misdiagnosis of fetal uterine effusion. CASE PRESENTATION: This paper reports the cases of two female fetuses with abnormal pelvic echoes in the third trimester, referred to a tertiary center to be screened for suspected pelvic teratoma and cystic mass, respectively. Ultrasound consultation revealed fetal uterine effusion. The two fetuses were delivered at our hospital after a full term. Re-examining the uterus and adnexa of the neonates revealed that the uterine effusion had subsided naturally. Another female fetus had a large cystic mass in the pelvic cavity in the third trimester, and prenatal examination indicated fetal hydrometrocolpos. The fetus was delivered at our hospital after a full term. The hydrometrocolpos existed even after birth. After consultation with a neonatal surgeon and gynecologist, the newborn was diagnosed with congenital imperforate hymen with hydrometrocolpos. Hymen puncture and open drainage led to a good prognosis. CONCLUSIONS: Prenatal ultrasonography plays an important role in diagnosing and differentiating between physiological and pathological fetal uterine effusion. It can help reduce misdiagnoses that can lead to incorrect clinical decisions.

A Combined CRISP3 and SPINK1 Prognostic Grade in EPS-Urine and Establishment of Models to Predict Prognosis of Patients With Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is characterized by significant heterogeneity. Thus, novel prognostic indicators are required to improve prognosis and treatment. METHODS: Cysteine rich secretory protein 3 (CRISP3) and serine peptidase inhibitor Kazal type 1 (SPINK1) levels in expressed prostatic secretion (EPS)-urine collected during digital rectal examination of 496 patients histologically diagnosed with PCa were detected via enzyme-linked immunosorbent assay. A combined CRISP3 and SPINK1 prognostic grade (CSPG) was defined using cut-off values from receiver operating characteristic curves. Log-rank Kaplan-Meier survival curves investigated differences in prognosis between groups. Univariate and multivariate Cox analyses investigated the CSPG relationship with biochemical recurrence (BCR), cancer-specific survival (CSS), and overall survival (OS). Three prognostic models were developed and validated. CONCLUSIONS: CRISP3 and SPINK1 levels increased with Gleason score progression, pathological T stage, and metastasis status. CSPG in EPS-urine, which was an effective independent prognostic variable, accurately predicted the prognosis of patients with PCa. Three clinical prognostic models using the CSPG for BCR, CSS, and OS were developed and validated.

Maternal serum Lamin A is a potential biomarker that can predict adverse pregnancy outcomes.

BACKGROUND: Maternal serum Lamin A (LMNA) was reported to have potential diagnostic value in the prenatal diagnosis of congenital heart disease (CHD). In this study, we aimed to further assess the prognostic value of maternal serum LMNA in predicting adverse pregnancy outcomes. METHODS: A prospective screening study was performed on singleton pregnancies at 15-18 weeks of gestation. After a routine test for alpha fetoprotein (AFP), chorionic gonadotropin (hCG), and unconjugated estriol (uE3), serum LMNA levels were measured. Serum LMNA levels were then converted into multiples of the median (MoM). The median MoM values for adverse pregnancy outcomes were compared with those in normal pregnancies. For diseases with differential LMNA expression in the prospective study, another case-control cohort was recruited. The diagnostic value of LMNA in these diseases was further evaluated. FINDINGS: Between January 1, 2017 and June 30, 2018, a total of 2906 singleton pregnancies were recruited. Of the 2,906 cases, 2711 had data available for analysis. Congenital structural abnormalities, chromosomal abnormalities, and obstetric complications were observed in 152 (5·6%), 15 (0·6%), and 278 (10·3%) patients, respectively. LMNA was downregulated in pregnancies with fetal CHD, fetal neural tube defects (NTD), and preeclampsia (PE). The case-control study cohort included 256 CHD, 60 NTD, 67 PE, and 400 normal pregnancies. The areas under the curve for the prenatal diagnoses of CHD, NTD, and PE were 0·875, 0·871, and 0·816, respectively. INTERPRETATION: Maternal serum LMNA was found to be a potential biomarker for the prenatal diagnosis of fetal CHD, NTD, and PE. FUNDING: National Key Research and Development Program, National Natural Science Foundation of China, LiaoNing Revitalization Talents Program, National Natural Science Foundation of Liaoning, and 345 Talent Project of Shengjing Hospital.

Fetal Abdominal Cystic Masses: Clinical Spectrum and Prenatal Ultrasound Diagnosis.

OBJECTIVES: To assess the diagnostic accuracy of prenatal ultrasound in detecting intra-abdominal masses derived from different systems. METHODS: Fetuses diagnosed with abdominal cystic masses during prenatal ultrasound were included in this study. The basic biological parameters of the fetus were measured in addition to the location of the cystic mass, the shape and size of the mass, the thickness of the cystic wall, dynamic changes, blood supply of the mass, and relationship with the surrounding organs. Whether the fetus also had other malformations was also recorded. Clinical data were followed up to 6 months after birth. RESULTS: Between January 1, 2019 and January 1, 2021, 247 fetuses were included, most of which contained renal/adrenal cystic masses (n = 93, 37.7%), followed by hepatobiliary system (n = 48, 19.4%), gastrointestinal tract (n = 45, 18.2%), reproductive system (n = 29, 11.7%), and ureter and bladder (n = 27, 10.9%) masses, respectively. The minority were masses in other systems (n = 5, 2.0%). The overall prenatal diagnostic accuracy was 90.7%. There were significant differences in each system (χ2  = 13.0, P < .05). The most accurate type of cyst was diagnosed from renal and adrenal (96.8%) cases, followed by ureter and bladder (92.6%) cases, gastrointestinal tract (91.1%), hepatobiliary system (85.4%), and reproductive system (82.8%). Other systems (60.0%) were the least accurate type. CONCLUSIONS: A wide variety of cystic masses can be accurately detected in the fetal abdomen, and most of these lesions can be accurately diagnosed during pregnancy.

Prognostic value of ulceration varies across Breslow thicknesses and clinical stages in acral melanoma: a retrospective study.

BACKGROUND: Ulceration is regarded as an adverse prognostic factor and is used together with tumour thickness to subcategorize patients with cutaneous melanoma. However, the prognostic impact of ulceration in acral melanoma (AM) is controversial. OBJECTIVES: To assess the prognostic impact of ulceration in AM and the variability across different Breslow thicknesses and clinical stages. METHODS: A multicentre retrospective study of patients diagnosed with AM between January 2000 and December 2017. Differences in melanoma-specific survival (MSS) between patients with and without ulceration were assessed using the multivariable Cox proportional hazards model and log-rank test. RESULTS: Among 1053 enrolled patients, 62.6% had ulceration. After a median follow-up of 61 months, patients with ulceration had a lower median MSS than those without: 66.1 months, 95% confidence interval (CI) 60.0-86.0 vs. not reached; hazard ratio 1.41, 95% CI 1.09-1.82; P = 0.012. Among patients with thin (≤ 1 mm) melanoma, the survival curves of patients with vs. without ulceration clearly separated over time (P < 0.001). No association between ulceration and MSS was observed for melanomas of thickness > 1 mm (subgroups of T2, T3 and T4; all P-values > 0.05) or patients with stage III disease (hazard ratio 1.09, 95% CI 0.71-1.68, P = 0.39). CONCLUSIONS: Ulceration is an independent negative prognostic factor for patients with AM, but the impact varies across Breslow thicknesses and clinical stages. Ulceration has a significant effect on prognosis for patients with thin (≤ 1 mm) melanoma, but there was no association between ulceration and survival in intermediate/thick AM or stage III AM. What is already known about this topic? Ulceration status is used together with Breslow tumour thickness to subcategorize patients into different stages according to the America Joint Committee on Cancer melanoma staging system. As one distinctive subtype of cutaneous melanoma, acral melanoma (AM) is characterized by poor survival outcomes due to delayed diagnosis and a high prevalence of negative prognostic and genetic features. The prognostic impact of ulceration in AM is still controversial. What does this study add? This was the first large-scale study to assess the prognostic and staging values of ulceration in patients with AM. Ulceration has a significant effect on prognosis for patients with thin (≤1 mm) melanoma, but no association between ulceration and survival was found in intermediate/thick or stage III AM. These findings should be considered when using ulceration-based staging systems.

Differentiation of cystic biliary atresia and choledochal cysts using prenatal ultrasonography.

PURPOSE: This study explored the performance of prenatal ultrasonography in the differential diagnosis of cystic biliary atresia (CBA) and choledochal cyst (CC). METHODS: Fetuses diagnosed with hepatic hilar cyst in the second trimester were included in this study. A series of prenatal ultrasound examinations were performed in the second and third trimesters. The diameter of the gallbladder (GB) and hepatic cyst were measured, as well as the wall thickness of the GB. The GB-cyst connection, visibility of the right hepatic artery (RHA), and other concomitant abnormalities were carefully evaluated. A neonatal transabdominal ultrasound examination was performed within 1 week after birth, and clinical data were followed up to 6 months after birth. RESULTS: Between January 1, 2016 and January 31, 2020, 53 fetuses diagnosed with hepatic hilar cyst were recruited. Eight were excluded because they were lost to follow-up. Among the 45 cases included in this study, 10 were diagnosed with CBA and 35 with CC after birth. Statistically significant differences were found in GB width, wall thickness, change in GB width, change in cyst length, GB-cyst connection, and RHA visibility between the CBA and CC groups. GB width showed the best diagnostic performance with an area under the curve (AUC) of 0.899. The combination of GB width, GB wall thickness, and GB-cyst connection yielded a comparable AUC of 0.971. CONCLUSION: The GB should be carefully evaluated in fetuses with hepatic hilar cyst. Prenatal ultrasound findings could provide suggestive parameters for the differential diagnosis of CBA from CC.