Diagnostic Predictive Value Research Articles

Papanicolaou Society of Cytopathology System vs World Health Organization of Reporting System for Pancreaticobiliary Cytopathology‐Comparison of Risk of Malignancy and Diagnostic Predictive Values: A 3 Year Retrospective Study in India

Papanicolaou Society of Cytopathology System vs World Health Organization of Reporting System for Pancreaticobiliary Cytopathology‐Comparison of Risk of Malignancy and Diagnostic Predictive Values: A 3 Year Retrospective Study in India

Evaluation of RT-QuIC Diagnostic Performance for Chronic Wasting Disease Detection Using Elk (Cervus canadensis) Ear Punches.

Sensitive and specific antemortem diagnostic tests are a prerequisite for effective management of chronic wasting disease (CWD). Paired with readily accessible samples that accurately reflect CWD status, the real-time quaking-induced conversion (RT-QuIC) assay has the potential to enable more effective CWD surveillance and interventions. We evaluated the feasibility of RT-QuIC as a CWD diagnostic test using 6-mm ear tissue biopsies from elk (Cervus canadensis). First, we evaluated the effect of ear spatial location on seeding activity. We observed an effect of ear punch spatial location on the amyloid formation rate (AFR): Samples collected from the periphery of the ear evidenced a statistically significant increase in AFR relative to ear punches from the ventral midline. Gross microdissection of an ear pinna suggested that there was more small nerve innervation around the periphery of the ear. Second, we evaluated the diagnostic sensitivity, specificity, and predictive value of RT-QuIC using ear punches from elk that had been previously diagnosed via ELISA testing. We evaluated the impact of nonstatistical and statistical approaches on diagnostic accuracy. Specificity and positive predictive value were perfect when statistical analyses were used to evaluate the binomial distribution (CWD positive versus CWD negative) of the data. Conversely, sensitivity and negative predictive value were modest, independent of the application of statistical analysis, indicating that RT-QuIC may be susceptible to false-negative data in this context. Taken together, our data support the idea that RT-QuIC, when paired with US Department of Agriculture-approved diagnostic tests, may provide more time to stakeholders for making major management decisions.

Late intervention for type II endoleak is not determined by early sac diameter or volume changes after EVAR.

To compare the diagnostic accuracy and predictive value of aneurysm sac volume measurement versus maximum diameter measurement of abdominal aortic aneurysm sac after endovascular aneurysm repair (EVAR) in patients with type II endoleak. Retrospective study on a cohort of 103 patients who presented with a type II endoleak after EVAR for infrarenal abdominal aortic aneurysm. Maximum diameter and volumetric measurements were calculated on computed tomography follow-up scans at 3 months and 1 year after index surgery. Pearson correlation coefficient was used to determine linear association between diameter and volume; Mann-Whitney U test was used to compare patients with and without later intervention for type II endoleak with regard to diameter and volume change. The correlation between diameter and volume measurement was high (Rho: 0.890-0.980 with P < 0.0001). In 38 out of 103 patients (37%) with type II endoleak, a later intervention for endoleak management was performed; early diameter (P = 0.097), or volume (P = 0.387) change could not predict risk for later intervention. Both diameter and volume measurements can be used in the imaging follow-up of patients with endoleak type II after EVAR; however early changes in diameter or volume of the aneurysm sac cannot predict late intervention for type II endoleak.

Inflammatory index is a promising biomarker for maintenance hemodialysis patients with cardiovascular disease

Background and objectivesMaintenance hemodialysis (MHD) patients are at a higher risk of cardiovascular disease (CVD), a common complication and leading cause of death. Persistent micro-inflammation is a unique feature of MHD. Given the established role of inflammation in the pathogenesis of atherosclerosis, this study aims to explore whether novel inflammatory markers (inflammation index) can serve as independent risk factors for CVD in MHD patients.MethodsA cross-sectional survey was conducted on patients from three dialysis centers, categorized into a CVD and non-CVD group based on medical history, laboratory tests, and physical examination. Fasting blood samples were collected from all participants for indicator testing.ResultsThe analysis of 209 patients revealed that 104 had concurrent CVD. Patients in the CVD group were significantly older and exhibited higher anxiety and depression scores. Forward stepwise multivariate logistic regression results identified the inflammation index neutrophil-to-lymphocyte ratio (NLR) (OR = 1.27, 95% CI 1.082–1.491, P < 0.05) and systemic immune-inflammation index (SII) (OR = 1.001, 95% CI 1.0001–1.002, P < 0.05) as independent risk factors for CVD in MHD patients. Receiver operating characteristic (ROC) curve analysis demonstrated that SII, platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and NLR all possess predictive diagnostic values for CVD events in this patient population.ConclusionsHemodialysis centers can utilize simple and cost-effective inflammatory markers to proactively identify patients at risk of CVD. Future research into how inflammation contributes to CVD in MHD is required.

Risk stratification for CNS infection: A potential tool to avoid unwarranted lumbar punctures – An observational study

ObjectiveCentral nervous system (CNS) infection poses a diagnostic challenge especially in elderly patients who frequently exhibit atypical symptoms. Our study aimed to identify patients with a low risk of CNS infection, in whom lumbar puncture (LP) could be avoided. MethodsObservational study of consecutive adult patients who underwent a LP in the emergency room (ER) of Hospital Universitari Vall d’Hebron between January 2017 and December 2021. We performed a univariate and multivariate analysis to identify factors associated with non-CNS infection. These factors were used to create a combined variable, and its diagnostic positive predictive value and specificity to detect patients without CNS infections were calculated. ResultsWe included 489 patients of which 77 (15.7%) were diagnosed with CNS infection. Median age was 62 years (IQR 41–78) and 240 (49.1%) were male. In the multivariate analysis, variables associated with non-CNS infection were female sex (OR 1.89; 95% CI 1.12–3.20), age older than 80 years (OR 3.14; 95% CI 1.20–8.19), previous cognitive impairment (OR 3.91; 95% CI 1.18–13.01), and clinical presentation without meningitis triad (fever, headache and neck stiffness) (OR 4.12; 95% CI 1.72–9.85). A composite variable encompassing age older than 80, cognitive impairment, and the absence of the meningitis triad was used as a diagnostic tool to identify patients with non-CNS infection, exhibiting a 98% positive predictive value and 99% specificity. ConclusionsThis study identifies factors associated with a low risk of CNS infection. Thus, a more precise clinical approach could help clinicians to detect patients who would not benefit from a LP.

A Loop-Mediated Isothermal Amplification Assay Utilizing Hydroxy Naphthol Blue (LAMP-HNB) for the Detection of Treponema pallidum Subspp. pallidum.

Treponema pallidum subspp. pallidum is a spirochaete bacterium that causes syphilis, one of the most common sexually transmitted diseases. Syphilis progresses through four distinct stages, each characterized by specific symptoms, namely primary, secondary, latent, and late (tertiary) syphilis. Serology has been considered the primary diagnostic approach. However, it is plagued by problems such as the limited specificity of nontreponemal tests and the inadequate correlation of treponemal tests with disease activity. In this study, we focused on the development of a loop-mediated isothermal amplification assay utilizing hydroxy naphthol blue (LAMP-HNB) for the diagnosis of T. pallidum subspp. pallidum. Specifically, this study seeks to determine the analytical sensitivity (limit of detection; LOD) and analytical specificity. Four hundred clinical serum samples were analyzed for diagnostic sensitivity, specificity, and predictive value, and each technique's 95% confidence intervals (95% CI, p < 0.05) were evaluated. The limit of detection for polymerase chain reaction with agarose gel electrophoresis (PCR-AGE), the loop-mediated isothermal amplification assay combined with agarose gel electrophoresis (LAMP-AGE), and LAMP-HNB were 116 pg/µL, 11.6 pg/µL, and 11.6 pg/ µL, respectively. Analytical specificity examinations indicated the absence of cross-reactivity with Leptospira interrogans, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, human immunodeficiency virus (HIV), and healthy human serum in PCR-AGE, LAMP-AGE, and LAMP-HNB. The diagnostic sensitivity, diagnostic specificity, positive predictive value (PPV), and negative predictive value (NPV) for PCR-AGE were 100.00 (100.00)%, 94.50 (94.40-94.60)%, 94.79 (94.69-94.88)%, and 100.00 (100.00)%, respectively. While, for LAMP-AGE and LAMP-HNB, they were 100.00 (100.00)%, 91.00 (90.87-91.13)%, 91.74 (91.63-91.86)%, and 100.00 (100.00)%, respectively. The LAMP-HNB test is simple, rapid, highly sensitive, and highly specific, without requiring expensive equipment. In the future, the LAMP-HNB assay may develop into a single-step diagnostic process, enabling the use as point-of-care testing for the diagnosis, prevention, and management of syphilis infection.

Application of Genetic Origin Analysis of Copy Number Variations in Non-Invasive Prenatal Testing.

This study aimed to assess the application of origin analysis of copy number variations (CNVs) in non-invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT. We enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV-Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell-free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked. A total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)-CNVs and 44 cases of F-CNVs. The occurrence of M/F-CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)-F-CNVs was high in cases where serological screening indicated intermediate, high-risk, or abnormal US findings (p<0.05). In the M/F-CNV group, most of the P/LP-CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5Mb in size, and nine (13.85%) were between 5 and 10Mb. In the F-CNV group, foetal P/LP-CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP-F-CNV fragments. The prenatal diagnostic rate and positive predictive value in the F-CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p<0.05). Genetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis.

The Integrated Transcriptome Bioinformatics Analysis of Energy Metabolism-Related Profiles for Dorsal Root Ganglion of Neuropathic Pain.

Neuropathic pain (NP) is a debilitating disease and is associated with energy metabolism alterations. This study aimed to identify energy metabolism-related differentially expressed genes (EMRDEGs) in NP, construct a diagnostic model, and analyze immune cell infiltration and single-cell gene expression characteristics of NP. GSE89224, GSE123919, and GSE134003 were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) analysis and an intersection with highly energy metabolism-related modules in weighted gene co-expression network analysis (WGCNA) was performed in GSE89224. Least absolute shrinkage and selection operator (LASSO), random forest, and logistic regression were used for model genes selection. NP samples were divided into high- and low-risk groups and different disease subtypes based on risk score of LASSO algorithm and consensus clustering analysis, respectively. Immune cell composition was estimated in different risk groups and NP subtypes. Datasets 134,003 were performed for identification of single-cell DEGs and functional enrichment. Cell-cell communications and pseudo-time analysis to reveal the expression profile of NP. A total of 38 EMRDEGs were obtained and are majorly enriched in metabolism about glioma and inflammation. LASSO, random forest, and logistic regression identified 6 model genes, which were Itpr1, Gng8, Socs3, Fscn1, Cckbr, and Camk1. The nomogram, based on six model genes, had a good predictive ability, concordance, and diagnostic value. The comparisons between different risk groups and NP subtypes identified important pathways and different immune cells component. The immune infiltration results majorly associated with inflammation and energy metabolism. Single-cell analysis revealed cell-cell communications and cells differentiation characteristics of NP. In conclusion, our results not only elucidate the involvement of energy metabolism in NP but also provides a robust diagnostic tool with six model genes. These findings might give insight into the pathogenesis of NP and provide effective therapeutic regimens for the treatment of NP.

Predictive diagnostic value of mean platelet volume to platelet count and neutrophil to lymphocyte ratios in the gray zone of prostate cancer with tPSA between 4 to 10 ng/mL.

Exploration of the Predictive Diagnostic Value of Mean Platelet Volume to Platelet Count Ratio (MPV/PLT,PVI) and Neutrophil-to-Lymphocyte Ratio (NLR) in the tPSA Gray Zone of Prostate Cancer. A retrospective study was conducted on 65 prostate cancer (Pca) patients and 52 benign prostatic hyperplasia (BPH) patients who underwent transperineal prostate biopsy at Xiangtan Central Hospital from December 2021 to December 2023. Descriptive statistics and logistic regression models were used to investigate the predictive diagnostic value of PVI and NLR in the tPSA gray zone of prostate cancer. Receiver operating characteristic (ROC) curves were constructed based on PVI and NLR values to determine the classification thresholds. A total of 117 patients were enrolled, including 65 cases of prostate cancer (PCa) and 52 cases of benign prostatic hyperplasia (BPH). There were no statistically significant differences in age, BMI, history of hypertension, history of diabetes, history of coronary heart disease, pre-biopsy white blood cell count, history of drinking, history of smoking, and tPSA between the PCa and BPH patients. The results of logistic regression analysis showed that PVI (OR=2.03, 95%CI: 1.34~3.07, P<0.00) and NLR (OR=0.32, 95%CI: 0.18~0.58, P<0.00) were independent predictors for diagnosing prostate cancer in the tPSA gray zone (VIF=1.04).The maximum area under the curve (AUC) for PVI was 0.70, with an optimal cut-off value of 0.05 (P ≤ 0.01). The maximum AUC for NLR was 0.76, with an optimal cut-off value of 2.86 (P ≤ 0.01).The calibration curve showed good consistency between the predicted and actual outcomes in both the PCa and BPH groups, indicating that the nomogram model had good predictive performance.When using PVI and NLR to plot the receiver operating characteristic (ROC) curves to predict the assessment of PCa in the tpsa gray zone, the area under the curve (AUC) for PVI was the largest at 0.70, with an optimal cutoff value of 0.05 (P ≤ 0.01). The AUC for NLR was the largest at 0.76, with an optimal cutoff value of 2.86 (P ≤ 0.01). PVI and NLR have certain predictive diagnostic value for Pca in the tPSA gray zone, and appropriate use of PVI and NLR can improve the positive rate of early screening for Pca in the gray zone.

Evaluation of the Seegene Allplex™ RV master assay for one-step simultaneous detection of eight respiratory viruses in nasopharyngeal specimens

BackgroundThe Seegene Allplex™ RV Master (RVM) assay is a one-step multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) system for detecting eight viral respiratory pathogens from nasopharyngeal swab, aspirate, and bronchoalveolar lavage specimens. The eight RVM targets are: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Influenza A (Flu A), Influenza B (Flu B), Human respiratory syncytial virus (RSV), adenovirus (AdV), rhinovirus (HRV), parainfluenza virus (PIV), and metapneumovirus (MPV). The assay is based on Seegene’s multiple detection temperature (MuDT) technology and provides cycle threshold (Ct) values for each of its viral targets upon PCR completion. ObjectiveWe aimed to evaluate the diagnostic performance of the RVM assay by calculating sensitivity, specificity, accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Overall Percent Agreement (OPA) compared to definite diagnosis and analogous reference assays. Study designDiagnostic sensitivity, specificity, accuracy, PPV, and NPV were calculated by comparing the results of the RVM assay to that of definite diagnosis assays; while PPA, NPA, and OPA were calculated by comparing results of the RVM assay to that of analogous reference products. Definite diagnosis and reference methods comprised whole genome sequencing and PCR genotyping, the Allplex™ SARS-CoV-2/FluA/FluB/RSV and Respiratory Panels 1, 2, and 3 assays (Seegene), and the Xpert® Xpress SARS-CoV-2/FluA/FluB/RSV Plus assay (Cepheid). Reproducibility of the RVM assay using fully-automated and semi-automated nucleic acid (NA) extraction workflows and as performed by independent operators was also assessed. In total, 249 positive respiratory specimens and at least 50 negative specimens for each target tested were used for this evaluation study. ResultsSensitivity, specificity, accuracy, PPV, NPV, PPA, NPA, and OPA ranged from 95.7 % to 100 % for detecting all eight targets tested on the RVM assay. Reproducibility PPA, NPA, and OPA between automated and semi-automated NA extraction workflows were all >97.9 %, while the reproducibility PPA, NPA and OPA between independent operators were all 100 %. ConclusionThese results demonstrate a high level of sensitivity, specificity, accuracy and diagnostic predictive value of the RVM assay and high agreement with comparable reference assays in identifying all eight of its targets. Taken together, our study underscores the diagnostic utility of the RVM assay in detecting eight viral respiratory pathogens.

Comparison Between Endobronchial-Guided Transbronchial Biopsy and Computed Tomography-Guided Transthoracic Lung Biopsy for the Diagnosis of Central Pulmonary Lesions.

Lung cancer is one of the most common malignant tumors at present. This study aimed to compare the diagnostic accuracy, complication rates, and predictive values of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) and electronic bronchoscopy-guided transbronchial lung biopsy (TBLB) for patients with central pulmonary lesions (CPLs) with a diameter ≥ 3 cm. We retrospectively included 110 patients with CPLs with a diameter ≥ 3 cm who underwent preoperative PTNB and TBLB examinations and ultimately underwent surgery to remove CPLs and obtained pathological results. Detailed information was collected in order to compare whether there was a difference between two groups. Data were processed using SPSS software (Version 26.0; IBM Corp). Data were compared by t-test or chi-square test. p < 0.05 was considered statistically significant. All patients underwent surgical treatment at the department of thoracic surgery and obtained a final pathological diagnosis. The rate of positive predictive value (PPV) was comparable between the two methods, and the negative predictive value (NPV) was significantly higher in the PTNB group compared with the TBLB group (p < 0.05). In addition, PTNB was more sensitive and accurate than TBLB (p < 0.05). However, the PTNB group had a higher probability of complications, and TBLB was a relatively safer examination method. PTNB demonstrated a higher accuracy and sensitivity than TBLB in the treatment of CPLs with a diameter ≥ 3 cm, but the complication rates of PTNB are relatively high. These methods exhibited different diagnostic accuracies and therefore should be selected based on different medical conditions.

Increased UBD Is a Potential Diagnostic and Prognostic Biomarker in Glioma.

Various studies have demonstrated that ubiquitin D (UBD) is overexpressed in different cancer types and may serve as a potential prognostic factor. However, additional research is necessary to establish the prognostic significance and possible role of UBD in glioma. Transcriptomic expression data from The Cancer Genome Atlas database (TCGA) and Chinese Glioma Genome Atlas (CGGA) were analyzed to identify UBD expression differences in tumor and normal tissues. The relative levels of UBD in glioma and normal tissues were determined using qRT-PCR and WB. Logistic regression analysis was performed to investigate the association between UBD expression and clinicopathological characteristics of glioma patients. To evaluate the diagnostic and prognostic predictive values of UBD, we used Kaplan-Meier survival curves, Cox regression analysis, diagnostic receiver operating characteristic (ROC) curves, and nomogram model. We also conducted wound healing assays, transwell assays, EdU assays, and colony formation assays to verify the UBD function. Gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as gene set enrichment analysis (GSEA), were employed to determine the functions of UBD. Finally, we performed the western blot assays to assess changes in EMT markers as well as p-PI3K, p-AKT, and p-mTOR expressions. Our study revealed a remarkable increase of UBD expression in glioma samples. Cox regression analysis demonstrated that high expression of UBD mRNA was an independent prognostic factor for overall survival (OS) in TCGA. ROC curve analysis showed that UBD expression levels could differentiate glioma from adjacent normal tissues accurately. Additionally, knockdown of UBD reduced the migration, invasion, and proliferation ability of glioma cells while UBD overexpression had the opposite effect. GSEA showed that the expression of UBD involved with various pathways including epithelial-mesenchymal transition (EMT), PI3K-AKT-mTOR signaling, P53 pathway, angiogenesis, inflammatory response, KRAS signaling, hypoxia, as well as TGF-β signaling. Furthermore, our findings suggest that UBD accelerates the activation of EMT and PI3K/AKT/mTOR pathway.

Precision in prostate cancer detection: integrating prostate-specific antigen density (PSAD) and the Prostate Imaging Reporting and Data System (PI-RADS) to provide additional risk stratification for a more accurate diagnostic decision.

This study focuses on integrating prostate-specific antigen density (PSAD) and Prostate Imaging Reporting and Data System (PI-RADS) for enhanced risk stratification in biopsy-naïve patients. A prospective study was conducted on 339 patients with suspected prostate cancer, utilizing PSAD and PI-RADS in combination. Logistic regression models were employed, and receiver operating characteristic (ROC) analysis performed to evaluate predictive performance. The patient cohort underwent multiparametric MRI, targeted biopsy, and systematic biopsy. When patients were stratified into four PSAD risk groups, the rate of clinically significant prostate cancer (csPCa) increased significantly with higher PSAD levels. Logistic regression confirmed the independent contribution of PI-RADS and PSAD, highlighting their role in the prediction of csPCa. Combined models showed superior performance, as evidenced by the area under the curve (AUC) for PI-RADS category and PSAD (0.756), which exceeded that of the individual predictors (PSA AUC, 0.627, PI-RADS AUC 0.689, PSAD AUC 0.708). This study concludes that combining PSAD and PI-RADS improves diagnostic accuracy and predictive value for csPCa in biopsy-naïve men, resulting in a promising strategy to provide additional risk stratification for more accurate diagnostic decision in biopsy-naïve patients, especially in the PI-RADS 3 group.

Correlation of cTfh cells and memory B cells with AMR after renal transplantation

Renal transplantation is the preferred treatment option for patients with end-stage renal disease (ESRD) in a clinical setting. Antibody mediated rejection (AMR) is one of the leading causes of graft dysfunction. To address the current shortcomings in the early diagnosis and treatment of AMR in clinical practice, this article analyzes the distribution of different circulating T follicular helper (cTfh) cell subtypes and B cell subpopulations in peripheral blood and detects the cytokine levels of chemokine ligand 13 (CXCL13), interleukin-21 (IL-21), and interleukin-4 (IL-4) related to cTfh cells in peripheral blood of kidney transplant recipients. Moreover, we also explore the correlation between cTfh cells, peripheral blood memory B cells, and AMR, their value as early predictive indicators of AMR, and explore potential therapeutic targets for AMR patients. Our results indicate that the proportion of cTfh cells increased at the onset of AMR, which plays an important role in antigen-specific B-cell immune regulation. Activation of cTfh cells in AMR patients correlates with phenotypes of memory B cells and plasma blasts. cTfh cells and memory B cells have promising diagnostic efficacies and predictive values for AMR. The proportion of cTfh cells to CD4+ T cells and the proportion of memory B cells to CD19+ B cells are correlated with serum creatinine levels, indicating that cTfh cells and memory B cells may be involved in the progression of AMR. In addition, the CXCL13, IL-21, and IL-4, which were associated with cTfh cells, may be involved in the onset of AMR.

Comparative Study on the Clinicopathologic and Molecular Characteristics of Primary and Secondary Diffuse Large B-cell Lymphoma in the Central Nervous System.

Diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive B-cell lymphoma with clinical and molecular heterogeneity. Primary CNS-DLBCL (PCNSL) affects the brain, eyes, leptomeninges, or spinal cord without systemic involvement. Secondary CNS-DLBCL (SCNSL) manifests concurrently with systemic lymphoma or as an isolated CNS relapse with poor prognosis. Next-generation sequencing (NGS) was used to identify genomic alterations in 32 PCNSL and 9 SCNSL cases. Single nucleotide variants and copy number variations in addition to the clinicopathologic data and proposed risk predictive values were compared to aid in diagnostic differentiation between the two types of lymphomas. The MCD genotype, characterized by mutations in MYD88 and CD79B, is the most common alteration in PCNSL and is associated with lower survival rates. The frequency of MYD88 mutation was significantly higher in PCNSL compared to SCNSL (75.0% vs. 33.3%; p=0.042). Recurrent copy number loss of 6p21 occurred in 56.1% of cases, more often in PCNSL (65.6%) than in SCNSL (22.2%) (p=0.028). Diagnostic positive predictive values (PPV) of MYD88 mutation and 6p21 loss for PCNSL were 89% and 91%, respectively. PPV of both alterations was 93% for the diagnosis of PCNSL. MYD88 mutation and 6p21 loss were significantly higher in PCNSL than in SCNSL, and novel risk prediction models based on these distinct genomic profiles can aid in the clinical differentiation of PCNSL and SCNSL.

Accuracy of contrast-enhanced CT in liver neoplasms in children under 2 years age

BackgroundMultiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases.ObjectiveTo evaluate the imaging features and diagnostic accuracy of computed tomography (CT) in liver tumors in children under 2 years.MethodsEighty-eight children under 2 years with treatment naive liver neoplasms and baseline contrast-enhanced CT were included in this institutional review board approved retrospective study. Two blinded onco-radiologists assessed these tumors in consensus. Findings assessed included enhancement pattern, lobulated appearance, cystic change, calcifications, central scar-like appearance, and metastases. The radiologists classified the lesion as hepatoblastoma, infantile hemangioma, mesenchymal hamartoma, rhabdoid tumor, or indeterminate, first based purely on imaging and then after alpha-fetoprotein (AFP) correlation. Multivariate analysis and methods of comparing means and frequencies were used for statistical analysis wherever applicable. Diagnostic accuracy, sensitivity, and positive predictive values were analyzed.ResultsThe mean age of the sample was 11.4 months (95% CI, 10.9–11.8) with 50/88 (57%) boys. The study included 72 hepatoblastomas, 6 hemangiomas, 4 mesenchymal hamartomas, and 6 rhabdoid tumors. Presence of calcifications, multilobular pattern of arterial enhancement, lobulated morphology, and central scar-like appearance was significantly associated with hepatoblastomas (P-value < 0.05). Fourteen out of eighty-eight lesions were called indeterminate based on imaging alone; six lesions remained indeterminate after AFP correlation. Pure radiology-based diagnostic accuracy was 81.8% (95% CI, 72.2–89.2%), which increased to 92.1% (95% CI, 84.3–96.7%) (P-value > 0.05) after AFP correlation, with one hepatoblastoma misdiagnosed as a rhabdoid tumor. If indeterminate lesions were excluded for biopsy, the accuracy would be 98.8% (95% CI, 93.4–99.9%).ConclusionCT had high accuracy for diagnosing liver neoplasms in the under 2-year age population after AFP correlation. Certain imaging features were significantly associated with the diagnosis of hepatoblastoma. A policy of biopsying only indeterminate lesions after CT and AFP correlation would avoid sampling in the majority of patients.Graphical

A molecular subtyping associated with the cGAS-STING pathway provides novel perspectives on the treatment of ulcerative colitis

Ulcerative colitis (UC) is characterized by an abnormal immune response, and the pathogenesis lacks clear understanding. The cGAS-STING pathway is an innate immune signaling pathway that plays a significant role in various pathophysiological processes. However, the role of the cGAS-STING pathway in UC remains largely unclear. In this study, we obtained transcriptome sequencing data from multiple publicly available databases. cGAS-STING related genes were obtained through literature search, and differentially expressed genes (DEGs) were analyzed using R package limma. Hub genes were identified through protein–protein interaction (PPI) network analysis and module construction. The ConsensuClusterPlus package was utilized to identify molecular subtypes based on hub genes. The therapeutic response, immune microenvironment, and biological pathways of subtypes were further investigated. A total of 18 DEGs were found in UC patients. We further identified IFI16, MB21D1 (CGAS), TMEM173 (STING) and TBK1 as the hub genes. These genes are highly expressed in UC. IFI16 exhibited the highest diagnostic value and predictive value for response to anti-TNF therapy. The expression level of IFI16 was higher in non-responders to anti-TNF therapy. Furthermore, a cluster analysis based on genes related to the cGAS-STING pathway revealed that patients with higher gene expression exhibited elevated immune burden and inflammation levels. This study is a pioneering analysis of cGAS-STING pathway-related genes in UC. These findings provide new insights for the diagnosis of UC and the prediction of therapeutic response.

Ultrasound Cut-Off Values for Rectus Femoris for Detecting Sarcopenia in Patients with Nutritional Risk.

A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.

Development and verification of machine learning model based on anogenital distance, penoscrotal distance, and 2D:4D finger ratio before puberty to predict hypospadias classification.

To describe the anatomical abnormalities of hypospadias before puberty using current commonly used anthropometric index data and predict postoperative diagnostic classification. Children with hypospadias before puberty who were initially treated at Sichuan Provincial People's Hospital from April 2021 to September 2022 were selected. We recorded their preoperative penoscrotal distance, anogenital distance, 2D:4D finger ratio, and postoperative hypospadias classification. The receiver operating character curve was used for univariate analysis of the diagnostic predictive value of each index for hypospadias classification in the training set. Binary logistic regression, random forest, and support vector machine models were constructed. In addition, we also prospectively collected data from October 2022 to September 2023 as a test set to verify the constructed machine learning models. This study included 389 cases, with 50 distal, 167 midshaft, and 172 proximal cases. In the validation set, the sensitivity of the binary LR, RF, and SVM was 17%, 17% and 0% for identifying the distal type, 61%, 55% and 64% for identifying the midshaft type, and 56%, 60% and 48% for identifying the proximal type, respectively. The sensitivity of the three-classification RF and SVM models was 17% and 17% for distal type, 64% and 73% for midshaft type, 60% and 60% for proximal type, respectively. In the Testing set, the sensitivity of the binary LR, RF and SVM was 6%, 0% and 0% for identifying the distal type, 64%, 55% and 66% for identifying the midshaft type, and 48%, 62% and 39% for identifying the proximal type, respectively. The sensitivity of the three-classification RF and SVM models was 12% and 0% for distal type, 57% and 77% for midshaft type, and 65% and 53% for proximal type, respectively. Compared with binary classification models, the sensitivity of the three-classification models for distal type was not improved. Anogenital distance and penoscrotal distance have a favorable predictive value for midshaft and proximal hypospadias, among which AGD2, with higher test efficiency and stability, is recommended as the preferred anogenital distance indicator. The 2D:4D finger ratio (RadioL, RadioR) has little predictive value for hypospadias classification.

Case Report: Giant bronchogenic cyst compressing the pericardium and the lung hilum

Introduction: The bronchogenic cyst is a congenital anomaly of the trachea and the bronchi resulting in a malformation that develop in the bronchial tree, most often in the middle mediastinum. It is a benign pathology, often asymptomatic, however in the case of a large bronchogenic cyst, signs of compression of the intra-thoracic organs appear and early surgery is necessary to avoid complications. Case presentation: A 49-year-old patient was referred to our department with dry cough, dyspnea and chest tightness progressing for six months. Radiological exploration concluded that a giant bronchogenic cyst, 90 mm in diameter, was very probable. Surgery was performed via a right posterolateral thoracotomy. Intraoperatively, there was a large cystic formation 100mm*80 mm of the middle mediastinum in intimate contact with the origin of the right pulmonary artery, the lower right pulmonary vein as well as the right atrium exerting a compressive effect on the bronchi. The lesion was firmly adhered to the pericardium. The cystic was ‘en bloc’ resected in totality. The postoperative course was uncomplicated. Histological examination confirmed diagnosis of a bronchogenic cyst. The patient was asymptomatic throughout the follow-up period. Clinical discussion: Apart from the possibility of malignant degeneration, a bronchogenic cyst can increase in size and become huge causing serious complications. Despite the predictive diagnostic value of imaging, definitive diagnosis of a bronchogenic cyst is confirmed by surgical excision and pathological examination. Conclusions: Surgery is almost obligatory especially if the cyst is above a certain size (about 60 mm) and in the case of giant bronchogenic cysts.