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Background IgA nephropathy (IgAN) is a common primary glomerulonephritis worldwide, and the improvement of glucocorticoid on the renal prognosis of IgAN patients with high risk of CKD progression remains unclear. Objective To explore the effect of glucocorticoid therapy on the therapeutic response and renal prognosis of IgAN patients with high risk of CKD progression. Methods IgAN patients with high risk of CKD progression were recruited in the First Affiliated Hospital of Zhengzhou University from January 2017 to October 2021 as study subjects and divided into the glucocorticoid treatment group and supportive treatment group according to whether glucocorticoid therapy was performed. Propensity matching method (PSM) was used to screen patients for cases by 1∶1 matching according to gender, age, 24 h urine protein and eGFR, the clinicopathological data of patients, disease remission, adverse reactions within 1 year were recorded. The patients were followed up from the date of initiation of supportive therapy until October 31, 2022. The primary endpoint event was defined as progression to end-stage renal disease (ESRD) or receiving dialysis. The composite endpoint event was defined as sustained decline in eGFR of more than 30% from baseline, or progression to ESRD, or receiving dialysis or death. Kaplan-Meier method was used to plot survival curves and log-rank test was used to compare differences in the cumulative incidence of the primary/composite endpoint events between the two groups of patients. Cox proportional hazards regression analysis was used to analyze the possible influencing factors of renal prognosis in IgAN patients with high risk of CKD progression. Results A total of 236 patients with primary IgAN met the inclusion criteria. After 1∶1 matching, 97 cases in the glucocorticoid treatment group were successfully matched with 97 cases in the supportive therapy group with balanced baseline data. The complete remission rate and partial remission rate of patients in the glucocorticoid treatment group were higher than those in supportive treatment group (χ2=6.171, P=0.013; χ2=3.973, P=0.046) . The median follow-up time was 18.00 (9.75, 28.00) months. Kaplan-Meier survival curve analysis showed that the cumulative incidence of primary endpoint event in the glucocorticoid treatment group was lower than the supportive treatment group (χ2=4.495, P=0.034) and the cumulative survival rate of composite endpoint event in the glucocorticoid therapy group was lower than the supportive therapy group (χ2=4.419, P=0.036) . Among the 236 patients who met the inclusion criteria, there were 177 patients with moderate proteinuria. After 1∶1 matching of the 177 patients on glucocorticoid treatment and supportive treatment by sex, age, 24 h urine protein and eGFR using PSM, 76 cases in each group were successfully matched. Kaplan-Meier survival curve analysis showed that the cumulative incidence of primary endpoint event in the patients on glucocorticoid treatment with moderate proteinuria was lower than those on supportive treatment with moderate proteinuria (χ2=4.127, P=0.042) ; and the cumulative survival rate of composite endpoint event in the patients on glucocorticoid treatment with moderate proteinuria was lower than those on supportive treatment with moderate proteinuria (χ2=4.934, P=0.026) . Multivariate Cox proportional hazard regression analysis showed that hemoglobin (HR=0.982) , serum creatinine (HR=1.019) , eGFR (HR=1.020) and 24-hour urine protein (HR=1.205) were influencing factors of primary endpoints event in IgAN patients with high risk of CKD progression. The incidence of infection in the glucocorticoid treatment group was higher than the supportive treatment group (P

The prognostic factors for patients with pure ovarian immature teratoma (POIT) and the role of adjuvant chemotherapy in stage IA G2-G3 and IB-IC POIT remains controversial. We conducted a retrospective study of 155 POIT patients treated in our hospital between 2000 and 2022. The recurrence-free survival (RFS), disease-specific survival (DSS), and potential prognostic factors of POIT patients were evaluated. Subgroup analysis was conducted in stage I other than stage IA G1 POIT. The median age at diagnosis was 23.0 years (range: 4.0 − 39.0), and 126 (81.3%), 2 (1.3%), 26 (16.8%), and 1 (0.6%) patients had FIGO stage I, stage II, stage III, and stage IV disease, respectively. Twenty-three patients relapsed and five died of the diseases after a median follow-up of 7.6 years, with a 5-year RFS and DSS rate of 86.0% and 97.0%, respectively. Multivariate analysis showed that positive postoperative tumour markers (TM) were the risk factor for recurrence in the overall cohort (hazard ratio [HR] 4.058, 95% CI 1.175 − 14.019, p = 0.027) and subgroup (HR 10.237, 95% CI 2.175 − 48.179, p = 0.003), and FIGO stage II–IV was the only factor for DSS in overall cohort (HR 7.751, 95% CI 1.281 − 46.895, p = 0.026). In 110 patients subjected to subgroup analysis, 29 patients received surveillance without chemotherapy and 81 patients were administered adjuvant chemotherapy. Multivariate analysis revealed active surveillance significantly increased the recurrence rate (5-year RFS of 75.7% vs. 93.6%, HR 7.562, 95% CI 2.441 − 23.424, p < 0.001) but not the death related to POIT (p = 0.338). Positive postoperative TM and FIGO stage II–IV were the prognostic factors for POIT. Active surveillance in stage I POIT of any grade may be practical for those with negative postoperative TM. Positive postoperative tumour markers and FIGO stage II–IV were the prognostic factors for pure ovarian immature teratoma. Active surveillance in stage I pure ovarian immature teratoma of any grade may be practical for those with negative postoperative tumor markers. [ABSTRACT FROM AUTHOR]

Hypokalemia is a common disorder in clinical settings; however, nonmolecular diagnostic testing cannot explain some causes of hypokalemia. To determine the etiology of clinically unexplained hypokalemia without hypertension (CUHypoNH) and to obtain a diagnostic yield of monogenic hypokalemia without hypertension in adults (MHNHA), we enrolled 82 patients with CUHypoNH for whole‐exome sequencing or targeted gene sequencing of genes associated with 4000 monogenic disorders. Through molecular diagnosis, 25 patients were diagnosed with monogenic hypokalemia, and a diagnostic yield of 30.5% was obtained. Among patients with MHNHA, 18 patients (18/82, 22.0% and 72% of MHNHA) with Gitelman syndrome accounted for the largest proportion. Among the 29 diagnostic variants found, eight mutations have not been reported previously; these include three point mutations, one frameshift mutation, and four exon deletions. Based on the clinical presentation of patients with CUHypoNH, the diagnostic yield of monogenic hypokalemia was the highest for chronic asymptomatic hypokalemia (8/11, 72.7%). Twenty‐one patients had concomitant hypomagnesemia, when accompanied with hypocalciuria, the molecular diagnostic yield of Gitelman syndrome increased to 88.2%. Overall, this study on hospitalized adult patients explored the etiology of CUHypoNH using high‐throughput sequencing. Molecular diagnosis of CUHypoNH is clinically significant in guiding precision treatment and improving disease prognosis. [ABSTRACT FROM AUTHOR]

Objective. Emerging evidence highlights the clinical implications of N6-methyladenosine (m6A) modification in HCC. Yet, the roles of m6A modification in modulating cancer immunity and shaping tumor microenvironment (TME) are undefined in hepatocellular carcinoma (HCC). Methods. Here, m6A modification classification was determined for HCC through 23 m6A modifier levels by employing consensus clustering approach. Prognosis analysis was presented for comparing the differences in survival outcomes. The ssGSEA and ESTIMATE approaches were adopted for evaluating the abundances of tumor-infiltrating immune cell populations. The m6A scoring system was computed for reflecting m6A modification classification via PCA algorithm. Results. Three m6A modifier-mediated modification patterns were established among HCC specimens, which were characterized by different prognosis, signaling pathways, and TME features. After extracting m6A phenotype-associated DEGs, we determined m6A scores in individual HCC and stratified patients into high- and low-score groups. Patients with low m6A score displayed the survival advantage and higher sensitivity to gemcitabine. Moreover, those with low m6A score possessed the better anti-PD-1/PD-L1 therapeutic response in the IMvigor210 immunotherapy cohort. Conclusion. Our findings highlighted that m6A modification exerted a nonnegligible role in remodeling diverse and complex TME. Quantification of the m6A modification patterns of individual HCC may enhance the comprehension of TME features and facilitate immunotherapeutic plans. [ABSTRACT FROM AUTHOR]

As the most common type of renal cell carcinoma (RCC), the renal clear cell carcinoma (ccRCC) is highly malignant and insensitive to chemotherapy or radiotherapy. Although systemic immunotherapies have been successfully applied to ccRCC in recent years, screening for patients who can benefit most from these therapies is still essential and challenging due to immunological heterogeneity of ccRCC patients. To this end, we implemented a series of deep investigation on the expression and clinic data of ccRCC from The Cancer Genome Atlas (TCGA) International Consortium for Cancer Genomics (ICGC). We identified a total of 946 immune-related genes that were differentially expressed. Among them, five independent genes, including SHC1, WNT5A, NRP1, TGFA, and IL4R, were significantly associated with survival and used to construct the immune-related prognostic differential gene signature (IRPDGs). Then the ccRCC patients were categorized into high-risk and low-risk subgroups based on the median risk score of the IRPDGs. IRPDGs subgroups displays distinct genomic and immunological characteristics. Known immunotherapy-related genes show different mutation burden, wherein the mutation rate of VHL was higher than 40% in the two IRPDGs subgroups, and SETD2 and BAP1 mutations differed most between two groups with higher frequency in the high-risk subgroup. Moreover, IRPDGs subgroups had different abundance in tumor-infiltrating immune cells (TIICs) with distinct immunotherapy efficacy. Plasma cells, regulatory cells (Tregs), follicular helper T cells (Tfh), and M0 macrophages were enriched in the high-risk group with a higher tumor immune dysfunction and rejection (TIDE) score. In contrast, the low-risk group had abundant M1 macrophages, mast cell resting and dendritic cell resting infiltrates with lower TIDE score and benefited more from immune checkpoint inhibitors (ICI) treatment. Compared with other biomarkers, such as TIDE and tumor inflammatory signatures (TIS), IRPDGs demonstrated to be a better biomarker for assessing the prognosis of ccRCC and the efficacy of ICI treatment with the promise in screening precise patients for specific immunotherapies. [ABSTRACT FROM AUTHOR]

Background: Necroptosis is closely related to the tumorigenesis and development of cancer. An increasing number of studies have demonstrated that targeting necroptosis could be a novel treatment strategy for cancer. However, the predictive potential of necroptosis-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) still needs to be clarified. This study aimed to construct a prognostic signature based on necroptosis-related lncRNAs to predict the prognosis of LUAD. Methods: We downloaded RNA sequencing data from The Cancer Genome Atlas database. Co-expression network analysis, univariate Cox regression, and least absolute shrinkage and selection operator were adopted to identify necroptosis-related prognostic lncRNAs. We constructed the predictive signature by multivariate Cox regression. Kaplan–Meier analysis, time-dependent receiver operating characteristics, nomogram, and calibration curves were used to validate and evaluate the signature. Subsequently, we used gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between the predictive signature and tumor immune microenvironment of risk groups. Finally, the correlation between the predictive signature and immune checkpoint expression of LUAD patients was also analyzed. Results: We constructed a signature composed of 7 necroptosis-related lncRNAs (AC026355.2, AC099850.3, AF131215.5, UST-AS2, ARHGAP26-AS1, FAM83A-AS1, and AC010999.2). The signature could serve as an independent predictor for LUAD patients. Compared with clinicopathological variables, the necroptosis-related lncRNA signature has a higher diagnostic efficiency, with the area under the receiver operating characteristic curve being 0.723. Meanwhile, when patients were stratified according to different clinicopathological variables, the overall survival of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the low-risk group. ssGSEA further confirmed that the predictive signature was significantly related to the immune status of LUAD patients. The immune checkpoint analysis displayed that low-risk patients had a higher immune checkpoint expression, such as CTLA-4, HAVCR2, PD-1, and TIGIT. This suggested that immunological function is more active in the low-risk group LUAD patients who might benefit from checkpoint blockade immunotherapies. Conclusion: The predictive signature can independently predict the prognosis of LUAD, helps elucidate the mechanism of necroptosis-related lncRNAs in LUAD, and provides immunotherapy guidance for patients with LUAD. [ABSTRACT FROM AUTHOR]

Context: The risk of persistent and recurrent disease in patients with differentiated thyroid cancer (DTC) is a continuum that ranges from very low to very high, even within the 3 primary risk categories. It is important to identify independent clinicopathological parameters to accurately predict clinical outcomes.Objective: To examine the association between pre-ablation stimulated thyroglobulin (ps-Tg) and persistent and recurrent disease in DTC patients and investigate whether incorporation of ps-Tg could provide a more individualized estimate of clinical outcomes.Design, Setting, and Participants: Medical records of 2524 DTC patients who underwent total thyroidectomy and radioiodine ablation between 2006 and 2018 were retrospectively reviewed.Main Outcome Measure: Ps-Tg was measured under thyroid hormone withdrawal before remnant ablation. Association of ps-Tg and clinical outcomes.Results: In multivariate analysis, age, American Thyroid Association (ATA) risk stratification, distant metastasis, ps-Tg, and cumulative administered activities were the independent predictive factors for persistent/recurrent disease. Receiver operating characteristic analysis identified ps-Tg cutoff (≤10.1 ng/mL) to predict disease-free status with a negative predictive value of 95%, and validated for all ATA categories. Integration of ps-Tg into ATA risk categories indicated that the presence of ps-Tg ≤ 10.1 ng/mL was associated with a significantly decreased chance of having persistent/recurrent disease in intermediate- and high-risk patients (9.9% to 4.1% in intermediate-risk patients, and 33.1% to 8.5% in high-risk patients).Conclusion: The ps-Tg (≤10.1 ng/mL) was a key predictor of clinical outcomes in DTC patients. Its incorporation as a variable in the ATA risk stratification system could more accurately predict clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Neck lymph node (LN) metastasis is a common feature of paediatric papillary thyroid cancer, and LN ratio (LNR) is defined as the ratio of the number of positive LNs excised to the total number of removed. Unlike in adults, few data are available regarding the clinical implication of LNR in the paediatric population. Our purpose was to investigate the association of LNR with clinical outcomes in paediatric papillary thyroid cancer. Design & Methods: The study retrospectively reviewed 136 consecutive children and adolescents with papillary thyroid cancer and LN involvement but no initial distant metastasis. Initial treatment, included in all patients a total thyroidectomy with central and/or lateral neck dissection followed by radioactive iodine ablation. Within the neck dissections, total number of LNs removed, total positive LNs and LN ratios were determined. The effect of clinicopathologic characteristics and intraoperative findings on persistent and recurrent diseases were analysed by univariate and multivariate analyses. Results: Median number of positive LNs was 9, and median LNR was 0.4. During a median follow‐up of 49 months (range, 12.0‐139 months), persistent disease occurred in 43 (31.6%) patients. The multivariable analysis showed that age and LNR were the independent factors predictive of persistent disease. Patients with a LNR >0.34 exhibited a threefold higher risk of persistent disease after initial therapy than the counterparts (P =.02). Conclusion: Our findings suggest that LNR was an independent determinant predictive of persistent disease after initial therapy in children and adolescents with papillary thyroid cancer. [ABSTRACT FROM AUTHOR]

Malignant melanoma represents a sort of neoplasm deriving from melanocytes or cells developing from melanocytes. The balance of energy and energy-associated body composition and body mass index could be altered by exercise, thereby directly affecting the microenvironment of neoplasm. However, few studies have examined the mechanism of genes induced by exercise and the pathways involved in melanoma. This study used three separate datasets to perform comprehensive bioinformatics analysis and then screened the probable genes and pathways in the process of exercise-promoted melanoma. In total, 1,627 differentially expressed genes (DEGs) induced by exercise were recognized. All selected genes were largely enriched in NF-kappa B, Chemokine signaling pathways, and the immune response after gene set enrichment analysis. The protein-protein interaction network was applied to excavate DEGs and identified the most relevant and pivotal genes. The top 6 hub genes (Itgb2, Wdfy4, Itgam, Cybb, Mmp2, and Parp14) were identified, and importantly, 5 hub genes (Itgb2, Wdfy4, Itgam, Cybb, and Parp14) were related to weak disease-free survival and overall survival (OS). In conclusion, our findings demonstrate the prognostic value of exercise-induced genes and uncovered the pathways of these genes in melanoma, implying that these genes might act as prognostic biomarkers for melanoma. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic value of post‐ablation whole‐body scintigraphy (PAS) in children with thyroid cancer following 131I therapy. Methods: A retrospective analysis of children with thyroid cancer who underwent remnant ablation was performed. PAS results were correlated with clinical and histopathologic characteristics of the primary tumor and compared with the follow‐up data. Results: One hundred and sixty‐eight children were eligible for the analysis. The median age was 17 years, and the majority were female (81.5%). In multivariate analysis, N1b classification and 131I ablative dose were associated with PAS positivity. After a median follow‐up of 49 months, 89 (71.8%) of 124 children with normal PAS achieved complete remission. Fifteen of 44 (34.1%) children with positive PAS had complete remission. Kaplan‐Meier analysis showed that positive PAS was negatively associated with cumulative complete remission rates (P <.001). Conclusions: PAS could provide prognostic information in children with thyroid cancer undergoing 131I therapy. [ABSTRACT FROM AUTHOR]

Purpose: To systemically investigate the prognostic value of pre-ablation stimulated thyroglobulin (s-Tg) in children and adolescents with differentiated thyroid cancer. Methods: Clinical records from 118 children and adolescents were retrospectively reviewed. Results: The median age was 16 years, and the majority were female (79.7%). All children and adolescents underwent total thyroidectomy and received radioactive iodine therapy. After a median follow-up of 5.3 years, 68 (57.6%) patients were disease free, while 50 patients (42.4%) had persistent/recurrent disease. In multivariate analysis, pre-ablation s-Tg and M1 were the independent predictive factors for persistent/recurrent disease. According to the receiver operating curve analysis, the best pre-ablation s-Tg cutoff to predict disease-free status was 17.8 ng/mL with a negative predictive value of 96.8%. Integration of pre-ablation s-Tg into American Thyroid Association pediatric risk categories indicated that the presence of pre-ablation s-Tg ≤17.8 ng/mL was associated with a decreased chance of having persistent/recurrent disease in intermediate- and high-risk patients (22.6% to 2.6% in intermediate-risk patients, and 64.4% to 5.6% in high-risk patients). Conclusions: Our findings suggest that pre-ablation s-Tg has the capability of predicting the clinical outcomes in children and adolescents with thyroid cancer. [ABSTRACT FROM AUTHOR]

The clinical features of cryptococcal meningitis (CM) in patients without predisposing diseases (PD) remain unclear. In sum, 162 of the 167 patients without PD and 162 of the 309 patients with PD were enrolled after propensity score matching. Demographic characteristics, symptoms, blood, and cerebrospinal fluid (CSF) characteristics were compared between the two groups. Kaplan-Meier curves and a Cox proportional hazards model were used to assess the factors associated with 10-week mortality. In total, approximately 35.1% of CM patients were without PD. CM patients without PD had blood profiles of higher white blood cells (WBC) [8.9(6.7–11.0) × 109/l], hemoglobin (128.4 ± 20.9 g/l), platelets [(226.2 ± 64.1) × 109/l], and serum albumin (41.2 ± 5.8 g/l) (all P ≤.001) and CSF profiles of lower glucose (2.0 ± 1.2 mmol/l), pleocytosis [65.0 (18.0–160.0) × 106/l] and higher total protein [0.9 (0.7–1.4)g/l] (all P <.05). CM patients without PD had lower Cryptococcus culture positivity in CSF (62.5% vs. 74.1%, P =.039) but higher 2-week of CSF culture sterilization rates (69.4% vs. 51.3%, P =.031). The overall 10-week survival rate was 84.7% in patients without PD and 81.1% in patients with PD (Log-rank P =.439). CSF glucose <1.5 mmol/l, CSF fungal burden >20 cells/high power field and treatment lacking amphotericin B had a 3–4 times higher risk of death in patients without PD, whereas serum albumin <35 g/l, CSF glucose < 1.5 mmol/l, and CSF WBC <55 × 106 cell/l were risk factors for patients with PD. CM patients without PD had unique blood and CSF profiles, especially, had lower Cryptococcus culture positivity in CSF, and higher 2-week CSF culture sterilization. Low CSF glucose levels, higher fungal burden, and treatment without amphotericin B were risk factors for 10-week mortality. [ABSTRACT FROM AUTHOR]

• A novel 4-gene signature model with high accuracy was built by SVM. • The model could simultaneously predict malignant risk of OPMDs and OSCC prognosis. • The reliability of 4 gene signatures have been confirmed in human samples by IHC. • The model provided an alternative for early diagnosis and prognosis of OSCC. Oral squamous cell carcinoma (OSCC) is often diagnosed at late stage with a poor prognosis. The study hereunder aimed to construct a multi-gene model to simultaneously promote early diagnosis of OSCC by evaluating malignant risk of oral potentially malignant disorders (OPMDs) and predict prognosis. 3 GEO datasets including OPMDs and OSCC samples were obtained for overlapping differentially expressed genes (DEGs) being screened. The predictive model was built with optimal DEGs by SVM algorithm, estimated by receiver operator characteristic curves and validated for double prediction via oral cancer-free survival (for malignant risk of OPMDs) and overall survival time (for OSCC) analysis respectively compared to other models. The protein expression of biomarkers in the model was validated in human samples by immunohistochemistry. A novel predictive model of 4-gene signature was built based on 12 common DEGs revealed from 3 GEO datasets. It could well distinguish OSCC from OPMDs and normal tissues. Both oral cancer-free survival and overall survival time analysis were significantly poorer in high-risk patients than in low-risk ones in Kaplan Meier survival curve respectively. The protein expression of biomarkers in OSCC was with significant difference compared to normal and OPMDs. The novel 4-gene signature model presents strong ability in simultaneous prediction of the malignant risk of OPMDs and OSCC progression, potentially benefiting both the early diagnosis and therapeutic outcomes of OSCC. [ABSTRACT FROM AUTHOR]

Background: The significance of human epidermal growth factor receptor 2 (Her2) and nucleus-associated antigen Ki-67 expression remains controversial in gastric adenocarcinoma (GaC). The aim of this study was to investigate the expression and clinicopathologic and prognostic significance of Her2 and Ki-67 in resected GaC without distant metastasis.Methods: Malignant tissues and clinicopathologic data were obtained from 195 patients with resected non-metastatic GaC. Immunohistochemistry staining was performed to examine the expression of Her2 and Ki-67; their association with clinicopathologic factors were investigated using logistic regression, and their association with survival was explored using Kaplan-Meier analysis and Cox proportional hazards regression.Results: Her2 was majorly expressed in cell membrane and Ki-67 in cell nucleus in non-metastatic GaC. Stronger Her2 expression was significantly associated with better tumor differentiation, neurovascular invasion, less advanced pathological tumor (pT) stage, and more advanced pathological node (pN) stage; while Ki-67 expression was not significantly associated with any investigated clinicopathologic factors. Patients with both negative Her2 and negative Ki-67 expression had poorer tumor differentiation, and more advanced pT and pathological tumor-node-metastasis (pTNM) stages; the association with pT and pTNM stages were further confirmed by multivariable analyses, especially in node-negative disease. Her2 or Ki-67 alone was not significantly associated with pTNM stage. A strongly positive (+++) Her2 expression was associated with poorer survival in multivariable analysis only (P = 0.047); while Ki-67 or combined expression was not significantly associated with prognosis.Conclusions: In non-metastatic GaC, Her2 expression and combined expression of Her2 and Ki-67 were associated with several clinicopathologic factors including tumor differentiation and stage, and only a +++ Her2 expression was associated with poorer prognosis in multivariable analysis with marginal significance in this study; while Ki-67 alone had both limited clinicopathologic and prognostic values. [ABSTRACT FROM AUTHOR]