Systematic review and meta-analysis of the association between bridging therapy and outcomes of chimeric antigen receptor T cell therapy in patients with large B cell lymphoma.

BACKGROUND: The existing evidence about the impact of bridging therapy (BT) on chimeric antigen receptor (CAR)-T cell therapy in patients with large B cell lymphoma (LBCL) is conflicting. Therefore, we reviewed all available evidence to examine the association between BT and CAR-T therapy outcomes by systematic review and meta-analysis approach. METHODS: Two reviewers independently searched Embase, PubMed, Web of Science, and Cochrane library to identify all records that described BT for LBCL treated with CAR-T. We then applied a fixed- or random-effects meta-analysis to estimate the pooled hazard ratios (HRs) and rate ratio (RRs) for efficacy and safety endpoints and assessed differences across various BT modalities. The Newcastle-Ottawa Scale was used to evaluate study quality. RESULTS: Twenty-six reports from 24 studies involving 2014 patients were included in the analysis. Pooled results showed that patients requiring BT had significantly worse 1-year overall survival rate (RR = 0.76, 95% confidence interval [CI] 0.68-0.85, P < 0.001), 1-year progression-free survival rate (RR = 0.71, 95% CI 0.60-0.85, P < 0.001), progression-free survival (HR = 1.35, 95% CI 1.07-1.69, P = 0.01), overall response rate (RR = 0.88, 95% CI 0.81-0.95, P = 0.001), complete response rate (RR = 0.78, 95% CI 0.65-0.93, P = 0.005), and grade ≥3 immune effector cell-associated neurotoxicity syndrome (RR = 1.43, 95% CI 1.10-1.87, P = 0.007), and tended to have poorer overall survival (HR = 1.42, 95% CI 0.99-2.02, P = 0.056) and grade ≥3 cytokine release syndrome (RR = 1.59, 95% CI 0.92-2.75, P = 0.096). Prolonged cytopenias were the common toxicity event associated with BT. Radiotherapy may serve as a promising BT option that can provide safe and effective disease control for patients with LBCL before CAR-T infusion. The inconsistency of patient baselines in the current study hindered further comparisons between different BT modalities. Most of the available evidence was rated as low quality because of concerns over low comparability. CONCLUSION: BT appears to be associated with comparatively poor efficacy and safety outcomes after CAR-T infusion. However, due to the considerable heterogeneity between the BT and non-BT cohorts at disease baseline, no definitive conclusions can be made for the true impact of BT on CAR-T until further randomized studies are conducted.

Decreased Serum Wnt Antagonist Levels in Patients With Active Acromegaly.

OBJECTIVE: The Wnt signaling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients. METHODS: We recruited 77 patients recently diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. At baseline and posttreatment, Wnt antagonists (sclerostin [SOST], dickkopf-related protein 1 [DKK-1], and Wnt inhibitory factor 1 [WIF-1]), bone turnover markers (osteocalcin, procollagen type 1 N-terminal propeptide [P1NP], and C-terminal telopeptide of type 1 collagen [CTX]) and the bone remodeling index were investigated. RESULTS: Acromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodeling index than controls (P < .01). Serum SOST, DKK-1, and WIF-1 levels were significantly decreased in patients compared to controls (all P < .01). Serum SOST and WIF-1 levels were negatively correlated with growth hormone levels; SOST levels were positively correlated with WIF-1. After treatment, serum bone turnover markers and the bone remodeling index decreased, while SOST and WIF-1 significantly increased (P < .05). DKK-1 levels did not change compared to baseline (P > .05). In biochemically controlled patients, SOST and WIF-1 levels and bone turnover markers were restored and did not differ from those of the control participants (all P > .05). CONCLUSION: Patients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists is a compensatory mechanism to counteract increased bone fragility in active acromegaly.

Resveratrol Reestablishes Mitochondrial Quality Control in Myocardial Ischemia/Reperfusion Injury through Sirt1/Sirt3-Mfn2-Parkin-PGC-1α Pathway.

Resveratrol is a natural polyphenol found in various plants. It has been widely studied on cardiovascular disorders. It is known that resveratrol can activate Sirtuin proteins and participate in cellular energy metabolism through a Sirtuin-dependent pathway. Here, we hypothesized that resveratrol may protect against myocardial ischemia/reperfusion injury (MIRI) through the target of Sirt1/Sirt3 on mitochondrial dynamics, cardiac autophagy, bioenergetics and oxidative damage in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. We observed that resveratrol could activate the Sirt1/Sirt3-FoxO pathway on myocardial mitochondria in H/R cardiomyocytes. Subsequently, we found that resveratrol repaired the fission-fusion balance, autophagic flux and mitochondrial biosynthesis compared by H/R group. These changes were followed by increased functional mitochondrial number, mitochondrial bioenergetics and a better mitochondrial antioxidant enzyme system. Meanwhile, these effects were antagonized by co-treatment with Selisistat (Ex527), a Sirtuin inhibitor. Together, our findings uncover the potential contribution of resveratrol in reestablishing a mitochondrial quality control network with Parkin, Mfn2 and PGC-1α as the key nodes.

Serum- and glucocorticoid-inducible kinase 1 promotes insulin resistance in adipocytes via degradation of insulin receptor substrate 1.

AIMS: Accumulating evidence indicates that serum- and glucocorticoid-inducible kinase 1 (SGK1) plays a role in the development of metabolic syndrome via a poorly understood mechanism. This study aimed to investigate the direct effect of SGK1 on insulin sensitivity in adipose tissue. MATERIALS AND METHODS: We ectopically expressed or silenced SGK1 in adipocytes via lentiviral transfection, measured glucose uptake and evaluated insulin signalling using western blotting. In vivo insulin resistance was measured at the whole-body and adipose tissue levels in db/db mice treated with an inhibitor of SGK1. RESULTS: After 8 weeks of SGK1 inhibitor treatment, the serum insulin level and homeostasis model assessment of insulin resistance index were significantly decreased, and AKT phosphorylation in adipose tissue was enhanced in db/db mice. Overexpression of constitutively active SGK1 in adipocytes in vitro decreased AKT phosphorylation and insulin-stimulated glucose uptake. Dexamethasone and oleic acid increased SGK1 expression and decreased AKT phosphorylation and insulin receptor substrate expression in adipocytes. Administration of an inhibitor of SGK1 or Lv-shSGK1 reversed the suppression of insulin signalling induced by dexamethasone and oleic acid. SGK1 overexpression increased FoxO1 phosphorylation, and administration of Lv-shSGK1 reversed an increase in FoxO1 phosphorylation induced by dexamethasone and oleic acid. CONCLUSIONS: Thus, SGK1 mediates the effect of glucocorticoids and high-fat feeding and induces insulin resistance in adipocytes. Our data suggest that SGK1 is a possible therapeutic target for metabolic syndrome and related complications.

Effect of adrenocorticotropic hormone stimulation during adrenal vein sampling for the subtyping of primary aldosteronism: a prospective study.

OBJECTIVE: Adrenal venous sampling (AVS) is key for primary aldosteronism subtype identification. However, the value of adrenocorticotropic hormone (ACTH) stimulation in AVS is still controversial. METHODS: In this prospective study, we investigated the role of continuous ACTH infusion on the performance and interpretation of bilateral simultaneous AVS using a standard protocol in 59 primary aldosteronism patients. We analyzed the selectivity index and lateralization index in AVS pre and post-ACTH and estimated the prognosis of patients who underwent adrenalectomy with different cutoff points of lateralization index post-ACTH. RESULTS: The confirmed success rate of bilateral adrenal vein catheterization increased from 84% pre-ACTH to 95% post-ACTH. Fifty percent of the patients had a decline in lateralization index post-ACTH, 30% of patients showed unilateral primary aldosteronism pre-ACTH but bilateral primary aldosteronism post-ACTH according to lateralization index at least 2 pre-ACTH and lateralization index at least 4 post-ACTH. The outcomes of the patients with primary aldosteronism after adrenalectomy indicated that all patients achieved clinical and biochemical success regardless of lateralization index at least 4 or less than 4 post-ACTH. Receiver operating characteristic curves showed that lateralization index cutoff 2.58 post-ACTH stimulation yielded the best threshold in lateralization with a sensitivity of 73.1% and a specificity of 92.9%. CONCLUSION: ACTH stimulation increased the AVS success rates in patients with primary aldosteronism, reduced lateralization index in some cases and decreased the proportion of identified unilateral primary aldosteronism, resulting in some patients losing the opportunity for disease cure. Compared with lateralization index at least 4, a lower cutoff point of lateralization index at least 2.58 after ACTH stimulation has better accuracy of lateralization diagnosis.

Comparable cognitive impairment was detected in MACS and CS and alleviated after remission of hypercortisolism in MACS.

Context: Few studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing's syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear. Objective: To compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function. Methods: We prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment. Results: Patients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P<0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329-10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411-25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P<0.05), whereas there was no improvement in the conservative treatment group. Conclusion: Patients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS.

Circadian clock and lipid metabolism disorders: a potential therapeutic strategy for cancer.

Recent research has emphasized the interaction between the circadian clock and lipid metabolism, particularly in relation to tumors. This review aims to explore how the circadian clock regulates lipid metabolism and its impact on carcinogenesis. Specifically, targeting key enzymes involved in fatty acid synthesis (SREBP, ACLY, ACC, FASN, and SCD) has been identified as a potential strategy for cancer therapy. By disrupting these enzymes, it may be possible to inhibit tumor growth by interfering with lipid metabolism. Transcription factors, like SREBP play a significant role in regulating fatty acid synthesis which is influenced by circadian clock genes such as BMAL1, REV-ERB and DEC. This suggests a strong connection between fatty acid synthesis and the circadian clock. Therefore, successful combination therapy should target fatty acid synthesis in addition to considering the timing and duration of drug use. Ultimately, personalized chronotherapy can enhance drug efficacy in cancer treatment and achieve treatment goals.

Impaired Cognitive Function in Patients With Autonomous Cortisol Secretion in Adrenal Incidentalomas.

CONTEXT: Glucocorticoids have potent effects on the central nervous system. However, while patients with Cushing syndrome frequently report impairments in cognitive function, studies investigating cognitive function in patients with autonomous cortisol secretion (ACS) in adrenal incidentalomas (AIs) are scarce. OBJECTIVE: The aim of the present study was to evaluate neurocognitive function in patients with ACS. METHODS: We prospectively recruited 63 patients with AI, 36 patients with nonfunctional adrenal adenoma (NFA) (46.5 ± 10.5 years), and 27 patients with ACS (48.6 ± 9.1 years); these patients underwent a battery of validated neuropsychological tests. ACS was diagnosed when serum cortisol levels after a 1-mg dexamethasone suppression test (cortisol1 mg DST) ≥ 50 nmol/L. RESULTS: Patients with ACS had higher frequency of subjective memory complaints (40.7% vs 13.9%, P < 0.05) and higher proportion of mild cognitive impairment (22.2% vs 2.8%, P < 0.05) than patients with NFA. Furthermore, patients with ACS had worse performance on working memory and the visuospatial/constructional domain than patients with NFA (all P < 0.05). Serum cortisol1 mg DST was negatively correlated with working memory and visuospatial/constructional domains (r = -0.307 and -0.306, respectively, all P < 0.05). Performance on working memory and visuospatial/constructional domains gradually deteriorated with increases in serum cortisol1 mg DST (all P values for trend < 0.05). Multivariate linear regression analysis showed that serum cortisol1 mg DST was a significant risk factor for impairment of working memory and visuospatial/constructional domains (B = -0.006 and -0.043, respectively, all P < 0.05). CONCLUSION: This study is the first to report that ACS is accompanied by impaired cognitive function. Consequently, cognitive function assessment should be incorporated into the clinical evaluation of patients with ACS. CLINICAL TRIAL REGISTRATION NUMBER: NCT05357456.

Increased Risk for Dementia in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Population-Based Studies.

Background: Mounting evidence suggests that there may be a causal relationship or common pathogenic pathway between inflammatory bowel disease (IBD) and dementia. However, inconsistent results have emerged from epidemiological studies. We therefore conducted this review to clarify the relationship between IBD and dementia. Methods: We systematically searched PubMed, Web of Science, Embase, and Cochrane library to identify all studies exploring the relationship between IBD and dementia published as of September 2021. Risk estimates were pooled using both fixed and random-effects models. Results: Six studies involving 2,334,472 subjects were included. Pooled results suggested that the risk of developing dementia significantly increased after IBD diagnosis (HR = 1.27, 95% CI: 1.10-1.47, P = 0.001), which did not vary by age, gender, dementia subtype, or IBD subtype. Whereas, the dementia incidence before IBD diagnosis and the comorbidity rate of dementia in IBD patients were similar to those without IBD (HR = 0.92, 95% CI: 0.68-1.25; 0.82, 95% CI: 0.64-1.06, respectively). However, current evidence was insufficient to establish a causal relationship. Conclusion: This study shows an unidirectional association between IBD and dementia; patients with IBD have an increased risk of dementia, and it may be beneficial to develop individualized dementia screening strategies for this population. Future research needs to further investigate whether effective therapies of IBD can reduce this risk and pathophysiological mechanisms of the association.

Expression and clinical significance of lncRNA TCL6 in serum of patients with preeclampsia.

Preeclampsia is a common syndrome in pregnancy and a leading cause of mortality of pregnant females and their infants. To investigate the diagnostic and prognostic utility of lncRNA T-cell leukemia/lymphoma 6 (TCL6) in patients with preeclampsia, 120 singleton pregnant females with preeclampsia and another 100 healthy pregnant control subjects were analyzed in the present study. The expression of lncRNA TCL6 in the serum of the included patients was detected. Receiver operating characteristic curve analysis was applied to evaluate the efficiency of lncRNA TCL6 in terms of preeclampsia diagnosis and grading. Kaplan-Meier analysis was adopted to assess the effect of lncRNA TCL6 expression on the rate of adverse pregnancy. Multivariate logistic regression was used to determine high-risk factors of adverse pregnancy. The results indicated that lncRNA TCL6 was significantly increased in the serum of patients with preeclampsia. Furthermore, TCL6 was elevated in subgroups of patients with early-onset or severe preeclampsia and with Haemolysis, Elevated Liver enzymes and Low Platelet count syndrome in comparison with other patients with preeclampsia. High expression of TCL6 in pregnant females corresponded to a higher rate of adverse pregnancy outcomes. Severe preeclampsia, early-onset preeclampsia and high TCL6 expression were identified as independent risk factors for adverse pregnancy outcomes. For each unit increase in TCL6 expression, a 9.5-fold increase of the risk of adverse maternal and fetal outcomes was determined. Collectively, high expression of lncRNA TCL6 may assist the diagnosis and grading of preeclampsia and may be adopted as an independent risk factor for adverse pregnancy outcomes.

Systemic immune-inflammation index as a potential biomarker of cardiovascular diseases: A systematic review and meta-analysis.

Background: Several studies have investigated the value of the systemic immune-inflammation index (SII) for predicting cardiovascular disease (CVD), but the results were inconsistent. Therefore, a meta-analysis and systematic review were conducted to assess the correlation between SII and risk of CVD. Materials and methods: Two investigators systematically searched PubMed, Embase, Web of Science, Cochrane library, and CINAHL databases to identify all studies that examined the association between SII levels and CVD. The risk estimates of CVD for people with high SII compared to those with low SII levels and the weighted mean difference (WMD) between the CVD and control groups were pooled using fixed- or random-effects models based on the heterogeneity test. We used the Newcastle-Ottawa Scale to assess the risk of bias in eligible studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to rate the certainty of evidence. Results: A total of 13 studies with 152,996 participants were included for analysis. The overall pooled results showed that higher SII was significantly associated with an increased risk of CVD (HR = 1.39, 95%CI: 1.20-1.61, P < 0.001). This increased risk could be observed in almost all CVD subtypes, including ischemic stroke (HR = 1.31, 95%CI: 1.06-1.63, P = 0.013), hemorrhagic stroke (HR = 1.22, 95%CI: 1.10-1.37, P < 0.001), myocardial infarction (HR = 1.11, 95%CI: 1.01-1.23, P = 0.027), and peripheral arterial disease (HR = 1.51, 95%CI: 1.18-1.93, P = 0.001). There were no significant but still similar trends in venous thrombosis (HR = 4.65, 95%CI: 0.66-32.71, P = 0.122), cerebral small vessel disease (HR = 1.09, 95%CI: 0.95-1.25, P = 0.233), and acute coronary syndrome (HR = 1.08, 95%CI: 0.96-1.22, P = 0.200). Furthermore, the pooled results showed that SII levels at the onset of CVD were significantly higher than that in the general population (WMD = 355.2, 95%CI: 234.8-475.6, P < 0.001), which was consistent across different CVD subtypes. The GRADE assessment suggested that the quality of current evidence from observational studies was low or very low. Conclusion: This study indicated that SII may be a potential biomarker for CVD development and elevated SII is associated with an increased risk of CVD. However, the quality of evidence is generally low. Additional well-designed studies are necessary to determine the optimal cutoff value and to characterize the benefited population.

A critical review of biochar-based materials for the remediation of heavy metal contaminated environment: Applications and practical evaluations.

The contamination of heavy metals (HMs) in the environment has aroused a global concern. The valid remediation of HM contaminated environment is a highly significant issue. As alternative to carbon materials, biochar has been vastly documented for the remediation of HM contaminated environment. However, there are some possible imperfections to meet the actual remediation tasks as the finite properties of raw biochar, and the remediation process is complex and unexpectedly. This review focuses on the progress made on environmental HM remediation by biochar-based materials within the past six years. The property analysis and key modifications of biochar are summarized inspired by their applicability or necessity for HM decontamination, and the environmental remediation as well as the implicated mechanisms are thoroughly elaborated from multiple pivotal sides. The evaluations of practical application associated with biochar amendment are also presented. Finally, some pertinent improvements and research directions are proposed. To our knowledge, this article is the first time to make a systematic summary on the reliability and practicability of biochar-based materials for environmental HM remediation, and critically pointed out the existing issues to facilitate the judicious design of biochar-based materials and understanding the research trends. It is also aims to provide reference for subsequent research and propel the practical applications.

Risk, Incidence, and Mortality of Breast Cancer in Primary Sjögren's Syndrome: A Systematic Review and Meta-Analysis.

Background: Primary Sjögren's syndrome (pSS) and breast cancer are a highly prevalent autoimmune disease and malignancy, respectively, both occurring predominantly in females. Whether there is a link between these two diseases is uncertain. We conducted a systematic review and meta-analysis to investigate the risk, incidence, and mortality of breast cancer in patients with pSS. Methods: We systematically searched Embase, PubMed, and Web of Science on January 31, 2022 to identify the study that assessed risk, incidence, or mortality of breast cancer in pSS. The fixed or random-effects models were applied to pool the effect estimates based on heterogeneity measured by Cochran's Q-test and Higgins' I2. Results: Ten studies involving 725,805 participants and 64,836 pSS patients were included in our analysis. The pooled result showed that, overall, pSS was not associated with the risk (SIR=0.92, 95%CI: 0.66-1.29, P=0.646) and mortality (HR = 0.78, 95%CI: 0.26-2.34, P = 0.664) of breast cancer; however, when stratified by geographic region, we found that patients with pSS in Asian countries (SIR=1.32, 95%CI: 1.10-1.58, P=0.003) and Argentina (SIR=3.76, 95%CI: 1.04-9.45, P=0.019) had an elevated risk of breast cancer, while pSS in Europe was associated with a reduced risk (SIR=0.61, 95%CI: 0.51-0.73, P<0.001). The pooled result from 28,635 female pSS patients indicated that the incidence of breast cancer was 2.15 (95% CI: 1.33-3.50) per 1000 person/years. Conclusion: This study suggests that there may be geographical differences in the association between pSS and breast cancer risk; patients with pSS in European countries are associated with a lower risk of breast cancer, while Asia and Argentina are the opposite. Future research is needed to further characterize the effect of pSS on breast cancer risk and the pathophysiological mechanisms underlying this association to unravel the complex relationship between the two.

Risk of dementia or Parkinson's disease in the presence of Sjögren's syndrome: A systematic review and meta-analysis.

Objective: Evidence from observational studies suggests that Sjögren's syndrome (SS) may contribute to an elevated risk of Parkinson's disease (PD) and dementia. However, few studies have been undertaken to summarize and assess the consistency of the data quantitatively. Therefore, we evaluated the risk of dementia and PD in SS patients through a systematic review and meta-analysis approach. Methods: Two reviewers independently conducted a systematic search of PubMed, Embase, and Web of Science databases (updated to February 14, 2022) to identify published literature on the association between SS and dementia or PD. The risk estimates of dementia or PD in patients with SS were pooled using fixed or random-effects models. Results: Of the 631 studies initially searched, 10 were eventually included. Pooled results suggested that the risk of developing dementia significantly increased in patients with SS (HR = 1.24, 95% CI: 1.15-1.33, P < 0.001), and such risk in females with SS was similar to that in males. The risk of PD was 1.36 times higher in SS (HR = 1.36, 95% CI: 1.23-1.50, P < 0.001). The association between SS and PD risk appeared to occur primarily in female patients (female: HR = 1.28, 95% CI: 1.21-1.35; P < 0.001 vs. male: HR = 1.00, 95% CI: 0.87-1.16, P = 0.962, respectively). No significant effect of age was observed on the risk of developing PD and dementia in SS patients. Conclusion: Our study supports that people with SS are at higher risk of PD and dementia than the general population. Further studies are needed to elucidate the underlying mechanisms and to assess whether interventions for SS have the potential to affect dementia and PD development.

Expression and clinical significance of VISTA and PD-L1 in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and challenging management. The present study aimed to investigate the expression of programmed death ligand-1 (PD-L1) and V-domain Ig-containing suppressor of T cell activation (VISTA) in ACC and their associations with clinicopathological features and survival outcomes. Immunohistochemistry was performed on formalin-fixed paraffin-embedded specimens from 54 ACC patients. Chi-square/Fisher's exact tests or independent samples t/Mann-Whitney U tests were performed to assess correlations between immunoscores and clinicopathological parameters. The Kaplan-Meier method and Cox regression were conducted for survival analysis and to identify independent predictors of overall (OS) and disease-free (DFS) survival. Results showed that VISTA was expressed in tumor cells (TCs) and tumor-infiltrating immune cells (TICs) in 81.5% (44/54) and 40.7% (22/54) of the patients, respectively. PD-L1 positivity was found in either TCs or TICs in 11.1% (6/54) of the patients. Patients with positive VISTA expression in TCs had a higher tumor stage (56.9% vs 20%, P = 0.036) and Ki-67 index (30.50 ± 23.51% vs 14.76 ± 11.75%, P = 0.006). However, PD-L1 positivity in either TCs or TICs had no association with patient clinicopathological features. A higher VISTA expression intensity, a larger area and a higher immunoscore were associated with increased risks of disease progression and overall mortality, but PD-L1 expression in TCs or TICs was not associated with OS or DFS. In conclusion, positive TC VISTA expression was correlated with pathological parameters related to malignancy in ACC patients. This finding provides novel evidence of the value of VISTA, in addition to PD-L1, as an immunotherapeutic target in ACC.

Radiomics Analysis on Digital Breast Tomosynthesis: Preoperative Evaluation of Lymphovascular Invasion Status in Invasive Breast Cancer.

RATIONALE AND OBJECTIVES: To develop a digital breast tomosynthesis (DBT)-based radiomics nomogram for preoperative evaluation of lymphovascular invasion (LVI) status in patients with invasive breast cancer (IBC). MATERIALS AND METHODS: A total of 135 patients with pathologically confirmed IBC who underwent preoperative DBT from July 2018 to May 2020 were retrospectively enrolled and randomized into the training and validation sets. Radiomics feature extraction was performed on the volume of interest (VOI) manually outlined. A four-step algorithmic was applied to screen the features with the highest predictive power in the training set for constructing the radiomics signature and calculating the correspondent radiomics score (Rad-score). Logistic regression analyses were utilized to develop a combined radiomics model that incorporated the DBT-reported clinicoradiological semantic features and Rad-score, which was visualized as a radiomics nomogram. RESULTS: The percentage of LVI-positive patients was 60.2% and 59.5% in the training and validation sets, respectively. The radiomics signature was constructed based on nine features selected from the 1218 radiomics features extracted. Higher Rad-score, maximum tumor diameter, and spiculate margin were independent risk factors for LVI. The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity of the radiomics nomogram were 0.905, 72.7%, and 94.6% in the training set, and 0.835, 80.0%, and 76.5% in the validation set, respectively; this data was higher than models incorporating clinicoradiological semantic features alone or the radiomics signature in both sets. CONCLUSION: Preoperative DBT-based combined radiomic nomogram could be a potential biomarker for LVI in patients with IBC.

Performance of DHEAS as a Screening Test for Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Prospective Study.

CONTEXT: Autonomous cortisol secretion (ACS) affects up to 30% of patients with adrenal incidentalomas (AIs). The current guidelines for ACS diagnosis are not decisive. A lower dehydroepiandrosterone sulfate (DHEAS) level is a potential biomarker, but the evidence is conflicting. OBJECTIVE: This prospective study aimed to evaluate and validate the ACS screening and diagnostic accuracy of DHEAS. METHODS AND PATIENTS: Recruited patients with AI were screened for adrenal medullary and cortisol hypersecretion. The diagnosis of ACS was based on a serum cortisol level ≥ 50 nmol/L following a 1-mg dexamethasone suppression test (DST) and a low-dose DST. Age- and sex-specific DHEAS ratios were also calculated. RESULTS: In the development cohort (45 ACS and 242 non-ACS patients), the areas under the receiver operator characteristic curves (AUCs) of DHEAS and the DHEAS ratio were 0.869 (95% CI 0.824-0.906) and 0.799 (95% CI 0.748-0.844), respectively. The optimal DHEAS cutoff for diagnosing ACS was 60 µg/dL, with a sensitivity of 75.6% (95% CI 60.5-87.1) and a specificity of 81.4% (95% CI 76.4-86.5). The midnight serum cortisol level had moderate diagnostic accuracy [AUC 0.875 (95% CI 0.831-0.911)]. Suppressed adrenocorticotropic hormone (≤2.2 pmol/L) had a lower sensitivity (55.6%), and the 24-hour urinary free cortisol lacked sensitivity and specificity [AUC 0.633 (95% CI 0.603-0.721)]. In the validation cohort (14 ACS and 45 non-ACS patients), the sensitivity and specificity of the optimized DHEAS cutoff were 71.4% (95% CI 41.9-91.6) and 82.2% (95% CI 68.0-92.0), respectively. CONCLUSIONS: A single basal measurement of DHEAS is valuable for identifying ACS. Because of its stability and ease of use, the DHEAS level could be used as an ACS screening test.

Highly efficient photocatalytic degradation of norfloxacin via Bi2Sn2O7/PDIH Z-scheme heterojunction: Influence and mechanism.

The severe pollution caused by antibiotics has prompted considerable concerns in recent decades. In this study, the Bi2Sn2O7/PDIH Z-scheme heterojunction photocatalyst was synthesized and highly photocatalytic activity on norfloxacin was obtained. The degradation of norfloxacin reached 98.71% in 90 min under visible light. The apparent rate constant of norfloxacin (0.4 903 min-1) was 3.65 and 20 times that of PDIH and the Bi2Sn2O7. Meanwhile, XPS, electrochemical, Photoluminescence spectroscopy and electron paramagnetic resonance results showed that Z-scheme charge-transfer process facilitated the spatial carrier separation and preserve redox capability. Furthermore, the degradation intermediates of norfloxacin and their toxicities were evaluated. Finally, in the view of the survey about the impact of different water matrices, it was found that the Bi2Sn2O7/PDIH maintained high efficiency in raw natural water. This work enriched inorganic/organic heterojunction engineering for PDIH, and provided the enormous potential for combining the Bi2Sn2O7 with PDIH to address the antibiotic pollution issues in the actual water treatment.

Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies.

Background: Common vaccinations may have impacts on dementia risk, but current evidence is inconsistent. We therefore investigated the association between vaccinations and dementia risk by systematic review and meta-analysis approach. Methods: We conducted an extensive search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared the risk of dementia in vaccinated versus unvaccinated populations. The adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were pooled as measures. Results: Of the 9124 records initially retrieved, 17 studies with 1857134 participants were included in our analysis. The overall pooled results showed that vaccinations were associated with a 35% lower dementia risk (HR=0.65, 95% CI: 0.60-0.71, Poverall effect < 0.001; I2 = 91.8%, Pheterogeneity<0.001). All types of vaccination were associated with a trend toward reduced dementia risk, with rabies (HR=0.43), tetanus & diphtheria & pertussis (Tdap) (HR=0.69), herpes zoster (HR=0.69), influenza (HR=0.74), hepatitis A (HR=0.78), typhoid (HR=0.80), and hepatitis B (HR=0.82) vaccinations being significant. Individuals with more full vaccination types and more annual influenza vaccinations were less likely to develop dementia. Gender and age had no effect on this association. Conclusion: Routine adult vaccinations are associated with a significant reduction in dementia risk and may be an effective strategy for dementia prevention. Further research is needed to elucidate the causal effects of this association and the underlying mechanisms.