Diagnostic efficacy and interobserver agreement among readers with variable experience of the Prostate Imaging for Recurrence Reporting system with whole-mount histology after androgen deprivation therapy as a reference.

Background: The Prostate Imaging for Recurrence Reporting (PI-RR) system was recently proposed to assess the local recurrence of prostate cancer (PCa), but its exact performance for the prostate after radiotherapy or radical prostatectomy is difficult to determine. We aimed to evaluate the diagnostic performance and interreader agreement of this system using whole-mount histology of the prostate after androgen deprivation therapy (ADT) as the standard of reference. Methods: In total, 119 patients with PCa post-ADT underwent multiparametric magnetic resonance imaging (mp-MRI) before prostatectomy. Three radiologists analyzed the MRI images independently, scoring imaging findings according to PI-RR. Spearman correlation was performed to assess the relationship between the percentage of sectors with residual cancer and PI-RR score. The diagnostic performance for detection of residual cancer was assessed on a per-sector basis. The chi-squared test was used to compare the cancer detection rate (CDR) among readers. Overall and pairwise interreader agreement in assigning PI-RR categories and residual cancer sectors with a score ≥3 or ≥4 were evaluated with the Cohen kappa coefficient. Results: Histology revealed 209 sectors with residual cancer. The percentage of pathologically positive sectors increased with the increase in PI-RR score for all readers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at a cutoff of score 3 ranged from 74.2% to 83.7%, 86.4% to 92.7%, 51.3% to 64.3%, and 95.4% to 96.9%, respectively, and at a cutoff of score 4, they ranged from 47.4% to 56.5%, 97.9% to 98.6%, 82.5% to 85.3%, and 91.6% to 92.9%, respectively. There was no significant difference among the CDR of readers. In PI-RR categories and detection of residual cancer sectors, overall interreader agreement was moderate for all readers, but agreement was higher between the more experienced readers (moderate to substantial) than between the more and less experienced readers (fair to moderate). Conclusions: MRI scoring with the PI-RR assessment provided accurate evaluation of PCa after ADT, but readers' experience influenced interreader agreement and cancer diagnosis.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy.

OBJECTIVES: Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify high-risk population. METHODS: We included EGPA patients hospitalized in our center from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac magnetic resonance imaging, and endomyocardial biopsy results, the patients were divided into 3 groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS: A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, p< 0.01), ANCA positivity decreased (41.33/31.82/14.86%, p< 0.01), and lung involvement reduced (73.33/72.73/43.24%, p= 0.02). In EGPA-EM, cardiac troponin further elevated (0.27 vs 6.00 ng/ml, p< 0.01), ejection fractions decreased (57.79 vs 33.20%, p< 0.01), while more ST-T abnormality was observed (41.89 vs 20.45%, p= 0.02). The prognosis of EGPA-EM was significantly worse, with 14.86% death rate, and 2-year event-free survival rate below 50%. Further, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [AUC 0.85 (95%CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS: We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given timely and anti-IL-5 antibodies be tested in trials.

Proinflammatory phenotype of B10 and B10pro cells elicited by TNF-α in rheumatoid arthritis.

OBJECTIVES: B10 and B10pro cells suppress immune responses via secreting interleukin (IL)-10. However, their regulators and underlying mechanisms, especially in human autoimmune diseases, are elusive. This study aimed to address these questions in rheumatoid arthritis (RA), one of the most common highly disabling autoimmune diseases. METHODS: The frequencies and functions of B10 and B10pro cells in healthy individuals and patients with RA were first analysed. The effects of proinflammatory cytokines, particularly tumour necrosis factor (TNF)-α on the quantity, stability and pathogenic phenotype of these cells, were then assessed in patients with RA before and after anti-TNF therapy. The underlying mechanisms were further investigated by scRNA-seq database reanalysis, transcriptome sequencing, TNF-α-/- and B cell-specific SHIP-1-/- mouse disease model studies. RESULTS: TNF-α was a key determinant for B10 cells. TNF-α elicited the proinflammatory feature of B10 and B10pro cells by downregulating IL-10, and upregulating interferon-γ and IL-17A. In patients with RA, B10 and B10pro cells were impaired with exacerbated proinflammatory phenotype, while anti-TNF therapy potently restored their frequencies and immunosuppressive functions, consistent with the increased B10 cells in TNF-α-/- mice. Mechanistically, TNF-α diminished B10 and B10pro cells by inhibiting their glycolysis and proliferation. TNF-α also regulated the phosphatidylinositol phosphate signalling of B10 and B10pro cells and dampened the expression of SHIP-1, a dominant phosphatidylinositol phosphatase regulator of these cells. CONCLUSIONS: TNF-α provoked the proinflammatory phenotype of B10 and B10pro cells by disturbing SHIP-1 in RA, contributing to the disease development. Reinstating the immunosuppressive property of B10 and B10pro cells might represent novel therapeutic approaches for RA.

A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Association of Pathological Features and Multiparametric MRI-Based Radiomics With TP53-Mutated Prostate Cancer.

BACKGROUND: TP53 mutations are associated with prostate cancer (PCa) prognosis and therapy. PURPOSE: To develop TP53 mutation classification models for PCa using MRI radiomics and clinicopathological features. STUDY TYPE: Retrospective. POPULATION: 388 patients with PCa from two centers (Center 1: 281 patients; Center 2: 107 patients). Cases from Center 1 were randomly divided into training and internal validation sets (7:3). Cases from Center 2 were used for external validation. FIELD STRENGTH/SEQUENCE: 3.0T/T2-weighted imaging, dynamic contrast-enhanced imaging, diffusion-weighted imaging. ASSESSMENT: Each patient's index tumor lesion was manually delineated on the above MRI images. Five clinicopathological and 428 radiomics features were obtained from each lesion. Radiomics features were selected by least absolute shrinkage and selection operator and binary logistic regression (LR) analysis, while clinicopathological features were selected using Mann-Whitney U test. Radiomics models were constructed using LR, support vector machine (SVM), and random forest (RF) classifiers. Clinicopathological-radiomics combined models were constructed using the selected radiomics and clinicopathological features with the aforementioned classifiers. STATISTICAL TESTS: Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC). P value <0.05 indicates statistically significant. RESULTS: In the internal validation set, the radiomics model had an AUC of 0.74 with the RF classifier, which was significantly higher than LR (AUC = 0.61), but similar to SVM (AUC = 0.69; P = 0.422). For the combined model, the AUC of RF model was 0.84, which was significantly higher than LR (0.64), but similar to SVM (0.80; P = 0.548). Both the combined RF and combined SVM models showed significantly higher AUCs than the radiomics models. In the external validation set, the combined RF and combined SVM models showed AUCs of 0.83 and 0.82. DATA CONCLUSION: Pathological-radiomics combined models with RF, SVM show the association of TP53 mutations and pathological-radiomics features of PCa. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Revealing Potential Genes Affecting Flocculation and/or Viability of Saccharomyces pastorianus by Comparative Genomic Analysis.

Yeast flocculation and viability are critical factors in beer production. Adequate flocculation of yeast at the end of fermentation helps to reduce off-flavors and cell separation, while high viability is beneficial for yeast reuse. In this study, we used comparative genomics to analyze the genome information on Saccharomyces pastorianus W01, and its spontaneous mutant W02 with appropriate weakened flocculation ability (better off-flavor reduction performance) and unwanted decreased viability, to investigate the effect of different gene expressions on yeast flocculation or/and viability. Our results indicate that knockout of CNE1, CIN5, SIN3, HP-3, YPR170W-B, and SCEPF1_0274000100 and overexpression of CNE1 and ALD2 significantly decreased the flocculation ability of W01, while knockout of EPL1 increased the flocculation ability of W01. Meanwhile, knockout of CIN5, YPR170W-B, OST5, SFT1, SCEPF1_0274000100, and EPL1 and overexpression of SWC3, ALD2, and HP-2 decreased the viability of W01. CIN5, EPL1, SCEPF1_0274000100, ALD2, and YPR170W-B have all been shown to affect yeast flocculation ability and viability.

The Formation of Stigma and Its Social Consequences on Chinese People Living With Lung Cancer: A Qualitative Study.

PURPOSE: To explore the formation of stigma toward lung cancer and its social consequences for Chinese patients living with this diagnosis. PARTICIPANTS & SETTING: A purposive sample of 19 patients with lung cancer were recruited in the outpatient clinic of a tertiary cancer center in southern China. METHODOLOGIC APPROACH: This is a descriptive qualitative study. Semistructured interviews were conducted to explore the formation of stigma toward lung cancer and its social consequences. Audio recordings were transcribed verbatim and coded by the thematic analysis approach. FINDINGS: The following three themes emerged from interviews: (a) sources of stigma, (b) stigma manifestations, and (c) social consequences of stigma. IMPLICATIONS FOR NURSING: Considering that the formation of lung cancer stigma is socioculturally specific, existing stereotypes and prejudice in Chinese society should be the focus of antistigma interventions at the population level. At the individual level, cancer concealment, resistance to cancer identity, and feelings of no longer being a normal person were three common manifestations that may be indicators for stigma screening among people with lung cancer. In addition, stigmas profoundly affected patients' social lives and their help-seeking behaviors, and medical staff should use effective strategies to alleviate stigma toward lung cancer and its effects.

Differentiation of bladder cancer stages using the vesical imaging -reporting and data system and apparent diffusion coefficient.

Background: T stage is closely related to the treatment and prognosis of patients with bladder cancer (BC). However, preoperative T staging is still challenging. Multiparametric magnetic resonance imaging (mpMRI) may be valuable. This study was performed to explore the value of the Vesical Imaging-Reporting and Data System (VI-RADS) and the volumetric apparent diffusion coefficient (ADC) histogram parameters in detecting T2 stage and below stage (≤T2 stage) from T3 stage and above stage (≥T3 stage) BCs. Methods: The study included 62 patients (mean age, males vs. females: 62.1±10.9 vs. 61.8±11.7 years) with BC pathologically confirmed by partial or radical cystectomy. All of the tumors were scored normatively by two radiologists using the VI-RADS scoring system by two radiologists. The volumetric ADC histogram of each lesion was obtained from the ADC maps. The Cochran-Armitage test was used to examine the relevance between VI-RADS scores and T stages. The Mann-Whitney U test was used to compare the histogram parameters between ≤T2 stage and ≥T3 stage BCs. A receiver operating characteristic (ROC) curve was used to assess the predictive power of each model. Results: The minimum ADC; mean ADC; median ADC; maximum ADC; and 10th, 25th, 75th, and 90th percentile ADC of ≤T2 stage BCs were significantly higher than those of ≥T3 stage BCs, while skewness and kurtosis had opposite results. VI-RADS achieved the highest area under the curve (AUC) of 0.834 among all parameters. The combination of VI-RADS, skewness and kurtosis yield a significantly higher AUC than VI-RADS alone (0.915 vs. 0.834, P=0.0478). Conclusions: VI-RADS and volume ADC histogram analysis can effectively discriminate between ≤T2 stage and ≥T3 stage BCs, and the volumetric ADC histogram can provide further information to supplement VI-RADS.

Factors Related to Functional Capacity Deterioration in Surgical Lung Cancer Patients: A Systematic Review.

BACKGROUND: A decline in functional capacity is anticipated after lung resection. However, the factors related to functional capacity deterioration in surgical lung cancer patients have not been systematically reviewed. OBJECTIVE: To investigate the factors related to functional capacity deterioration and the trajectory of functional capacity after lung cancer surgery. METHODS: PubMed, CINAHL, Scopus, and SPORTDiscus were searched between January 2010 and July 2022. Two reviewers conducted a critical appraisal of individual sources. Twenty-one studies met the inclusion criteria. RESULTS: This review presents evidence for risk factors related to functional capacity deterioration after lung cancer surgery, including patient characteristics (age), preoperative clinical factors (vital capacity, quadriceps force, B-type natriuretic peptide level), surgery-related factors (surgical procedure, duration of chest tube drainage, postoperative complications), and postoperative clinical factor (C-reactive protein level). Most patients had a significant decline in functional capacity in the short term (≤1 month from surgery). In the medium term (1 to ≤6 months from surgery), although the functional capacity did not return to the preoperative level, the decline became insignificant. CONCLUSIONS: This study is the first to review factors related to functional capacity in lung cancer patients. The findings can help clinicians to better identify patients at risk of functional capacity decline and allocate clinical resources more efficiently. IMPLICATIONS FOR PRACTICE: The risk factors related to the functional capacity decline in surgical lung cancer patients should be evaluated routinely during perioperative nursing assessments. Preoperative and postoperative nursing interventions can potentially improve modifiable risk factors and prevent functional capacity deterioration.

The effects of exercise with or without dietary advice on muscle mass, muscle strength, and physical functioning among older cancer survivors: a meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the effect of exercise with or without dietary advice on muscle mass, muscle strength and physical functioning (including perceived physical functioning and physical performance) in old cancer survivors. METHODS: A systematic literature search was undertaken in May 2022 by searching multiple databases. Randomized controlled trials (RCTs) that compared exercise with or without dietary advice to control group among old cancer survivors were screened. Meta-analyses were conducted to evaluate the effects of exercise with or without dietary advice on muscle mass, muscle strength, and physical functioning. RESULTS: Data from 21 trials were included in this study, including 16 exercise trials and 5 exercise + dietary advice studies. Regarding exercise, evidence supported its significant benefits on muscle strength among old cancer survivors, while no effect was seen on physical functioning and muscle mass. Concerning exercise combined with dietary advice, meta-analysis showed overall benefits on physical functioning, while limited study examined muscle mass and strength. As for safety and feasibility of interventions, low recruitment rate, moderate compliance, and few adverse events were reported. CONCLUSIONS: Exercise combined with dietary advice is a more effective approach for old cancer survivors in improving physical functioning compared with exercise alone. Future study is needed to explore the effects of exercise combined with dietary advice on combating sarcopenia. As recruitment and compliance among old cancer survivors were challenging, strategies to stimulate their motivation and promote habitual healthy behaviour are warranted. IMPLICATIONS FOR CANCER SURVIVORS: It is necessary for old cancer survivors to receive exercise and dietary support to improve physical functioning.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy: using whole-mount histopathology as reference standard.

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

Relative basal myocardial weakness: differentiating dermatomyositis and polymyositis with cardiac involvement from viral myocarditis using speckle-tracking echocardiography and quantification of myocardial work.

Background: Both viral infection and autoimmune diseases like dermatomyositis (DM) and polymyositis (PM) can cause myocarditis and inflammatory cardiomyopathy. It is of great importance to identify underlying etiologies and initiate appropriate treatment. This study aimed to describe the pattern of regional longitudinal strain (LS) and myocardial work in PM/DM patients with cardiac involvement and investigate the usefulness of the pattern to differentiate PM/DM from acute viral myocarditis (AVM) in the clinical setting. Methods: A total of 46 PM/DM patients with cardiac involvement, 24 patients with AVM, and 30 healthy control participants (HCs) were included. Regional myocardial work and strain analyses were performed using two-dimensional (2D) echocardiography to calculate relative basal LS and myocardial work parameters and investigate their value for differential diagnosis. Results: PM and DM are characterized by a pattern of basal myocardial weakness with LS (basal, mid, and apical segments: -15.0±4.4, -17.1±4.7, and -21.4±6.5, respectively), myocardial work index (basal, mid, and apical segments: 1,193±432, 1,272±394, and 1,431±451, respectively), and constructive work (basal, mid, and apical segments: 1,512±422, 1,628±413, and 1,912±433, respectively) that show a base-to-apex gradient in which the myocardium at the base is more severely injured that that of the apex. On cardiovascular magnetic resonance, the positive rate of late gadolinium enhancement was also significantly higher in the basal segments (64%) than the mid (44%) and apical (28%) segments (P=0.038). A relative basal LS of 0.43, defined using the equation [average basal LS/(average mid LS + average apical LS)], had an area under curve (AUC) of 0.88 with high sensitivity (88%) and specificity (78%) to differentiate PM/DM from AVM. Using multivariate logistic regression analysis, relative basal injury of myocardium and creatine kinase elevation were strongly correlated with proximal skeletal muscle weakness according to manual muscle testing (P=0.036 and P=0.010, respectively). Conclusions: Similar to the typical proximal muscle weakness of limbs, PM/DM patients also presented with regionally decreased LS and myocardial work of the basal myocardium. A "basal weakness" pattern is easily recognizable and can be used to accurately differentiate PM/DM with cardiac involvement from AVM.

TNF-α Inhibitors and Other Biologic Agents for the Treatment of Immune Checkpoint Inhibitor-Induced Myocarditis.

With anti-PD-1 antibodies serving as a representative drug, immune checkpoint inhibitors (ICIs) have become the main drugs used to treat many advanced malignant tumors. However, immune-related adverse events (irAEs), which might involve multiple organ disorders, should not be ignored. ICI-induced myocarditis is an uncommon but life-threatening irAE. Glucocorticoids are the first choice of treatment for patients with ICI-induced myocarditis, but high proportions of steroid-refractory and steroid-resistant cases persist. According to present guidelines, tumor necrosis factor alpha (TNF-α) inhibitors are recommended for patients who fail to respond to steroid therapy and suffer from severe cardiac toxicity, although evidence-based studies are lacking. On the other hand, TNF-α inhibitors are contraindicated in patients with moderate-to-severe heart failure. This review summarizes real-world data from TNF-α inhibitors and other biologic agents for ICI-induced myocarditis to provide more evidence of the efficacy and safety of TNF-α inhibitors and other biologic agents.

Fat Attenuation Index of Renal Cell Carcinoma Reveals Biological Characteristics and Survival Outcome.

Purpose: The computed tomography fat attenuation index (FAI) is an ideal quantifiable imaging factor to identify the inflammation degree of peri-tumor adipose tissue. We aimed to verify whether FAI could reflect peri-tumor adipose inflammation, predict the survival outcome of renal cell carcinoma (RCC), and discover transcriptomic features of tumor tissues and adjacent adipocytes. Materials and Methods: Two clinical cohorts (Fudan University Shanghai Cancer Center [FUSCC] cohort [n=129] and TCGA cohort [n=218]) were used to explore the association between FAI and clinical outcome. A prospective cohort (n = 19) was used to discover the molecular phenotyping of peri-tumor adipose tissue and tumor tissue according to their FAI value. A clinical cohort (n = 32) in which patients received cyto-reductive surgery was used to reveal the dynamic change of FAI. Results: A high peri-tumor FAI was significantly associated with a worse outcome in both the FUSCC (HR = 2.28, p = 0.01) and the TCGA cohort (HR = 2.24, p <0.001). The analysis of the RNA expression of paired RCC tissue and peri-tumor fat tissue showed synchronized alterations in pathways such as cytokine-cytokine receptor interaction and complement and coagulation cascades. RCC tissues showed significant alterations in the neuroactive ligand-receptor interaction pathway. Immune deconvolution analysis showed enhanced infiltration of macrophages in high FAI tumor tissues with a lower angiogenesis level. We also observed synchronous dynamic changes in FAI and tumor size after targeted therapy. Conclusion: In summary, FAI could be used in RCC to reflect the biological characteristics and tumor immune micro-environment of both the tumor and the peri-tumor adipose. High peri-tumor FAI had the potential to predict a worse survival outcome in various cohorts. This study demonstrates that the crosstalk exists between a tumor and its micro-environment and could be reflected easily by imaging procedures, which could facilitate clinical decision making.

PD-1 inhibitor induces myocarditis by reducing regulatory T cells, activating inflammatory responses, promoting myocardial apoptosis and autophagy.

The present study aimed to explore the pathogenesis of autoimmune myocarditis induced by PD-1 inhibitors and their potential therapeutic targets. Mouse models of autoimmune myocarditis induced by PD-1 inhibitor in mouse models of polymyositis were established. The expression level of PD-1 and regulatory T cells (Tregs), CD4, CD8 + T cells, inflammation, apoptosis and autophagy-related factors, including IL-6, TGF-ß, AMA-M2, Fas/FasL, LC3 and p62 were detected in peripheral blood, muscle or myocardium of mice in each group, using ELISA, RT-PCR, Western Blot and immunofluorescence. In addition, HE and TUNEL staining and ultrastructural scanning were performed on the myocardium of mice in each group. Results showed that the expression level of PD-1 in the two myositis groups was significantly lower than that in the control group, and the level of PD-1 was lower in the myocarditis group than that in the polymyositis group. In the myocardium, TGF-ß, p62, and Tregs proportion showed the same expression level trend as PD-1, while CD8, IL-6, IL-10 and LC3 showed the opposite trend. Levels of Fas/FasL were significantly higher in both myositis groups, but were slightly lower in the myocarditis group, as was AMA-M2. Inflammation, apoptosis, and autophagy were observed in both myositis groups, but were more severe in the myocarditis group. In summary, the decreased expression level of PD-1 leads to decreased Tregs level in the myocardium, aggravated inflammatory response, apoptosis and autophagy, which may be the pathological mechanism of myocarditis induced by PD-1 inhibitors.

Prognostic value of left atrial mechanics in cardiac light-chain amyloidosis with preserved ejection fraction: a cohort study.

BACKGROUND: Light-chain amyloidosis is a plasma cell disorder associated with poor outcomes, especially when the heart is involved. The characteristics of left atrial (LA) function and its prognostic implications in cardiac amyloidosis (CA) have not been fully investigated. METHODS: Between April 2014 and June 2019, 93 patients with a diagnosis of CA, normal left ventricular ejection fraction (LVEF) and sinus rhythm were included. Their clinical, baseline echocardiographic and follow-up data were investigated. LA function, including LA strain and strain rate, was assessed using 2D speckle tracking echocardiography in different LA functional phases. RESULTS: Among all patients, 38 (40.9%) died. Multivariate Cox regression analyses showed that LA mechanics regarding LA reservoir and booster pump functions were independent predictors for overall survival. Traditional echocardiographic parameters for LA structure like LA volume index and LA width were not associated with mortality. Moreover, LA strain and strain rate in reservoir and contractile phases improved the discrimination and goodness of fit of the conventional prognostic model, the Mayo criteria 2004 and 2012, in our study population. Decreased LA mechanics were associated with impaired left ventricular (LV) systolic and diastolic function, and LA reservoir and contractile functions were associated with LA structure. CONCLUSIONS: Assessment of LA reservoir and contractile functions via 2D speckle tracking echocardiographic LA mechanical indices provide clinical and prognostic insights into cardiac light-chain amyloidosis patients, especially those with preserved EF and sinus rhythm. Emphasizing the monitoring of LA function may be beneficial for the prognosis prediction of CA.

Differentiation of Prostate Cancer and Stromal Hyperplasia in the Transition Zone With Monoexponential, Stretched-Exponential Diffusion-Weighted Imaging and Diffusion Kurtosis Imaging in a Reduced Number of b Values: Correlation With Whole-Mount Pathology.

OBJECTIVES: The aims of the study were to explore the feasibility of generating a monoexponential model (MEM), stretched-exponential model (SEM) based diffusion-weighted imaging (DWI), and diffusion kurtosis imaging (DKI) by applying the same set of reduced b values and to compare their effectiveness in distinguishing prostate cancer from stromal hyperplasia (SH) in the transition zone (TZ) area. METHODS: An analysis of 75 patients who underwent preoperative DWI ( b values of 0, 700, 1400, 2000 s/mm 2 ) was performed. All lesions were localized on magnetic resonance images according to whole-mount histopathological correlations. The apparent diffusion coefficient (ADC), water molecular diffusion heterogeneity index (α), distributed diffusion coefficient (DDC), mean diffusivity (MD), and mean kurtosis (MK) values were calculated and compared between the TZ cancer and SH groups. Receiver operating characteristic analysis and areas under the receiver operating characteristic curve (AUCs) were carried out for all parameters. RESULTS: Compared with the SH group, the ADC, DDC, α, and MD values of the TZ cancer group were significantly reduced, while the MK value was significantly increased (all P < 0.05). The AUCs of the ADC, DDC, α, MD, and MK were 0.828, 0.801, 0.813, 0.822, and 0.882, respectively. The AUC of MK was significantly higher than that of the other parameters (all P < 0.05). CONCLUSIONS: When using the reduced b -value set, all parameters from MEM, SEM, based DWI, and DKI can effectively distinguish TZ cancer from SH. Among them, DKI demonstrated potential clinical superiority over the others in TZ cancer diagnosis.

Ultrasensitive Chemodynamic Therapy: Bimetallic Peroxide Triggers High pH-Activated, Synergistic Effect/H2 O2 Self-Supply-Mediated Cascade Fenton Chemistry.

Recently, nanoparticle-triggered in situ catalytic Fenton/Fenton-like reaction is widely explored for tumor-specific chemodynamic therapy (CDT). However, despite the great potential of CDT in tumor treatment, insensitive response to the relatively high pH of the tumor sites and the insufficient intratumoral H2 O2 level leads to limited efficiency of most Fenton/Fenton-like reactions, which greatly imped its clinical conversion. This paper reports the fabrication of Fenton-type bimetallic peroxides for ultrasensitive chemodynamic therapy with high pH-activated, synergistic effect/H2 O2 self-supply-mediated cascade Fenton chemistry for the first time. The observations reveal that these bimetallic peroxides exhibit an ultrasensitive acid-activated decomposition-mediated Fenton-like reaction at the relatively high pH of 6.5-7.0, accompanied with highly increased •OH generation efficiency (especially, 40-60-fold increase at pH 7.0) by the metal-mediated synergistic effect-enhanced Fenton chemistry as well as in situ self-generated H2 O2 supplement. Moreover, the bimetallic peroxides exhibit high tumor accumulation which along with a high-efficiency tumor catalytic-therapeutic with negligible side effects in vivo. Developing these novel bimetallic peroxides, together with the already demonstrated capacity of the key metals (Fe, Mn, Cu, etc.) for magnetic resonance imaging or photodynamic/immune-enhanced therapy, will propel interest in development of smart high-efficiency nanoplatform for cancer theranostics.