A causal effect study of cortical morphology and related covariate networks in classical trigeminal neuralgia patients.

Structural covariance networks and causal effects within can provide critical information on gray matter reorganization and disease-related hierarchical changes. Based on the T1WI data of 43 classical trigeminal neuralgia patients and 45 controls, we constructed morphological similarity networks of cortical thickness, sulcal depth, fractal dimension, and gyrification index. Moreover, causal structural covariance network analyses were conducted in regions with morphological abnormalities or altered nodal properties, respectively. We found that patients showed reduced sulcal depth, gyrification index, and fractal dimension, especially in the salience network and the default mode network. Additionally, the integration of the fractal dimension and sulcal depth networks was significantly reduced, accompanied by decreased nodal efficiency of the bilateral temporal poles, and right pericalcarine cortex within the sulcal depth network. Negative causal effects existed from the left insula to the right caudal anterior cingulate cortex in the gyrification index map, also from bilateral temporal poles to right pericalcarine cortex within the sulcal depth network. Collectively, patients exhibited impaired integrity of the covariance networks in addition to the abnormal gray matter morphology in the salience network and default mode network. Furthermore, the patients may experience progressive impairment in the salience network and from the limbic system to the sensory system in network topology, respectively.

Joint effect of atrial fibrillation and obesity on mortality in critically ill patients.

BACKGROUND: The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. METHODS: Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. RESULTS: The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p < 0.001), while obesity was linked to a 13.9% reduction in mortality risk (p < 0.001). The protective effect of obesity on mortality was similar in patients with (HR = 0.85) and without AF (HR = 0.86). AF led to a slightly higher risk of mortality in patients without obesity (HR = 1.16) compared to those with obesity (HR = 1.13). Kaplan-Meier survival curves highlighted that non-obese patients with AF had the lowest survival rate, whereas the highest survival was observed in obese patients without AF. CONCLUSIONS: AF significantly increased 1-year mortality risk in critically ill patients, whereas obesity was associated with a decreased mortality risk. The most adverse survival outcomes were identified in non-obese patients with AF.

Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.

Combination of IVIM with DCE-MRI for diagnostic and prognostic evaluation of breast cancer.

PURPOSE: To identify the most effective combination of DCE-MRI (Ktrans,Kep) and IVIM (D,f) and analyze the correlations of these parameters with prognostic indicators (ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size) to improve the diagnostic and prognostic efficiency in breast cancer. METHODS: This is a prospective study. We performed T1WI, T2WI, IVIM, DCE-MRI at 3 T MRI examinations on benign and malignant breast lesions that met the inclusion criteria. We also collected pathological results of corresponding lesions, including ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size. The diagnostic efficacy of DCE-MRI, IVIM imaging, and their combination for benign and malignant breast lesions was assessed. Correlations between the DCE-MRI and IVIM parameters and prognostic indicators were assessed. RESULTS: Overall,59 female patients with 62 lesions (22 benign lesions and 40 malignant lesions) were included in this study. The malignant group showed significantly lower D values (p < 0.05) and significantly higher Ktrans, Kep, and f values (p < 0.05). The AUC values of DCE, IVIM, DCE + IVIM were 0.828, 0.882, 0.901. Ktrans, Kep, D and f values were correlated with the pathological grade (p < 0.05); Ktrans was negatively correlated with ER expression (r = -0.519, p < 0.05); Kep was correlated with PR expression and the Ki-67 index (r = -0.489, 0.330, p < 0.05); the DCE and IVIM parameters showed no significant correlations with the HER2 and ALN (p > 0.05). Tumor diameter was correlated with the Kep, D and f values (r = 0.246, -0.278, 0.293; p < 0.05). CONCLUSION: IVIM and DCE-MRI allowed differential diagnosis of benign and malignant breast lesions, and their combination showed significantly better diagnostic efficiency. DCE- and IVIM-derived parameters showed correlations with some prognostic factors for breast cancer.

Activation pattern of the coronary sinus facilitates the differentiation for ventricular outflow tract arrhythmias.

INTRODUCTION: The accuracy of surface ECG algorithms for predicting the origin of outflow tract ventricular arrhythmias (OT-VAs) might be questioned. Intracardiac electrograms recorded at anatomic landmarks could provide new predictive insights. We aim to evaluate the efficacy of a novel criterion utilizing the activation pattern of the coronary sinus (CS) in localizing OT-VAs, including VAs originating from the right ventricular outflow tract (RVOT), endocardial left ventricular outflow tract (Endo-LVOT), and epicardial left ventricular outflow tract (Epi-LVOT). METHODS: We measured the ventricular activation time of the mitral annulus (MA) from the onset of the earliest QRS complex of VAs to the initial deflection over the isoelectric line at local signals, namely the QRS-MA interval. The activation at 3 and 12 o'clock of the MA was recorded as the QRS-MA3 and QRS-MA12 intervals, respectively. Their predictive values were compared to previous ECG algorithms. RESULTS: A total of 68 patients with OT-VAs were enrolled (51 for development and 17 for validation). From early to late, the ventricular activation sequences at MA12 were as follows: Epi-LVOT, Endo-LVOT, and RVOT. In LBBB morphology OT-VAs, the QRS-MA12 interval was significantly earlier for LVOT origins than RVOT origins. In the combined cohort of development and validation cohort, a cut-off value of ≤10 ms predicted the LVOT origin with a sensitivity of 100% and specificity of 78%. The QRS-MA12 interval ≤ -24 ms additionally predicted epicardial LVOT sites of origin. CONCLUSIONS: The QRS-MA interval could accurately differentiate the OT-VAs localization.

Moderating effect of education on glymphatic function and cognitive performance in mild cognitive impairment.

Objective: This research aims to investigate putative mechanisms between glymphatic activity and cognition in mild cognitive impairment (MCI) and analyzes whether the relationship between cognitive reserve (CR) and cognition was mediated by glymphatic activity. Methods: 54 MCI patients and 31 NCs were enrolled to evaluate the bilateral diffusivity along the perivascular spaces and to acquire an index for diffusivity along the perivascular space (ALPS-index) on diffusion tensor imaging (DTI). The year of education was used as a proxy for CR. The ALPS-index was compared between two groups and correlation analyses among the ALPS-index, cognitive function, and CR were conducted. Mediation analyses were applied to investigate the correlations among CR, glymphatic activity and cognition. Results: MCI group had a significantly lower right ALPS-index and whole brain ALPS-index, but higher bilateral diffusivity along the y-axis in projection fiber area (Dyproj) than NCs. In MCI group, the left Dyproj was negatively related to cognitive test scores and CR, the whole brain ALPS-index was positively correlated with cognitive test scores and CR. Mediation analysis demonstrated that glymphatic activity partially mediated the correlations between CR and cognitive function. Conclusion: MCI exhibited decreased glymphatic activity compared to NCs. CR has a protective effect against cognitive decline in MCI, and this effect may be partially mediated by changes in glymphatic activity.

Prediction of prostate cancer aggressiveness using magnetic resonance imaging radiomics: a dual-center study.

PURPOSE: The Gleason score (GS) and positive needles are crucial aggressive indicators of prostate cancer (PCa). This study aimed to investigate the usefulness of magnetic resonance imaging (MRI) radiomics models in predicting GS and positive needles of systematic biopsy in PCa. MATERIAL AND METHODS: A total of 218 patients with pathologically proven PCa were retrospectively recruited from 2 centers. Small-field-of-view high-resolution T2-weighted imaging and post-contrast delayed sequences were selected to extract radiomics features. Then, analysis of variance and recursive feature elimination were applied to remove redundant features. Radiomics models for predicting GS and positive needles were constructed based on MRI and various classifiers, including support vector machine, linear discriminant analysis, logistic regression (LR), and LR using the least absolute shrinkage and selection operator. The models were evaluated with the area under the curve (AUC) of the receiver-operating characteristic. RESULTS: The 11 features were chosen as the primary feature subset for the GS prediction, whereas the 5 features were chosen for positive needle prediction. LR was chosen as classifier to construct the radiomics models. For GS prediction, the AUC of the radiomics models was 0.811, 0.814, and 0.717 in the training, internal validation, and external validation sets, respectively. For positive needle prediction, the AUC was 0.806, 0.811, and 0.791 in the training, internal validation, and external validation sets, respectively. CONCLUSIONS: MRI radiomics models are suitable for predicting GS and positive needles of systematic biopsy in PCa. The models can be used to identify aggressive PCa using a noninvasive, repeatable, and accurate diagnostic method.

Functional magnetic resonance imaging for staging chronic kidney disease: a systematic review and meta-analysis.

INTRODUCTION: The commonly used clinical indicators are not sensitive and comprehensive enough to evaluate the early staging of chronic kidney disease (CKD). This study aimed to evaluate the differences in arterial spin labeling (ASL) and blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-MRI) parameter values among patients at various stages of chronic kidney disease and healthy individuals. METHODS: Electronic databases PubMed, Web of Science, Cochrane, and Embase were searched from inception to March 29, 2024, to identify relevant studies on ASL and BOLD in CKD. The renal blood flow (RBF) and apparent relaxation rate (R2*) values were obtained from healthy individuals and patients with various stages of CKD. The meta-analysis was conducted using STATA version 12.0. The random-effects model was used to obtain estimates of the effects, and the results were expressed as 95% confidence intervals (CIs) and mean differences (MDs) of continuous variables. RESULTS: A total of 18 published studies were included in this meta-analysis. The cortical RBF and R2* values and medulla RBF values were considerably distinct between patients with various stages of CKD and healthy controls (MD, - 78.162; 95% CI, - 85.103 to - 71.221; MD, 2.440; 95% CI, 1.843 to 3.037; and MD, - 36.787; 95% CI, - 47.107 to - 26.468, respectively). No obvious difference in medulla R2* values was noted between patients with various stages of CKD and healthy controls (MD, - 1.475; 95% CI, - 4.646 to 1.696). CONCLUSION: ASL and BOLD may provide complementary and distinct information regarding renal function and could potentially be used together to gain a more comprehensive understanding of renal physiology.

Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus.

Background: This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements. Methods: A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (Daxon), axial extra-axonal space diffusivity (De,//), and radial extra-axonal space diffusivity (De,⊥) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized. Results: In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, De,∥, and De,⊥ in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively (P < 0.05, TFCE-corrected). De,⊥ detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, De,⊥ in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (ß = 0.433, P < 0.001) and a longer disease duration (ß = 0.438, P < 0.001). Conclusions: WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. De,⊥ could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.

Altered cortical thickness-based structural covariance networks in type 2 diabetes mellitus.

Cognitive impairment is a common complication of type 2 diabetes mellitus (T2DM), and early cognitive dysfunction may be associated with abnormal changes in the cerebral cortex. This retrospective study aimed to investigate the cortical thickness-based structural topological network changes in T2DM patients without mild cognitive impairment (MCI). Fifty-six T2DM patients and 59 healthy controls underwent neuropsychological assessments and sagittal 3-dimensional T1-weighted structural magnetic resonance imaging. Then, we combined cortical thickness-based assessments with graph theoretical analysis to explore the abnormalities in structural covariance networks in T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. T2DM patients exhibited significantly lower clustering coefficient (C) and local efficiency (Elocal) values and showed nodal property disorders in the occipital cortical, inferior temporal, and inferior frontal regions, the precuneus, and the precentral and insular gyri. Moreover, the structural topological network changes in multiple nodes were correlated with the findings of neuropsychological tests in T2DM patients. Thus, while T2DM patients without MCI showed a relatively normal global network, the local topological organization of the structural network was disordered. Moreover, the impaired ventral visual pathway may be involved in the neural mechanism of visual cognitive impairment in T2DM patients. This study enriched the characteristics of gray matter structure changes in early cognitive dysfunction in T2DM patients.

MRI Diagnosis of Coronary Artery Lesions in Children With Kawasaki Disease and Their Correlation With Inflammatory Factors.

BACKGROUND: Ultrasonography (US), as a routine examination for evaluating coronary artery lesions (CAL) in children with Kawasaki disease (KD), has strong subjectivity and limitations. Non-contrast enhanced coronary magnetic resonance angiography (NCE-CMRA) is sensitive and reliable in displaying the segments of coronary arteries (CA). PURPOSE: To evaluate the CA using NCE-CMRA, to compare NCE-CMRA with US, and to assess the correlation between KD-related inflammatory factors and the occurrence of CAL. STUDY TYPE: Retrospective. POPULATION: 61 children with KD who had undergone NCE-CMRA. Ultimately, 52 cases were included (32 males and 20 females), with an average of 5.9 ± 0.3 years old. FIELD STRENGTH/SEQUENCE: 3-T, 3D balanced turbo field echo sequence. ASSESSMENT: NCE-CMRA and US coronary visualization rates were compared in 41 children who were imaged with both techniques. Inflammatory factors were compared between CAL and normal coronary artery (NCA) subgroups. In the CAL group, correlations of these inflammatory factors with CAL parameters were investigated. STATISTICAL TESTS: Comparison between groups was performed by the two independent samples t-test; the comparison of enumeration data between groups was performed by chi-square test. Receiver operating characteristic (ROC) curve analysis was performed to determine the sensitivity of inflammatory factors for detecting CAL. The correlation between CAL and inflammatory indexes was analyzed by multiple linear regression. A P value <0.05 was considered statistically significant. RESULTS: NCE-CMRA visualized significantly more segments than US (76% vs. 46%). There were significant differences in PLT, CRP, ESR, and D-dimer between the CAL and NCA groups. ROC curve analysis showed that the sensitivities of these four indicators in diagnosing CAL were 39%, 44%, 72%, and 61%, respectively, at cut-off points of 562.5 × 109 /L, 48.93 mg/L, 45.5 mm/h, and 0.5 mg/L, respectively. DATA CONCLUSION: The combination of NCE-CMRA and inflammatory factors is helpful for the early diagnosis and disease severity of CAL in children with KD. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

A comparison of the performance of 68Ga-Pentixafor PET/CT versus adrenal vein sampling for subtype diagnosis in primary aldosteronism.

Objective: To investigate the diagnostic efficiency and prognostic value of 68Ga-Pentixafor PET/CT in comparison with adrenal vein sampling (AVS) for functional lateralization in primary aldosteronism (PA). Histology and long-term clinical follow-up normally serve as the gold standard for such diagnosis. Methods: We prospectively recruited 26 patients diagnosed with PA. All patients underwent 68Ga-Pentixafor PET/CT and AVS. Postsurgical biochemical and clinical outcomes of patients with unilateral primary aldosteronism (UPA), as diagnosed by PET/CT or AVS, were assessed by applying standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Immunohistochemistry (IHC) was performed to detect the expression of aldosterone synthase (CYP11B2) and CXCR4. Results: On total, 19 patients were diagnosed with UPA; of these, 13 patients were lateralized by both PET/CT and AVS, four patients were lateralized by PET-only, and two by AVS-only. Seven subjects with no lateralization on AVS and PET received medical therapy. All patients achieved complete biochemical success except one with nodular hyperplasia lateralized by AVS alone. The consistency between PET/CT and AVS outcomes was 77% (20/26). Moreover, CYP11B2-positive nodules were all CXCR4-positive and showed positive findings on PET. Patients who achieved complete biochemical and clinical success had a higher uptake on PET as well as stronger expression levels of CXCR4 and CYP11B2. Conclusion: Our analysis showed that 68Ga-Pentixafor PET/CT could enable non-invasive diagnosis in most patients with PA and identify additional cases of unilateral and surgically curable PA which could not be classified by AVS. 68Ga-Pentixafor PET/CT should be considered as a first-line test for the future classification of PA.

Gross Hematuria Does not Affect the Selection of Nephrectomy Types for Clinical Stage 1 Clear Cell Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study.

PURPOSE: This study aimed to discuss the correlation between gross hematuria and postoperative upstaging (from T1 to T3a) in patients with cT1 clear cell renal cell carcinoma (ccRCC) and to compare oncologic outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) in patients with gross hematuria. METHODS: A total of 2145 patients who met the criteria were enrolled in the study (including 363 patients with gross hematuria). The least absolute selection and shrinkage operator logistic regression was used to evaluate the risk factor of postoperative pathological upstaging. The propensity score matching (PSM) and stable inverse probability of treatment weighting (IPTW) analysis were used to balance the confounding factors. The Kaplan-Meier analysis and multivariate Cox proportional risk regression model were used to assess the prognosis. RESULTS: Gross hematuria was a risk factor of postoperative pathological upstaging (odds ratio [OR] = 3.96; 95% confidence interval [CI] 2.44-6.42; P < 0.001). After PSM and stable IPTW adjustment, the characteristics were similar in corresponding patients in the PN and RN groups. In the PSM cohort, PN did not have a statistically significant impact on recurrence-free survival (hazard ratio [HR] = 1.48; 95% CI 0.25-8.88; P = 0.67), metastasis-free survival (HR = 1.24; 95% CI 0.33-4.66; P = 0.75), and overall survival (HR = 1.46; 95% CI 0.31-6.73; P = 0.63) compared with RN. The results were confirmed in sensitivity analyses. CONCLUSIONS: Although gross hematuria was associated with postoperative pathological upstaging in patients with cT1 ccRCC, PN should still be the preferred treatment for such patients.

Optimal timing of GnRH antagonist initiation in IVF-ET: a retrospective cohort study on advanced maternal age women.

Background: Several studies have compared the effects of fixed and flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization and embryo transfer (IVF-ET). However, which GnRH-ant initiation strategy is better remains controversial. Moreover, no studies have assessed the optimal timing of GnRH-ant initiation in women of advanced maternal age (AMA). Methods: In this retrospective cohort study, a total of 472 infertile women aged ≥ 35 years old undergoing their first IVF cycle from August 2015 to September 2021 at a tertiary academic medical center were recruited, of whom 136 followed fixed GnRH-ant protocol and 336 followed flexible GnRH-ant protocol. The primary outcomes measured were the cumulative live birth rate (CLBR) per IVF cycle and the time to live birth (TTLB) from the date of oocyte retrieval. Cox proportional models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of CLBR regarding GnRH-ant timing. Results: No significant difference in CLBR was found between the fixed and flexible GnRH-ant groups (27.9% vs 20.5%, p=0.105). The TTLB was also comparable between groups (10.56 vs 10.30 months, p=0.782). The Kaplan-Meier analysis for CLBR also showed comparable results between groups (P=0.351, HR=0.83; 95%CI: 0.56-1.23). After establishing a multiple Cox proportional hazard model, the fixed GnRH-ant group still had comparable CLBR with the flexible GnRH-ant group (HR=0.85; 95%CI: 0.53-1.38; P=0.518). Subgroup and sensitivity analyses also demonstrated similar results. Conclusion: GnRH-ant protocols can be tailored to the needs of AMA women, and timing of GnRH-ant initiation can be adjusted flexibly.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer.

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.

Patients with high nuclear grade pT1-ccRCC are more suitable for radical nephrectomy than partial nephrectomy: a multicenter retrospective study using propensity score.

BACKGROUND: Partial nephrectomy (PN) is usually recommended for T1 stage clear cell renal cell carcinoma (ccRCC) regardless of the nuclear grades. However, the question remains unresolved as to whether PN is non-inferior to RN in patients with T1-ccRCC at higher risk of recurrence. In fact, we found that patients with high nuclear grades treated with PN had poorer prognosis compared with those treated with radical nephrectomy (RN). Therefore, this study was designed to evaluate the associations of PN and RN in the four nuclear grade subsets with oncologic outcomes. METHODS: A retrospective study was conducted in three Chinese urological centers that included 1,714 patients who underwent PN or RN for sporadic, unilateral, pT1, N0, and M0 ccRCC without positive surgical margins and neoadjuvant therapy between 2010 and 2019. Associations of nephrectomy type with local ipsilateral recurrence, distant metastases, and all-cause mortality (ACM) were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazards regression models after overlap weighting (OW). RESULTS: A total of 1675 patients entered the OW cohort. After OW, in comparison to PN, RN associated with a reduced risk of local ipsilateral recurrence in the G2 subset (HR = 0.148, 95% CI 0.046-0.474; p < 0.05), G3 subset (HR = 0.097, 95% CI 0.021-0.455; p < 0.05), and G4 subset (HR = 0.091, 95% CI 0.011-0.736; p < 0.05), and resulting in increased five-year local recurrence-free survival rates of 7.0%, 17.9%, and 36.2%, respectively. An association between RN and a reduced risk of distant metastases in the G4 subset (HR = 0.071, 95% CI 0.016-0.325; p < 0.05), with the five-year distant metastases-free survival rate increasing by 33.1% was also observed. No significant difference in ACM between PN and RN was identified. CONCLUSIONS: Our findings substantiate that opting for RN, as opposed to PN, is more advantageous for local recurrence-free survival and distant metastases-free survival in patients with high nuclear grade (especially G4) pT1-ccRCC. We recommend placing a heightened emphasis on enhancing preoperative nuclear grade assessment, as it can significantly influence the choice of surgical plan. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ID: ChiCTR2200063333).

Prognostic significance of quantitative electrocardiographic parameters in patients with non-high-risk pulmonary embolism.

BACKGROUND: Electrocardiogram (ECG) abnormalities indicating right ventricular strain have been reported to have prognostic value in severe cases of acute pulmonary embolism (PE). We aimed to analyze the prognostic significance of other quantitative ECG parameters in non-high-risk acute PE. METHODS: Consecutive patients with non-high-risk acute PE were prospectively enrolled. The following baseline ECG parameters were collected: rhythm, heart rate, QRS axis, right bundle branch block (RBBB) pattern, S1Q3T3 pattern, T-wave inversion, ST-segment elevation, Qr in lead V1, PR Interval, QRS complex duration, QT interval, P-wave amplitude and duration, R- and S-wave amplitudes. The primary endpoint was early discharge within three days. Associations between ECG parameters and early discharge were analyzed. RESULTS: Overall, 383 patients were enrolled (median age: 67 years, 57% female): 277 (72.3%) with low-risk and 106 (27.7%) with intermediate-risk. The two groups of patients differed in several ECG signs of right ventricular strain and many other quantitative parameters like R- and S-wave amplitudes. In the multivariate logistic regression analysis, the S-wave depth in lead V5 (S-V5) was the only independent prognostic factor for early discharge (odds ratio = 0.137, 95% confidence interval = 0.031-0.613, p = 0.009). The optimum cutoff value of S-V5 for predicting early discharge derived from the receiver operative characteristic curve was 0.15 mv (c-statistic = 0.66, p =0.003). CONCLUSIONS: Several ECG signs of right ventricular strain and many other quantitative parameters were associated with disease severity in non-high-risk acute PE. An S-V5 lesser than 0.15 mv was predictive for early discharge in these patients.

SGLT2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis.

AIMS: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to July 1, 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases, or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. RESULTS: Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favorable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over one year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95%CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and chronic kidney diseases. CONCLUSION: For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.

The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population. Further research is warranted to investigate the potential benefit of SGLT2 inhibitors in AF.

Structural and functional connectivity alteration patterns of the cingulate gyrus in Type 2 diabetes.

OBJECTIVE: We aimed to reveal the role of structural and functional alterations of cingulate gyrus in early cognitive impairment in Type 2 diabetes mellitus (T2DM) patients. METHODS: Fifty-six T2DM patients and 60 healthy controls (HCs) underwent a neuropsychological assessment and sagittal three-dimensional T1-weighted and resting-state functional MRI. Differences in the cortical thickness of the cingulate cortex and the functional connectivity (FC) of the nine subregions of the cingulate gyrus and the whole brain were compared between T2DM patients and HCs. Correlation analysis was performed between cortex thickness and FC and the participants' clinical/cognitive variables. RESULTS: The cortical thickness of the cingulate gyrus was not significantly different between T2DM patients and HCs. However, the T2DM patients showed significantly lower FC between the pregenual ACC (pACC) and the bilateral hippocampus, significantly higher FC between the pACC and bilateral lateral prefrontal cortex (LPFC) and left precentral gyrus, and significantly lower FC between the retrosplenial cortex (RSC) and right cerebellar Crus I. The FC between the pACC and the left hippocampus was negatively correlated with the FC between the pACC and LPFC (r = -0.306, p = 0.022). INTERPRETATION: The pACC and the RSC show dysfunctional connectivity before the appearance of structural abnormalities in T2DM patients. Abnormal FC of the pACC with the bilateral hippocampus and LPFC may imply a neural compensatory mechanism for memory function. These findings provide valuable information and new directions for possible interventions for the T2DM-related cognitive impairment.