Search

IntroductionAcute kidney injury (AKI) is notably prevalent after cardiac surgery for patients with active infective endocarditis. This study aims to create a machine learning model to predict AKI in this high-risk group, improving upon existing models by focusing specifically on endocarditis-related surgeries.MethodsWe analyzed medical records from 527 patients who underwent cardiac surgery for active infective endocarditis from January 2012 to December 2023. Feature selection was performed using LASSO regression. These features informed the development of machine learning models, including logistic regression, linear and radial basis function support vector machines, XGBoost, decision trees, and random forests. The optimal model was selected based on ROC curve AUC. Model performance was assessed through discrimination, calibration, and clinical utility, with explanations provided by SHAP values.ResultsPost-surgical AKI was observed in 261 patients (49.53%). LASSO regression identified 25 significant features for the models. Among the six algorithms tested, the radial basis function support vector machine (RBF-SVM) had the highest AUC at 0.771. The 15 most critical features were valve replacement, pre-operative hypertension, large vegetations, NYHA class, alcoholism, age, post-operative low cardiac output syndrome, TyG index, pre-operative creatinine clearance, cardiopulmonary bypass duration, intra-operative red blood cell transfusion, intra-operative urine output, pre-operative hemoglobin levels, and timing of surgery.ConclusionCompared to standard cardiac surgery, AKI occurs more frequently and with a more complex etiology in surgeries for active infective endocarditis. Machine learning models enable early prediction of post-surgical AKI, facilitating targeted perioperative optimization and risk stratification in this distinct patient group.

Tobacco continuous cropping is prevalent in intensive tobacco agriculture but often leads to microbial community imbalance, soil nutrient deficiency, and decreased crop productivity. While the tobacco-rape rotation has demonstrated significant benefits in increasing tobacco yield. Microorganisms play a crucial role in soil nutrient cycling and crop productivity. However, the internal mechanism of tobacco-rape rotation affecting tobacco yield through microbe-soil interaction is still unclear. In this study, two treatments, tobacco continuous cropping (TC) and tobacco-rape rotation (TR) were used to investigate how planting systems affect soil microbial diversity and community structure, and whether these changes subsequently affect crop yields. The results showed that compared with TC, TR significantly increased the Shannon index, Chao1 index, ACE index of bacteria and fungi, indicating increased microbial α-diversity. On the one hand, TR may directly affect the bacterial and fungal community structure due to the specificity of root morphology and root exudates in rape. Compared with TC, TR significantly increased the proportion of beneficial bacterial and fungal taxa while significantly reduced soil-borne pathogens. Additionally, TR enhanced the scale and complexity of microbial co-occurrence networks, promoting potential synergies between bacterial OTUs. On the other hand, TR indirectly changed microbial community composition by improving soil chemical properties and changing microbial life history strategies. Compared with TC, TR significantly increased the relative abundance of copiotrophs while reduced oligotrophs. Notably, TR significantly increased tobacco yield by 39.6% compared with TC. The relationships among yield, microbial community and soil chemical properties indicated that planting systems had the greatest total effect on tobacco yield, and the microbial community, particularly bacteria, had the greatest direct effect on tobacco yield. Our findings highlighted the potential of tobacco-rape rotation to increase yield by both directly and indirectly optimizing microbial community structure.

ObjectiveThe occurrence of acute kidney injury (AKI) is common following cardiac surgery, especially among patients characterized with systemic lupus erythematosus (SLE), but studies on this clinical scenario have been limited by the rarity of SLE. We aimed to explore the risk predictors and outcomes with regards to postoperative AKI among cardiac-surgical patients concomitant with SLE.MethodsThis was a single-center retrospective study performed in a tertiary hospital. Adult patients diagnosed with SLE who underwent cardiac surgery within the last 22 years were enrolled. Essential variables, including patient-, surgery- and anesthesia-related information, were collected from the medical record system. The definition of AKI was derived from the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Risk predictors suspected to be linked with post-surgical AKI were calculated using the univariable and multivariable analyses.ResultsOf all 59 SLE patients undergoing cardiac surgery, 57 were ultimately enrolled into the analysis. AKI occurred in 29 patients (50.9%), who had significantly longer extubation time (median difference 1.0 day, P

IntroductionLeft atrial dissection is a rare event, typically associated with cardiac manipulation. We report the first case of a left atrial dissection caused by parasitic infectious endocarditis, which required the use of patch repair for the damaged mitral annulus and valve.Case PresentationTo treat heart failure in a 43-year-old man with left atrial dissection, we performed a patch repair of the mitral annulus and valve using autologous pericardium.ConclusionWe encourage novel surgery for complicated infectious endocarditis.

ObjectivePatients with connective tissue disease have a poor prognosis after receiving cardiac surgery. This study described the clinical scenarios and investigated factors correlated with acute kidney injury (AKI) after on-pump cardiac surgery in patients with systemic lupus erythematosus (SLE) or vasculitis.MethodsPatients with SLE or vasculitis who underwent on-pump cardiac surgery from March 2002 to March 2022 were enrolled, while patients with preoperative renal dysfunction were excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Uni- and multivariable analyses were performed to identify potential factors associated with postoperative AKI.ResultsAmong 123 patients enrolled, 39 (31.7%) developed AKI within seven days after receiving on-pump cardiac surgery. Four patients died in the hospital, resulting in an overall in-hospital mortality of 3.3%, and all deaths occurred in the AKI group. Patients in the AKI group also had longer ICU stays (median difference 3.0 day, 95% CI: 1.0–4.0, P

Fertilizer-based biofortification is a strategy for combating worldwide malnutrition of zinc (Zn), iron (Fe) and selenium (Se). Field experiments were conducted to investigate the effects of foliar treatments on concentrations of Zn, Fe, Se, N and bioavailability of Zn and Fe in grains of three maize cultivars grown at three locations. We compared the efficacy of ZnO nanoparticles (ZnO-NPs), Zn complexed chitosan nanoparticles (Zn-CNPs), conventional ZnSO4 and a cocktail solution (containing Zn, Fe and Se). All treatments were foliar-applied at rate of 452 mg Zn L–1, plus urea. Applying ten-fold less Zn (at rate of 45.2 mg Zn L–1) plus urea in the form of ZnO-NPs, Zn-CNPs, or ZnSO4 resulted in no increase, or a negligible increase, in grain Zn concentration compared with deionized water. By contrast, among the different Zn sources plus urea applied by foliar sprays, conventional ZnSO4 was the most efficient in improving grain Zn concentration. Furthermore, foliar application of a cocktail solution effectively improved grain concentrations of Zn, Fe, Se and N simultaneously, without a grain yield trade-off. For example, the average grain concentrations were simultaneously increased from 13.8 to 22.1 mg kg–1 for Zn, from 17.2 to 22.1 mg kg–1for Fe, from 21.4 to 413.5 ug kg–1 for Se and from 13.8 to 14.7 g kg–1 for N by foliar application of a cocktail solution. Because grain yield was significantly negatively correlated with grain nutrient concentrations, the magnitude of increase in grain concentrations of Zn and Fe was most pronounced in the maize cultivar with the lowest grain yield (Zhengdan958 grown in Linyi). Foliar application of a cocktail solution also significantly decreased the phytic acid (PA) concentration, ratios of PA/Fe and PA/Zn in grains, indicating an increased bioavailability of Fe and Zn for human health. In conclusion, we found that a foliar application of a cocktail solution including Zn, Fe, Se and N was most effective for biofortification, but that the grains with the lowest yield contained the greatest concentration of these elements. This finding highlights the need to breed maize varieties that are capable of achieving both high grain yield and high grain nutritional quality to address food security and human health challenges.

Bone cement embolism is a known complication after a kyphoplasty operation. Cement embolisms without immediate fatal complication such as cardiac perforation or hypoxemia were often stable during observation. We report a case of a large volume bone cement embolism involving the right ventricle and the pulmonary artery system. The patient developed mild exertional shortness of breath and chest pain after a percutaneous kyphoplasty (PKP) operation 10 years ago. However, her mild symptoms were attributed to multiple myeloma, and no chest imaging was taken until the symptoms exacerbated after a COVID-19 infection 6 months ago. A large, tree-branch-shaped embolus was found, causing severe obstruction of the ascending and middle-lobe branch of the right pulmonary artery. The pulmonary perfusion scintigraphy demonstrated an impaired perfusion of the right upper and middle lobe. An open-heart removal was performed, and the symptoms were relieved afterward. We report this case to highlight the importance of routine chest imaging after a PKP operation and to claim that open-heart removal for chronic cement pulmonary embolism is technically feasible and safe.

BackgroundFor metastatic prostate cancer (mPCa), radical prostatectomy (RP) and radiation therapy (RT) may improve overall survival (OS) and cancer-specific survival (CSS). Compared with RT, RP shows significant advantages in improving patient outcomes. External beam radiation therapy (EBRT) even slightly elevates CSM with no statistical difference in OS compared with no local treatment (NLT).ObjectiveTo evaluate OS and CSS after local treatment (LT) (including RP and RT) versus NLT in mPCa.Design, setting, and participantsWithin the Surveillance, Epidemiology and End Results (SEER) database (2000-2018), 20098 patients with metastatic prostate cancer were selected in this study, of which 19433 patients had no local treatment, 377 patients with radical prostate treatment, and 288 patients with RT.Outcome measurements and statistical analysisMultivariable competing risks regression analysis after propensity score matching (PSM) was used to calculate CSM. Multivariable Cox regression analysis was used to identify the risk factors. Kaplan-Meier methods were used to calculate OS.Results and limitationsA total of 20098 patients were included: NLT (n = 19433), RP (n=377) and RT (n=288). In a competing risk regression analysis after PSM (ratio 1:1), RP resulted in a significantly lower CSM (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.29-0.45) than NLT, while RT showed a slightly lower CSM (HR 0.77, 95% CI 0.63-0.95). In a competing risk regression analysis after PSM (ratio 1:1), RP led to a lower CSM (HR 0.56, 95% CI 0.41-0.76) versus RT. As for all-cause mortality (ACM), RP (HR 0.37, 95% CI 0.31-0.45) and RT (HR 0.66, 95% CI 0.56-0.79). also showed a downward trend. In terms of OS, RP and RT significantly improved the survival probability compared with NLT, with the effect of RP being more pronounced. Obviously, older age, Gleason scores ≥8, AJCC T3-T4 stage, AJCC N1, AJCC M1b-M1c were all associated with higher CSM (P

ObjectiveThe Chinese version of 15-item negative symptom assessment (NSA-15) is an instrument with a three-factor structure specifically validated for assessing negative symptoms of schizophrenia. To provide a reference for future practical applications in the recognition of schizophrenia patients with negative symptoms, this study aimed to determine an appropriate NSA-15 cutoff score regarding negative symptoms to identify prominent negative symptoms (PNS).MethodsA total of 199 participants with schizophrenia were recruited and divided into the PNS group (n = 79) and non-PNS group (n = 120) according to scale for assessment of negative symptoms (SANS) scores. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal NSA-15 cutoff score for identifying PNS.ResultsThe optimal cutoff NSA-15 score for identifying PNS was 40. Communication, emotion and motivation factors in the NSA-15 had cutoffs of 13, 6, and 16, respectively. The communication factor score had slightly better discrimination than scores on the other two factors. The discriminant ability of the global rating of the NSA-15 was not as good as that of the NSA-15 total score (area under the curve (AUC): 0.873 vs. 0.944).ConclusionThe optimal NSA-15 cutoff scores for identifying PNS in schizophrenia were determined in this study. The NSA-15 provides a convenient and easy-to-use assessment for identifying patients with PNS in Chinese clinical situations. The communication factor of the NSA-15 also has excellent discrimination.

Background and objectivesAutoimmune hepatitis (AIH) is characterized by the expansion and accumulation of pathogenic T cells in liver. Although CD6 and its ligand activated leukocyte cell adhesion molecule (ALCAM) are involved in the evolution of multiple inflammatory diseases, their roles in the pathogenesis of AIH remain unknown. Herein, we aimed to investigate ALCAM-CD6 axis in AIH development.MethodsImmunohistochemistry was performed to examine hepatic expression of CD6 and ALCAM. The concentration of serum ALCAM was evaluated by ELISA. The phenotypes of liver infiltrating T cells were determined by flow cytometry. Primary human CD4+ T cells were used for functional studies.ResultsOur data showed that patients with AIH exhibited significantly higher expression of CD6 in the liver as compared to primary biliary cholangitis (PBC), chronic hepatitis B (CHB), non-alcoholic liver disease (NAFLD), and healthy controls (HC). In addition, hepatic CD6 expression was strongly correlated with disease severity of AIH. CD6 was mainly expressed on CD4+ T cells in the liver and intrahepatic CD6highCD4+ T cells demonstrated stronger proinflammatory response and proliferation features than CD6low counterparts in both AIH and HC. ALCAM, the ligand of CD6, was highly expressed in the hepatocytes of AIH and serum ALCAM was strongly associated with clinical indices of AIH. Interestingly, close spatial location between CD6+CD4+ T cells and ALCAM+ hepatocytes was observed. Finally, we found that CD6highCD4+ T cells showed enhanced capacity of trans-endothelial migration in vitro, which could be promoted by recombinant ALCAM.ConclusionsOur study found that ALCAM-CD6 axis was upregulated in the AIH liver, suggesting a potential target for alleviating AIH.

The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophils in sinonasal tissues were assessed via immunofluorescence staining. The 95th percentile of tissue neutrophil numbers in control subjects was selected as a cut-off to define neutrophil-high (Neu-high) or neutrophil-low (Neu-low) nasal polyps (NPs). The levels of 34 inflammatory mediators in sinonasal tissues were analyzed using Bio-Plex assay. Purified human peripheral blood neutrophils were incubated with nasal tissue homogenates, and the apoptotic neutrophils were assessed via flow cytometry. The cut-off for Neu-high NPs was >10 myeloperoxidase positive cells/high-power field. Compared with Neu-low NPs, Neu-high NPs had higher tissue levels of IL-1β, IL-1Ra, IL-6, IL-8, G-CSF, MCP-1, and MIP-1α, but lower levels of IL-5, IL-13, IgE, and eosinophils. Principal component and multiple correspondence analyses revealed mixed type 1, type 2, and type 3 endotypes for Neu-low NPs, and predominant type 1 and type 3 endotypes for Neu-high NPs. Neu-high NPs had lower percentages of apoptotic neutrophils than Neu-low NPs. The numbers of neutrophils and the percentages of apoptotic neutrophils correlated with G-CSF and IL-6 levels in the NPs. Tissue homogenates from Neu-high NPs, but not those from Neu-low NPs, suppressed neutrophil apoptosis in vitro, which was reversed by anti-G-CSF treatment. Tissue neutrophil numbers were associated with difficult-to-treat disease in patients with CRSwNP after surgery. We propose that G-CSF promotes neutrophilic inflammation by inhibiting neutrophil apoptosis in CRSwNP. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma is one of the most common tumors in the urinary system, among which clear cell renal cell carcinoma is the most common subtype with poor prognosis. As one of the tumors closely related to lipid metabolism, the role of fatty acid metabolism in ccRCC was investigated to predict the prognosis and guide treatment strategies. RNA-seq and clinical information of patients with ccRCC and expression microarray of human renal cell carcinoma cell lines were obtained from TCGA and GEO databases. Fatty acid metabolism–related risk signature was established by the univariate Cox regression and LASSO analysis to predict patient prognosis and response to different treatment modalities. Using the fatty acid metabolism risk signature, the risk score for each sample in the TCGA cohort was calculated and divided into high-risk and low-risk groups, with the cutoff point being the median. Patients with higher risk scores had a poorer prognosis than those with lower risk scores. The response of each sample to immunotherapy was predicted from the “TIDE” algorithm, while the sensitivity of each sample to sunitinib was obtained using the “pRRophetic” R package. Patients with lower risk scores had higher expression of PD-L1 and better efficacy for sunitinib than those in the high-risk group and were less likely to develop drug resistance, while patients with high-risk scores had a strong response to the anti-CTLA4 antibody therapy. A nomogram was constructed by independent prognostic factors to predict the 1-, 3-, and 5-year survival. According to the calibration curves, the nomogram had an excellent ability to predict survival for patients with ccRCC. Therefore, the fatty acid metabolism risk signature we established can not only predict the survival of patients with ccRCC but also predict patient response to targeted therapy and immunotherapy to provide optimal treatment strategies for patients.

Introduction: Fever of unknown origin (FUO) and hemodynamic instability are complications that develop after cardiac surgery combined with cardiopulmonary bypass (CPB) for heart disease. Patients who develop fever with hemodynamic instability after cardiac surgery may have systemic inflammatory response syndrome or sepsis. Cardiopulmonary bypass (CPB) is a technique that temporarily takes over the function of the heart and lungs during cardiac surgery. Recent reports suggest that early bloodstream infections of patients undergoing CPB are due to gram-negative bacteria that are present in the intestinal flora. The theory of intestinal flora translocation has growing evidence. Intestinal ischemia-reperfusion that occurs during cardiac surgery with CPB will induce a systemic inflammatory reaction and may cause intestinal flora translocation. Does this systemic reaction cause sepsis? We therefore propose this protocol to determine whether the changes in the intestinal flora in patients after cardiac surgery with CPB are related to sepsis.Methods and Analysis: This study is a prospective observational case–control study to analyze the variation in the intestinal microflora and metabolites in patients undergoing cardiac surgery with CPB and to observe the outcomes of patients with routine clinical interventions. The control group will include healthy people without intestinal illness. Feces and blood samples will be acquired 1 day before cardiac surgery and within 24–72 h after cardiac surgery, and will be used for genomics and metabolomics analyses. Demographic data describing age, sex, main diagnosis, and past medical history and data related to the CPB time and application of antibiotics are available. Sequential (sepsis-related) organ failure assessment, infection-related laboratory items, infection site, and pathogenic microorganisms, and nutrition, and gastrointestinal function assessment are additionally recorded. Group analysis of data will be conducted according to the outcomes (sepsis vs. non-sepsis and survivors vs. non-survivors).Ethics and Dissemination: This protocol has been ethically approved by the Ethics Committee of Peking Union Medical College (ID: ZS-1612). Informed consent will be obtained before subject enrolment, and data will be stored in a secured database. The results will be submitted to international peer-reviewed journals and presented at international conferences.Trial Registration Number: NCT04032938.

Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride. Functional alterations of circulating MAIT cells were also detected in NAFLD patients, such as the increased production of IL-4 whereas the decreased production of IFN-γ and TNF-α. Furthermore, elevated expression of CXCR6 was observed in circulating MAIT cells of patients. Meanwhile, we found an increased number of MAIT cells in the livers of NAFLD, and the number was even greater in patients with higher NAFLD activity score. Moreover, activated MAIT cells induced monocytes/macrophages differentiation into M2 phenotype in vitro. Additionally, MAIT cells were enriched and displayed Th2 type cytokines profile in livers of wild type mice fed with methionine and choline deficient diet (MCD). Notably, mice deficient of MAIT cells exhibited more severe hepatic steatosis and inflammation upon MCD, accompanied with more CD11c+ proinflammatory macrophages (M1) and less CD206+ anti-inflammatory macrophages (M2) in livers. Our results indicate that MAIT cells protect against inflammation in NAFLD through producing regulatory cytokines and inducing anti-inflammatory macrophage polarization, which may provide novel therapeutic strategies for NAFLD.

CXC chemokine receptor 3 (CXCR3), a receptor for the C-X-C motif chemokines (CXCL) CXCL9, CXCL10, and CXCL11, which not only plays a role in chemotaxis but also regulates differentiation and development of memory and effector T cell populations. Herein, we explored the function of CXCR3 in the modulation of different organ-specific autoimmune diseases in interleukin (IL)-2 receptor deficiency (CD25−/−) mice, a murine model for both cholangitis and colitis. We observed higher levels of CXCL9 and CXCL10 in the liver and colon and higher expression of CXCR3 on T cells of the CD25−/− mice compared with control animals. Deletion of CXCR3 resulted in enhanced liver inflammation but alleviated colitis. These changes in liver and colon pathology after CXCR3 deletion were associated with increased numbers of hepatic CD4+ and CD8+ T cells, in particular effector memory CD8+ T cells, as well as decreased T cells in mesenteric lymph nodes and colon lamina propria. In addition, increased interferon-γ response and decreased IL-17A response was observed in both liver and colon after CXCR3 deletion. CXCR3 modulated the functions of T cells involved in different autoimmune diseases, whereas the consequence of such modulation was organ-specific regarding to their effects on disease severity. Our findings emphasize the importance of extra caution in immunotherapy for organ-specific autoimmune diseases, as therapeutic interventions aiming at a target such as CXCR3 for certain disease could result in adverse effects in an unrelated organ.

Background and aims: Tetraspanin proteins are closely related to the functional changes of B cells, including antigen presentation, production of cytokines, and transduction. We aim to explore the potential role of Tetraspanin 1 (TSPAN1) in the biological activities of B cells in AIH. Methods and results: Herein, this study found that numbers of cells expressing TSPAN1 were significantly increased in AIH patients compared to PBC, chronic hepatitis B, and healthy control (P < 0.0001). Moreover, there was a positive correlation between numbers of TSPAN1+ cells and AIH disease severity (P < 0.0001). Immunofluorescence staining further confirmed that TSPAN1 was primarily expressed on CD19+ B cells. Flow-cytometric analysis showed that TSPAN1+ B cells secreted more inflammatory cytokines and expressed higher level of CD86 than TSPAN1- B cells. Furthermore, compared with TSAPN1- cells, the expression of CXCR3 on TSPAN1+ cells was also higher. Meanwhile, CXCL10, the ligand of CXCR3, was significantly elevated in the liver of AIH (P < 0.01) and had positive correlation with the quantities of TSPAN1 (P < 0.05). Interestingly, the numbers of TSPAN1+ B cells were decreased in AIH patients after immunosuppressive therapy. Conclusions: TSPAN1+ B cells in the liver may promote the progression of AIH via secreting cytokines and presenting antigens. The chemotactic movement of TSPAN1+ B cells toward the liver of AIH was possibly due to CXCR3 - CXCL10 interaction. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application. Method: According to the FDA's Adverse Event Reporting System (FAERS), from January 2004 to September 2021, we chose "Osteonecrosis of the jaw (10064658)" and "Exposed bone in jaw (10071014)" as preferred terms, "antiresorptive drugs" as the target drugs, and primary suspect drug as the drug role code in the dataset. We evaluated the association between drugs and adverse events by using reporting odds ratio (ROR) based on disproportionality analysis. We took the High-Level Terms (HLT) of MedDRA® as the classification level of indications to calculate ROR to compare the signal difference of ONJ in different indications. In addition, patients with antiresorptive-induced osteonecrosis of the jaw and the time of onset of the condition following different antiresorptive medications were collected for the study. Results: The FAERS contained 18,421 reports relating to jaw osteonecrosis from January 2004 to September 2021. A total of eight antiresorptive agents were included in the analysis. From high to low, the ROR of ONJ induced by antiresorptive agents (regardless of indication) is pamidronate (ROR = 494.8), zoledronic acid (ROR = 431.9), denosumab (ROR = 194.8), alendronate (ROR = 151.2), risedronate (ROR = 140.2), etidronic acid (ROR = 64.5), ibandronate (ROR = 40.8), and romosozumab (ROR = 6.4). HLT ROR values for "metabolic bone disorders" were the lowest for each drug, while HLT ROR values were high for "tumor-related indications," including breast and nipple neoplasms malignant, plasma cell myelomas, and prostatic neoplasms malignant. The onset time for osteonecrosis of the jaw as median (Q1, Q3), osteoporosis-related indications, and the onset time for ONJ were 730 (368, 1268), 489.5 (236.3, 909.8), 722.5 (314, 1055), 761 (368, 1720), and 153 (50, 346) for zoledronic acid, denosumab, ibandronate, risedronate, and romosozumab, respectively. Cancer-related indications: the onset time for ONJ were 680.5 (255.3, 1283), 488 (245, 851), and 696.5 (347, 1087) for zoledronic acid, denosumab, and pamidronate, respectively. Conclusion: When antiresorptive drugs are used for metastasis, they have the largest risk signal, followed by malignancy, and the smallest is osteoporosis. The onset time of ONJ may not be related to the indications. The onset time of ONJ for BPs was about 2 years, denosumab about 1.3 years, and romosozumab less than 1 year, which may be related to sequential treatment. When used according to the instructions, the risk of ONJ caused by denosumab was higher than that of zoledronic acid, regardless of the indication. Based on these findings, researchers will continue to monitor and identify risk factors. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about the detailed spectrum of the cause of death associated with prostate cancer (PCa). This study systematically characterized the cause of death among patients with PCa. Methods: Patients aged 40 years and older with primary PCa were identified from the Surveillance, Epidemiology, and End Results program. Mortality rates were estimated. Standardized mortality ratios (SMRs) of non-cancer deaths were calculated to evaluate the risk of death and to compare with the cancer-free population. Results: This study included 1,170,489 patients with PCa. There were 501,262 deaths, of which27.4%were due toPCa and57.0%were due tonon-cancer causes. Non-cancer deaths increased over time from 1975 to 2016, and index cancer death decreased continually. The risk of non-cancer deathswas 1.45 times (SMR, 1.45;95%confidence interval [CI], 1.45-1.46) that of the general population. Cardiovascular diseasewas the most common non-cancer cause of death, accounting for 30.2% of all deaths among PCa patients. Alzheimer's disease (SMR, 3.92; 95% CI, 3.85-4.00) had the highest risk of death. The mortality rate and SMR of noncancer deaths increased with increased follow-up after diagnosis. Conclusion: Instead of the index cancer, non-cancer comorbidities were the leading cause of death among patients with PCa, and the risk of non-cancer deaths was much higher than among the general population. Clinicians and researchers should be aware of this trend to conduct timely and targeted interventions. [ABSTRACT FROM AUTHOR]

Objective: To quantitatively evaluate the impaired perfusion status of patients with symptomatic internal carotid artery (ICA) steno-occlusive disease and to explore the risk factors of impaired perfusion with computed tomography perfusion (CTP). Methods: The clinical and imaging data of 187 patients with ICA steno-occlusive disease were retrospectively analyzed. The ICA stenosis rate was divided into Grades I–IV (70–79%; 80–89%; 90–99%; 100%), and the circle of Willis was classified as four types (types I–IV). According to the literature, the value of cerebral blood flow/cerebral blood volume (CBF/CBV) of 7.55/min was used as cut-off to predict symptomatic patients. All patients were categorized into two groups: those with impaired perfusion [ n = 99 (52.9%)] and those without impaired perfusion [ n = 88 (47.1%)]. Symmetrical bilateral internal watershed areas were selected as the regions of interest (ROIs). Statistical analysis was made on the status of impaired perfusion and the risk factors of impaired perfusion. Results: Univariate analysis revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), types of the circle of Willis, and clinical features at admission differed between the two groups (patients with or without impaired perfusion) (p < 0.05). Multiple logistic stepwise regression analysis showed that MAP [odds ratio (OR) = 0.946, 95% confidential interval (CI) = 0.917–0.974, p < 0.001] and type IV (type I vs. IV: OR = 4.987, 95% CI = 1.955–12.723, p = 0.001) at admission were independently associated with impaired perfusion in the internal watershed areas. Conclusion: MAP and the type of circle of Willis at admission are independent risk factors associated with the impaired perfusion in patients with ICA steno-occlusive disease. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates the occurrence and development of diabetic complications relates to not only constant high plasma glucose, but also glucose fluctuations which affect various kinds of molecular mechanisms in various target cells and tissues. In this review, we detail reactive oxygen species and their potentially damaging effects upon glucose fluctuations and resultant downstream regulation of protein signaling pathways, including protein kinase C, protein kinase B, nuclear factor-κB, and the mitogen-activated protein kinase signaling pathway. A deeper understanding of glucose-fluctuation-related molecular mechanisms in the development of diabetic complications may enable more potential target therapies in future. [ABSTRACT FROM AUTHOR]

Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder that is primarily due to disruption of the development of neural crest cells. The onset of associated symptoms in both eyes accompanied by extraocular developmental defects is referred to as ARS. Cardiac defects associated with ARS have been reported, but the extent of the cardiac defects has yet to be defined. We report a case of a 17-year-old girl with ARS with typical facial malformations and severe mitral and tricuspid valve insufficiency. The patient was diagnosed with secondary glaucoma detected on ophthalmologic examination. Echocardiography showed severe mitral and tricuspid valve insufficiency. This case provides further evidence of the association of ARS with cardiac malformations and extends the reported range of cardiac malformations in patients with ARS.

Background: Cardiac paragangliomas (CPGLs) are rare neuroendocrine tumors that are easily overlooked and difficult to diagnose. Detailed comprehensive data regarding CPGL diagnosis and outcome are lacking.Methods: We retrospectively analyzed a cohort of 27 CPGL patients. This cohort represents the largest such cohort reported to date.Results: The prevalence of trilogy symptoms (concurrent palpitations, hyperhidrosis, and headache) was frequent (9/27, 33.3%). Sensitivity of echocardiography and contrast-enhanced computed tomography for localization of CPGL were 81.8% and 87%, respectively. Octreotide scintigraphy showed 100% sensitivity for detecting GPCLs, while sensitivity of I131-metaiodoben-zylguanidine scintigraphy was only 32.9%. Multiple tumors were found in 29.6% of patients. Most CPGLs originated from the epicardium or root of the great vessels (92.9%) and were mostly supplied by the coronary arteries and their branches (95.7%). Twenty-four patients underwent surgical treatment. Although local invasion was present in 40.0% of patients, it did not affect long-term outcome. Mean follow-up was 6.9 ± 3.6 years. Biochemical remission was achieved in 85% of patients. The recurrence rate was 15%.Conclusions: Manifestations of CPGLs are non-specific and they can be difficult to detect on imaging examinations. Octreotide scintigraphy should be performed in patients with suspected paragangliomas to screen for multiple lesions. Surgical resection of CPGLs can achieve symptom relief and biochemical remission.

Whole-prostate gland (WPG) segmentation plays a significant role in prostate volume measurement, treatment, and biopsy planning. This study evaluated a previously developed automatic WPG segmentation, deep attentive neural network (DANN), on a large, continuous patient cohort to test its feasibility in a clinical setting. With IRB approval and HIPAA compliance, the study cohort included 3,698 3T MRI scans acquired between 2016 and 2020. In total, 335 MRI scans were used to train the model, and 3,210 and 100 were used to conduct the qualitative and quantitative evaluation of the model. In addition, the DANN-enabled prostate volume estimation was evaluated by using 50 MRI scans in comparison with manual prostate volume estimation. For qualitative evaluation, visual grading was used to evaluate the performance of WPG segmentation by two abdominal radiologists, and DANN demonstrated either acceptable or excellent performance in over 96% of the testing cohort on the WPG or each prostate sub-portion (apex, midgland, or base). Two radiologists reached a substantial agreement on WPG and midgland segmentation (κ = 0.75 and 0.63) and moderate agreement on apex and base segmentation (κ = 0.56 and 0.60). For quantitative evaluation, DANN demonstrated a dice similarity coefficient of 0.93 ± 0.02, significantly higher than other baseline methods, such as DeepLab v3+ and UNet (both p values < 0.05). For the volume measurement, 96% of the evaluation cohort achieved differences between the DANN-enabled and manual volume measurement within 95% limits of agreement. In conclusion, the study showed that the DANN achieved sufficient and consistent WPG segmentation on a large, continuous study cohort, demonstrating its great potential to serve as a tool to measure prostate volume.