Autonomous Needle Navigation in Subretinal Injections via iOCT.

Subretinal injection is an effective method for direct delivery of therapeutic agents to treat prevalent subretinal diseases. Among the challenges for surgeons are physiological hand tremor, difficulty resolving single-micron scale depth perception, and lack of tactile feedback. The recent introduction of intraoperative Optical Coherence Tomography (iOCT) enables precise depth information during subretinal surgery. However, even when relying on iOCT, achieving the required micron-scale precision remains a significant surgical challenge. This work presents a robot-assisted workflow for high-precision autonomous needle navigation for subretinal injection. The workflow includes online registration between robot and iOCT coordinates; tool-tip localization in iOCT coordinates using a Convolutional Neural Network (CNN); and tool-tip planning and tracking system using real-time Model Predictive Control (MPC). The proposed workflow is validated using a silicone eye phantom and ex vivo porcine eyes. The experimental results demonstrate that the mean error to reach the user-defined target and the mean procedure duration are within an acceptable precision range. The proposed workflow achieves a 100% success rate for subretinal injection, while maintaining scleral forces at the scleral insertion point below 15mN throughout the navigation procedures.

Autonomous Needle Navigation in Retinal Microsurgery: Evaluation in ex vivo Porcine Eyes.

Important challenges in retinal microsurgery include prolonged operating time, inadequate force feedback, and poor depth perception due to a constrained top-down view of the surgery. The introduction of robot-assisted technology could potentially deal with such challenges and improve the surgeon's performance. Motivated by such challenges, this work develops a strategy for autonomous needle navigation in retinal microsurgery aiming to achieve precise manipulation, reduced end-to-end surgery time, and enhanced safety. This is accomplished through real-time geometry estimation and chance-constrained Model Predictive Control (MPC) resulting in high positional accuracy while keeping scleral forces within a safe level. The robotic system is validated using both open-sky and intact (with lens and partial vitreous removal) ex vivo porcine eyes. The experimental results demonstrate that the generation of safe control trajectories is robust to small motions associated with head drift. The mean navigation time and scleral force for MPC navigation experiments are 7.208 s and 11.97 mN, which can be considered efficient and well within acceptable safe limits. The resulting mean errors along lateral directions of the retina are below 0.06 mm, which is below the typical hand tremor amplitude in retinal microsurgery.

Robotic Navigation Autonomy for Subretinal Injection via Intelligent Real-Time Virtual iOCT Volume Slicing.

In the last decade, various robotic platforms have been introduced that could support delicate retinal surgeries. Concurrently, to provide semantic understanding of the surgical area, recent advances have enabled microscope-integrated intraoperative Optical Coherent Tomography (iOCT) with high-resolution 3D imaging at near video rate. The combination of robotics and semantic understanding enables task autonomy in robotic retinal surgery, such as for subretinal injection. This procedure requires precise needle insertion for best treatment outcomes. However, merging robotic systems with iOCT introduces new challenges. These include, but are not limited to high demands on data processing rates and dynamic registration of these systems during the procedure. In this work, we propose a framework for autonomous robotic navigation for subretinal injection, based on intelligent real-time processing of iOCT volumes. Our method consists of an instrument pose estimation method, an online registration between the robotic and the iOCT system, and trajectory planning tailored for navigation to an injection target. We also introduce intelligent virtual B-scans, a volume slicing approach for rapid instrument pose estimation, which is enabled by Convolutional Neural Networks (CNNs). Our experiments on ex-vivo porcine eyes demonstrate the precision and repeatability of the method. Finally, we discuss identified challenges in this work and suggest potential solutions to further the development of such systems.

Associations of air pollution and greenness with global burden of breast cancer: an ecological study.

Despite the significance of the associations of air pollution and greenness with the risk of breast cancer, this topic has not been investigated on a global scale. We conducted an ecological study using 7 years of data from 162 countries. Disability-adjusted life years (DALYs) and incidence data were used to represent the breast cancer disease burden. Particulate matter with a diameter < 2.5 µm (PM2.5), ozone (O3), nitrogen dioxide (NO2), and the normalized difference vegetation index (NDVI) were adopted as our exposures. We employed generalized linear mixed models to explore the relationship between air pollution and greenness on breast cancer disease burden. The rate ratio (RR) and its 95% confidence interval (CI) indicate the effect size. There is a positive association between air pollution and the burden of breast cancer disease. Contrarily, per interquartile range increment in NDVI was negatively associated with DALYs and incidence. In terms of air pollutants and breast cancer, NDVI seems to have a significant influence on the relationship between these two conditions. A higher amount of greenness helps to alleviate the negative association of air pollution on breast cancer. PM2.5 and O3 play a mediating role in the relationship between greenness and breast cancer disease burden. In areas with higher levels of greenness, there is a possibility that the inverse association between air pollutants and the burden of breast cancer may be influenced.

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway.

OBJECTIVES: This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. METHODS: The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. RESULTS: LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1ß signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. CONCLUSION: LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.

Acute kidney injury after infant cardiac surgery: a comparison of pRIFLE, KDIGO, and pROCK definitions.

BACKGROUND: KDIGO and pRIFLE classifications are commonly used in pediatric acute kidney injury (AKI). As a novel AKI definition, pROCK considered the high variability of serum creatinine in children. This study aimed to compare the above three definitions for AKI in infants undergoing cardiac surgery. METHODS: We analyzed a clinical cohort of 413 infants undergoing cardiac surgery. AKI was defined and staged according to pRIFLE, KDIGO, and pROCK, respectively. Incidence differences and diagnostic agreement across definitions were assessed. The association between postoperative outcomes and AKI by each definition was investigated. RESULTS: Postoperative AKI was identified in 185 (44.8%), 160 (38.7%), and 77 (18.6%) patients according to pRIFLE, KDIGO, and pROCK, respectively. The agreement between pRIFLE and KDIGO was almost perfect (κ = 0.88), while there was only a slight agreement between pROCK and them. AKI by pROCK was independently associated with adverse outcomes (p = 0.003) and prolonged mechanical ventilation (p = 0.002). CONCLUSIONS: There were considerable differences in AKI incidence and staging among definitions. Compared with pRIFLE and KDIGO, AKI defined by pROCK was significantly reduced and better associated with postoperative adverse outcomes.

CIRP attenuates acute kidney injury after hypothermic cardiovascular surgery by inhibiting PHD3/HIF-1α-mediated ROS-TGF-ß1/p38 MAPK activation and mitochondrial apoptotic pathways.

BACKGROUND: The ischemia-reperfusion (IR) environment during deep hypothermic circulatory arrest (DHCA) cardiovascular surgery is a major cause of acute kidney injury (AKI), which lacks preventive measure and treatment. It was reported that cold inducible RNA-binding protein (CIRP) can be induced under hypoxic and hypothermic stress and may have a protective effect on multiple organs. The purpose of this study was to investigate whether CIRP could exert renoprotective effect during hypothermic IR and the potential mechanisms. METHODS: Utilizing RNA-sequencing, we compared the differences in gene expression between Cirp knockout rats and wild-type rats after DHCA and screened the possible mechanisms. Then, we established the hypothermic oxygen-glucose deprivation (OGD) model using HK-2 cells transfected with siRNA to verify the downstream pathways and explore potential pharmacological approach. The effects of CIRP and enarodustat (JTZ-951) on renal IR injury (IRI) were investigated in vivo and in vitro using multiple levels of pathological and molecular biological experiments. RESULTS: We discovered that Cirp knockout significantly upregulated rat Phd3 expression, which is the key regulator of HIF-1α, thereby inhibiting HIF-1α after DHCA. In addition, deletion of Cirp in rat model promoted apoptosis and aggravated renal injury by reactive oxygen species (ROS) accumulation and significant activation of the TGF-ß1/p38 MAPK inflammatory pathway. Then, based on the HK-2 cell model of hypothermic OGD, we found that CIRP silencing significantly stimulated the expression of the TGF-ß1/p38 MAPK inflammatory pathway by activating the PHD3/HIF-1α axis, and induced more severe apoptosis through the mitochondrial cytochrome c-Apaf-1-caspase 9 and FADD-caspase 8 death receptor pathways compared with untransfected cells. However, silencing PHD3 remarkably activated the expression of HIF-1α and alleviated the apoptosis of HK-2 cells in hypothermic OGD. On this basis, by pretreating HK-2 and rats with enarodustat, a novel HIF-1α stabilizer, we found that enarodustat significantly mitigated renal cellular apoptosis under hypothermic IR and reversed the aggravated IRI induced by CIRP defect, both in vitro and in vivo. CONCLUSION: Our findings indicated that CIRP may confer renoprotection against hypothermic IRI by suppressing PHD3/HIF-1α-mediated apoptosis. PHD3 inhibitors and HIF-1α stabilizers may have clinical value in renal IRI.

Development and Validation of a Nomogram for Predicting Heparin Resistance in Neonates and Young Infants Undergoing Cardiac Surgery: A Retrospective Study.

BACKGROUND: Heparin resistance (HR) is a common finding in pediatric cardiac surgery and generally refers to decreased sensitivity to heparin. Antithrombin (AT) deficiency is considered the primary mechanism of HR; however, the etiology of HR may be multifactorial. Early identification of HR might help optimize heparin anticoagulation management. This study aimed to develop a predictive nomogram for HR in neonates and young infants undergoing cardiac surgery. METHODS: From January 2020 to August 2022, a total of 296 pediatric patients 1 to 180 days of age were included in this retrospective study. The patients were randomly divided into development and validation cohorts in a 7:3 ratio. Univariable logistic regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regularization were used for variable selection. A multivariable logistic regression was performed to identify predictors and establish a nomogram to predict HR risk. Discrimination, calibration, and clinical usefulness were assessed in the development and validation cohorts. RESULTS: After the multistep variable selection, AT activity, platelet count, and fibrinogen were predictors for HR in neonates and young infants. The prediction model constructed using these 3 factors achieved an area under the receiver operating characteristic curve (ROC-AUC) of 0.874 and 0.873 in the development and validation cohorts. The Hosmer-Lemeshow test did not find evidence of a lack of fit (P = .768). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the model performed well in neonate and infant subgroups. CONCLUSIONS: A nomogram based on preoperative variables was developed to predict the HR risk in neonates and young infants undergoing cardiac surgery. This provides clinicians with a simple tool for the early prediction of HR, which may help optimize heparin anticoagulation strategies in this vulnerable patient population.

CT features and risk factors of pulmonary cement embolism after vertebroplasty or kyphoplasty in patients with vertebral compression fracture: a retrospective cohort study.

Background: Pulmonary cement embolism (PCE) caused by cement leakage is one of the complications of percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP). The aim of our study was to explore the imaging features on computed tomography (CT) and analyze the risk factors of PCE in patients with a vertebral compression fracture to compare the incidences of PCE caused by PVP and PKP. Methods: In this single-center, retrospective study, 373 patients (96 males and 277 females; mean age 76.2±9.4 years) from January 2017 to December 2020 who underwent PVP or PKP for treatment of vertebral compression fracture in the China-Japan Friendship Hospital were retrospectively included. Their clinical data were recorded, and their postprocedural chest CT scans were reviewed and evaluated for PCE. Results: Of the 373 patients, 258 patients underwent PVP while the other 115 underwent PKP. PCE was found on the postprocedural chest CT scans in 64 patients (17.2%), including 47 patients with PVP and 17 patients with PKP. The incidence of PCE of PVP and PKP was similar (χ2=0.660; P=0.460). The typical CT findings of PCE were multiple linear or branching radiopaque densities in pulmonary arteries. The upper lobes of bilateral lungs were the most frequently involved. In addition, postprocedural chest CT demonstrated that 103 cases had cement emboli in the azygos vein, and 8 cases had cement emboli in the inferior vena cava. Binary logistic regression analysis demonstrated that PVP or PKP in the T9 vertebra [odds ratio (OR) =4.222; 95% CI: 1.490-11.966] and cement emboli in the azygos vein (OR =7.647; 95% CI: 3.937-14.856) or the inferior vena cava (OR =42.701; 95% CI: 7.525-242.302) were the risk factors of PCE. Conclusions: The incidence of PCE during PVP or PKP was 17.2%. Postprocedural chest CT clearly showed PCE as branching hyperdense or radiopaque lesions confined within the pulmonary artery courses. PVP or PKP in the T9 vertebra and cement emboli in the azygos vein or the inferior vena cava were risk factors for PCE.

Discovery of Barakacin and Its Derivatives as Novel Antiviral and Fungicidal Agents.

Pesticides are essential for the development of agriculture. It is urgent to develop green, safe and efficient pesticides. Bisindole alkaloids have unique and concise structures and broad biological activities, which make them an important leading skeleton in the creation of new pesticides. In this work, we synthesized bisindole alkaloid barakacin in a simple seven-step process, and simultaneously designed and synthesized a series of its derivatives. Biological activity research indicated that most of these compounds displayed good antiviral activities against tobacco mosaic virus (TMV). Among them, compound 14b exerted a superior inhibitory effect in comparison to commercially available antiviral agent ribavirin, and could be expected to become a novel antiviral candidate. Molecular biology experiments and molecular docking research found that the potential target of compound 14b was TMV coat protein (CP). These compounds also showed broad-spectrum anti-fungal activities against seven kinds of plant fungi.

Idiopathic pulmonary fibrosis disease progression: a dynamic quantitative chest computed tomography follow-up analysis.

Background: To clarify whether dynamic quantification of variables derived from chest high-resolution computed tomography (HRCT) can assess the progression of idiopathic pulmonary fibrosis (IPF). Methods: Patients with IPF who underwent serial computed tomography (CT) imaging were retrospectively enrolled. Several structural abnormalities seen on HRCT in IPF were segmented and quantified. Patients were divided into 2 groups according to their pulmonary function test (PFT) results: those with disease stabilization and those with disease progression, and differences between the groups were analyzed. Results: There were no statistically significant differences between the 2 patient groups for the following parameters: baseline PFTs, total lesion extent, lesion extent at different sites in the lungs, and pulmonary vessel-related parameters (with P values ranging from 0.057 to 0.894). Median changes in total lung volume, total lesion volume, and total lesion ratio were significantly higher in patients with worsening disease compared with those with stable disease (P<0.001). There was a significant increase in total lesion volume of 214.73 mL [interquartile range (IQR), 68.26 to 501.46 mL] compared with 3.67 mL (IQR, -71.70 to 85.33 mL) in the disease progression group compared with the disease stability group (P=0.001). The decline in pulmonary vessel volume and number of pulmonary vessel branches was more pronounced in the group with functional worsening compared with the group with functional stability. Moreover, changes in lesion volume ratio were negatively correlated with changes in diffusing capacity of the lungs for carbon monoxide (DLco) during follow-up (R=-0.57, P<0.001), and changes in pulmonary vessel-related parameters demonstrated positive correlation with DLco (with R ranging from 0.27 to 0.53, P<0.001) and forced vital capacity (FVC) (with R ranging from 0.44 to 0.61, P<0.001). Conclusions: Changes in CT-related parameters during follow-up may have better predictive performance compared with baseline imaging parameters and PFTs for disease progression in IPF.

Goal-directed perfusion for reducing acute kidney injury in cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) is a common complication following cardiopulmonary bypass (CPB) which can affect morbidity and mortality. Goal-directed perfusion (GDP) intended to avoid the nadir oxygen delivery index below the critical value is associated with reduced postoperative AKI. However, current studies suggested that GDP can only decrease the incidence of AKI stage 1 but showed no effects on AKI stages 2-3 and mortality. The objective of the present meta-analysis is to deter the effects of GDP on postoperative AKI in any stage and mortality following cardiac surgery. METHODS: MEDLINE, Embase, and the Cochrane Library were searched to identify all clinical trials comparing GDP with control (standard care) during cardiopulmonary bypass conducting in adults undergoing cardiac surgery. The primary outcome was postoperative acute kidney injury. Secondary outcomes included postoperative mortality and length of ICU stay. Data synthesis was obtained by using risk ratio with 95% confidence interval by a random-effects model. RESULT: From 1094 potential studies, 3 trials enrolling 777 patients were included. Meta-analysis suggested the GDP strategy based on DO2i reduced postoperative AKI compared with standard CPB management (RR = 0.52; 95% CI: 0.38-0.70; p < .0001), especially in AKI stage I (RR = 0.47; 95% CI: 0.33-0.66; p < .0001). But the GDP strategy did not reduce the incidence of severe AKI (stages 2-3) and postoperative mortality. CONCLUSION: The GDP strategy based on DO2i during CPB obviously reduces AKI stage 1 and thus reduces overall AKI incidence. But it shows no effects on severe AKI (stages 2-3) and mortality.

Association of high-sensitivity C-reactive protein and anemia with acute kidney injury in neonates.

Background: The association of high-sensitivity C-reactive protein (hsCRP) and anemia with postoperative acute kidney injury (AKI) in neonates with congenital heart disease (CHD) is still unclear. The purpose of this study was to examine whether anemia-associated AKI is modulated by hsCRP in neonates. Methods: This study included 253 consecutive neonatal patients who underwent CHD surgery in a national tertiary hospital. We investigated the association between postoperative AKI with baseline hsCRP, anemia, and their interaction by multivariable logistic regression analyses. Results: The incidence of AKI was 24.1% in the entire cohort. After being adjusted for covariates, hsCRP level was negatively correlated with AKI (P < 0.01 for 1 mg/L threshold), whereas anemia emerged as an independent risk factor of AKI (P = 0.02). In addition, there was a significant interaction between anemia and hsCRP level (P = 0.01). In neonates with hsCRP < 1 mg/L, anemia was positively associated with AKI (P = 0.03). However, no significant association was found between anemia and AKI in the context of hsCRP ≥ 1 mg/L. Combination of anemia and hsCRP < 1 mg/L was independently correlated with the risk of AKI (P < 0.01), while concomitant anemia and hsCRP ≥ 1 mg/L or hsCRP < 1 mg/L combined with non-anemia was not. Conclusions: In neonates with CHD, the risk of anemia-associated AKI may be modulated by hsCRP level. Attention should be paid to neonates with preoperative anemia and baseline hsCRP < 1 mg/L to reduce the risk of postoperative AKI.

Mortality prediction in pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation: A comparison of scoring systems.

Background: Pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients have high mortality and morbidity. There are currently three scoring systems available to predict mortality: the Pediatric Extracorporeal Membrane Oxygenation Prediction (PEP) model, Precannulation Pediatric Survival After VA-ECMO (Pedi-SAVE) score, and Postcannulation Pedi-SAVE score. These methods provide risk stratification scores for pediatric patients requiring ECMO for cardiac support. However, comparative validation of these scoring systems remains scarce. We aim to assess the ability of these models to predict outcomes in a cohort of pediatric patients undergoing VA-ECMO after cardiac surgery, and identify predictors of in-hospital mortality. Methods: A retrospective analysis of 101 children admitted to Fuwai Hospital who received VA-ECMO from January 1, 2010 to December 31, 2020 was performed. Patients were divided into two groups, survivors (n = 49) and non-survivors (n = 52) according to in-hospital mortality. PEP model and Pedi-SAVE scores were calculated. The primary outcomes were the risk factors of in-hospital mortality, and the ability of the PEP model, Precannulation Pedi-SAVE and Postcannulation Pedi-SAVE scores to predict in-hospital mortality. Results: Postcannulation Pedi-SAVE score accessing the entire ECMO process had the greatest area under receiver operator curve (AUROC), 0.816 [95% confidence interval (CI): 0.733-0.899]. Pre-ECMO PEP model could predict in-hospital mortality [AUROC = 0.691 (95% CI: 0.565-0.817)], and Precannulation Pedi-SAVE score had the poorest prediction [AUROC = 0.582(95% CI: 0.471-0.694)]. Lactate value at ECMO implantation [OR = 1.199 (1.064-1.351), P = 0.003] and infectious complications [OR = 5.169 (1.652-16.172), P = 0.005] were independent risk factors for in-hospital mortality. Conclusion: Pediatric cardiac ECMO scoring systems, including multiple risk factors before and during ECMO, were found to be useful in this cohort. Both the pre-ECMO PEP model and the Postcannulation Pedi-SAVE score were found to have high predictive value for in-hospital mortality in pediatric postcardiotomy VA-ECMO.

Quantitative analysis of high-resolution computed tomography features of idiopathic pulmonary fibrosis: a structure-function correlation study.

Background: The quantitative analysis of high-resolution computed tomography (HRCT) is increasingly being used to quantify the severity and evaluate the prognosis of disease. Our aim was to quantify the HRCT features of idiopathic pulmonary fibrosis (IPF) and identify their association with pulmonary function tests. Methods: This was a retrospective, single-center, clinical research study. Patients with IPF were retrospectively included. Pulmonary segmentation was performed using the deep learning-based method. Radiologists manually segmented 4 findings of IPF, including honeycombing (HC), reticular pattern (RE), traction bronchiectasis (TRBR), and ground glass opacity (GGO). Pulmonary vessels were segmented with the automatic integration segmentation method. All segmentation results were quantified by the corresponding segmentation software. Correlations between the volume of the 4 findings on HRCT, volume of the lesions at different sites, pulmonary vascular-related parameters, and pulmonary function tests were analyzed. Results: A total of 101 IPF patients (93 males) with a median age of 63 years [interquartile range (IQR), 58 to 68 years] were included in this study. Total lesion extent demonstrated a stronger negative correlation with diffusion capacity for carbon monoxide (DLco) compared to HC, RE, and TRBR [total lesion ratio, correlation coefficient (r) =-0.67, P<0.001; HC, r=-0.45, P<0.001; RE, r=-0.41, P<0.001; TRBR, r=-0.25, P<0.05, respectively]. Correlations with lung function were similar among various lesion sites with r from -0.38 to -0.61 (P<0.001). Pulmonary artery volume (PAV) displayed a slightly increased positive association with the DLco compared to total pulmonary vascular volume (PVV); for PAV, r=0.41 and P<0.001 and for total PVV, r=0.36 and P<0.001. Additionally, total lesion extent, HC, and RE indicated a negative relationship with vascular-related parameters, and the strength of the correlations was independent of lesion site. Conclusions: Quantitative analysis of HRCT features of IPF indicated a decline in function and an aggravation of vascular destruction with increasing lesion extent. Furthermore, a positive correlation between vascular-related parameters and pulmonary function was confirmed. This co-linearity indicated the potential of vascular-related parameters as new objective markers for evaluating the severity of IPF.

Risk factors and outcomes associated with acute kidney injury following extracardiac total cavopulmonary connection: a retrospective observational study.

Background: Total cavopulmonary connection (TCPC) is an important operation for the treatment of complex congenital heart disease. Epidemiology and outcomes for pediatric patients with acute kidney injury (AKI) following extracardiac TCPC have not been well documented. This study investigates the prevalence, risk factors, and outcomes of AKI in children after extracardiac TCPC surgery. Methods: We retrospectively evaluated patients (age at surgery <18 years) who underwent extracardiac TCPC surgery between January 2008 and January 2020 in the Pediatric Cardiac Surgical Center of Fuwai Hospital, Beijing, China. AKI was defined according to the pediatric-modified risk, injury, failure, loss of function, and end-stage renal disease criteria. Results: A total of 377 pediatric patients were included in this study; 123 patients (32.6%) had some degree of AKI. Among the patients with AKI, 101 (82.1%) were diagnosed with AKI-risk (AKI-R), while 22 (17.9%) were diagnosed with acute kidney injury/failure (AKI/F) (16 with AKI, and 6 with AKF). Preoperative estimated creatinine clearance (OR: 1.039, 95% CI: 1.024-1.055, P<0.001), neutrophil-to-lymphocyte ratio (OR: 1.208, 95% CI: 1.128-1.294, P<0.001), and renal perfusion pressure (OR: 0.962, 95% CI: 0.938-0.986, P=0.002) on postoperative day (POD) 0 were significantly associated with AKI after TCPC. Having previously undergone a bidirectional Glenn was significantly associated with the severity of postoperative AKI (OR: 0.253, 95% CI: 0.088-0.731, P=0.011). Furthermore, AKI was associated with prolonged mechanical ventilation time, prolonged intensive care unit stay, and composite adverse outcome. Compared with non-AKI patients, the 10-year survival rate of patients with severe AKI was significantly lower (95.5% vs. 65.9%, P=0.009). Conclusions: Although the incidence of AKI was high in patients undergoing TCPC surgery, most cases were AKI-R. Severe AKI was significantly associated with early adverse outcomes and poor long-term survival.

Preoperative Iron Deficiency Is Associated With Increased Blood Transfusion in Infants Undergoing Cardiac Surgery.

Background: Iron deficiency (ID) is common in patients undergoing cardiac surgery, which is associated with adverse outcomes. However, the relevance of ID in congenital heart disease is still unclear. This study aimed to investigate the characteristics of preoperative ID and its association with clinical outcomes in infants undergoing cardiac surgery with cardiopulmonary bypass. Methods: In this retrospective study, 314 patients undergoing cardiac surgery were assigned into three groups according to their preoperative ID status. Absolute ID was defined by serum ferritin <12 µg/L, and functional ID was defined by serum ferritin level at 12-30 µg/L and transferrin saturation <20%. Baseline characteristics were compared between groups and multiple logistic regression was used to identify predictors for ID. The association between ID and clinical outcomes, including allogenic blood transfusion requirements, was also evaluated. Results: Among the 314 patients included, 32.5% were absolute ID and 28.7% were functional ID. Patients with absolute ID were more often of higher weight, cyanotic heart disease, and anemia. The presence of absolute ID was associated with an increase in postoperative blood transfusion (OR 1.837, 95% CI 1.016-3.321, p = 0.044). There was no significant difference in postoperative morbidity, mortality, and the length of hospital stay. Conclusions: Absolute ID was associated with preoperative anemia and cyanotic heart disease, and was an independent risk factor for postoperative blood transfusion. Further research should better explore the definition of ID and its impact on outcomes in pediatric cardiac surgery.

Assessment of correlations between sildenafil use and comorbidities and lifestyle factors using wastewater-based epidemiology.

Sildenafil (SIL) is widely used to treat erectile dysfunction. Information on its consumption and the factors influencing its use is limited in China. In this study, we sampled composite influent wastewater samples from 33 Chinese cities and analyzed SIL using liquid chromatography-tandem mass spectrometry. SIL consumption was estimated using wastewater-based epidemiology (WBE) and ranged from 10.6 mg/d/1000 people to 132 mg/d/1000 people, with a mean of 53 mg/d/1000 people. Prescription sales (3570 kg) accounted for 13.3% of the estimated SIL use (26842 kg) in 2018, thereby implying that SIL illicit use was greater than prescription use in China. Some regional differences were observed in SIL use, which was significantly higher in North China than South China (p < 0.05), thereby reflecting that the prevalence of SIL was affected by differences in lifestyle and socioeconomic factors. We found significant positive correlations between SIL use and consumption of allopurinol, hydrochlorothiazide, nicotine, and alcohol, thereby suggesting that the prevalence of SIL was associated with the prevalence of gout, hypertension, smoking, and drinking. Moreover, age structures, internet use, and marriage rates were positively correlated with SIL use, whereas the unemployment rate was negatively correlated with SIL use. Our study demonstrates that WBE is valuable for medical research to investigate licit and illicit drug use and to assess the underlying associations of different chemical uses.

Right ventricular end-systolic remodeling index on cardiac magnetic resonance imaging: comparison with other functional markers in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) can provide important metrics of pulmonary hypertension. In the current study, we investigated whether the CMR-derived right ventricular end-systolic remodeling index (RVESRI) could be a metric in assessing the function and hemodynamics of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: A total of 64 patients (45±14 years, 37 males), including 46 patients with CTEPH and 18 patients with chronic pulmonary thromboembolism (CTE), were retrospectively enrolled. All patients underwent right heart catheterization and CMR within 7 days. RVESRI, right ventricular eccentricity index, right ventricular end-diastolic and end-systolic volume index, right ventricular ejection fraction, right ventricular cardiac output, and strain were analyzed on cine images of CMR. Hemodynamic parameters including mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output were obtained from right heart catheterization. RESULTS: RVESRI of all patients was 1.50 (IQR, 1.26-1.90). Compared with CTE patients, RVESRI in patients with CTEPH was significantly increased (U=27.5, P<0.001). The interclass correlation coefficients of intra-observer reproducibility and inter-observer reproducibility for RVESRI measurement were 0.96 (95% CI, 0.93-0.97) and 0.99 (95% CI, 0.98-0.99), respectively. RVESRI positively correlated with right ventricular end-diastolic and end-systolic volume index and right ventricular global longitudinal strain (r=0.79, 0.83, 0.62, P<0.001), while it was negatively correlated with right ventricular ejection fraction (r=-0.64, P<0.001), right ventricular cardiac output (r=-0.50, P<0.001), and right ventricular eccentricity index (r=-0.81, P<0.001). RVESRI had a positive correlation with mean pulmonary arterial pressure (r=0.65, P<0.001) and pulmonary vascular resistance (r=0.69, P<0.001), while it was negatively correlated with cardiac output (r=-0.64, P<0.001). The receiver operating characteristic curve indicated that RVESRI >1.35 had a sensitivity of 97.8% and specificity of 83.3% in predicting mean pulmonary arterial pressure ≥25 mmHg, and its area under the curve (AUC) was 0.96±0.02. Meanwhile, the AUC of RVESRI was similar to RVEI (Z=1.635, P=0.102) and was more than the diameter of the main pulmonary artery (MPA) (Z=2.26, P=0.02) and the ratio of the MPA and ascending aorta diameter (MPA/AAo) (Z=3.826, P<0.001) in predicting mean pulmonary arterial pressure ≥25 mmHg. CONCLUSIONS: RVESRI measured on CMR is a simple and reproducible metric in assessing right ventricular function and hemodynamics in CTEPH patients.

Quantification of pulmonary vessel volumes on low-dose computed tomography in a healthy male Chinese population: the effects of aging and smoking.

BACKGROUND: This study sought to determine pulmonary vascular volumes (PVVs) on low-dose computed tomography (LDCT) in a healthy male Chinese population and analyze the effects of aging and smoking on PVVs. METHODS: A total of 1,320 healthy male participants (comprising 720 non-smokers, 445 smokers, and 155 ex-smokers) who underwent LDCT were retrospectively included in this study. Their demographic data and smoking status data were collected. An automatic integration segmentation approach for LDCT was used to segment pulmonary vessels semi-automatically. The PVVs of the whole lung, left lung, and right lung on LDCT were calculated, and correlations between PVVs and age and smoking status were then compared. RESULTS: The inter-rater correlation coefficient of the whole lung, left lung, and right lung PVVs was 0.98 [95% confidence interval (CI): 0.95-0.99], 0.97 (95% CI: 0.93-0.98), and 0.97 (95% CI: 0.94-0.99), respectively. The intra-class correlation coefficient of the whole lung left lung, and right lung PVVs was 0.98 (95% CI: 0.95-0.99), 0.96 (95% CI: 0.95-0.99), and 0.96 (95% CI: 0.92-0.98), respectively. In non-smokers, PVVs decreased with age. The PVVs of heavy smokers were higher than those of light smokers, ex-smokers, and non-smokers. The PVVs of ex-smokers were comparable to those of light smokers. CONCLUSIONS: The PVVs measured on LDCT tended to decrease with age in healthy male non-smokers gradually. Compared to non-smokers, the PVVs of smokers increased, even with the normal lung function.