Usefulness of risk assessment tools in predicting hemodynamic outcome after balloon pulmonary angioplasty: a comparative analysis.

OBJECTIVES: Several parameters of widely used risk assessment tools for pulmonary arterial hypertension (PAH) have been linked to hemodynamic outcomes of balloon pulmonary angioplasty (BPA). Therefore, we aimed to determine whether these risk assessment tools could be used to predict hemodynamic outcomes following BPA. METHODS: In this retrospective study, we included 139 patients with chronic thromboembolic pulmonary hypertension who had undergone BPA at Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). We compared the accuracies of seven well-validated risk assessment tools for predicting hemodynamic outcomes following BPA. A favorable hemodynamic outcome was defined as a mean pulmonary arterial pressure < 30 mmHg at follow-up. RESULTS: The baseline risk profiles varied significantly among the risk assessment tools. The US Registry to Evaluate Early and Long-Term PAH Disease Management risk scales and the French risk assessment tools rated most patients as high-risk, while the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) series and laboratory examination-based risk scales categorized most patients as having intermediate-risk profile. COMPERA 2.0 (4-strata) exhibited the highest predictive power among all risk stratifications. Noninvasive risk stratification (COMPERA 2.0 [3-strata]) showed a comparable predictive ability to that of invasive risk stratification (COMPERA 1.0) (area under the curve 0.649 vs. 0.648). Moreover, incorporating diffusing capacity of the lungs for carbon monoxide and tricuspid regurgitation velocity into COMPERA 2.0 (4-strata) further enhanced its predictive power (net reclassification index 0.153, 95% confidence interval 0.009-0.298, p = 0.038). Additionally, this refined COMPERA version had a high calibration accuracy (slope 0.96). CONCLUSION: Although the risk strata distribution varied among different risk assessment tools, the proportion of patients achieving favorable hemodynamics decreased with the escalation of risk stratification in most models. The well-validated risk assessment tools for PAH could also predict hemodynamic outcomes following BPA, and the refined COMPERA 2.0 model exhibited the highest predictive ability among these. Applying risk assessment tools before BPA can facilitate early identification of patients in need of closer monitoring and more intensive interventions, contributing to a better prognosis after BPA.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Blood urea nitrogen to serum albumin ratio as a new indicator of disease severity and prognosis in idiopathic pulmonary artery hypertension.

BACKGROUND: Emerging evidence has shown that the blood urea nitrogen to serum albumin ratio (BAR) is associated with the severity and prognosis of heart failure. However, its role in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study investigated the associations between BAR and functional status, echocardiographic findings, hemodynamics, and long-term outcomes among patients with IPAH. METHODS: This study included consecutive patients who underwent right heart catheterization (RHC) and were diagnosed with IPAH between January 2013 and January 2018 at Fuwai Hospital. The primary outcome was the worsening of clinical symptoms. Spearman correlation coefficients were used to evaluate the association between the BAR and established markers of IPAH severity. Receiver operating characteristic (ROC) curve analysis was used to determine BAR's optimal cut-off and predictive performance. Kaplan-Meier analysis and Cox proportional hazard models assessed the relationship between BAR and clinical worsening. RESULTS: A total of 340 patients with IPAH were included in this study. BAR correlated with well-validated variables that reflected the severity of IPAH, such as World Health Organization functional class, 6-min walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, mixed venous oxygen saturation, and cardiac index. Kaplan-Meier curves indicated that patients with BAR＞3.80 had a significantly higher clinical worsening rate (log-rank test, P < 0.001) than those with BAR≤3.80. Multivariate Cox analysis showed that BAR could independently predict clinical worsening [hazard ratio(HR):2.642, 95 % confidence interval (CI):1.659-4.208, P < 0.001]. In addition, BAR provided additional predictive value for the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk assessment score. CONCLUSIONS: BAR reflects disease severity and is independently associated with the prognosis of patients with IPAH.

Mechano-sensor Piezo1 inhibits glucagon production in pancreatic α-cells.

OBJECTIVE: Glucagon is a critical hormone regulating glucose metabolism. It stimulates the liver to release glucose under low blood sugar conditions, thereby maintaining blood glucose stability. Excessive glucagon secretion and hyperglycemia is observed in individuals with diabetes. Precise modulation of glucagon is significant to maintain glucose homeostasis. Piezo1 is a mechanosensitive ion channel capable of converting extracellular mechanical forces into intracellular signals, thus regulating hormonal synthesis and secretion. This study aims to investigate the role of Piezo1 in regulating glucagon production in α cells. METHODS: The effects of Piezo1 on glucagon production were examined in normal- or high-fat diet fed α cell-specific Piezo1 knockout mice (Gcg-Piezo1-/-), and the murine pancreatic α cell line αTC1-6. Expression of Proglucagon was investigated by real-time PCR and western blotting. Plasma glucagon and insulin were detected by enzyme immunoassay. RESULTS: Under both normal- and high-fat diet conditions, Gcg-Piezo1-/- mice exhibited increased pancreatic α cell proportion, hyperglucagonemia, impaired glucose tolerance, and activated pancreatic mTORC1 signaling. Activation of Piezo1 by its agonist Yoda1 or overexpression of Piezo1 led to decreased glucagon synthesis and suppressed mTOR signaling pathway in αTC1-6 cells. Additionally, the levels of glucagon in the medium were also reduced. Conversely, knockdown of Piezo1 produced opposite effects. CONCLUSION: Our study uncovers the regulatory role of the Piezo1 ion channel in α cells. Piezo1 influences glucagon production by affecting mTOR signaling pathway.

Tumor biomarkers in evaluating the severity and prognosis of idiopathic pulmonary arterial hypertension: A comprehensive analysis.

Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014-2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163-3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001-1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well-validated PH biomarkers, CA125 was still of prognostic value in the low-risk patients (HR: 1.014, 95% CI: 1.004-1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

Optimal short-term outcomes in balloon pulmonary angioplasty: the minimum frequency of three sessions annually.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is typically performed in a sequential manner. OBJECTIVES: This study aimed to determine the lowest frequency of BPA for patients who could not reach treatment goals in a short period. DESIGN: Retrospective cohort. METHODS: We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of performed BPA sessions or treated pulmonary vessels or the ratio of the number of treated pulmonary vessels/the number of baseline lesions (T/P) prior to the initial occurrence of clinical outcome or censored date, we divided patients into different groups. The principal outcome was clinical worsening. RESULTS: After stratifying patients by the number of performed BPA sessions, most baseline parameters were comparable among groups. During follow-up, 31 (16.7%) of 186 patients experienced clinical worsening. The 6-month cumulative clinical worsening-free survival rates of ⩾2 performed sessions group were significantly higher than that of 1 performed session group. The 12-month cumulative rates of clinical worsening-free survival exhibited a declining pattern in the subsequent sequence: ⩾3, 2, and 1 performed BPA sessions, and this trend persisted when follow-up time exceeded 12 months. The 6-, 12-, and 24-month cumulative clinical worsening-free survival rates were comparable between patients with 3 and ⩾4 performed BPA sessions. Similar results were also observed when stratifying patients by the accumulative number of treated pulmonary vessels (⩽8, 9-16, ⩾17) and T/P (⩽0.789, 0.790-1.263, ⩾1.264). CONCLUSION: To achieve optimal short-term outcomes, patients might need to undergo ⩾2 BPA sessions or have ⩾9 pulmonary vessels treated or have T/P ⩾0.790 within 6 months, and undergo ⩾3 BPA sessions or have ⩾17 pulmonary vessels treated or have T/P ⩾1.264 within 12 months.

The least number of BPA session to reach a favorable outcomeWhy was the study done? Balloon pulmonary angioplasty (BPA) has been recommended for patients with chronic thromboembolic pulmonary hypertension, which can significantly improve patients' hemodynamics. However, BPA is typically performed in a stepwise manner, and the duration from the initial session to the final session could extend over a year. If patients could not quickly undergo adequate number of BPA sessions and reach hemodynamic target due to various reasons, what is the best frequency of BPA for them? What did the researchers do? We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of BPA sessions, we divided patients into different groups to identify the best frequency of BPA to improve prognosis. What did the researchers find? Patients who received at least two BPA sessions within six months had significantly better prognosis than those with one BPA session. Patients who received at least three BPA sessions within a year had significantly better prognosis than those with two BPA sessions. What do the findings mean? To achieve optimal short-term outcome, patients might need to undergo at least two BPA sessions within six months, and undergo at least three BPA sessions within a year.

Role of the Systemic Inflammatory Response Index in Predicting Disease Severity and Prognosis in Idiopathic Pulmonary Arterial Hypertension.

Introduction: Mounting evidence indicates a possible connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure, but its role in idiopathic pulmonary arterial hypertension (IPAH) is not well understood. This study aimed to investigate the relationship between SIRI and variables such as functional ability, echocardiography results, hemodynamic measurements, and long-term outcomes in patients with IPAH. Methods: The study included 426 consecutive IPAH patients who underwent right heart catheterization at Fuwai Hospital from January 2013 to December 2020. SIRI was calculated using composite inflammation indicators from routine blood tests. The main outcome measure was clinical deterioration. Spearman correlation coefficients were used to assess associations between SIRI and indicators of IPAH severity. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal SIRI threshold and predictive ability. Kaplan-Meier analysis and Cox proportional hazard models were used to examine the relationship between SIRI and clinical deterioration. Results: SIRI showed positive associations with indicators such as N-terminal pro-brain natriuretic peptide, right ventricular end-diastolic diameter, pericardial effusion, mean pulmonary arterial pressure, and pulmonary vascular resistance. Conversely, SIRI had inverse relationships with 6-minute walking distance and left ventricular end-diastolic diameter. Kaplan-Meier curves revealed a significantly higher rate of clinical deterioration in individuals with SIRI > 0.741 compared to those with SIRI ≤ 0.741 (P < 0.001). Adjusted Cox analysis showed SIRI remained an independent predictor of clinical worsening (hazard ratio 1.366, 95% confidence interval 1.073-1.738, P = 0.011). ROC analysis demonstrated SIRI provided additional predictive value beyond the risk assessment score of the European Society of Cardiology/European Respiratory Society. Discussion: In summary, SIRI could predict the severity and prognosis of IPAH independently. It was associated with various indicators of IPAH severity and was a significant predictor of clinical deterioration. SIRI also offered additional predictive value beyond existing risk assessment scores.

Sleep-disordered breathing patterns and prognosis in pulmonary arterial hypertension: A cluster analysis of nocturnal cardiorespiratory signals.

BACKGROUND: Sleep-disordered breathing (SDB) is common among pulmonary arterial hypertension (PAH) patients and has been associated with unfavorable outcomes. This study aims to cluster overnight cardiorespiratory signals to investigate PAH phenotypes and examining their prognostic implications. METHODS: In this retrospective cohort study, we recruited consecutive PAH patients who underwent right heart catheterization and nocturnal cardiorespiratory polygraphy to evaluate SDB. Cluster analysis was employed to classify patients based on their SDB patterns. Cox regression analysis and Kaplan-Meier curves were utilized to assess the association between cluster membership and clinical outcomes. Logistic regression was used to identify risk factors associated with the cluster at higher risk of adverse outcomes. RESULTS: The study comprised 386 PAH patients, with a mean age of 44.7 ± 17.0 years, of which 46.6 % were male. Three distinct clusters of PAH patients were identified: Cluster 1 (N = 182) presented with minimal SDB, Cluster 2 (N = 125) displayed obstructive sleep apnea (OSA) without significant hypoxemia, and Cluster 3 (N = 79) exhibited predominantly severe hypoxemic burden along with comorbid OSA. Notably, patients in Cluster 3 had an independent association with an increased risk of clinical worsening (hazard ratio 1.96, 95 % confidence interval [CI] 1.08-3.56, P = 0.027) compared to those in Clusters 1, even after adjusting for common confounders. The rate of clinical worsening for PAH-related events and mortality was higher in Cluster 3 than in Clusters 1 and 2 (26.6 % vs. 12.6 % and 19.2 %, respectively, log-rank P = 0.024). Moreover, the left ventricular mass index was identified as an independent risk factor for Cluster 3 (odds ratios 1.01, 95 % CI 1.00-1.02, P = 0.004). CONCLUSIONS: Patients with PAH who have nocturnal hypoxemia and OSA had worse clinical outcomes compared to those with only minimal SDB. Tailored management strategies that address both PAH and nocturnal hypoxemia may be effective in improving clinical outcomes.

Angiographic classification of total occlusion and its implication on balloon pulmonary angioplasty.

AIMS: Despite refinements in balloon pulmonary angioplasty (BPA), total occlusion remains a challenge in chronic thromboembolic pulmonary hypertension (CTEPH). Owing to their low success and high complication rates, most interventional cardiologists are reluctant to address total occlusion, and there is a paucity of literature on BPA performance in total occlusion. We aimed to classify total occlusion according to morphology and present an illustrative approach for devising a tailored treatment strategy for each distinct type of total occlusion. METHODS AND RESULTS: All patients diagnosed with CTEPH who underwent BPA between May 2018 and May 2022 at Fuwai Hospital in Beijing, China, were included retrospectively. A total of 204 patients with CTEPH who underwent BPA were included in this study. Among these, 38 occluded lesions were addressed in 33 patients. Based on the morphology, we categorized the lesions into three groups: pointed-head, round-head, and orifice occlusions. Pointed-head occlusion could be successfully addressed using soft-tip wire, round-head occlusion warranted hard-tip wire and stronger backup, and orifice occlusion warranted the strongest backup force. The success rates for each group were as follows: pointed-head (95.45%), round-head (46.15%), and orifice occlusion (33.33%), with orifice occlusion having the highest complication rate (50%). The classification of occlusion was associated with BPA success (round-head occlusion vs. pointed-head occlusion, OR 24.500, 95% CI 2.498-240.318, P = 0.006; orifice occlusion vs. pointed-head occlusion, OR 42.000, 95% CI 3.034-581.434, P = 0.005). CONCLUSIONS: Occlusion morphology has a significant impact on BPA success and complication rates. A treatment strategy tailored to each specific occlusive lesion, as outlined in the present study, has the potential to serve as a valuable guide for clinical practitioners.

Development and validation of a nomogram for predicting hemodynamic response to balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) can effectively alleviate pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Identifying predictors of unfavorable hemodynamic response to BPA is essential to guide clinical practice. Therefore, our objective was to construct and validate a nomogram to facilitate clinicians predicting hemodynamic response to BPA. METHODS: Patients with CTEPH and underwent BPA from May 2018 to April 2022 were retrospectively collected. Favorable hemodynamic response to BPA was defined as a mean pulmonary arterial pressure ≤30 mmHg and/or a reduction in pulmonary vascular resistance ≥30 % at follow-up. RESULTS: A total of 155 patients were included. At baseline, patients with favorable hemodynamic response had significantly lower proportion of occlusive lesions (11.11 % vs. 26.32 %, P = 0.017), higher diffusing capacity of the lungs for carbon monoxide (63.77 % ± 14.10 % vs. 59.11 % ± 11.78 %, P = 0.039), and better cardiac morphology than counterparts. LASSO regression and random forest were used to construct prediction models respectively. The LASSO regression model demonstrated better predictive ability and accuracy than the random forest model, as evidenced by higher area under curve (0.745 vs. 0.740) and lower Brier score (0.192 vs. 0.195). A nomogram was constructed based on the LASSO regression model, consisting of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter, number of treated pulmonary vessels and proportion of occlusion lesions. High predictive ability of the LASSO model was preserved in validation (C index 0.744). CONCLUSIONS: The current study constructed a nomogram with high accuracy in predicting BPA hemodynamic outcome, which could facilitate decision-making in clinical practice.

Impact of Obstructive Sleep Apnea on Disease Severity and Adverse Outcomes in Patients with Acute Pulmonary Embolism.

Purpose: Acute pulmonary embolism (PE) poses a life-threatening risk with high mortality rates. While the coexistence of PE and obstructive sleep apnea (OSA) is gaining recognition, its influence on PE severity and prognosis remains uncertain. This study aims to investigate the associations between OSA and disease severity, as well as outcomes, in patients with acute PE. Patients and Methods: We conducted a retrospective cohort study on patients diagnosed with acute PE who had undergone previous cardiorespiratory polygraphy. OSA severity was assessed using the apnea-hypopnea index (AHI) derived from cardiorespiratory polygraphy. The severity of acute PE was evaluated using the simplified Pulmonary Embolism Severity Index (sPESI) score. Logistic regression analysis was performed to investigate the associations between AHI and the risk of belonging to the sPESI≥1 group. Cox regression analysis was used to examine the relationship between AHI and long-term adverse events, defined as a composite of all-cause mortality and non-fatal cardiovascular events. Results: Among 145 acute PE patients (mean age 62.2 years, 49.7% male), 94 (64.8%) had OSA. Patients with OSA had a significantly higher proportion of sPESI≥1 (89.4% vs 68.6%, p=0.002) than non-OSA patients. Each unit increase in AHI was associated with a 15% increased risk of severe PE (sPESI≥1) (odds ratio: 1.15, 95% CI 1.05-1.26, p=0.002) after adjusting for confounders. During a median follow-up of 15.2 months, 27 (18.6%) patients experienced adverse events. Increased AHI independently predicted a higher risk of adverse events (hazard ratio: 1.03, 95% CI: 1.00-1.05, p=0.026), even after adjusting for potential confounders. AHI ≥8 events/h was associated with a significantly higher adjusted hazard ratio of 2.56 (95% CI: 1.15-5.72, p=0.022) for adverse events compared to AHI <8 events. Conclusion: OSA is common in acute PE patients and is linked to increased disease severity and adverse outcomes. Implementing routine OSA screening and management may aid risk stratification and improve outcomes in acute PE patients.

The potential of cystatin C as a predictive biomarker in pulmonary hypertension.

BACKGROUND: Cystatin C is a novel biomarker to identify renal dysfunction and cardiovascular risk. OBJECTIVE: The aim of this study was to investigate the role of cystatin C in non-invasive risk prediction in a large cohort of patients with pre-capillary pulmonary hypertension (PH). METHOD: We retrospectively analyzed pre-capillary PH patients with available cystatin C and hemodynamic data derived from right heart catheterization. RESULTS: A total of 398 consecutive patients with confirmed pre-capillary PH were recruited from Fuwai Hospital between November 2020 and November 2021. Over a median duration of 282 days, 72 (18.1%) of these patients experienced clinical worsening. Cystatin C levels significantly correlated with cardiac index (r = -0.286, P < 0.001), mixed venous oxygen saturation (r = -0.216, P < 0.001), and tricuspid annular plane systolic excursion (r = -0.236, P < 0.001), and high cystatin C levels independently predicted a poor prognosis after adjusting potential confounders in different models (all P < 0.05). A three-group non-invasive risk model was constructed based on the combined assessment of the cystatin C and WHO-FC using dichotomous cut-off value. Those patients with higher cystatin C (≥ 1.0 mg/L) and a worse WHO-FC experienced the highest risk of endpoint occurrence. The predictive capacity of this model was comparable to that of an existing invasive risk stratification model (area under curve: 0.657 vs 0.643, P = 0.619). CONCLUSIONS: Cystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH. A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration.

The influence of successor's implicit power and explicit power on dual innovation---The mediating effect of board dissent.

This study explores the influence of the power of family business successors on firm innovation under the theory of social embeddedness. Based on the 2000-2019 unbalanced panel data of listed Chinese family enterprises, this study empirically examines the differences in the influence of the implicit and explicit power of successors on incremental and radical innovation respectively. Our findings show that explicit power has a more positive impact on incremental innovation, while implicit power is more conducive to promoting radical innovation. In addition, the study finds that the reason why the explicit power of succession does not have a significant impact on radical innovation, that is, the reason why board dissent is not related to radical innovation, is that some of the major innovation decisions in the enterprise are not all made at formal meetings. The research conclusions not only extend the theoretical application of social embeddedness in family enterprises, but also provide certain practical guidance for promoting enterprise innovation.

In vitro particle image velocity measurements in a model root canal: flow around a polymer rotary finishing file.

INTRODUCTION: Root canal irrigation is vital to thorough debridement and disinfection, but the mechanisms that contribute to its effectiveness are complex and uncertain. Traditionally, studies in this area have relied on before-and-after static comparisons to assess effectiveness, but new in situ tools are being developed to provide real-time assessments of irrigation. The aim in this work was to measure a cross section of the velocity field in the fluid flow around a polymer rotary finishing file in a model root canal. METHODS: Fluorescent microparticles were seeded into an optically accessible acrylic root canal model. A polymer rotary finishing file was activated in a static position. After laser excitation, fluorescence from the microparticles was imaged onto a frame-transfer camera. Two consecutive images were cross-correlated to provide a measurement of a projected, 2-dimensional velocity field. RESULTS: The method reveals that fluid velocities can be much higher than the velocity of the file because of the shape of the file. Furthermore, these high velocities are in the axial direction of the canal rather than only in the direct of motion of the file. CONCLUSIONS: Particle image velocimetry indicates that fluid velocities induced by the rotating file can be much larger than the speed of the file. Particle image velocimetry can provide qualitative insight and quantitative measurements that may be useful for validating computational fluid dynamic models and connecting clinical observations to physical explanations in dental research.