Ischemic Research Articles

Assisting significance of lncRNA ASB16-AS1 in the early detection and prognosis prediction of patients with deep venous thrombosis

BackgroundDeep venous thrombosis (DVT) is a kind of vascular obstruction, that commonly and widely occurs in lower limbs. Due to the lack of obvious symptoms in the early stage, the rate of misdiagnosis and missed diagnosis is high. This study evaluated the expression and significance of lncRNA ASB16-AS1 (ASB16-AS1) in DVT aiming to identify a novel biomarker for its screening and monitoring.MethodsThere were 77 DVT patients and 62 healthy individuals included in this study. Plasma ASB16-AS1 level was evaluated using PCR and compared between DVT and healthy groups. The diagnostic and prognostic values of ASB16-AS1 were assessed with ROC and Cox analyses. The correlation of ASB16-AS1 with patients’ conditions, inflammation, and oxidative stress was evaluated by Spearman correlation analysis.ResultsASB16-AS1 was significantly upregulated in DVT (P < 0.001), which could discriminate DVT patients from healthy individuals with high sensitivity and specificity (AUC of ROC = 0.858). Increased ASB16-AS1 was associated with the incidence of complications (P = 0.033) and especially for pulmonary embolism in patients (P = 0.029). ASB16-AS1 was negatively correlated with prothrombin time (PT, r = -0.763), antithrombin level (AT, r = -0.711), and international normalized ratio (INR, r = -0.764), and showed positive correlation with fibrinogen (FIB, r = 0.793) and D-dimer (D-D, r = 0.731). Additionally, ASB16-AS1 was positively correlated with pro-inflammation cytokines (rIL−6 = 0.853, rIL−10 = -0.836, rhsCRP = 0.787) and pro-oxidative stress factors (rSOD = -0.751, rMDA = 0.842, r8-isoPGF2α = 0.840).ConclusionUpregulated ASB16-AS1 was identified as a diagnostic and prognostic biomarker of DVT and was closely associated with inflammation and oxidative stress during DVT.

Vitreous hemorrhage in patients with uveitis: a comparative study between adults and children.

To compare clinical findings and visual outcomes of vitreous hemorrhage (VH) associated with uveitis in adults versus children. A retrospective comparative study. There were 36 adults (44 eyes) and 10 children (12 eyes). Median age was 35years in the adult group and 9.5years in the pediatric group. VH was the presenting manifestation of the underlying uveitis in 45.7% of patients. VH in the adult group was more frequently associated with vascular sheathing, retinal hemorrhages, and extensive peripheral retinal ischemia on fluorescein angiography (FA), whereas VH in the pediatric group was associated with a significantly lower presenting visual acuity, and more frequently with vitritis and non-occlusive retinal vasculitis with fern-like retinal capillaritis. The most common source of bleeding was ischemia-driven retinal or optic disc neovascularization in the adult group (81.8%, p ≤ 0.001) and inflammation-driven optic disc neovascularization in the pediatric group (66.6%, p ≤ 0.001). A retinal vasoproliferative tumor was the cause of VH in one child (1.8%). Tuberculosis and Behçet's uveitis were the most common etiologies of uveitis in the adult group. Idiopathic intermediate uveitis/pars planitis was the leading cause of VH in the pediatric group. The mean final visual acuity was significantly higher in the pediatric group (20/25) than in the adult group (20/50) (p = 0.045). VH associated with uveitis has a distinctive clinical and etiological profile between adults and children. The main source of bleeding was ischemia-driven neovascularization in adults and inflammation-driven neovascularization in children.

Cardiac resynchronization therapy in heart failure based on Strauss criteria for left bundle branch block.

The left bundle branch block (LBBB) is a strong predictor of response to cardiac resynchronization therapy (CRT). However, a significant number of patients do not respond to the treatment. The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St-LBBB) on CRT response, hospitalizations, ventricular arrhythmia (VA) events and mortality. This study is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided into two groups according to the fulfilment or not of St-LBBB criteria. The study included 82 patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy [46 (56%) with St-LBBB and 36 (44%) with non-St-LBBB]. Patients with St-LBBB showed higher CRT response rates compared with those with non-St-LBBB (P<0.01), while the group with NICM exhibited the greatest benefit (P<0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (P<0.0001) compared with the non-St-LBBB group. According to Kaplan-Meier time curves, this was primarily evident in patients with NICM (P<0.0001). CRT responders displayed significantly fewer VA events (P<0.001) and lower mortality rates (P<0.0001) than non-responders. Kaplan-Meier estimates demonstrated a significantly lower incidence of VAs in NICM patients with St-LBBB (P=0.049) compared with ICM patients with St-LBBB (P=0.25). Lower mortality rates were observed in CRT responders than non-responders (P<0.0001), with the group of NICM with St-LBBB criteria exhibiting the greatest benefit (P=0.0238). Patients with NICM and St-LBBB present the greatest benefit concerning CRT response, HF hospitalizations, VA events and mortality. Although St-LBBB criteria seem to improve patient selection for CRT, more data are needed to elucidate the role of St-LBBB criteria in this setting.

Cadmium exposure induces inflammation, oxidative stress and DNA damage in HUVEC and promotes THP-1 adhesion: A possible mechanism on the formation of atherosclerotic plaque.

Observational studies have shown that cadmium exposure increases the risk of cardiovascular disease, but the underlying mechanism is still unclear. Atherosclerotic plaque can cause vascular obstruction, which is important for the death from cardiovascular disease. Cell damage and monocyte adhesion are two early events in atherosclerotic plaque formation that can be induced by cadmium exposure, but the mechanism remains to be determined. This study was carried out to investigate the toxicity of cadmium in HUVECs and the effect of cadmium on the adhesion of THP-1 cells, and further explored the possible mechanisms. Rhodamine staining, DCFH-DA staining, Hoechst33258 staining, morphological observation and western blot were used to detect mitochondrial membrane potential, ROS, apoptosis, cell adhesion, signaling pathways and cell adhesion factors respectively. The results indicated that cadmium exposure increased the level of ROS, activated MAPK signaling pathway and resulted in cellular oxidative stress in HUVECs. Exposure to cadmium made nuclear shrinkage, activated DNA damage response pathways and mitochondria-mediated intrinsic apoptosis pathway in HUVECs. Cadmium exposure activated the NLRP3 inflammasome and NF-κB signaling pathway, led to the upregulation of inflammatory cytokines in HUVECs. In addition, cadmium exposure also upregulated the adhesion factors including ICAM-1, VCAM-1 and E-Selectin via NF-κB signaling pathway and resulted in the adhesion of THP-1 cells. The present study elucidated that cadmium could damage the HUVECs and promote the adhesion of THP-1 cells, which clarified the toxicity of cadmium in HUVECs and revealed the possible mechanism for the occurrence of cardiovascular disease induced by cadmium.

Acute alterations in blood lactate in the setting of transient stress induced myocardial ischaemia

Abstract Background An elevation in resting venous blood lactate levels ([La-]b) in conditions of myocardial hypoperfusion is associated with adverse prognosis and survival. This investigation aimed to assess changes in venous [La-]b levels induced by dobutamine stress in the presence and absence of myocardial ischaemia and adverse outcomes at 1-year. Methods 404 consecutive patients (mean age 70±10 years, 243 male) reporting chest pain underwent dobutamine stress echocardiography and were categorised as ischaemic (IS) or non-ischaemic (NI) responders. Conventional and global longitudinal strain (GLS) echocardiographic measures were recorded at rest. Venous [La-]b samples were acquired at rest, peak stress and 1, 3, 5 and 10-minutes into recovery using a commercially available Lactate Pro 2 device. Results There were no significant differences in [La-]b concentrations between IS (1.75±0.76 mmol×L-1) and NI (1.73±0.60 mmol×L-1) responders at baseline (p=0.592). However, [La-]b concentrations were significantly greater at peak stress (1.83±0.57 vs. 1.68±0.60 mmol×L-1), 1 (1.90±0.56 vs. 1.73±0.71 mmol×L-1), 3 (1.97±0.56 vs. 1.73±0.71 mmol×L-1), 5 (1.98±0.60 vs. 1.74±0.70 mmol×L-1), and 10-minutes (2.01±0.63 vs. 1.76±0.71 mmol×L-1) into recovery between IS and NI responders (all p&amp;lt;0.001), respectfully. GLS was significantly lower in IS compared to NI responders (-15.5±2.9 vs -16.2±2.7%, p=0.02) at baseline. In patients who experienced an adverse cardiac event during 1-year of follow-up, GLS (-14.4±2.7 vs -16.1±2.8%, p&amp;lt;0.001) and [La-]b concentrations were significantly lower at baseline (1.54±0.55 mmol×L-1 vs. 1.78±0.70 mmol×L-1, p=0.02), as were [La-]b concentrations at 5 (1.68±0.55 mmol×L-1 vs. 1.88±0.68 mmol×L-1, p=0.04) and 10-minutes (1.70±0.56 mmol×L-1 vs. 1.93±0.71 mmol×L-1, p=0.02) into recovery compared to patients who did not experience an adverse event, respectively. GLS (HR 1.21; 95% CI 1.11 to 1.33, p&amp;lt;0.001) and [La-]b concentrations at 10-minutes into recovery (HR 0.54; 95% CI 0.33 to 0.85, p=0.01) were significant independent predictors of an adverse event. Conclusions Transient myocardial ischaemia is associated with a significant elevation in [La-]b concentrations, which extends into the recovery period, compared to NI responders. A blunted metabolic response to dobutamine stress and attenuated longitudinal myocardial mechanics are independently associated with short-term adverse events.

Temporal profiling of M-TEER-related complications.

Transcatheter edge-to-edge repair of the mitral valve (M-TEER) is known for its low complication rates. However, the optimal level and duration of post-procedural care remain unclear. This study aimed to identify the specific timeframe of post-procedural complications following M-TEER. We conducted a retrospective analysis of 865 patients who underwent M-TEER at the University Hospital Düsseldorf between August 2010 and August 2023. Our analysis focused on a comprehensive examination of all acute post-procedural complications (1-100h), considering the time point of occurrence or diagnosis. The complication analysed included cardiogenic shock, pericardial tamponade, stroke, cardiac arrhythmias, bleeding, acute kidney injury, myocardial infarction, peripheral vascular ischaemia and in-hospital mortality. The median age was 80 (74, 84) years, and the EuroScore II was high (6.5 [4.0, 12.0] %). Functional mitral regurgitation (MR) was more common than degenerative or mixed MR (69% vs. 20%. respectively; 11%). Technical success rate was 97.2%. Overall, acute post-procedural complications occurred in 87 patients (10.1%). Most complications (75.9%) occurred within the first 4h post-procedure. 12.6% of the complications occurred during the period between 4 and 24h post-procedure, and 11.5% of the complications happened between 24 and 100h post-procedure. Life-threatening complications were observed only within the first 4h post-procedure. The majority of post-procedural complications after M-TEER occur within the first 4h, with pericardial tamponade and major bleeding occurring only during this period. These findings provide valuable insight for physicians in determining the optimal surveillance and monitoring duration after M-TEER within clinical settings.

Role of C-Reactive Protein as a Predictor of Early Revascularization and Mortality in Advanced Peripheral Arterial Disease

Background: Elevated high-sensitivity C-reactive protein (hsCRP) levels are associated with poor cardiovascular outcomes, particularly in patients with advanced peripheral arterial disease (PAD). This study aimed to assess the impact of hsCRP on clinical characteristics and long-term outcomes in a cohort of PAD patients. Methods: A total of 346 patients with advanced PAD were enrolled and stratified into two groups based on their median hsCRP level (Group 1: &lt;0.32 mg/dL, Group 2: &gt;0.32 mg/dL). The patients were followed for a mean of 102.70 ± 44.13 months. Their clinical characteristics, comorbidities, and long-term cardiovascular events, including myocardial and/or peripheral revascularization, ischemia, and death, were analyzed. This study evaluated two composite endpoints: major adverse cardiovascular events (MACEs) and major adverse peripheral events (MAPEs). MACEs comprised fatal cardiovascular events, cerebral ischemia, cardiac infarction, myocardial revascularization, acute peripheral arterial occlusion, and peripheral reperfusion. MAPEs included carotid reperfusion, acute peripheral arterial occlusion, and lower limb revascularization. Results: The patients in Group 2 had a higher body mass index, waist circumference, and waist–hip ratio compared to those in Group 1 (all p &lt; 0.05). Inflammatory markers, including fibrinogen and the erythrocyte sedimentation rate, were significantly elevated in Group 2 (both p &lt; 0.01). While the overall incidence of peripheral revascularization was similar between groups, these interventions occurred significantly earlier in Group 2 (28.24 ± 38.87 months vs. 67.04 ± 49.97 months, p = 0.004; HR: 2.015, 95% CI: 1.134–3.580, p = 0.017). The MAPEs were comparable in number, but occurred earlier in Group 2 (36.60 ± 37.35 months vs. 66.19 ± 48.18 months, p &lt; 0.01; HR: 1.99, 95% CI: 1.238–3.181, p = 0.004). Similarly, the MACEs had an earlier onset in Group 2 (40.31 ± 38.95 months vs. 55.89 ± 46.33 months, p = 0.04; HR: 1.62, 95% CI: 0.983–1.987, p = 0.062). A total of 169 deaths were recorded during the follow-up. Group 2 exhibited a significantly higher mortality rate (56% vs. 42%, p &lt; 0.01) and an earlier trend in mortality (76.58 ± 43.53 months vs. 84.86 ± 5.18 months), although this difference did not reach statistical significance (p = 0.22). Conclusions: Elevated hsCRP levels (&gt;0.32 mg/dL) are associated with a worse clinical profile and earlier adverse events in patients with advanced PAD. Group 2 experienced significantly earlier peripheral revascularization, MACEs, and MAPEs. The mortality rates were also significantly higher, highlighting the prognostic value of hsCRP in this population.

Vascular flow alteration is a dominant pattern of liver pathology in patients with orthotopic lung transplants: a retrospective observational study.

The number of orthotopic lung transplants (OLT) has skyrocketed since the 1960s, generating an ever-increasing cohort of post-OLT patients. Many challenges exist in the post-OLT timeframe, including donor graft dysfunction, infection, malignancy, and immunosuppression-related conditions. A rather elusive topic in the posttransplant setting remains the impact of the underlying disease process and donor lungs on other organ systems and the complications arising from the complex physiologic interactions. The liver represents a vital organ often impacted in many ways by the lung transplant procedure. Also, there is a higher likelihood of adverse outcomes in OLT recipients who have significant liver pathology. Yet little is known about the morphologic changes in liver after patients have received an OLT. In this study we retrospectively reviewed liver pathology cases obtained after the patient received an OLT. Histology was reviewed by three pathologists and evaluated with a standardized checklist format. In our cohort, we found morphologic features of hepatic injury in the form of vascular outflow obstruction, nodular regenerative hyperplasia, portal vessel changes, and steatosis/steatohepatitis, but there was a striking absence of advanced fibrosis in our cohort. Here we present the first comprehensive account of morphologic changes in livers of post-OLT patients. We believe that this information will aid clinical decision-making during monitoring of hepatic function and fibrosis in patients with OLT and other complex pulmonary diagnoses.

Development and validation of a Prediction Model for Chronic Thromboembolic Pulmonary Disease

BackgroundAcute pulmonary embolism (APE) is a critical disease with a high mortality rate, some of the surviving patients may develop chronic thromboembolic pulmonary disease (CTEPD), which affects the patient’s prognosis. However, the research on the early diagnosis of CTEPD is limited. This study aimed to establish a prediction model for earlier identification of CTEPD.MethodsThis prospective study included 464 consecutive patients with APE confirmed between January 2020 and September 2023, at 7 centers from China. After follow-up for at least 3 months, the patients were divided into the CTEPD and non-CTEPD groups based on symptoms and computed tomography pulmonary angiography (CTPA) or pulmonary ventilation perfusion (V/Q) scans showing residual thrombosis. The independent risk factors for CTEPD were identified via univariate and multivariate logistic regression analyses. Next, a nomogram of predictive model was established, and validation was completed via decision curve analysis (DCA) and receiver operating characteristic curve analysis.ResultIn total, 130 (28%) patients presented with CTEPD, 17% (22/130) of CTEPD patients developed chronic thromboembolic pulmonary hypertension (CTEPH). Based on the multivariate analysis, a time interval from symptoms onset to diagnosis (time-to-diagnosis) ≥ 15 days (95% confidence interval [CI]: 3.392–14.972, p < 0.001), recurrent pulmonary embolism (RPE) (95%CI: 1.560–17.300, p = 0.007), right ventricular dysfunction (RVD) (95%CI: 1.042–6.437, p = 0.040), central embolus (95%CI: 1.776–7.383, p < 0.001) and residual pulmonary vascular obstruction (RPVO) > 10% (95%CI: 4.884–21.449, p < 0.001) were identified as the independent predictors of CTEPD. Then, A prediction model with a C-index of 0.895 (95% CI 0.863–0.927) was established for high-risk patients. The nomogram had an excellent predictive performance for earlier identification of CTEPD, with an area under the curve of 0.908 (95%CI: 0.875–0.941) in the training cohort and 0.875 (95%CI: 0.803–0.947) in the validation cohort.ConclusionThe current study established and validated a reliable nomogram for predicting CTEPD, which would assist clinicians identify the high-risk patients for CTEPD earlier.

Invasive Cardiopulmonary Exercise Testing in Chronic Thromboembolic Pulmonary Disease; Obesity and the VE/VCO2 Relationship.

Background: Invasive cardiopulmonary exercise testing (iCPET) provides valuable insight into dyspnea in patients with chronic thromboembolic pulmonary disease, in part through an increased relationship of minute ventilation to CO2 production (VE/VCO2). Obesity lowers the VE/VCO2 in patients without cardiopulmonary disease; however, whether this holds true in obese subjects with chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) is unknown. Objective: Report on the iCPET findings of patients with CTEPH and CTEPD and investigate the relationship between obesity and gas exchange parameters, especially VE/VCO2 in these patients. Methods: Retrospective analysis of CTEPH and CTEPD patients undergoing iCPET. Results: We studied 60 patients; 34 (56.7%) had CTEPH and 26 (43.3%) had CTEPD. The mean age was 61.2 ± 14 years and the mean BMI was 31.8 ± 8.3 mg/kg2. A higher VE/VCO2 (41.9 ± 10.2 vs. 36.8 ± 8.9; p = 0.045) was observed in CTEPH vs. CTEPD. There was an inverse relationship between the VE/VCO2 slope and BMI. For an increase of 1 point in BMI, the VE/VCO2 slope fell by 0.6 in CTEPD and 0.35 in CTEPH (p < 0.001). The mean VE/VCO2 slope in CTEPH and CTEPD groups was 48.6 ± 10.4 in BMI < 25 and 31.3 ± 6.5 in BMI > 35 (p < 0.001). The lower VE/VCO2 slope in obesity relates to an increased VCO2/work rate relationship; there was no difference in the VE/work relationship. Conclusions: The VE/VCO2 slope is markedly reduced by obesity, independent of the level of pulmonary vascular obstruction in CTEPH or CTEPD. Thus, obesity masks key physiologic evidence of pulmonary vascular obstruction on the gas exchange assessment of obese individuals.

Rare Presentation of Echinococcal Disease: A Systematic Review on Arterial Hydatid Cyst.

Echinococcosis is a parasitic disease caused by Echinococcus granulosus that most commonly affects the liver (70%) and lungs (20%). Despite rarely reported, arterial echinococcosis represents a severe and potentially life-threatening condition but management strategies and related outcomes have not been fully investigated. A comprehensive review of the international English literature was performed on PubMed, Scopus, and Web of Science from inception to May 30, 2024 to identify relevant articles about arterial echinococcosis. Data regarding epidemiology, pathogenesis, clinical presentation, diagnostic methods, and treatment were investigated. A total of 143 articles were screened and 30 articles were included. Overall 32 cases were identified. About half of the patients were female (18, 56.2%) and the mean age was 40.6years (range 12-60years). Echinococcus cyst was more commonly detected on the aorta (27, 84.3%) in association or not with other cysts on the iliofemoral axis. Five cases (15.2%) affected only peripheral arteries. Most patients presented with chronic pain due to vascular obstruction or thromboembolism, while one patient was asymptomatic. In most cases (31, 96.8%) a total surgical excision was done in association with antiparasitic treatment using albendazole (17, 53.1%) or mebendazole (4, 12.5%). Arterial reconstruction was required in 19 cases (59.4%) and done with prosthetic substitutes or bovine pericardium. Only one case (3%) was treated with an endovascular approach. Four patients (12.5%) died in-hospital from hemorrhagic shock (3) or respiratory failure (1). During the follow-up period (mean 14months, range 2-72months) only one recurrence was reported. Arterial echinococcosis is an extremely rare condition that may potentially be lethal. The current review showed favorable outcomes following complete surgical excision and antiparasitic drug that currently remain the only definitive treatment.

Evaluation of Peripheral Circulatory Changes Following Hydrotherapy and Controlled Physical Training in Patients with Atherosclerotic Lower Limb Ischemia.

One hundred participants (both male and female) aged between 39 and 79 years old (60.0 ± 11.6) were included in the analysis, all diagnosed with peripheral circulation disorders. The participants were assigned to two groups. The study group received 10 whirlpool treatments of the lower limbs and a personalized training program. The control group only participated in the training sessions. Pre- and post-intervention evaluations included impedance plethysmography and the six-minute walk test (6MWT). Assessing the results of local flow parameters, after the procedures, a statistically significant increase in the pulse wave amplitude (PAmpl, p < 0.001) and systolic slope (PSlope, p < 0.001) values was found, as well as a statistically significant decrease in the crest time (CT, p < 0.001) and propagation time (PT, p = 0.007) values in the study group, which indicates an improvement in blood flow in the peripheral circulation. Also, in the 6 min walk test, a statistically significant increase in the walking distance was noted in the study group after the procedures. Physical training, combined with whirlpool massage treatment, has a beneficial effect on improving peripheral blood flow assessed by impedance plethysmography, as well as patients' tolerance to physical exercise. The inclusion of hydrotherapy as part of cardiovascular rehabilitation protocols in patients with peripheral ischemia is a promising form of conservative treatment.

Timing of Iliofemoral Vein Stent Implantation after Mechanical Thrombectomy for Acute Iliofemoral Venous Thrombosis.

Comparison of the treatment effects of immediate stent implantation vs staged stent implantation after AngioJet mechanical thrombectomy in patients with acute iliofemoral venous thrombosis. A study included 80 patients with acute iliofemoral venous thrombosis formed between June 2021 and February 2023. They were divided into two groups: the direct implantation group (37 patients, 9 males) and the staged implantation group (43 patients, 10 males). Venous angiography and Villata scoring were used to assess patency rates and the occurrence of post-thrombotic syndrome (PTS). A one-year follow-up was conducted and a multiple-factor Cox regression model was used to analyze the clinical factors affecting patency rates. Surgery was successfully completed without serious complications or deaths during follow-up. The direct implantation group had significantly shorter hospital stays and surgical times compared to the staged implantation group (p < 0.001). Both groups showed a decrease in Villata scores (p < 0.001), and the direct group had higher scores than the staged group at 12 months post-surgery (p < 0.001). One year after the procedure, there was no significant difference in stent patency rates (p = 0.658), but postoperative scores at one month (p = 0.012) and stent length (p = 0.015) had a significant impact. For acute iliofemoral venous thrombosis, both direct stent implantation and staged implantation are effective. The direct implantation procedure has shorter hospital stays and surgical times, while staged implantation has a lower long-term risk of post-thrombotic syndrome (PTS). Villata scores at one month after surgery can predict the risk of vascular obstruction. Longer stents may reduce the risk of postoperative obstruction.

Defining the causes for Fontan circulatory failure in total cavopulmonary connection patients.

This study aims to identify causes of failure in Fontan patients with a total cavopulmonary connection. We conducted a comprehensive review of all patients who underwent a total cavopulmonary connection procedure at our centre between 1988 and 2023, aiming to identify and analyze the factors contributing to Fontan failure (defined as mortality, heart transplantation, Fontan takedown, protein-losing enteropathy, plastic bronchitis, or New York Heart Association Functional Classification class III or IV). The study included 217 patients (median age at time of Fontan completion 3.7 years) with a median follow-up of 12.7 years (IQR, 7.2; 17.7). Systolic ventricular function decreased significantly over time in patients with right ventricular dominant morphology (P = 0.002), while systolic ventricular function remained stable in patients with left ventricular dominant morphology. Fontan failure occurred in 24 patients, with estimated freedom from Fontan failure rates of 97.7% (95% CI, 95-99) at 1 year, 93.9% (95% CI, 89-97) at 15 years and 77.2% (95% CI, 65-86) at 20 years follow-up. Systolic ventricular dysfunction was the most common cause of failure (29%), followed by atrioventricular valve regurgitation (16.7%), a high pulmonary vascular resistance (16.7%), restrictive pathophysiology (16.7%) and obstruction (12.5%). Patients with right ventricular dominance developed most often systolic ventricular dysfunction, while patients with left ventricular dominant morphology developed most often restrictive pathophysiology or a high pulmonary vascular resistance. Approximately 10% of patients experienced Fontan failure within 15 years postoperatively. Patients with right ventricular dominance experienced progressive decline due to systolic dysfunction, while those with left ventricular dominance exhibited failure due to restrictive pathophysiology or high pulmonary vascular resistance.

Exploring the Endothelin-1 pathway in chronic thromboembolic pulmonary hypertension microvasculopathy.

Targeted vasopeptide therapies have significantly advanced the management of pulmonary arterial hypertension (PAH). However, due to insufficient preclinical evidence regarding the involvement of the endothelin-1 (ET-1) pathway in chronic thromboembolic pulmonary hypertension (CTEPH) pathophysiology, the potential of ET-1 receptor antagonism in treating CTEPH remains uncertain. In this study, we investigated the role of the ET-1 pathway in CTEPH microvasculopathy using a multifaceted approach. Plasma ET-1 levels were measured in a cohort of 59 CTEPH patients and 41 healthy controls. Additionally, we evaluated the expression of key ET-1 pathway members in pulmonary explants from CTEPH, idiopathic PAH, and control patients. We used an in vitro system to test the hypothesis that the turbulent flow, observed near the vascular obstructions pathognomonic of CTEPH, enhances ET-1 expression. Our findings were further validated in vivo using a CTEPH piglet model that contains distinct regions representing pre- and post-thrombus lung territories. We found a twofold increase in circulating ET-1 levels in CTEPH patients compared to healthy subjects. Pulmonary explants from CTEPH patients exhibited pronounced overexpression of ET-1, endothelin receptor A (ETA), and phosphorylated myosin light chain (p-MLC) in muscularized pulmonary microvessels, suggesting heightened vascular contraction. In vitro experiments showed that turbulent flow facilitates ET-1 secretion compared to laminar flow regions. Additionally, in the CTEPH piglet model, elevated plasma ET-1 levels were observed compared to controls. Immunofluorescence and confocal microscopy analyses confirmed increased ETA and p-MLC in remodeled arteries from both pulmonary territories. However, ET-1 protein elevation was exclusively observed in the obstructed territory. These findings collectively indicate impaired vascular tone in microvessels of CTEPH patients and the CTEPH piglet model. Furthermore, our data implicates the ET-1 pathway in microvasculopathy, with turbulent flow playing a pathological role. These insights underscore the potential utility of ET-1 receptor antagonists as a promising therapeutic approach for CTEPH treatment.

Central retinal artery occlusion following surgery for thyroid eye disease: A case report.

Thyroid eye disease (TED) is the most common orbital disorder in adults and significantly affects patient health. Orbital decompression surgery is an important treatment option. Central retinal artery occlusion (CRAO) after orbital medial wall decompression is rare in patients with TED. Therefore, the earlier the identification and treatment, the more likely it is to reduce visual impairment. This paper examines a case of CRAO occurring postoperatively in a patient who underwent medial wall orbital decompression for TED. Central retinal artery occlusion. During the operation, the pupil was dilated, and eye massage and peribulbal injection of atropine were performed immediately. Fundus fluorescein angiography suggested the possibility of CRAO. Intravenous methylprednisolone 1000 mg, mannitol 50 g, ginkgo biloba extract 20 mL, nimodipine 20 mg tid, cobamamide 0.5 mg tid, and oral citicoline 0.2 g tid, along with periocular injection of atropine and hyperbaric oxygen therapy were also administered. Fifteen days after onset, the patient's retinal edema and retinal blood perfusion greatly improved. The patient's visual acuity recovered from counting fingers to 0.6. Retinal vascular obstruction is a serious threat to vision; therefore, early detection and treatment are very important.

Heart Transplantation Outcomes in Patients With Hypertrophic Cardiomyopathy in the Era of Mechanical Circulatory Support.

Mechanical circulatory support has emerged as a vital therapeutic modality for patients awaiting heart transplantation (HT). However, it is unknown how it affected the characteristics and post-HT outcomes of patients with hypertrophic cardiomyopathy (HCM). This retrospective cohort study analyzed adult HT recipients from the International Society for Heart and Lung Transplantation registry (1998-2017). Two equal-duration eras were defined: era 1 1998-2007 and era 2 2008-2017. Patients with HCM were compared across the two eras (n1 = 742 and n2 = 1,211) and within each era, they were contrasted with individuals with nonischemic (NICM) (n1 = 15,964 and n2 = 20,394) and ischemic cardiomyopathy (ICM) (n1 = 14,140 and n2 = 12,986). Across eras, the number of HTs among patients with HCM increased by 63%. The rate of recipients with HCM in the intensive care unit (ICU) supported with intra-aortic balloon pump (IABP) increased, yet their pre-HT functional status improved, and 5 year post-HT survival remained unchanged and favorable. In era 2, at the time of HT, patients with HCM were more frequently than their NICM and ICM counterparts in the ICU and supported with inotropes. In the same era, 1 and 5 year survival were more favorable in HCM compared to ICM and comparable to NICM.

Non‐occlusive mesenteric ischemia developing post‐chemotherapy for oral squamous cell carcinoma: A case report and literature review

AbstractBackgroundNon‐occlusive mesenteric ischemia (NOMI) is a rare, symptom‐scarce condition characterized by rapid progression and high mortality.Case presentationA 63‐year‐old male, after recovering from neutropenia following paclitaxel and cetuximab therapy, developed abdominal distension without subjective symptoms. Dynamic CT imaging suggested ischemia in the superior mesenteric artery region without vascular obstruction, leading to a diagnosis of NOMI. With no clear signs of intestinal necrosis, conservative treatment was chosen, but the patient succumbed within 14 h.ConclusionCancer chemotherapy agents may induce intestinal ischemia. Stomatologists should be aware of this disease and facilitate timely referral to specialists for appropriate medical care.

A bovine model of hypoxia-induced pulmonary hypertension reveals a gradient of immune and matrisome response with a complement signature found in circulation.

Pulmonary hypertension (PH) is a progressive vascular disease characterized by vascular remodeling, stiffening, and luminal obstruction, driven by dysregulated cell proliferation, inflammation, and extracellular matrix (ECM) alterations. Despite the recognized contribution of ECM dysregulation to PH pathogenesis, the precise molecular alterations in the matrisome remain poorly understood. In this study, we employed a matrisome-focused proteomics approach to map the protein composition in a young bovine calf model of acute hypoxia-induced PH. Our findings reveal distinct alterations in the matrisome along the pulmonary vascular axis, with the most prominent changes observed in the main pulmonary artery. Key alterations included a strong immune response and wound repair signature, characterized by increased levels of complement components, coagulation cascade proteins, and provisional matrix markers. In addition, we observed upregulation of ECM-modifying enzymes, growth factors, and core ECM proteins implicated in vascular stiffening, such as collagens, periostin, tenascin-C, and fibrin(ogen). Notably, these alterations correlated with increased mean pulmonary arterial pressure and vascular remodeling. In the plasma, we identified increased levels of complement components, indicating a systemic inflammatory response accompanying the vascular remodeling. Our findings shed light on the dynamic matrisome remodeling in early-stage PH, implicating a wound-healing trajectory with distinct patterns from the main pulmonary artery to the distal vasculature. This study provides novel insights into the immune cell infiltration and matrisome alterations associated with PH pathogenesis and highlights potential biomarkers and therapeutic targets within the matrisome landscape.NEW & NOTEWORTHY Extensive immune cell infiltration and matrisome alterations associated with hypoxia-induced pulmonary hypertension in a large mammal model. Matrisome components correlate with increased resistance to identify candidate alterations that drive biomechanical manifestations of the disease.

Design, Synthesis, and Anti-Inflammatory Activity Evaluation of Novel Indanone Derivatives for the Treatment of Vascular Dementia.

Vascular dementia (VaD) is a neurodegenerative disease resulting from cerebral vascular obstruction, leading to cognitive impairment, and currently lacks effective treatment options.Due to its complex pathogenesis, multi-target drug design (MTDLs) strategies are considered among the most promising therapeutic approaches. In this study, we designed and synthesized a series of novel indanone derivatives targeting targets related to vascular health and dementia. The results indicated that compound C5exhibited excellent acetylcholinesterase inhibitory activity (IC50= 1.16 ± 0.41 μM) and anti-platelet aggregation activity (IC50= 4.92 ± 0.10 μM) within ranges of 0.1-1000 μM and 0.03-300 μM, respectively, possibly mediated by molecular docking interactions. Furthermore, compound C5demonstrated protective effects on cells at concentrations ≤50 μM, significantly reducing the release of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) in a concentration-dependent manner, showcasing its potent neuroinflammatory inhibitory effects. Anti-inflammatory therapies are regarded as effective strategies for treating VaD. Therefore, compound C5holds promise as a novel candidate drug for further investigation into the treatment of vascular dementia.