Preoperative prediction of hepatocellular carcinoma microvascular invasion based on magnetic resonance imaging feature extraction artificial neural network.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence is highly correlated with increased mortality. Microvascular invasion (MVI) is indicative of aggressive tumor biology in HCC. AIM: To construct an artificial neural network (ANN) capable of accurately predicting MVI presence in HCC using magnetic resonance imaging. METHODS: This study included 255 patients with HCC with tumors < 3 cm. Radiologists annotated the tumors on the T1-weighted plain MR images. Subsequently, a three-layer ANN was constructed using image features as inputs to predict MVI status in patients with HCC. Postoperative pathological examination is considered the gold standard for determining MVI. Receiver operating characteristic analysis was used to evaluate the effectiveness of the algorithm. RESULTS: Using the bagging strategy to vote for 50 classifier classification results, a prediction model yielded an area under the curve (AUC) of 0.79. Moreover, correlation analysis revealed that alpha-fetoprotein values and tumor volume were not significantly correlated with the occurrence of MVI, whereas tumor sphericity was significantly correlated with MVI (P < 0.01). CONCLUSION: Analysis of variable correlations regarding MVI in tumors with diameters < 3 cm should prioritize tumor sphericity. The ANN model demonstrated strong predictive MVI for patients with HCC (AUC = 0.79).

A Review of the Role of Tests of Coronary Reactivity in Clinical Practice.

Vasoreactivity testing is used by cardiologists in the diagnosis of coronary spasm endotypes, such as epicardial and microvascular spasm. Intracoronary injection of acetylcholine and ergonovine is defined as a standard class I method according to the Coronary Vasomotion Disorder (COVADIS) Group. Because single vasoreactivity testing may have some clinical limitations in detecting the presence of coronary spasm, supplementary or sequential vasoreactivity testing should be reconsidered. The majority of cardiologists do not consider pseudonegative results when performing these vasoreactivity tests. Vasoreactivity testing may have some limitations when it comes to documenting clinical spasm. In the future, cardiologists around the world should use multiple vasoreactivity tests to verify the presence or absence of epicardial and microvascular spasms in the cardiac catheterisation laboratory.

Metabolic syndrome traits differentially and cumulatively influence micro- and macrovascular disease risk in patients with MASLD.

INTRODUCTION: The cumulative impact of metabolic syndrome (MetS) components on micro- and macrovascular disease in metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to determine whether the number of the MetS components increases the risk of micro- and macrovascular disease in patients with MASLD. METHODS: We performed a retrospective cohort study of electronic medical records using the TriNetX network, a global federated database. The exposure arm was patients with hepatic steatosis (defined via International Classification of Diseases, 10th Revision coding, or modified hepatic steatosis index), and ≥1 MetS components (obesity/central adiposity, insulin resistance, hypertension, or dyslipidaemia), compared with a reference arm of adults without any MetS components or hepatic steatosis. Our propensity score matched (1:1) for confounders with 5 years of follow-up. Primary outcomes included microvascular (peripheral neuropathy, retinopathy, and nephropathy) and macrovascular (cardiovascular events, cerebrovascular accidents, and peripheral vascular disease) disease. Secondary analyses assessed the impact of additional MetS components on these outcomes, as well as the impact of sex. RESULTS: MASLD, defined by hepatic steatosis and insulin resistance (n = 15 937), carried the highest risk of microvascular disease (HR 13.93 (95% CI 8.55-22.68)), whilst MASLD, defined by hepatic steatosis and hypertension (n = 53 028), carried the highest risk of macrovascular disease (7.23 (6.45-8.13)). MASLD with all MetS components carried greatest risk of both micro- (31.20 (28.88-33.70) (n = 462 789)) and macrovascular (8.04 (7.33-8.82) (n = 336 010)) disease. CONCLUSION: We demonstrate a differential effect of MetS components on micro- and macrovascular disease risk in patients with MASLD, with a cumulative impact of multiple MetS on overall risk. The impact of MetS components was most pronounced in women. Aggressive metabolic risk factor management is critical for prevention of micro- and macrovascular complications.

Comparison of Ticagrelor with Clopidogrel on Coronary Microvascular Dysfunction Following Acute Myocardial Infarction Using Angiography-Derived Index of Microcirculatory Resistance.

PURPOSE: This research aimed to assess the impact of ticagrelor and clopidogrel on coronary microvascular dysfunction (CMD) and prognosis following acute myocardial infarction (AMI), using the angiography-derived index of microcirculatory resistance (angio-IMR) as a non-invasive assessment tool. METHODS: In this retrospective study, angio-IMR was performed to evaluate CMD before and after dual antiplatelet therapy (DAPT) with either ticagrelor (90 mg twice daily, n = 184) or clopidogrel (75 mg once daily, n = 72). The primary endpoint is the improvement of CMD evaluated by angio-IMR (delta angio-IMR) following DAPT. Secondary endpoints included myocardial reinfarction and readmission for heart failure during 2-year follow-up. RESULTS: Compared with clopidogrel, ticagrelor exhibited a significantly higher delta angio-IMR [- 3.09 (5.14) versus - 1.99 (1.91), P = 0.008], indicating a superior improvement of CMD with ticagrelor treatment. Multivariate Cox regression indicated that ticagrelor treatment was related to a reduced risk of readmission for heart failure [8 (4.3) versus 9 (12.5), adjusted HR = 0.329; 95% CI = 0.116-0.934; P = 0.018] and myocardial reinfarction [7 (3.8) versus 8 (11.1), adjusted HR = 0.349; 95% CI = 0.125-0.975; P = 0.026]. Furthermore, ticagrelor treatment serves as an independent predictor of readmission for heart failure (HR = 0.322; 95% CI = 0.110-0.943; P = 0.039). CONCLUSION: The results of this study indicate a potential association between ticagrelor treatment and improved CMD, as well as a reduced risk of cardiovascular events, including myocardial reinfarction and readmission for heart failure in AMI patients. Further randomized controlled trials are necessary to confirm the potential benefits of ticagrelor on CMD and cardiovascular prognosis. This clinical trial was registered in www. CLINICALTRIALS: gov (NCT05978726).

Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. ß-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS: YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. ß-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.

Reverse Takotsubo cardiomyopathy in the setting of small bowel obstruction: a case report.

Introduction and importance: Stress cardiomyopathy refers to a syndrome of acute but reversible left ventricular dysfunction, often triggered by emotional or physical stress. Reverse Takotsubo cardiomyopathy is an uncommon variant that occurs in about 5% of cases. Classically, it has been known to be following a catecholamine surge due to physical or emotional stress. This case highlights the importance for physicians to be aware of the possibility of developing stress cardiomyopathy in patients with acute intra-abdominal processes. Case presentation: Forty-one-year-old Caucasian female with was admitted with an acute small bowel obstruction. After failing conservative management, it was decided to proceed with surgery. After induction with anesthesia but prior to the surgeons first incision, the patient developed a tachyarrhythmia with hemodynamic compromise requiring the surgery to be aborted. That evening, she developed chest pain with concerns for an acute coronary syndrome. She was taken urgently to the for invasive angiography, which demonstrated reverse Takotsubo. Clinical discussion: Intra-abdominal processes and intubation have previously been reported be catalyst for this disease process. This patient had multiple stressors including mechanical bowel obstruction and anesthesia after failing conservative management. The diagnosis was confirmed by coronary angiography and left ventriculogram, and followed up with repeat outpatient echocardiography. Conclusion: A case of small bowel obstruction that developed reverse Takotsubo preceded by sustained ventricular tachycardia after intubation. The patient did well and had complete recovery cardiac function. Risk factors and underlining mechanism for the different variants of stress cardiomyopathy are not well understood, further investigation is warranted.

Utility of Microvascular Reconstruction in Gastrointestinal Cancer Surgery During Complex Resections and Emergency Salvage.

Major gastrointestinal surgical resections and subsequent reconstruction can occasionally need arterial or venous resection, can encounter variant anatomy, or may lead to injury to vessels. These can lead to arterial and/or venous insufficiency of viscera like the stomach, liver, colon, or spleen. Left unaddressed, these can lead to, partial or total, organ ischemia or necrosis. This can trigger a cascade of systemic clinical complications resulting in significant morbidity or even mortality. The aim of this case series is to highlight the utility of microvascular plastic surgical principles and practices in countering these vascular insufficiencies in emergency situations. Retrospective analysis of consecutive cases from March 2014 to May 2022, where intervention for emergency salvage of viscera was done. Microvascular surgical intervention for the vascular insufficient organ was performed, either by primary repair of vessels, use of interposition vein grafts, or anastomosis to a new source vessel (supercharging/super-drainage). Patients were monitored postoperatively for any signs of necrosis of viscera. Microvascular intervention was done in 21 cases: seven cases of supercharging of the gastric tube following esophagectomy, two cases of stomach salvage following pylorus-preserving pancreatoduodectomy, eight cases of hepatic artery restoration, two cases of splenic artery repair, and one each of colon salvage during coloplasty, etc. We were able to salvage the viscera of 20 cases. Arterial and venous insufficiencies can be predictably and safely reversed by precise microvascular techniques. Potentially, many greater numbers of patients can benefit from a microvascular approach to complex resections, injury, and viscera salvage.

Coronary microvascular dysfunction in autoimmune rheumatic diseases: beyond coronary flow velocity reserve.

Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of disorders characterized by an inappropriate immune reactivity against different body tissues. Patients affected by ARDs present increased cardiovascular morbidity and mortality, which significantly impacts long-term prognosis. Endothelial dysfunction, inflammation, oxidative stress, and autoimmunity are strictly involved in atherosclerosis progression and coronary microvascular dysfunction (CMD), both of which contribute to increased cardiovascular risk. CMD represents the inability of the coronary microvasculature to respond with vasodilation to increased cardiac metabolic demands and can be assessed by non-invasive and invasive imaging tests. Coronary flow velocity reserve assessed by echocardiography has been demonstrated to accurately identify ARDs patients with CMD. However, stress cardiac magnetic resonance (CMR) accurately assesses myocardial ischemia, perfusion, and viability in ARDs patients. The myocardial perfusion reserve index (MPRI) is a robust semiquantitative imaging marker that represents the vasodilatory capacity of the coronary microcirculation in response to a vasodilator stress. In the absence of significant coronary stenosis, ARDs patients revealed a reduced MPRI in comparison with the general population, regardless of the presence of myocardial fibrosis. Identification of CMD in asymptomatic patients could be crucial to precociously start targeted medical therapy, avoiding major adverse cardiac events in this clinical setting. This review aims to summarize the current evidence regarding CMD in ARDs patients, focusing on the role of stress CMR and the promising myocardial perfusion analysis.

Navigating the Landscape of Coronary Microvascular Research: Trends, Triumphs, and Challenges Ahead.

Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the microcirculation that impair myocardial perfusion. CMD plays a pivotal role in numerous cardiovascular diseases, including myocardial ischemia with non-obstructive coronary arteries, heart failure, and acute coronary syndromes. This review summarizes recent advances in CMD pathophysiology, assessment, and treatment strategies, as well as ongoing challenges and future research directions. Signaling pathways implicated in CMD pathogenesis include adenosine monophosphate-activated protein kinase/Krüppel-like factor 2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang II), endothelin-1 (ET-1), RhoA/Rho kinase, and insulin signaling. Dysregulation of these pathways leads to endothelial dysfunction, the hallmark of CMD. Treatment strategies aim to reduce myocardial oxygen demand, improve microcirculatory function, and restore endothelial homeostasis through mechanisms including vasodilation, anti-inflammation, and antioxidant effects. Traditional Chinese medicine (TCM) compounds exhibit therapeutic potential through multi-targeted actions. Small molecules and regenerative approaches offer precision therapies. However, challenges remain in translating findings to clinical practice and developing effective pharmacotherapies. Integration of engineering with medicine through microfabrication, tissue engineering and AI presents opportunities to advance the diagnosis, prediction, and treatment of CMD.

Free bone flap reconstruction in retrosigmoid approach for microvascular decompression: a comparative cohort study.

Titanium plates and screws are common material used for rigid bone flap fixation after retrosigmoid craniotomy such as microvascular decompression (MVD). We conducted this study to evaluate outcomes of the free bone flap cranioplasty without fixation in MVD and compared its postoperative complication rate with routine methods. We retrospectively reviewed all patients who underwent MVD at our institution from May 2017 to August 2022. Patients were divided into two groups according to whether the bone flap was fixed or not. Follow-ups periods spanned 6-28 months after the operation. Of 189 patients who underwent MVDs via retrosigmoid approach, 79 cases (42%) had their bone flaps replaced without titanium fixation after craniotomies (< 3 cm x 3 cm). Compared to fixed bone flap group, free bone flap group had shorter operative time (105.56 ± 15.87 min vs. 113.72 ± 17.80 min, P = 0.001), less in-patient costs (¥23059.66 ± 4488.54 vs. ¥27714.82 ± 2705.74, P < 0.001), and less proportion of postoperative headache and incisional pain (43.0% vs. 60.9%, P = 0.015). One case of incisional cerebrospinal fluid leak happened in free bone flap group while one case of incisional infection happened in fixed bone flap group. No statistical difference in bone flap displacement, duration of postoperative hospital stays or complication rate was found between the two groups. Nineteen patients in free bone flap group received long-term CT follow-up and all were proved to have good skull union. This study proves that free bone flap cranioplasty in MVD without titanium plate fixation can shorten the operation time and reduce hospitalization expenditure without increasing complication rates.

Microvascular decompression for oculomotor nerve palsy due to non-aneurysmal neurovaslur conflict: 5 cases report and literature review.

BACKGROUND: Oculomotor nerve palsy (ONP) is frequently caused by aneurysm compression and diabetes mellitus. However, non-aneurysmal compression (nAVC) of the oculomotor nerve is a condition rarely reported in the literature. Cases treated with microvascular decompression (MVD) for nAVC-induced ONP (nAVC-ONP) are exceptionally rare. METHODS: Between October 2022 and October 2023, we performed MVD surgery on five patients diagnosed with nAVC-ONP. The clinical symptoms, imaging characteristics, and intraoperative findings of these patients were reviewed and analyzed using a self-developed evaluation scale (S-T Evaluation Scale) to guide diagnosis and corresponding treatment plans. RESULTS: All patients underwent MVDs and demonstrated favorable recovery and a good prognosis. No postoperative complications occurred in any of the patients. The superior cerebellar artery (SCA) and posterior cerebral artery (PCA) were common offending vessels in these cases. CONCLUSION: Neurovascular conflict has been proposed as another possible cause of ONP in a limited number of cases. Based on our findings, MVD is a potentially effective solution for patients experiencing oculomotor nerve palsy resulting from non-aneurysmal neurovascular conflicts. It holds great promise for significantly alleviating symptoms and improving overall quality of life..

Optical coherence tomography angiography of the retina and choroid in systemic diseases.

Optical coherence tomography angiography (OCTA) has transformed ocular vascular imaging, revealing microvascular changes linked to various systemic diseases. This review explores its applications in diabetes, hypertension, cardiovascular diseases, and neurodegenerative diseases. While OCTA provides a valuable window into the body's microvasculature, interpreting the findings can be complex. Additionally, challenges exist due to the relative non-specificity of its findings where changes observed in OCTA might not be unique to a specific disease, variations between OCTA machines, the lack of a standardized normative database for comparison, and potential image artifacts. Despite these limitations, OCTA holds immense potential for the future. The review highlights promising advancements like quantitative analysis of OCTA images, integration of artificial intelligence for faster and more accurate interpretation, and multi-modal imaging combining OCTA with other techniques for a more comprehensive characterization of the ocular vasculature. Furthermore, OCTA's potential future role in personalized medicine, enabling tailored treatment plans based on individual OCTA findings, community screening programs for early disease detection, and longitudinal studies tracking disease progression over time is also discussed. In conclusion, OCTA presents a significant opportunity to improve our understanding and management of systemic diseases. Addressing current limitations and pursuing these exciting future directions can solidify OCTA as an indispensable tool for diagnosis, monitoring disease progression, and potentially guiding treatment decisions across various systemic health conditions.

Superb microvascular ultrasound is a promising non-invasive diagnostic tool to assess a ventriculoperitoneal shunt system function: a feasibility study.

The objective of this pilot study was to assess the reliability of superb microvascular ultrasound (SMI) for the measurement of the cerebrospinal fluid (CSF) flow within VPS systems as an indirect sign for shunt dysfunction. Asymptomatic hydrocephalus patients, with a VPS system implanted between 2017 and 2021, were prospectively enrolled in the study. Using SMI, the CSF flow within the proximal and distal catheters were analysed. Before and after pumping the shunt reservoir, intraabdominal free fluid, optical nerve sheath diameter (ONSD), and papilla diameter (PD) were evaluated and correlated with the amount of valve activation. Nineteen patients were included. A flow was detectable in 100% (N = 19) patients in the proximal and in 89.5% (N = 17) in the distal catheter. The distal catheter tip was detectable in 27.7% (N = 5) patients. Free intraabdominal fluid was initially detected in 21.4% (N = 4) patients and in 57.9% (N = 11) at the end of the examination (P = 0.049). ONSD was significantly lower after pump activation (4.4 ± 0.9 mm versus 4.1 ± 0.8 mm, P = 0.049). Both peak velocity and flow volume per second were higher in proximal compared to distal catheters (32.2 ± 45.2 versus 5.6 ± 3.7 cm/sec, P = 0.015; 16.6 ± 9.5 ml/sec versus 5.1 ± 4.0 ml/sec, P = 0.001, respectively). No correlation was found between the number of pump activations and the changes in ONSD (P = 0.975) or PD (P = 0.820). SMI appears to be a very promising non-invasive diagnostic tool to assess CSF flow within the VPS systems and therefore affirm their function. Furthermore, appearance of free intraperitoneal fluid followed by repeated compression of a shunt reservoir indicates an intact functioning shunt system.

Nerve sonography to detect intraneural microvascularity in patients with peripheral neuropathy.

OBJECTIVE: We assessed microvessel flow within peripheral nerves using nerve sonography in patients with peripheral neuropathy. METHODS: This study included consecutive patients with peripheral neuropathy who were admitted to our hospital. The patients were divided into two groups: inflammatory neuropathies for immune-mediated neuropathies, such as Guillain - Barré syndrome and chronic inflammatory demyelinating polyneuropathy, and the rest were defined as non-inflammatory neuropathies. We assessed nerve size and intraneural blood flow at four sites on each median and ulnar nerve. Blood flow was evaluated using color Doppler imaging, advanced dynamic flow (ADF), and superb microvascular imaging (SMI) techniques. RESULTS: Thirty-nine patients (median age, 60.0 years; 20 male) were enrolled in this study. An increase in intraneural blood flow was observed in five patients when evaluated by color Doppler, five patients by ADF, and 13 patients by SMI. An overall analysis of the three methods showed that intraneural blood flow was significantly higher in patients with inflammatory neuropathy than in those with non-inflammatory neuropathy (54.2% vs. 0%, p = 0.0005). CONCLUSIONS: Intraneural hypervascularization is more frequent in patients with inflammatory neuropathy than in those with non-inflammatory neuropathy. SIGNIFICANCE: Evaluation of microvessel flow within peripheral nerves may contribute to the diagnosis of peripheral neuropathy.

Intimal Macrovascular Pericytes: Their Role in Vascular Biology and Atherogenesis.

Atherosclerosis remains a major challenge to global healthcare despite decades of research and constant trials of novel therapeutic approaches. One feature that makes atherosclerosis treatment so elusive is an insufficient understanding of its origins and the early stages of the pathological process, which limits our means of effective prevention of the disease. Macrovascular pericytes are cells with distinct shapes that are located in the arterial wall of larger vessels and are in many aspects similar to microvascular pericytes that maintain the functionality of small vessels and capillaries. This cell type combines the residual contractile function of smooth muscle cells with a distinct stellar shape that allows these cells to make numerous contacts between themselves and the adjacent endothelial layer. Moreover, pericytes can take part in the immune defense and are able to take up lipids in the course of atherosclerotic lesion development. In growing atherosclerotic plaques, the morphology and function of pericytes change dramatically due to phagocytic and synthetic phenotypes that are actively involved in lipid accumulation and extracellular matrix synthesis. In this review, we summarize our knowledge of this less-studied cell type and its role in atherosclerosis.

Microvascular resistance reserve: impact on health status and myocardial perfusion after revascularization in chronic coronary syndrome.

BACKGROUND AND AIMS: The microvascular resistance reserve (MRR) is a novel invasive index of the microcirculation, which is independent of epicardial stenoses, and MRR has both diagnostic and prognostic implications. This study investigates whether MRR is associated with health status outcomes by revascularization in patients with moderate coronary stenoses. METHODS: Consecutive patients with stable chest pain and moderate (30-90% diameter) stenoses on invasive coronary angiography (n=222) underwent invasive physiology assessment. Revascularization was performed by guideline recommendations. At baseline and follow-up, health status and myocardial perfusion were assessed by Seattle Angina Questionnaire (SAQ) and positron emission tomography. The primary endpoint was freedom from angina at follow-up with secondary endpoints including changes in health status by SAQ domains and myocardial perfusion by MRR and revascularization status. Low MRR was defined as ≤3.0. RESULTS: Freedom from angina occurred in 38/173 patients. In multivariate analyses, MRR was associated with freedom from angina at follow-up (odds ratio 0.860, 95% confidence interval 0.740-0.987). By MRR and revascularization groups, patients with normal MRR who did not undergo revascularization, and patients with abnormal MRR who underwent revascularization, improved health status of angina frequency (mean difference SAQ angina frequency score 8.5 [3.07-13.11] and 13.5 [2.82-23.16], respectively). For both groups, health status of physical limitation (mean difference in SAQ physical limitation score 9.7 [4.79-11.93] and 8.7 [0.53-13.88], respectively) and general health status (mean difference in SAQ summary score 9.3 [5.18-12.50] and 10.8 [2.51-17.28], respectively) also improved. Only patients with abnormal MRR who underwent revascularization improved myocardial perfusion. CONCLUSIONS: In patients with moderate coronary stenoses, MRR seems to predict symptomatic and perfusion benefit of revascularization.

Glycoprotein IIb/IIIa Inhibitors in Acute Myocardial Infarction and Angiographic Microvascular Obstruction: The REVERSE-FLOW Trial.

BACKGROUND AND AIMS: Glycoprotein (GP) IIb/IIIa inhibitors are recommended in acute myocardial infarction (AMI) for bailout treatment in case of angiographic microvascular obstruction (MVO), also termed no-reflow phenomenon, after percutaneous coronary intervention (PCI) with, however, lacking evidence (class IIa, level C). METHODS: The investigator-initiated, international, multicenter REVERSE-FLOW trial randomized 120 patients with AMI and Thrombolysis In Myocardial Infarction flow grade ≤2 after primary PCI to optimal medical therapy with or without GP IIb/IIIa inhibitor. The primary endpoint was infarct size (%LV) assessed by cardiac magnetic resonance (CMR). Secondary endpoints included CMR-derived MVO and 30-day adverse clinical events. The trial is registered with ClinicalTrials.gov: NCT02739711. RESULTS: The population was predominantly male (76.7%) with a median age of 66 years and ST-elevation myocardial infarction in 73.3% of patients. Clinical and angiographic characteristics were well balanced between the cohorts. Patients in the treatment group (n=62) received eptifibatide (n=41) or tirofiban (n=21). Infarct size assessed by CMR imaging was similar in both study groups (25.4% of left ventricular mass [LV] vs. 25.2%LV; p=0.386). However, the number of patients with evidence of CMR-derived MVO (74.5% vs. 92.2%; p=0.017) and the extent of MVO (2.1%LV vs. 3.4%LV; p=0.025) were significantly reduced in the GP IIb/IIIa inhibitor group compared to controls. Thirty-day outcome showed an increased bleeding risk after GP IIb/IIIa inhibitor administration restricted to non-life-threatening bleedings (22.6% vs. 6.9%; p=0.016) without differences in all-cause mortality (4.8% vs. 3.4%; p=0.703). CONCLUSIONS: Bailout GP IIb/IIIa inhibition in AMI patients with angiographic MVO failed to reduce the primary endpoint infarct size but decreased CMR-derived MVO and led to an increase in non-fatal bleeding events.

Inhibition of 15-prostaglandin dehydrogenase attenuates acetaminophen-induced liver injury via suppression of apoptosis in liver endothelial cells.

Hepatic microvascular disruption caused by injury to liver sinusoidal endothelial cells (LSECs) is an aggravating factor for drug-induced liver injury (DILI). It is suggested that prostaglandin E2 (PGE2) may be able to attenuate LSEC injury. However, it is also known that 15-keto PGE2, a metabolite of PGE2 produced by 15-prostaglandin dehydrogenase (15-PGDH) that is not a ligand of PGE2 receptors, suppresses inflammatory acute liver injury as a ligand of peroxisome proliferator-activated receptor γ. In this study, we aimed to understand whether 15-PGDH activity is essential for preventing DILI by suppressing hepatic microvascular disruption in a mouse model of acetaminophen (APAP)-induced liver injury. To inhibit 15-PGDH activity prior to APAP-induced LSEC injury, we administered the 15-PGDH inhibitor, SW033291, 1 h before and 3 h after APAP treatment. We observed that LSEC injury preceded hepatocellular injury in APAP administered mice. Hepatic endogenous PGE2 levels did not increase up till the initiation of LSEC injury but rather increased after hepatocellular injury. Moreover, hepatic 15-PGDH activity was downregulated in APAP-induced liver injury. The inhibition of 15-PGDH attenuated LSEC injury and subsequently hepatic injury by inhibiting apoptosis in APAP administered mice. Our in vitro studies also suggested that PGE2 inhibited APAP-induced apoptosis via the EP4/PI3K pathway in endothelial cells. Therefore, a decrease in 15-PGDH activity would be beneficial for preventing APAP-induced liver injury by attenuating LSEC injury.