Nanoparticles for Thrombus Diagnosis and Therapy: Emerging Trends in Thrombus-theranostics.

Cardiovascular disease is one of the chief factors that cause ischemic stroke, myocardial infarction, and venous thromboembolism. The elements that speed up thrombosis include nutritional consumption, physical activity, and oxidative stress. Even though the precise etiology and pathophysiology remain difficult topics that primarily rely on traditional medicine. The diagnosis and management of thrombosis are being developed using discrete non-invasive and non-surgical approaches. One of the emerging promising approach is ultrasound and photoacoustic imaging. The advancement of nanomedicines offers concentrated therapy and diagnosis, imparting efficacy and fewer side effects which is more significant than conventional medicine. This study addresses the potential of nanomedicines as theranostic agents for the treatment of thrombosis. In this article, we describe the factors that lead to thrombosis and its consequences, as well as summarize the findings of studies on thrombus formation in preclinical and clinical models and also provide insights on nanoparticles for thrombus imaging and therapy.

Near-infrared-II photoacoustic imaging and photo-triggered synergistic treatment of thrombosis via fibrin-specific homopolymer nanoparticles.

The formation of an occlusive thrombus in the blood vessel is the main culprit for numerous life-threatening cardiovascular diseases that represent the leading cause of morbidity and mortality worldwide. Herein, we develop a polymer nanoplatform that integrates long-wavelength second near-infrared (NIR-II) photoacoustic imaging-based thrombosis detection and antithrombotic activity. We design and synthesize a semiconducting homopolymer with strong absorption in the NIR-II region and molecular motion that boosts photothermal conversion and photoacoustic signal. We dope the homopolymer with a thermosensitive nitric oxide donor to formulate a nanoplatform, on which a fibrin-specific ligand is functionalized to ensure selective thrombus targeting. We show that with strong NIR-II light harvesting capability, bright photoacoustic signal and active thrombus accumulation ability, the NIR-II photoacoustic nanoprobes are able to sensitively and selectively delineate thrombi. We find that the nanoplatform also displays rapid and efficient blood clot removal activity with nearly complete blood flow restoration in both carotid thrombosis models and low extremity arterial thrombosis models under NIR-II light trigger by integrating a thrombus-localized photothermal effect and on-demand nitric oxide release. This nanoplatform offers a versatile approach for the diagnosis and treatment of life-threatening diseases caused by various thrombotic disorders.

Efficacy and Adverse Reactions of Transcatheter Arterial Chemoembolization Combined with Apatinib in the Treatment of HCC with PVTT: A Meta-Analysis.

Background: Hepatocellular carcinoma is a major contributor to cancer-related deaths in China and ranks among the most prevalent malignant tumors. . The study aimed to assess the efficacy and adverse reactions of transcatheter arterial chemoembolization combined with apatinib in treating hepatocellular carcinoma with portal vein tumor thrombus. Methods: When treating hepatocellular carcinoma with a portal vein tumor thrombus, the computer retrieves eight databases to find controlled trials on the effects of transcatheter arterial chemoembolization combined with apatinib. The Cochrane Library, WanFang databases EMbase, PubMed, Web of Science, China Biomedical Literature Database (CBM), & CNKI are all retrieved by the computer. "Transcatheter arterial chemoembolization", "apatinib", & "hepatocellular carcinoma" are the search terms. As this a meta-analysis, Utilizing RevMan 5.3 software, data analysis was carried out following a thorough assessment of the quality of the literature. Results: This meta-analysis finally contained 7 papers. According to a meta-analysis, the disease control rate of the test category was considerably greater than that of the control category (odd Ratio OR: 1.65; 95% Cl: 1.17,2.33; P = .01). The experimental cohort's level of VEGF was substantially lower than that of the control group (standardized mean difference SMD:-25.38; 95% Cl: -28.69,-21.79; P < .01). According to a meta-analysis, caspase-8 levels in the group that underwent the experiment were substantially greater than those in the control category (SMD: 15.12; 95% Cl: 12.09, 18.15; P < .01). The test control experienced considerably less pain than the control sample (OR: 0.86; 95% Cl: 0.75,0.99; P = .033). Conclusion: The findings of this trial indicate that individuals with HCC & PVTT may benefit from TACE & apatinib together, as evidenced by disease control rate, VEGF, Caspase-8, pain, hypertension, nausea and vomiting, and more reputable studies are required to support the aforementioned conclusions.

A Spiky Silver-Iron Oxide Nanoparticle for Highly Efficient Targeted Photothermal Therapy and Multimodal Imaging of Thrombosis.

Thrombosis and its complications are responsible for 30% of annual deaths. Limitations of methods for diagnosing and treating thrombosis highlight the need for improvements. Agents that provide simultaneous diagnostic and therapeutic activities (theranostics) are paramount for an accurate diagnosis and rapid treatment. In this study, silver-iron oxide nanoparticles (AgIONPs) are developed for highly efficient targeted photothermal therapy and imaging of thrombosis. Small iron oxide nanoparticles are employed as seeding agents for the generation of a new class of spiky silver nanoparticles with strong absorbance in the near-infrared range. The AgIONPs are biofunctionalized with binding ligands for targeting thrombi. Photoacoustic and fluorescence imaging demonstrate the highly specific binding of AgIONPs to the thrombus when functionalized with a single chain antibody targeting activated platelets. Photothermal thrombolysis in vivo shows an increase in the temperature of thrombi and a full restoration of blood flow for targeted group but not in the non-targeted group. Thrombolysis from targeted groups is significantly improved (p < 0.0001) in comparison to the standard thrombolytic used in the clinic. Assays show no apparent side effects of AgIONPs. Altogether, this work suggests that AgIONPs are potential theranostic agents for thrombosis.

Efficacy of TACE+Radiofrequency Ablation+Sorafenib in the Treatment of Patients with Recurrent Liver Cancer and Construction of Prediction Model.

Objective: This study is aimed at exploring the efficacy of transarterial chemotherapy embolization (TACE)+radiofrequency ablation+sorafenib in the treatment of patients with recurrent liver cancer and at constructing its prediction model. Methods: A total of 60 patients with recurrent liver cancer treated in our hospital from March 2020 to March 2022 were enrolled and divided into two groups according to treatment methods, with 30 patients in each group. Group A adopted TACE+radiofrequency ablation+sorafenib therapy while group B adopted TACE+radiofrequency ablation therapy. Clinical efficacy, complications, and adverse reactions of the two groups were observed. A total of 30 patients with nonrecurrent liver cancer in the same period were enrolled. 60 patients with recurrent liver cancer and 30 patients with nonrecurrent liver cancer were taken as the recurrence group and the nonrecurrence group, respectively. The baseline data and clinical data of the patients were queried by the Hospital Information System. The data included age, gender, Child-Pugh grade, HBV/HCV infection, portal vein tumor thrombus, degree of differentiation, vascular invasion, serum alpha fetal protein (AFP) level, number of tumors, maximum diameter of tumors, and number of nodules. The logistic regression analysis was used to analyze the independent risk factors for liver cancer recurrence. The Hosmer-Lemeshow test was used to analyze the degree of fitting between the prediction model and the standard curve. The ROC curve was used to analyze the predictive value of the model for liver cancer recurrence. Results: The objective effective rate and disease control rate in group A (33.33% and 70.00%) were higher than those in group B (10.00% and 43.33%), and the differences were statistically significant (both P < 0.05). There were no significant differences in the incidence of complications such as embolism syndrome, hand and foot skin reaction, gastrointestinal reaction, hypertension, diaphragmatic injury and bleeding, and biliary leakage and fever between the two groups (all P > 0.05). The proportions of patients in the recurrence group with portal vein tumor thrombus (PVTT), medium and high degree of differentiation, combined with vascular invasion, serum AFP level ≥ 400 ng/dL, multiple tumors, maximum tumor diameter ≥ 5 cm, combined with cirrhosis, and polynodules were all higher than those in the nonrecurrence group; the differences were statistically significant (all P < 0.05). Complication of PVTT, the degree of medium and high differentiation, and the maximum tumor diameter ≥ 5 cm were independent risk factors for recurrence of liver cancer (all P < 0.05). The prediction model of liver cancer recurrence was obtained by multiple regression analysis, P = 1/[1 + e -(-5.441 + 6.154∗PVTT + 3.475∗differentiateddegree + 3.001∗maximumdiameteroftumor)]. The Hosmer-Lemeshow test showed that χ 2 = 1.558 (P = 0.992). According to the ROC curve analysis, the AUC, SE, and 95% CI value of the prediction model for liver cancer recurrence were 0.977, 0.012, and 0.953-1.000, respectively. Conclusion: TACE+radiofrequency ablation+sorafenib is effective in the treatment of recurrent liver cancer, and the prediction model established based on the risk factor has high predictive value for patients with recurrent liver cancer.

Clot-targeted magnetic hyperthermia permeabilizes blood clots to make them more susceptible to thrombolysis.

BACKGROUND: Thrombolysis is a frontline treatment for stroke, which involves the application of tissue plasminogen activator (tPA) to trigger endogenous clot-degradation pathways. However, it is only effective within 4.5 h of symptom onset because of clot contraction preventing tPA permeation into the clot. Magnetic hyperthermia (MH) mediated by tumor-targeted magnetic nanoparticles is used to treat cancer by using local heat generation to trigger apoptosis of cancer cells. OBJECTIVES: To develop clot-targeting magnetic nanoparticles to deliver MH to the surface of human blood clots, and to assess whether this can improve the efficacy of thrombolysis of contracted blood clots. METHODS: Clot-targeting magnetic nanoparticles were developed by functionalizing iron oxide nanoparticles with an antibody recognizing activated integrin αIIbß3 (PAC-1). The magnetic properties of the PAC-1-tagged magnetic nanoparticles were characterized and optimized to deliver clot-targeted MH. RESULTS: Clot-targeted MH increases the efficacy of tPA-mediated thrombolysis in contracted human blood clots, leading to a reduction in clot weight. MH increases the permeability of the clots to tPA, facilitating their breakdown. Scanning electron microscopy reveals that this effect is elicited through enhanced fibrin breakdown and triggering the disruption of red blood cells on the surface of the clot. Importantly, endothelial cells viability in a three-dimensional blood vessel model is unaffected by exposure to MH. CONCLUSIONS: This study demonstrates that clot-targeted MH can enhance the thrombolysis of contracted human blood clots and can be safely applied to enhance the timeframe in which thrombolysis is effective.

Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study.

BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated. METHODS: In this open-label, single-center, randomized trial (ClinicalTrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model. RESULTS: Between December 30, 2018 and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of 16.1 months, patients in arm L had a higher median TTP (4.7 vs 3.1 months; hazard ratio [HR], 0.55; 95% CI, 0.32-0.95; P = .029) and objective response rate (53.1% vs 25.0%, P = .039) versus arm S. Multivariable analysis showed that TACE plus lenvatinib was significantly associated with higher TTP versus TACE plus sorafenib (HR, 0.50; 95% CI, 0.28-0.90; P = .021). Comparable safety profiles were observed in arms L and S. CONCLUSIONS: TACE plus lenvatinib was safe, well tolerated, and had favorable efficacy versus TACE plus sorafenib in patients with advanced HCC with PVTT and large tumor burden. LAY SUMMARY: Hepatocellular carcinoma with portal vein tumor thrombus has a poor prognosis. In addition, most phase 3 trials of drugs for hepatocellular carcinoma exclude patients with major portal vein invasion, and treatment options for these patients are limited. Transarterial chemoembolization has shown promising efficacy in these patients, especially in combination with systemic treatment or radiotherapy. However, transarterial chemoembolization plus lenvatinib has not been investigated in this setting. This open-label, single-center, randomized trial showed that transarterial chemoembolization plus lenvatinib is safe, well tolerated, and has favorable efficacy versus transarterial chemoembolization plus sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey.

In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund's adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.

Severe Acute Thromboinflammation: Case Report of Individualized Homeopathic Treatment.

Thromboinflammation is a still not well-understood phenomenon, which has recently come to the foreground as a function of its relevance in the pathophysiology of coronavirus disease 2019 (COVID-19). The patient described in the present case report exhibited acute fever, giant urticaria, elevated acute phase reactants, and very high d-dimer levels, thus characterizing thromboinflammation. She was diagnosed as a COVID-19 suspect case, which was not confirmed; urticarial vasculitis was ruled out. Homeopathic treatment was started with the earliest clinical manifestations, resulting in rapid and drastic reduction of inflammation and hypercoagulability within the first 12 hours, and full recovery on 10-day follow-up assessment. This case demonstrates the effectiveness of homeopathy in a severe acute disorder, and points to the need to include laboratory testing in homeopathic clinical assessment to achieve an accurate picture of disease, and to avoid the risk of passing over life-threatening disorders.

Anticoagulation and Transjugular Intrahepatic Portosystemic Shunt for the Management of Portal Vein Thrombosis in Cirrhosis: A Prospective Observational Study.

INTRODUCTION: Current guidelines recommend anticoagulation as the mainstay of portal vein thrombosis (PVT) treatment in cirrhosis. However, because of the heterogeneity of PVT, anticoagulation alone does not always achieve satisfactory results. This study aimed to prospectively evaluate an individualized management algorithm using a wait-and-see strategy (i.e., no treatment), anticoagulation, and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT in cirrhosis. METHODS: Between February 2014 and June 2018, 396 consecutive patients with cirrhosis with nonmalignant PVT were prospectively included in a tertiary care center, of which 48 patients (12.1%) were untreated, 63 patients (15.9%) underwent anticoagulation, 88 patients (22.2%) underwent TIPS, and 197 patients (49.8%) received TIPS plus post-TIPS anticoagulation. The decision of treatment option mainly depends on the stage of liver disease (symptomatic portal hypertension or not) and degree and extension of thrombus. RESULTS: During a median 31.7 months of follow-up period, 312 patients (81.3%) achieved partial (n = 25) or complete (n = 287) recanalization, with 9 (3.1%) having rethrombosis, 64 patients (16.2%) developed major bleeding (anticoagulation-related bleeding in 7 [1.8%]), 88 patients (22.2%) developed overt hepatic encephalopathy, and 100 patients (25.3%) died. In multivariate competing risk regression models, TIPS and anticoagulation were associated with a higher probability of recanalization. Long-term anticoagulation using enoxaparin or rivaroxaban rather than warfarin was associated with a decreased risk of rethrombosis and an improved survival, without increasing the risk of bleeding. However, the presence of complete superior mesenteric vein thrombosis was associated with a lower recanalization rate, increased risk of major bleeding, and poor prognosis. DISCUSSION: In patients with cirrhosis with PVT, the individualized treatment algorithm achieves a high-probability recanalization, with low rates of portal hypertensive complications and adverse events.

COVID-19 pandemic and STEMI: pathway activation and outcomes from the pan-London heart attack group.

OBJECTIVES: To understand the impact of COVID-19 on delivery and outcomes of primary percutaneous coronary intervention (PPCI). Furthermore, to compare clinical presentation and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) with active COVID-19 against those without COVID-19. METHODS: We systematically analysed 348 STEMI cases presenting to the PPCI programme in London during the peak of the pandemic (1 March to 30 April 2020) and compared with 440 cases from the same period in 2019. Outcomes of interest included ambulance response times, timeliness of revascularisation, angiographic and procedural characteristics, and in-hospital clinical outcomes RESULTS: There was a 21% reduction in STEMI admissions and longer ambulance response times (87 (62-118) min in 2020 vs 75 (57-95) min in 2019, p<0.001), but that this was not associated with a delays in achieving revascularisation once in hospital (48 (34-65) min in 2020 vs 48 (35-70) min in 2019, p=0.35) or increased mortality (10.9% (38) in 2020 vs 8.6% (38) in 2019, p=0.28). 46 patients with active COVID-19 were more thrombotic and more likely to have intensive care unit admissions (32.6% (15) vs 9.3% (28), OR 5.74 (95%CI 2.24 to 9.89), p<0.001). They also had increased length of stay (4 (3-9) days vs 3 (2-4) days, p<0.001) and a higher mortality (21.7% (10) vs 9.3% (28), OR 2.72 (95% CI 1.25 to 5.82), p=0.012) compared with patients having PPCI without COVID-19. CONCLUSION: These findings suggest that PPCI pathways can be maintained during unprecedented healthcare emergencies but confirms the high mortality of STEMI in the context of concomitant COVID-19 infection characterised by a heightened state of thrombogenicity.

Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management.

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.

Bacteria-triggered tumor-specific thrombosis to enable potent photothermal immunotherapy of cancer.

We discovered that attenuated Salmonella after intravenous injection would proliferate within various types of solid tumors but show rapid clearance in normal organs, without rendering notable toxicity. Bacteria-induced inflammation would trigger thrombosis in the infected tumors by destroying tumor blood vessels. Six types of tested tumors would all turn into darkened color with strong near-infrared absorbance, as observed by photoacoustic imaging. Under laser irradiation, those bacterial-infected tumors would be effectively ablated. Because of the immune-stimulation function, such bacteria-based photothermal therapy (PTT) would subsequently trigger antitumor immune responses, which could be further enhanced by immune checkpoint blockade to effectively suppress the growth of abscopal tumors. A robust immune memory effect to reject rechallenged tumors is also observed after bacteria-based PTT. Our work demonstrates that bacteria by themselves could act as a tumor-specific PTT agent to enable photoimmunotherapy cancer therapy to inhibit tumor metastasis and recurrence.

Use of Embolectomy With Local Anesthesia for Anticoagulation Failure in Radial Artery Thrombosis.

OBJECTIVE: Although prevention of radial artery thrombosis and cardiac complications after interventions using radial access is well investigated, there is yet no clinical study that completely evaluated access-related complications. However, there is still no consensus on what exact treatment should be used in these patients. In clinical practice, analgesic, anticoagulant, and antiplatelet treatments usually improve symptoms in patients with pain; however, in some patients, complaints may persist and may not respond to these treatments. In these patients, low-risk embolectomy with a small skin incision may be beneficial. METHODS: A total of 102 patients with radial artery thrombosis after cardiac catheterization were included in the study between 2016 March and 2018 December. After the patients' initial evaluation, anticoagulation with enoxaparin or tinzaparin and antiplatelet therapy with acetylsalicylic acid and oral/local analgesic/anti-inflammatory and local anesthetic therapy were administered for 1 month. Patients whose symptoms resolved after medical treatment were followed up as outpatients. Embolectomy was performed in consenting patients who did not respond to the medical treatment. RESULTS: Of 102 patients included in the study, 33 underwent embolectomy, whereas 69 received only medical treatment. None of the patients experienced any complications, morbidity, or mortality in the peroperative period and during the medical treatment. The pretreatment symptom scores of patients who actively use their hands in daily life and profession were significantly higher than the scores of patients who are relatively less active (P = .013). Pretreatment symptom scores were negatively correlated with age (r = -0.584); symptom scores increased significantly with the decrease of patient age. No benefit from medical treatment and need for surgery was significantly greater in patients who are younger and use their hands actively in daily life and profession (P = .028). The decrease in symptom scores after treatment was significantly greater in the surgical group than in the medical group (P = .003). CONCLUSION: Radial access should be exercised with care in patients who may develop significant thrombosis-related complaints and it is necessary to decide whether radial access is essential. If patients have ongoing symptoms despite medical treatment, embolectomy can be considered as a treatment option.

Too Much of a Good Thing? Cerebral Sinovenous Thrombosis Due to Excessive Milk Intake Associated Anemia.

INTRODUCTION: In young children, excessive cow's milk intake causes iron-deficiency anemia, which is associated with hypercoagulable states. We present a case series of 4 toddlers with excessive milk intake iron-deficiency anemia and cerebral sinovenous thrombosis. METHODS: Retrospective chart review of 4 patients was performed for patients with cerebral sinovenous thrombosis and iron-deficiency anemia secondary to excessive milk intake. Iron-deficiency anemia was defined as hemoglobin <11 mg/dL, mean corpuscular volume <70 fL, and serum ferritin <12 µg/L. Excessive milk intake was defined as consumption of >24 oz daily. Clinical, laboratory, and radiographic features were reviewed. RESULTS: Age ranged from 12 to 24 months. Average hemoglobin, hematocrit, mean corpuscular volume, and ferritin levels were 6.1 g/dL, 22.7 g/dL, 52.7 fL, and 3.2 ng/mL, respectively. Daily milk consumption ranged from 40 to 60 oz. All patients presented with focal neurologic deficits, including seizures in 3. The location of cerebral sinovenous thrombosis varied, and 3 patients had venous infarcts, one of them hemorrhagic. All patients had a limited diet and were described as "picky eaters" by their parents, and only 1 had transitioned of a bottle. All patients were treated with anticoagulation, iron supplementation, and extensive dietary counseling to reduce cow's milk intake. CONCLUSION: Iron-deficiency anemia due to excessive milk intake is an important and preventable etiology of pediatric cerebral sinovenous thrombosis. Focused anticipatory guidance is necessary for at-risk groups to prevent this neurologic emergency.

Safety and efficacy of endovascular implantation of a portal vein stent combined with iodine-125 seed-strips followed by transcatheter arterial chemoembolization with sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombosis.

OBJECTIVE: To assess the safety and efficacy of endovascular implantation of a portal vein stent combined with iodine-125 seed-strips followed by transcatheter arterial chemoembolization with sorafenib (PVS-125I-TACE-S) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS: Between January 2015 and July 2017, 18 patients with PVTT caused by HCC that were treated with PVS-125I-TACE-S were reviewed. The technical success, complications, changes in liver function from baseline values due to subsequent endovascular implantation of a portal vein stent combined with iodine-125 seed-strips (PVS-125I), time-to-tumor progression (TTP) and overall survival (OS) were observed. RESULTS: The technical success rate was 100%. Adverse events (AEs) were managed successfully, with no occurrence of procedure-related deaths. Liver function test values after PVS-125I were not significantly different than baseline values (P＞0.05). The median TTP was 7.0 months (range: 4.2-9.9 months). In Vp3 PVTT, the TTP was 9.7 months (range: 8.8-10.5 months), and in Vp4 PVTT, the TTP was 4.2 months (range: 2.8-5.6 months). The median OS was 10.0 months (range: 7.0-13.1 months). In Vp3 PVTT, OS was 11.9 months (range: 9.2-14.5 months), and in Vp4 PVTT, OS was 7.2 months (range: 3.8-10.7 months). CONCLUSIONS: PVS-125I-TACE-S is safe for patients with HCC with PVTT and may extend the TTP and survival of patients with Vp4 PVTT. ADVANCES IN KNOWLEDGE: PVS implantation promptly restored flow in the obstructed portal vein, which can reduce the risk of hepatic failure and upper gastrointestinal bleeding. Implantation of iodine-125 seed-strips may directly expose the portal tumor thrombus to radiation and kill cancer cells. Their combined use with TACE-S has a strong scientific rationale.

Carbon monoxide poisoning can act as a stress test to reveal underlying coronary artery disease: case report.

Carbon monoxide (CO) poisoning presents with many different cardiac effects, but one important presentation is its effect as a CO stress test to reveal underlying coronary artery disease (CAD). There are a limited number of publications detailing this phenomenon, but after CO intoxication it is important to suspect CAD in association with mild troponin leak or non-ST segment elevation myocardial infarction (NSTEMI) shown on electrocardiogram (EKG). We recently treated three patients with CO poisoning who had underlying CAD. In the first case a man presented to the emergency department with CO toxicity and an ST segment elevation myocardial infarction (STEMI), resulting in emergent angioplasty and the discovery of severe CAD. The second case involved an individual who presented with CO poisoning with rising troponin levels. An angioplasty discovered a stable 90% occlusion. The third case was a patient with CO poisoning and transient inferior T wave inversion EKG with borderline troponin elevation. Angioplasty showed only 30% occlusion, so the patient's presentation was likely due to direct CO cardiac toxicity. These cases demonstrate the varied presentations that CO poisoning can have on patients with underlying heart disease.

A Vascular Thrombus Therapy Method Based on Magnetic-Induced Vibration.

A vascular thrombus therapy method based on magnetic-induced vibration is presented. It is a mechanicalway of removing vascular thrombus that adopts the combined use of two concepts, namely (i) magnetic-induced vibration of magnetostrictive materials and (ii) changes in physical form of thrombus under high-frequency impact and vibration. This method has many advantages that (i) eliminate the side effects of drug treatment, (ii) reduce the complexity of traditional mechanical method, and (iii) improve the reliability of treatment. Practical results obtained from the simulations and experiments are included. They verify the proposed system and indicate that this method can effectively treat vascular thrombus and reduce patient's suffering and costs. Bioelectromagnetics. 2019;40:391-401. © 2019 Bioelectromagnetics Society.