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Promoter DNA hypermethylation is an important biomarker of hepatocellular carcinoma (HCC), supporting the potential utility of demethylating agents in this disease. Guadecitabine (SGI-110) is a second-generation hypomethylating agent formulated as a dinucleotide of decitabine and deoxyguanosine that yields longer half-life and more extended decitabine exposure than decitabine IV infusion. Here we performed preclinical evaluation of SGI-110 in HCC models to guide the design of a phase I/II clinical trial. HCC cell lines and xenograft models were used to determine the antitumor activity of SGI-110 as a single agent and in combination with oxaliplatin. Pretreatment with low doses of SGI-110 significantly synergized with oxaliplatin yielding enhanced cytotoxicity. The combination of SGI-110 and oxaliplatin was well tolerated and significantly delayed tumor growth in mice compared to oxaliplatin alone. Bromouridine-labeled RNA sequencing (Bru-seq) was employed to elucidate the effects of SGI-110 and/or oxaliplatin on genome-wide transcription. SGI-110 and the combination treatment inhibited the expression of genes involved in WNT/EGF/IGF signaling. DNMT1 and survivin were identified as novel PD markers to monitor the efficacy of the combination treatment. In conclusion, SGI-110 priming sensitizes HCC cells to oxaliplatin by inhibiting distinct signaling pathways. We expect that this combination treatment will show low toxicity and high efficacy in patients. Our study supports the use of the combination of low doses of SGI-110 and oxaliplatin in HCC patients. [ABSTRACT FROM AUTHOR]

Abstract: Right and left heart failure are very common clinical syndromes with close correlation. Right-sided or right ventricular heart failure usually occurs as a result of left-sided failure. We report a very rare case of transition from right heart failure due to pulmonary embolism, followed by its resolution, to left heart failure due to Tako-tsubo syndrome within 48 h of hospitalization. [Copyright &y& Elsevier]

Abstract: Introduction: Omega-3 polyunsaturated fatty acids (PUFA) have demonstrated to have antiarrhythmic properties. However, randomized studies have shown inconsistent results. Objective: We aimed to analyze the effect of omega-3 PUFA on preventing potentially fatal ventricular arrhythmias and sudden cardiac death. Methods: Randomized trials comparing omega-3 PUFA to placebo and reporting sudden cardiac death (SCD) or first implanted cardioverter-defibrillator (ICD) event for ventricular tachycardia or fibrillation were included in this study. A meta-analysis using a random effects model was performed and results were expressed in terms of Odds Ratio (OR) and 95% Confidence Interval (CI) after evaluating for interstudy heterogeneity using I 2. The reported data were extracted on the basis of the intention-to-treat principle. Results: A total of 32,919 patients were included in nine trials; 16,465 patients received omega-3 PUFA and 16,454 received placebo. When comparing omega-3 PUFA to placebo, there was nonsignificant risk reduction of SCD or ventricular arrhythmias (OR = 0.82 [95% CI: 0.60–1.21], p = 0.21 I 2 = 49.7%). Conclusion: Dietary supplementation with omega-3 PUFA does not affect the risk of SCD or ventricular arrhythmias. [Copyright &y& Elsevier]

Abstract: Purpose and medical hypothesis: Rest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit “mechanical inflammation”. Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported. Methods: Between March 2007 and February 2010, we conducted a retrospective study on all patients admitted to our center for acute pericarditis. Diagnosis criteria included two of the following ones: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical electrocardiogram (ECG) findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. Results: We included 73 patients. Median age was 38years (interquartiles 28–51) and median hospitalization duration was 2.0days (1.5–3.0). Median heart rate was 88.0beats per minute (bpm) on admission (interquartiles 76.0–100.0) and 72.0 on discharge (65.0–80.0). Heart rate on admission was significantly correlated with CRP peak (p <0.001), independently of temperature on admission, hospitalization duration and age. Recurrences occurred within 1month in 32% of patients. Heart rate on hospital discharge was correlated with recurrence, independently of age. Conclusion: In acute pericarditis, heart rate on admission is independently correlated with CRP levels and heart rate on discharge seems to be independently correlated to recurrence. This could suggest a link between heart rate and pericardial inflammation. [Copyright &y& Elsevier]

Abstract: Background: Several studies have looked at the effects on mood and quality of life (QOL) among patients who underwent on-pump coronary artery bypass grafting (CABG), but few have reported on off-pump CABG (OPCABG). Methods: We recruited 50 patients undergoing OPCABG. The day before CABG, patients were interviewed using 4 questionnaires: the Beck Depression Index (BDI), Beck Anxiety Index (BAI), Sheehan Disability Scale (SDS), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The process was repeated at 1, 3, 6, and 9 months. Results: One month postoperatively, patients showed increased levels of depression (Δ 1.67 in the mean BDI score, P < .05) and disability (Δ 5.28 in the mean SDS score, P < .001) and decreases levels of anxiety (Δ 3.7 in the mean BAI score, P < .001) and QOL compared with baseline. When compared with the first month, at 9 months patients were significantly less depressed (Δ 3.58 in the mean BDI score, P < .001), were less disabled (Δ 5.34 in the mean SDS score, P < .001), and had better QOL (Δ 3.82 in the mean Q-LES-Q score, P = .014). At 9 months, 44% had some degree of depression and 48% had low QOL. Conclusion: Despite that all scores returned to or below baseline at 9 months, a high percentage of patients still had depressive symptoms and overall poor quality of life (QOL). BDI scores at baseline are good predictors of QOL at all measured intervals. This should make physicians more prudent in diagnosing and observing these patients. [Copyright &y& Elsevier]

Dabigatran, a direct thrombin inhibitor, is one of the new oral anticoagulants. As more patients receive treatment with Dabigatran, and as the clinical indications for Dabigatran use expand, reporting serious adverse effects is fundamental to future safety assessment. Although patients taking Dabigatran had fewer life-threatening bleeds when compared to Coumadin, those events continue to be reported. We describe, in the same patient, a sanguineous pleuro pericardial effusion that was diagnosed incidentally on a pre-ablation cardiac CT angiography. The diagnosis was made approximately two months after initiating Dabigatran treatment for non-valvular atrial fibrillation in a 63-year-old patient. [ABSTRACT FROM AUTHOR]

Dysphagia is a rare manifestation of sarcoidosis. It is more commonly the result of esophageal compression by enlarged mediastinal lymph nodes rather than direct esophageal involvement and rarely secondary to neurosarcoidosis and oropharyngeal dysphagia. We report a 54 year old female presenting with a six month history of worsening dysphagia. She denied respiratory symptoms. Physical exam was normal. ESR was 61 mm/hr. Serum ACE level was 65 mcg/L. Chest X-ray was normal. Esophagram revealed a large amount of contrast pooling in pharyngeal recesses with intermittent laryngeal aspiration. Swallow videofluorography showed a decreased retraction of the base of the tongue, limited laryngeal elevation, and a large amount of contrast pooling in pharyngeal recesses with intermittent laryngeal aspiration. EGD showed a normal opening of the upper esophageal sphincter and the cricopharyngeus appeared normal. Proximal esophageal biopsies were normal. Brain MRI with gadolinium was normal. Lumbar puncture was performed. CSF showed a moderate pleocytosis, a WBC count of 19 with 97% lymphocytes, an elevated total protein level of 85 mg/dl (15-60). Neck CT scan showed no oropharyngeal tissue thickening or infiltration, no masses or enlarged lymph nodes. Chest CT scan showed enlarged intrathoracic lymph nodes and no esophageal compression. Bronchoscopy showed the vocal cords to be intact, and the CD4/CD8 ratio in BAL was 5.3. Subcarinal lymph node EBUS biopsy revealed non caseating granulomas. The patient was started on IV methylprednisolone. Three days later, the swallow videofluorography showed a near complete response to steroids. The patient tolerated regular consistency diet with thin liquids, and she was discharged on a slow taper of prednisone over a period of three months. A unique case of isolated dysphagia unmasking bulbar neurosarcoidosis and pulmonary sarcoidosis is herein reported. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is rising in incidence and remains a leading cause of cancer-related death. After a decade of disappointing trials following the approval of sorafenib for patients with advanced HCC, a number of tyrosine kinase inhibitors (TKIs) and monoclonal antibodies targeting angiogenesis and immune checkpoints have recently been approved. The phase 3 CELESTIAL trial demonstrated improved progression-free and overall survival with the TKI cabozantinib compared to placebo, supporting it as a treatment option for patients with advanced HCC previously treated with sorafenib. Cabozantinib blocks multiple key pathways of HCC pathogenesis, including VEGFR, MET, and the TAM (TYRO3, AXL, MER) family of receptor kinases, and promotes an immune-permissive tumor microenvironment. Here, we review the mechanisms of action of cabozantinib, including effects on tumor growth and its immunomodulatory properties, providing pre-clinical rationale for combination strategies with checkpoint inhibitors. We discuss the design and outcomes of CELESTIAL including improved survival across subgroups defined by age, disease etiology, baseline AFP level, prior therapies (including duration of prior sorafenib), and tumor burden. Cabozantinib had a manageable safety profile with dose modification. Studies combining cabozantinib with atezolizumab (COSMIC-312) and durvalumab (CAMILLA) in the first and second-line settings are ongoing, as well as a neoadjuvant study of cabozantinib with nivolumab. Future investigations are warranted to define the use of cabozantinib in patients with Child-Pugh B liver function and identify markers predictive of clinical benefit. The role of cabozantinib in HCC continues to evolve with an anticipated role in immunotherapy combinations. [ABSTRACT FROM AUTHOR]

Background: Insufficient recruitment of participants remains a critical roadblock to successful clinical research, particularly clinical trials. Social media provide new ways for connecting potential participants with research opportunities. Researchers suggest that the social network Twitter may serve as a rich avenue for exploring how patients communicate about their health issues and increasing enrollment in cancer clinical trials. However, there is a lack of evidence that Twitter offers practical utility and impact. Objective: This pilot study aimed to examine the feasibility and impact of using Twitter monitoring data (ie, user activity and their conversations about cancer-related conditions and concerns expressed by Twitter users in Los Angeles County) as a tool for enhancing clinical trial recruitment at a comprehensive cancer center. Methods: We will conduct a mixed-methods interrupted time series study design with a before-and-after social media recruitment intervention. On the basis of a preliminary analysis of eligible trials, we plan to onboard at least 84 clinical trials across 6 disease categories: breast cancer, colon cancer, kidney cancer, lymphoma, non-small cell lung cancer, and prostate cancer that are open to accrual at the University of Southern California (USC) Norris Comprehensive Cancer Center. We will monitor messages about these 6 cancer conditions posted by Twitter users in Los Angeles County. Recruitment for the trials will occur through the Twitter account (@USCTrials). Primary study outcomes--feasibility and acceptance of the social media intervention among targeted Twitter users and the study teams of the onboarded trials--will be assessed using qualitative interviews and the 4-point Likert scale and by calculating the proportion of targeted Twitter users who engaged with outreach messages. Second, impact of the social media intervention will be measured by calculating the proportion of enrollees in trials. The enrollment rate will be compared between the active intervention period and the prior 10 months as historical control for each disease trial group. This study has been funded by the National Center for Advancing Translational Science through a Clinical and Translational Science Award. Study approval was obtained from the clinical investigations committee at USC Norris and the institutional review board at USC. Results: Recruitment on Twitter started in February 2018. Data collection will be completed in November 2018. Conclusions: This pilot project will provide preliminary data and practical insight into the application of publicly available Twitter data to identify and recruit clinical trial participants across 6 cancer disease types. We will shed light on the acceptance of the social media intervention among Twitter users and study team members of the onboarded trials. If successful, the findings will inform a multisite randomized controlled trial to determine the efficacy of the social media intervention across different locations and populations. [ABSTRACT FROM AUTHOR]

Introduction Vasovagal syncope is generally benign but may associated to pacing indication. We report two cases of vasovagal requiring pacemaker implantation. A leadless pacemaker was preferred to conventional pacing. Clinical cases: two women aged 24 and 16, were showing repetitive faintness. They presented prodromal symptoms, without triggering factor, that lead to collapse accompanied by convulsions or serious traumas. After a full neurological check-up and elimination of underlying cardiopathy, the diagnosis of vagal syncope with major cardioinhibitory component was made: for one through an implantable loop recorder with sinusal pauses of more than one minute, for the other with a positive tilt test and demonstration of a 18 seconds sinusal pause on a 72 h Holter ECG. The postural and the beta-blocker treatment being inefficient, pacing was decided. A Medtronic MICRA was implanted, via the right femoral vein, on the interventricular septum. Mean procedure time was 50 minutes. Micra was positioned at the first attempt in both patients with thresholds < 0.5 V. No complications were observed and both patients were treated in our outpatient clinic. No syncope occurred since then in both patients over a follow-up of 2 and 12 months without significant change in electrical parameters. Conclusion Even if the DDDR pacing is to be favoured as first intention in this indication, the new leadless pacemakers show many advantages: no surgical approach, infections and haemorrhages decrease, displacement risk decrease, aesthetic keeping up with a same longevity to current simple room pacemakers. Thus, leadless pacemaker can be discussed for young patients with indication for pacing associated to vagal syncope. However, data is lacking in these patients, particularly concerning long-term follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Ginseng is a frequently used food additive and considered to be relatively safe. Long QT syndrome can be hereditary or acquired. It presents as syncope, sudden cardiac death, or seizures. We report the novel case of a female patient without cardiovascular risk factors who developed prolonged QT with subsequent torsades de pointes during periods in which she was drinking large amounts of ginseng. [Copyright &y& Elsevier]

It is well described that certain group of patients do not display the typical symptoms of myocardial infarction (MI). Elderly patients, diabetics and those with previous coronary artery bypass graft surgery are at high risk for silent MI. The diagnosis of Acute MI in the emergency room (ER) is mainly based on the electrocardiogram (EKG) findings of ST elevations or new onset left bundle branch block which is supported by the clinical presentation and positive biomarkers when present. The diagnoses can sometimes become challenging when the patient is asymptomatic and has coincidental finding of hyperkalemia with diffuse ST segment elevations simulating that seen with electrolyte disturbance. Despite the well known pseudoinfarction pattern of hyperkalemia, acute MI should be ruled out first. A high index of suspicion is needed, especially in high risk patients. We think that in rare clinical situation when the diagnosis is in doubt, MI should be ruled out, as time has a high impact on patient mortality. An urgent bedside echocardiogram is very beneficial in excluding regional wall motion abnormalities and preventing any delay in destination therapy for transmural MI. We present a 67 years old female with history of diabetes and chronic kidney disease sent by her nephrologist to the ER for severe hyperkalemia (Potassium 7.2 milliequivalent/L). She was found to have ST elevations on EKG despite having no chest pain or distress. On cardiac catheterization she had a total occlusion of the proximal left circumflex artery, with a filling defect consistent with large thrombus. [ABSTRACT FROM AUTHOR]

Purpose Acute pericarditis is rather frequent. Annual incidence is estimated to 27.7 new cases per 100,000 inhabitants in Europe. About 5% of all non-ischemic chest pains admitted at emergencies could be pericarditis. Most of the patients are young patients, with a significant cost to society, particularly as regards hospitalizations. Indeed, pericarditis represents 1% of all hospitalizations in department of cardiology. It could be very interesting if clinical presentation and especially heart rate could help predict duration of hospitalizations. Methods Between March 2007 and February 2010, we conducted a retrospective study concerning all patients admitted in our center for acute pericarditis. Diagnosis criteria included 2 among the 4 following: typical chest pain, friction rub, pericardial effusion on echocardiography, or typical ECG findings. We evaluated hospital events (heart failure, acute pains, death) and biology during hospitalization (CRP on admission, on days 1, 2, 3, and especially peak). At one month, clinical events were recorded through phone calls when not noticed in clinical settings. Results We included 73 patients. Mean age was 41.0 y (CI 95% 37.2-44.8) and mean hospitalization duration was 3.5 d (2.5-4.5). Heart rate on admission was 88 bpm (83.6-92.4) and 71.8 bpm (68.9-74.7) on discharge. CRP peak was strongly correlated with heart rate (r=0.54; p<0.0001) and with hospitalization duration (r=0.8; p=0.007). Finally, we found a positive correlation between heart rate on admission and duration of hospitalizations (r=0,226; p<0.06). Fever was scarcely observed (21%), and was not correlated with heart rate and with CRP. Conclusion In acute pericarditis, cardiac frequency at admission is correlated with hospitalization duration, and could be a new prognostic marker. This point deserves to be explored, in order to reduce hospitalization duration. [ABSTRACT FROM AUTHOR]