Patent foramen ovale diagnosis: The importance of provocative maneuvers

Patent foramen ovale (PFO) is a frequent congenital anomaly, but massive right‐to‐left shunt (RTLS) is normally prevented by higher pressures in left heart chambers. However, mechanical ventilation with positive end‐expiratory pressure (PEEP) can significantly increase right atrial pressure, accentuating the RTLS, mainly after major cardiothoracic surgery. We report a patient admitted to the intensive care unit after cardiac surgery. Pre‐ and intraoperative transesophageal echocardiography only described an aneurysmal interatrial septum with no shunt. However, high‐PEEP ventilation induced a paradoxical response with life‐threatening hypoxemia, triggering further echocardiographic evaluation, revealing massive RTLS across a stretch PFO. Provocative maneuvers (Valsalva/PEEP) significantly increase echocardiographic sensitivity, unmasking silent PFO. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45 :58–61, 2017     

TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression

The TGF-beta signaling network plays a complex role in carcinogenesis because it has the potential to act as either a tumor suppressor or a pro-oncogenic pathway. Currently, it is not known whether TGF-beta can switch from tumor suppressor to pro-oncogenic factor during the course of carcinogenic progression in a single cell lineage with a defined initiating oncogenic event or whether the specific nature of the response is determined by cell type and molecular etiology. To address this question, we have introduced a dominant negative type II TGF-beta receptor into a series of genetically related human breast-derived cell lines representing different stages in the progression process. We show that decreased TGF-beta responsiveness alone cannot initiate tumorigenesis but that it can cooperate with an initiating oncogenic lesion to make a premalignant breast cell tumorigenic and a low-grade tumorigenic cell line histologically and proliferatively more aggressive. In a high-grade tumorigenic cell line, however, reduced TGF-beta responsiveness has no effect on primary tumorigenesis but significantly decreases metastasis. Our results demonstrate a causal role for loss of TGF-beta responsiveness in promoting breast cancer progression up to the stage of advanced, histologically aggressive, but nonmetastatic disease and suggest that at that point TGF-beta switches from tumor suppressor to prometastatic factor.     

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

Background

Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.

Relation between C-reactive protein, treadmill exercise testing, and inducible myocardial ischemia

This study examined the relation between high-sensitivity C-reactive protein (CRP), exercise-induced myocardial ischemia, and exercise tolerance in 288 stable patients who underwent maximal treadmill stress testing. CRP was correlated with peak exercise workload, which was consistent with the long-term predictive value of peak workload and CRP for outcome events. There was no correlation of high-sensitivity CRP with stress-induced ischemia, which is consistent with a lack of correlation between CRP and the degree of chronic luminal coronary arterial narrowing.     

Expression and Activity Patterns of Nitric Oxide Synthases and Antioxidant Enzymes Reveal a Substantial Heterogeneity Between Cardiac and Vascular Aging in the Rat

We investigated the effects of aging and ischemia–reperfusion (I/R) injury on the expression and activity of nitric oxide (^•NO) synthases and superoxide dismutase (SOD) isoforms. To this end we perfused excised hearts from young (6 months old) and old (31–34 months old) rats according to the Langendorff technique. The isolated hearts were, after baseline perfusion for 30 min, either subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion or were control-perfused (60 min normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained unchanged with increasing age and remained unaltered by I/R. However, SOD activity decreased from 7.55 ± 0.1 U/mg protein in young hearts to 5.94 ± 0.44 in old hearts (P<0.05). Furthermore, I/R led to a further decrease in enzyme activity (to 6.35 ± 0.41 U/mg protein; P<0.05) in myocardium of young, but not in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine levels could be detected. Endothelial NOS (eNOS) expression and activity remained unchanged in aged left ventricles, irrespective of I/R injury. This was in steep contrast to peripheral (renal and femoral) arteries obtained from the same animals where a marked age-associated increase of eNOS protein expression could be demonstrated. Inducible NOS expression was undetectable either in the peripheral arteries or in the left ventricle, irrespective of age. In particular when associated with an acute pathology, which is furthermore limited to a certain time frame, changes in the aged myocardium with respect to enzymes crucially involved in maintaining the redox homeostasis, seem to be much less pronounced or even absent compared to the vascular aging process. This may point to heterogeneity in the molecular regulation of the cardiovascular aging process.     

Sex-related bedside clinical variables associated with survival of older inpatients with heart failure

BACKGROUND: Little is known about sex-related differences in factors affecting prognosis of heart failure (HF). We prospectively investigated the relationship between bedside clinical variables and survival of older females vs. males with HF. METHODS: Included were consecutive unselected inpatients, age >/=60 years, admitted for various acute conditions. HF was chronic and of diverse etiologies. Follow-up extended up to 5 years. All-cause mortality was registered and statistically analyzed for association with in-hospital clinical variables. RESULTS: Included were 162 females and 200 males. Survival rates were 52.4% and 59%, respectively, (P=0.1). Advanced age and renal dysfunction (RD) were associated with low survival in both sexes (P<0.03 and 0.02, P<0.001 and 0.01, respectively). An association with low survival was found with respect to; admission for pulmonary edema (P<0.02), using furosemide >/=80 mg/day (P<0.005) and severe HF [NYHA class III-IV (P<0.01)] in females, as well as for hypokalemia (P<0.03) and hypocalcemia (P<0.03) in males. On multivariate analysis RD (P<0.001), increasing age (P=0.008) and furosemide dosage >/=80 mg (P=0.02) were most significantly associated with low survival in females, while RD only was significantly associated with low survival in males (P=0.03). CONCLUSIONS: Several clinical variables, which affect prognosis in older HF patients are sex-related and probably carry practical significance.     

The Role of Helicobacter pylori in Children with Recurrent Abdominal Pain

Objectives: Our major goals in this study were to determine the prevalence of Helicobacter pylori among Israeli children with recurrent abdominal pain and to establish whether a link exists between eradication of Helicobacter pylori and the recovery from abdominal pain. The alternative target was to examine whether the serological test can replace endoscopy in children. Methods: Upper gastrointestinal endoscopy was performed in 80 children with recurrent abdominal pain. During endoscopy, antral biopsies were taken and sent for histo-logical and bacteriological examination. Results: The prevalence of H. pylori , which was indicated by Gram stain and urease test, was 54%. The positive cases were treated with bismuth combined with amoxycillin and metronidazole. Two months after completion of the treatment, 34 patients were reexamined. Twenty-nine of them (85%) became symptom free, and five (15%) remained symptomatic. These five children were retreated, and they also became symptom free. Eight months after completion of treatment, all 34 patients were reexamined and found to be asymptomatic. Conclusions: We found a high prevalence of H. pylori (54%) among Israeli children with recurrent abdominal pain; we also found that symptoms were effectively and significantly reduced by the eradication of H. pylori . The endoscopic examination cannot be replaced by serological test.     

First morning standing up may be risky in acutely ill older inpatients

Information about orthostatic hypotension (OH) among elderly patients hospitalized for acute conditions in short-term facilities is scarce. Many older inpatients carry various predisposing factors for OH. However, its existence goes frequently unrecognized. In this context, first morning standing up following admission for an acute disease may be dangerous. The aim of this study was to investigate OH and associated manifestations in this situation. OH (> or = 20 mmHg systolic and/or (> or =10 mmHg diastolic blood pressure fall), heart rate, arrhythmias and appearance of dizziness or palpitations were recorded in 121 sequential inpatients aged >65 years, prior to and 1, 3 and 5 min following first morning standing. OH occurred in 64.5% of patients, while dizziness and/or palpitations appeared in 76%. Severe adverse effects were registered in 11.5% of OH patients. Significantly associated with OH were: bed rest lasting 9-24 h (vs (< or = 8 h, p<0.001), appearance of dizziness or palpitations (p<0.001 and p=0.005, respectively), heart failure (p=0.02) and renal dysfunction (p=0.04). OH and/or associated symptoms are frequent in acutely ill older inpatients on first morning standing up following nocturnal bed rest. The ominous potential consequences call for alertness to this phenomenon and application of appropriate preventive measures.