Optimal antithrombotic management of anticoagulated patients with a history of myocardial infarction

A common clinical dilemma exists for optimal antithrombotic management of a patient requiring oral anticoagulation (such as venous thromboembolism) and continued secondary myocardial infarction prophylaxis. Often aspirin will be continued concomitantly with the indicated oral anticoagulation therapy; however, additional benefits and increased risks of this practice have not been established. A systematic literature review was conducted to determine the benefits and risks of antithrombotic treatment strategies. Five clinical trials met the inclusion criteria and were evaluated to answer this clinical question.     

Aberrant expression of E-cadherin in cervical intraepithelial neoplasia correlates with a false-negative Papanicolaou smear

OBJECTIVES: E-cadherin is responsible for cell adhesion in normal cervical epithelium. It is normally absent in the superficial epithelial layers, allowing for exfoliation. We investigated the correlation between E-cadherin distribution and Papanicolaou smear in subjects with cervical dysplasia. STUDY DESIGN: Tissue samples from 25 women with cervical dysplasia were tested for E-cadherin, beta-catenin, and alpha-catenin expression by immunohistochemistry. The expression pattern of these proteins, whether full thickness or restricted to the basal layers, was correlated with the Papanicolaou smear result. RESULTS: Of 12 women with normal Papanicolaou smears, 10 of 11 informative cases demonstrated E-cadherin expression throughout all epithelial layers. Eight of 10 informative cases with an abnormal Papanicolaou smear showed E-cadherin only at the basal layers. Alpha-catenin was distributed throughout the entire epithelium in samples of all 25 women. CONCLUSIONS: Expression of E-cadherin throughout all epithelial layers was correlated with a false-negative Papanicolaou smear. It is likely that aberrant persistence of E-cadherin in these lesions interferes with the exfoliation of abnormal cells.     

Improving return-to-work after childbirth: design of the Mom@Work study,a randomised controlled trial and cohort study

Background  

Many women suffer from health problems after giving birth, which can lead to sick leave. About 30% of Dutch workers are on sick leave after maternity leave. Structural contact of supervisors with employees on maternity leave, supported by early medical advice of occupational physicians, may increase the chances of return-to-work after maternity leave. In addition, to understand the process of sick leave and return-to-work after childbirth it is important to gain insight into which factors hinder return-to-work after childbirth, as well, as which prognostic factors lead to the development of postpartum health complaints. In this paper, the design of the Mom@Work study is described.     

EPLINβ Is Involved in the Assembly of Cadherin-catenin Complexes in Osteoblasts and Affects Bone Formation

Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms: EPLINα and EPLINβ. In this study, we investigated the role of EPLINβ in osteoblasts using EPLINβ-deficient (EPLINβ^GT/GT) mice. The skeletal phenotype of EPLINβ^GT/GT mice is indistinguishable from the wildtype (WT), but bone properties and strength were significantly decreased compared with WT littermates. Histomorphological analysis revealed altered organization of bone spicules and osteoblast cell arrangement, and decreased alkaline phosphatase activity in EPLINβ^GT/GT mouse bones. Transmission electron microscopy revealed wider intercellular spaces between osteoblasts in EPLINβ^GT/GT mice, suggesting aberrant cell adhesion. In EPLINβ^GT/GT osteoblasts, α- and β-catenins and F-actin were observed at the cell membrane, but OB-cadherin was localized at the perinuclear region, indicating that cadherin-catenin complexes were not formed. EPLINβ knockdown in MC3T3-e1 osteoblast cells showed similar results as in calvaria cell cultures. Bone formation markers, such as RUNX2, Osterix, ALP, and Col1a1 mRNA were reduced in EPLINβ knockdown cells, suggesting an important role for EPLINβ in osteoblast formation. In conclusion, we propose that EPLINβ is involved in the assembly of cadherin-catenin complexes in osteoblasts and affects bone formation.     

Investigating the link of <Emphasis Type="Italic">ACAD10</Emphasis> deficiency to type 2 diabetes mellitus

The Native American Pima population has the highest incidence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) of any reported population, but the pathophysiologic mechanism is unknown. Genetic studies in Pima Indians have linked acyl-CoA dehydrogenase 10 (ACAD10) gene polymorphisms, among others, to this predisposition. The gene codes for a protein with a C-terminus region that is structurally similar to members of a family of flavoenzymes—the acyl-CoA dehydrogenases (ACADs)—that catalyze α,β-dehydrogenation reactions, including the first step in mitochondrial FAO (FAO), and intermediary reactions in amino acids catabolism. Dysregulation of FAO and an increase in plasma acylcarnitines are recognized as important in the pathophysiology of IR and T2DM. To investigate the deficiency of ACAD10 as a monogenic risk factor for T2DM in human, an Acad-deficient mouse was generated and characterized. The deficient mice exhibit an abnormal glucose tolerance test and elevated insulin levels. Blood acylcarnitine analysis shows an increase in long-chain species in the older mice. Nonspecific variable pattern of elevated short-terminal branch-chain acylcarnitines in a variety of tissues was also observed. Acad10 mice accumulate excess abdominal adipose tissue, develop an early inflammatory liver process, exhibit fasting rhabdomyolysis, and have abnormal skeletal muscle mitochondria. Our results identify Acad10 as a genetic determinant of T2DM in mice and provide a model to further investigate genetic determinants for insulin resistance in humans.     

A giant Brunner gland hamartoma successfully treated by endoscopic excision followed by transanal retrieval: A case report

Rationale:Brunner gland hamartoma (BGH) is a rare tumor of the duodenum. Although BGH is a benign tumor, larger lesion with gastrointestinal symptoms requires tumor removal. We report a giant BGH, successfully treated by endoscopic excision followed by transanal retrieval.Patient concerns:A 38-year-old woman complained of severe anemia, tarry stool, and vomiting.Diagnoses:Esophagogastroduodenoscopy (EGD) showed a pedunculated giant submucosal mass at the duodenal bulb.Interventions:We attempted to remove it because the lesion seemed to be responsible for patient''s anemia and vomiting. The lesion had clear but bulky stalk. We carefully cut the stalk using needle-knife and IT knife2. We tried to retrieve specimen, but the mass could not pass through the pyloric ring because of its size. Then we tried to obtain the specimen from anus. Polyethylene glycol solution was administered to accelerate rapid excretion.Outcomes:The mass was successfully removed and was histologically confirmed as a giant BGH, measuring 55 mm in size.Lessons:Reports about endoscopic resection of giant BGH are rare. Moreover, our case is the first report of transanal retrieval of resected specimen using polyethylene glycol solution. Endoscopic resection of BGH is less-invasive but can be more challenging if the mass is large. Our case provides useful option for endoscopic treatment of giant BGH.     

Successful resolution of a left ventricular thrombus with apixaban treatment following acute myocardial infarction

A 62-year-old man was admitted to our emergency department owing to prolonged chest pain that had lasted for 3 h. An electrocardiogram showed ST elevation in leads I, aV_L, and V1-6, and the patient’s laboratory revealed elevated myocardial necrosis marker levels. Emergency coronary angiography showed total occlusion of the proximal left anterior descending coronary artery. Subsequent percutaneous coronary intervention was performed by balloon angioplasty followed by stent implantation, and the patient showed improvement. However, echocardiographic examination 2 weeks after the percutaneous coronary intervention showed a thrombus (40 × 14 mm) in the apex of the left ventricle. In addition to dual antiplatelet therapy, apixaban was administered as anticoagulant therapy for the left ventricular thrombus. The size of the thrombus gradually decreased, and magnetic resonance imaging performed approximately 6 weeks after the initial apixaban administration showed no thrombus without a thromboembolic event. This case demonstrates that left ventricular thrombus can be resolved with apixaban treatment. Apixaban may be an effective alternative to vitamin K antagonist for some patients with acute myocardial infarction complicated by left ventricular thrombus.     

LPA5 signaling is involved in multiple sclerosis-mediated neuropathic pain in the cuprizone mouse model

Lysophosphatidic acid (LPA) and LPA1 receptor signaling play a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. However, LPA and its signaling in the brain are still poorly understood. In the present study, we revealed that the LPA5 receptor expression in corpus callosum elevated after the initiation of demyelination, and the hyperalgesia through Aδ-fibers following cuprizone-induced demyelination was mediated by LPA5 signaling. These data suggest that LPA5 signaling may play a key role in the mechanisms underlying neuropathic pain following demyelination in the brain.     

Metaanalysis of Survival,Complications, and Imaging Response following Chemotherapy-based Transarterial Therapy in Patients with Unresectable Intrahepatic Cholangiocarcinoma

PurposeUnresectable intrahepatic cholangiocarcinoma represents a devastating illness with poor outcomes when treated with standard systemic therapies. Several smaller nonrandomized outcomes studies have been reported for such patients undergoing transarterial therapies. A metaanalysis was performed to assess primary clinical and imaging outcomes, as well as complication rates, following transarterial interventions in this patient population.Materials and MethodsBy using standard search techniques and metaanalysis methodology, published reports (published in 2012 and before) evaluating survival, complications, and imaging response following transarterial treatments for patients with unresectable intrahepatic cholangiocarcinoma were identified and evaluated.ResultsA total of 16 articles (N = 542 subjects) met the inclusion criteria and are included. Overall survival times were 15.7 months±5.8 and 13.4 months±6.7 from the time of diagnosis and time of first treatment, respectively. The overall weighted 1-year survival rate was 58.0%±14.5. More than three fourths of all subjects (76.8%) exhibited a response or stable disease on postprocedure imaging; 18.9% of all subjects experienced severe toxicities (National Cancer Institute/World Health Organization grade≥3), and most experienced some form of postembolization syndrome. Overall 30-day mortality rate was 0.7%.ConclusionsAs demonstrated by this metaanalysis, transarterial chemotherapy-based treatments for cholangiocarcinoma appears to confer a survival benefit of 2–7 months compared with systemic therapies, demonstrate a favorable response by imaging criteria, and have an acceptable postprocedural complication profile. Such therapies should be strongly considered in the treatment of patients with this devastating illness.