Citations

ObjectiveTo review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder.MethodA systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 – May, 2013) was conducted. Case‐control and cohort studies of bipolar disorder patients age 15 or older with myocardial infarction or stroke as outcomes were included. Two independent reviewers extracted data and assessed quality. Estimates of effect were summarized using random‐effects meta‐analysis.ResultsFive cohort studies including 13 115 911 participants (27 092 bipolar) were included. Due to the use of registers, different statistical methods, and inconsistent adjustment for confounders, there was significant methodological heterogeneity among studies. The exploratory meta‐analysis yielded no evidence for a significant increase in the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96–1.24, P = 0.20; I2 = 6%]. While there was evidence of significant study heterogeneity, the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95% CI 1.29–2.35; P = 0.0003; I2 = 83%).ConclusionThere may be a differential risk of myocardial infarction and stroke in patients with bipolar disorder. Confidence in these pooled estimates was limited by the small number of studies, significant heterogeneity and dissimilar methodological features.

ABSTRACT We describe a case of shoulder hemiarthroplasty infection with Desulfovibrio legallii . Antimicrobial susceptibilities of 36 Desulfovibrio isolates are presented. Metronidazole and carbapenems exhibited reliable activity, although piperacillin-tazobactam did not. Eleven previous cases of Desulfovibrio infection are reviewed; most arose from a gastrointestinal tract-related source.

Abstract Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis. Recent findings suggest that ECD is a clonal disorder, marked by recurrent BRAFV600E mutations in >50% of patients, in which chronic uncontrolled inflammation is an important mediator of disease pathogenesis. Although ∼500 to 550 cases have been described in the literature to date, increased physician awareness has driven a dramatic increase in ECD diagnoses over the last decade. ECD frequently involves multiple organ systems and has historically lacked effective therapies. Given the protean clinical manifestations and the lack of a consensus-derived approach for the management of ECD, we provide here the first multidisciplinary consensus guidelines for the clinical management of ECD. These recommendations were outlined at the First International Medical Symposium for ECD, comprised of a comprehensive group of international academicians with expertise in the pathophysiology and therapy of ECD. Detailed recommendations on the initial clinical, laboratory, and radiographic assessment of ECD patients are presented in addition to treatment recommendations based on critical appraisal of the literature and clinical experience. These formalized consensus descriptions will hopefully facilitate ongoing and future research efforts in this disorder.

Abstract Pancreatic ductal adenocarcinoma (PDA) arises at the convergence of genetic alterations in KRAS with a fostering microenvironment shaped by immune cell influx and fibrotic changes; identification of the earliest tumorigenic molecular mediators evokes the proverbial chicken and egg problem. Matrix metalloproteinases (MMP) are key drivers of tumor progression that originate primarily from stromal cells activated by the developing tumor. Here, MMP3, known to be expressed in PDA, was found to be associated with expression of Rac1b, a tumorigenic splice isoform of Rac1, in all stages of pancreatic cancer. Using a large cohort of human PDA tissue biopsies specimens, both MMP3 and Rac1b are expressed in PDA cells, that the expression levels of the two markers are highly correlated, and that the subcellular distribution of Rac1b in PDA is significantly associated with patient outcome. Using transgenic mouse models, coexpression of MMP3 with activated KRAS in pancreatic acinar cells stimulates metaplasia and immune cell infiltration, priming the stromal microenvironment for early tumor development. Finally, exposure of cultured pancreatic cancer cells to recombinant MMP3 stimulates expression of Rac1b, increases cellular invasiveness, and activation of tumorigenic transcriptional profiles. Implications: MMP3 acts as a coconspirator of oncogenic KRAS in pancreatic cancer tumorigenesis and progression, both through Rac1b-mediated phenotypic control of pancreatic cancer cells themselves, and by giving rise to the tumorigenic microenvironment; these findings also point to inhibition of this pathway as a potential therapeutic strategy for pancreatic cancer. Mol Cancer Res; 12(10); 1430–9. ©2014 AACR.

Patients with apical ballooning syndrome may develop dynamic left ventricular outflow obstruction due to systolic anterior motion of the mitral valve leaflet and secondary functional mitral regurgitation, causing decreased cardiac output and hypotension. If suspected, bedside echocardiography will quickly confirm this complication. Positive inotropic/chronotropic agents should be avoided as they may exacerbate outflow tract obstruction, resulting in further hemodynamic compromise.