Citations

Chronic neutrophilic leukemia (CNL) is a potentially aggressive myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of ≥25 × 109/L (of which >80% are neutrophils) and with <10 and <1% circulating immature granulocytes and blasts, respectively without dysplasia, clinical, or molecular criteria for other myeloproliferative disorders, nor an identifiable cause for physiologic neutrophilia in the absence of markers of myeloid clonality. Such a pathogenic clonal marker has now been identified as a somatic activating mutation of CSF3R, most commonly CSF3R T618I, thus demanding revision of the current WHO diagnostic classification to include the molecular criterion of mutated CSF3R. The clinical presentation, disease course and prognosis of CSF‐R mutated CNL have been recently outlined. Co‐operative mutations in SETBP1 and ASXL1 appear to be of prognostic significance and correlate with disease progression. Advances in the understanding of the molecular pathogenesis of CNL, have not yet fully translated into satisfactory therapeutic strategies, but the foundations for these are strengthening. Am. J. Hematol. 91:342–349, 2016. © 2015 Wiley Periodicals, Inc.

ObjectivesTo investigate the utility and safety of the GuideLiner “mother‐and‐child” catheter system during transradial and transfemoral percutaneous coronary intervention (PCI).BackgroundIn patients with complex coronary anatomy, stent delivery can be challenging and result in procedural failure and complications. The GuideLiner is a coaxial guide extension system designed to enable deep vessel engagement and facilitate device delivery. The purpose of this study was to evaluate procedural success and safety in a series of GuideLiner‐facilitated PCI.MethodsSingle center retrospective study of PCI utilizing the GuideLiner catheter between February 2010 and October 2014. Patients who underwent PCI without GuideLiner use during the same time period were used as controls for comparison.ResultsA total of 363 cases of GuideLiner‐facilitated PCI were identified from 6,088 unique PCI procedures performed during this same time period. Patients in the GuideLiner group were older (mean age 71.5 vs. 67.8, P < 0.001) and had more multivessel disease (72% vs. 63%, P = 0.001) compared with controls. Type C lesions were present in 78% of GuideLiner cases. Procedural success resulting in successful device delivery with the GuideLiner catheter was 80.2%. Stent deformation associated with GuideLiner use occurred in 2.2% (8/363), with the incidence of this complication decreasing over device iterations. Coronary dissection attributed to GuideLiner occurred in 3.3% (12/363) and became less frequent over the study period.ConclusionsIn this consecutive series of GuideLiner supported PCI, the guide extension system enabled procedural success in the majority. A decline in device‐associated complications over time may be attributed to operator learning curve, patient selection, and improvement in catheter design. © 2015 Wiley Periodicals, Inc.

In the United States alone, there are currently approximately 14.5 million cancer survivors, and this number is expected to increase to 20 million by 2020. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), stroke, critical limb ischemia, arrhythmias, and heart failure, independently from the direct myocardial or pericardial damage from the malignancy itself. Consequently, the need for invasive evaluation and management in the cardiac catheterization laboratory (CCL) for such patients has been increasing. In recognition of the need for a document on special considerations for cancer patients in the CCL, the Society for Cardiovascular Angiography and Interventions (SCAI) commissioned a consensus group to provide recommendations based on the published medical literature and on the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients. © 2015 Wiley Periodicals, Inc.

ObjectivesTo compare the in‐hospital outcomes in cirrhosis patients undergoing transcatheter aortic valve replacement (TAVR) versus those undergoing surgical aortic valve replacement (SAVR).BackgroundOver the last 10 years, TAVR has emerged as a therapeutic option for treating severe aortic stenosis in high‐risk patients. Cirrhosis patients have a high risk of operative morbidity and mortality while undergoing cardiac surgery. This study's hypothesis was that TAVR is a safer alternative compared to SAVR in cirrhosis patients.MethodsThe study population was derived from the National Inpatient Sample (NIS) for the years 2011–2012 using ICD‐9‐CM procedure codes 35.21 and 35.22 for SAVR, and 35.05 and 35.06 for TAVR. Patients <50 years of age and those who concomitantly underwent other valvular procedures were excluded. ICD‐9‐CM diagnosis codes were used to identify patients with liver cirrhosis, portal hypertension, and esophageal varices. Using propensity score matching, two matched cohorts were derived in which the outcomes were compared using appropriate statistical tests.ResultsThere were 30 patients in the SAVR and TAVR group each. Compared to the TAVR group, the patients in SAVR group had significantly higher rate of transfusion of whole blood or blood products (p = 0.037), longer mean postprocedural length of stay (p = 0.006), and nonsignificantly higher mean cost of hospitalization (p = 0.2), any complications rate (p = 0.09), and liver complications rate (p = 0.4). In‐hospital mortality rate was same in the both the groups. No patients in the TAVR group required open‐heart surgery or cardiopulmonary bypass.ConclusionTAVR could be a viable option for aortic valve replacement in cirrhosis patients. © 2015 Wiley Periodicals, Inc.

Celiac disease (CD) is a common chronic immune disease triggered by gluten. Gliadin peptides pass through the epithelial layers, either paracellularly or transcellularly, to launch a potent adaptive immune response in the lamina propria. This aberrant immune response leads to diverse gastrointestinal and extra-gastrointestinal symptoms. Currently, the only treatment for CD is a strict lifelong adherence to a gluten-free diet (GFD), which can be challenging. An early effect of gluten in CD is an increase in gut permeability. Larazotide acetate, also known as AT-1001, is a synthetic peptide developed as a permeability regulator primarily targeting CD. In vitro studies indicate that larazotide acetate is capable of inhibiting the actin rearrangement caused by gliadin and clinical studies have been conducted using this peptide as a therapy for CD.

Objective To summarise articles reporting on burnout among medical students and residents (trainees) in a narrative review. Methods MEDLINE was searched for peer‐reviewed, English language articles published between 1990 and 2015 reporting on burnout among trainees. The search used combinations of Medical Subject Heading terms medical student , resident , internship and residency, and burnout, professional . Reference lists of articles were reviewed to identify additional studies. A subset of high‐quality studies was selected. Results Studies suggest a high prevalence of burnout among trainees, with levels higher than in the general population. Burnout can undermine trainees’ professional development, place patients at risk, and contribute to a variety of personal consequences, including suicidal ideation. Factors within the learning and work environment, rather than individual attributes, are the major drivers of burnout. Limited data are available regarding how to best address trainee burnout, but multi‐pronged efforts, with attention to culture, the learning and work environment and individual behaviours, are needed to promote trainees’ wellness and to help those in distress. Conclusion Medical training is a stressful time. Large, prospective studies are needed to identify cause‒effect relationships and the best approaches for improving the trainee experience.

AbstractPersistent opening of the mitochondrial permeability transition pore (PTP), an inner membrane channel, leads to mitochondrial dysfunction and renders the PTP a therapeutic target for a host of life‐threatening diseases. Herein, we report our effort toward identifying small‐molecule inhibitors of this target through structure–activity relationship optimization studies, which led to the identification of several potent analogues around the N‐phenylbenzamide compound series identified by high‐throughput screening. In particular, compound 4 (3‐(benzyloxy)‐5‐chloro‐N‐(4‐(piperidin‐1‐ylmethyl)phenyl)benzamide) displayed noteworthy inhibitory activity in the mitochondrial swelling assay (EC50=280 nm), poor‐to‐very‐good physicochemical as well as in vitro pharmacokinetic properties, and conferred very high calcium retention capacity to mitochondria. From the data, we believe compound 4 in this series represents a promising lead for the development of PTP inhibitors of pharmacological relevance.

Colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. This is in spite of widespread, effective measures of preventive screening, and also major advances in treatment options. Despite advances in cytotoxic and targeted therapy, resistance to chemotherapy remains one of the greatest challenges in long-term management of incurable metastatic disease and eventually contributes to death as tumors accumulate means of evading treatment. We performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, and the ASCO Annual Symposium abstracts through June 2015 for the purpose of this review. We discuss the current state of knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies now in use for the treatment of CRC.