Contemporary NSTEMI management: the role of the hospitalist.

Non-ST-segment elevation myocardial infarction (NSTEMI) is defined as elevated cardiac biomarkers of necrosis in the absence of persistent ST-segment elevation in the setting of anginal symptoms or other acute event. It carries a poorer prognosis than most ST-segment elevation events, owing to the typical comorbidity burden of the older NSTEMI patients as well as diverse etiologies that add complexity to therapeutic decision-making. It may result from an acute atherothrombotic event (\u27Type 1\u27) or as the result of other causes of mismatch of myocardial oxygen supply and demand (\u27Type 2\u27). Regardless of type and other clinical factors, the hospital medicine specialist is increasingly responsible for managing or coordinating the care of these patients. Following published guidelines for risk stratification and basing anti-anginal, anticoagulant, antiplatelet, other pharmacologic therapies, and overall management approach on that individualized patient risk assessment can be expected to result in better short- and long-term clinical outcomes, including near-term readmission and recurrent events. We present here a review of the evidence basis and expert commentary to assist the hospitalist in achieving those improved outcomes in NSTEMI. Given that the Society for Hospital Medicine cites care of patients with acute coronary syndrome as a core competency for hospitalists, it is essential that those specialists stay current on optimal NSTEMI care

High-Performance Atomically-Thin Room-Temperature NO2 Sensor.

The development of room-temperature sensing devices for detecting small concentrations of molecular species is imperative for a wide range of low-power sensor applications. We demonstrate a room-temperature, highly sensitive, selective, stable, and reversible chemical sensor based on a monolayer of the transition-metal dichalcogenide Re0.5Nb0.5S2. The sensing device exhibits a thickness-dependent carrier type, and upon exposure to NO2 molecules, its electrical resistance considerably increases or decreases depending on the layer number. The sensor is selective to NO2 with only minimal response to other gases such as NH3, CH2O, and CO2. In the presence of humidity, not only are the sensing properties not deteriorated but also the monolayer sensor shows complete reversibility with fast recovery at room temperature. We present a theoretical analysis of the sensing platform and identify the atomically sensitive transduction mechanism

Primary intraocular lymphoma.

Primary intraocular lymphoma (PIOL) is an ocular malignancy that is a subset of primary central system lymphoma (PCNSL). Approximately one-third of PIOL patients will have concurrent PCNSL at presentation, and 42-92% will develop PCNSL within a mean of 8-29 months. Although rare, the incidence has been rising in both immunocompromised and immunocompetent populations. The majority of PIOL is diffuse large B-cell lymphoma, though rare T-cell variants are described. Recently, PIOL has been classified by main site of involvement in the eye, with vitreoretinal lymphoma as the most common type of ocular lymphoma related to PCNSL. Diagnosis remains challenging for ophthalmologists and pathologists. PIOL can masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other neoplasms such as metastatic cancers. Laboratory diagnosis by cytology has been much aided by the use of immunocytochemistry, flow cytometry, biochemical finding of interleukin changes (IL10:IL6 ratio > 1), and cellular microdissection with polymerase chain reaction amplification for clonality. Use of several tests improves the diagnostic yield. Approaches to treatment have centered on systemic methotrexate-based chemotherapy, often with cytarabine (Ara-C) and radiotherapy. Use of intravitreal chemotherapy with methotrexate (0.4 mg/0.1 mL) is promising in controlling ocular disease, and intravitreal rituximab (anti-CD20 monoclonal antibody) has also been tried. Despite these advances, prognosis remains poor

Maritoclax and Dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner

The anti-apoptotic BCL-2 family proteins are important targets for cancer chemotherapy. Specific and potent inhibitors of the BCL-2 family, such as ABT-263 (navitoclax) and ABT-199, are only effective against some members of the BCL-2 family but do not target MCL-1, which is commonly amplified in tumors and associated with chemoresistance. In this report, the selectivity and potency of two putative MCL-1 inhibitors, dinaciclib and maritoclax, were assessed. Although both compounds induced Bax/Bak- and caspase-9-dependent apoptosis, dinaciclib was more potent than maritoclax in downregulating MCL-1 and also in inducing apoptosis. However, the compounds induced apoptosis, even in cells lacking MCL-1, suggesting multiple mechanisms of cell death. Furthermore, maritoclax induced extensive mitochondrial fragmentation, and a Bax/Bak- but MCL-1-independent accumulation of mitochondrial reactive oxygen species (ROS), with an accompanying loss of complexes I and III of the electron transport chain. ROS scavengers, such as MitoQ, could not salvage maritoclax-mediated effects on mitochondrial structure and function. Taken together, our data demonstrate that neither dinaciclib nor maritoclax exclusively target MCL-1. Although dinaciclib is clearly not a specific MCL-1 inhibitor, its ability to rapidly downregulate MCL-1 may be beneficial in many clinical settings, where it may reverse chemoresistance or sensitize to other chemotherapeutic agents

Impact of Clopidogrel Pretreatment on Ischemic Complications of PCI among Bivalirudin-Treated Patients: Results from the EVENT Registry

Computational Infrastructure and Informatics Poster SessionBackground: Although clopidogrel (CLO) pretreatment benefits PCI patients with acute coronary syndromes, these benefits are less well-established among elective PCI patients—particularly when treated with the direct thrombin inhibitor (DTI), bivalirudin. The effect of timing of CLO pretreatment on ischemic complications in these patients is also unknown. Methods: We used data from the multicenter EVENT registry to assess the association of clopidogrel pretreatment (600 mg 2 hr pre-PCI, 300 mg 6 hrs pre-PCI, or 75 mg/d for 1 week) with PCI-related complications in patients undergoing elective PCI with a DTI as planned antithrombotic. The primary endpoint was the composite of in-hospital death or MI (peak CKMB > 3 x ULN). Results: Between 01/05 and 12/07, 3568 pts underwent elective PCI and 1913 (54%) received DTI as planned anticoagulant (37% diabetics, age 65±10 y). Clopidogrel pre-treatment was used in 923 (48%). There were no differences in in-hospital or 1 year ischemic or bleeding events in relation to clopidogrel pretreatment in both unadjusted and adjusted analyses (see Table). There was a trend toward lower rates of death or MI with earlier pretreatment, however [Odds ratios vs. no pretreatment: >1 week 0.48 (95% CI 0.08 - 2.73); > 6 h OR 0.69 (95% CI 0.11 - 4.45) and 2-6 h OR 0.77 (95% CI 0.18 - 3.31)]. Conclusion: Among unselected patients undergoing elective PCI with DTI as the planned anticoagulant, clopidogrel pretreatment was common, but was not associated with a reduced risk of ischemic complications