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Treatment of acute pulmonary embolism: update on newer pharmacologic and interventional strategies.

Wed, 03/18/2015 - 3:29am
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Treatment of acute pulmonary embolism: update on newer pharmacologic and interventional strategies.

Biomed Res Int. 2014;2014:410341

Authors: Pelliccia F, Schiariti M, Terzano C, Keylani AM, D'Agostino DC, Speziale G, Greco C, Gaudio C

Abstract
Acute pulmonary embolism (PE) is a common complication in hospitalized patients, spanning multiple patient populations and crossing various therapeutic disciplines. Current treatment paradigm in patients with massive PE mandates prompt risk stratification with aggressive therapeutic strategies. With the advent of endovascular technologies, various catheter-based thrombectomy and thrombolytic devices are available to treat patients with massive or submassive PE. In this paper, a variety of newer treatment strategies for PE are analyzed, with special emphasis on various interventional treatment strategies. Clinical evidence for utilizing endovascular treatment modalities, based on our institutional experience as well as a literature review, is provided.

PMID: 25025049 [PubMed - indexed for MEDLINE]

Rebound Coagulopathy in Patients With Snakebite Presenting With Marked Initial Coagulopathy.

Fri, 03/13/2015 - 3:29am

Rebound Coagulopathy in Patients With Snakebite Presenting With Marked Initial Coagulopathy.

Wilderness Environ Med. 2015 Mar 7;

Authors: Witham WR, McNeill C, Patel S

Abstract
OBJECTIVE: An estimated 70% of patients with pit viper snakebites require antivenom to treat serious complications such as coagulopathy. Evidence-based guidance is limited for the appropriate administration of Crotalinae Polyvalent Immune Fab (FabAV) and the duration of laboratory follow-up. The objective of our study was to assess the incidence of marked and recurrent envenomation coagulopathy at our trauma center and identify practice patterns that may prevent serious complications.
METHODS: A retrospective case review was conducted over a 3-year period on patients treated for symptomatic snakebite injury. Case records were reviewed for the inclusion criteria of international normalized ratio (INR) greater than 2.0. The exclusion criterion was limited to patients receiving anticoagulant therapy.
RESULTS: In all, 61 patients were identified on retrospective chart review and 3 patients (4.9%) met inclusion criteria. Two of the 3 patients had marked rebound coagulopathy requiring readmission and additional treatment. In our small series, 2 patients presenting after crotaline envenomation with increased INR (>6.0), decreased fibrinogen (<60 mg/dL), and decreased platelet count (<100,000/mL) had recurrent coagulopathy and were asymptomatic, and recurrence was noted only with follow-up laboratory testing. All patients responded positively within a matter of hours to repeat FabAV administration, with resolution of rebound coagulopathy.
CONCLUSIONS: We recommend periodic monitoring of patients with increased INR, decreased fibrinogen, and decreased platelet count. Patients should be monitored for 10 to 14 days after envenomation to identify asymptomatic rebound coagulopathy. Prompt readministration of FabAV appears to correct the coagulopathy.

PMID: 25758759 [PubMed - as supplied by publisher]

A revised definition for cure of childhood acute lymphoblastic leukemia.

Fri, 03/13/2015 - 3:29am
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A revised definition for cure of childhood acute lymphoblastic leukemia.

Leukemia. 2014 Dec;28(12):2336-43

Authors: Pui CH, Pei D, Campana D, Cheng C, Sandlund JT, Bowman WP, Hudson MM, Ribeiro RC, Raimondi SC, Jeha S, Howard SC, Bhojwani D, Inaba H, Rubnitz JE, Metzger ML, Gruber TA, Coustan-Smith E, Downing JR, Leung WH, Relling MV, Evans WE

Abstract
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).

PMID: 24781017 [PubMed - indexed for MEDLINE]

Role of C/EBP homologous protein in retinal ganglion cell death after ischemia/reperfusion injury.

Thu, 03/12/2015 - 3:29am
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Role of C/EBP homologous protein in retinal ganglion cell death after ischemia/reperfusion injury.

Invest Ophthalmol Vis Sci. 2015 Jan;56(1):221-31

Authors: Nashine S, Liu Y, Kim BJ, Clark AF, Pang IH

Abstract
PURPOSE: To investigate the role of C/EBP homologous protein (CHOP), a proapoptotic protein, and the unfolded protein response (UPR) marker that is involved in endoplasmic reticulum (ER) stress-mediated apoptosis in mouse retinal ganglion cell (RGC) death following ischemia/reperfusion (I/R) injury.
METHODS: Retinal I/R injury was induced in adult C57BL/6J wild-type (WT) and CHOP knockout (Chop(-/-)) mice by raising IOP to 120 mm Hg for 60 minutes. Expression of CHOP and other UPR markers was studied by Western blot and immunohistochemistry. Retinal ganglion cell counts were performed in retinal flat mounts stained with an RGC marker. Retinal ganglion cell function was evaluated by scotopic threshold response (STR) electroretinography.
RESULTS: In WT mice, retinal CHOP was upregulated by 30% in I/R-injured eyes compared to uninjured eyes 3 days after injury (P < 0.05). Immunohistochemistry confirmed CHOP upregulation specifically in RGCs. CHOP knockout did not affect baseline RGC density or STR amplitude. Ischemia/reperfusion injury decreased RGC densities and STR amplitudes in both WT and Chop(-/-) mice. However, survival of RGCs in I/R-injured Chop(-/-) mouse was 48% higher (P < 0.05) than that in I/R-injured WT mouse 3 days after I/R injury. Similarly, RGC density was significantly higher in Chop(-/-) eyes at 7, 14, and 28 days after I/R injury. Scotopic threshold response amplitudes of Chop(-/-) mice were significantly higher at 3 and 7 days after I/R than those of WT mice.
CONCLUSIONS: Absence of CHOP partially protects against RGC loss and reduction in retinal function after I/R injury, indicating that CHOP and, thus, ER stress play an important role in RGC apoptosis in retinal I/R injury.

PMID: 25414185 [PubMed - indexed for MEDLINE]

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