Citations

Abstract Detection of guanylyl cyclase C mRNA in lymph nodes of resected stage II colorectal cancer is highly correlated with the risk of tumor recurrence. If validated, these results could have significant implications for the selection of patients for adjuvant therapy in this disease. Clin Cancer Res; 17(10); 3053–5. ©2011 AACR.

Background and Purpose— Maturing techniques have spurred widespread implementation of endovascular embolectomy therapy for ischemic stroke. We evaluated a large administrative database to determine outcomes in patients treated with endovascular embolectomy in the general population. Methods— Using the National Inpatient Sample, we evaluated outcomes of patients treated for acute ischemic stroke in the United States from 2006 to 2008. Patients who had an ischemic stroke and underwent endovascular clot retrieval were identified. Morbidity, defined as “discharge to long-term facility,” and mortality were evaluated as a function of patient age and of concomitant thrombolytic agent administration. Results— For 2006 to 2008, a total of 3864 patients received endovascular clot retrieval with 266 (6.9%) patients in 2006, 800 (20.7) patients in 2007, and 2798 (72.4%) patients in 2008. The discharge to a long-term facility rate was 51.3% (1983 of 3864). The in-hospital mortality rate was 24.3% (940 of 3864). For patients <65 years old, the rate of in-hospital death was 17.1% (283 of 1658) as compared with a rate of 29.7% (656 of 2206) for patients ≥65 years old ( P <0.0001). The rate of discharge to a long-term facility was 47.6% (789 of 1658) for patients <65 years old and 54.1% (1193 of 2206) for patients ≥65 years old ( P <0.0001). The rate of intracranial hemorrhage was 15.5% without concomitant thrombolysis and 20.0% with concomitant thrombolysis ( P =0.0009). Conclusions— Rates of morbidity and mortality remain high for patients with acute stroke, even in the setting of endovascular embolectomy. Advanced age portends a worse outcome and patients treated with concomitant use of thrombolytic agent had higher rates of intracranial hemorrhage than those without such therapy.

The mechanisms of increased rectal stiffness in women with fecal incontinence (FI) and rectal urgency are not understood. Our hypothesis was that distention-induced activation of mechanosensitive L-type calcium channels in smooth muscle contributes to increased rectal stiffness in FI. Anal pressures, rectal distensibility (compliance, capacity, and contractile response to sinusoidal oscillation), and rectal sensation were assessed before and after oral nifedipine (30 + 10 mg) or placebo in 16 women with FI and 16 asymptomatic women. At baseline, FI patients had a lower anal pressure increment during squeeze (health, 66.9 ± 7.6: FI, 28.6 ± 5.9, mean ± SE, P ≤ 0.01), lower rectal capacity ( P = 0.052), and higher rectal pressures during sinusoidal oscillation (health, 13.7 ± 3.2: FI, 21.7 ± 1.4, mean ± SE, P = 0.02) than the healthy women, which suggests an exaggerated rectal contractile response to distention. Nifedipine decreased mean BP, increased heart rate ( P = 0.01 vs. placebo), and reduced anal resting pressure ( P ≤ 0.01) but did not significantly modify rectal distensibility in health or FI. Plasma nifedipine concentrations (health, 103 ± 21 ng/ml: FI, 162 ± 34 ng/ml) were correlated with increased rectal compliance ( r = 0.6, P = 0.02) in all study participants and, in healthy subjects, with decreased rectal pressures during sinusoidal oscillation ( r = 0.86, P = 0.01), indicative of reduced stiffness. No consistent effects on rectal perception were observed. These observations confirm that FI is associated with anal weakness and increased rectal stiffness. At therapeutic plasma concentrations, nifedipine reduced anal resting pressure but did not improve rectal distensibility in FI, outcomes that argue against a predominant contribution of myogenic L-type calcium channels to reduced rectal distensibility in FI.

Abstract In an international collaborative study, a central histologic review identified 891 patients with essential thrombocythemia, strictly defined by World Health Organization criteria. After a median follow-up of 6.2 years, 109 (12%) patients experienced arterial (n = 79) or venous (n = 37) thrombosis. In multivariable analysis, predictors of arterial thrombosis included age more than 60 years (P = .03; hazard ratio [HR] = 1.7), thrombosis history (P = .003; HR = 2.1), cardiovascular risk factors including tobacco use, hypertension, or diabetes mellitus (P = .007; HR = 1.9), leukocytosis (> 11 × 109/L; P = .04; HR = 1.7), and presence of JAK2V617F (P = .009; HR = 2.6). In contrast, only male gender predicted venous thrombosis. Platelet count more than 1000 × 109/L was associated with a lower risk of arterial thrombosis (P = .007; HR = 0.4). These associations, except the one with leukocytosis, remained significant (or near significant) when analysis was restricted to JAK2V617F-positive cases. The current study clarifies the contribution of specific disease and host characteristics to the risk of arterial versus venous thrombosis in essential thrombocythemia.

Although the Fontan procedure has been enormously successful in palliation of single-ventricle patients, many seem to experience progressive failure of the Fontan circulation over time. Ventricular assist devices (VADs) have developed into stable platforms for long-term support of adult patients with heart failure. Given the success of axial flow devices, it was hypothesized that the technology could provide clinical benefit to failing Fontan patients. The aim of this study was to use a computer model to evaluate VAD support in failing Fontan physiology. A computer model of Fontan circulation with heart failure was developed and the HeartMate II (HM II) (Thoratec Corp) axial flow ventricular assist device was connected to this model in a systemic configuration to examine its impact. Cardiac catheterization data from 7 patients (8 catheterization studies) with failing Fontan physiology were applied to this model to evaluate the impact of using the HM II in this manner. When the HM II was used in a systemic configuration at 8000 rpm, there was a 35% decrease in the systemic venous pressure in the Fontan circuit and a 63% decrease in pulmonary capillary wedge pressure with a resultant 41% increase in CI. The model also predicted patient-specific parameters where the VAD may not benefit the patient, such as fixed elevated pulmonary vascular resistance, low systemic ventricular end-diastolic pressure, and high unresponsive systemic vascular resistance. These data suggest a potential benefit from application of axial flow VAD technology in the management of failing Fontan physiology. Clinical correlation will allow for refinement of this model as a predictive tool in discerning which patients may benefit from placement of a VAD and what issues must be addressed prior to implanting the device.

Taxanes are highly active chemotherapeutic agents in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-paclitaxel is a solvent free, albumin-bound 130-nanometer particle formulation of paclitaxel (Abraxane®, Abraxis Bioscience), which was developed to avoid toxicities of the Cremophor vehicle used in solvent-based paclitaxel. In a phase III clinical trial, nab-paclitaxel demonstrated higher response rates, better safety and side-effect profile compared to conventional paclitaxel, and improved survival in patients receiving it as second line therapy. Higher doses can be administered over a shorter infusion time without the need for special infusion sets or pre-medications. It is now approved in the US for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, where prior therapy included an anthracycline. Recently, several phase II studies have suggested a role for nab-paclitaxel as a single agent and in combination with other agents for first-line treatment of metastatic breast cancer.