A facile method to prepare superparamagnetic iron oxide and hydrophobic drug-encapsulated biodegradable polyurethane nanoparticles.

Superparamagnetic iron oxide nanoparticles (SPIO NPs) have a wide range of biomedical applications such as in magnetic resonance imaging, targeting, and hyperthermia therapy. Aggregation of SPIO NPs can occur because of the hydrophobic surface and high surface energy of SPIO NPs. Here, we developed a facile method to encapsulate SPIO NPs in amphiphilic biodegradable polymer. Anionic biodegradable polyurethane nanoparticles (PU NPs) with ~35 nm size and different chemistry were prepared by waterborne processes. SPIO NPs were synthesized by chemical co-precipitation. SPIO NPs were then added to the aqueous dispersion of PU NPs, followed by application of high-frequency (~20 kHz) ultrasonic vibration for 3 min. This method rendered SPIO-PU hybrid NPs (size ~110 nm) suspended in water. SPIO-PU hybrid NPs contained ~50-60 wt% SPIO and retained the superparamagnetic property (evaluated by a magnetometer) as well as high contrast in magnetic resonance imaging. SPIO-PU NPs also showed the ability to provide cell hyperthermic treatment. Using the same ultrasonic method, hydrophobic drug (Vitamin K3 [VK3]) or (9-(methylaminomethyl) anthracene [MAMA]) could also be encapsulated in PU NPs. The VK3-PU or MAMA-PU hybrid NPs had ~35 nm size and different release profiles for PUs with different chemistry. The encapsulation efficiency for VK3 and MAMA was high (~95%) without burst release. The encapsulation mechanism may be attributed to the low glass transition temperature (Tg) and good mechanical compliance of PU NPs. The new encapsulation method involving waterborne biodegradable PU NPs is simple, rapid, and effective to produce multimodular NP carriers.

Risk factors associated with adverse drug events among older adults in emergency department.

BACKGROUND: Little is known about the emergency department (ED) visits from drug-related injury among older adults in Taiwan. This study seeks to identify risk factors associated with adverse drug events (ADEs) leading to ED visits. METHODS: We prospectively conducted a case-control study of patients 65years and older presenting to the ED. ED visits between March 1, 2009 and Feb 28, 2010 identified by investigators for suspected ADEs were further assessed by using the Naranjo Adverse Drug Reaction probability scale. For each patient with an ADE, a control was selected and time-matched from the ED population of the study hospital. The association between the risk of adverse drug events and triage, age, gender, serum alanine transaminase (ALT), serum creatinine, number of medications, and Charlson Comorbidity Index scores were analyzed using logistic regression. RESULTS: Of 20,628 visits, 295 ADEs were physician-documented in older adults. Independent risk factors for ADEs included number of medications (adjusted odds ratio [OR]=4.1; 95% confidence interval [CI] 2.4-6.9 for 3-7 drugs; adjusted OR=6.4; 95% CI 3.7-11.0 for 8 or more drugs) and increased concentration of serum creatinine (adjusted OR=1.5; 95% CI 1.1-2.2). Diuretics, analgesics, cardiovascular agents, anti-diabetic agents and anticoagulants were the medications most commonly associated with an ADE leading to ED visits. CONCLUSIONS: This study suggests that prevention efforts should be focused on older patients with renal insufficiency and polypharmacy who are using high risk medications such as anticoagulants, diuretics, cardiovascular agents, analgesics, and anti-diabetic agents.

Severe bleeding after antithrombotic therapy in urosepsis masquerading as myocardial infarction.

Cardiac dysfunction is common in patients with severe sepsis and septic shock. We present a 71-year-old woman with Escherichia coli urosepsis and sepsis-induced myocardial injury masquerading as non-ST elevated myocardial ischemia. Spontaneous psoas hematoma requiring blood transfusion and intracranial hemorrhage developed after antiplatelet and anticoagulant therapies, even in therapeutic doses. The patient was managed conservatively and recovered well with minor residual hemiparesis. Bleeding complications are a common risk of antithrombotic therapy. It is therefore crucial to weigh the impact of efficacy against safety. Old age, female gender, renal insufficiency and sepsis character increased the risk of bleeding in this patient. A misinterpretation of elevated cardiac troponin I may give rise to a diagnostic dilemma and cause unnecessary morbidity.

Technical feasibility of laparoscopic total mesorectal excision for patients with low rectal cancer after concurrent radiation and chemotherapy with bevacizumab plus FOLFOX.

BACKGROUND: This study aimed to evaluate the technical feasibility of laparoscopic total mesorectal excision (TME) for the treatment of low rectal cancer after concurrent chemoradiation therapy (CCRT) with bevacizumab and FOLFOX. METHODS: Patients with clinical T3, T4, or N1-2 rectal cancer were subjected to a preoperative CCRT protocol with FOLFOX and bevacizumab (5 mg/kg) biweekly for 6 cycles followed by a standardized laparoscopic TME procedure, as detailed in the attached video. RESULTS: The treatment protocol was completed by 28 patients. Scrutiny of the video indicated that the dissection plane was a little blurred due to preoperative CCRT, but this did not significantly increase the technical difficulties. Laparoscopic TME was efficiently performed with acceptable operation time (214.4 ± 44.4 min). However, the median blood loss (420 ml; range, 120-1,200 ml) in this series was significantly greater than in the historic series without bevacizumab therapy. Bevacizumab seems not to increase the severity of FOLFOX-related liver steatosis and sinusoidal dilation. One operative mortality (3.6%) occurred. Six patients (21.4%) presented with postoperative complications including upper gastrointestinal bleeding, deep vein thrombosis, pelvic abscess, wound infection, enterocutaneous fistula, and perineal fistula. The patients presented with mild postoperative pain and had a quick convalescence. The addition of bevacizumab to FOLFOX achieved a superior pathologic response for 78.3% of the patients, whose residual tumor cells were very few (< 10% microscopic field). CONCLUSIONS: Based on the controllable surgical complications and minimal invasiveness in the current patient series, laparoscopic TME is shown to be technically feasible and can be recommended for patients with advanced lower rectal cancer requiring preoperative CCRT using bevacizumab as the additional therapeutic agent.

Video. Laparoscopic dissection of Denonvilliers' fascia and implications for total mesorectal excision for treatment of rectal cancer.

AIM: To inspect Denonvilliers' fascia and its relationship with neighboring oncologically and functionally important anatomic structures by laparoscopic approach. METHODS: A total of 112 patients with middle or low rectal cancer were successfully treated by laparoscopic total mesorectal excision (TME). Digital versatile disk (DVD) recordings were retrieved for scrutiny of the whole dissection process of Denonvilliers' fascia and its contiguous anatomic structures. RESULTS: As highlighted in the attached video footage, for nearly all male patients (91%, n = 58), the boundaries of Denonvilliers' fascia could be clearly recognized by laparoscopy. Denonvilliers' fascia, varying in nature from a fragile translucent fibrous layer to a tough leathery membrane, manifests itself as a trapezoidal "apron" covering the glistening fatty tissues of the anterior mesorectum. Anterior dissection in TME can be efficiently continued downwards "in front of" Denonvilliers' fascia. When the prostate is reached, the natural surgical plane halts, and the dissection plane should be shifted to behind this fascia. In contrast, in female patients, Denonvilliers' fascia was much less obvious as a distinct fibrous layer than in male patients. The most appropriate term for the structure in between the rectum and vagina may be rectovaginal septum, in which there is no natural surgical plane, rather than Denonvilliers' fascia. CONCLUSIONS: By laparoscopic approach, the nature of Denonvilliers' fasciae in male and female patients can be better defined and facilitates more precise laparoscopic total mesorectal excision for rectal cancer.