Kidney post-transplant monitoring of urinary glycosaminoglycans/proteoglycans and monokine induced by IFN-γ (MIG)

Allograft rejection during the first year after renal transplantation can lead to persistent allograft dysfunction and reduced long-term graft survival. Thus, it is important to define early predictors of kidney damage, less invasive than allograft biopsy. Urinary glycosaminoglycan/proteoglycan concentration and distribution, N-acetyl-β-(d)-glucosaminidase (NAG), and monokine induced by IFN-γ (MIG) levels were evaluated in the immediate post-transplant and during a 1-year follow-up. We observed increased urinary levels of MIG, urinary trypsin inhibitor and its degradation products, the lack of urinary heparan sulfate excretion, and the decreased chondroitin sulfate relative content at day 1 post-transplant in most patients who developed complications in the postoperative period. Moreover, urinary MIG levels showed significant correlations with NAG, C-reactive protein, and GFR at day 1 post-transplant. The monitoring of glycosaminoglycan/proteoglycan urinary pattern and the levels of urine MIG could serve as useful markers for predicting possible complications of transplantation, unraveling an early inflammatory state, on whose basis the immunosuppressive therapy could be appropriately modified.     

Laparoscopic Gastric Band Migration: Role of Environmental Factors in the Experience of a Single Team in Three Operating Rooms

Stomach erosion after gastric banding represents one of its least studied complications, despite the fact that the modalities of presentation and treatment have been clarified in recent years. Associations between this complication and specific surgical factors related to the patient have not been reported. We evaluated the incidence of this complication in various operating environments, to identify a possible association with a specific risk factor. A total of 250 patients underwent gastric banding between 2006 and 2008 and were followed for at least 1 year of follow-up. The procedure was performed in three Centers by the same surgical team. Center A was selected for the learning curve, in the initial phase of the study. All surgeries were performed with standardized techniques. An annual endoscopic evaluation was performed during first 12 months. The data from the three Centers were evaluated comparatively, to assess the incidence of migration and compare sterilization and perioperative preparation techniques. Between May 2006 and December 2008, 140 patients operated on at Center A, 70 at Center B, and 50 at Center C were included. Twelve cases of intragastric migration were observed (4.8% of the entire cohort): two cases at Center A (1.4%) and 10 cases at Center C (25%; A vs. C and A vs. B, p?<?0.05); no cases of erosions were observed in Center B of 50 patients (0%; reviewer 1, comment 1). From a retrospective observation, no significant difference in sterilization techniques was observed, while there were differences in perioperative preparation, although these are not objectifiable parameters.     

Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted > or = 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.     

Heliosphere® Bag in the Treatment of Severe Obesity: Preliminary Experience

Background: Various intragastric balloons have been used in obese patients for temporary weight loss. Recently, a new balloon, the Heliosphere^? Bag, was proposed. In a preliminary study, we evaluated the safety and efficacy of this device. Methods: The Heliosphere^? Bag was used in 10 patients, selected according to the guidelines for obesity surgery. The manufacturer's instructions were followed in positioning the device. Heliosphere^? Bag positioning was performed, after diagnostic endoscopy, under unconscious sedation. After placement, the balloon was slowly inflated with 840-960 cc of air, which gives the inflated final volume of 650-700 cc of air, as the air is compressed. On the first and second post-treatment day, intravenous saline (30-35 ml/kg/d) with omeprazole (20 mg/d), ondansetron (8 mg/d) and butylscopolamine bromide (20 mg t.i.d.) were given to all patients. All patients from day 3 after placement began liquid diet and were discharged home on day 4 on a 1000 kcal diet (carbohydrate 146 g, lipid 68 g, protein 1 g/kg ideal weight). After 6 months, the Heliosphere^? Bag was removed. The patients were followed monthly, and complications and their treatment, post-placement symptoms, BMI and %EWL were recorded. Data were expressed as mean ± SD. Results: From Sept-Dec 2004, 10 patients (5M/5F) underwent Heliosphere^? Bag placement, with age 35.2 ± 15.7 years (17-49), BMI 43.3 ± 8.1 kg/m² (35-51.2), and weight 126.8 ± 23.7 kg (98.4-148). Heliosphere^? Bag positioning was quite difficult in all patients due to low pliancy and large size of the bag, causing patient discomfort. System failure at time of Heliosphere^? Bag positioning was observed in 5/10 patients (50%). At time of removal, the Heliosphere^? Bag was not found in the stomach in one patient. In 3 other patients, the balloon was found partially deflated. At the time of balloon removal after 6 months, BMI was 37.4 ± 13.4 (28.9-42.1) and %EWL was 29.1 ± 20.1 (9.0-57.4). BMI loss was 5.2 ± 13.1 (1.9-11.2) and mean weight loss was 17.5 ± 16.2 kg (5-33). Conclusions: Although weight loss was satisfactory, this device cannot be considered an advance for the temporary treatment of morbid obesity. This balloon still has some instrumental and technical problems that need to be solved: high rate of system failure at positioning, high rate of spontaneous deflation, absence of a marker such as methylene blue, and large size with low pliability that cause significant patient discomfort.     

Use of advanced modeling techniques to optimize thermal packaging designs

Through a detailed case study the authors demonstrate, for the first time, the capability of using advanced modeling techniques to correctly simulate the transient temperature response of a convective flow-based thermal shipper design. The objective of this case study was to demonstrate that simulation could be utilized to design a 2-inch-wall polyurethane (PUR) shipper to hold its product box temperature between 2 and 8 °C over the prescribed 96-h summer profile (product box is the portion of the shipper that is occupied by the payload). Results obtained from numerical simulation are in excellent agreement with empirical chamber data (within ±1 °C at all times), and geometrical locations of simulation maximum and minimum temperature match well with the corresponding chamber temperature measurements. Furthermore, a control simulation test case was run (results taken from identical product box locations) to compare the coupled conduction-convection model with a conduction-only model, which to date has been the state-of-the-art method. For the conduction-only simulation, all fluid elements were replaced with "solid" elements of identical size and assigned thermal properties of air. While results from the coupled thermal/fluid model closely correlated with the empirical data (±1 °C), the conduction-only model was unable to correctly capture the payload temperature trends, showing a sizeable error compared to empirical values (ΔT > 6 °C). A modeling technique capable of correctly capturing the thermal behavior of passively refrigerated shippers can be used to quickly evaluate and optimize new packaging designs. Such a capability provides a means to reduce the cost and required design time of shippers while simultaneously improving their performance. Another advantage comes from using thermal modeling (assuming a validated model is available) to predict the temperature distribution in a shipper that is exposed to ambient temperatures which were not bracketed during its validation. LAY ABSTRACT: Thermal packaging is routinely used by the pharmaceutical industry to provide passive and active temperature control of their thermally sensitive products from manufacture through end use (termed the cold chain). In this study, the authors focus on passive temperature control (passive control does not require any external energy source and is entirely based on specific and/or latent heat of shipper components). As temperature-sensitive pharmaceuticals are being transported over longer distances, cold chain reliability is essential. To achieve reliability, a significant amount of time and resources must be invested in design, test, and production of optimized temperature-controlled packaging solutions. To shorten the cumbersome trial and error approach (design/test/design/test …), computer simulation (virtual prototyping and testing of thermal shippers) is a promising method. Although several companies have attempted to develop such a tool, there has been limited success to date. Through a detailed case study the authors demonstrate, for the first time, the capability of using advanced modeling techniques to correctly simulate the transient temperature response of a coupled conductive/convective-based thermal shipper. A modeling technique capable of correctly capturing shipper thermal behavior can be used to develop packaging designs more quickly, reducing up-front costs while also improving shipper performance.