Chest CT scoring for evaluation of lung sequelae in congenital diaphragmatic hernia survivors

Objectives Data on long-term structural lung abnormalities in survivors of congenital diaphragmatic hernia (CDH) is scarce. The purpose of this study was to develop a chest computed tomography (CT) score to assess the structural lung sequelae in CDH survivors and to study the correlation between the CT scoring and clinical parameters in the neonatal period and at 1 year of follow-up. Methods A prospective, clinical follow-up program is organised for CDH survivors at the University Hospital of Leuven including a chest CT at the age of 1 year. The CT scoring used and evaluated, named CDH-CT score, was adapted from the revised Aukland score for chronic lung disease of prematurity. Results Thirty-five patients were included. All CT scans showed some pulmonary abnormalities, ranging from very mild to severe. The mean total CT score was 16 (IQR: 9-23), with the greatest contribution from the subscores for decreased attenuation (5; IQR: 2-8), subpleural linear and triangular opacities (4; IQR: 3-5), and atelectasis/consolidation (2; IQR: 1-3). Interobserver and intraobserver agreement was very good for the total score (ICC coefficient > 0.9). Total CT score correlated with number of neonatal days ventilated/on oxygen as well as with respiratory symptoms and feeding problems at 1 year of age. Conclusion The CDH-CT scoring tool has a good intraobserver and interobserver repeatability and correlates with relevant clinical parameters. This holds promise for its use in clinical follow-up and as outcome parameter in clinical interventional studies

Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer

Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 mu g PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTX-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D= 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer

Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells

Hyperbaric Oxygen Therapy: Solution for Difficult to Heal Acute Wounds? Systematic Review

Hyperbaric oxygen therapy (HBOT) is used to treat various wound types. However, the possible beneficial and harmful effects of HBOT for acute wounds are unclear. We undertook a systematic review to evaluate the effectiveness of HBOT compared to other interventions on wound healing and adverse effects in patients with acute wounds. To detect all available randomized controlled trials (RCTs) we searched five relevant databases up to March 2010. Trial selection, quality assessment, data extraction, and data synthesis were conducted by two of the authors independently. We included five trials, totaling 360 patients. These trials, with some methodologic flaws, included different kinds of wound and focused on different outcome parameters, which prohibited meta-analysis. A French trial (n = 36 patients) reported that significantly more crush wounds healed with HBOT than with sham HBOT [relative risk (RR) 1.70, 95% confidence interval (CI) 1.11-2.61]. Moreover, there were significantly fewer additional surgical procedures required with HBOT (RR 1.60, 95% CI 1.03-2.50), and there was significantly less tissue necrosis (RR 1.70, 95% CI 1.11-2.61). In one of two American trials (n = 141) burn wounds healed significantly quicker with HBOT (P <0.005) than with routine burn care. A British trial (n = 48) compared HBOT with usual care. HBOT resulted in a significantly higher percentage of healthy graft area in split skin grafts (RR 3.50, 95% CI 1.35-9.11). In a Chinese trial (n = 145) HBOT did not significantly improve flap survival in patients with limb skin defects. HBOT, if readily available, appears effective for the management of acute, difficult to heal wound

Oiconomy Pricing - Real price of cocoa liquor from single origin beans, Sierra Leone

Tradin Organic is a Dutch B2B company, which sources, distributes, and processes organic food ingredients to the international food market. Within its wide product portfolio, the case is single origin, organic cocoa liquor, from cocoa beans which are cultivated by smallholder farmers, located in Sierra Leone. The cocoa beans are bought in from the smallholder farmers and processed in a factory owned by Tradin Organic and stationed in The Netherlands. Tradin Organic has several impact programs aimed at to improving the environmental and social sustainability of the cocoa supplychain but has not yet quantified the externalities associated with the product

Oiconomy Pricing - Real price of cocoa liquor from single origin beans, Sierra Leone

Tradin Organic is a Dutch B2B company, which sources, distributes, and processes organic food ingredients to the international food market. Within its wide product portfolio, the case is single origin, organic cocoa liquor, from cocoa beans which are cultivated by smallholder farmers, located in Sierra Leone. The cocoa beans are bought in from the smallholder farmers and processed in a factory owned by Tradin Organic and stationed in The Netherlands. Tradin Organic has several impact programs aimed at to improving the environmental and social sustainability of the cocoa supplychain but has not yet quantified the externalities associated with the product

A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42

Introduction: The ability to identify individuals at increased genetic risk for Alzheimer's disease (AD) may streamline biomarker and drug trials and aid clinical and personal decision making. Methods: We evaluated the discriminative ability of a genetic risk score (GRS) covering 22 published genetic risk loci forADin 1162 Flanders-BelgianADpatients and 1019 controls and assessed correlations with family history, onset age, and cerebrospinal fluid (CSF) biomarkers (A beta(1-42), T-Tau, P-Tau(181P)). Results: A GRS including all single nucleotide polymorphisms (SNPs) and age-specific APOE epsilon 4 weights reached area under the curve (AUC) 0.70, which increased to AUC 0.78 for patients with familial predisposition. Risk of AD increased with GRS (odds ratio, 2.32 (95% confidence interval 2.08-2.58 per unit; P < 1.0e(-15)). Onset age and CSF Ab1-42 decreased with increasing GRS (P-onset_age 5 9.0e(-11); P-A beta = 8.9e(-7)). Discussion: The discriminative ability of this 22-SNP GRS is still limited, but these data illustrate that incorporation of age-specific weights improves discriminative ability. GRS-phenotype correlations highlight the feasibility of identifying individuals at highest susceptibility. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association