Investigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepoints.

BACKGROUND: Distinct sets of microbes contribute to colorectal cancer (CRC) initiation and progression. Some occur due to the evolving intestinal environment but may not contribute to disease. In contrast, others may play an important role at particular times during the tumorigenic process. Here, we describe changes in the microbiota and host over the course of azoxymethane (AOM)-induced tumorigenesis. METHODS: Mice were administered AOM or PBS and were euthanised 8, 12, 24 and 48 weeks later. Samples were analysed using 16S rRNA gene sequencing, UPLC-MS and qRT-PCR. RESULTS: The microbiota and bile acid profile showed distinct changes at each timepoint. The inflammatory response became apparent at weeks 12 and 24. Moreover, significant correlations between individual taxa, cytokines and bile acids were detected. One co-abundance group (CAG) differed significantly between PBS- and AOM-treated mice at week 24. Correlation analysis also revealed significant associations between CAGs, bile acids and the bile acid transporter, ASBT. Aberrant crypt foci and adenomas were first detectable at weeks 24 and 48, respectively. CONCLUSION: The observed changes precede host hyperplastic transformation and may represent early therapeutic targets for the prevention or management of CRC at specific timepoints in the tumorigenic process.

Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy.

BACKGROUND: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention. METHODS: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging. RESULTS: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p = 0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging. CONCLUSIONS: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.

Interrogation of a longitudinal, national pharmacy claims dataset to explore factors that predict the need for add-on therapy in older and socioeconomically disadvantaged Australians with type 2 diabetes mellitus patients (T2DM).

PURPOSE: The management of type 2 diabetes mellitus (T2DM) is complex. The aim of this work is to explore factors that predict the need for add-on therapy in patients with T2DM in the community. METHODS: We accessed longitudinal, pharmacy payment claim records from the national Pharmaceutical Benefits Scheme (PBS) (Subsidises costs of medicines: government pays difference between patient co-payments, lower in concessional patients, and additional cost of drug.) for the period January 2006 to September 2014 (EREC/MI3127) from a 10% random sample of the Australian population validated to be representative of the population by the Australian Bureau of Statistics (ABS). Likely, T2DM patients were identified as those having been dispensed a single anti-hyperglycaemic drug (monotherapy). The time taken and possible factors that might lead to the addition of a second therapy were examined. An examination was made of trends in the co-prescription of either antihypertensive or anti-hyperlipidaemic agents in relation to the time (± 3 years) of initiating an anti-hyperglycaemic agent. RESULTS: Most (83%) presumed T2DM patients were initiated with metformin. The average time until the second agent was added was 4.8 years (95% CI 4.7-4.9). Satisfactory adherence, age, male gender, initiating therapy after 2012 and initiating with a sulphonylurea drug all were significant risks for add-on therapy. There was no overall trend in the initiation of antihypertensive and/or anti-hyperlipidaemic agents with respect to the time of anti-hyperglycaemic initiation. CONCLUSION: The usefulness of a longitudinal dataset of pharmacy-claim records is demonstrated. Over half of all older and socioeconmically disadvantaged T2DM patients captured in this longitudinal claims database will be prescribed a second anti-hyperglycaemic agent within 5 years of their first drug therapy. Several factors can predict the risk of prescription of add-on therapy, and these should be considered when prescribing medications to treat T2DM.

Experimental foundation for in vivo measurement of the elasticity of the aorta in computed tomography angiography.

OBJECTIVE: This study was performed to determine the feasibility of measuring the elastic properties of the arterial wall in vivo. To prove this concept, elastic parameters were calculated from an aortic model of elastic behavior similar to a human aorta using computed tomography angiography (CTA) images. METHODS: We first constructed an aortic model from polydimethylsiloxane (PDMS). This model was inserted into a pulsatile flow loop. The model was then placed inside a computed tomography scanner. To estimate the elasticity values, we measured the cross-sectional area and the pressure changes in the model during each phase of the simulated cardiac cycle. A discrete wavelet transform (DWT) algorithm was applied to the CTA data to calculate the geometric changes in the pulsatile model over a simulated cardiac cycle for various pulsatile rates and elasticity values of the PDMS material. The elastic modulus of the aortic model wall was derived from these geometric changes. The elastic moduli derived from the CTA data were compared with those obtained by testing strips of the same PDMS material in a tensile testing machine. Our two aortic models had elastic values at both extremes of those found in normal human aortas. RESULTS: The results show a good comparison between the elastic values derived from the CTA data and those obtained in a tensile testing machine. In addition, the elasticity values were found to be independent of the pulsatile rate for mixing ratios of 6:1 and 9:1 (p = .12 and p = .22, respectively). CONCLUSIONS: The elastic modulus of a pulsatile aortic model may be measured by electrocardiographically-gated multi-detector CTA protocol. This preliminary study suggests the possibility of determining non-invasively the elastic properties of a living, functioning aorta using CTA data.

Clinical presentations and outcomes of systemic lupus erythematosus patients with infection admitted to the intensive care unit.

OBJECTIVE: The objective of this article is to investigate clinical presentations and outcomes of systemic lupus erythematosus (SLE) patients with infection admitted to the intensive care unit (ICU). METHODS: SLE patients with infection, SLE patients with noninfectious causes, and non-SLE patients with infection were identified from the Cooper University Hospital Project IMPACT database between 2002 and 2010. We examined demographic data, APACHE II scores, physiologic data, laboratory data, length of stay in the ICU and hospital, and mortality of the three groups. RESULTS: Twenty-five SLE patients with infection, 45 SLE patients with noninfectious causes, and 1466 non-SLE patients with infection were included in the study. SLE patients with infection had higher APACHE II scores, higher maximum temperature, higher minimum and maximum heart rate (HR), lower minimum and maximum systolic blood pressure (SBP), and longer ICU length of stay in comparison to SLE patients with noninfectious causes. There were no statistical differences in white blood cell (WBC) count. SLE patients with infection had a higher mortality compared to SLE patients with noninfectious causes. There was no difference in mortality between SLE patients with infection and non-SLE patients with infection. CONCLUSION: SLE patients with infection in the ICU had a higher mortality and a higher APACHE II score compared to SLE patients with noninfectious causes in the ICU. Their physiologic signs including temperature, HR, and SBP were more reflective of infection than their WBC count.

MDCT findings of aortic branch artery pseudoaneurysms associated with type B intramural haematoma.

PURPOSE: The purpose of this study was to evaluate prevalence, morphological characteristics and evolution of aortic branch artery pseudoaneurysms associated with type B aortic intramural haematoma (IMH) using multidetector computed tomography (MDCT). MATERIALS AND METHODS: We enrolled 14 patients (nine men; mean age 64.6±9.6; range 42-75 years) with a diagnosis in the acute phase of type B IMH without evidence of intimal tear. All patients underwent clinical and MDCT follow-up. RESULTS: Twenty-two pseudoaneurysms in six patients (6/14, 43%) were observed at MDCT. In the majority of patients (5/6, 83%) the pseudoaneurysms were multiple and involved the branches of the descending thoracic aorta (14/22, 64%), mainly the intercostal arteries (11/22, 50%). At a mean follow-up of 10.6±8.7 months, 21 pseudoaneurysms showed resolution, reduction or dimensional stability (95%), whereas only one increased in size (5%). CONCLUSIONS: Aortic branch artery pseudoaneurysms associated with IMH may be considered a benign disease, as the majority of cases resolved or did not change in size, with haematoma resorption. However, because a dynamic change in pseudoaneurysms in the acute and subacute phases was frequently observed, close clinical and imaging follow-up is mandatory.

Unusual paraneoplastic syndromes of breast carcinoma: a combination of cerebellar degeneration and Lambert-Eaton Myasthenic Syndrome.

INTRODUCTION: Paraneoplastic neurological disorders are rare complications of breast carcinoma. Lambert-Eaton Myasthenic Syndrome (LEMS) is most commonly associated with small cell lung cancer. However, a combination of LEMS and subacute cerebellar degeneration as paraneoplastic syndromes is extremely rare, and has never been described in association with breast cancer. CASE: We report for the first time an unusual association of LEMS and paraneoplastic subacute cerebellar degeneration with breast carcinoma. CONCLUSION: In patients with atypical LEMS, when there is no evidence of respiratory malignancy, breast cancer should be included in the differential diagnosis.

Issues for researchers to consider when using health-related quality of life outcomes in cancer research.

Maintaining quality of life for patients with cancer is a key factor when developing services related to diagnosis, treatment, recovery and/or terminal care. This paper questions whether health-related quality of life (HRQoL) is an appropriate measure of quality of life given that it does not assess factors reported by patients as being most influential, e.g. contact with family and social/cultural interaction. Ambiguity related to the definition and understanding of anxiety, depression and distress as outcomes commonly used by clinicians and researchers when measuring HRQoL in cancer research is also addressed by this paper. The findings of many cancer studies are interpreted and presented on very broad and poorly defined concepts thus preventing the development of a coherent and true understanding of how these outcomes influence quality of life for cancer patients. The authors of this paper conclude that the documentation and clear explanation of the concepts underpinning the choice of instrument and study design is essential but also the inclusion of outcomes related to social support and interaction would provide a more accurate account of quality of life issues in cancer research.

Retention of mechanical properties and cytocompatibility of a phosphate-based glass fiber/polylactic acid composite.

Polymers prepared from polylactic acid (PLA) have found a multitude of uses as medical devices. The main advantage of having a material that degrades is so that an implant would not necessitate a second surgical event for removal. In addition, the biodegradation may offer other advantages. In this study, fibers produced from a quaternary phosphate-based glass (PBG) in the system 50P(2)O(5)-40CaO-5Na(2)O-5Fe(2)O(3) (nontreated and heat-treated) were used to reinforce the biodegradable polymer, PLA. Fiber properties were investigated, along with the mechanical and degradation properties and cytocompatibility of the composites produced. Retention of mechanical properties overtime was also evaluated. The mean fiber strength for the phosphate glass fibers was 456 MPa with a modulus value of 51.5 GPa. Weibull analysis revealed a shape and scale parameter value of 3.37 and 508, respectively. The flexural strength of the composites matched that for cortical bone; however, the modulus values were lower than those required for cortical bone. After 6 weeks of degradation in deionized water, 50% of the strength values obtained was maintained. The composite degradation properties revealed a 14% mass loss for the nontreated and a 10% mass loss for the heat-treated fiber composites. It was also seen that by heat-treating the fibers, chemical and physical degradation occurred much slower. The pH profiles also revealed that nontreated fibers degraded quicker, thus correlating well with the degradation profiles. The in vitro cell culture experiments revealed both PLA (alone) and the heat-treated fiber composites maintained higher cell viability as compared to the nontreated fiber composites. This was attributed to the slower degradation release profiles of the heat-treated composites as compared to the nontreated fiber composites. SEM analyses revealed a porous structure after degradation, and it is clear that there are possibilities here to tailor the distribution of porosity within polymer matrices.

Aortic growth rates in chronic aortic dissection.

AIM: To determine and compare rates of descending aortic enlargement and complications in chronic aortic dissection with and without a proximal aortic graft. METHODS AND MATERIALS: Fifty-two patients with dissection involving the descending aorta and who had undergone at least two computed tomography (CT) examinations at our institution between November, 1993 and February, 2004 were identified, including 24 non-operated patients (four type A, 20 type B) and 28 operated patients (type A). CT examinations per patient ranged from two to 10, and follow-up ranged from 1-123 months (mean 49 months, median 38.5 months). On each CT image, the aortic short axis (SA), false lumen (FL), and true lumen (TL) diameters were measured at the longitudinal midpoint of the dissection and at the point of maximum aortic diameter. Complications were tabulated, including aortic rupture and aortic enlargement requiring surgery. RESULTS: For non-operated patients, the midpoint and maximum point SA, TL, and FL diameters increased significantly over time. For operated patients, the midpoint and maximum point SA and FL diameters increased significantly over time. In both groups, aortic enlargement was predominantly due to FL expansion. Diameter increases in non-operated patients were significantly larger than those in operated patients. The rate of change in aortic diameter was constant, regardless of aortic size. Four non-operated and six operated patients developed aortic complications. CONCLUSIONS: In patients with a dissection involving the descending thoracic aorta, the FL increased in diameter over time, at a constant rate, and to a greater degree in non-operated patients (mostly type B) compared with operated patients (all type A).

Carbon dioxide angiography: a simple and safe system of delivery.

Carbon dioxide (CO2) is an established alternate angiographic contrast agent, which can be delivered by pump or hand injection. We describe a simple, safe and inexpensive hand injection system that delivers a known volume of CO2 at atmospheric pressure and prevents contamination with room air.

Broadband polarization correction with programmable liquid-crystal modulator arrays.

We demonstrate a novel method of parallel, multiwavelength state-of-polarization (SOP) correction. Using a new liquid-crystal modulator array design, we are able to rotate the distorted input SOP spectrum to a fixed linear state on a wavelength-by-wavelength basis. We report experimental correction of up to 25.5-dB polarization-dependent loss over a 13-nm bandwidth around 1550 nm.

Venous covered stent: successful occlusion of a symptomatic internal iliac arteriovenous fistula.

We report the placement of a covered stent within the internal iliac vein (IIV) to occlude a symptomatic iatrogenic internal iliac arteriovenous fistula following an abdominal aortic graft. Angiography revealed a direct communication between an internal iliac graft to artery anastomosis and the right IIV with rapid shunting into the inferior vena cava and a small associated pseudoaneurysm. Femoral, brachial or axillary arterial access was precluded. The fistula was successfully occluded by a stent-graft placed in the IIV. Arteriovenous fistula can be treated in a number of ways including covered stent placement on the arterial side. To the best of our knowledge this is the first time placement in a vein has been described. Where access is difficult or the procedure carries a high risk of complication, a venous covered stent may offer an alternative.

Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism.

OBJECTIVE: To describe the methodological challenges and decisions made in developing a multisite, controlled study of risperidone in children and adolescents with autism. METHODS: Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums, aggressive and/or self-injurious behaviors. These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects. Additional ethical and scientific issues concern the length of trial and sample size. RESULTS: We undertook a short-term, placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder. This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety. Finally, a placebo-controlled discontinuation study tested the need for continuous treatment. CONCLUSIONS: In the absence of standard pharmacological treatment for children with autistic disorder, a placebo-controlled study remains the most appropriate method of testing efficacy and safety. The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation.

Evaluation of a hemostasis model for teaching ovariohysterectomy in veterinary surgery.

OBJECTIVE: To evaluate the efficacy of a reusable plastic model mimicking the anatomy and hemodynamics of the canine female genital tract for teaching basic surgical skills and ovariohysterectomy. SAMPLE POPULATION: 40 veterinary students of the class of 1998. STUDY DESIGN: Prospective study. METHODS: Students'confidence level and experience in private practice was evaluated via questionnaire before training. Students in 2 groups performed an ovariohysterectomy on cadavers (group C, n = 20) or on the model (Group M, n = 20) for 2 hours. Students' psychomotor and basic surgical skills were objectively assessed by the following tests: ligation of a foam cylinder, passing a needle through the eyelets of an electronic suture board, and ligating latex tubing. Results were compared before and after training and within and between groups. The ability of students to perform an ovariohysterectomy in a live dog after training was compared between groups with a scoring system. RESULTS: Students in both groups had similar surgical experience and basic skills before training. The results of the psychomotor and basic surgical skills tests were better in group M after training than group C. The improvement of each student in performing these tasks also increased when students were trained with the model. Scores assigned to students performing an ovariohysterectomy in a live dog were higher in group M (31.45 +/- 1.15) than in group C (20.7 +/- 1.42). CONCLUSION: The model was more effective than cadavers in teaching basic surgical skills and ovariohysterectomy in dogs.

Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone.

This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.