Can Experienced Observers Differentiate between Lipoma and Well-Differentiated Liposarcoma Using Only MRI?

Well-differentiated liposarcoma represents a radiographic diagnostic dilemma. To determine the accuracy, interrater reliability, and relationship of stranding, nodularity, and size in the MRI differentiation of lipoma and well-differentiated liposarcoma, MRI scans of 60 patients with large (\u3e5 cm), deep, pathologically proven lipomas or well-differentiated liposarcomas were examined by 10 observers with subspecialty training blinded to diagnosis. Observers indicated whether the amount of stranding, nodularity, and size of each tumor suggested a benign or malignant diagnosis and rendered a diagnosis of lipoma or well-differentiated liposarcoma. The accuracy, reliability, and relationship of stranding, nodularity, and size to diagnosis were calculated for all samples. 69% of reader MRI diagnoses agreed with final pathology diagnosis (95% CI 65-73%). Readers tended to err choosing a diagnosis of liposarcoma, correctly identifying lipomas in 63% of cases (95% CI 58-69%) and liposarcomas in 75% of cases (95% CI 69-80%). Assessment of the relationship of stranding, nodularity, and size to correct diagnosis showed that the presence of each was associated with a decreased likelihood of a lipoma pathological diagnosis (P \u3c 0.01). While the radiographic diagnosis of lipoma or well-differentiated liposarcoma cannot be made with 100% certainty, experienced observers have a 69% chance of rendering a correct diagnosis

Superficial Soft-Tissue Sarcomas Rarely Require Advanced Soft-Tissue Reconstruction Following Resection

Objective: Soft-tissue sarcomas are most frequently located deep within myofascial compartments. Superficial soft-tissue sarcomas (S-STS) are relatively less common and may be managed differently than deep sarcomas because generous resection margins are often possible without sacrificing critical structures. We sought to investigate the frequency and types of soft-tissue reconstructive procedures that are required following excision of S-STS. Methods: We reviewed 457 consecutively treated patients with S-STS with a minimum 2-year follow-up from our prospectively maintained database between 1989 and 2009. Results: Mean follow-up was 10.5 years (range, 2–23). Four hundred twenty-one tumors (91%) were excised with negative margins, 38 (8.3%) had microscopically positive margins, and three (0.7%) had grossly positive margins. One patient required an amputation. In 271 (58%) patients, the wounds were closed primarily. In comparison, 93 patients (20%) required a rotation flap, 70 (15%) required a split-thickness skin graft, and 23 (5%) underwent a free tissue transfer (ie, advanced reconstructive procedure). The overall complication rate was 12%, although 43% of patients undergoing free tissue transfer developed complications (P = 0.04). An unplanned excision before referral to our center was a risk factor for local recurrence (P = 0.03) when residual tumor was recovered in the reexcision specimen pathologically. Conclusions: Although concern about the morbidity associated with a free tissue transfer (ie, advanced reconstructive procedure) may potentially limit the adequacy of resection in some patients with S-STS, the results of this study showed that the majority of patients had complete excisions with negative margins and primary closure. Obtaining a negative margin when excising a known or suspected S-STS rarely requires an advanced reconstructive procedure and almost never results in loss of limb

The Value of MRI in Distinguishing Subtypes of Lipomatous Extremity Tumors Needs Reassessment in the Era of MDM2 and CDK4 Testing

Introduction. Extremity lipomas and well-differentiated liposarcomas (WDLs) are difficult to distinguish on MR imaging. We sought to evaluate the accuracy of MRI interpretation using MDM2 amplification, via fluorescence in-situ hybridization (FISH), as the gold standard for pathologic diagnosis. Furthermore, we aimed to investigate the utility of a diagnostic formula proposed in the literature. Methods. We retrospectively collected 49 patients with lipomas or WDLs utilizing MDM2 for pathologic diagnosis. Four expert readers interpreted each patient\u27s MRI independently and provided a diagnosis. Additionally, a formula based on imaging characteristics (i.e. tumor depth, diameter, presence of septa, and internal cystic change) was used to predict the pathologic diagnosis. The accuracy and reliability of imaging-based diagnoses were then analyzed in comparison to the MDM2 pathologic diagnoses. Results. The accuracy of MRI readers was 73.5% (95% CI 61-86%) with substantial interobserver agreement (κ = 0.7022). The formula had an accuracy of 71%, which was not significantly different from the readers (p = 0.71). The formula and expert observers had similar sensitivity (83% versus 83%) and specificity (64.5% versus 67.7%; p = 0.659) for detecting WDLs. Conclusion. The accuracy of both our readers and the formula suggests that MRI remains unreliable for distinguishing between lipoma and WDLs

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effectiveness of a smartphone application to promote physical activity in primary care:the SMART MOVE randomised controlled trial

Background Physical inactivity is a major, potentially modifiable, risk factor for cardiovascular disease, cancer, and other chronic diseases. Effective, simple, and generalisable interventions that will increase physical activity in populations are needed. Aim To evaluate the effectiveness of a smartphone application (app) to increase physical activity in primary care. Design and setting An 8-week, open-label, randomised controlled trial in rural, primary care in the west of Ireland. Method Android smartphone users >16 years of age were recruited. All participants were provided with similar physical activity goals and information on the benefits of exercise. The intervention group was provided with a smartphone app and detailed instructions on how to use it to achieve these goals. The primary outcome was change in physical activity, as measured by a daily step count between baseline and follow-up. Results A total of 139 patients were referred by their primary care health professional or self-referred. In total, 37 (27%) were screened out and 12 (9%) declined to participate, leaving 90 (65%) patients who were randomised. Of these, 78 provided baseline data (intervention = 37; control = 41) and 77 provided outcome data (intervention = 37; control = 40). The mean daily step count at baseline for intervention and control groups was 4365 and 5138 steps per day respectively. After adjusting, there was evidence of a significant treatment effect (P = 0.009); the difference in mean improvement in daily step count from week 1 to week 8 inclusive was 1029 (95% confidence interval 214 to 1843) steps per day, favouring the intervention. Improvements in physical activity in the intervention group were sustained until the end of the trial. Conclusion A simple smartphone app significantly increased physical activity over 8 weeks in a primary care population

Sexual counselling for patients with cardiovascular disease: protocol for a pilot study of the charms sexual counselling intervention

Introduction Sexual problems are common with cardiovascular disease, and can negatively impact quality of life. To address sexual problems, guidelines have identified the importance of sexual counselling during cardiac rehabilitation, yet this is rarely provided. The Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention aims to improve the provision of sexual counselling in cardiac rehabilitation in Ireland. Methods and analysis This is a multicentre pilot study for the CHARMS intervention, a complex, multilevel intervention delivered within hospital-based cardiac rehabilitation programmes. The intervention includes (1) training in sexual counselling for staff, (2) a staff-led patient education and support intervention embedded within the cardiac rehabilitation programme, (3) a patient information booklet and (4) an awareness raising poster. The intervention will be delivered in two randomly selected cardiac rehabilitation centres. In each centre 30 patients will be recruited, and partners will also be invited to participate. Data will be collected from staff and patients/partners at T1 (study entry), T2 (3-month follow-up) and T3 (6-month follow-up). The primary outcome for patients/partners will be scores on the Sexual Self-Perception and Adjustment Questionnaire. Secondary outcomes for patients/partners will include relationship satisfaction; satisfaction with and barriers to sexual counselling in services; sexual activity, functioning and knowledge; physical and psychological well-being. Secondary outcomes for staff will include sexuality-related practice; barriers to sexual counselling; self-ratings of capability, opportunity and motivation; sexual attitudes and beliefs; knowledge of cardiovascular disease and sex. Fidelity of intervention delivery will be assessed using trainer self-reports, researcher-coded audio recordings and exit interviews. Longitudinal feasibility data will be gathered from patients/partners and staff via questionnaires and interviews. Ethics and dissemination This study is approved by the Research Ethics Committee (REC) of the National University of Ireland, Galway. Findings will be disseminated to cardiac rehabilitation staff, patients/partners and relevant policymakers via appropriate publications and presentations

Sexual counselling for patients with cardiovascular disease: protocol for a pilot study of the CHARMS sexual counselling intervention.

Introduction Sexual problems are common with cardiovascular disease, and can negatively impact quality of life. To address sexual problems, guidelines have identified the importance of sexual counselling during cardiac rehabilitation, yet this is rarely provided. The Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention aims to improve the provision of sexual counselling in cardiac rehabilitation in Ireland.Methods and analysis This is a multicentre pilot study for the CHARMS intervention, a complex, multilevel intervention delivered within hospital-based cardiac rehabilitation programmes. The intervention includes (1) training in sexual counselling for staff, (2) a staff-led patient education and support intervention embedded within the cardiac rehabilitation programme, (3) a patient information booklet and (4) an awareness raising poster. The intervention will be delivered in two randomly selected cardiac rehabilitation centres. In each centre 30 patients will be recruited, and partners will also be invited to participate. Data will be collected from staff and patients/partners at T1 (study entry), T2 (3-month follow-up) and T3 (6-month follow-up). The primary outcome for patients/partners will be scores on the Sexual Self-Perception and Adjustment Questionnaire. Secondary outcomes for patients/partners will include relationship satisfaction; satisfaction with and barriers to sexual counselling in services; sexual activity, functioning and knowledge; physical and psychological well-being. Secondary outcomes for staff will include sexuality-related practice; barriers to sexual counselling; self-ratings of capability, opportunity and motivation; sexual attitudes and beliefs; knowledge of cardiovascular disease and sex. Fidelity of intervention delivery will be assessed using trainer self-reports, researcher-coded audio recordings and exit interviews. Longitudinal feasibility data will be gathered from patients/partners and staff via questionnaires and interviews.Ethics and dissemination This study is approved by the Research Ethics Committee (REC) of the National University of Ireland, Galway. Findings will be disseminated to cardiac rehabilitation staff, patients/partners and relevant policymakers via appropriate publications and presentations.PUBLISHEDpeer-reviewe

Effect of Lactobacillus salivarius Bacteriocin Abp118 on the Mouse and Pig Intestinal Microbiota

Lactobacilli are Gram-positive bacteria that are a subdominant element in the human gastrointestinal microbiota, and which are commonly used in the food industry. Some lactobacilli are considered probiotic, and have been associated with health benefits. However, there is very little culture-independent information on how consumed probiotic microorganisms might affect the entire intestinal microbiota. We therefore studied the impact of the administration of Lactobacillus salivarius UCC118, a microorganism well characterized for its probiotic properties, on the composition of the intestinal microbiota in two model animals. UCC118 has anti-infective activity due to production of the bacteriocin Abp118, a broad-spectrum class IIb bacteriocin, which we hypothesized could impact the microbiota. Mice and pigs were administered wild-type (WT) L. salivarius UCC118 cells, or a mutant lacking bacteriocin production. The microbiota composition was determined by pyrosequencing of 16S rRNA gene amplicons from faeces. The data show that L. salivarius UCC118 administration had no significant effect on proportions of major phyla comprising the mouse microbiota, whether the strain was producing bacteriocin or not. However, L. salivarius UCC118 WT administration led to a significant decrease in Spirochaetes levels, the third major phylum in the untreated pig microbiota. In both pigs and mice, L. salivarius UCC118 administration had an effect on Firmicutes genus members. This effect was not observed when the mutant strain was administered, and was thus associated with bacteriocin production. Surprisingly, in both models, L. salivarius UCC118 administration and production of Abp118 had an effect on Gram-negative microorganisms, even though Abp118 is normally not active in vitro against this group of microorganisms. Thus L. salivarius UCC118 administration has a significant but subtle impact on mouse and pig microbiota, by a mechanism that seems at least partially bacteriocin-dependentThis work was supported by a Principal Investigator award (07/IN.1/B1780) from Science Foundation Ireland to Dr. O\u27Toole. Dr. Neville was the recipient of an Embark studentship from the Irish Research Council for Science Engineering and Technology

Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial

Background Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. Methods This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0.90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. Findings Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0.72, 95% CI 0.57-0.90, p=0.0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0.54 95% CI 0.35-0.82, p=0.0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0.86, 95% CI 0.69-1.08, p=0.19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0.67, 95% CI 0.45-1.00, p=0.05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1.61, 95% CI 1.12-2.31, p=0.0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1.68, 95% CI 1.17-2.40; p=0.0043). Interpretation Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding