Metastatic appendicular soft tissue sarcoma:treatment and survival outcomes of 2,553 patients from the SEER database

Introduction: Patients with soft tissue sarcoma (STS) that present with metastasis at diagnosis have a dire prognosis. Within this patient population, we sought to assess: (1) demographic and clinical characteristics, (2) metastatic patterns, (3) treatment strategies, and (4) disease-specific survival (DSS).Materials and Methods: The SEER database was queried to identify patients with histologically confirmed STS of the pelvis or extremity. Univariate and multivariate analysis was performed using the Cox proportional hazards model. Disease-specific survival (DSS) was analyzed using the Kaplan-Meier method.Results: A total of 22,683 patients were retrieved, out of which 2,553 (11.3%) had metastasis at diagnosis. Leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), liposarcoma, synovial sarcoma, spindle cell sarcoma, and alveolar rhabdomyosarcoma (A-RMS) were the six most common STS presenting with metastasis. Among patients with metastasis, 53.7% and 33.2% of patients had primary tumors located in the lower limb and pelvis, respectively. Lung was the most common site of metastasis in all subtypes except A-RMS, in which bone metastases and lymph node (LN) predominated (85.2% and 62.1%, respectively). Chemotherapy and radiotherapy were associated with higher DSS (HR = 0.788 and HR = 0.755, respectively). Five-year DSS was below 20% in all tumor histologies. Two-year DSS for patients with synchronous lung and liver metastases was 28%.Conclusion: Although the lung was the most common site of metastasis, metastatic patterns are highly variable depending on tumor histology. Metastatic A-RMS is most commonly presented with regional LN and bone involvement. Disease-specific survival remained poor for patients with metastatic disease at presentation regardless of (neo)-adjuvant radiotherapy or chemotherapy.</p

Metastatic appendicular soft tissue sarcoma:treatment and survival outcomes of 2,553 patients from the SEER database

Introduction: Patients with soft tissue sarcoma (STS) that present with metastasis at diagnosis have a dire prognosis. Within this patient population, we sought to assess: (1) demographic and clinical characteristics, (2) metastatic patterns, (3) treatment strategies, and (4) disease-specific survival (DSS).Materials and Methods: The SEER database was queried to identify patients with histologically confirmed STS of the pelvis or extremity. Univariate and multivariate analysis was performed using the Cox proportional hazards model. Disease-specific survival (DSS) was analyzed using the Kaplan-Meier method.Results: A total of 22,683 patients were retrieved, out of which 2,553 (11.3%) had metastasis at diagnosis. Leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), liposarcoma, synovial sarcoma, spindle cell sarcoma, and alveolar rhabdomyosarcoma (A-RMS) were the six most common STS presenting with metastasis. Among patients with metastasis, 53.7% and 33.2% of patients had primary tumors located in the lower limb and pelvis, respectively. Lung was the most common site of metastasis in all subtypes except A-RMS, in which bone metastases and lymph node (LN) predominated (85.2% and 62.1%, respectively). Chemotherapy and radiotherapy were associated with higher DSS (HR = 0.788 and HR = 0.755, respectively). Five-year DSS was below 20% in all tumor histologies. Two-year DSS for patients with synchronous lung and liver metastases was 28%.Conclusion: Although the lung was the most common site of metastasis, metastatic patterns are highly variable depending on tumor histology. Metastatic A-RMS is most commonly presented with regional LN and bone involvement. Disease-specific survival remained poor for patients with metastatic disease at presentation regardless of (neo)-adjuvant radiotherapy or chemotherapy.</p

Methodologies for in vitro and in vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms

KT acknowledges receipt of a mandate of Industrial Research Fund (IOFm/05/022). JB acknowledges funding from the European Research Council Advanced Award 3400867/RAPLODAPT and the Israel Science Foundation grant # 314/13 (www.isf.il). NG acknowledges the Wellcome Trust and MRC for funding. CD acknowledges funding from the Agence Nationale de Recherche (ANR-10-LABX-62-IBEID). CJN acknowledges funding from the National Institutes of Health R35GM124594 and R21AI125801. AW is supported by the Wellcome Trust Strategic Award (grant 097377), the MRC Centre for Medical Mycology (grant MR/N006364/1) at the University of Aberdeen MaCA: outside this study MaCA has received personal speaker’s honoraria the past five years from Astellas, Basilea, Gilead, MSD, Pfizer, T2Candida, and Novartis. She has received research grants and contract work paid to the Statens Serum Institute from Astellas, Basilea, Gilead, MSD, NovaBiotics, Pfizer, T2Biosystems, F2G, Cidara, and Amplyx. CAM acknowledges the Wellcome Trust and the MRC MR/N006364/1. PVD, TC and KT acknowledge the FWO research community: Biology and ecology of bacterial and fungal biofilms in humans (FWO WO.009.16N). AAB acknowledges the Deutsche Forschungsgemeinschaft – CRC FungiNet.Peer reviewedPublisher PD

Personalised randomised controlled trial designs-a new paradigm to define optimal treatments for carbapenem-resistant infections.

Antimicrobial resistance is impacting treatment decisions for, and patient outcomes from, bacterial infections worldwide, with particular threats from infections with carbapenem-resistant Enterobacteriaceae, Acinetobacter baumanii, or Pseudomonas aeruginosa. Numerous areas of clinical uncertainty surround the treatment of these highly resistant infections, yet substantial obstacles exist to the design and conduct of treatment trials for carbapenem-resistant bacterial infections. These include the lack of a widely acceptable optimised standard of care and control regimens, varying antimicrobial susceptibilities and clinical contraindications making specific intervention regimens infeasible, and diagnostic and recruitment challenges. The current single comparator trials are not designed to answer the urgent public health question, identified as a high priority by WHO, of what are the best regimens out of the available options that will significantly reduce morbidity, costs, and mortality. This scenario has an analogy in network meta-analysis, which compares multiple treatments in an evidence synthesis to rank the best of a set of available treatments. To address these obstacles, we propose extending the network meta-analysis approach to individual randomisation of patients. We refer to this approach as a Personalised RAndomised Controlled Trial (PRACTical) design that compares multiple treatments in an evidence synthesis, to identify, overall, which is the best treatment out of a set of available treatments to recommend, or how these different treatments rank against each other. In this Personal View, we summarise the design principles of personalised randomised controlled trial designs. Specifically, of a network of different potential regimens for life-threatening carbapenem-resistant infections, each patient would be randomly assigned only to regimens considered clinically reasonable for that patient at that time, incorporating antimicrobial susceptibility, toxicity profile, pharmacometric properties, availability, and physician assessment. Analysis can use both direct and indirect comparisons across the network, analogous to network meta-analysis. This new trial design will maximise the relevance of the findings to each individual patient, and enable the top-ranked regimens from any personalised randomisation list to be identified, in terms of both efficacy and safety

Validation of tissue microarray technology in squamous cell carcinoma of the esophagus

Tissue microarray (TMA) technology has been developed to facilitate high-throughput immunohistochemical and in situ hybridization analysis of tissues by inserting small tissue biopsy cores into a single paraffin block. Several studies have revealed novel prognostic biomarkers in esophageal squamous cell carcinoma (ESCC) by means of TMA technology, although this technique has not yet been validated for these tumors. Because representativeness of the donor tissue cores may be a disadvantage compared to full sections, the aim of this study was to assess if TMA technology provides representative immunohistochemical results in ESCC. A TMA was constructed containing triplicate cores of 108 formalin-fixed, paraffin-embedded squamous cell carcinomas of the esophagus. The agreement in the differentiation grade and immunohistochemical staining scores of CK5/6, CK14, E-cadherin, Ki-67, and p53 between TMA cores and a subset of 64 randomly selected donor paraffin blocks was determined using kappa statistics. The concurrence between TMA cores and donor blocks was moderate for Ki-67 (κ = 0.42) and E-cadherin (κ = 0.47), substantial for differentiation grade (κ = 0.65) and CK14 (κ = 0.71), and almost perfect for p53 (κ = 0.86) and CK5/6 (κ = 0.93). TMA technology appears to be a valid method for immunohistochemical analysis of molecular markers in ESCC provided that the staining pattern in the tumor is homogeneous

Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy

Background: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. Methods: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m(2) of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. Results: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P=0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A(2) receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P=0.06). Conclusions: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, .) In a randomized, controlled trial involving patients with membranous nephropathy, rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission for up to 24 months.Genentech; Fulk Family Foundation6 month embargo; published July 4, 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Critical Assessment of Metagenome Interpretation:A benchmark of metagenomics software

International audienceIn metagenome analysis, computational methods for assembly, taxonomic profilingand binning are key components facilitating downstream biological datainterpretation. However, a lack of consensus about benchmarking datasets andevaluation metrics complicates proper performance assessment. The CriticalAssessment of Metagenome Interpretation (CAMI) challenge has engaged the globaldeveloper community to benchmark their programs on datasets of unprecedentedcomplexity and realism. Benchmark metagenomes were generated from newlysequenced ~700 microorganisms and ~600 novel viruses and plasmids, includinggenomes with varying degrees of relatedness to each other and to publicly availableones and representing common experimental setups. Across all datasets, assemblyand genome binning programs performed well for species represented by individualgenomes, while performance was substantially affected by the presence of relatedstrains. Taxonomic profiling and binning programs were proficient at high taxonomicranks, with a notable performance decrease below the family level. Parametersettings substantially impacted performances, underscoring the importance ofprogram reproducibility. While highlighting current challenges in computationalmetagenomics, the CAMI results provide a roadmap for software selection to answerspecific research questions