Early Outcomes of Cemented versus Cementless Total Knee Arthroplasty

Introduction. Total knee arthroplasty (TKA) has been provento be very effective for long-term pain relief in the degenerativeknee. Few studies have investigated short-term clinicaland functional outcomes between the cemented and cementlessTKA. The specific aim of this study was to assess the potentialdifference of functional outcomes in the early postoperativeperiod between these two surgical options usingthe Knee Society Score (KSS) and range of motion (ROM). Methods. A total of 164 knees that had undergone TKA by a singlesurgeon at a single institution between 2007 and 2010 were reviewed.Three different TKA prosthetic designs (cruciate retaining(CR), posterior stabilized (PS) and cruciate substituting (CS))were included. Data collection included patient demographics,pre- and post-operative ROM, and pre- and post-operative KSSat each visit (1.5 months, 3 months, and 12 months). Two separateKSS scores were assigned: functional score and clinical score. Results. Sixty-seven knees underwent cemented TKA and 97knees underwent cementless TKA. No significant differencewas recognized in either age or body mass index for thesetwo TKA groups. The cementless group showed a significantearly ROM improvement after 1.5 months post-operative (p <0.05), while the cemented group showed ROM improvementonly after three months post-operative. No significant differencewas detected in terms of KSS between the cemented andcementless TKA groups at each measured time period. Bothgroups showed marked KSS improvement (cemented: 135%,cementless: 125%) after 1.5 months post-operative and theKSS seemed to be stabilized after three months post-operativefor both groups (cemented: p = 0.36; cementless: p = 0.07). Conclusions. There was a significant early ROM improvementfor the cementless TKA group compared to the cementedTKA group, but no statistical significant difference was notedin KSS in the early post-operative period when comparing cementedand cementless TKA groups. The findings provide evidencethat cementless TKA patients can undergo an identicalpost-operative protocol to cemented TKA, without concernsabout implant stability or function. KS J Med 2016;9(4):93-98

Prevention of restenosis after coronary balloon angioplasty: rationale and design of the Fluvavastatin Angioplasty Restenosis (FLARE) Trial

Prevention of restenosis after successful percutaneous transluminal coronary balloon angioplasty (PTCA) continues to present the greatest therapeutic challenge in interventional cardiology. Experimental and pathological studies describe restenosis as no more than the biologic healing response to arterial injury. Studies of serial quantitative coronary angiography have demonstrated that this biologic process may be measured as the loss in minimal luminal diameter (MLD) from post-PTCA to follow-up angiography and that it is essentially ubiquitous and normally distributed. Thus, quantitative coronary angiography has become the gold standard for evaluation of the angiographic outcome of clinical trials of new agents and devices aimed at prevention of restenosis. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation, and thus may control the neointimal response, which forms the kernel of restenosis. Experimental evidence suggests that fluvastatin may exert a greater direct inhibitory effect on proliferating vascular myocytes than other HMG-CoA reductase inhibitors, independent of any lipid-lowering action. The Fluvastatin Angioplasty Restenosis (FLARE) Trial was conceived, in collaboration between the Thoraxcenter, Erasmus University, Rotterdam, The Netherlands, and Sandoz Pharma, to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful single-lesion PTCA. Treatment of suitable patients begins 2 weeks before PTCA and continues after successful PTCA (residual diameter stenosis < 50%, without major cardiac complications) to follow-up angiography at 26 +/- 2 weeks. Restenosis is measured by quantitative coronary angiography at a core laboratory as the loss in MLD from post-PTCA to follow-up angiography. It is calculated (90% power, alpha = 0.05) that 730 evaluable patients will be needed to tes

Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

Purpose: The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients. Methods: Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI). Results: Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival. Conclusions: We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival

Survival, pathologic response, and genomics in CALGB 40601 (Alliance), a neoadjuvant Phase III trial of paclitaxel-trastuzumab with or without lapatinib in HER2-positive breast cancer

PURPOSE CALGB 40601 assessed whether dual versus single human epidermal growth factor receptor 2 (HER2) -targeting drugs added to neoadjuvant chemotherapy increased pathologic complete response (pCR). Here, we report relapse-free survival (RFS), overall survival (OS), and gene expression signatures that predict pCR and survival. PATIENTS AND METHODS Three hundred five women with untreated stage II and III HER2-positive breast cancer were randomly assigned to receive weekly paclitaxel combined with trastuzumab plus lapatinib (THL), trastuzumab (TH), or lapatinib (TL). The primary end point was pCR, and secondary end points included RFS, OS, and gene expression analyses. mRNA sequencing was performed on 264 pretreatment samples. RESULTS One hundred eighteen patients were randomly allocated to THL, 120 to TH, and 67 to TL. At more than 7 years of follow-up, THL had significantly better RFS and OS than did TH (RFS hazard ratio, 0.32; 95% CI, 0.14 to 0.71; P 5.005; OS hazard ratio, 0.34; 95% CI, 0.12 to 0.94; P 5.037), with no difference between TH and TL. Of 688 previously described gene expression signatures, significant associations were found in 215 with pCR, 45 with RFS, and only 22 with both pCR and RFS (3.2%). Specifically, eight immune signatures were significantly correlated with a higher pCR rate and better RFS. Among patients with residual disease, the immunoglobulin G signature was an independent, good prognostic factor, whereas the HER2-enriched signature, which was associated with a higher pCR rate, showed a significantly shorter RFS. CONCLUSION In CALGB 40601, dual HER2-targeting resulted in significant RFS and OS benefits. Integration of intrinsic subtype and immune signatures allowed for the prediction of pCR and RFS, both overall and within the residual disease group. These approaches may provide means for rational escalation and de-escalation treatment strategies in HER2-positive breast cancer

Analysis of glycoprotein processing in the endoplasmic reticulum using synthetic oligosaccharides

Protein quality control (QC) in the endoplasmic reticulum (ER) comprises many steps, including folding and transport of nascent proteins as well as degradation of misfolded proteins. Recent studies have revealed that high-mannose-type glycans play a pivotal role in the QC process. To gain knowledge about the molecular basis of this process with well-defined homogeneous compounds, we achieved a convergent synthesis of high-mannose-type glycans and their functionalized derivatives. We focused on analyses of UDP-Glc: glycoprotein glucosyltransferase (UGGT) and ER Glucosidase II, which play crucial roles in glycoprotein QC; however, their specificities remain unclear. In addition, we established an in vitro assay system mimicking the in vivo condition which is highly crowded because of the presence of various biomacromolecules

Sustainability, certification, and regulation of biochar

Biochar has a relatively long half-life in soil and can fundamentally alter soil properties, processes, and ecosystem services. The prospect of global-scale biochar application to soils highlights the importance of a sophisticated and rigorous certification procedure. The objective of this work was to discuss the concept of integrating biochar properties with environmental and socioeconomic factors, in a sustainable biochar certification procedure that optimizes complementarity and compatibility between these factors over relevant time periods. Biochar effects and behavior should also be modelled at temporal scales similar to its expected functional lifetime in soils. Finally, when existing soil data are insufficient, soil sampling and analysis procedures need to be described as part of a biochar certification procedure.O “biochar” tem um tempo de meia-vida no solo relativamente longo e pode alterar substancialmente as propriedades, processos e funções do solo. A perspectiva da aplicação de “biochar” aos solos, em escala global, evidencia a importância de se lhe atribuir um processo de certificação sofisticado e rigoroso. O objetivo deste trabalho foi discutir o conceito da integração das propriedades do “biochar” com os fatores ambientais e socioeconômicos relevantes do local de aplicação selecionado, como parte de um procedimento de certificação sustentável que otimize a complementaridade e a compatibilidade entre esses fatores, em períodos de tempo relevantes. Os efeitos e o comportamento do “biochar” devem, também, ser modelados em escalas temporais similares às de seu tempo de vida funcional nos solos do local selecionado. Finalmente, onde os dados existentes sobre as características do solo forem insuficientes, procedimentos de amostragem e análise do solo devem ser descritos como parte do procedimento de certificação do “biochar”.publishe

Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2

The hadronic structure function of the photon F_2^gamma is measured as a function of Bjorken x and of the factorisation scale Q^2 using data taken by the OPAL detector at LEP. Previous OPAL measurements of the x dependence of F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted by QCD, the data show positive scaling violations in F_2^gamma. Several parameterisations of F_2^gamma are in agreement with the measurements whereas the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001, Ascona, Switzerlan