CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas

OBJECTIVES: The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). METHODS: This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. RESULTS: A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CONCLUSION: CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma

Purpose: Marginal zone lymphoma (MZL) is an uncommon non-Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/ refractory (R/R) MZL. Patients and Methods: Patients with R/R MZL were enrolled in the phase II MAGNOLIA (BGB-3111-214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification. Results: Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRCassessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months. Treatment was well tolerated with the majority of adverse events (AE) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in 2 patients; 1 patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, 4 patients discontinued treatment due to AEs, none of which were considered treatment-related by the investigators. Conclusions: Zanubrutinib demonstrated highORRand CR rate with durable disease control and a favorable safety profile in patients with R/R MZL. _2021 The Authors; Published by the American Association for Cancer Research

Supernatant from Bifidobacterium Differentially Modulates Transduction Signaling Pathways for Biological Functions of Human Dendritic Cells

International audienceBACKGROUND:Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn) could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK), glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K) pathways on biological functions of human monocyte-derived DCs treated with BbC50sn.METHODOLOGY/PRINCIPAL FINDINGS:DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS) or Zymosan, with or without specific inhibitors of p38MAPK (SB203580), ERK (PD98059), PI3K (LY294002) and GSK3 (SB216763). We found that 1) the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2) p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3) ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4) BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS.CONCLUSION/SIGNIFICANCE:We report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria

Intensive care of the cancer patient: recent achievements and remaining challenges

A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of patients with solid and hematological malignancies benefit from intensive care support, with dramatically decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation (BMT) have less adverse prognostic implications than two decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill patients with cancer, we outline an easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to patients with cancer who can benefit. Lastly, we propose a research agenda to address unanswered questions

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery

Cumulative Effect of Fertilizer and Organic Spray (Banana Pseudostem Sap or Vermiwash) on Yield, Quality, Uptake and Economics of Linseed (Linum usitatissimum L.)

The study on linseed aimed to investigate the effectiveness of fertilizer and organic spray of banana pseudostem sap or vermiwash on yield, quality, uptake and economics of the crop was conducted at College Farm, N. M. College of Agriculture, Navsari Agricultural University, Navsari during rabi season of 2019-20. The experiment was laid out in Randomized Block Design with four replicates. The experimental field was fairly leveled and uniform. The treatments comprising of T1(50% RDF),T2 (50% RDF + Foliar spray of 1% vermiwash at 30 and 60 DAS), T3 (50% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS), T4(75% RDF), T5 (75% RDF + Foliar spray of 1% vermiwash at 30 and 60 DAS), T6 (75% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS), T7(100% RDF),T8 (100% RDF + Foliar spray of 1% vermiwash at 30 and 60 DAS) and T9(100% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS).The result indicated significant differences on seed yield, oil yield and nutrient uptake in the seed and stover. Treatment T9 outperformed the other treatments by registering maximum yield, oil yield and nutrient uptake in the seed and stover, gross return, net return and benefit cost ratio.&nbsp; It could be concluded that to obtain better yield, quality, uptake and economics of rabi linseed crop the crop should be applied with 100% RDF(60-30-00 N-P2O5-K2O kg ha-1) and foliar spray of 1% vermiwash or 1% banana pseudostem sap at 30 and 60 DAS

Effect of Inorganic Fertilizer and Organic Foliar Spray on Growth, Yield Attributes and Yield of Linseed

Aims: To evaluate the effect of fertilizer and organic foliar spray on growth, yield attributes and yield of linseed. Study Design: The experiment was laid out in randomized block design with four replications. Place and Duration of Study:&nbsp; A field experiment was carried out at College Farm, N. M. College of Agriculture, Navsari during rabi season of 2019-20. Methodology: The study comprised of nine different treatments viz., T1(50% RDF),T2 (50% RDF + Foliar spray of 1% vermiwash at 30 and 60 DAS), T3 (50% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS), T4(75% RDF), T5 (75% RDF + Foliar spray of 1% vermiwash at 30 and 60 DAS), T6 (75% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS), T7(100% RDF),T8 (100% RDF + Foliar spray of 1% vermiwash at 30 and 60 DAS) and T9(100% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS). Results: From the results, it was observed that an application of 100% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS (T9) resulted in significantly higher values of plant height (63.37 cm at 90 DAS), number of branches plant-1 (6.94 at 90 DAS), number of capsules plant-1 (51.85), number of seeds capsules-1 (8.95) and seed weight plant-1 (1.89). Significantly higher seed yield (1157 kg ha-1) and stover yield (2051 kg ha-1) of linseed were observed with the application of 100% RDF + Foliar spray of 1% banana pseudostem sap at 30 and 60 DAS (T9). Conclusion: It can be concluded that, application of 100% RDF (60-30-00 N- P2O5-K2O kg ha-1) + Foliar spray of 1% banana pseudostem sap or vermiwash at 30 and 60 DAS was found to be the most viable option for getting higher growth and yield in linseed