Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis

IntroductionNon-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies.MethodsWe conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution.ResultsTwo-hundred twenty-three adults (aged = 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG< 500 mg/mL. For this analysis, we grouped DLBCL (n=90), Primary CNS (n=5), and Burkitt lymphoma (n=1) together as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and Waldenstrom macroglobulinemia (n=5) were low-grade. The incidence of hypogammaglobulinemia in our cohort of both high and low-grade lymphoma patients was 13.5% (n=30). Across all NHL subtypes, individuals with baseline IgG< 500 mg/dL showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI: 1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG=500 mg/dL. There was a higher hospitalization rate (3.237, CI: 1.77-6.051, p=0.0017) in those with high-grade lymphoma with hypogammaglobulinemia when compared with low-grade. There was no statistically significant difference in individuals who were alive after three years in those with baseline IgG<500 mg/dL.DiscussionOur study is the first to analyze incidence of hypogammaglobulinemia at the time of diagnosis of NHL as a potential biomarker of interest for future outcomes including hospitalization and infection

Influencia de la poda química en la biomasa y desarrollo radical de "Pinus pinaster" Ait. y "Pinus radiata" D. Don

Ante la preocupación existente por los problemas de estabilidad encontrados en numerosas plantaciones, este trabajo analiza el efecto en vivero de varios tratamientos de producción de planta en contenedor con la finalidad de mejorar la calidad de la misma. Para ello, fueron producidas en vivero dos de las especies más utilizadas en las repoblaciones realizadas en la cornisa cantábrica en los últimos años: Pinus pinaster Ait. y Pinus radiata D. Don. Se emplearon diferentes tipos de contenedor (Forest Pot 250, Cetap 54-Universal y Planfor) y se cubrieron las paredes de los dos primeros con CuCO3, en distintas concentraciones (0; 1,5; 3; 4,5%). Ambas especies mostraron un comportamiento diferente ante el tratamiento con cobre en función del contenedor, siendo P. pinaster la especie menos sensible en cuanto a la modificación de sus relaciones alométricas. Por lo general, la tendencia observada de todos los tratamientos de cobre en P. radiata fue el incremento de diámetro, altura y peso seco aéreo, observándose diferencias estadísticamente significativas en la relación altura-diámetro para ambas especies forestales respecto a los valores obtenidos en los tratamientos control. A todo ese conjunto de cambios se debe añadir finalmente una modificación de la arquitectura del sistema radicular de las plantas tratadas. La poda química ha demostrado ser un método eficaz para rectificar algunas limitaciones derivadas de las deformaciones radicales como consecuencia de la producción de planta en contenedor

Asymptomatic detection of SARS-CoV-2 among cancer patients receiving infusional anti-cancer therapy.

BackgroundLittle is known regarding the rate and clinical outcomes of asymptomatic carriers of SARS-CoV-2 among patients with cancer. Detection of asymptomatic carriers is important in this population given the use of myelosuppressive and immunomodulating therapies. Understanding the asymptomatic carrier rate will help to develop mitigation strategies in this high-risk cohort.MethodsRetrospective cohort analysis of an asymptomatic screening protocol which required patients receiving infusional anti-cancer therapy to undergo a symptom/exposure screen and SARS-CoV-2 PCR testing 24-96 h prior to their infusion. The primary outcome of this analysis was the rate of asymptomatic SARS-CoV-2 infection. Secondary outcomes included the rate of COVID-19-related hospitalization and mortality and delays in oncologic therapy.ResultsAmong a cohort of 2691 cancer patients who underwent asymptomatic screening, 1.6% (N = 43/2691) of patients were found to be SARS-CoV-2 positive on asymptomatic screening. 11.6% (N = 5/43) of the cohort ultimately developed COVID-19-related symptoms. Four patients required hospitalization for complications of COVID-19 infection. No patient died from COVID-related complications. 97.7% (N = 42/43) had their anti-cancer therapy delayed or deferred with a median delay of 21 days (range: 7-77 days).ConclusionsOverall, among a cohort of active cancer patients receiving anti-cancer therapy, an asymptomatic SARS-CoV2 PCR-based screening protocol detected a small cohort of asymptomatic carriers. The majority of these patients remained asymptomatic on long-term follow-up and outcomes were much more favorable compared to previously described outcomes of cancer patients with symptomatic COVID-19 infection

K-edge digital subtraction imaging based on a dichromatic and compact x-ray source

none11This work proposes a compact dichromatic imaging system for the application of the K-edge digital subtraction technique based on a conventional x-ray tube and a monochromator system. A quasi-monochromatic x-ray beam at the energy of iodine K-edge is produced by Bragg diffraction on a mosaic crystal. Two thin adjacent beams with energies that bracket the K-edge discontinuity are obtained fromthe diffracted beam bymeans of a proper collimation system. They are then detected using an array of Si detectors. A home-made phantom is used to study the image quality as a function of iodine concentration. Signal and signal-to-noise ratio analysis has also been performed. The results are compared with theoretical expectations.noneA. Sarnelli; A. Taibi; A. Tuffanelli; G. Baldazzi; D. Bollini; A. E. Cabal Rodriguez; M. Gombia; F. Prino; L. Ramello; E. Tomassi; M. GambacciniA. Sarnelli; A. Taibi; A. Tuffanelli; G. Baldazzi; D. Bollini; A. E. Cabal Rodriguez; M. Gombia; F. Prino; L. Ramello; E. Tomassi; M. Gambaccin

Analysis of CDK12 alterations in a pan-cancer database.

BACKGROUND: CDK12 inactivation leading to increased neoantigen burden has been hypothesized to sensitize tumors to immune checkpoint inhibition. Pan-cancer data regarding the frequency of CDK12 alterations are limited. We aimed to characterize CDK12 alterations across all cancer types through real-world clinical-grade sequencing. METHODS: This was a single-center retrospective analysis of 4994 cancer patients who underwent tissue or blood genomic profiling, including CDK12 assessment, conducted as part of routine care from December 2012 to January 2020. Prevalence, clinical characteristics, and treatment outcomes of patients with tumors with pathogenic CDK12 alterations were described. RESULTS: In all, 39 (0.78%, n = 39/4994) patients had pathogenic CDK12 alterations. Among CDK12-altered tumors, the most common organ site was prostate (n = 9, 23.1%) followed by colorectal (n = 5, 12.8%). Adenocarcinoma was the most common histology (n = 26, 66.7%). Median follow-up from time of diagnosis was 4.02 years. Median overall survival from time of metastasis was 4.43 years (95% CI: 3.11-5.74). Ten patients with CDK12-altered tumors received at least one immune checkpoint inhibitor-containing regimen. The majority of patients (n = 6/10, 60%) experienced an objective response. Progression-free survival for patients who had metastatic disease and received a checkpoint inhibitor-containing regimen was 1.16 years (95% CI: 0.32-2.00). CONCLUSION: CDK12 alterations are rare events across hematologic and solid tumor malignancies. They represent a clinically distinct molecular cancer subtype which may have increased responsiveness to checkpoint inhibition. Prospective studies are warranted to investigate checkpoint inhibition in CDK12-altered tumors

Topological constraints and chromosome organization in eukaryotes: a physical point of view

New experimental tools capable of probing the three-dimensional organization of eukaryotic genomes with an unprecedented level of detail have been developed in the last few years. In the quest for a quantitative understanding of experimental results, several polymer models for chromatin organization were introduced and critically evaluated. In the present article, I give a brief introduction to the physical basis of chromosome organization, and recall the experimental evidence in favour of the importance of topological constraints for the description of chromosome conformations in eukaryotes

Electron Tomography of Cryo-Immobilized Plant Tissue: A Novel Approach to Studying 3D Macromolecular Architecture of Mature Plant Cell Walls In Situ

<div><p>Cost-effective production of lignocellulosic biofuel requires efficient breakdown of cell walls present in plant biomass to retrieve the wall polysaccharides for fermentation. In-depth knowledge of plant cell wall composition is therefore essential for improving the fuel production process. The precise spatial three-dimensional (3D) organization of cellulose, hemicellulose, pectin and lignin within plant cell walls remains unclear to date since the microscopy techniques used so far have been limited to two-dimensional, topographic or low-resolution imaging, or required isolation or chemical extraction of the cell walls. In this paper we demonstrate that by cryo-immobilizing fresh tissue, then either cryo-sectioning or freeze-substituting and resin embedding, followed by cryo- or room temperature (RT) electron tomography, respectively, we can visualize previously unseen details of plant cell wall architecture in 3D, at macromolecular resolution (∼2 nm), and in near-native state. Qualitative and quantitative analyses showed that wall organization of cryo-immobilized samples were preserved remarkably better than conventionally prepared samples that suffer substantial extraction. Lignin-less primary cell walls were well preserved in both self-pressurized rapidly frozen (SPRF), cryo-sectioned samples as well as high-pressure frozen, freeze-substituted and resin embedded (HPF-FS-resin) samples. Lignin-rich secondary cell walls appeared featureless in HPF-FS-resin sections presumably due to poor stain penetration, but their macromolecular features could be visualized in unprecedented details in our cryo-sections. While cryo-tomography of vitreous tissue sections is currently proving to be instrumental in developing 3D models of lignin-rich secondary cell walls, here we confirm that the technically easier method of RT-tomography of HPF-FS-resin sections could be used immediately for routine study of low-lignin cell walls. As a proof of principle, we characterized the primary cell walls of a mutant (<i>cob-6</i>) and wild type Arabidopsis hypocotyl parenchyma cells by RT-tomography of HPF-FS-resin sections, and detected a small but significant difference in spatial organization of cellulose microfibrils in the mutant walls.</p></div

The electron tomography data collection and segmentation process used on Arabidopsis primary cell walls randomly chosen from chemically fixed samples.

<p>A. 2D projection image of cell wall. B. Slice of reconstructed tomogram. Bars = 250 nm. C. Sub-area of tomogram. D. Electron dense cell wall components selected by thresholding (selected areas outlined in red). E. Segmentation map of thresholded cell wall components (white). F. Mesh surface rendering of threshold segmentation map. Bars = 100nm. G-I. Small representative 3D volumes of the segmented cell wall showing orientation of filamentous cellulose microfibrils (arrow) and hemicellulose cross-connections (*). G- Top view showing microfibrils running approximately along the axis of cell elongation (Z-axis). H- Side view showing a single layer of microfibrils. I - Side view showing neighboring layers of microfibrils. Bars = 5 nm.</p