Investigating the accuracy and precision of TE‐dependent versus multi‐echo QSM using Laplacian‐based methods at 3 T

Purpose: Multi‐echo gradient‐recalled echo acquisitions for QSM enable optimizing the SNR for several tissue types through multi‐echo (TE) combination or investigating temporal variations in the susceptibility (potentially reflecting tissue microstructure) by calculating one QSM image at each TE (TE‐dependent QSM). In contrast with multi‐echo QSM, applying Laplacian‐based methods (LBMs) for phase unwrapping and background field removal to single TEs could introduce nonlinear temporal variations (independent of tissue microstructure) into the measured susceptibility. Here, we aimed to compare the effect of LBMs on the QSM susceptibilities in TE‐dependent versus multi‐echo QSM. Methods: TE–dependent recalled echo data simulated in a numerical head phantom and gradient‐recalled echo images acquired at 3 T in 10 healthy volunteers. Several QSM pipelines were tested, including four distinct LBMs: sophisticated harmonic artifact reduction for phase data (SHARP), variable‐radius sophisticated harmonic artifact reduction for phase data (V‐SHARP), Laplacian boundary value background field removal (LBV), and one‐step total generalized variation (TGV). Results from distinct pipelines were compared using visual inspection, summary statistics of susceptibility in deep gray matter/white matter/venous regions of interest, and, in the healthy volunteers, regional susceptibility bias analysis and nonparametric tests. Results: Multi‐echo versus TE‐dependent QSM had higher regional accuracy, especially in high‐susceptibility regions and at shorter TEs. Everywhere except in the veins, a processing pipeline incorporating TGV provided the most temporally stable TE‐dependent QSM results with an accuracy similar to multi‐echo QSM. Conclusions: For TE‐dependent QSM, carefully choosing LBMs can minimize the introduction of LBM‐related nonlinear temporal susceptibility variations

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010. They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.Fil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: von Karsa, Lawrence. International Agency for Research on Cancer; FranciaFil: Patrick, J.. NHS Cancer Screening Programmes Sheffield; Reino Unido. University of Oxford; Reino UnidoFil: Segnan, N.. International Agency for Research on Cancer; Francia. AO Città della Salute e della Scienza di Torino; ItaliaFil: Atkin, W.. Imperial College London; Reino UnidoFil: Halloran, S.. University of Surrey; Reino UnidoFil: Saito, H.. National Cancer Centre; JapónFil: Sauvaget, C.. International Agency for Research on Cancer; FranciaFil: Scharpantgen, A.. Ministry of Health; LuxemburgoFil: Schmiegel, W.. Ruhr-Universität Bochum; AlemaniaFil: Senore, C.. AO Città della Salute e della Scienza di Torino; ItaliaFil: Siddiqi, M.. Cancer Foundation of India; IndiaFil: Sighoko, D.. University of Chicago; Estados Unidos. Formerly International Agency for Research on Cancer; FranciaFil: Smith, R.. American Cancer Society; Estados UnidosFil: Smith S.. University Hospitals Coventry & Warwickshire NHS Trust; Reino UnidoFil: Suchanek, S.. Charles University; República ChecaFil: Suonio, E.. International Agency for Research on Cancer; FranciaFil: Tong, W.. Chinese Academy of Sciences; República de ChinaFil: Törnberg, S.. Stockholm Gotland Regional Cancer Centre. Department of Cancer Screening; SueciaFil: Van Cutsem, E.. Katholikie Universiteit Leuven; BélgicaFil: Vignatelli, L.. Agenzia Sanitaria e Sociale Regionale; ItaliaFil: Villain, P.. University of Oxford; Reino UnidoFil: Voti, L.. Formerly International Agency for Research on Cancer; Francia. University of Miami; Estados UnidosFil: Watanabe, H.. Niigata University; JapónFil: Watson, J.. University of Oxford; Reino UnidoFil: Winawer, S.. Memorial Sloan–Kettering Cancer Center; Estados UnidosFil: Young, G.. Flinders University. Gastrointestinal Services; AustraliaFil: Zaksas, V.. State Patient Fund; LituaniaFil: Zappa, M.. Cancer Prevention and Research Institute; ItaliaFil: Valori, R.. NHS Endoscopy; Reino Unid

Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a "mix-and-match" principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia

Breast cancer screening in the Czech Republic: time trends in performance indicators during the first seven years of the organised programme

<p>Abstract</p> <p>Background</p> <p>The Czech Breast Cancer Screening Programme (CBCSP) was initiated in September 2002 by establishing a network of accredited centres. The aim of this article is to describe progress in the programme quality over time after the inception of the organised programme.</p> <p>Methods</p> <p>The CBCSP is monitored using an information system consisting of three principal components: 1) the national cancer registry, 2) a screening registry collecting data on all screening examinations, further assessments and final diagnoses at accredited programme centres, and 3) administrative databases of healthcare payers. Key performance indicators from the European Guidelines have been adopted for continuous monitoring.</p> <p>Results</p> <p>Breast cancer incidence in the Czech Republic has steadily been increasing, however with a growing proportion of less advanced stages. The mortality rate has recently stabilised. The screening registry includes 2,083,285 records on screening episodes between 2002 and 2008. In 2007-2008, 51% of eligible women aged 45-69 were screened. In 2008, the detection rates were 6.1 and 3.7 per 1,000 women in initial and subsequent screening respectively. Corresponding recall rates are 3.9% and 2.2%, however, it is necessary to pay attention to further assessment performed during the screening visits. Benign to malignant open biopsy ratio was 0.1. Of invasive cases detected in screening, 35.6% was less than 10 mm in diameter. Values of early performance indicators, as measured by both crude and standardized estimates, are generally improving and fulfil desirable targets set by European Guidelines.</p> <p>Conclusions</p> <p>Mammography screening in the Czech Republic underwent successful transformation from opportunistic prevention to an organised programme. Values of early indicators confirm continuous improvement in different aspects of process quality. Further stimulation of participation through invitation system is necessary to exploit the full potential of screening mammography at the population level.</p

Quality assurance in pathology in colorectal cancer screening and diagnosis—European recommendations

In Europe, colorectal cancer is the most common newly diagnosed cancer and the second most common cause of cancer deaths, accounting for approximately 436,000 incident cases and 212,000 deaths in 2008. The potential of high-quality screening to improve control of the disease has been recognized by the Council of the European Union who issued a recommendation on cancer screening in 2003. Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document consists of ten chapters and an extensive evidence base. The content of the chapter dealing with pathology in colorectal cancer screening and diagnosis is presented here in order to promote international discussion and collaboration leading to improvements in colorectal cancer screening and diagnosis by making the principles and standards recommended in the new EU Guidelines known to a wider scientific community

Annex to Quirke et al. Quality assurance in pathology in colorectal cancer screening and diagnosis: annotations of colorectal lesions

Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document includes a chapter on pathology with pan-European recommendations which take into account the diversity and heterogeneity of health care systems across the EU. The present paper is based on the annex to the pathology chapter which attempts to describe in greater depth some of the issues raised in the chapter in greater depth, particularly details of special interest to pathologists. It is presented here to make the relevant discussion known to a wider scientific audience

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation