Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases : multicentre study of 80 patients

Objectives To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). Methods Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. Results We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), Conclusions CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs

Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed

A new brain dedicated PET scanner with 4D detector information

[EN] In this article, we present the geometrical design and preliminary results of a high sensitivity organ-specific Positron Emission Tomography (PET) system dedicated to the study of the human brain. The system, called 4D-PET, will allow accurate imaging of brain studies due to its expected high sensitivity, high 3D spatial resolution and, by including precise photon time of flight (TOF) information, a boosted signal-to-noise ratio (SNR). The 4D-PET system incorporates an innovative detector design based on crystal slabs (semi-monolithic) that enables accurate 3D photon impact positioning (including photon Depth of Interaction (DOI) measurement), while providing a precise determination of the photon arrival time to the detector. The detector includes a novel readout system that reduces the number of detector signals in a ratio of 4:1 thus, alleviating complexity and cost. The analog output signals are fed to the TOFPET2 ASIC (PETsys) for scalability purposes. The present manuscript reports the evaluation of the 4D-PET detector, achieving best values 3D resolution values of <1.6 mm (pixelated axis), 2.7±0.5 mm (monolithic axis) and 3.4±1.1 (DOI axis) mm; 359 ± 7 ps coincidence time resolution (CTR); 10.2±1.5 % energy resolution; and sensitivity of 16.2% at the center of the scanner (simulated). Moreover, a comprehensive description of the 4D-PET architecture (that includes 320 detectors), some pictures of its mechanical assembly, and simulations on the expected image quality are provided.This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant Agreement No. 695536). This work was supported in part by the Spanish Government Grants Generalitat Valenciana, APOSTD/2019/086 and APOSTD/2020/139.We thank financial support from Generalitat Valenciana through the program Equipamiento e Infraestructuras FEDER 2021-22 IDIFEDER/2021/004González-Montoro, A.; Barbera Ballester, J.; Sanchez-Gonzalo, D.; Mondejar, Á.; Freire-López-Fando, M.; Díaz González, K.; Lucero-Ruiz, A.... (2022). A new brain dedicated PET scanner with 4D detector information. Bio-Algorithms and Medical-Systems. 18(1):107-119. https://doi.org/10.2478/bioal-2022-008310711918

Outpatient Parenteral Antibiotic Treatment for Infective Endocarditis: A Prospective Cohort Study From the GAMES Cohort

BACKGROUND: Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious for treating infective endocarditis (IE). However, the 2001 Infectious Diseases Society of America (IDSA) criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). METHODS: Retrospective analysis of data from a multicenter, prospective cohort study of 2000 consecutive IE patients in 25 Spanish hospitals (2008-2012) was performed. RESULTS: A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (interquartile range [IQR], 56-76), and 57% had native-valve IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). Median length of antibiotic treatment was 42 days (IQR, 32-54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P < .001), 1.4% of patients relapsed, and 10.9% were readmitted during the first 3 months after discharge (no significant differences compared with HBAT). Charlson score (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04-1.42; P = .01) and cardiac surgery (OR, 0.24; 95% CI, .09-.63; P = .04) were associated with 1-year mortality, whereas aortic valve involvement (OR, 0.47; 95% CI, .22-.98; P = .007) was the only predictor of 1-year readmission. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. CONCLUSIONS: OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA. OPAT criteria should therefore be expanded