Immunological aspects involved in the degeneration of cryopreserved arterial allografts

Introduction: Cryopreserved arterial allografts have remained an option in patients requiring distal revascularization or associated with vascular infection, in the absence of a valid autogenous saphenous vein. The objective of this study is to describe the different clinical, anatomopathological, and immunological findings related to vascular transplant rejection. Methods: In a prospective trial, 35 patients who underwent cryopreserved allogeneic arterial bypass were studied, including demographics and conduit patency. Anti-HLA antibody production was stablished prior to the surgery, 7 days, 1, 3 months, and every 3 months since. Clinical and ultrasound evaluation was added after the first month. Donor HLA-typing was retrieved whenever available, allowing for the characterization and quantification of donor specific antibodies. Cytotoxic crossmatch test was also performed. A second group of patients with allograft degenerations registered during the follow up period was studied. In this group, exclusively for aneurysm description and histopathological analysis, they were included those degenerated vascular transplants from the original series, but also those implanted prior to the beginning of the study and degraded during follow up. Results: All patients studied displayed an increase in anti-HLA antibodies one month after the intervention, regarding bypass patency. In total, 14 patients fulfilled requirements for the study of donor specific antibodies, equally showing IgG production detectable one month after surgery. The presence of complement-fixing antibodies was also confirmed. Antibody levels were not related to graft degeneration. No specific immune markers able to predict aneurysmal development and evolution were found. From the original group, 3 patients suffered aneurysmal degeneration during follow up, together with 9 bypasses previously implanted. Average time until the first degeneration was 33 ± 19.7 months, with 30.6 ± 17.7 and 54.5 ± 2.5 months for a second and third degeneration, when occurring. Therefore, subsequent vascular transplants frequently augmented the time for new degenerations, despite increasing sensibilization. Samples from eight degenerated allografts were available for analysis, unexpectedly showing inflammatory infiltrate in only four cases and immune complex deposition in 7. Conclusions: Immune response against vascular transplants was confirmed in all cases, but chronic rejection did not necessarily provoke bypass degradation or reduced the time for new aneurysms to develop in subsequent allografts.FUNDING: This research was supported by grant PI17/00714 from the Spanish I + D + i 2013–2016 State Program, which was cofunded by Instituto de Salud Carlos III and the European Regional Development Fund (ERDF). ACKNOWLEDGMENTS: The authors wish to thank Dr. Aurora Astudillo, Head of the Department of Pathology at Central University Hospital of Asturias, for her collaboration and interest in making this study possible

Management Mathematics for european schools

Beyond the topics, the Mathematics folklore says that pupils think that this field is a boring, non-practical mental exercise, far apart from daily life. This thought is influencing the entire education system and even society, motivating important lack of mathematical skills among students. This work presents experiences, developed within the MaMaEuSch project oriented to stimulate and enforce the study of Mathematics among the students in the High-School education level

Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial

[EN] Microwave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA as well as morphology of corresponding ablation zones. HCC and MT patients with 1.5-4 cm tumors, suitable for ablation, were randomized into MWA or RFA Groups. The primary endpoint was short-to-long diameter ratio of ablation zone (SLR). Primary technical success (TS) and a cumulative local tumor progression (LTP) after a median 2-year follow-up were compared. Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, five patients were excluded. MWA created larger ablation zones than RFA (p = 0.036) although without differences in SLR (0.5 for both groups, p = 0.229). The TS was achieved in 98% (46/47) and 90% (45/50) (p = 0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66-5.3], p = 0.238) of tumors in MWA vs. RFA Group, respectively. Major complications were found in 5 cases (11%) vs. 2 cases (4%), without statistical significance. MWA and RFA show similar SLR, effectiveness and safety in liver tumors between 1.5 and 4 cm.This work was supported by a grant for medical research from Spanish Government (FIS-PI12/00799) and by the Spanish Ministerio de Ciencia, Innovacion y Universidades under "Programa Estatal de I+D+i Orientada a los Retos de la Sociedad", Grant RTI2018-094357-B-C21.Radosevic, A.; Quesada, R.; Serlavos, C.; Sánchez, J.; Zugazaga, A.; Sierra, A.; Coll, S.... (2022). Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial. Scientific Reports. 12(1):1-10. https://doi.org/10.1038/s41598-021-03802-xS11012

Metastatic gallbladder adenocarcinoma with signet-ring cells: A case report

<p>Abstract</p> <p>Introduction</p> <p>Signet-ring cell carcinoma is a rare and aggressive variant of mucinous adenocarcinoma. Only a few cases of gallbladder adenocarcinoma with signet-ring cells have been reported and because of this there is a lack of knowledge about the behavior and biology of this pathology.</p> <p>Case presentation</p> <p>We present the case of a 63-year-old Arab man with gallbladder signet-ring cell adenocarcinoma. He had an elective cholecystectomy and refused chemotherapy. Two months later, a small hepatic metastatic nodule was found, and nine months later he presented with multiple metastases in the liver, lymphatic nodes, both pleuras, peritoneum and subcutaneous tissue.</p> <p>Conclusion</p> <p>The proliferation of signet-ring cells in a gallbladder adenocarcinoma worsens the prognosis of an already adverse neoplasm. New lines of treatment in chemotherapy, such as cisplatin, or new biological therapy, such as monoclonal antibody c-myc oncogene, should be encouraged to improve the survival and life quality of these oncologic patients.</p

TAO Conceptual Design Report: A Precision Measurement of the Reactor Antineutrino Spectrum with Sub-percent Energy Resolution

The Taishan Antineutrino Observatory (TAO, also known as JUNO-TAO) is a satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO). A ton-level liquid scintillator detector will be placed at about 30 m from a core of the Taishan Nuclear Power Plant. The reactor antineutrino spectrum will be measured with sub-percent energy resolution, to provide a reference spectrum for future reactor neutrino experiments, and to provide a benchmark measurement to test nuclear databases. A spherical acrylic vessel containing 2.8 ton gadolinium-doped liquid scintillator will be viewed by 10 m^2 Silicon Photomultipliers (SiPMs) of &gt;50% photon detection efficiency with almost full coverage. The photoelectron yield is about 4500 per MeV, an order higher than any existing large-scale liquid scintillator detectors. The detector operates at -50 degree C to lower the dark noise of SiPMs to an acceptable level. The detector will measure about 2000 reactor antineutrinos per day, and is designed to be well shielded from cosmogenic backgrounds and ambient radioactivities to have about 10% background-to-signal ratio. The experiment is expected to start operation in 2022

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

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

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO