SARS-CoV-2-reactive T-cell receptors isolated from convalescent COVID-19 patients confer potent T-cell effector function

Both B cells and T cells are involved in an effective immune response to SARS-CoV-2, the disease-causing virus of COVID-19. While B cells—with the indispensable help of CD4⁺ T cells—are essential to generate neutralizing antibodies, T cells on their own have been recognized as another major player in effective anti-SARS-CoV-2 immunity. In this report, we provide insights into the characteristics of individual HLA-A*02:01- and HLA-A*24:02-restricted SARS-CoV-2-reactive TCRs, isolated from convalescent COVID-19 patients. We observed that SARS-CoV-2-reactive T-cell populations were clearly detectable in convalescent samples and that TCRs isolated from these T cell clones were highly functional upon ectopic re-expression. The SARS-CoV-2-reactive TCRs described in this report mediated potent TCR signaling in reporter assays with low nanomolar EC50 values. We further demonstrate that these SARS-CoV-2-reactive TCRs conferred powerful T-cell effector function to primary CD8⁺ T cells as evident by a robust anti-SARS-CoV-2 IFN-γ response and in vitro cytotoxicity. We also provide an example of a long-lasting anti-SARS-CoV-2 memory response by reisolation of one of the retrieved TCRs 5 months after initial sampling. Taken together, these findings contribute to a better understanding of anti-SARS-CoV-2 T-cell immunity and may contribute to paving the way toward immunotherapeutics approaches targeting SARS-CoV-2.     

Measuring the polymerization stress of self-adhesive resin composite cements by crack propagation

Clinical Oral Investigations - To test the polymerization stress of nine self-adhesive resin composite cements (G-CEM, iCEM, Bifix SE, Maxcem Elite, PANAVIA SA, SoloCem, SmartCem 2, SpeedCEM, RelyX...     

Liver cirrhosis in glycogen storage disease Ib

Glycogen storage disease Ib is an inborn error of carbohydrate metabolism leading to impaired glycogenolysis and gluconeogenesis. Cardinal symptoms include fasting hypoglycemia, lactic acidosis and hepatomegaly as well as neutropenia. We report for the first time on the development of liver cirrhosis in a nine-year-old boy in the course of glycogen storage disease Ib and discuss possible underlying pathomechanisms.     

Immune response to Helicobacter pylori infection and gastric cancer development

Gastric adenocarcinoma is a global health concern, and Helicobacter pylori (H. pylori) infection is the main risk factor for its occurrence. Of note, the immune response against the pathogen seems to be a determining factor for gastric oncogenesis, and increasing evidence have emphasized several host and bacterium factors that probably influence in this setting. The development of an inflammatory process against H. pylori involves a wide range of mechanisms such as the activation of pattern recognition receptors and intracellular pathways resulting in the production of proinflammatory cytokines by gastric epithelial cells. This process culminates in the establishment of distinct immune response profiles that result from the cytokine-induced differentiation of T naïve cells into specific T helper cells. Cytokines released from each type of T helper cell orchestrate the immune system and interfere in the development of gastric cancer in idiosyncratic ways. Moreover, variants in genes such as single nucleotide polymorphisms have been associated with variable predispositions for the occurrence of gastric malignancy because they influence both the intensity of gene expression and the affinity of the resultant molecule with its receptor. In addition, various repercussions related to some H. pylori virulence factors seem to substantially influence the host immune response against the infection, and many of them have been associated with gastric tumorigenesis.     

Estimation of pulse pressure variation and cardiac output in patients having major abdominal surgery: a comparison between a mobile application for snapshot pulse wave analysis and invasive pulse wave analysis

Pulse pressure variation (PPV) and cardiac output (CO) can guide perioperative fluid management. Capstesia (Galenic App, Vitoria-Gasteiz, Spain) is a mobile application for snapshot pulse wave analysis (PWAsnap) and estimates PPV and CO using pulse wave analysis of a snapshot of the arterial blood pressure waveform displayed on any patient monitor. We evaluated the PPV and CO measurement performance of PWAsnap in adults having major abdominal surgery. In a prospective study, we simultaneously measured PPV and CO using PWAsnap installed on a tablet computer (PPV_PWAsnap, CO_PWAsnap) and using invasive internally calibrated pulse wave analysis (ProAQT; Pulsion Medical Systems, Feldkirchen, Germany; PPV_ProAQT, CO_ProAQT). We determined the diagnostic accuracy of PPV_PWAsnap in comparison to PPV_ProAQT according to three predefined PPV categories and by computing Cohen’s kappa coefficient. We compared CO_ProAQT and CO_PWAsnap using Bland-Altman analysis, the percentage error, and four quadrant plot/concordance rate analysis to determine trending ability. We analyzed 190 paired PPV and CO measurements from 38 patients. The overall diagnostic agreement between PPV_PWAsnap and PPV_ProAQT across the three predefined PPV categories was 64.7% with a Cohen’s kappa coefficient of 0.45. The mean (±?standard deviation) of the differences between CO_PWAsnap and CO_ProAQT was 0.6?±?1.3 L min^??1 (95% limits of agreement 3.1 to ??1.9 L min^??1) with a percentage error of 48.7% and a concordance rate of 45.1%. In adults having major abdominal surgery, PPV_PWAsnap moderately agrees with PPV_ProAQT. The absolute and trending agreement between CO_PWAsnap with CO_ProAQT is poor. Technical improvements are needed before PWAsnap can be recommended for hemodynamic monitoring.