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Fifty-nine adult Filipino patients suffering from typhoid fever documented by blood culture were randomly allocated to one of three different drug regimens. Nineteen patients received 3 g ceftriaxone iv once daily for three days. Twenty patients received 4 g ceftriaxone iv once daily for three days and 20 patients received oral chloramphenicol 3 g daily in divided doses for two days followed by 2 g daily for 12 days. Eighteen patients were cured (95%) with 3 g of ceftriaxone for three days. All patients receiving 4 g ceftriaxone per day for three days or chloramphenicol for 14 days were cured. In the ceftriaxone groups two patients developed typhoid fever 30 and 45 days respectively after completion of treatment and one further patient had evidence of reinfection. Three patients relapsed within 15 to 17 days in the chloramphenicol group. Fever subsided in most patients between six and eight days, with three patients having a prolonged and moderate fever for 11 days in the ceftriaxone groups. This study suggests that a short treatment of three days of typhoid fever with ceftriaxone (3 or 4 g once daily) is adequate and not hazardous as far as relapses are concerned. [ABSTRACT FROM AUTHOR]

There is great heterogeneity in lengths of stay in interventional cardiology but the number of outpatient procedures is increasing. The expected benefits of an outpatient procedure are numerous and non-inferiority of this strategy has been demonstrated. Proper selection of patients eligible for this treatment is essential to minimize the risks of unplanned hospitalization and early complications. It is based on clinical, medico-social and organizational criteria. Perfect management of the care pathway based on an organizational unit and a geographical unit is essential., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent n'avoir aucun lien d'intérêt en lien avec cet article., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this postmarket clinical study was to assess the safety and efficacy of the latest generation polymer-free sirolimus-eluting stents (PF-SES) in an all-comers population comparing outcomes in stable coronary artery disease (CAD) versus acute coronary syndrome (ACS) in France., Background: The efficacy and safety of the first-generation PF-SES have already been demonstrated by randomized controlled trials and "all-comers" observational studies., Methods: For this all-comers observational, prospective, multicenter study, 1456 patients were recruited in 22 French centers. The primary endpoint was target lesion revascularization (TLR) rate at 12 months and secondary endpoints included major adverse cardiac events (MACE) and bleeding., Results: 895 patients had stable CAD and 561 had ACS. At 12 months, 2% of patients had a TLR, with similar rates between stable CAD and ACS (1.9% vs 2.2%, p  = 0.7). The overall MACE rate was 5.2% with an expected higher rate in patients with ACS as compared to those with stable CAD (7.3% vs 3.9%, p  = 0.007). The overall bleeding event rate was 4.5%, with similar rates in stable CAD as compared to ACS patients (3.8% vs 5.6%, p  = 0.3). Dual antiplatelet therapy (DAPT) interruptions prior to the recommended duration occurred in 41.7% of patients with no increase in MACE rates as compared to patients who did not prematurely interrupt DAPT (3.9% vs 6.1%, p  = 0.073)., Conclusions: The latest generation PF-SES is associated with low clinical event rates in these all-comers patients. There was a high rate of prematurely terminated DAPT, without any effect on MACE at 12 months. This trial is registered with NCT03809715., Competing Interests: Quentin Landolff, Marine Quillot, Fabien Picard, Georgios Sideris, Raphael Lasserre, and René Koning report consulting fees from B. Braun. The other authors have no conflicts of interest to declare., (Copyright © 2023 Quentin Landolff et al.)

To mount appropriate responses, T cells integrate complex sequences of receptor stimuli perceived during transient interactions with antigen-presenting cells. Although it has been hypothesized that the dynamics of these interactions influence the outcome of T cell activation, methodological limitations have hindered its formal demonstration. Here, we have engineered the Light-inducible T cell engager (LiTE) system, a recombinant optogenetics-based molecular tool targeting the T cell receptor (TCR). The LiTE system constitutes a reversible molecular switch displaying exquisite reactivity. As proof of concept, we dissect how specific temporal patterns of TCR stimulation shape T cell activation. We established that CD4 + T cells respond to intermittent TCR stimulation more efficiently than their CD8 + T cells counterparts and provide evidence that distinct sequences of TCR stimulation encode different cytokine programs. Finally, we show that the LiTE system could be exploited to create light-activated bispecific T cell engagers and manipulate tumor cell killing. Overall, the LiTE system provides opportunities to understand how T cells integrate TCR stimulations and to trigger T cell cytotoxicity with high spatiotemporal control.

Adenomatous polyposis coli (APC) is a polarity regulator and tumor suppressor associated with familial adenomatous polyposis and colorectal cancer development. Although extensively studied in epithelial transformation, the effect of APC on T lymphocyte activation remains poorly defined. We found that APC ensures T cell receptor-triggered activation through Nuclear Factor of Activated T cells (NFAT), since APC is necessary for NFAT's nuclear localization in a microtubule-dependent fashion and for NFAT-driven transcription leading to cytokine gene expression. Interestingly, NFAT forms clusters juxtaposed with microtubules. Ultimately, mouse Apc deficiency reduces the presence of NFAT in the nucleus of intestinal regulatory T cells (Tregs) and impairs Treg differentiation and the acquisition of a suppressive phenotype, which is characterized by the production of the anti-inflammatory cytokine IL-10. These findings suggest a dual role for APC mutations in colorectal cancer development, where mutations drive the initiation of epithelial neoplasms and also reduce Treg-mediated suppression of the detrimental inflammation that enhances cancer growth., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3). FIP3 overexpression or silencing and its ability to interact with Rab11 modify Lck subcellular localization and its delivery to the immunological synapse. Importantly, FIP3-dependent Lck localization controls early TCR signaling events, such as tyrosine phosphorylation of TCRζ, ZAP70, and LAT and intracellular calcium concentration, as well as IL-2 gene expression. Interestingly, FIP3 controls both steady-state and poststimulation phosphotyrosine and calcium levels. Finally, our findings indicate that FIP3 modulates TCR-CD3 cell surface expression via the regulation of steady-state Lck-mediated TCRζ phosphorylation, which in turn controls TCRζ protein levels. This may influence long-term T cell activation in response to TCR-CD3 stimulation. Therefore, our data underscore the importance of finely regulated endosomal traffic in TCR signal transduction and T cell activation leading to IL-2 production., (Copyright © 2017 by The American Association of Immunologists, Inc.)

The immunological synapse generation and function is the result of a T-cell polarization process that depends on the orchestrated action of the actin and microtubule cytoskeleton and of intracellular vesicle traffic. However, how these events are coordinated is ill defined. Since Rab and Rho families of GTPases control intracellular vesicle traffic and cytoskeleton reorganization, respectively, we investigated their possible interplay. We show here that a significant fraction of Rac1 is associated with Rab11-positive recycling endosomes. Moreover, the Rab11 effector FIP3 controls Rac1 intracellular localization and Rac1 targeting to the immunological synapse. FIP3 regulates, in a Rac1-dependent manner, key morphological events, like T-cell spreading and synapse symmetry. Finally, Rab11-/FIP3-mediated regulation is necessary for T-cell activation leading to cytokine production. Therefore, Rac1 endosomal traffic is key to regulate T-cell activation., (© 2016 The Authors.)