An Unusual Case of Vasospastic Angina Resulting in Multiple Episodes of Cardiac Arrest.

Coronary vasospasm is a well-recognized cause of angina (also known as Prinzmetal angina) and a common cause of admissions to the emergency department and coronary intensive care units. It is however an uncommon cause of cardiac arrest. We describe a patient with multiple episodes of chest pain followed by cardiac arrest in pulseless electrical activity (PEA) due to coronary vasospasm. Telemetry and electrocardiography showed ST-segment elevation followed by PEA. Each event was short-lived and resolved after a maximum of six minutes of advanced life support measures. The patient was started on treatment with a dihydropyridine calcium channel blocker (CCB) and nitroglycerin patch with no further episodes recorded to date.

Catheter-Related Right Atrial Endocarditis in a Dialysis Patient.

Hemodialysis catheters are frequently used for vascular access in end-stage chronic kidney disease patients lacking mature arteriovenous fistula. The incidence of infective endocarditis in hemodialysis patients is higher than in the general population and is associated with severe and potentially life-threatening complications. A high index of suspicion is imperative for early diagnosis and timely intervention to enhance the prognosis of this high-mortality condition. Imaging studies, like transthoracic and transesophageal echocardiography, are crucial for prompt diagnosis. We present a case of a 36-year-old woman undergoing hemodialysis, whose prolonged use of a permanent catheter led to the development of infective endocarditis complicated with septic pulmonary embolism. Our case report presents an example of right atrial endocarditis with a poor outcome due to delayed diagnosis.

Pleural Sarcoidosis and Occult Lymphatic Anthracosis: An Unusual Symptomatic Association.

Sarcoidosis is a chronic multisystemic inflammatory disease of unknown aetiology. Virtually any organ or system can be involved, resulting in a wide range of clinical presentation. Pleural sarcoidosis is rare. Pleural effusion can only be attributed to pleural sarcoidosis in the presence of pleural non-caseating epithelioid granulomas and after excluding other granulomatous diseases. Anthracosis is a pneumoconiosis associated with thoracic adenopathies and bronchial disease, and it is usually asymptomatic. The authors present a case of a middle-aged man hospitalized due to cough, right-sided pleuritic chest pain and trepopnoea. LEARNING POINTS: To pursue a systematic and exhaustive investigation of pleuraleffusion until a definitive diagnosis is established.To recognize atypical presentations of sarcoidosis with a high degree of suspicion whenever the initial investigation is inconclusive.

CD70-CD27 interactions provide survival and proliferative signals that regulate T cell receptor-driven activation of human γδ peripheral blood lymphocytes.

Human Vγ9Vδ2 T cells are potent anti-tumor lymphocytes that specifically respond to pyrophosphate (phospho-) antigens, which constitute the basis of current γδ T-cell-based immunotherapy strategies. Despite a clear involvement of the TCR, the costimulation requirements of Vγ9Vδ2 T cells remain ill-defined. Here, we show that the expression of the CD27 receptor by the vast majority of Vγ9Vδ2 peripheral blood lymphocytes endows them with enhanced proliferative capacity upon ligation by its unique ligand CD70, a tumor necrosis factor superfamily member expressed on lymphoma B-cells but also on TCR-activated γδ T cells. Moreover, Vγ9Vδ2 T-cell treatment with soluble recombinant CD70 induced calcium signals and increased transcription of anti-apoptotic Bcl2a1 and cell-cycle-promoting Cyclin D2 genes. We further demonstrate that the manipulation of CD70-CD27 interactions significantly impacted on Vγ9Vδ2 T-cell survival, proliferation and cytokine secretion, in both loss-of-function and gain-of-function experiments. Thus, CD27 coreceptor signals strongly promoted the expansion of Th1-biased, CD27(+) Vγ9Vδ2 peripheral blood lymphocytes in the context of TCR-mediated stimulation with phosphoantigens. These data collectively establish a novel role for the CD70-CD27 axis in human γδ T-cell activation and hence open new perspectives for its modulation in clinical settings.

Cutting edge: adaptive versus innate receptor signals selectively control the pool sizes of murine IFN-γ- or IL-17-producing γδ T cells upon infection.

γδ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ T cells. Thus, MyD88 deficiency severely impaired the response to malaria infection of CD27((-)), IL-17A-producing γδ T cells, but not of IFN-γ-producing γδ cells. Instead, the latter compartment was severely contracted by ablating CD27, which synergizes with TCRγδ in the induction of antiapoptotic mediators and cell cycle-promoting genes in CD27((+)), IFN-γ-secreting γδ T cells. Hence, innate versus adaptive receptors differentially control the peripheral pool sizes of discrete proinflammatory γδ T cell subsets during immune responses to infection.

Highly active microbial phosphoantigen induces rapid yet sustained MEK/Erk- and PI-3K/Akt-mediated signal transduction in anti-tumor human gammadelta T-cells.

BACKGROUND: The unique responsiveness of Vgamma9Vdelta2 T-cells, the major gammadelta subset of human peripheral blood, to non-peptidic prenyl pyrophosphate antigens constitutes the basis of current gammadelta T-cell-based cancer immunotherapy strategies. However, the molecular mechanisms responsible for phosphoantigen-mediated activation of human gammadelta T-cells remain unclear. In particular, previous reports have described a very slow kinetics of activation of T-cell receptor (TCR)-associated signal transduction pathways by isopentenyl pyrophosphate and bromohydrin pyrophosphate, seemingly incompatible with direct binding of these antigens to the Vgamma9Vdelta2 TCR. Here we have studied the most potent natural phosphoantigen yet identified, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), produced by Eubacteria and Protozoa, and examined its gammadelta T-cell activation and anti-tumor properties. METHODOLOGY/PRINCIPAL FINDINGS: We have performed a comparative study between HMB-PP and the anti-CD3epsilon monoclonal antibody OKT3, used as a reference inducer of bona fide TCR signaling, and followed multiple cellular and molecular gammadelta T-cell activation events. We show that HMB-PP activates MEK/Erk and PI-3K/Akt pathways as rapidly as OKT3, and induces an almost identical transcriptional profile in Vgamma9(+) T-cells. Moreover, MEK/Erk and PI-3K/Akt activities are indispensable for the cellular effects of HMB-PP, including gammadelta T-cell activation, proliferation and anti-tumor cytotoxicity, which are also abolished upon antibody blockade of the Vgamma9(+) TCR Surprisingly, HMB-PP treatment does not induce down-modulation of surface TCR levels, and thereby sustains gammadelta T-cell activation upon re-stimulation. This ultimately translates in potent human gammadelta T-cell anti-tumor function both in vitro and in vivo upon transplantation of human leukemia cells into lymphopenic mice, CONCLUSIONS/SIGNIFICANCE: The development of efficient cancer immunotherapy strategies critically depends on our capacity to maximize anti-tumor effector T-cell responses. By characterizing the intracellular mechanisms of HMB-PP-mediated activation of the highly cytotoxic Vgamma9(+) T-cell subset, our data strongly support the usage of this microbial antigen in novel cancer clinical trials.