Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry.

Background: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry.

Methods: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain.

Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study.

The relationship between thyroid function and cardiac disease is complex. Both hypothyroidism and thyrotoxicosis can predispose to ventricular arrhythmia and other major adverse cardiovascular events (MACE), so that a U-shaped relationship between thyroid signaling and the incidence of MACE has been postulated. Moreover, recently published data suggest an association between thyroid hormone concentration and the risk of sudden cardiac death (SCD) even in euthyroid populations with high-normal FT4 levels.

Aspergillus Polymerase Chain Reaction-An Update on Technical Recommendations, Clinical Applications, and Justification for Inclusion in the Second Revision of the EORTC/MSGERC Definitions of Invasive Fungal Disease.

Aspergillus polymerase chain reaction testing of blood and respiratory samples has recently been included in the second revision of the EORTC/MSGERC definitions for classifying invasive fungal disease. This is a result of considerable efforts to standardize methodology, the availability of commercial assays and external quality control programs, and additional clinical validation. This supporting article provides both clinical and technical justifications for its inclusion while also summarizing recent advances and likely future developments in the molecular diagnosis of invasive aspergillosis.

Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model.

High-throughput RNA sequencing (RNA-seq) is routinely applied to study diverse biological processes; however, when performed separately on interacting organisms, systemic noise intrinsic to RNA extraction, library preparation, and sequencing hampers the identification of cross-species interaction nodes. Here, we develop triple RNA-seq to simultaneously detect transcriptomes of monocyte-derived dendritic cells (moDCs) infected with the frequently co-occurring pulmonary pathogens Aspergillus fumigatus and human cytomegalovirus (CMV). Comparing expression patterns after co-infection with those after single infections, our data reveal synergistic effects and mutual interferences between host responses to the two pathogens.

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

Background: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants.

The Fungal PCR Initiative's evaluation of in-house and commercial Pneumocystis jirovecii qPCR assays: Toward a standard for a diagnostics assay.

Quantitative real-time PCR (qPCR) is increasingly used to detect Pneumocystis jirovecii for the diagnosis of Pneumocystis pneumonia (PCP), but there are differences in the nucleic acids targeted, DNA only versus whole nucleic acid (WNA), and also the target genes for amplification. Through the Fungal PCR Initiative, a working group of the International Society for Human and Animal Mycology, a multicenter and monocenter evaluation of PCP qPCR assays was performed. For the multicenter study, 16 reference laboratories from eight different countries, performing 20 assays analyzed a panel consisting of two negative and three PCP positive samples.

Treatment with etanercept and low monocyte concentration contribute to the risk of invasive aspergillosis in patients post allogeneic stem cell transplantation.

Invasive aspergillosis (IA) is a life-threatening complication among allogeneic hematopoietic stem cell transplant (alloSCT) recipients. Despite well known risk factors and different available assays, diagnosis of invasive aspergillosis remains challenging. 103 clinical variables from patients with hematological malignancies and subsequent alloSCT were collected.

Validation of a simplified in vitro Transwell model of the alveolar surface to assess host immunity induced by different morphotypes of Aspergillus fumigatus.

Interactions between fungal pathogens such as Aspergillus fumigatus with host alveolar epithelium and innate immune cells are crucial in the defense against opportunistic fungal infections. In this study a simplified Transwell system with a confluent layer of A549 cells acted as a model for the alveolar surface. A.

Size matters - how the immune system deals with fungal hyphae.

Fungal hyphae constitute a special challenge for the immune system, since they are too large to be phagocytosed. This review summarizes our current knowledge on those immune cells that are able to attack and eliminate hyphae and we discuss the different means that are employed by these cells in order to kill hyphae.

Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase.

Background: The Nod-like receptor NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK) are protagonists in innate and adaptive immunity, respectively. NLRP3 senses exogenous and endogenous insults, leading to inflammasome activation, which occurs spontaneously in patients with Muckle-Wells syndrome; BTK mutations cause the genetic immunodeficiency X-linked agammaglobulinemia (XLA). However, to date, few proteins that regulate NLRP3 inflammasome activity in human primary immune cells have been identified, and clinically promising pharmacologic targeting strategies remain elusive.

Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis.

Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy.

Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling.

Background: Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF.

Polymorphonuclear neutrophils and granulocytic myeloid-derived suppressor cells inhibit natural killer cell activity toward Aspergillus fumigatus.

Invasive aspergillosis is a devastating infectious disease in immunocompromised patients. Besides neutrophils and macrophages, natural killer (NK) cells have recently emerged as important players in immunity to this infection. It was shown that NK cells comprise an essential role in the clearance of Aspergillus fumigatus (A.

Control of relapsed or refractory acute myeloid leukemia by clofarabine in preparation for allogeneic stem cell transplant.

Allogeneic stem cell transplant is indicated for patients with refractory or relapsed acute myeloid leukemia (AML). Since elimination of the leukemic load is thought to be a prerequisite for treatment success, we here investigate toxicity and anti-leukemic activity of a clofarabine-AraC salvage protocol preceding transplant. In this retrospective analysis, we observed induction of objective remissions in 86% of patients receiving clofarabine-AraC as compared to 83% with sequential high dose AraC/mitoxantrone (S-HAM) and 50% after mitoxantrone/topotecane/AraC (MTC) salvage strategies.

Second degree AV block and severely impaired contractility in cardiac myxedema: a case report.

The heart is a major target organ for thyroid hormone action. Severe overt hypothyroidism can result in diastolic hypertension, lowered cardiac output, impaired left ventricular contractility and diastolic relaxation, pericardial effusion and bradycardia. However, the function of the atrial pacemaker is usually normal and the degree by which the heart rate slows down is often modest.

Identification of Aspergillus fumigatus Surface Components That Mediate Interaction of Conidia and Hyphae With Human Platelets.

Background: Platelets were recently identified as a part of innate immunity. They are activated by contact with Aspergillus fumigatus; putative consequences include antifungal defense but also thrombosis, excessive inflammation, and thrombocytopenia. We aimed to identify those fungal surface structures that mediate interaction with platelets.

Primary culture and transfection of epithelial cells of human small intestine.

Background: So far, no techniques are available for primary culture and efficient transfection of human small-intestinal enterocytes, which would provide a valuable tool to investigate intestinal function.

Methods: Human small-intestinal biopsy specimens were treated with collagenase and dispase. Resulting crypt units were cultured for several days.