Research Spotlight

Ueno, H. (2016). “Human Circulating T Follicular Helper Cell Subsets in Health and Disease. ” J Clin Immunol. Mar 17. [Epub ahead of print]

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T follicular helper (Tfh) cells are specialized to provide help to B cells and to induce durable antibody response. Our knowledge on the biology of Tfh cells and their contribution to disease has significantly increased in the past decade. In particular, recent discoveries of functionally distinct subsets within circulating Tfh (cTfh) cells in human blood have provided clues to assess the ongoing Tfh responses in healthy subjects after vaccinations and in patients with autoimmune diseases. The immune pathways associated with Tfh cell differentiation in humans are also getting revealed. In this review, I will first summarize the subsets within human cTfh cells, and discuss their alterations in patients with autoimmune diseases. Then I will discuss the mechanisms associated with the aberrant Tfh responses in human autoimmune diseases.

Roberts, W. C., V. S. Won, A. Vasudevan, J. M. Ko and J. M. Guileyardo (2016). “Frequency of Massive Cardiac Adiposity (Floating Heart) at Necropsy and Comparison of Clinical and Morphologic Variables With Cases With Nonmassive Cardiac Adiposity at a Single Texas Hospital, 2013 to 2014.” Am J Cardiol Mar;117(6): 1006-1013.

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Body weight continues to increase worldwide primarily because of the increase in body fat. This study analyzes the frequency of massive adiposity at autopsy determined by the ability of the heart to float in a container of 10% formaldehyde (because adipose tissue is lighter than myocardium) and compares certain findings in the patients with floating to those with nonfloating hearts. The hearts studied at necropsy during a 2-year period (2013 to 2014) at Baylor University Medical Center were carefully “cleaned” and weighed by the same person and tested as to their ability to float in a container of formaldehyde, an indication of severe cardiac adiposity. Of the 146 hearts studied, 76 (52%) floated in a container of formaldehyde and 70 (48%) did not. Comparison of the 76 patients with floating hearts with the 70 with nonfloating hearts showed significant differences in ages (62 +/- 13 vs 58 +/- 14 years). No significant differences between the 2 groups were found in gender, body mass index, frequency of systemic hypertension or diabetes mellitus, either acute or healed myocardial infarction, or whether death was due to a coronary or a noncoronary condition. A weak correlation was found between body mass index and heart weight in both men and women and in both floating and nonfloating hearts. The massive quantity of cardiac adipose tissue (floating heart) appears to have increased enormously in recent decades in the United States.

Ramsay, M. A. and J. F. Trotter (2016). “The INR is only one side of the coagulation cascade: time to watch the clot.” Anaesthesia. Mar 31. [Epub ahead of print]

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The prothrombin time (PT)-derived international normalized ratio (INR) is frequently used to assess the risk of bleeding for patients receiving warfarin, or who have had liver surgery, liver dysfunction or transplantation. Anaesthetists will rely on it when assessing the potential for neuraxial hematoma formation when placing or removing an epidural catheter. It is also a key component of the Model for End-stage Liver Disease (MELD) score, which is an objective means of predicting 90-day patient survival in patients on the liver transplant waiting list, and is used to prioritize donor organs to the most needy patients. The accuracy of PT measurement has been questioned as there is marked variability in the sensitivity of the thromboplastin reagents used in its determination . . . It has now been well demonstrated that in liver disease, particularly liver cirrhosis, there is a reduction in the production of both pro- and anticoagulants by the liver. Therefore, the PT-derived INR only measures the procoagulant side of the cascade and not the anticoagulant side. (Excerpt from editorial; no abstract.)

Rahimi, R. S. and D. C. Rockey (2016). “Acute on chronic liver failure: definitions, treatments and outcomes.” Curr Opin Gastroenterol. 2016 May;32(3):172-81.

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PURPOSE OF REVIEW: Acute on chronic liver failure (ACLF) causes significant morbidity and mortality in patients with cirrhosis and/or chronic liver disease (CLD). The purpose of this review is to highlight recent studies that have better defined ACLF, and to highlight current outcomes and treatment strategies. RECENT FINDINGS: Currently, there are no clear definitions for ACLF; however, ACLF requires a precipitating event that occurs in the setting of cirrhosis and/or CLD, and progresses rapidly to multiorgan failure with high mortality. Most precipitants of ACLF are due to infections, leading to inflammatory cascades, hence early treatment with antibiotics in these cases might show benefit. Prognosis in ACLF typically depends on the number of extrahepatic organs affected. Potential biomarkers in ACLF may result in early detection and risk stratification; however, further research is needed. ACLF portends a poor prognosis; however, rescue therapy with liver transplantation has been considered in selected cases. SUMMARY: ACLF is a common and devastating complication of cirrhosis or CLD. ACLF usually requires a precipitating event and rapid progression to multiorgan failure with high mortality. Although signs and symptoms might overlap in patients with ACLF and those with decompensated cirrhosis, the two entities should be distinguished separately (although it is challenging to differentiate these in certain cases). Furthermore, diagnosing each entity should be based on a variety of clinical indicators, laboratory data and precipitating factors, in order to determine the best possible targeted treatment strategies. Refinement in the clinical definitions for ACLF may lead to better management and possibly better outcomes if recognized early.

Packer, M. (2016). “Unbelievable Folly of Clinical Trials in Heart Failure: The Inconvenient Truth About How Investigators and Guidelines Weigh Evidence.” Circ Heart Fail April 9(4).

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Despite significant advances in the treatment of chronic heart failure during the past 30 years, there is a broad consensus that new treatments are needed because morbidity and mortality in this disorder remain unacceptably high. Nevertheless, the development of new drugs for chronic heart failure has waned during the past 20 years; the quantity of novel agents in clinical testing and the number of well-designed clinical trials have diminished to a small fraction of that seen in the 1980s and 1990s. Some have suggested that investment in heart failure has declined because the primary mechanisms of the disorder are poorly understood, because the promising results of phase II trials are frequently not confirmed in large-scale definitive studies, and because the large-scale clinical trials needed for regulatory approval have often become prohibitively expensive.2,3 We know that clinical research in heart failure is extremely challenging, and so we beg innovators in the pharmaceutical and device industries to be patient, and we plead with sponsors to invest in large-scale investigations because the need is so great. Yet, when we critically examine how we react to data, it may not be too surprising that meaningful clinical trials in heart failure are becoming increasingly scarce. Do cardiologists act as if the results of clinical trials in heart failure really matter? (Excerpt from text; no abstract.)