Cardiac CT Imaging of Plaque Vulnerability: Hype or Hope?

Advances in cardiovascular computed tomography (CT) have resulted in an excellent ability to exclude coronary heart disease (CHD). Anatomical information, functional information, and spectral information can already be obtained with current CT technologies. Moreover, novel developments such as targeted nanoparticle contrast agents, photon-counting CT, and phase contrast CT will further enhance the diagnostic value of cardiovascular CT. This review provides an overview of current state of the art and future cardiovascular CT imaging.     

State of the Art of Combined Heart-Lung Transplantation for Advanced Cardiac and Pulmonary Dysfunction

Over the last several decades, significant advances and improvements in care of transplant patients have resulted in markedly improved outcomes. A number of options are available for patients with advanced cardiopulmonary dysfunction requiring transplantation. There is a debate about when isolated heart or isolated lung transplantation is no longer possible or advisable and combined heart-lung transplantation is justified. Organ availability and allocation severely limit the latter option to very few well-selected patients. We review practice patterns, trends, and outcomes after triple-organ heart-lung transplant (HLTx) worldwide, as well as our own experience with heart-lung transplant in the modern era.     

Juvenile Fibromyalgia: Different from the Adult Chronic Pain Syndrome?

While a majority of research has focused on adult fibromyalgia (FM), recent evidence has provided insights into the presence and impact of FM in children and adolescents. Commonly referred as juvenile fibromyalgia (JFM), youths, particularly adolescent girls, present with persistent widespread pain and cardinal symptoms observed in adult FM. A majority of youth with JFM continue to experience symptoms into adulthood, which highlights the importance of early recognition and intervention. Some differences are observed between adult and juvenile-onset FM syndrome with regard to comorbidities (e.g., joint hypermobility is common in JFM). Psychological comorbidities are common but less severe in JFM. Compared to adult FM, approved pharmacological treatments for JFM are lacking, but non-pharmacologic approaches (e.g., cognitive-behavioral therapy and exercise) show promise. A number of conceptual issues still remain including (1) directly comparing similarities and differences in symptoms and (2) identifying shared and unique mechanisms underlying FM in adults and youths.     

Hypertension in Pregnancy: Defining Blood Pressure Goals and the Value of Biomarkers for Preeclampsia

Hypertensive disorders in pregnancy have been the cause of much clinical dilemma, affecting up to 10 % of all pregnancies. The precise blood pressure to achieve in a pregnant woman is usually a battle between minimizing end organ damage to the mother and providing adequate perfusion to the placenta and the fetus. This predicament is becoming more, not less, frequent as maternal ages increase in high resource nations. Biomarkers to predict preeclampsia, a subcategory of hypertension in pregnancy, have always been elusive. The discovery of angiogenic factors relevant to preeclampsia in the last decade, however, has propelled much needed research, both in the basic science and clinical arenas. In this review, we summarize the latest clinical studies and international guidelines on blood pressure goals in pregnancy, and discuss the most promising of biomarkers to predict or diagnose preeclampsia.     

SAPHO Syndrome: Current Developments and Approaches to Clinical Treatment

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare autoimmune disease which, due to its clinical presentation and symptoms, is often misdiagnosed and unrecognized. Its main features are prominent inflammatory cutaneous and articular manifestations. Treatments with immunosuppressive drugs have been used for the management of SAPHO with variable results. To date, the use of anti-TNF-α agents has proved to be an effective alternative to conventional treatment for unresponsive or refractory SAPHO cases. TNF-α is a pro-inflammatory cytokine and pivotal regulator of other cytokines, including IL-1 β, IL-6, and IL-8, involved in inflammation, acute-phase response induction, and chemotaxis. IL-1 inhibition strategies with anakinra have shown efficacy as first and second lines of treatment. In this review, we will describe the main characteristics of biological drugs currently used for SAPHO syndrome. We also describe some of the promising therapeutic effects of ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure of multiple drugs including anti-TNF-α and anakinra. We discuss the use and impact of the new anti-IL-1 antagonists involved in the IL-17 blockade, in particular for the most difficult-to-treat SAPHO cases.     

Pharmacoeconomics of Biosimilars: What Is There to Gain from Them?

Despite representing a breakthrough in the treatment of immune-mediated rheumatic diseases, the direct costs of biotechnological therapies represent a burden to healthcare budgets worldwide. Furthermore, several studies demonstrated that socioeconomically constrained countries have poorer access to these therapies and this has consequences on the optimal management of rheumatic patients. Experience with small peptide biosimilars like filgrastim and epoetin confirmed significant cost savings but revealed variable market uptake. In this report, we summarize the available budget impact models and discuss possible determinants of the pharmacoeconomic performance of antirheumatic biosimilar drugs.     

Predictors of Poor Outcome in ANCA-Associated Vasculitis (AAV)

It is important to recognize factors that might predict poor outcome and prognosis in patients with AAV. The predictors reported in the literature encompass genetic, histopathological, and clinical ones. Genetic studies (genetic predictors) have found genes that are associated with prediction of poor response to treatment, deterioration of renal function, and risk of mortality. Histopathological studies (histopathological predictors) have shown that sclerotic renal lesions are associated with increased risk of progression to end-stage renal disease and death. Lastly, scores (clinical predictors) obtained with tool as FFS, Maldini risk score, VDI, and emerging new biomarkers could potentially be helpful in assessment of prognosis in the future.     

The Traveling Microbiome

Given the recent interest in the human gut microbiome in health and disease, we have undertaken a review of the role of the gut microbiome as it relates to travel. Considering the microbiome as the interface with the external world of the traveler, not only from the perspective of protection from enteric infection by colonization resistance but also the possibility that a traveler’s unique microbiome may place him or her at lesser or greater risk for enteric infection. We review available data on travel, travelers’ diarrhea, and the use of antibiotics as it relates to changes in the microbiome and the acquisition of multi-drug-resistant bacteria and explore the interplay of these factors in the development of dysbiosis and the post-infectious sequelae of TD, specifically PI-IBS. In addition, we explore whether dietary changes in travel affect the gut microbiome in a way which modulates gastrointestinal function and susceptibility to infection and discuss whether pre- or probiotics have any meaningful role in prevention or treatment of TD. Finally, a discussion of important research gaps and opportunities in this area is identified.     

Central Nervous System Device Infections

Nosocomial meningitis can occur in association with central nervous system (CNS) devices such as cerebrospinal shunts or drains, intrathecal pumps, and deep brain stimulators and carry substantial morbidity and mortality. Diagnosing and treating these infections may be challenging to physicians as cerebrospinal fluid cultures may be negative due to previous antibiotic therapy and cerebrospinal abnormalities may be secondary to the primary neurosurgical issue that prompted the placement of the CNS device (e.g., “chemical meningitis” due to intracranial hemorrhage). Besides antibiotic therapy given intravenously and sometimes intrathecally, removal of the device with repeat cultures prior to re-implantation is key in achieving successful outcomes.     

Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges

Sepsis is life-threating organ dysfunction due to infection. Incidence of sepsis is increasing and the short-term mortality is improving, generating more sepsis survivors. These sepsis survivors suffer from additional morbidities such as higher risk of readmissions, cardiovascular disease, cognitive impairment and of death, for years following index sepsis episode. In the first year following index sepsis episode, approximately 60 % of sepsis survivors have at least one rehospitalisation episode, which is most often due to infection and one in six sepsis survivors die. Sepsis survivors also have a higher risk of cognitive impairment and cardiovascular disease contributing to the reduced life expectancy seen in this population, when assessed with life table comparisons. For optimal design of interventional trials to reduce these bad outcomes in sepsis survivors, in-depth understanding of major risk factors for these morbid events, their modifiability and a causal relationship to the pathobiology of sepsis is essential. This review highlights the recent advances, clinical and methodological challenges in our understanding of these morbid events in sepsis survivors.