Stents without restenosis--true or a myth?

Routine stent implantations have significantly improved the results of percutaneous coronary angioplasty. In relation to balloon dilatation, the intervention success is improved, while restenosis as well as recurrence of progressive atherosclerotic disease at the site of previous dilatation are significantly reduced. In complicated interventional procedures such as dilatation of multi-vessels, long lesions, left main lesion, bifurcation lesions, dilatation of small vessels, and lesions in patients with diabetes mellitus in spite of stent implantation, the incidence of restenosis remains high, about 30%-50%. The introduction of drug-eluting stents (DES) such as sirolimus, paclitaxel and dexamethasone in interventional cardiology has brought important improvement with a significantly decreasing incidence of in-stent restenosis. Despite great enthusiasm and very good initial results, it should not be forgotten that the usage of these stents is still experimental, with many questions, especially concerning longterm results and use of DES in complicated interventional procedures.     

Elite HIV controllers: myth or reality?

Despite the varying disease progression rates, the majority of HIV-infected individuals eventually progress to AIDS. There is a subset of HIV-positive individuals, who maintain high CD4+ and CD8+ T-cell counts, remain therapy naive and persistently infected with HIV-1 for more than 15 to 20 years. In light of current observations, this subset can be divided into two groups. One shows low detectable plasma viremia (< 5000 HIV-RNA copies/ml), termed long-term nonprogressors. A second group shows plasma HIV-RNA values persistently below 50 copies/ml throughout the course of infection, and termed "elite" or "natural controllers". The features common between both groups are the presence of high CD4+ and CD8+ T-cell counts, strong immune responses, and low but variable cellular proviral DNA load. The group of HIV-positive long-term nonprogressor individuals comprises about 1% of the total HIV population in the world, whereas the "elite" controllers may be much less. Why do some people deteriorate faster, while others remain normal both symptomatically and immunologically for decades? There is a renewed interest in HIV-positive individuals who have survived since the period close to the earlier part of the HIV pandemic in the 1980s and have remained drug-naive. As very little is known about "elite" controllers, the findings discussed here are largely based on previously known and newly emerging aspects of HIV pathogenesis in the context of the long-term nonprogressor group. It is believed that data emerging on long-term nonprogressors will allow us to make scientific inferences to further our research on "elite" controllers. Aspects dealing with cellular, humoral, innate, and adaptive immunity, which are relevant to nonprogressive HIV disease, are beyond the scope of this review.     

Strong linea alba: myth or reality?

The traditional approach of repairing the linea alba, while operating on ventral hernias, is based on the premise that the linea alba is a strong layer and can reinforce the abdominal wall. This deeply entrenched view of most surgeons has resulted in numerous techniques which invariably include the linea alba as a part of the repair. On the contrary, this article proposes a hypothesis that the linea alba is a weak layer and varies widely in individuals with respect to its anatomy. It is especially weak in elderly, obese and multiparous patients in whom ventral hernias are common. The ‘white line’ - literal translation of ‘linea alba’ - becomes wide and attenuated in these patients; this ‘white area’ or ‘rus alba’ is more susceptible to tissue failure. We termed this the “Sick Linea Alba Complex” (SLAC) and hypothesize that the linea alba should be excluded from rather than included in the repair of ventral hernias in order to minimize recurrence rates.     

Chimeras — no longer a myth

Since its first successful application less than 15 years ago, allogeneic marrow transplantation has been used with continuously improving results for the treatment of severe aplastic anemia, leukemia and congenital immunodeficiency syndromes. With this background, a recent meeting¹ provided an excellent opportunity to critically review problems and achievements of marrow transplant and non-transplant approaches to the treatment of malignant and nonmalignant lymphohemopoietic disorders.     

HIV viral load: the myth of the undetectable?

There is a wealth of data supporting the use of viral load measurements to monitor therapy. Indeed, clinical drug trial endpoints routinely include the proportion of patients with a plasma viral load reduction of greater than 0.5 log(10), or greater than 1 log(10). Since a higher viral load reflects increased amounts of virus replication, it would seem desirable to reduce this replication as far as possible, so that the goal of therapy has become one of viral undetectability in plasma. However, virological suppression to undetectable levels is not an absolute determinant of outcome because recent observational cohort data suggest that any significant reduction of viral load is associated with clinical benefit. There are also technical problems when attempting to measure undetectability, with lower limits of detection of 400 or 50 RNA copies/ml of plasma being driven more by the performance of commercial assays than by any inherent cut-off value with proven prognostic significance. Furthermore, the obsession with undetectability has created the concept of the 'viral blip', or 'intermittent viraemia' commonly defined as a single viral load measurement of between 50 and 400 copies/ml, preceded and followed by consistent measurements of less than 50 copies/ml, in a patient receiving therapy. Such blips should be considered in the context of frequent transient changes in viral load which occur below the lower limit of detection by existing laboratory assays. In my view, there remains a misunderstanding about the importance ascribed to these relatively minor changes in lower detection limits, when considered against the background of virus within the body as a whole. I also consider other possible uses of HIV-1 quantification in clinical practice, such as identifying the inherent potency of antiviral regimens.     

Extremely and pandrug-resistant bacteria extra-deaths: myth or reality?

In 2009, the European Centre for Disease Prevention and Control (ECDC) estimated that multidrug-resistant (MDR) bacterial infections were responsible for 25,000 extra-deaths per year. In 2015, another report estimated that 12,500 extra-deaths were attributable to MDR bacteria every year in France. Recently, the United Nations claimed that resistance to antimicrobials was a global scourge, forecasting 10 million deaths in 2050. Surprisingly, our antibiotic resistance surveillance system in Marseille, France, did not allowed us to observe similar trends. We herein compared our data on extremely drug-resistant (XDR)/pandrug-resistant (PDR) patient extra-deaths to evaluations and predictions from these reports. First, we retrospectively collect and analyze antibiotic resistance data produced by our settings between November 2009 and March 2015 to look for 30-day deaths attributable to XDR/PDR strains belonging to 11 bacterial species/genus. In parallel, we performed a PubMed literature search to look for articles published prior to July 2016 and describing human deaths due to PDR strains. Overall, 35,723 patients were infected by at least one bacterial species/genus of interest and 85 by XDR/PDR strains. Of these patients, only one death was attributable to a XDR bacterial infection in a patient with strong comorbidities and two consecutive septic shocks. Our literature review shows that only four articles described human deaths due to PDR bacteria. All together, these data allowed us to conclude that there is a large discrepancy between the real count of deaths attributable to XDR/PDR bacteria and alarmist predictions.     

Type 1 1/2 diabetes: myth or reality?

The disease process in classical Type 1 diabetes patients (IDDM) is believed to be autoimmune. In contrast, the disease process in classical Type 2 diabetes patients (NIDDM) is not autoimmune and a decreased sensitivity to insulin action is the main abnormality. The clinical distinction of Type 1 diabetes versus Type 2 diabetes is recognized to be imperfect and has limitations. There is a group of individuals (Type 1 1/2 diabetes), who present like typical NIDDM, but have some of the immunological and clinical features of IDDM. We review the current medical literature on Type 1 1/2 diabetes with special reference to its clinical characteristics, natural history and pathophysiology. Since the distinction between these two forms of diabetes may have important therapeutic implications especially with regards to the benefits of insulin therapy in patients with Type 1 1/2 diabetes and because of the need for uniformity in its diagnosis we recommend that both clinical plus biochemical criteria (the presence of ICA and/or GAD Ab, HLA typing and tests to quantify beta cell function) be used to make a diagnosis. Comparative studies in the area of cytokine production, T cell reactivity and autoantibody clustering between classic Type 1 diabetes and Type 1 1/2 diabetes patients are needed as are studies with the animal model of Type 1 1/2 diabetes, Psammomys obesus.     

Mitochondrial cascade hypothesis of Alzheimer's disease: myth or reality?

Mitochondria are recognized to play a pivotal role in neuronal cell survival or death because they are regulators of both energy metabolism and apoptotic pathways. Morphologic, biochemical, and molecular genetic studies suggest that mitochondria might be a convergence point for neurodegeneration, including Alzheimer's disease (AD). The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress. However, the question, "Is mitochondrial dysfunction a necessary step in neurodegeneration?" is still unanswered. This review presents the ways in which malfunctioning mitochondria and oxidative stress might contribute to neuronal death in AD.     

Infection and vaccination in chronic fatigue syndrome: myth or reality?

Chronic fatigue syndrome (CFS) is characterized by severe disabling fatigue lasting for more than 6 months associated with physical and mental disturbances such as headache, arthralgia, myalgia, memory impairment, sore throat and tender lymph nodes. The exact pathogenesis is still unknown. Several models were proposed to explain its etiology including chronic infection, endocrine dysfunction, autonomic imbalance, depression, decreased immunity states and an aberrant reaction to infection. No convincing evidence was found to support any of the suggested pathogenic mechanisms. The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 dominant response. When the response fails to be switched-off, a chronic immune activation occurs and clinically expressed as the symptomatology of CFS. Vaccinations are used in order to stimulate the immune system to induce a persistent immunity against the favorable antigens. Several syndromes that contain chronic fatigue as one of their symptoms, such as "Gulf war syndrome" and macrophagic myofasciitis were related to vaccinations. Can vaccinations induce the aberrant immune response of CFS? Little is known about this issue. There are some reports on CFS occurring after vaccination, but few prospective and retrospective studies failed to find such an association. A working group of the Canadian Laboratory Center for Disease Control (LCDC) that was founded in order to examine the suspected association between CFS and vaccinations concluded that there is no evidence that relates CFS to vaccination. Further studies are requested to examine this issue since it is very conceivable that if infection can lead to CFS, vaccination may also lead to it in the same immune-mediated pathogenesis.     

Epstein-Barr virus positive anaplastic large cell lymphoma: myth or reality?

The World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissue, 2008 edition, states that anaplastic large cell lymphoma (ALCL) is "consistently negative for Epstein-Barr virus (EBV)". The statement made by the WHO has led to the widespread belief that EBV can have no pathogenic role in ALCL. Herein we report a case of an immunocompetent 35-year-old male who presented with hemophagocytic syndrome secondary to lymphoma for which diagnostic material consisted solely of a bone marrow biopsy. The biopsy demonstrated large anaplastic cells which were uniformly positive for surface CD3, CD30 (strong membranous and Golgi expression), CD45, TIA-1 and Granzyme B but negative for ALK-1. In-situ hybridization was strongly positive for EBER in the large neoplastic cells. The uniformity of CD30 expression and positivity for cytotoxic markers on the anaplastic tumor cells raised the diagnostic possibility of an EBV-associated ALCL, ALK-. Discussion of this case as well as a retrospective review of 64 cases of reported of EBV+ ALCL are presented.