Hydrogel wound dressings: where do we stand in 2003?

Among the many categories of advanced wound dressing products available today, hydrogels are popular because they are effective, comfortable, easy to use, and cost effective. With proper use, these agents provide control of wound surface hydration, sometimes absorbing excess exudate and often providing moisture. This review describes the chemistry of hydrogels, the physiology of their interaction with the wound surface, and their role in patient care. Hydrogels have been proven effective in facilitating repair of pressure, diabetic, vascular, burn, and other wounds, and they have supplanted saline-moistened gauze for many applications. Clinical evidence suggests that no particular hydrogel is significantly more efficacious than any other, implying that other factors such as cost and ease of use may guide clinician choice of product within this class of wound dressings.     

Immunomodulation of asthma: where do we stand?

Conclusions Better treatment options should reduce symptoms, enhance quality of life, improve the course of disease, reverse pathogenetic and physiologic changes, have few side effects, and be cost effective. Because of the heterogeneous nature of asthma, specific agents will probably work best for selected types of patients. However, regardless of the obstacles, ongoing research into the wide range of therapeutic possibilities will provide new insights into the pathogenesis of allergic respiratory diseases.     

Islet transplantation: where do we stand now?

After many years of limited success in islet transplantation, researchers developing this procedure have made great strides, and several centers have now reported that islet transplantation can result in long‐term insulin independence for patients with type 1 diabetes mellitus. The improved quality of life achieved in some islet allograft recipients suggests that this important line of investigation should proceed. Yet, several factors limit the technique and these hurdles must be overcome before it can be considered a practical treatment for the millions of individuals with diabetes, be it type 1 or type 2. Most obvious is the gross disparity between the number of islets available for clinical transplantation and the number of patients with diabetes who might benefit. Other important limitations, too often lost in the discussion, include complications associated with the technique itself, the toxicity of currently available immunosuppressive drugs, and the imperfect glycemia control achieved in most patients. In fact, our ongoing analysis as to whether transplantation‐based therapy improves survival for patients with type 1 diabetes suggests that, for many at least, the opposite may be true. Two variables, as yet undefined, also need to be considered: (1) can the procedure, when done well, prevent or reverse diabetes‐associated complications and (2) what are the long‐term consequences of intrahepatic islets? Published in 2003 by John Wiley & Sons, Ltd.     

Atrial fibrillation in chronic non-cardiac disease: where do we stand?

Atrial fibrillation is the most common arrhythmia, and is associated with increased risk of stroke and death. Most of present knowledge is derived from studies in patients with cardiac disease whilst limited information is available for patients with several chronic non-cardiac conditions like cancer, chronic obstructive pulmonary disease and chronic kidney disease. Although millions of patients are affected and are at risk of adverse prognosis due to co-existent atrial fibrillation, we are left with very limited guidance for management of atrial fibrillation itself and prevention of complications in those patients. In this paper, we review data on incidence, prognostic importance and treatment modalities of atrial fibrillation in patients with cancer, chronic obstructive pulmonary disease, and chronic kidney disease.     

Overall mortality in diabetes mellitus: where do we stand today?

Life expectancy for a patient with type 2 diabetes remains substantially shorter than an equivalent individual without diabetes, largely because of a greater risk of cardiovascular disease. Diabetes is also associated with an increased incidence of many types of cancer, suggesting that malignancy may also contribute to higher rates of mortality. Hyperglycemia is one of the key risk factors for diabetes-associated macro- and microvascular disease, and as such, intensive glycemic control is associated with improved outcomes for patients, including a reduction in this risk of death from any cause, when initiated early in the disease course. Recent trials in patients with more advanced disease have failed to demonstrate a mortality benefit with intensive glycemic control, although this may reflect their short observation period. Intensive multifactorial therapy, including lifestyle intervention and control of hyperglycemia, hypertension, lipids, thrombosis, and microalbuminuria, is likely to be the best strategy against diabetes-associated macrovascular mortality. However, analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial indicates that there may be a subpopulation of patients who are unable to achieve glycemic targets with intensive therapy and that aggressive intensification of treatment in this group may increase mortality risk. It remains to be determined whether the relationship between diabetes and malignancy is causal or whether they share common risk factors. Current recommendations for a healthy lifestyle based on good diet, physical exercise, and weight management in order to control diabetes-related complications are likely to apply in reducing the risk of many forms of cancer and should be advocated for all patients.     

Viscoelastic tests in liver disease: where do we stand now?

Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.     

Prognostic indices in chronic lymphocytic leukaemia: where do we stand how do we proceed?

The remarkable clinical heterogeneity in chronic lymphocytic leukaemia (CLL) has highlighted the need for prognostic and predictive algorithms that can be employed in clinical practice to assist patient management and therapy decisions. Over the last 20 years, this research field has been rewarding and many novel prognostic factors have been identified, especially at the molecular genetic level. Whilst detection of recurrent cytogenetic aberrations and determination of the immunoglobulin heavy variable gene somatic hypermutation status have an established role in outcome prediction, next‐generation sequencing has recently revealed novel mutated genes with clinical relevance (e.g. NOTCH1, SF3B1 and BIRC3). Efforts have been made to combine variables into prognostic indices; however, none has been universally adopted. Although a unifying model for all groups of patients and in all situations is appealing, this may prove difficult to attain. Alternatively, focused efforts on patient subgroups in the same clinical context and at certain clinically relevant ‘decision points’, that is at diagnosis and at initiation of first‐line or subsequent treatments, may provide a more accurate approach. In this review, we discuss the advantages and disadvantages as well as the clinical applicability of three recently proposed prognostic models, the MD Anderson nomogram, the integrated cytogenetic and mutational model and the CLL‐international prognostic index. We also consider future directions taking into account novel aspects of the disease, such as the tumour microenvironment and the dynamics of (sub)clonal evolution. These aspects are particularly relevant in view of the increasing number of new targeted therapies that have recently emerged.     

Pathophysiology of thrombotic APS: where do we stand?

The antiphospholipid syndrome (APS) is diagnosed when patients with thrombotic complications or foetal losses have elevated levels of antiphospholipid antibodies in their plasmas. The term APS is confusing, because the pathogenic auto-antibodies are not directed against phospholipids but towards a plasma protein, β(2)-glycoprotein I. For many years the reason why auto-antibodies against β(2)-glycoprotein I were pro-thrombotic was unclear, because man and mice deficient in β(2)-glycoprotein I do not express a clear phenotype. Animal models in which passive transfer of patient antibodies into mice resulted in an increased thrombotic response have provided novel insights in the importance of this protein in the pathology of APS.     

Living liver donor mortality: where do we stand?

OBJECTIVE: To explore the use of medical journals, lay media, registries, and transplant center websites to discuss living liver donor mortality. METHODS: To study the incidence of and circumstances relating to living liver donor death, medical journals and lay print media were searched to create a case summary of worldwide living liver donor deaths. The United Network for Organ Sharing (UNOS) and European Liver Transplant Registry (ELTR) were also queried for information regarding living liver donor deaths. Lastly, the Websites of United States transplant centers offering living liver donation were reviewed to identify whether or not death was stated as a donor risk. RESULTS: Literature review revealed 14 living liver donor deaths. One of the five deaths occurring in the United States had been reported to UNOS. One of the 14 cases had been reported only in lay literature, and another only in the ELTR. In at least five cases, surgical complications were not the cause of donor death. Among the 62 transplant center Websites, only 12 centers (19%) specifically mentioned death as a donation risk. Eight of these 12 centers (67%) mentioned death in terms of percent mortality risk; however, risk rates spanned a 10-fold range from 0.2% to 2%. CONCLUSION: Potential living liver donors are best served by accurate information about donor mortality. Access to such data is difficult and these individuals would benefit by a worldwide living liver donor registry and peer-reviewed publication of donor mortality.     

Stem cell therapy in heart failure: where do we stand and where are we heading?

Heart failure is a multifactorial and complex debilitating disease facing limitations in available pharmacological therapeutics. To cure such a disease, cardiac regeneration has been envisioned using stem cells. A few clinical trials using bone marrow-derived stem cells have been carried out without conclusive results. Stem cells of other origins should therefore be considered for future trials. In this article, the advantages and disadvantages of the most promising stem cells to be used in cell therapy are reviewed. The remaining challenges of cell therapy of heart failure are also presented.