Micronutrients against oxidative stress - time for clinical recommendations?

ABSTRACT: Antioxidant micronutrient supplementation may be beneficial for critically ill patients. Often, cocktails of antioxidant micronutrients are used. Consequently, meta-analyses of available randomized controlled trials of antioxidant micronutrient supplementation are of particular interest. Because the majority of randomized controlled trials included in these meta-analyses use a combination of several antioxidant micronutrients, conclusions are difficult to draw. The scientific step to take now is to gain more knowledge about antioxidant mechanisms by coupling plasma concentrations to effects and outcomes.     

Preventable mortality evaluation in the ICU

ABSTRACT: Mortality is the most widely measured outcome parameter. Improvement of this outcome parameter in critical care is nowadays expected not to come from new technologies or treatment, but from delivering the right care at the right moment in a safe way. The measurement of mortality as an outcome parameter confronts us with a problem in providing follow-up to the results. Especially when proven structure and process interventions are applied already, the cause of a suboptimal performance cannot be deduced easily. One possibility is to evaluate the causes of death and to judge preventability. In this article we explore the opportunities and difficulties of a tool to evaluate preventable mortality in the ICU.     

Benefits and risks of manual hyperinflation in intubated and mechanically ventilated intensive care unit-patients: a systematic review

ABSTRACT: INTRODUCTION: Manual hyperinflation (MH), a frequently applied maneuver in critically ill intubated and mechanically ventilated patients, is suggested to mimic a cough so that airway secretions are mobilized towards the larger airways where they can easily be removed. As such, MH could prevent plugging of the airways. METHOD: We performed a search in the databases of Medline, Embase and the Cochrane Library from January 1990 to April 2012. We systematically reviewed the literature on evidence for postulated benefits and risks of MH in critically ill intubated and mechanically ventilated patients. RESULTS: The search identified 50 articles, of which 19 were considered relevant. We included 13 interventional studies and 6 observational studies. The number of studies evaluating physiological effects of MH is limited. Trials differed too much to permit meta-analysis. It is uncertain whether MH was applied similarly in the retrieved studies. Finally, most studies are underpowered to show clinical benefit of MH. Use of MH is associated with short-term improvements in lung compliance, oxygenation and secretion clearance, without changes in outcomes. MH has been reported to be associated with short-term and probably clinically insignificant side-effects, including decreases in cardiac output, alterations of heart rates and increased central venous pressures. CONCLUSIONS: Studies have failed to show MH benefits critically ill intubated and mechanically ventilated patients. MH is infrequently associated with short-term side-effects.     

A PROBLEM OF GUILT: AN EXPLORATION OF FEELINGS OF GUILT AS AN OBSTACLE TO PSYCHIC CHANGE

There are two processes which are both called guilt; feelings of remorse and wishes to make reparation which are in the service of development, and persecutory guilt which is experienced as crippling and pervasive but which cannot be mediated by forgiveness or reparation and is sterile and anti‐development. The author argues that in adult life these feelings are often not on a continuum but are essentially different internal systems. The main drivers for the acquisition and maintenance of persecutory guilt are discussed. Persecutory guilt is a considerable obstacle to internal change and needs to be replaced by the feelings which lead towards reparation if there is to be progress; such progress can be disallowed because the patient feels too worthless to be reprieved. The paper uses examples from a psychotherapy group to illustrate the points.     

Protein tyrosine phosphatases in glioma biology

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas.     

Long-term duration of function of ovarian tissue transplants: case reports

These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian tissue transplanted, and two women underwent fresh ovarian tissue transplants. The function of ovarian cortical strips has continued for more than 7 years in these three women, with the birth of eight healthy babies following a single graft per patient. In addition to these three cases, transplantation (repeatedly in some cases) of cryopreserved ovarian tissue has restored reproductive function to all other women in the study centres’ programmes for some years. The sustained longevity of function of the transplanted tissue suggests that it may also be possible to postpone the normal time of menopause or to alleviate its symptoms.These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian tissue transplanted, and two women underwent fresh ovarian tissue transplants. Function of ovarian cortical strips has continued for more than 7 years in these three women, with the birth of eight healthy babies following a single graft per patient. In addition to these three cases, transplantation (repeatedly in some cases) of cryopreserved ovarian tissue has restored reproductive function to all other women in our programmes for some years. The sustained longevity of function of the transplanted tissue suggests that it may also be possible to postpone the normal time of menopause or to alleviate its symptoms.