Emerging studies of the urinary proteome: the end of the beginning?

PURPOSE OF REVIEW: Urinary proteomics is a rapidly growing field, holding the promise of discovery of biomarkers of various disease processes and elucidation of pathophysiologic mechanisms of disease states. This may be true not only for renal disease but for diseases of other organs and systemic disorders. RECENT FINDINGS: Recent advances in separation technologies and rapid, high-throughput, and accurate protein detection and identification now permit rigorous examination of complex biological fluids. This review sketches the progress achieved in recent years and the existing hurdles in describing a normal urinary proteome, its aberrations in pathological conditions, and the search for biomarkers of several renal and non-renal diseases. SUMMARY: The first wave of urinary proteomic studies has now arrived and their results are summarized. Future lines of investigation are delineated.     

Stem cell therapy for ischemic heart disease: beginning or end of the road?

Despite improvements in emergency treatment, myocardial infarction is often the beginning of a downward spiral leading to congestive heart failure. Other than heart transplantation, current therapeutic means aim at enabling the organism to survive with a heart that is working at a fraction of its original capacity. It is therefore no surprise that cardiac stem cell therapy has raised many hopes. However, neither the ideal source and type of stem cell nor the critical cell number and mode of application have been defined so far. Early reports on myocardial repair by adult bone marrow stem cells from rodent models promoted an unparalleled boost of clinical and experimental cell therapy studies. The phenomenon of stem/progenitor cell-induced angiogenesis in ischemic myocardium has ever since been reproduced by numerous groups in a variety of small and large animal models. Myogenesis, however, is an altogether different matter. Many of the initial clinical studies were fueled by the suggestion that early hematopoietic stem cells have a plasticity high enough to enable cross-lineage differentiation into cells of cardiomyocyte phenotype, but the initial enthusiasm has largely faded. The myogenic potential of stroma cell-derived mesenchymal stem cells is much better documented in animal models, but transfer to the clinical setting faces a variety of obstacles. In clinical pilot trials, we and others have demonstrated the feasibility and safety of administering progenitor cells derived from autologous bone marrow to the myocardium of patients with ischemic heart disease. Clinical efficacy data are still rare, but the few controlled trials that have been completed uniformly show a tendency towards better heart function in cell-treated patients. This review is an attempt to describe the scientific basis for cardiac cell therapy from the point of view of the clinician, focusing on problems that arise with beginning translation into the clinical setting.     

Cervical arthroplasty: the beginning, the middle, the end?

Cervical arthroplasty has developed as an alternative to spinal fusion for the treatment of cervical radiculopathy and myelopathy. The popularity of artificial discs has grown as the evidence of complications following arthrodesis has increased, making the theoretical advantages (motion preservation, altering the natural history of disease, prevention of adjacent segment disease) of disc replacement more attractive. However, as more discs are implanted and the length of follow-up increases, reported complications such as heterotopic ossification, device migration and spontaneous fusion of arthroplasty devices are growing. As a result, surgeons and patients face a challenge when deciding between motion-preserving or fusion surgery. Currently, there is inadequate evidence to promote extensive use of artificial discs for cervical spondylosis, despite promising short-term and intermediate clinical outcomes. However, there is also insufficient evidence to cease using them completely. The use of arthroplasty over fusion in the long term can only be justified if the incidence of adjacent segment disease decreases as a result. Despite the level of investment and research into arthroplasty outcomes, long-term follow-up has yet to be completed and has not convincingly demonstrated the effect of artificial discs on adjacent segment disease. Further long-term randomised trials are necessary to determine whether cervical arthroplasty is able to reduce the incidence of adjacent segment disease and, in doing so, replace arthrodesis as the gold standard treatment for cervical spondylosis.     

The role of prospective randomized clinical trials in pediatric surgery: state of the art?

PURPOSE: This study sought to determine the role of randomized controlled trials (RCT) in the evolution of pediatric surgical practice. METHODS: The authors used a computer-assisted literature search to identify all clinical trials related to pediatric surgery published in the English-language literature from 1966 through 1999. Each article was reviewed in detail for purpose, content, conduct, and quality of the trial. The authors assessed quality with a previously validated instrument (Chalmers Qualitative Assessment). RESULTS: The authors identified 134 RCTs related to pediatric surgery over the past 33 years. This accounts for 0.17% of 80,377 articles published in the field. The areas of surgery studied were analgesia 65 (49%), antibiotics 17 (13%), extracorporeal membrane oxygenation (ECMO) 9 (7%), gastrointestinal, burns, oncology, minimally invasive surgery, vascular access, congenital anomalies, and trauma (each <5%). Only 16 (12%) trials compared 2 surgical therapies, 9 (7%) compared a medical versus a surgical therapy, and 109 (81%) compared 2 medical therapies in surgical patients. Fourteen (10%) RCTs were funded by peer-reviewed agencies. Only 17 (13%) RCTs included a biostatistician as an author or a consultant. Trial design included calculation of sample size and statistical power in 21 (16%) RCTs. Method of randomization was reported in only 51 (38%). The test statistic and observed probability value was reported in 15 (11%). CONCLUSIONS: Clinical trials are used infrequently to answer questions related to pediatric surgery. When RCTs are utilized, they often suffer from poor trial design, inadequate statistical analysis, and incomplete reporting. Pediatric surgery could benefit from increased expertise, funding, and participation in clinical trials.     

Posterior decompression and stabilization for metastatic compression of the thoracic spinal cord: is this procedure still state of the art?

Study Design:Retrospective study utilizing the standard patient data documentation of a spinal cord injury (SCI) unit.Objective:To examine the efficacy and outcome of posterior decompression and stabilization for metastatic cord compression.Setting:Orthopedic university hospital with large SCI unit.Methods:The 34 consecutive patients who had presented with symptoms of spinal cord compression due to metastatic disease and progressive neurologic deficit were treated using a uniform surgical approach (posterior decompression and stabilization). After surgery, all treatment options available in a full-featured SCI unit were applied as necessary and suitable. Outcome was rated concerning neurologic function (American Spinal Injury Association, ASIA), functional status (Functional Independence Measure) and pain. The results were compared to the published results, focusing on publications describing results of anterior surgical approaches to the spine.Results:Evaluation of the results of the ASIA exams showed that progression of the neurologic deficit could be stopped in the majority of cases-however recovery of neurologic function was rare. The functional status could be improved markedly and good pain reduction was achieved.Conclusion:Immediate surgery can be recommended if the general condition of the patient warrants surgical intervention. Using accepted standards of documentation for SCI, a clear perspective of the results that can be expected is provided. Comparing the results of this study with the current literature there is no evidence that anterior approaches are superior.Spinal Cord (2008) 46, 595-602; doi:10.1038/sc.2008.11; published online 4 March 2008.     

Polythelia: still a marker of urinary tract anomalies in children?

OBJECTIVE: Supernumerary nipples (SNN), or polythelia, are the most common form of the accessory mammary tissue malformation. The frequency of this condition ranges from 0.2% to 5.6% depending on various factors. This condition is associated with several anomalies, although this association is often controversial. The aim of this study was to evaluate the association between SNN and kidney/urinary tract (K/UT) anomalies, where anomalies is taken to mean functional disorders, malformations and diseases. MATERIAL AND METHODS: A case-control study was performed. The study evaluated 166 children (case group) referred to the Pediatric Nephrology Unit of the Department of Pediatrics of the Catholic University of Rome and 182 children (control group) admitted to the Department of Pediatrics because of pathologies not involving the urinary tract. RESULTS: There were 11 children with SNN in the case group, and only two patients in the control group (6.62% vs 1.09%, p<0.05). CONCLUSION: The results show a high incidence of K/UT anomalies in children with SNN, and therefore K/UT should be investigated in this specific population.     

Impact of renin angiotensin system blockade on renal function in health and disease: an end or a beginning?

Substantial reduction of functioning nephrons from any origin is followed by a relentless progression to chronic renal failure. This progression continues long after the acute nephropathy and its initiating events have subsided. Glomerular hypertension and hyperfiltration are the major contributors to this progressive nephron loss. Studies on the adverse effects of hemodynamic changes and attempts to define the modalities that slow the rate of progression of renal disease have been among the dominant trends in modern nephrology. Numerous animal studies as well as recent clinical trials indicate that blockade of the renin angiotensin system effectively retards progression of nephropathy from diverse origins.     

The older surgical patient – to operate or not? A state of the art review

The increasing age and subsequent medical complexity of patients presenting for surgery grants the opportunity to examine the processes and delivery of peri-operative care. There is a need to redesign peri-operative pathways allowing room for shared decision making and personalised, evidence-based care. In times of financial constraint, this is no easy task. However, neglecting to transform services now may lead to challenges in the sustainability of the provision of peri-operative care in the long-term. Challenges in redesigning peri-operative care pathways include identification and optimisation of those at highest peri-operative risk to inform the difficult conversations surrounding the appropriateness of surgery. The moral burden of these conversations on patient and professionals alike is increasingly recognised and managing this issue requires innovative models of collaborative, multidisciplinary and interprofessional working. To operate or not can be a challenging question to answer with a number of different perspectives to consider; not least that of the patient.