Protecting podocytes: how good do we need to be?

Progression of many glomerular diseases has been firmly tied to a loss of podocytes, followed by a deterioration of glomerular architectural stability eventuating in segmental, and ultimately global, sclerosis. Recent studies have begun to clarify the nature of the autonomous (disease-independent) aspects of this process, as well as to explore mechanistically the 'unreasonable effectiveness' of angiotensin blockade in slowing glomerular disease progression. Quantitative monitoring of podocyte loss (e.g., to assess therapy) remains a challenge.     

Appendix mass: do we know how to treat it?

INTRODUCTION: The traditional management of appendiceal mass has been an initial conservative approach followed by interval appendicectomy. More recently, the necessity of interval appendicectomy has been questioned by a growing amount of evidence in the surgical literature. The aim of this study was to review the available scientific evidence and to determine how appendiceal masses are currently being managed in the Mid-Trent region by general surgeons. PATIENTS & METHODS: A literature search using Medline, Embase, Cinahl, HMIC and Biosis was carried out. A personal or telephonic survey of all consultants and specialist registrars working in general surgery in the Mid-Trent region (n = 67) was conducted recording their management protocol of 3 different clinical scenarios--a 14-year-old boy, a 29-year-old female and a 68-year-old male. Responses of the questionnaire were entered to a database in Microsoft Access 2000 and analysed. RESULTS: The results showed that there was difference of opinion on the management of appendix mass in either scenario. Appendectomy (interval or emergency) is still practised by 75% of general surgeons in the Mid-Trent region and less that 25% manage asymptomatic appendix mass without interval appendectomy. Additionally, specialist registrars appear more likely not to offer patients interval appendicectomy after successful conservative management (P < 0.05). CONCLUSIONS: At present, there is no agreed consensus on the management of appendiceal mass. There is a need to develop a protocol for the management of this common problem.     

Starting dialysis is dangerous: how do we balance the risk?

Recent studies of timing of dialysis initiation have challenged the recent trend to earlier initiation of therapy. The observed outcomes though are a consequence of the balance between the risks of advanced uremia versus the inherent dangers relating to dialysis therapy itself. Many of these risks are inherent in how dialysis treatment is currently carried out, and may indeed be amenable to mitigation, through refinement of clinical practice (and potentially modality choice). This article aims to lay out a discussion relating to patient outcomes being the composite result of this balance, pivoting on the vulnerability of a particular patient to these attendant risks.     

Diagnosis of deep vein thrombosis: how many tests do we need?

The requirement for a safe diagnostic strategy should be based on an overall post-test incidence of venous thromboembolism (VTE) of less than 1% during 3 month follow-up. Compression ultrasonography (CUS) has a negative predictive value (NPV) of 97 to 98% indicating a post-CUS incidence of deep vein thrombosis (DVT) of 2 to 3%. A post-CUS DVT incidence of 3% implicates that 90 to 120 DVTs per 1 million inhabitants will be overlooked each year indicating the need to improve the diagnostic work-up of DVT as much as possible. The qualitative D-dimer test (SimpliRed) has a sensitivity of 82 to 89% and a negative predictive value of 94 to 95% indicating a 5 to 6% post-test incidence of DVT, which is not sensitive enough for venous thrombosis exclusion. The post-test DVT incidence could be reduced from 3.2% to 0.6% in one study and from 11% to 2% in another study by the combination of a normal CUS and low clinical score and from 4.5% to 1.6% by the combination of low clinical score and a negative SimpliRed test in one study. The combination of a negative CUS and a negative SimpliRed test reduced the post-test incidence of DVT from 2.6% to < 1% or even < 1% in two management studies without the need of a repeated CUS on the basis of which anticoagulant therapy can safely be withheld. The rapid quantitative turbidimetric D-dimer assay (Tinaquant) has a sensitivity and a negative predictive value (NPV) of 97.7% with a 2.3% post-test incidence of DVT. The combination of a normal Tinaquant D-Dimer test result plus a low to moderate clinical score reduces the post-test incidence of DVT from 2.3 to 0.6% without the need of CUS testing in 29% of patients with suspected DVT. The rapid ELISA VIDAS D-dimer assay has a sensitivity and NPV of 98.6 and 99.5% in two management studies for the exclusion of DVT irrespective of clinical score. The combination of a normal ELISA VIDAS D-Dimer test with clinical score assessment will reduce the post-test DVT incidence of less than 0.5% and the need for CUS testing by 40 to 50%. It is concluded that the sequential use of a rapid quantitative D-dimer test, clinical score and CUS appears to be safe and the most cost-effective diagnostic work-up of DVT.     

Clinical pig liver xenotransplantation: how far do we have to go?

As pigs are currently the preferred species for organ xenotransplantation, initial experience in liver xenotransplantation with wild-type (WT) pigs, advances in the development of genetically modified pigs, and recent studies using livers from them are reviewed. The xenotransplantation of livers from pigs transgenic for the human complement regulatory protein (CRP) CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- additionally transgenic for the CRP CD46 (GTKO/CD46 pigs) is associated with the survival of approximately 1 week. Satisfactory hepatic function has been documented, lending support to the concept that the pig liver might provide a bridge to allotransplantation. However, although significant features of rejection have not been documented, the development of an immediate thrombocytopenia after graft reperfusion is problematic and leads to spontaneous hemorrhage within the body cavities, native organs, and graft. Current studies are being directed to understand the factors causing the activation, aggregation, or phagocytosis of platelets, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes, and Kupffer cells. If this problem can be resolved, a clinical trial of pig liver xenotransplantation as a bridge to allotransplantation may be both feasible and justified.     

Aortic root remodeling operation: how do we tailor a tube graft?

BACKGROUND: In aortic root remodeling operation, it is difficult to perform graft sizing and tailor a graft appropriately. Thus the aim of this study was to create guidelines for sizing and tailoring that would help to standardize the operation. METHODS: We studied the anatomy of the aortic root and assessed the reliability of three equations reported to assist in graft sizing with aortic root casts obtained from 127 cadavers. RESULTS: Yacoub's equation and ours accurately predicted the diameter at the sinotubular junction. Three cusps of the aortic valve were not equal in size. Sinus height of the aortic root was unpredictable. CONCLUSIONS: Based on these results, we recommend that aortic root remodeling operation should be performed as follows: (1) graft sizing should be performed using Yacoub's way or our way; (2) the tube graft should be cut into three parts in proportion to the size of each cusp; and (3) the position of the commissures in the tube graft should be secured with sutures first, and the depth of the sinuses should be determined later.     

Trends in patient and technique survival in peritoneal dialysis and strategies: how are we doing and how can we do better?

The best data on long term trends in patient and technique survival on dialysis come from North America. Mortality rates on both peritoneal (PD) and hemodialysis (HD) have fallen over the past one to two decades in both the US and Canada with the decline in the US being relatively greater in older and diabetic patients. There is some suggestion that this improvement may be proportionately greater in PD, relative to HD, patients in both the US and Canada. Overall, mortality rates on PD are similar to, or better than, those on HD in the early years of treatment, except in older US diabetic patients. In later years, patients on HD do relatively better than those on PD in the US but not in Canada. The biggest cause of mortality on dialysis is cardiovascular disease and the risk factors for this in the dialysis population generally, and particularly on PD, are reviewed, including newly appreciated ones such as hyperhomocysteinemia, high lipoprotein (a) levels and inflammation/malnutrition. Possible preventative and therapeutic strategies are also considered. Technique failure (TF) rates are high in PD but Canadian data suggest they have fallen over the past 20 years, primarily due to a reduction in cases due to peritonitis. TF rates due to inadequate dialysis have increased and an interpretation of this as well as an approach to reducing it are suggested.     

Obesity,metabolic and bariatric surgery,and cancer prevention: what do we need to learn and how do we get there?

Obesity and associated metabolic dysfunction are on the rise in the United States and around the world. Metabolic dysfunction often leads to chronic disease, including cancer. Recent evidence suggests that weight loss among individuals with obesity may decrease cancer risk. Metabolic and bariatric surgery (MBS) leads to greater maximum and sustained weight loss than nonsurgical dietary strategies and demonstrates the most convincing evidence that weight loss lowers cancer risk. Caloric restriction diets combined with GLP-1 receptor agonists demonstrate weight loss intermediate between MBS and other nonsurgical diet strategies so long as individuals consistently take the medication. Weight regain after initial loss is a major problem with all weight loss strategies. To better prevent cancer in individuals with obesity, we need to individualize weight loss strategies, determining what strategy works for a given individual and how to implement it. We need to learn (1) what an individual’s impediments to initial and sustained weight loss are; (2) what the optimal weight loss strategy, be it diet modification, diet modification + medication, or MBS followed by diet modification, is; (3) how exercise(s) should be incorporated into weight loss strategies; (4) where medications fit into the treatment strategy of individuals with obesity; and (5) what the mechanisms driving the influence of MBS on cancer risk are. We also need to (6) explore expanding the eligibility of MBS to individuals with a body mass index <35 kg/m². Answers to these questions require a better understanding of how MBS impacts cancer risk, including in which groups (women versus men, which racial and ethnic groups, which cancers, which MBS procedure) MBS works best to reduce risk. The National Cancer Institute, through new funding opportunities, hopes to advance our understanding of how obesity drives cancer risk and how individuals with obesity can prevent cancer development and, among those with cancer, prevent disease recurrence.