The role of mycophenolate in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis.

Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy.

INTRODUCTION: Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up. AIM: The aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN. PATIENTS-METHODS: Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens. RESULTS: Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p = 0.04, respectively. CONCLUSIONS: Long term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients.

AIMS: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. METHODS AND RESULTS: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15-85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112-376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. CONCLUSIONS: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

Preoperative Anxiety in Greek Children and Their Parents When Presenting for Routine Surgery.

BACKGROUND: A surgical operation in pediatric patients is a rather stressful experience for both children and their parents. The aim of this study was to assess the effect of specific demographic characteristics in parent's and children's preoperative anxiety. METHODS: The sample was composed of 128 Greek-speaking children (1-14 years of age) who had to undergo minor surgery in a University General Hospital. Before surgical operation, the Spielberger State-Trait Anxiety Inventory (STAI) questionnaire and a questionnaire for the social-demographic characteristics were completed by the parents. Children's preoperative anxiety was evaluated using the Modified Yale Preoperative Anxiety Scale (m-YPAS). RESULTS: The independent predictors of increased anxiety levels in parents are child's age (p=0.024) and gender (girls: p=0.008), living in rural areas (parents: p < 0.001; children: p=0.009), being a mother (p=0.046), high or low education level (p=0.031), a no premedicated child (p=0.007), and high baseline parental anxiety (p=0.003). Previous hospitalization (p=0.019), high situational parental anxiety (p < 0.001), no premedication (p=0.014), and being the only child in the family (p=0.045) are found to be the main determinants of preoperative anxiety control in children. CONCLUSIONS: This study identifies possible risk factors of preoperative anxiety in parents and their children, which are high parental anxiety, child's age, no premedication, being the only child in the family, living in rural areas, education level, and previous hospitalization.

The family of 14-3-3 proteins and specifically 14-3-3σ are up-regulated during the development of renal pathologies.

Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14-3-3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression.

IgA nephropathy in Greece: data from the registry of the Hellenic Society of Nephrology.

BACKGROUND: Natural history, predisposing factors to an unfavourable outcome and the effect of various therapeutic regimens were evaluated in a cohort of 457 patients with immunoglobulin A nephropathy (IgAN) and follow-up of at least 12 months. METHODS: Patients with normal renal function and proteinuria <1 g/24 h as well as those with serum creatinine (SCr) >2.5 mg/dL and/or severe glomerulosclerosis received no treatment. Patients with normal or impaired renal function and proteinuria >1 g/24 h for >6 months received daily oral prednisolone or a 3-day course of intravenous (IV) methylprednisolone followed by oral prednisolone per os every other day or a combination of prednisolone and azathioprine. The clinical outcome was estimated using the primary endpoints of end-stage renal disease and/or doubling of baseline SCr. RESULTS: The overall 10-year renal survival was 90.8%, while end-stage renal disease and doubling of baseline SCr developed in 9.2% and 14.7% of patients, respectively. Risk factors related to the primary endpoints were elevated baseline SCr, arterial hypertension, persistent proteinuria >0.5 g/24 h and severity of tubulointerstial fibrosis. There was no difference in the clinical outcome of patients treated by the two regimens of corticosteroids; nevertheless, remission of proteinuria was more frequent in patients who received IV methylprednisolone (P = 0.000). The combination of prednisolone with azathioprine was not superior to IV methylprednisolone followed by oral prednisolone. Side effects related to immunossuppressive drugs were observed in 12.8% of patients. CONCLUSION: The clinical outcome of patients with IgAN was related to the severity of clinical and histological involvement. The addition of azathioprine to a corticosteroid-based regimen for IgAN does not improve renal outcome.

Vitamin D3 ameliorates podocyte injury through the nephrin signalling pathway.

Renal podocytes form the main filtration barrier possessing unique phenotype maintained by proteins including podocalyxin and nephrin, which are modulated in pathological conditions. In diabetic nephropathy (DN), podocytes become structurally and functionally compromised. Nephrin, a structural backbone protein of the slit diaphragm, acts as regulator of podocyte intracellular signalling with renoprotective role. Vitamin D3 through its receptor, VDR, provides renal protection in DN but limited data exist about its effect on podocytes. In this study, we used isolated rat glomeruli to assess podocalyxin and nephrin expression after treatment with the 1,25-dihydroxyvitamin D3 analogue paricalcitol in the presence of normal and diabetic glucose levels. The role of 1,25-dihydroxyvitamin D3 (calcitriol) and its analogue, paricalcitol, on podocyte morphology and survival was also investigated in the streptozotocin (STZ)-diabetic animal model. In our ex vivo model, glomeruli exhibited high glucose-mediated down-regulation of podocalyxin, and nephrin, while paricalcitol reversed the high glucose-induced decrease of nephrin and podocalyxin expression. Paricalcitol treatment enhanced VDR expression and promoted VDR and RXR co-localization in the nucleus. Our data also indicated that hyperglycaemia impaired survival of cultured glomeruli and suggested that the implemented nephrin down-regulation was reversed by paricalcitol treatment, initiating Akt signal transduction which may be involved in glomerular survival. Our findings were further verified in vivo, as in the STZ-diabetic animal model, calcitriol and paricalcitol treatment resulted in significant amelioration of hyperglycaemia and restoration of nephrin signalling, suggesting that calcitriol and paricalcitol may provide molecular bases for protection against loss of the permselective renal barrier in DN.

Ethanol combined with heparin as a locking solution for the prevention of catheter related blood stream infections in hemodialysis patients: A prospective randomized study.

INTRODUCTION: Ethanol lock solution has been mainly administered in paediatric and home parenteral nutrition patients in order to prevent catheter related blood stream infections (CRBSI). Its utility in hemodialysis (HD) patients with non-tunneled-uncuffed catheter (NTC) has been poorly explored. METHODS: We conducted a prospective randomized study in chronic HD patients requiring a newly inserted NTC-while awaiting for the maturation of an already established arteriovenous fistula (AVF) or arteriovenous graft (AVG) or tunneled-cuffed catheter insertion. Patients were randomized in two groups: Group A, where the lock solution was ethanol 70% + unfractionated heparin 2000 U/mL and group B, that received only unfractionated heparin 2000 U/mL. Primary end point was CRBSIs whereas exit site infections, thrombotic and bleeding episodes were the secondary end points. FINDINGS: One hundred three HD patients were enrolled in the study (group A, n = 52; group B, n = 51). The median number of catheter days was 32 for group A (range: 23-39) and 34 (range: 27-40) for group B with no statistically significant difference between the two groups. Group A (ethanol + heparin) demonstrated 4/52 episodes (7.69%) of CRBSI whereas Group B (heparin) 11/51 episodes (21.57%) (P = 0.04). CRBSI rates per 1000 catheter days were 2.53/1000 catheter days for group A and 6.7/1000 catheter days for group B (P = 0.04). Mean cumulative infection-free catheter survival in the ethanol group did not differ significantly compared to the heparin group (log-rank test = 2.99, P = 0.08). Thrombotic episodes did not differ between the two groups. DISCUSSION: Locking of NTCs in HD patients with ethanol 70% + unfractionated heparin reduces CRBSI rates without increasing the thrombotic episodes.

Cost calculations during "dire straits": a cost-of-illness analysis of regular hemodialysis for end-stage renal disease in Greece.

PURPOSE: More than 3 million people worldwide suffer from end-stage renal disease (ESRD). Even though regular hemodialysis is considered very costly, it is still the most commonly used method of treatment in Greece. The aim of this study is to provide a current estimate of the annual patient cost for ESRD-related regular hemodialysis, especially during a period of economic instability for Greece. METHODS: Data was collected from 113 anonymous patient files from 3 dialysis units. The cost analysis includes the following parameters: hospitalization, disposable supplies, medication, meals, contaminants, human resources and equipment depreciation/utilization. RESULTS: The cost of a regular hemodialysis session was estimated at €177.12. Human resources account for 43.53% of the hemodialysis cost, while expendable supplies and medication account for 24.79% and 21.16%, respectively. The total annual cost of ESRD per patient was calculated at €34,012.31, which breaks down into €27,630.72 (81.24%) for hemodialysis, €4,800.64 (14.11%) for hospitalization, €1,454.84 (4.28%) for laboratory tests and €126.11 (0.37%) for microsurgery. CONCLUSIONS: ESRD entails a significant economic burden for the Greek health care system. In a current context of ongoing austerity measures, which severely pressure the health care budget, further research should be performed in order to identify possible ways to reduce costs and improve management of the disease.

Lack of significant intraoperative coagulopathy in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) indicates that epidural anaesthesia is a safe option.

PURPOSE: The purpose of this study is to evaluate the fluctuations of coagulation parameters during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) and confirm beyond doubt that epidural anaesthesia is safe with this type of operations. MATERIALS AND METHODS: This is a prospective clinical study of consecutive patients who had cytoreductive surgery and HIPEC. An epidural catheter was inserted into all patients. Peripheral venous blood samples in specific time points of the procedure were tested for complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, D-dimer, and expression of the GpIIb/IIIa platelet receptor. RESULTS: A total of 51 consecutive patients were included in this study. The initial mean (SD) platelet count decreased significantly to a mean of 250.6 (105.4) 10(9)/L (p < 0.001). Fibrinogen levels decreased to 295.9 (127.4) mg/dL (p = 0.009). D-dimer levels increased to 5.3 (3.1) mg/dL (p < 0.001). APTT increased from 30.8 (5.8) s to 35.1 (4.6). The mean INR increased significantly to 1.5 (0.5) (p < 0.001). The total number of GpIIb/IIIa platelet receptors showed no significant variation throughout the measurements and was 72603.2 before HIPEC, 80772.4 during, and 77432.1 after. All the parameters examined, despite significant fluctuations remained in levels that would permit perioperative epidural analgesia. No related complications were recorded. CONCLUSION: Our results support the belief that epidural analgesia is a safe option in cytoreductive surgery and HIPEC despite certain intraoperative fluctuations in coagulation parameters. It is of major importance to regulate any abnormalities observed during surgery. There are no available data regarding the occurrence of coagulopathy in the post-operative period.

Hemodynamic Monitoring During Heated Intraoperative Intraperitoneal Chemotherapy Using the FloTrac/Vigileo System.

Cytoreductive surgery with HIPEC has provided a chance for long-term survival in selected patients. However, perioperative management remains a challenge for the anesthesiology team. The aim of this study was to evaluate the changes in hemodynamic parameters during hyperthermic intraperitoneal chemotherapy (HIPEC) using the FloTrac/Vigileo system. Forty-one consecutive patients undergoing cytoreductive surgery and HIPEC were enrolled. Heart rate (HR), esophageal temperature, and cardiac output (CO) steadily increased until the end of HIPEC. In the first half of HIPEC, systolic blood pressure (SBP) and central venous pressure (CVP) increased whereas systemic vascular resistance (SVR) decreased; SVR stabilized in the second half. Diastolic blood pressure (DBP), mean arterial pressure (MAP), and stroke volume (SV) showed no significant variation. Male gender was related to increased CVP, CO, and SV, and decreased SVR; age >55 years was related to increased SBP, and peritoneal cancer index (PCI) was correlated with HR, DBP, and SV. PCI >14 was associated with increased HR and decreased DBP and MAP. American Society of Anesthesiologists score >1 was related to decreased CO and SV. Patients undergoing HIPEC develop a hyperdynamic circulatory state because of the increased temperature, characterized by a steady decrease in SVR and continuous increase in HR and CO. FloTrac/Vigileo system may provide an easy-to-handle, noninvasive monitoring tool.

Multicenter epidemiological study to assess the population of CKD patients in Greece: results from the PRESTAR study.

BACKGROUND: Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD. METHODS: Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement. RESULTS: A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR<40 ml/min/1.73 m2) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers. CONCLUSIONS: In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage.

Conservative care in Europe--nephrologists' experience with the decision not to start renal replacement therapy.

BACKGROUND: For some patients with end-stage renal disease (ESRD), providing conservative care until death may be an acceptable alternative for renal replacement therapy (RRT). We aimed to estimate the occurrence of conservative care in Europe and evaluated opinions about which factors nephrologists consider important in their decision not to offer RRT. METHODS: With a web-based survey sent to nephrologists in 11 European countries, we inquired how often RRT was not started in 2009 and how specific factors would influence the nephrologists' decision to provide conservative care. We compared subgroups by nephrologist and facility characteristics using chi-square tests and Mann-Whitney U tests. RESULTS: We received 433 responses. Nephrologists decided to offer conservative care in 10% of their patients [interquartile range (IQR) 5-20%]. An additional 5% (IQR 2-10%) of the patients chose conservative care as they refused when nephrologists intended to start RRT. Patient preference (93%), severe clinical conditions (93%), vascular dementia (84%) and low physical functional status (75%) were considered extremely or quite important in the nephrologists' decision to provide conservative care. Nephrologists from countries with a low incidence of RRT, not-for-profit centres and public centres more often scored these factors as extremely or quite important than their counterparts from high-incidence countries, for-profit centres and private centres. CONCLUSIONS: Nephrologists estimated conservative care was provided to up to 15% of their patients in 2009. The presence of severe clinical conditions, vascular dementia and a low physical functional status are important factors in the decision-making not to start RRT. Patient preference was considered as a very important factor, confirming the importance of extensive patient education and shared decision-making.

Surgical or endovascular therapy of abdominal penetrating aortic ulcers and their natural history: a systematic review.

Little is known regarding the outcomes of endovascular and surgical treatment of penetrating ulcers in the abdominal aorta. The potential benefit of conservative management of asymptomatic disease is also debatable. A systematic review of the literature was undertaken to investigate these issues.

Effect of interscalene brachial plexus block on heart rate variability.

BACKGROUND: Interscalene brachial plexus block (ISB) may be followed by cardiovascular instability. Until date, there is no clear picture available about the underlying mechanisms of ISB. In this study, we aimed to determine the changes in heart rate variability (HRV) parameters after ISB and the differences between right- and left-sided ISBs. METHODS: We prospectively studied 24 patients operated for shoulder surgery in sitting position and divided them into two respective groups: R (right-sided block = 14 pts) and L (left-sided block = 10 pts). HRV data were taken before and 30 min after the block. Ropivacaine without ephedrine was used for the ISB through an insulated block needle connected to a nerve stimulator. Statistical analysis implemented chi-square, Student's and t-paired tests. Skewed distributions were analyzed after logarithmic transformation. RESULTS: All the studied patients had successful blocks. Horner's syndrome signs were observed in 33.3% of the patients (R = 5/14, L = 3/10; [P = 0.769]). There were no significant differences in pre-block HRV between the groups. The application of ISB had differential effect on HRV variables: R-blocks increased QRS and QTc durations and InPNN50, while a statistical decrease was seen in InLF. L-blocks did not show any significant changes. These changes indicate a reduced sympathetic and an increased parasympathetic influence on the heart's autonomic flow after R-block. CONCLUSIONS: Based on the obtained results we conclude that ISB, possibly through extension of block to the ipsilateral stellate ganglion, alters the autonomic outflow to the central circulatory system in a way depending on the block's side.

Paricalcitol effects on activities and metabolism of platelet activating factor and on inflammatory cytokines in hemodialysis patients.

PURPOSE: Paricalcitol improves the inflammatory status of hemodialysis patients. PAF is a strong inflammatory mediator which is produced during hemodialysis. We studied the effects of paricalcitol on PAF and other inflammatory mediators implicated in chronic kidney disease (CKD). METHODS: We examined the in vitro effects of paricalcitol on PAF/thrombin-induced aggregation as well as on the activities of PAF-basic metabolic enzymes, lyso-PAF acetyltransferase (Lyso-PAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol cholinephospho-transferase (PAF-CPT) and PAF-acetylhydrolase (PAF-AH) in blood cells from healthy volunteers. In addition, the in vivo effects of paricalcitol on the above these enzymes were examined in plasma and blood cells of hemodialysis patients who had not received any type of vitamin D treatment during the last three months before and after receiving paricalcitol for a month. Finally, IL-12p70, IL-1ß, IL-6, IL-8 and TNF-α were measured. RESULTS: Paricalcitol inhibited in vitro PAF/thrombin-induced platelet aggregation and the inhibitory effect was comparable with that of PAF/thrombin antagonists. In addition, paricalcitol inhibited in vitro PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while much higher concentrations of paricalcitol were needed to inhibit Lyso-PAF-AT activity. Similarly, in hemodialysis patients, paricalcitol treatment reduced PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while it could not influence Lyso-PAF-AT activity. On the other hand, paricalcitol therapy reduced IL-8, IL-1ß, and TNF-α. CONCLUSIONS: These results further support the beneficial effects of vitamin D treatment in hemodialysis patients, since it strongly affects PAF/thrombin activities, PAF-metabolism, and IL-8, IL-1ß and TNF-α circulating levels.

Epidural anesthesia followed by epidural analgesia produces less inflammatory response than spinal anesthesia followed by intravenous morphine analgesia in patients with total knee arthroplasty.

BACKGROUND: Anesthesia and inflammatory response have been studied in major abdominal and thoracic surgical procedures, but not in major orthopaedic reconstructive procedures such as total knee arthroplasty. Most studies have compared general anesthesia with epidural anesthesia, but none has compared epidural with spinal. MATERIAL/METHODS: In a prospective randomized study, 2 groups of patients scheduled for total knee arthroplasty for osteoarthritis were evaluated regarding the inflammatory response to 2 types of regional anesthesia. In 30 patients (Group A) with spinal anesthesia followed by intravenous morphine analgesia, and in 26 patients (Group B) with epidural anesthesia followed by epidural analgesia, the inflammatory response was assessed through the calculation of leucocyte concentration (WBC), C-reactive protein (CRP), monocyte chemotactic protein 1 (MCP-1), interleukins (IL-1, IL-6, IL-10, IL-18), TNF-a, and leucocyte activation molecules CD11b and CD62l, in 3 blood samples (immediately before induction to anesthesia, immediately after closure of the operative wound, and at 24 hours post-operatively). RESULTS: The MCP-1 values showed a statistically significant increase (p<0.02) in the group of patients with spinal anesthesia. Of the leucocyte activation molecules, a high statistically significant increase was noticed in the expression of CD11b on monocytes in the sample taken 24 hours post-operatively in the patients of group A. Similarly, CD62l expression on neutrophils showed a high statistically significant reduction in the sample taken 24 hours post-operatively in the group of patients with spinal anesthesia compared to the group of patients with epidural anesthesia. CONCLUSIONS: Our results show that epidural anesthesia followed by epidural analgesia produced less inflammatory response compared with spinal anesthesia followed by intravenous morphine analgesia in patients operated on with total knee arthroplasty, and that the most sensitive markers of those investigated were the CD11b and CD62l leucocyte activation molecules.

Hybrid endografts combinations for the treatment of endoleak in endovascular abdominal aortic aneurysm repair.

Hybrid endografting in endovascular abdominal aortic aneurysm repair (EVAR) is defined as the process of placing a series of two or more different types of covered stents, usually to treat a complex abdominal aortic aneurysm (AAA) or a primary or secondary endoleak. We describe the treatment of a type III, a type Ib, and a type Ia endoleak in three patients respectively, using hybrid solutions, assembling components from different manufacturers. An update of the current clinical and experimental evidence on the application of anatomically compatible, hybrid endograft systems in conventional EVAR is also provided.

Factors influencing the decision to start renal replacement therapy: results of a survey among European nephrologists.

BACKGROUND: Little is known about the criteria nephrologists use in the decision of when to start renal replacement therapy (RRT) in early referred adult patients. We evaluated opinions of European nephrologists on the decision for when to start RRT. STUDY DESIGN: European web-based survey. PREDICTORS: Patient presentations described as uncomplicated patients, patients with unfavorable clinical and unfavorable social conditions, or patients with specific clinical, social, and logistical factors. SETTING & PARTICIPANTS: Nephrologists from 11 European countries. OUTCOMES & MEASUREMENTS: We studied opinions of European nephrologists about the influence of clinical, social, and logistical factors on decision making regarding when to start RRT, reflecting practices in place in 2009. Questions included target levels of kidney function at the start of RRT and factors accelerating or postponing RRT initiation. Using linear regression, we studied determinants of target estimated glomerular filtration rate (eGFR) at the start of RRT. RESULTS: We received 433 completed surveys. The median target eGFR selected to start RRT in uncomplicated patients was 10.0 (25th-75th percentile, 8.0-10.0) mL/min/1.73 m(2). Level of excretory kidney function was considered the most important factor in decision making regarding uncomplicated patients (selected by 54% of respondents); in patients with unfavorable clinical versus social conditions, this factor was selected by 24% versus 32%, respectively. Acute clinical factors such as life-threatening hyperkalemia refractory to medical therapy (100%) and uremic pericarditis (98%) elicited a preference for an immediate start, whereas patient preference (69%) and vascular dementia (66%) postponed the start. Higher target eGFRs were reported by respondents from high- versus low-RRT-incidence countries (10.4 [95% CI, 9.9-10.9] vs 9.1 mL/min/1.73 m(2)) and from for-profit versus not-for-profit centers (10.1 [95% CI, 9.5-10.7] vs 9.5 mL/min/1.73 m(2)). LIMITATIONS: We were unable to calculate the exact response rate and examined opinions rather than practice for 433 nephrologists. CONCLUSIONS: Only for uncomplicated patients did half the nephrologists consider excretory kidney function as the most important factor. Future studies should assess the weight of each factor affecting decision making.