Multiple subcutaneous haematomas of the legs causing skin necrosis in an elderly patient affected by corticosteroid-induced skin atrophy: Case report and review of literature.

Corticosteroid-induced skin atrophy (CISA) consists of a thinning of the skin and subcutaneous tissues, representing the natural consequence of a prolonged glucocorticosteroids use, both systemic as well as topical. It is characterised by the loss of elasticity and skin thickness, associated with an increased skin fragility leading to ecchymoses, haematomas, and steroid purpura. The management of CISA is a challenge for physicians, as the pathology is reversible in a minimal percentage of cases and only after a short topical steroid or low-dose course therapy. Often wounds with large loss of substance represent the more common complication, after a surgical drainage which is often necessary. Skin necrosis with compartment syndrome of a leg is another potential risk for these patients. Here, we report a case of an elderly patient affected by multiple subcutaneous haematomas of the legs causing skin necrosis, arisen after the use of anticoagulants for a deep venous thrombosis. The patient was successfully treated with surgical drainage, negative pressure wound therapy (NPWT), and porcine xenograft with no complications. Finally, we discuss the evidence of the current literature on topic.

A pharmacoeconomic analysis of phosphate binders cost-effectiveness in the RISCAVID study.

BACKGROUND: A pharmacoeconomic analysis of the RISCAVID database aimed at assessing the cost effectiveness of phosphate binders in preventing CV mortality and morbidity over 7 years was performed. METHODS: Morbid or fatal events occurring in 750 chronic HD patients were recorded. Statistical analysis evaluated the distribution of variables and the effect of sevelamer on survival. A cost-effectiveness evaluation was performed using a probabilistic model based on a Markov chain. RESULTS: Multivariate analysis showed that treatment with sevelamer was associated with a reduced stroke incidence by 52% (p = 0.04) and reduced levels of C-reactive protein (p < 0.01). Cost-effectiveness evaluation evidenced a 33% decrease in hospital-days for patients treated with sevelamer, with and without comorbidities compared to patients undergoing calcium binders treatment. CONCLUSION: Treatment with sevelamer was associated with a reduced risk of stroke in HD patients, with a clear saving on disease-related costs for the Italian National Healthcare System.

Anaemia and resistance to erythropoiesis-stimulating agents as prognostic factors in haemodialysis patients: results from the RISCAVID study.

BACKGROUND: Resistance to erythropoiesis-stimulating agents (ESAs) is often associated with chronic inflammation. Here, we investigated how anaemia, ESA resistance and the plasma levels of biological markers of inflammation could influence all-cause and cardiovascular disease morbidity and mortality. METHODS: Seven hundred and fifty-three haemodialysis (HD) patients (mean age 66 ± 14.2 years, mean dialytic age 70 ± 77 months and diabetes 18.8%) were enrolled and followed-up for 36 months. Demographic, clinical and laboratory data, co-morbidity conditions, administered drugs, all-cause mortality and fatal/non-fatal cardiovascular (CV) events were recorded. We measured ESA resistance index, C-reactive protein (CRP) and interleukin-6 (IL-6). RESULTS: Six hundred and fifty-one patients (86.4%) received ESAs. Patients with haemoglobin level <11 g/dL (n = 225) showed increased risk of CV [relative risk (RR) 1.415, 95% confidence interval (CI) 1.046-1.914] and overall mortality (RR 1.897, 95% CI 1.423-2.530) versus patients with haemoglobin levels >11 g/dL. ESA resistance values categorized into quartiles (Quartile I <5.6, Quartile II 5.7-9.6, Quartile III 9.7-15.4 and Quartile IV >15.4) correlated with all-cause mortality and fatal/non-fatal CV events (RR 1.97, 95% CI 1.392-2.786; RR 1.619, 95% CI 1.123-2.332, respectively). Furthermore, albumin was significantly reduced versus reference patients and correlated with all-cause mortality and CV events; CRP levels were higher in hyporesponders (Quartile IV) (P < 0.001) and predicted all-cause mortality and CV events. IL-6 but not CRP was a strong predictor of ESA resistance. CONCLUSIONS: ESA responsiveness can be considered a strong prognostic factor in HD patients and seems to be tightly related to protein-energy wasting and inflammation.

A vitamin E-coated polysulfone membrane reduces serum levels of inflammatory markers and resistance to erythropoietin-stimulating agents in hemodialysis patients: results of a randomized cross-over multicenter trial.

BACKGROUND: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anemia. Vitamin E is a fat-soluble antioxidant that plays a central role in reducing lipid peroxidation and inhibiting the generation of reactive oxygen species. The aim of this cross-over randomized study was to compare the effects of a vitamin E-coated polysulfone (Vit E PS) membrane and a non-vitamin E-coated polysulfone (PS) membrane on inflammatory markers and resistance to erythropoietin-stimulating agents (ESAs). METHODS: After a 1-month run-in period of standard bicarbonate dialysis with a synthetic membrane, 62 patients of both genders, and older than 18 years, dialysis vintage 48 ± 27 months, BMI 22 ± 3 (from 13 different dialysis units) were randomized (A-B or B-A) in a cross-over design to Vit E PS (treatment A) and to PS (treatment B) both for 6 months. C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations were determined by a sandwich enzyme immunoassay at baseline and every 2 months; red blood cell count, ESA dose and ESA resistance index (ERI) were assessed monthly. RESULTS: Hemoglobin (Hb) levels significantly increased in the Vit E PS group from 11.1 ± 0.6 g/dl at baseline to 11.5 ± 0.7 at 6 months (p < 0.001) and remained unchanged in the PS group. Although ESA dosage remained stable during the observation periods in both groups, ERI was significantly reduced in the Vit E PS group from 10.3 ± 2.2 IU-dl/kg/g Hb week at baseline to 9.2 ± 1.7 at 6 months (p < 0.001). No significant variation of ERI was observed in the PS group. A significant reduction in plasma CRP and IL-6 levels was observed in the Vit E PS group: CRP from 6.7 ± 4.8 to 4.8 ± 2.2 mg/l (p < 0.001) and IL-6 from 12.1 ± 1.4 to 7.5 ± 0.4 pg/ml (p < 0.05). In the PS group, CRP varied from 6.2 ± 4.0 to 6.4 ± 3.7, and IL-6 from 10.6 ± 2.1 to 9.6 ± 3.5 (p = n.s.). CONCLUSIONS: Treatment with Vit E PS membranes seems to lead to a reduction in ESA dosage in HD patients; in addition, a low chronic inflammatory response may contribute to a sparing effect on exogenous ESA requirements.

Impact of calcium, phosphate, PTH abnormalities and management on mortality in hemodialysis: results from the RISCAVID study.

BACKGROUND: Despite substantial progress in medical care, the mortality rate remains unacceptably high in dialysis patients. Evidence suggests that bone mineral dismetabolism (CKD-MBD) might contribute to this burden of death. However, to date only a few papers have investigated the clinical relevance of serum mineral derangements and the impact of different therapeutic strategies on mortality in a homogeneous cohort of south European dialysis patients. METHODS: The RISCAVID study was a prospective, observational study in which all patients receiving hemodialysis (HD) in the north-western region of Toscany in June 2004 were enrolled (N=757) and followed up for 24 months. RESULTS: At study entry, only 71 (9%) patients of the entire study cohort exhibited an optimal control of serum phosphorous (Pi), calcium (Ca), calciumX-phosphorous product (CAXPi) and intact parathyroidhormone (iPTH) according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical guidelines. Despite a similar prevalence, the severity of CKD-MBD appeared different to the results reported in the USA. Interestingly, none of the serum biomarkers or number of serum biomarkers within KDOQI targets was independently associated with all-cause and cardiovascular (CV) mortality. Among treatments, Sevelamer was the only drug independently associated with lower all-cause and cardiovascular mortality (p<0.001). CONCLUSION: The RISCAVID study highlights the difficulty of controlling bone mineral metabolism in HD patients and lends support to the hypothesis that a carefully chosen phosphate binder might impact survival in HD patients.

Effects on inflammatory and nutritional markers of haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over randomized multicentre trial.

BACKGROUND: HFR [double chamber haemodiafiltration (HDF) with reinfusion of regenerated ultrafiltrate] is a novel dialytic method which combines the processes of diffusion, convection and adsorbance. In this technique an adsorbent cartridge of resin and charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The aim of this multicentre randomized cross-over study was to compare HFR to online HDF in terms of inflammatory and nutritional parameters. METHODS: After a 1 month run-in period of standard bicarbonate dialysis (HD) with a synthetic membrane, 25 chronic dialytic patients were randomized (A-B or B-A) to be treated by HFR (A) with a two-chamber filter (SG 8 Plus - high permeability Polysulphone HF 0.7 m2 + SMC 1.95 sqm; Bellco, Mirandola, Italy) or by online sterile bicarbonate HDF. Each study period of 4 months was separated by 1 month of HD and the entire length of the study was 10 months. CRP levels were measured by a highly sensitive nephelometric assay (Dade, Behring) with a sensitivity of 0.1 microg/ml. Cytokine concentrations were determined by EIA [Interleukin (IL) 6, Biosource, USA and IL-10 Bender MED-Systems, Vienna]. The sensitivity thresholds were < 5 pg/ml for IL-6 and < 8 pg/ml for IL-10. Serum leptin was determined with a ELISA method (Biosource, USA). All parameters were determined monthly in patients starting a midweek dialytic session. RESULTS: Plasma CRP and IL-6 were significantly reduced during the 4 months of HFR and HDF: CRP from 8.0 +/- 3.2 to 5.6 +/- 3.4 mg/l with HFR (P < 0.05) and from 9.4 +/- 4.3 to 5.9 +/- 3.9 mg/l with HDF (P < 0.05). IL-6 decreased from 14.8 +/- 6.3 to 10.1 +/- 3.2 with HFR (P < 0.02) and from 12.1 +/- 4.2 to 9.6 +/- 3.7 with HDF (P = ns) with a percentage decrease after 4 months of 32% with HFR vs 21% with HDF. During the 1 month wash-out period with HD, CRP increased from 5.7 +/- 3.6 to 8.7 +/- 3.9 mg/l (P < 0.01) and IL-6 from 10 +/- 3.4 to 13.5 +/- 5.2 pg/ml (P < 0.01). A significant increase in IL-10 was detected either in HFR (from 4.8 +/- 2.1 to 6.89 +/- 1.7 pg/ml) and in HDF (from 3.3 +/- 1.7 to 8.95 +/- 4.3 pg/ml; P < 0.05) after 4 months. No significant variation in serum leptin levels were observed during the study. CRP and IL-6 were highly correlated (r = 0.54; P < 0.001) as was serum albumin and prealbumin (r = 0.39; P < 0.001). Serum albumin was negatively correlated with CRP (r = -0.26; P < 0.01) and IL-6 (r = -0.19; P < 0.05); serum prealbumin was correlated with IL-6 (r = 0.37; P < 0.001) and with CRP (r = 0.24; P < 0.01). CONCLUSIONS: Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are highly biocompatible techniques and no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers. Further studies with a longer follow-up are needed to evaluate the clinical relevance of the online endogenous reinfusion to counteract the chronic inflammatory state of the uraemic patient.