Survival of incident patients on high-volume online hemodiafiltration compared to low-volume online hemodiafiltration and high-flux hemodialysis

Background

Hemodiafiltration is becoming a preferred treatment modality for dialysis patients in many countries. The volume of substitution fluid delivered has been indicated as an independent mortality risk factor. The aim of this study is to compare patient survival on three different treatment modalities: high-flux hemodialysis, low-volume online HDF (oHDF) and high-volume oHDF.

Methods

Incident hemodialysis and oHDF patients treated in 13 NephroCare centers in Bosnia and Herzegovina, Serbia and Slovenia between January 1, 2007, and December 31, 2011, were included in this epidemiological cohort study. High-volume oHDF was defined as substitution volume higher than the median substitution volume infused, otherwise low-volume. Main predictor was treatment modality at baseline and in time-dependent model. Other predictors were age, gender, diabetes mellitus, cerebrovascular accident, arrhythmia, hemoglobin and C-reactive protein.

Results

Four hundred and forty-two patients were included in the study. Median substitution fluid volume was 20.4 L. Mean difference between the oHDF groups in substitution fluid volume was 8.3 ± 5.2 L [95 % confidence intervals (95 % CI) 7.1–9.5, p < 0.0001]. The unadjusted hazard ratios (HR) with 95 % CI compared to high-flux HD were 0.87 (0.5–1.5) for low-volume oHDF and 0.29 (0.13–0.63) for high-volume oHDF. After the adjustment for covariates, the HR for patients on low-volume oHDF remained statistically insignificant compared to high-flux HD (0.84; 95 % CI 0.46–1.53), while patients on high-volume oHDF showed a marked and significantly lower HR (0.29; 95 % CI 0.13–0.68) than patients on high-flux HD in baseline model. While this effect failed to reach significance in the time-dependent model (HR 0.477; 95 % CI 0.196–1.161), possibly due to an inadequate sample size here, the consistency of results in both models supports the robustness of the findings. After switching from high-flux hemodialysis to oHDF, mean hemoglobin and albumin levels did not change significantly. Mean erythropoietin resistance index (ERI) and erythropoiesis stimulating agents (ESA) consumption decreased significantly (p = 0.02, p = 0.03, respectively).

Conclusions

The median substitution volume used in these three countries for post-dilutional oHDF is 20.4 L. oHDF is associated with significant reductions in ERI and ESA consumption. Only high-volume oHDF is associated with improved survival compared to high-flux hemodialysis.     

Simple "closed-circuit" group-specific immunoadsorption system for ABO-incompatible kidney transplants.

There is a need for improvement of the detection and treatment of the antibody-mediated graft rejection for ABO-incompatible kidney transplant recipients. With the development of novel pre-conditioning protocols, which employ anti-CD20 antibody, therapeutic plasma exchange plus extracorporeal immunoadsorption and standard immunosuppression application, together with the use of more sensitive and objective assays for immunological monitoring, patients that were not candidates for kidney transplant in the past, are now being transplanted. We have designed a pre-conditioning protocol for ABO-incompatible kidney transplants based on TPE plus our own simple "closed-circuit" immunoadsorption technique - combined by anti-CD20, standard immunosuppressive treatment, and without splenectomy. The results obtained in this study strongly support our hypothesis leading to the conclusion that this protocol can be used successfully, with high-quality ABO antibody depletion (p<0.001) and beneficial clinical findings. The application of this protocol is safe, and not associated with alteration in normal plasma constituent levels or with occurrence of any side effects of apheresis or clinical consequences. Finally, this pre-conditioning protocol radically reduces the treatment-cost. Definitive conclusions can only be drawn from larger, randomized, controlled clinical trials.     

Changes in muscle tissue oxygenation during stagnant ischemia in septic patients

Objective To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock.Design and setting Prospective observational study in the medical ICU of a general hospital.Patients and participants Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15).Interventions Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm.Measurements and results Thenar muscle tissue oxygen saturation (StO₂) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO₂ before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO₂ decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (–7.0 [–3.6, –11.0] %/min vs. –10.4 [–7.8, –13.3] %/min vs. –19.5 [–12.3, –23.3] vs. –37.4 [–27.3, –56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO₂ decrease did not differ between the septic shock, severe sepsis, and localized infection groups (–17.0 [–9.3, –28.9] %/min vs. –19.9 [–13.3, –23.6] %/min vs. –23.1 [–20.7, –26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO₂ decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001).Conclusions After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.     

Bone metabolism during interferon-alpha treatment of essential thrombocythemia

In-vitro studies have demonstrated that interferon (IFN) has an inhibitory effect on bone formation. Changes in bone metabolism were investigated in 19 patients treated for essential thrombocythemia with IFN-alpha. Serum biochemical parameters of bone remodeling [total alkaline phosphatase, osteocalcin, type-I procollagen carboxy-terminal propeptide (PICP), cross-linked telopeptide type-I collagen (ICTP)] and mineral metabolism (total calcium, inorganic phosphate, parathyroid hormone, 25-hydroxyvitamin D) were measured before and after long-term IFN-alpha treatment. The effects of the cumulative IFN-alpha dose and duration of therapy on biochemical markers of bone metabolism were analyzed. No uniform trend or pattern was observed in the measured biochemical parameters except for ICTP, which decreased after treatment. Correlations indicated modulation of bone metabolism, i.e. remodeling with suppression of resorption, as a consequence of therapy with IFN-alpha.     

Combined Thrombophilic Risk Factors and Essential Thrombocythemia in Patient with Recurrent Venous Thromboembolic Episodes—Thirty-Three-Year Follow-Up

We present the case of a 64 year-old female patient, with a clearly positive family history of venous thromboembolism (VTE), multiple VTE episodes (massive pulmonary embolism, ovarian venous plexus thrombosis, deep venous thrombosis with submassive pulmonary embolism and second deep venous thrombosis) and myocardial infarction.Laboratory tests revealed the resistance to the activated protein C, elevated FVIII and PAI-1. The patient was found to be a heterozygous carrier of FV Leiden, MTHFR C677T and PAI-1 4G/5G mutations. She was diagnosed with essential thrombocythemia at the age of 60.The thirty-three-year follow-up of our patient and detection of recurrent thrombotic episodes in the light of multiple coagulation defects with proved acquired risk factors, contributes to the risk stratification in the group of patients with very high risk. In case of our patient, we stress inadequacy of widely-accepted standard prevention measures. In our opinion, patients with very high risk require additional mechanic and specific medicament methods of VTE prevention.     

Prognostic value of additional pathological variables for long-term survival after curative resection of rectal cancer

AIM: To evaluate the prognostic value of some pathological variables in rectal cancer survival. METHODS: 247 patients who underwent curative resection of rectal cancer were included in the study. The influence on survival of five pathological variables (histopathological tumor type, histopathological tumor grade differentiation, blood vessel invasion, perineural invasion and lymphatic invasion) was assessed using statistical analyses. RESULTS: Overall 5-year survival was 71.2%. Univariate analysis of all tested variables showed an effect on survival but only the effect of lymphatic invasion was statistically significant. At stages three and four it had a negative effect on survival (P = 0.0212). Lymphatic invasion also significantly affected cancer related survival in multivariate analysis at stages three and four. At lower stages (stage 0, stage 1 and stage 2) multivariate analysis showed a negative effect of perineural invasion on cancer related survival. CONCLUSION: Patients with lymphatic and perineural invasion have a higher risk for rectal cancer related death after curative resection. Examination of these variables should be an important step in detecting patients with a poorer prognosis.     

Can we improve the clinical risk score? The prognostic value of p53, Ki-67 and thymidylate synthase in patients undergoing radical resection of colorectal liver metastases

Objectives: The aim of this study was to assess whether biological markers can provide prognostic information additional to that supplied by the clinical risk score (CRS) in patients with colorectal liver metastases.Methods: A retrospective review of a prospectively maintained database was conducted. Patients selected for this study were treated between 1996 and 2011 with potentially curative liver surgery. Expressions of p53, Ki-67 and thymidylate synthase were assayed using immunohistochemical techniques on tissue microarrays.Results: A total of 98 (24%) of 406 patients met the inclusion criteria. The median follow-up was 103 months. Analysis revealed a correlation between p53 protein overexpression and high CRS (P = 0.058). Following multivariate analysis, only high CRS remained as an independent negative prognostic predictor of survival (P = 0.018), as well as an indicator of early recurrence of disease (P = 0.010). Of the biological markers investigated, only Ki-67 overexpression was identified as a positive predictor of survival on multivariate analysis (P = 0.038).Conclusions: Ki-67 overexpression was a positive predictor of survival. Only high CRS remained an independent negative prognostic predictor.     

Pulmonary microthrombi during left ventricular assist device implantation

Critically ill heart failure patients undergoing left ventricular assist device implantation have alterations in their coagulation profiles; as a result, hemorrhagic complications during the postoperative period are the most common and serious problems during device support of these patients. The use of aprotinin therapy is generally accepted for reducing bleeding after coronary artery bypass grafting procedures, heart transplantation, and insertion of a left ventricular assist device. We describe the case of a patient who had a suprasystemic increase in pulmonary artery pressure, caused by thromboembolic occlusion of the pulmonary arterioles after urgent implantation of a left ventricular assist device. The complications developed after the patient was weaned from cardiopulmonary bypass and heparinization was reversed with protamine. Although the thrombosis was successfully reversed with intraoperative administration of tissue plasminogen activator directly to the pulmonary artery, the patient died of massive hemorrhage 6 hours later. To our knowledge, the direct application of tissue plasminogen activator into the pulmonary artery in such a catastrophic situation has not been used elsewhere.     

Acute presentation of a solid pseudopapillary tumor of the pancreas

We report a case of acute presentation of a solid pseudopapillary tumor of the pancreas in a young boy who had suffered a blunt abdominal trauma. Urgently performed CT examination and repeated ultrasound revealed a subhepatic mass, which gradually increased in size, but the imaging features were not specific enough to permit a precise diagnosis. Because signs of peritoneal irritation and increased circulatory instability gradually developed within the hours of observation, the decision was made to perform an urgent exploratory laparotomy. The exploration revealed a hematoperitoneum and a large hematoma-like subhepatic bleeding mass. Further exploration showed that this mass was a tumor arising from the head of the pancreas, which had ruptured on the surface. A curative pancreatoduodenectomy was performed. Pathohistological examination of the resected specimen revealed a solid pseudopapillary tumor of the pancreas, an extremely rare tumor predominantly occurring in adolescent girls and in young adult women. It has a favorable prognosis if resected radically. The boy in our report is feeling well 36 months after the operation.     

Do C1q or IgM nephropathies predict disease severity in children with minimal change nephrotic syndrome?

Background

It has been suggested that C1q and immunoglobulin M (IgM) nephropathy are variants of minimal change nephrotic syndrome (MCNS). Many researchers believe that these two conditions signify a worse prognosis for children with MCNS in comparison with immunofluorescence (IF)-negative MCNS. The aim of our study was to determine the prognostic significance of C1q nephropathy and IgM nephropathy in children with MCNS.

Methods

Fifty-five children with MCNS who had been biopsied over the course of 24 years at our institution were retrospectively categorized into three groups on the basis of IF microscopy findings: IF-negative MCNS (29/55 patients), MCNS with IgM nephropathy (19/55 patients), and MCNS with C1q nephropathy (7/55 patients). Clinical characteristics at disease presentation, clinical course, and renal outcome were compared between groups during the median follow-up period of 16.9 years (minimum 1.0, maximum 31.1 years).

Results

No statistically significant differences in clinical characteristics at disease presentation, clinical course, and renal outcome were found. Children with IgM nephropathy, C1q nephropathy, and IF-negative MCNS were clinically indistinguishable.

Conclusions

We concluded that C1q or IgM nephropathy variants do not seem to signify a worse prognosis in children with MCNS in comparison with IF-negative MCNS.