Venous blood gases in the assessment of respiratory failure in patients undergoing sleep studies: a randomized study.

STUDY OBJECTIVES: Venous blood gases (VBGs) are not consistently considered suitable surrogates for arterial blood gases (ABGs) in assessing acute respiratory failure due to variable measurement error. The physiological stability of patients with chronic ventilatory failure may lead to improved agreement in this setting. METHODS: Adults requiring ABGs for sleep or ventilation titration studies had VBGs drawn before or after each ABG, in a randomized order. Veno-arterial correlation and agreement were examined for carbon dioxide tension (PCO2), pH, oxygen tension (PO2) and oxygen saturation (SO2). RESULTS: We analyzed 115 VBG-ABG pairs from 61 patients. Arterial and venous measures were correlated (with p<0.05) for PCO2 (r=0.84) and pH (r=0.72), but not for PO2 or SO2. Adjusted mean veno-arterial differences (95% limits of agreement) were +5.0mmHg (-4.4 to +14.4) for PCO2; -0.02 (-0.09 to +0.04) for pH; -34.3mmHg (-78.5 to +10.0) for PO2; and -23.9% (-61.3 to +13.5) for SO2. VBGs obtained from the dorsal hand demonstrated a lower mean PCO2 veno-arterial difference (p<0.01). A venous PCO2 threshold of ≥45.8mmHg was >95% sensitive for arterial hypercapnia, so measurements below this can exclude the diagnosis without an ABG. A venous PCO2 threshold of ≥53.7mmHg was >95% specific for arterial hypercapnia, so such readings can be assumed diagnostic. The area under the receiver operating characteristic curve of 0.91 indicated high discriminatory capacity. CONCLUSIONS: A venous PCO2 <45.8mmHg or ≥53.7mmHg would exclude or diagnose hypercapnia, respectively, in patients referred for sleep studies, but VBGs are poor surrogates for ABGs where precision is important. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Register; Name: A comparison of arterial and blood gas analyses in sleep studies; Identifier: ACTRN12617000562370; URL https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372717.

Emergency department testing is feasible but ineffective to eliminate hepatitis C in Denmark.

BACKGROUND: As direct-acting antiviral treatment for hepatitis C virus (HCV) is widely available in Denmark, the hindrance to achieving elimination lies in identifying infections. Effective identification relies on screening in high-risk populations. Here, we report the outcomes of a risk-based, point-of-care (POC) screening strategy in a Danish emergency department (ED). METHODS: During a three-month period, ED patients at Odense University Hospital were screened for risk factors and offered POC HCV-antibody (HCV-Ab) testing. Reactive results were followed up by confirmatory venepuncture testing. The main outcome measure was prevalence of HCV-antibodies. Secondary outcome measures were prevalence of risk factors and an evaluation of feasibility of ED screening. RESULTS: During study times, 1831 (55.7%) of 3288 presentations to the ED were eligible for screening. Six hundred and seventy-three (36.8%) were approached, of which 514 (28.1%) participated and 159 (8.7%) declined. Of 514 participants, 339 (66%) reported one or more risk factors, and 489 (95.1%) underwent HCV-Ab testing. Four (0.8%) had a reactive HCV-Ab test. No active infections of HCV were found. The risk factor of having injected drugs was present in all HCV-Ab positive patients. Compared to participants, patients who could not be approached had a lower prevalence of previously diagnosed hepatitis C- and risk-factor-associated diagnoses. CONCLUSIONS: The risk factor of injecting drug use had the highest yield for HCV-Ab positivity. Additional risk factors did not contribute to case-finding. This screening strategy was feasible but ineffective. Further testing strategies will be necessary to identify the remaining hepatitis C patients in Denmark.

Hospital-acquired complications in intensive care unit patients with diabetes: A before-and-after study of a conventional versus liberal glucose control protocol.

BACKGROUND: Critically ill patients with diabetes mellitus (DM) are at increased risk of in-hospital complications and the optimal glycemic target for such patients remains unclear. A more liberal approach to glucose control has recently been suggested for patients with DM, but uncertainty remains regarding its impact on complications. METHODS: We aimed to test the hypothesis that complications would be more common with a liberal glycemic target in ICU patients with DM. Thus, we compared hospital-acquired complications in the first 400 critically ill patients with DM included in a sequential before-and-after trial of liberal (glucose target: 10-14 mmol/L) vs conventional (glucose target: 6-10 mmol/L) glucose control. RESULTS: Of the 400 patients studied, 165 (82.5%) patients in the liberal and 177 (88.5%) in the conventional-control group were coded for at least one hospital-acquired complication (P = 0.09). When comparing clinically relevant complications diagnosed between ICU admission and hospital discharge, we found no difference in the odds for infectious (adjusted odds ratio [aOR] for liberal-control: 1.15 [95% CI: 0.68-1.96], P = 0.60), cardiovascular (aOR 1.40 [95% CI: 0.63-3.12], P = 0.41) or neurological complications (aOR: 1.07 [95% CI: 0.61-1.86], P = 0.81), acute kidney injury (aOR 0.83 [95% CI: 0.43-1.58], P = 0.56) or hospital mortality (aOR: 1.09 [95% CI: 0.59-2.02], P = 0.77) between the liberal and the conventional-control group. CONCLUSION: In this prospective before-and-after study, liberal glucose control was not associated with an increased risk of hospital-acquired infectious, cardiovascular, renal or neurological complications in critically ill patients with diabetes.

Magnesium sulfate therapy after cardiac surgery: a before-and-after study comparing strategies involving bolus and continuous infusion.

BACKGROUND: Magnesium therapy may reduce the risk of atrial fibrillation after cardiac surgery. However, studies are heterogeneous in relation to dosage and method of delivery and no studies have directly compared the biochemical effect of different delivery strategies. AIMS: We conducted a before-and-after study to compare the effects of two strategies of magnesium delivery after cardiac surgery. METHODS: We conducted a prospective interventional before-and-after study. We enrolled patients admitted to the intensive care unit (ICU) after cardiac surgery and with no history of renal failure. The before period consisted of a single 20 mmol of magnesium sulfate bolus administered over one hour. The after period comprised a 10 mmol magnesium loading dose over one hour followed by a continuous infusion at 3 mmol/h for 12 hours. We measured serum and urine magnesium levels at baseline (T0), at the end of loading dose (T1), 6 (T2) and 12 hours after the intervention (T3). RESULTS: We enrolled 60 patients (30 in each group) with similar baseline characteristics. In the before period, patients had a higher peak serum magnesium level at T1 (1.88 ± 0.06 v 1.59 ± 0.04 mmo/L; P < 0.001) compared with the after period. However, at 6 hours, patients in the after period had a significantly higher magnesium level (1.61 ± 0.04 v 1.29 ± 0.26 mmol/L; P < 0.001) and this level remained higher at 12 hours (1.70 ± 0.05 v 1.17 ± 0.02; P < 0.001), leading to increased time-weighted magnesaemia (P < 0.001). These changes occurred despite a significantly increased urinary magnesium concentration, fractional excretion of magnesium, and magnesium clearance, which paralleled changes in magnesaemia (P < 0.001). CONCLUSIONS: The strategy of a 10 mmol magnesium bolus followed by a continuous infusion over 12 hours achieved a more sustained and moderately elevated magnesium concentration in comparison to a single 20 mmol bolus, despite increased urinary losses of magnesium. Further studies are required to assess a more extended continuous infusion.

Liberal Glucose Control in ICU Patients With Diabetes: A Before-and-After Study.

OBJECTIVES: To assess the feasibility, biochemical efficacy, and safety of liberal versus conventional glucose control in ICU patients with diabetes. DESIGN: Prospective, open-label, sequential period study. SETTING: A 22-bed mixed ICU of a tertiary hospital in Australia. PATIENTS: We compared 350 consecutive patients with diabetes admitted over 15 months who received liberal glucose control with a preintervention control population of 350 consecutive patients with diabetes who received conventional glucose control. INTERVENTIONS: Liberal control patients received insulin therapy if glucose was greater than 14 mmol/L (target: 10-14 mmol/L [180-252 mg/dL]). Conventional control patients received insulin therapy if glucose was greater than 10 mmol/L (target: 6-10 mmol/L [108-180 mg/dL]). MEASUREMENTS AND MAIN RESULTS: We assessed separation in blood glucose, insulin requirements, occurrence of hypoglycemia (blood glucose ≤ 3.9 mmol/L [70 mg/dL]), creatinine and white cell count levels, and clinical outcomes. The median (interquartile range) time-weighted average blood glucose concentration was significantly higher in the liberal control group (11.0 mmol/L [8.7-12.0 mmol/L]; 198 mg/dL [157-216 mg/dL]) than in the conventional control group (9.6 mmol/L [8.5-11.0 mmol/L]; 173 mg/dL [153-198 mg/dL]; p < 0.001). Overall, 132 liberal control patients (37.7%) and 188 conventional control patients (53.7%) received insulin in ICU (p < 0.001). Hypoglycemia occurred in 6.6% and 8.6%, respectively (p = 0.32). Among 314 patients with glycated hemoglobin A1c greater than or equal to 7%, hypoglycemia occurred in 4.1% and 9.6%, respectively (p = 0.053). Trajectories of creatinine and white cell count were similar in the groups. In multivariable analyses, we found no independent association between glucose control and mortality, duration of mechanical ventilation, or ICU-free days to day 30. CONCLUSIONS: In ICU patients with diabetes, during a period of liberal glucose control, insulin administration, and among patients with hemoglobin A1c greater than or equal to 7%, the prevalence of hypoglycemia was reduced, without negatively affecting serum creatinine, the white cell count response, or other clinical outcomes. (Trial Registration: Australian New Zealand Clinical Trials Registry; ACTRN12615000216516).

Magnesium supplementation: Pharmacokinetics in cardiac surgery patients with normal renal function.

BACKGROUND: Intravenous magnesium is routinely administered in intensive care units (ICU) to treat arrhythmias after cardiothoracic surgery. There are no data on the pharmacokinetics of continuous magnesium infusion therapy. OBJECTIVE: To investigate the pharmacokinetics of continuous magnesium infusion, focusing on serum and urinary magnesium concentration, volume of distribution and half-life. METHODS: We administered a 10 mmol bolus of magnesium-sulfate followed by a continuous infusion of 3 mmol/h for 12 h in twenty cardiac surgery patients. We obtained blood and urine samples prior to magnesium administration and after one, six, and 12 h. RESULTS: Median magnesium levels increased from 1.09 (IQR 1.00-1.23) mmol/L to 1.59 (1.45-1.76) mmol/L after 60 min (p < .001), followed by 1.53 (1.48-1.71) and 1.59 (1.48-1.76) mmol/L after 6 and 12 h. Urinary magnesium concentration increased from 9.2 (5.0-13.9) mmol/L to 17 (13.6-21.6) mmol/L after 60 min (p < .001). Cumulative urinary magnesium excretion was 28 mmol (60.9% of the dose given). The volume of distribution was 0.25 (0.22-0.30) L/kg. There were no episodes of severe hypermagnesemia (≥3 mmol/L). CONCLUSION: Combined bolus and continuous magnesium infusion therapy leads to a significant and stable increase in magnesium serum concentration despite increased renal excretion and redistribution.

Pharmacokinetics of Magnesium Bolus Therapy in Cardiothoracic Surgery.

OBJECTIVE: To investigate the pharmacokinetics of a 20 mmol magnesium bolus in regards to serum and urinary magnesium concentration, volume of distribution, and half-life. DESIGN: Prospective, experimental study. SETTING: A university-affiliated teaching hospital. PARTICIPANTS: Twenty consecutive cardiac surgery patients treated with magnesium bolus therapy for prevention of arrhythmia. INTERVENTIONS: A 20-mmol bolus of magnesium sulfate was administered intravenously. MEASUREMENTS AND MAIN RESULTS: Median magnesium levels increased from 1.04 (interquartile range 0.94-1.23) mmol/L to 1.72 (1.57-2.14) mmol/L after 60 minutes of magnesium infusion (p < 0.001) but decreased to 1.27 (1.21-1.36) and 1.16 (1.11-1.21) mmol/L after 6 and 12 hours, respectively. Urinary magnesium concentration increased from 6.3 (4.2-14.5) mmol/L to 19.1 (7.4-34.5) mmol/L after 60 minutes (p < 0.001), followed by 22.7 (18.4-36.7) and 15 (8.4-19.7) mmol/L after 6 and 12 hours, respectively. Over the 12-hour observation period, the cumulative urinary magnesium excretion was 19.1 mmol (95.5% of the dose given). The median magnesium clearance was 10 (4.7-15.8) mL/min and increased to 14.9 (3.8-20.7; p = 0.934) mL/min at 60 minutes. The estimated volume of distribution was 0.31 (0.28-0.34) L/kg. CONCLUSION: Magnesium bolus therapy after cardiac surgery leads to a significant but short-lived increase of magnesium serum concentration due to renal excretion and distribution, and the magnesium balance is neutral after 12 hours.

Peripheral venoarterial extracorporeal membrane oxygenation for severe hyperlactataemia after cardiac surgery: a pilot study.

BACKGROUND: Severe hyperlactataemia in patients after cardiac surgery is associated with poor prognosis and implies possible splanchnic hypoperfusion. Peripheral venoarterial extracorporeal membrane oxygenation (splanchnic ECMO) may be more effective at reducing lactic acidosis for these patients. OBJECTIVE: To investigate whether splanchnic ECMO attenuates hyperlactataemia and liver enzyme release in these patients, despite them having a cardiac index > 2 L/min/m2 and a mixed venous oxygen saturation > 55%. DESIGN AND PARTICIPANTS: Retrospective matched case- control study of patients treated with splanchnic ECMO for hyperlactataemia. Seven patients who had had cardiac surgery were treated with splanchnic ECMO compared with seven matched control patients. RESULTS: We observed a mean decrease in lactate levels from 9.9 mmol/L (SD, 2.9 mmol/L) to 1.4 mmol/L (SD, 0.6 mmol/L) in patients receiving 48 hours of splanchnic ECMO, compared with a mean of 10.4 mmol/L (SD, 2.8 mmol/L) to 4.4 mmol/L (SD, 5 mmol/L) during 48 hours in control patients (P < 0.0001). Normalisation of lactate levels (to < 2 mmol/L) was achieved within a mean of 16.3 hours (SD, 14.6 hours) with splanchnic ECMO, compared with 38.3 hours (SD, 23.8 hours) in the control group (P = 0.029). The median increase in alanine aminotransferase level with splanchnic ECMO was 68% (range, -84% to 2015%) compared with 158% (range: 0%-6024%) (not significant) in control patients. CONCLUSION: In a selected cohort of patients who had had cardiac surgery with severe post-operative hyperlactataemia, despite an acceptable cardiac index and a mixed venous oxygen saturation, splanchnic ECMO appeared to reduce overall lactate levels and time to normalisation of lactataemia.

Effect of combined treatment with immunoadsorption and membrane filtration on plasma coagulation--Results of a randomized controlled crossover study.

The combined use of immunoadsorption (IA) and membrane filtration (MF) may markedly enhance removal of IgM and complement component C1q, supporting its use as an element of recipient desensitization in antibody-incompatible transplantation. However, coagulation factor removal may contribute to altered hemostasis, posing a risk of bleeding in the perioperative setting. This secondary endpoint analysis of standard coagulation assays and rotational thromboelastometry (ROTEM®) was performed in the context of a randomized controlled crossover study designed to assess the effect of combined IA (GAM-146-peptide) and MF on levels of ABO antigen-specific IgM. Fourteen patients with autoimmune disorders were randomized to a single treatment with IA+MF followed by IA alone, or vice versa. MF was found to markedly enhance fibrinogen depletion (57% vs. 28% median decrease after IA alone, P < 0.001), whereby four patients showed post-treatment fibrinogen concentrations below 100 mg dL(-1). In support of a critical contribution of fibrinogen depletion to impaired coagulation, extrinsically activated ROTEM(®) analysis revealed a marked reduction in fibrinogen-dependent clot formation upon IA+MF (59% median decrease in FIBTEM mean clot firmness (MCF) as compared to 24% after IA alone, P < 0.001). Moreover, the addition of MF led to a substantial prolongation of activated partial thromboplastin time, possibly due to depletion of macromolecular coagulation factors contributing to intrinsically activated coagulation. Our study demonstrates substantial effects of combined IA+MF on clot formation, which may be mainly attributable to fibrinogen depletion. We suggest that the use of combined apheresis in the setting of transplant surgery may necessitate a careful monitoring of coagulation.

An acetate-buffered balanced crystalloid versus 0.9% saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial.

BACKGROUND: Recent studies have shown a decline in glomerular filtration rate and increased renal vasoconstriction after administration of normal saline when compared with IV solutions with less chloride. In this study, we investigated the impact of normal saline versus a chloride-reduced, acetate-buffered crystalloid on the incidence of hyperkalemia during cadaveric renal transplantation. The incidence of metabolic acidosis and kidney function were secondary aims. METHODS: In this prospective randomized controlled trial, 150 patients received normal saline or an acetate-buffered balanced crystalloid during and after cadaveric renal transplantation. Venous blood gases were obtained at the start of anesthesia and every 30 minutes until discharge from the postoperative surveillance unit. Serum creatinine and 24-hour urine output were obtained on postoperative days 1, 3, and 7. RESULTS: Patients received a similar amount of fluid (median: 2625mL [interquartile range: 2000 to 3100] vs 2500 mL [2000 to 3050], P = 0.83). Hyperkalemia, defined as serum potassium >5.9 mmol/L, occurred in 13 patients (17%) in the saline and 15 (21%) in the balanced group (P = 0.56; difference between proportions -0.037 [-16.5% to 8.9%]). Minimum base excess was lower in the saline group compared with the balanced regimen (-4.5 mmol/L [-6 to -2.4] vs -2.6 mmol/L [-4 to -1], P < 0.001) and maximum chloride was significantly higher in the saline group (109 mmol/L [107 to 111] vs 107 mmol/L [105 to 109], P < 0.001). No difference in creatinine or urine output was seen postoperatively. Significantly more patients needed catecholamines in the saline group (30% vs 15%, P = 0.03). CONCLUSIONS: The incidence of hyperkalemia differed by less than 17% between groups. Use of balanced crystalloid resulted in less hyperchloremia and metabolic acidosis. Significantly more patients in the saline group required administration of catecholamines for circulatory support.

Fibrinogen reduction and bleeding complications in plasma exchange, immunoadsorption and a combination of the two.

BACKGROUND: Immunoadsorption (IAS) and therapeutic plasma exchange (TPE) are considered safe although fibrinogen is removed. To date no comparison of fibrinogen reduction and associated risk of bleeding in apheresis exists. METHODS: Retrospective analysis of TPE, three IAS adsorbers, and combined TPE/IAS regarding fibrinogen reduction and bleeding incidence in 67 patients (1,032 treatments). RESULTS: TPE and TPE/IAS reduced fibrinogen by 64 ± 11% and 58 ± 9%, leading to concentrations <100 mg/dl in 20 and 17% of treatments, respectively. IAS decreased fibrinogen less than TPE (26 ± 6%, p < 0.0001), resulting in fibrinogen concentrations <100 mg/dl in 1% of treatments. The processed volume correlated with reduction in TPE (r = 0.64, p < 0.01), but not in IAS. Bleeding occurred in 1.3% (IAS), 2.3% (TPE) and 3.1% (TPE/IAS) of treatments. CONCLUSION: Hypofibrinogenemia occurs in 20% of patients after TPE and TPE/IAS, but rarely after IAS. IAS removes fibrinogen independently of volume processed. Overall, bleeding is rare in apheresis.

Long-term outcome of anti-glomerular basement membrane antibody disease treated with immunoadsorption.

BACKGROUND: Anti-glomerular basement membrane (GBM) antibody disease may lead to acute crescentic glomerulonephritis with poor renal prognosis. Current therapy favours plasma exchange (PE) for removal of pathogenic antibodies. Immunoadsorption (IAS) is superior to PE regarding efficiency of antibody-removal and safety. Apart from anecdotal data, there is no systemic analysis of the long-term effects of IAS on anti-GBM-disease and antibody kinetics. OBJECTIVE: To examine the long-term effect of high-frequency IAS combined with standard immunosuppression on patient and renal survival in patients with anti-GBM-disease and to quantify antibody removal and kinetics through IAS. DESIGN: Retrospective review of patients treated with IAS for anti-GBM-antibody disease confirmed by biopsy and/or anti-GBM-antibodies. SETTING: University Hospital of Vienna, Austria. PARTICIPANTS: 10 patients with anti-GBM-disease treated with IAS. MEASUREMENTS: Patient and renal survival, renal histology, anti-GBM-antibodies. RESULTS: Anti-GBM-antibodies were reduced by the first 9 IAS treatments (mean number of 23) to negative levels in all patients. Renal survival was 40% at diagnosis, 70% after the end of IAS, 63% after one year and 50% at the end of observation (mean 84 months, range 9 to 186). Dialysis dependency was successfully reversed in three of six patients. Patient survival was 90% at the end of observation. CONCLUSION: IAS efficiently eliminates anti-GBM-antibodies suggesting non-inferiority to PE with regard to renal and patient survival. Hence IAS should be considered as a valuable treatment option for anti-GBM-disease, especially in patients presenting with a high percentage of crescents and dialysis dependency due to an unusual high proportion of responders.

ABO antibody and complement depletion by immunoadsorption combined with membrane filtration--a randomized, controlled, cross-over trial.

BACKGROUND: Potent antibody depletion techniques have paved the way to successful ABO-incompatible transplantation. Considering its efficiency regarding IgG removal, the use of non-antigen-specific semi-selective immunoadsorption (IA) has been advocated. One attractive strategy to overcome the caveat of incomplete IgM depletion and to interfere with complement activation could be the adjunctive use of membrane filtration (MF) to enhance the removal of macromolecules. METHODS: To investigate the depletion efficiency of semi-selective IA plus MF, we conducted a randomized, controlled, cross-over trial including patients on regular IA treatment for indications outside recipient desensitization. According to the results of sample size calculation, 14 subjects were enrolled. Two treatment sequences, a single session of IA plus MF followed by IA alone after ≥7 days (and vice versa), were analysed. RESULTS: IA plus MF markedly enhanced the median per cent reduction of ABO-specific IgM determined by flow cytometry (primary end point; 59 versus 23%, P < 0.001) and haemagglutination (2 versus 1 titre steps, P < 0.001), respectively. Combined treatment also substantially lowered C1q concentrations (86 versus 58% reduction, P < 0.001) and the functionality of classical complement as reflected by impaired in vitro C3 activation capability. IgG was strongly reduced without any additional effect of MF. CONCLUSIONS: We demonstrate that the innovative strategy of combining MF with semi-selective IA may substantially increase IgM elimination and affect classical complement activation. Our findings suggest that this new treatment concept could be an efficient strategy for recipient desensitization in ABO- and HLA-incompatible transplantation.

Lupus nephritis: prolonged immunoadsorption (IAS) reduces proteinuria and stabilizes global disease activity.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by pathogenic autoantibodies, which can be removed by extracorporeal procedures. While previous studies have shown short-term efficacy of immunoadsorption (IAS) in SLE, no information on long-term benefit and safety is available. METHODS: IAS was offered to patients with highly active renal disease when conventional therapy had failed. Eleven patients entered the prolonged IAS programme and were followed for up to 10 years (mean 6.4 ± 3.5). Efficacy of IAS was determined by reduction in proteinuria (primary outcome), global disease activity [SLE Disease Activity Index (SLEDAI)] and anti-double-stranded DNA (anti-dsDNA) levels (secondary outcomes). Full/partial remission was defined as ≤ 0.5/≤ 1.0 g/day for proteinuria, ≤ 5/≤ 8 for SLEDAI and ≤ 25/≤ 50 IU/mL for anti-dsDNA levels. We further assessed flares, infections, malignancies and procedure-related adverse events. RESULTS: Short-term IAS (≤ 1 year) resulted in a significant reduction of proteinuria (9.2 ± 3.7 to 2.3 ± 2.4, P = 0.0001), disease activity (SLEDAI 19 ± 8 to 4 ± 2, P = 0.0004) and dsDNA levels (168 ± 205 to 45 ± 34, P = 0.001). In patients without remission after 1 year (n = 5), prolonged IAS decreased proteinuria from 4.3 ± 2.4 to 0.5 ± 0.4 g/day, P = 0.02. At the end of observation, complete remission in proteinuria was achieved in seven patients (64%) and partial remission in two (18%) additional patients. One patient flared and was discontinued; in all other patients, disease activity and anti-dsDNA stabilized at remission levels. Flares (0.28 ± 0.30) and infections (0.66 ± 0.70 per patient/year) were relatively uncommon; no malignancies, anaphylactic or orthostatic adverse events were observed. CONCLUSION: IAS is effective in short-term use but prolonged IAS can provide additional therapeutic benefit while showing an acceptable safety profile. The vast majority of initially therapy-refractory patients met the remission criteria at the end of observation.

Metabolic control and vascular diseases under oral antidiabetic drug versus insulin therapy and/or diet alone during the first year of hemodialysis in type 2 diabetic patients with ESRD.

INTRODUCTION: Uremic type 2 diabetic patients on hemodialysis need various types of antidiabetic therapies. The aim of the present study was to identify differences between patients on oral antidiabetic drug therapy or insulin substitution or diet therapy alone during their first year of hemodialysis. PATIENTS AND METHODS: Sixty-four type 2 diabetic patients who had started hemodialysis (HD) at our dialysis center between 2003 and 2007 were included in the study. Kidney-transplanted patients (n = 1) and those with chronic infectious or malignant diseases (n = 4) were excluded. Patients were divided into three groups according to their antidiabetic therapy: group 1 consisted of patients on oral antidiabetic drug therapy (n = 12), group 2 of those on insulin therapy (n = 42), and group 3 of those being treated with diet alone (n = 10). At the start of HD and 12 months later, we measured fasting plasma glucose (FPG), HbA1c, the incidence of hypoglycemia (n/patient/month), cholesterol, triglycerides, body weight, and insulin requirements in the insulin-treated group. C-peptide was only measured at the start of dialysis. We evaluated changes in antidiabetic therapy during the first year on dialysis, and the prevalence of vascular disease in each group at the start of HD. RESULTS: FPG and HbA1c values were similar in all groups at the start of HD and after 1 year. Hypoglycemia occurred more frequently in insulin-treated patients; however, the difference was not significant. Cholesterol levels were similar in all groups, whereas triglycerides were significantly lower in insulin-treated patients (138 ± 28 vs. 176 ± 46 mg/dl; P < 0.05). Body weight was similar in all groups. No significant change in body weight was observed in any group after 12 months on dialysis. At the start of HD, C-peptide levels were lower in insulin-treated patients than in the other groups (1.8 ± 0.9 ng/ml vs. 2.2 ± 1.1 and 2.4 ± 1.1 ng/ml; P < 0.05). During the first 12 months on HD, two patients from group 1 were shifted to group 3 (diet alone), while four patients could reduce their drug dosage (33%). However, two subjects became insulin-dependent. In group 2, insulin therapy could be terminated in two cases, while the insulin dose could be reduced in 20 patients (48%). In group 3, one patient was switched to oral antidiabetic therapy. The prevalence of vascular disease was slightly higher in group 3 (NS). CONCLUSION: Within 1 year after the start of HD, the dose of sulfonylurea as well as insulin could be reduced in a large majority of patients. Metabolic control was similar in all groups. Only triglycerides were significantly lower in group 2. The frequency of hypoglycemia and the prevalence of vascular disease were just slightly higher in the group on insulin therapy.

Gross proteinuria and subacute renal failure after coronary angiography - a case report of cholesterol crystal embolization.

We report on a 55-year-old man who was admitted with increased serum-creatinine (3.4 mg/dl), gross proteinuria (4.6 g/24 h) and arterial hypertension. The medical history included hyperlipidemia, coronary artery disease (CAD) and a recent coronary angiography, but normal serum-creatinine and no proteinuria before coronary intervention. Serology and urinary analysis did not show any signs of a systemic disease. A renal biopsy, however, revealed multiple cholesterol crystal emboli in small vessels along with a typical infiltration of eosinophilic granulocytes. The patient was subsequently treated with an angiotensin-receptor-1 (AT1R) blocker and high-dose statins and was then evaluated for LDL-apheresis. Gross proteinuria was largely unaffected by (AT1R) blockade and renal function further declined necessitating, initiation of hemodialysis. Renal CCE with profound proteinuria is an unusual presentation of acute renal failure, potentially misleading and thereby prolonging correct diagnostics of a rare entity. Identification of high-risk patients is of utmost importance as efficient therapeutic strategies do not exist.

The position of the amino group on the benzene ring is critical for mesalamine's improvement of replication fidelity.

BACKGROUND: Individuals with ulcerative colitis are at high risk of developing colitis-associated cancer. 5-Aminosalicylate (5-ASA) protects from cancer by its antiinflammatory activity as well as by altering cell growth, inducing apoptosis, and reducing replication errors. So far neither 5-ASA's structural specificity nor its pharmacophore group have been identified. Here we compared 5-ASA with its analogs (4-ASA and 3-ASA) and its metabolite N-acetyl-5-ASA (NAc-5-ASA). METHODS: Superoxide scavenging was analyzed by lucigenin-amplified chemiluminescence. Cell growth, cell cycle distribution, and replication fidelity at a (CA)13 microsatellite were measured in HCT116 and HT29 colon epithelial cells by MTT and flow cytometry. Nuclear protein extracts were blotted for replication protein A (RPA), claspin, p53, and p53(Ser15). RESULTS: All compounds inhibited the growth of colon epithelial cells at a similar level and displayed potent scavenging properties, with 3-ASA being the most active, followed by 5-ASA, 4-ASA, and NAc-5-ASA. Besides 5-ASA, only 4-ASA caused an increase in the S-phase population (56%-69% and 49%-62% in HCT116 and HT29 cells, respectively). This was accompanied by nuclear recruitment of replication proteins RPA and claspin as well as phosphorylation of p53(Ser15), both of which were weaker or absent with 3-ASA or NAc-5-ASA. 5-ASA was the only compound that lowered mutations at a (CA)13 microsatellite. CONCLUSIONS: 5-ASA shares its growth inhibitory and superoxide scavenging properties with its structural analogs and metabolite, but the position of the amino group is critical for reducing replication errors.

Impact of smoking on progression of vascular diseases and patient survival in type-1 diabetic patients after simultaneous kidney-pancreas transplantation in a single centre.

We evaluated the impact of smoking on the progression of macro-angiopathy as well as patient and graft survival in 35 type-1 diabetic patients with simultaneous kidney-pancreas transplantation (SKPT). According to their smoking history, the patients were divided into smokers (n = 12) and nonsmokers (n = 23). Mean observation period was 80 (12-168) vs. 84 (12-228) months. The prevalence of vascular diseases as well as the incidence of vascular complications during the observation period was evaluated in each group. Graft- and patient survival were calculated. The prevalence of all vascular diseases was higher in the smokers with prior SKPT at the start as also at the end of study; however, the differences were not significant. In addition, the incidence of vascular complications (stroke, myocardial infarction and amputation) during the follow-up period was higher in the smoking group. Taking all vascular complications together (events/patient/year) the difference was significant (0.105 vs. 0.066, P < 0.05). One- and 5-year patient survival was 100% and 75% for smokers vs. 100% and 91% for nonsmokers. One- and 5-year pancreas graft survival at the same time was 100% and 75% in living smokers as well as 100% and 83% in the nonsmokers: We conclude that smoking after SKPT is associated with a progression of macro-angiopathy. Additionally, mortality after SKPT tends to be higher in smoking patients.