The role of apheresis and insulin therapy in hypertriglyceridemic acute pancreatitis-a concise review.

Severe hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP) and is involved in its pathogenesis. Chylomicrons increase blood viscosity and induce ischemia, while free fatty acids induce inflammation and distant organ damage. Conservative treatment options include fasting and insulin; limited evidence shows their comparable efficacy. Plasma exchange might provide more rapid lowering of triglycerides and amelioration of systemic effects of severe AP. Available data from controlled studies show only moderately faster lowering of triglycerides with apheresis (about 70% vs. 50% with conservative treatment within 24 h) and limited data from non-randomized studies show no improvement in clinical outcomes. New evidence is expected soon from ongoing large randomized trials. Until then, insulin may be used in mild HTG-AP and plasma exchange should be considered only in severe HTG-AP, especially if the decline of triglycerides with conservative treatment is slow, and in HTG-AP during pregnancy.

A matched case-control study on the effectiveness of extracorporeal cytokine adsorption in critically ill patients.

Extracorporeal cytokine adsorption aims to reduce cytokine levels in critically ill patients. However, little convincing data exist to support its widespread use. This retrospective study compared interleukin-6 (IL-6) levels in patients treated with or without cytokine adsorber (CytoSorb®). Intensive care patients between Jan 2017 and Dec 2021 who had at least two IL-6 measurements were included. They were divided into an adsorber group and a standard of care group. We screened 3865 patients and included 52 patients in the adsorber group and 94 patients in the standard of care group. Matching was performed and the groups were compared regarding IL-6, lactate, CRP, procalcitonin, vasopressor requirement, and mortality rate. After matching, there were 21 patients in each group. Patients had similar age, ECMO and renal replacement therapy use, baseline noradrenaline requirement, serum lactate, pH, CRP, and IL-6 levels. There were no significant differences in the time course of IL-6, lactate, CRP, procalcitonin and noradrenaline requirement between groups. Two-day and ICU mortality and Kaplan-Meier estimated survival were also comparable. In this matched case-control study no difference in IL-6, inflammatory parameters, noradrenaline requirement or mortality was observed between patients treated with adsorber or standard of care.

The Role of Ultrasound Examination in the Assessment of Suitability of Calcified Arteries for Vascular Access Creation-Mini Review.

Arterial calcifications are present in 20-40% of patients with end-stage kidney disease and are more frequent among the elderly and diabetics. They reduce the possibility of arterio-venous fistula (AVF) formation and maturation and increase the likelihood of complications, especially distal ischemia. This review focuses on methods for detecting arterial calcifications and assessing the suitability of calcified arteries for providing inflow before the construction of an AVF. The importance of a clinical examination is stressed. A grading system is proposed for quantifying the severity of calcifications in the arteries of the arm with B-mode and Doppler ultrasound exams. Functional tests to assess the suitability of the artery to provide adequate inflow to the AVF are discussed, including Doppler indices (peak systolic velocity and resistive index during reactive hyperemia). Possible predictors of the development of distal ischemia are discussed (finger pressure, digital brachial index, acceleration and acceleration time), as well as the outcomes of AVFs placed on calcified arteries. It is concluded that a noninvasive ultrasound examination is probably the best tool for a morphologic and functional assessment of the arteries. An arterial assessment is of utmost importance if we are to create distal radiocephalic AVFs in our elderly patients whenever possible without burdening them with futile surgical attempts.

Doppler ultrasound assessment of calcified radial arteries prior to radio-cephalic arterio-venous fistula placement: an observational study.

BACKGROUND: In elderly and diabetic patients, arterial calcifications are prevalent and result in worse outcomes of arterio-venous fistulas (AVFs). Optimal ultrasound criteria for assessment of calcified arteries are unknown. We report our experience with ultrasound assessment of calcified arteries prior to placement of radio-cephalic (RC) AVFs. MATERIAL AND METHODS: We included 85 patients in whom a RC-AVF placement was planned. Patients were divided according to the presence of radial artery calcifications into a calcified group (moderate/severe calcifications, N = 18) and control group (no changes/mild atherosclerosis, N = 67). Doppler ultrasound parameters were analyzed in the calcified group with focus on assessment of the artery, including grading of calcifications and Doppler measurements at rest and during reactive hyperemia (RH). RESULTS: In the calcified group mean patients' age was 72 ± 11 years, 72% were diabetics, mean resistance index (RI) during RH was 0.78 ± 0.09 (range 0.63-0.90). In 14 (78%) patients an AVF was successfully placed and in 12 it matured (67% maturation rate). A lower RI at rest was observed in the primary failure sub-group with high area under the ROC curve (0.89) and a cut-off value of 0.90 for RI. There was no difference in RI at RH between failed and matured AVFs. 1-year secondary patency was 66% and in eight patients with follow-up ultrasound available, blood flow was 350-1300 ml/min. For comparison, in the control group a radio-cephalic AVF was placed in all patients, primary failure rate was 6%, maturation rate 85% and 1-year secondary patency was 77%. CONCLUSIONS: Our very limited experience suggests that successful RC-AVF placement and maturation with good 1-year patency rates is possible in patients with moderately/severely calcified arteries and RI during RH of up to 0.90.

Effect of CytoSorb Coupled with Hemodialysis on Interleukin-6 and Hemodynamic Parameters in Patients with Systemic Inflammatory Response Syndrome: A Retrospective Cohort Study.

Excessive release of cytokines during systemic inflammatory response syndrome (SIRS) often leads to refractory hypotension and multiple organ failure with high mortality. Cytokine removal with hemoadsorption has emerged as a possible adjuvant therapy, but data on interleukin-6 (IL-6) reduction and outcomes in clinical practice are scarce. We aimed to evaluate the effect of CytoSorb hemoadsorption on laboratory and clinical outcomes in shocked patients with SIRS. We designed a retrospective analysis of all patients with SIRS treated with CytoSorb in intensive care units (ICU). IL-6, laboratory and hemodynamic parameters were analyzed at approximate time intervals during CytoSorb treatment in the whole cohort and in a subgroup with septic shock. Observed and predicted mortality rates were compared. We included 118 patients with various etiologies of SIRS (septic shock 69%, post-resuscitation shock 16%, SIRS with acute pancreatitis 6%, other 9%); in all but one patient, CytoSorb was coupled with renal replacement therapy. A statistically significant decrease in IL-6 and vasopressor index with an increase in pH and mean arterial pressure was observed from 6 h onward. The reduction of lactate became significant at 48 h. Results were similar in a subgroup of patients with septic shock. Observed ICU and in-hospital mortalities were lower than predicted by Sequential Organ Failure Assessment (SOFA) (61% vs. 79%, p = 0.005) and Acute Physiology and Chronic Health Evaluation (APACHE) II (64% vs. 78%, p = 0.031) scores. To conclude, hemoadsorption in shocked patients with SIRS was associated with a rapid decrease in IL-6 and hemodynamic improvement, with improved observed vs. predicted survival. These results need to be confirmed in a randomized study.

Comparable Triglyceride Reduction With Plasma Exchange and Insulin in Acute Pancreatitis - A Randomized Trial.

Background and Aims: Both insulin and plasma exchange (PE) are used in hypertriglyceridemic acute pancreatitis (HTG-AP). Our aim was to compare the efficacy of both treatments. Methods: A randomized, parallel group study performed in a tertiary hospital in 22 HTG-AP patients with non-severe prognosis and triglycerides between 15 and 40 mmol/L. Patients were randomized to daily PE or insulin infusion until triglycerides were <10 mmol/L. Primary outcome was % reduction in triglycerides within 24 h. Secondary outcomes were days needed to lower triglycerides <10 mmol/L, highest CRP and percentage of patients with a severe course of pancreatitis. Results: There was a trend toward a greater decrease in triglycerides within the first 24 h in the PE group (67 ± 17% vs. 53 ± 17%, p = 0.07), but the absolute difference was modest [mean difference of 6 mmol/L (14% of initial value)]. Triglycerides fell below 10 mmol/L in a median (IQR) of 1 (1-2) and 2 (1-2) days, respectively (p = 0.25). Secondary outcomes related to disease severity were also comparable: highest CRP 229 vs. 211 mg/L (p = 0.69) and severe course of pancreatitis in 2/11 cases in both groups (p = 1.0). Regarding treatment complications, there was one mild hypoglycemia and one allergic reaction during PE. Survival was 100% in both groups. Conclusion: There was no significant difference, but only a trend toward a greater decrease in triglycerides with PE, and the clinical course was also comparable. These results do not support universal use of PE in patients with HTG-AP. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02622854].

Extracorporeal Removal of Myoglobin in Patients with Rhabdomyolysis and Acute Kidney Injury: Comparison of High and Medium Cut-Off Membrane and an Adsorber Cartridge.

INTRODUCTION: The role of extracorporeal myoglobin removal in the treatment of rhabdomyolysis-associated severe acute kidney injury (AKI) is not yet fully established. High cut-off (HCO) and medium cut-off (MCO) dialysis membrane and cytokine adsorber (CytoSorb®) have been used to this purpose in clinical practice. The data on comparative effectiveness of those methods are scarce. METHODS: In this single-center retrospective study, we included patients with AKI and concomitant rhabdomyolysis (myoglobin >20,000 µg/L), who underwent at least one extracorporeal myoglobin removal procedure. The main outcome parameter was myoglobin reduction ratio, whereas albumin was assessed as a safety parameter. RESULTS: We analyzed data for 15 patients, who underwent 28 procedures (13 HCO, 9 MCO, and 6 adsorber). Pre-treatment serum myoglobin levels were similar between the groups and myoglobin reduction was significant in HCO (p = 0.03) and MCO groups (p < 0.01) and borderline significant in adsorber group (p = 0.06). Reduction ratios were comparable between the groups (median 0.64 (inter-quartile range IQR 0.13-0.72), 0.54 (IQR 0.51-0.61) and 0.50 (IQR 0.37-0.62), respectively, p = 0.83). Both pre- and post-procedure serum albumin levels were significantly lower in the MCO group. However, with routine albumin substitution in the HCO group only, serum albumin remained stable during the procedures in all subgroups. CONCLUSIONS: Novel MCO membrane might represent the optimal mode of treatment of severe rhabdomyolysis-associated AKI, as it allows for efficient removal of myoglobin, avoids albumin supplementation and is associated with lower costs. For patients requiring cytokine removal, the adsorption capsule can simultaneously reduce cytokine and myoglobin levels.

Treatment of preeclampsia at extremely preterm gestation with therapeutic plasma exchange.

AIMS: Different forms of apheresis have been proposed as potential therapeutic approaches to remove soluble Fms-like tyrosine kinase-1 (sFlt-1) and allow safe pregnancy prolongation in cases of extremely preterm preeclampsia. This is a follow-up study presenting our experiences with therapeutic plasma exchange (TPE) in 5 women with preeclampsia at < 28 weeks of gestational age. MATERIALS AND METHODS: All women received standard treatment for preeclampsia and 2 - 3 TPE treatments per week. Blood samples for sFlt-1 and placental growth factor (PlGF) measurements were collected before and after each TPE. RESULTS: Seventeen TPE procedures were performed, 2 - 5 per patient. TPE significantly reduced sFlt-1 (by 35 ± 6%), sFlt-1/PlGF ratio (by 24 ± 13%), and to a lesser degree also PlGF (by 12 ± 16%), with a rebound observed on day 1 post procedure. TPE procedures were well tolerated by pregnant women and fetuses. Stabilization of sFlt-1 allowed pregnancy prolongation for a median of 8 (range 2 - 14) days from first TPE and for a median of 10 (range 4 - 17) days from hospital admission. There were no signs of increased risks of adverse neonatal outcome associated with TPE. One neonate died due to extreme prematurity 3 days after delivery, 2 had bronchopulmonary dysplasia, and 1 had retinopathy of prematurity. CONCLUSION: This study provides new evidence of effective reduction in sFlt-1 and sFlt-1/PlGF ratio with TPE treatment, which seems to allow a clinically meaningful prolongation of pregnancy. Controlled studies are necessary to convincingly show the potential benefit of apheresis treatment in preeclampsia at extremely preterm gestation.

A national cohort study on hemodialysis arteriovenous fistulas after kidney transplantation - long-term patency, use and complications.

OBJECTIVE: To describe the long-term hemodialysis arteriovenous fistula (AVF) patency, incidence of AVF use, incidence and nature of AVF complications and surgery in patients after kidney transplantation. PATIENTS AND METHODS: We retrospectively analysed the AVF outcome and complications in all adult kidney allograft recipients transplanted between January 1st, 2000 and December 31, 2015 with a functional AVF at the time of transplantation. Follow-up was until December 31, 2019. RESULTS: We included 626 patients. Median AVF follow-up was 4.9 years. One month after kidney transplantation estimated AVF patency rate was 90%, at 1 year it was 82%, at 3 years it was 70% and at 5 years it was 61%; median estimated AVF patency was 7.9 years. The main cause of AVF failure was spontaneous thrombosis occurring in 76% of AVF failure cases, whereas 24% of AVFs were ligated or extirpated. In a Cox multivariate model female sex and grafts were independently associated with more frequent AVF thrombosis. AVF was used in about one third of our patients. AVF-related complications occurred in 29% of patients and included: growing aneurysms, complicated thrombosis, high-flow AVF, signs of distal hypoperfusion, venous hypertension, trauma of the AVF arm, or pain in the AVF/arm. CONCLUSIONS: AVFs remain functional after kidney transplantation in the majority of patients and are often re-used after graft failure. AVF-related complications are common and require proper care.

Biocompatibility Parameters with Standard and Increased Dose of Citrate in Hemodialysis-A Randomized Trial.

BACKGROUND: The dose of citrate needed in regional citrate anticoagulation (RCA) to achieve optimal biocompatibility is unknown. We performed a randomized trial comparing two doses (ACTRN12613001340729). METHODS: In 30 patients a single hemodialysis with either standard (2.7 mmol/L) or increased dose of citrate (4 mmol/L) was performed. C5a-desArg, myeloperoxidase (MPO), thrombin-antithrombin complex (TAT), and platelet factor 4 (PF4) were measured and the inner surface of the dialyzer fibers was evaluated with scanning electron microscopy (SEM). RESULTS: A good separation of anticoagulation effect was achieved (post-filter ionized calcium 0.20 vs. 0.31 mmol/L, p < 0.05). There was no effect of citrate dose on any of the biocompatibility parameters; transient and parallel increase in PF4 after 30 min and parallel increase in TAT after 4 h were observed. There were no visually detected clotting problems within the circuit and no significant hypocalcemia in either group. SEM clotting score was excellent and comparable in both groups (p = 0.59). CONCLUSIONS: Given the excellent results in both groups, absence of between group differences and inability of the increased dose of citrate to completely blunt the small residual increase in PF4 and TAT, we conclude that the standard dose of citrate seems sufficient in RCA for chronic hemodialysis.

Therapeutic plasma exchange and dextran-sulfate plasma adsorption as extracorporeal treatments of extremely preterm preeclampsia with fetal growth restriction.

AIM: To evaluate effectiveness and safety of therapeutic plasma exchange (TPE) and dextran-sulfate plasma adsorption (DSA) for extracorporeal removal of soluble Fms-like tyrosine kinase-1 (sFlt-1) as part of expectant management of preeclampsia at extremely preterm gestational age. METHODS: Retrospective case series of six patients with preeclampsia at <28 weeks of gestation, treated with DSA or TPE. Laboratory results, clinical characteristics and neonatal outcomes were collected from charts and National Perinatal Information System. RESULTS: Fetal growth restriction (FGR) was diagnosed in all cases. Pregnancy was prolonged for a median of 14 (range 5-74) days from admission and 10 (3-73) days from first apheresis. A mixed effects model showed a decrease in sFlt-1 and sFlt-1/PlGF ratio during DSA/TPE (significant effect of time [before/after]), which was comparable between DSA and TPE (no effect of procedure type). Median absolute reduction in sFlt-1 was 42% (inter-quartile range [IQR] 13%-57%) during DSA and 34% (16%-40%) during TPE; for sFlt-1/PlGF ratio it was 29% (22%-36%) and 38% (29%-42%), respectively. All procedures were well tolerated by fetuses. Anaphylactoid reaction, often with angioedema, occurred in 4/6 patients undergoing DSA and was attributed to bradykinin activation. One patient developed wound hematoma after cesarean section, possibly attributed to depletion coagulopathy. CONCLUSIONS: As potential novel treatment of early preeclampsia, a non-selective and widely available TPE was comparable to DSA regarding sFlt-1 reduction but was associated with fewer side-effects. Both seem to allow maternal stabilization and pregnancy prolongation even when early preeclampsia is complicated by FGR.

Clinical and dialysis-related characteristics of extremely long-term hemodialysis survivors: Three case reports.

More than 40-year hemodialysis survivors are living evidence of the achievements of hemodialysis therapy. We present the case reports of three patients treated by chronic hemodialysis for 47 (Patient 1), 43 (Patient 2), and 42 years (Patient 3) from a single center. These patients possess characteristics that were already shown to be associated with improved long-term survival: initiation of hemodialysis at a young age, absence of diabetes, and a relatively low and stable body weight with good nutritional status. Although all of them underwent complications of long-term hemodialysis treatment, they lived (Patient 3), or are still living (Patients 1 and 2), an independent and full life. Their hemodialysis prescriptions included long sessions with a moderate blood flow rate, state-of-the-art hemodialysis technology, vascular access surgeries and care provided by nephrologists, good overall management of chronic kidney disease, and preventive measures and/or immediate action in case of cardiovascular disease.

Regional citrate anticoagulation for continuous renal replacement therapy in newborns and infants: Focus on citrate accumulation.

Continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in newborns and infants is challenging and accumulation of citrate can occur. There are only a few studies reporting the detailed data on RCA. We aimed to analyze RCA-CRRT at our institution with focus on citrate accumulation. Critically ill newborns and infants up to 11 kg of body weight (BW), treated with RCA-CRRT in the 2011-2016 period were included in this retrospective observational study. Prismaflex(R) and Multifiltrate-CiCa(R) dialysis monitors were used with either automated or manual RCA. Data was collected regarding the circuit lifetime, parameters of RCA, markers of citrate accumulation (total/ionized calcium ratio > 2.5), and metabolic complications. We included 10 children with mean age of 2.6 ± 3.8 months and BW of 4.6 ± 2.7 kg. In-hospital mortality was 60%. RCA-CRRT parameters were: blood flow 46 ± 9 mL/min (12 ± 5 mL/min/kg BW), citrate dose 2.8 ± 0.6 mmol/L of blood resulting in estimated citrate load to the patient of 1.7 ± 0.8 mmol/h/kg BW. In total, 57 dialysis circuits were used with mean filter lifetime of 39 ± 29 h. Citrate accumulation (total/ionized calcium ratio > 2.5) was observed in 7/10 patients and in 14/57 (25%) of circuits; those circuits were performed in children with lower age and BW, had higher relative blood flow and citrate load, while citrate dose was similar. When citrate load to the patient was used to predict citrate accumulation, AUC under the ROC curve was 0.78 and 1.7 mmol/h/kg BW was considered the optimal cutoff value (sensitivity 71% and specificity 72%). CRRT with RCA using equipment, developed for adult population, is feasible in newborns and infants. Signs of citrate accumulation developed relatively often. To prevent it, we suggest avoiding citrate loads above 1.7 mmol/h/kg BW, which can best be achieved by keeping the blood flow below 9 mL/min/kg BW.

Distal Arterial Embolization from an Abandoned Native Brachio-Cephalic Fistula: A Case Report.

Abandoned thrombosed arterivenous fistulas are usually left in place with very rare complications. We describe a case of distal embolization from a thrombosed aneurismatic arteriovenous brachiocephalic fistula in a patient who vigorously used the affected arm for pushing his wheelchair. Vigorous physical activity with the hand bearing arteriovenous fistula (AVF) should probably be discouraged even after AVF thrombosis and especially, if the initial part of fistula vein is aneurysmatic. Antiagregation therapy should be considered in such cases.

Influence of citrate concentration on the activation of blood cells in an in vitro dialysis setup.

BACKGROUND: Regional citrate anticoagulation has been associated with enhanced biocompatibility in hemodialysis, but the optimal dose of citrate remains to be established. Here, we compared parameters related to cellular activation during in vitro dialysis, using two doses of citrate. METHODS: Human whole blood, anticoagulated with either 3 mM or 4 mM of citrate, was recirculated in an in vitro miniaturized dialysis setup. Complement (C3a-desArg), soluble platelet factor 4 (PF4), thromboxane B2 (TXB2), myeloperoxidase (MPO), as well as platelet- and red blood cell-derived extracellular vesicles (EV) were quantified during recirculation. Dialyzer fibers were examined by scanning electron microscopy after recirculation to assess the activation of clotting and the deposition of blood cells. RESULTS: Increases in markers of platelet and leukocyte activation, PF4, TXB2, and MPO were comparable between both citrate groups. Complement activation tended to be lower at higher citrate concentration, but the difference between the two citrate groups did not reach significance. A strong increase in EVs, particularly platelet-derived EVs, was observed during in vitro dialysis for both citrate groups, which was significantly less pronounced in the high citrate group at the end of the experiment. Assessment of dialyzer clotting scores after analysis of individual fibers by scanning electron microscopy revealed significantly lower scores in the high citrate group. CONCLUSIONS: Our data indicate that an increase in the citrate concentration from 3 mM to 4 mM further dampens cellular activation, thereby improving biocompatibility. A concentration of 4 mM citrate might therefore be optimal for use in clinical practice.