Serological Response to SARS-CoV-2 Vaccine in Hemodialyzed Patients and the Association with Later COVID-19 Positivity.

BACKGROUND: The effectiveness of the COVID-19 vaccine may differ in hemodialysis patients. The aim of this prospective multicenter study was to determine the degree of serological response to the SARS-CoV-2 vaccine in the population of dialysis patients and its association with later SARS-CoV-2 infections. METHODS: A blood sample was taken for the determination of COVID-19 serological status (IgG antibodies) in 706 dialysis patients 16 weeks after vaccination with the second dose (Pfizer-BioNTech). RESULTS: Only 314 (44.5%) hemodialyzed patients had a satisfactory response to the COVID-19 vaccine. Eighty-two patients (11.6%) had a borderline response, while 310 patients (43.9%) had an unsatisfactory (negative) post-vaccinal antibody titer. A longer dialysis vintage had an increased odds ratio (OR) of 1.01 for the occurrence of COVID-19 positivity after vaccination. In the group of subsequently positive patients, 28 patients (13.6%) died from complications of COVID-19. We have found differences in mean survival time between patients with and without appropriate responses to vaccination in favor of patients with a satisfactory serological response. CONCLUSIONS: The results showed that the dialysis population will not have the same serological response to the vaccine as the general population. The majority of dialysis patients did not develop a severe clinical picture or die at the time of positivity for COVID-19.

[Treatment of anemia in chronic kidney disease--position statement of the Croatian Society for Nephrology, Dialysis and Transplantation and review of the KDIGO and ERPB guidelines]. / Lijecenje anemije u kronicnoj bubreznoj bolesti--stav hrvatskog drustva za nefrologiju, dijalizu i transplantaciju i osvrt na preporuke KDIGO i ERBP.

Renal anemia is the result of chronic kidney disease (CKD) and deteriorates with disease progression. Anemia may be the first sign of kidney disease. In all patients with anemia and CKD, diagnostic evaluation is required. Prior to diagnosing renal anemia, it is necessary to eliminate the other possible causes. Direct correlation between the concentration of hemoglobin and the stage of renal failure is well known. Early development of anemia is common in diabetic patients. Correction of anemia may slow the progression of CKD. Anemia is an independent risk factor for developing cardiovascular disease in patients with CKD. Treatment of anemia in patients with CKD is based on current guidelines. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anemia in CKD patients and ERBP (European Renal Best Practice) group its position statement and comments on the KDIGO guidelines. The Croatian Society of Nephrology, Dialysis and Transplantation (HDNDT) has already published its own guidelines based on the recommendations and positive experience of European and international professional societies, as well as on own experience. The latest version of Croatian guidelines was published in 2008. Since then, on the basis of research and clinical practice, there have been numerous changes in the modern understanding of the treatment of anemia in CKD. Consequently, HDNDT hereby publishes a review of the recent recommendations of international professional societies, expressing the attitude about treating anemia in CKD as a basis for new guidelines tailored to the present time.

Visfatin is not associated with inflammatory markers in patients on hemodialysis.

BACKGROUND: Cardiovascular events are a major cause of death in patients with end-stage renal disease. Endothelial dysfunction represents a key event in atherosclerosis development and has been implicated in the pathophysiology of different forms of cardiovascular disease, including chronic kidney disease. In recent years, visfatin, a ubiquitous adipokine, has been described as a potent marker of endothelial inflammation and dysfunction. The aim of the study was to investigate the association of visfatin with well-known markers of inflammation and endothelial dysfunction. METHODS: Serum and plasma samples from 66 patients (40 males and 26 females) treated by hemodialysis were analysed for visfatin, fibrinogen, CRP, PAI-1 levels. Visfatin was determined by ELISA method while CRP, fibrinogen and PAL-1 were obtained by standard laboratory methods. RESULTS: We observed statistically significant correlation between visfatin level and fibrinogen (r = 0.51; p = 0.008) and the time on dialysis in female patients (r = 0.70; p < 0.001). PAI-1 and CRP did not correlate with visfatin in males nor in females. CONCLUSIONS: Visfatin is correlated with time on dialysis and with fibrinogen only in female dialysis patients. To confirm this, further studies are needed with a higher number of patients.

Bilateral Pseudomonas aeruginosa endogenous endophthalmitis in an immune-competent patient with nosocomial urosepsis following abdominal surgery.

Endogenous endophthalmitis is a vision-threatening condition that results from hematogenous spread of infection to the eye, originating from a distant primary focus. It is considered as a rare entity that predominantly occurs in immune-compromised patients. We present a case of a critically ill immune-competent patient who underwent abdominal surgery later followed by nosocomial urosepsis complicated with bilateral Pseudomonas aeruginosa endogenous endophthalmitis that resulted in blindness. This case is clinically important because of the absence of predisposing factors for this kind of eye infection.

[The impact of heparin bolus from dysfunctional lumen of dual lumen central venous catheter on activated partial thromboplastin time during hemodialysis: is additional heparinization necessary?]. / Utjecaj bolusa heparina iz nefunkcionalnog lumena dvoluminalnog centralnog venskog katetera na vrijednosti aktiviranog parcijalnog tromboplastinskog vremena tijekom hemodijalize: da li je potrebna dodatna heparinizacija tijekom hemodijalize?

AIM: The aim of the study was to determine the influence of the heparin bolus, which was administered to a patient due to incapability to aspire heparin from the dysfunctional lumen of dual lumen central venous catheter (CVK), on activated partial thromboplastin time (APTT) values during hemodialysis (HD), as well as to determine the need of additional administration of heparin during HD. PATIENTS AND METHODS: The first group of examinees consisted of 19 patients with chronic renal failure (CRF) on whom the dual lumen CVK was applied as temporary vascular access, whereby the aspiration of heparin from one of its lumens was impossible. Prior to HD, a coagulogram was determined for all the patients. The testing of this group was carried out in accordance with two different protocols: protocol A and protocol B. Under protocol A, 7,500 IU of unfractioned heparin was injected into the patients' circulation from the dysfunctional lumen of CVK. During the four-hour HD process, APTT were determined after ten minutes, after hours 1, 2 and 3, and at the end of HD. During HD, no heparin was administered and every hour during HD there was visual evidence of blood clots in portions of the extracorporeal circuit system. Under protocol B, the APTT values were determined in the same group of patients according to the previous protocol, with the exception of 750 IU of heparin per hour being administered by continuous infusion to the patients during hours 3 and 4. The second group of examinees consisted of patients with CRF who have undergone dialysis via an arteriovenous fistula, while the testing was carried out under protocol C. The examinees in this group received a bolus of 2,500 IU of heparin at the beginning of HD, followed by a continuous administration of 750 IU of heparin per hour during the first three hours of HD (a total of 4,750 IU during the entire HD). During hour 4, HD was carried out without the administration of heparin. The protocol of determining APTT was identical to that carried out on the previous group of patients. RESULTS: APTT values prior to HD: A=34.5 +/- 4.27 sec., B=32.38 +/- 4.16 sec. (p=0.457), C=33.66 +/- 3.63 sec. (p=0.245 in relation to protocol A and p=0.281 in relation to protocol B). APTT values ten minutes after the administration of the heparin bolus: A=210 +/- 21.42 sec., B=204.83 +/- 20.82 sec. (p=0.453), C=47.88 +/- 4.26 sec. (p=0.000 in relation to protocols A and B). APTT values after one hour: A=156 +/- 32.76 sec., B=159.66 +/- 30.39 sec. (p=0.377), C=43.88 +/- 4.5 sec. (p=0.000 in relation to protocols A and B). APTT values after two hours: A=81.54 +/- 0.41 sec., B=74.61 +/- 36.39 sec. (p=0.331), C=40.55 +/- 5.29 sec. (p=0.000 in relation to protocols A and B). APTT values after three hours: A=49.6 +/- 8.38 sec., B=59 +/- 8.93 sec. (p=0.395), C=37.88 +/- 2.58 sec. (p=0.000 in relation to protocols A and B). APTT values at the end of HD: A=40.5 +/- 3.97 sec., B=51.44 +/- 5.07 sec. (p=0.154), C=36.66 +/- 4.22 sec. (p=0.399 in relation to protocol A and p=0.222 in relation to protocol B). Clotting was noticed during the third hour of HD in 11 (57.89%) patients under protocol A, in two (10.5%) patients under protocol B and in three (15.78%) patients under protocol C. After comparing proportions for protocols A and C p=0.02, for protocols B and C p=0.998 and for protocols A and B p=0.006 CONCLUSION: Patients who received the heparin bolus from the dysfunctional lumen of dual lumen CVK needed an additional administration of heparin during hours 3 and 4 of HD in order to reduce the frequency of clotting in the extracorporeal circuit system. The frequency of clotting during HD in this study was not dependent on the total dosage of administered heparin, but rather on the means of its administration.

Survival analysis of 314 episodes of sepsis in medical intensive care unit in university hospital: impact of intensive care unit performance and antimicrobial therapy.

AIM: To evaluate epidemiology of sepsis in medical intensive care unit (ICU) in a university hospital, and the impact of ICU performance and appropriate empirical antibiotic therapy on survival of septic patients. METHODS: Observational, partly prospective study conducted over 6 years assessed all patients meeting the criteria for sepsis at ICU admission at the Sisters of Mercy University Hospital. Clinical presentation of sepsis was defined according to 2001 International Sepsis Definitions Conference. Demographic data, admission category, source of infection, severity of sepsis, ICU or hospital stay and outcome, ICU performance, and appropriateness of empirical antibiotic therapy were analyzed. RESULTS: The analysis included 314 of 5022 (6.3%) patients admitted to ICU during the study period. There were 176 (56.1%) ICU survivors. At the ICU admission, sepsis was present in 100 (31.8%), severe sepsis in 89 (28.6%), and septic shock in 125 (39.8%) patients with mortality rates 17%, 33.7%, 72.1%, respectively. During ICU treatment, 244 (77.7%) patients developed at least one organ dysfunction syndrome. Of 138 (43.9%) patients who met the criteria for septic shock, 107 (75.4) were non-survivors (P<0.001). Factors associated with in-ICU mortality were acquisition of sepsis at another department (odds ratio [OR] 0.06; 95% confidence interval [CI], 0.02-0.19), winter season (OR 0.42; 0.20-0.89), limited mobility (OR 0.28; 0.14-0.59), ICU length of stay (OR 0.82; 0.75-0.91), sepsis-related organ failure assessment (SOFA) score on day 1 (OR 0.80; 0.72-0.89), history of global heart failure (OR 0.33; 0.16-0.67), chronic obstructive pulmonary disease (COPD)-connected respiratory failure (OR 0.50; 0.27-0.93), septic shock present during ICU treatment (OR 0.03; 0.01-0.10), and negative blood culture at admission (OR 2.60; 0.81-6.23). Microbiological documentation of sepsis was obtained in 235 (74.8%) patients. Urinary tract infections were present in 168 (53.5%) patients, followed by skin or soft tissue infections in 58 (18.5%) and lower respiratory tract infections in 44 (14.0%) patients. Lower respiratory tract as focus of sepsis was connected with worse outcome (P<0.001). Empirical antibiotic treatment was considered adequate in 107 (60.8%) survivors and 42 (30.4%) non-survivors. Patients treated with adequate empirical antibiotic therapy had significantly higher survival time in hospital (log-rank, P=0.001). CONCLUSION: The mortality rate of sepsis was unacceptably high. The odds for poor outcome increased with acquisition of sepsis at another department, winter season, limited mobility, higher SOFA score on day 1, history of chronic global heart failure, COPD-connected respiratory failure, and septic shock present during ICU treatment, whereas longer ICU length of stay, positive blood culture, and adequate empirical antibiotic therapy were protective factors.

[Recirculation of urea and dialysis efficiency using dual-lumen dialysis catheters in various locations: may the venous lumen of the catheter be used as the arterial lumen and vice versa?]. / Recirkulacija ureje i ucinkovitost dijalize pri uporabi dvoluminalnih dijaliznih katetera razlicite lokalizacije: smije li se venski krak katetera rabiti kao arterijski i obrnuto?

AIM: To measure percentage of urea recirculation in hemodialysis by a dual-lumen central venous catheters of various localisations (e.g. jugular, subclavian and femoral), and also in cases when the venous lumen of the catheter is used as arterial lumen, and vice versa, and under these conditions to evaluate the efficiency of hemodialysis based on the measurements of urea reduction ratio. METHODS: Percentage of urea recirculation was measured in the patients with acute and chronic renal failure who underwent hemodialysis by a temporary dual-lumen central venous catheter of different localisations (jugular n = 16, subclavian n = 20, femoral n = 20). The measurements were done in cases when arterial line was connected to arterial lumen of the catheter, and venous line to the venous lumen of the catheter (correct connection = RI), and vice versa, i.e., when arterial line was connected to venous lumen of the catheter, and venous line was connected to arterial lumen of the catheter (reversed connection = R2). The efficiency of hemodialysis was evaluated by measuring urea reduction ratio in cases with the reversed (R2) connection. RESULTS: Statistically significant differences were found between R1 and R2 for jugular catheters (R1 = 2.38 +/- 1.09%, R2 = 7.59 +/- 1.42%, n = 16, p = 0), for subclavian catheters (R1 = 3.03 +/- 3.15%, R2 = 15.8 +/- 7.18, n = 20, p = 0), and for femoral catheters (R1 = 9 +/- 6.56%, R2 = 29.2 +/- 11.8%, n = 20, p = 0). Statistically significant differences were also found between R1 of jugular catheters and R1 of subclavian catheters (2.38 +/- 1.09%, n = 16 and 3.03 +/- 3.15%, n = 20, p = 0.0001), further on between R1 of jugular and R1 of femoral catheters (2.38 +/- 1.09%, n = 16 and 9 +/- 6.56%, n = 20, p = 0), as well as between R1 of subclavian and R1 of femoral catheters (2.38 +/- 1.09%, n = 20 and 9 +/- 6.56%, n = 20, p = 0.0001). Also statistically significant differences were found between R2 of jugular and subclavian catheters (7.59 +/- 1.42%, n = 16 and 15.8 +/- 7.18%, n = 20, p = 0.0003), between R2 of jugular and femoral catheters (7.59 +/- 1.42%, n = 16 and 29.2 +/- 11.8%, n = 20, p = 0.0007), and between R2 of subclavian and R2 of femoral catheters (15.8 +/- 7.18%, n = 20 and 29.2 +/- 11.8%, n = 20, p = 0.0029). The measurements of urea reduction ratio that we have done for some of the catheters under R2 conditions showed a statistically significant difference between femoral and subclavian catheters (51.45 +/- 5.62%, n = 20 and 63.75 +/- 7.61, n = 20, p = 0), and between femoral and jugular catheters (51.45 +/- 5.62%, n = 20 and 64.3 +/- 5.23%, n = 16, p = 0). No statistical differences were found in urea reduction ratio between jugular and subclavian catheters (64.3 +/- 5.23, n = 16 and 63.75 +/- 7.61%, n = 20, p = 0.8). CONCLUSION: When hemodialysis is delivered by a correct blood lines connection the measurements have shown a decrease in urea recirculation by 5% for jugular and subclavian catheters, and 5%-10% for femoral catheters. However, in cases when the venous lumen of the catheter is used as an arterial lumen, and vice versa, urea recirculation is below 10% for jugular catheters; whereas in femoral catheters the percentage is higher than 20%. Despite so high percentage of urea recirculation, that we obtained for such use of the catheters, urea reduction ratio in hemodialysis via jugular and subclavian catheters is > 60%, whereas via femoral catheters, the percentage is significantly lower. Consequently, the efficiency of hemodialysis is reduced, and such use of femoral catheters should therefore be avoided.

Clinical and neurohumoral response to posture, physical exercise, and ascites treatment in Child-Pugh C liver cirrhosis: randomized prospective trial.

AIM: To assess clinical and neurohumoral response to posture, physical exercise, and ascites treatment in patients with Child-Pugh C liver cirrhosis and tense ascites. METHOD: Fifty patients with Child-Pugh C liver cirrhosis and tense ascites were randomly allocated into 5 groups. Thirty patients were treated with paracentesis of 6 L of acites paralleled by plasma volume expansion with 200 mL of 20% low sodium albumin (10 patients), 600 mL fresh frozen plasma (10 patients), or 900 mL solution of synthetic gelatine (10 patients), ie, doses with comparable oncotic power, and bed rest for 24 h before and after the procedure. They were compared with 10 patients treated with paracentesis of 6 L of ascites without plasma volume expansion and no bed rest, and 10 patients treated with 40 mg of furosemide IV daily and no bed rest. Mean arterial pressure, heart rate, body weight loss, urine flow rate, creatinine clearance, plasma renin activity, plasma aldosterone concentration, and plasma atrial natriuretic peptide (ANP) were measured before the procedure and 6 hours, 2, 3, and 6 days after the procedure. RESULTS: Diuretic treatment and paracentesis of 6 L of ascites without plasma volume expansion and no bed rest 24 h before and after the procedure were associated with significant hypotension (p<0.01) during 6 days of the trial, tachycardia (p<0.01) on day 1 and 2 (p=0.012), lower total body weight loss (p=0.007), increase in plasma renin activity 6 hours after the beginning of the study (p=0.025) and on day 6 (p=0.024), increase in plasma aldosterone concentration on day 6 (p=0.030), no significant change in plasma ANP levels, and decrease in creatinine clearance on day 6 (p=0.046). Albumin was superior to the other plasma expanders. Comparison between groups treated with plasma volume expansion did not show significant differences in measured parameters at any time during the study. The differences were found in the amount of needed volume of each substitute, daily sodium balance on day 1 of the trial, increase in plasma aldosterone concentration in bed rest-paracentesis-polygeline group on day 6, and the increase in plasma ANP on day 1 (p=0.077), which was proportional to the amount of infused volume. CONCLUSION: Therapeutic paracentesis of 6 L of ascites, bed rest 24 h before and after the procedure, and intravenous substitution of volume with albumin, fresh frozen plasma, and solution of synthetic gelatine were safe, rapid, and effective treatments, provided that intravascular volume was substituted simultaneously.

[Is transfusion of a single dose of concentrated erythrocytes poor clinical practice?]. / Je li transfuzija jedne doze koncentriranih eritrocita losa klinicka praksa.

The aim of the study was to determine whether a single unit of red blood cell (RBC) transfusion is a true criterion of poor patient care. Medical records of 148 patients, 76 (51.4%) males, 72 (48.6%) females, mean age 66.88 +/- 14.56 years who have received a single unit RBC transfusion at the Department of Medicine in the period from 1997 to 2000 were retrospectively studied. Pretransfusion mean hemoglobin (Hb) value (Hb1) was 85.0 +/- 12.0 (mod 78) g/L, increasing to (Hb2) 96.9 +/- 11.8 (mod 90) g/L after transfusion and the last measured value (Hb3) was 98.2 +/- 13.4 (mod 102) g/L. Six patients (66.6%) of 9 with decrease in Hb3 value (group A) died, 13 patients (35.1%) of 37 with raise in Hb3 level < 5 g/L (group B) and 5-10 g/L (group C) died during the hospital stay vs. 7 patients (6.8%) of 102 with Hb3 level raise > 10 g/L (group D). The differences between the Hb2 and Hb1 values were significant considerably from the differences between the Hb3 and Hb1 values (p = 0.001), as well as the difference in the distribution of differences between Hb2 and Hb1 (p 0.028) and Hb3 and Hb1 (p = 0.001) according to the disease outcome and the difference in mortality of men and women (p = 0.021). 38.4% of the deceased patients were from the group of coronary syndrome and/or heart failure. Statistically significant were the differences between the arterial oxygen tension (PaO2) at Hb1 and Hb2 (p = 0.0001), as well as between the arterial oxygen saturation (SaO2) at the Hb1 and Hb2 values (p = 0.0001). There is no strict clinical indication for a single unit of RBC transfusion. Determinants of the need and amount of RBC transfusion except hemoglobin value include the etiology and duration of the anemia, the patient's ability to compensate for decreased oxygen carrying capacity and tissue oxygen requirements. The majority of a single unit RBC transfusion was appropriate for the clinical situation. Our data indicate that the use of smaller volumes of allogenic RBC transfusion was not a bad clinical practice.

Intensive care units in Croatia: 2001 survey.

AIM: To establish a framework for the Intensive Care Units (ICU) Register in Croatia, and examine the relation between their present organization and medical practices and their outcome performances. METHODS: The survey of a total of 123 ICUs in Croatia was conducted between February 1 and October 31, 2001. Census questionnaires were filled out by ICU chiefs of staff. Demographic data, data on hospital and ICU structure and organization, disposable equipment, admission and discharge decision-making, outcome, and patient demographic data were collected for February 1, 2001. Descriptive statistics was used for data analysis. RESULTS: On February 1, 2001, there were 123 ICUs in Croatia. The questionnaire was filled out by 117 ICU chiefs of staff (95% response rate). The total number of ICUs beds was 900, comprising 3.3% of all hospital beds. Croatian ICUs were divided into 13 subtypes; 89% of them were adjoined to hospital departments of various subspecialties and only 13 (11%) were freestanding. The number of ICUs per hospital, number of ICU beds, quantity of disposable equipment, and number of permanently employed medical and nursing staff within hospitals and individual units increased as hospitals enlarged. Also, the number of mixed surgical/medical and coronary care/medical units decreased, and specialized units became prevalent. The mortality data in Croatian ICUs were similar to those reported elsewhere in the world: the lowest mortality was found in psychiatric ICUs (3%) and the highest in an ICU for infective diseases (30%), followed by neurological (19%), medical (17%), and respiratory (16%) ICUs. CONCLUSION: Establishing a database on intensive care medicine and assessing the performance of ICUs in Croatia could serve as a model for improvement of ICU service in other transition countries.

[Pregnancy in patients treated with hemodialysis and peritoneal dialysis: review of the literature and management guidelines]. / Trudnoca u bolesnica lijecenih hemodijalizom i peritonejskom dijalizom: pregled literature za vodenje trudnoce i poroda.

Pregnancy in patients suffering from chronic renal disease is still a rare phenomenon due to a number of factors that impair fertility in such patients, in spite of a number of new treatment techniques that have been introduced recently, e.g. renal replacement therapy with biocompatible dialysis membranes, highflux dialyzers, erythropoietins, and new types of peritoneal dialysis and higher level of care for such patients. Yet, when pregnancy occurs, it is possible to provide a safe outcome for both the mother and fetus. However, optimal conditions for hemodialysis and peritoneal dialysis should be provided. The data on pregnancy in patients suffereing from chronic renal disease are rather scarce, and have been derived from registers of dialyzed patients from few countries. Unfortunately, no such data are known for the patients in Croatia. This review deals with the specific approach to hemodialysis and peritoneal dialysis in patients with pregnancy and end-stage renal disease. Particular attention is paid to specific problems associated with gestation, delivery and care for patients, with special reference to prenatal and neonatal care.