Use of Therapeutic Apheresis methods in Neurology patients.

The therapeutic apheresis consists of a continuously improving therapeutic method for diseases with high mortality and morbidity, especially in cases with poor outcome by using current medications. Neurology is one the most famous and at the same most interesting era of apheresis intervention in clinical practice.

Therapeutic Apheresis and Nephrologist: New and old aspects.

The clinical efficacy of therapeutic apheresis is still controversial. We undertook a retrospective review of apheresis treatment to ascertain its safety and efficacy. The therapeutic apheresis consists of a continuously improving therapeutic method for diseases with high mortality and morbidity, especially in cases with poor outcome by using current medications.

Use of therapeutic apheresis methods during pregnancy.

This review will focus on the current application of TA in pregnancy and possible aspects for future studies. It seems that scientific interest and field for further research in pregnancy is lately focused in specific removal of pathogens implicated in the physiologic mechanism of pre-eclampsia/HELLP syndrome as well as recurrent pregnancy failure.

Dialysis Patients Respond Adequately to Influenza Vaccination Irrespective of Dialysis Modality and Chronic Inflammation.

(1) Background: Chronic inflammation and suboptimal immune responses to vaccinations are considered to be aspects of immune dysregulation in patients that are undergoing dialysis. The present study aimed to evaluate immune responses in hemodialysis (HD) and online hemodiafiltration (OL-HDF) patients to a seasonal inactivated quadrivalent influenza vaccine (IQIV). (2) Methods: We enrolled 172 chronic dialysis patients (87 on HD and 85 on OL-HDF) and 18 control subjects without chronic kidney disease in a prospective, cross-sectional cohort study. Participants were vaccinated with a seasonal IQIV, and antibody titers using the hemagglutination inhibition (HI) assay were determined before vaccination (month 0) and 1, 3, and 6 months thereafter. Demographics and inflammatory markers (CRP, IL-6, IL-1ß) were recorded at month 0. The primary endpoints were the rates of seroresponse (SR), defined as a four-fold increase in the HI titer, and seroprotection (SP), defined as HI titer ≥ 1/40 throughout the study period. Statistical analyses were conducted in R (version 3.6.3) statistical software. The differences between groups were analyzed using chi-square and t-test analyses for dichotomous and continuous variables, respectively. To identify independent determinants of SR and SP, generalized linear models were built with response or protection per virus strain as the dependent variable and group, age, sex, time (month 0, 1, 3, 6), diabetes, IL-6, dialysis vintage, HD access, and HDF volume as independent explanatory variables. (3) Results: SR and SP rates were similar between control subjects, and dialysis patients were not affected by dialysis modality. SP rates were high (> 70%) at the beginning of the study and practically reached 100% after vaccination in all study groups. These results applied to all four virus strains that were included in the IQIV. IL-6 levels significantly differed between study groups, with HD patients displaying the highest values, but this did not affect SP rates. (4) Conclusions: Dialysis patients respond to influenza immunization adequately and similarly to the general population. Thus, annual vaccination policies should be encouraged in dialysis units. OL-HDF reduces chronic inflammation; however, this has no impact on SR rates.

Soluble urokinase plasminogen activator receptor and its complicated role in hemodialysis (HD) patients with Covid-19 infection.

BACKROUND: Soluble urokinase plasminogen receptor (suPAR) is a protein in the blood that has been described to reflect the severity status of systemic inflammation. AIMS AND OBJECTIVE: We investigated the association between admission suPAR levels and severity and outcome of HD patients with Covid-19 infection. MATERIALS AND METHODS: In an observational study of adult HD patients hospitalized for Covid-19, we measured suPAR levels in plasma samples. The time table for those measurements were as follows: at the beginning of admission, after a hemoperfusion (HP) session for those patients that received them, and just before discharge. RESULTS: Of the 17 patients (7 were male), 13 patients received HP (mean age: 74 years old). The median suPAR level was 12.94 ng/ml. For those who undertook HP in HD unit the median suPAR level before the session was 12.95 ng/mil and 6.2 ng/ml at the end of each session (p < 0.05). 3 patients had a suPAR level below 7 ng/ml. 2 of them survived without developing pleural effusions. 7 patients were discharged from the hospital with median suPAR level 12.08 ng/ml which did not differ significantly from the median suPAR level of the deceased ones (13.68 ng/ml). CONCLUSION: Admission levels of suPAR in HD patients hospitalized for Covid-19 do not seem to be predictive for their clinical course in general. Chronic Kidney Disease and its relation to suPAR independently of patients' inflammation status may be the key component for our notice. Despite that, in patients where low levels of suPAR combined with absence of pleural effusions the prognosis was excellent.

Effectiveness of hemoperfusion (HP) in hemodialysis (HD) patients with Covid-19 infection.

INTRODUCTION: The aims of this study are to observe the clinical course of all patients affected by infection with SARS-CoV-2 undergoing HD focusing on the impact of HP. METHODS: Patients were divided into Group A: HD sessions with HP and Group B: patients without HP. We registered all the data regarding patients' clinical course. RESULTS: 13 patients have been enrolled in group A. 9 patients were discharged from the hospital after 43 days (range: 35-56). 30 days was the mean hospitalization stay for the deceased. We did not observe any side effects with HP cartridges. 9 patients did not receive HP during their hospitalization. For those who represented as symptomatic, 8 out of 9 patients died after 6 days of hospitalization (range: 1-14), 2 of them in ICU. CONCLUSION: HP seems to be a helpful, safe and quite efficient tool in the battle against Covid-19 in HD patients.

HCV viraemia in anti-HCV-negative haemodialysis patients: Do we need HCV RNA detection test?

BACKGROUND: Hepatitis C virus (HCV) infection is still common among dialysis patients, but the natural history of HCV in this group is not completely understood. The KDIGO HCV guidelines of 2009 recommend that chronic haemodialysis patients be screened for HCV antibody upon admission to the dialysis clinic and every 6 months thereafter if susceptible to HCV infection. However, previous studies have shown the presence of HCV viraemia in anti-HCV-negative haemodialysis patients as up to 22%. OBJECTIVES: To evaluate the presence of HCV viraemia, using HCV RNA detection, among anti-HCV-negative haemodialysis patients from a tertiary dialysis unit in Athens. METHODS: We enrolled 41 anti-HCV-negative haemodialysis patients diagnosed with third-generation enzyme immunoassay. HCV viraemia was evaluated using a sensitive (cut-off: 12 IU/mL) reverse transcriptase polymerase chain reaction (COBAS AmpliPrep/TaqMan system) for HCV RNA. RESULTS: None of the 41 anti-HCV-negative haemodialysis patients were shown to be viraemic. CONCLUSIONS: Routine HCV RNA testing appears not to be necessary in anti-HCV-negative haemodialysis patients.

Evidence for Hypothalamus-Pituitary-Adrenal Axis and Immune Alterations at Prodrome of Psychosis in Males.

We aimed to investigate the inflammatory substrate in psychosis by evaluating both the Hypothalamus-Pituitary-Adrenal axis function and immune state at prodrome. This involved the recruitment of Ultra High Risk (UHR) of Psychosis subjects, Healthy Controls (HC) and patients with established Schizophrenia (CHRON). Serum cortisol at 3 different times throughout the day was measured. The Dexamethasone Suppression Test was performed plus 12 circulating cytokines were measured. The UHR subjects presented increased IL-4 levels compared with both the HC and CHRON patients. In contrast the UHR differed only from the CHRON group regarding the endocrine parameters. In conclusion, IL-4 appears to play a key role at prodrome.

Evidence for increased immune mobilization in First Episode Psychosis compared with the prodromal stage in males.

The aim of the study was to gauge both the immune and neuroendocrine function in Ultra High Risk for psychosis (UHR) subjects and compare them with a cohort presenting with First Episode Psychosis (FEP). We recruited two groups, the first group consisted of 12 UHR males and the second of 25 males with FEP. We measured serum cortisol levels at 08:00, 12:00, 18:00 with their Area Under Curve with respect to the ground (AUCg) and the increase (AUCi) and we measured serum cytokines levels, Interleukin-1a, IL-1a, IL-2, IL-4,IL-5,IL-6,IL-8, IL-10,IL-12, IL-17a, Tumor Necrosis Factor-a (TNF-a), Interferon-γ (IFN-γ). Dexamethasone Suppression Test (DST) was also performed . The results suggest higher levels of both pro-inflammatory (TNF-a, IL-2, IL-12, IFN-γ) and anti-inflammatory (IL-10) cytokines in the FEP group compared with the UHR counterparts. Regarding the HPA axis function, the prodromal subjects showed a trend for higher AUCg and AUCi change/decrease cortisol levels. On the contrary, the DST results did not differ between the groups. No significant associations were demonstrated within each group among cytokines, cortisol and psychopathology. The findings favor a hypothesis of a relatively increased mobilization of both the pro- and anti-inflammatory cytokine networks, in FEP compared with that of UHR subjects.

Adult polycystic kidney disease: who needs hospital follow-up?

Clinical data from 120 adult patients with genetically undifferentiated polycystic kidney disease who had been followed up for more than 3 months (range 3-172) were reviewed in order to try to identify clinical indicators that might predict deterioration in renal function. They were split into two groups dependent on whether annualized fall in estimated glomerular filtration rate (ΔeGFR mL/min/1.73 m(2) /year) was statistically significant or not. Only 26 patients (22%) had a statistically significantly decreasing ΔeGFR with a median decrease of -2.6 mL/min/1.73 m(2) /year (range -6.2 to -0.7). There was no difference in initial age, gender, or racial distributions between the groups or in initial eGFR. Follow-up was longer (median 86, range 23-172 months vs. 46, range 3-161 months; P = 0.002) and initial blood pressure values tended to be lower (with mean systolic values of 128 vs. 148 mm Hg; P = 0.02) in the group with statistically significant fall in ΔeGFR, but this trend failed to achieve an a priori level of statistical significance. However, the proportion of patients with initial systolic blood pressure ≤ 144 developing a statistically significant fall in ΔeGFR was 0.26 (95% confidence interval = 0.13 to 0.45). No differences were found in initial hemoglobin or cholesterol concentrations. Overall, the annualized rate of decrease in eGFR tended to be greater in those with the higher initial eGFR (P = 0.04), but correlation was poor (rho(2) = 0.04) and failed to achieve an a priori level of statistical significance. No statistically significant correlation was found between ΔeGFR and any other variable. Only those patients with polycystic kidney disease with a statistically significant annualized decrease in eGFR may need to be referred for hospital follow-up in the renal clinic. This simple selection would reduce referrals by 78%.

Osmolal gap in hemodialyzed uremic patients.

Osmolality is an expression of the number of particles in a given weight of solvent (mOsm). Measured osmolality is determined by the osmometer, and calculated osmolality is estimated by 2xNa + UN/2.8 + glucose/18. The difference between measured and calculated osmolality is the osmolal gap. The purpose of the present study is to determine the measured and the calculated osmolality and the osmolal gap in hemodialyzed uremic patients, pre- and post-hemodialysis (HD). In 24 uremic patients under regular HD, blood samples pre- and post-HD were collected, and serum osmolality measured (osmometer) and calculated (2xNa + UN/2.8 + glucose/18) and the osmolal gap (measured-calculated osmolality) were determined. Also, the same parameters were determined in 22 healthy subjects (control). According to our findings, the measured osmolality in patients is significantly higher pre- and post-HD in comparison to that of controls, but post-HD is significantly lower than pre-HD. Also, calculated osmolality is significantly higher pre- and post-HD in comparison to that of controls, but the value post-HD is significantly lower than the pre-HD. The osmolal gap of patients pre-HD (11 ± 2.08) and post-HD (7.29 ± 1.94) is significantly higher (P < 0.001) in comparison to that of controls (3.18 ± 1.46); also, the value post-HD is significantly decreased in comparison to the value pre-HD (P < 0.001). Uremic hemodialyzed patients present high measured and calculated osmolality pre-HD that remains high post-HD in comparison to that of controls in spite of the significant decrease post-HD in comparison to that of pre-HD. Also, the osmolal gap is high pre-HD and, in spite of the decrease, remains high post-HD. In comparison to that of controls, the high osmolal gap indirectly indicates the presence of unidentified endogenous osmoles in the serum of uremic patients which partly are removed during HD.

Effect of cyclosporine therapy with low doses of corticosteroids on idiopathic nephrotic syndrome.

Cyclosporine (CyA) has an immunosuppressive effect that might suggest a therapeutic role in idiopathic glomerular conditions. We focused on the optimization of CyA treatment control in patients with idiopathic nephrotic syndrome by using trough-level CyA measurements (C0) and the 2-h postdose levels (C2). Twenty-two patients (14 male, 8 female) with idiopathic nephrotic syndrome and the mean age of 51 +/- 18 months (mean [M] +/- standard deviation [SD]) were enrolled in our study during a period of 10 months (range: 3-18 months). All of the patients received CyA (2-3 mg/kg) in combination with methylprednisolone. In the present study protocol CyA concentrations (C0, C2), renal function, lipid profile, and degree of proteinuria were determined. The mean proteinuria of our patients before treatment was 11 972 +/- 7953 mg/24 H (+/-SD) and the mean creatinine level (Cr) was 0.99 +/- 0.37 mg/dL (+/-SD). Proteinuria decreased significantly already from the first month of therapy with CyA to 3578 +/- 2470 mg/24 H (M+/- SD), and during the whole study period this reduction was significant (0.56 +/- 0.37 gr/24 H (M +/- SD), P < 0.05). At the same time renal function preserved, 1.09 +/- 0.48 mg/dL (M +/- SD). The blood levels of C0 were 135.10 +/- 97.36 ng/mL (M +/- SD) and the blood levels of C2 were 725 +/- 256 ng/mL (M +/- SD) at the first month of therapy. At the same time renal function preserved, 1.09 +/- 0.48 mg/dL (M +/- SD). Total cholesterol levels reduced significantly during study period (276.89 +/- 45.57 to 200.67 +/- 40.27 mg/dL [M +/- SD]). The mean number of antihypertensive medication remained the same. The whole therapeutic protocol did not provoke any kind of side effects and CyA was quite tolerated by our patients. Treatment of idiopathic nephrotic syndrome with low doses of CyA with methylprednisolone leads to remission of proteinuria without deterioration of renal function. Blood levels of C0 for monitoring and treatment of nephrotic syndrome agrees with recent literature, while our study focus on establishing the proper levels of C2 for the treatment of nephrotic syndrome. The efficacy of CyA is combined with safety and tolerance.

INR deviations in hemodialyzed patients under low dose oral anticoagulant therapy.

The aim of this retrospective study was to evaluate the International Normalized Ratio (INR) in hemodialyzed uremic patients under treatment with oral anticoagulation drugs. Eleven out of one hundred and forty-two uremic hemodialyzed patients in our unit were included in the study. These 11 patients aged from 70 to 85 (mean: 76 years) were under oral anticoagulation treatment for protection from thromboembolic events. They received 1 mg acenocumarol daily with the therapeutic goal of achieving an INR between 2 and 2.5 units. During the last year, the number of total INR determinations was 129. Based on the INR levels, measurements were classified into three categories of anticoagulation, termed "under-anticoagulation", "target-anticoagulation", and "over-anticoagulation". The number, the percentage, and the mean value (+/-SD) of INR measurements for each category, respectively, were under-anticoagulation: 39, 30%, 1.78 +/- 0.14; target-anticoagulation: 48, 37.5%, 2.20 +/- 0.14; and over-anticoagulation: 42, 32.5%, 3.14 +/- 0.64. The mean value +/-SD of all INR determinations (n=129) was 2.34 +/-0.65. No thromboembolic or major bleeding events occurred in our patients with these INR. In conclusion, in elderly, hemodialyzed uremic patients with indications for oral anticoagulation treatment, adequate and safe INR levels can be achieved in a high proportion without serious deviations from the therapeutic goal by using low doses of drugs. Therefore, oral anticoagulation therapy should not be considered automatically contra-indicated in this patient group.

CD4/CD8 T-cell ratio in peritoneal dialysis effluents predicts the outcome of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.

This study aimed to clarify the role of peritoneal T-lymphocytes in peritoneal immune defense mechanisms. This study was designed to examine the changes in T-cell subpopulations during peritonitis in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Our observations were correlated to responses to treatment and with outcomes. The present study was carried out in 20 patients (8 males, 12 females) under CAPD. Peritonitis was diagnosed according to the criteria defined by the Ad Hoc Advisory Committee on Peritonitis Management. Peritoneal dialysate effluent (PDE) samples were collected from our patients, and lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3-/16+56+, CD4/CD8 ratio) were quantitated by using monoclonal antibodies. CD4/CD8 ratio was measured every day during peritonitis until the patients had completely recovered. The serial measurements of the CD4/CD8 ratio made in the PDE during peritonitis followed two patterns: the first pattern was characterized by a progressive increase in the CD4/CD8 ratio. The CD4/CD8 ratios on days 5, 6, and 7 were significantly higher than those on day 1 (P < 0.05). Overall, the patients who exhibited pattern 1 had favorable clinical courses. The second pattern was characterized by high initial CD4/CD8 ratios, which progressively decreased significantly (P < 0.05). This second pattern was associated with a delayed clinical response to treatment. Symptoms and signs of peritonitis persisted beyond 72 h. The pattern of the CD4/CD8 ratio in PDE may determine the outcome of peritonitis in CAPD patients.

The role of pure diffuse mesangial hypercellularity in patients with proteinuria.

BACKGROUND: Pure diffuse mesangial hypercellularity (DMH), in its primary form, is a relatively rare histological finding, and scant data exist in the literature regarding its clinical course and prognosis in nephrotic adults with this diagnosis. METHODS: We retrospectively analyzed the clinical and histological data of 8 out of 41 patients with the above diagnosis in regard to response to the treatment, outcome and prognostic indicators. RESULTS: Six patients received oral prednisolone as initial therapy, five of whom receiving it as monotherapy at first. The two other patients did not receive anything at all. Three out of the above six patients received prednisolone either with cyclophosphamide or with cyclosporine (CyA). Three patients responded with complete remission, two showed partial remission, and one did not respond at all. During follow-up, none of the patients with complete response appeared to have relapse. The two patients with initial partial response to steroids received CyA in combination with low dose of oral prednisolone. The other patient who did not respond at all from the beginning did not receive anything more due to his bad general condition. Plasma creatinine remained stable in those with complete or partial response to treatment. None of the clinical characteristics was found to be predictive of the degree of renal function impairment at the time of renal biopsy. The three patients with partial or no response were characterized by the severity of mesangial hypercellularity. Patients with complete or partial response to therapy did not differ with regard to age, plasma creatinine, and severity of proteinuria at biopsy. Presence of mesangial IgM was not associated with poor or satisfactory response. In general, no clinical feature at the time of biopsy was predictive of a response to therapy. CONCLUSIONS: At present, it seems that adult patients with DMH and proteinuria represent a heterogeneous group with different clinical courses despite a similar morphological appearance in initial biopsies. We conclude that serial biopsies taken at regular intervals coupled with a longer follow-up may provide answers concerning the real intensity of DMH.

Neuroendocrine stimulatory tests of hypothalamus-pituitary-adrenal axis in psoriasis and correlative implications with psychopathological and immune parameters.

Psoriasis constitutes one of the most representative examples of psychosomatic disorders. The published work investigating the psychological parameters and the way they interact during the course of the disease is extensive, whereas only a few studies have focused on the neuroendocrine framework of psoriasis. In the present study, the objective was to investigate the neuroendocrine parameters of psoriasis and the way they interact with psychopathological and immune variables. Patients with psoriasis (n=24) and the same number of matched healthy controls underwent psychiatric evaluation with interviews and psychometric questionnaires. Both of the groups underwent the corticotropin-releasing hormone (CRH) test and the dexamethasone suppression test (DST) to investigate functional parameters of the hypothalamus-pituitary-adrenal (HPA) axis. The evaluation of immune variables included the estimation of the distribution of T-cell and natural killer lymphocytes. Levels of depressive and anxiety features were increased within subjects with psoriasis and they were significantly correlated with stressful life events and the extent of the disease. The adrenocorticotrophic hormone and cortisol levels increased after CRH infusion without significant differences between the two groups and the psoriatic subjects' cortisol suppression after DST was within normal range, though relatively blunted. No significant correlations were identified among neuroendocrine, psychopathological and immune parameters. No particular neuroendocrine profile has been identified among psoriatic patients and the hypothesized interaction with psychopathological and immune parameters was not replicated. Nevertheless, it is still premature to exclude the possibility that a subtle latent alteration of the HPA axis function might exist, in psoriasis, either stemming from the psychopathology or from the disease per se.