59 research outputs found
Coupled Plasma Filtration Adsorption Application for Liver and Thyroid Toxins
No full textCoupled plasma filtration and adsorption (CPFA) is a detoxification system that combines a plasma adsorption circuit and a continuous renal replacement therapy circuit. Its main application is for sepsis and septic shock with or without acute renal failure. Several recent studies have suggested that CPFA can reduce the mortality when the volume of plasma absorbed on the styrenic resin is at least >0.18 L/kg/day. At present, new applications for CPFA are under investigation, also in patients without significant kidney failure. We report here a successful case of CPFA use during acute liver failure, with a complete recovery of liver function in a patient after severe cholangitis and relapsing hemolytic anemia. The resin enabled the removal of bilirubin and protein-bound toxins, while the hemofilter removed the hydrophilic toxins such as ammonia and non-protein-bound toxins as free bilirubin. We also describe a second case of CPFA application during thyrotoxicosis to achieve free triiodothyronine (FT3) and free thyroxin (FT4) adsorptions. The CPFA efficacy seems to exceed that obtained by plasma exchange (PEX) as to FT3 and FT4 adsorptions. The resin allowed the adsorption of FT3 and FT4. The role of the hemofilter is to enhance the hemodynamic tolerance of the extracorporeal treatment and remove water-soluble toxins. The reduced duration of CPFA treatments, in case of normal renal function, is confirmed by the assessment of the resin cartridge saturation. Thus, multipurpose CPFA can play a role in the case of resistance to current medical therapy or as a bridge to liver transplantation or thyroidectomy
Interleukin-6 and Outcome of Chronic Hemodialysis Patients with SARS-CoV-2 Pneumonia
No full textBackground and Objectives: Chronic hemodialysis (CHD) patients are at increased risk of SARS-CoV-2 infection and the related complications and mortality of COVID-19 due to the high rate of comorbidities combined with advanced age. This observational study investigated the clinical manifestations of SARS-CoV-2 infection in CHD and the risk factors for patients′ death. Materials and Methods: The study included 26 CHD patients with SARS-CoV-2 pneumonia detected by positive RT-PCR on nasopharyngeal swabs and high-resolution computed tomography at hospital admission, aged 71 + 5.9 years, 14 of which (53.8%) were male, 20 (77%) under hemodiafiltration, and 6 (23%) on standard hemodialysis, with a median follow-up of 30 days. Results: Simple logistic regression analysis revealed that the factors associated with a higher risk of death were older age (OR: 1.133; 95%CI: 1.028–1.326, p = 0.0057), IL-6 levels at admission (OR: 1.014; 95%CI: 1.004–1.028, p = 0.0053), and C-reactive protein (OR: 1.424; 95%CI: 1.158–2.044, p < 0.0001). In the multiple logistic regression model, circulating IL-6 values at admission remained the only significant prognosticator of death. The ROC curve indicated the discriminatory cut-off value of 38.20 pg/mL of blood IL-6 for predicting death in chronic hemodialysis patients with SARS-CoV-2 pneumonia (sensitivity: 100%; specificity: 78%; AUC: 0.8750; p = 0.0027). Conclusions: This study identified a threshold of IL-6 levels at hospital admission for death risk in CHD patients with SARS-CoV-2 pneumonia. This might represent a valuable outcome predictor, feasibly better than other clinical, radiological, or laboratory parameters and preceding the IL-6 peak, which is unpredictable
Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?
No full textBackground: Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been implicated in vascular calcification pathogenesis. CKD-MBD results in alterations in the number and function of circulating endothelial progenitor cells (EPCs), physiological regulators of angiogenesis and vessel repair, commonly defined as proangiogenic progenitor cells (PACs) by the antigen pattern CD34+CD133+KDR+CD45-and putative EPCs by the pattern CD34+CD133-KDR+CD45-. These cells might acquire a calcifying phenotype in CKD-MBD, expressing mineralization biomarkers. We investigated the expression of vitamin D receptor (VDR) and osteocalcin (OC) on EPCs of healthy individuals and haemodialysis patients, and their possible associations with circulating biomarkers of inflammation and vascular calcification. Methods: We compared EPC counts, expressing VDR or OC, in 23 healthy subjects versus 53 haemodialysis patients, 17 of them without vitamin D receptor agonist (VDRA) therapy and 35 treated with calcitriol (n = 17) or paricalcitol (n = 18). The correlations with serum levels of inflammatory and calcification indexes were also analysed. Results: All subsets expressing VDR or OC were significantly higher in haemodialysis patients compared with healthy controls, but PACs were increased only in VDRA treatment subgroup, while putative EPCs showed a similar rise also in untreated patients. In VDRA-untreated patients, OC+ PACs correlated positively with calcium levels, while in VDRA-treated patients, VDR+ PACs correlated positively with interleukin 6 levels, and OC+ PACs correlated positively 25-hydroxyvitamin D levels. Conclusions: Our data suggest that in CKD-MBD, EPCs undergo an endothelial-to-procalcific shift, representing a risk factor for vascular calcification. A link between mineral disorders and vitamin D replacement therapy emerged, with potential adverse effects for CKD patients
An unusual spontaneous recanalization by multiple palmar arteriovenous connections of a chronically occluded radiocephalic hemodialysis fistula
No full textPreservation of a vascular access is crucial in the management of hemodialysis patients. In this regard, percutaneous transluminal angioplasty (PTA) is an effective tool if performed after an adequate understanding of preliminary fistulograms. The present case showed a chronic dysfunction of a radial-cephalic arteriovenous fistula (AVF) due to arterial occlusion and partially relieved by the spontaneous development of multiple small arteriovenous connections in the palmar region of the hand. This dense network had been so far able to ensure a sufficient retrograde blood flow for an effective hemodialytic performance. The angioplasty of the post-anastomotic stenotic segment of the radial artery was effective in restoring this neoformed AVF patency
Analisi molecolare della regione genomica di controllo della trascrizione genica del Polyomavirus umano JC in pazienti trattati con farmaci biologici: dati preliminari di uno studio longitudinale.
No full textScopo del lavoro. Il Polyomavirus umano JC (JCV) è un virus a DNA responsabile della leucoencefalopatia multifocale progressiva (PML), una rara malattia demielinizzante ad esito talvolta fatale. L’infezione primaria si traduce in uno stato di latenza virale descritta nel 50-90% della popolazione. La regione di controllo della trascrizione virale (TCR), nella sua variante archetipa non patogena (CY), è suddivisa in 6 box (A-B-C-D-E-F), i cui riarrangiamenti portano alla formazione di varianti virulente. Recentemente, casi di PML sono stati osservati dopo terapia con biologici. Gli scopi di questo studio sono: 1. valutare la prevalenza dell’infezione da JCV in pazienti con malattie reumatiche infiammatorie croniche (MRIC) o sclerosi multipla (SM) candidati al trattamento con biologici; 2. analizzare la sequenza genomica della TCR di JCV in campioni di urina e plasma e in cellule mononucleate del sangue periferico (PBMC) per individuare eventuali riarrangiamenti. Materiali e Metodi. Dopo aver ottenuto il consenso informato, abbiamo arruolato pazienti adulti consecutivi affetti da MRIC candidati al trattamento con anti-TNF e con SM candidati al trattamento con natalizumab. I pazienti sono stati sottoposti a prelievo di sangue venoso e raccolta di campioni urinari prima dell’inizio della terapia con biologici e ogni 4 mesi nel corso del primo anno di trattamento per valutare la viremia e la viruria da JCV. La viruria e la viremia da JCV e l’analisi delle sequenze genomiche sono state valutate rispettivamente mediante PCR quantitativa e qualitativa. Risultati. Sono stati arruolati 17 pazienti con MRIC (F/M: 13/4; età mediana: 57 anni [range 38-79]; durata media di malattia: 111 mesi [DS: 84,5; I.C. 95%: 1,28]) e 21 con SM (F/M: 11/10; età mediana: 35 anni [range 19-51]; durata media di malattia: 102,29 mesi [DS 39,9; I.C. 95% 0,55]). Prima dell’inizio del trattamento, 11 pazienti (65%) con MRIC mostravano una viruria significativamente più elevata (mediana 7,35 log10 gEq/mL; range: 3,87-8,13 log10 gEq/mL) rispetto a quella osservata in 3 pazienti (14%) con SM (mediana: 4,70 log10 gEq/mL; range: 3,48-6,04 log10 gEq/mL) (p<0.05), ma non viremia. Nei campioni di urina è stata isolata solo la variante CY di JCV. Dopo 1 anno di terapia con natalizumab, dai PBMC di 2 pazienti con SM è stata isolata una sequenza della TCR di JCV con una delezione del box B e una duplicazione del box C. Conclusioni. I risultati preliminari di questo studio indicano che i pazienti affetti da MRIC sono maggiormente predisposti alla riattivazione del virus JC a livello renale, osservabile come viruria, rispetto ai pazienti con SM. Inoltre, per un’accurata stratificazione del rischio di insorgenza di PML in pazienti trattati con biologici, è importante studiare i riarrangiamenti della TCR nei PBMC, da considerarsi validi biomarcatori ematologici della virulenza di JCV
Analysis of polyomavirus JC noncoding control region rearrangements in autoimmune diseases during treatment with natalizumab and anti-TNF agents
No full textProgressive multifocal leukoencephalopathy (PML) onset, caused bypolyomavirus JC (JCV) in patients affected by autoimmune diseasesduring biological agents (BA) treatment, raised concerns about the safetyprofile of these agents. Therefore, the aims of this study were the monitoring of JCV reactivation in patients with different autoimmune diseasestreated with natalizumab or anti-TNF agents, performing quantitativePCR of biological samples collected at moment of recruitment (t0)andevery 4 months (t1, t2, t3, t4) for almost 16 months of treatment, andrearrangements’analysis of JCV archetype CY noncoding control region(NCCR), constitutively divided in six boxes (A–B–C–D–E–F). Resultsshowed that att0, patients with chronic inflammatory rheumatic diseasespresented a JCV load in the urine significantly higher than that in patientswith multiple sclerosis (MS) and Crohn’s disease (CD). Moreover, thenumber of JCV-positive MS patients significantly increases during 1 yearof natalizumab treatment. Finally, the analysis of NCCR sequencesshowed the presence of archetype CY in all urine samples. Aremarkable result was the presence of a particular NCCR sequencewith a structural organization that resembles the JCV pathogenicMad-1 variant in colorectal biopsies, collected from CD patientsafter 16 months of infliximab treatment. Furthermore, sequencesisolated at t3from peripheral blood mononuclear cells of MS patients showed a NCCR with a box C duplication and a box Bdeletion. In conclusion, these rearranged NCCRs may be considereda marker of JCV virulence already in the first 16 months of BAtreatment, although none of these patients developed PML
HEPATIC REGENERATION WITH COUPLED PLASMAFILTRATION AND ADSORPTION FOR LIVER EXTRACORPOREAL DETOXIFICATION (HERCOLE STUDY)
No full textINTRODUCTION AND AIMS: CPFA (Coupled plasma filtration and adsorption) is currently used in the treatment of severe sepsis with the intention of removing the proinflammatory mediators from the systemic circulation. Some evidence exist about the bilirubin adsorbing ability of the neutral styrenic resin which is part of the extracorporeal circuit of CPFA. The aim of this study is to assess efficacy and safety of CPFA in extracorporeal detoxification of liver toxins in patients affected by acute or acute-onchronic liver failure (Figure 1).
METHODS: Twelve patients (age 23 - 73 years) with acute (n 1⁄4 3) or acute-on-chronic (n 1⁄4 9) liver failure were enrolled. A total of 31 CPFA treatments were carried out. Each CPFA treatment lasted 6 hours. Unfractionated heparin was used as anticoagulation of the extracorporeal circuit in 19 CPFA sessions; citrate anticoagulation with the concomitant infusion of calcium chloride in 12 CPFA sessions. The number of treatment for each patient was established on his/her clinical status. The reduction ratios per session of bilirubin and bile acids were considered. Hemoglobin, platelets, white blood cells, coagulation tests, urea, creatinine and electrolytes were also checked on starting CPFA and at the end of CPFA, as biocompatibility measures.
RESULTS: All sessions were well tolerated by the patients. Alcohol was the most common etiology of the liver injury (n 1⁄4 9), 1 patient was affected by acute cholangitis and Fisher-Evans syndrome, 1 had a viral etiology, and 1 patient had a postoperative jaundice. Median reduction rate per session for total bilirubin was 28.8% (range 2.2 - 40.5); for direct bilirubin was 32.7 (range 8.3 - 48.9); for indirect bilirubin was 29.5% (range 6.5 - 65.4); for bile acids was 28.9% (16.7 - 59.7); for lactic acid was 30% (range -57.2%- 55.6%). In 10 out of 12 patients was observed a recovery of liver function. At one year of follow-up 2 patients died during the hospitalization; 6 patients are followed like outpatients, recovered their basal liver function and 1 of them is no more in the waiting list for the transplant. As to the remaining 4 patients who have not yet completed the one year follow-up, 2 out of 4 are still alive after a 6-month follow-up and recovered their basal liver function, 1 patient underwent a successful liver transplantation, the last patient is still alive after a 3-month follow up.
CONCLUSIONS: Although CPFA is a non-standardized technique for the liver failure, its use in patients with acute or acute-on-chronic liver failure has shown favorable effects on safety and efficacy in terms of detoxification. Thus it is considerable a “bridge technique” toward the liver transplant and the recovery of basal liver function
An unusual spontaneous recanalization by multiple palmar arteriovenous connections of a chronically occluded radiocephalic hemodialysis fistula
No full textPreservation of a vascular access is crucial in the management of hemodialysis patients. In this regard, percutaneous transluminal angioplasty (PTA) is an effective tool if performed after an adequate understanding of preliminary fistulograms. The present case showed a chronic dysfunction of a radial-cephalic arteriovenous fistula (AVF) due to arterial occlusion and partially relieved by the spontaneous development of multiple small arteriovenous connections in the palmar region of the hand. This dense network had been so far able to ensure a sufficient retrograde blood flow for an effective hemodialytic performance. The angioplasty of the post-anastomotic stenotic segment of the radial artery was effective in restoring this neoformed AVF patency
Increased prevalence of Human Polyomavirus JC viruria in Chronic Inflammatory Rheumatic Diseases patients in treatment with anti-TNF α: a 18 month follow-up study.
No full textChronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the aetiological agent of the Progressive Multifocal Leukoencephalopathy (PML).The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12) and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p=0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B and 4.Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients
- …
