As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were very significant (P < 0.01), whereas the changes of International Normalized Ratio (INR) were not significant. Also the modifications of albumin, total protein, sodium, potassium and calcium were not significant. In conclusion, four out of nine patients with PNF are alive without a second transplantation and were discharged after about 48 days; four out of nine underwent OLT, while one out of nine died; five out of six patients with DF are alive without a second transplantation, and they were discharged after an average time of 55.5 days, one out of six died; six out of nine patients with fulminant hepatitis underwent OLT and four of these are alive, while two died due to sepsis; three patients are alive without OLT. Four patients with AOCHF underwent OLT and are alive, three patients are alive and on a waiting list, two died while on a waiting list and one patient who experienced reactivation of HBV infection during chemotherapy for non-Hodgkin's lymphoma is alive. In spite of the limited numb...

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Solid organ transplant patients are at a higher risk for poor CoronaVirus Disease‐2019 (COVID‐19)‐related outcomes and have been included as a priority group in the vaccination strategy worldwide. We assessed the safety and efficacy of a two‐dose vaccination cycle with mRNA‐based COVID‐19 vaccine (BNT162b2) among 82 kidney transplant outpatients followed in our center in Rome, Italy. After a median of 43 post‐vaccine days, a SARS‐CoV‐2 anti‐Spike seroprevalence of 52.4% (n = 43/82) was observed. No impact of the vaccination on antibody‐mediated rejection or graft function was observed, and no significant safety concerns were reported. Moreover, no de novo HLA‐donor‐specific antibodies (DSA) were detected during the follow‐up period. Only one patient with pre‐vaccination HLA‐DSA did not experience an increased intensity of the existing HLA‐DSA. During the follow‐up, only one infection (mild COVID‐19) was observed in a patient after receiving the first vaccine dose. According to the multivariable logistic regression analysis, lack of seroconversion after two‐dose vaccination independently associated with patient age ≥60 years (OR = 4.50; P = .02) and use of anti‐metabolite as an immunosuppressant drug (OR = 5.26; P = .004). Among younger patients not taking anti‐metabolites, the seroconversion rate was high (92.9%). Further larger studies are needed to assess the best COVID‐19 vaccination strategy in transplanted patients.

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Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out.The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P < 0.001, P = 0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P < 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P < 0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P < 0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons–Smith classification) in patients on conservative therapy, and Grade 2–3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D.In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological, and cognitive disorders, might enable a better quality of life and a major compliance with a probable reduction in the healthcare costs.

SUPPLEMENT nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn n As reported in the literature, the mortality rate for patients with Acute Hepatic Failure (AHF) approaches 80 % in cases in which liver transplantation is not possible.Post transplant mortality depends on the seriousness of the neurological condition at the time of the operation (20 % in I-II degree coma patients and 44 % in III degree coma patients). This is the rationale for extracorporeal depuration treatment, as a bridge to transplantation, both in AHF and in Primary Non Function (PNF) cases.The recirculating molecular adsorption system (MARS), whose only function is to depurate through a "hybrid" membrane removing toxic substances related to albumin, has advantage in that it can be used for long periods. The aim of this study is to report on our experience in the use of MARS on 10 AHF patients (4 PNF, 2 delayed non function, 4 fulminant hepatitis). The average age was 41,8 years (range 23-56), 6 were male, 4 female. All had bilirubin 8805; 15 mg/ dl and ammonia 8805; 160 g/dl. MARS was applied for 8 € 1,5 hours a day. The average number of treatments was 6,4 (range 1-24).The EEG, hepatic and renal parameters were monitored before and after the treatment, while the hemodynamic parameters were monitored during the treatment.No hemodynamic complications occured during the treatment. A significant reduction in bilirubin (p < 0,01) and ammonia (p < 0,01) was observed. the average INR level at the onset of treatment was 2,05, at the end 1,59. After the treatment there was an improvement in neurological conditions. Three of the PNF patients recovered function of the transplanted organ and survived without further transplantations. The same applies for the two patients with delayed non function. All fulminant hepatitis patients were successfully bridged to transplantation, three subsquently died from complications, one was discharged in good condition.On the basis of our preliminary studies, the MARS treatment was found to be safe with a high tolerance rate, having a role in AHF treatment as bridge to liver transplantation or waiting for the graft to recover its functionality.

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