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Background: Patients undergoing allogeneic stem-cell transplantation (allo-SCT) have reduced responses to vaccines due to immunosuppressive status linked to GvHD prophylaxis and treatment. In our study, we compared humoral responses to anti-SARS-CoV-2 mRNA vaccine, and infection onset, according to patients and transplant features; we also evaluated cellular response in patients without seroconversion., Methods: We tested antibodies titer after second and third vaccine doses. Antibodies were detected through an immune-enzymatic assay. In a patients' subgroup without seroconversion, we tested cell-mediated responses evaluating interferon-gamma release by T-lymphocytes exposed to virus spike protein., Results: Seroconversion rate increased from 66% at 30 days to 81% at 90 days after the second dose; it was 97% at 150 days after the third dose. We found a significant association between seroconversion after the second dose and two variables: shorter interval between allo-SCT and vaccination; ongoing immunosuppression. Twelve of 19 patients (63%) without antibodies after the second dose did not show cellular responses. Nineteen percent of patients developed SARS-CoV-2 infection after the third dose, with favorable outcome in all cases. Patients within 12 months after allo-SCT showed a significantly higher infection risk., Conclusions: Our study suggests that an interval shorter than 12 months between allo-SCT and first vaccine dose and/or ongoing immunosuppression were associated with humoral and cellular response deficiency after two doses. Third dose induced an increased and sustained humoral response in the majority of patients. However, patients within 1 year after allo-SCT remained at higher infection risk and may be candidate for prophylaxis with anti-SARS-CoV-2 monoclonal antibodies., (© 2023 Wiley Periodicals LLC.)

Background: We investigated the effects of single (SL-ET) and double leg (DL-ET) high-intensity interval training on O2 deficit (O2Def) and mean response time (MRT) during square-wave moderate-intensity exercise (DL-MOD), and on the amplitude of V˙O2p slow component (SCamp), during heavy intensity exercise (DL-HVY), on 33 patients (heart transplant = 13, kidney transplanted = 11 and liver transplanted = 9). Methods: Patients performed DL incremental step exercise to exhaustion, two DL-MOD tests, and a DL-HVY trial before and after 24 sessions of SL-ET (n = 17) or DL-ET (n = 16). Results: After SL-ET, O2Def, MRT and SCamp decreased by 16.4% ± 13.7 (p = 0.008), by 15.6% ± 13.7 (p = 0.004) and by 35% ± 31 (p = 0.002), respectively. After DL-ET, they dropped by 24.9% ± 16.2 (p < 0.0001), by 25.9% ± 13.6 (p < 0.0001) and by 38% ± 52 (p = 0.0003), respectively. The magnitude of improvement of O2Def, MRT, and SCamp was not significantly different between SL-ET and DL-ET after training. Conclusions: We conclude that SL-ET is as effective as DL-ET if we aim to improve V˙O2p kinetics in transplanted patients and suggest that the slower, V˙O2p kinetics is mainly caused by the impairment of peripherals exchanges likely due to the immunosuppressive medications and disuse.

Background & Aims: The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls., Methods: LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose., Results: One hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively., Conclusions: In COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients., Lay Summary: The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil., Competing Interests: Conflicts of interest The authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Despite current advances in liver transplant surgery, post-operative early allograft dysfunction still complicates the patient prognosis and graft survival. The transition from the donor has not been yet fully understood, and no study quantifies if and how the liver function changes through its transfer to the recipient. The indocyanine green dye plasma disappearance rate (ICG-PDR) is a simple validated tool of liver function assessment. The variation rate between the donor and recipient ICG-PDR still needs to be investigated., Materials and Methods: Single-center retrospective study. ICG-PDR determinations were performed before graft retrieval (T1) and 24 hours after transplant (T2). The ICG-PDR relative variation rate between T1 and T2 was calculated to assess the graft function and suffering/recovering. Matched data were compared with the MEAF model of graft dysfunction., Objective: To investigate whether the variation rate between the donor ICG-PDR value and the recipient ICG-PDR measurement on first postoperative day (POD1) can be associated with the MEAF score., Results: 36 ICG-PDR measurements between 18 donors and 18 graft recipients were performed. The mean donor ICG-PDR was 22.64 (SD 6.35), and the mean receiver's ICG-PDR on 1st POD was 17.68 (SD 6.60), with a mean MEAF value of 4.51 (SD 1.23). Pearson's test stressed a good, linear inverse correlation between the ICG-PDR relative variation and the MEAF values, correlation coefficient -0.580 (p = 0.012)., Conclusion: The direct correlation between the donor to recipient ICG-PDR variation rate and MEAF was found. Measurements at T1 and T2 showed an up- or downtrend of the graft performance that reflect the MEAF values., Competing Interests: The authors have declared that no competing interests exist.

Maximal oxygen consumption ( V̇ O 2max ) is impaired in heart (HTx), kidney (KTx), and liver (LTx) transplanted recipients and the contribution of the cardiovascular, central, and peripheral (muscular) factors in affecting V̇ O 2max improvement after endurance training (ET) has never been quantified in these patients. ET protocols involving single leg cycling (SL) elicit larger improvements of the peripheral factors affecting O 2 diffusion and utilization than the double leg (DL) cycling ET. Therefore, this study aimed to compare the effects of SL-ET vs DL-ET on V̇ O 2max . We determined the DL- V̇ O 2max and maximal cardiac output before and after 24 SL-ET vs DL-ET sessions on 33 patients (HTx = 13, KTx = 11 and LTx = 9). The DL- V̇ O 2max increased by 13.8% ± 8.7 ( p  < 0.001) following the SL-ET, due to a larger maximal O 2 systemic extraction; meanwhile, V̇ O 2max in DL-ET increased by 18.6% ± 12.7 ( p  < 0.001) because of concomitant central and peripheral adaptations. We speculate that in transplanted recipients, SL-ET is as effective as DL-ET to improve V̇ O 2max and that the impaired peripheral O 2 extraction and/or utilization play an important role in limiting V̇ O 2max in these types of patients. Novelty: SL-ET increases V̇ O 2max in transplanted recipients because of improved peripheral O 2 extraction and/or utilization. SL-ET is as successful as DL-ET to improve the cardiorespiratory fitness in transplanted recipients. The model of V̇ O 2max limitation indicates the peripheral factors as a remarkable limitation to the V̇ O 2max in these patients.

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

We here report the case of a patient with systemic capillary leak syndrome (SCLS). This syndrome is a rare condition characterized by recurrent episodes of hypotension with hemoconcentration and hypoproteinemia. It is due to unexplained episodic capillary hyperpermeabilty that results in fluid and protein shift from the intravascular to the interstitial space: generalized edema, shock and renal failure follow. A 59 yo man was admitted to our intensive care unit because of unexplained shock with hemoconcentration, renal failure, and metabolic acidosis. Previous attemps to reverse shock in a medical ward with crystalloids and dopamine failed. An abdominal CT scan, a TEE, and chest X ray study were inconclusive. No sign or history of major infections or anaphylaxis were present. The patient was resuscitated with massive fluid infusions and norepinephrine on the guide of a Swan Ganz catheter. The diagnosis was made on the basis of a previous episode of severe shock complicated with renal failure and a compartment syndrome, the hemoconcentration, and the negative cardiopulmonary findings. A small amount of monoclonal immunoglobulin G, kappa chain, found in the serum confirmed the diagnosis. The SCLS should be considered in the differential diagnosis of idiopathic and anaphylactic shock. Patients may benefit from a prophylactic treatment with theophilline and terbutaline.