BackgroundClinical presentation, electrophysiological subtype, and outcome of the Guillain–Barre' Syndrome (GBS) may differ between patients from different geographical regions. This study aims to assess clinical–neurophysiological features of an adult, Italian GBS cohort over 11 years.MethodsRetrospective (from 1 January 2011 to 31 December 2021) analysis was carried out on patients admitted to the Siena University Hospital who fulfilled the GBS diagnostic criteria. Demographic data, clinical characteristics, treatment, need of mechanical ventilation (MV), laboratory and electrophysiological tests, preceding infections/vaccination/other conditions, and comorbidities were collected for each patient.ResultsA total of 84 patients (51 men, median age of 61 years), were identified. GBS subtype was classified as acute inflammatory demyelinating polyneuropathy (AIDP) in the 66.6% of patients, acute motor/sensory axonal neuropathy (AMAN/AMSAN) in 20.2%, and the Miller Fisher syndrome in 5 (5.9%). Flu syndrome and gastrointestinal infection were the most common preceding conditions. In total, five (5.9%) subjects had concomitant cytomegalovirus (CMV) infection. Cranial nerve involvement occurred in 34.5% of subjects. Differences between the axonal and AIDP forms of GBS concerned the presence of anti-ganglioside antibodies. In total, seven (8.33%) patients required MV.DiscussionThe epidemiological and clinical characteristics of GBS in different countries are constantly evolving, especially in relation to environmental changes. This study provides updated clinical-epidemiological information in an Italian cohort.

HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

Summary Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell‐derived extracellular vesicles (HLSC‐EVs) are able to reduce liver injury and promote regeneration. We investigated the efficacy of a reconditioning strategy with HLSC‐EVs in an experimental model of NMP. Following total hepatectomy, rat livers were divided into 4 groups: (i) healthy livers, (ii) warm ischemic livers (60 min of warm ischemia), (iii) warm ischemic livers treated with 5 × 108 HLSC‐EVs/g‐liver, and (iv) warm ischemic livers treated with a 25 × 108 HLSC‐EVs/g‐liver. NMP lasted 6 h and HLSC‐EVs (Unicyte AG, Germany) were administered within the first 15 min. Compared to controls, HLSC‐EV treatment significantly reduced transaminases release. Moreover, HLSC‐EVs enhanced liver metabolism by promoting phosphate utilization and pH self‐regulation. As compared to controls, the higher dose of HLSC‐EV was associated with significantly higher bile production and lower intrahepatic resistance. Histologically, this group showed reduced necrosis and enhanced proliferation. In conclusion, HLSC‐EV treatment during NMP was feasible and effective in reducing injury in a DCD model with prolonged warm ischemia.

Hepatic ischemia-reperfusion injury (IRI) is observed in liver transplantation and hepato-biliary surgery and is associated with an inflammatory response. Human liver stem cell-derived extracellular vesicles (HLSC-EV) have been demonstrated to reduce liver damage in different experimental settings by accelerating regeneration and by modulating inflammation. The aim of the present study was to investigate whether HLSC-EV may protect liver from IRI in a mouse experimental model. Segmental IRI was obtained by selective clamping of intrahepatic pedicles for 90 min followed by 6 h of reperfusion. HLSC-EV were administered intravenously at the end of the ischemic period and histopathological and biochemical alterations were evaluated in comparison with controls injected with vehicle alone. Intra liver localization of labeled HLSC-EV was assessed by in in vivo Imaging System (IVIS) and the internalization into hepatocytes was confirmed by fluorescence analyses. As compared to the control group, administration of 3 × 109 particles (EV1 group) significantly reduced alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) release, necrosis extension and cytokines expression (TNF-α, CCL-2 and CXCL-10). However, the administration of an increased dose of HLSC-EV (7.5 × 109 particles, EV2 group) showed no significant improvement in respect to controls at enzyme and histology levels, despite a significantly lower cytokine expression. In conclusion, this study demonstrated that 3 × 109 HLSC-EV were able to modulate hepatic IRI by preserving tissue integrity and by reducing transaminases release and inflammatory cytokines expression. By contrast, a higher dose was ineffective suggesting a restricted window of biological activity.

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Perihilar cholangiocarcinomas (pCCA) are rare yet aggressive tumors originating from the bile ducts. While surgery remains the mainstay of treatment, only a minority of patients are amenable to curative resection, and the prognosis of unresectable patients is dismal. The introduction of liver transplantation (LT) after neoadjuvant chemoradiation for unresectable pCCA in 1993 represented a major breakthrough, and it has been associated with 5-year survival rates consistently >50%. Despite these encouraging results, pCCA has remained a niche indication for LT, which is most likely due to the need for stringent candidate selection and the challenges in preoperative and surgical management. Machine perfusion (MP) has recently been reintroduced as an alternative to static cold storage to improve liver preservation from extended criteria donors. Aside from being associated with superior graft preservation, MP technology allows for the safe extension of preservation time and the testing of liver viability prior to implantation, which are characteristics that may be especially useful in the setting of LT for pCCA. This review summarizes current surgical strategies for pCCA treatment, with a focus on unmet needs that have contributed to the limited spread of LT for pCCA and how MP could be used in this setting, with a particular emphasis on the possibility of expanding the donor pool and improving transplant logistics.

Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective study was conducted from 2016 to 2020. Pre- and postoperative data of HCC patients undergoing LT were analyzed. Recipients of a D-HOPE-treated graft were compared to those of livers preserved using static cold storage (SCS). The primary endpoint was recurrence-free survival (RFS). Results: Of 326 patients, 246 received an SCS-preserved liver and 80 received a D-HOPE-treated graft (donation after brain death (DBD), n = 66; donation after circulatory death (DCD), n = 14). Donors of D-HOPE-treated grafts were older and had higher BMI. All DCD donors were treated by normothermic regional perfusion and D-HOPE. The groups were comparable in terms of HCC features and estimated 5-year RFS according to the Metroticket 2.0 model. D-HOPE did not reduce HCC recurrence (D-HOPE 10%; SCS 8.9%; p = 0.95), which was confirmed using Bayesian model averaging and inverse probability of treatment weighting-adjusted RFS analysis. Postoperative outcomes were comparable between groups, except for lower AST and ALT peak in the D-HOPE group. Conclusions: In this single-center study, D-HOPE did not reduce HCC recurrence but allowed utilizing livers from extended criteria donors with comparable outcomes, improving access to LT for patients suffering from HCC.

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