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Background: The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. Methods: A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin‐containing regimens were compared and a literature review was conducted. Results: We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62 years (interquartile range 50‐20). There were no significant differences between patients treated with rifabutin (n = 12), rifampin (n = 14), and non‐rifamycins (n = 5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P =.21), side effects (25%, 37.5%, and 20%, respectively; P =.74), or mortality (16.7%, 35.7%, and 0%, respectively; P =.21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin‐containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. Conclusions: Rifabutin‐containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients. [ABSTRACT FROM AUTHOR]

Background and purpose: Cholangiocarcinoma is an infrequent neoplasm barely studied with 18F-FDG-PET/CT. We evaluated the metabolic behavior of cholangiocarcinoma in PET/CT according to its location (intra or extrahepatic) and analyzed the relationship between metabolic parameters of the primary tumor and tumor markers (CA19-9 and CEA), determining their prognostic significance.Methods: Retrospective study of PET/CT of 60 patients with untreated cholangiocarcinoma, divided into two groups according to tumor location. FDG uptake was evaluated visually and semiquantitatively [SUVmax and tumor-to-liver ratio (TLR)], and differences between intra and extrahepatic cholangiocarcinomas were tested, both for FDG uptake in the primary tumor and for the presence of regional or distant disease (per-patient), as well as regarding tumor marker levels. A correlation between metabolic parameters and tumor markers was performed, and prognostic value of these factors was determined (univariate and multivariate analyses).Results: Intrahepatic cholangiocarcinomas were significantly more FDG-avid than extrahepatic ones (p = 0.006 for SUVmax; p = 0.002 for TLR). There were differences neither between both groups considering the capacity of PET/CT to detect regional (p = 0.261) and distant involvement (p = 0.876), nor regarding the levels of tumor markers (p = 0.160 for CA19-9; p = 0.708 for CEA). Metabolic parameters and tumor markers showed a weak positive correlation (R2 0.22-0.27). At the multivariate analysis, advanced stage (p = 0.024), increased CEA (p = 0.022), and higher TLR (p = 0.003) were significantly related with shorter overall survival.Conclusions: Intra and extrahepatic cholangiocarcinomas behave differently on PET/CT, though no differences between both groups exist in its capacity to detect regional or distant disease. Metabolic parameters and levels of tumor markers seem to relate with tumor burden, impacting in prognosis. [ABSTRACT FROM AUTHOR]

Background: Several scores have been developed to stratify the risk of graft loss in controlled donation after circulatory death (cDCD). However, their performance is unsatisfactory in the Spanish population, where most cDCD livers are recovered using normothermic regional perfusion (NRP). Consequently, we explored the role of different machine learning-based classifiers as predictive models for graft survival. A risk stratification score integrated with the model of end-stage liver disease score in a donor-recipient (D-R) matching system was developed., Methods: This retrospective multicenter cohort study used 539 D-R pairs of cDCD livers recovered with NRP, including 20 donor, recipient, and NRP variables. The following machine learning-based classifiers were evaluated: logistic regression, ridge classifier, support vector classifier, multilayer perceptron, and random forest. The endpoints were the 3- and 12-mo graft survival rates. A 3- and 12-mo risk score was developed using the best model obtained., Results: Logistic regression yielded the best performance at 3 mo (area under the receiver operating characteristic curve = 0.82) and 12 mo (area under the receiver operating characteristic curve = 0.83). A D-R matching system was proposed on the basis of the current model of end-stage liver disease score and cDCD-NRP risk score., Conclusions: The satisfactory performance of the proposed score within the study population suggests a significant potential to support liver allocation in cDCD-NRP grafts. External validation is challenging, but this methodology may be explored in other regions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.

Colorectal liver metastases grow following different histologic growth patterns (HGPs), classified as desmoplastic and nondesmoplastic (dHGP, non-dHGP), being the latter associated with worst prognosis. This study aimed to investigate the tumor microenvironment (TME) between HGPs supporting different survival. Multiplexed immunohistochemical staining was performed with the Opal7 system in a 100-patients cohort to evaluate the tumor-liver interface with three different cell panels: lymphoid, myeloid, and carcinoma-associated fibroblasts. Differences between HGPs were assessed by Mann-Whitney U test with Pratt correction and Holm-Bonferroni multitest adjustment. Cytotoxic T-cells were more abundant in tumoral areas of dHGP, while non-dHGP had higher macrophages infiltration, Th2, CD163 + , and Calprotectin + cells as well as higher pSMAD2 expression. Regarding carcinoma-associated fibroblasts, several subsets expressing COL1A1 were enriched in dHGP, while αSMA low _single cells were present at higher densities in non-dHGP. Interestingly, Calprotectin + cells confer better prognoses in non-dHGP, identifying a subgroup of good outcome patients that unexpectedly also show an enrichment in other myeloid cells. In summary, our results illustrate different TME landscapes with respect to HGPs. dHGP presents a higher degree of immunocompetence, higher amounts of Collagen 1 as well as lesser presence of myeloid cell populations, features that might be influencing on the better prognosis of encapsulated metastases., Competing Interests: All authors do not have any financial and personal relationships with other people, institutes, or organizations that could inappropriately influence their work. Additionally, all authors declare that they do not have a close relationship with, or a strong antipathy to, a person whose interests may be affected by publication of the article, an academic link or rivalry with someone whose interests may be affected by publication of the article, membership in a political party or special interest group whose interests may be affected by publication of the article, or a deep personal or religious conviction that may have affected what the author wrote and that readers should be aware of when reading the article. There is no other conflict of interest to disclose., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Burnout is increasingly relevant among healthcare professionals. The aim of this study is to describe the prevalence of burnout and other parameters of professional satisfaction among different specialists dedicated to Liver Transplantation (LT) in transplant teams. A working group from the Spanish Society of LT designed a survey with 39 questions evaluating the prevalence of parameters related to professional satisfaction, including burnout. It was distributed among 496 specialists dedicated to liver transplantation in Spanish transplant teams. Responders included surgeons (49%), hepatologists (27%), anesthesiologists (16%), intensivists (4%), and other specialties (4%). Among responders, 78% reported some degree of burnout. Moreover, 46% of responders did not see themselves working in transplantation in 5 years. The rates of burnout and dissatisfaction among anesthesiologists and surgeons were higher than other specialists. The highest levels of dissatisfaction were in economic remuneration and work-life balance. Being younger than 60 years old and non-head of department showed to be risk factors of burnout. In conclusion, the prevalence of burnout among LT physicians in Spain was notably high. Among the various specialties, anesthesiologists and surgeons exhibited the highest dissatisfaction rates. The results of this work may be of interest to healthcare management and planning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sanchez-Antolín, Blanco-Fernández, Campos-Varela, Ruiz, Álamo, Otero, Pascual and Lladó.)

Introduction: Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear., Methods: We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination., Results: We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion., Discussion: Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Donadeu, Gomez-Olles, Casanova, Torija, Lopez-Meseguer, Boada-Pérez, Kervella, Crespo, Carrera-Muñoz, Campos-Varela, Castells, Cortese, Esperalba, Fernández-Naval, Quintero, Muñoz, Agüero, Gonzalez-Costello, Lladó, Favà, Cañas, del Mar de la Hoz-Caballero, Meneghini, Torres, Juvé, Hafkamp, Vila, Robles, Buzón, Toapanta, Zúñiga, Monforte, Saez-Giménez, Len, Arcos, Miret, Ariceta, Pardo, Martínez, Moreso and Bestard.)

Introduction: Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18 months., Methods: The primary endpoints were the response rate, defined as those patients with an increase of < 2 points on the Neurological Impairment Score (NIS) from baseline, and the change in the NIS score from baseline. Secondary endpoints included the Quantitative Sensory Test, 10-m walk test, quality of life (Norfolk), and disability (Rasch-built Overall Disability Scale). As safety parameters, the evidence of graft rejection, changes in immunosuppressive trough levels and changes in antiviral and allogeneic cellular immunity before and 12 months after tafamidis treatment were also assessed., Results: Six patients (85.7%) had responded at 18-months. Compared to baseline, we observed non-statistically significant improvement in mean NIS score at 6 months (- 2.54 points, CI - 5.92 to 0.84), 12 months (- 3.25 points; CI - 6.63 to 0.13), and 18 months (- 2.35 points; CI - 5.74 to 1.02). Changes in the Quantitative Sensory Test, 10-m walk tests and the quality of life and disability questionnaires were not statistically significant. The use of tafamidis did not induce relevant side effects or drug interactions. Also, no acute rejections events nor changes in functional adaptive immunity were observed., Conclusion: Our study supports the safety and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Tafamidis shows promise as a useful treatment in the clinical management of these patients. Future randomized placebo-controlled clinical trials with longer follow-up durations are needed., (© 2024. The Author(s).)

Background: Iatrogenic bile duct injury (BDI) during cholecystectomy is associated with a complex and heterogeneous management owing to the burden of morbidity until their definitive treatment. This study aimed to define the textbook outcomes (TOs) after BDI with the purpose to indicate the ideal treatment and to improve it management., Methods: We collected data from patients with an BDI between 1990 and 2022 from 27 hospitals. TO was defined as a successful conservative treatment of the iatrogenic BDI or only minor complications after BDI or patients in whom the first repair resolves the iatrogenic BDI without complications or with minor complications., Results: We included 808 patients and a total of 394 patients (46.9%) achieved TO. Overall complications in TO and non-TO groups were 11.9% and 86%, respectively (P < .001). Major complications and mortality in the non-TO group were 57.4% and 9.2%, respectively. The use of end-to-end bile duct anastomosis repair was higher in the non-TO group (23.1 vs 7.8, P < .001). Factors associated with achieving a TO were injury in a specialized center (adjusted odds ratio [aOR], 4.01; 95% CI, 2.68-5.99; P < .001), transfer for a first repair (aOR, 5.72; 95% CI, 3.51-9.34; P < .001), conservative management (aOR, 5.00; 95% CI, 1.63-15.36; P = .005), or surgical management (aOR, 2.45; 95% CI, 1.50-4.00; P < .001)., Conclusion: TO largely depends on where the BDI is managed and the type of injury. It allows hepatobiliary centers to identify domains of improvement of perioperative management of patients with BDI., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLM) and its indication and results have varied in the last 30 years., Methods: All patients operated on for CRLM in our centre from 1990 to 2021 were prospectively collected, establishing 3 subgroups based on the year of the first surgery: group A 1990-1999, group B 2000-2010, group C 2011-2021. Clinical characteristics and the results of survival, recurrence and prognostic factors were compared., Results: 1736 hepatectomies were included (Group A n = 208; Group B n = 770; Group C n = 758). Patients in group C had better survival at 5 and 10 years (A 40.5%/28.2%; B 45.9%/32.2%; C 51.6%/33.1%, p = 0.013), although there were no differences between groups in overall recurrence at 5 and 10 years (A 73%/75.7%; B 67.6%/69.2%, and C 63.9%/66%, p = 0.524), nor in liver recurrence (A 46.4%/48.2%; B 45.8%/48.2%; and C 44.4%/48.4%, p = 0.899). An improvement was observed in median survival after recurrence, being 19 months, 23 months, and 31 months (groups A, B and C respectively). Prognostic factors of long-term survival changed over the 3 study periods. The only ones that remained relevant in the last decade were the presence of >4 liver metastasis, extrahepatic disease at the time of hepatectomy, and intraoperative blood transfusion., Conclusions: Survival after surgery for CRLM has improved significantly, although this cannot be explained by a reduction in overall and hepatic recurrence, but rather by an improvement in post-recurrence survival. Involvement of the resection margin has lost prognostic value in the last decade., (Copyright © 2024 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Machine perfusion of solid human organs is an old technique, and the basic principles were presented as early as 1855 by Claude Barnard. More than 50 years ago, the first perfusion system was used in clinical kidney transplantation. Despite the well-known benefits of dynamic organ preservation and significant medical and technical development in the last decades, perfusion devices are still not in routine use. This article describes the various challenges to implement this technology in practice, critically analyzing the role of all involved stakeholders, including clinicians, hospitals, regulatory, and industry, on the background of regional differences worldwide. The clinical need for this technology is discussed first, followed by the current status of research and the impact of costs and regulations. Considering the need for strong collaborations between clinical users, regulatory bodies, and industry, integrated road maps and pathways required to achieve a wider implementation are presented. The role of research development, clear regulatory pathways, and the need for more flexible reimbursement schemes is discussed together with potential solutions to address the most relevant hurdles. This article paints an overall picture of the current liver perfusion landscape and highlights the role of clinical, regulatory, and financial stakeholders worldwide., (Copyright © 2023 American Association for the Study of Liver Diseases.)

The goal of the Spanish Society for Liver Transplantation (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, in November 2022, the 10th Consensus Document Meeting was held, with the participation of experts from the 26 authorized Spanish liver transplantation programs. This edition discusses Enhanced Recovery After Liver Transplantation, dividing needed actions into three periods: preoperative, intraoperative and postoperative. The evaluated evidence and the consensus conclusions for each of these topics are described., (Copyright © 2023 Asociación Española de Cirugía and Asociación Española de Gastroenterología (AEG). Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: To decide treatment of hepatic cysts diagnosis between simple hepatic cyst (SHC) and cystic mucinous neoplasm (CMN). Radiological features are not patognomonic. Some studies have suggested the utility of intracystic tumor markers., Methods: Retrospective analysis of our prospective database including patients treated due to symptomatic SHC from 2003 to 2021. The aim of the study was to evaluate the results of treatment of symptomatic SHC and the usefulness of the determination of intracystic "carcinoembryonic antigen" (CEA) and "carbohydrate antigen" CA 19.9., Results: 50 patients diagnosed and treated for symptomatic SHC were included. In 15 patients the first treatment was percutaneous drainage. In 35 patients the first treatment was laparoscopic fenestration. Four patients were diagnosed of premalignant or malignant liver cystic lesions (MCN, IPMN, lymphoma B); three of them required surgery after initial fenestration and pathological diagnosis. Median CEA and CA 19-9 were 196 μg/L and 227.321 U/mL respectively. Patients with malignant or premalignant pathology did not have higher levels of intracystic tumor markers. Positive predictive value was 0% for both markers, and negative predictive value was 89% and 91% respectively., Conclusion: Values of intracystic tumor markers CEA and CA 19-9 do not allow distinguishing simple cysts from cystic liver neoplasms. The most effective treatment for symptomatic simple liver cysts is surgical fenestration. The pathological analysis of the wall of the cysts enables the correct diagnosis, allowing to indicate a surgical reintervention in cases of hepatic cyst neoplasia., (Copyright © 2023. Published by Elsevier España, S.L.U.)

A 74-year-old female was admitted for painless jaundice. Laboratory tests showed hyperbilirubinemia, cholestasis, normal coagulation, and Ca19-9:163U/L. The CT-scan reported dilation of the intrahepatic and extrahepatic bile ducts secondary to a 24mm tumor in the intrapancreatic common bile duct. The magnetic cholangioresonance showed multiple endoluminal polypoid lesions, suggestive of intraductal papillary neoplasm of the bile duct (IPNB). The endoscopic bile duct brushing was non-conclusive.

Data comparing long-term effectiveness and safety of once-daily tacrolimus formulations in de novo liver transplantation are scarce. We compared the effectiveness, pharmacokinetic profile, and safety of LCPT (Envarsus) and PR-Tac (Advagraf) for up to 12 months post-transplant. Adult de novo liver transplant recipients who started IR-Tac (Prograf) and were converted to LCPT or PR-Tac 3-5 days post-transplant were included. Data from 163 patients were analyzed, 87 treated with LCPT and 76 with PR-Tac. The incidence of treatment failure was 30.5% in the LCPT group versus 23.0% in the PR-Tac group (p = .291). Biopsy-proven acute rejection (BPAR) was reported in 26.8% of patients in the LCPT group and 17.6% in the PR-Tac group (p = .166). Graft loss was experienced in one patient (1.2%) in the LCPT group and three patients (4.1%) in the PR-Tac group (p = .346). Death was registered in three patients (3.7%) in the LCPT group and three patients (4.1%) in the PR-Tac group (p > .999). Patients in the LCPT group showed 45.7% higher relative bioavailability (C min /total daily dose [TDD]; p < .01) with similar C min and 33.3% lower TDD versus PR-Tac (p < .01). The evolution of renal function, safety profile, and the incidence of post-transplant renal failure, dyslipidemia, obesity, hypertension, and diabetes mellitus were similar in patients treated with LCPT and PR-Tac. In de novo liver transplant patients, LCPT and PR-Tac showed comparable effectiveness with higher relative bioavailability, similar C min and lower TDD in the LCPT group. Renal function, safety, and post-transplant complications were comparable in LCPT and PR-Tac groups., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Thoracoabdominal (TA) normothermic regional perfusion (NRP) should allow the safe recovery of heart and liver grafts simultaneously in the context of controlled donation after circulatory death (cDCD). We present the initial results of cDCD liver transplantation with simultaneous liver and heart procurement in Spain until October 2021. Outcomes were compared with a matched cohort of cDCD with abdominal NRP (A-NRP) from participating institutions. Primary endpoints comprised early allograft dysfunction (EAD) or primary non-function (PNF), and the development of ischemic-type biliary lesions (ITBL). Six transplants were performed using cDCD with TA-NRP during the study period. Donors were significantly younger in the TA-NRP group than in the A-NRP group (median 45.6 years and 62.9 years respectively, p  = 0.011), with a median functional warm ischemia time of 12.5 min in the study group and 13 min in the control group. Patient characteristics, procurement times, and surgical baseline characteristics did not differ significantly between groups. No patient in the study group developed EAD or PNF, and over a median follow-up of 9.8 months, none developed ITBL or graft loss. Extending A-NRP to TA-NRP for cardiac procurement may be technically challenging, but it is both feasible and safe, showing comparable postoperative outcomes to A-NRP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Secanella, Alconchel, López-Monclús, Toledo-Martínez, Barrios, Ramírez, Jiménez-Garrido, Rodríguez-Sanjuán, Royo-Villanova, Moreno-González and Lladó.)

Orthotopic liver transplantation (OLT) was the first treatment able to modify the natural course of hereditary transthyretin (ATTRv) amyloidosis, which is a rare and fatal disorder caused by the accumulation of misfolded transthyretin (TTR) variants in different organs and tissues and which leads to a progressive and multisystem dysfunction. Because the liver is the main source of TTR, OLT dramatically reduces the production of the pathogenic TTR variant, which should prevent amyloid formation and halt disease progression. However, amyloidosis progression may occur after OLT due to wild-type TTR deposition, especially in the nerves and heart. In this review, we discuss the disease features influencing OLT outcomes and the clinical manifestations of ATTRv amyloidosis progression post-OLT to improve our understanding of disease worsening after OLT and optimize the follow-up and clinical management of these patients. By conducting a literature review on the PubMed database, we identified patient characteristics that have been associated with worse post-OLT outcomes, including late-onset V50M and non-V50M variants, age >40 years, long disease duration, advanced neuropathy and autonomic dysfunction, and malnutrition. Regarding post-OLT mortality, deaths occurring within the first year after OLT were mainly associated with fatal graft complications and infectious diseases, whereas cardiovascular-related deaths usually occurred later. Considering the diverse clinical manifestations of ATTRv amyloidosis progression post-OLT, including worsening neuropathy and/or cardiomyopathy, autonomic dysfunction, and oculoleptomeningeal involvement, we present advice on the most relevant tests for assessing disease progression post-OLT. Finally, we discuss the use of new therapies based on TTR stabilizers and TTR mRNA silencers for the treatment of ATTRv amyloidosis patients post-OLT., Competing Interests: CC – Disclosure: Funding for advisory boards from Alexion-AstraZeneca Rare Diseases, Alnylam Pharmaceuticals Inc., Sobi, CSL Behring, Pfizer Inc., Argnex Inc, UCB Pharma, and PharmaNex. Speaker funding from Alexion-AstraZeneca Rare Diseases, Sobi, Alnylam Pharmaceuticals Inc., Ferrer Inc, CSL Behring, and Pfizer Inc. Research support from CSL Behring, Pfizer Inc, and Alexion-AstraZeneca Rare Diseases. LL – Disclosure: The author declares that they received a research grant from Alnylam. CB – Disclosure: The author declares that they received honoraria from Pfizer, Alnylam, Akcea, and Sobi. PVPS – Disclosure: The author declares that they received travel grants for meetings from Alnylam Pharmaceuticals Inc. and Sobi; speaker funding from Alnylam Pharmaceuticals Inc. and Sobi; research support from CSL Behring, Pfizer Inc., Alnylam Pharmaceuticals Inc., and Alexion-AstraZeneca Rare Diseases. FMB – Disclosure: The author declares that received honoraria as speaker and research grants from Alnylam, Pfizer, and Sobi. IALL – Disclosure: The author declares that received honoraria as speaker from Alnylam, Pfizer, and Sobi. MCBC – Disclosure: The author declares that there is no conflict of interest. JGM – Disclosure: The author declares that received honoraria as speaker from Alnylam, Pfizer, and Sobi., (© The Author(s), 2023.)

Objective: Incidental gallbladder lesions are common in imaging studies, although it is not always easy to discriminate benign lesions from gallbladder cancer with conventional imaging procedures. The present study aims to assess the capacity of positron emission tomography/computed tomography (PET/CT) with 2-[ 18 F]FDG to distinguish between benign and malignant pathology of the gallbladder, compared with conventional imaging techniques (contrast-enhanced CT or magnetic resonance imaging)., Methods: Positron emission tomography/CT and conventional imaging studies of 53 patients with gallbladder lesions were evaluated and visually classified as benign, malignant, or inconclusive. Agreement between PET/CT and conventional imaging was determined, and imaging findings were correlated with histology or follow-up. Positron emission tomography/CT images were also analyzed semiquantitatively (SUV max and maximum tumor-to-liver ratio [TLR max ]). The presence of adenopathies and distant metastases was assessed and compared between both imaging procedures., Results: According to histology or follow-up, 33 patients (62%) had a malignant process and 20 (38%) had benign lesions. Positron emission tomography/CT and conventional imaging showed a moderate agreement ( κ = 0.59). Conventional imaging classified more studies as inconclusive compared with PET/CT (17.0% and 7.5%, respectively), although both procedures showed a similar accuracy. Malignant lesions had significantly higher SUV max and, especially, TLR max (0.89 and 2.38 [ P = 0.00028] for benign and malignant lesions, respectively). Positron emission tomography/CT identified more pathologic adenopathies and distant metastases, and patients with regional or distant spread had higher SUV max and TLR max in the gallbladder., Conclusions: Positron emission tomography/CT is accurate to distinguish between benign and malignant pathology of the gallbladder, with a similar performance to conventional imaging procedures but with less inconclusive results. Malignant lesions present higher SUV max and TLR max values., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rombauts, Bodro, Daniel Gumucio, Carbonell, Favà, Lladó, González-Costello, Oppenheimer, Castel-Lavilla, Len, Marquez-Algaba, Nuvials-Casals, Martínez González, Lacasa, Carratalà and Sabé.)

Introduction: Alzheimer's disease (AD) is the most frequent cause of cognitive impairment. Improving knowledge of dementia management through health education for health professionals can improve clinical and community care in home and specialist settings. It is important to guarantee good dementia knowledge in health students, and it is necessary to evaluate it with a good standardized tool. The aim of the current study was to assess the psychometric properties of the DKAS-S with cohorts of Ecuadorian health students, to compare these results with a former validation in Spanish health students and to analyse the level of knowledge according to different variables., Methods: We performed a cross-sectional study to assess the validity, reliability and feasibility of the DKAS-S by comparing two different cohorts of health students (nursing and psychologists)., Results: A total of 659 students from Spain (n = 233) and Ecuador (n = 426) completed the DKAS-S (mean age 24.02 (6.35) years old), and 52.80% were nursing students. The DKAS-S showed good internal consistency in the Ecuadorian cohort (Cronbach's α = 0.76). No significant difference was found between Spanish and Ecuadorian students (p = 0.767) in the global scale score, but there were differences in some subscales. Psychologist students scored significantly higher on the global scale than nursing students (32.08 (9.51) vs. 27.49 (7.15); p < 0.001)). Students with a family history of cognitive impairment scored higher on the global scale, and those who had contact with people with dementia obtained better results on the global scale., Conclusions: We confirmed that the DKAS-S is an adequate and useful instrument to measure levels of knowledge about dementia among health students in Spanish-speaking communities. It is a reliable and valid measure with good psychometric properties. Understanding health students' knowledge about dementia will allow better adaptation of academic plans to train better health professionals., (© 2023. The Author(s).)

Background & Aims: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT., Methods: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021., Results: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001)., Conclusions: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed., Impact and Implications: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: Norfloxacin is indicated as primary or secondary prophylaxis for spontaneous bacterial peritonitis in patients with cirrhosis. A history of spontaneous bacterial peritonitis favors colonization by multidrug-resistant bacteria. Infections caused by these bacteria increase morbidity and mortality after transplant. We investigated prophylactic norfloxacin as a risk factor for multidrug-resistant bacterial infections in the early posttransplant period., Materials and Methods: This prospective cohort study included all adult liver recipients in 2 centers between 2015 and 2016. Recipients were classified into 2 groups according to whether or not they received prophylactic norfloxacin pretransplant. Data collection from liver recipients included pretransplant and first month after transplant clinical and microbiological data. Demographic and clinical data of corresponding donors were also collected., Results: We included 157 liver recipients: 54 (34.6%) received norfloxacin and 103 (65.6%) did not received norfloxacin. There were 63 postoperative infections in 47 recipients (29.9%); 17/63 (27%) were multidrug- resistant bacterial infections. The urinary tract was the most commonly affected site (10/17 episodes, 58.8%), and Klebsiella pneumoniae was the microorganism most often isolated (8/17, 47.1%). Incidence of multidrug-resistant bacterial infection was higher in the norfloxacin group (22.2% vs 4.9%; relative risk = 5.6, 95% CI, 1.85-16.89; P = .001).This association was significant after controlling for most confounding factors, including pretransplant vasoactive support (P = .03), Model for End-Stage Liver Disease score (P = .01), previous spontaneous bacterial peritonitis (P = .02), chronic renal impairment (P = .005), number of packed red blood cells (P = .004), use of antilymphocyte globulin as induction (P = .006), and hepatocellular carcinoma (P = .02), but not pre- transplant antibiotic treatment (P = .06)., Conclusions: For recipients who have received prophylactic norfloxacin, clinicians should be aware of the high risk of multidrug-resistant bacterial infections during the first month after liver transplant.