First consensus document of waiting list prioritization for liver transplantation by the Spanish Society of Liver Transplantation (SETH).

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.

Neuropsychological and biopsychosocial evolution, therapeutic adherence and unmet care needs during paediatric transplantation: study protocol of a mixed-methods design (observational cohort study and focus groups) - the TransplantKIDS mental health project.

The present article describes the protocol of a mixed-methods study (an observational cohort design and focus groups), aimed to examine neuropsychological functioning and other biopsychosocial outcomes, therapeutic adherence and unmet care needs in paediatric population undergoing solid organ or allogeneic hematopoietic transplant during the pre- and post-transplant phases. Following a multi-method/multi-source approach, neuropsychological domains will be comprehensively measured with objective tests (SDMT, K-CPT 2/CPT 3, TAVECI/TAVEC, WISC-V/WAIS-IV Vocabulary and Digit Span subtests, Verbal Fluency tests, Stroop, ROCF, and TONI-4); ecological executive functioning, affective and behavioral domains, pain intensity/interference, sleep quality and therapeutic adherence will be assessed through questionnaires (parent/legal guardians-reported: BRIEF-2 and BASC-3; and self-reported: BASC-3, BPI, PROMIS, AIQ and SMAQ); and blood levels of prescribed drugs will be taken from each patient's medical history. These outcomes will be measured at pre-transplant and at 4-weeks and 6-months post-transplant phases. The estimated sample size was 60 patients (any type of transplant, solid organ, or hematopoietic) from La Paz University Hospital (Madrid, Spain). Finally, three focus group sessions will be organized with patients, parents/guardians, and transplant clinicians (n = 15, with 5 participants per group), in order to qualitatively identify unmet care needs during the pre-, and post-transplant stages of the process. The study protocol was registered at ClinicalTrials.gov (NCT05441436).

The Role of Indocyanine Green in Pediatric Gastrointestinal Surgery: Systematic Review.

The use of near-infrared fluorescence imaging with indocyanine green (ICG) is actually considered as a very useful tool in decision-making strategy during challenging surgical procedures with a growing evidence in the literature. Our aim is to perform a systematic review focusing on ICG applications in gastrointestinal surgery. We conducted a systematic review with narrative synthesis in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using PubMed, Medline, and EMBASE databases to identify articles describing the gastrointestinal perioperative use of ICG in children. We extracted data on study design, demographics, surgical indications, ICG dose, and perioperative outcomes. Eleven articles, including 94 pediatric patients, from 2013 to 2022 met the inclusion criteria for narrative synthesis in our systematic review, of which 6/11 (54.5%) were case reports, 4/11 (36.4%) were retrospective studies, and 1/11 (0.1%) were case series. Current clinical applications of ICG in gastrointestinal pediatric surgery included: esophagogastric surgery in 4/11 articles (36.4%), intestinal and pancreatic surgery in 3/11 articles (27.2%), and colorectal surgery in 4/11 articles (36.4%). ICG fluorescence in gastrointestinal pediatric surgery is a promising and safe technology that facilitates intraoperative localization of anatomical structures to achieve a more precise dissection and avoid injury to other adjacent tissues. It can be considered as a meaningful tool for assessing intestinal viability, as it provides objective data on tissue perfusion, and can impact the intraoperative decision in reconstructive surgeries requiring anastomosis. Future studies are needed to confirm these initial promising results. The lack of comparative and prospective studies is still the main limitation.

Parental Presence during Induction of Anesthesia and Emergence Delirium Influence the Incidence of Postoperative Maladaptive Behavioral Changes.

OBJECTIVE: Surgical intervention in pediatric patients can cause variable degrees of psychological stress with potential consequences in the perioperative period and even in the long term, after hospital discharge in the form of behavioral changes days and months later. The aim of our study was to determine which preoperative preparation strategy reduces postoperative maladaptive behavioral changes in children undergoing ambulatory pediatric surgery. MATERIALS AND METHODS: This prospective observational study included 638 pediatric American Society of Anesthesiologists physical status I or II patients who underwent ambulatory pediatric surgery. They were grouped into four preoperative preparation groups: not premedicated (NADA), premedicated with midazolam (MDZ), parental presence during induction of anesthesia (PPIA), and parental presence during induction of anesthesia and premedicated with midazolam (PPIA + MDZ). All patients included in the study were contacted by telephone during 1 year posthospital discharge to assess the postoperative maladaptive behavioral changes using the Posthospitalization Behavior Questionnaire (PHBQ). We performed a multivariate analysis to evaluate the influence of type of preparation and behavioral changes. RESULTS: Patients in the PPIA and PPIA + MDZ preparation groups presented less postoperative maladaptive behavioral changes compared to patients in the NADA and MDZ groups (odds ratio [OR]: 1.8 [1.1-2.8] and OR 2.2 [1.03-4.49]) during the first week and first month. The intensity of emergence delirium measured by the Pediatric Anesthesia Emergence Delirium (PAED) scale increases the probability of postoperative maladaptive behavioral changes (OR: 1.05 [1.006-1.103]). CONCLUSION: The presence of parents during induction of anesthesia (PPIA and PPIA + MDZ) is a very effective strategy in reducing postoperative behavioral changes. These benefits are more significant in children under 5 years of age.

How does the number of training years in pediatric surgery affect appendectomy outcomes?

INTRODUCTION: Appendectomy has traditionally been considered as a training operation for junior pediatric surgeons during their training period. However, with the increase of laparoscopic appendectomy, there has been a growing concern about the performance of this procedure by junior trainees. Our aim is to analyze intra-/postoperative appendectomy outcomes according to the number of training years during Pediatric Surgical residency training program. METHODS: A retrospective study was performed in patients who underwent appendectomy between 2018 and 2021 in our institution, who were divided into 5 groups according to the number of training years of the junior surgeon who performed the intervention (Y1-Y5). Demographics, complicated appendicitis rate, operation time, and postoperative complications were compared. A stratified analysis according to the technique performed (open/laparoscopic) was performed. RESULTS: A total of 1274 appendectomized patients were analyzed, of which 1257 (98.7%) were operated on by junior trainees (81 in Y1; 407 in Y2; 337 in Y3; 261 in Y4; and 171 in Y5) without demographic differences between groups. As the year of training increased, an elevation in complicated appendicitis rate was observed, although without statistically significant differences. However, laparoscopic/open appendectomies ratio increased with increasing year of training (p < 0.001). Operative time decreased significantly with increasing year of training (p < 0.001), both in open and laparoscopic appendectomies. There were no significant differences in postoperative complications, nor in the stratified analysis according to surgical technique. CONCLUSION: Appendectomy performed by junior pediatric surgery trainees can be considered a safe procedure from the first year of training, regardless of the technique used.

Familial CD45RA- T cells to treat severe refractory infections in immunocompromised patients.

Background: Immunocompromised patients are susceptible to high-risk opportunistic infections and malignant diseases. Most antiviral and antifungal drugs are quite toxic, relatively ineffective, and induce resistance in the long term. The transfer of pathogen-specific Cytotoxic T-Lymphocytes has shown a minimal toxicity profile and effectiveness in treating Cytomegalovirus, Adenovirus, Epstein - Barr virus, BK Virus and Aspergillus infections, but this therapy have the main limitations of regulatory issues, high cost, and absence of public cell banks. However, CD45RA- cells containing pathogen-specific memory T-cells involve a less complex manufacturing and regulatory process and are cheaper, feasible, safe, and potentially effective. Methods: We present preliminary data from six immunocompromised patients: four who had severe infectious diseases and two who had EBV lymphoproliferative disease. All of them underwent multiple safe familial CD45RA- T-cell infusions as adoptive passive cell therapy, containing Cytomegalovirus, Epstein - Barr virus, BK virus, and Aspergillus-specific memory T-cells. We also present the method for selecting the best donors for CD45RA- cells in each case and the procedure to isolate and store these cells. Results: The infusions were safe, there was no case of graft-versus host disease, and they showed a clear clinical benefit. The patients treated for BK virus nephritis, Cytomegalovirus encephalitis, Cytomegalovirus reactivation, and disseminated invasive aspergillosis experienced pathogen clearance, complete resolution of symptoms in 4-6 weeks and a lymphocyte increase in 3 of 4 cases after 3-4 months. Donor T cell transient microchimerism was detected in one patient. The two patients treated for EBV lymphoproliferative disease underwent chemotherapy and several infusions of CD45RA- memory T-cells containing EBV cytotoxic lymphocytes. Donor T-cell microchimerism was observed in both patients. The viremia cleared in one of the patients, and in the other, despite the viremia not clearing, hepatic lymphoproliferative disease remained stable and was ultimately cured with EBV-specific Cytotoxic T-Lymphocytes. Conclusion: The use of familial CD45RA- T-cells containing specific Cytotoxic T-lymphocytes is a feasible, safe and potential effective approach for treating severe pathogen infections in immunocompromised patients through a third party donor. Furthermore, this approach might be of universal use with fewer institutional and regulatory barriers.

When less is more: Experimental Bishop-Koop technique for reduction in the use of laboratory animals for intestinal pathophysiological studies.

The use of animals to gain knowledge and understanding of diseases needs to be reduced and refined. In the field of intestinal research, because of the complexity of the gut immune system, living models testing is mandatory. Based on the 3Rs (replacement, reduction and refinement) principles, we aimed to developed and apply the derived-intestinal surgical procedure described by Bishop and Koop (BK) in rats to refine experimental gastrointestinal procedures and reduce the number of animals used for research employing two models of intestinal inflammation: intestinal ischemia-reperfusion injury and chemical-induced colitis. Our results show the feasibility of the application of the BK technique in rodents, with good success after surgical procedure in both small and large intestine (100% survival, clinical recovery and weight regain). A considerable reduction in the use of the number of rats in both intestinal inflammation models (80% in case of intestinal ischemia-reperfusion damage and 66.6% in chemical-induced colitis in our experimental design) was achieved. Compared with conventional experimental models described by various research groups, we report excellent reproducibility of intestinal damage and functionality, survival rate and clinical status of the animals when BK is applied.

Mortality predictive factors in congenital hepatic hemangioma: a case-control study.

Congenital hepatic hemangiomas (CHHs) are benign vascular tumors whose clinical, histological, and genetic correlation has recently been described in patients with long-term survival, although no mortality risk factors have been identified to date. The aim of this study is to analyze predictors of mortality in patients with CHH. A retrospective single-center case-control study of consecutive CHH patients diagnosed in our institution between 1991 and 2021 was performed, who were classified into two groups according to their survival. Demographic, gestational, imaging, and laboratory data at diagnosis were collected and compared between both groups. A total of 29 patients were included (12 males; 17 females) of whom 5 died as a result of CHH evolution due to cardiac failure and coagulopathy, with a median age of 11 days until death. No differences in demographic or gestational data were reported. There were neither differences when comparing imaging tests, nor in location, number of affected liver segments, or CHH estimated volume. Upon laboratory data at diagnosis, deceased patients had a significant elevation of median liver enzymes [glutamic-oxaloacetic transaminase (359 u/L vs. 45 u/L; p < 0.01) and glutamic-pyruvic transaminase (313 u/L vs. 20 u/L; p < 0. 01)], as well as a decreased median platelet count (85,250/µL vs. 337,000/µL; p < 0.01), prothrombin activity (54% vs. 93%; p < 0.01), and fibrinogen (131 mg/dL vs. 284 mg/dL; p < 0.01), with no differences in blood count or biochemistry data. CONCLUSIONS: CHH clinical behavior can be innocuous or life-threatening. Thrombocytopenia, coagulation disorders, and increased liver enzymes at diagnosis seem to be the main predictors of mortality. WHAT IS KNOWN: • Congenital Hepatic Hemangiomas (CHHs) are benign vascular tumors whose clinical behavior can be innocuous or life-threatening. WHAT IS NEW: • Thrombocytopenia, coagulation disorders and increased liver enzymes at diagnosis seem to be the main predictors of mortality in these patients.

Indocyanine green navigation in minimally invasive resection of multiple metachronous pulmonary metastases of hepatoblastoma.

Pulmonary metastases from hepatoblastoma (HB) have traditionally been identified by preoperative computed tomography scan image evaluation, and intraoperative visual and palpatory examinations through thoracotomy have been generally recommended. However, the safety and accuracy of surgery can be problematic in patients with small multiple lung metastases due to postoperative respiratory dysfunction risk secondary to decreased residual lung capacity in wedge resections. We present an 8-month-old patient with metastatic HB with multiple metachronous pulmonary lesions in whom thoracoscopic lung resections were performed guided by indocyanine green (ICG) administered intravenously 24 h earlier (0.5 mg/kg). ICG fluorescence allowed identification and limited resection of lung parenchyma, avoiding postoperative respiratory dysfunction. A total of 16 lung lesions were resected during four operations (two bilateral and two right thoracoscopies), with no postoperative complications. ICG-guided thoracoscopic surgery allowed identification and resection of metastatic nodules in both lungs during the same procedure, achieving a hospital stay of less than 3 days for each intervention. The patient is currently 24 months old and remains asymptomatic, with no distant disease at the last imaging control. ICG-guided resection via a thoracoscopic approach is particularly useful in patients with multiple and/or metachronous metastases requiring multiple surgical interventions.

Impact of muscle mass on the prognosis of liver transplantation for infants with biliary atresia.

Background: Sarcopenia in adult cirrhotic patients is associated with increased morbidity and mortality whereas in children it is still being studied. Anthropometric variables in cirrhotic children are not reliable for assessing muscle mass as they may be altered by ascites, edema, and organomegaly. Measuring the area of the psoas showed good correlation with muscle mass in adults. We aimed to study in cirrhotic infants undergoing liver transplantation the association of the psoas area with liver transplant prognosis as well as with several analytical and anthropometric parameters used to evaluate nutritional status. Methods: Retrospective cohort of 29 infants with cirrhosis due to biliary atresia who underwent abdominal CT scan as a pre-transplant study. We measured the psoas muscle index (PMI) at L4-L5 since it best correlates with muscle mass in pediatric patients. As there are no validated cut-off points to define sarcopenia in children under one year of age, PMI was recorded as a continuous variable and correlated with different prognostic, clinical, and analytical variables. The SPSS 17.0 package was used for statistical analysis and a P < 0.05 was considered significant. Results: 29 infants (10 boys, 19 girls) were studied. 62% were Caucasian and the rest were South American. The mean age at CT scan was 8.5 months (range 3-15 months). There was a negative correlation between PMI and days of admission prior to liver transplant, previous infections, and bone fractures. Among the analytical parameters, cholinesterase, albumin, and prealbumin correlated positively with PMI (P < 0.05). No relationship was observed with anthropometric parameters: weight, height, BMI, brachial perimeter, or bioimpedance. During surgery, patients with lower PMI had a greater need for plasma transfusion, and in the immediate postoperative period, there was a longer stay in intensive care, more days of mechanical ventilation, and more days of hospital admission (P < 0.05). On the contrary, no relationship was found with other complications: bleeding, re-interventions, biliary leaks, rejection, thrombosis, re-transplantation, or infections. Conclusions: The decrease in muscle mass is associated with increased morbidity in infants with biliary atresia undergoing liver transplantation. Muscle mass in these patients cannot be adequately assessed with anthropometric measurements commonly used in the clinic.

Nonhepatic Cancer in the Pediatric Liver Transplant Population: Guidelines From the ILTS-SETH Consensus Conference.

The incidence and geographical distribution of cancers in children are dramatically different from the adult population. Consequent to improvements in postcancer survival, there is a progressive increase in the number of patients requiring liver transplantation (LT) who are in remission from pretransplant malignancy (PTM). Conventionally, however, PTM has been considered a relative contraindication to LT. Furthermore, with improving post-LT survival now extending beyond decades, the cumulative effect of immunosuppression and the increasing risk of de novo cancers need to be acknowledged. A working group was formed to evaluate, discuss, and retrieve all the evidence and provide guidelines with regards to best practices surrounding nonhepatic cancer in the pediatric LT (PLT) population. Further subsections of research included (a) extrahepatic solid tumors, leukemia, lymphoma, and other hematological disturbances before PLT and (b) malignancies following PLT (including posttransplant lymphoproliferative disorders). This guidance provides a collection of evidence-based expert opinions, consensus, and best practices on nonhepatic cancers in PLT.

Parental Presence during Induction of Anesthesia Improves Compliance of the Child and Reduces Emergence Delirium.

INTRODUCTION: Preoperative stress and anxiety in pediatric patients are associated with poor compliance during induction of anesthesia and a higher incidence of postoperative maladaptive behaviors. The aim of our study was to determine which preoperative preparation strategy improves compliance of the child during induction and decreases the incidence and intensity of emergence delirium (ED) in children undergoing ambulatory pediatric surgery. MATERIALS AND METHODS: This prospective observational study included 638 pediatric American Society of Anesthesiologists I-II patients who underwent ambulatory pediatric surgery, grouped into four preoperative preparation groups: NADA (not premedicated), MDZ (premedicated with midazolam), PPIA (parental presence during induction of anesthesia), and PPIA + MDZ. The results were subsequently analyzed in four age subgroups: Group 1 (0-12 months), Group 2 (13-60 months), Group 3 (61-96 months), and Group 4 (> 96 months). Preoperative anxiety (modified Yale Preoperative Anxiety Scale [m-YPAS]), compliance of the child during induction (Induction Compliance Checklist [: ICC]), and ED (Pediatric Anesthesia Emergence Delirium scale) were analyzed in each group. RESULTS: Eighty-one percent of patients in the PPIA + MDZ preparation group presented a perfect compliance during the induction of anesthesia (ICC = 0), less preoperative anxiety (mean score m-YPAS = 26), less probability of ED (odds ratio: 10, 5 [3-37.5]; p < 0.05), and less ED intensity compared with the NADA group (1.2 vs. 5.8; p = 0.001). CONCLUSION: PPIA associated with midazolam premedication improves compliance during induction and decreases the incidence and intensity of ED.

Graft infusion of adipose-derived mesenchymal stromal cells to prevent rejection in experimental intestinal transplantation: A feasibility study.

BACKGROUND: Mesenchymal stromal cells (MSC) have been proposed as a promising complement to standard immunosuppression in solid organ transplantation because of their immunomodulatory properties. The present work addresses the role of adipose-derived MSC (Ad-MSC) in an experimental model of acute rejection in small bowel transplantation (SBT). MATERIAL/METHODS: Heterotopic allogeneic SBT was performed. A single dose of 1.5x106 Ad-MSC was intra-arterially delivered just before graft reperfusion. Animals were divided into CONTROL (CTRL), CONTROL+Ad-MSC (CTRL_MSC), tacrolimus (TAC), and TAC+Ad-MSC (TAC_MSC) groups. Each Ad-MSC groups was subdivided in autologous and allogeneic third-party groups. RESULTS: Rejection rate and severity were similar in MSC-treated and untreated animals. CTRL_MSC animals showed a decrease in macrophages, T-cell (CD4, CD8, and Foxp3 subsets) and B-cell counts in the graft compared with CTRL, this decrease was attenuated in TAC_MSC animals. Pro- and anti-inflammatory cytokines and some chemokines and growth factors increased in CTRL_MSC animals, especially in the allogeneic group, whereas milder changes were seen in the TAC groups. CONCLUSION: Ad-MSC did not prevent rejection when administered just before reperfusion. However, they showed immunomodulatory effects that could be relevant for a longer-term outcome. Interference between tacrolimus and the MSC effects should be addressed in further studies.

Effectiveness of immunosuppression minimisation, conversion or withdrawal strategies in paediatric solid organ and haematopoietic stem cell transplantation: a protocol of a systematic review and meta-analysis.

INTRODUCTION: Paediatric transplantation is the only curative therapeutic procedure for several end-stage rare diseases affecting different organs and body systems, causing altogether great impact in European children's health and quality of life. Transplanted children shift their primary disease to a chronic condition of immunosuppression to avoid rejection. Longer life expectancy in children poses a greater risk of prolonged and severe side effects related to long-term immunosuppressive (IS) disabilities and secondary cancer susceptibility. The goal remains to find the best combination of IS agents that optimises allograft survival by preventing acute rejection while limiting drug toxicities. This systematic review will aim to determine the optimal IS strategy within the so-called minimisation, conversion or withdrawal strategies. METHODS AND ANALYSIS: We will search the following databases with no language restrictions: Cochrane Central Register of Controlled Trials in the Cochrane Library, OvidSP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; OvidSP Embase Classic+Embase; Ebsco CINAHL Plus, complete database; WHO International Clinical Trials Registry Platform search portal. We will include controlled and uncontrolled clinical trials along with any prospective or retrospective study that includes a universal cohort (all participants from a centre/region/city over a certain period). Cases series and cross-sectional studies are excluded. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. The outcomes included in this review are: patient survival, acute graft rejection, chronic graft rejection, diabetes, graft function, graft loss, chronic graft versus host disease, acute graft versus host disease, surgical complications, infusion complications, post-transplant lymphoproliferative disease, liver function, renal function, cognition, depression, health-related quality of life, hospitalisation, high blood pressure, low blood pressure, cancer-other, cancer-skin, cardiovascular disease, bacterial infection, Epstein-Barr infection, cytomegalovirus infection, other viral infections and growth.