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Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions.The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered.A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx.A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.

Liver transplant (LT) is the standard therapy for end-stage liver disease. Advances in surgical techniques and immunosuppression protocols improved the results of LT by increasing long-term survival. Nevertheless, an adequate match between the donor and recipient is paramount for avoiding futile liver transplants. We aimed to identify the prognostic factors in donor-recipient LT matching.Retrospective analysis of adult LT was conducted from January 2006 to December 2018, which included the following transplant modalities: deceased donor LT (DDLT), living donor LT (LDLT), combined liver-kidney transplant (CLKT), and domino LT (DLT).Among 1101 patients who underwent LT, 958 patients underwent DDLT, 92 patients underwent LDLT, 45 patients underwent CLKT, and 6 patients underwent DLT. The overall survival (OS) in 1, 5, and 10 years were 89%, 83%, and 82%, respectively. For DDLT, OS in 1, 5, and 10 years were 91%, 84%, and 82%, respectively. For LDLT, OS in 1, 5, and 10 years were 89%, 72%, and 69%, respectively. For CKLT, OS in 1, 5, and 10 years were 90%, 71%, and 71%, respectively. None of the DLT patients died. For DDLT, the factors that affected OS were the presence of fulminant liver failure (odds ratio [OR], 2.23; 95% CI, 1.18-4.18; P = .001), hemodialysis before LT (OR, 2.12; 95% CI, 1.27-3.5; P = .004), retransplant (OR, 4.74; 95% CI, 2.75-8.17; P = .000), and recipient age60 years (OR, 1.86; 95% CI, 1.27-2.73; P = .001). For hospitalization before LT (due to an acute-on-chronic liver failure), the OR was 2.10 (95% CI, 1.29-3.42; P = .003). Donor intensive care unit time7 days (OR, 1.46; 95% CI, 1.04-2.06; P = .02) was also associated with overall mortality.We identified prognostic factors in donor-recipient LT matching. Furthermore, we demonstrated that an adequate organ allocation with donor-recipient selection might increase graft survival and reduce waiting list mortality.

Donor hepatic artery thrombosis (dHAT) identified during liver procurement and backtable is a rare and little-reported event that can make liver transplants unfeasible.This is a retrospective study of dHAT identified during liver grafts procurements or backtable procedures. All grafts were recovered from brain-dead donors. The demographic characteristics of the donors and the incidence of dHAT were analyzed. The data were also compared to a cohort of donors without dHAT.There was a total of 486 donors during the study period. The incidence of dHAT was 1.85% (n = 9). The diagnosis of dHAT was made during procurement in 5 cases (55.5%) and during the backtable in 4 (44.4%). Most donors were female (n = 5), with an average BMI of 28.14 ± 6.9 kg/mThe occurrence of dHAT before liver procurement is a rare event, however it may become a treacherous pitfall if the diagnosis is late. Grafts with anatomic variations recovered from women with brain death due to stroke and with past history of hypertension seem to be at a higher risk of presenting dHAT.

Liver transplantation in an animal model is challenging due to hemodynamics and intraoperative anesthetic care. Several models are described in the literature employing different techniques such as venovenous bypass or aortic cross-clamping to maintain hemodynamic stability, although few groups keep the animal alive in the postoperative period. This study aims to evaluate a liver transplantation clinical model in pigs without venovenous bypass or aortic cross-clamping.Male pigs weighing 20 to 35 kg underwent liver transplantation surgery without using venovenous bypass or aorta cross-clamping. Protocols were approved by the Animal Care and Use Committee of the University of São Paulo, Brazil.Ten LTs were performed. Cold ischemia and warm ischemia were 119 ± 33.28 minutes and 26 ± 9.6 minutes, respectively. Hemodynamic changes were significantly higher after the postrevasculazation phase: heart rate (P.001), medium arterial pressure (P.001), and cardiac output (P = .03). Hypotension was treated with intravenous fluids and, in some cases, with vasoactive drugs especially during the post-reperfusion period. No animals died during the procedure and almost survival until the first postoperative day. Serum aspartate aminotransferase and lactate increased their values in the post-reperfusion phase.Practice-based on laboratory animals improves surgical skills and the development of experimental models aimed at new advances in this field. Perfecting our technique on the swine model, we could move forward to create a small-for-size model, test new therapeutic strategies, and define the boundaries for safely performing an enlarged liver resection or a partial liver graft transplant.

Pancreas transplantation remains a challenging procedure for small and medium-sized transplants teams, despite improvements in graft survival. Data regarding the impact of the procurement team's experience on the outcomes of pancreas transplant are lacking. The objective of this study was to evaluate risk factors that lead to pancreatic allograft thrombosis, especially the experience of the pancreas procurement team.A retrospective study of 137 patients who underwent pancreas transplantation between March 2005 and May 2017 was conducted. Donor's and recipient characteristics were evaluated as well as their relationship to pancreatic allograft thrombosis. Cases were divided according to the number of pancreas procurements previously done by the procurement surgeon: group 1 (30 to 40 retrievals) and group 2 (≥40 retrievals).Simultaneous pancreas-kidney transplants accounted for 89.8% of cases (n = 123). Surgeons from group 2 performed 62.8% (n = 86) of the procurements. The graft was removed in 19 cases (13.8%) due to thrombosis. In univariate analysis, lower experience of the retrieval team was associated with allograft loss (P = .04). In multivariate analysis, donor intensive care unit time ≥5 days (P = .03) and lower experience of the procurement team were associated with increased risk of pancreatic allograft thrombosis (P = .02), whereas recipient's age from 30 to 40 years (P = .018) or ≥40 years (P = .02) was found as a protective factor.Pancreatic allograft thrombosis remains an important cause of graft loss in pancreas transplantation. Recipient's age, prolonged donor intensive care unit time, and lower experience of the procurement team directly influence pancreatic allograft thrombosis.

BackgroundIsolated intestinal transplantation (IT) is indicated in cases of intestinal failure (IF) in the absence of severe liver dysfunction. Short bowel syndrome (SBS) is the most frequent IF etiology, and due to the absence or considerable reduction of intestinal loops in the abdominal cavity in these patients, there is atrophy and muscle retraction of the abdominal wall, leading to loss of the abdominal domain and elasticity and preventing the primary closure of the abdominal wall. This study aimed to describe a technique for the closure of the abdominal wall after IT without using prostheses.MethodsFour patients underwent IT with the impossibility of primary closure of the abdominal wall. We describe a novel technique, associating a series of vacuum-assisted closure dressings, components separation, and relaxation incisions.ResultsAll patients presented a successful closure of the abdominal wall with the described technique, with no complications related to the abdominal wall.ConclusionThe technique proved to be safe, effective, and reproducible as an option for abdominal wall closure after IT. Employing this technique in a greater number of cases is necessary to confirm these results.

Introduction: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). Methods: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. Results: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies’ results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. Conclusion: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

Terlipressin is widely used for treatment of hepatorenal syndrome and variceal bleeding in cirrhotic patients. However, it may be associated with side effects, especially those related to vasoconstriction, such as myocardial infarction or intestinal ischemia. This is a case report of a cirrhotic patient with nonvariceal upper gastrointestinal bleeding after duodenal necrosis due to the use of terlipressin, a novel side effect not yet described in literature to the best of our knowledge.A 51-year-old male patient, with alcoholic liver cirrhosis and hepatitis C virus infection, was admitted presenting oliguria associated with severe ascites and lower limb edema. His Model for End Stage Liver Disease-Sodium score was 19 and his serum creatine level was 2.12 mg/dL. Albumin infusion was performed for 48 hours, but his serum creatinine level reached 3.46 mg/dL. Terlipressin infusion was started in continuous infusion and serum creatinine levels progressively decreased. However, the patient presented hemorrhagic shock secondary to hematemesis after 7 days. Upper digestive endoscopy showed an extensive ulcerated lesion in the duodenal bulb, reaching 70% of its lumen, with hematic residues and necrotic foci. Terlipressin was suspended and proton pump inhibitors were started. Despite intensive care, the patient developed severe encephalopathy and reentrant seizures. He eventually died 10 days after the bleeding event.We described a case of nonvariceal upper gastrointestinal bleeding secondary to duodenal necrosis, which was caused by visceral ischemia induced by terlipressin. Given its fatality potential, this novel side effect should be remembered when using this medication in cirrhotic patients.

COVID-19 has spread worldwide and has become a public health emergency and a pandemic of international concern. The solid organ donation system was no different. This study aimed to investigate the effect of COVID-19 on the liver transplant (LT) system in Brazilian territory.We retrospectively reviewed all liver donor records allocated in São Paulo State, Brazil, 1 year before and 1 year during the COVID-19 pandemic. We defined the pre-COVID-19 (PRE) period as between April 2019 and April 2020 and the post-COVID-19 (POST) period as between April 2020 and April 2021. Moreover, we compared LT performed in our institution during these periods. To evaluate outcomes, we compared 30-day survival after LT.In the PRE period, 1452 livers were offered for donation in São Paulo State and other Brazilian territories. Of these, 592 were used in LT. In the POST period, 1314 livers were offered for donation, but only 477 were used in LT. Organ refusal was higher in the POST period (P.05). Our center performed 127 and 156 LTs in these periods, respectively, and an increase above 20% was significant (P = .039). There was no difference in 30-day survival between the periods (87.2% vs 87.9%, P.5, respectively).The COVID-19 pandemic harmed potential and allocated donors and LTs performed. However, it is possible to maintain the LT volume of a transplant center without compromising survival outcomes through preventive strategies against COVID-19 propagation.

Background: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic. Methods: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were “COVID-19” and “Liver transplantation”. Results: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5-44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%. Conclusion: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790)

BACKGROUND Adequate donor and recipient matching in liver transplantation is crucial to improve patient survival. Our objective was to propose and validate a new model for predicting outcomes using donor and recipient scoring criteria. MATERIAL AND METHODS We retrospectively analyzed data of all patients (n=932) who underwent liver transplantation (n=1106) from January 2006 to December 2018. For score standardization, 30% (n=280) of patients were randomly selected for analysis and divided into 3 categories: ≤4 points, 5 to 8 points, and8 points. Scoring system validation was performed on a dataset with 70% (n=652) of the patients. RESULTS Survival of the stratified group (30%) was significant (P0.001). Scores of 4 to 8 points presented lower risk of death (1.74 [CI 0.97-3.13; P=0.062]), while8 points presented higher risk (2.74 [CI 1.36-5.57; P=0.005]). In the validation score (70%), global survival was significant (P0.0016); patients with scores of 4 to 8 points had lower risk of death (1.16 [CI 1.16-2.38; P=0.005]); and scores8 points (2.22 [CI 1.40-3.50; P0.001]), retransplant, fulminant hepatitis, previous large abdominal/biliary tree surgery, MELD score, and serum creatinine before liver transplantation1.5 mg/dL (P0.05) presented higher risk. Individual recipient factors with 4 to 8 points had a lower risk of death (2.29 [CI 1.82-2.87; P0.0001]) than those with scores8 points (4.02 [CI 2.22-7.26; P0.0001]). CONCLUSIONS A novel prognostic-based scoring system using donor and recipient characteristics was proposed and clinically validated. Two-factor scoring indicated the superiority of the predictability outcome and improved prediction of higher mortality.

Liver transplantation has come a long way and is now regarded as the gold standard treatment for end-stage liver failure. The great majority of livers utilized in transplantation come from brain-dead donors. A broad inflammatory response characterizes BD, resulting in multiorgan damage. This process is primarily mediated by cytokines, which increase the immunogenicity of the graft. In male Lewis rats, we evaluated the immune response in a BD liver donor and compared it to that of a control group. We studied two groups: Control and BD (rats subjected to BD by increasing intracranial pressure). After the induction of BD, there was an intense rise in blood pressure followed by a fall. There were no significant differences observed between the groups. Blood tissue and hepatic tissue analyzes showed an increase in plasma concentrations of liver enzymes (AST, ALT, LDH and ALP), in addition to pro-inflammatory cytokines and macrophages in liver tissue in animals submitted to BD. The current study found that BD is a multifaceted process that elicits both a systemic immune response and a local inflammatory response in liver tissue. Our findings strongly suggested that the immunogenicity of plasma and liver increased with time following BD.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay. This study presents the specific ERAS Society recommendations for liver transplantation (LT) based on the best available evidence and on expert consensus. METHODS: PubMed and ClinicalTrials.gov were searched in April 2019 for published and ongoing RCTs on LT in the last 15 years. Studies were selected by 5 independent reviewers, and were eligible if focusing on each validated ERAS items in the area of adult LT. An e-Delphi method was used with an extended interdisciplinary panel of experts to validate the final recommendations. RESULTS: Forty-three articles were included in the systematic review. Consensus was reached among experts after the second round. Patients should be screened for malnutrition and treated whenever possible. Prophylactic nasogastric intubation and prophylactic abdominal drainage may be omitted, and early extubation should be considered. Early oral intake, mobilization and multimodal-balanced analgesia are recommended. CONCLUSIONS: The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the e-Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.PROSPERO CRD4201913279.

The classic piggyback technique uses the union of the 3 hepatic veins to perform the cavo-caval anastomosis. However, due to the lateral localization of the right hepatic vein, the partial clamping of the vena cava in this technique significantly reduces the venous return to the right atrium. To avoid this, we adopted in 2015 a modified piggyback technique, in which we use the common trunk of the middle and left hepatic veins and also perform a lateral incision toward the right in the anterior wall of the vena cava in order to widen the final ostium of the cavo-caval anastomosis. The aim of the study was to analyze the incidence of hepatic venous outflow obstruction between those 2 techniques.Retrospective study of liver transplant recipients undergoing venography for suspected hepatic venous outflow obstruction from January 2009 to June 2021. Patients undergoing transplantation with living donors or split grafts and pediatric cases were excluded from the study.From January 2009 to December 2014 and from January 2015 to June 2021, 587 (group 1) and 730 (group 2) deceased-donor liver transplants were performed with the classic and the modified piggyback techniques, respectively. The incidence of cases with suspected hepatic venous outflow obstruction in groups 1 and 2 were 1.87% (n = 11) and 0.95% (n = 7), respectively (P = 0,15). The number of confirmed patients with outflow blockage that required endovascular treatment during venography in groups 1 and 2 were 4 (0.68%) and 5 (0.68%), respectively (P = 0,31).This modified piggyback technique did not increase the incidence of hepatic venous outflow obstruction at our service.

The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM).We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION".Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process.The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.

Identifying anatomic variations of the hepatic artery is essential in liver transplantation. The artery supply is crucial for the procedure's success, and, in some cases of anatomic variations, they need reconstruction. Hepatic artery thrombosis is a severe vascular complication. This study evaluated the prevalence of anatomic variations and correlated arterial reconstructions with hepatic artery thrombosis.We performed a retrospective analysis of medical records, adult patients undergoing liver transplant, donor's arterial anatomy, arterial reconstructions, and thrombosis after transplant from January 2019 to December 2020.Among 226 cases, 71% had normal anatomy. All these patients met Michel's classification subtypes, of which 161 (71%) were class I, which is the most common. The second most common variation was class II, with 25 donors (11%), followed by class III, with 17 donors (7.5%). Anatomic artery variations were a risk factor for hepatic artery thrombosis development (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.1-22.5; P = .002). In the same way, the artery reconstruction was associated with hepatic artery thrombosis arising with postoperative time (OR, 18.0; 95% CI, 4.9-57.5; P.001). Global hepatic artery thrombosis occurred in 11 cases (4.87%).Anatomic hepatic artery variations are frequent and do not make liver transplant unfeasible. However, variations that require reconstruction may raise the risk of thrombosis.

Living donor liver transplant (LDLT) is a valuable therapeutic option for overcoming the deceased donor shortage. Modified right lobe graft (MRLG) keeps the middle hepatic vein (MHV) trunk with the remnant liver to improve donor safety. Hemostasis in the MHV tributary reconstruction can be tricky; surgical stitches and energy coagulation are ineffective. Fibrin glues are excellent vascular sealants but are poor in maintaining hemostasis in an active hemorrhage or preventing resection surface-related complications after liver resection. We propose applying fibrin sealant during back table graft preparation to seal the hepatic edge and MHV reconstruction to avoid bleeding after graft revascularization.Our retrospective cohort study included all adult patients undergoing LDLT between August 2017 and December 2021. During the back table procedure, we performed the reconstruction of the inferior right hepatic vein and/or MHV tributaries from segment 5 (V5) and segment 8 (V8) using a vein harvested from a nonrelated deceased donor. Before initiating the hepatic graft implantation, we applied fibrin sealant in the resected parenchyma, especially in the V5 and V8 anastomosis, to seal the hepatic edge and hepatic vein reconstruction.No bleeding was identified in the hepatic edge, and blood product transfusion was unnecessary for any recipients after reperfusion.In LDLT using MRLG with MHV reconstruction, the fibrin sealant, when applied on the raw hepatic surface, and vascular reconstruction during back table graft preparation avoided bleeding after graft revascularization.

The number of elderly patients who have end-stage liver disease and require liver transplantation has dramatically increased. On the other hand, liver grafts from elderly donors have been offered more frequently for transplantation. The present study aims to analyze the results of liver transplants performed with donors and recipients aged ≥70 years.We performed a single-center retrospective study of deceased donors liver transplants that involved recipients aged ≥7070 years or recipients who received grafts from donors aged ≥70 years from 2011 to 2021. A literature review on the results of liver transplantation in elderly recipients was also performed.Thirty septuagenarian recipients were included; their overall 1- and 5-years survival was 80% and 76.6%, respectively. The prevalence of recipients aged ≥70 years in our department was 2.65%. Twenty recipients received grafts form septuagenarian donors; their overall 1- and 5-years survival was 75%. The prevalence of donors aged ≥70 years in our department was 1%. In the literature review, 17 articles were analyzed. The 5-years survival of recipients aged ≥70 years ranged from 47.1% to 78.5%.Septuagenarian recipients and patients who received grafts from elderly brain-dead donors present adequate overall survival after liver transplantation. Optimized donor-recipient matching is paramount for achieving good outcomes. The combination of high-risk donors with septuagenarian recipients should be avoided as well as using grafts of elderly donors that present others risk factors. Thus, the age of the donor or recipient alone cannot be considered an absolute contraindication for liver transplantation.

Short bowel syndrome is the most common etiology of intestinal failure, resulting from either resections of different intestinal segments or a congenital condition. Due to the absence or considerable reduction of intestinal loops in the abdominal cavity, patients with short bowel syndrome present with atrophy and muscle retraction of the abdominal wall, which leads to loss of abdominal domain and elasticity. This complication is an aggravating factor of intestinal transplantation since it can prevent the primary closure of the abdominal wall. A vast array of surgical techniques to overcome the challenges of the complexity of the abdominal wall have been described in the literature. The aim of our study was to review the modalities of abdominal wall closure in intestinal/multivisceral transplantation. Our study consisted of a systematic review following the methodological instructions described in the PRISMA guidelines. Duplicate studies and studies that did not meet the criteria for the systematic review were excluded, especially those without relevance and an explicit relationship with the investigated theme. After this step, 63 articles were included in our study. The results obtained with these techniques have been encouraging, but a high incidence of wound complications in some reports has raised concerns. There is no consensus among transplantation centers regarding which technique would be ideal and with higher success rates and lower rates of complications.

Made available in DSpace on 2022-04-28T19:52:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background Setting up new liver transplant (LT) centers is essential for countries with organ shortages. However, good outcomes require experience, because LT learning depends on a high number of surgeries. This study aims to describe how a new center was set up from a partnership between the new center and an experienced one. The step-by-step preparation process, the time needed and the results of the new center are depicted. Material and methods The mentoring process lasted 40 months, in which half of the 52 patients included on the transplant list received LT. After the mentorship, a 22-month period was also analyzed, in which 46 new patients were added to the waiting list and nine were operated on. Results The 30-day survival rates during (92.3%) and after (66.7%) the partnership were similar to the other LT centers in the same region, as well as the rates of longer periods. The waiting time on the LT list, the characteristics of the donors and the ischemia times did not differ during or after the mentorship. Conclusion The partnership between universities is a suitable way to set up LT centers, achieving good results for the institutions and the patients involved. Liver and Digestive Organs Transplantation Division Gastroenterology Department Clinical Hospital of São Paulo University - HCFMUSP São Paulo Faculty of Medicine Universidade de São Paulo - USP, São Paulo Gastroenterology Division Botucatu Faculty of Medicine Universidade Estadual Paulista Júlio de Mesquita Filho - UNESP, São Paulo Anesthesiology Division and Anesthesiology Laboratory LIM08 Surgery Department Clinical Hospital of São Paulo University - HCFMUSP São Paulo Faculty of Medicine Universidade de São Paulo - USP, São Paulo Gastroenterology Division Botucatu Faculty of Medicine Universidade Estadual Paulista Júlio de Mesquita Filho - UNESP, São Paulo FAPESP: 2017/25592-9

Brain death (BD) is characterized by a complex inflammatory response, resulting in dysfunction of potentially transplantable organs. This process is modulated by cytokines, which amplify graft immunogenicity. We have investigated the inflammatory response in an animal model of BD and analyzed the effects of thalidomide, a drug with powerful immunomodulatory properties.BD was induced in male Lewis rats. We studied three groups: Control (sham-operated rats) (n = 6), BD (rats subjected to brain death) (n = 6) and BD + Thalid (BD rats treated with one dose of thalidomide (200 mg/Kg), administered by gavage) (n = 6). Six hours after BD, serum levels of urea and creatinine, as well as systemic and renal tissue protein levels of TNF-α and IL-6, were analyzed. We also determined the mRNA expression of ET-1, and macrophage infiltration by immunohistochemistry.BD induced a striking inflammatory status, demonstrated by a significant increase of plasma cytokines: TNF-α (2.8 ± 4.3 pg/mL [BD] vs. 9.4 ± 2.8 pg/mL [Control]), and IL-6 (6219.5 ± 1380.6 pg/mL [BD] vs. 1854.7 ± 822.6 pg/mL [Control]), and in the renal tissue: TNF-α (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.4 relative expression [Control]; p 0.05), and IL-6 (4.0 ± 0.4 relative expression [BD] vs. 1.0 ± 0.3 relative expression [Control]; p 0.05). Moreover, BD increased macrophages infiltration (2.47 ± 0.07 cells/field [BD] vs. 1.20 ± 0.05 cells/field [Control]; p 0.05), and ET-1 gene expression (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.2 relative expression [Control]; p 0.05). In addition, we have observed deterioration in renal function, characterized by an increase of urea (194.7 ± 25.0 mg/dL [BD] vs. 108.0 ± 14.2 mg/dL [Control]; p 0.05) and creatinine (1.4 ± 0.04 mg/dL [BD] vs. 1.0 ± 0.07 mg/dL [Control]; p 0.05) levels. Thalidomide administration significantly reduced plasma cytokines: TNF-α (5.1 ± 1.4 pg/mL [BD + Thalid] vs. BD; p 0.05), and IL-6 (1056.5 ± 488.3 pg/mL [BD + Thalid] vs. BD; p 0.05), as well as in the renal tissue: TNF-α (1.5 ± 0.2 relative expression [BD + Thalid] vs. BD; p 0.05), and IL-6 (2.1 ± 0.3 relative expression [BD + Thalid] vs. BD; p 0.05). Thalidomide treatment also induced a significant decrease in the expression of ET-1 (1.4 ± 0.3 relative expression [BD + Thalid] vs. BD; p 0.05), and macrophages infiltration (1.17 ± 0.06 cells/field [BD + Thalid] vs. BD; p 0.05). Also thalidomide prevented kidney function failure by reduced urea (148.3 ± 4.4 mg/dL [BD + Thalid] vs. BD; p 0.05), and creatinine (1.1 ± 0.14 mg/dL [BD + Thalid] vs. BD; p 0.05).The immunomodulatory properties of thalidomide were effective in decreasing systemic and local immunologic response, leading to diminished renal damage, as reflected in the decrease of urea and creatinine levels. These results suggest that use of thalidomide may represent a potential strategy for treating in BD kidney organ donors.

The prevalence of hernias in patient with cirrhosis can reach up to 40%. The pathophysiology of cirrhosis is closely linked to that of the umbilical hernia, but other types are also common in this population. The aim of this study is to evaluate factors that influence in the prognosis after hernia repair in patients with cirrhosis. A historical cohort of 6419 patients submitted to hernia repair was gathered. Clinical, epidemiological data and hernia characteristics were obtained. For patient with cirrhosis, data from exams, surgery and follow-up outcomes were also analyzed. Survival curves were constructed to assess the impact of clinical and surgical variables on survival. 342 of the 6352 herniated patients were cirrhotic. Patient with cirrhosis had a higher prevalence of umbilical hernia (67.5% × 24.2%, P .001) and a lower prevalence of epigastric (1.8% × 9.0%, P .001) and lumbar (0% × 0.18%, P = .022). There were no significant differences in relation to inguinal hernia (P = .609). Ascites was present in 70.1% of patient with cirrhosis and its prevalence was different in relation to the type of hernia (P .001). The survival curve showed higher mortality for emergency surgery, MELD 14 and ascites (HR 12.6 [3.79-41.65], 4.5 [2.00-10.34], and 6.1 [1.15-20.70], respectively, P .05). Hernia correction surgery in patient with cirrhosis has a high mortality, especially when performed under urgent conditions associated with more severe clinical conditions of patients, such as the presence of ascites and elevated MELD.

Introdução: A Doença Hepática Gordurosa não Alcoólica (DHGNA) abrange um largo espectro de doença, podendo se apresentar como esteatose simples, esteato-hepatite não alcoólica (EHNA), cirrose e carcinoma hepatocelular (CHC). A biópsia hepática ainda é o padrão-ouro para avaliação de fibrose. Há necessidade de se buscar marcadores não invasivos de fibrose e que também possam ser eficientes em predizer a evolução para EHNA, cirrose e CHC. Sua evolução é influenciada por fatores ambientais, genéticos e epigenéticos. Os microRNAs são biomarcadores em potencial que podem influenciar na evolução da DHGNA por diversas vias e atuando em diferentes mecanismos envolvidos em sua patogênese. Objetivos: Avaliar o papel dos microRNAs miR-21, miR-29a, miR-122, miR-155 e miR-181a na expressão fenotípica da DHGNA, correlacionando seus níveis séricos com os diversos estágios da doença. Métodos: Estudo transversal realizado em 108 pacientes com DHGNA diagnosticados por biópsia hepática. Na análise histológica foram avaliados os graus de fibrose e NAFLD activity score (NAS). Foram calculados o FIB-4 e o NAFLD fibrosis score e comparados com o grau de fibrose pela biópsia. A expressão de microRNAs foi testada por qPCR. A comparação entre as distribuições dos valores de microRNA de acordo com a presença ou ausência de fibrose clinicamente significativa (F2-4) foi realizada pelo teste de Mann- Whitney. As correlações entre os parâmetros foram determinadas pela correlação de Spearman. A expressão sérica de microRNAs também foi comparada com o NAS da biópsia e com parâmetros clínicos e laboratoriais coletados no momento da biópsia. Uma análise de regressão logística multivariada foi realizada para construção de um escore para a predição de fibrose utilizando o FIB-4 e o [Ln(miRNA-181a)] como variáveis independentes. Resultados: Fibrose clinicamente significativa (F2-F4) foi presente em 42,6% (46/108) dos casos. Não houve correlação entre os níveis séricos dos microRNAs miR-21, miR-29a, miR-122 e miR-155 com os graus de fibrose determinados por biópsia hepática. Por outro lado, o miRNA-181a apresentou diferenças estatisticamente significativas entre os dois grupos (p=0,017). O FIB-4 mostrou uma AUC na curva ROC de 0,667 para predizer fibrose clinicamente significativa (F2-F4). Quando avaliado por meio do escore em associação com o Ln(miR-181a), houve melhora da curva ROC, com AUC de 0,71. Não houve correlação entre os níveis séricos dos microRNAs miR-21, miR-29a, miR-122, miR-155 e miR-181a com os graus de atividade inflamatória avaliados pelo NAS. Houve uma correlação fraca, porém com significância estatística (p

Introdução: O transplante uterino foi desenvolvido para o tratamento de pacientes portadoras de infertilidade por fator uterino exclusivo, e por se tratar de uma nova modalidade de transplante, ainda existe espaço para o seu aprimoramento técnico. Um fator que sabidamente impacta na sobrevida do enxerto em transplante de órgãos de uma maneira geral é o tempo de isquemia quente. No transplante de útero, especificamente, são realizadas pelo menos duas anastomoses vasculares de cada lado do útero e a revascularização do enxerto acontece, quando as pinças vasculares das artérias e veias são liberadas em ambos os lados, simultaneamente. Por este motivo é esperado que o tempo de isquemia quente no transplante uterino seja consideravelmente longo. Objetivos: O objetivo do trabalho foi descrever a técnica sequencial de revascularização do enxerto uterino, que tem o intuito de reduzir o tempo de isquemia quente do procedimento e compará-la com a técnica de revascularização simultânea. Métodos: Para o procedimento foi realizada a técnica de autotransplante uterino e foram utilizadas dez ovelhas adultas com cerca de 45kg, não prenhas, divididas em dois grupos: grupo de revascularização simultânea (5 animais) e grupo de revascularização sequencial do enxerto (5 animais). Para a avaliação dos grupos analisamos os tempos de procedimento e isquemia quente, a macroscopia do enxerto, além das análises hemodinâmica, laboratorial e histológica do útero. Resultados: No presente trabalho, foi descrito passo a passo a técnica de revascularização sequencial do enxerto uterino e demostrado ser esta factível e de fácil execução. Na comparação com a técnica simultânea, ambos os grupos tiveram tempo de procedimento cirúrgico semelhantes, e o tempo de isquemia quente foi significativamente menor no grupo de revascularização sequencial, com medianas de 32min no grupo sequencial versus 72min no simultâneo (p = 0,008). A macroscopia do enxerto e os parâmetros hemodinâmicos, laboratoriais e histológicos avaliados foram semelhantes entre os grupos estudados. Conclusão: A técnica de revascularização sequencial se mostrou factível e de fácil execução e reduziu de forma significativa o tempo de isquemia quente no modelo de autotransplante uterino em ovelhas, sem comprometer a viabilidade do enxerto Introduction: Uterine transplantation was developed for the treatment of exclusive uterine factor infertility, and as it is a new modality of transplantation, there is still room for technical improvement. A factor that impacts graft survival in organ transplantation is the warm ischemia time. In uterine transplantation specifically, at least two vascular anastomoses are performed on each side of the uterus and the graft revascularization takes place when the vascular clamps of the arteries and veins are released on both sides simultaneously. For this reason, the warm ischemia time in the uterine transplant is expected to be considerably long. Objectives: The purpose of this study was to describe a sequential technique of uterine graft revascularization, which aims to reduce the warm ischemia time of the procedure and to compare it with the simultaneous revascularization technique. Methods: For the procedure, the uterine auto transplantation technique was performed using ten non-pregnant adult ewes, weighing about 45kg and divided in two groups: simultaneous revascularization group (5 animals) and sequential graft revascularization group (5 animals). To evaluate the groups, we analyzed the procedure and warm ischemia times, graft macroscopy, hemodynamic, laboratory and histological parameters of the uterus. Results: The technique of sequential revascularization of the uterine graft was described step by step and demonstrated to be feasible and easy to perform. In comparison with the simultaneous technique, the groups had similar surgical procedure times and the warm ischemia time was significantly shorter in the sequential revascularization group, with medians of 32min in the sequential group versus 72min in the simultaneous (p.0.008). The graft macroscopy and hemodynamic, laboratory and histological parameters evaluated were similar between the groups. Conclusion: The sequential revascularization technique proved to be feasible and easy to perform and efficiently reduced the warm ischemia time in the sheep uterine auto transplantation model, without compromising graft viability

Nos últimos 50 anos, o transplante de fígado tem evoluído rapidamente, despontando como terapia definitiva para a insuficiência hepática em estágio terminal. A grande maioria dos fígados usados para transplantes são obtidos de doadores com diagnóstico de morte encefálica (ME). A ME é caracterizada por uma resposta inflamatória generalizada que resulta em deterioração dos órgãos periféricos. Esse processo é mediado principalmente por citocinas, que amplificam a imunogenicidade do enxerto. Nesse contexto, investigamos a resposta imunológica em um modelo de ME e analisamos os efeitos da talidomida, uma droga com propriedades imunomoduladoras. A ME foi induzida em ratos Lewis machos. Foram estudados 3 grupos: Controle (animais sham-operados); ME (animais submetidos à ME através do aumento da pressão intracraniana); ME + Talidomida (animais submetidos a ME tratados com talidomida). 6 horas após a ME, analisamos a PAM, os níveis plasmáticos das enzimas AST, ALT, LDH, ALP, além da expressão de mediadores da resposta imune (TNF-, IL-1, IL-6 e IL-10) no tecido hepático e na circulação sistêmica. Além disso, determinamos a expressão gênica de MHC Classe I e MHC Classe II, bem como o infiltrado de macrófagos no fígado. Ensaios de Gel-Shift e Super-Shift também foram realizados para avaliar a atividade do NF-B e o envolvimento das subunidades p50, p65 e c-Rel no tecido hepático. As propriedades imunomoduladoras da talidomida foram eficazes em reduzir as citocinas pró-inflamatórias (local e plasmática), além do infiltrado de macrófagos, levando a uma melhora da lesão hepática, determinada pela redução das enzimas circulantes. Os efeitos da talidomida ocorreram, possivelmente, por meio da supressão da ativação do NF-B. Tomado em conjunto, esses resultados apresentam fortes evidências que os efeitos imunomoduladores da talidomida parecem prevenir o aumento da imunogenicidade no tecido hepático durante a ME, um processo aparentemente mediado pela atividade do NF-B. Ademais, esses achados fornecem importantes insights para a utilização da talidomida como droga imunossupressora e, talvez, como um alvo para futuras terapias direcionadas para melhorar a imunogenicidade do enxerto e, consequentemente, no impacto potencial da sobrevida do órgão transplantado Over the past 50 years, liver transplantation has advanced dramatically and is considered the definitive therapy for end-stage liver failure. A vast majority of the livers used for transplantation are obtained from brain-dead donors. Brain death (BD) is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify the graft immunogenicity. Thus, we investigated the immunological response in a brain death liver donor model and analyzed the effects of thalidomide, a drug with powerful immunomodulatory properties. BD was induced in male Lewis rats. We studied three groups: Control (sham-operated rats), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalidomide (BD rats receiving thalidomide after brain death). 6 hours after BD, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-, IL1-, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-B, and macrophage infiltration. NF-B was also examined by Gel-Shift, and p50, p65 and c-Rel subunits by Super-Shift. The immunomodulatory properties of thalidomide were effective in decreasing systemic and local pro-inflammatory cytokines, as well as inflammatory cell infiltration, leading to an improvement of liver damage as reflected in decreased hepatic enzymes levels. Furthermore, the immunomodulatory effects of thalidomide possibly were through suppression of NF-B activation. In addition, these data show evidence of potent immunomodulatory effects of thalidomide that appear to prevent increased immunogenicity. Taken together, these data provide key insights into the understanding of the immune response in brain dead organ donor, as well as to the potential use of thalidomide as a immunosuppressant and, perhaps, as a target for future therapies directed towards ameliorate the graft immunogenicity, and beneficial effect in outcome after transplantation

A febre amarela é uma febre hemorrágica, viral e endêmica de regiões tropicais na América Central e do Sul e no continente Africano, afetando principalmente humanos e primatas não-humanos, causada pelo vírus da Febre Amarela (YFV). O recente surto de Febre amarela no Brasil foi um dos mais graves nos tempos atuais disseminando-se para áreas com baixa cobertura vacinal. Durante os picos dos surtos, foi possível observar uma diferença na evolução clínica dos pacientes que trouxe o questionamento se o vírus poderia ter apresentado mutações que levassem a uma alteração no quadro clínico. O presente estudo avaliou a diversidade genética do vírus da Febre Amarela dos casos internados no Hospital das Clínicas da Faculdade de Medicina de São Paulo, que sobreviveram à infecção durante o surto ocorrido em São Paulo nos anos de 2018 e 2019 e determinou a carga viral bem como o genótipo da cepa viral circulante. Para a realização deste estudo foram utilizadas amostras de soro e/ou urina positivas para o vírus da Febre Amarela, que foram submetidas à extração do RNA viral e em seguida à amplificação de cDNA. O sequenciamento de nova geração foi realizado e posteriormente feita a análise de dados utilizando ferramentas de bioinformática próprias para gerar as informações sobre a qualidade e cobertura das sequências a fim de realizar a montagem do genoma viral, análises das variantes e análises filogenéticas. Utilizando essa estratégia, foram obtidos 39 genomas quase completos, sendo possível a análise da diversidade genética viral entre os grupos de 2018 e 2019. Foram encontradas 46 substituições nucleotídicas (nt), sendo 20 delas substituições não sinônimas, com destaque para as posições 195 nt (presente em 60% das amostras de 2019) e 218 nt no capsídeo (presente em 28,6% das amostras de 2018), 5055 nt na NS3 presente em 100% das amostras deste estudo e 10.104 nt na NS5 (42,85% de 2018 e 96% de 2019), proteína polimerase do vírus. A única substituição nucleotídica encontrada neste estudo previamente publicada foi na posição 5055 nt da proteína NS3. Analisando as árvores filogenéticas, os genomas foram classificados como genótipo Sul Americano I subgrupo E, sendo este resultado comparado com estudos previamente publicados e de acordo com o descrito. É possível observar que 85,7% da casuística deste estudo é composta por pacientes do sexo masculino. Mapeamentos geográficos do provável local de infecção dos pacientes incluídos no estudo, demonstraram que o surto de 2018 teve uma maior concentração na região da Grande São Paulo, chegando ao litoral paulista, e o surto de 2019 concentrou-se, em sua maior parte, no Vale do Ribeira. Este estudo sugere que os vírus circulantes nos surtos de 2018 e 2019 são distintos, porém para um melhor entendimento do impacto das variantes sobre a patogênese viral, é necessária uma análise in silico. Em geral, as análises aqui realizadas permitem um melhor entendimento do genoma do YFV circulante em São Paulo e contribui para futuros estudos virológicos e epidemiológicos Yellow fever is a viral and endemic hemorrhagic fever from tropical regions in the Central and South Americas and Africa, affecting mainly humans and nonhuman primates, caused by the Yellow Fever virus (YFV). The recent outbreak of yellow fever in Brazil has been one of the most severe in the last decades, spreading to areas with low vaccine coverage. During the peak of the 2018-2019 outbreak, it was possible to observe a difference in the clinical evolution of the patients and it raised questions of whether the virus could have had mutations that led to milder clinical symptoms. The present study aimed to evaluate the genetic diversity of Yellow fever virus of Hospital das Clinicas da Faculdade de Medicina de Sao Paulo, hospitalized cases that survived the infection during the recent outbreak, in order to determine the viral load and genotype of the circulating viral strain in Sao Paulo. YFV-positive serum and / or urine samples were subjected to viral RNA extraction and then cDNA amplification. New generation sequencing and data analyses were carried out using bioinformatics tools for quality and coverage analysis for genome assembly, variant and phylogenetic analyses. Almost thirty-nine nearly complete YFV genomes were obtained and genetic diversity analysis comparing the circulating virus strains during 2018 and 2019, allowed us to find 46 nucleotides (nt) substitutions, and 21 of them were non-synonymous substitutions, highlighting the positions 195nt (60% of samples from 2019) and 218nt (28.6% of samples from 2018) in capsid protein, 5055nt (100% of samples) in NS3 protein and 10.104 in NS5 protein (42.85% of samples from 2018 and 96% samples from 2019). Phylogenetic analysis demonstrated that all YFV strains circulating during the outbreak form a unique major clade with the South American IE genotype. This finding was compared with previously published studies and is in accordance with what has been described so far. In conclusion, it was possible to describe that 85.7% of all patients enrolled in this study are male and the peak from 2018 YFV outbreak was concentrated in Greater Sao Paulo, going to the coast but the peak from 2019 outbreak was more concentrated in Vale do Ribeira. Our findings suggest that 2018 and 2019 circulating viruses were distinct from each other however for a better understanding of how these variants affect the viral pathogenesis it is necessary to perform an in silico analysis. Overall, our findings provide an overview of YFV genome characterization in Sao Paulo and contribute for future virological and epidemiological studies