Evidence for widespread translation of 5' untranslated regions.

Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments derive from just one source, 5' untranslated regions. Across the human genome we find evidence for 192 translated upstream regions, most of which would produce protein isoforms with extended N-terminal ends. Almost all of these N-terminal extensions are from highly abundant genes, which suggests that the novel regions we detect are just the tip of the iceberg. These upstream regions have characteristics that are not typical of coding exons. Their GC-content is remarkably high, even higher than 5' regions in other genes, and a large majority have non-canonical start codons. Although some novel upstream regions have cross-species conservation - five have orthologues in invertebrates for example - the reading frames of two thirds are not conserved beyond simians. These non-conserved regions also have no evidence of purifying selection, which suggests that much of this translation is not functional. In addition, non-conserved upstream regions have significantly more peptides in cancer cell lines than would be expected, a strong indication that an aberrant or noisy translation initiation process may play an important role in translation from upstream regions.

Differences between Patients with Sporadic and Familial Pheochromocytoma-Is It Possible to Avoid Genetic Testing in Certain Patients?

BACKGROUND: Pheochromocytoma (PHEO) is a rare neuroendocrine tumour with a strong genetic link, which therefore may modify its clinical behaviour and prognosis. The aim of the study is to evaluate the epidemiological and clinical differences between patients with sporadic and familial PHEO, as well as the specific differences in the index cases. METHODS: A retrospective analysis of 136 patients in a tertiary hospital (1984-2021). Epidemiological, clinical, and histological variables were analysed. STATISTICS: SPSS 28.0 software was used. Univariate and multivariate logistic regression analyses were performed. p < 0.05 was considered statistically significant. RESULTS: 64.71% of the cases (n = 88) presented a genetic mutation (familial cases). Additionally, 32.39% (n = 23) corresponded to index cases and the rest to screening cases. The main differences between patients with familial and sporadic PHEO were age (OR = 0.93 (0.89-0.97)), blood pressure-related symptoms (OR = 0.22 (0.06-0.89)), bilaterality (OR = 15.49 (3.76-63.84)), and size (OR = 0.70 (0.54-0.92)). Among patients with sporadic PHEO and index cases, only bilaterality was significant (OR = 13.53 (1.24-144.34)). CONCLUSIONS: Patients with familial PHEO diagnosed by screening differ from sporadic cases in terms of age, clinical features, and size. However, patients with sporadic PHEO only differ from index cases by a lower presence of bilaterality, which reaffirms the importance of genetic screening of patients with PHEO and their relatives.

miR-218-5p, miR-124-3p and miR-23b-3p act synergistically to modulate the expression of NACC1, proliferation, and apoptosis in C-33A and CaSki cells.

Background: In cervical cancer (CC), miR-218-5p, -124-3p, and -23b-3p act as tumor suppressors. These miRNAs have specific and common target genes that modulate apoptosis, proliferation, invasion, and migration; biological processes involved in cancer. Methods: miR-218-5p, -124-3p, and -23b-3p mimics were transfected into C-33A and CaSki cells, and RT-qPCR was used to quantify the level of each miRNA and NACC1. Proliferation was assessed by BrdU and apoptosis by Annexin V/PI. In the TCGA and The Human Protein Atlas databases, the level of NACC1 mRNA and protein (putative target of the three miRNAs) was analyzed in CC and normal tissue. The relationship of NACC1 with the overall survival in CC was analyzed in GEPIA2. NACC1 mRNA and protein levels were higher in CC tissues compared with cervical tissue without injury. Results: An increased expression of NACC1 was associated with lower overall survival in CC patients. The levels of miR-218-5p, -124-3p, and -23b-3p were lower, and NACC1 was higher in C-33A and CaSki cells compared to HaCaT cells. The increase of miR-218-5p, -124-3p, and -23b-3p induced a significant decrease in NACC1 mRNA. The transfection of the three miRNAs together caused more drastic changes in the level of NACC1, in the proliferation, and in the apoptosis with respect to the individual transfections of each miRNA. Conclusion: The results indicate that miR-218-5p, -124-3p, and -23b-3p act synergistically to decrease NACC1 expression and proliferation while promoting apoptosis in C-33A and CaSki cells. The levels of NACC1, miR-218-5p, -124-3p, and -23b-3p may be a potential prognostic indicator in CC.

Autophagy sustains mitochondrial respiration and determines resistance to BRAFV600E inhibition in thyroid carcinoma cells.

BRAFV600E is the most prevalent mutation in thyroid cancer and correlates with poor prognosis and therapy resistance. Although selective inhibitors of BRAFV600E have been developed, more advanced tumors such as anaplastic thyroid carcinomas show a poor response in clinical trials. Therefore, the study of alternative survival mechanisms is needed. Since metabolic changes have been related to malignant progression, in this work we explore metabolic dependencies of thyroid tumor cells to exploit them therapeutically. Our results show that respiration of thyroid carcinoma cells is highly dependent on fatty acid oxidation and, in turn, fatty acid mitochondrial availability is regulated through macroautophagy/autophagy. Furthermore, we show that both lysosomal inhibition and the knockout of the essential autophagy gene, ATG7, lead to enhanced lipolysis; although this effect is not essential for survival of thyroid carcinoma cells. We also demonstrate that following inhibition of either autophagy or fatty acid oxidation, thyroid tumor cells compensate oxidative phosphorylation deficiency with an increase in glycolysis. In contrast to lipolysis induction, upon autophagy inhibition, glycolytic boost in autophagy-deficient cells is essential for survival and, importantly, correlates with a higher sensitivity to the BRAFV600E selective inhibitor, vemurafenib. In agreement, downregulation of the glycolytic pathway results in enhanced mitochondrial respiration and vemurafenib resistance. Our work provides new insights into the role of autophagy in thyroid cancer metabolism and supports mitochondrial targeting in combination with vemurafenib to eliminate BRAFV600E-positive thyroid carcinoma cells.Abbreviations: AMP: adenosine monophosphate; ATC: anaplastic thyroid carcinoma; ATG: autophagy related; ATP: adenosine triphosphate; BRAF: B-Raf proto-oncogene, serine/threonine kinase; Cas9: CRISPR-associated protein; CREB: cAMP responsive element binding protein; CRISPR: clustered regularly interspaced short palindromic repeats; 2DG: 2-deoxyglucose; FA: fatty acid; FAO: fatty acid oxidation; FASN: fatty acid synthase; FCCP: trifluoromethoxy carbonyl cyanide phenylhydrazone; LAMP1: lysosomal associated membrane protein 1; LIPE/HSL: lipase E, hormone sensitive type; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation; PRKA/PKA: protein kinase cAMP-activated; PTC: papillary thyroid carcinoma; SREBF1/SREBP1: sterol regulatory element binding transcription factor 1.

Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti-Inflammatory Effects.

In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034 µM in A-431, 2.67 µM in MCF-7, and 3.64 µM in AGS) without showing activity on the non-tumorigenic cell line (>100 µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.

Tumor microenvironment in thyroid cancer: Immune cells, patterns, and novel treatments.

The tumor immune microenvironment of thyroid cancer is the heterogeneous histological space in which tumor cells coexist with host cells. Published data from this review were identified by search and selection database of Pubmed, Elsevier, and Science Direct. Searching was made in two steps using different keywords. In thyroid pathology, the inflammatory response is very important, and might have a key role finding new diagnostic and therapeutic methods, particularly in thyroid cancer. Different immune cells may be more or less present in different types of thyroid cancer and may even have different functions, hence the importance of knowing their presence in different thyroid tumor pathologies. Cancer-related inflammation could be a useful target for new diagnostic and therapeutic strategies by analyzing peritumoral and intratumoral immune cells in different types of thyroid tumors. Moreover, novel strategies for thyroid cancer treatments, such as monoclonal antibodies targeting checkpoint inhibitors, are emerging as promising alternatives.

Protocolization of multicenter clinical studies in the digital era. Is useful data centralization by a data-manager?

INTRODUCTION: In multicenter studies, the protocolization of data is a critical phase that can generate biases.The objective is to analyze the concordance and reliability of the data obtained in a clinical multicenter study between the protocolization in the center of origin and the centralized protocolization of the data by a data -manager. METHODS: National multicenter clinical study about an infrequent carcinoma. A double protocolization of the data is carried out: (a) center of origin; and (b) centralized by a data manager: The concordance between the data is analyzed for the global data and for the two groups of the project: (a) study group (Familiar carcinoma, 30 researchers protocolize); (b) control group (Sporadic carcinoma, 4 people protocolize). Interobserver variability is evaluated using Cohen's kappa coefficient. RESULTS: The study includes a total of 689 patients with carcinoma, 252 in the study group and 437 in the control group. Regarding the concordance analysis of the tumor stage, 2.5% of disagreements were observed and the concordance between people who protocolize was near perfect (Kappa = 0.931). Regarding the evaluation of the recurrence risk, disagreements occurred in 7% of the cases and the concordance was near perfect (Kappa = 0.819). Regarding the sonography evaluation (TIRADS), the disagreements were 6.9% and the concordance was near perfect (Kappa = 0.922). Also, 4.6% of transcription errors were detected. CONCLUSIONS: In multicenter clinical studies, the centralized data protocolization o by a data-manager seems to present similar results to the direct protocolization in the database in the center of origin.

Prognostic impact of coronary lesions and its revascularization in a 5-year follow-up after the TAVI procedure.

BACKGROUND: Coronary artery disease (CAD) is a common finding in patients undergoing transcatheter aortic valve implantation (TAVI). However, its prognostic significance and its management remains controversial. AIMS: This study sought to determine whether the presence of CAD, its complexity, and angiography-guided percutaneous coronary intervention (PCI) are associated with outcomes after TAVI. METHODS: All patients undergoing TAVI at a tertiary referral center between 2008 and 2018 were included in a prospective observational study. Baseline SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score (SS) and a residual SS after PCI were calculated. The endpoints on the 5 year follow-up were all-cause mortality and a composite of mayor cardiovascular adverse events (MACE). RESULTS: In 379 patients, the presence of CAD and its complexity were not significantly associated with worse 5-year survival after TAVI, with a mortality for SS0 of 45%; for SS 1-22 of 36.5% (HR 0.77; 95% CI 0.53-1.11, p = 0.15) and for SS > 22 of 42.1% (HR 1.24; 95% CI 0.59-2.63, p = 0.57). Regarding the combined event of MACE, there were also no statistically significant differences between patients with CAD and without CAD (56.8% in patients without CAD and 54.9% in patients with CAD; HR 1.06; 95% CI 0.79-1.43, p = 0.7). Angiography-guided PCI or completeness of revascularization was not associated with different outcomes. CONCLUSIONS: In the present analysis, neither the presence nor the extent of CAD, nor the degree of revascularization, was associated with a prognostic impact in patients undergoing TAVI at 5-year follow-up.

Adverse Clinical Outcomes and Associated Predictors in Rivaroxaban-Treated Atrial Fibrillation Patients With Renal Impairment.

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.

Model for predicting early and late-onset postoperative pulmonary complications in perioperative patients receiving neuromuscular blockade: a secondary analysis.

Pulmonary complications continue to be the most common adverse event after surgery. The main objective was to carry out two independent predictive models, both for early pulmonary complications in the Post-Anesthesia Care Unit and late-onset pulmonary complications after 30 postoperative days. The secondary objective was to determine whether presenting early complications subsequently causes patients to have other late-onset events. This is a secondary analysis of a cohort study. 714 patients were divided into four groups depending on the neuromuscular blocking agent, and spontaneous or pharmacological reversal. Incidence of late-onset complications if we have not previously had any early complications was 4.96%. If the patient has previously had early complications the incidence of late-onset complications was 22.02%. If airway obstruction occurs, the risk of atelectasis increased from 6.88 to 22.58% (p = 0.002). If hypoxemia occurs, the incidence increased from 5.82 to 21.79% (p < 0.001). Based on our predictive models, we conclude that diabetes mellitus and preoperative anemia are two risk factors for early and late-onset postoperative pulmonary complications, respectively. Hypoxemia and airway obstruction in Post-Anesthesia Care Unit increased four times the risk of the development of pneumonia and atelectasis at 30 postoperative days.

Postoperative negative-pressure incision therapy after liver transplant (PONILITRANS study): A randomized controlled trial.

BACKGROUND: Postoperative complications of surgical incisions are frequent in liver transplantation. However, evidence justifying the use of incisional negative pressure wound therapy to improve surgical wound outcomes remains limited. METHODS: Participating patients were randomly assigned to receive incisional negative pressure wound therapy or standard surgical dressing on the closed surgical incision of the liver transplantation. The primary endpoint was surgical site infection incidence 30 days postoperatively. The secondary endpoints included surgical site events (ie, surgical site infection, dehiscence, hematoma, and seroma) and wound quality of life. RESULTS: Between December 2018 and September 2021, 108 patients (54 in the incisional negative pressure wound therapy group and 54 in the control group) were enrolled in this study. The incidence of surgical site infection at 30 days postoperatively was 7.4% in the treatment group and 13% in the control group (P = .34). The rate of surgical site events was similar in the treatment in the and control group (27.8% vs 29.6%, P = .83). In relation to wound quality of life, the mean score was 75.20 ± 7.27 in the incisional negative pressure wound therapy group and 72.82 ± 10.57 in the control group (P = .23). CONCLUSION: The prophylactic use of negative pressure wound therapy on primarily closed incisions did not significantly reduce incisional surgical site infection and surgical site event rates after liver transplantation compared with standard surgical dressings.

Laparoscopic surgery in 3D improves results and surgeon convenience in sleeve gastrectomy for morbid obesity.

PURPOSE: Advanced laparoscopic procedures are still challenging. One critical issue is the lack of stereoscopic vision. The aim of this surgical study is to evaluate whether 3D vision offers any advantages for surgical performance over 2D vision during sleeve gastrectomy for morbid obesity using a laparoscopic system that allows changing between 2D and 3D optics. METHODS: A total of 78 patients were analyzed, with 37 in the 2D group and 41 in the 3D group. Performance time, hospital stay, complications, and early outcomes were collected. To assess the quality of the 2D and 3D techniques, visual analog scales from 0 to 10 were designed, and image quality, depth of field, precision in performing tasks, and general ergonomics were measured. RESULTS: According to the vision system used, the mean duration of surgery was 85 ± 16.8 min for patients operated on with the 2D system and 69 ± 16.9 min for those operated on with the 3D system. There were no significant differences between the overall percentages of complications according to the type of vision used. However, postoperative complications were more severe in the 2D laparoscopy group. The average length of stay was shorter for patients in the 3D group. Regarding the differences perceived by the surgeon, the depth of field and the precision of tasks were better in the 3D vision group. CONCLUSION: The 3D system provided greater depth perception and precision in more complex tasks, enabling safer surgery. This led to a reduction in the operative time and hospital stay. Moreover, the severity of complications was less.

[Evaluation of the telematic consultation in endocrine surgery during confinement due to COVID-19]. / Evaluación de la consulta telemática en cirugía endocrina durante el confinamiento por COVID-19.

BACKGROUND: The coronavirus disease pandemic of 2019 (COVID-19) made necessary to remodel the hospital's clinical consultations. OBJECTIVE: To evaluate the telematic consultation in endocrine surgery, as well as to select the group of patients susceptible to perform a telematic consultation in the future according to this assessment. METHODS: The study population were patients who had a clinical consultation by telephone. The evaluation was made with the Net Promoter Score (NPS). STATISTICAL ANALYSIS: SPSS v.28, X2 test and a multivariate analysis. RESULTS: 55 patients were analyzed. The NPS was +16, 24 promoters (43.6%) and 15 detractors (27.2%). There were differences between those whose main reason for consultation was malignant pathology (OR 4.5; p = 0.033). The NPS between malignant vs. non-malignant pathology was -13 vs. +38 (p > 0.001). The evaluation of the telematic consultations for the future was: telephone (83% very well), video call (58%), videoconference (19%). CONCLUSIONS: The evaluation of the telephone consultation has been good, finding a better assessment among patients with non-malignant pathology. Its future implementation could be necessary, being the telephone the preferred way.

Goiter surgery recommendations in sub-Saharan Africa in humanitarian cooperation.

Background: The standard treatment for endemic goiter is usually total thyroidectomy. In low- and middle-income countries, the management of thyroid disease, which is commonplace in fully developed countries, is not always possible. The purpose of this study is to establish a treatment algorithm to calculate the extent of thyroidectomy based on the risk factors of each patient. Methods: This is a retrospective observational study conducted during the period between 2017 and 2019. A total of 287 patients with thyroid pathology were treated in Maragua Hospital (Kenya). The results of surgical treatment were analyzed after the implementation of an individualized treatment protocol. Results: One hundred and sixty patients with different types of goiter underwent surgery: solitary nodule (54.4%), multi-nodular goiter (30.6%), diffuse goiter (10.6%), and intrathoracic goiter (3.8%). The techniques used were hemithyroidectomy (78.8%), Dunhill thyroidectomy (9.4%), bilateral subtotal thyroidectomy (6.9%), and total thyroidectomy (3.1%). There was no mortality. The surgical morbidity rate was 16% (only one major complication (3b)). Two cases of dysphonia were resolved in the first week. There were three cases of symptomatic hypocalcaemia, two of which resolved in the first week and the other of which was definitive. The follow-up at 6 months was 67%. The cancer rate found in the resection specimens was 5%. Discussion: The implementation of individualized surgical protocols for thyroid surgery in sub-Saharan Africa can improve outcomes. The cooperation projects can increase access to complex surgical treatment for patients with limited resources in low- and middle-income countries.

Endometrial area of the blood flow as a marker of endometritis in equine.

In this study, uterine blood flow area (BFA) has been evaluated for the first time using power Doppler ultrasound (PD) as a marker of endometritis in mares and jennies. The uterine BFA in healthy mares was greater in oestrus than in diestrus (p < .001). However, differences in endometrial blood flow between oestrus and diestrus were not observed in mares with endometritis. The uterine blood flow in healthy jennies is not affected by the oestrus cycle. Both species showed an increase in endometrial BFA in pathological uterine conditions compared to controls. BFA was a good marker of endometritis with an area under curve (AUC) (estrus:0.94 (p < .001) diestrus:0.98 (p < .001) in mares and AUC (0.91 (p < .0001) in jennies. The results of this preliminary study suggest that PD ultrasound in combination with computerized image analysis has the potential to be a very useful tool in the diagnosis of endometritis.

Use of rivaroxaban attenuates renal function impairment in patients with atrial fibrillation: insights of the EMIR study.

BACKGROUND: In atrial fibrillation (AF) patients on vitamin K antagonists, a progressive deterioration of renal function is common but there is limited evidence with long-term use of rivaroxaban. Herein, we investigated the change in renal function in AF patients after 2 years of rivaroxaban treatment. METHODS: The EMIR registry is an observational and multicentre study including AF patients treated with rivaroxaban for at least 6 months prior to inclusion. Changes in analytical parameters were recorded during 2 years of follow-up. Renal function was estimated using the Cockroft-Gault equation. RESULTS: 1433 patients (638, 44.5% women, mean age of 74.2 ± 9.7 years) were included. Creatinine clearance (CrCl) was available at baseline and at 2 years in 1085 patients. At inclusion, 33.2% of patients had impaired renal function (CrCl <60 ml/min). At 2 years, we were not able to find changes in the proportion of patients with impaired renal function, which increased to 34.6% (p = 0.290). However, the baseline mean CrCl was 76.0 ± 30.5 ml/min and slightly improved at 2 years (77.0 ± 31.8 ml/min; p = 0.014). Overall, the proportion of patients with CrCl <60 ml/min at baseline that had CrCl ≥60 ml/min at 2 years was significantly higher compared to that of patients with CrCl ≥60 ml/min at baseline and CrCl <60 ml/min after (22.2% vs. 13.1%; p < 0.001) CONCLUSIONS: In AF patients on long-term rivaroxaban therapy, a decrease in renal function was not observed. We even observed a slight improvement in the patients with renal impairment. These results reinforce the idea that rivaroxaban may be a safe option even in patients with renal impairment.

Multidisciplinary consensus on nutritional and metabolic therapy in enhanced recovery after abdominal surgery programs: NutRICA Project.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) care pathways include evidence-based items designed to accelerate recovery after surgery. Interdisciplinarity is one of the key points of ERAS programs. OBJECTIVE: To prepare a consensus document among the members of the Nutrition Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Group for Multimodal Rehabilitation (GERM), in which the goal is to homogenize the nutritional and metabolic management of patients included in an ERAS program. METHODS: 69 specialists in Endocrinology and Nutrition and 85 members of the GERM participated in the project. After a literature review, 79 statements were proposed, divided into 5 sections: 17 of general characteristics, 28 referring to the preoperative period, 4 to the intraoperative, 13 to the perioperative and 17 to the postoperative period. The degree of consensus was determined through a Delphi process of 2 circulations that was ratified by a consistency analysis. RESULTS: Overall, in 61 of the 79 statements there was a consistent agreement, with the degree of consensus being greater among members of the SEEN (64/79) than members of the GERM (59/79). Within the 18 statements where a consistent agreement was not reached, we should highlight some important nutritional strategies such as muscle mass assessment, the start of early oral feeding or pharmaconutrition. CONCLUSION: Consensus was reached on the vast majority of the nutritional measures and care included in ERAS programs. Due to the lack of agreement on certain key points, it is necessary to continue working closely with both societies to improve the recovery of the surgical patients.

Biomarkers of Early Liver Graft Damage in Circulatory Death and Brain Death Donors: A Propensity Score Matching Analysis.

BACKGROUND: Donation after circulatory death (DCD) is related to a warm ischemia time and more complications compared with traditional donors (donation after brain death [DBD]). METHODS: This study included biopsy samples retrospectively collected from November 2014 to December 2018 to compare histologic and biological markers of DCD and DBD liver grafts. The analysis includes marker of early apoptosis (p21), senescence (telomerase reverse transcriptase [TERT]), cell damage (caspase-3 active), endothelial damage (vascular endothelial growth factor), stem cell (CD90), hypoxia (HIF1A), inflammatory activation (COX-2), and cross-organ allograft rejection (CD44). A propensity score matching (PSM) was used to match patients receiving DCD livers to those receiving DBD livers. We analyzed the immunohistochemical initial liver damage-related warm ischemia time. RESULTS: Positive staining expression of liver damage biomarkers (COX-2, CD44, TERT, HIF1A, and CD90) was found, but no significant differences were found between DCD and DBD and with ischemic cholangiopathy. After PSM, there was a significant relationship between CD90 and male donors (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.07-0.91), TERT with donor sodium (OR, 1.11; 95% CI, 1.02-1.2), HIF1A with steatosis (OR, 0.33; 95% CI, 0.13-0.83), and CD44 with donor vasoactive drugs (OR, 0.36; 95% CI, 0.13-1) and glutamic oxaloacetic transaminase 1 week increase (OR, 1.01; 95% CI, 1-1.03). CONCLUSIONS: DCD immunohistochemical initial liver damage was found to behave similarly to DBD. The increase in complications and cholangiopathy associated with warm ischemia could be related to a different later phenomenon.