Programmed 'disarming' of the neutrophil proteome reduces the magnitude of inflammation.

The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.

High-resolution simulations of chromatin folding at genomic rearrangements in malignant B cells provide mechanistic insights into proto-oncogene deregulation.

Genomic rearrangements are known to result in proto-oncogene deregulation in many cancers, but the link to 3D genome structure remains poorly understood. Here, we used the highly predictive heteromorphic polymer (HiP-HoP) model to predict chromatin conformations at the proto-oncogene CCND1 in healthy and malignant B cells. After confirming that the model gives good predictions of Hi-C data for the nonmalignant human B cell-derived cell line GM12878, we generated predictions for two cancer cell lines, U266 and Z-138. These possess genome rearrangements involving CCND1 and the immunoglobulin heavy locus (IGH), which we mapped using targeted genome sequencing. Our simulations showed that a rearrangement in U266 cells where a single IGH super-enhancer is inserted next to CCND1 leaves the local topologically associated domain (TAD) structure intact. We also observed extensive changes in enhancer-promoter interactions within the TAD, suggesting that it is the downstream chromatin remodeling which gives rise to the oncogene activation, rather than the presence of the inserted super-enhancer DNA sequence per se. Simulations of the IGH-CCND1 reciprocal translocation in Z-138 cells revealed that an oncogenic fusion TAD is created, encompassing CCND1 and the IGH super-enhancers. We predicted how the structure and expression of CCND1 changes in these different cell lines, validating this using qPCR and fluorescence in situ hybridization microscopy. Our work demonstrates the power of polymer simulations to predict differences in chromatin interactions and gene expression for different translocation breakpoints.

Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers.

Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often called enhancer hijacking We analyzed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH) and proto-oncogene CCND1 that are common in B cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterized the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with hijacking of super-enhancers of other common oncogenes in B cell (MAF, MYC, and FGFR3/NSD2) and T cell malignancies (LMO2, TLX3, and TAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept of epigenomic translocation, in which the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers.

Dynamics of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes.

Broad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain-associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells. Although broad domains preferentially associate with cell identity and tumor suppressor genes in normal thymocytes, they flag key oncogenes in T-ALL samples. Moreover, the expression of broad domain-associated genes, both coding and noncoding, is frequently deregulated in T-ALL. Using two distinct leukemic models, we showed that the ectopic expression of T-ALL oncogenic transcription factor preferentially impacts the expression of broad domain-associated genes in preleukemic cells. Finally, an H3K4me3 demethylase inhibitor differentially targets T-ALL cell lines depending on the extent and number of broad domains. Our results show that the regulation of broad H3K4me3 domains is associated with leukemogenesis, and suggest that the presence of these structures might be used for epigenetic prioritization of cancer-relevant genes, including long noncoding RNAs.

Broad H3K4me3 domains: Maintaining cellular identity and their implication in super-enhancer hijacking.

The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non-coding genome. Recent advances in epigenomic profiling have uncovered non-coding gene proximal promoters and distal enhancers of transcription genome-wide. Extension of promoter-associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3-BD), is a signature of constitutive expression of cell-type-specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3-BDs over oncogenes is a cancer-specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super-enhancers (SE), by proto-oncogenes results in the presence of H3K4me3-BDs over the gene body. Therefore, H3K4me3-BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers.

Esearch3D: propagating gene expression in chromatin networks to illuminate active enhancers.

Most cell type-specific genes are regulated by the interaction of enhancers with their promoters. The identification of enhancers is not trivial as enhancers are diverse in their characteristics and dynamic in their interaction partners. We present Esearch3D, a new method that exploits network theory approaches to identify active enhancers. Our work is based on the fact that enhancers act as a source of regulatory information to increase the rate of transcription of their target genes and that the flow of this information is mediated by the folding of chromatin in the three-dimensional (3D) nuclear space between the enhancer and the target gene promoter. Esearch3D reverse engineers this flow of information to calculate the likelihood of enhancer activity in intergenic regions by propagating the transcription levels of genes across 3D genome networks. Regions predicted to have high enhancer activity are shown to be enriched in annotations indicative of enhancer activity. These include: enhancer-associated histone marks, bidirectional CAGE-seq, STARR-seq, P300, RNA polymerase II and expression quantitative trait loci (eQTLs). Esearch3D leverages the relationship between chromatin architecture and transcription, allowing the prediction of active enhancers and an understanding of the complex underpinnings of regulatory networks. The method is available at: https://github.com/InfOmics/Esearch3D and https://doi.org/10.5281/zenodo.7737123.

miRNA Expression in Fibroblastic Foci within Idiopathic Pulmonary Fibrosis Lungs Reveals Novel Disease-Relevant Pathways.

miRNAs are 22 nucleotides long and belong to a class of noncoding RNAs that plays an important role in regulating gene expression at a post-transcriptional level. Studies show aberrant levels of miRNAs to be associated with profibrotic processes in idiopathic pulmonary fibrosis (IPF). However, most of these studies used whole IPF tissue or in vitro monocultures in which fibrosis was artificially induced. The current study used laser microdissection to collect fibroblastic foci (FF), the key pathologic lesion in IPF, isolated miRNAs, and compared their expression levels with those found in whole IPF lung tissue and/or in vitro cultured fibroblast from IPF or normal lungs. Sequencing libraries were generated, and data generated were bioinformatically analyzed. A total of 18 miRNAs were significantly overexpressed in FF tissue when compared with whole IPF tissue. Of those, 15 were unique to FF. Comparison of FF with cultured IPF fibroblasts also revealed differences in miRNA composition that impacted several signaling pathways. The miRNA composition of FF is both overlapping and distinct from that of whole IPF tissue or cultured IPF fibroblasts and highlights the importance of characterizing FF biology as a phenotypically and functionally discrete tissue microenvironment.

An Entropic Analysis of Social Demonstrations.

Social media has dramatically influenced how individuals and groups express their demands, concerns, and aspirations during social demonstrations. The study of X or Twitter hashtags during those events has revealed the presence of some temporal points characterised by high correlation among their participants. It has also been reported that the connectivity presents a modular-to-nested transition at the point of maximum correlation. The present study aims to determine whether it is possible to characterise this transition using entropic-based tools. Our results show that entropic analysis can effectively find the transition point to the nested structure, allowing researchers to know that the transition occurs without the need for a network representation. The entropic analysis also shows that the modular-to-nested transition is characterised not by the diversity in the number of hashtags users post but by how many hashtags they share.

External Validation of Two Scoring Tools to Predict the Operative Duration and Open Conversion of Elective Laparoscopic Cholecystectomy in a Mexican Population.

INTRODUCTION: This study aimed to evaluate the use of laparoscopic cholecystectomy (LC) operative time (CholeS score) and conversion to an open procedure (CLOC score) outside their validation dataset in Mexican population. METHODS: Patients >18 years who underwent elective LC were analyzed in a single-center retrospective chart review study. Association between scores (CholeS and CLOC) with operative time and conversion to open procedures was assessed with Spearman correlation. The predictive accuracy of the CholeS score and CLOC score was evaluated by receiver operator characteristic. RESULTS: 200 patients were included in the study (33 excluded for emergency case or missing data). Spearman coefficient correlations between CholeS or CLOC score and operative time were 0.456 (p < 0.0001) and 0.356 (p < 0.0001), respectively. Area under the curve (AUC) for operative prediction time (>90 min) by CholeS score was 0.786 with a 3.5-point cutoff (80% sensitivity and 63.2% specificity). AUC for open conversion (CLOC score) was 0.78 with a 5-point cutoff (60% sensitivity and 91% specificity). The CLOC score had a 0.740 AUC (64% sensitivity and 72.8% specificity) for operative time >90 min. CONCLUSIONS: The CholeS and the CLOC scores predicted LC long operative time and risk for conversion to an open procedure, respectively, outside their original validation set.

Effect of postruminal supply of linseed oil in dairy cows: 2. Milk fatty acid profile and oxidative stability.

Our objective was to study the effect of increasing postruminal supply of linseed oil (L-oil), as a source of cis-9, cis-12, cis-15 18:3, on milk fatty acid profile and to assess the resulting impact on the development of volatile degradation products during the storage of homogenized milk. Five Holstein dairy cows fitted with a rumen cannula were randomly distributed in a 5 × 5 Latin square design. Abomasal infusion of L-oil was performed at the rate of 0, 75, 150, 300, and 600 ml/d during periods of 14 d. The concentration of cis-9, cis-12, cis-15 18:3 in milk fat increased linearly with L-oil dose. Concentrations of primary (conjugated diene and triene hydroperoxides) and secondary oxidation products (1-octen-3-one, propanal, hexanal, trans-2 + cis-3-hexenals, cis-4-heptenal, trans-2, cis-6-nonadienal trans-2, trans-4-nonadienal) increased during 11 d of storage at 4°C of homogenized milk under fluorescent light. The magnitude of the increase (difference between final and initial measurements) was linearly greater for all nine lipid oxidation products evaluated in response to increasing level of infusion. Results of the current experiment have shown that milk enriched in cis-9, cis-12, cis-15 18:3 via postruminal supply of L-oil is highly prone to oxidative degradation. This low oxidative stability, exposed under controlled experimental conditions, would represent a major obstacle to those who aim to market milk enriched in polyunsaturated fatty acids.

Effect of postruminal supply of linseed oil in dairy cows: 1. Production performance and fate of postruminally available α-linolenic acid.

Triacylglycerols (TAG) are the primary sources of preformed fatty acids (FA) for lipid synthesis in the mammary gland. However, polyunsaturated FA escaping ruminal biohydrogenation are selectively incorporated into cholesterol esters (CE) and phospholipids (PL). The aim of the current experiment was to study the effects of abomasal infusion of increasing amount of linseed oil (L-oil) on plasma distribution of α-linolenic acid (α-LA) and its transfer efficiency into milk fat. Five rumen-fistulated Holstein cows were randomly distributed in a 5 × 5 Latin square design. Abomasal infusion of L-oil (55.9% α-LA) was performed at the rate of 0, 75, 150, 300, and 600 ml/d. Concentrations of α-LA increased quadratically in TAG, PL, and CE; a less steep slope was observed with an inflexion at an infusion rate of 300 ml L-oil per day. The increase in plasma concentration of α-LA was of a lower magnitude in CE as compared with the other two fractions, resulting in a quadratic decrease in relative proportion of this FA circulating as CE. The transfer efficiency into milk fat increased from 0 to 150 ml L-oil infused, and a plateau was maintained thereafter with greater levels of infusion (quadratic response). This pattern resembles the quadratic response of the relative proportion of α-LA circulating as TAG, and the relative concentration of this FA in TAG. Increasing the postruminal supply of α-LA partly overcame the segregation mechanism of absorbed polyunsaturated FA in different plasma lipid classes. Proportionately more α-LA was then esterified as TAG, at the expense of CE, increasing its efficiency of transfer into milk fat. This mechanism appears to be surpassed in its turn when L-oil infusion was increased over 150 ml/d. Nevertheless, the yield of α-LA in milk fat continued to increase, but at a slower rate at the highest levels of infusion.

Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation.

Previous studies demonstrated that enzymatic hydrolysis enhances wheat bran (WB) biological properties. This study evaluated the immunostimulatory effect of a WB hydrolysate (HYD) and a mousse enriched with HYD (MH) before and after in vitro digestion on murine and human macrophages. The antiproliferative activity of the harvested macrophage supernatant on colorectal cancer (CRC) cells was also analyzed. MH showed significantly higher content than control mousse (M) in soluble poly- and oligosaccharides (OLSC), as well as total soluble phenolic compounds (TSPC). Although in vitro gastrointestinal digestion slightly reduced the TSPC bioaccessibility of MH, ferulic acid (FA) levels remained stable. HYD showed the highest antioxidant activity followed by MH, which demonstrated a greater antioxidant activity before and after digestion as compared with M. RAW264.7 and THP-1 cells released the highest amounts of pro-inflammatory cytokines after being treated with 0.5 mg/mL of digested WB samples. Treatment with digested HYD-stimulated RAW264.7 supernatant for 96 h showed the most anticancer effect, and spent medium reduced cancer cell colonies more than direct WB sample treatments. Although a lack of inner mitochondrial membrane potential alteration was found, increased Bax:Bcl-2 ratio and caspase-3 expression suggested activation of the mitochondrial apoptotic pathway when CRC cells were treated with macrophage supernatants. Intracellular reactive oxygen species (ROS) were positively correlated with the cell viability in CRC cells exposed to RAW264.7 supernatants (r = 0.78, p < 0.05) but was not correlated in CRC cells treated with THP-1 conditioned media. Supernatant from WB-stimulated THP-1 cells may be able to stimulate ROS production in HT-29 cells, leading to a decrease of viable cells in a time-dependent manner. Therefore, our present study revealed a novel anti-tumour mechanism of HYD through the stimulation of cytokine production in macrophages and the indirect inhibition of cell proliferation, colony formation, and activation of pro-apoptotic proteins expression in CRC cells.

Association of Netrin 1 with hsCRP in Subjects with Obesity and Recent Diagnosis of Type 2 Diabetes.

Netrin 1 (Ntn1) is a cell migration protein with an anti-inflammatory effect, which may play a key role in the pathological development of type 2 diabetes (T2D). In this study, we evaluate the relationships between the serum concentrations of Ntn1, glucose, and high-sensitivity C-reactive Protein (hsCRP). We carried out a cross-sectional study including 90 individuals divided into three groups (n = 30): healthy subjects, individuals with obesity without glucose alterations, and individuals with newly diagnosed T2D. Serum concentrations of Ntn1 and hs-CRP were determined by enzyme-linked immunosorbent assay (ELISA). The serum concentration of Ntn1 was higher in individuals with newly diagnosed T2D (0.33 ± 0.22 ng/mL), in comparison to healthy subjects and individuals with obesity (0.13 ± 0.06 and 0.15 ± 0.07 ng/mL, respectively). In addition, we observed a positive association between the levels of Ntn1 and hsCRP (rho = 0.443; p < 0.001) as well as with serum glucose (rho = −0.110; p = 0.05). The serum concentration of Ntn1 was higher in individuals with T2D, in comparison with the other groups in this study, and presented a positive correlation with hsCRP. Therefore, Ntn1 can be considered a promising risk biomarker and a potential therapeutic target for T2D.

Intronic CNVs and gene expression variation in human populations.

Introns can be extraordinarily large and they account for the majority of the DNA sequence in human genes. However, little is known about their population patterns of structural variation and their functional implication. By combining the most extensive maps of CNVs in human populations, we have found that intronic losses are the most frequent copy number variants (CNVs) in protein-coding genes in human, with 12,986 intronic deletions, affecting 4,147 genes (including 1,154 essential genes and 1,638 disease-related genes). This intronic length variation results in dozens of genes showing extreme population variability in size, with 40 genes with 10 or more different sizes and up to 150 allelic sizes. Intronic losses are frequent in evolutionarily ancient genes that are highly conserved at the protein sequence level. This result contrasts with losses overlapping exons, which are observed less often than expected by chance and almost exclusively affect primate-specific genes. An integrated analysis of CNVs and RNA-seq data showed that intronic loss can be associated with significant differences in gene expression levels in the population (CNV-eQTLs). These intronic CNV-eQTLs regions are enriched for intronic enhancers and can be associated with expression differences of other genes showing long distance intron-promoter 3D interactions. Our data suggests that intronic structural variation of protein-coding genes makes an important contribution to the variability of gene expression and splicing in human populations.

Milk yield and composition in dairy goats fed extruded flaxseed or a high-palmitic acid fat supplement.

We compared the potential of dietary lipid supplements of different fatty acid compositions to affect milk performance when early lactation dairy goats were fed a high-concentrate diet. Thirty Alpine goats at 23 ± 5 d in milk were allocated to 1 of 10 blocks according to parity and milk fat concentration. Within each block, goats were randomly assigned to receive, during a period of 41 d, either CONT) a basal diet with a forage to concentrate ratio of 45:55, used as control, or PALM) the basal diet + 2% of a palmitic acid-enriched fat supplement, or FLAX) the basal diet + 7% of extruded flaxseed. Body weight, dry matter intake and milk yield were not different between treatments. As compared with CONT, goats fed PALM and FLAX had a greater milk fat concentration. Moreover, milk fat yield was numerically (but non-significantly) greater with PALM than with CONT. Milk fat from goats receiving PALM had a greater concentration of 16:0 as compared with CONT and FLAX, whereas a greater concentration of cis-9, cis-12, cis-15 18:3 was observed when goats were fed FLAX as compared with CONT and PALM. Under the conditions of the current experiment, dietary fat supplementation had only minor impacts on the yield of major milk constituents, with the exception of a modest increase in fat yield when goats were fed PALM. The impact of a greater concentration of 16:0 in milk fat of goats receiving this feed ingredient on the nutritive value of dairy products remains to be determined.

Performance of the American College of Surgeons National Surgical Quality Improvement calculator for early postoperative outcomes following bile duct repair hepaticojejunostomy.

PURPOSE: A Roux-en-Y hepaticojejunostomy (HJ) is the preferred method for repairing bile duct injuries (BDIs). The American College of Surgeons (ACS) established the National Surgical Quality Improvement Program (NSQIP) online risk calculator to predict risks for morbidity and mortality. The objective of the study is to assess the use of the ACS NSQIP calculator for patients undergoing HJ for BDI repairs outside the NSQIP cohort. METHODS: An IRB-approved retrospective study of Bismuth-Strasberg type E BDI HJ (2008-2020) was performed. Clinical data was introduced in the NSQIP calculator, and morbidity and mortality were determined. Perioperative risk factors were obtained. Comparisons of postoperative complications and NSQIP-predicted complication rate were carried out. RESULTS: Eighty-two patients were included (age: 42.2 ± 15.7 years; 81% female; BMI 27.1 ± 4.4 kg/m2). The most common injury was E4 (36.3%). A total of 40.2% patients had a 30-day complication. Mortality was 2.4%. Preoperative sepsis and high body mass index (p = 0.01) were significantly related to complications (p = 0.01) (univariate analysis). Older age (p = 0.01) and higher ASA class (p = 0.02) were significantly related to mortality (univariate analysis). None was statistically significant in multivariate analysis. Comparison between morbidity and mortality and the calculated NSQIP was not statistically significant. Postoperative mortality had a statistically significant trend (C-value = 0.72, p = 0.055). CONCLUSION: Preoperative sepsis, high body mass index, age, and ASA classification were associated with worse outcomes in HJ BDI repair. The ACS NSQIP calculator did not have a good performance in a population outside the NSQIP data. Further larger studies will need to corroborate these results.

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment.

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.

Pulse-Cereal Blend Extrusion for Improving the Antioxidant Properties of a Gluten-Free Flour.

Extrusion is an interesting technological tool that facilitates pulse formulation into flour mixtures, with tailored fibre content, total antioxidant capacity (TAC) and glycemic index (GI) among other components in final formulas. The gluten-free (GF) market has significantly grown during the last years. GF products have evolved from specialty health foods to products targeted to the general population and not only associated to celiac consumers. This study evaluates how temperature, cereal base (rice/corn) and pulse concentration affect extruded flour properties and which conditions are more efficient to develop a gluten-free flour with high TAC and low GI. Additionally, it evaluated the effect of this optimal formula after the baking process. The results showed an increase of total phenol (TP) and antioxidant activity with extrusion, with a temperature-dependent effect (130 °C ≥ 120 °C ≥ 110 °C), which may imply an enhanced bioaccessibility of phenolics compounds after extraction. Extrusion increased GI in comparison to native flour; however, a dough temperature of 130 °C resulted in a significantly (p ≤ 0.05) lower GI than that observed for 110-120 °C doughs, probably associated to the pastification that occurred at higher temperatures, which would decrease the degree of gelatinization of the starches and therefore a significant (p ≤ 0.05) GI reduction. Corn-lentil flour showed higher antioxidant properties and lower GI index in comparison with rice-lentil blends. The formulation of the optimal blend flour into a baked product (muffin) resulted in a significant loss of antioxidant properties, with the exception of the reducing power (FRAP), although the final antioxidant values of the baked product were in the range of the original native flour blend before any process.

Factors associated with patency loss and actuarial patency rate following post-cholecystectomy bile duct injury repair: long-term follow-up.

PURPOSE: Several factors may contribute to bile duct injury (BDI) repair failure. The objective of our study was to evaluate factors that contribute to the loss of patency and influence the actuarial patency rate of BDI repairs in an 11-year period. METHODS: Retrospective review study of patients who underwent a hepaticojejunostomy for a type E Bismuth-Strasberg BDI (2008-2019). The outcomes are the following: primary patency attained, loss of primary patency, and actuarial primary patency rate. Logistic regression for loss of patency and Cox regression for actuarial patency rate were used. RESULTS: Seventy-nine patients (age 42.3 ± 15.8 years, 81% female) were studied. Most common index operation was open cholecystectomy (60.8%). Most common Bismuth-Strasberg lesion was E4 (38%). Primary patency was 93.4%. Mean follow-up was 36 ± 34 months. Ten-year actuarial patency was 53.9%. Factors associated with loss of patency were vasculobiliary injury, biliary stents, and 90-day biliary complications (univariate); number of surgeries before repair and postoperative cholangitis (univariate and multivariate) (p < 0.05). Factors that impacted actuarial patency rate were (univariate analysis) 90-day biliary complications; postoperative cholangitis and index treatment period stenosis (p < 0.05). No factors impacted actuarial patency rate in multivariate analysis. CONCLUSION: Postoperative cholangitis is associated with loss of patency and had potentially detrimental effect on the actuarial patency rate in BDI repair.

Differences in Post-Cholecystectomy Bile Duct Injury Care: A Comparative Analysis of 2 Different Health-Care Public Institutions in a Low- and Middle-Income Country: Southeast Mexico.

BACKGROUND: Mexican health system structure allows us to study the differences in bile duct injury (BDI) management. The study aimed to assess the differences in patients with complex BDI in 2 different public sector institutions using a new proposed standard terminology. METHODS: Retrospective review (2008-2019) in 2 public institutions (IMSS/SESVER). Bismuth-Strasberg E injuries with hepaticojejunostomy were included. Data are presented in a tabular reporting system. The outcomes were percent of patients attaining primary patency, loss of primary patency, and actuarial primary patency rate. RESULTS: Seventy-eight patients (IMSS: n = 37; SESVER: n = 41) without differences in demographic and preoperative assessment were studied. BDI occurred mostly in outside hospitals. Open cholecystectomy was the most common index operation in SESVER (73%, p = 0.02). IMSS had more surgeries (p = 0.007) and repair attempts (p = 0.06) prior to referral. Magnetic resonance cholangiopancreatography was more commonly used in IMSS patients. Biliary stents (45%) and cholangitis (29%) were more common in IMSS (p < 0.05). IMSS patients had longer follow-up than SESVER (p < 0.05). No differences in primary patency rates (IMSS: 89%, SESVER: 97%) and actuarial patency rates were noted. DISCUSSION: Despite differences in referral, preoperative, and operative events, good BDI repair outcomes can be achieved. Longer follow-up is needed to monitor these outcomes.