A three-year experience with the balloon expandable GORE® VIABAHN® VBX in the treatment of thoraco-abdominal aortic aneurysms within the EXPAND Trial.

OBJECTIVE: The EXPAND registry is a post-market, multicenter registry that aims at evaluating the safety and performance of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis (VBX stent) implanted in peripheral vessels. This subgroup analysis assesses the three-year outcomes of the VBX stent as a bridging stent-graft (BSG) for visceral vessels during branched endovascular aortic repair (BEVAR). METHODS: This prospective, multicenter, observational registry includes 16 European sites. Patients were enrolled from November 2018 to March 2022. Endpoints included three-year primary patency (PP), secondary patency (SP), and stent graft-related death and serious adverse events (SAE). RESULTS: Seventy-three patients of whom 57 (78.1%) were male with a mean age of 73 years (± 8.1) were included. At three years, 42 (57.5%) patients returned for follow-up. Overall, 223 target vessels (TV) were treated. The estimated freedom from loss of TV primary patency was 93.6%. Per target vessel primary patency rates were 97.0% for the celiac trunk, 93.9% for the superior mesenteric artery (SMA), 91.2% for the left renal artery, and 92.5% for the right renal artery. The overall estimated freedom from loss of secondary patency was 96.8%, and freedom from target vessel instability was 94.5%. CONCLUSIONS: The VBX stent demonstrated excellent sustained results at three years with almost 94% primary patency, 97% secondary patency, and 94.5% freedom from target vessel instability. Patency in the renal arteries was lower than in the celiac trunk and SMA. The VBX stent appears to be a reliable bridging stent for target vessels in BEVAR.

NRF2 translation block by inhibition of cap-dependent initiation sensitizes lymphoma cells to ferroptosis and CAR-T immunotherapy.

Cancers coopt stress-response pathways to drive oncogenesis, dodge immune surveillance, and resist cytotoxic therapies. Several of these provide protection from ferroptosis, iron-mediated oxidative cell death. Here, we found dramatic sensitization to ferroptosis upon disruption of cap-dependent translation in diffuse large B-cell lymphoma (DLBCL). Specifically, rocaglate inhibitors of the eIF4A1 RNA helicase synergized with pharmacologic ferroptosis inducers, driven by a collapse of glutathione production that protects polyunsaturated fatty acids from ferroptotic oxidation. These effects occur despite initial up-regulation of specific protective factors. We find lost translation of NRF2, oncogenic master regulator of antioxidant gene-expression, is a key consequence of eIF4A1 inhibition. In vivo, combination of the clinical rocaglate zotatifin with a pharmacologically optimized ferroptosis inducer eradicated DLBCL patient derived xenografts. Moreover, we found zotatifin pre-exposure sensitized DLBCL to CD19-directed chimeric antigen receptor (CAR-19) T cells. Translational disruption therefore provides new opportunities to leverage therapeutic impacts of ferroptosis inducers including cytotoxic immunotherapies.

Neuromuscular impairment at different stages of human sarcopenia.

BACKGROUND: Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. METHODS: We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants. RESULTS: Thirty-nine older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross-sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: P < 0.0001; Y vs. PS: P = 0.0169), suggestive of age-related impaired NMJ transmission. Increased C-terminal agrin fragment (P < 0.0001) and altered caveolin 3 protein expression were consistent with age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups (P < 0.0001), confirming age-related loss of MUs. An age-related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle denervation and axonal damage, evinced by the increase in neural cell adhesion molecule-positive fibres (Y vs. NS: P < 0.0001; Y vs. S: P = 0.02) and the increase in serum concentration of neurofilament light chain (P < 0.0001), respectively. Notably, most of these MU and NMJ parameters did not differ when comparing older individuals with or without sarcopenia. CONCLUSIONS: Alterations in MU properties, axonal damage, an altered innervation profile and NMJ instability are prominent features of the ageing of the neuromuscular system. These neuromuscular alterations are accompanied by muscle wasting and weakness; however, they appear to precede clinically diagnosed sarcopenia, as they are already detectable in older NS individuals.

A Proposal for the RNAome at the Dawn of the Last Universal Common Ancestor.

From the most ancient RNAs, which followed an RNY pattern and folded into small hairpins, modern RNA molecules evolved by two different pathways, dubbed Extended Genetic Code 1 and 2, finally conforming to the current standard genetic code. Herein, we describe the evolutionary path of the RNAome based on these evolutionary routes. In general, all the RNA molecules analysed contain portions encoded by both genetic codes, but crucial features seem to be better recovered by Extended 2 triplets. In particular, the whole Peptidyl Transferase Centre, anti-Shine-Dalgarno motif, and a characteristic quadruplet of the RNA moiety of RNAse-P are clearly unveiled. Differences between bacteria and archaea are also detected; in most cases, the biological sequences are more stable than their controls. We then describe an evolutionary trajectory of the RNAome formation, based on two complementary evolutionary routes: one leading to the formation of essentials, while the other complemented the molecules, with the cooperative assembly of their constituents giving rise to modern RNAs.

One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy.

Mavacamten is a first-in-class cardiac myosin ATPase inhibitor, approved by the United States Food and Drug Administration for the treatment of hypertrophic cardiomyopathy with obstructive physiology (oHCM). Here, we present the real-world use of mavacamten in 50 patients with oHCM at a tertiary care referral center. In both our highlighted case and in our aggregate data, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and New York Heart Association symptom class. Moreover, in our center's experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: we note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Moreover, our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings.

Propensity Score-matched Analysis Comparing Robotic Versus Laparoscopic Minor Liver Resections of the Anterolateral Segments: an International Multi-center Study of 10,517 Cases.

OBJECTIVE: To compare the outcomes of robotic minor liver resections (RMLR) versus laparoscopic (L) MLR of the anterolateral segments. BACKGROUND: Robotic liver surgery has been gaining prominence over the years with increasing usage for a myriad of hepatic resections. Robotic liver resections(RLR) has demonstrated non-inferiority to laparoscopic(L)LR while illustrating advantages over conventional laparoscopy especially for technically difficult and major LR. However, the advantage of RMLR for the anterolateral(AL) (segments II, III, IVb, V and VI) segments, has not been clearly demonstrated. METHODS: Between 2008 to 2022, 15,356 of 29,861 patients from 68 international centres underwent robotic(R) or laparoscopic minor liver resections (LMLR) for the AL segments Propensity score matching (PSM) analysis was performed for matched analysis. RESULTS: 10,517 patients met the study criteria of which 1,481 underwent RMLR and 9,036 underwent LMLR. A PSM cohort of 1,401 patients in each group were identified for analysis. Compared to the LMLR cohort, the RMLR cohort demonstrated significantly lower median blood loss (75ml vs. 100ml, P<0.001), decreased blood transfusion (3.1% vs. 5.4%, P=0.003), lower incidence of major morbidity (2.5% vs. 4.6%, P=0.004), lower proportion of open conversion (1.2% vs. 4.5%, P<0.001), shorter post operative stay (4 days vs. 5 days, P<0.001), but higher rate of 30-day readmission (3.5% vs. 2.1%, P=0.042). These results were then validated by a 1:2 PSM analysis. In the subset analysis for 3,614 patients with cirrhosis, RMLR showed lower median blood loss, decreased blood transfusion, lower open conversion and shorter post operative stay than LMLR. CONCLUSION: RMLR demonstrated statistically significant advantages over LMLR even for resections in the AL segments although most of the observed clinical differences were minimal.

Classification of Premature Ventricular Contractions in Athletes During Routine Preparticipation Exams.

BACKGROUND: Large-scale data on incidental premature ventricular contraction (PVC) prevalence and morphologies have been lacking, leaving many providers without guidance on further cardiac testing for patients with incidental PVCs on ECG. Athletes offer an intriguing cohort to understand the clinical significance, prevalence, and common morphologies of incidental PVCs because they often undergo ECG screening during preparticipation exams. METHODS: Digital ECGs were obtained from 10 728 screened athletes aged 14 to 35 years during mass screenings in schools and professional sports teams between 2014 and 2021. A retrospective analysis of ECGs with PVCs was performed using the simultaneous display of frontal (limb) and horizontal (precordial) plane leads. PVCs were coded for morphology and categorized as benign or nonbenign using recommended criteria. RESULTS: Twenty-six athletes (0.24%) were found to have at least 1 PVC. Among these, 50% were female, 65% were White, 8% were Asian, 4% were Hispanic, and 23% were Black. Nineteen of the 26 (73%) ECGs had PVCs with a left bundle branch block pattern compared with 7 (27%) with a right bundle branch block pattern. Twenty-four ECGs (96%) had PVCs with benign patterns, including 18 with right ventricular outflow tract, 5 with left anterior fascicle, and 2 with left posterior fascicle morphology. CONCLUSIONS: There is a low prevalence of PVCs on routine ECG screening of young athletes, and most PVCs are of benign morphology in this population. This study highlights the value of using digital ECG recorders with simultaneous lead display to guide decision-making about further cardiac testing and referrals in young athletes with PVCs. Using our results and review of the literature, we propose methods and algorithms of PVC evaluation on screening ECGs to help guide many providers with risk stratification and decision-making about further cardiac testing and electrophysiology referrals in young athletes with PVCs.

Medullary carcinomas of the nonampullary small intestine: association with coeliac disease, mismatch repair deficiency, PD-L1 expression, and favourable prognosis.

AIM: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs). METHODS AND RESULTS: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death-ligand 1 (PD-L1) and mismatch repair proteins was performed in both SB-MCs and NM-SBAs. SB-MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein-Barr virus (EBV)-encoded RNAs by in-situ hybridization. MLH1 promoter methylation status was evaluated in MLH1-deficient cases. Eleven SB-MCs and 149 NM-SBAs were identified. One (9%) SB-MC was EBV-positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB-MCs, both with isolated loss of ARID1A. Compared with NM-SBAs, SB-MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD-L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB-MC patients compared to NM-SBA cases (P = 0.02). CONCLUSION: SB-MCs represent a distinct histologic subtype, with peculiar features compared to NM-SBAs, including association with coeliac disease, dMMR, PD-L1 expression, and better prognosis.

Endovascular Conversion of a Failed Nellix AAA-Repair by a Custom-Made Branched Device.

PURPOSE: This technical note presents a case of a patient with a failed Nellix device (Endologix, Irvine, Calif) who was not deemed fit for open conversion. Our planned approach for repair involved an endovascular procedure utilizing a custom-made branched device. TECHNIQUE: An endovascular repair was performed via a custom-made four outer branched device in conjunction with a custom-made bifurcated graft featuring inverted limbs (Cook Inc., Bloomington, Ind). All branches were connected to the target vessel with Gore Viabahn VBX balloon-expandable covered stents (Gore & Associates Inc.). CONCLUSION: Endovascular conversion with branched endovascular repair in a patient not deemed fit for open surgery was successfully performed, thereby reducing the risk of a high morbid and mortal procedure. CLINICAL IMPACT: Novel useful treatment solution of failed EVAR with Nellix device.

Chitosan membranes incorporating Aloe vera glycolic extract with joint synthesis of silver nanoparticles for the treatment of skin lesions.

New wound dressings based on polymeric membranes have been widely exploited for clinical applications to assist in the healing process and prevent additional complications (e.g., bacterial infections). Here we propose the development of a new production method of polymeric membranes based on chitosan, incorporating glycolic extract of Aloe vera with joint synthesis of silver nanoparticles for use as a new bioactive dressing. The membranes were obtained by casting technique, and their morphological, physicochemical characteristics, degree of swelling, degradation profile and antimicrobial activity evaluated. Morphological analyzes confirmed the synthesis and presence of silver nanoparticles in the polymeric membrane. The chemical compatibility between the materials was demonstrated through thermal analysis (TGA and DSC) combined with ATR-FTIR tests, showing the complexation of the membranes (Mb-Ch-Ex.Av-NPs). All membranes were characterized as hydrophilic material (with a contact angle (Ó©) < 90°); however, the highest degree of swelling was obtained for the chitosan. (Mb-Ch) membrane (69.91 ± 5.75%) and the lowest for Mb-Ch-Ex.Av-NPs (26.62 ± 8.93%). On the other hand, the degradation profile was higher for Mb-Ch-Ex.Av-NPs (77.85 ± 7.51%) and lower for Mb-Ch (57.60 ± 2.29%). The manufactured bioactive dressings showed activity against Escherichia coli and Staphylococcus aureus. Our work confirmed the development of translucent and flexible chitosan-based membranes, incorporating Aloe vera glycolic extract with joint synthesis of silver nanoparticles for use as a new bioactive dressing, with proven antimicrobial activity.

Simple models vs. deep learning in detecting low ejection fraction from the electrocardiogram.

Aims: Deep learning methods have recently gained success in detecting left ventricular systolic dysfunction (LVSD) from electrocardiogram (ECG) waveforms. Despite their high level of accuracy, they are difficult to interpret and deploy broadly in the clinical setting. In this study, we set out to determine whether simpler models based on standard ECG measurements could detect LVSD with similar accuracy to that of deep learning models. Methods and results: Using an observational data set of 40 994 matched 12-lead ECGs and transthoracic echocardiograms, we trained a range of models with increasing complexity to detect LVSD based on ECG waveforms and derived measurements. The training data were acquired from the Stanford University Medical Center. External validation data were acquired from the Columbia Medical Center and the UK Biobank. The Stanford data set consisted of 40 994 matched ECGs and echocardiograms, of which 9.72% had LVSD. A random forest model using 555 discrete, automated measurements achieved an area under the receiver operator characteristic curve (AUC) of 0.92 (0.91-0.93), similar to a deep learning waveform model with an AUC of 0.94 (0.93-0.94). A logistic regression model based on five measurements achieved high performance [AUC of 0.86 (0.85-0.87)], close to a deep learning model and better than N-terminal prohormone brain natriuretic peptide (NT-proBNP). Finally, we found that simpler models were more portable across sites, with experiments at two independent, external sites. Conclusion: Our study demonstrates the value of simple electrocardiographic models that perform nearly as well as deep learning models, while being much easier to implement and interpret.

Inequities in atrial fibrillation trials: An analysis of participant race, ethnicity, and sex over time.

BACKGROUND: Despite the importance of racial and ethnic representation in clinical trials, limited data exist about the enrollment trends of these groups in atrial fibrillation (AF) trials over time. OBJECTIVE: The purpose of this study was to examine the characteristics of contemporary AF clinical trials and to evaluate their association with race and ethnicity over time. METHODS: We performed a systematic search of all completed AF trials registered in ClinicalTrials.gov from conception to December 31, 2023, and manually extracted composition of race/ethnicity. We stratified trials by study characteristics, including impact factor, publication status, funding source, and location. We calculated the participation to prevalence ratio (PPR) by dividing the percentage of non-White participants by the percentage of non-White participants in the disease population (PPR of 0.8-1.2 suggests proportional representation) over time. RESULTS: We identified 277 completed AF trials encompassing a total of 1,933,441 adults, with a median proportion of non-White at 12% (interquartile range, 6%-27%), 121 (43.7%) device focused, and 184 (66.4%) funded by industry. Only 36.1% of trials reported comprehensive race information. Overall, non-White participants were underrepresented (PPR = 0.511; P < .001), including Black (PPR = 0.263) and Hispanic (PPR = 0.337) participants. The proportion of non-White participants did not change significantly between 2000 and 2023 (11% vs 9%; P = .343). CONCLUSION: Despite greater awareness, race/ethnicity reporting and representation of non-White groups in AF clinical trials are poor and have not improved significantly over time. These findings demand additional recruitment efforts and novel recruitment policies to ensure adequate representation of these demographic subgroups in future AF clinical trials.

Spaceflight on the ISS changed the skeletal muscle proteome of two astronauts.

Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres. We here extend the data analysis of the astronaut dataset and show compartment-resolved changes in the mitochondrial proteome, remodeling of the extracellular matrix and of the antioxidant response. The astronauts differed in their level of onboard physical exercise, which correlated with their respective preservation of muscle mass and force at landing in previous analyses. We show that the mitochondrial proteome downregulation during spaceflight, particularly the inner membrane and matrix, was dramatic for both astronauts. The expression of autophagy regulators and reactive oxygen species scavengers, however, showed partially opposite expression trends in the two subjects, possibly correlating with their level of onboard exercise. As mitochondria are primarily affected in many different tissues during spaceflight, we hypothesize that reactive oxygen species (ROS) rather than mechanical unloading per se could be the primary cause of skeletal muscle mitochondrial damage in space. Onboard physical exercise might have a strong direct effect on the prevention of muscle atrophy through mechanotransduction and a subsidiary effect on mitochondrial quality control, possibly through upregulation of autophagy and anti-oxidant responses.

Defining Global Benchmarks for Laparoscopic Right Posterior Sectionectomy/H67: An International Multicenter Study.

OBJECTIVE: We aimed to establish global benchmark outcomes indicators for L-RPS/H67. BACKGROUND: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted. METHODS: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff. RESULTS: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively. CONCLUSIONS: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.

Factors Associated with and Impact of Open Conversion in Laparoscopic and Robotic Minor Liver Resections: An International Multicenter Study of 10,541 Patients.

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

Upwelling-driven variation of sound speed profile in a Brazilian bay monitored by a coastal acquisition system.

Sound speed profiles in the ocean are determined by seawater properties, where horizontal variability of thermal stratification modulates sonar detection distance. This work assesses the impacts of upwelling dynamics on sound speed profile in enclosed coastal areas by means of temperature observations acquired with a low-cost platform in Anjos Cove, Cabo Frio, Brazil. The Integrated Acquisition System for Research in Acoustics (IARA) consists of a customized 10-meter-long chain of smart temperature sensors (±0.1°C accuracy) mounted in an anchored vertical cable and an echo sounder for tide level measurements. From 2021 to 2023 a number of intrusion events of the cold South Atlantic Central Water (SACW) took place along the Cabo Frio continental shelf, some of which were recorded in the inner region of the Anjos Cove by IARA. Sound speed profiles computed by applying TEOS-10 standards indicate that the sound propagation within Anjos Cove varies often, i.e., several orders of magnitude, under the influence of SACW intrusion events. The phenomenon reflects information from deeper waters on a coastal scale, even at small depths.

Evaluation of coagulation profile in dogs with ACTH-dependent hyperadrenocorticism compared to healthy dogs by rotational thromboelastometry (ROTEM).

Despite their low morbidity, thromboembolic events in hyperadrenocorticism are associated with high mortality. Identifying the main hemostatic abnormalities will improve the prophylactic approach of these canine patients. The aim of this study was to evaluate hemostatic alterations related with ACTH-dependent HAC and its association with hypercoagulable state. For this purpose, 25 dogs diagnosed with ACTH-dependent HAC were compared with 28 healthy dogs as a control group. The hemostatic variables included platelet count, antithrombin, fibrinogen, D-dimer, PT, aPTT, rotational thromboelastometry (ROTEM) and platelet aggregation. Results showed a hypercoagulable state in 32% (8/25) dogs by ROTEM, which had at least 2 of the next features: decreased coagulation time (CT) or clot formation time (CFT) on INTEM (5/25) or EXTEM (4/25); increased maximum clot firmness (MCF) on INTEM (9/25), EXTEM (6/25) and FIBTEM (9/25). These same variables had a significant difference (P≤ 0.05) compared with the control group, as well as the parameters of α-angle and CT. Median fibrinogen levels (310 vs.178 mg/dL), mean platelet aggregation (11.1 vs. 7.9 Ohms), median platelet count (360 vs. 225 ×103/µL) and mean antithrombin activity (140 vs. 119%) were increased in ACTH-dependent HAC dogs compared to control group. PT (7.1 vs. 8.0 seconds) and aPTT (11.6 vs. 15.2 seconds) were also shortened in ACTH-dependent HAC dogs. Our findings confirm the presence of a hypercoagulable tendency in dogs with HAC. Although multifactorial, fibrinogen concentration and MCF FIBTEM showed the relevance of this protein for hypercoagulability in HAC.