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Objective: To assess the effect of admission cardiotocography (ACTG) versus intermittent auscultation (IA) of the fetal heart (FH) in low-risk pregnancy during assessment for possible labour on caesarean section rates.Design: A parallel multicentre randomised trial.Setting: Three maternity units in the Republic of Ireland.Population: Healthy, low-risk pregnant women, at term and ≥ 18 years old, who provided written informed consent.Methods: Women were randomised to receive IA of the FH or 20 minutes ACTG on admission for possible labour onset, using remote telephone randomisation. Both groups received IA during labour, with conversion to continuous CTG as clinically indicated.Main Outcome Measures: Caesarean section (primary outcome), obstetric interventions (e.g. continuous CTG during labour, fetal blood sampling, augmentation of labour) and neonatal morbidity (e.g. metabolic acidosis, admission to the neonatal intensive care unit, neonatal death).Results: Based on 3034 women (1513 and 1521 randomised to IA and ACTG, respectively), there was no statistical difference between the groups in caesarean section [130 (8.6%) and 105 (6.9%) for IA and ACTG groups, respectively; relative risk (RR) 1.24; 95% CI 0.97-1.58], or in any other outcome except for use of continuous CTG during labour, which was lower in the IA group (RR 0.90, 95% CI 0.86-0.93).Conclusion: Our study demonstrates no differences in obstetric or neonatal outcomes between IA and ACTG for women with possible labour onset, other than an increased risk for continuous CTG in women receiving ACTG.Tweetable Abstract: No differences in outcomes between intermittent auscultation and admission cardiotocography for women with possible labour onset. [ABSTRACT FROM AUTHOR]

Background and Purpose: The uterine pathophysiology underlying inflammatory conditions such as chorioamnionitis remains largely unclear. As we have shown that beta(3)-adrenoceptors act as regulators of myometrial inflammation, we wanted to investigate the potential role of beta(3)-adrenoceptors in preventing uterine remodelling induced by inflammation.Experimental Approach: The consequences of human chorioamnionitis on myometrial remodelling were characterized by Sirius Red staining and metalloproteinase (MMP) expression, and compared with the effects of incubating human myometrial samples with Escherichia coli lipopolysaccharide (LPS) in vitro. We also assessed the effect of SAR150640, a selective beta(3)-adrenoceptor agonist, on the production and activity of MMPs.Key Results: Chorioamnionitis was associated with a 46% decrease in total collagen, as well as over-expression of MMP2 (+61%) and MMP9 (+84%); both effects were reproduced by incubation with LPS (10 microg x mL(-1), 48 h). LPS-induced over-expression of MMP2 and MMP9 in normal human myometrium was paralleled by an overactivity of the proteins. Both over-expression and overactivity were prevented by the beta(3)-adrenoceptor agonist SAR150640 in a concentration-dependent manner. SAR150640, by itself, did not exhibit any effect on MMP production in control tissues.Conclusions and Implications: This study shows that inflammation was associated with an intense remodelling of human myometrium, a process likely to be explained by MMP activation. Our study emphasizes the potential therapeutic relevance of beta(3)-adrenoceptor agonists to the treatment of preterm labour and other uterine inflammatory conditions. [ABSTRACT FROM AUTHOR]

Abstract Objectives: To investigate the obstetric antecedents for preterm delivery (PTD) in an Irish urban obstetric population, and to evaluate the incidence and outcome of such deliveries. Study design: A retrospective observational study of all preterm deliveries at the Rotunda Hospital, Dublin during the six-year period 1997-2002. The findings for early preterm deliveries (EPTD) (24+0-31+6 weeks' gestation), and late preterm deliveries (LPTD) (32+0-36+6 weeks' gestation) were analyzed separately. Results: There were 38,795 deliveries after 24 weeks' gestation or >500 g birth weight, of which 2839 (7.3%) were preterm. Of all preterm deliveries, 626 (22.1%) were EPTD and 2213 (77.9%) were LPTD, resulting in an EPTD rate of 1.6% and an LPTD rate of 5.7%. Spontaneous unexplained preterm delivery accounted for 1221 (43.0%) of preterm deliveries (PTD), and of these 213 (34%) cases were EPTD and 1008 (45.5%) LPTD. The other most frequently observed obstetric causative factors, in order of importance, were multiple gestation (676; 23.8% of PTD), hypertensive disorders of pregnancy (243; 8.6%), antepartum hemorrhage (194; 6.8%), stillbirth (105; 3.7%), intrauterine growth restriction (53; 1.9%) and preterm prelabor rupture of membranes+/-chorioamnionitis (32; 1.1%). There were 75 early neonatal deaths among infants born prematurely, plus 105 stillbirths, resulting in a perinatal mortality rate of 63 per 1000 for PTD (n=180), which on subsequent analysis was 158 per 1000 for EPTD (n=99) and 37 per 1000 for LPTD (n=81). Conclusions: These data outline the obstetric factors linked to preterm delivery within a recent Irish urban obstetric population. Spontaneous idiopathic preterm labor was the principle causative factor in 43% of all preterm deliveries, and represents the proportion of women for whom future therapeutic intervention may be of benefit. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the association between placental histological abnormalities and birthweight discordance and growth restriction in twin pregnancies. Study Design: We performed a multicenter, prospective study of twin pregnancies. Placentas were examined for evidence of infarction, retroplacental hemorrhage, chorangioma, subchorial fibrin, or abnormal villus maturation. Association of placental lesions with chorionicity, birthweight discordance, and growth restriction were assessed. Results: In all, 668 twin pairs were studied, 21.1% monochorionic and 78.9% dichorionic. Histological abnormalities were more frequent in placentas of smaller twins of birthweight discordant pairs (P = .02) and in placentas of small for gestational age infants (P = .0001) when compared to controls. The association of placental abnormalities with both birthweight discordance and small for gestational age was significant for dichorionic twins (P = .01 and .0001, respectively). No such association was seen in monochorionic twins. Conclusion: In a large, prospective, multicenter study, we observed a strong relationship between abnormalities of placental histology and birthweight discordance and growth restriction in dichorionic, but not monochorionic, twin pregnancies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Obesity is an increasing problem in obstetric practice. Apelin, secreted by adipocytes, is present in increased serum concentrations in an obese state. Our group has previously highlighted that the adipokines leptin and ghrelin have a potential role in metabolic modulation of uterine contractility in obese women. The aim of this study was to evaluate the effects of apelin on human uterine contractility in vitro. STUDY DESIGN: Biopsies of human myometrium were obtained at elective cesarean section. Myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of apelin in the concentration range of 1 nmol/L to 1 [mu]mol/L. Control experiments were performed simultaneously. RESULTS: Apelin exerted an inhibitory effect on spontaneous and oxytocin induced contractions in human myometrium. The mean maximal inhibition values were 36.8 ± 6.4% for spontaneous (n = 6; P = .002) and 30.4 ± 4.6% for oxytocin-induced contractions (n = 6; P < .0001). CONCLUSION: Apelin inhibits human uterine contractility in vitro, raising the possibility that such metabolic modulation may play a physiological role in obese parturients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to evaluate the impact of noncentral placental cord insertion on birthweight discordance in twins. STUDY DESIGN: We performed a multicenter, prospective trial of twin pregnancies. Placental cord insertion was documented as central, marginal, or velamentous according to a defined protocol. Association of the placental cord insertion site with chorionicity, birthweight discordance, and growth restriction were assessed. RESULTS: Eight hundred sixteen twin pairs were evaluated; 165 pairs were monochorionic, and 651 pairs were dichorionic. Monochorionic twins had higher rates of marginal (P = .0068) and velamentous (P < .0001) placental cord insertion. Noncentral placental cord insertion was more frequent in smaller twins of discordant pairs than control pairs (29.8% vs 19.1%; P = .004). Velamentous placental cord insertion in monochorionic twins was associated significantly with birthweight discordance (odds ratio, 3.5; 95% confidence interval, 1.3-9.4) and growth restriction (odds ratio, 4; 95% confidence interval, 1.1-14.3). CONCLUSION: Noncentral placental cord insertion contributes to birthweight discordance in monochorionic twin pregnancies. Sonographic delineation of placental cord insertion may be of value in antenatal assessment of twin pregnancies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was aimed at assessing the role of leptin on human myometrium, by studying its receptor expression in pregnant myometrium and the interaction of leptin with inflammation-induced apoptosis. STUDY DESIGN: Myometrial samples were obtained from women with uncomplicated pregnancies who underwent cesarean delivery at term before labor onset. The effect of leptin on apoptosis was assessed by the incubation of myometrial strips with leptin (10(-10) to 10(-8) mol/L; 48 hours) before lipopolysaccharide treatment (10 [mu]g/mL; 48 hours). RESULTS: Long and short leptin receptor isoforms were expressed in myometrial cells of pregnant women. Leptin prevented lipopolysaccharide-induced apoptosis, in a concentration-dependent manner, by down-regulating cleaved caspase-3 and BCL2-associated X protein and up-regulating BCL2 expression. This effect was mediated specifically through leptin receptor stimulation, followed by ERK1/2 signaling pathway activation. CONCLUSION: These results suggest a new potential pathway that is involved in delivery disorders of obese women and propose a role for the leptin-induced inhibition of myometrial apoptosis in the development of such disorders. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to establish predictors of vaginal twin birth and evaluate perinatal morbidity according to mode of delivery. STUDY DESIGN: One thousand twenty-eight twin pregnancies were prospectively recruited. For this prespecified secondary analysis, obstetric characteristics and a composite of adverse perinatal outcome were compared according to the success or failure of a trial of labor and further compared with those undergoing elective cesarean delivery. Perinatal outcomes were adjusted for chorionicity and gestational age using a linear model for continuous data and logistic regression for binary data. RESULTS: Nine hundred seventy-one twin pregnancies met the criteria for inclusion. A trial of labor was considered for 441 (45%) and was successful in 338 of 441 (77%). The cesarean delivery rate for the second twin was 4% (14 of 351). Multiparity and spontaneous conception predicted vaginal birth. No statistically significant differences in perinatal morbidity were observed. CONCLUSION: A high prospect of successful and safe vaginal delivery can be achieved with trial of twin labor. [ABSTRACT FROM AUTHOR]

Objectives: While methods of endovascular carotid artery stenting have improved over time, concerns surrounding the safety and efficacy of stenting for blunt carotid injury (BCI) remain. This study aims to present our approach to carotid artery stenting (CAS) by incorporating new technologies such as flow-diverting stents and circuits., Methods: There is no robust evidence to support routine carotid artery stenting; however, there are several therapeutic options and approaches for treating BCI that currently require an individualized approach. Endovascular stenting and specific stent selection are largely dictated by the disease process the surgeon intends to treat. We will discuss patient selection, medical management, and the most common revascularization techniques, including transfemoral stenting, trans-carotid arterial revascularization using flow reversal, and stent-assisting coiling., Results: It must be stressed that endovascular intervention is not an alternative to or preclusive of antithrombotic or anticoagulant therapy. In the setting of BCI, transfemoral CAS is most appropriate in patients who are symptomatic, have a rapidly progressing or large lesion, and do not have a soft thrombus present due to risk of embolism. Unlike transfemoral CAS, TCAR offers an elegant solution for embolic protection when patients have a soft thrombus present. In the case of a large pseudoaneurysm, we perform stent-assisted coiling., Conclusions: We practice selective endovascular intervention, stenting lesions that are flow-limiting or have large or rapidly expanding pseudoaneurysms, and only in patients for whom anticoagulation and antiplatelet agents are not contraindicated. As technology and investigation progress, the concerns regarding the safety and the role of endovascular intervention in the treatment of BCI will be more clearly defined., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The Human Acellular Vessel (HAV) is a novel, off-the-shelf biologic conduit being evaluated for arterial reconstructions. Regulatory studies in peripheral arterial disease (PAD) to date have consisted of single-arm cohorts with no comparator groups to contrast performance against established standards. This study aimed to compare outcomes of the HAV with autologous great saphenous vein (GSV) in patients with advanced PAD undergoing infrageniculate bypass., Methods: Patients with advanced PAD and no autologous conduit who underwent bypass with the 6-mm diameter HAV (Group 1; n = 34) (March 2021-February 2024) were compared with a multicenter historical cohort who had bypass with single-segment GSV (group 2; n = 88) (January 2017-December 2022). The HAV was used under an Investigational New Drug protocol issued by the Food and Drug Administration (FDA) under the agency's Expanded Access Program., Results: Demographics were comparable between groups (mean age 69 ± 10 years; 71% male). Group 1 had higher rates of tobacco use (37 pack-years vs 28 pack-years; P = .059), coronary artery disease (71% vs 43%; P = .007), and prior coronary artery bypass grafting (38% vs 14%; P = .003). Group 1 had more patients classified as wound, ischemia, and foot infection clinical stage 4 (56% vs 33%; P = .018) and with previous index leg revascularizations (97% vs 53%; P < .001). Both groups had a similar number of patients with chronic limb-threatening ischemia (Rutherford class 4-6) (88% vs 86%; P = .693) and Global Anatomic Staging System stage III (91% vs 96%; P = .346). Group 1 required a composite conduit (two HAV sewn together) in 85% of bypasses. The tibial vessels were the target in 79% of group 1 and 100% of group 2 (P < .001). Group 1 had a lower mean operative time (364 minutes vs 464 minutes; P < .001). At a median of 12 months, major amputation-free survival (73% vs 81%; P = .55) and overall survival (84% vs 88%; P = .20) were comparable. Group 1 had lower rates of primary patency (36% vs 50%; P = .044), primary-assisted patency (45% vs 72%; P = .002), and secondary patency (64% vs 72%; P = .003) compared with group 2., Conclusions: Implanted under Food and Drug Administration Expanded Access provisions, the HAV was more likely to be used in redo operations and cases with more advanced limb ischemia than GSV. Despite modest primary patency, the HAV demonstrated resilience in a complex cohort with no autologous conduit options, achieving good secondary patency and providing major amputation-free survival comparable with GSV at 12 months., Competing Interests: Disclosures Humacyte Inc provides funding to Mayo Clinic to support the performance of this IND study. T.E.R. serves in a clinical advisory role for Humacyte, Inc., with funds paid to Mayo Clinic., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis., Objective: To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department., Design: Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone., Setting: United Kingdom Major Trauma Centres., Participants: Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta., Interventions: Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta., Main Outcome Measures: Primary: Mortality at 90 days. Secondary: Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. Health economic: Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon., Data Sources: Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data)., Results: Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at any time point. Death due to haemorrhage was more common in the standard care plus resuscitative endovascular balloon occlusion of the aorta group than in the standard care group. There were no serious adverse device effects. Resuscitative endovascular balloon occlusion of the aorta is less costly (probability 99%), due to the competing mortality risk but also substantially less effective in terms of lifetime quality-adjusted life-years (probability 91%)., Limitations: The size of the study reflects the relative infrequency of exsanguinating traumatic haemorrhage in the United Kingdom. There were some baseline imbalances between groups, but adjusted analyses had little effect on the estimates., Conclusions: This is the first randomised trial of the addition of resuscitative endovascular balloon occlusion of the aorta to standard care in the management of exsanguinating haemorrhage. All the analyses suggest that a strategy of standard care plus resuscitative endovascular balloon occlusion of the aorta is potentially harmful., Future Work: The role (if any) of resuscitative endovascular balloon occlusion of the aorta in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required., Trial Registration: This trial is registered as ISRCTN16184981., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and is published in full in Health Technology Assessment ; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information.

Objective: Type B intramural hematoma (IMH) is often managed medically, yet may progress to dissection, aneurysmal dilation, or rupture. The aim of this study was to report the natural history of medically managed Type B IMH, and factors associated with progression., Methods: We reviewed patients with medically managed Type B IMH between January 1995 to December 2022 at a single center. Any patients with immediate surgical or endovascular intervention were excluded. Demographic profiles, comorbidities, imaging, and follow-up details were reviewed. Patients were divided into two groups: Group 1 had isolated IMH, and Group 2 had IMH along with aneurysm or dissection at the time of presentation. On follow-up, progression was defined as degeneration to aneurysm/dissection or increase in the thickness of IMH in Group 1. In Group 2, progression was an increase in the size of aneurysm or development of new dissection., Results: Of 104 patients with Type B IMH during the study period, 92 were medically managed. The median age was 77 years, and 45 (48.9%) were females. Comorbidities included hypertension (83.7%), hypercholesterolemia (44.6%), and active smoking (47.8%). Mean Society for Vascular Surger comorbidity score was 6.3. Mean IMH thickness and aortic diameter at presentation were 8.9 mm and 38.3 mm, respectively. Median follow-up was 55 months. Overall survival at 1 year and 5 years was 85.8% and 61.9%, respectively. During follow-up, 19 patients (20.7%) required intervention, more common in Group 2 (Group 1, 8/66; 12.3% vs Group 2, 11/26; 42.3%; P = .001). This resulted in higher freedom from intervention in Group 1 at 1 year (93.5% vs 62.7%) and 5 years (87.5% vs 51.1%; P < .001). Indication for intervention was dissection (n = 4), aneurysm (n = 12), and progression of IMH (n = 3). In Group 1, progression was seen in 25 (37.9%), three (4.5%) remained stable, 29 (43.9%) had complete resolution of IMH, and nine patients were lost to follow-up. In Group 2, 11 patients (42.3%) had progression, seven (26.9%) remained stable, and eight were lost to follow-up. IMH thickness at presentation >7.2 mm is associated with both increased odds of progression (odds ratio, 3.3; 95% confidence interval, 1.2-11.1; P = .03) and intervention (odds ratio, 5.5; 95% confidence interval, 1.3-36.9; P = .03) during the follow-up., Conclusions: Although many patients with Type B IMH managed medically stabilize or regress, progression or need for intervention can occur in up to 40% of cases. This is associated with the presence of aneurysm, dissection, and IMH thickness. Long-term follow-up is mandatory as late interventions occur, particularly for higher risk patients., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Type II endoleaks (T2ELs) are the most common cause of reintervention after endovascular aneurysm repair (EVAR). Although most resolve spontaneously, the long-term implications of T2ELs remain elusive. We aim to evaluate the impact of persistent and late T2ELs on clinical outcomes after EVAR., Methods: This was a single-institution retrospective review of patients who underwent EVAR for degenerative infrarenal abdominal aortic aneurysm between January 2010 and June 2022 with no type I (T1EL) or III (T3EL) endoleak seen at EVAR completion. Patients were categorized based on T2EL status. Group 1 included patients with never detected or transient T2ELs (detected at EVAR completion but not after). Group 2 encompassed persistent T2ELs (seen at EVAR completion and again during follow-up) and late T2ELs (detected for the first time at any point during follow-up). Time-to-event analysis was conducted using a time-dependent approach to T2EL status. Primary outcomes included freedom from sac enlargement (SE), aneurysm-related reinterventions, and overall survival., Results: A total of 803 patients met inclusion criteria. Group 1 included 418 patients (52%), of which 85% had no T2ELs and 15% had transient T2ELs. Group 2 had 385 patients; 23% had persistent T2ELs, and 77% developed a new T2EL. Patients in group 1 had a higher prevalence of smoking (88% vs 83%; P < .001), chronic obstructive pulmonary disease (33% vs 25%; P = .008), chronic kidney disease (13% vs 8%; P = .021), and a higher mean Society for Vascular Surgery score (7 vs 6 points; P = .049). No differences were found in aneurysm diameter or morphology. Mean follow-up was 5 years for the entire cohort. In Group 2, 58 patients (15%) underwent T2EL treatment, most commonly transarterial embolization. At 10 years after EVAR, Group 2 was associated with lower freedom from SE (P < .001) and abdominal aortic aneurysm-related reinterventions (P < .001) and comparable overall survival (P = .42). More T1ELs were detected during follow-up in Group 2 (6 [1%] vs 20 [5%]; P = .004), with 15 (75%) of these detected at a median of 3 years after the T2EL. No difference between groups was observed in explant (0.7% vs 2.1%; P = .130) or aneurysm rupture (0.5% vs 1.3%; P = .269) rates., Conclusions: One-half of patients treated with infrarenal EVAR developed persistent/late T2ELs, which are associated with a higher risk of SE and reinterventions. No difference in overall survival or aneurysm rupture risk was seen at 10 years, based on T2EL status or T2EL intervention. A conservative approach to T2ELs may be appropriate for most patients with absent T1ELs or T3ELs., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Thoracic Endovascular Aortic Repair (TEVAR) is well established in humans. Despite widespread use, additional research questions related to thoracic aortic stenting and endovascular innovation require large animal models. Translating human TEVAR devices and techniques into animal models, however, is a challenge even for experienced endovascular surgeons looking to develop a large animal TEVAR model.This article describes swine-specific strategies to deploy human TEVAR stent grafts, delineate how to select, size, prepare, and re-use human stents and deployment systems in swine, and how to translate human imaging modalities to large animal TEVAR., Methods: We describe a selection of related TEVAR models and techniques in Yorkshire swine to support scientific inquiry. This includes an animal husbandry and pre-operative preparation and planning program. All imaged specimens in this paper are castrated male Yorkshire swine in the 60-80 kg range and underwent TEVAR with the Medtronic Navion stent and deployment system., Results: To study human aortic stent grafts in swine, the animals generally must be at least 50 kgs to guarantee a 2 cm internal aortic diameter at the left subclavian, and for the iliac arteries to accommodate the human deployment system. Swine will have longer torsos and shorter iliofemoral segments than a human of the same weight which can make human deployment systems too short to reach the left subclavian from the femoral arteries in larger animals. We provide techniques to overcome this, including open iliac access or upside-down carotid TEVAR, which may be particularly useful if the scientific data would be confounded by iliofemoral access.Unlike humans that present clinically with axial imaging, swine will generally not have preoperative imaging, and many translational research laboratories do not have access to inexpensive preoperative CT, or any intraoperative CT scanning, which we are fortunate to have. We describe, therefore, several strategies for imaging in this setting including TEVAR via C-arm fluoroscopy and with or without in-laboratory CT scanning. Due to the low-resource setting of most large animal laboratories, as compared to a human hybrid room, we also describe several techniques to reduce cost and reuse materials, including the stent grafts, which at the end of non-survival experiments can be recovered during necropsy, cleaned, reinserted into the deployment device and reused on additional animals., Conclusions: This article describes a collection of related techniques and tips to translate human TEVAR imaging, sizing/selection, deployment, and anatomy to swine research. Using this framework alone, an experienced human vascular or endovascular surgeon may develop a complete aortic stenting animal model with strategies for scientific data acquisition., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Reducing growth and limiting metabolism are strategies that allow bacteria to survive exposure to environmental stress and antibiotics. During infection, uropathogenic Escherichia coli (UPEC) may enter a quiescent state that enables them to reemerge after the completion of successful antibiotic treatment. Many clinical isolates, including the well-characterized UPEC strain CFT073, also enter a metabolite-dependent, quiescent state in vitro that is reversible with cues, including peptidoglycan-derived peptides and amino acids. Here, we show that quiescent UPEC is antibiotic tolerant and demonstrate that metabolic flux in the tricarboxylic acid (TCA) cycle regulates the UPEC quiescent state via succinyl-CoA. We also demonstrate that the transcriptional regulator complex integration host factor and the FtsZ-interacting protein ZapE, which is important for E. coli division during stress, are essential for UPEC to enter the quiescent state. Notably, in addition to engaging FtsZ and late-stage cell division proteins, ZapE also interacts directly with TCA cycle enzymes in bacterial two-hybrid assays. We report direct interactions between the succinate dehydrogenase complex subunit SdhC, the late-stage cell division protein FtsN, and ZapE. These interactions may enable communication between oxidative metabolism and the cell division machinery in UPEC. Moreover, these interactions are conserved in an E. coli K-12 strain. This work suggests that there is coordination among the two fundamental and essential pathways that regulate overall growth, quiescence, and antibiotic susceptibility., Importance: Uropathogenic Escherichia coli (UPEC) are the leading cause of urinary tract infections (UTIs). Upon invasion into bladder epithelial cells, UPEC establish quiescent intracellular reservoirs that may lead to antibiotic tolerance and recurrent UTIs. Here, we demonstrate using an in vitro system that quiescent UPEC cells are tolerant to ampicillin and have decreased metabolism characterized by succinyl-CoA limitation. We identify the global regulator integration host factor complex and the cell division protein ZapE as critical modifiers of quiescence and antibiotic tolerance. Finally, we show that ZapE interacts with components of both the cell division machinery and the tricarboxylic acid cycle, and this interaction is conserved in non-pathogenic E. coli , establishing a novel link between cell division and metabolism., Competing Interests: The authors declare no conflict of interest.

Purpose: To evaluate effectiveness and safety of large-bore mechanical thrombectomy of intermediate- or high-risk pulmonary embolism (PE) and factors associated with effectiveness., Materials and Methods: A retrospective review of 257 patients with intermediate- or high-risk PE who underwent mechanical thrombectomy using the Flowtriever system (Inari Medical, Irvine, California) between July 2019 and November 2021 was conducted. Data were analyzed using the linear regression and Kaplan-Meier methods with a Type 1 error set at 0.05., Results: Patients' mean age was 62 years, and 51% were male. PE risk was classified as high, intermediate-high, and intermediate-low in 37 (14%), 201 (78%), and 18 (7%) of the patients, respectively. Procedural technical success was 100%. The mean pulmonary artery pressure (MPAP) decreased from a mean of 32 mmHg (SD ± 9) before to 24 mmHg (SD ± 9) after thrombectomy (mean decrease, 8 mmHg [SD ± 6]; P < .0001). Immediate complications occurred in 2% of the patients. Postprocedural 30-day and all-time PE-attributable mortality in a mean of 1.3-year follow-up was 2% and 6%, respectively. In multivariate analysis, the presence of lower extremity DVT at presentation (β ± SE, -7.60 ± 3.22; P = .019) and a higher prethrombectomy MPAP (β ± SE, -0.19 ± 0.04; P < .001) were associated with lower degrees of decrease in MPAP in the intermediate-high-risk PE group. Among 14 patients with postthrombectomy PE-attributable mortality, 13 had postthrombectomy MPAPs of >20 mmHg., Conclusions: Large-bore aspiration thrombectomy is a safe and effective treatment for reducing PAP in patients with intermediate- or high-risk PE. Postthrombectomy MPAPs of >20 mmHg might indicate postthrombectomy PE-attributable mortality in high-risk patients., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background:  Calvarial defects are severe injuries that can result from a wide array of etiologies. Reconstructive modalities for these clinical challenges include autologous bone grafting or cranioplasty with biocompatible alloplastic materials. Unfortunately, both approaches are limited by factors such as donor site morbidly, tissue availability, and infection. Calvarial transplantation offers the potential opportunity to address skull defect form and functional needs by replacing "like-with-like" tissue but remains poorly investigated., Methods:  Three adult human cadavers underwent circumferential dissection and osteotomy to raise the entire scalp and skull en-bloc. The vascular pedicles of the scalp were assessed for patency and perfused with color dye, iohexol contrast agent for computed tomography (CT) angiography, and indocyanine green for SPY-Portable Handheld Imager assessment of perfusion to the skull., Results:  Gross changes were appreciated to the scalp with color dye, but not to bone. CT angiography and SPY-Portable Handheld Imager assessment confirmed perfusion from the vessels of the scalp to the skull beyond midline., Conclusion:  Calvarial transplantation may be a technically viable option for skull defect reconstruction that requires vascularized composite tissues (bone and soft tissue) for optimal outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Acute proximal superior mesenteric artery (SMA) occlusion is highly lethal, and adjuncts are needed to mitigate ischemic injury until definitive therapy. We hypothesized that raising mean arterial pressure (MAP) >90 mmHg with norepinephrine may delay irreversible bowel ischemia by increasing gastroduodenal artery (GDA) flow despite possible pressor-induced vasospasm., Methods: 12 anesthetized swine underwent laparotomy, GDA flow probe placement, and proximal SMA exposure and clamping. Animals were randomized between conventional therapy (CT) versus targeted MAP >90 mmHg (MAP push; MP) where norepinephrine was titrated after 45 min of SMA occlusion. Animals were followed until bowel death or 4 h. Kaplan-Meier bowel survival, mean normalized GDA flow, and histology were compared., Results: 12 swine (mean 57.8 ± 7.6 kgs) were included, six per group. Baseline weight, HR, MAP and GDA flows were not different. Within 5 min following SMA clamping, all 12 animals had an increase in MAP without other intervention from 81.7 to 105.5 mmHg (29.1%, P < 0.01) with a concomitant 74.9% increase in GDA flow as compared to baseline (P < 0.01). Beyond 45 min postclamp, MAP was greater in the MP group as intended, as were GDA flows. Median time to irreversibly ischemic bowel was 31% longer for MAP push animals (CT: 178 versus MP: 233 min, P = 0.006), Hazard Ratio of CT 8.85 (95% CI: 1.86-42.06); 3/6 MP animals versus 0/6 CT animals with bowel survived to predetermined end point., Conclusions: In this swine model of acute complete proximal SMA occlusion, increasing MAP >90 mmHg with norepinephrine was associated with an increase in macrovascular blood flow through the GDA and bowel survival. Norepinephrine was not associated with worse bowel survival and a MAP push may increase the time window where ischemic bowel can be salvaged., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Patients with chronic limb-threatening ischemia (CLTI) and no great saphenous vein to use as a conduit for arterial bypass have a high risk for amputation despite advances in medical and endovascular therapies. This report presents findings from a U.S. Food and Drug Administration (FDA) supported study of the Human Acellular Vessel (HAV) (Humacyte Inc.) used as a conduit for arterial bypass in patients with CLTI and inadequate or absent autologous conduit., Methods: The HAV is a 6-mm, 40-cm vessel created from human vascular smooth muscle cells seeded onto a polyglycolic acid scaffold pulsed in a bioreactor for 8 weeks as cells proliferate and the scaffold dissolves. The resultant vessel is decellularized, creating a nonimmunogenic conduit composed of collagen, elastin, and extracellular matrix. The FDA issued an Investigational New Drug for an intermediate-sized, single-center study of the HAV under the agency's Expanded Access Program in patients with advanced CLTI and inadequate or absent autologous conduit. Technical results and clinical outcomes were analyzed and reported., Results: Between March 2021 and July 2023, 29 patients (20 males; mean age, 71 ± 11 years) underwent limb salvage operation using the HAV as a bypass conduit. Most patients had advanced CLTI (Rutherford class 5/6 in 72%; wound, ischemia, and foot infection stage 3/4 in 83%), and 97% had previously failed revascularization(s) of the extremity. Two HAVs were sewn together to attain the needed bypass length in 24 patients (83%). Bypasses were to tibial arteries in 23 patients (79%) and to the popliteal artery in 6 (21%). Technical success was 100%, and the 30-day mortality rate was 7% (2 patients). With 100% follow-up (median, 9.3 months), the limb salvage rate was 86% (25/29 patients). There were 16 reinterventions to restore secondary patency, of which 15 (94%) were successful. Primary and secondary patency of the HAV at 9 months were 59% and 71%, respectively., Conclusions: The HAV has demonstrated short- to intermediate-term safety and efficacy as an arterial bypass conduit in a complex cohort of patients with limb-threatening ischemia and no autologous options. This experience using the FDA's Expanded Access Program provides real-world data to inform regulatory deliberations and future trials of the HAV, including the study of the vessel as a first-line bypass conduit in less severe cases of chronic limb ischemia., Competing Interests: Disclosures T.E.R. has served in a clinical advisory role for Humacyte, Inc., the funds for which are paid to the Mayo Clinic; Humacyte provides funding to support the performance of this IND study to Mayo Clinic. The other authors have no competing interests., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Pressure-volume (PV) loop analysis is a sophisticated invasive approach to quantifying load-dependent and independent measures of cardiac function. Biventricular (BV) PV loops allow left and right ventricular function to be quantified simultaneously and independently, which is important for conditions and certain physiologic states, such as ventricular decoupling or acute physiologic changes. BV PV loops can be performed in an entirely endovascular, percutaneous, and closed-chest setting. This technique is helpful in a survival animal model, as a percutaneous monitoring system during endovascular device experiments, or in cases where chest wall compliance is being tested or may be a confounder. In this article, we describe the end-to-end implementation of a completely endovascular, totally percutaneous, and closed-chest large animal model to obtain contemporaneous BV PV loops in 40 to 70 kg swine. We describe the associated surgical and technical challenges and our solutions to obtaining endovascular BV PV loops, closed-chest cardiac output, and stroke volume (including validation of the correction factor necessary for thermodilution), as well as how to perform endovascular inferior vena cava occlusion in this swine model. We also include techniques for data acquisition and analysis that are required for this method., Competing Interests: None., (© 2024 by the Society for Vascular Surgery. Published by Elsevier Inc.)

Across living organisms, division is necessary for cell survival and passing heritable information to the next generation. For this reason, cell division is highly conserved among eukaryotes and prokaryotes. Among the most highly conserved cell division proteins in eukaryotes are tubulin and actin. Tubulin polymerizes to form microtubules, which assemble into cytoskeletal structures in eukaryotes, such as the mitotic spindle that pulls chromatids apart during mitosis. Actin polymerizes to form a morphological framework for the eukaryotic cell, or cytoskeleton, that undergoes reorganization during mitosis. In prokaryotes, two of the most highly conserved cell division proteins are the tubulin homolog FtsZ and the actin homolog FtsA. In this chapter, the functions of the essential bacterial cell division proteins FtsZ and FtsA and their roles in assembly of the divisome at the septum, the site of cell division, will be discussed. In most bacteria, including Escherichia coli, the tubulin homolog FtsZ polymerizes at midcell, and this step is crucial for recruitment of many other proteins to the division site. For this reason, both FtsZ abundance and polymerization are tightly regulated by a variety of proteins. The actin-like FtsA protein polymerizes and tethers FtsZ polymers to the cytoplasmic membrane. Additionally, FtsA interacts with later stage cell division proteins, which are essential for division and for building the new cell wall at the septum. Recent studies have investigated how actin-like polymerization of FtsA on the lipid membrane may impact division, and we will discuss this and other ways that division in bacteria is regulated through FtsZ and FtsA., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The surgical management of prostate cancer through radical prostatectomy has the potential to impact patients' sexual function, including erectile dysfunction and Peyronie's disease (PD). Historical data suggests the incidence of PD in post-prostatectomy patients is higher than in the general population at 15.9%. Our study objective was to measure the rate of the development of PD among patients that receive penile rehabilitation (PR) regimen prior to and immediately after radical prostatectomy. In this study, we retrospectively reviewed the charts of 581 patients who were diagnosed with prostate cancer, treated with radical prostatectomy, and engaged in a PR program. Patients with the diagnosis of PD prior to prostatectomy were excluded from this study. The PR program consists of daily tadalafil, L-citrulline, and weekly vacuum erectile device with the option of intracavernosal injections if patients fail to respond to the regular regimen. We found the incidence of PD to be 2.9%, suggesting that PR regimens programs may be associated with a reduced incidence of PD in post-prostatectomy patients. Ten (out of 17) patients were diagnosed with PD after 2 years of follow up. The return of erections was not statistically different among patients who developed PD and the rest of the patients. Prospective, multi-institutional trials will be required to elucidate whether PR can prevent the development of PD in this patient population., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-281/coif). J.N.M. serves as a consultant to Boston Scientific Corporation, Endo Pharmaceuticals, and Halozyme Therapeutics and receives compensation. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Importance: Bleeding is the most common cause of preventable death after trauma., Objective: To determine the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) when used in the emergency department along with standard care vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage., Design, Setting, and Participants: Pragmatic, bayesian, randomized clinical trial conducted at 16 major trauma centers in the UK. Patients aged 16 years or older with exsanguinating hemorrhage were enrolled between October 2017 and March 2022 and followed up for 90 days., Intervention: Patients were randomly assigned (1:1 allocation) to a strategy that included REBOA and standard care (n = 46) or standard care alone (n = 44)., Main Outcomes and Measures: The primary outcome was all-cause mortality at 90 days. Ten secondary outcomes included mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours; the need for definitive hemorrhage control procedures; time to commencement of definitive hemorrhage control procedures; complications; length of stay; blood product use; and cause of death., Results: Of the 90 patients (median age, 41 years [IQR, 31-59 years]; 62 [69%] were male; and the median Injury Severity Score was 41 [IQR, 29-50]) randomized, 89 were included in the primary outcome analysis because 1 patient in the standard care alone group declined to provide consent for continued participation and data collection 4 days after enrollment. At 90 days, 25 of 46 patients (54%) had experienced all-cause mortality in the REBOA and standard care group vs 18 of 43 patients (42%) in the standard care alone group (odds ratio [OR], 1.58 [95% credible interval, 0.72-3.52]; posterior probability of an OR >1 [indicating increased odds of death with REBOA], 86.9%). Among the 10 secondary outcomes, the ORs for mortality and the posterior probabilities of an OR greater than 1 for 6-month, in-hospital, and 24-, 6-, or 3-hour mortality were all increased in the REBOA and standard care group, and the ORs were increased with earlier mortality end points. There were more deaths due to bleeding in the REBOA and standard care group (8 of 25 patients [32%]) than in standard care alone group (3 of 18 patients [17%]), and most occurred within 24 hours., Conclusions and Relevance: In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone., Trial Registration: isrctn.org Identifier: ISRCTN16184981.

Background: Thoracic aortic stent grafts are thought to decrease aortic compliance and may contribute to hypertension and heart failure after thoracic endovascular aortic repair (TEVAR). Left ventricular (LV) biomechanics immediately after TEVAR, however, have not been quantified. Pressure-volume (PV) loop analysis provides gold-standard LV functional information. The aim of this study is to use an LV PV loop catheter and analysis to characterize the LV biomechanics before and acutely after TEVAR., Methods: Anesthetized Yorkshire swine (N = 6) were percutaneously instrumented with an LV PV loop catheter. A 20 mm × 10 cm stent graft was deployed distal to the left subclavian via the femoral artery under fluoroscopy. Cardiac biomechanics were assessed before and after TEVAR. As a sensitivity analysis, inferior vena cava occlusion with PV loop assessment was performed pre and post-TEVAR in 1 animal to obtain preload and afterload-independent end-systolic and end-diastolic PV relationships (ESPVR and EDPVR)., Results: All animals underwent successful instrumentation and TEVAR. Post-TEVAR, all 6 animals had higher mean LV ESP (106 vs. 118 mm Hg, P = 0.04), with no change in the EDPVR. inferior vena cava occlusion also moved the ESPVR curve upward and leftward, indicating increased LV work per unit time. There was no augmentation of EDPVR following TEVAR (P > 0.05). Postmortem exams in all animals revealed appropriate stent placement and no technical complications., Conclusions: TEVAR was associated with an acute increase in LV end-systolic pressure and shift in the ESPVR, indicating increased ventricular work. This data provides potential mechanistic insights into the development of post-TEVAR hypertension and heart failure. Future stent graft innovation should focus on minimizing the changes in cardiac physiology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Approximately 3% of pregnancies are diagnosed with a fetal anomaly, of which a proportion is fatal or life-limiting. The introduction of legislation for termination of pregnancy in Ireland in 2019 for conditions "likely to lead to the death of the fetus" made termination of pregnancy for "fatal fetal anomaly" an option for pregnant women in Ireland., Objective: This study examined all cases of termination of pregnancy performed for major fetal anomaly over the first 3 years of service implementation, including cases that did not meet the legal criteria, resulting in women traveling outside Ireland for abortion care., Study Design: A retrospective service evaluation of tertiary fetal medicine clinics in 2 tertiary maternity hospitals between 2019 and 2021 was undertaken. We compared pregnancies of patients diagnosed with fatal fetal anomaly who underwent termination of pregnancy in Ireland with those of patients who did not meet the legal criteria and hence traveled outside Ireland for termination of pregnancy., Results: Overall, 139 pregnancies met the inclusion criteria; 83 (59.7%) patients had termination of pregnancy in the tertiary maternity hospital (local), and 56 (40.3%) traveled abroad, mainly to the United Kingdom. Demographic characteristics were similar between the 2 groups, as was gestation at diagnosis and delivery. All cases where termination of pregnancy was local were discussed at fetal medicine multidisciplinary meetings, as opposed to 34% of cases of patients who ultimately traveled outside Ireland for termination of pregnancy. The most common indication (25/83; 30.1%) for local termination of pregnancy was trisomy 18, followed by anencephaly. Traveling to obtain abortion care was mainly due to diagnosis of trisomy 21 (30/56; 53.6%), followed by other multiple structural anomalies/syndromes deemed locally as not meeting the legal criteria., Conclusion: Legislation for termination of pregnancy for fetal anomaly, restricted to fatal diagnoses, is difficult to implement, requires significant multidisciplinary input, and can lead to limited services for pregnancies diagnosed with major fetal anomalies. Our findings emphasize the impact of legislative barriers to abortion care for fetal anomaly and the need for policies and services that support women's access to termination of pregnancy for fetal anomaly., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prehospital resuscitation is a dynamic field now being energized by new technologies and a shift in thinking regarding intravascular resuscitation. Growing evidence discourages use of intravenous (IV) crystalloid and colloid solutions in trauma, whereas blood products, particularly whole blood, are becoming preferred. Although randomized clinical trials validating definitive resuscitative protocols are still lacking, most preclinical and clinical indicators support this approach. In addition, emerging technologies such as external and endovascular hemorrhage control devices and extracorporeal perfusion are now being used routinely, even in the prehospital setting in many countries, generating new lines of emerging investigations for trauma specialists., (Copyright © 2023 Elsevier Inc. All rights reserved.)