Distal Events Research Articles

Intraoperative Invasive Coronary Angiography after Coronary Artery Bypass Grafting.

The aim of this study was to prospectively evaluate the feasibility and safety of intraoperative invasive coronary angiography (ICA) following coronary artery bypass grafting using a mobile angiography C-arm. Between August 2020 and December 2021, 18 patients were enrolled for intraoperative ICA following coronary artery bypass grafting. After skin closure, ICA was performed including angiography of all established bypass grafts via a mobile angiography system by an interventional cardiologist. Data on graft patency, stenosis, and kinking were assessed. Grafts were rated on an ordinal scale ranging from very poor (1) to excellent (5). Furthermore, the impact of ICA compared with flow measurement was assessed using the ordinal Likert scale ranging from (I) worse to (V) much better. The ICA was considered better (V) compared with transient flow measurement in 38 (93%) and comparable (III) in 3 (7%) distal anastomoses. ICA impacted clinical or surgical decision-making in three patients (17%). In one patient, dual antiplatelet therapy for 6 months was initiated and rethoracotomy was needed in two (11%) patients with bypass graft revision and additional bypass grafting for graft occlusion. There were no cerebral and distal embolic events or access vessel complications observed and no postoperative acute kidney injury occurred. Intraoperative angiography after coronary bypass grafting is safe. Using a mobile angiographic device, graft patency, and function assessment was superior to transit time flow measurement leading to further consequences in a relevant number of patients. Therefore, it has the potential to reduce postoperative myocardial injury and improve survival.

Distal Events Following Emergent Operation for DeBakey Type I Aortic Dissection.

The goal of this study is to examine early and Mid-term results after surgical treatment of acute DeBakey type I aortic dissection (AIAD) and the effect of the range of aortic arch replacement on overall survival and prevention of distal aortic events. Between March 2002 and July 2020, a total of 374 AIAD aortic repairs were reviewed. One hundred fifty-four (41.2%) patients had total arch replacement (TAR), while 220 (58.8%) had hemi- or partial arch replacement (PAR). Operative mortality did not show a significant difference (7.7% in PAR, 13.0 % in TAR, p = 0.096). Survival at 5 years showed no difference (77.8% in TAR, 72.6% in PAR, p = 0.14). Freedom from reoperations and re-interventions, as well as composite aortic events in the distal aorta, were comparable across groups (p=0.21, 0.84, and 0.91, respectively). The inverse provability of treatment weighting-adjusted model displayed higher 5-year freedom from reoperations and aortic events in the TAR group (p = 0.029 and 0.054, respectively) Conclusion: The extent of Arch replacement is determined based on the patient's background, making it difficult to compare the superiority of both surgical methods. However, TAR for appropriately selected patients may provide the benefit of avoiding aortic events in the long-term.

Methylation Mesa define functional regulatory elements for targeted gene activation.

DNA methylation and mRNA expression correlations are often presented with inconsistent evidence supporting causal regulation. We hypothesized that causal regulatory methylation elements would exhibit heightened demethylation sensitivity. To investigate, we analyzed 20 whole genomic bisulfite sequenced samples before and after demethylation and identified narrow width (45 294 bp) elements within a short plateau, termed Methylation Mesa (MM). The Mesa signature was conserved across species and was independent of CpG islands. Mesa also demonstrate high concordance with primed and active histone marks. To assess causality, we developed CRISPR DiR, a highly precise targeted demethylation technology. Targeted demethylation of a Mesa triggers locus and distal chromatin rewiring events that initiate mRNA expression significantly greater than promoter CpG island targeting. Thus, Mesa are self-sustaining epigenetic regulatory elements that maintain long-term gene activation through focused demethylation only within the Mesa core, resulting in subsequent histone modifications and chromatin rewiring events that interact with distal elements also marked as Mesas.

Pressure Monitoring of Disposal Reservoirs in North‐Central Oklahoma: Implications for Seismicity and Geostorage

AbstractDisposal of industrial wastewater and activities such as underground sequestration depend upon pressure conditions within deep geologic reservoirs. Sometimes, injection and storage are associated with induced seismicity, suggested to result from reservoir compartmentalization, leakage into faults, or other mechanisms in the subsurface. To understand subsurface pressure conditions within a major regional disposal reservoir, the Arbuckle Group of Oklahoma, we monitored the water levels in 15 inactive injection wells. The wells were monitored at 30‐s intervals, with eight wells monitored since September 2016, and an additional seven from July 2017. All the wells were monitored until early March 2020. Since 2016, hydraulic head decreased in 13 of the 15 wells, proportional to near‐borehole fluid pressure even considering decreasing regional injection volumes during this period. The well pressures respond to three types of perturbations: (i) gravitational fluctuations (a.k.a. solid‐earth tides) (ii) distal and proximal earthquakes, and (iii) injections into nearby wells. Parameterization of tidal responses illustrates that the near wellbore environments have negative fluid flux (i.e., are leaking). Earthquakes cause differing pressure responses from well to well, with some highly sensitive to proximal events, some to distal events, and some apparently insensitive. Injections have variable impacts in some cases masking tidal and earthquake pressure signals. Collectively, there appears to be a threshold injection rate above which well pressure becomes less sensitive to the volume of injections within 15 km. Multi‐scale geological structure and temporal permeability changes are likely controlling the pressure field, indicating leakage of fluids across the system.

In vitro and in vivo evaluation of a novel wired transmission pH-combined photographic catheter for ambulatory gastroesophageal reflux monitoring (with videos).

Twenty-four-hour pH-impedance monitoring is an important diagnostic approach for gastroesophageal reflux disease (GERD). Reflux monitoring results cannot be synchronized with ambulatory motility imaging of the esophageal sphincter. We have designed a novel wired transmission pH-combined photographic catheter (WT-CPC) for the synchronous acquisition of reflux image and pH. Different patterns of reflux events were simulated to perform in a porcine gastroesophageal reflux model in vitro. The live porcine model of gastroesophageal reflux was established in three Bama pigs. Monitoring was conducted with the WT-CPC and pH-impedance catheter simultaneously. Measurements included the number and proportion of reflux events, as well as acid exposure time (AET). The detection rates of WT-CPC for distal and horizontal acid reflux events were significantly higher compared to those of pH-impedance catheters (100% vs. 14.29%, 100% vs. 57.14%, P < 0.05). There was no significant difference between the two methods in proximal acid reflux events (P = 0.217). Regarding mixed reflux events, WT-CPC exhibited higher detection rates for distal events than pH-impedance catheter (100% vs. 42.86%, P < 0.05). However, there was no significant difference between the two methods for proximal reflux events (P > 0.05). Both methods showed similar results for horizontal reflux events. A porcine gastroesophageal reflux model was successfully established and utilized for reflux monitoring. A total of 28 episodes of reflux were detected within 6.5min. The detection rate achieved by WT-CPC for reflux events was significantly higher than that obtained by pH-impedance (100% vs. 78.57%, P = 0.023). The WT-CPC has demonstrated reflux monitoring capabilities in an isolated reflux organ model. It also showed good operability and performance in the porcine model. The WT-CPC holds promising potential to provide valuable diagnostic evidence for GERD.

Risk factors for proximal and distal aortic events after type A acute aortic dissection.

Type A acute aortic dissection (TAAAD) is a life-threatening condition often requiring emergency surgery, with approximately 30% of patients needing reoperation. This study aimed to identify predictors of long-term aortic events from early postoperative computed tomography (CT) examinations. A total of 336 cases underwent TAAAD surgery at two institutions between 2002 and 2018. Of these, 302 patients received CT examinations immediately after initial TAAAD surgery. Predictors of aortic events were evaluated from these early postoperative CT exams. Aortic events were defined as any events involving aortic-related death, open surgery, reoperation, endovascular stenting, or thoracic aorta diameter enlargement to ≥ 55mm. Excluding 34 in-hospital deaths (10.1%; 34/336), the 1-, 5-, and 10-year actuarial survival rates after primary TAAAD surgery were 98.2%, 88.6%, and 81.7%, respectively. Over a mean follow-up period of 7.4 ± 5.1years, 67 aortic events (proximal: 19, distal: 45, both: 3) were observed. Freedom from proximal aortic events was 98.6%, 93.9%, and 85.2% at 1, 5, and 10years, respectively. Proximal anastomosis new entry was identified as a significant risk factor for aortic events, with a 92% vs. 42% incidence at 10years (p < 0.001). Freedom from distal aortic events was 99.6%, 84.5%, and 67.2% at 1, 5, and 10years, respectively. A false/true area ratio greater than 1 and distal anastomosis new entry were significant risk factors for aortic events (low-risk group: 83.3% vs. high-risk group: 42.3% at 10years, p < 0.001). Detailed analysis of early postoperative CT scans following primary TAAAD surgery may help identify predictors of subsequent aortic events, potentially improving long-term patient management and outcomes.

Updating local and global probabilities during maze navigation.

We examined the human ability to encode and utilize local and global uncertainty information during a navigational task. Participants were tasked with navigating a virtual maze in which wall locations were obscured. Local cues and a global direction provided guidance. The validities of the global and local cues were separately and jointly varied across the two experiments. The results demonstrated that participants effectively utilized both global and local cues for navigation with a stronger reliance on local cues and a heightened precision in estimating their reliability. Our findings suggest that the representation of uncertainty for proximate events can be dissociated from that of distal events. Furthermore, humans effectively integrate both forms of information when making decisions during navigation tasks. This research advances our understanding of uncertainty processing and its implications for decision making in complex environments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Impact of valve-sparing aortic root replacement on aortic fluid dynamics and biomechanics in patients with syndromic heritable thoracic aortic disease

Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV). Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo). All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm2/s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR. In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk.

Impact of Residual Entry Tears in the Descending Aorta After Type A Dissection

BackgroundAggressive resection/exclusion of the primary entry in the descending aorta remains controversial in older patients with acute type A aortic dissection (ATAAD). We investigated the effect of residual primary entry in the descending aorta in younger and older groups. MethodsPatients with ATAAD who underwent emergency operation (n = 1103) were divided into younger (<70 years; n = 681) and older (≥70 years; n = 422) cohorts. Each cohort was further divided into groups with or without residual primary entry in the descending aorta. After propensity score matching, 179 and 71 matched pairs were obtained in the younger and older cohorts, respectively. Surgical outcomes were compared between the residual and nonresidual groups in each age cohort. ResultsIn the younger cohort, the cumulative incidence rate of distal aortic events was significantly higher in the residual than in the nonresidual group at 10 years (35% [95% CI, 27%-44%] vs 22% [95% CI, 15%-31%], P = .001). However, in the older group, residual or nonresidual primary entry did not affect the rates at 10 years (11% [95% CI, 5%-20%] vs 9% [95% CI, 4%-17%], P = .75). Multivariate analysis identified age <70 years (hazard ratio, 2.188; 95% CI, 1.493-3.205; P < .001) and residual primary entry at the descending aorta (hazard ratio, 2.142; 95% CI, 1.559-2.943; P < .001) as significant predictors for distal aortic events. ConclusionsAggressive resection/exclusion of the primary entry in the descending aorta should be considered for patients aged <70 years to avoid distal aortic events; however, it might not always be appropriate for the older patients ≥70 years.

Utilizing a long sheath to minimize atheroma manipulation (minimal manipulation approach) during Zone 1 and 2 thoracic endovascular aortic repair with a shaggy aorta.

We have adopted a simple and reproducible approach, "minimal manipulation approach," since January 2021 in five patients to minimize the risk of thromboembolic events during Zone 1 and 2 thoracic endovascular aortic repair (TEVARs) with shaggy aorta. The approach consists of two parts: ① Use of a 65-cm-long sheath (dry seal) to deliver the endografts without touching the protruding atheroma. Covering the atheroma with the first endograft delivered at Zone 3 to the mid-descending aorta (paving the aorta), and second endograft insertion and deployment through the paved aorta with first endograft. ② Protection of the left subclavian artery using balloon catheter during TEVAR. No in-hospital mortality was recorded, and none of the patients had stroke, spinal cord ischemia, or distal embolic events.

(181) Prior Radiation Therapy is Associated with Increased Risk of Intra-Operative Complications in Patients Undergoing Primary Inflatable Penile Prosthesis Placement: Results from a Large Multi-Institutional Collaborative

Abstract Introduction Radiation therapy (RT) can predispose the onset of corporal fibrosis and microvasculopathy. The impact of RT on intra-operative complications is not well described in the literature. Objective In this study, we assess intra-operative and post-operative outcomes among patients with or without prior history of RT following primary Inflatable Penile Prosthesis (IPP) implantation. Methods We performed a multicenter, retrospective analysis of men undergoing primary IPP placement between January 2015 and December 2022. A total of 3530 patients were identified, of which 3319 had no prior history of RT and 211 patients had history of RT. After 1:1 propensity score matching for all confounding variables, 211 patients with a history of RT were compared to 211 nonradiated patients for intra-operative and post-operative outcomes. Chi-square and Mann-Whitney tests were used for statistical analysis for categorial and continuous variables respectively. For multivariable analysis, we used a forward stepwise model and included significant variables found on pre-operative characteristics of patients. Kaplan-Meier time to event analysis were compared with Mantel-Cox log-rank test. Results Patients with history of RT encountered more intra-operative complications (4.3% vs 0.9%, p=0.032); specifically, these men experienced more distal crossover events (1.9% vs 0, p=0.044). On multivariable analysis, history of prior RT (OR 5.29, 95% CI 1.07-26.3, p=0.041) and diabetes mellitus (OR 10.5, 95% CI 2.58-43.5, p=0.01) were associated with increased risk of intra-operative complications. History of obesity (OR 0.11, 95% CI 0.01-0.91, p=0.040) reduced risk of intra-operative complications. There was no significant difference in early or late post-operative non-infectious complications between both groups and there was also no significant difference in risk of post-operative complications within 24 months on Kaplan Meier analysis (log rank p=0.9). Conclusions In this large multi-institutional cohort, history of RT is an independent predictor of intra-operative complications but not post-operative complications during primary IPP placement. These findings may help inform patient-specific counseling while guiding surgical planning to prevent untoward morbidity following surgery. Disclosure No.

The Efficacy of Second-Stage Endovascular Repair Strategy for Acute Type A Aortic Dissection.

To evaluate the usefulness of a hybrid treatment strategy for acute type A aortic dissection (AAAD). We retrospectively evaluated the outcomes of 39 partial arch replacements (PAR; 26 male/13 female, mean age=67.9 years) in 62 patients with AAAD operated at our hospital from January 2019 to January 2023. The technique included PAR with graft-designed landing length and translocated the brachiocephalic artery inflow site during the initial surgery to minimize the invasiveness of the surgery. Thereafter, second-stage thoracic endovascular aortic repair (second TEVAR) for distal aortic events in the chronic phase was performed. There was 1 case of 30-day mortality (2.6%) and 2 cases of postprocedural cerebral infarction (5.1%). The cumulative survival rates were 97.4%/1 year and 97.4%/3 years. The cumulative freedom from aorta-related second-stage procedure for the distal aortic event after initial PAR, which was performed in 13 patients (33.3%), was 63.9%/1 year and 59.7%/3 years. All patients requiring re-intervention after initial PAR underwent a second TEVAR with a 100% success rate and no postoperative complications. Initial PAR for AAAD in anticipation of the second TEVAR is a valuable strategy for enabling minimally invasive additional treatment of aorta-related re-intervention for distal aortic events in the chronic phase. This study provides detailed information on the hybrid aortic repair strategy of the initial open partial arch repair and second staged endovascular repair for the acute type A aortic dissection. Based on this study, distal aortic re-intervention after initial open partial arch repair was necessary only in about 30% of cases, and no cases of SCI were observed in the initial treatment or in the second-stage endovascular repair and no cases of distal SINE were observed after the second staged endovascular repair. Overall, the results suggest that limiting the initial open partial arch repair can achieve good perioperative and early outcomes of initial surgery, and that second staged endovascular re-intervention for distal aortic events can be performed reliably, safely, and with minimal invasiveness.

Efficacy and Safety of Atherectomy Combined With Balloon Angioplasty vs Balloon Angioplasty Alone in Patients With Femoro-Popliteal Lesions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Balloon angioplasty (BA), including drug-coated balloons (DCBs) and percutaneous transluminal angioplasty (PTA), has traditionally been used to treat femoral-popliteal lesions. However, in recent years, atherectomy (ATH) has been proposed as a complementary approach. To assess the effectiveness of ATH compared with BA alone in patients with femoral-popliteal artery lesions, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We included RCTs that focused on patients with femoral-popliteal artery lesions and reported data on the use of ATH and BA therapy. Two reviewers conducted a literature search, refined the data, and assessed the risk of bias. We included a total of 6 RCTs involving 399 patients with femoral-popliteal artery lesions. The use of ATH in combination with BA appeared to improve the patency rate at 12 months (odds ratio [OR]=2.04, 95% confidence interval [CI]=1.14-3.62). In addition, ATH with BA was associated with lower major amputation rates (MD=2.01, 95% CI=0.06-0.77, p=0.02) and a decreased likelihood of bailout stenting (OR=0.07, 95% CI=0.02-0.25, p=0.001). However, there were no statistically significant differences between the groups in terms of target lesion revascularization (TLR) at 12 months, major adverse cardiovascular events (MACEs), and distal embolization events. In addition, we performed subgroup analysis for different ATH devices and BA types. Based on this meta-analysis, it can be concluded that the use of ATH in combination with BA is a safe and effective method for treating femoral-popliteal artery lesions. In addition, the patency rate at 1 year is superior to treatment with BA alone. Atherectomy also reduces the likelihood of amputation and bailout stenting. Clinicians should consider these findings when designing future RCTs and developing clinical practice guidelines. This meta-analysis summarises a number of existing studies to advance understanding of the atherectomy devices and to reveal its potential. This new technique, when compared with drug coated balloon, shows the possibility of obtaining better clinical outcomes in femoro-popliteal lesions than drug-coated balloon alone, such as higher 12-month primary patency rates as shown in some studies. Currently, it is important to consider the appropriate technology applicable for individualised treatment. atherectomy devices seem to provide clinicians with additional options in clinical practice and to benefit patients in the future. This requires more high quality studies to explore the role and benefits of atherectomy devices in femoro-popliteal lesions.

Genome-Wide Methylation Sensitive Elements Demarcate Targetable Regulatory Elements for Controllable Gene Activation

There are multiple published studies correlating DNA methylation with gene expression, but to date, most are associative in nature without precise localization of causal elements. Multiple CpG destinations have been described with inconsistent evidence supporting their causal association with transcription. This has hampered adoption and use of methylation signatures as biomarkers or for targeted therapies. This has had consequent effects in hindering mechanistic understanding in how global demethylation agents lead to responses in some patients, but not others. With this state of the literature in mind, we set out to better understand and locate causal methylation regulatory loci genome-wide. We hypothesized that causal methylation regulatory elements possess heightened sensitivity to regulatory signals such as “demethylate”; signals that can be introduced using hypo-methylating agents (HMAs) typically used in treatment of Myelodysplastic syndromes and Acute Myeloid Leukemia. We thus analyzed 19 whole-genomic bisulfite sequenced sample pairs (pre/post-demethylation in patients, cell lines, and in murine in vivo samples) and identified previously undescribed DNA methylation sensitive elements throughout the genome, which we call Methylation Mesas (MMs) based on the profile shape observed in naïve and post-HMA treated sample. These narrow-width MMs range typically between 45-300bp wide and are present throughout the genome with greater abundance in noncoding and intragenic regions than in promoter-CpG islands. We also demonstrate that MM show an up to 90% concordant overlap with primed and active histone marks by means of a compiled histone mark footprint map using 60 human and 59 murine ENCODE datasets for each respective species, suggesting a functional role for MMs as regulatory elements with transcriptional potential. While HMA's enable identification of MM's genome-wide, their mode of action renders them unsuitable for ascertaining the direct transcriptional potential of any singular locus. Therefore, in order to ascertain the causal role of MM for transcriptional regulation, we developed a fine-resolution targeted demethylation technology(CRISPR-DiR), leveraging our previously published findings that DNA methyltransferase I (DNMT1) can be blocked by DNMT1-interacting RNAs (DiR). Compared with other targeted demethylation technologies with wider effect windows (eg. CRISPR-TET1), CRISPR-DiR shows superior locus specificity thus serving as an ideal tool to identify causal regulatory elements. Using tumor suppressor p16 as an example, we elucidated that demethylation of a single MM in the first exon is sufficient to trigger locus and distal chromatin rewiring events that natively initiate expression to a significantly greater extent than promoter CpG island targeting alone. Similar CRISPR-DiR activation is also observed in four additional, natively silenced tumor suppressor genes, one of which has no annotated CpG island. In summary, we have identified a previously undescribed narrow-width DNA methylation sensitive regulatory element, consistent across all epigenomes investigated, located largely independent of the promoter CpG island dogma, yet initiating gene transcription more potently. Identification of said elements paves the way for future studies to better understand the mechanisms of how mutations in DNA methyltransferases lead to disease, how global hypomethylating agents can lead to a response in diseases such as MDS and AML but can also activate oncogenes, and finally development of targeted therapies.

Esophageal pH-monitoring in nonbrachycephalic dogs; a reference.

To establish parameters that describe acidic gastroesophageal reflux (GER) events in nonbrachycephalic, hospitalized dogs without gastrointestinal disease following short total intravenous anesthesia, to establish upper reference limits for parameters that describe GER. Clinical prospective study. Healthy, client-owned dogs presenting for elective orthopedic surgery. Dogs were sedated with IM methadone (0.2 mg/kg) and medetomidine (5 ug/kg), followed by alfaxalone total intravenous anesthesia. The Digitrapper esophageal dual pH monitoring probe was placed transnasally into the esophagus. Dogs were unsedated during the subsequent recording period. A GER event was defined as esophageal pH less than 4.0. Parameters that described GER were: (1) number of GER events per hour, and (2) cumulative esophageal acid exposure (percentage of recording duration) at each sensor. Upper reference limits were calculated for each parameter. Thirty-five dogs were included (median age 7 years, range 1-12). The median recording duration was 21.1 h (range 13.6-29.3). Productive regurgitation was not noted in any dog. The median number of distal and proximal GER events per hour was 0.3 (range 0-4.3) and 0 (range 0-1), respectively. The median cumulative distal and proximal esophageal acid exposure was 0.2% (range 0.3-9%) and 0% (range 0%-1%), respectively. Upper reference limits for distal and proximal GER per hour was 2.4 and 0.4, respectively, and, for cumulative distal and proximal esophageal acid exposure, 2.3% and 0%, respectively. Dogs undergoing esophageal pH monitoring in a similar hospital setting with parameters above these upper reference limits have excessive GER.

Early clinical outcomes and molecular smooth muscle cell phenotyping using a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome

ObjectivesPatients with Loeys-Dietz syndrome demonstrate a heightened risk of distal thoracic aortic events after valve-sparing aortic root replacement. This study assesses the clinical risks and hemodynamic consequences of a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome and characterizes smooth muscle cell phenotype in Loeys-Dietz syndrome aneurysmal and normal-sized downstream aorta. MethodsPatients with genetically confirmed Loeys-Dietz syndrome (n = 8) underwent prophylactic aortic arch replacement during valve-sparing aortic root replacement. Four-dimensional flow magnetic resonance imaging studies were performed in 4 patients with Loeys-Dietz syndrome (valve-sparing aortic root replacement + arch) and compared with patients with contemporary Marfan syndrome (valve-sparing aortic root replacement only, n = 5) and control patients (without aortopathy, n = 5). Aortic tissues from 4 patients with Loeys-Dietz syndrome and 2 organ donors were processed for anatomically segmented single-cell RNA sequencing and histologic assessment. ResultsPatients with Loeys-Dietz syndrome valve-sparing aortic root replacement + arch had no deaths, major morbidity, or aortic events in a median of 2 years follow-up. Four-dimensional magnetic resonance imaging demonstrated altered flow parameters in patients with postoperative aortopathy relative to controls, but no clear deleterious changes due to arch replacement. Integrated analysis of aortic single-cell RNA sequencing data (>49,000 cells) identified a continuum of abnormal smooth muscle cell phenotypic modulation in Loeys-Dietz syndrome defined by reduced contractility and enriched extracellular matrix synthesis, adhesion receptors, and transforming growth factor-beta signaling. These modulated smooth muscle cells populated the Loeys-Dietz syndrome tunica media with gradually reduced density from the overtly aneurysmal root to the nondilated arch. ConclusionsPatients with Loeys-Dietz syndrome demonstrated excellent surgical outcomes without overt downstream flow or shear stress disturbances after concomitant valve-sparing aortic root replacement + arch operations. Abnormal smooth muscle cell–mediated aortic remodeling occurs within the normal diameter, clinically at-risk Loeys-Dietz syndrome arch segment. These initial clinical and pathophysiologic findings support concomitant arch replacement in Loeys-Dietz syndrome.

Hegel's Philosophy of Sound

Abstract This essay offers an introduction to Hegel's philosophy of sound as elaborated in the 1830 Encyclopaedia of the Philosophical Sciences in Basic Outline. The first section begins with essential context for interpreting the a priori status of nature and sound in Hegel's Philosophy of Nature. Next, I develop a general account of the Aristotelian character of Hegel's ‘Physics’, and a commentary on the categories of specific gravity and cohesion leading up to sound (and heat) in the ‘Physics of Particular Individuality’. The second section provides an exegetical portrait of Hegel's metaphysics of sound. I first reconstruct Hegel's ontology of sound from the subsection on ‘Sound’ (Der Klang), and then outline his theory of auditory perception. The third section compares Hegel's philosophy of sound to leading views in contemporary philosophy of sound. I argue that Hegel offers a hylomorphic version of a located event theory of sound, which I suggest is more phenomenologically adequate than the modern acoustic view, and more metaphysically consistent than other distal event theories of sound.

Fate of the distal aorta following root replacement in Marfan syndrome: a propensity score matched study.

The aortic root is the most frequent segment involved in Marfan syndrome. However, Marfan syndrome is a systemic hereditary connective tissue disorder, and knowledge regarding the outcomes of the native distal aorta after prophylactic aortic root surgery is limited. From April 2010 to December 2020, 226 patients with Marfan syndrome and 1,200 patients without Marfan syndrome who underwent Bentall procedures were included in this study. By propensity score matching, 134 patients were assigned to each group. Clinical manifestations and follow-up data were acquired from hospital records and telephone contact. The cumulative incidence of aortic events was estimated in Marfan and non-Marfan patients with death as a competing risk. Patients with and without Marfan syndrome had similar baseline characteristics after propensity score matching. Differences in the aortic root (62.25 ± 11.96 vs. 54.03 ± 13.76, P < .001) and ascending aorta (37.71 ± 9.86 vs. 48.16 ± 16.01, P < .001) remained after matching. No difference was observed in the frequency of aortic adverse events between the two groups (10.5% vs. 4.6%, P = 0.106). The cumulative incidence of aortic events was not different between Marfan and non-Marfan patients (15.03% ± 4.72% vs. 4.18% ± 2.06%, P = 0.147). Multivariate Cox regression indicated no significant impact of Marfan syndrome on distal aortic events (HR: 1.172, 95% CI: 0.263-5.230, P = 0.835). Descending and abdominal aortic diameter above normal at the initial procedure were associated with the risk of distal aortic events (HR: 20.735, P = .003, HR: 22.981, P = .002, respectively). New-onset events of the residual aorta in patients undergoing Bentall procedures between the Marfan and non-Marfan groups were not significantly different. Distal aortic diameter above normal at initial surgery was associated with a higher risk of adverse aortic events.

Bilateral axillary aneurysm repair by open surgery: A case report

Axillary aneurysms are rare pathologies and although most of them are the result of traumatic events, there is a percentage that is due to atherosclerotic disease or is the result of a degenerative process over time. Once the aneurysm develops, it can cause distal ischemic events and/or neurological symptoms related to embolism or compression. Therefore, the diagnosis and treatment of axillary aneurysms is crucial for the patient. Most of them can be treated effectively by surgical excision and vascular grafting. We present a case of a patient with bilateral axillary aneurysms diagnosed after embolic complications.

What’s figurative about figurative language?

Traditional accounts of figures of speech identify a long list of rhetorical devices that collectively comprise the domain of figurative language. But what does it really mean to say that some instance of speech or writing is part of “figurative language”? This article considers several possible ways of thinking about figurative language by taking a closer look at what “figurative” really means. A main theme of this assessment views figurative in terms of the human figure or body. I outline one possible way that diverse, even more peripheral, figures of speech relate to bodily experience and embodied thought. Figurative language may be special precisely because it demonstrates, and not simply describes, speakers’ thoughts and attitudes regarding mostly distal events and abstract ideas. These demonstrations are evoked via embodied simulation processes in which listeners imagine themselves enacting the actions referred to in different figures of speech. This perspective offers a distinct theory of how diverse figures of speech ultimately fit within larger psychological and linguistic theories of meaning and interpersonal communication.