Determinants of Mortality and Mid-Term Outcomes After Transcarotid Artery Revascularization and Transfemoral Carotid Artery Stenting.

OBJECTIVES: The potential benefit of transcarotid artery revascularization (TCAR) over transfemoral carotid artery stenting (tfCAS) has been studied in the perioperative period with lower rates of stroke and death; however, data on mid-term outcomes are limited. We aimed to evaluate 3-year outcomes after TCAR and tfCAS and determine the primary predictors of 30-day and 1-year mortality following TCAR. METHODS: Data from the Vascular Quality Initiative for patients undergoing TCAR or tfCAS from January 2016 to December 2022 were analyzed. 1:1 propensity score matching using the nearest-neighbor method was used to adjust baseline demographics and clinical characteristics. Kaplan-Meier survival analysis and Cox Proportional Hazard Regression were used to evaluate long-term outcomes. Iterative stepwise multiple logistic regression analysis and Cox Proportional Hazard Regression were used to identify predictors of 30-day and 1-year mortality, respectively, based upon preoperative, intraoperative, and postoperative factors. RESULTS: A total of 70 237 patients were included in analysis (TCAR=58.7%, tfCAS=41.3%). Transcarotid artery revascularization patients were older and had higher rates of comorbid conditions and high-risk medical and anatomic features than tfCAS patients. Propensity score matching yielded 22 322 pairs with no major differences between groups except that TCAR patients were older (71.6 years vs 70.8 years). At 3 years, TCAR was associated with a 24% reduction in hazard of death compared with tfCAS (hazard ratio [HR]=0.76, 95% confidence interval [CI]=0.71-0.82, p<0.001), for both symptomatic and asymptomatic patients. This survival advantage was established in the first 6 months (HR=0.59, 95% CI=0.53-0.62, p<0.001), with no difference in mortality risk from 6 months to 36 months (HR=0.95, 95% CI=0.86-1.05, p=0.31). Transcarotid artery revascularization was also associated with decreased hazard for 3-year stroke (HR=0.81, 95% CI=0.66-0.99, p=0.04) and stroke or death (HR=0.81, 95% CI=0.76-0.87, p<0.001) compared with tfCAS. The top predictors for 30-day and 1-year mortality were postoperative complications. The primary independent predictor was the occurrence of postoperative stroke. CONCLUSIONS: Transcarotid artery revascularization had a sustained mid-term survival advantage associated over tfCAS, with the benefit being established primarily within the first 6 months. Notably, our findings highlight the importance of postoperative stroke as the primary independent predictor for 30-day and 1-year mortal. CLINICAL IMPACT: The ongoing debate over the superiority of TCAR compared to tfCAS and CEA has been limited by a lack of comparative studies examining the impact of pre-operative symptoms on outcomes. Furthermore, data are scarce on mid-term outcomes for TCAR beyond the perioperative period. As a result, it remains uncertain whether the initial benefits of stroke and death reduction observed with TCAR over tfCAS persist beyond one year. Our study addresses these gaps in the literature, offering evidence to enable clinicians to assess the efficacy of TCAR for up to three years. Additionally, our study seeks to identify risk factors for postoperative mortality following TCAR, facilitating optimal patient stratification.

Neck radiation is not associated with increased risk of perioperative adverse events after transcarotid artery revascularization or transfemoral carotid artery stenting.

OBJECTIVE: It is unclear whether patients with prior neck radiation therapy (RT) are at high risk for carotid artery stenting (CAS). We aimed to delineate 30-day perioperative and 3-year long-term outcomes in patients treated for radiation-induced stenotic lesions by the transfemoral carotid artery stenting (TFCAS) or transcarotid artery revascularization (TCAR) approach to determine comparative risk and to ascertain the optimal intervention in this cohort. METHODS: Data were extracted from the Vascular Quality Initiative CAS registry for patients with prior neck radiation who had undergone either TCAR or TFCAS. The Student t-test and the χ2 test were used to compare baseline patient characteristics. Multivariable logistic regression and Cox Hazard Proportional analysis were used to compare perioperative and long-term differences between patients with and without prior neck radiation following TCAR and TFCAS. Kaplan-Meier estimator was used to determine the incidence of 3-year adverse events. RESULTS: A total of 72,656 patients (TCAR, 40,879; TFCAS, 31,777) were included in the analysis. Of these, 4151 patients had a history of neck radiation. Patients with a history of neck radiation were more likely to be younger, white, and have fewer comorbidities than patients with no neck radiation history. After adjustment for confounding factors, there was no difference in relative risk of 30-day perioperative stroke (P = .11), death (P = .36), or myocardial infarction (MI) (P = .61) between TCAR patients with or without a history of neck radiation. The odds of stroke/death (P = .10) and stroke/death/MI (P = .07) were also not statistically significant. In patients with prior neck radiation, TCAR had lower odds for in-hospital stroke/death/MI (odds ratio, 0.59; 95% confidence interval [CI], 0.35-0.99; P = .05) and access site complications than TFCAS. At year 3, patients with prior neck radiation had an increased hazard for mortality after TCAR (hazard ratio [HR], 1.24; 95% CI, 1.02-1.51; P = .04) and TFCAS (HR, 1.33; 95% CI, 1.12-1.58; P = .001). Patients with prior neck radiation also experienced an increased hazard for reintervention after TCAR (HR, 2.16; 95% CI, 1.45-3.20; P < .001) and TFCAS (HR, 1.67; 95% CI, 1.02-2.73; P<.001). CONCLUSIONS: Patients with prior neck radiation had a similar relative risk of 30-day perioperative adverse events as patients with no neck radiation after adjustment for baseline demographics and disease characteristics. In these patients, TCAR was associated with reduced odds of perioperative stroke/death/MI as compared with TFCAS. However, patients with prior neck radiation were at increased risk for 3-year mortality and reintervention.

Use of Spinal Anesthesia during Thoracic Endovascular Aortic Repair.

BACKGROUND: The purpose of this study was to assess outcomes after spinal anesthesia (SA) versus general anesthesia (GA) in patients undergoing thoracic endograft placement and to evaluate the adjunctive use of cerebrospinal fluid drainage (CSFD) placement. METHODS: A single-center retrospective review of patients that underwent thoracic endograft placement from 2001 to 2019 was performed. Patients were stratified based on the type of anesthesia they received: GA, SA or epidural, GA with CSFD, and SA with CSFD. Primary outcomes included 30-day mortality and length of stay (LOS). Baseline characteristics were analyzed with Student's t-test and Pearson's chi-squared test. Multivariate logistic regression analysis was performed to identify risk factors for 30-day mortality and longer LOS. RESULTS: A total of 333 patients underwent thoracic endograft placement; 104 patients received SA, 180 patients received GA, 30 patients received GA and CSFD, and 19 patients received SA and CSFD. Of the total patients, 16.2% underwent thoracic endograft placement for type B aortic dissection, 3.3% for type A aortic dissection, and 12.3% for penetrating ulcer. The mean age of the study population was 68.7 years old. Patients undergoing SA were older with a mean age of 73.4 years versus 64.7 years for patients undergoing GA (P < 0.001). Spinal anesthesia (SA) was preferred in patients at high risk for GA (>75 years old: 52.9% vs. 33.3%, P < 0.001; renal comorbidities: 20.6% vs. 10.6%, P = 0.03, and current smokers: 26.7% vs. 9.6%, P < 0.001). Length of stay (LOS) was decreased in the SA group (4.29 days vs. 9.70 days, P < 0.001). There was a lower incidence of spinal cord ischemia in the SA group (1.0% vs. 2.2%, P = 0.44), as well as significantly decreased 30-day mortality (0% vs. 5.6%, P = 0.01), reintervention (19.2% vs. 26.8%, P = 0.02), and return to the operating room (6.8% vs. 12.7%, P = 0.02). Of the 19 patients that had SA + CSFD, there were no signs and symptoms of spinal cord ischemia and decreased incidence of perioperative complications (0% vs. 33.3%, P = 0.01). There was no difference in the risk for intraoperative complications, neurologic complications, or 30-day mortality between GA + CSFD patients versus SA + CSFD patients. Age >75 (P = 0.002), intraoperative complications (P < 0.001), and perioperative complications (P = 0.02) were associated with increased mortality after thoracic endograft placement per multivariate logistic regression analysis. CONCLUSIONS: Spinal anesthesia (SA) in select high-risk patients was associated with reduced 30-day mortality, neurologic complications, and LOS compared to GA. The concurrent use of spinal drainage and SA had satisfactory results compared to spinal drainage and GA.

Carotid stenosis patients with a remote history of cerebrovascular events have increased risk of major adverse events over asymptomatic patients.

INTRODUCTION: Asymptomatic patients with a remote history of transient ischemic attack (TIA) or stroke are not well studied as a separate population from asymptomatic patients with no prior history of TIA or stroke. We compared in-hospital outcomes after transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS) among symptomatic patients, patients with a remote history of neurologic symptoms, and asymptomatic patients. METHODS: Data from patients in the Vascular Quality Initiative database who underwent TCAR (January 2017 to April 2020) or TFCAS (May 2005 to April 2020) were analyzed. Symptomatic status was defined as TIA and/or stroke occurring within 180 days before the procedure. Asymptomatic status was divided into patients with no history of TIA/stroke (asymptomatic) and patients with a history of TIA/stroke occurring more than 180 days before the procedure (remote history of neurologic symptoms). The Student t-test and Pearson χ2 test were used to compare baseline patient characteristics and outcomes. Multivariate logistic regression was used to adjust for significant between-group differences in baseline characteristics. RESULTS: There were 7158 patients who underwent TCAR (symptomatic: 2574, asymptomatic: 3689, and asymptomatic with a remote history of neurologic symptoms: 895) and 18,023 patients who underwent TFCAS (symptomatic: 6195, asymptomatic: 10,333, and asymptomatic with a remote history of neurologic symptoms: 1495). Regardless of symptom status, the mean patient age was 73 years for TCAR and 69 years for TFCAS. A total of 64% of patients in the study were male and 36% of patients were female. The mean long-term follow-up data ranged between 208 and 331 days within the three patient groups. Carotid stenosis patients with a remote history of neurologic symptoms had higher rates of TIA, stroke, TIA/stroke, stroke/death, and stroke/death/myocardial infarction than asymptomatic patients, and these rates were similar to those of symptomatic patients. Comparing TCAR and TFCAS among patients with a remote history of neurologic symptoms, there were statistically significant reductions in the odds of stroke/death (odds ratio: 0.46, 95% confidence interval: 0.27-0.84, P = .011) and stroke/death/myocardial infarction (odds ratio: 0.51, 95% confidence interval: 0.30-0.87, P = .013) after TCAR. This was likely driven by the increased rate of death after TFCAS in patients with a remote history of neurologic symptoms (0.9%) compared with asymptomatic patients (0.6%). CONCLUSIONS: Asymptomatic patients with a remote history of TIA/stroke do not have the same outcomes as asymptomatic patients without a history of TIA/stroke and are at higher risk of adverse in-hospital events. Patients with a remote history of TIA/stroke have increased risk of in-hospital death after TFCAS and may benefit from TCAR.

Comparison of Transcarotid Artery Revascularization and Transfemoral Carotid Artery Stenting Based on High Risk Anatomic Characteristics.

BACKGROUND: Anatomic details affecting the adverse outcomes following carotid artery stenting have not been well characterized. We compared in-hospital outcomes following transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS) among symptomatic and asymptomatic patients stratified by degree of lesion calcification and aortic arch type. METHODS: Data from patients in the Society for Vascular Surgery's Vascular Quality Initiative database undergoing TCAR (January 2017 to April 2020) or TFCAS (May 2005 to April 2020) and had non-missing grading on carotid artery calcification or aortic arch type was analyzed. Degree of calcification was stratified into 3 groups: none, ≤ 50% calcification, and >50% calcification. Arch type was stratified as Type I, Type II, and Type III. RESULTS: A total of 9,868 patients (TCAR: 4,224; TFCAS: 5,644) were included in the calcification analysis. TCAR patients were generally older, white, smokers, and had more comorbidities than TFCAS patients. Among the symptomatic patients, there was no difference in rates of stroke, stroke/transient ischemic attack (TIA), and myocardial infarction (MI) by calcification severity between TCAR and TFCAS. However, there was a trend towards increased risk in all 3 events with higher calcification only after TFCAS. Symptomatic patients with severe (>50%) calcification had lower rates of death (TCAR: 0.9% vs. TFCAS: 2.8%, P = 0.013), stroke/death (TCAR: 2.7% vs. TFCAS: 5.8%, P = 0.006), stroke/death/MI (TCAR: 3.3% vs. TFCAS: 6.5%, P = 0.007), and postop complications (TCAR: 6.0% vs. TFCAS: 12.4%, P < 0.001) after TCAR compared to TFCAS. Furthermore, TCAR had lower risk of mortality at all degrees of calcification compared to TFCAS. Similar findings were noted among asymptomatic TCAR patients with >50% calcification, in which the rates of death (TCAR: 0.4% vs. TFCAS: 1.1%, P = 0.080) and stroke/death (TCAR: 1.5% vs. TFCAS: 3.1%, P = 0.029) were reduced. A comparison of TCAR to TFCAS by arch type showed that rates of stroke/death after TCAR were similar regardless of arch complexity (Type I: 2.6% vs. Type II: 2.8%), but increased after TFCAS with complex, high risk anatomy (Type I: 4.2% vs. Type II: 5.2%). CONCLUSIONS: While increased calcification increased rates of adverse events after TFCAS, this trend was not observed after TCAR, which also had lower rates of death and stroke/death among patients with severe calcification. Furthermore, TCAR had lower risk of mortality than TFCAS across all degrees of calcification. TFCAS was associated with increased risk of stroke/death with complex aortic arch anatomy, however, rates of stroke/death after TCAR were similar regardless of arch complexity. Our results suggests that TCAR should be preferentially considered in revascularization of patients with anatomy considered high-risk for TFCAS.

Krt5+/Krt15+ foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress.

The effective prevention of tumor initiation, especially for potentially inoperable tumors, will be beneficial to obtain an overall higher quality of our health and life. Hence, thorough understanding of the pathophysiological mechanisms of early tumor formation arising from identifiable cellular origins is required to develop efficient preventative and early treatment options for each tumor type. Here, using genetically engineered mouse models, we provide preclinical experimental evidence for a long-standing open question regarding the pathophysiological potential of a microenvironmental and physiological stressor in tumor development, gastric acid-mediated regional microscopic injury in foregut squamous epithelia. This study demonstrates the association of gastric acid stress with Cyclooxygenase-2-dependent tumor formation originating from tumor-competent Krt5+/Krt15+ foregut basal progenitor cells. Our findings suggest that clinical management of microenvironmental stressor-mediated microscopic injury may be important in delaying tumor initiation from foregut basal progenitor cells expressing pre-existing tumorigenic mutation(s) and genetic alteration(s).

Sirt5 is dispensable for BrafV600E -mediated cutaneous melanoma development and growth in vivo.

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for BrafV600E -mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (TyrCreERT2/+ ; BrafLSL-V600E/+ ; Ptenflox/flox ) to Sirt5-/- knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5-/- mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for BrafV600E -mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.

Laboratory Rearing of Stable Flies and Other Muscoid Diptera.

Stable flies, Stomoxys calcitrans, are serious pests of livestock, humans, companion animals and wildlife worldwide. During the last 20+ years, changes in agronomic practices resulted in serious outbreaks of stable flies in several countries. These outbreaks disrupted livestock production and human recreation resulting in public demands for increasing research and management efforts for this pest. A simple and inexpensive procedure for rearing stable flies for laboratory studies is presented. The procedure uses locally available diet components, equipment and supplies. The procedure can be adapted for rearing other muscoid flies including face fly (Musca autumnalis), horn fly (Haematobia irritans), and house fly (Musca domestica). The procedure produces stable fly puparia averaging 12.5 mg and ~35% egg to adult survival. Approximately 3000 flies are produced in each pan.

Melanocyte Stem Cell Activation and Translocation Initiate Cutaneous Melanoma in Response to UV Exposure.

Melanoma is one of the deadliest cancers, yet the cells of origin and mechanisms of tumor initiation remain unclear. The majority of melanomas emerge from clear skin without a precursor lesion, but it is unknown whether these melanomas can arise from melanocyte stem cells (MCSCs). Here we employ mouse models to define the role of MCSCs as melanoma cells of origin, demonstrate that MCSC quiescence acts as a tumor suppressor, and identify the extrinsic environmental and molecular factors required for the critical early steps of melanoma initiation. Specifically, melanomas originate from melanoma-competent MCSCs upon stimulation by UVB, which induces MCSC activation and translocation via an inflammation-dependent process. Moreover, the chromatin-remodeling factor Hmga2 in the skin plays a critical role in UVB-mediated melanomagenesis. These findings delineate melanoma formation from melanoma-competent MCSCs following extrinsic stimuli, and they suggest that abrogation of Hmga2 function in the microenvironment can suppress MCSC-originating cutaneous melanomas.

Precipitation and Temperature Effects on Stable Fly (Diptera: Muscidae) Population Dynamics.

The dynamics of stable fly, Stomoxys calcitrans (L.), populations relative to temperature and precipitation were evaluated in a 13-yr study in eastern Nebraska. During the course of the study, >1.7 million stable flies were collected on an array of 25 sticky traps. A log-normal model using degree-days with a 15 °C threshold and weekly lags 0-4 for temperature and 2-7 for precipitation provided the best fit with the observed data. The relationships of temperature and precipitation to stable fly trap catches were both curvilinear, with maxima at 6.6 degree-day-15 (≈22 °C) and 7.4 mm precipitation per day, respectively. The temperature and precipitation model accounted for 72% of the variance in seasonal trap catches.

Augmenting Laboratory Rearing of Stable Fly (Diptera: Muscidae) Larvae With Ammoniacal Salts.

Stable flies are blood feeding parasites and serious pests of livestock. The immature stages develop in decaying materials which frequently have high ammonium content. We added various ammonium salts to our laboratory stable fly rearing medium and measured their effect on size and survival as well as the physical properties of the used media. The addition of ammonium hydroxide, ammonium phosphate and ammonium sulfate reduced larval survival. These compounds decreased pH and increased ammonium content of the used media. Ammonium bicarbonate had no effect on pH and marginally increased ammonium while increasing survival twofold. The optimal level of ammonium bicarbonate was 50 g (0.63 mol) per pan. Larval survival decreased when pH was outside the range of 8.5 to 9.0.

Environmental Parameters Associated With Stable Fly (Diptera: Muscidae) Development at Hay Feeding Sites.

Substrates composed of hay residues, dung, and urine accumulate around winter hay feeding sites in cattle pastures, providing developmental habitats for stable flies. The objective of this study was to relate physiochemical and microbial properties of these substrates to the presence or absence of stable fly larvae. Properties included pH, temperature, moisture, ammonium concentration, electrical conductivity, and numbers of coliform, fecal coliform, Escherichia coli, and Enterococcus bacteria. Each physiochemical sample was classified as a function of belonging to one of the three 2-m concentric zones radiating from the feeder as well as presence or absence of larvae. In total, 538 samples were collected from 13 sites during 2005-2011. Stable fly larvae were most likely to be found in moist, slightly alkaline substrates with high levels of ammonium and low temperature. The probability of larvae being present in a sample was the highest when the moisture content was 347% relative to dry weight and the average pH was 8.4. Larvae were recovered within all zones, with a nonsignificant, but slightly higher, percentage of samples containing larvae taken 2-4 m from the center. All methods used to enumerate bacteria, except total coliform, indicated decreasing concentrations in hay bale residue throughout the summer. In addition to the environmental parameters, cumulative degree day 10°C had a significant effect on the probability of observing stable fly larvae in a sample, indicating that unidentified seasonal effects also influenced immature stable fly populations.

External Morphology of Stable Fly (Diptera: Muscidae) Larvae.

Scanning electron microscopy was used to examine the external morphology of first-, second-, and third-instar stable flies (Stomoxys calcitrans (L.)). In the cephalic region, the antennae, labial lobe, and maxillary palpi are morphologically similar among instars. Antennae comprise a prominent anterior dome that is the primary site of olfaction, while the maxillary palpi are innervated with mechano- and chemosensilla and scolopodia. The ventral organ and facial mask, also located in the pseudocephalon, are not well-developed in first instars, but become progressively more so in the subsequent instars. When the pseudocephalon is partially retracted, anterior spines cusp around the oral ridges of the facial mask. This indicates the anterior spinose band may be used in conjunction with the facial mask in predigestion. Functional anterior spiracles are absent on first instars, but become evident as a pair of palmate spiracular processes with five to seven lobes in second and third instars. A pair of Keilin's organs, functioning as hygroreceptors, is located on each thoracic segment. Abdominal segments are marked with ventral creeping welts, the anal pad, anus, papillae, and posterior spiracles. Ventral creeping welts are thought to aid in locomotion, while the anal pad acts as an osmoregulatory structure. Posterior spiracles are modified from round spiracular discs with two straight slits in the first instar to triangular discs with two and three sinuous slits in the second and third instars, respectively.