Winter break? The effect of overwintering on immune gene expression in wood frogs.

Among terrestrial ectotherms, hibernation is a common response to extreme cold temperatures and is associated with reduced physiological rates, including immunity. When winter wanes and temperatures increase, so too do vital rates of both ectothermic hosts and their parasites. Due to metabolic scaling, if parasite activity springs back faster than host immune functions then cold seasons and transitions between cold and warm seasons may represent periods of vulnerability for ectothermic hosts. Understanding host regulation of physiological rates at seasonal junctions is a first step toward identifying thermal mismatches between hosts and parasites. Here we show that immune gene expression is responsive to transitions into and out of the cold season in a winter-adapted amphibian, the wood frog (Lithobates sylvaticus), and that frogs experienced parasitism by at least two nematode species throughout the entirety of the cold season. In both splenic and skin tissues, we observed a decrease in immune gene expression going from fall to winter, observed no changes between winter and emergence from hibernation, and observed increases in immune gene expression after hibernation ended. At all timepoints, differentially expressed genes from spleens were more highly enriched for immune system processes than those from ventral skin, especially with respect to terms related to adaptive immune processes. Infection with nematode lungworms was also associated with upregulation of immune processes in the spleen. We suggest that rather than being a period of stagnation, during which physiological processes and infection potential cease, the cold season is immunologically dynamic, requiring coordinated regulation of many biological processes, and that the reemergence period may be an important time during which hosts invest in preparatory immunity.

Outcomes Following Carotid Revascularization in Patients with Prior Ipsilateral Carotid Artery Stenting in the Vascular Quality Initiative.

OBJECTIVES: The outcomes of carotid revascularization in patients with prior carotid artery stenting remain understudied. Prior research has not reported the outcomes after Transcarotid artery revascularization (TCAR) in patients with previous carotid artery stenting. In this study, we compared the peri-operative outcomes of TCAR, tfCAS and CEA in patients with prior ipsilateral CAS using the VQI. METHODS: Using the Vascular Quality Initiative data from 2016 to 2023, we identified patients who underwent TCAR, tfCAS, or CEA following prior ipsilateral carotid artery stenting. We included covariates such as age, race, sex, BMI, comorbidities (hypertension, diabetes, prior CAD, prior CABG/PCI, CHF, renal dysfunction, smoking, COPD, anemia), symptom status, urgency, ipsilateral stenosis, and contralateral occlusion into a regression model to compute propensity scores for treatment assignment. We then used the propensity scores for inverse probability-weighting and weighted logistic regression to compare in-hospital stroke, in-hospital death, stroke/death, postoperative myocardial infarction (MI), stroke/death/MI, 30-day mortality and cranial nerve injury (CNI) following TCAR, tfCAS, and CEA. We also analyzed trends in the proportions of patients undergoing the three revascularization procedures over time using Cochrane-Armitage trend testing. RESULTS: We identified 2,137 patients undergoing revascularization following prior ipsilateral carotid stenting: 668 TCAR patients (31%), 1128 tfCAS patients (53%) and 341 CEA patients (16%). In asymptomatic patients, TCAR was associated with a lower yet not statistically significant in-hospital stroke/death than tfCAS (TCAR vs tfCAS: 0.7% vs 2.0%,aOR:0.33[0.11-1.05]; p=0.06), and similar odds of stroke/death with CEA (TCAR vs CEA: 0.7% vs 0.9%,aOR:0.80[0.16-3.98]; p=0.8). Compared with CEA, TCAR was associated with lower odds of post-operative MI (0.1% vs 14%,aOR:0.02[0.00-0.10]; p<0.001), stroke/death/MI (0.8% vs 15%,aOR:0.05[0.01-0.25]; p<0.001), and CNI (0.1% vs 3.8%,aOR:0.04[0.00-0.30]; p=0.002) in this patient population. In symptomatic patients, TCAR had an unacceptably elevated in-hospital stroke/death rate of 5.1% with lower rates of CNI than CEA. We also found an increasing trend in the proportion of patients undergoing TCAR following prior ipsilateral carotid stenting (2016 to 2023: 14% to 41%), with a relative decrease in proportions of tfCAS (61% to 45%) and CEA (25% to 14%) (p<.001). CONCLUSIONS: In asymptomatic patients with prior ipsilateral carotid artery stenting, TCAR was associated with lower odds of in-hospital stroke/death compared with tfCAS, with comparable stroke/death but lower postoperative MI and CNI rates compared with CEA. In symptomatic patients, TCAR was associated with unacceptably elevated in-hospital stroke/death rates. In line with the post-procedure outcomes, there has been a steady increase in the proportion of patients with prior ipsilateral stenting undergoing TCAR over time.

Multi-Material Decomposition Using Spectral Diffusion Posterior Sampling.

Many spectral CT applications require accurate material decomposition. Existing material decomposition algorithms are often susceptible to significant noise magnification or, in the case of one-step model-based approaches, hampered by slow convergence rates and large computational requirements. In this work, we proposed a novel framework - spectral diffusion posterior sampling (spectral DPS) - for one-step reconstruction and multi-material decomposition, which combines sophisticated prior information captured by one-time unsupervised learning and an arbitrary analytic physical system model. Spectral DPS is built upon a general DPS framework for nonlinear inverse problems. Several strategies developed in previous work, including jumpstart sampling, Jacobian approximation, and multi-step likelihood updates are applied facilitate stable and accurate decompositions. The effectiveness of spectral DPS was evaluated on a simulated dual-layer and a kV-switching spectral system as well as on a physical cone-beam CT (CBCT) test bench. In simulation studies, spectral DPS improved PSNR by 27.49% to 71.93% over baseline DPS and by 26.53% to 57.30% over MBMD, depending on the the region of interest. In physical phantom study, spectral DPS achieved a <1% error in estimating the mean density in a homogeneous region. Compared with baseline DPS, spectral DPS effectively avoided generating false structures in the homogeneous phantom and reduced the variability around edges. Both simulation and physical phantom studies demonstrated the superior performance of spectral DPS for stable and accurate material decomposition.

Anti-phosphohistone H3 (PHH3) as a proliferation marker to assess mitotic activity and to grade neuroendocrine neoplasms of hepatopancreaticobiliary (HPB) system.

BACKGROUND: The world health organization (WHO) classification of neuroendocrine neoplasms (NENs, i.e. neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs)) of the gastrointestinal system involves grading of these tumors by mitotic count (i.e. H and E mitotic index or Haematoxylin and Eosin mitotic index [HE-MI] and Mindbomb E3 ubiquitin protein ligase 1 labelling index (MIB1-LI) into Grade 1 (G1), Grade 2 (G2), or Grade 3 (G3). However, the assessment of HE-MI and MIB1-LI is hindered by several factors that contribute to discordance between these two grading methods. Clinical data demonstrate the dependency of prognosis on grade. OBJECTIVES: The objective of this study was to compare the grading of NENs of the hepatopancreatobiliary (HPB) system using Anti-phosphohistone H3 mitotic index (i.e. PHH3-MI), HE-MI and MIB1-LI. MATERIALS AND METHODS: In a cohort of 140 NENs selected from January 2011 to August 2019, the concordance and correlation between HE-MI, MIB1-LI and PHH3-MI grading methods were analysed using Cohen's weighted kappa (κ) statistics and Spearman's correlation (ρ), respectively. Receiver operating characteristic (ROC) curve and cut-off analyses were done to determine optimal PHH3-MI cut-off values to grade NENs. RESULTS: The rates of discordance between HE-MI vs. MIB1-LI, PHH3-MI vs. MIB1-LI and PHH3-MI vs. HE-MI were 52% (κ =0.416), 29% (κ =0.64) and 41% (κ =0.508), respectively. There was a significant correlation between the grading methods. PHH3-MI had good overall sensitivity and specificity at cut-offs 2 and 17 in distinguishing between G1 vs. G2, and G2 vs. G3 tumors, respectively. CONCLUSION: PHH3 immunolabeling allowed for quick and easy identification of mitotic figures (MF). It had the highest concordance with MIB1-LI. At cut-off values of 2 and 17, there was good overall sensitivity and specificity. The interobserver agreement was excellent.

Birth outcomes and survival by sex among newborns and children under 2 in the Birhan Cohort: a prospective cohort study in the Amhara Region of Ethiopia.

INTRODUCTION: Despite the progress in reducing child mortality, the rate remains high, particularly in sub-Saharan African countries. Limited data exist on child survival and other birth outcomes by sex. This study compared survival rates and birth outcomes by sex among neonates and children under 2 in Ethiopia. METHODS: Women who gave birth after 28 weeks of gestation and their newborns were included in the analysis. Survival probabilities were estimated for males and females in the neonatal period as well as the 2-year period following birth using Kaplan-Meier curves. HRs and 95% CIs were compared between males and females under 2. Descriptive statistics and χ2 tests were used to determine the sex-disaggregated variation in the birth outcomes of preterm birth, low birth weight (LBW), stillbirth, small for gestational age (SGA) and large for gestational age (LGA). RESULTS: The study included a total of 3904 women and child pairs. The neonatal mortality rate for males (3.4%, 95% CI 2.6% to 4.2%) was higher compared with females (1.7%, 95% CI 1.1% to 2.3%). The hazard of death during the first 28 days of life was approximately two times higher for males compared with females (HR 1.99, 95% CI 1.30 to 3.06) but was not significantly different after this period. While there was a non-significant difference between males and females in the proportion of preterm, LBW and LGA births, we found a significantly higher proportion of stillbirth (2.7% vs 1.3%, p=0.003) and SGA (20.5% vs 15.6%, p<0.001) for males compared with females. CONCLUSIONS: This study identified a significant sex difference in mortality and birth outcomes. We recommend focusing future research on the mechanisms of these sex differences in order to better design intervention programmes to reduce disparities and improve outcomes for neonates.

Invasion and Amplification of Endogenous Retroviruses in Dasyuridae Marsupial Genomes.

Retroviruses are an ancient viral family that have globally coevolved with vertebrates and impacted their evolution. In Australia, a continent that has been geographically isolated for millions of years, little is known about retroviruses in wildlife, despite the devastating impacts of a retrovirus on endangered koala populations. We therefore sought to identify and characterize Australian retroviruses through reconstruction of endogenous retroviruses from marsupial genomes, in particular the Tasmanian devil due to its high cancer incidence. We screened 19 marsupial genomes and identified over 80,000 endogenous retrovirus fragments which we classified into eight retrovirus clades. The retroviruses were similar to either Betaretrovirus (5/8) or Gammaretrovirus (3/8) retroviruses, but formed distinct phylogenetic clades compared to extant retroviruses. One of the clades (MEBrv 3) lost an envelope but retained retrotranspositional activity, subsequently amplifying throughout all Dasyuridae genomes. Overall, we provide insights into Australian retrovirus evolution and identify a highly active endogenous retrovirus within Dasyuridae genomes.

Identifying prey capture events of a free-ranging marine predator using bio-logger data and deep learning.

Marine predators are integral to the functioning of marine ecosystems, and their consumption requirements should be integrated into ecosystem-based management policies. However, estimating prey consumption in diving marine predators requires innovative methods as predator-prey interactions are rarely observable. We developed a novel method, validated by animal-borne video, that uses tri-axial acceleration and depth data to quantify prey capture rates in chinstrap penguins (Pygoscelis antarctica). These penguins are important consumers of Antarctic krill (Euphausia superba), a commercially harvested crustacean central to the Southern Ocean food web. We collected a large data set (n = 41 individuals) comprising overlapping video, accelerometer and depth data from foraging penguins. Prey captures were manually identified in videos, and those observations were used in supervised training of two deep learning neural networks (convolutional neural network (CNN) and V-Net). Although the CNN and V-Net architectures and input data pipelines differed, both trained models were able to predict prey captures from new acceleration and depth data (linear regression slope of predictions against video-observed prey captures = 1.13; R 2 ≈ 0.86). Our results illustrate that deep learning algorithms offer a means to process the large quantities of data generated by contemporary bio-logging sensors to robustly estimate prey capture events in diving marine predators.

Impact of patient habitus and acquisition protocol on iodine quantification in dual-source photon-counting computed tomography.

Purpose: Evaluation of iodine quantification accuracy with varying iterative reconstruction level, patient habitus, and acquisition mode on a first-generation dual-source photon-counting computed tomography (PCCT) system. Approach: A multi-energy CT phantom with and without its extension ring equipped with various iodine inserts (0.2 to 15.0 mg/ml) was scanned over a range of radiation dose levels ( CTDI vol 0.5 to 15.0 mGy) using two tube voltages (120, 140 kVp) and two different source modes (single-, dual-source). To assess the agreement between nominal and measured iodine concentrations, iodine density maps at different iterative reconstruction levels were utilized to calculate root mean square error (RMSE) and generate Bland-Altman plots by grouping radiation dose levels (ultra-low: < 1.5 ; low: 1.5 to 5; medium: 5 to 15 mGy) and iodine concentrations (low: < 5 ; high: 5 to 15 mg/mL). Results: Overall, quantification of iodine concentrations was accurate and reliable even at ultra-low radiation dose levels. RMSE ranged from 0.25 to 0.37, 0.20 to 0.38, and 0.25 to 0.37 mg/ml for ultra-low, low, and medium radiation dose levels, respectively. Similarly, RMSE was stable at 0.31, 0.28, 0.33, and 0.30 mg/ml for tube voltage and source mode combinations. Ultimately, the accuracy of iodine quantification was higher for the phantom without an extension ring (RMSE 0.21 mg/mL) and did not vary across different levels of iterative reconstruction. Conclusions: The first-generation PCCT allows for accurate iodine quantification over a wide range of iodine concentrations and radiation dose levels. Stable accuracy across iterative reconstruction levels may allow further radiation exposure reductions without affecting quantitative results.

Estimates and determinants of health facility delivery in the Birhan cohort in Ethiopia.

Health facility delivery is one of the critical indicators to monitor progress towards the provision of skilled delivery care and reduction in perinatal mortality. In Ethiopia, utilization of health facilities for skilled delivery care has been increasing but varies greatly by region and among specific socio-demography groups. We aimed to measure the prevalence and determinants of health facility delivery in the Amhara region in Ethiopia. From December 2018 to November 2020, we conducted a longitudinal study from a cohort of 2801 pregnant women and described the location of delivery and the association with determinants. We interviewed a subset of women who delivered in the community and analyzed responses using the three delays model to understand reasons for not using health facility services. A multivariable poisson regression model with robust error variance was used to estimate the presence and magnitude of association between location of delivery and the determinants. Of the 2,482 pregnant women followed through to birth, 73.6% (n = 1,826) gave birth in health facilities, 24.3% (n = 604) gave birth at home and 2.1% (n = 52) delivered on the way to a health facility. Determinants associated with increased likelihood of delivery at a health facility included formal maternal education, shorter travel times to health facilities, primiparity, higher wealth index and having attended at least one ANC visit. Most common reasons mothers gave for not delivering in a health facility were delays in individual/family decision to seek care. The proportion of deliveries occurring in health facilities is increasing but falls below targets. Interventions that focus on the identified social-demographic determinants and delays are warranted.

CT Reconstruction using Diffusion Posterior Sampling conditioned on a Nonlinear Measurement Model.

Diffusion models have been demonstrated as powerful deep learning tools for image generation in CT reconstruction and restoration. Recently, diffusion posterior sampling, where a score-based diffusion prior is combined with a likelihood model, has been used to produce high quality CT images given low-quality measurements. This technique is attractive since it permits a one-time, unsupervised training of a CT prior; which can then be incorporated with an arbitrary data model. However, current methods rely on a linear model of x-ray CT physics to reconstruct or restore images. While it is common to linearize the transmission tomography reconstruction problem, this is an approximation to the true and inherently nonlinear forward model. We propose a new method that solves the inverse problem of nonlinear CT image reconstruction via diffusion posterior sampling. We implement a traditional unconditional diffusion model by training a prior score function estimator, and apply Bayes rule to combine this prior with a measurement likelihood score function derived from the nonlinear physical model to arrive at a posterior score function that can be used to sample the reverse-time diffusion process. This plug-and-play method allows incorporation of a diffusion-based prior with generalized nonlinear CT image reconstruction into multiple CT system designs with different forward models, without the need for any additional training. We develop the algorithm that performs this reconstruction, including an ordered-subsets variant for accelerated processing and demonstrate the technique in both fully sampled low dose data and sparse-view geometries using a single unsupervised training of the prior.

Comparison of open and endovascular left subclavian artery revascularization for zone 2 thoracic endovascular aortic repair.

OBJECTIVE: In patients undergoing elective thoracic endovascular aortic repair (TEVAR) and left subclavian artery (LSA) coverage, routine preoperative LSA revascularization is recommended. However, in the current endovascular era, the optimal surgical approach is debated. We compared baseline characteristics, procedural details, and perioperative outcomes of patients undergoing open or endovascular LSA revascularization in the setting of TEVAR. METHODS: Adult patients undergoing TEVAR with zone 2 proximal landing and LSA revascularization between 2013 and 2023 were identified in the Vascular Quality Initiative. We excluded patients with traumatic aortic injury, aortic thrombus, or ruptured presentations, and stratified based on revascularization type (open vs any endovascular). Open LSA revascularization included surgical bypass or transposition. Endovascular LSA revascularization included single-branch, fenestration, or parallel stent grafting. Primary outcomes were stroke, spinal cord ischemia (SCI), and perioperative mortality (Pearson's χ2 test). Multivariable logistic regression was used to evaluate associations between revascularization type and primary outcomes. Secondarily, we studied other in-hospital complications and 5-year mortality (Kaplan-Meier, multivariable Cox regression). Sensitivity analyses were performed in patients undergoing concomitant LSA revascularization to TEVAR. RESULTS: Of 2489 patients, 1842 (74%) underwent open and 647 (26%) endovascular LSA revascularization. Demographics and comorbidities were similar between open and endovascular cohorts. Compared with open, endovascular revascularization had shorter procedure times (median, 135 minutes vs 174 minutes; P < .001), longer fluoroscopy times (median, 23 minutes vs 16 minutes; P < .001), lower estimated blood loss (median, 100 mL vs 123 mL; P < .001), and less preoperative spinal drain use (40% vs 49%; P < .001). Patients undergoing endovascular revascularization were more likely to present urgently (24% vs 19%) or emergently (7.4% vs 3.4%) (P < .001). Compared with open, endovascular patients experienced lower stroke rates (2.6% vs 4.8%; P = .026; adjusted odds ratio [aOR], 0.50 [95% confidence interval (CI), 0.25-0.90]), but had comparable SCI (2.9% vs 3.5%; P = .60; aOR, 0.64 [95% CI, 0.31-1.22]) and perioperative mortality (3.1% vs 3.3%; P = .94; aOR, 0.71 [95% CI, 0.34-1.37]). Compared with open, endovascular LSA revascularization had lower rates of overall composite in-hospital complications (20% vs 27%; P < .001; aOR, 0.64 [95% CI, 0.49-0.83]) and shorter overall hospital stay (7 vs 8 days; P < .001). After adjustment, 5-year mortality was similar among groups (adjusted hazard ratio, 0.85; 95% CI, 0.64-1.13). Sensitivity analyses supported the primary analysis with similar outcomes. CONCLUSIONS: In patients undergoing TEVAR starting in zone 2, endovascular LSA revascularization had lower rates of postoperative stroke and overall composite in-hospital complications, but similar SCI, perioperative mortality, and 5-year mortality rates compared with open LSA revascularization. Future comparative studies are needed to evaluate the mid- to long-term safety of endovascular LSA revascularization and assess differences between specific endovascular techniques.

Outcomes of carotid revascularization stratified by procedure in patients with an estimated glomerular filtration rate of <30 and dialysis patients.

OBJECTIVE: Renal failure is a predictor of adverse outcomes in carotid revascularization. There has been debate regarding the benefit of revascularization in patients with severe chronic kidney disease or on dialysis. METHODS: Patients in the Vascular Quality Initiative undergoing transcarotid artery revascularization (TCAR), transfemoral carotid artery stenting (tfCAS), or CEA between 2016 and 2023 with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2 or on dialysis were included. Patients were divided into cohorts based on procedure. Additional analyses were performed for patients on dialysis only and by symptomatology. Primary outcomes were perioperative stroke/death/myocardial infarction (MI) (SDM). Secondary outcomes included perioperative death, stroke, MI, cranial nerve injury, and stroke/death. Inverse probability of treatment weighting was performed based on treatment assignment to TCAR, tfCAS, and CEA patients and adjusted for demographics, comorbidities, and preoperative symptoms. The χ2 test and multivariable logistic regression analysis were used to evaluate the association of procedure with perioperative outcomes in the weighted cohort. Five-year survival was evaluated using Kaplan-Meier and weighted Cox regression. RESULTS: In the weighted cohort, 13,851 patients with an eGFR of <30 (2506 on dialysis) underwent TCAR (3639; 704 on dialysis), tfCAS (1975; 393 on dialysis), or CEA (8237; 1409 on dialysis) during the study period. Compared with TCAR, CEA had higher odds of SDM (2.8% vs 3.6%; adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.00-1.61; P = .049), and MI (0.7% vs 1.5%; aOR, 2.00; 95% CI, 1.31-3.05; P = .001). Compared with TCAR, rates of SDM (2.8% vs 5.8%), stroke (1.2% vs 2.6%), and death (0.9% vs 2.4%) were all higher for tfCAS. In asymptomatic patients CEA patients had higher odds of MI (0.7% vs 1.3%; aOR, 1.85; 95% CI, 1.15-2.97; P = .011) and cranial nerve injury (0.3% vs 1.9%; aOR, 7.23; 95% CI, 3.28-15.9; P < .001). Like in the primary analysis, asymptomatic tfCAS patients demonstrated higher odds of death and stroke/death. Symptomatic CEA patients demonstrated no difference in stroke, death, or stroke/death. Although tfCAS patients demonstrated higher odds of death, stroke, MI, stroke/death, and SDM. In both groups, the 5-year survival was similar for TCAR and CEA (eGFR <30, 75.1% vs 74.2%; aHR, 1.06; P = .3) and lower for tfCAS (eGFR <30, 75.1% vs 70.4%; aHR, 1.44; P < .001). CONCLUSIONS: CEA and TCAR had similar odds of stroke and death and are both a reasonable choice in this population; however, TCAR may be better in patients with an increased risk of MI. Additionally, tfCAS patients were more likely to have worse outcomes after weighting for symptom status. Finally, although patients with a reduced eGFR have worse outcomes than their healthy peers, this analysis shows that the majority of patients survive long enough to benefit from the potential stroke risk reduction provided by all revascularization procedures.

The association between sex and outcomes after thoracic endovascular repair for acute type B aortic dissection.

OBJECTIVE: Prior literature has found worse outcomes for female patients after endovascular repair of abdominal aortic aneurysm and mixed findings after thoracic endovascular aortic repair (TEVAR) for thoracic aortic aneurysm. However, the influence of sex on outcomes after TEVAR for acute type B aortic dissection (aTBAD) is not fully elucidated. METHODS: We identified patients who underwent TEVAR for aTBAD (<30 days) in the Vascular Quality Initiative from 2014 to 2022. We excluded patients with an entry tear or stent seal within the ascending aorta or aortic arch and patients with an unknown proximal tear location. Included patients were stratified by biological sex, and we analyzed perioperative outcomes and 5-year mortality with multivariable logistic regression and Cox regression analysis, respectively. Furthermore, we analyzed adjusted variables for interaction with female sex. RESULTS: We included 1626 patients, 33% of whom were female. At presentation, female patients were significantly older (65 [interquartile range: 54, 75] years vs 56 [interquartile range: 49, 68] years; P = .01). Regarding indications for repair, female patients had higher rates of pain (85% vs 80%; P = .02) and lower rates of malperfusion (23% vs 35%; P < .001), specifically mesenteric, renal, and lower limb malperfusion. Female patients had a lower proportion of proximal repairs in zone 2 (39% vs 48%; P < .01). After TEVAR for aTBAD, female sex was associated with comparable odds of perioperative mortality to males (8.1 vs 9.2%; adjusted odds ratio [aOR]: 0.79 [95% confidence interval (CI): 0.51-1.20]). Regarding perioperative complications, female sex was associated with lower odds for cardiac complications (2.3% vs 4.7%; aOR: 0.52 [95% CI: 0.26-0.97]), but all other complications were comparable between sexes. Compared with male sex, female sex was associated with similar risk for 5-year mortality (26% vs 23%; adjusted hazard ratio: 1.01 [95% CI: 0.77-1.32]). On testing variables for interaction with sex, female sex was associated with lower perioperative and 5-year mortality at older ages relative to males (aOR: 0.96 [0.93-0.99] | adjusted hazard ratio: 0.97 [0.95-0.99]) and higher odds of perioperative mortality when mesenteric malperfusion was present (OR: 2.71 [1.04-6.96]). CONCLUSIONS: Female patients were older, less likely to have complicated dissection, and had more distal proximal landing zones. After TEVAR for aTBAD, female sex was associated with similar perioperative and 5-year mortality to male sex, but lower odds of in-hospital cardiac complications. Interaction analysis showed that females were at additional risk for perioperative mortality when mesenteric ischemia was present. These data suggest that TEVAR for aTBAD overall has a similar safety profile in females as it does for males.

Lifelike PixelPrint phantoms for assessing clinical image quality and dose reduction capabilities of a deep learning CT reconstruction algorithm.

Deep learning CT reconstruction (DLR) has become increasingly popular as a method for improving image quality and reducing radiation exposure. Due to their nonlinear nature, these algorithms result in resolution and noise performance which are object-dependent. Therefore, traditional CT phantoms, which lack realistic tissue morphology, have become inadequate for assessing clinical imaging performance. We propose to utilize 3D-printed PixelPrint phantoms, which exhibit lifelike attenuation profiles, textures, and structures, as a better tool for evaluating DLR performance. In this study, we evaluate a DLR algorithm (Precise Image (PI), Philips Healthcare) using a custom PixelPrint lung phantom and perform head-to-head comparisons between DLR, iterative reconstruction, and filtered back projection (FBP) with scans acquired at a broad range of radiation exposures (CTDIvol: 0.5, 1, 2, 4, 6, 9, 12, 15, 19, and 20 mGy). We compared the performance of each resultant image using noise, peak signal to noise ratio (PSNR), structural similarity index (SSIM), feature-based similarity index (FSIM), information theoretic-based statistic similarity measure (ISSM) and universal image quality index (UIQ). Iterative reconstruction at 9 mGy matches the image quality of FBP at 12 mGy (diagnostic reference level) for all metrics, demonstrating a dose reduction capability of 25%. Meanwhile, DLR matches the image quality of diagnostic reference level FBP images at doses between 4 - 9 mGy, demonstrating dose reduction capabilities between 25% and 67%. This study shows that DLR allows for reduced radiation dose compared to both FBP and iterative reconstruction without compromising image quality. Furthermore, PixelPrint phantoms offer more realistic testing conditions compared to traditional phantoms in the evaluation of novel CT technologies. This, in turn, promotes the translation of new technologies, such as DLR, into clinical practice.

Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses.

The ventral tegmental area (VTA) contains projection neurons that release the neurotransmitters dopamine, GABA, and/or glutamate from distal synapses. VTA also contains GABA neurons that synapse locally on to VTA dopamine neurons, synapses widely credited to a population of so-called VTA interneurons. Interneurons in cortex, striatum, and elsewhere have well-defined morphological features, physiological properties, and molecular markers, but such features have not been clearly described in VTA. Indeed, there is scant evidence that local and distal synapses originate from separate populations of VTA GABA neurons. In this study we tested whether several markers expressed in non-dopamine VTA neurons are selective markers of interneurons, defined as neurons that synapse locally but not distally. Challenging previous assumptions, we found that VTA neurons genetically defined by expression of parvalbumin, somatostatin, neurotensin, or mu-opioid receptor project to known VTA targets including nucleus accumbens, ventral pallidum, lateral habenula, and prefrontal cortex. Moreover, we provide evidence that VTA GABA and glutamate projection neurons make functional inhibitory or excitatory synapses locally within VTA. These findings suggest that local collaterals of VTA projection neurons could mediate functions prior attributed to VTA interneurons. This study underscores the need for a refined understanding of VTA connectivity to explain how heterogeneous VTA circuits mediate diverse functions related to reward, motivation, or addiction.

MFN2 coordinates mitochondria motility with α-tubulin acetylation and this regulation is disrupted in CMT2A.

Mitofusin-2 (MFN2), a large GTPase residing in the mitochondrial outer membrane and mutated in Charcot-Marie-Tooth type 2 disease (CMT2A), is a regulator of mitochondrial fusion and tethering with the ER. The role of MFN2 in mitochondrial transport has however remained elusive. Like MFN2, acetylated microtubules play key roles in mitochondria dynamics. Nevertheless, it is unknown if the α-tubulin acetylation cycle functionally interacts with MFN2. Here, we show that mitochondrial contacts with microtubules are sites of α-tubulin acetylation, which occurs through MFN2-mediated recruitment of α-tubulin acetyltransferase 1 (ATAT1). This activity is critical for MFN2-dependent regulation of mitochondria transport, and axonal degeneration caused by CMT2A MFN2 associated R94W and T105M mutations may depend on the inability to release ATAT1 at sites of mitochondrial contacts with microtubules. Our findings reveal a function for mitochondria in α-tubulin acetylation and suggest that disruption of this activity plays a role in the onset of MFN2-dependent CMT2A.

Predictors of prolonged length of stay after elective carotid revascularization.

OBJECTIVE: Postoperative day-one discharge is used as a quality-of-care indicator after carotid revascularization. This study identifies predictors of prolonged length of stay (pLOS), defined as a postprocedural LOS of >1 day, after elective carotid revascularization. METHODS: Patients undergoing carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TFCAS) in the Vascular Quality Initiative between 2016 and 2022 were included in this analysis. Multivariable logistic regression analysis was used to identify predictors of pLOS, defined as a postprocedural LOS of >1 day, after each procedure. RESULTS: A total of 118,625 elective cases were included. pLOS was observed in nearly 23.2% of patients undergoing carotid revascularization. Major adverse events, including neurological, cardiac, infectious, and bleeding complications, occurred in 5.2% of patients and were the most significant contributor to pLOS after the three procedures. Age, female sex, non-White race, insurance status, high comorbidity index, prior ipsilateral CEA, non-ambulatory status, symptomatic presentation, surgeries occurring on Friday, and postoperative hypo- or hypertension were significantly associated with pLOS across all three procedures. For CEA, additional predictors included contralateral carotid artery occlusion, preoperative use of dual antiplatelets and anticoagulation, low physician volume (<11 cases/year), and drain use. For TCAR, preoperative anticoagulation use, low physician case volume (<6 cases/year), no protamine use, and post-stent dilatation intraoperatively were associated with pLOS. One-year analysis showed a significant association between pLOS and increased mortality for all three procedures; CEA (hazard ratio [HR],1.64; 95% confidence interval [CI], 1.49-1.82), TCAR (HR,1.56; 95% CI, 1.35-1.80), and TFCAS (HR, 1.33; 95%CI, 1.08-1.64) (all P < .05). CONCLUSIONS: A postoperative LOS of more than 1 day is not uncommon after carotid revascularization. Procedure-related complications are the most common drivers of pLOS. Identifying patients who are risk for pLOS highlights quality improvement strategies that can optimize short and 1-year outcomes of patients undergoing carotid revascularization.

Seven years of the transcarotid artery revascularization surveillance project, comparison to transfemoral stenting and endarterectomy.

OBJECTIVE: This study utilizes the latest data from the Vascular Quality Initiative (VQI), which now encompasses over 50,000 transcarotid artery revascularization (TCAR) procedures, to offer a sizeable dataset for comparing the effectiveness and safety of TCAR, transfemoral carotid artery stenting (tfCAS), and carotid endarterectomy (CEA). Given this substantial dataset, we are now able to compare outcomes overall and stratified by symptom status across revascularization techniques. METHODS: Utilizing VQI data from September 2016 to August 2023, we conducted a risk-adjusted analysis by applying inverse probability of treatment weighting to compare in-hospital outcomes between TCAR vs tfCAS, CEA vs tfCAS, and TCAR vs CEA. Our primary outcome measure was in-hospital stroke/death. Secondary outcomes included myocardial infarction and cranial nerve injury. RESULTS: A total of 50,068 patients underwent TCAR, 25,361 patients underwent tfCAS, and 122,737 patients underwent CEA. TCAR patients were older, more likely to have coronary artery disease, chronic kidney disease, and undergo coronary artery bypass grafting/percutaneous coronary intervention as well as prior contralateral CEA/CAS compared with both CEA and tfCAS. TfCAS had higher odds of stroke/death when compared with TCAR (2.9% vs 1.6%; adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.65-2.06; P < .001) and CEA (2.9% vs 1.3%; aOR, 2.21; 95% CI, 2.01-2.43; P < .001). CEA had slightly lower odds of stroke/death compared with TCAR (1.3% vs 1.6%; aOR, 0.83; 95% CI, 0.76-0.91; P < .001). TfCAS had lower odds of cranial nerve injury compared with TCAR (0.0% vs 0.3%; aOR, 0.00; 95% CI, 0.00-0.00; P < .001) and CEA (0.0% vs 2.3%; aOR, 0.00; 95% CI, 0.0-0.0; P < .001) as well as lower odds of myocardial infarction compared with CEA (0.4% vs 0.6%; aOR, 0.67; 95% CI, 0.54-0.84; P < .001). CEA compared with TCAR had higher odds of myocardial infarction (0.6% vs 0.5%; aOR, 1.31; 95% CI, 1.13-1.54; P < .001) and cranial nerve injury (2.3% vs 0.3%; aOR, 9.42; 95% CI, 7.78-11.4; P < .001). CONCLUSIONS: Although tfCAS may be beneficial for select patients, the lower stroke/death rates associated with CEA and TCAR are preferred. When deciding between CEA and TCAR, it is important to weigh additional procedural factors and outcomes such as myocardial infarction and cranial nerve injury, particularly when stroke/death rates are similar. Additionally, evaluating subgroups that may benefit from one procedure over another is essential for informed decision-making and enhanced patient care in the treatment of carotid stenosis.

Endovascular Inferior Vena Cava Filters Placed in Duplicated Inferior Vena Cava Syndrome.

Duplicated inferior vena cava (D-IVC) is a relatively rare anatomical anomaly. Clinically, these anomalies are incidentally found on computed tomography (CT) or magnetic resonance imaging (MRI). Lack of pre-operative identification of this congenital malformation can lead to incomplete protection against thromboembolism or hemorrhage. We present a case of a 71-year-old male with a duplicated inferior vena cava who underwent insertion of bilateral inferior vena cava filters for deep vein thrombosis (DVT) management.