In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates.

Gene-editing technologies, which include the CRISPR-Cas nucleases1-3 and CRISPR base editors4,5, have the potential to permanently modify disease-causing genes in patients6. The demonstration of durable editing in target organs of nonhuman primates is a key step before in vivo administration of gene editors to patients in clinical trials. Here we demonstrate that CRISPR base editors that are delivered in vivo using lipid nanoparticles can efficiently and precisely modify disease-related genes in living cynomolgus monkeys (Macaca fascicularis). We observed a near-complete knockdown of PCSK9 in the liver after a single infusion of lipid nanoparticles, with concomitant reductions in blood levels of PCSK9 and low-density lipoprotein cholesterol of approximately 90% and about 60%, respectively; all of these changes remained stable for at least 8 months after a single-dose treatment. In addition to supporting a 'once-and-done' approach to the reduction of low-density lipoprotein cholesterol and the treatment of atherosclerotic cardiovascular disease (the leading cause of death worldwide7), our results provide a proof-of-concept for how CRISPR base editors can be productively applied to make precise single-nucleotide changes in therapeutic target genes in the liver, and potentially in other organs.

Unfermented ß-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. METHODS: Colonic biopsies cultured ex vivo and cell lines in vitro were incubated with oligofructose (5 g/L), or fermentation supernatants (24-hour anaerobic fermentation) and immune responses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative polymerase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classification of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. RESULTS: Unfermented dietary ß-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining ß-fructan supplementation. The proinflammatory response to intact ß-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of ß-fructans by human gut whole microbiota cultures reduced the proinflammatory response, but only when microbes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. CONCLUSION: Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health database (clinicaltrials.gov identification number NCT02865707).

Effectiveness of Very Brief Advice on Tobacco Cessation: A Systematic Review and Meta-Analysis.

BACKGROUND: Very brief advice (VBA; ≤ 3 min) on quitting is practical and scalable during brief medical interactions with patients who smoke. This study aims to synthesize the effectiveness of VBA for smoking cessation and summarize the implementation strategies. METHODS: We searched randomized controlled trials aiming at tobacco abstinence and comparing VBA versus no smoking advice or no contact from Medline, Embase, CINAHL, Cochrane Library, PsycInfo databases, six Chinese databases, two trial registries ClinicalTrials.gov and WHO-ICTRP from inception to September 30, 2023. Grading of Recommendations, Assessment, Development, and Evaluations framework was used to assess the certainty of the evidence of the meta-analytic findings. The outcomes were self-reported long-term tobacco abstinence at least 6 months after treatment initiation, earlier than 6 months after treatment initiation, and quit attempts. Effect sizes were computed as risk ratio (RR) with 95% CI using frequentist random-effect models. DATA SYNTHESIS: Thirteen randomized controlled trials from 15 articles (n = 26,437) were included. There was moderate-certainty evidence that VBA significantly increased self-reported tobacco abstinence at ≥ 6 months in the adjusted model (adjusted risk ratio ARR 1.17, 95% CI: 1.07-1.27) compared with controls. The sensitivity analysis showed similar results when abstinence was verified by biochemical validation (n = 6 studies, RR 1.53, 95% CI 0.98-2.40). There was high-certainty evidence that VBA significantly increased abstinence at < 6 months (ARR 1.22, 95% CI: 1.01-1.47). Evidence of effect on quit attempts (ARR 1.03, 95% CI 0.97-1.08) was of very low certainty. DISCUSSION: VBA delivered in a clinical setting is effective in increasing self-reported tobacco abstinence, which provides support for wider adoption in clinical practice.

Fatigue Test Method to Evaluate the 50 Year Durability of Venous Stents.

OBJECTIVE: Iliofemoral venous obstructive disease can result in significant, potentially debilitating symptoms that can negatively affect quality of life. Unlike arterial disease, patients with deep venous disease have a significantly lower median age, therefore the need for long term stent patency becomes a matter of decades rather than years. Furthermore, iliofemoral lesions frequently require stent placement across the inguinal ligament. Such stents are subject to dynamic stress from leg movement and associated concerns for device fatigue, resulting in stent fracture. The aim of this study was to describe an in vitro 50 year stent fatigue test method designed to assess durability against dynamic stress induced device fracture. METHODS: Through literature review, cadaver studies, and computer modelling, the most challenging loading was confirmed to be hip flexion across the inguinal ligament. This occurs when the patient adjusts between a seated and standing position. Sit to stand hip flexion at the inguinal ligament was effectively simulated on the bench in this in vitro experimental study. RESULTS: When tested under challenge parameters, hip flexion was reliably found to cause fractures in non-venous nitinol stents. However, a dedicated self expanding nitinol venous stent, engineered for improved durability, underwent up to 50 years of simulated loading on the bench with 15% (3/20) of stents experiencing fractures at 50 years, compared with fractures in 35% (14/40) of non-venous stents tested to 1.4 years; no statistical testing was performed as durations do not match and the objective was to demonstrate the test method). CONCLUSION: The presented fatigue test method is a suitable approach for evaluating the durability of stents intended for venous use. Venous stents demonstrated superior fatigue resistance compared with non-venous stents via in vitro hip flexion testing.

Clinical report: Virtual reality enables comparable contrast sensitivity measurements to in-office testing (pilot study).

SIGNIFICANCE: Vision health disparities largely stem from inaccessibility to vision specialists. To improve patient access to vision tests and to expedite clinical workflows, it is important to assess the viability of virtual reality (VR) as a modality for evaluating contrast sensitivity. PURPOSE: This study aimed to assess the validity of a VR version of the Pelli-Robson contrast sensitivity test by comparing its results with those of the corresponding in-office test. METHODS: Twenty-eight participants (mean ± standard deviation age, 37.3 ± 20.5 years) with corrected vision were recruited for testing on a voluntary basis with randomized administration of the in-office test followed by the VR analog or vice versa. Nineteen participants took each test twice to assess test-retest consistency in each modality. Virtual reality tests were conducted on a commercial Pico Neo Eye 2 VR headset, which has a 4K screen resolution. The environment for both tests was controlled by the participant for location and lighting. RESULTS: Similar sensitivity scores were obtained between testing modalities in both the right (n = 28 participants; Wilcoxon match-paired signed rank [SR], p=0.7) and left eyes (n = 28 participants; Wilcoxon match-paired SR, p=0.7). In addition, similar test-retest scores were found for VR (n = 19 participants; Wilcoxon match-paired SR, p=1.0) or in-office (n = 19 participants; Wilcoxon match-paired SR, p=1.0) tests. Virtual reality Pelli-Robson results correlated well with in-office test results in variably diseased participants (n = 14 eyes from 7 participants, R2 = 0.93, p<0.0001). CONCLUSIONS: In this pilot trial, we demonstrated that VR Pelli-Robson measurements of corrected vision align with those of in-office modalities, suggesting that this may be a reliable method of implementing this test in a more interactive and accessible manner.

In vitro quantification of stent-graft behaviour during chimney thoracic endovascular aortic repair.

OBJECTIVE: To quantify dynamic gutter phenomena and endograft deformations during double chimney thoracic endovascular aortic repair (ch-TEVAR) in a physiological model of the thoracic aorta subjected to pulsatile haemodynamic conditions. METHODS: Two in vitro procedures revascularizing the brachiocephalic trunk and left common carotid artery were performed representing both balloon-expandable (BE, Ankura-BeGraft) and self-expandable (SE, Ankura-Viabahn) double ch-TEVAR configurations. Retrospectively gated computed tomography (CT) was used to evaluate endograft behaviour. Device interactions were characterised according to gutter volume, gutter surface deviation, and endograft deformation (D-ratio) at end-diastolic and peak-systolic aortic pressure. RESULTS: Use of BE chimney grafts resulted in three times total gutter volume compared to SE chimney grafts. Gutter volumes were observed to vary dynamically between the end-diastolic and peak-systolic phases of the cardiac cycle, with the most substantial change associated with the BE configuration. Chimney graft deformations were dependent on device type, with SE devices exhibiting up to twice the deformation as BE devices. When adjacent, SE chimney grafts were observed to support each other, and thus tended towards a more consistently circular shape. CONCLUSION: Gutter and chimney graft behaviour were dependent on device type, and exhibited both spatial and temporal variability. This study emphasises notable differences between BE and SE double ch-TEVAR configurations which should be considered when evaluating risk of endoleak. The findings reported here also support the use of gated CT to better identify device-related complications with ch-TEVAR, and can be used in the design of next generation devices.

Can GPT-4 revolutionize otolaryngology? Navigating opportunities and ethical considerations.

Otolaryngologists can enhance workflow efficiency, provide better patient care, and advance medical research and education by integrating artificial intelligence (AI) into their practices. GPT-4 technology is a revolutionary and contemporary example of AI that may apply to otolaryngology. The knowledge of otolaryngologists should be supplemented, not replaced when using GPT-4 to make critical medical decisions and provide individualized patient care. In our thorough examination, we explore the potential uses of the groundbreaking GPT-4 technology in the field of otolaryngology, covering aspects such as potential outcomes and technical boundaries. Additionally, we delve into the intricate and intellectually challenging dilemmas that emerge when incorporating GPT-4 into otolaryngology, considering the ethical considerations inherent in its implementation. Our stance is that GPT-4 has the potential to be very helpful. Its capabilities, which include aid in clinical decision-making, patient care, and administrative job automation, present exciting possibilities for enhancing patient outcomes, boosting the efficiency of healthcare delivery, and enhancing patient experiences. Even though there are still certain obstacles and limitations, the progress made so far shows that GPT-4 can be a valuable tool for modern medicine. GPT-4 may play a more significant role in clinical practice as technology develops, helping medical professionals deliver high-quality care tailored to every patient's unique needs.

A phylogenomic analysis of Limosilactobacillus reuteri reveals ancient and stable evolutionary relationships with rodents and birds and zoonotic transmission to humans.

BACKGROUND: Gut microbes play crucial roles in the development and health of their animal hosts. However, the evolutionary relationships of gut microbes with vertebrate hosts, and the consequences that arise for the ecology and lifestyle of the microbes are still insufficiently understood. Specifically, the mechanisms by which strain-level diversity evolved, the degree by which lineages remain stably associated with hosts, and how their evolutionary history influences their ecological performance remain a critical gap in our understanding of vertebrate-microbe symbiosis. RESULTS: This study presents the characterization of an extended collection of strains of Limosilactobacillus reuteri and closely related species from a wide variety of hosts by phylogenomic and comparative genomic analyses combined with colonization experiments in mice to gain insight into the long-term evolutionary relationship of a bacterial symbiont with vertebrates. The phylogenetic analysis of L. reuteri revealed early-branching lineages that primarily consist of isolates from rodents (four lineages) and birds (one lineage), while lineages dominated by strains from herbivores, humans, pigs, and primates arose more recently and were less host specific. Strains from rodent lineages, despite their phylogenetic divergence, showed tight clustering in gene-content-based analyses. These L. reuteri strains but not those ones from non-rodent lineages efficiently colonize the forestomach epithelium of germ-free mice. The findings support a long-term evolutionary relationships of L. reuteri lineages with rodents and a stable host switch to birds. Associations of L. reuteri with other host species are likely more dynamic and transient. Interestingly, human isolates of L. reuteri cluster phylogenetically closely with strains from domesticated animals, such as chickens and herbivores, suggesting zoonotic transmissions. CONCLUSIONS: Overall, this study demonstrates that the evolutionary relationship of a vertebrate gut symbiont can be stable in particular hosts over time scales that allow major adaptations and specialization, but also emphasizes the diversity of symbiont lifestyles even within a single bacterial species. For L. reuteri, symbiont lifestyles ranged from autochthonous, likely based on vertical transmission and stably aligned to rodents and birds over evolutionary time, to allochthonous possibly reliant on zoonotic transmission in humans. Such information contributes to our ability to use these microbes in microbial-based therapeutics.

Renovisceral artery alterations due to branched endovascular aortic repair and respiratory-induced deformations.

OBJECTIVE: This study quantified respiratory-induced dynamics of branch vessels before and after thoracoabdominal aortic aneurysm (TAAA) branched endovascular aneurysm repair (bEVAR). METHODS: Patients with TAAA were recruited prospectively and treated with bEVAR, predominantly with Zenith t-Branch and BeGraft Peripheral PLUS bridging stents. Using SimVascular software, three-dimensional geometric models of the vessels and implants were constructed from computed tomography angiograms during both inspiratory and expiratory breath-holds, preoperatively and postoperatively. From these models, branch take-off angles, end-stent angles (transition from distal end of stent to native artery), and curvatures were computed. Paired, two-tailed t tests were performed to compare inspiratory vs expiratory geometry and pre- vs postoperative deformations. RESULTS: We evaluated 52 (12 celiac arteries [CA], 15 superior mesenteric arteries [SMA], and 25 renal arteries [RA]) branched renovisceral vessels with bridging stents in 15 patients. Implantation of bridging stents caused branch take-off angle to shift inferiorly in the SMA (P = .015) and RA (P = .014) and decreased the respiratory-induced branch angle motion in the CA and SMA by approximately 50%. End-stent angle increased from before to after bEVAR for the CA (P = .005), SMA (P = .020), and RA (P < .001); however, respiratory-induced deformation was unchanged. Bridging stents did not experience significant bending owing to respiration. CONCLUSIONS: The decrease in respiratory-induced deformation of branch take-off angle from before to after bEVAR should decrease the risk of device disengagement and endoleak. The unchanging respiratory-induced end-stent bending, from before to after bEVAR, means that bEVAR maintains native vessel dynamics distal to the bridging stents. This factor minimizes the risk of tissue irritation owing to respiratory cycles, boding well for branch vessel patency. The longer bridging stent paths associated with bEVAR may enable smoother paths subject to less dynamic bending, and potentially lower fatigue risk, compared with fenestrated EVAR.

Reasons for ineligibility for clinical trials of patients with medication-resistant epilepsy.

Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for exclusion. Among 212 patients with medication-resistant epilepsy, 144 and 28 patients met the criteria for focal or generalized onset epilepsy, respectively. Overall, 9.4% (n = 20) patients were eligible for trials (19 focal onset and one generalized onset). Most patients were excluded from the study due to insufficient seizure frequency (58% of focal onset, 55% of generalized onset). A small proportion of patients with medication-resistant epilepsy were eligible for trials based on common selection criteria. These eligible patients may not be representative of the general population of patients with medication-resistant epilepsy. Insufficient seizure frequency was the most common reason for exclusion.

Intensive sampling of the umbra and penumbra improves clinically significant prostate cancer detection and reduces risk of grade group upgrading at radical prostatectomy.

PURPOSE: Our objective is to evaluate the clinically significant prostate cancer detection rate of overlapping and perilesional systematic biopsy cores and its impact on grade group (GG) concordance at prostatectomy. MATERIALS AND METHODS: Biopsy maps of those undergoing MRI-targeted (TB) and systematic biopsy (SB) were reviewed to reclassify systematic cores. Perilesional (PL) cores were defined as adjacent cores within 10 mm of the target lesion ("penumbra") whilst overlap (OL) cores were defined as cores within the ROI itself ("umbra"). All other cores were designated as distant cores (DC). The incremental csPCa detection rate (GG ≥ 2) and the rate of GG upgrading on prostatectomy as OL, PL and DC sequentially added to TB were determined. RESULTS: Out of the 398 patients included, the median number of OL and PL cores was 5 (IQR 4-7) and 5 (IQR 3-6) respectively. OL cores detected more csPCa than PL cores (31 vs 16%, p < 0.001). OL and PL cores improved the csPCa detection rate of TB from 34 to 39% (p < 0.001) and 37% (p = 0.001) respectively. TB+OL+PL had greater csPCa detection compared to just TB+OL (41 vs 39%, p = 0.016) and TB+PL (41 vs 37%, p < 0.001). Of the 104 patients who underwent prostatectomy, GG upgrading rate for TB+OL+PL was lower compared to TB (21 vs 36%, p < 0.001) and was not significantly different compared to TB+OL+PL+DC (21 vs 19%, p = 0.500). CONCLUSION: A biopsy strategy incorporating both intensive sampling of the umbra and penumbra improved csPCa detection and reduced risk of GG upgrading at prostatectomy.

Cardiac Pulsatile Helical Deformation of the Thoracic Aorta Before and After Thoracic Endovascular Aortic Repair of Type B Dissections.

PURPOSE: Type B aortic dissections propagate with either achiral (nonspiraling) or right-handed chiral (spiraling) morphology, have mobile dissection flaps, and are often treated with thoracic endovascular aortic repair (TEVAR). We aim to quantify cardiac-induced helical deformation of the true lumen of type B aortic dissections before and after TEVAR. MATERIAL AND METHODS: Retrospective cardiac-gated computed tomography (CT) images before and after TEVAR of type B aortic dissections were used to construct systolic and diastolic 3-dimensional (3D) surface models, including true lumen, whole lumen (true+false lumens), and branch vessels. This was followed by extraction of true lumen helicity (helical angle, twist, and radius) and cross-sectional (area, circumference, and minor/major diameter ratio) metrics. Deformations between systole and diastole were quantified, and deformations between pre- and post-TEVAR were compared. RESULTS: Eleven TEVAR patients (59.9±4.6 years) were included in this study. Pre-TEVAR, there were no significant cardiac-induced deformations of helical metrics; however, post-TEVAR, significant deformation was observed for the true lumen proximal angular position. Pre-TEVAR, cardiac-induced deformations of all cross-sectional metrics were significant; however, only area and circumference deformations remained significant post-TEVAR. There were no significant differences of pulsatile deformation from pre- to post-TEVAR. Variance of proximal angular position and cross-sectional circumference deformation decreased after TEVAR. CONCLUSION: Pre-TEVAR, type B aortic dissections did not exhibit significant helical cardiac-induced deformation, indicating that the true and false lumens move in unison (do not move with respect to each other). Post-TEVAR, true lumens exhibited significant cardiac-induced deformation of proximal angular position, suggesting that exclusion of the false lumen leads to greater rotational deformations of the true lumen and lack of true lumen major/minor deformation post-TEVAR means that the endograft promotes static circularity. Population variance of deformations is muted after TEVAR, and dissection acuity influences pulsatile deformation while pre-TEVAR chirality does not. CLINICAL IMPACT: Description of thoracic aortic dissection helical morphology and dynamics, and understanding the impact of thoracic endovascular aortic repair (TEVAR) on dissection helicity, are important for improving endovascular treatment. These findings provide nuance to the complex shape and motion of the true and false lumens, enabling clinicians to better stratify dissection disease. The impact of TEVAR on dissection helicity provides a description of how treatment alters morphology and motion, and may provide clues for treatment durability. Finally, the helical component to endograft deformation is important to form comprehensive boundary conditions for testing and developing new endovascular devices.

Pulsatile Deformations of a Conformable Descending Thoracic Aortic Endograft in Aneurysm, Dissection, and Blunt Traumatic Aortic Injury Patients.

PURPOSE: This study presents analytic techniques to quantify cardiac pulsatility-induced deformations of thoracic aortic endografts in patients with thoracic aortic aneurysm (TAA), dissection (TAD), and blunt thoracic aortic injury (BTAI) after thoracic endovascular aortic repair (TEVAR). TECHNIQUE: We analyzed 19 image data sets from 14 patients treated for TAA, TAD, and BTAI with cardiac-gated post-TEVAR CTs. Systolic and diastolic geometric models were constructed and diametric, axial, and bending deformations were quantified. For patients with cardiac-gated pre-op scans, the damping of pulsatile diametric distension was computed. Maximum localized diametric distension was 2.4±1.0%, 4.2±1.7%, and 5.5±1.6%, and axial deformation was 0.0±0.1%, -0.1±0.3%, and 1.1±0.6% in the endografts of TAA, TAD, and BTAI cohorts, respectively. Diametric distension damping from pre- to post-TEVAR was ~50%. Diametric and bending deformations were localized at certain axial positions on the endograft, and the inner curve bends more than the centerline, especially adjacent to overlapping regions. CONCLUSION: The presented techniques support investigation of multi-axial endograft deformations between disease causes and geometric locations on the device. Discretized quantification of deformation is needed to define device fatigue testing conditions and predict device durability in patients. CLINICAL IMPACT: This study demonstrates analytic techniques to quantify discretized deformation of thoracic endografts. Cardiac-resolved computed tomography is sometimes acquired for surgical planning and follow-up, however, the dynamic data are not typically used to quantify pulsatile deformations. Our analytic techniques extract the centerline and surface geometry of the stented thoracic aorta during the cardiac cycle, which are used to quantify diametric, axial, and bending deformations to provide better understanding of device durability and impact on the native anatomy.

Ascending Aortic Endograft and Thoracic Aortic Deformation After Ascending Thoracic Endovascular Aortic Repair.

PURPOSE: We aim to quantify multiaxial cardiac pulsatility-induced deformation of the thoracic aorta after ascending thoracic endovascular aortic repair (TEVAR) as a part of the GORE ARISE Early Feasibility Study. MATERIALS AND METHODS: Fifteen patients (7 females and 8 males, age 73±9 years) with ascending TEVAR underwent computed tomography angiography with retrospective cardiac gating. Geometric modeling of the thoracic aorta was performed; geometric features including axial length, effective diameter, and centerline, inner surface, and outer surface curvatures were quantified for systole and diastole; and pulsatile deformations were calculated for the ascending aorta, arch, and descending aorta. RESULTS: From diastole to systole, the ascending endograft exhibited straightening of the centerline (0.224±0.039 to 0.217±0.039 cm-1, p<0.05) and outer surface (0.181±0.028 to 0.177±0.029 cm-1, p<0.05) curvatures. No significant changes were observed for inner surface curvature, diameter, or axial length in the ascending endograft. The aortic arch did not exhibit any significant deformation in axial length, diameter, or curvature. The descending aorta exhibited small but significant expansion of effective diameter from 2.59±0.46 to 2.63±0.44 cm (p<0.05). CONCLUSION: Compared with the native ascending aorta (from prior literature), ascending TEVAR damps axial and bending pulsatile deformations of the ascending aorta similar to how descending TEVAR damps descending aortic deformations, while diametric deformations are damped to a greater extent. Downstream diametric and bending pulsatility of the native descending aorta was muted compared with that in patients without ascending TEVAR (from prior literature). Deformation data from this study can be used to evaluate the mechanical durability of ascending aortic devices and inform physicians about the downstream effects of ascending TEVAR to help predict remodeling and guide future interventional strategies. CLINICAL IMPACT: This study quantified local deformations of both stented ascending and native descending aortas to reveal the biomechanical impact of ascending TEVAR on the entire thoracic aorta, and reported that the ascending TEVAR muted cardiac-induced deformation of the stented ascending aorta and native descending aorta. Understanding of in vivo deformations of the stented ascending aorta, aortic arch and descending aorta can inform physicians about the downstream effects of ascending TEVAR. Notable reduction of compliance may lead to cardiac remodeling and long-term systemic complications. This is the first report which included dedicated deformation data regarding ascending aortic endograft from clinical trial.

Impact of renal chimney intra-aortic stent length on branch and end-stent angle in chimney endovascular aneurysm repair and endovascular aneurysm sealing configurations.

OBJECTIVE: Practice patterns and durability of parallel stent graft techniques in complex endovascular aneurysm repair (EVAR) remain poorly defined. We aimed to quantify and compare the impact of renal chimney intra-aortic stent length (IASL) on geometric deformations of renal arteries in complex EVAR. METHODS: Thirty-eight nonconsecutive patients underwent EVAR utilizing parallel stent graft techniques (chimney EVAR [chEVAR], n = 28; chimney endovascular aneurysm sealing [chEVAS], n = 10) between 2010 and 2016. A total of 59 renal chimney stent grafts were used. Geometric quantification was derived from three-dimensional model-based centerline extraction. Renal chimney intra-aortic stent length (IASL) was defined as the length of chimney stent that extended from the proximal edge of the chimney stent to the ostium of the corresponding renal artery. RESULTS: Mean IASL for both left and right renal arteries in the cohort was 35.7 mm. Renal arteries containing chimney IASL <30 mm trended toward a greater branch angle (135.4 vs. 127.8°, p = .06). Left renal arteries showed significantly greater branch angle among those with IASL <40 mm (135.5 vs. 121.7°, p = .045). Mean IASL for renal arteries in chEVAR was significantly longer compared to chEVAS (39.2 vs. 26.3 mm, p = .003). No difference was noted in overall branch angle or end-stent angle based on procedure type. ChEVAR with IASL <30 mm had significantly greater end-stent angle (48.2 vs. 33.5°, p = .03). In contrast, chEVAS patients showed no difference in end-stent angle based on IASL thresholds, but did have significantly greater branch angle among those with IASL <30 mm when grouped by both all renal arteries (133.5 vs. 113.5°, p = .004) and right renal arteries (134.3 vs. 111.6°, p = .02). CONCLUSIONS: Renal chimney stents with longer IASL appear to exhibit less renal artery deformation, suggesting a more gradual and perpendicular transition of the chimney stent across the renal ostium.

Eponyms of Upper Extremity Surgical Approaches: A Historical Perspective.

Numerous eponymous surgical approaches are used in the treatment of upper extremity pathology, especially in the trauma setting. Knowledge of anatomy and planes is critical to maximize visualization, achieve anatomic reduction, and avoid iatrogenic injury to critical neurovascular structures. Understanding the history of these commonly used eponymous upper extremity approaches (Kaplan, Kocher, Boyd, Thompson, and Henry) provides a humanistic perspective of each of these surgeons' narratives, which shaped their description of anatomic approaches that have forever changed the course of hand and upper extremity surgeries, providing greater means and possibilities to treat our patients.

Trans-fat labelling information on prepackaged foods and beverages sold in Hong Kong in 2019.

OBJECTIVE: To examine the labelling status of trans-fat of pre-packaged foods sold in Hong Kong. DESIGN: Data from 19 027 items in the 2019 FoodSwitch Hong Kong database were used. Ingredient lists were screened to identify specific (e.g. partially hydrogenated vegetable oil, PHVO) and non-specific trans-fat ingredient indicators (e.g. hydrogenated oil). Trans-fat content was obtained from the on-pack nutrition labels, which was converted into proportion of total fat (%total fat). Descriptive statistics were calculated for trans-fat content and the number of specific, non-specific and total trans-fat ingredients indicators found on the ingredients lists. Comparisons were made between regions using one-way ANOVA and χ2 for continuous and categorical variables, respectively. SETTING: Cross-sectional audit. PARTICIPANTS: Not applicable. RESULTS: A total of 729 items (3·8 % of all products) reported to contain industrially produced trans-fat, with a median of 0·4 g/100 g or 100 ml (interquartile range (IQR): 0·1-0·6) and 1·2 %totalfat (IQR: 0·6-2·9). 'Bread and bakery products' had the highest proportion of items with industrially produced trans-fat (18·9 %). 'Non-alcoholic beverages' had the highest proportion of products of 'false negatives' labelling (e.g. labelled as 0 trans-fat but contains PHVO; 59·3 %). The majority of products with trans-fat indicator originated from Asia (70 %). CONCLUSIONS: According to the labelling ∼4 % of pre-packaged food and beverages sold in Hong Kong in 2019 contained industrially produced trans-fat, and a third of these had trans-fat >2 %total fat. The ambiguous trans-fat labelling in Hong Kong may not effectively assist consumers in identifying products free from industrially produced trans-fat.

Improving PMUT Receive Sensitivity via DC Bias and Piezoelectric Composition.

The receive sensitivity of lead zirconate titanate (PZT) piezoelectric micromachined ultrasound transducers (PMUTs) was improved by applying a DC bias during operation. The PMUT receive sensitivity is governed by the voltage piezoelectric coefficient, h31,f. With applied DC biases (up to 15 V) on a 2 µm PbZr0.52Ti0.48O3 film, e31,f increased 1.6 times, permittivity decreased by a factor of 0.6, and the voltage coefficient increased by ~2.5 times. For released PMUT devices, the ultrasound receive sensitivity improved by 2.5 times and the photoacoustic signal improved 1.9 times with 15 V applied DC bias. B-mode photoacoustic imaging experiments showed that with DC bias, the PMUT received clearer photoacoustic signals from pencil leads at 4.3 cm, compared to 3.7 cm without DC bias.

Prostatic ductal adenocarcinoma variant predicts worse pathological and oncological outcomes: Insight from over 1000 consecutive patients from a large prospective uro-oncology registry.

OBJECTIVE: To evaluate if prostatic ductal adenocarcinoma (PDA) independently predicts poorer pathological and oncological outcomes after radical prostatectomy (RP). METHODS AND MATERIALS: Utilizing a large prospective uro-oncology registry, clinicopathological parameters of 1027 consecutive patients who underwent RP (2008-2017) were recorded. Oncological outcomes were determined by failure to achieve unrecordable PSA postoperatively and biochemical failure (BCF). RESULTS: PDA was present in 79 (7.7%) patients, whereas 948 (92.3%) patients had conventional prostatic acinar adenocarcinoma (PAA). Patients with PDA were older (mean 64.4 vs. 62.8-years old; p = .045), had higher PSA at diagnosis (mean 12.53 vs. 10.80 ng/ml; p = .034), and a higher percentage of positive biopsy cores (mean 39.34 vs. 30.53%; p = .006). Compared to PAA, PDA exhibited a more aggressive tumor biology: (1) Grade groups 4 or 5 (26.6 vs. 9.4%, p < .001), (2) tumor multifocality (89.9 vs. 83.6%; p = .049), and (3) tumor size (mean 2.97 vs. 2.00 cm; p < .001). On multivariate analysis, PDA was independently associated with locally advanced disease (p = .002, hazard ratio [HR]: 2.786, 95% confidence interval [CI]: 1.473-5.263), with a trend towards positive surgical margins (p = .055) and nodal involvement (p = .061). Translating the poorer pathological features to oncological outcomes, presence of PDA independently predicted less likelihood of achieving unrecordable PSA (p = .019, HR: 2.368, 95% CI: 1.152-4.868, and higher BCF (p = .028, HR: 1.918, 95% CI: 1.074-3.423). Subgroup analysis demonstrated that a higher ductal component greater than 15% proportionally predicted worse oncological outcomes, with a shorter time to BCF of 14.3 months compared to 19.8 months in patients with ductal component lesser than 15% (p = .040, HR: 2.660, 95% CI: 1.046-6.757). CONCLUSION: PDA is independently associated with adverse pathological and oncological outcomes after RP. A higher proportion of PDA supports a higher BCF rate with a shorter time interval. An aggressive extirpative approach with close monitoring of postoperative serum PSA levels is warranted for these patients.

Quantification of true lumen helical morphology and chirality in type B aortic dissections.

Chirality is a fundamental property in many biological systems. Motivated by previous observations of helical aortic blood flow, aortic tissue fibers, and propagation of aortic dissections, we introduce methods to characterize helical morphology of aortic dissections. After validation on computer-generated phantoms, the methods were applied to patients with type B dissection. For this cohort, there was a distinct bimodal distribution of helical propagation of the dissection with either achiral or exclusively right-handed chirality, with no intermediate cases or left-handed cases. This clear grouping indicates that dissection propagation favors these two modes, which is potentially due to the right-handedness of helical aortic blood flow and cell orientation. The characterization of dissection chirality and quantification of helical morphology advances our understanding of dissection pathology and lays a foundation for applications in clinical research and treatment practice. For example, the chirality and magnitude of helical metrics of dissections may indicate risk of dissection progression, help define treatment and surveillance strategies, and enable development of novel devices that account for various helical morphologies.NEW & NOTEWORTHY A novel definition of helical propagation of type B aortic dissections reveals a distinct bimodality, with the true lumen being either achiral (nonhelical) or exclusively right-handed. This right-handed chirality is consistent with anatomic and physiological phenomena such as right-handed twist during left ventricle contraction, helical blood flow, and tissue fiber direction. The helical character of aortic dissections may be useful for pathology research, diagnostics, treatment selection, therapeutic durability prediction, and aortic device design.