SDF4CHD: Generative modeling of cardiac anatomies with congenital heart defects.

Congenital heart disease (CHD) encompasses a spectrum of cardiovascular structural abnormalities, often requiring customized treatment plans for individual patients. Computational modeling and analysis of these unique cardiac anatomies can improve diagnosis and treatment planning and may ultimately lead to improved outcomes. Deep learning (DL) methods have demonstrated the potential to enable efficient treatment planning by automating cardiac segmentation and mesh construction for patients with normal cardiac anatomies. However, CHDs are often rare, making it challenging to acquire sufficiently large patient cohorts for training such DL models. Generative modeling of cardiac anatomies has the potential to fill this gap via the generation of virtual cohorts; however, prior approaches were largely designed for normal anatomies and cannot readily capture the significant topological variations seen in CHD patients. Therefore, we propose a type- and shape-disentangled generative approach suitable to capture the wide spectrum of cardiac anatomies observed in different CHD types and synthesize differently shaped cardiac anatomies that preserve the unique topology for specific CHD types. Our DL approach represents generic whole heart anatomies with CHD type-specific abnormalities implicitly using signed distance fields (SDF) based on CHD type diagnosis. To capture the shape-specific variations, we then learn invertible deformations to morph the learned CHD type-specific anatomies and reconstruct patient-specific shapes. After training with a dataset containing the cardiac anatomies of 67 patients spanning 6 CHD types and 14 combinations of CHD types, our method successfully captures divergent anatomical variations across different types and the meaningful intermediate CHD states across the spectrum of related CHD diagnoses. Additionally, our method demonstrates superior performance in CHD anatomy generation in terms of CHD-type correctness and shape plausibility. It also exhibits comparable generalization performance when reconstructing unseen cardiac anatomies. Moreover, our approach shows potential in augmenting image-segmentation pairs for rarer CHD types to significantly enhance cardiac segmentation accuracy for CHDs. Furthermore, it enables the generation of CHD cardiac meshes for computational simulation, facilitating a systematic examination of the impact of CHDs on cardiac functions.

Type VI Collagen Deficiency Causes Enhanced Periodontal Tissue Destruction.

The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.

Effect of graft sizing in valve-sparing aortic root replacement for bicuspid aortic valve: The Goldilocks ratio.

Objective: To investigate the effect of graft sizing on valve performance in valve-sparing aortic root replacement for bicuspid aortic valve. Methods: In addition to a diseased control model, 3 representative groups-free-edge length to aortic/graft diameter (FELAD) ratio <1.3, 1.5 to 1.64, and >1.7-were replicated in explanted porcine aortic roots (n = 3) using straight grafts sized respective to the native free-edge length. They were run on a validated ex vivo univentricular system under physiological parameters for 20 cycles. All groups were tested within the same aortic root to minimize inter-root differences. Outcomes included transvalvular gradient, regurgitation fraction, and orifice area. Linear mixed effects model and pairwise comparisons were employed to compare outcomes across groups. Results: The diseased control had mean transvalvular gradient 10.9 ± 6.30 mm Hg, regurgitation fraction 32.5 ± 4.91%, and orifice area 1.52 ± 0.12 cm2. In ex vivo analysis, all repair groups had improved regurgitation compared with control (P < .001). FELAD <1.3 had the greatest amount of regurgitation among the repair groups (P < .001) and 1.5-1.64 the least (P < .001). FELAD <1.3 and >1.7 exhibited greater mean gradient compared with both control and 1.5 to 1.64 (P < .001). Among the repair groups, 1.5 to 1.64 had the largest orifice area, and >1.7 the smallest (P < .001). Conclusions: For a symmetric bicuspid aortic valve, performance after valve-sparing aortic root replacement shows a bimodal distribution across graft size. As the FELAD ratio departs from 1.5 to 1.64 in either direction, significant increases in transvalvular gradient are observed. FELAD <1.3 may also result in suboptimal improvement of baseline regurgitation.

Trapped between food, heat, and insects: Movement of moose (Alces alces) and exposure to flies in the boreal forest of Alaska.

Moose (Alces alces) in the boreal forest habitats of Alaska are unlike other northern ungulates because they tolerate high densities of flies (Diptera) even though flies cause wounds and infections during the warm summer months. Moose move to find food and to find relief from overheating (hyperthermia) but do they avoid flies? We used GPS collars to measure the rate of movement (m⋅h-1) and the time spent (min⋅day-1) by enclosed moose in four habitats: wetlands, black spruce, early seral boreal forest, and late seral boreal forest. Fly traps were used in each habitat to quantify spatio-temporal abundance. Average daily air temperatures increased into July when peak biomass of forage for moose was greatest in early seral boreal forest habitats (424.46 vs. 25.15 kg⋅ha-1 on average in the other habitats). Average daily air temperatures were 1.7°C cooler in black spruce than other habitats, but fly abundance was greatest in black spruce (approximately 4-fold greater on average than the other habitats). Moose increased their movement rate with counts of biting flies (mosquitoes, black flies, horse and deer flies), but not non-biting flies (coprophagous flies). However, as air temperature increased (above 14.7°C) moose spent more time in fly-abundant black spruce, than early seral boreal forest, showing great tolerance for mosquitoes. Warm summer temperatures appear to cause moose to trade-off foraging in fly-sparse habitats for resting and dissipating heat in shady, wet habitats with abundant flies that adversely affect the fitness of moose.

Robust Responses of Female Caribou to Changes in Food Supply.

AbstractUngulates can respond to changes in food supply by altering foraging behavior, digestive function, and metabolism. A multifaceted response to an environmental change is considered robust. Short seasons of plant growth make herbivores sensitive to changes in food supply because maintenance and production must be accomplished in less time with fewer options in a more fragile response. Caribou live at high latitudes where short summers constrain their response to changes in food supply. We measured the ability of female caribou to resist and tolerate changes in the quality and quantity of their food supply during winter and summer. Caribou resisted changes in food abundance and quality by changing food intake and physical activity with changes in daily temperature within each season. Peak food intake rose by 134% from winter pregnancy to summer lactation (98 vs. 229 g kg-0.75 d-1), as digestible requirements to maintain the body increased by 85% for energy (1,164 vs. 2,155 kJ kg-0.75 d-1) and by 266% for N (0.79 vs. 2.89 g N kg-0.75 d-1). Caribou required a diet with a digestible content of 12 kJ g-1 and 0.8% N in pregnancy, 18 kJ g-1 and 1.9% N in early lactation, and 11 kJ g-1 and 1.2% N in late lactation, which corresponds with the phenology of the wild diet. Female caribou tolerated restriction of ad lib. food intake to 58% of their energy requirement (680 vs. 1,164 kJ kg-0.75 d-1) during winter pregnancy and to 84% of their energy requirement (1,814 vs. 2,155 kJ kg-0.75 d-1) during summer lactation without a change in stress level, as indicated by fecal corticosterone concentration. Conversely, caribou can respond to increased availability of food with a spare capacity to process digestible energy and N at 123% (2,642 vs. 2,155 kJ kg-0.75 d-1) and 145% (4.20 vs. 2.89 g N kg-0.75 d-1) of those respective requirements during lactation. Robust responses to changes in food supply allow caribou to sustain reproduction, which would buffer demographic response. However, herds may decline when thresholds of behavioral resistance and physiological tolerance are frequently exceeded. Therefore, the challenge for managing declining populations of caribou and other robust species is to identify declines in robustness before their response becomes fragile.

Morphological Features Among Gaussian, Sagittal, and Tangential Curvature Maps in Normal and Keratoconus Eyes Using Anterior Segment Optical Coherence Tomography.

PURPOSE: To investigate and compare the morphological features and differences among Gaussian, Sagittal, and Tangential anterior corneal curvature maps obtained with an anterior segment optical coherence tomographer combined with a Placido disc MS-39 device in keratoconus (KC) and normal eyes. METHODS: Prospective, cross-sectional study including 37 KC and 51 healthy eyes. The pattern of astigmatism and maximum keratometry (Kmax), keratometry at the thinnest point (Ktp) and 2 mm diameter (K 2mm ), and inferior-superior dioptric asymmetry values were obtained and calculated from Gaussian, Tangential, and Sagittal curvature maps using the MS-39 (CSO). RESULTS: In KC eyes, an asymmetric bowtie pattern was observed in 64.86% (24/37), 64.86% (24/37), and 0% in the Sagittal, Tangential, and Gaussian maps, respectively. In normal eyes, 51.0% (26/51), 51.0% (26/51), and 0% showed a symmetric bowtie pattern in the Sagittal, Tangential, and Gaussian maps, respectively. There was a significant difference for the variables Kmax, Ktp, and K 2mm inferior among the Gaussian, Tangential, and Sagittal maps in both normal and KC groups. Sensitivity discriminating between normal and KC eyes was 100%, 97.3%, and 90.9% and specificity was 94.1%, 100%, and 100% for Kmax coming from the Tangential, Gaussian, and Sagittal maps, respectively. CONCLUSIONS: Gaussian maps displayed significantly different morphological features when compared with Sagittal and Tangential maps in normal and KC eyes. Anterior curvature maps from Gaussian maps do not show the morphological pattern of symmetric bowtie in normal eyes nor asymmetric bowtie in KC eyes. Kmax from Gaussian maps are more specific, however less sensitive than Tangential maps in discriminating KC from normal eyes.

Estimating Mineral Requirements of Wild Herbivores: Modelling Arctic Caribou (Rangifer tarandus granti) in Summer.

Mineral requirements are poorly described for most wildlife. Consequently, the role of forage minerals in movement and productivity are poorly understood for sedentary and migratory ungulates, such as reindeer and caribou (Rangifer tarandus). We applied estimates of maintenance, lactation, body mass change, and antler growth to production curves (body mass, daily intake, and milk yield) for female caribou to calculate their mineral requirements over summer. The total requirements (mg or g·d-1) were divided by the daily intake (kg·d-1) to estimate the minimum concentration of minerals required in the diet (mg or g·kg-1) to balance demand. The daily requirements (mg·d-1) of all minerals increased from parturition to the end of summer. The minimum dietary concentrations (mg·kg-1) of macro-minerals (Ca, P, Mg, Na, K) declined as food intake (kg·d-1) increased over summer. The minimum dietary concentrations (Fe, Mn, Cu, Zn) were heavily influenced by body mass gain, which increased through late lactation even though food intakes rose. Our modeling framework can be applied to other wild ungulates to assess the impacts of changing forage phenology, plant community compositions, or environmental disturbances on movement and productivity.

Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis.

Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome.

Simulation-based design of bicuspidization of the aortic valve.

OBJECTIVE: Severe congenital aortic valve pathology in the growing patient remains a challenging clinical scenario. Bicuspidization of the diseased aortic valve has proven to be a promising repair technique with acceptable durability. However, most understanding of the procedure is empirical and retrospective. This work seeks to design the optimal gross morphology associated with surgical bicuspidization with simulations based on the hypothesis that modifications to the free edge length cause or relieve stenosis. METHODS: Model bicuspid valves were constructed with varying free edge lengths and gross morphology. Fluid-structure interaction simulations were conducted in a single patient-specific model geometry. The models were evaluated for primary targets of stenosis and regurgitation. Secondary targets were assessed and included qualitative hemodynamics, geometric height, effective height, orifice area, and billow. RESULTS: Stenosis decreased with increasing free edge length and was pronounced with free edge length less than or equal to 1.3 times the annular diameter d. With free edge length 1.5d or greater, no stenosis occurred. All models were free of regurgitation. Substantial billow occurred with free edge length 1.7d or greater. CONCLUSIONS: Free edge length 1.5d or greater was required to avoid aortic stenosis in simulations. Cases with free edge length 1.7d or greater showed excessive billow and other changes in gross morphology. Cases with free edge length 1.5d to 1.6d have a total free edge length approximately equal to the annular circumference and appeared optimal. These effects should be studied in vitro and in animal studies.

Strength in Numbers: A SWOT Analysis of Plastic Surgery.

Background: Plastic surgeons comprise the minority of practicing surgeons, with an even smaller minority practicing in an academic setting. As the practice of medicine and the systems in which we operate continue to evolve, it is essential that plastic surgeons have a say in the changing landscape. This study conducted a strengths, weaknesses, opportunities, and threats (SWOT) analysis of plastic surgery to identify unifying strengths and common threats. Methods: An electronic survey was distributed to American Council of Academic Plastic Surgeons' Winter Meeting attendees on three separate occasions preceding the meeting. Respondents were asked to provide demographic information and to identify the top three strengths, weaknesses, opportunities, and threats (SWOT analysis) for the specialty. Subgroup analyses were performed based on demographic characteristics. Results: A total of 187 responses were received from meeting attendees, representing an 89.0% response rate. Most respondents were non-Hispanic (78.6%), White (66.8%), women (59.5%), and faculty/independent physicians (65.8%). The most identified strength in plastic surgery was our problem-solving abilities (62.0%). The most identified weakness was poor public perception of plastic surgery (54.0%). The most identified opportunity was demonstration of value to health systems (67.9%), and the most identified threat was scope of practice creep by other specialties (78.1%). The SWOT analysis identified lack of surgeon diversity as a key weakness, improvement of surgeon diversity as a key opportunity, and lack of diversity among plastic surgeons as a key threat to the specialty. Conclusion: Only through a diverse but united front can we effectively use our strengths to face our threats and employ opportunities to overcome our weaknesses.

SDF4CHD: Generative Modeling of Cardiac Anatomies with Congenital Heart Defects.

Congenital heart disease (CHD) encompasses a spectrum of cardiovascular structural abnormalities, often requiring customized treatment plans for individual patients. Computational modeling and analysis of these unique cardiac anatomies can improve diagnosis and treatment planning and may ultimately lead to improved outcomes. Deep learning (DL) methods have demonstrated the potential to enable efficient treatment planning by automating cardiac segmentation and mesh construction for patients with normal cardiac anatomies. However, CHDs are often rare, making it challenging to acquire sufficiently large patient cohorts for training such DL models. Generative modeling of cardiac anatomies has the potential to fill this gap via the generation of virtual cohorts; however, prior approaches were largely designed for normal anatomies and cannot readily capture the significant topological variations seen in CHD patients. Therefore, we propose a type- and shape-disentangled generative approach suitable to capture the wide spectrum of cardiac anatomies observed in different CHD types and synthesize differently shaped cardiac anatomies that preserve the unique topology for specific CHD types. Our DL approach represents generic whole heart anatomies with CHD type-specific abnormalities implicitly using signed distance fields (SDF) based on CHD type diagnosis, which conveniently captures divergent anatomical variations across different types and represents meaningful intermediate CHD states. To capture the shape-specific variations, we then learn invertible deformations to morph the learned CHD type-specific anatomies and reconstruct patient-specific shapes. Our approach has the potential to augment the image-segmentation pairs for rarer CHD types for cardiac segmentation and generate cohorts of CHD cardiac meshes for computational simulation.

Simulation-Based Design of Bicuspidization of the Aortic Valve.

OBJECTIVE: Severe congenital aortic valve pathology in the growing patient remains a challenging clinical scenario. Bicuspidization of the diseased aortic valve has proven to be a promising repair technique with acceptable durability. However, most understanding of the procedure is empirical and retrospective. This work seeks to design the optimal gross morphology associated with surgical bicuspidization with simulations, based on the hypothesis that modifications to the free edge length cause or relieve stenosis. METHODS: Model bicuspid valves were constructed with varying free edge lengths and gross morphology. Fluid-structure interaction simulations were conducted in a single patient-specific model geometry. The models were evaluated for primary targets of stenosis and regurgitation. Secondary targets were assessed and included qualitative hemodynamics, geometric height, effective height, orifice area and prolapse. RESULTS: Stenosis decreased with increasing free edge length and was pronounced with free edge length less than or equal to 1.3 times the annular diameter d. With free edge length 1.5d or greater, no stenosis occurred. All models were free of regurgitation. Substantial prolapse occurred with free edge length greater than or equal to 1.7d. CONCLUSIONS: Free edge length greater than or equal to 1.5d was required to avoid aortic stenosis in simulations. Cases with free edge length greater than or equal to 1.7d showed excessive prolapse and other changes in gross morphology. Cases with free edge length 1.5-1.6d have a total free edge length approximately equal to the annular circumference and appeared optimal. These effects should be studied in vitro and in animal studies.

Acid-base and electrolyte evaluation in dogs with upper GI obstruction: 115 dogs (2015-2021).

OBJECTIVES: Metabolic alkalosis, although uncommon in small animals, has been previously associated with gastrointestinal obstructions. Depending on the population and disease process evaluated, previous prevalence of metabolic alkalosis is reported as ranging from 2% to 45% in canine patients. The objective of this study was to determine the prevalence of metabolic alkalosis and other acid-base and electrolyte disorders in a cohort of dogs with a confirmed upper gastrointestinal obstruction. MATERIALS AND METHODS: Electronic medical records were reviewed to identify dogs who presented for vomiting with evidence of an upper gastrointestinal obstruction from January 2015 to October 2021. Patients were enrolled only if a preoperative venous blood gas was obtained and analysed in house. Traditional acid-base analysis was utilised to determine an acid-base status before relieving the obstruction. When available, post-operative venous acid-base status was determined within 24 hours after surgery, and compared to preoperative results. RESULTS: A total of 115 dogs were included in the study. Twenty-five out of 115 (22%) dogs displayed either a simple metabolic alkalosis or a mixed acid-base disturbance before surgery. Twenty-seven out of 115 dogs (37%) had a normal acid-base status at entry. Seventy-one dogs had pre- and post-operative venous blood gas results available. Metabolic alkalosis was resolved in nearly all patients post-operatively, with no patients displaying a simple metabolic alkalosis. A mixed metabolic acidosis and respiratory alkalosis was the most common condition post-operatively, found in 25 of 71 (35%) dogs. Severe derangements of electrolytes were infrequent preoperatively (3/115; 2.6%). A majority of patients in this study exhibited hypokalaemia (64.4%), hypochloraemia (72.8%) and hyponatraemia (77.4%) on preoperative venous blood gases. Venous pH, Pv CO2 , bicarbonate and base excess were significantly higher preoperatively when compared to the post-operative results. CLINICAL SIGNIFICANCE: This study found the prevalence of pre-operative metabolic alkalosis in dogs with a documented upper gastrointestinal obstruction to be lower than previously reported. Surgical or endoscopic alleviation of the upper gastrointestinal obstruction resulted in resolution of metabolic alkalosis in nearly all patients.

Portable Diffuse Reflectance Spectroscopy of Potato Leaves for Pre-Symptomatic Detection of Late Blight Disease.

We report on the use of leaf diffuse reflectance spectroscopy for plant disease detection. A smartphone-operated, compact diffused reflectance spectrophotometer is used for field collection of leaf diffuse reflectance spectra to enable pre-symptomatic detection of the progression of potato late blight disease post inoculation with oomycete pathogen Phytophthora infestans. Neural-network-based analysis predicts infection with >96% accuracy, only 24 h after inoculation with the pathogen, and nine days before visual late blight symptoms appear. Our study demonstrates the potential of using portable optical spectroscopy in tandem with machine learning analysis for early diagnosis of plant diseases.

The Ratings Game: Demographic and Practice Factors Affecting Yelp Ratings of Plastic Surgeons.

BACKGROUND: Review platforms such as Yelp are increasingly used by patients establishing care and may contain substantial information regarding patient preferences and potential biases. The authors' aims were to (1) analyze patient satisfaction through identifying factors associated with positive and negative patient reviews for plastic surgery providers across the United States, and (2) investigate the association between overall rating and different physician and practice factors based on gender and race. METHODS: Reviews of plastic surgery provider practices from cities across seven different regions within the United States were obtained from Yelp. Quantitative and qualitative analyses were performed. Chi-square tests were used to determine whether race or sex was associated with overall rating (of five stars) and qualitative themes. RESULTS: A total of 5210 reviews met inclusion criteria; 80.3% received a five-star rating and 13.5% received a one-star rating. Positive Yelp reviews and higher ratings were associated with positive comments regarding surgical and injectable outcomes, physical examination, communication, competency/knowledge base, temperament, scheduling, and staff interactions. When the following factors were mentioned negatively, the practice was more likely to receive a lower rating: temperament, communication, cost consciousness, surgical and injectable outcomes, physical examination, billing/insurance, scheduling, interactions with staff, and wait times. No association was identified in terms of overall physician rating based on sex or race; however, there were differences noted in distribution of positive and negative themes. CONCLUSIONS: Patient reviews on Yelp indicate that several physician and practice factors influence patient satisfaction. The themes reported in this study may be used by plastic surgery providers to identify areas for practice improvement to enhance the overall patient experience.

Sores of boreal moose reveal a previously unknown genetic lineage of parasitic nematode within the genus Onchocerca.

Long-standing reports of open sores on the hind legs of moose (Alces alces) have been recorded in Alaska (as well as Canada, Europe, and Michigan), eliciting concerns about causes and infection. We used histological and genomic methods to investigate the sores from 20 adult moose on the Kenai Peninsula, Alaska. We paired this with thermal imagery and molt scoring of adult moose to further describe sore formation and understand its timing. Severe, ulcerative and eosinophilic dermatitis was found in all moose with sores present, and microfilariae within intraepidermal pustules were additionally found in four samples. Genetic analysis of sores from moose revealed a previously unknown genetic lineage of Onchocerca. Adult moose molt and lose their barrier of protection against flies in June and July during peak fly activity, leaving them vulnerable and allowing the development of sores. In summary, our results indicate that the cause for the sores on the hindleg of moose is a previously unknown genetic lineage of Onchocerca, probably transmitted by black flies, in timing with the molt cycle of adult moose. These sores leave moose exposed to pathogens, making them vulnerable, and challenging their health and fitness.

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.

Diversifying cardiac intensive care unit models: Successful example of an operating surgeon-led unit.

Objective: The intensivist-led cardiovascular intensive care unit model is the standard of care in cardiac surgery. This study examines whether a cardiovascular intensive care unit model that uses operating cardiac surgeons, cardiothoracic surgery residents, and advanced practice providers is associated with comparable outcomes. Methods: This is a single-institution review of the first 400 cardiac surgery patients admitted to an operating surgeon-led cardiovascular intensive care unit from 2020 to 2022. Inclusion criteria are elective status and operations managed by both cardiovascular intensive care unit models (aortic operations, valve operations, coronary operations, septal myectomy). Patients from the surgeon-led cardiovascular intensive care unit were exact matched by operation type and 1:1 propensity score matched with controls from the traditional cardiovascular intensive care unit using a logistic regression model that included age, sex, preoperative mortality risk, incision type, and use of cardiopulmonary bypass and circulatory arrest. Primary outcome was total postoperative length of stay. Secondary outcomes included postoperative intensive care unit length of stay, 30-day mortality, 30-day Society of Thoracic Surgeons-defined morbidity (permanent stroke, renal failure, cardiac reoperation, prolonged intubation, deep sternal infection), packed red cell transfusions, and vasopressor use. Outcomes between the 2 groups were compared using chi-square, Fisher exact test, or 2-sample t test as appropriate. Results: A total of 400 patients from the surgeon-led cardiovascular intensive care unit (mean age 61.2 ± 12.8 years, 131 female patients [33%], 346 patients [86.5%] with European System for Cardiac Operative Risk Evaluation II <2%) and their matched controls were included. The most common operations across both units were coronary artery bypass grafting (n = 318, 39.8%) and mitral valve repair or replacement (n = 238, 29.8%). Approximately half of the operations were performed via sternotomy (n = 462, 57.8%). There were 3 (0.2%) in-hospital deaths, and 47 patients (5.9%) had a 30-day complication. The total length of stay was significantly shorter for the surgeon-led cardiovascular intensive care unit patients (6.3 vs 7.0 days, P = .028), and intensive care unit length of stay trended in the same direction (2.5 vs 2.9 days, P = .16). Intensive care unit readmission rates, 30-day mortality, and 30-day morbidity were not significantly different between cardiovascular intensive care unit models. The surgeon-led cardiovascular intensive care unit was associated with fewer postoperative red blood cell transfusions in the cardiovascular intensive care unit (P = .002) and decreased vasopressor use (P = .001). Conclusions: In its first 2 years, the surgeon-led cardiovascular intensive care unit demonstrated comparable outcomes to the traditional cardiovascular intensive care unit with significant improvements in total length of stay, postoperative transfusions in the cardiovascular intensive care unit, and vasopressor use. This early success exemplifies how an operating surgeon-led cardiovascular intensive care unit can provide similar outcomes to the standard-of-care model for patients undergoing elective cardiac surgery.

Innominate artery patency after direct cannulation in neonates.

Objective: The study objective was to determine the short-term incidence of innominate artery stenosis for neonates who underwent direct innominate artery cannulation during the Norwood procedure. Methods: This is a retrospective, single-institution review of 92 patients who underwent the Norwood procedure with direct innominate artery cannulation from 2006 to 2017. The primary outcome was angiographic evidence of patency at pre-Glenn cardiac catheterization. Patient characteristics, intraoperative surgical and hemodynamic measurements, and postoperative neurologic findings were recorded. Results: At a median age of 5.0 days, 92 neonates underwent the Norwood procedure with direct innominate artery cannulation. These patients underwent cardiac catheterization at a median of 3.0 months after the index operation. In 5 of 92 patients with catheterization images available for review, there was angiographic evidence of mild innominate artery stenosis, and none had moderate or severe stenosis. Review of follow-up records did not reveal evidence of clinically significant stenosis or innominate artery reintervention. Conclusions: In neonates undergoing the Norwood procedure with direct innominate cannulation, innominate artery stenosis was uncommon and clinically significant stenosis did not occur.