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Objective: To compare the survival of patients who attended surveillance after endovascular aneurysm repair (EVAR) with those who were non-compliant. Data sources: MEDLINE and Embase were searched using the Ovid interface. Review methods: A systematic review was conducted complying with the PRISMA guidelines. Eligible studies compared survival in EVAR surveillance compliant patients with non-compliant patients. Non-compliance was defined as failure to attend at least one post-EVAR follow up. The risk of bias was assessed with the Newcastle–Ottawa scale, and the certainty of evidence using the GRADE framework. Primary outcomes were survival and aneurysm related death. Effect measures were the hazard ratio (HR) or odds ratio (OR) and 95% confidence interval (CI) calculated using the inverse variance or Mantel–Haenszel statistical method and random effects models. Results: Thirteen cohort studies with a total of 22 762 patients were included. Eight studies were deemed high risk of bias. The pooled proportion of patients who were non-compliant with EVAR surveillance was 43% (95% CI 36 – 51). No statistically significant difference was found in the hazard of all cause mortality (HR 1.04, 95% CI 0.61 – 1.77), aneurysm related mortality (HR 1.80, 95% CI 0.85–3.80), or secondary intervention (HR 0.66, 95% CI 0.31 – 1.41) between patients who had incomplete and complete follow up after EVAR. The odds of aneurysm rupture were lower in non-compliant patients (OR 0.63, 95% CI 0.39 – 1.01). The certainty of evidence was very low for all outcomes. Subgroup analysis for patients who had no surveillance vs. those with complete surveillance showed no significant difference in all cause mortality (HR 1.10, 95% CI 0.43 – 2.80). Conclusion: Patients who were non-compliant with EVAR surveillance had similar survival to those who were compliant. These findings question the value of intense surveillance in all patients post-EVAR and highlight the need for further research on individualised or risk adjusted surveillance.

Introduction Cardiac perforation is a rare life-threatening complication of cardiac catheterization. There is very little published literature detailing risk factors for cardiac perforation and outcomes from this complication in children. Materials and Methods This was a retrospective study analyzing the cardiac catheterization case registry of the Congenital Cardiovascular Interventional Study Consortium. Children aged Results Cardiac perforation occurred in 50 patients from a total of 36,986 (0.14%). Cardiac perforation was more likely to occur in younger, smaller patients undergoing urgent /emergent and interventional procedures (pppConclusions Cardiac perforation during cardiac catheterization is a life-threatening complication with a range of associated secondary complications. Higher CRISP score, lower age and radio-frequency perforation of pulmonary valve are independent predictors.

The ability to generate 3-dimensional models of the developing human kidney via the directed differentiation of pluripotent stem cells-termed kidney organoids-has been hailed as a major advance in experimental nephrology. Although these provide an opportunity to interrogate human development, model-specific kidney diseases facilitate drug screening and even deliver bioengineered tissue; most of these prophetic end points remain to be realized. Indeed, at present we are still finding out what we can learn and what we cannot learn from this approach. In this review, we will summarize the approaches available to generate models of the human kidney from stem cells, the existing successful applications of kidney organoids, their limitations, and remaining challenges.

Artificial intelligence (AI) and machine learning (ML) have seen increasingly intimate integration with medicine and healthcare in the last 2 decades. The objective of this study was to summarize all current applications of AI and ML in the vascular surgery literature and to conduct a bibliometric analysis of published studies.A comprehensive literature search was conducted through Embase, MEDLINE, and Ovid HealthStar from inception until February 19, 2021. Reporting of this study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Title and abstract screening, full-text screening, and data extraction were conducted in duplicate. Data extracted included study metadata, the clinical area of study within vascular surgery, type of AI/ML method used, dataset, and the application of AI/ML. Publishing journals were classified as having either a clinical scope or technical scope. The author academic background was classified as clinical, nonclinical (e.g., engineering), or both, depending on author affiliation.The initial search identified 7,434 studies, of which 249 were included for a final analysis. The rate of publications is exponentially increasing, with 158 (63%) studies being published in the last 5 years alone. Studies were most commonly related to carotid artery disease (118, 47%), abdominal aortic aneurysms (51, 20%), and peripheral arterial disease (26, 10%). Study authors employed an average of 1.50 (range: 1-6) distinct AI methods in their studies. The application of AI/ML methods broadly related to predictive models (54, 22%), image segmentation (49, 19.4%), diagnostic methods (46, 18%), or multiple combined applications (91, 37%). The most commonly used AI/ML methods were artificial neural networks (155/378 use cases, 41%), support vector machines (64, 17%), k-nearest neighbors algorithm (26, 7%), and random forests (23, 6%). Datasets to which these AI/ML methods were applied frequently involved ultrasound images (87, 35%), computed tomography (CT) images (42, 17%), clinical data (34, 14%), or multiple datasets (36, 14%). Overall, 22 (9%) studies were published in journals specific to vascular surgery, with the majority (147/249, 59%) being published in journals with a scope related to computer science or engineering. Among 1,576 publishing authors, 46% had exclusively a clinical background, 48% a nonclinical background, and 5% had both a clinical and nonclinical background.There is an exponentially growing body of literature describing the use of AI and ML in vascular surgery. There is a focus on carotid artery disease and abdominal aortic disease, with many other areas of vascular surgery under-represented. Neural networks and support vector machines composed most AI methods in the literature. As AI/ML continue to see expanded applications in the field, it is important that vascular surgeons appreciate its potential and limitations. In addition, as it sees increasing use, there is a need for clinicians with expertise in AI/ML methods who can optimize its transition into daily practice.

Objective: Management of antithrombotic therapy in patients undergoing elective fenestrated branched endovascular aortic repair (F-BEVAR) is not standardised, nor are there any recommendations from current guidelines. By designing an international expert based Delphi consensus, the study aimed to create recommendations on the pre-, intra-, and post-operative management of antithrombotic therapy in patients scheduled for elective F-BEVAR in high volume centres.Methods: Eight facilitators created appropriate statements regarding the study topic that were voted on, using a four point Likert scale, by a selected panel of international experts using a three round modified Delphi consensus process. Based on the experts’ responses, only those statements reaching Grade A (full agreement ≥ 75%) or B (overall agreement ≥ 80% and full disagreement < 5%) were included in the final document. The round answers’ consistency was graded using Cohen's k, the intraclass correlation coefficient, and, in case of double re-submission, the Fleiss k.Results: Sixty-seven experts were included in the final analysis and voted the initial 43 statements related to pre- (n = 15), intra- (n = 10), and post-operative (n = 18) management of antithrombotic drugs. At the end of the process, six statements (13%) were rejected, 20 statements (44%) received a Grade B consensus, and 18 statements (40%) reached a Grade A consensus. Most statements (27; 71%) exhibited very high or high consistency grades, and 11 (29%) a fair or poor grading. The intra-operative statements mostly concentrated on threshold for and monitoring of proper heparinisation. The pre- and post-operative statements mainly focused on indications for dual antiplatelet therapy and its management, considering the possible need for cerebrospinal fluid drainage.Conclusion: Based on the elevated strength and high consistency of this international expert based Delphi consensus, most of the statements might guide current clinical management of antithrombotic therapy for elective F-BEVAR. Future studies are needed to clarify the debated issues.

Previous studies have demonstrated important geographic variations in peripheral artery disease (PAD) management despite existing guidelines. We assessed differences in patient characteristics, procedural technique, and outcomes for PAD interventions in Canada versus United States.The Vascular Quality Initiative (VQI) was used to identify all patients who underwent endovascular intervention or surgical bypass for PAD between 2010 and 2019 in Canada and United States. Independent t-test and chi-square test were performed to assess differences between countries in terms of demographic, clinical, and procedural characteristics. The primary outcome was the percentage of interventions performed for claudication versus chronic limb-threatening ischemia (CLTI). Perioperative outcomes were in-hospital mortality and index limb amputation. The long-term outcome was 1-year amputation-free survival. Univariate/multivariate logistic regression and Cox proportional hazards analysis were performed to investigate associations between region and outcomes.A total of 246,770 US patients and 3,467 Canadian patients underwent revascularization for PAD during the study period. There was a higher proportion of endovascular interventions in the US (75.9% vs. 69.2%, OR 1.41 [95% CI 1.31-1.51], P0.001). American patients were younger with more comorbidities, including hypertension, diabetes, and coronary artery disease. The percentage of interventions performed for claudication was significantly higher in the US (42.3% vs. 35.7%, OR 1.31 [95% CI 1.22-1.44], P0.001). This persisted after controlling for demographic, clinical, and procedural characteristics (adjusted OR 1.05 [95% CI 1.01-1.10], P = 0.02). Perioperative outcomes were similar between countries after adjustment for baseline differences: in-hospital mortality (adjusted OR 1.07 [95% CI 0.69-1.62], P= 0.75) and index limb amputation (adjusted OR 0.67 [95% CI 0.43-1.07], P= 0.09). However, 1-year amputation-free survival was higher in the US (84.1% vs. 71.0%, HR 1.61 [95% CI 1.47-1.76], P0.001). Multivariable Cox proportional hazards analysis demonstrated that the factor most strongly associated with index limb amputation or death at 1-year was intervention for CLTI (HR 1.56 [95% CI 1.54-1.58], P0.001).There are significant variations in PAD management between US and Canada. In particular, a higher proportion of interventions are performed for claudication rather than CLTI in the US compared to Canada. This is an important contributor to the higher 1-year amputation-free survival rate in US patients. Reasons for these differences should be assessed by future studies and evidence-based care may be standardized by targeted quality improvement projects.

Previous studies have demonstrated significant geographic variations in the management of abdominal aortic aneurysms (AAA) despite standard guidelines. Differences in patient selection, operative technique, and outcomes for AAA repair in Canada versus United States were assessed.The Vascular Quality Initiative was used to identify all patients who underwent elective endovascular or open AAA repair between 2010 and 2019 in Canada and the United States. Demographic, clinical, and procedural characteristics were recorded and differences between countries were assessed using independent t test and χThere were 51,455 U.S. patients and 1451 Canadian patients who underwent AAA repair in Vascular Quality Initiative sites during the study period. There was a higher proportion of endovascular repairs in the United States (83.7% vs 68.4%; odds ratio [OR], 2.38; 95% confidence interval [CI], 2.13-2.63; P .001). U.S. patients had more comorbidities, including hypertension, congestive heart failure, chronic kidney disease, and prior revascularization. The percentage of AAA repaired below recommended thresholds was significantly higher in the United States (38.8% vs 15.2%; OR, 3.57; 95% CI, 3.03-4.17; P .001). This difference persisted after controlling for demographic, clinical, and procedural characteristics (adjusted OR, 3.57; 95% CI, 2.63-4.17; P .001). Factors that predicted AAA repair below recommended thresholds were U.S. region (adjusted OR, 3.57; 95% CI, 3.03-4.17), male sex (adjusted OR, 2.89; 95% CI, 2.72-3.07), and endovascular repair (adjusted OR, 2.08; 95% CI, 1.95-2.21). The in-hospital mortality rate was low (1.0% vs 0.8%) and the 1-year rate mortality was similar between countries (hazard ratio, 0.96; 95% CI, 0.70-1.31; P = .79).There are significant variations in AAA management between Canada and the United States. A greater proportion of U.S. patients underwent AAA repair below the recommended diameter thresholds. This finding is partly driven by a higher percentage of endovascular repairs. Despite these differences, the perioperative and 1-year mortality rates are similar. Future studies should investigate reasons for these variations and quality improvement projects are needed to standardize care.

The transport and chemical identification of microplastics and nanoplastics (MNPs) are critical to the concerns over plastic accumulation in the environment. Transient MNP species present unique challenges for isolation and analysis due to many factors such as their size, color, surface properties, morphology, and potential for chemical change. These factors contribute to the eventual environmental and toxicological impact of MNPs. As analytical methods and instrumentation continue to be developed for this application, analytical test materials will play an important role. Here, a direct mass spectrometry screening method was developed to rapidly characterize manufactured and weathered MNPs, complementing lengthy pyrolysis-GC-MS analyses. The chromatography-free measurements took advantage of Kendrick mass defect analysis, in-source collision induced dissociation, and advancements in machine learning approaches for data analysis of the complex mass spectra. In this study, we applied Gaussian mixture models and fuzzy c-means clustering for the unsupervised analysis of MNP sample spectra, incorporating clustering stability and information criterion measurements to determine latent dimensionality. These models provided insight into the composition of mixed and weathered MNP samples. The multiparametric data acquisition and machine learning approach presented improved confidence in polymer identification and differentiation.

Management of carotid bifurcation stenosis in stroke prevention has been the subject of extensive investigations, including multiple randomized controlled trials. The proper treatment of patients with carotid bifurcation disease is of major interest to vascular surgeons and other vascular specialists. In 2011, the Society for Vascular Surgery published guidelines for the treatment of carotid artery disease. At the time, several randomized trials, comparing carotid endarterectomy (CEA) and carotid artery stenting (CAS), were reported. Since the 2011 guidelines, several studies and a few systematic reviews comparing CEA and CAS have been reported, and the role of medical management has been reemphasized. In the present publication, we have updated and expanded on the 2011 guidelines with specific emphasis on five areas: (1) is CEA recommended over maximal medical therapy for low-risk patients; (2) is CEA recommended over transfemoral CAS for low surgical risk patients with symptomatic carotid artery stenosis of50%; (3) the timing of carotid intervention for patients presenting with acute stroke; (4) screening for carotid artery stenosis in asymptomatic patients; and (5) the optimal sequence of intervention for patients with combined carotid and coronary artery disease. A separate implementation document will address other important clinical issues in extracranial cerebrovascular disease. Recommendations are made using the GRADE (grades of recommendation assessment, development, and evaluation) approach, as was used for other Society for Vascular Surgery guidelines. The committee recommends CEA as the first-line treatment for symptomatic low-risk surgical patients with stenosis of 50% to 99% and asymptomatic patients with stenosis of 70% to 99%. The perioperative risk of stroke and death in asymptomatic patients must be 3% to ensure benefit for the patient. In patients with recent stable stroke (modified Rankin scale score, 0-2), carotid revascularization is considered appropriate for symptomatic patients with50% stenosis and should be performed as soon as the patient is neurologically stable after 48 hours but definitely 14 days after symptom onset. In the general population, screening for clinically asymptomatic carotid artery stenosis in patients without cerebrovascular symptoms or significant risk factors for carotid artery disease is not recommended. In selected asymptomatic patients with an increased risk of carotid stenosis, we suggest screening for clinically asymptomatic carotid artery stenosis as long as the patients would potentially be fit for and willing to consider carotid intervention if significant stenosis is discovered. For patients with symptomatic carotid stenosis of 50% to 99%, who require both CEA and coronary artery bypass grafting, we suggest CEA before, or concomitant with, coronary artery bypass grafting to potentially reduce the risk of stroke and stroke/death. The sequencing of the intervention depends on the clinical presentation and institutional experience.

Formation of a bird-beak configuration in thoracic endovascular aortic repair (TEVAR) has been shown to be influenced by various factors. However, the main cause of bird-beak formation remains poorly understood. The hypothesis has been that the geometric and mechanical properties of both the aorta and the stent graft contribute to the formation and extent of a bird-beak configuration. The goal of the present study was to use parameter-based computational simulations of TEVAR to predict for bird-beak formation and identify its most significant contributing factors.In the present study, we considered five parameters for the computational simulations of TEVAR, including aortic curvature, aortic arch angle, age as a surrogate for thoracic aortic tissue properties, TEVAR landing zone, and stent graft oversizing. Using an experimental design approach, computational models for 160 TEVAR scenarios were developed by varying the values of the simulation parameters within clinically relevant ranges. The bird-beak length and angle were used as metrics to evaluate the simulation results. Statistical analysis of the simulation data using a random forest model was conducted to identify significant parameters and interactions.The mean ± standard deviation of the bird-beak length and angle across 160 simulations were 4.32 ± 4.87 mm and 9.16° ± 12.21°, respectively. The largest mean bird-beak length and angle were found in the most distal location in zone 0 (10.04 mm) and zone 2 (21.48°), respectively. An inverse correlation was found between the aortic arch angle and the bird-beak length and angle. In ∼75% of the scenarios, increased stent graft oversizing either fully resolved the presence of the bird-beak configuration or had reduced its size. In the remaining 25%, oversizing minimally changed the bird-beak length and enlarged the bird-beak angle, which mainly occurred in cases with a smaller aortic arch angle and landing zones near the arch apex. This was justified by the mechanism of stent graft bending in the arch angulation. The aortic curvature and tissue properties were shown to be statistically insignificant in relation to bird-beak formation.Significant parameters predictive of a bird-beak configuration in TEVAR were identified, and the trends in which each parameter influenced the bird-beak size were determined. The findings from the present study can inform the surgical planning and device selection process with the goal of minimizing bird-beak formation.

Objective Current EAST guidelines recommend against routine carotid intervention for patients with blunt carotid artery injury (BCI), but offer limited information on its role for BCI patients presenting with neurological deficit. Our goal was to describe the contemporary management and outcomes of patients presenting with BCI and neurological deficit unrelated to head injury. Methods We identified all adults who sustained a BCI between 2010 and 2017 in the American College of Surgeons Trauma Quality Improvement Program. We extracted patient demographics, injury characteristics (carotid and non-carotid), as well as the frequency, timing and approach of carotid intervention. Presence of neurological deficit unrelated to head injury at presentation was determined using Abbreviated Injury Scale codes. The main outcomes were in-hospital mortality and home discharge. Patients with and without neurological deficit at presentation were compared through multivariable logistic regression modeling. Among those with neurological deficit at presentation, the associations between carotid intervention (open or endovascular) and the outcomes were also assessed through multivariable logistic regression. Results We identified 5,788 patients with BCI of whom 383 (7%) presented with neurological deficit unrelated to head injury. Among the 296 patients (5%) who underwent carotid intervention, 36 (12%) had presented with neurological deficit unrelated to head injury. Interventions were most often endovascular (68% [200/296]) and within a median time of 32 h (IQR 5–203). In-hospital mortality was 16% (918/5,788), and in-hospital stroke prevalence was 6% (336/5,788). When comparing patients with and without neurological deficit at presentation, those with deficits were more frequently managed with an intervention. After adjustment, the likelihood of mortality was higher (OR [95% CI] = 2.16 [1.63–2.85]) and the likelihood of home discharge lower (OR [95% CI] = 0.29 [0.21–0.40]) among patients presenting with neurological deficit. Among those with neurological deficit, carotid intervention was positively associated with home discharge (OR [95% CI] = 2.96 [1.21–7.23]), but not with in-hospital mortality (OR [95% CI] = 0.87 [0.36–2.10]). Results were similar in the subgroup of patients with isolated BCI (2,971/5,788). Conclusions Intervention in BCI patients presenting with neurological deficit may contribute to a greater likelihood of home discharge but not reduced in-hospital mortality.

The need for rapid chemical analyses and new analytical tools in forensic laboratories continues to grow due to case backlogs, difficult-to-analyze cases, and identification of previously unseen materials such as new psychoactive substances. To adapt to these needs, the forensics community has been pursuing the use of ambient ionization mass spectrometry, and more specifically direct analysis in real time mass spectrometry (DART-MS), for a wide range of applications. From the inception of DART-MS forensic applications have been researched with demonstrations ranging from drugs of abuse to inorganic gunshot residue to printer inks to insect identification. This article presents a review of research demonstrating the use of DART-MS for forensically relevant samples over the past five years. To provide more context, background on the technique, sampling approaches, and data analysis methods are presented along with a discussion on the potential future and research needs of the technology.

The reverse fragility index (RFI) describes the number of event conversions needed to convert a statistically non-significant dichotomous outcome to significant. The objective of this study was to assess the RFI of vascular surgery randomized controlled trials (RCTs) comparing endovascular vs. open surgery in the treatment of abdominal aortic aneurysms (AAA), carotid artery stenosis (CAS), and peripheral artery disease (PAD).MEDLINE and Embase were searched for RCTs investigating AAA, CAS, or PAD with statistically non-significant binary primary outcomes. The primary outcome of this study was the median RFI. Calculation of the RFI was done by creating two-by-two contingency tables and subtracting events from the group with fewer events while adding non-events to the same group until a two-tailed Fisher exact test produced a statistically significant result (p≤0.05).Of 4187 articles, 49 studies reporting 103 different primary endpoints were included. The overall median RFI was 7 (IQR 5, 13). The specific RFIs for AAA, CAS, and PAD were 10 (6-15.5), 6 (5-9.5), and 7 (5.5 -10) respectively. 42 (47%) endpoints had a loss to follow-up greater than RFI, of which 10 (24%) were AAA trials, 23 (55%) CAS trials, and 9 (21%) PAD trials. Pearson correlation demonstrated a significant positive relationship between a study's RFI to the impact factor of its publishing journal (r=0.38 [95% CI 0.20 to 0.54], p0.01), length of follow-up (r=0.43 [95% CI: 0.26 to 0.58], p0.01), and sample size (r = 0.28, 95% CI: 0.09 to 0.45, p0.01).A small number of events (median 7) were required to change the outcome of negative RCTs from statistically non-significant to significant with 47% of studies missing data that could have reversed the finding of its primary outcome. Reporting of the RFI relative to the loss-to-follow-up may be of benefit in future trials and provide confidence towards the robustness of P-value.

OBJECTIVE: The objective of this study was to evaluate the relationship between ascending aortic geometry and biomechanical properties. METHODS: Preoperative computed tomography scans from ascending aortic aneurysm patients were analyzed using a center line technique (n = 68). Aortic length was measured from annulus to innominate artery, and maximal diameter from this segment was recorded. Biaxial tensile testing of excised tissue was performed to derive biomechanical parameters energy loss (efficiency in performing the Windkessel function) and modulus of elasticity (stiffness). Delamination testing (simulation of dissection) was performed to derive delamination strength (strength between tissue layers). RESULTS: Aortic diameter weakly correlated with energy loss (r(2) = 0.10; P 55 mm (n = 33) demonstrated higher energy loss than those 110 mm (n = 37) did not exhibit a difference in energy loss (P = .40), modulus of elasticity (P = .69), or delamination strength (P = .68) compared with aortas

Crystal polymorphism of pharmaceutical compounds directly impacts resulting physicochemical characteristics, a critical aspect in active pharmaceutical ingredient (API) production. Tools to characterize and chemically map these polymorphs at the single particle scale remain important to advancing directed manufacture of targeted polymorphs. Here, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed for chemically imaging inkjet printed acetaminophen samples. ToF-SIMS generates large datasets of high spatial resolution images. Extracting relevant data and peaks of interest can be laborious for, and biased by, users. Advances in machine learning approaches have introduced many supervised and unsupervised methods for data analysis. In this study, we apply non-negative matrix factorization (NMF) for the unsupervised analysis of ToF-SIMS chemical image data. More specifically, an expanded variant of NMF, NMFk, was employed to determine the dataset’s latent dimensionality. NMFk combines the spectral unmixing of traditional NMF with k-means clustering of the resulting factors and an optimization of the reconstruction and clustering. The method was used to identify the number of polymorph phases – and their representative mass spectra – generated from inkjet printed acetaminophen samples. Amorphous, crystalline form I, and crystalline form II polymorphs were observed. The learned polymorph mass spectra were then used to map the learned polymorphs onto subsequent particle samples of acetaminophen. Finally, NMFk also enabled the decomposition of mixed particle samples (i.e., migraine medicine), learning the number of compounds and their composition. The extracted constituent phase mass spectra – representing single compounds – were searched against mass spectral libraries for identification.

Background:Pericardiocentesis is the invasive percutaneous procedure for acute and chronic excessive accumulation of pericardial fluid. There is a paucity of data on the effectiveness and safety of pericardiocentesis in children.Objectives:To evaluate the effectiveness and safety of pericardiocentesis and factors associated with acute procedural failure and adverse events.Methods:This was a single-centered retrospective study to describe all the children aged ≤20 years who underwent pericardiocentesis. Data on demographics, etiologies of pericardial effusion, and repeat intervention at follow-up were collected.Results:A total of 127 patients underwent 153 pericardiocentesis. The median age was 6.5 years (1 day–20 years) with weight of 17 kg (0.5–125). Most common etiology was post-pericardiotomy syndrome (n = 56, 44%), followed by infectious (12%), malignant (10%), and iatrogenic (9%). Pericardiocentesis was performed more commonly in the catheterisation laboratory (n = 86, 59%). Concurrent pericardial drain placement was performed in 67 patients (53%). Acute procedural success was 92% (141/153). Repeat intervention was performed in 33 patients (22%). The incidence of adverse events was 4.6% (7/153): hemopericardium requiring emergent surgery (n = 2); hemopericardium with hypotension (n = 2); seizure with anesthesia induction (n = 1); and right ventricle puncture with needle (n = 2). Pericardiocentesis at the bedside had a higher rate of acute procedural failure than that in the catheterisation lab (17 versus 1%, p < 0.01). No identifiable risk factors were associated with adverse events.Conclusions:Pericardiocentesis was life-saving in children with its high effectiveness and safety even in urgent situations. Although initial pericardiocentesis was effective, one of five patients required re-intervention for recurrent pericardial effusion.

Arteriovenous fistula (AVF) creation is used to palliate complex cyanotic heart diseases. We report an adult patient with AVF creation who subsequently developed severe left subclavian vein stenosis, causing significant left arm swelling. Covered stent placement successfully treated the venous stenosis, resulting in the normalization of his left arm swelling.

Patient prosthesis mismatch (PPM) is an important factor of the outcome in transcatheter aortic valve implantation. However, the impact of PPM in transcatheter pulmonic valve implantation (TPVI) has not been studied. Based on the narrowest valve stent diameters in two views of fluoroscopy, internal geometric orifice area (GOA) of the valve stent was calculated and indexed by body surface area (BSA), deriving iGOA. To define PPM in TPVI, receiver operating characteristics (ROC) curve analysis for iGOA for predicting significant residual right ventricular outflow tract (RVOT) gradient was used to derive the optimal cut-off value of iGOA. Our cohort were divided into 2 groups: PPM versus non-PPM. The clinical data were compared between 2 groups. TPVI was performed using Melody valve in 101 patients. Significant RVOT residual pressure gradient (≥ 15 mmHg) was observed in 31 patients (39.6%). Over a mean follow up periods of 6.9 ± 2.7 years, 22 patients (21.8%) required repeat interventions (16 transcatheter, 11 surgical, and both in 5 patients). Based on the ROC analysis, the best cut-off value of iGOA was 1.25 cm2/m2 (area under the curve 0.873, p

Transcatheter closure of patent ductus arteriosus (PDA) in premature infants is a feasible, safe, and an effective alternative to surgical ligation and may be performed with an implant success rate of 97%. Major procedural complications related to transcatheter PDA closure in extremely low birth weight (ELBW) infants are relatively infrequent (

RNA interference (RNAi) is a natural biological pathway that inhibits gene expression by targeted degradation or translational inhibition of cytoplasmic messenger RNA (mRNA) by the RNA induced silencing complex. RNAi has long been exploited in laboratory research to study the biological consequences of the reduced expression of a gene of interest. More recently RNAi has been demonstrated as a therapeutic avenue for rare metabolic diseases. This review presents an overview of the cellular RNAi machinery as well as therapeutic RNAi design and delivery. As a clinical example we present primary hyperoxaluria, an ultra-rare inherited disease of increased hepatic oxalate production which leads to recurrent calcium oxalate kidney stones. In the most common form of the disease (Type 1), end-stage kidney disease occurs in childhood or young adulthood, often necessitating combined kidney and liver transplantation. In this context we discuss nedosiran (Dicerna Pharmaceuticals, Inc.) and lumasiran (Alnylam Pharmaceuticals), which are both novel RNAi therapies for primary hyperoxaluria which selectively reduce hepatic expression of lactate dehydrogenase and glycolate oxidase respectively, reducing hepatic oxalate production and urinary oxalate levels. Finally, we consider future optimizations advances in RNAi therapies.

Previous studies have demonstrated significant sex differences in vascular surgery outcomes. We assessed stroke or death rates following carotid endarterectomy (CEA) in women versus men.The Vascular Quality Initiative was used to identify all patients who underwent CEA between 2010 and 2019. Demographic, clinical, and procedural characteristics were recorded and differences between women and men were assessed using independent t-test and chi-squared test. The primary outcomes were 30-day and 1-year stroke or death. Associations between sex and outcomes were assessed using univariate/multivariate logistic regression and Cox proportional hazards analysis.Overall, 52,137 women and 79,974 men underwent CEA in Vascular Quality Initiative sites during the study period. Women were younger (70.3 vs. 70.5 years, P 0.001) and more likely to have hypertension (89.2% vs. 88.9%, P 0.05) and diabetes (36.2% vs. 35.8%, P 0.001) but less likely to be diagnosed with coronary artery disease (23.2% vs. 31.0%, P 0.001). A greater proportion of men were receiving cardiovascular risk reduction medications and had symptomatic carotid stenosis (28.5% vs. 26.7%, P 0.001). Women had shorter procedure times (113 vs. 122 min, P 0.001) and were less likely to receive electroencephalography neuromonitoring (27.9% vs. 28.8%, P 0.001), drain (35.9% vs. 37.3%, P 0.001), and protamine (67.4% vs. 68.0%, P 0.01). Stroke or death at 30 days (1.9% vs. 1.8%, P = 0.60) and 1 year (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.94-1.01, P = 0.20) were similar between groups, which persisted in asymptomatic patients (HR 0.97, 95% CI 0.93-1.01, P = 0.17) and symptomatic patients (HR 0.99, 95% CI 0.93-1.05, P = 0.71). The similarities in 1-year stroke or death rates existed in both the United States (HR 0.96, 95% CI 0.92-1.01, P = 0.09) and Canada (HR 1.21, 95% CI 0.47-3.11, P = 0.70).Despite sex differences in clinical and procedural characteristics, women and men have similar 30-day and 1-year outcomes following CEA.

Several specialties treat thoracic aortic disease, resulting in multiple patient care pathways. This study aimed to characterize these varied care models to guide health policy.A 57-question e-survey was sent to staff cardiac surgeons, cardiologists, interventional radiologists, and vascular surgeons at 7 Canadian medical societies.For 914 physicians, the response rate was 76% (86 of 113) for cardiac surgeons, 40% (58 of 146) for vascular surgeons, 24% (34 of 140) for radiologists, and 14% (70 of 515) for cardiologists. Several services admitted type B dissections (vascular 37%, cardiology 31%, cardiac 18%, other 7%), and care was heterogeneous. Ownership of disease management was overestimated relative to the perspective of the other specialties. Type A dissection admissions and treatment were more uniform, but emergent call coverage varied. A 24/7 aortic specialist on-call schedule was present only 4% of the time. "Aortic" case rounds promoted attendance by a broader aortic specialty contingency relative to rounds that were specialty specific. Although 89% of respondents felt an aortic team was best for patient care, only 54% worked at an institution with an aortic team present, and only 28% utilized an aortic clinic. Questions designed to define an aortic team derived 63 different combinations.Thoracic aortic disease follows a network of undefined and variable care pathways, despite its high-risk population in need of complex treatment considerations. Multidisciplinary aortic teams and clinics exist in low volume, and the "aortic team" remains an obscure construct. A multispecialty initiative to define the aortic team and outline standardized navigation pathways within the health systems hospitals is advocated.La prise en charge de la maladie de l'aorte thoracique peut faire appel à plusieurs spécialités, ce qui a pour effet de multiplier les trajectoires de soins des patients. Cette étude visait à caractériser ces différents modèles de soins afin d'éclairer l'élaboration des politiques de santé.Un sondage électronique de 57 questions a été envoyé aux chirurgiens cardiaques, aux cardiologues, aux radiologistes interventionnels et aux chirurgiens vasculaires membres de 7 associations médicales canadiennes.Sur un total de 914 médecins, le taux de réponse a été de 76 % (86 sur 113) chez les chirurgiens cardiaques, de 40 % (58 sur 146) chez les chirurgiens vasculaires, de 24 % (34 sur 140) chez les radiologistes et de 14 % (70 sur 515) chez les cardiologues. Plusieurs services avaient admis des cas de dissection aortique de type B (chirurgie vasculaire 37 %, cardiologie 31 %, chirurgie cardiaque 18 %, autre 7 %) et les soins étaient hétérogènes. Les spécialistes surestimaient leur responsabilité de la prise en charge des cas par rapport à celle des autres spécialistes. Les admissions de cas de dissection de type A et leur traitement étaient plus uniformes, mais la présence de spécialistes de garde pouvant traiter les cas urgents était variable. La présence continue d'un spécialiste de l'aorte de garde n'était observée que pendant 4 % du temps. Les séances de discussion de cas « aortiques » favorisaient la participation par une gamme plus large de spécialistes de l'aorte que les discussions axées sur une spécialité donnée. Si 89 % des répondants estimaient qu'une équipe « aortique » était la meilleure option pour les soins aux patients, ils n'étaient que 54 % à travailler dans un établissement disposant d'une telle équipe et 28 % à utiliser les services d'une clinique de l'aorte. En réponse aux questions portant sur les éléments constitutifs d'une équipe aortique, 63 combinaisons différentes de spécialités ont été proposées.La prise en charge de la maladie de l'aorte thoracique emprunte un dédale de trajectoires de soins non définies et variables, alors que sa population à haut risque a besoin de traitements complexes. Les équipes multidisciplinaires et les cliniques spécialisées dans le traitement de l'aorte sont rares, et la notion d' « équipe aortique » demeure un concept obscur. Nous préconisons une initiative réunissant des spécialistes de différents domaines pour définir les éléments constitutifs d'une équipe aortique et établir des trajectoires de navigation normalisées au sein des hôpitaux du système de santé.

Femoral artery thrombosis (FAT) is an adverse event post-catheterization. We decided to study the incidence and risk factors of FAT before and after initiation of a pulse loss monitoring program. All cardiac catheterization cases performed using femoral arterial vascular access were retrospectively reviewed. The study period was divided into two eras: before (era 1), and after the initiation of the protocol (era 2). The primary outcome was FAT requiring therapy. Univariable and multivariable logistic regression models were used to identify factors associated with FAT. Receiver operating characteristic curve were generated to predict FAT. Our cohort consisted of 2,388 cases including 467 (19.6%) infants weighing

Endovascular aortic aneurysm repair of complex aortic aneurysms requires incorporation of side branches using specially designed aortic stent grafts with fenestrations, directional branches, or parallel stent grafts. These techniques have been increasingly used and reported in the literature. The purpose of this document is to clarify and to update terminology, classification systems, measurement techniques, and end point definitions that are recommended for reports dealing with endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms involving the renal and mesenteric arteries.

Advancement in rapid targeted chemical analysis of homemade and improvised explosive devices is critical for the identification of explosives-based hazards and threats. Gradient elution moving boundary electrophoresis (GEMBE), a robust electrokinetic separation technique, was employed for the separation and detection of common inorganic oxidizers from frequently encountered fuel-oxidizer mixtures. The GEMBE system incorporated sample and run buffer reservoirs, a short capillary (5 cm), an applied electric field, and a pressure-driven counterflow. GEMBE provided a separation format that allowed for continuous injection of sample, selectivity of analytes, and no sample cleanup or filtration prior to analysis. Nitrate, chlorate, and perchlorate oxidizers were successfully detected from low explosive propellants (e.g., black powders and black powder substitutes), pyrotechnics (e.g., flash powder), and tertiary explosive mixtures (e.g., ammonium nitrate- and potassium chlorate-based fuel-oxidizer mixtures). Separation of these mixtures exhibited detection without interference from a plethora of additional organic and inorganic fuels, enabled single particle analysis, and demonstrated semiquantitative capabilities. The bulk counterflow successfully excluded difficult components from fouling the capillary, yielding estimated limits of detection down to approximately 10 μmol/L. Finally, nitrate was separated and detected from postblast debris collected and directly analyzed from two nitrate-based charges.

Background:Percutaneous balloon pericardiotomy is a percutaneous procedure that creates a window in the parietal pericardium by balloon dilation. The use of percutaneous balloon pericardiotomy has not been reported well in children.Objectives:The objective of this study was to describe the single centre experience of percutaneous balloon pericardiotomy in children.Methods:This was a retrospective study to describe all the children aged Results:A total of 13 percutaneous balloon pericardiotomy’s were performed in 11 children at the median age of 12 years (range 1.8–19). The etiologies of pericardial effusion were post-pericardiotomy syndrome (n = 4), restrictive cardiomyopathy (n = 1), autoimmune diseases (n = 3), malignancy (n = 2), and idiopathic (n = 1). Two patients received two percutaneous balloon pericardiotomy. The technical success of percutaneous balloon pericardiotomy was 100% with no acute adverse events (balloon rupture or local bleeding). Five (45%) required re-intervention and ultimately three required a surgical pericardial window 6 to 35 days after the percutaneous balloon pericardiotomy. As a result, ultimate procedural success rate was 73% (8/11).Conclusion:Percutaneous balloon pericardiotomy was performed safely with high technical success in children. Percutaneous balloon pericardiotomy may be considered for recurrent and persistent pericardial effusion, before considering a surgical pericardial window.

Background Peripheral arterial disease (PAD) affects more than 150 million people worldwide and is associated with high rates of lower extremity amputation, myocardial infarction, stroke and death. Fatty acid binding protein 3 (FABP3) is released into circulation in patients with skeletal muscle injury. In this pilot study, we investigated a possible association between PAD and blood levels of FABP3. Methods Blood samples were collected from patients with clinical symptoms and diagnostic findings indicative of PAD (PAD group; ankle-brachial index [ABI] 0.9; n = 75) presenting to vascular surgery ambulatory clinics at St. Michael's Hospital. Plasma samples were analyzed by protein multiplex to quantify FABP3 levels. Results PAD patients were found to have higher blood levels of FABP3 compared to patients without PAD (mean 3.90 ± 1.69 vs 2.03 ± 0.78; P < .001). A subgroup analysis demonstrated that the FABP3 levels were increased by almost two-fold in patients with PAD, independent of coronary artery disease (P < .001) or diabetes mellitus status (P < .001). Moreover, a significant negative correlation between FABP3 and the ABI was observed in PAD and patients without PAD matched groups (r = –0.51; P = .001). Last, immunohistochemistry demonstrated elevated expressions of FABP3 within skeletal muscle obtained from patients with the most severe form of PAD, chronic limb-threatening ischemia, when compared with patients without PAD. Conclusions Patients with PAD have elevated plasma levels of FABP3. An increasing severity of PAD is associated with higher FABP3 levels., Clinical Relevance There is a pressing need for a simple, readily accessible, blood-based biomarker for PAD. In this study, we found elevated levels of FABP3 in patients with PAD. This increase in FABP3 was irrespective of history of coronary artery disease or diabetes. Furthermore, our data suggest that an increasing severity of PAD is associated with higher FABP3 levels. Subsequently, FABP3 may be a potential diagnostic biomarker for PAD. However, further studies are needed to confirm the capability of FABP3 to serve as a valid and reliable biomarker for PAD.

Portable analytical instrumentation that can provide an alarm indication for the presence of explosives and related components is critical for the identification of explosives-based hazards and threats. Many explosives incident reports involve an inorganic oxidizer-fuel mixture which can include pyrotechnics, fireworks, flash powders, black powders, black powder substitutes, and improvised or homemade explosives. A portable CE instrument with targeted analysis of common inorganic oxidizer ions, for example, chlorate, perchlorate, and nitrate, was used here as a rapid detection platform. Unlike frequently used gas-phase separation and detection instrumentation such as ion mobility spectrometry (IMS), an automated liquid extraction mechanism is required for CE separation using acetate paper sample collection wipes. Target inorganic oxidizers were inkjet-printed onto sample wipes to investigate instrument response relative to the collected analyte spatial distribution. Overall, analyte signal intensities increased with off-center sample deposition due to improved sample extraction from wipes and no change in response was observed for varied array distributions across wipes. The system demonstrated sub 200 ng detection limits for all target analytes, with further improvement when normalizing to an internal standard.

Background Use of neuraxial anaesthesia for open abdominal aortic aneurysm repair is postulated to reduce mortality and morbidity. This study aimed to determine the 90-day outcomes after elective open abdominal aortic aneurysm repair in patients receiving combined general and neuraxial anaesthesia vs general anaesthesia alone. Methods A retrospective population-based cohort study was conducted from 2003 to 2016. All patients ≥40 yr old undergoing open abdominal aortic aneurysm repair were included. The propensity score was used to construct inverse probability of treatment weighted regression models to assess differences in 90-day outcomes. Results A total of 10 447 elective open abdominal aortic aneurysm repairs were identified; 9003 (86%) patients received combined general and neuraxial anaesthesia and 1444 (14%) received general anaesthesia alone. Combined anaesthesia was associated with significantly lower hazards for all-cause mortality (hazard ratio [HR]=0.47; 95% confidence interval [CI], 0.37–0.61) and major adverse cardiovascular events (HR=0.72; 95% CI, 0.60–0.86). Combined patients were at lower odds for acute kidney injury (odds ratio [OR]=0.66; 95% CI, 0.49–0.89), respiratory failure (OR=0.41; 95% CI, 0.36–0.47), and limb complications (OR=0.30; 95% CI, 0.25–0.37), with higher odds of being discharged home (OR=1.32; 95% CI, 1.15–1.51). Combined anaesthesia was also associated with significant mechanical ventilation and ICU and hospital length of stay benefits. Conclusions Combined general and neuraxial anaesthesia in elective open abdominal aortic aneurysm repair is associated with reduced 90-day mortality and morbidity. Neuraxial anaesthesia should be considered as a routine adjunct to general anaesthesia for elective open abdominal aortic aneurysm repair.

Sex differences in aortic surgery outcomes are commonly reported. However, data on ruptured abdominal aortic aneurysm (rAAA) repair outcomes in women vs men are limited.To assess differences in perioperative and long-term mortality following rAAA repair in women vs men.A multicenter, retrospective cohort study was conducted using the Vascular Quality Initiative database, which prospectively captures information on patients who undergo vascular surgery across 796 academic and community hospitals in North America. All patients who underwent endovascular or open rAAA repair between January 1, 2003, and December 31, 2019, were included. Outcomes were assessed up to January 1, 2020.Patient sex.Demographic, clinical, and procedural characteristics were recorded, and differences between women vs men were assessed using independent t test and χ2 test. The primary outcomes were in-hospital and 8-year mortality. Associations between sex and outcomes were analyzed using univariable and multivariable logistic regression and Cox proportional hazards regression analysis.A total of 1160 (21.9%) women and 4148 (78.1%) men underwent rAAA repair during the study period. There was a similar proportion of endovascular repairs in women and men (654 [56.4%] vs 2386 [57.5%]). Women were older (mean [SD] age, 75.8 [9.3] vs 71.7 [9.6] years), more likely to have chronic kidney disease (718 [61.9%] vs 2184 [52.7%]), and presented with ruptured aneurysms of smaller diameters (mean [SD] 68 [18.2] vs 78 [30.2] mm). In-hospital mortality was higher in women (34.4% vs 26.6%; odds ratio, 1.44; 95% CI, 1.25-1.66), which persisted after adjusting for demographic, clinical, and procedural characteristics (adjusted odds ratio, 1.36; 95% CI, 1.12-1.66; P = .002). Eight-year survival was lower in women (36.7% vs 49.5%; hazard ratio, 1.25; 95% CI, 1.04-1.50; P = .02), which persisted when stratified by endovascular and open repair. This survival difference existed in both the US and Canada. Variables associated with long-term mortality in women included older age and chronic kidney disease.Women who underwent rAAA repair had higher perioperative and 8-year mortality rates following both endovascular and open repair compared with men. Older age and higher rates of chronic kidney disease in women were associated with higher mortality rates. These findings suggest that future studies should assess the reasons for these disparities and whether opportunities exist to improve AAA care for women.

To compare the survival of patients who attended surveillance after endovascular aneurysm repair (EVAR) with those who were non-compliant.MEDLINE and Embase were searched using the Ovid interface.A systematic review was conducted complying with the PRISMA guidelines. Eligible studies compared survival in EVAR surveillance compliant patients versus non-compliant patients. Non-compliance was defined as failure to attend at least one post-EVAR follow-up. The risk of bias was assessed with the Newcastle-Ottawa scale, and the certainty of evidence using the GRADE framework. Primary outcomes were survival and aneurysm-related mortality. Effect measures were the hazard ratio (HR) or odd ratio (OR) and 95% confidence interval (CI) calculated using the inverse variance or Mantel-Haenszel statistical method and random-effects models.Thirteen cohort studies with a total of 22,762 patients were included. Eight studies were deemed high risk of bias. The pooled proportion of patients who were non-compliant with EVAR surveillance was 43% (95% CI 36%-51%). No statistically significant difference was found in the hazard of all-cause mortality (HR 1.04, 95% CI 0.61-1.77), aneurysm-related mortality (HR 1.80, 95% CI 0.85-3.80), or secondary intervention (HR 0.66, 95% CI 0.31-1.41) between patients who had incomplete and complete follow-up after EVAR. The odds of aneurysm rupture were lower in non-compliant patients (OR 0.63, 95% CI 0.39-1.01). The certainty of evidence was very low for all outcomes. Subgroup analysis for patients who had no surveillance versus those with complete surveillance showed no significant difference in all-cause mortality (HR 1.10, 95% CI 0.43-2.80).Patients who were non-compliant with EVAR surveillance had similar survival to those who were compliant. The findings question the value of intense surveillance in all patients post-EVAR and highlight the need for further research on individualized or risk-adjusted surveillance.

Chronic kidney disease; Pediatric nephrology; Urology Malaltia renal crònica; Nefrologia pediàtrica; Urologia Enfermedad renal crónica; Nefrología pediátrica; Urología Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90–180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs −1664 [1190], respectively; difference, 5172; 95% CI 2929–7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (

Transcatheter patent ductus arteriosus (PDA) device closure is increasingly performed in extremely premature infants. Contrast angiography improves the procedural safety and effectiveness by precise anatomic delineation. Contrast nephropathy is a concern in clinically ill premature infants, especially with the presence of renal insufficiency. We hypothesized that the benefit of transcatheter PDA closure outweighs the harm of contrast nephropathy in extremely premature infants. A total of 160 infants underwent successful transcatheter (n = 59) and surgical (n = 101) PDA closure at a median age of 26 (7 to 78) days. The surgical group had a lower procedural weight (870 vs 960 g, p = 0.014). In the transcatheter group, serum creatinine decreased from 0.48 to 0.45 mg/100 ml at 24 hours (p = 0.003, n = 59) and decreased further to 0.37 mg/100 ml at 5 to 7 days after closure (plt;0.001). Median contrast amount was 1.9 ml/kg (0.6 to 6.1). In 8 infants with pre-existing renal insufficiency who underwent transcatheter closure, serum creatine significantly improved from 1.44 to 1.36 mg/100 ml at 24 hours and 0.79 mg/100 ml at 5 to 7 days after closure (plt;0.001). There was no difference in improvement of serum creatinine between transcatheter and surgical closure groups. In conclusion, despite the use of contrast, serum creatinine significantly improved with transcatheter PDA closure even in infants with pre-existing renal insufficiency. Contrast angiography should not be discouraged for transcatheter PDA closure because of the concern for contrast nephropathy in extremely premature infants.

Transfemoral and right transjugular approach has been described for transcatheter pulmonary valve implantation (TPVI). However, the use of left transjugular approach through the left superior vena cava to coronary sinus has not been well described. We present a 22-year-old male with Tetralogy of Fallot status post transannular patch, who underwent successful TPVI using the Sapien valve, preceded by pre-stenting of native right ventricular outflow tract. All the transcatheter intervention was performed through the left superior vena cava to coronary sinus.

Advances in the speed and accessibility of genomic sequencing are broadening the application of this technology to rapid, acute care diagnostics and pre-conception carrier screening. In both circumstances, genetic counselling plays a critical role in preparing couples for the strengths and limitations of the testing. For pre-conception carrier screening in particular, it is important that parents and clinicians are aware that even in the absence of an identified risk for recessive disease, a baby with a genetic condition may still be conceived. As an example, we present the genomic journey of a couple who underwent pre-conception carrier screening and following a low-risk result, delivered a baby boy who was diagnosed with Type 1 Bartter syndrome. Ultra-rapid, post-natal, trio whole genome sequencing resolved both parents as carriers of pathogenic variants in SLC12A1, a gene not included in the original pre-conception screening panel. This family's story highlights (i) the intricacy of gene selection for pre-conception screening panels, (ii) the benefits of high-quality pre-test genetic counselling in supporting families through adverse genomic findings and (iii) the role rapid genomics can play in resolving uncertainty for families and clinicians in circumstances where suspicion of genetic disease exists. This article is accompanied by a Patient Voice perspective written by the child's parents, placing emphasis on the essential role genetic counselling played in their journey.