Spontaneous coronary artery dissection is infrequent in individuals with heritable thoracic aortic disease despite partially shared genetic susceptibility.

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), TGFBR2 (N = 2), TGFBR1 (N = 1), and PRKG1 (N = 1). Individuals with SCAD had an increased frequency of iliac artery dissection (25.0% vs. 5.1%, p = 0.047). The prevalence of SCAD among individuals with TAD is low. The identification of pathogenic variants in genes previously described in individuals with SCAD, particularly those underlying vascular Ehlers-Danlos, Marfan syndrome, and Loeys-Dietz syndrome, is consistent with prior reports from clinical SCAD series. Further research is needed to identify specific genetic influences on SCAD risk.

Disclosure of clinically actionable genetic variants to thoracic aortic dissection biobank participants.

BACKGROUND: Disclosure of pathogenic variants to thoracic aortic dissection biobank participants was implemented. The impact and costs, including confirmatory genetic testing in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, were evaluated. METHODS: We exome sequenced 240 cases with thoracic aortic dissection and 258 controls, then examined 11 aortopathy genes. Pathogenic variants in 6 aortopathy genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 participants, representing 10.8% of the cohort (26/240). A second research sample was used to validate the initial findings. Mailed letters to participants disclosed that a potentially disease causing DNA alteration had been identified (neither the gene nor variant was disclosed). Participants were offered clinical genetic counseling and confirmatory genetic testing in a CLIA laboratory. RESULTS: Excluding 6 participants who were deceased or lost to follow-up, 20 participants received the disclosure letter, 10 of whom proceeded with genetic counseling, confirmatory genetic testing, and enrolled in a survey study. Participants reported satisfaction with the letter (4.2 ± 0.7) and genetic counseling (4.4 ± 0.4; [out of 5, respectively]). The psychosocial impact was characterized by low decisional regret (11.5 ± 11.6) and distress (16.0 ± 4.2, [out of 100, respectively]). The average cost for 26 participants was $400, including validation and sending letters. The average cost for those who received genetic counseling and CLIA laboratory confirmation was $605. CONCLUSIONS: Participants were satisfied with the return of clinically significant biobank genetic results and CLIA laboratory testing; however, the process required significant time and resources. These findings illustrate the trade-offs involved for researchers considering returning research genetic results.

Complex and Potentially Harmful Medication Patterns in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Complex medication regimens, often present in heart failure with preserved ejection fraction, may increase the risk of adverse drug effects and harm. We sought to characterize this complexity by determining the prevalence of polypharmacy, potentially inappropriate medications, and therapeutic competition (where a medication for 1 condition may worsen another condition) in 1 of the few dedicated heart failure with preserved ejection fraction programs in the United States. METHODS: We conducted chart review on 231 patients with heart failure with preserved ejection fraction seen in the University of Michigan's Heart Failure with Preserved Ejection Fraction Clinic between July 2016 and September 2019. We recorded: 1) standing medications to determine the presence of polypharmacy, defined as ≥10 medications; 2) potentially inappropriate medications based on the 2016 American Heart Association Scientific Statement on drugs that pose a major risk of causing or exacerbating heart failure, the 2019 Beers Criteria update, or a previously described list of medications associated with geriatric syndromes; and 3) competing conditions and subsequent medications that could create therapeutic competition. RESULTS: The prevalence of polypharmacy was 74%, and the prevalence of potentially inappropriate medications was 100%. Competing conditions were present in 81% of patients, of whom 49% took a medication that created therapeutic competition. CONCLUSION: In addition to confirming that polypharmacy was highly prevalent, we found that potentially inappropriate medications and therapeutic competition were also frequently present. This supports the urgent need to develop patient-centered approaches to mitigate the negative effects of complex medication regimens endemic to adults with heart failure with preserved ejection fraction.

The Impact of Videolaryngoscopy on Endotracheal Intubation Success by a Pediatric/Neonatal Critical Care Transport Team.

INTRODUCTION: Endotracheal intubation may be required for the transport of critically ill neonates and children. Data suggest that first pass success (FPS) is associated with lower rates of complications. Thus, understanding factors associated with FPS can have important implications for clinical outcomes. We aimed to determine the impact of videolaryngoscopy (VL) on FPS by a pediatric critical care transport team (CCTT). Methods: We performed a retrospective cross-sectional study on pediatric patients (≤ 18 years of age) requiring endotracheal intubation by a tertiary care-based pediatric CCTT between 2011 and 2019. Patients were categorized as neonatal (≤ 28 days of age, either preterm or term) or pediatric (> 28 days of age). All intubation attempts using VL were performed with the C-MAC videolaryngoscope. Our primary outcome was rate of FPS. Descriptive statistics of patient, provider, and procedure characteristics were calculated. Multivariate regression was used to test the association between FPS and type of laryngoscope (video versus direct) adjusting for significant clinical predictors. Results: Over the study period, 135 patients were intubated by the CCTT. Sixty percent of these patients were neonates, and 40% were pediatric. The overall FPS rate was 61%, with lower rates in neonates (54%) and higher rates in pediatric patients (70%). Use of videolaryngoscopy increased over the study period. First pass success rate using the C-MAC videolaryngoscope was 72% compared to 42% for direct laryngoscopy across the whole study population. In adjusted analyses, FPS using VL was significantly higher in the pediatric patient population (aOR 12.42 [95%CI 3.33, 46.29]), but not in neonates (aOR 1.08 [0.44, 2.63]). Use of VL increased significantly over the study period. Conclusion: We found use of a C-MAC videolaryngoscope by a critical care transport team was associated with improved FPS during endotracheal intubation of pediatric patients but not neonates, after controlling for other patient and provider characteristics. In addition to the impact on FPS, use of VL may offer additional educational and quality benefits.

Prevalence and staging of non-alcoholic fatty liver disease among patients with heart failure with preserved ejection fraction.

Insulin resistance and altered energy metabolism is common in non-alcoholic fatty liver disease (NAFLD) and appears to also be associated with myocardial dysfunction. We aimed to evaluate prevalence, staging and clinical features correlated with NAFLD among patients with heart failure with preserved ejection fraction (HFpEF). Adults with HFpEF were prospectively enrolled. Demographic and clinical data were collected. NAFLD was defined based on liver biopsy, abdominal imaging or ICD-coding and the absence of other liver diseases. Descriptive, bivariate and multivariable analyses were performed. 181 patients were analyzed. The median age was 70 with 89% white, 59% female, median BMI 35.1, and 48% with diabetes. NAFLD was present in 27% of the full cohort and 50% of those with imaging. In patients with imaging, multivariable analysis identified diabetes (OR 3.38, 95% CI 1.29-8.88) and BMI (OR 1.11, 95% CI 1.04-1.19) as independent correlates of NAFLD. 54% of NAFLD patients had a NAFLD fibrosis score consistent with advanced fibrosis. Cirrhosis was present in 6.6% of patients overall and 11.5% with imaging. NAFLD patients had a higher frequency of advanced heart failure (75% vs 55%, p 0.01). NAFLD has a two-fold higher prevalence in HFpEF compared to the general population and is independently associated with BMI and diabetes. Patients with HFpEF and NAFLD also appeared to have more advanced fibrosis including cirrhosis suggesting a potential synergistic effect of cardiac dysfunction on fibrosis risk in NAFLD. This data supports consideration for evaluation of underlying liver disease in HFpEF patients.

Clinical Implications of Identifying Pathogenic Variants in Individuals With Thoracic Aortic Dissection.

BACKGROUND: Thoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or family members. METHODS: We performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity. RESULTS: Twenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 versus 57 years), higher rates of root aneurysm (54% versus 30%), less hypertension (15% versus 57%), lower rates of smoking (19% versus 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed that pathogenic variant carrier status was significantly associated with age <50 (odds ratio [OR], 5.5; 95% CI, 1.6-19.7), no history of hypertension (OR, 5.6; 95% CI, 1.4-22.3), and family history of aortic disease (mother: OR, 5.7; 95% CI, 1.4-22.3, siblings: OR, 5.1; 95% CI, 1.1-23.9, children: OR, 6.0; 95% CI, 1.4-26.7). CONCLUSIONS: Clinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with a thoracic aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset <50 years, family history of thoracic aortic disease, and no history of hypertension.

Predictors of a drainable suppurative adenitis among children presenting with cervical adenopathy.

OBJECTIVES: We sought to identify predictors for a drainable suppurative adenitis [DSA] among patients presenting with acute cervical lymphadenitis. METHODS: A retrospective cross sectional study of all patients admitted to an urban pediatric tertiary care emergency department over a 15 year period. Otherwise healthy patients who underwent imaging for an evaluation of cervical lymphadenitis were included. Cases were identified using a text-search module followed by manual review. We excluded immunocompromised patients and those with lymphadenopathy felt to be not directly infected (i.e. reactive) or that was not acute (symptom duration >28 days). Data collected included: age, gender, duration of symptoms, highest recorded temperature, physical exam findings, laboratory and imaging results, and surgical findings. A DSA was defined as >1.5 cm in diameter on imaging. We performed binary logistic regression to determine independent clinical predictors of a DSA. RESULTS: Three hundred sixty-one patients met inclusion criteria. Three hundred six patients (85%) had a CT scan, 55 (15%) had an ultrasound and 33 (9%) had both. DSA was identified in 71 (20%) patients. Clinical features independently associated with a DSA included absence of clinical pharyngitis, WBC >15,000/mm3, age ≤3 years, anterior cervical chain location, largest palpable diameter on exam >3 cm and prior antibiotic treatment of >24 h. The presence of fever, skin erythema, or fluctuance on examination, was not found to be predictive of DSA. CONCLUSIONS: We identified independent predictors of DSA among children presenting with cervical adenitis. Risk can be stratified into risk groups based on these clinical features.

Lower Extremity Function Is Independently Associated With Hospitalization Burden in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Frailty reflects decreased resilience to physiological stressors; its prevalence and prognosis are not fully defined in heart failure with preserved ejection fraction (HFpEF). METHODS: The Short Physical Performance Battery (SPPB) was prospectively obtained in 114 outpatients with HFpEF. The SPPB tests gait speed, tandem balance, and timed chair rises, each scored from 0 to 4 points. Severe and mild frailty were respectively defined as an SPPB score ≤6 and 7-9 points. We used risk-adjusted logistic, Poisson, and negative binominal regression, respectively, to assess the relationship between SPPB score and risk of death or all-cause hospitalization, number of hospitalizations, and days hospitalized or dead longer than 6 months. RESULTS: Patients were similar to other HFpEF cohorts (age 68 ± 13 years, 58% female, body mass index 36 ± 8 kg/m2, multiple comorbidities). Mean SPPB score was 6.9 ± 3.2, and 80% of patients were at least mildly frail. Over a 6-month period, the SPPB score independently predicted death or all-cause hospitalization (odds ratio 0.81 per point, 95% confidence interval [CI] 0.69-0.94, P = .006), number of hospitalizations (incidence rate ratio 0.92 per point, 95% CI 0.86-0.97, P = .006), and days hospitalized or dead (incidence rate ratio 0.85 per point, 95% CI 0.73-0.99, P = .04). CONCLUSIONS: Lower extremity function, as measured by the SPPB, independently predicts hospitalization burden in outpatients with HFpEF. Additional studies are warranted to explore shared mechanisms and treatment implications of frailty in HFpEF.

Trigeminal Nerve Root Demyelination Not Seen in Six Horses Diagnosed with Trigeminal-Mediated Headshaking.

Trigeminal-mediated headshaking is an idiopathic neuropathic facial pain syndrome in horses. There are clinical similarities to trigeminal neuralgia, a neuropathic facial pain syndrome in man, which is usually caused by demyelination of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. Our hypothesis was that the neuropathological substrate of headshaking in horses is similar to that of trigeminal neuralgia in man. Trigeminal nerves, nerve roots, ganglia, infraorbital, and caudal nasal nerves from horse abattoir specimens and from horses euthanized due to trigeminal-mediated headshaking were removed, fixed, and processed for histological assessment by a veterinary pathologist and a neuropathologist with particular experience of trigeminal neuralgia histology. No histological differences were detected between samples from horses with headshaking and those from normal horses. These results suggest that trigeminal-mediated headshaking may have a different pathological substrate from trigeminal neuralgia in man.

Examining the Washington State Breastfeeding-Friendly Policy Development Process Using the Advocacy Coalition Framework.

Objectives Breastfeeding promotion is increasingly recognized as a key public health strategy. Policies can promote breastfeeding by creating supportive environments and addressing challenges. In 2014, the Washington State legislature considered bills to create a voluntary recognition system for breastfeeding-friendly hospitals, clinics, worksites and childcare settings. These Breastfeeding-Friendly Washington (BFW) bills (SB 6298 and HB 2329) did not pass. Methods The purpose of this case study was to analyze the policy development process for the BFW bills using the Advocacy Coalition Framework. Data were collected through semi-structured interviews with key stakeholders in the state policy process, and document review. We used thematic analysis to identify deductive and inductive themes. Results Though all policy actors indicated general support for breastfeeding, two main coalitions (proponents and opponents) diverged in their support of the BFW bills as policy solutions to address barriers to breastfeeding. We conducted 29 interviews with mainly bill proponents, and 54 documents confirmed data about bill opponents. Proponents supported the bills given increasingly strong evidence of breastfeeding's benefits and that public policy could address environmental challenges to breastfeeding. Opponents saw the bills as government overreach into the private matter of choosing to breastfeed. Opposition to the bills came late in the session, and proponents felt opponents' messaging misconstrued the intent of the legislation. Conclusions for Practice Key learnings for developing breastfeeding-friendly state policies include analyzing differences between proponents' and opponents' beliefs, framing advocacy messages beyond individuals and health, expanding the coalition outside of traditional health entities, and anticipating the opposition.

Development of a Novel Medial Synoviocentesis Approach to the Bicipital Bursa in an Equine Cadaver Model.

OBJECTIVE: To describe the volume and dimensions of the bicipital bursa and its position in relation to bony and soft tissue structures, in order to develop a novel medial synoviocentesis approach to the bicipital bursa. STUDY DESIGN: Cadaveric study. ANIMALS: Adult equine cadaver limbs (n=19). METHODS: Bicipital bursa dimensions, volume, and relationship to bony structures were obtained from positive contrast computed tomography images after distension of the bursa (n=7). Following an intra-bursal injection of polyurethane resin, the bicipital bursa (n=4) was dissected and its relationship to soft tissue structures described. After computed tomography and dissection, a novel medial bicipital bursocentesis approach was investigated on intact cadavers (n=8). RESULTS: Median (range) of measurements were: length 9.02 cm (8.48-9.45 cm); width 7.06 cm (6.71-8.01 cm); and volume 51 mL (45-58 mL). The medial aspect of the bicipital bursa was located at the junction of the subclavius and biceps muscles, which corresponds with the externally visible lateral pectoral sulcus. Needle insertion 5-10 mm craniolateral to the center of the lateral pectoral sulcus midway between the palpable distal aspect of the deltoid tuberosity and the cranial part of the greater tubercle was found to be a reliable landmark for the novel medial bursocentesis approach. This approach was successful in all cadavers. CONCLUSION: The novel approach to the bicipital bursa provided access to the medial aspect of the bursa and is an alternative to the lateral approaches. Further validation in live horses is warranted to establish the safety and efficacy of this technique.

The effect of breech presentation on the accuracy of estimated fetal weight.

To determine whether fetal presentation affects the accuracy of ultrasonographic estimated fetal weight (EFW). This is a retrospective cohort study of singleton pregnancies that underwent ultrasonographic EFW within 3 weeks of delivery at a single institution from 1993 to 2008. Breech presenting fetuses were compared with those presenting cephalic. EFW using the Hadlock formula was compared with actual birth weight (ABW) and reported as mean difference and mean percentage difference. Differences were also considered categorically. Subgroup analyses were performed of women who delivered within 4 days of scan and excluding women with comorbidities. Ability to detect small and large for gestational age infants was compared. Evaluation of 3770 patients, 183 (4.9%) breech presenting and 3587 (95.1%) cephalic presenting revealed no difference in mean gram difference (-222.1 g ± 312.6 vs. -210.7 g ± 793.2, p = 0.084), respectively, or ability to accurately predict within 10% of ABW (adjusted odds ratio [AOR] 1.23; 95% CI, 0.89,1.69; p = 0.208). Subgroup analyses revealed similar results. There was no difference in the ability to detect small and large for gestational age infants. Presentation does not demonstrably affect the accuracy of ultrasonographic EFW when utilizing the Hadlock formula.

Sonographic evaluation and the pregnancy complicated by diabetes.

Sonography is a fundamental tool in the management of pregnancies affected by maternal diabetes. Purposeful use of ultrasound in each trimester provides an invaluable amount of information about the developing fetus including gestational age and growth patterns, anatomical structure and function, assessment of fetal well-being, and prediction of adverse outcome. There are great ongoing research efforts in this field of prenatal diagnosis and management, yet even more are needed.

Discussion: 'Congenital toxoplasmosis' by Berrébi et al.

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Berrébi A, Assouline C, Bessières M-H, et al. Long-term outcome of children with congenital toxoplasmosis. Am J Obstet Gynecol 2010;203:552.e1-6.