Systematic review and meta-analysis of right subclavian artery variants and their correlation with cervical-thoracic clinical conditions.

BACKGROUND: A high incidence of anatomical variations in the origin of the branches of the aortic arch has been reported, Nowadays, this variation is considered the most frequent in the aortic arch, its prevalence being estimated between 0.5% and 2.5% of the population. To understand its origin, knowledge of embryonic development is necessary. METHODS: We searched the MEDLINE, Scopus, Web of Science, Google Scholar, Cumulative Index to Nursing and Allied Health Literature, and Latin-American literature and caribean of health sciences databases with dates ranging from their inception to June 2023. Study selection, data extraction, and methodological quality were assessed with the guaranteed tool for anatomical studies (Anatomical Quality Assurance). Finally, the pooled prevalence was estimated using a random effects model. RESULTS: Thirty-nine studies were found that met the eligibility criteria. Twenty studies with a total of 41,178 subjects were included in the analysis. The overall prevalence of an ARSA variant was 1% (95% confidence interval = 1%-2%), the clinical findings found are that if ARSA is symptomatic it could produce changes in the hemodynamic function of the thoracocervical region in addition to other associated symptomatic complications in surrounding structures. CONCLUSIONS: ARSA can cause several types of alterations in the cervical or thoracic region, resulting in various clinical complications, such as lusory dysphagia. Hence, knowing this variant is extremely important for surgeons, especially those who treat the cervico-thoracic region. The low prevalence of ARSA means that many professionals are completely unaware of its existence and possible course and origin. Therefore, this study provides detailed knowledge of ARSA so that professionals can make better diagnoses and treatment of ARSA.

Aberrant Right Subclavian Artery: Demographics, Morphological Features and Follow up CT Scans Dynamics.

Introduction: Aberrant right subclavian artery (ARSA) is the most common of the aortic arch anomalies, occurring in .5% to 1% of the population. There is no standardized follow up protocol, especially in the asymptomatic cases. The purpose of the present study was to evaluate the natural history of ARSA and the role of serial CT scans. Methods: This is a single-center retrospective study of patients with ARSA depicted on chest computed tomography (CT) scans between February 2013 and July 2022. Data were collected from their medical records. Measurements of the aorta at different segments including the aortic diameter at the orifice of ARSA, and ARSA at ostium followed by 1 cm intervals were collected, as well as for follow-up CT scans. Results: 65 patients were diagnosed with ARSA, 70.8% of whom were women. The average age for the cohort was 58.569 ± 16.99 years. The median follow up time was 4 years (range 0-10 years), KM estimated survival after ARSA diagnosis at 1 and 5 years as 97% and 93%, respectively. Nineteen patients had a second CT scan and were included in the morphological CT dynamic analysis, on average of 29 ± 27 months apart (range 7-108). The mean ARSA diameter at origin was larger in the second scan 16.91 ± 4.31 mm compared to the initial scan 16.31 ± 4.96 mm, (P = .04).The mean aortic arch diameter in the first and second CT were 28.54 ± 4.24 and 29.64 ± 5.14 (P = .10), respectively. All other measurements did not disclose any significant enlargement over time. Conclusions: Our cohort demonstrate a benign natural history of ARSA with slow growth rates. However, due to our small sample size we can't draw a clinically sound recommendation on the need for imaging follow up, and further larger cohort with longer follow up interval are required.

Isolated Vascular Rings Are Common Cardiovascular Malformations.

OBJECTIVE: We investigated the prevalence of isolated vascular rings in the general population of Southern Nevada. METHODS: We identified those prenatally and postnatally diagnosed with an isolated vascular ring between January 2014 and December 2021. We included only those with vascular or ligamentous structures completely encircling the trachea and esophagus. To investigate the prevalence of isolated vascular rings, we included only those with situs solitus, levocardia, and no significant intracardiac malformations. RESULTS: We identified 112 patients. Of the 112, 66 (59%) were female. There were approximately 211,000 total live births in Southern Nevada for the study period, for an overall prevalence of 5.3 isolated vascular rings per 10 000 live births. However, for the years 2014 to 2017, the average prevalence figure was 3.5 per 10 000 live births, and for the years 2018 to 2021, the average prevalence figure was 7.1 (range 6.5-8.0) per 10 000 live births. Simultaneously, the prenatal detection rate rose from 66% to 86%. CONCLUSIONS: Isolated vascular rings are common cardiovascular malformations. As prenatal detection rates in the Southern Nevada general population approach 90%, the prevalence figures for isolated vascular rings appear to asymptote at about 7 per 10 000 live births.

Incidencia y características de los pacientes portadores de defectos congénitos en el Servicio de Neonatología del Centro Hospitalario Pereira Rossell 2016-2020: 5 años de experiencia / Incidence and characteristics of patients with congenital defects at the Pereira Rossell Hospital's Neonatology Department in 2016-2020: 5 years experience / Incidência e características dos pacientes com defeitos congênitos no Serviço de Neonatologia do Centro Hospitalar Pereira Rossell 2016-2020: 5 anos de experiencia

Los defectos congénitos son alteraciones morfológicas que se originan durante la vida intrauterina que se presentan hasta en un 5% de los recién nacidos vivos. Tienen múltiples etiologías, siendo esta multifactorial en el 90% de los casos. Se realizó un estudio observacional, prospectivo, descriptivo incluyendo a todos los recién nacidos portadores de defectos congénitos en el período 2016-2020. El objetivo de este trabajo es determinar la incidencia de defectos congénitos en recién nacidos del Centro Hospitalario Pereira Rossell en el período mencionado, así como conocer su distribución por aparatos y sistemas, las características demográficas de esta población, la prevalencia de diagnóstico prenatal y la exposición materna a factores de riesgo durante la organogénesis. Se obtuvo una incidencia de 1,7% (423 recién nacidos afectados en 24.870 nacimientos), de los cuales el 34,98% contaba con diagnóstico prenatal. El sistema cardiovascular fue el que presentó una mayor frecuencia de alteraciones, y el defecto congénito más frecuentemente observado individualmente fue la gastrosquisis, con una incidencia de 15,28 cada 10.000 nacidos vivos. La diabetes gestacional se presentó en el 17,25% de las gestantes. Este trabajo nos permitió conocer la incidencia de defectos congénitos, así como su distribución por aparatos y sistemas. Este tipo de sistemas de vigilancia resultan fundamentales para identificar elementos a mejorar, que permitan disminuir la morbilidad y mortalidad de estos pacientes y también identificar precozmente factores de riesgo que aumenten estas patologías de forma significativa.

Congenital birth defects are morphological disturbances originated during gestation and present in up to 5% of live births. They have multiple etiologies, in 90% of cases of multifactorial origin. A longitudinal, prospective, observational study was carried out and it included all patients with congenital birth defects in 2016-2020. The main objective of this study was to determine the incidence of newborns with congenital birth defects between 2016 and 2020, to determine their distribution by organ, to describe their demographic characteristics, to calculate the prevalence of prenatal diagnosis and to identify maternal risk factors. We obtained an incidence of 1,7% (423 affected newborns in 24870 live births), 34,98% had prenatal diagnoses. The cardiovascular system was the most frequently affected and when classified by individual birth defect, the most frequently observed was gastroschisis with 15.28 cases in 10,000 live births. Gestational diabetes was the maternal risk factor most frequently observed with 17, 25%. This study enabled us to know the incidence of congenital birth defects and their distribution by different organs at our center. These surveillance systems are key to identify areas of potential improvement that might enable us to mitigate morbidity and mortality in this group of patients.

Os defeitos congênitos são alterações morfológicas que se originam durante a vida intrauterina e ocorrem em até 5% dos recém-nascidos vivos. Possuem múltiplas etiologias, sendo multifatoriais em 90% dos casos. Realizou-se um estudo observacional, prospectivo e descritivo incluindo todos os recém-nascidos com defeitos congênitos no período 2016-2020. O objetivo deste trabalho foi determinar a incidência de defeitos congênitos em recém-nascidos do Centro Hospitalar Pereira Rossell no período 2016-2020, bem como conhecer sua distribuição por órgãos e sistemas, as características demográficas dessa população, a prevalência de diagnóstico pré-natal e exposição materna a fatores de risco durante a organogênese. Obteve-se uma incidência de 1,7% (423 recém-nascidos afetados em 24.870 nascimentos), dos quais 34,98% tiveram diagnóstico pré-natal. O sistema cardiovascular foi o que apresentou maior frequência de alterações, e o defeito congênito mais observado individualmente foi a gastrosquise com incidência de 15,28 em cada 10.000 nascidos vivos. O diabetes gestacional ocorreu em 17,25% das gestantes. Este paper permitiu conhecer a incidência de defeitos congênitos, bem como sua distribuição por órgãos e sistemas. Estes tipos de sistemas de vigilância são essenciais para identificar elementos a melhorar, que permitam reduzir a morbilidade e mortalidade desses pacientes e também identificar precocemente fatores de risco que aumentam significativamente essas patologias.

Prenatal diagnosis of aberrant right subclavian artery: a literature review.

The primary aim of this review is to estimate the prevalence of ARSA both in euploid fetuses as well as in fetuses with Down Syndrome. Secondary objectives were to estimate the association of ARSA with cardiac anomalies and chromosomal defects, especially trisomy 21 and 22q11 deletion (DiGeorge Syndrome). The incidence of ARSA in normal population varies from 0.35% to 3.5%, based on different studies. Since the first reported association between ARSA and trisomy 21 in 2015 until today, several studies have emerged to confirm different degrees of this correlation. Indeed, ARSA appears to be a clinically useful prenatal ultrasound marker for trisomy 21. Particularly, most recent studies concluded that ARSA as a non-isolated finding can be used as screening for Down syndrome. However, when ARSA is an isolated finding, various studies proved that there is no significant correlation with Down syndrome. Apart from these, ARSA appears to be associated with other chromosomal abnormalities, such as 22q11 deletion, cardiac defects and other morphological anomalies. As a conclusion ARSA should be characterized as isolated or non-isolated, as the non - isolated ARSA appears to be a clinically useful marker of Down syndrome and thus, additional testing is required when diagnosed.

Adverse cardiovascular responses of engineered nanomaterials: Current understanding of molecular mechanisms and future challenges.

Nanotechnology is spanning multiple fields of study from materials science to computer engineering and drug discovery. Since the early 21st century, nanotechnology and nano-enabled research have received great attention and governmental funding accompanied with interest to ensure human and environmental safety of engineered nanomaterials (ENMs). Optimal functioning of the cardiovascular (CV) system is of utmost importance for the overall health of the body. Following exposure, ENMs essentially end up in the circulation (at least partially) and hence it is key to assess any associated adverse CV consequences. Accumulating research suggests that exposure to ENMs (different compositions and physicochemical properties) has the capacity to directly and indirectly interact with CV components resulting in adverse events and worsening of CV complications. However, the underlying molecular mechanisms driving these events remain to be elucidated. In this article, we review state-of-art literature on ENM-associated adverse CV responses and discuss the potential underlying molecular mechanisms.

Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children.

Importance: Information on underlying conditions and severe COVID-19 illness among children is limited. Objective: To examine the risk of severe COVID-19 illness among children associated with underlying medical conditions and medical complexity. Design, Setting, and Participants: This cross-sectional study included patients aged 18 years and younger with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification code U07.1 (COVID-19) or B97.29 (other coronavirus) during an emergency department or inpatient encounter from March 2020 through January 2021. Data were collected from the Premier Healthcare Database Special COVID-19 Release, which included data from more than 800 US hospitals. Multivariable generalized linear models, controlling for patient and hospital characteristics, were used to estimate adjusted risk of severe COVID-19 illness associated with underlying medical conditions and medical complexity. Exposures: Underlying medical conditions and medical complexity (ie, presence of complex or noncomplex chronic disease). Main Outcomes and Measures: Hospitalization and severe illness when hospitalized (ie, combined outcome of intensive care unit admission, invasive mechanical ventilation, or death). Results: Among 43 465 patients with COVID-19 aged 18 years or younger, the median (interquartile range) age was 12 (4-16) years, 22 943 (52.8%) were female patients, and 12 491 (28.7%) had underlying medical conditions. The most common diagnosed conditions were asthma (4416 [10.2%]), neurodevelopmental disorders (1690 [3.9%]), anxiety and fear-related disorders (1374 [3.2%]), depressive disorders (1209 [2.8%]), and obesity (1071 [2.5%]). The strongest risk factors for hospitalization were type 1 diabetes (adjusted risk ratio [aRR], 4.60; 95% CI, 3.91-5.42) and obesity (aRR, 3.07; 95% CI, 2.66-3.54), and the strongest risk factors for severe COVID-19 illness were type 1 diabetes (aRR, 2.38; 95% CI, 2.06-2.76) and cardiac and circulatory congenital anomalies (aRR, 1.72; 95% CI, 1.48-1.99). Prematurity was a risk factor for severe COVID-19 illness among children younger than 2 years (aRR, 1.83; 95% CI, 1.47-2.29). Chronic and complex chronic disease were risk factors for hospitalization, with aRRs of 2.91 (95% CI, 2.63-3.23) and 7.86 (95% CI, 6.91-8.95), respectively, as well as for severe COVID-19 illness, with aRRs of 1.95 (95% CI, 1.69-2.26) and 2.86 (95% CI, 2.47-3.32), respectively. Conclusions and Relevance: This cross-sectional study found a higher risk of severe COVID-19 illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes, cardiac and circulatory congenital anomalies, and obesity. Health care practitioners could consider the potential need for close observation and cautious clinical management of children with these conditions and COVID-19.

Relationship between non-headache symptoms and right to left shunt in episodic migraine. A single-center cross-sectional study.

The relationship between right to left shunt (RLS) and non-headache symptoms (NHS) in episodic migraine is unknown. This study aimed to investigate the incidence and classification of RLS in episodic migraineurs, calculate the occurrence rate of NHS, and analyze the associations between RLS and NHS. We consecutively recruited 204 episodic migraine patients. Contrast-enhanced transcranial doppler was adopted to screen RLS. Structured questionnaire via face-to-face survey was conducted to collect clinical data. A total of 172 episodic migraineurs were included in the final analysis, of which 20 cases were migraine with aura. The positive rate of RLS was 47.1%, of which 50 cases (29.0%) had small shunt (Grade 1) and 31 cases (18.1%) had mid-large shunt (Grade 2-4). The most common NHS was nausea (115 (66.9%)), followed by headache aggravation with physical activity (96 (55.8%)), dizziness (93 (54.1%)), vomiting (77 (44.8%)) and phonophobia (74 (43.0%)). Yawning was more common in Grade 2-4 group than Grade 0 group (p = 0.012), while no statistical differences among other groups. Grade 2-4 group had a higher rate of headache aggravation with physical activity than grade 0 group (p = 0.008). Binary logistic regression analysis showed that yawning at premonitory phase, headache aggravation with physical activity and cranial autonomic symptoms during attack are independent predictors of RLS. In conclusion, yawning and headache aggravation with physical activity are more common in migraine patients with RLS. Besides aura, particular NHS may also serve as indicators for screening RLS in episodic migraineurs.

Congenital polyvalvular disease expands the cardiac phenotype of the RASopathies.

The RASopathies are a group of similar genetic syndromes with cardiovascular abnormalities, characteristic facial features, short stature, abnormalities of the skin and musculoskeletal system, and variable neurodevelopmental challenges. The most common cardiovascular abnormalities include pulmonary valvular stenosis and hypertrophic cardiomyopathy. Congenital polyvalvular disease (CPVD) refers to congenital dysplasia of two or more cardiac valves. We diagnosed a RASopathy in two individuals with CPVD and noted that CPVD in RASopathies has rarely been reported in the literature. Thus, we performed a retrospective chart review and literature review to investigate the association and characterize the phenotype of CPVD in the RASopathies. CPVD was present in 2.5% (n = 6/243) of individuals in our RASopathy cohort. Involvement of two cardiac valves, commonly the aortic and pulmonic valves, was seen in the majority of individuals (6/8; 75%) in our cohort, but only 27% (3/11) of reported CPVD and RASopathy cases in the literature. CPVD should be considered an associated cardiovascular phenotype of the RASopathies, which has implications for diagnosis and management.

Predictive value of aberrant right subclavian artery for fetal chromosome aneuploidy in women of advanced maternal age.

BACKGROUND: In the entire population, an aberrant right subclavian artery (ARSA) is closely associated with chromosomal abnormalities. ARSA with additional ultrasonic findings would increase risk of chromosomal abnormalities. The risk of fetal chromosomal abnormalities increased exponentially with the maternal age. These risks in the advanced maternal age (AMA) group are uncertain. This study aimed to determine the incidence of ARSA in Chinese AMA and non-AMA women and the frequency of aneuploidy among AMA and non-AMA women with ARSA. METHODS: This retrospective study included 13,690 singleton pregnancies, were divided into AMA and non-AMA groups. Integrated obstetric ultrasonic screening, biochemical screening, noninvasive prenatal screening, and fetal karyotype analysis were analyzed. RESULTS: The overall incidence of ARSA was 0.69%, with no difference between age groups. The incidence of chromosomal abnormalities in the AMA group (37 / 2860) was much higher than that of the non-AMA group. The risk of chromosomal abnormalities significantly increased with both ARSA detected and additional ultrasound findings. With combined ARSA and AMA, the likelihood of the incidence of chromosomal abnormalities increased. Chimerism (45X / 46XX) was found with isolated ARSA in AMA pregnancies. CONCLUSION: There is a high prevalence of chromosomal abnormalities in fetuses of AMA women. ARSA increases the risk of chromosomal abnormalities in both age groups, especially combined with ARSA. When ARSA occurs in AMA women, it confers a high likelihood of chromosomal abnormalities.

Selective serotonin reuptake inhibitors and the risk of congenital anomalies: a systematic review of current meta-analyses.

Objective: A review of current meta-analyses examining the relationship between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and congenital anomalies. Methods: PubMed was searched for meta-analyses published in English language between January 2010 and April 2020 by using the following combinations of key words: meta-analysis, pregnancy, antidepressant, SSRI, citalopram, escitalopram, fuloxetine, paroxetine, sertraline, fluvoxamine, neonatal outcome, birth outcome, congenital malformation, congenital anomaly, birth defect, cardiac malformation and heart defect. Results: A total of 15 meta-analyses met the search criteria. These meta-analyses consistently suggested a significant positive association between the use of SSRIs in general and paroxetine and fluoxetine in particular and the risk of major congenital anomalies. The data also showed a consistency in increased cardiovascular defects in infants due to maternal use of paroxetine. The risk of cardiovascular defects in infants of women using SSRIs in general and fluoxetine and sertraline in particular was controversial. Conclusion: Further large-scale prospective observational studies and meta-analyses on the effects of individual SSRIs other than paroxetine, especially escitalopram and fluvoxamine, are required to reach definitive conclusions.

Ultrasonic detection of fetal persistent right umbilical vein and incidence and significance of concomitant anomalies.

BACKGROUND: Persistent right umbilical vein (PRUV) is characterized by atresia of the left umbilical vein while the right umbilical vein remains open. Given the limited sample size of most studies, the incidence of PRUV and the status of concomitant anomalies may not be fully reflected. Thus, we studied the incidence of fetal PRUV and its concomitant anomalies on a larger scale using our hospital database. This study hoped to address the following questions: Does PRUV increase the risk of fetal anomalies? If the PRUV fetus also has a single umbilical artery (SUA), does the risk of fetal anomaly increase further? What is the positive predictive value of PRUV for fetal anomalies? METHODS: This retrospective study analyzed 756 cases of fetal PRUV at our hospital from January 2007 to April 2017. Prenatal ultrasound and color Doppler images were assessed. All PRUV fetuses underwent echocardiography and detailed ultrasound examinations of other systems. Newborn status was obtained via the database or by telephone follow-up. RESULTS: A total of 435,428 pregnant women underwent prenatal ultrasonography at 16-40 weeks, the incidence of fetal PRUV was 0.17%, and 102 fetuses (13.5%) developed other anomalies. Two complicated cases had trisomy 18. PRUV was associated with a higher incidence of fetal anomalies. When fetal anomalies were classified by body systems, PRUV was associated with a higher incidence of cardiovascular, nervous, urinary, skeletal, digestive, and respiratory system anomalies. The positive predictive values of a PRUV for any fetal anomalies and cardiovascular anomalies were 13.5% (95%CI, 11.2-16.2%) and 5.4% (95%CI, 4.0-7.3%), respectively. SUA further increases the risk of PRUV fetuses with other anomalies and cardiovascular anomalies. CONCLUSIONS: Detailed prenatal ultrasonography and echocardiography should be performed in fetuses with PRUV to rule out anomalies in other systems. When the PRUV is combined with SUA, echocardiography is particularly important. Fetuses with complicated PRUV should undergo chromosomal examination. Although isolated fetal PRUV prognosis is good, complicated PRUV prognosis depends on the type and severity of the concomitant anomalies.

Associated anomalies in cases with congenital clubfoot.

Congenital clubfoot CTEV is a common congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with CTEV often have other non-CTEV associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with CTEV were collected in all livebirths, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 504 cases with CTEV, representing a prevalence of 13.02 per 10,000, 107 (21.2%) had associated anomalies. There were 31 (6.1%) cases with chromosomal abnormalities, and 21 (4.2%) non-chromosomal recognized dysmorphic conditions including syndromes: 6 arthrogryposis multiplex congenita, 2 22q11.2 microdeletion, and one fetal alcohol syndrome. Fifty-five (10.9%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the cardiovascular, the central nervous, the urinary, the orofacial, and the musculoskeletal systems were the most common other anomalies in the cases with MCA. The anomalies associated with CTEV could be classified into a recognizable malformation syndrome in 52 of the 107 cases (48.6%) with associated anomalies. This study included special strengths: it is population-based, each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion the overall prevalence of associated anomalies, one of five cases, emphasizes the need for a screening for other anomalies in cases with CTEV.

Seguimiento a muy largo plazo de pacientes sometidos a cierre de defectos septales interauriculares / Long-term outcomes after percutaneous atrial septal deffects closure

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Intermittent absent and reversed umbilical artery flows in appropriately grown monochorionic diamniotic twins in relation to proximate cord insertion: A harmful combination?

OBJECTIVE: To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome. METHODS: The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated. RESULTS: iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress. CONCLUSION: iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.

Association of aberrant subclavian arteries with aortic pathology and proposed classification system.

OBJECTIVE: Aberrant subclavian artery (aSCA) is a rare anatomic variant whose association with other aortic branch variations and aortic pathology has yet to be established. Knowledge of such an association could be relevant to recommendations for screening and awareness as associated variations are important for operative planning. We describe the incidence of aSCA variations, its association with aortic pathology, and a proposed classification system. METHODS: The thoracic cross-sectional imaging database at Keck Hospital of the University of Southern California from 2006 to 2018 was queried for presence of aSCA. Studies were evaluated for aSCA laterality, variant anatomy, and aortic and branch vessel disease. Medical records were reviewed for associated symptoms and diagnoses. The primary outcome was association of aSCA with aortic pathology (aneurysm or dissection). Secondary outcomes were comparison of right and left aSCA, comparison between the sexes, and creation of a proposed classification system. RESULTS: Of 98,580 axial imaging studies, 810 studies (0.82%) were identified with aSCA in 312 unique patients. Right aSCA made up the majority of cases (90.1%). All aSCAs had a retroesophageal course. Kommerell's diverticulum (KD) was present in 184 (59%) with an average diameter of 1.67 cm (range, 1.2-3.3 cm). KD was more frequent (84% vs 56%; P = .0003) and larger (2.05 cm vs 1.61 cm; P < .0001) in left aSCA patients. When present, KD was more often symptomatic in left aSCA compared with right aSCA (77.4% vs 49.1%; P = .005). Dysphagia, chest pain, reflux, and asthma were all more common in left aSCA patients. KD was also more common in men (73.3% vs 50%; P < .0001) and larger in men (1.81 cm vs 1.54 cm; P < .0001) but with no difference in symptoms between sexes. Our proposed classification system based on aortic arch branching is as follows: type 1, left arch with right aSCA (59.9%); type 2, left arch with common carotid trunk and right aSCA (30.1%); type 3, right arch with left aSCA (9.6%); and type 4, right arch with common carotid trunk and left aSCA (0.3%). Subtypes describe the right vertebral artery (RVA) and left vertebral artery (LVA) origin: subclavian (s, RVA 90.1%, LVA 96.8%), carotid (c, RVA 9.6%, LVA 0.3%), or arch (a, RVA 0.3%, LVA 2.9%). Overall, 9.9% (31/312) had associated aortic pathology, although the study was underpowered to detect a difference between right aSCA and left aSCA (9.3% vs 16.1%; P = .213). Type 3 and type 4 arches more often have associated aortic pathology, KD, and symptoms. CONCLUSIONS: aSCAs are frequently symptomatic and commonly associated with aortic dissection and aneurysm. Our proposed classification scheme depicts all four aSCA arch variants and accounts for vertebral artery origin variation. These variants are common, and vertebral anatomy can differ greatly. Knowledge of these anatomic variations is critical to planning for endovascular and open repair of aortic arch pathology.

Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study.

OBJECTIVE: To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children. DESIGN: Population based cohort study. SETTING: The UK Clinical Practice Research Datalink. PARTICIPANTS: The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort. MAIN OUTCOME MEASURES: Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder. RESULTS: Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses. CONCLUSIONS: Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available. TRIAL REGISTRATION: ClinicalTrials.gov NCT03948620.

High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes: 20-Year Follow-up of a Phase 3 Randomized Clinical Trial.

Importance: Trials of adjuvant high-dose chemotherapy (HDCT) have failed to show a survival benefit in unselected patients with breast cancer, but long-term follow-up is lacking. Objective: To determine 20-year efficacy and safety outcomes of a large trial of adjuvant HDCT vs conventional-dose chemotherapy (CDCT) for patients with stage III breast cancer. Design, Setting, and Participants: This secondary analysis used data from a randomized phase 3 multicenter clinical trial of 885 women younger than 56 years with breast cancer and 4 or more involved axillary lymph nodes conducted from August 1, 1993, to July 31, 1999. Additional follow-up data were collected between June 1, 2016, and December 31, 2017, from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from February 1, 2018, to October 14, 2019. Interventions: Participants were randomized 1:1 to receive 5 cycles of CDCT consisting of fluorouracil, 500 mg/m2, epirubicin, 90 mg/m2, and cyclophosphamide, 500 mg/m2, or HDCT in which the first 4 cycles were identical to CDCT and the fifth cycle was replaced by cyclophosphamide, 6000 mg/m2, thiotepa, 480 mg/m2, and carboplatin, 1600 mg/m2, followed by hematopoietic stem cell transplant. Main Outcomes and Measures: Main end points were overall survival and safety and cumulative incidence risk of a second malignant neoplasm or cardiovascular events. Results: Of the 885 women in the study (mean [SD] age, 44.5 [6.6] years), 442 were randomized to receive HDCT, and 443 were randomized to receive CDCT. With 20.4 years median follow-up (interquartile range, 19.2-22.0 years), the 20-year overall survival was 45.3% with HDCT and 41.5% with CDCT (hazard ratio, 0.89; 95% CI, 0.75-1.06). The absolute improvement in 20-year overall survival was 14.6% (hazard ratio, 0.72; 95% CI, 0.54-0.95) for patients with 10 or more invoved axillary lymph nodes and 15.4% (hazard ratio, 0.67; 95% CI, 0.42-1.05) for patients with triple-negative breast cancer. The cumulative incidence risk of a second malignant neoplasm at 20 years or major cardiovascular events was similar in both treatment groups (20-year cumulative incidence risk for second malignant neoplasm was 12.1% in the HDCT group vs 16.2% in the CDCT group, P = .10), although patients in the HDCT group more often had hypertension (21.7% vs 14.3%, P = .02), hypercholesterolemia (15.7% vs 10.6%, P = .04), and dysrhythmias (8.6% vs 4.6%, P = .005). Conclusions and Relevance: High-dose chemotherapy provided no long-term survival benefit in unselected patients with stage III breast cancer but did provide improved overall survival in very high-risk patients (ie, with ≥10 involved axillary lymph nodes). High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT03087409.

Birth defects in Taiwan: A 10-year nationwide population-based, cohort study.

BACKGROUND/PURPOSE: Birth defects (BDs) are main causes of mortality and disability in infants and children. The aims of this study were to analyze the prevalence, types and risk factors of BDs in Taiwan. METHODS: Data of all births (including live and stillbirths), types, characteristics, and associated risk factors of BDs were obtained from the National Birth Registry and National Health Insurance Research Data base in Taiwan between 2005 and 2014. Birth defects were coded according to International Classification of Diseases 9th Revision-Clinical Modification codes 740-759. RESULTS: A total of 55,299 infants were diagnosed as having BDs among 2,033,004 births. The prevalence of BDs was 271.66 per 10,000 births. The prevalence of BDs did not change significantly between 2005 and 2014, there was a higher birth rate and lower BDs in 2012 (year of dragon) in Taiwan. The most common type of BDs was cardiovascular abnormalities, and ventricular septal defect was the most common disease. Extreme maternal age (<18 years or ≧30 years), preterm, and low birth weight were associated with BDs. Maternal diseases associated with BDs included hypertension, cardiovascular diseases, renal diseases, genitourinary infections, anemia, mental disorders, and diabetes mellitus. CONCLUSION: The prevalence of BDs was 271.66 per 10,000 births. The most common types of BDs were cardiovascular abnormalities. If we can reduce maternal chronic diseases, we will decrease the prevalence of BDs.

Bovine aortic arch: Prevalence in human fetuses.

OBJECTIVE: "Bovine aortic arch" is the second most common variant of aortic arch branching, in which only two branches originate directly from the aorta. The prevalence of this condition has been reported in different studies to be around 6% in human fetuses and 11-27% in the adult population. In this study, we describe the prevalence of bovine aortic arch in fetuses, and assess the prevalence of concomitant fetal anomalies. METHODS: A retrospective analysis of 417 fetuses between 15-40 weeks of gestation. Data regarding branching of the fetal aortic arch and other fetal anomalies were collected by fetal echocardiography and/or fetal ultrasonography. RESULTS: A bovine arch was found in 20/413 fetuses (4.8%, 95CI 3.1-7.3%), of whom 14/310 (4.5%) had no fetal anomalies, and 6/77 (7.8%) exhibited minor changes (P = .241). None of the 26 fetuses with major anomalies had a bovine arch. CONCLUSION: Fetuses in this study had a lower prevalence of bovine aortic arch than that previously reported in adults, most probably due to differences in the population examined. This study was underpowered to determine that bovine arch is a common anatomic variant, and is not associated with fetal anomalies.