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Multimedia Manual of Cardiothoracic... Jun 2024Single-stage total aortic replacement represents a comprehensive approach for patients at high risk of aorta-related complications between procedures. It not only avoids...
Single-stage total aortic replacement represents a comprehensive approach for patients at high risk of aorta-related complications between procedures. It not only avoids staged surgical treatment but also facilitates quicker rehabilitation. Opting for a radical surgery in such cases can yield superior outcomes compared with a staged approach, making it particularly suitable for young patients with aorta-related risk factors. Moreover, a single-stage aorta repair reduces the likelihood of subsequent aortic interventions.
Topics: Humans; Aortic Dissection; Marfan Syndrome; Blood Vessel Prosthesis Implantation; Aortic Aneurysm, Thoracic; Male; Adult
PubMed: 38869837
DOI: 10.1510/mmcts.2024.017 -
Journal of Cardiothoracic Surgery Jun 2024Marfan Syndrome is an autosomal dominant disease caused by pathogenetic variants in the FBN1 gene. The progressive dilatation of the aorta and the potential risk of...
BACKGROUND
Marfan Syndrome is an autosomal dominant disease caused by pathogenetic variants in the FBN1 gene. The progressive dilatation of the aorta and the potential risk of acute aortic syndromes influence the prognosis of these patients. We aim to describe population characteristics, long-term survival, and re-intervention patterns in patients who underwent aortic surgery with a previously confirmed clinical diagnosis of Marfan Syndrome in a middle-income country.
METHODS
A retrospective single-center case series study was conducted. All Marfan Syndrome patients who underwent aortic procedures from 2004 until 2021 were included. Qualitative variables were frequency-presented, while quantitative ones adopted mean ± standard deviation. A subgroup analysis between elective and emergent procedures was conducted. Kaplan-Meier plots depicted cumulative survival and re-intervention-free. Control appointments and government data tracked out-of-hospital mortality.
RESULTS
Fifty patients were identified. The mean age was 38.79 ± 14.41 years, with a male-to-female ratio of 2:1. Common comorbidities included aortic valve regurgitation (66%) and hypertension (50%). Aortic aneurysms were observed in 64% without dissection and 36% with dissection. Surgical procedures comprised elective (52%) and emergent cases (48%). The most common surgery performed was the David procedure (64%), and the Bentall procedure (14%). The in-hospital mortality rate was 4%. Complications included stroke (10%), and acute kidney injury (6%). The average follow-up was 8.88 ± 5.78 years. Survival rates at 5, 10, and 15 years were 89%, 73%, and 68%, respectively. Reintervention rates at 1, 2.5, and 5 years were 10%, 14%, and 17%, respectively. The emergent subgroup was younger (37.58 ± 14.49 years), had the largest number of Stanford A aortic dissections, presented hemodynamic instability (41.67%), and had a higher requirement of reinterventions in the first 5 years of follow-up (p = 0.030).
CONCLUSION
In our study, surveillance programs played a pivotal role in sustaining high survival rates and identifying re-intervention requirements. However, challenges persist, as 48% of the patients required emergent surgery. Despite not affecting survival rates, a greater requirement for reinterventions was observed, emphasizing the necessity of timely diagnosis. Enhanced educational initiatives for healthcare providers and increased patient involvement in follow-up programs are imperative to address these concerns.
Topics: Humans; Marfan Syndrome; Male; Female; Retrospective Studies; Adult; Middle Aged; Aortic Dissection; Young Adult; Aortic Aneurysm
PubMed: 38849906
DOI: 10.1186/s13019-024-02793-w -
Ophthalmology Science 2024Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the ( (). In addition to typical phenotypes such as ectopia lentis (EL) and aortic...
PURPOSE
Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the ( (). In addition to typical phenotypes such as ectopia lentis (EL) and aortic dilation, patients with MFS are prone to ocular posterior segment abnormalities, including retinal detachment (RD), maculopathy, and posterior staphyloma (PS). This study aims to investigate the correlations between genotype and posterior segment abnormalities within a Chinese cohort of MFS.
DESIGN
Retrospective study.
PARTICIPANTS
One hundred twenty-one eyes of 121 patients with confirmed mutations between January 2015 and May 2023 were included.
METHODS
Comprehensive ophthalmic examination findings were reviewed, and the incidence of RD, atrophic, tractional, and neovascular maculopathy (ATN classification system), and PS was analyzed between different genotype groups. Only the more severely affected eye from each patient was included.
MAIN OUTCOME MEASURES
Clinical features and risk factors.
RESULTS
Of 121 patients, 60 eyes (49.59%) exhibited posterior segment abnormalities, including RD (4, 3.31%), maculopathy (47, 38.84%), and PS (54, 44.63%). The mean age was 11.53 ± 11.66 years, with 79.34% of patients <20 years old. The location and region of mutations were found to be associated with the incidence of maculopathy ( = 0.013, = 0.033) and PS ( = 0.043, = 0.036). Mutations in the middle region had a lower incidence of maculopathy and PS ( = 0.028 and = 0.006, respectively) than those in C-terminal region. Mutations in the transforming growth factor-β (TGF-β) regulating sequence exhibited a higher incidence of maculopathy and PS ( = 0.020, = 0.040). Importantly, the location and region of mutations were also associated with the incidence of atrophic maculopathy ( = 0.013 and = 0.033, respectively). Mutations in the middle region had a significantly lower probability of atrophic maculopathy ( = 0.006), while mutations in the TGF-β regulating region had a higher incidence of atrophic maculopathy ( = 0.020).
CONCLUSIONS
Maculopathy and PS were associated with the location and region of mutations. Patients with mutations in the TGF-β regulating region faced an increased risk of developing retinopathy.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38840780
DOI: 10.1016/j.xops.2024.100526 -
Journal of Epidemiology and Global... Jun 2024To analyze the clinical characteristics of Brucella endocarditis (BE) and observe the factors related to death to provide guidance for clinical treatment.
OBJECTIVE
To analyze the clinical characteristics of Brucella endocarditis (BE) and observe the factors related to death to provide guidance for clinical treatment.
METHODS
This study examined all patients with BE admitted to The First People's Hospital of Kashi Prefecture between January 2017 and November 2023. Clinical characteristics and follow-up outcomes were collected for analysis.
RESULTS
This study revealed 774 cases of brucellosis and 14 cases of BE, with an overall incidence rate of 1.88%. Most of the patients were male (71.43%) and lived in areas where brucellosis is common. Patients ranged in age from 26 to 68 years. Common symptoms reported among patients included chest tightness and fatigue, and a significant portion also presented with congestive heart failure. Most patients exhibited normal white blood cell counts (WBC) but had elevated levels of C-reactive protein (CRP). Transthoracic ultrasound (TTE) revealed cardiac valve vegetation in all patients, along with positive blood cultures. Six patients (42.86%) completed heart surgery, and ten (71.43%) completed anti-infection treatment. Six patients died, five of whom did not undergo surgery. The other patient with Marfan syndrome died after surgery. Sex, WBC count, neutrophil (NEUT) and total bilirubin (TBIL) were significant factors associated with regression in BE patients (P < 0.05) according to univariate analysis.
CONCLUSIONS
Patients with BE in Kashi have a severe clinical presentation at diagnosis, but early detection with improved cardiac ultrasound and aggressive treatment can improve the prognosis.
PubMed: 38829489
DOI: 10.1007/s44197-024-00232-6 -
Cureus May 2024Patients with Marfan syndrome have a constellation of clinical features and a heterogeneous phenotype. The purpose of this study is to report a 47-year-old male patient...
Patients with Marfan syndrome have a constellation of clinical features and a heterogeneous phenotype. The purpose of this study is to report a 47-year-old male patient with an unusual variant in the gene causing Marfan syndrome. The patient with musculoskeletal, cardiovascular, and ocular findings compatible with Marfan syndrome had an unusual pathogenic mutation on the gene. The patient was examined by at least one of the authors (NJI). The patient's clinical findings were compatible with Marfan syndrome. Our patient had a unique mutation in the gene (c.8054A>G p.His2685Arg) located on exon 65. Next-generation sequencing was done using the Invitae panel. This variant was categorized as one of uncertain significance. This patient's variant on the gene leading to the syndrome has scant data associated with it and this is the first time it is reported from Puerto Rico.
PubMed: 38826987
DOI: 10.7759/cureus.59452 -
Cureus Apr 2024Marfan syndrome (MFS) is a rare hereditary connective tissue disorder with autosomal dominant inheritance associated with an increased risk of cardiovascular...
Marfan syndrome (MFS) is a rare hereditary connective tissue disorder with autosomal dominant inheritance associated with an increased risk of cardiovascular complications due to connective tissue fragility. Acute myocardial infarction during pregnancy is also a rare event associated with poor maternal and fetal outcomes. Herein, we report a case of a 30-year-old pregnant woman with a known history of MFS. The patient had been treated surgically for an ascending aorta aneurysm and mechanical prosthetic aortic valve repair. She presented at 12 weeks of gestation with severe chest pain, which proved to be acute myocardial infarction. This is believed to be the first case of this complex medical condition presented in the first trimester of pregnancy.
PubMed: 38807841
DOI: 10.7759/cureus.59182 -
International Journal of Molecular... May 2024Fibrillin-1 and fibrillin-2, encoded by and , respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of...
Fibrillin-1 and fibrillin-2, encoded by and , respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.
Topics: Humans; Fibrillin-1; Marfan Syndrome; Fibrillin-2; Male; Infant, Newborn; Heart Defects, Congenital; High-Throughput Nucleotide Sequencing; Female; Polymorphism, Single Nucleotide; Mutation; Genomics; Phenotype; Exome Sequencing; Adipokines
PubMed: 38791509
DOI: 10.3390/ijms25105469 -
Genes May 2024When stroke occurs in pediatric age, it might be mistakenly interpreted as non-accidental head injury (NAHI). In these situations, a multidisciplinary approach is... (Review)
Review
When stroke occurs in pediatric age, it might be mistakenly interpreted as non-accidental head injury (NAHI). In these situations, a multidisciplinary approach is fundamental, including a thorough personal and familial history, along with accurate physical examination and additional investigations. Especially when the clinical picture is uncertain, it is important to remember that certain genetic conditions can cause bleeding inside the brain, which may resemble NAHI. Pediatric strokes occurring around the time of birth can also be an initial sign of undiagnosed genetic disorders. Hence, it is crucial to conduct a thorough evaluation, including genetic testing, when there is a suspicion of NAHI but the symptoms are unclear. In these cases, a characteristic set of symptoms is often observed. This study aims to summarize some of the genetic causes of hemorrhagic stroke in the pediatric population, thus mimicking non-accidental head injury, considering elements that can be useful in characterizing pathologies. A systematic review of genetic disorders that may cause ICH in children was carried out according to the Preferred Reporting Item for Systematic Review (PRISMA) standards. We selected 10 articles regarding the main genetic diseases in stroke; we additionally selected 11 papers concerning patients with pediatric stroke and genetic diseases, or studies outlining the characteristics of stroke in these patients. The disorders we identified were Moyamoya disease (MMD), , pathogenic variant, Ehlers-Danlos syndrome (E-D), neurofibromatosis type 1 (Nf1), sickle cell disease (SCD), cerebral cavernous malformations (CCM), hereditary hemorrhagic telangiectasia (HHT) and Marfan syndrome. In conclusion, this paper provides a comprehensive overview of the genetic disorders that could be tested in children when there is a suspicion of NAHI but an unclear picture.
Topics: Humans; Hemorrhagic Stroke; Child, Preschool; Genetic Testing; Craniocerebral Trauma; Infant; Diagnosis, Differential
PubMed: 38790247
DOI: 10.3390/genes15050618 -
Orphanet Journal of Rare Diseases May 2024Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1).
BACKGROUND
Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1).
METHODS
A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses.
RESULTS
Two cis-compound benign intronic variants of FBN1 (c.3464-4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein's secondary structure by interfering with one disulfide bond between Cys and Cys and causing the extension of an anti-parallel β sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis.
CONCLUSIONS
To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.
Topics: Humans; Fibrillin-1; Marfan Syndrome; Female; Male; Pedigree; Mosaicism; Adult; Introns; INDEL Mutation; Middle Aged; Adipokines
PubMed: 38773661
DOI: 10.1186/s13023-024-03139-4 -
Global Heart 2024Patients diagnosed with Marfan syndrome or a related syndrome require frequent aorta monitoring using imaging techniques like transthoracic echocardiography (TTE) and...
Updated 2022 ACC/AHA Guideline Improves Concordance Between TTE and CT in Monitoring Marfan Snydrome and Related Disorders, but Relevant Measurement Differences Remain Frequent.
BACKGROUND
Patients diagnosed with Marfan syndrome or a related syndrome require frequent aorta monitoring using imaging techniques like transthoracic echocardiography (TTE) and computed tomography (CT). Accurate aortic measurement is crucial, as even slight enlargement (>2 mm) often necessitates surgical intervention. The 2022 ACC/AHA guideline for Aortic Disease Diagnosis and Management includes updated imaging recommendations. We aimed to compare these with the 2010 guideline.
METHODS
This retrospective study involved 137 patients with Marfan syndrome or a related disorder, undergoing TTE and ECG-triggered CT. Aortic diameter measurements were taken based on the old 2010 guideline (TTE: inner edge to inner edge, CT: external diameter) and the new 2022 guideline (TTE: leading edge to leading edge, CT: internal diameter). Bland-Altman plots compared measurement differences.
RESULTS
Using the 2022 guideline significantly reduced differences outside the clinical agreement limit from 49% to 26% for the aortic sinus and from 41% to 29% for the ascending aorta. Mean differences were -0.30 mm for the aortic sinus and +1.12 mm for the ascending aorta using the 2022 guideline, compared to -2.66 mm and +1.21 mm using the 2010 guideline.
CONCLUSION
This study demonstrates for the first time that the 2022 ACC/AHA guideline improves concordance between ECG-triggered CT and TTE measurements in Marfan syndrome patients, crucial for preventing life-threatening aortic complications. However, the frequency of differences >2 mm remains high.
CLINICAL RELEVANCE/APPLICATION
Accurate aortic diameter measurement is vital for patients at risk of fatal aortic complications. While the 2022 guideline enhances concordance between imaging modalities, frequent differences >2 mm persist, potentially impacting decisions on aortic repair. The risk of repeat radiation exposure from ECG-triggered CT, considered the 'gold standard', continues to be justified.
Topics: Humans; Marfan Syndrome; Retrospective Studies; Male; Female; Echocardiography; Adult; Tomography, X-Ray Computed; Middle Aged; Practice Guidelines as Topic; United States; Young Adult; Aorta; Adolescent
PubMed: 38737456
DOI: 10.5334/gh.1322