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Biomolecules & Biomedicine Jun 2024Dear Editor, We have read the article "The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan...
Letter regarding "The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders".
Dear Editor, We have read the article "The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders", recently published in your esteemed journal. We are a team dedicated to diagnosing, approaching, and managing patients with connective tissue disorders, particularly hypermobile spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS). We appreciate the research group's effort to address the complexity of connective tissue disorders using a multi-panel genetic approach and their analysis of genotype-phenotype associations in a cohort of Mexican patients. However, we would like to express our concern regarding two specific points that we consider crucial for the comprehensive understanding and management of these disorders. Read more in the PDF.
PubMed: 38912888
DOI: 10.17305/bb.2024.10799 -
Advances in Experimental Medicine and... 2024Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and...
Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.
Topics: Humans; Chromosome Aberrations; DNA Copy Number Variations; Genetic Predisposition to Disease; Heart Septal Defects, Ventricular; Mutation; Transcription Factors
PubMed: 38884729
DOI: 10.1007/978-3-031-44087-8_27 -
The Annals of Thoracic Surgery Jun 2024Characteristics, practice patterns, and clinical outcomes of secondary spontaneous pneumothorax (SSP) with heritable connective tissue disorders (Marfan, Ehlers-Danlos,...
BACKGROUND
Characteristics, practice patterns, and clinical outcomes of secondary spontaneous pneumothorax (SSP) with heritable connective tissue disorders (Marfan, Ehlers-Danlos, and Birt-Hogg-Dubé syndromes) are unclear.
METHODS
A nationwide Japanese inpatient database that included data of 524 patients with SSP (884 hospitalizations) and 137,821 with primary spontaneous pneumothorax between July 2010 and March 2020 was used in this study. Hospitalization for SSP (n = 884) was categorized into surgical (n = 459) and nonsurgical (n = 425) groups, and the patient characteristics, treatment, and outcomes were compared between the groups. Multivariable analyses were performed to evaluate risk factors for pneumothorax recurrence. We also compared the characteristics of patients with different underlying heritable connective tissue disorders.
RESULTS
Compared with the nonsurgical group, the surgical group had less frequent readmission for pneumothorax (26% vs 44%; hazard ratio, 0.47; 95% CI, 0.38-0.58). Young patients (2.46; 1.83-3.32) or those with Birt-Hogg-Dubé syndrome (2.53; 1.77-3.63) had a high risk of recurrence. Pneumothorax occurred frequently in teenagers with Marfan syndrome, in those aged 20 to 39 years with Ehlers-Danlos syndrome, and in those aged ≥40 years with Birt-Hogg-Dubé syndrome.
CONCLUSIONS
Detailed information on the characteristics and clinical course of SSP in heritable connective tissue disorders will aid in the clinical decision-making process.
PubMed: 38878950
DOI: 10.1016/j.athoracsur.2024.05.037 -
Radiographics : a Review Publication of... Jul 2024A variety of systemic conditions involve the thorax and the eyes. While subtle or nonspecific eye symptoms can be the initial clinical manifestation of some disorders,... (Review)
Review
A variety of systemic conditions involve the thorax and the eyes. While subtle or nonspecific eye symptoms can be the initial clinical manifestation of some disorders, there can be additional manifestations in the thorax that lead to a specific diagnosis and affect patient outcomes. For instance, the initial clinical manifestation of Sjögren syndrome is dry eye or xerophthalmia; however, the presence of Sjögren lung disease represents a fourfold increase in mortality. Likewise, patients with acute sarcoidosis can initially present with pain and redness of the eye from uveitis in addition to fever and parotitis. Nearly 90% of patients with sarcoidosis have thoracic involvement, and the ophthalmologic symptoms can precede the thoracic symptoms by several years in some cases. Furthermore, a diagnosis made in one system can result in the screening of other organs as well as prompt genetic evaluation and examination of family members, such as in the setting of Marfan syndrome or Ehlers-Danlos syndrome. Multimodality imaging, particularly CT and MRI, plays a vital role in identification and characterization of these conditions. While it is helpful for ophthalmologists to be knowledgeable about these conditions and their associations so that they can order the pertinent radiologic studies, it is also important for radiologists to use the clues from ophthalmologic examination in addition to imaging findings to suggest a specific diagnosis. Systemic conditions with thoracic and ophthalmologic manifestations can be categorized as infectious, inflammatory, autoimmune, neoplastic, or hereditary in origin. The authors describe a spectrum of these conditions based on their underlying cause. RSNA, 2024.
Topics: Humans; Eye Diseases; Thoracic Diseases; Diagnosis, Differential; Multimodal Imaging
PubMed: 38870047
DOI: 10.1148/rg.230132 -
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 -
Neurological Sciences : Official... Jun 2024Neurological abnormalities have been frequently reported in individuals with Marfan Syndrome (MFS). However, available data relies solely on retrospective studies...
BACKGROUND AND AIMS
Neurological abnormalities have been frequently reported in individuals with Marfan Syndrome (MFS). However, available data relies solely on retrospective studies predating current diagnostic criteria.
METHODS
Cross-sectional study comprehensively investigating neurological abnormalities within a prospective cohort of adults (≥ 18 years) with genetically confirmed MFS referred to an Italian hub center for heritable connective tissue diseases (Jan. 1st - Nov. 15th, 2021).
RESULTS
We included a total of 38 individuals (53% female). The commonest neurological symptom was migraine (58%), usually without aura (73%). Neuropsychological testing was generally unremarkable, whilst anxiety and depression were highly prevalent within our cohort (42% and 34%, respectively). The most frequent brain parenchymal abnormality was the presence of cortico-subcortical hypointense spots on brain MRI T2* Gradient-Echo sequences (39%), which were found only in patients with a prior history of aortic surgery. Migraineurs had a higher frequency of brain vessels tortuosity vs. individuals without migraine (73% vs. 31%; p = 0.027) and showed higher average and maximum tortuosity indexes in both anterior and posterior circulation brain vessels (all p < 0.05). At univariate regression analysis, the presence of brain vessels tortuosity was significantly associated with a higher risk of migraine (OR 5.87, CI 95% 1.42-24.11; p = 0.014).
CONCLUSIONS
Our study confirms that neurological abnormalities are frequent in individuals with MFS. While migraine appears to be associated with brain vessels tortuosity, brain parenchymal abnormalities are typical of individuals with a prior history of aortic surgery. Larger prospective studies are needed to understand the relationship between parenchymal abnormalities and long-term cognitive outcomes.
PubMed: 38837112
DOI: 10.1007/s10072-024-07625-2 -
BMJ Case Reports Jun 2024
Topics: Humans; Male; Diagnosis, Differential; Marfan Syndrome; Pneumothorax; Tomography, X-Ray Computed; Adolescent
PubMed: 38834310
DOI: 10.1136/bcr-2024-260843 -
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