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Background: Variations in renal veins are quite common, and most people do not experience issues due to them. However, these variations are important for healthcare professionals, especially in surgical procedures and imaging studies, as precise knowledge of vascular anatomy is essential to avoid complications during medical interventions. The purpose of this study was to expose the frequency of anatomical variations in the renal vein (RV) and detail their relationship with the retroperitoneal and renal regions. Methods: A systematic search was conducted in the Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception until January 2024. Two authors independently carried out the search, study selection, and data extraction and assessed methodological quality using a quality assurance tool for anatomical studies (AQUA). Ultimately, consolidated prevalence was estimated using a random effects model. Results: In total, 91 studies meeting the eligibility criteria were identified. This study included 91 investigations with a total of 46,664 subjects; the meta-analysis encompassed 64 studies. The overall prevalence of multiple renal veins was 5%, with a confidence interval (CI) of 4% to 5%. The prevalence of the renal vein trajectory was 5%, with a CI of 4% to 5%. The prevalence of renal vein branching was 3%, with a CI of 0% to 6%. Lastly, the prevalence of unusual renal vein origin was 2%, with a CI of 1% to 4%. Conclusions: The analysis of these variants is crucial for both surgical clinical management and the treatment of patients with renal transplant and hemodialysis.
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Background: Glioblastoma is a primary malignant brain tumor; it is aggressive with a high degree of malignancy and unfavorable prognosis and is the most common type of malignant brain tumor. Glioblastomas can be located in the brain, cerebellum, brainstem, and spinal cord, originating from glial cells, particularly astrocytes. Methods: The databases MEDLINE, Scopus, Web of Science, Google Scholar, and CINAHL were researched up to January 2024. Two authors independently performed the search, study selection, and data extraction. Methodological quality was evaluated with an assurance tool for anatomical studies (AQUA). The statistical mean, standard deviation, and difference of means calculated with the Student's t-test for presence between hemispheres and presence in the frontal and temporal lobes were analyzed. Results: A total of 123 studies met the established selection criteria, with a total of 6224 patients. In relation to the mean, GBM between hemispheres had a mean of 33.36 (SD 58.00) in the right hemisphere and a mean of 34.70 (SD 65.07) in the left hemisphere, due to the difference in averages between hemispheres. There were no statistically significant differences, p = 0.35. For the comparison between the presence of GBM in the frontal lobe and the temporal lobe, there was a mean in the frontal lobe of 23.23 (SD 40.03), while in the temporal lobe, the mean was 22.05 (SD 43.50), and for the difference in means between the frontal lobe and the temporal lobe, there was no statistically significant difference for the presence of GBM, p = 0.178. Conclusions: We believe that before a treatment, it will always be correct to know where the GBM is located and how it behaves clinically, in order to generate correct conservative or surgical treatment guidelines for each patient. We believe that more detailed studies are also needed to show why GBM is associated more with some regions than others, despite the brain structure being homologous to other regions in which GMB occurs less frequently, which is why knowing its predominant presence in brain regions is very important.
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BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.
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Miocardite , Miocárdio , Sistema de Registros , Humanos , Miocardite/patologia , Miocardite/diagnóstico , Miocardite/mortalidade , Masculino , Criança , Feminino , Adolescente , Adulto , Biópsia/métodos , Pré-Escolar , Prognóstico , Pessoa de Meia-Idade , Miocárdio/patologia , Transplante de Coração/estatística & dados numéricos , Europa (Continente)/epidemiologia , Desfibriladores Implantáveis , Coração AuxiliarRESUMO
BACKGROUND: Recent literature highlights anomalous cranial nerves in the sinonasal region, notably in the sphenoid and maxillary sinuses, linked to anatomical factors. However, data on the suspended infraorbital canal (IOC) variant is scarce in cross-sectional imaging. Anatomical variations in the sphenoid sinuses, including optic, maxillary, and vidian nerves, raise interest among specialists involved in advanced sinonasal procedures. The infraorbital nerve's (ION) course along the orbital floor and its abnormal positioning within the orbital and maxillary sinus region pose risks of iatrogenic complications. A comprehensive radiological assessment is crucial before sinonasal surgeries. Cone-beam computed tomography (CBCT) is preferred for its spatial resolution and reduced radiation exposure. OBJECTIVE: The aim of this study was to describe the prevalence of anatomical variants of the infraorbital canal (IOC) and report its association with clinical condition or surgical implication. METHODS: We searched Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to June 2023. Two authors independently performed the search, study selection, data extraction, and assessed the methodological quality with assurance tool for anatomical studies (AQUA). Finally, the pooled prevalence was estimated using a random effects model. RESULTS: Preliminary results show that three types are prevalent, type 1: the IOC does not bulge into the maxillary sinus (MS); therefore, the infraorbital foramen through the anterior wall of MS could be used for identification of the ION. Type 2: the IOC divided the orbital floor into medial and lateral aspects. Type 3: the IOC hangs in the MS and the entire orbital floor lying above the IOC. From which the clinical implications where mainly surgical, in type 1 the infraorbital foramen through the anterior wall of MS could be used for identification of the ION, while in type 2, since the lateral orbital floor could not be directly accessed an inferiorly transposition of ION is helpful to expose the lateral orbital wall directly with a 0 scope; or using angled endoscopes and instruments, however, the authors opinion is that direct exposure potentially facilitates the visualization and management in complex situations such as residual or recurrent mass, foreign body, and fracture located at the lateral aspect of the canal. Lastly, in type 3, the ION it's easily exposed with a 0° scope. CONCLUSIONS: This systematic review identified four IOC variants: Type 1, within or below the MS roof; Type 2, partially protruding into the sinus; Type 3, fully protruding into the sinus or suspended from the roof; and Type 4, in the orbital floor. Clinical recommendations aim to prevent nerve injuries and enhance preoperative assessments. However, the lack of consistent statistical methods limits robust associations between IOC variants and clinical outcomes. Data heterogeneity and the absence of standardized reporting impede meta-analysis. Future research should prioritize detailed reporting, objective measurements, and statistical approaches for a comprehensive understanding of IOC variants and their clinical implications. Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/UGYFZ .
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Variação Anatômica , Tomografia Computadorizada de Feixe Cônico , Órbita , Humanos , Nervos Cranianos/anatomia & histologia , Nervos Cranianos/diagnóstico por imagem , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/anatomia & histologia , Seio Maxilar/cirurgia , Órbita/anatomia & histologia , Órbita/diagnóstico por imagem , Seio Esfenoidal/anatomia & histologia , Seio Esfenoidal/diagnóstico por imagemRESUMO
BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Adulto , Feminino , Humanos , Masculino , Arritmias Cardíacas , Insuficiência Cardíaca/genética , Estudos Retrospectivos , Volume Sistólico , Disfunção Ventricular Esquerda/genética , Função Ventricular EsquerdaRESUMO
BACKGROUND: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. RESULTS: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). CONCLUSIONS: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.
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Distrofias Hereditárias da Córnea , Doença de Fabry , Feminino , Humanos , Estudos Retrospectivos , Cognição , Doença de Fabry/epidemiologia , Doença de Fabry/genética , FenótipoRESUMO
AIMS: The aim of this study was to synthesize the evidence on the effect of the current therapies over the pathophysiological and clinical characteristics of patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: A systematic review and meta-analysis of 41 studies identified from 1383 retrieved from PubMed, Web of Science, and Cochrane was conducted. Therapies were grouped in pharmacological, invasive and physical exercise. Pharmacological agents had no effect on functional capacity measured by VO2max (1.11 mL/kg/min; 95% CI: -0.04, 2.25, P < 0.05). Invasive septal reduction therapies increased VO2max (+3.2 mL/kg/min; 95% CI: 1.78, 4.60, P < 0.05). Structured physical exercise programmes did not report contraindications and evidenced the highest increases on functional capacity (VO2max + 4.33 mL/kg/min; 95% CI: 0.20, 8.45, P < 0.05). Patients with left ventricular outflow tract (LVOT) obstruction at rest improved their VO2max to a greater extent compared with those without resting LVOT obstruction (2.82 mL/kg/min; 95% CI: 1.97, 3.67 vs. 1.18; 95% CI: 0.62, 1.74, P < 0.05). Peak LVOT gradient was reduced with the three treatment options with the highest reduction observed for invasive therapies. Left ventricular ejection fraction was reduced in pharmacological and invasive procedures. No effect was observed after physical exercise. Symptomatic status improved with the three options and to a greater extent with invasive procedures. CONCLUSIONS: Invasive septal reduction therapies increase VO2max, improve symptomatic status, and reduce resting and peak LVOT gradient, thus might be considered in obstructive patients. Physical exercise emerges as a coadjuvant therapy, which is safe and associated with benefits on functional capacity. Pharmacological agents improve reported NYHA class, but not functional capacity.
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Cardiomiopatia Hipertrófica , Função Ventricular Esquerda , Humanos , Volume Sistólico , Cardiomiopatia Hipertrófica/complicaçõesRESUMO
Heart failure (HF) and cancer are responsible for 50% of all deaths in middle-aged people. These diseases are tightly linked, which is supported by recent epidemiological studies and case control studies, demonstrating that HF patients have a higher risk to develop cancer such as lung and breast cancer. For HF patients, a one-size-fits-all clinical management strategy is not effective and patient management represents a major economical and clinical burden. Anti-cancer treatments-mediated cardiotoxicity, leading to HF have been extensively studied. However, recent studies showed that even before the initiation of cancer therapy, cancer patients presented impairments in the cardiovascular functions and exercise capacity. Thus, the optimal cardioprotective and surveillance strategies should be applied to cancer patients with pre-existing HF. Recently, preclinical studies addressed the hypothesis that there is bilateral interaction between cardiac injury and cancer development. Understanding of molecular mechanisms of HF-cancer interaction can define the profiles of bilateral signaling networks, and identify the disease-specific biomarkers and possibly therapeutic targets. Here we discuss the shared pathological events, and some treatments of cancer- and HF-mediated risk incidence. Finally, we address the evidences on bilateral connection between cardiac injury (HF and early cardiac remodeling) and cancer through secreted factors (secretoms).
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AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.
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Displasia Arritmogênica Ventricular Direita , Arritmias Cardíacas , Displasia Arritmogênica Ventricular Direita/genética , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Genótipo , Humanos , Medição de Risco , Fatores de RiscoRESUMO
AIMS: Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure, and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure. METHODS AND RESULTS: Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and five control samples were analysed by RNA-Seq (discovery group). These cases presented with cardiac arrhythmias and had a normal right ventricular function. The RNA-Seq analysis identified â¼5000 differentially expressed genes (DEGs), which predicted suppression of the Hippo and canonical WNT pathways, among others. Dysregulated genes and pathways, identified by RNA-Seq, were tested for validation in the right and left ventricular tissues from five independent autopsy-confirmed ACM cases with defined mutations (validation group), who were victims of SCD and had no history of heart failure. Protein levels and nuclear localization of the cWNT and Hippo pathway transcriptional regulators were reduced in the right and left ventricular validation samples. In contrast, levels of acetyltransferase EP300, known to suppress the Hippo and canonical WNT pathways, were increased and its bona fide target TP53 was acetylated. RNA-Seq data identified apical junction, reflective of cell-cell attachment, as the most disrupted biological pathway, which were corroborated by disrupted desmosomes and intermediate filament structures. Moreover, the DEGs also predicted dysregulation of over a dozen canonical signal transduction pathways, including the Tec kinase and integrin signalling pathways. The changes were associated with increased apoptosis and fibro-adipogenesis in the ACM hearts. CONCLUSION: Altered apical junction structures are associated with activation of the EP300-TP53 and suppression of the Hippo/cWNT pathways in human ACM caused by defined mutations in the absence of an overt heart failure. The findings implicate altered mechanotransduction in the pathogenesis of ACM.
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Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Insuficiência Cardíaca , Arritmias Cardíacas/metabolismo , Cardiomiopatias/metabolismo , Morte Súbita Cardíaca/etiologia , Proteína p300 Associada a E1A/metabolismo , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Humanos , Mecanotransdução Celular , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Via de Sinalização WntRESUMO
BACKGROUND: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. METHODS: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). RESULTS: Median follow-up was 49 (18-105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P=0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04-3.44]; P=0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30-2.04]; P<0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis (P=0.07). CONCLUSIONS: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.
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Cardiomiopatia Dilatada/genética , Conectina/genética , Variação Genética , Disfunção Ventricular Esquerda/genética , Função Ventricular Esquerda/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Europa (Continente) , Feminino , Predisposição Genética para Doença , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , New South Wales , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais , Volume Sistólico/genética , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia , Remodelação VentricularRESUMO
BACKGROUND: Among the various steps of a penile inversion feminizing genitoplasty, reconstruction of the clitoris and labia minora remains the most challenging procedure. AIM: This study aims to evaluate surgical outcomes of neoclitoroplasty performed before and after the introduction of the labia minora's creation in our surgical technique. METHODS: A retrospective analysis was carried out comparing 2 groups of patients that underwent penile inversion feminizing surgery: group A (64 patients) who had labia minora and clitoral hood creation and group B (103 patients) who did not. OUTCOMES: To describe the surgical technique and outcomes of clitorolabiaplasty in male-to-female gender-affirmation surgery. RESULTS: Concerning overall complication rates, there were significant differences in the incidence of hemorrhage and urethral stenosis (P < .01). Hemorrhage surrounding the urethra and labia was identified in 40 patients (group A: n = 8 [12.5%]; group B: n = 32 [31%]) (P = .006). Neomeatal stenosis occurred in 17 patients (group A: n = 1 [1.5%]; group B: n = 16 [15.5%]) (P = .003). Partial necrosis of the clitoris occurred in 2 cases (group A: n = 0; group B: n = 2 [1.9%]) (P = .52). Necrosis of the labia majora occurred in 3 cases (group A: n = 0; group B: n = 3 [2.9%]) (P = .28). 5 patients (group A: n = 2 (3.1%); group B: n = 3 [2.9%]) (P = .93) developed rectovaginal fistula. 6 patients experienced neovaginal canal stricture (group A: n = 3 [4.6%]; group B: n = 3 [2.9%]) (P = .54). 2 patients (group A: n = 0; group B: n = 2 [1.9%]) (P = .52) reported introital stenosis; Persistent granulation tissue inside the neovagina that required in-office treatments occurred in 4 cases (group A: n = 2 [3.1%]; group B: n = 2 [1.9%]) (P = .62). Wound dehiscence occurred in 23 patients (group A: n = 13 [20.3%]; group B: n = 10 [9.7%]) (P = .05). 24 patients (group A: n = 3 [4.6%]; group B: n = 21 [20.3%]) (P = .004) underwent 28 different types of aesthetic refinements. CLINICAL IMPLICATIONS: Incorporating the creation of labia minora and clitoral hood in one step is a safe and viable option in patients undergoing male-to-female gender-affirmation surgery. STRENGTHS & LIMITATIONS: Strength of the study is the large cohort of patients included and the consistent surgical technique. To our knowledge, this is the first study that compares with a control group, the introduction of labia minora creation in male-to-female gender-affirmation surgery. Limitations include the retrospective nature of the study and the absence of patient-reported outcomes measures. CONCLUSION: Technical refinements of our technique led to a significative reduction in urethral stenosis and postoperative hemorrhage without an increased risk of major complications. Raigosa M, Avvedimento S, Descarrega J, et al. Refinement Procedures for Clitorolabiaplasty in Male-to-Female Gender-Affirmation Surgery: More than an Aesthetic Procedure. J Sex Med 2020;17:2508-2517.
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Procedimentos de Cirurgia Plástica , Cirurgia de Readequação Sexual , Clitóris/cirurgia , Estética , Feminino , Humanos , Masculino , Estudos Retrospectivos , Vulva/cirurgiaRESUMO
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A (GLA) gene that leads to reduced or undetectable α-galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD-related heart disease and expert consensus recommendations for its management.
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Doença de Fabry , Insuficiência Cardíaca , Consenso , Terapia de Reposição de Enzimas , Doença de Fabry/complicações , Doença de Fabry/genética , Doença de Fabry/terapia , Humanos , alfa-Galactosidase/genéticaRESUMO
BACKGROUND: Congenital disorder of glycosylation (CDG) type I is a group of rare disorders caused by recessive mutations in up to 25 genes that impair the N-glycan precursor formation and its transfer to proteins resulting in hypoglycosylation of multiple proteins. Congenital disorder of glycosylation causes multisystem defects usually with psychomotor delay that is diagnosed in the infancy. We aim to supply further evidences supporting that CDG may be underestimated. METHODS: Antithrombin and factor XI were studied by chromogenic and coagulometric methods. Hypoglycosylation of plasma proteins was evaluated by western blot, HPLC, Q-TOF, and RP-LC-MRM-MS. Genetic analysis included whole exome, Sanger sequencing, and PCR-allele specific assay. RESULTS: We here present an intriguing patient with an exceptional phenotype: 25-year-old women with a ventricular septal defect and severe idiopathic scoliosis but no facial dysmorphism, who dances as a professional, and has a University degree. Congenital disorder of glycosylation diagnosis started through the identification of antithrombin deficiency without SERPINC1 defect and the detection of hypoglycosylated forms. Increased levels of hypoglycosylated forms of F XI (also with significant deficiency) and transferrin were also detected. Whole exome analysis showed a novel homozygous ALG12 variant c.77T>A, p.(Val26Asp) supporting an ALG12-CDG diagnosis. It also showed three new variants in KMT2D, and a mild, known ALG6 variant. CONCLUSIONS: This novel ALG12-CDG patient (the 13th reported) underlines the heterogeneity of this CDG and broadens its phenotypical spectrum, supports that these disorders are underestimated, and suggests that combination of global hypoglycosylation with specific gene defects might determine the clinical manifestations of CDG patients.
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Defeitos Congênitos da Glicosilação/genética , Comunicação Interventricular/genética , Manosiltransferases/genética , Fenótipo , Escoliose/genética , Sucesso Acadêmico , Adulto , Defeitos Congênitos da Glicosilação/patologia , Proteínas de Ligação a DNA/genética , Feminino , Glucosiltransferases/genética , Comunicação Interventricular/patologia , Humanos , Proteínas de Membrana/genética , Mutação , Proteínas de Neoplasias/genética , Escoliose/patologiaRESUMO
Cancer therapy-induced cardiomyopathy (CCM) manifests as left ventricular (LV) dysfunction and heart failure (HF). It is associated withparticular pharmacological agents and it is typically dose dependent, but significant individual variability has been observed. History of prior cardiac disease, abuse of toxics, cardiac overload conditions, age, and genetic predisposing factors modulate the degree of the cardiac reserve and the response to the injury. Genetic/familial cardiomyopathies (CMY) are increasingly recognized in general populations with an estimated prevalence of 1:250. Association between cardiac and oncologic diseases regarding genetics involves not only the toxicity process, but pathogenicity. Genetic variants in germinal cells that cause CMY (LMNA, RAS/MAPK) can increase susceptibility for certain types of cancer. The study of mutations found in cancer cells (somatic) has revealed the implication of genes commonly associated with the development of CMY. In particular, desmosomal mutations have been related to increased undifferentiation and invasiveness of cancer. In this article, the authors review the knowledge on the relevance of environmental and genetic background in CCM and give insights into the shared genetic role in the pathogenicity of the cancer process and development of CMY.
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We aimed to analyze the nasopalatine canal shape and anatomical variations of the buccal bone wall and compare the effect of the presence or absence of the central maxillary incisors on the nasopalatine canal. The shape of the nasopalatine canal and the dimensions of the buccal bone wall were measured in 150 patients who underwent a cone-beam computed tomography study. We found that the most prevalent shape of the nasopalatine canal was funnel (31%) and the most common direction-course was slanted-straight (33%). The buccal bone wall in relation to the nasopalatine canal was thickest at the anterior nasal spine level and narrowest at the level of the most anterior-inferior point of the buccal cortex of the maxilla. A statistically significant difference was detected between morphology and direction-course of the nasopalatine canal and dental status. In sum, the study of the nasopalatine canal showed multiple variations. Precise knowledge of these variations may help to decrease the incidence of complications during implantology treatment and during facial and dental surgery.
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Boca Edêntula/diagnóstico por imagem , Osso Nasal/diagnóstico por imagem , Cavidade Nasal/diagnóstico por imagem , Palato/diagnóstico por imagem , Bochecha/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Humanos , Maxila/diagnóstico por imagemRESUMO
Arrhythmogenic cardiomyopathy (ACM) encompasses a group of inherited cardiomyopathies including arrhythmogenic right ventricular cardiomyopathy (ARVC) whose molecular disease mechanism is associated with dysregulation of the canonical WNT signalling pathway. Recent evidence indicates that ARVC and ACM caused by pathogenic variants in the FLNC gene encoding filamin C, a major cardiac structural protein, may have different molecular mechanisms of pathogenesis. We sought to identify dysregulated biological pathways in FLNC-associated ACM. RNA was extracted from seven paraffin-embedded left ventricular tissue samples from deceased ACM patients carrying FLNC variants and sequenced. Transcript levels of 623 genes were upregulated and 486 genes were reduced in ACM in comparison to control samples. The cell adhesion pathway and ILK signalling were among the prominent dysregulated pathways in ACM. Consistent with these findings, transcript levels of cell adhesion genes JAM2, NEO1, VCAM1 and PTPRC were upregulated in ACM samples. Moreover, several actin-associated genes, including FLNC, VCL, PARVB and MYL7, were suppressed, suggesting dysregulation of the actin cytoskeleton. Analysis of the transcriptome for dysregulated biological pathways predicted activation of inflammation and apoptosis and suppression of oxidative phosphorylation and MTORC1 signalling in ACM. Our data suggests dysregulated cell adhesion and ILK signalling as novel putative pathogenic mechanisms of ACM caused by FLNC variants which are distinct from the postulated disease mechanism of classic ARVC caused by desmosomal gene mutations. This knowledge could help in the design of future gene therapy strategies which would target specific components of these pathways and potentially lead to novel treatments for ACM.
Assuntos
Displasia Arritmogênica Ventricular Direita/genética , DNA/genética , Filaminas/genética , Predisposição Genética para Doença , Mutação , Displasia Arritmogênica Ventricular Direita/metabolismo , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Análise Mutacional de DNA , Filaminas/metabolismo , Perfilação da Expressão Gênica , Humanos , FenótipoRESUMO
BACKGROUND: Pathogenic variants in the filamin C (FLNC) gene are associated with inherited cardiomyopathies including dilated cardiomyopathy with an arrhythmogenic phenotype. We evaluated FLNC variants in arrhythmogenic cardiomyopathy (ACM) and investigated the disease mechanism at a molecular level. METHODS: 120 gene-elusive ACM patients who fulfilled diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) were screened by whole exome sequencing. Fixed cardiac tissue from FLNC variant carriers who had died suddenly was investigated by histology and immunohistochemistry. RESULTS: Novel or rare FLNC variants, four null and five variants of unknown significance, were identified in nine ACM probands (7.5%). In FLNC null variant carriers (including family members, nâ¯=â¯16) Task Force diagnostic electrocardiogram repolarization/depolarization abnormalities were uncommon (19%), echocardiography was normal in 69%, while 56% had >500 ventricular ectopics/24â¯h or ventricular tachycardia on Holter and 67% had late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI). Ten gene positive individuals (63%) had abnormalities on ECG or CMRI that are not included in the current diagnostic criteria for ARVC. Immunohistochemistry showed altered key protein distribution, distinctive from that observed in ARVC, predominantly in the left ventricle. CONCLUSIONS: ACM associated with FLNC variants presents with a distinctive phenotype characterized by Holter arrhythmia and LGE on CMRI with unremarkable ECG and echocardiographic findings. Clinical presentation in asymptomatic mutation carriers at risk of sudden death may include abnormalities which are currently non-diagnostic for ARVC. At the molecular level, the pathogenic mechanism related to FLNC appears different to classic forms of ARVC caused by desmosomal mutations.
Assuntos
Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Filaminas , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/genética , Meios de Contraste , Filaminas/genética , Gadolínio , Humanos , Mutação , FenótipoRESUMO
BACKGROUND CONTEXT: The retrotransverse foramen (RTF), arcuate foramen (AF), unclosed transverse foramen (UTF) and posterior atlas arch defects (PAAD) are anatomic variations of the atlas vertebra that surgeons must be aware of before spine surgery is performed. PURPOSE: To analyze the prevalence of the AF, RTF, UTF, and PAAD. STUDY DESIGN: Ex-vivo anatomical study. PATIENT SAMPLE: Two hundred eighteen atlas vertebrae obtained from 100 Caucasian subjects and 118 sub-Saharan African subjects (48 Sotho subjects, 35 Xhosa subjects and 35 Zulu subjects). METHODS: We studied 218 atlas vertebrae from skeletons of the Raymond A. Dart Collection in order to analyze the prevalence of AF, RTF, UTF, and PAAD in both Caucasian and sub-Saharan African subjects. OUTCOME MEASURES: Not applicable. RESULTS: Sixty-nine (31.2%) atlases presented anatomical variants: 64 (29.3%) presented one anatomical variant, 4 (1.8%) presented two, and 1 (0.5%) presented three. AF, RTF, UTF, Type A and Type E defects were present in 35 (16.1%), 17 (7.8%), 17 (7.8%), 5 (2.3%), and 1 (0.5%) vertebrae, respectively. The vertebrae with two anatomical variants presented a bilateral UTF and a Type A defect, a bilateral AF and a Type A defect, a right UTF and a left AF, and a right UTF and a Type E defect. The vertebra with three anatomical variants presented a bilateral RTF, a left UTF, and a left AF. No sex differences in prevalence of the RTF (p=.775), AF (p=.605), UTF (p=.408) and Type A defects (p=1.000) were found in the sub-Saharan African and Caucasian groups (RTF, p=.306; AF, p=.346; UTF, p=.121; Type A defects, p=.561). Comparison between the sub-Saharan African (all subjects) and the Caucasian group revealed no differences in the UTF (p=.105), AF (p=.144), RTF (p=.542) and Type A defects (p=.521) prevalence. Also, no differences in the prevalence of the UTF (p=.515), AF (p=.278), and RTF (p=.857) between Zulu, Xhosa and Sotho subjects were found. Neither were found sex differences in the prevalence of UTF, RTF and AF in Zulu (p=.805, p=.234, p=.129), Xhosa (p=.269, p=.181, p=.309), and Sotho subjects (p=.062, p=.590, p=.106). CONCLUSIONS: The present study has revealed no sex differences in the prevalence of AF, UTF, RTF or PAAD in both Caucasian and sub-Saharan African subjects. This research has also indicated no differences in the prevalence of the UTF, AF and RTF between Zulu, Xhosa and Sotho subjects. In addition, this study has revealed no differences in the Type A, UTF, AF, and RTF prevalence between the sub-Saharan African (all subjects) and the Caucasian subjects. These variations may be known by surgeons before spine surgery for better planning.