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Frontiers in Cardiovascular Medicine 2024This case report details the identification of a novel likely pathogenic splicing variant in the TTN gene, associated with dilated cardiomyopathy (DCM), in a 42-year-old...
This case report details the identification of a novel likely pathogenic splicing variant in the TTN gene, associated with dilated cardiomyopathy (DCM), in a 42-year-old male patient presenting with early-onset heart failure and reduced ejection fraction. DCM is a nonischemic heart condition characterized by left biventricular dilation and systolic dysfunction, with approximately one-third of cases being familial and often linked to genetic mutations. The TTN gene, encoding the largest human protein essential for muscle contraction and sarcomere structure, is implicated in about 25% of DCM cases through mutations, especially truncating variants. Our investigation revealed a previously unreported G > C mutation at the splice acceptor site in intron 356 of TTN, confirmed by Sanger sequencing and not found in population databases, suggesting a novel contribution to the understanding of DCM etiology. The case emphasizes the critical role of the TTN gene in cardiac function and the genetic complexity underlying DCM. A comprehensive literature review highlighted the prevalence and significance of splice variants in the TTN gene, particularly those affecting the titin A-band, which is known for its role in muscle contraction and stability. This variant's identification underscores the importance of genetic screening in patients with DCM, offering insights into the disease's familial transmission and potential therapeutic targets. Our findings contribute to the expanding knowledge of genetic factors in DCM, demonstrating the necessity of integrating genetic diagnostics in cardiovascular medicine. This case supports the growing evidence linking splicing mutations in specific regions of the TTN gene to DCM development and underscores the importance of genetic counseling and testing in managing heart disease.
PubMed: 38938651
DOI: 10.3389/fcvm.2024.1387063 -
JACC. Advances Oct 2023Clinical outcomes of bicuspid aortic valve (BAV) patients with ascending aortic diameters ≥50 mm who are under surveillance are poorly defined.
BACKGROUND
Clinical outcomes of bicuspid aortic valve (BAV) patients with ascending aortic diameters ≥50 mm who are under surveillance are poorly defined.
OBJECTIVES
The purpose of this study was to assess clinical outcomes in BAV patients with ascending aorta ≥50 mm.
METHODS
Multicenter retrospective cohort study of BAV adults with ascending aorta diameters ≥50 mm by transthoracic echocardiography (TTE). Patients were categorized into 50 to 54 mm and ≥55 mm groups. Clinical outcomes were aortic dissection (AoD), aorta surgery, surgical mortality, and all-cause death.
RESULTS
Of 875 consecutive BAV patients (age 60 ± 13 years, 86% men, aortic diameter 51 mm [interquartile range (IQR): 50-53 mm]), 328 (37%) underwent early surgery ≤3 months from index TTE. Of the remaining 547 patients under surveillance, 496 had diameters 50 to 54 mm and 51 had diameters ≥55 mm and were collectively followed for 7.51 (IQR: 3.98-12.20) years. Of 496 patients with diameters 50 to 54 mm under surveillance, 266 (54%) underwent surgery 2.0 (IQR: 0.77-4.16) years from index TTE. AoD occurred in 9/496 (1.8%) patients for an incidence of 0.4 cases per 100 person-years, surgical mortality was 5/266 (1.9%); and ≥moderate aortic stenosis (but not aorta size) was associated with all-cause death, hazard ratio: 2.05 (95% CI: 1.32-3.20), = 0.001. Conversely, in 547 total patients under surveillance (including 50-54 mm and ≥55 mm), both aorta size and ≥moderate aortic stenosis were associated with all-cause death (both ≤ 0.027). AoD rate in patients ≥55 mm under surveillance was 5.9%.
CONCLUSIONS
In BAV patients with ascending aorta 50 to 54 mm under surveillance, AoD incidence is low and the overall rates of AoD and surgical mortality are similar, suggesting clinical equivalence between surgical and surveillance strategies. Conversely, patients with aortas ≥55 mm should undergo surgery. Aortic stenosis is associated with all-cause death in these patients.
PubMed: 38938356
DOI: 10.1016/j.jacadv.2023.100626 -
Hepatology Communications Jul 2024The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.
BACKGROUND
The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.
METHODS
Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).
RESULTS
Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF.
CONCLUSIONS
We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.
Topics: Animals; Myosin-Light-Chain Phosphatase; Mice; Disease Models, Animal; Liver Cirrhosis; Cholestasis; Gallbladder Diseases; Gallbladder; Male; Mice, Knockout
PubMed: 38934703
DOI: 10.1097/HC9.0000000000000473 -
Journal of Inflammation Research 2024Significant gastrointestinal hemorrhages, resulting from long-term compression of the duodenum by a hepatic pseudoaneurysm (HAPA), is an extremely rare condition. In...
AIM
Significant gastrointestinal hemorrhages, resulting from long-term compression of the duodenum by a hepatic pseudoaneurysm (HAPA), is an extremely rare condition. In fact, when the pseudoaneurysm is small in diameter, diagnosis can be particularly challenging. Timely and effective diagnosis and treatment is therefore of great significance, and in this case, endoscopy, combined with intravascular therapy, can provide an effective approach, especially since it removes the need for surgery while yielding favorable outcomes.
CASE SUMMARY
A 75-year-old old man presented to the hospital's emergency department with hematemesis and black stool. Despite conservative treatments such as "acid suppression, fluid resupply, hemostasis and blood transfusion", no significant improvement was noted. Emergency gastroscopy subsequently revealed an ulcer in the duodenal bulb (Figure 1), with an exposed thrombotic head and active bleeding on the surface. In addition, abdominal computed tomography (Figure 2) showed no obvious HAPA manifestations. After unsuccessful endoscopic hemostasis, angiography was performed (Figure 3) and a pseudotumor-like dilatation measuring 5.56 mm in diameter was found at the distal end of the proximal branch vessel of the common hepatic artery. Following spring coil embolization (Figure 4), the patient's condition improved and he was discharged from the hospital, with a follow-up after six months showing no signs of recurrence or complications.
CONCLUSION
Duodenal ulcer hemorrhages due to small hepatic pseudoaneurysms are very rare, with endoscopic intervention being effective for such cases.
PubMed: 38933359
DOI: 10.2147/JIR.S467969 -
Turk Gogus Kalp Damar Cerrahisi Dergisi Apr 2024This study aimed to investigate the safety and efficacy of transverse aortic arch stenting and evaluate the course of hypertension and the act of arch stenting on...
BACKGROUND
This study aimed to investigate the safety and efficacy of transverse aortic arch stenting and evaluate the course of hypertension and the act of arch stenting on systemic hypertension.
METHODS
The transverse aortic arch stenting procedures between January 2007 and May 2023 were retrospectively analyzed. Detailed procedure information, technical aspects, pressure measurements, angiographic data, balloons and stents used, complications, and immediate results were examined. Early and mid-term results were assessed.
RESULTS
Eighteen patients (10 males and 8 females; mean age: 14.5±5.3 years; range, 4 to 23 years) were included in the study, all of whom were hypertensive before the procedure. The mean weight was 56.8±19.6 kg. In seven patients, the stent struts had to be dilated due to the stent causing jailing at the entrance of nearby arch vessels. After stenting, there was a significant increase in arch diameter and a decrease in ascending aorta pressure and the pressure gradient across the aorta. There were no early mortality or major complications. Late migration of the stent was observed in one patient. Three patients became normotensive immediately after the intervention, and five became drug-free during the follow-up. The requirement for dual antihypertensive therapy was significantly reduced.
CONCLUSION
Residual transverse arch lesions may contribute to the persistence of systemic hypertension after coarctation treatment. Transverse arch stent implantation can be performed safely with favorable outcomes, facilitating better blood pressure control. However, it should be noted that these patients remain at risk for lifelong hypertension and should be closely monitored in this regard.
PubMed: 38933307
DOI: 10.5606/tgkdc.dergisi.2024.25931 -
Acta Endocrinologica (Bucharest,... 2023This study aimed to determine predictive clinical and endoscopic ultrasound (EUS) features for pancreatic neuroendocrine tumor (PNET) diagnosis, utilizing EUS-guided...
BACKGROUND
This study aimed to determine predictive clinical and endoscopic ultrasound (EUS) features for pancreatic neuroendocrine tumor (PNET) diagnosis, utilizing EUS-guided tissue acquisition.
METHODS
A prospective study from 2018-2022 included patients with pancreatic masses undergoing EUS with elastography. Univariate binomial logistic regression followed by multiple logistic regression with significant predictors was employed. A forward selection algorithm identified optimal models based on predictor numbers. Variables encompassed EUS tumor characteristics (e.g., location, size, margins, echogenicity, vascularity on Doppler, main pancreatic duct dilation, elastography appearance, vascular invasion, and hypoechoic rim), alongside demographic and risk factors (smoking, alcohol, diabetes).
RESULTS
We evaluated 165 patients (24 PNETs). EUS features significantly linked with PNET diagnosis were well-defined margins (79% . 26%, p < 0.001), blue elastography appearance (46% . 9.9%, p < 0.001), vascularization (67% . 25%, p < 0.001), hypoechoic rim (46% . 10%, p < 0.001). The top-performing model, with 89.1% accuracy, included two predictors: a homogeneous lesion (OR, 95% CI) and a hypoechoic rim (OR, 95% CI).
CONCLUSIONS
EUS appearance can differentiate PNETs from non-PNETs, with the hypoechoic rim being an independent predictor of PNET diagnosis. The most effective predictive model for PNETs combined the homogeneous lesion and presence of the hypoechoic rim.
PubMed: 38933251
DOI: 10.4183/aeb.2023.407 -
Annals of Pediatric Cardiology 2024Transcatheter closure of superior vena cava (SVC) form of sinus venosus defects (SVDs) using covered stents is emerging as an alternative to surgery in the current... (Review)
Review
Transcatheter closure of superior vena cava (SVC) form of sinus venosus defects (SVDs) using covered stents is emerging as an alternative to surgery in the current decade. A covered stent placed in the cavoatrial junction creates a roof for the right upper pulmonary vein (RUPV) that stops the left-to-right shunt and redirects the vein to the left atrium. While surgical literature has clearly documented the incidence of stenosis of SVC and RUPV, sinus nodal dysfunction, and persistent residual shunts following surgical correction, it is imperative to have similar data after this new transcatheter intervention on the incidence of complications and follow-up outcomes. Since patients with pretricuspid shunts are often clinically asymptomatic, correction is primarily performed to prevent a persistent right heart volume overload and allow remodeling of the heart chambers. Any residual left-to-right shunt after a correction will result in persistent right heart dilatation. Residual flows can result from various mechanisms, including lack of apposition of the covered stent to the free edge of the SVD, fabric breach, and persistent anomalous drainage of additional right-sided pulmonary veins that drain very high in the SVC or can be due to a coexistent defect in the oval fossa. This review analyzes the different mechanisms, explains the transesophageal and angiographic images for each one, and offers solutions tailored for various reasons. Different mechanisms warrant different treatment principles. A solution for residual shunt from one mechanism may not be appropriate for residual flow through another mechanism. A thorough understanding would aid the operator in effective interventions for these SVDs.
PubMed: 38933051
DOI: 10.4103/apc.apc_190_23 -
Frontiers in Cardiovascular Medicine 2024Severe tricuspid regurgitation (TR) causing cyanosis with patent foramen ovale (PFO) and right-to-left atrial shunting requires a precise diagnosis for optimal therapy....
BACKGROUND
Severe tricuspid regurgitation (TR) causing cyanosis with patent foramen ovale (PFO) and right-to-left atrial shunting requires a precise diagnosis for optimal therapy. Tricuspid valve prolapse (TVP) can lead to TR and is sometimes overlooked, especially in complex cases with factors like pulmonary hypertension (PH). We present an infant with cyanosis and profound TR after high-altitude exposure, initially misattributed to PH but found to be primarily due to spontaneous chordae tendineae rupture and TVP. This case underscores the challenges in diagnosing TR-induced cyanosis.
CASE PRESENTATION
The 3-month-old infant rapidly developed cyanosis, hypoxemia, right atrial enlargement, severe tricuspid regurgitation (TR), and patent foramen ovale (PFO) shunting after high-altitude exposure. Although echocardiography revealed tricuspid valve prolapse (TVP), initial consideration linked TR and right-to-left shunting to pulmonary hypertension (PH) due to the temporal correlation with rapid altitude exposure. Despite hemodynamic stability and the absence of respiratory distress after respiratory support and combined PH medication therapy, the persistent hypoxemia did not reverse as expected. This treatment outcome and repeated echocardiograms reminded us that TR was primarily caused by TVP rather than PH alone. Intraoperative exploration confirmed that TVP was caused by a rupture of TV chordae tendineae and anterior papillary muscle head, and the chordae tendineae/papillary muscle connection was reconstructed. After surgery, this patient was noncyanotic with an excellent long-term prognosis, a trivial TR with normal TV function being observed echocardiographically.
CONCLUSIONS
TR-induced cyanosis can be not only a consequence of PH and right-sided heart dilation but also a primary condition. Repetitive reassessment should be undertaken with caution, particularly when patients are not improving on therapy in the setting of conditions known to predisposition to secondary TR. Since TVP caused by rupture of the chordae or papillary muscles is rare but fatal in children, early diagnosis is clinically substantial to proper management and satisfactory long-term outcomes.
PubMed: 38932987
DOI: 10.3389/fcvm.2024.1335218 -
Journal of the Belgian Society of... 2024Aneurysmal dilatations can affect any aortic segment and represent the result of various causes, atherosclerotic disease being the most common and frequently involved....
Aneurysmal dilatations can affect any aortic segment and represent the result of various causes, atherosclerotic disease being the most common and frequently involved. We hereby illustrate a case of a patient with thoracic aortic aneurysm rupture due to extensive atherosclerotic disease, with multiple complex penetrating ulcerated atherosclerotic plaques located in the descending aorta. CT angiography evaluation included a comprehensive description of imaging features and extent of the thoracic aortic aneurysm, the presence of thrombus, relationship to adjacent structures and branches, associated complications. Thoracic aortic aneurysm rupture due to extensive atherosclerotic disease with multiple penetrating ulcers.
PubMed: 38932986
DOI: 10.5334/jbsr.3314 -
Sensors (Basel, Switzerland) Jun 2024Transformer-based methodologies in object detection have recently piqued considerable interest and have produced impressive results. DETR, an end-to-end object detection...
Transformer-based methodologies in object detection have recently piqued considerable interest and have produced impressive results. DETR, an end-to-end object detection framework, ingeniously integrates the Transformer architecture, traditionally used in NLP, into computer vision for sequence-to-sequence prediction. Its enhanced variant, DINO, featuring improved denoising anchor boxes, has showcased remarkable performance on the COCO val2017 dataset. However, it often encounters challenges when applied to scenarios involving small object detection. Thus, we propose an innovative method for feature enhancement tailored to recursive prediction tasks, with a particular emphasis on augmenting small object detection performance. It primarily involves three enhancements: refining the backbone to favor feature maps that are more sensitive to small targets, incrementally augmenting the number of queries for small objects, and advancing the loss function for better performance. Specifically, The study incorporated the Switchable Atrous Convolution (SAC) mechanism, which features adaptable dilated convolutions, to increment the receptive field and thus elevate the innate feature extraction capabilities of the primary network concerning diminutive objects. Subsequently, a Recursive Small Object Prediction (RSP) module was designed to enhance the feature extraction of the prediction head for more precise network operations. Finally, the loss function was augmented with the Normalized Wasserstein Distance (NWD) metric, tailoring the loss function to suit small object detection better. The efficacy of the proposed model is empirically confirmed via testing on the VISDRONE2019 dataset. The comprehensive array of experiments indicates that our proposed model outperforms the extant DINO model in terms of average precision (AP) small object detection.
PubMed: 38931640
DOI: 10.3390/s24123856