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American Journal of Clinical and... 2024Sex-determining region Y-box 2 (SOX2) is a transcription factor with a central role in embryologic development. SOX2 is also an oncogene in several cancer types. Prior...
Sex-determining region Y-box 2 (SOX2) is a transcription factor with a central role in embryologic development. SOX2 is also an oncogene in several cancer types. Prior work by our group has shown SOX2 activity associates with cell cycle dysregulation in early-stage bladder cancer. The present study was thus undertaken to broadly investigate SOX2 in bladder cancer, with emphasis on associations with tumor stage, clinical outcomes, and tumorigenicity. Gene expression was quantified by immunohistochemistry in an established tissue microarray (n=303 cystectomy specimens, all stages) and whole tissue sections of noninvasive papillary urothelial carcinoma (n=25). Gene expression by RNA sequencing was evaluated in non-muscle invasive and muscle-invasive cohorts from publicly available repositories. By immunohistochemistry, SOX2 was expressed in 40% of whole tissue sections of noninvasive papillary carcinoma, which correlated with expression by RNA sequencing (r=0.6, P=0.001, Spearman correlation). Expression tended to be focal (median H-score =6). SOX2 was expressed in only 9% of TMA cases, consistent with focal expression. expression was substantially higher in muscle-invasive compared with noninvasive papillary urothelial carcinoma by RNA sequencing (P<0.001, Wilcoxon rank sum test). expression associated with stage progression in lamina-propria invasive cancers (hazard ratio =2, P=0.05, Cox model, binary, RNA sequencing) but not noninvasive papillary cancers (P=0.5, Cox model, binary, RNA sequencing). expression did not associate with overall survival in muscle-invasive carcinoma. Activity of SOX2 in bladder cancer was tested using murine allografts created with MB49 cells that express human SOX2 (MB49-SOX). MB49-SOX allografts expressed this protein focally by immunohistochemistry, much like human tumors. Compared with controls, MB49 allografts demonstrated larger tumor size (P=0.03, Wilcoxon rank sum test) and higher tumor burden in mesenteric metastases (P=0.009, Wilcoxon rank sum test). Though SOX2 expression is focal within tumors, it may drive tumorigenesis, increase growth rate, and promote aggressive features of bladder cancer, particularly stage progression of early-stage disease.
PubMed: 38736621
DOI: 10.62347/MEQO6014 -
International Journal of Molecular... Apr 2024Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG)...
Spatial Distribution of Macrophage and Lymphocyte Subtypes within Tumor Microenvironment to Predict Recurrence of Non-Muscle-Invasive Papillary Urothelial Carcinoma after BCG Immunotherapy.
Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial-stromal interface zone compartments and their distribution, represented by an epithelial-stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, -value = 0.0002), CD8 (HR: 0.0379, -value = 0.005), and ICOS (HR: 0.0768, -value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, -value = 0.0001) and T1 tumor stage (HR: 2.04, -value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, -value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment.
Topics: Humans; Tumor Microenvironment; Urinary Bladder Neoplasms; Male; BCG Vaccine; Neoplasm Recurrence, Local; Female; Immunotherapy; Aged; Middle Aged; Macrophages; Carcinoma, Papillary; Lymphocyte Subsets; Prognosis; Aged, 80 and over
PubMed: 38731992
DOI: 10.3390/ijms25094776 -
Journal of Clinical Medicine May 2024Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac...
Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies.
PubMed: 38731198
DOI: 10.3390/jcm13092669 -
Radiographics : a Review Publication of... Jun 2024Cardiac tumors, although rare, carry high morbidity and mortality rates. They are commonly first identified either at echocardiography or incidentally at...
Cardiac tumors, although rare, carry high morbidity and mortality rates. They are commonly first identified either at echocardiography or incidentally at thoracoabdominal CT performed for noncardiac indications. Multimodality imaging often helps to determine the cause of these masses. Cardiac tumors comprise a distinct category in the World Health Organization (WHO) classification of tumors. The updated 2021 WHO classification of tumors of the heart incorporates new entities and reclassifies others. In the new classification system, papillary fibroelastoma is recognized as the most common primary cardiac neoplasm. Pseudotumors including thrombi and anatomic variants (eg, crista terminalis, accessory papillary muscles, or coumadin ridge) are the most common intracardiac masses identified at imaging. Cardiac metastases are substantially more common than primary cardiac tumors. Although echocardiography is usually the first examination, cardiac MRI is the modality of choice for the identification and characterization of cardiac masses. Cardiac CT serves as an alternative in patients who cannot tolerate MRI. PET performed with CT or MRI enables metabolic characterization of malignant cardiac masses. Imaging individualized to a particular tumor type and location is crucial for treatment planning. Tumor terminology changes as our understanding of tumor biology and behavior evolves. Familiarity with the updated classification system is important as a guide to radiologic investigation and medical or surgical management. RSNA, 2024
Topics: Humans; Echocardiography; Heart Neoplasms; Magnetic Resonance Imaging; Multimodal Imaging; Tomography, X-Ray Computed; World Health Organization
PubMed: 38722782
DOI: 10.1148/rg.230126 -
Kyobu Geka. the Japanese Journal of... May 2024A 59-year-old man was admitted to our hospital with left hemiplegia. A computed tomography( CT) scan and echocardiography revealed a cerebral infarction in the right...
A 59-year-old man was admitted to our hospital with left hemiplegia. A computed tomography( CT) scan and echocardiography revealed a cerebral infarction in the right middle cerebral artery's territory, as well as a large pseudoaneurysm (4×3 cm) of the lateral left ventricular wall. The patient agreed to undergo cardiac surgery because of the high risk of rupture and recurrent cerebral infarctions. Owing to the high probability of damaging the posterior papillary muscle and coronary arteries, an extracardiac approach was used, and the pseudoaneurysm cavity was closed using double-patch repair. The patient was discharged from the hospital on the 12th postoperative day without any complications. Both postoperative CT and echocardiography showed closure of the cavity.
Topics: Humans; Male; Aneurysm, False; Middle Aged; Cerebral Infarction; Heart Ventricles; Tomography, X-Ray Computed; Heart Aneurysm
PubMed: 38720606
DOI: No ID Found -
Kidney & Blood Pressure Research 2024To improve the clinical evaluation of the prognosis of papillary renal cell carcinoma (PRCC), we screened a model to predict the survival of patients with mutations in...
BACKGROUND
To improve the clinical evaluation of the prognosis of papillary renal cell carcinoma (PRCC), we screened a model to predict the survival of patients with mutations in related genes.
METHODS
We downloaded RNA sequencing information from all patients with PRCC in TCGA. We first analyzed the differences in genes and the enrichment of these differences. Then, by selecting mutant genes, constructing a protein-protein interaction network, least absolute shrinkage and selection operator regression, and multivariable Cox regression, a prognosis model was constructed. Additionally, the model was validated using external data sets. We analyzed the immune infiltration of PRCC and the correlation between the model and popular targets. Finally, we performed tissue microarray analysis and immunohistochemistry to verify the expression levels of the three genes.
RESULTS
We constructed a three-gene (never in mitosis gene A-related kinase 2 [NEK2], centromere protein A [CENPA], and GINS complex subunit 2 [GINS2]) model. The verification results indicated that the model had a good prediction effect. We also developed a visual nomogram. Enrichment analysis revealed the major pathways involved in muscle system processes. Immunoassays showed that the expression level of CENPA was positively correlated with PD-1 and CTLA4 expression levels. Immunohistochemical and tissue microarray results showed that these three genes were highly expressed in PRCC, which was consistent with the predicted results in the database.
CONCLUSION
We constructed and verified a three-gene model to predict the patient survival. The results show that the model has a good prediction effect.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Mutation; Prognosis; Chromosomal Proteins, Non-Histone; Protein Interaction Maps; Male; CTLA-4 Antigen; Nomograms; Programmed Cell Death 1 Receptor; Female
PubMed: 38714185
DOI: 10.1159/000539096 -
Cureus Apr 2024The mucous membrane fold, which facilitates the attachment of the gingiva, alveolar mucosa, and the periosteum surrounding the lips and cheek, is known as the frenum....
The mucous membrane fold, which facilitates the attachment of the gingiva, alveolar mucosa, and the periosteum surrounding the lips and cheek, is known as the frenum. The frenal attachment at the gingival or papillary level may comprise periodontal health due to difficulty with plaque adherence or muscle pull. The management of such aberrant frenal attachment becomes necessary to avoid the associated future problems, such as midline diastema and periodontal attachment loss, which might lead to aesthetic problems and tooth mobility. The treatment modalities involve frenectomy using Miller's technique, conventional technique, Z-plasty, and V-Y plasty types of frenectomy procedures. The patient's requirements, specific indications, and intended results determine the method. This case report illustrates the utilisation of the V-Y plasty technique for the frenectomy of a papillary-type labial frenal attachment in a 19-year-old female patient. V-Y plasty proved to be an efficient technique for removing the aberrant labial frenum attachment, and the results were highly satisfactory, with less scar formation. V-Y plasty is reliable for covering defects and elongating the frenum area, giving desired clinical outcomes.
PubMed: 38707118
DOI: 10.7759/cureus.57663 -
Cureus Mar 2024Perioperative management of patients with myopathies can be challenging due to the increased risk of malignant hyperthermia (MH) and anesthesia-induced rhabdomyolysis...
Perioperative management of patients with myopathies can be challenging due to the increased risk of malignant hyperthermia (MH) and anesthesia-induced rhabdomyolysis (AIR). However, currently, there is no evidence regarding the optimal anesthetic management for paraneoplastic necrotizing myopathy (PNM) (total intravenous anesthetic vs. volatile anesthetics). Here, I report a case where anesthesia was administered safely using volatile anesthetics. A 63-year-old female presented with PNM associated with papillary thyroid carcinoma, necessitating urgent thyroidectomy. The patient, previously diagnosed with anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibody-associated myopathy, exhibited progressive weakness and dysphagia, prompting suspicion of PNM. The patient's compromised respiratory status, attributed to tracheal compression by a large goiter, necessitated an urgent thyroidectomy. Anesthetic management considerations included the potential effect of HMGCR-M on respiratory muscles and the need for careful planning to mitigate postoperative complications. The patient underwent total thyroidectomy, left central compartment clearance, and tracheostomy. The surgery proceeded uneventfully, with meticulous monitoring and adjustment of anesthetic agents to maintain hemodynamic stability. Postoperatively, the patient recovered well, demonstrating complete resolution of neurological symptoms during a three-month follow-up. The case underscores the importance of recognizing paraneoplastic syndromes in the context of thyroid surgery and highlights potential challenges faced by anesthesiologists. Despite the lack of established safety data for anesthetic drugs in HMGCR-M necrotizing myopathy, the case demonstrates the successful use of sevoflurane and rocuronium.
PubMed: 38694410
DOI: 10.7759/cureus.57351 -
Journal of the American College of... May 2024Severe acute mitral regurgitation after myocardial infarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its... (Review)
Review
Severe acute mitral regurgitation after myocardial infarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its incidence is <1%, mitral regurgitation after acute myocardial infarction frequently causes hemodynamic instability, pulmonary edema, and cardiogenic shock. Medical management has the worst prognosis, and mortality has not changed in decades. Surgery represents the gold standard, but it is associated with high rates of morbidity and mortality. Recently, transcatheter interventions have opened a new door for management that may improve survival. Mechanical circulatory support restores vital organ perfusion and offers the opportunity for a steadier surgical repair. This review focuses on the diagnosis and the interventional management, both surgical and transcatheter, with a glance on future perspectives to enhance patient management and eventually decrease mortality.
Topics: Humans; Mitral Valve Insufficiency; Myocardial Infarction; Severity of Illness Index; Cardiac Catheterization; Disease Management
PubMed: 38692830
DOI: 10.1016/j.jacc.2023.09.840 -
Medical Engineering & Physics May 2024Early detection of cardiovascular diseases is based on accurate quantification of the left ventricle (LV) function parameters. In this paper, we propose a fully...
OBJECTIVE
Early detection of cardiovascular diseases is based on accurate quantification of the left ventricle (LV) function parameters. In this paper, we propose a fully automatic framework for LV volume and mass quantification from 2D-cine MR images already segmented using U-Net.
METHODS
The general framework consists of three main steps: Data preparation including automatic LV localization using a convolution neural network (CNN) and application of morphological operations to exclude papillary muscles from the LV cavity. The second step consists in automatically extracting the LV contours using U-Net architecture. Finally, by integrating temporal information which is manifested by a spatial motion of myocytes as a third dimension, we calculated LV volume, LV ejection fraction (LVEF) and left ventricle mass (LVM). Based on these parameters, we detected and quantified cardiac contraction abnormalities using Python software.
RESULTS
CNN was trained with 35 patients and tested on 15 patients from the ACDC database with an accuracy of 99,15 %. U-Net architecture was trained using ACDC database and evaluated using local dataset with a Dice similarity coefficient (DSC) of 99,78 % and a Hausdorff Distance (HD) of 4.468 mm (p < 0,001). Quantification results showed a strong correlation with physiological measures with a Pearson correlation coefficient (PCC) of 0,991 for LV volume, 0.962 for LVEF, 0.98 for stroke volume (SV) and 0.923 for LVM after pillars' elimination. Clinically, our method allows regional and accurate identification of pathological myocardial segments and can serve as a diagnostic aid tool of cardiac contraction abnormalities.
CONCLUSION
Experimental results prove the usefulness of the proposed method for LV volume and function quantification and verify its potential clinical applicability.
Topics: Humans; Heart Ventricles; Magnetic Resonance Imaging, Cine; Automation; Papillary Muscles; Image Processing, Computer-Assisted; Organ Size; Male; Middle Aged; Neural Networks, Computer; Female; Stroke Volume
PubMed: 38692762
DOI: 10.1016/j.medengphy.2024.104162