scholarly journals NFB-16. mTOROPATHIES AND SUBEPENDYMAL GIANT CELL ASTROCYTOMAS: PREDICTIVE VALUE OF GERMINAL TSC1/2 MUTATIONS SCREENING IN FAMILIAL CASES

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii420-iii420
Author(s):  
Nouha Bouayed Abdelmoula ◽  
Walid Smaoui ◽  
Balkiss Abdelmoula ◽  
Samir Aloulou ◽  
Imen Masmoudi ◽  
...  
Keyword(s):  
Giant Cell ◽  
Predictive Value ◽  
Cell Function ◽  
Mutational Analysis ◽  
Early Recognition ◽  
Mutation Screening ◽  
Molecular Defect ◽  
Low Grade ◽  
Familial Cases ◽  
Tsc1 Gene

Abstract mTOR controls several important aspects of cell function particularly in the nervous system. Its hyperactivation has been involved in tuberous sclerosis complex (TSC) and other mTORopathies as well as drug-resistant epilepsy. Mutations in TSC1 and TSC2 genes cause loss of normal inhibition of mTORC1 complex, leading to cell overgrowth and disruptions in synaptogenesis. Many children and adults with TSC harbour neurologic defects especially subependymal giant cell astrocytomas (SEGAs) in the brain. Here, we have performed mutational analysis followed by a genetic counselling for a Tunisian family from Sfax town harboring epileptic seizures associated to a neurocutaneous disorder. Index cases were referred for renal angiolipomas (RAL) associated to seizures crisis and were diagnosed as having TSC. The first 26-year-old patient complained of epilepsy since the age of 22 with left temporal crisis related to cortical tubers near the Heschl’s gyrus. His brother, a 36-year-old man presented more severe epileptic crisis (since 15 years-old), multiples RAL, subependymal nodules, and a rapid evolution of his mTORopathy with tumoral progression of his renal and central nerve lesions: renal cell carcinoma and SEGAs. TSC1 gene mutation screening showed heterozygous two bp deletion at codons 213 and 214 of exon 5. SEGAs are rare, low-grade glioneuronal brain tumors that occur almost exclusively in TSC patients but can lead to nervous complications. We showed through this report, the predictive value of germinal TSC mutations screening in familial cases, because early recognition of the molecular defect may lead to appropriate management of the tumoral progression.

scholarly journals Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma

2021 ◽  
Author(s):  
Ignacio Ruz-Caracuel ◽  
Álvaro López-Janeiro ◽  
Victoria Heredia-Soto ◽  
Jorge L. Ramón-Patino ◽  
Laura Yébenes ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Mismatch Repair ◽  
Predictive Value ◽  
Early Stage ◽  
Disease Free Survival ◽  
Low Grade ◽  
Beta Catenin ◽  
Free Survival ◽  
Disease Free ◽  
Risk Of Relapse

AbstractLow-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours. Graphical abstract

Cranial arteritis: treatment is urgent

1984 ◽  
Vol 22 (3) ◽  
pp. 11-12
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Early Recognition ◽  
Prompt Treatment

Cranial (temporal or giant-cell) arteritis is a debilitating condition commonest in those aged over 70 years and therefore likely to become more widespread as this population increases. One serious manifestation is blindness which develops rapidly and is usually irreversible. This can be prevented by early recognition of the disease and prompt treatment with a corticosteroid.

scholarly journals Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation Modulator Abatacept

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianna Santopaolo ◽  
Niall Sullivan ◽  
Anita Coral Thomas ◽  
Valeria Vincenza Alvino ◽  
Lindsay B. Nicholson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
T Cells ◽  
Insulin Sensitivity ◽  
Adaptive Immunity ◽  
Cell Function ◽  
Immune Cell ◽  
Low Grade ◽  
Cardiac Damage

Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function.Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance.Results: Patients with T2D showed increased frequencies of BM CD4+ (2.8-fold, p = 0.001) and CD8+ T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4+ (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8+ fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity.Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.

scholarly journals Positive Predictive Value of the Giant Cell Arteritis Diagnosis in the Danish National Patient Registry: A Validation Study

2020 ◽  
Vol Volume 12 ◽  
pp. 731-736
Author(s):  
Peter Engholm Hjort ◽  
Philip Therkildsen ◽  
Berit Dalsgaard Nielsen ◽  
Ib Tønder Hansen ◽  
Mette Nørgaard ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Validation Study ◽  
Predictive Value ◽  
Patient Registry ◽  
National Patient Registry ◽  
Danish National Patient Registry ◽  
National Patient

Intraarticular Nodular Fasciitis of the Knee With MHY9-USP6 Fusion: A Case Report

2020 ◽  
Vol 28 (6) ◽  
pp. 672-677 ◽  
Author(s):  
Jasminka Igrec ◽  
Iva Brčić ◽  
Renato Igrec ◽  
Marko Bergovec ◽  
Karl Kashofer ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Smooth Muscle Actin ◽  
Malignant Lesion ◽  
Cell Tumor ◽  
Malignant Neoplasms ◽  
Low Grade ◽  
Nodular Fasciitis ◽  
Tenosynovial Giant Cell Tumor ◽  
Mesenchymal Neoplasm

Background. Nodular fasciitis (NF) is a self-limiting, benign mesenchymal neoplasm of fibroblastic/myofibroblastic origin. Due to the fast growth, cellularity, and frequently observed high mitotic count, it is commonly misdiagnosed as a sarcoma, often resulting in overtreatment. Intraarticular examples of NF are extremely rare. Radiologically, NF can mimic fibroma of the tendon sheath, tenosynovial giant cell tumor, and synovial chondromatosis. Histology can vary from hypercellular, mitotically active lesions to fibrotic, less cellular ones, and can, therefore, mimic other benign and low-grade malignant neoplasms. Recently, the MYH9-USP6 fusion has been found in up to 92% of NF. Case Presentation. In this article, we report a case of a 38-year-old patient with an intraarticular lesion, radiologically suspicious of tenosynovial giant cell tumor. Histology demonstrated a spindle cell lesion composed of fibroblasts/myofibroblasts embedded in a highly collagenous/hyalinized stroma, partly arranged in short fascicles. Extravasated erythrocytes and rare mitotic figures were present. Immunohistochemically, tumor cells expressed smooth muscle actin and were negative for desmin, β-catenin, CD34, and SOX10. These findings rendered the diagnosis of NF. Molecular analysis using next-generation sequencing (Archer FusionPlex Sarcoma Panel) revealed gene rearrangement involving USP6 and MYH9 supporting the diagnosis of NF in the knee joint. Conclusions. Radiological and histological features of NF can overlap with other benign and low-grade malignant lesion. Identification of the USP6 gene rearrangements or finding of the MYH9-USP6 fusion, especially in core needle biopsies and in the lesions occurring at unusual sites, can result in adequate therapeutic approach avoiding overtreatment.

KRAS Mutation: Should We Test for It, and Does It Matter?

2013 ◽  
Vol 31 (8) ◽  
pp. 1112-1121 ◽  
Author(s):  
Patrick J. Roberts ◽  
Thomas E. Stinchcombe
Keyword(s):  
Lung Cancer ◽  
Monoclonal Antibodies ◽  
Predictive Value ◽  
Clinical Utility ◽  
Mutational Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Mutational Status ◽  
Egfr Tki

Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Previously, lung cancer was simplistically divided into non–small-cell lung cancer (NSCLC) and small-cell lung cancer. However, in the last decade, we have gone from a simplistic binary system of classifying lung cancer to defining NSCLC on the basis of molecular subsets. KRAS mutations represent the most common molecular change in NSCLC. The presence of KRAS mutation has been shown to be associated with a poor prognosis in NSCLC, but this is of little clinical utility. More important is determining the clinical utility of KRAS mutational analysis for predicting benefit of chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), anti-EGFR monoclonal antibodies, or other novel therapeutics. Current data does not support the routine use of KRAS mutational analysis for predicting chemotherapy benefit. Additionally, there was significant interest in using KRAS status to select patients for EGFR TKI and anti-EGFR monoclonal antibodies. However, the EGFR mutational status has demonstrated significant predictive value in the selection of patients for EGFR TKI therapy and is now the preferred test. An association between KRAS mutational status and benefit of anti-EGFR monoclonal antibodies has not been demonstrated in NSCLC. Here we review, in the context of NSCLC, the underlying biology of KRAS mutations, the predictive value of KRAS mutations for therapeutic intervention, and the integration of KRAS mutational testing into our current clinical paradigms.

scholarly journals Visual inspection of cervix with acetic acid as a feasible screening test for cervical neoplasia among women attending at OPD in Rajshahi Medical College Hospital

KYAMC Journal ◽  
2018 ◽  
Vol 9 (2) ◽  
pp. 56-60
Author(s):  
Nahid Yusuf ◽  
Md Ahmed Ali ◽  
Nazmun Nahar ◽  
Shipra Chaudhury ◽  
Md Zillur Rahman
Keyword(s):  
Acetic Acid ◽  
Predictive Value ◽  
Urban Areas ◽  
Visual Inspection ◽  
Pap Smear ◽  
Low Cost ◽  
Low Grade ◽  
College Hospital ◽  
Health Care Centre ◽  
Simple Method

Background: Visual inspection of cervix after application of 3-5% acetic acid (VIA) is a potential alternative to Pap smear cytology for screening of cervical cancer in resource poor settings.Objectives: This study was to evaluate the performance of visual inspection based screening approach in the detection of precancerous and early cancerous lesions of the cervix.Materials & Methods: VIA was carried out in 540 eligible women attending Gynae OPD. Detection of well-defined, opaque, acetowhite lesion close to squamocolumnar junction or in transitional zone of the cervix constituted positive VIA. All screened women evaluated by colposcopy and biopsy were taken from colposcopically suspected areas. The final diagnosis was based on histology.Results: Out of 540 patients, 328 were VIA negative and 212 were VIA positive. Colposcopy showed normal results in 340 cases, low grade CIN in 138 cases, high grade CIN in 44 cases and cancer in 18 cases. There were biopsy proven chronic cervicitis and metaplastic changes in 423 cases, CIN I in 66 cases, CIN II in 25 cases, CIN III / carcinoma-in-situ in 5 cases. The sensitivity of VIA was 74.36%, specificity 70.45%, positive predictive value 41.04%, & negative predictive value 90.85%.Conclusion: VIA can differentiate a normal cervix from a precancerous cervix with reasonable accuracy. As it is low cost and simple method, it can be set in any hospital or any health care centre of rural or urban areas of poor resource settings.KYAMC Journal Vol. 9, No.-2, July 2018, Page 56-60

scholarly journals Procalcitonin – A Reliable Marker for Diagnosis of Neonatal Sepsis in Compare to CRP

2018 ◽  
Vol 42 (1) ◽  
pp. 19-25
Author(s):  
Jesmin Akter ◽  
Forrukh Ahammad ◽  
Tahmina Begum
Keyword(s):  
Early Diagnosis ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Neonatal Sepsis ◽  
Predictive Value ◽  
Early Recognition ◽  
Care Hospital ◽  
Suspected Sepsis ◽  
Reliable Marker ◽  
Serum Crp

Background: Early recognition and diagnosis of neonatal sepsis are difficult because of the variable and non-specific clinical presentation of this condition. It is extremely important to make an early diagnosis of neonatal sepsis for prompt institution of antimicrobial therapy. So the objective of the study was to evaluate the efficacy of serum procalcitonin as a reliable marker in diagnosis of neonatal sepsis.Methodology: This cross sectional analytical study was carried out in the Special Care Baby Unit of a tertiary level care hospital in Bangladesh from September 2012 to May 2013. Total 75 newborn with suspected sepsis were included in the study. Specimens of blood were obtained from each neonate prior to commencement of antibiotic for sepsis work up. Serum CRP and procalcitoninlevels were measured. The data from blood cultures were used as the gold standard to evaluate the optimum sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the Receiver Operative Characteristic (ROC) curves.Results:Among total 75 newborns included in this study, 49.3% (37) newborn were diagnosed as proven sepsis and 50.7% (38) newborn as clinical sepsis.The procalcitonin (PCT) was high in 58.7% (500-<2000 pg/ml) newborn and remarkably high (2000-<10000) in 36% newborn with sepsis. At a cut-off value > 500pg/ml, the sensitivity of PCT in detecting sepsis was 48.6%, its specificity 76.3%, positive predictive value was 66.7%, and negative predictive value was 60.4% whereas the sensitivity of CRP for predicting sepsis was 35.1%, specificity 78.9%, positive predictive value 61.9% and negative predictive value was 55.6%. The area under the ROC curve for procalcitonin(0.653) was significantly higher than CRP (0.571).Conclusion:Serum PCT was superior to serum CRP level in terms of early diagnosis of neonatal sepsis, in detecting the severity of sepsis. PCT is a reliable marker than CRP in the diagnosis of neonatal sepsis.Bangladesh J Child Health 2018; VOL 42 (1) :19-25

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