67 research outputs found
Development of PancRISK, a urine biomarker-based risk score for stratified screening of pancreatic cancer patients
© The Author(s) 2019. Published by Springer Nature on behalf of Cancer Research UK.BACKGROUND: An accurate and simple risk prediction model that would facilitate earlier detection of pancreatic adenocarcinoma (PDAC) is not available at present. In this study, we compare different algorithms of risk prediction in order to select the best one for constructing a biomarker-based risk score, PancRISK. METHODS: Three hundred and seventy-nine patients with available measurements of three urine biomarkers, (LYVE1, REG1B and TFF1) using retrospectively collected samples, as well as creatinine and age, were randomly split into training and validation sets, following stratification into cases (PDAC) and controls (healthy patients). Several machine learning algorithms were used, and their performance characteristics were compared. The latter included AUC (area under ROC curve) and sensitivity at clinically relevant specificity. RESULTS: None of the algorithms significantly outperformed all others. A logistic regression model, the easiest to interpret, was incorporated into a PancRISK score and subsequently evaluated on the whole data set. The PancRISK performance could be even further improved when CA19-9, commonly used PDAC biomarker, is added to the model. CONCLUSION: PancRISK score enables easy interpretation of the biomarker panel data and is currently being tested to confirm that it can be used for stratification of patients at risk of developing pancreatic cancer completely non-invasively, using urine samples.Peer reviewe
The Social Significance of the Cluster in the Economy
Transition of the Russian Federation's policy to the innovative way of economic and social development is indispensable imperative to ensure its output to a leading position in the modern globalized world. Among the wide range of means, methods, forms, the mechanisms by which it is possible sharp acceleration of the process of formation of an innovative economy in our country, a special place belongs to the cluster approach. International scientific community is justified, and the practice of developed countries proved that the cluster approach to the structuring of the national economy and regional systems are an important source to improve production efficiency, increase its competitiveness, and increase public welfare. Questions of cluster formation and management of the development of the Russian economy in recent years, becomes the subject of numerous studies by Russian scientists - economists. Cluster policies are becoming increasingly recognized in public authorities. Moreover, there are already official documents, which examine the content and direction of the cluster policy.
Keywords: society, cluster, economy, innovation, importance, competitiveness
JEL Classifications: A19, O35, O3
Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography
Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Youngâs modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p <0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer â low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors
ĐĐ°ŃŃŃĐ”ĐœĐžĐ” ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐżĐŸĐ»Đ° 45,Đ„/46,XY: ĐșĐ»ĐžĐœĐžĐșĐŸ-Đ»Đ°Đ±ĐŸŃĐ°ŃĐŸŃĐœĐ°Ń Ń Đ°ŃĐ°ĐșŃĐ”ŃĐžŃŃĐžĐșĐ° паŃĐžĐ”ĐœŃĐŸĐČ
Aim. To study the clinical and laboratory characteristics of patients with disorders of sex development (DSD) 45,Đ„/46,Đ„Y.Materials and methods. The study included 248 patients with genital malformations from early neonatal period to 18 years. The group of patients with DSD 45,Đ„/46,Đ„Y was formed according to the results of cytogenetic and molecular cytogenetic examination. Anthropometric data, external and internal genitalia, hormonal parameters in mini-pubertal, neutral and pubertal periods were assessed; histological examination of the gonads and screening of development malformations were performed.Results. DSD of 46,Đ„Y karyotype was revealed in 48% (120/248) cases, 46,Đ„Đ„ DSD â 38% (93/248), DSD with sex chromosome pathology â 14% (35/248) patients. Chromosome DSD was represented by Klinefelter syndrome, Shereshevsky â Ulrich â Turner syndrome, chimeric DSD, and ovotesticular DSD, but the majority of patients had mosaicism 45,Đ„/46,Đ„Y (65%). In the group of patients with NFP 45,X/46,XY, the median degree of masculinization of the external genitalia by the scale of the external masculinization score (EMS) was 3 [1; 5,5]. Among the defects of external genitalia in most cases (82%, 18/22) there was a combination of cryptorchidism with hypospadias. Derivatives of the Mueller ducts were detected in 91% (20/22) of patients. Most patients (77%) adapt the male passport field. There were no statistically significant differences in the structure of the external and internal genitalia between the groups of patients adapted in the male and female passport fields.The analysis of hormonal indexes revealed a positive correlation between the content of basal testosteron in the mini-pubertal period and the index of masculinization of the external genitalia by the EMS scale (p = 0,002; r = 0,9). In the period of mini-puberty an increase in the level of gonadotropic hormones was detected in 89% (8/9) of children, a combined increase of luteinizing and follicle-stimulating hormones (FSH) being observed in 33% (3/9), an isolated increase of FSH â in 56% (5/9) of cases. In the pubertal period hypergonadotropic hypogonadism was revealed in 75% (3/4) of patients.The results of the histological study of the gonads were heterogenous. Gonads are represented by a different degree of dysgenesis of testicular tissue: from a mild, histologically-like gonad in cryptorchidism to streak and ovotestis.Among the extragonadal manifestations of the disease, inguinal hernia (86%), heart defects (77%) and kidney defects (36%) are prominent. Pathological growth retardation was diagnosed in 23% of children.Conclusion. In the structure of the disease chromosomal DSD accounts for 14% of observations. A group of patients with DSD 45,X/46,XY is heterogenous in the degree of gonadal dysgenesis, the structure of the external and internal genitalia.ĐŠĐ”Đ»Ń ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ. ĐĐ·ŃŃĐžŃŃ ĐșĐ»ĐžĐœĐžĐșĐŸ-Đ»Đ°Đ±ĐŸŃĐ°ŃĐŸŃĐœŃŃ Ń
Đ°ŃĐ°ĐșŃĐ”ŃĐžŃŃĐžĐșŃ ĐżĐ°ŃĐžĐ”ĐœŃĐŸĐČ Ń ĐœĐ°ŃŃŃĐ”ĐœĐžĐ”ĐŒ ŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐžŃ ĐżĐŸĐ»Đ° (ĐĐ€Đ) 45,Đ„/46,Đ„Y.ĐĐ°ŃĐ”ŃОал Đž ĐŒĐ”ŃĐŸĐŽŃ. Đ ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžĐ” ĐČĐșĐ»ŃŃĐ”ĐœŃ 248 паŃĐžĐ”ĐœŃĐŸĐČ Ń ĐœĐ”ĐżŃĐ°ĐČОлŃĐœŃĐŒ ŃŃŃĐŸĐ”ĐœĐžĐ”ĐŒ ĐœĐ°ŃŃĐ¶ĐœŃŃ
ĐłĐ”ĐœĐžŃалОĐč ĐŸŃ ŃĐ°ĐœĐœĐ”ĐłĐŸ ĐœĐ”ĐŸĐœĐ°ŃĐ°Đ»ŃĐœĐŸĐłĐŸ пДŃĐžĐŸĐŽĐ° ĐŽĐŸ 18 лДŃ. ĐĐŸ ŃДзŃĐ»ŃŃĐ°ŃĐ°ĐŒ ŃĐžŃĐŸĐłĐ”ĐœĐ”ŃĐžŃĐ”ŃĐșĐŸĐłĐŸ Đž ĐŒĐŸĐ»Đ”ĐșŃĐ»ŃŃĐœĐŸ-ŃĐžŃĐŸĐłĐ”ĐœĐ”ŃĐžŃĐ”ŃĐșĐŸĐłĐŸ ĐŸĐ±ŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžĐč ŃŃĐŸŃĐŒĐžŃĐŸĐČĐ°ĐœĐ° ĐłŃŃппа паŃĐžĐ”ĐœŃĐŸĐČ Ń ĐĐ€Đ, ĐŸĐ±ŃŃĐ»ĐŸĐČĐ»Đ”ĐœĐœĐŸĐłĐŸ ĐŒĐŸĐ·Đ°ĐžŃĐžĐ·ĐŒĐŸĐŒ 45,Đ„/46,Đ„Y. ĐŃĐŸĐČĐ”ĐŽĐ”ĐœĐ° ĐŸŃĐ”ĐœĐșĐ° Đ°ĐœŃŃĐŸĐżĐŸĐŒĐ”ŃŃĐžŃĐ”ŃĐșĐžŃ
ĐżĐŸĐșĐ°Đ·Đ°ŃДлДĐč, ĐœĐ°ŃŃĐ¶ĐœŃŃ
Đž ĐČĐœŃŃŃĐ”ĐœĐœĐžŃ
ĐłĐ”ĐœĐžŃалОĐč, ĐłĐŸŃĐŒĐŸĐœĐ°Đ»ŃĐœŃŃ
ĐżĐŸĐșĐ°Đ·Đ°ŃДлДĐč ĐČ ĐŒĐžĐœĐž-ĐżŃбДŃŃĐ°ŃĐ”, ĐœĐ”ĐčŃŃĐ°Đ»ŃĐœĐŸĐŒ Đž ĐżŃбДŃŃĐ°ŃĐœĐŸĐŒ пДŃĐžĐŸĐŽĐ°Ń
, гОŃŃĐŸĐ»ĐŸĐłĐžŃĐ”ŃĐșĐŸĐ” ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžĐ” ĐłĐŸĐœĐ°ĐŽ, ŃĐșŃĐžĐœĐžĐœĐł ĐżĐŸŃĐŸĐșĐŸĐČ ŃĐ°Đ·ĐČĐžŃĐžŃ.РДзŃĐ»ŃŃĐ°ŃŃ. ĐĐ€Đ Ń ĐșĐ°ŃĐžĐŸŃĐžĐżĐŸĐŒ 46,Đ„Y ĐČŃŃĐČĐ»Đ”ĐœĐŸ ĐČ 48% (120/248) ŃĐ»ŃŃĐ°Đ”ĐČ, Ń ĐșĐ°ŃĐžĐŸŃĐžĐżĐŸĐŒ 46,Đ„Đ„ â ĐČ 38% (93/248), ĐĐ€Đ Ń ĐżĐ°ŃĐŸĐ»ĐŸĐłĐžĐ”Đč ĐżĐŸĐ»ĐŸĐČŃŃ
Ń
ŃĐŸĐŒĐŸŃĐŸĐŒ â ĐČ 14% (35/248) ĐœĐ°Đ±Đ»ŃĐŽĐ”ĐœĐžĐč. Đ„ŃĐŸĐŒĐŸŃĐŸĐŒĐœĐŸĐ” ĐЀРпŃДЎŃŃĐ°ĐČĐ»Đ”ĐœĐŸ ŃлДЎŃŃŃĐžĐŒĐž ĐČĐ°ŃĐžĐ°ĐœŃĐ°ĐŒĐž: ŃĐžĐœĐŽŃĐŸĐŒŃ ĐĐ»ŃĐčĐœŃДлŃŃĐ”ŃĐ°, КДŃĐ”ŃĐ”ĐČŃĐșĐŸĐłĐŸ â ĐŁĐ»ŃŃĐžŃ
Đ° â йДŃĐœĐ”ŃĐ°, Ń
ĐžĐŒĐ”ŃĐžĐ·ĐŒ, ĐŸĐČĐŸŃĐ”ŃŃĐžĐșŃĐ»ŃŃĐœĐŸĐ”, ĐœĐŸ Đ±ĐŸĐ»ŃŃŃŃ ŃĐ°ŃŃŃ ŃĐŸŃŃĐ°ĐČОлО паŃĐžĐ”ĐœŃŃ Ń ĐŒĐŸĐ·Đ°ĐžŃĐžĐ·ĐŒĐŸĐŒ 45,Đ„/46,Đ„Y (65%). Đ ĐłŃŃппД паŃĐžĐ”ĐœŃĐŸĐČ Ń ĐЀР45,Đ„/46,Đ„Y ĐŒĐ”ĐŽĐžĐ°ĐœĐ° cŃĐ”ĐżĐ”ĐœĐž ĐŒĐ°ŃĐșŃĐ»ĐžĐœĐžĐ·Đ°ŃОО ĐœĐ°ŃŃĐ¶ĐœŃŃ
ĐłĐ”ĐœĐžŃалОĐč ĐżĐŸ ŃĐșалД External Masculinization Score (EMS) ŃĐŸŃŃĐ°ĐČОла 3 [1; 5,5]. ĐĄŃДЎО ĐżĐŸŃĐŸĐșĐŸĐČ ŃĐ°Đ·ĐČĐžŃĐžŃ ĐœĐ°ŃŃĐ¶ĐœŃŃ
ĐłĐ”ĐœĐžŃалОĐč ĐČ Đ±ĐŸĐ»ŃŃĐžĐœŃŃĐČĐ” ŃĐ»ŃŃĐ°Đ”ĐČ (82%, 18/22) ĐžĐŒĐ”Đ»ĐŸ ĐŒĐ”ŃŃĐŸ ŃĐŸŃĐ”ŃĐ°ĐœĐžĐ” ĐșŃОпŃĐŸŃŃ
ĐžĐ·ĐŒĐ° Ń ĐłĐžĐżĐŸŃпаЎОДĐč. ĐĐ”ŃĐžĐČĐ°ŃŃ ĐŃллДŃĐŸĐČŃŃ
ĐżŃĐŸŃĐŸĐșĐŸĐČ ĐČŃŃĐČĐ»Đ”ĐœŃ Ń 91% (20/22) паŃĐžĐ”ĐœŃĐŸĐČ. ĐĐŸĐ»ŃŃĐ°Ń ŃĐ°ŃŃŃ ĐżĐ°ŃĐžĐ”ĐœŃĐŸĐČ (77%) Đ°ĐŽĐ°ĐżŃĐžŃŃĐ”ŃŃŃ ĐČ ĐŒŃжŃĐșĐŸĐŒ паŃĐżĐŸŃŃĐœĐŸĐŒ ĐżĐŸĐ»Đ”. ĐĐ” ĐČŃŃĐČĐ»Đ”ĐœĐŸ ŃŃĐ°ŃĐžŃŃĐžŃĐ”ŃĐșĐž Đ·ĐœĐ°ŃĐžĐŒŃŃ
ŃазлОŃĐžĐč ĐČ ŃŃŃĐŸĐ”ĐœĐžĐž ĐœĐ°ŃŃĐ¶ĐœŃŃ
Đž ĐČĐœŃŃŃĐ”ĐœĐœĐžŃ
ĐłĐ”ĐœĐžŃалОĐč ĐŒĐ”Đ¶ĐŽŃ ĐłŃŃĐżĐżĐ°ĐŒĐž паŃĐžĐ”ĐœŃĐŸĐČ, Đ°ĐŽĐ°ĐżŃĐžŃŃĐ”ĐŒŃŃ
ĐČ ĐŒŃжŃĐșĐŸĐŒ Đž Đ¶Đ”ĐœŃĐșĐŸĐŒ паŃĐżĐŸŃŃĐœĐŸĐŒ ĐżĐŸĐ»Đ”.ĐŃĐž Đ°ĐœĐ°Đ»ĐžĐ·Đ” ĐłĐŸŃĐŒĐŸĐœĐ°Đ»ŃĐœŃŃ
ĐżĐŸĐșĐ°Đ·Đ°ŃДлДĐč ĐČŃŃĐČĐ»Đ”ĐœĐ° ĐżĐŸĐ»ĐŸĐ¶ĐžŃДлŃĐœĐ°Ń ĐșĐŸŃŃДлŃŃĐžĐŸĐœĐœĐ°Ń ĐČĐ·Đ°ĐžĐŒĐŸŃĐČŃĐ·Ń ĐŒĐ”Đ¶ĐŽŃ ŃĐŸĐŽĐ”ŃĐ¶Đ°ĐœĐžĐ”ĐŒ базалŃĐœĐŸĐłĐŸ ŃĐ”ŃŃĐŸŃŃĐ”ŃĐŸĐœĐ° ĐČ ĐżĐ”ŃĐžĐŸĐŽ ĐŒĐžĐœĐž-ĐżŃбДŃŃĐ°ŃĐ° Đž ĐžĐœĐŽĐ”ĐșŃĐŸĐŒ ĐŒĐ°ŃĐșŃĐ»ĐžĐœĐžĐ·Đ°ŃОО ĐœĐ°ŃŃĐ¶ĐœŃŃ
ĐłĐ”ĐœĐžŃалОĐč ĐżĐŸ ŃĐșалД EMS (Ń = 0,002; r = 0,9). РпДŃĐžĐŸĐŽ ĐŒĐžĐœĐž-ĐżŃбДŃŃĐ°ŃĐ° ĐżĐŸĐČŃŃĐ”ĐœĐžĐ” ŃŃĐŸĐČĐœŃ ĐłĐŸĐœĐ°ĐŽĐŸŃŃĐŸĐżĐœŃŃ
ĐłĐŸŃĐŒĐŸĐœĐŸĐČ ĐČŃŃĐČĐ»Đ”ĐœĐŸ Ń 89% (8/9) ĐŽĐ”ŃĐ”Đč, Оз ĐșĐŸŃĐŸŃŃŃ
ŃĐŸŃĐ”ŃĐ°ĐœĐœĐŸĐ” ĐżĐŸĐČŃŃĐ”ĐœĐžĐ” Đ»ŃŃĐ”ĐžĐœĐžĐ·ĐžŃŃŃŃĐ”ĐłĐŸ ĐłĐŸŃĐŒĐŸĐœĐ° Đž ŃĐŸĐ»Đ»ĐžĐșŃĐ»ĐŸŃŃĐžĐŒŃлОŃŃŃŃĐ”ĐłĐŸ ĐłĐŸŃĐŒĐŸĐœĐ° (ЀХĐ) ĐŸŃĐŒĐ”ŃĐ”ĐœĐŸ ĐČ 33% (3/9), ĐžĐ·ĐŸĐ»ĐžŃĐŸĐČĐ°ĐœĐœĐŸĐ” ĐżĐŸĐČŃŃĐ”ĐœĐžĐ” ЀХРĐČ 56% (5/9) ŃĐ»ŃŃĐ°Đ”ĐČ. Đ ĐżŃбДŃŃĐ°ŃĐœĐŸĐŒ пДŃĐžĐŸĐŽĐ” Ń 75% (3/4) паŃĐžĐ”ĐœŃĐŸĐČ ĐČŃŃĐČĐ»Đ”Đœ гОпДŃĐłĐŸĐœĐ°ĐŽĐŸŃŃĐŸĐżĐœŃĐč ĐłĐžĐżĐŸĐłĐŸĐœĐ°ĐŽĐžĐ·ĐŒ.ĐĐŸ ŃДзŃĐ»ŃŃĐ°ŃĐ°ĐŒ гОŃŃĐŸĐ»ĐŸĐłĐžŃĐ”ŃĐșĐŸĐłĐŸ ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ ĐłĐŸĐœĐ°ĐŽ ĐŸŃĐŒĐ”ŃĐ”ĐœĐ° гДŃĐ”ŃĐŸĐłĐ”ĐœĐœĐ°Ń ĐșĐ°ŃŃĐžĐœĐ°. ĐĐŸĐœĐ°ĐŽŃ ĐżŃДЎŃŃĐ°ĐČĐ»Đ”ĐœŃ ŃазлОŃĐœĐŸĐč ŃŃĐ”ĐżĐ”ĐœŃŃ ĐŽĐžŃĐłĐ”ĐœĐ”Đ·ĐžĐž ŃĐ”ŃŃĐžĐșŃĐ»ŃŃĐœĐŸĐč ŃĐșĐ°ĐœĐž: ĐŸŃ Đ»Đ”ĐłĐșĐŸĐč, блОзĐșĐŸĐč Đș гОŃŃĐŸĐ»ĐŸĐłĐžŃĐ”ŃĐșĐŸĐŒŃ ŃŃŃĐŸĐ”ĐœĐžŃ ĐłĐŸĐœĐ°ĐŽ ĐżŃĐž ĐșŃОпŃĐŸŃŃ
ĐžĐ·ĐŒĐ”, ĐŽĐŸ streak Đž ĐŸĐČĐŸŃĐ”ŃŃĐžŃ.ĐĄŃДЎО ĐČĐœĐ”ĐłĐŸĐœĐ°ĐŽĐœŃŃ
ĐżŃĐŸŃĐČĐ»Đ”ĐœĐžĐč Đ·Đ°Đ±ĐŸĐ»Đ”ĐČĐ°ĐœĐžŃ Đ»ĐžĐŽĐžŃŃŃŃ ĐżĐ°Ń
ĐŸĐČŃĐ” ĐłŃŃжО (86%), ĐżĐŸŃĐŸĐșĐž ŃĐ”ŃĐŽŃĐ° (77%) Đž ĐżĐŸŃĐ”Đș (36%). ĐĐ°ŃĐŸĐ»ĐŸĐłĐžŃĐ”ŃĐșĐ°Ń Đ·Đ°ĐŽĐ”ŃжĐșĐ° ŃĐŸŃŃĐ° ĐŽĐžĐ°ĐłĐœĐŸŃŃĐžŃĐŸĐČĐ°ĐœĐ° Ń 23% ĐŽĐ”ŃĐ”Đč.ĐŃĐČĐŸĐŽŃ. Đ ŃŃŃŃĐșŃŃŃĐ” Đ·Đ°Đ±ĐŸĐ»Đ”ĐČĐ°ĐœĐžŃ ĐœĐ° Ń
ŃĐŸĐŒĐŸŃĐŸĐŒĐœĐŸĐ” ĐЀРпŃĐžŃ
ĐŸĐŽĐžŃŃŃ 14% ĐœĐ°Đ±Đ»ŃĐŽĐ”ĐœĐžĐč. ĐŃŃппа паŃĐžĐ”ĐœŃĐŸĐČ Ń ĐЀР45,Đ„/46,Đ„Y гДŃĐ”ŃĐŸĐłĐ”ĐœĐœĐ° ĐżĐŸ ŃŃĐ”ĐżĐ”ĐœĐž ĐŽĐžŃĐłĐ”ĐœĐ”Đ·ĐžĐž ĐłĐŸĐœĐ°ĐŽ, ŃŃŃĐŸĐ”ĐœĐžŃ ĐœĐ°ŃŃĐ¶ĐœŃŃ
Đž ĐČĐœŃŃŃĐ”ĐœĐœĐžŃ
ĐżĐŸĐ»ĐŸĐČŃŃ
ĐŸŃĐłĐ°ĐœĐŸĐČ
Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples
This research was funded by the National Institute for Health
Research (NIHR) University College London Hospitals (UCLH)
Biomedical Research Centre. UKCTOCS was core funded by the
Medical Research Council, Cancer Research UK, and the
Department of Health with additional support from the Eve
Appeal, Special Trustees of Bartâs and the London, and Special
Trustees of UCLH. OB and JFT also received support from the Eve
Appeal Gynaecological Cancer Research Trust and Cancer
Research UK PRC Programme Grant A12677
Genetic landscape in Russian patients with familial left ventricular noncompaction
BackgroundLeft ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).MethodsAll index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.ResultsA total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants â8 of 54 (14.8%) âhave not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 â7.37; p <0.001) per variant after adjustment for sex, age, and family.ConclusionOverall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients
Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.
Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (â„2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of â„1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch
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