Association of cerebellar volume with cognitive and motor function in adults with congenital heart disease.

INTRODUCTION: Patients with congenital heart disease (CHD) are at risk for cognitive and motor function impairments, brain injury, and smaller total brain volumes. The specific vulnerability of the cerebellum and its role in cognitive and motor functions in adults with congenital heart disease is not well defined. METHODS: Forty-three patients with CHD and 53 controls between 18 and 32 years underwent brain magnetic resonance imaging and cognitive, executive (EF), and motor function assessment. Cerebellar volumes were obtained using EasyMeasure and SUIT Toolbox. Associations between cerebellar volumes and cognitive and motor function were calculated using linear models. RESULTS: General cognitive and pure motor functions were lower in patients compared to controls (P < 0.05). Executive functions were within the normal range. While total cerebellar volumes and the anterior lobes were similar in patients and controls (P > 0.1), the posterior cerebellar lobe was smaller in patients with more complex CHD (P = 0.006). Smaller posterior cerebellar gray matter was not associated with cognitive functions. Smaller anterior cerebellar gray matter was not significantly related to motor functions (P > 0.1). CONCLUSION: In adults with CHD, cerebellar volume was largely unimpaired. Patients with more complex CHD may be vulnerable to changes in the posterior cerebellar gray matter. We found no significant contribution of cerebellar gray matter to cognitive and motor impairments. More advanced imaging techniques are necessary to clarify the contribution of the cerebellum to cognitive and motor functions.

Postoperative Improvement of Brain Maturation in Infants With Congenital Heart Disease.

Children with severe congenital heart disease are at risk for neurodevelopmental impairments. We examined brain maturation in infants undergoing neonatal cardiopulmonary bypass surgery or hybrid procedure for hypoplastic left heart syndrome compared to controls. This is a prospective cohort study on term-born infants with congenital heart disease with cerebral MRI pre- and postoperatively. Healthy infants served as controls. Brain maturation was measured using a semiquantitative scoring system. The progress of brain maturation from the preoperative to postoperative MRI within patients was compared. Neurodevelopment was assessed at 1 year with the Bayley Scales of Infant and Toddler Development III. A total of 92 patients with congenital heart disease and 46 controls were studied. Median total maturation score in patients was 12 (interquartile range 10.6-13.0) preoperatively and 14 (12.0-15.0) postoperatively, in controls it was 14 (13.0-15.0). Median time interval between scans was 19 days (interquartile range 14-26). After correction for postmenstrual age at MRI, the pre- and postoperative maturation score was lower in patients compared to controls (preoperative P = 0.01, postoperative P = 0.03) and increased between pre- and postoperative assessment (P ≤ 0.001). Brain maturation scores did not correlate with neurodevelopmental outcome at 1 year, when corrected for socioeconomic status and postmenstrual age at MRI. This study confirms delayed brain maturation in children with congenital heart disease, and despite neonatal cardiac bypass surgery followed by postoperative intensive care medicine brain maturation is ongoing. We encourage further investigation in outcome prediction in this population, potentially by combining more advanced MRI measures with clinical methods.

Prognostic value of MIB-1 proliferation index in solitary fibrous tumors of the pleura implemented in a new score - a multicenter study.

BACKGROUND: Although the majority of solitary fibrous tumors of the pleura (SFTP) follow a benign course, 10-25% of patients suffer from recurrence or metastatic disease. Several scoring models have been proposed to predict the outcome. However, none of these included immunohistochemical (IHC) markers as possible prognosticators. METHODS: In this multicenter study, we collected clinical data and formalin-fixed and paraffin-embedded (FFPE) tissue blocks of patients with histologically proven SFTP which had been surgically resected between 2000 und 2015. After systematic and extensive IHC staining on tissue microarrays, the results were analyzed and compared to histomorphological and clinical data for their possible prognostic value. RESULTS: In total, 78 patients (mean age 61 ± 11 years) were included. Of these, 9 patients (11%) had an adverse outcome including SFTP recurrence (n = 6) or SFTP-related death (n = 3). Mean overall survival was 172 ± 13 months. 1 and 10-year event-free survival rates were 99% and 93%. In the multivariable analysis only MIB-1 proliferation index (Ki-67) ≥10% (HR 12.3, CI 1.1-139.5, p = 0.043), ≥4 mitoses per 10 high power fields (HR 36.5, CI 1.2-1103.7, p = 0.039) and tumor size larger than 10 cm (HR 81.8, CI 1.7-4016.8, p = 0.027) were independently associated with adverse outcome. CONCLUSION: A high proliferation rate by MIB-1 IHC was associated with impaired outcome. Upon this, we established a new score using mitosis, necrosis, size of the tumor and MIB-1, which performed better than the traditional scores in our data set. This prognostic score could help to better evaluate outcome of SFTP, but requires external validation.

Low tissue levels of miR-125b predict malignancy in solitary fibrous tumors of the pleura.

BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) are rare neoplasia of the chest. A subset of SFTP follows a malignant course, sometimes several years after complete resection. Traditional scoring systems based on clinical and histological features are poor predictors of biological behavior. This study aimed to investigate tumor-associated miRNAs expression as novel biomarkers to predict the clinical behavior of SFTP. METHODS: Formalin-fixed and paraffin-embedded SFTP tissues blocks from patients surgically resected between 1992 and 2013 at two tertiary care teaching hospitals were included. SFTP tumors were categorized as either malignant or benign variants according to the WHO classification. Following miRNAs levels were measured: let-7a, miR-16b, miR-17, miR-21, miR-31, miR-34a, miR-92a, miR-125a, miR-125b, miR-195-5b, miR-203a, and miR-223. Differential gene expressions which were calculated with the threshold cycle (Ct) method were compared among the two variants. RESULTS: Thirty-eight patients (40% male, mean age 62.2 (±10.9) years) were included. Expression levels of miR-125b showed a significant difference between benign compared to malignant variants (-3.08 ± 0.93 vs. -2.22 ± 1.36, p = 0.0068). Furthermore, lower levels of miR-125b were found to be associated with increased tumor size (p = 0.0414). Thus, downregulation of miR-125b indicates malignant transformation. All other investigated miRNAs were not associated with grading of SFTP. CONCLUSIONS: Our data suggest a potential role of miR-125b in the pathogenesis of tumor growth and malignant transformation of SFTP, respectively. Further studies have to address the potential use of miRNA-125b as a biomarker or therapeutic target in SFTP.