Impaired Cerebellar Functional Connectivity in Schizophrenia Patients and Their Healthy Siblings

The long-standing notion of schizophrenia as a disorder of connectivity is supported by emerging evidence from recent neuroimaging studies, suggesting impairments of both structural and functional connectivity in schizophrenia. However, investigations are generally restricted to supratentorial brain regions, thereby excluding the cerebellum. As increasing evidence suggests that the cerebellum contributes to cognitive and affective processing, aberrant connectivity in schizophrenia may include cerebellar dysconnectivity. Moreover, as schizophrenia is highly heritable, unaffected family members of schizophrenia patients may exhibit similar connectivity profiles. The present study applies resting-state functional magnetic resonance imaging to determine cerebellar functional connectivity profiles, and the familial component of cerebellar connectivity profiles, in 62 schizophrenia patients and 67 siblings of schizophrenia patients. Compared to healthy control subjects, schizophrenia patients showed impaired functional connectivity between the cerebellum and several left-sided cerebral regions, including the hippocampus, thalamus, middle cingulate gyrus, triangular part of the inferior frontal gyrus, supplementary motor area, and lingual gyrus (all p < 0.0025, whole-brain significant). Importantly, siblings of schizophrenia patients showed several similarities to patients in cerebellar functional connectivity, suggesting that cerebellar dysconnectivity in schizophrenia might be related to familial factors. In conclusion, our findings suggest that dysconnectivity in schizophrenia involves the cerebellum and that this defect may be related to the risk to develop the illness

Self-regulation in the pre-adolescent brain

Self-regulation refers to the ability to monitor and modulate emotions, behavior, and cognition, which in turn allows us to achieve goals and adapt to ever changing circumstances. This trait develops from early infancy well into adulthood, and features both low-level executive functions such as reactive inhibition, as well as higher level executive functions such as proactive inhibition. Development of self-regulation is linked to brain maturation in adolescence and adulthood. However, how self-regulation in daily life relates to brain functioning in pre-adolescent children is not known. To this aim, we have analyzed data from 640 children aged 8–11, who performed a stop-signal anticipation task combined with functional magnetic resonance imaging, in addition to questionnaire data on self-regulation. We find that pre-adolescent boys and girls who display higher levels of self-regulation, are better able to employ proactive inhibitory control strategies, exhibit stronger frontal activation and more functional coupling between cortical and subcortical areas of the brain. Furthermore, we demonstrate that pre-adolescent children show significant activation in areas of the brain that were previously only associated with reactive and proactive inhibition in adults and adolescents. Thus, already in pre-adolescent children, frontal-striatal brain areas are active during self-regulatory behavior

Motor Network Degeneration in Amyotrophic Lateral Sclerosis: A Structural and Functional Connectivity Study

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by motor neuron degeneration. How this disease affects the central motor network is largely unknown. Here, we combined for the first time structural and functional imaging measures on the motor network in patients with ALS and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Structural measures included whole brain cortical thickness and diffusion tensor imaging (DTI) of crucial motor tracts. These structural measures were combined with functional connectivity analysis of the motor network based on resting state fMRI. Focal cortical thinning was observed in the primary motor area in patients with ALS compared to controls and was found to correlate with disease progression. DTI revealed reduced FA values in the corpus callosum and in the rostral part of the corticospinal tract. Overall functional organisation of the motor network was unchanged in patients with ALS compared to healthy controls, however the level of functional connectedness was significantly correlated with disease progression rate. Patients with increased connectedness appear to have a more progressive disease course. CONCLUSIONS/SIGNIFICANCE: We demonstrate structural motor network deterioration in ALS with preserved functional connectivity measures. The positive correlation between functional connectedness of the motor network and disease progression rate could suggest spread of disease along functional connections of the motor network

Effect of Extending the Original Eligibility Criteria for the CROSS Neoadjuvant Chemoradiotherapy on Toxicity and Survival in Esophageal Cancer

Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC. The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy. Group 1 consisted of 89 patients who met the CROSS criteria, and group 2 consisted of 72 patients who met the extended eligibility criteria, i.e. a tumor length greater than 8 cm (n = 24), more than 10% weight loss (n = 35), more than 2-4 cm extension in the stomach (n = 21), celiac lymph node metastasis (n = 13), and/or age over 75 years (n = 2). The study assessed the differences in nCRT-associated toxicity [National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) grade3] and 90-day postoperative mortality. Moreover, the prognostic value for OS was assessed with multivariate Cox regression analysis. No difference was found in nCRT-associated toxicity (P = 0.117), postoperative complications (P = 0.783), and 90-day mortality (P = 0.492). The OS differed significantly (P = 0.004), with a median of 37.3 months [95% confidence interval (CI), 10.4-64.2 months] for group 1 and 17.2 months (95% CI 13.8-20.7 months) for group 2. Pathologic N stage (P = 0.023), pathologic T stage (P = 0.043), and group 2 (P = 0.008) were independent prognostic factors for OS. Extension of the CROSS study eligibility criteria for nCRT did not affect nCRT-associated toxicity, postoperative complications, and postoperative mortality, but was prognostic for OS

Effect of Extending the Original CROSS Criteria on Tumor Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients:A National Multicenter Cohort Analysis

BACKGROUND: Extending the original criteria of the Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study (CROSS) in daily practice may increase the treatment outcome of esophageal cancer (EC) patients. This retrospective national cohort study assessed the impact on the pathologic complete response (pCR) rate and surgical outcome. PATIENTS AND METHODS: Data from EC patients treated between 2009 and 2017 were collected from the national Dutch Upper Gastrointestinal Cancer Audit database. Patients had locally advanced EC (cT1/N+ or cT2-4a/N0-3/M0) and were treated according to the CROSS regimen. CROSS (n = 1942) and the extended CROSS (e-CROSS; n = 1359) represent patients fulfilling the original or extended CROSS criteria, respectively. The primary outcome was total pCR (ypT0N0), while secondary outcomes were local esophageal pCR (ypT0), surgical radicality, and postoperative morbidity and mortality. RESULTS: Overall, CROSS and e-CROSS did not differ in total or local pCR rate, although a trend was observed (23.2% vs. 20.4%, p = 0.052; and 26.7% vs. 23.8%, p = 0.061). When stratifying by histology, the pCR rate was higher in the CROSS group compared with e-CROSS in squamous cell carcinomas (48.2% vs. 33.3%, p = 0.000) but not in adenocarcinomas (16.8% vs. 16.9%, p = 0.908). Surgical radicality did not differ between groups. Postoperative mortality (3.2% vs. 4.6%, p = 0.037) and morbidity (58.3% vs. 61.8%, p = 0.048) were higher in e-CROSS. CONCLUSION: Extending the CROSS inclusion criteria for neoadjuvant chemoradiotherapy in routine clinical practice of EC patients had no impact on the pCR rate and on radicality, but was associated with increased postoperative mortality and morbidity. Importantly, effects differed between histological subtypes. Hence, in future studies, we should carefully reconsider who will benefit most in the real-world setting

Utility of preoperative CT-based body metrics in relation to postoperative complications in pediatric liver transplant recipients

BACKGROUND: Computed tomography (CT) derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat index (ScFI) are measurable components of sarcopenia, frailty, and nutrition. While these body metrics are advocated in adults for predicting postoperative outcomes after liver transplantation (LT), little is known about the value in pediatric populations. This study assessed the relation between preoperative CT-based body metrics and postoperative short-term outcomes in pediatric LT recipients. METHODS: Patients aged 0-18 years who underwent a primary LT were retrospectively included (N=101, median age 0.5 years, range 0.2-17.1). SMI, PMI, and ScFI were derived from preoperative axial CT slices. Postoperative outcomes and complications within 90 days were correlated with the CT-based body metrics. To classify postoperative infections, the Clavien-Dindo (CD) classification was used. Subgroup analyses were performed for age groups (10 years old). An optimal threshold for test performance was defined using Youden's J-statistic and receiver operating characteristic curve as appropriate. RESULTS: ScFI was significantly (P=0.001) correlated with moderate to severe postoperative infections (CD grade 3-5) in children <1 year old, with the optimal ScFI threshold being ≤27.1 cm2 /m2 (sensitivity 80.4% and specificity 77.8%). A weak negative correlation between SMI and the total duration of hospital stay (R=-0.33, P=0.010) and intensive care unit stay (R=-0.32, P 0.013) was observed in children <1 year old. No other associations between CT-based body metrics and postoperative outcomes were shown. CONCLUSIONS: In children <1 year old with cirrhotic liver disease undergoing LT, pre-operative CT-based body metrics were correlated with moderate to severe postoperative infections (ScFI), and with longer duration of hospital and ICU stay (SMI), and thus can be considered important tools for pre-LT risk assessment

Complaints and complications associated with removal of the mandibular third molar. A prospective clinical study

OBJECTIVE: To study the incidence of complaints and complications after removal of the mandibular third molar and to evaluate the influence of this procedure on functioning of the patient during the first post-surgical week. DESIGN: Prospective, clinical. SETTING: Department of Oral and Maxillofacial Surgery, University Hospital Groningen. METHODS: Patients referred for removal of a mandibular third molar were asked to return one week after the procedure and to keep a daily record of the use of pain medication, duration of the pain and intensity of the pain. RESULTS: Removal of mandibular third molars resulted in an overall complication rate of 12%. Pain medication was used more frequently and for a longer period by patients with post-surgical complications. Due to complaints following the removal of the mandibular third molar, the mean absence from work was one and a half day. Work was generally resumed with decreased perceived efficiency. CONCLUSION: After this commonly performed procedure in dento-alveolar surgery most of the patients were hampered as a result of pain during the first four post-surgical days. Over 10% of the patients developed complications leading to more frequently and prolonged use of pain medication. Removal of the mandibular third molar gave rise to complaints which influenced the patients relatively strong in their daily functioning.</p