Glioma-Induced Disruption of Resting-State Functional Connectivity and Amplitude of Low-Frequency Fluctuations in the Salience Network

BACKGROUND AND PURPOSE:Cognitive challenges are prevalent in survivors of glioma, but their neurobiology is incompletely understood. The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on resting-state functional connectivity and amplitude of low-frequency fluctuations of the salience network, a key neural network associated with cognition.MATERIALS AND METHODS:Sixty-nine patients with glioma (mean age, 48.74 [SD, 14.32] years) who underwent resting-state fMRI were compared with 31 healthy controls (mean age, 49.68 [SD, 15.54] years). We identified 4 salience network ROIs: left/right dorsal anterior cingulate cortex and left/right anterior insula. Average salience network resting-state functional connectivity and amplitude of low-frequency fluctuations within the 4 salience network ROIs were computed.RESULTS:Patients with gliomas showed decreased overall salience network resting-state functional connectivity (P = .001) and increased amplitude of low-frequency fluctuations in all salience network ROIs (P < .01) except in the left dorsal anterior cingulate cortex. Compared with controls, patients with left-sided gliomas showed increased amplitude of low-frequency fluctuations in the right dorsal anterior cingulate cortex (P = .002) and right anterior insula (P < .001), and patients with right-sided gliomas showed increased amplitude of low-frequency fluctuations in the left anterior insula (P = .002). Anterior tumors were associated with decreased salience network resting-state functional connectivity (P < .001) and increased amplitude of low-frequency fluctuations in the right anterior insula, left anterior insula, and right dorsal anterior cingulate cortex. Patients with high-grade gliomas had decreased salience network resting-state functional connectivity compared with healthy controls (P < .05). The right anterior insula showed increased amplitude of low-frequency fluctuations in patients with grade II and IV gliomas compared with controls (P < .01).CONCLUSIONS:By demonstrating decreased resting-state functional connectivity and an increased amplitude of low-frequency fluctuations related to the salience network in patients with glioma, this study adds to our understanding of the neurobiology underpinning observable cognitive deficits in these patients. In addition to more conventional functional connectivity, amplitude of low-frequency fluctuations is a promising functional-imaging biomarker of tumor-induced vascular and neural pathology.

Detrimental effects of cancer on cognitive function and, consequently, on the quality of life are emerging as a key focus of cancer survivorship both in research and clinical practice.^1,2 Brain tumors have been shown to affect memory, processing, and attention in patients; however, their underlying neurobiology is incompletely understood.³ Using resting-state functional MR imaging (rsfMRI) to evaluate changes in cognitive resting-state networks may provide a better understanding of the pathology underlying the observable cognitive disruptions in gliomas, the most common primary brain tumor in adults.A “triple network model” of neurocognitive pathology has been proposed, which encompasses the default mode network, involved in mind wandering; the central executive network, involved in decision-making; and the salience network (SN), implicated in modulating activation of the default mode network and central executive network by detecting the presence of salient stimuli.^4-8 While previous rsfMRI research has largely focused on tumor-induced changes in the default mode network,^9,10 our study examined the less-studied SN, a network rooted in the anterior insula and the dorsal anterior cingulate cortex.⁶Prior studies evaluating gliomas and SN resting-state functional connectivity (RSFC) provided conflicting results in small patient samples: Maesawa et al¹⁰ found no significant differences in the SN in 12 patients, while Liu et al¹¹ more recently found decreased SN connectivity in 13 patients. Gliomas impact the integrity of the neurovascular unit to varying degrees, resulting in neurovascular uncoupling that has been reported to confound fMRI interpretations in patients with brain tumors.^12-14 Additionally, research has reported neuronal plasticity manifested by structural reorganization and functional remodeling of neural networks in patients with gliomas with possible alterations in clinically observable cognitive manifestations.^15-17 An rsfMRI metric, the amplitude of low-frequency fluctuations (ALFF), has recently shown promise as a biomarker for brain plasticity and hemodynamic characterization, including neurovascular uncoupling in patients with gliomas.^15-19The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on overall RSFC and regional normalized ALFF within the SN in a large patient population. We hypothesized that there would be decreased average SN RSFC and altered ALFF in patients with gliomas compared with healthy controls. Recent studies have acknowledged that gliomas have variable effects on network integrity based on lesion location and proximity to network ROIs,^20-22 and unilateral gliomas can be associated with plasticity in both the ipsilateral and contralateral hemispheres.^11,17 Research also supports differences in resting-state network reorganization in aggressive high-grade gliomas compared with slower-growing low-grade gliomas.^20,23 Therefore, we also hypothesized that there would be differences in average SN RSFC and regional ALFF in patients based on the anterior-versus-posterior location, hemispheric side, and grade of glioma.     

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Short-term prognosis of patients with acute coronary syndromes through the evaluation of physical activity status, the adoption of Mediterranean diet and smoking habits: the Greek Acute Coronary Syndromes (GREECS) study.

PURPOSE: Our aim was to evaluate whether healthy dietary habits, physical activity and non-smoking are associated with less severe acute coronary syndromes and better short-term prognosis. SUBJECTS AND METHODS: From October 2003 to September 2004, 2172 patients (1649 males), hospitalized for severe acute coronary syndromes in six major hospitals in Greece were included in the study. The severity of severe acute coronary syndromes was assessed through troponin-I and maximum creatinine kinase MB levels, while 30-day recurrent event rate (death or rehospitalization for cardiovascular disease, angioplasty or coronary artery bypass surgery) was used to evaluate the prognosis of the patients. A 'healthy index' that assessed adherence to the Mediterranean diet, moderate alcohol intake, physical activity and abstinence from smoking was developed (range 0-4). RESULTS: One unit increment in the healthy index was associated with -12.4+/-2.4 ng/ml decrease in troponin I levels (P=0.001) and -9.7+/-2.5 ng/ml decrease in maximum creatinine kinase MB levels (P=0.001). The in-hospital mortality rate was 3.2% in males and 5.7% in females (i.e. overall 82 deaths, P=0.009); during the first 30 days following hospitalization the event rate was 15.7% in males and 16.3% in females (P=0.001). Values of the healthy index above one (i.e. presence of two or more protective factors) seemed to be associated with 44-84% lower risk of having recurrent events (P<0.001), even after various adjustments were made. CONCLUSION: Among patients who had had severe acute coronary syndromes, a healthy lifestyle seemed to be associated with less severe cardiac events and lower risk of death or rehospitalization 30 days after the event.     

Chronische Transplantatdysfunktion

Chronic transplant dysfunction is a complex dynamic pathogenic process. Clinically, a decrease in glomerular filtration rate (GFR) becomes apparent leading to chronic renal insufficiency and dialysis or death from cardiovascular events. Chronic transplant dysfunction can develop into a chronic alIograft nephropathy (CAN) as a specific entity with dynamic progression. CAN includes a collection of immunologic and non-immunologic factors, rejection, ischemia time, donor and recipient characteristics and toxicity of calcineurin inhibitors. Despite improvements in immunosuppression, the long-range prognosis of renal allografts has not improved. Whether modern immunosuppressive concepts with reduction or avoidance of calcineurin inhibitors and a therapy based on antimetabolites, such as mycophenolate or mTOR-inhibitors could lead to a prolongation of transplant survival, remains to be seen.     

Per‐oral transgastric abdominal surgery

Laparoscopic surgery has several advantages over traditional surgery because it has been shown to be less invasive. The next logical step in the evolution of minimally invasive surgery may be to eliminate all abdominal incisions. The natural orifices provide a port of entry via the gastrointestinal tract to the peritoneal cavity. This approach would require the creation of a perforation, which is considered to be a major complication of endoscopy with significant morbidity and mortality. However, there are several recent studies that have described the technical feasibility and safety of a per‐oral transgastric approach to the peritoneal cavity using conventional endoscopes. Theoretically, this approach could reduce postoperative abdominal wall pain, wound infection, hernia formation, and adhesions. This article aims to summarize the current status of transgastric surgery, currently referred to as natural orifice transluminal endoscopic surgery (NOTES), and to address some of its future challenges.     

Sex‐related Disparity in Surgical Mortality among Pediatric Patients

Background. It has been reported that gender differences in cardiovascular outcomes found in adults also are present in children who undergo surgical repair for congenital heart disease. Methods. California statewide hospital discharge data 1989–99 were used to study outcomes in children <18 years undergoing cardiac surgery. Hospital discharge data were linked to death registry data to study postdischarge death within 30 days of discharge. We used logistic regression to evaluate the effect of gender on mortality controlling for age, race and ethnicity, type of insurance, household income, date and month of surgery, type of admission, hospital case volume, and various types of procedures. Results. There were 25 402 cardiac surgery cases with 1505 in‐hospital deaths (mortality rate of 5.92%). An additional 37 deaths occurred within 30 days after hospital discharge. Crude mortality rates for males (5.99%) and females (5.84%) were not significantly different. However, fewer neonates were female and females underwent a higher proportion of low‐risk procedures than males. Logistic regression revealed that females, compared with males, had a significantly higher odds ratio (OR) for in‐hospital mortality (OR = 1.18, P < .01) and overall (up to 30 days post discharge) mortality (OR = 1.18, P < .01). The risk‐adjusted length of hospital stay was similar between females and males while charges per hospital day were slightly higher in females than males. The prevalence of Down syndrome, pulmonary hypertension, and failure to thrive were higher in females. Conclusions. Female gender is associated with an 18% higher in‐hospital and 30‐day postdischarge mortality as compared with male gender. There was no difference in length of hospital stay between males and females. The mechanism by which female gender acts as a risk factor requires further investigation.     

Littoral‐cell angioma as a rare cause of splenomegaly

We report the case of a littoral‐cell angioma of the spleen, a recently described benign vascular tumour, whose imaging and pathological characteristics have been discussed only by a few authors. The diagnosis was made after elective splenectomy. The CT images, scintigraphy and histological specimens are presented, and differential diagnoses discussed.