Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control.

AIMS: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). MATERIALS AND METHODS: Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated. RESULTS: Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46-50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). CONCLUSIONS: High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. REGISTRATION NUMBER TRIAL: ID NCT00700856 https://clinicaltrials.gov.

Eating habits and sleep quality in individuals with type 1 diabetes on continuous glucose monitoring and insulin pump.

BACKGROUND AND AIMS: Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM). METHODS AND RESULTS: In a cross-sectional study, dietary habits (7-day food diary, EPIC questionnaire) and sleep quality (Pittsburgh Sleep Quality Index questionnaire) were assessed in 59 men and 58 women with T1D, aged 19-79 years, using CGM and insulin pump. Differences in dietary habits and blood glucose after dinner (6 h) between participants differing in sleep quality, sleep duration, and sleep onset latency were evaluated. Bad Sleepers (n = 81) were twice as prevalent as Good Sleepers (n = 36) and had a significantly higher intake of fat than Good Sleepers (dinner: 30.7 ± 10.7 vs. 24.0 ± 10.5 g, p = 0.004). Short sleepers had a significantly higher usual intake (g/1000 kcal) of coffee and tea (90.4 ± 71.7 vs. 62.0 ± 35.6), alcoholic (47.8 ± 51.1 vs. 28.9 ± 31.5) and carbonated beverages (21.8 ± 38.1 vs. 9.3 ± 17.2) (p < 0.05 for all) than Long Sleepers. Long Sleep Onset Latency was associated with a significantly higher fat intake at dinner (41.8 ± 7.4 vs. 38.1 ± 9.1 % total energy, p = 0.029) than Short Sleep Onset Latency. No significant differences in post-dinner blood glucose levels were detected between participants with good or bad sleep quality. CONCLUSION: Sleep disruption is common in T1D and is associated with unhealthy dietary choices, especially at dinner, independently of post-dinner blood glucose control.

Diffusion tensor imaging in detecting gliomas sub-regions of infiltration, local and remote recurrences: a systematic review.

Given that glioma cells tend to infiltrate and migrate along WM tracts, leading to demyelination and axonal injuries, Diffusion Tensor Imaging (DTI) emerged as a promising tool for identifying major "high-risk areas" of recurrence within the peritumoral brain zone (PBZ) or at a distance throughout the adjacents white matter tracts. Of our systematic review is to answer the following research question: In patients with brain tumor, is DTI able to recognizes within the peri-tumoral brain zone (PBZ) areas more prone to local (near the surgical cavity) or remote recurrence compared to the conventional imaging techniques?. We conducted a comprehensive literature search to identify relevant studies in line with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. 15 papers were deemed compatible with our research question and included. To enhance the paper's readability, we have categorized our findings into two distinct groups: the first delves into the role of DTI in detecting PBZ sub-regions of infiltration and local recurrences (n = 8), while the second group explores the feasibility of DTI in detecting white matter tract infiltration and remote recurrences (n = 7). DTI values and, within a broader framework, radiomics investigations can provide precise, voxel-by-voxel insights into the state of PBZ and recurrences. Better defining the regions at risk for potential recurrence within the PBZ and along WM bundles will allow targeted therapy.

From data to practice: brain meningioma treatment in elderly patients - a survey of the Italian Society of Neurosurgery (SINch®) and systematic review and meta-analysis.

The management of meningioma in elderly patients (MEP) presents a complex and evolving challenge. Data available offer conflicting information on treatment options and complications. This survey aimed to examine the current approach to MEP, comparing the national profile to data in the current literature. A survey addressing the treatments options and management of meningioma in elderly was designed on behalf of SINch® (Società Italiana di Neurochirurgia) and sent via email to all Chiefs of Neurosurgical Departments. The survey remained open for responses from May 5th, 2022, until November 21st, 2022. A search of the literature published between January 2000 and March 2023, in accordance to PRISMA guidelines, was included. A total of 51 Neurosurgical centers participated in the survey. The caseload profile of each center influences the choice of treatment selection (Stereotactic Radiosurgery versus open surgery) (p = 0.01) and the consolidated practice of discussing cases within a multidisciplinary group (p = 0.02). The pooled meta-analysis demonstrated a significant increased risk in the elderly group for permanent deficits (p < 0.00001), postoperative infections (p = 0.0004) and hemorrhage (p = 0.0001), perioperative mortality (p < 0.00001), and medical complications (p < 0.00001) as compared to the young population. This study presents the initial comprehensive analysis of the existing trends in the surgical management of MEP in Italy. The significant variation in practices primarily stems from the absence of standardized guidelines. While most centers have adopted an integrated approach, there is a need to promote a multidisciplinary care model. Prospective studies are needed to gather robust evidence in this clinical setting.

Management and treatment of brain tumors during pregnancy: an Italian survey.

PURPOSE: The management of brain tumors during pregnancy is challenging. The clinical rarity and prognostic heterogeneity of such condition makes it difficult to develop standardized guidelines of treatment. The aim of this study was to assess the treatment options used in pregnant women with brain tumors that are currently used in Italy, considering the management of these patients reported in current literature in this field. METHODS: A survey addressing the treatments options and management of brain tumors during pregnancy was designed on behalf of an ad-hoc task-force Neuro-Oncology committee of the Società Italiana di Neurochirurgia (SINch) to analyze the management of pregnant patients with brain tumors. We conducted a search of the literature published between January 2011 and September 2021, using MEDLINE (PubMed) in accordance to PRISMA guidelines. Data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. RESULTS: A total of 18 Neurosurgical centers participated in the survey. A total of 31 pregnant women were included in this retrospective study. Meningiomas and gliomas were the two most common types of brain tumors diagnosed during pregnancy. An emergency surgical procedure was required in 12.9% of cases. CONCLUSION: A multidisciplinary and tailored approach is fundamental. In women showing clinical stability, neurosurgical options should preferably be delayed if possible, and considered during the second trimester or after delivery. In patients with acute neurological symptoms or tumor progression, medical abortion in the first trimester or a C-section in the second and third trimester need to be considered.

Resection versus biopsy for management of primary central nervous system lymphoma: a meta-analysis.

The role of surgery in the management of primary central nervous system lymphomas (PCNSL) is currently confined to diagnosis. However, over recent years, an increasing number of papers have suggested a possible positive prognostic impact of surgery in selected cases. The present work aims to perform a meta-analysis of the available literature evidence. A meta-analysis with meta-regression on the role of surgical resection compared to biopsy in the management of PCNSL was conducted according to the PRISMA statement, searching MEDLINE via PubMed and Embase. The random effect model was used. The quality of evidence was assessed using the GRADE framework. After screening 1395 records, we included 11 papers in our analysis. Patients who underwent surgical resection harbored superficial and single-lesion tumors. At 1-, 2-, and 5-year follow-up, progression-free survival did not differ between the two groups, while overall survival favored resection, even if in a non-significant fashion. Meta-regression analysis showed that the overall survival rate at 2 years, but not at 1 or 5 years, was significantly influenced by tumor location. There were no differences in terms of age, sex, Karnofsky performance status, adjuvant therapy, or procedure-related complications. Overall, the quality of evidence is low. The results of the present meta-analysis do not change the current standard of care for PCNSL. However, surgery could be non-inferior to biopsy with an acceptable risk profile in selected patients harboring single and superficial lesions. The low quality of evidence prompts future randomized studies.

Is There a Role for Machine Learning in Liquid Biopsy for Brain Tumors? A Systematic Review.

The paucity of studies available in the literature on brain tumors demonstrates that liquid biopsy (LB) is not currently applied for central nervous system (CNS) cancers. The purpose of this systematic review focused on the application of machine learning (ML) to LB for brain tumors to provide practical guidance for neurosurgeons to understand the state-of-the-art practices and open challenges. The herein presented study was conducted in accordance with the PRISMA-P (preferred reporting items for systematic review and meta-analysis protocols) guidelines. An online literature search was launched on PubMed/Medline, Scopus, and Web of Science databases using the following query: "((Liquid biopsy) AND (Glioblastoma OR Brain tumor) AND (Machine learning OR Artificial Intelligence))". The last database search was conducted in April 2023. Upon the full-text review, 14 articles were included in the study. These were then divided into two subgroups: those dealing with applications of machine learning to liquid biopsy in the field of brain tumors, which is the main aim of this review (n = 8); and those dealing with applications of machine learning to liquid biopsy in the diagnosis of other tumors (n = 6). Although studies on the application of ML to LB in the field of brain tumors are still in their infancy, the rapid development of new techniques, as evidenced by the increase in publications on the subject in the past two years, may in the future allow for rapid, accurate, and noninvasive analysis of tumor data. Thus making it possible to identify key features in the LB samples that are associated with the presence of a brain tumor. These features could then be used by doctors for disease monitoring and treatment planning.

Neuromodulation for Brain Tumors: Myth or Reality? A Narrative Review.

In recent years, research on brain cancers has turned towards the study of the interplay between the tumor and its host, the normal brain. Starting from the establishment of a parallelism between neurogenesis and gliomagenesis, the influence of neuronal activity on the development of brain tumors, particularly gliomas, has been partially unveiled. Notably, direct electrochemical synapses between neurons and glioma cells have been identified, paving the way for new approaches for the cure of brain cancers. Since this novel field of study has been defined "cancer neuroscience", anticancer therapeutic approaches exploiting these discoveries can be referred to as "cancer neuromodulation". In the present review, we provide an up-to-date description of the novel findings and of the therapeutic neuromodulation perspectives in cancer neuroscience. We focus both on more traditional oncologic approaches, aimed at modulating the major pathways involved in cancer neuroscience through drugs or genetic engineering techniques, and on electric stimulation proposals; the latter is at the cutting-edge of neuro-oncology.

Lumbar interbody fusion using oblique (OLIF) and lateral (LLIF) approaches for degenerative spine disorders: a meta-analysis of the comparative studies.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Historically, posterior approaches to the lumbar spine have allowed surgeons to manage degenerative conditions affecting the lumbar spine. However, spinal muscles injury, post-surgical vertebral instability, cerebrospinal fluid (CSF) leakage, and failed back surgery syndrome (FBSS) represent severe complications that may occur after these surgeries. Lumbar interbody fusion using anterior (ALIF), oblique (OLIF), or lateral (LLIF) approaches may represent valuable surgical alternatives, in case fusion is indicated on single or multiple levels. METHODS: The present study is a systematic review, conducted according to the PRISMA statement, of comparative studies on OLIF, and LLIF for degenerative spine disorders, and a meta-analysis of their clinical-radiological outcomes and complications. RESULTS: After screening 1472 papers on PubMed, Scopus, and Cochrane Library, only 3 papers were included in the present study. 318 patients were included for data meta-analysis, 128 in OLIF group, and 190 in LLIF group. There were no significative differences in terms of surgical (intraoperative blood loss and surgical duration) and clinical (VAS-back, VAS-leg, and ODI scores) outcomes, or fusion rates at last follow-up (> 2 years). Significantly higher rates of abdominal complications, system failure, and vascular injuries were recorded in the OLIF group. Conversely, postoperative neurological symptoms and psoas weakness were significatively more common in LLIF group. CONCLUSIONS: The meta-analysis suggests that OLIF and LLIF are both effective for lumbar degenerative disorders, although each of them presents specific complications and this should represent a relevant element in the surgical planning.

Uncooked cornstarch for the prevention of hypoglycemic events.

Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases -i.e. glycogen storage diseases and other rare disorders - and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.

A wheat aleurone-rich diet improves oxidative stress but does not influence glucose metabolism in overweight/obese individuals: Results from a randomized controlled trial.

BACKGROUND AND AIMS: Aleurone is the innermost layer of wheat bran, rich in fiber, minerals, vitamins, phenolic compounds, and betaine. The metabolic effects of aleurone rich foods are still unknown. Our aim was to investigate the effects of consuming a Wheat Aleurone rich diet vs. a Refined Wheat diet for 8 weeks on fasting and postprandial glycemic and lipid metabolism, inflammation, and oxidative stress in overweight/obese individuals. METHODS AND RESULTS: According to a randomized cross-over study design, 23 overweight/obese individuals, age 56 ± 9 years (M±SD), were assigned to two isoenergetic diet - Wheat Aleurone and Refined Wheat diets - for 8 weeks. The diets were similar for macronutrient composition but different for the aleurone content (40-50 g/day in the Wheat Aleurone diet). After each diet, fasting and postprandial plasma metabolic profile, ferulic acid metabolites and 8-isoprostane concentrations in 24-h urine samples were evaluated. Compared with the Refined Wheat Diet, the Wheat Aleurone Diet increased fasting plasma concentrations of betaine by 15% (p = 0.042) and decreased the excretion of 8-isoprostane by 33% (p = 0.035). Conversely, it did not affect the fasting and postprandial glucose, insulin and triglyceride responses, homocysteine, and C-Reactive Protein concentrations, nor excretion of phenolic metabolites. CONCLUSION: An 8-week Wheat Aleurone Diet improves the oxidative stress and increases plasma betaine levels in overweight/obese individuals with an increased cardiometabolic risk. However, further studies with longer duration and larger sample size are needed to evaluate the benefits of aleurone-rich foods on glucose and lipid metabolism in individuals with more severe metabolic abnormalities. CLINICAL TRIAL REGISTRY NUMBER: NCT02150356, (https://clinicaltrials.gov).

Immunoregulatory effects of glioma-associated stem cells on the glioblastoma peritumoral microenvironment: a differential PD-L1 expression from core to periphery?

OBJECTIVE: Glioma-associated stem cells (GASCs) have been indicated as possible players in supporting growth and recurrence in glioblastoma. However, their role in modulating immune response in the peritumoral area has not yet been described. In this study, the authors aimed to investigate programmed death-ligand 1 (PD-L1) differential expression at the protein level in GASCs derived from different tumor areas (core, periphery, and surrounding healthy brain). METHODS: Tumor tissue samples were collected from patients who underwent surgery for a histopathologically confirmed diagnosis of glioblastoma. Sampling sites were confirmed via neuronavigation and categorized on 5-aminolevulinic acid (5-ALA) fluorescence as bright (ALA+), pale (ALA PALE), or negative (ALA-), which corresponds to the tumor mass, infiltrated peritumoral area, and healthy brain, respectively, during surgery. GASCs were first isolated from the 3 regions and analyzed; then Western blot analysis was used to evaluate the level of PD-L1 expression in the GASCs. RESULTS: Overall, 7 patients were included in the study. For all patients, the mean values ± SD of PD-L1 expression in GASCs for ALA+, ALA PALE, and ALA- were 1.12 ± 1.14, 0.89 ± 0.63, and 0.57 ± 0.18, respectively. The differentially expressed values of PD-L1 in GASCs sampled from the 3 areas were found to be significant (p < 0.05) for 3 of the 7 patients: patient S470 (ALA+ vs ALA- and ALA PALE vs ALA-), patient S473 (ALA+ vs ALA PALE and ALA PALE vs ALA-), and patient S509 (ALA+ vs ALA-). CONCLUSIONS: This analysis showed, for the first time, that GASCs expressed a constitutive level of PD-L1 and that PD-L1 expression in GASCs was not uniform among patients or within the same patient. GASC analysis combined with 5-ALA-guided sampling (from core to periphery) made it possible to highlight the role of the tumor microenvironment at the infiltrating margin, which might cause clinical resistance, opening interesting perspectives for the future.

The prevalence of imposter syndrome among young neurosurgeons and residents in neurosurgery: a multicentric study.

OBJECTIVE: Imposter syndrome (IS) occurs when high-achieving individuals have a pervasive sense of self-doubt combined with fear of being exposed as a fraud, despite objective measures of success. This is one of the main causes of burnout among professionals, threatening their mental health and general well-being. The prevalence and severity of IS among neurosurgery residents and young neurosurgeons has not been yet studied. The primary outcomes of this study were the prevalence and severity of IS. METHODS: An anonymous cross-sectional survey including both a demographic questionnaire (Clance Imposter Phenomenon Survey) and compensatory mechanisms was distributed to young neurosurgeons and residents in neurosurgery in Italy. RESULTS: A total of 103 responses were collected. The prevalence rate was 81.6%. Among the respondents with IS, 42.7% showed moderate signs, 27.2% frequent, and only 11.7% had an intense symptomatology. Level of education, female sex, and academic achievements were all identified as predictive factors of IS. CONCLUSIONS: A total of 81.6% of respondents reported potentially significant levels. The implications of IS on both the outcomes in patients and the well-being of neurosurgeons should be evaluated in future studies.

Are oral anticoagulants a risk factor for mild traumatic brain injury progression? A single-center experience focused on of direct oral anticoagulants and vitamin K antagonists.

BACKGROUND: Mild traumatic brain injury (TBI) in anticoagulated patients is a common challenge for emergency departments because of lack of appropriate epidemiological data and huge management variability for those under oral anticoagulation therapy. Given the discrepancies between guidelines, the aim of the present study was to quantify the association between oral anticoagulant therapy (either vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC)) and the post-traumatic intracranial hemorrhage worsening compared to admission CT scan. METHODS: We included all consecutive records of patients admitted to our emergency department for mild TBI as chief complaint and with a positive admission CT scan. After statistical univariate comparison, cause-specific hazard ratio (HR) and 95% confidence interval (CI) were determined with the use of Cox proportional hazard model. RESULTS: In the study period, 4667 patients had a CT scan for mild TBI; 439 (9.4%) were found to have intracranial hemorrhage. Among these patients, 299 (68.1%) were prescribed observation and control CT: 46 (15.38%) were on anticoagulant therapy, 23 (50%) on VKA, and 23 (50%) on DOAC. In multivariate analysis, only oral anticoagulation therapy was significantly associated to an increased risk of intracranial hemorrhage progression (HR 2.58; 95% CI 1.411-4.703; p = .002 and HR 1.9; 95% CI 1.004-3.735; p = .0048 for VKA and DOAC, respectively). Surgery was due to isolated subdural hematoma in 87.5% of cases, to subdural hematoma associated with intraparenchymal hemorrhage in 9.38% and to intraparenchymal hemorrhage only in 3.12%; 13 cases (4.35%) deceased in intensive care unit. CONCLUSIONS: In our series, anticoagulation was associated to a significant increase in intracranial progression, leaving the question open as to what this implies in current clinical practice; subdural hematoma was the major finding associated to evolution and surgery. Against this background, further studies are needed to clarify patients' management and DOAC safety profile compared to VKA in mild TBI.

Bedside Ultrasound for Ventricular Size Monitoring in Patients with PEEK Cranioplasty: A Preliminary Experience of Technical Feasibility in Neurotrauma Setting.

BACKGROUND: Posttraumatic hydrocephalus is a known complication after traumatic brain injury, particularly affecting patients undergoing decompressive craniectomy. Posttraumatic hydrocephalus monitoring in these patients represents a common issue in neurosurgical practice. Patients require periodical assessments by means of computed tomography (CT) scans. This study presents a preliminary institutional series in which ultrasound was used as a bedside imaging technique to monitor ventricular size in patients harboring a polyetheretherketone (PEEK) cranioplasty. Exploiting the PEEK cranioplasty permeability to echoes, we evaluated the feasibility of this bedside imaging method in monitoring hydrocephalus evolution, determining effects of ventriculo-peritoneal shunt, and excluding complications. METHODS: Eight patients with traumatic brain injury harboring PEEK cranioplasty following decompressive craniectomy were prospectively evaluated. Ultrasound measurements were compared with CT scan data taken the same day, and ventricular morphometry parameters were compared. RESULTS: Ultrasound images through the PEEK cranioplasty were of high quality and intracranial anatomy was distinctly evaluated. A strong correlation was observed between ultrasound and CT measurements. Concerning distance between lateral ventricles frontal horns (IFH) and the diameter of the third ventricle (TV), we found a strong correlation between transcranial sonography and CT measurements in preventriculoperitoneal shunt (rho = 0.92 and p = 0.01 for IFH; rho = 0.99 and p = 0.008 for TV) and in postventriculoperitoneal shunt examinations (rho = 0.95 and p = 0.03 for IFH; rho = 0.97 and p = 0.03 for TV). The mean error rate between transcranial sonography and CT scan was 1.77 ± 0.91 mm for preoperative IFH, 0.65 ± 0.27 mm for preoperative TV, 2.18 ± 0.82 mm for postoperative IFH, and 0.48 ± 0.21 mm for postoperative TV. CONCLUSIONS: Transcranial ultrasound could represent a simplification of the follow-up and management of ventricular size of patients undergoing PEEK cranioplasty. Even if this is a small series, our preliminary results could widen the potential benefits of PEEK, not only as effective material for cranial reconstruction but also, in selected clinical conditions, as a reliable window to explore intracranial content and to monitor ventricular sizes and shunt functioning.

Dietary influence on adiponectin in patients with type 2 diabetes.

BACKGROUND: Here, we evaluate the effects of a diet rich in low-glycaemic index carbohydrates and fibre (CHO/Fibre diet) or monounsaturated fatty acids (MUFA diet), on fasting and postprandial adiponectin concentrations and their relationship with the beneficial effects of the experimental diets on postprandial glucose metabolism and liver fat in type 2 diabetes (T2D). METHODS: Fasting and postprandial adiponectin plasma concentrations were measured before and after dietary interventions in the participants to a randomized controlled trial (NCT01025856), wherein 37 men and 8 women with T2D, aged 35-70 years, followed a CHO/Fibre diet or a MUFA diet for an 8-week period. Hepatic fat content by 1 H NMR and fasting and postprandial plasma glucose and insulin measurements were also available. RESULTS: Fasting adiponectin plasma levels did not change after both diets. Postprandial adiponectin significantly increased after the CHO/fibre diet (9.9 ± 1.6 µg/mL vs. 10.8 ± 2.3 µg/mL; P = .033) but not after the MUFA diet (10.6 ± 1.8 µg/mL vs. 10.6 ± 1.6 µg/mL; P = .935) with a significant difference between changes (P = .035). In the combined CHO/Fibre and MUFA groups, fasting and postprandial adiponectin significantly and inversely correlated with postprandial insulin iAUC at baseline and after intervention, and with liver fat content after intervention. CONCLUSIONS: A diet rich in CHO/Fibre increased postprandial plasma adiponectin significantly more than a MUFA diet in patients with T2D. Independently of diet, adiponectin levels associated with postprandial insulin concentrations. The dietary interventions modulated the relationship between adiponectin and liver fat.

The Pro12Ala polymorphism of PPARγ2 modulates beta cell function and failure to oral glucose-lowering drugs in patients with type 2 diabetes.

BACKGROUND: We evaluate whether the Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 (PPARγ2) has a role in the progression of diabetes by modulating the occurrence of treatment failure to glucose-lowering drugs. METHODS: We studied 215 patients with type 2 diabetes participating in the Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents Intervention Trial study. All participants were insufficiently controlled (glycated haemoglobin [HbA1c ] 7.0%-9.0%) with metformin 2 g/day and were randomly allocated to add-on pioglitazone or a sulfonylurea. Treatment failure was defined as HbA1c ≥8% on two consecutive visits, 3 months apart. RESULTS: Carriers or non-carriers of the polymorphism had similar age, body mass index, and diabetes duration. Ala carriers had lower fasting plasma insulin, better insulin sensitivity (Homeostasis Model Assessment [HOMA]2-%S), and worse beta cell secretion (HOMA2-%B) than non-carriers. During 24 months of follow-up, 32.5% among the Ala carriers and 8.6% among non-carriers (P < 0.001) developed treatment failure with a cumulative incidence of 18.6 vs 4.6/100 person-years. Those patients who developed treatment failure were older, had a younger age at diabetes diagnosis (48 ± 10 vs 52 ± 7 years; P = 0.032), higher HbA1c (8.1 ± 0.5 vs 7.7 ± 0.5%; P < 0.001), and lower HOMA2-%B (30 ± 12 vs 46 ± 29; P = 0.015) at study entry, as compared to those who did not develop treatment failure. At multivariate analysis, the Pro12Ala polymorphism was significantly associated with treatment failure (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.79-11.1; P < 0.001); HbA1c at study entry was the other independent predictor of failure in this study population. CONCLUSION: The Pro12Ala polymorphism is associated with a greater insulin sensitivity, reduced beta cell function and a substantially increased risk of treatment failure.

Personalised support of brain tumour patients during radiotherapy based on psychological profile and quality of life.

PURPOSE: Psychological distress in primary malignant brain tumour (PMBT) patients is associated with poorer outcomes. Radiotherapy (RT) often induces side effects that significantly influence patients' quality of life (QoL), with potential impact on survival. We evaluated distress, anxiety, depression, and QoL over time to identify patients with difficulties in these areas who required more intense psychological support. METHODS: Psychological questionnaires-Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy (FACT-G and FACT-Br)-were completed at the beginning (T0), in the middle (T1), directly after RT (T2), and 3 months after RT (T3). We personalised the psychological support provided for each patient with a minimum of three sessions ('typical' schedule) and a maximum of eight sessions ('intensive' schedule), depending on the patients' psychological profiles, clinical evaluations, and requests. Patients' survival was evaluated in the glioblastoma multiforme (GBM) patients, with an explorative intent. RESULTS: Fifty-nine consecutive PMBT patients receiving post-operative RT were included. For patients who were reported as 'not distressed' at T0, no statistically significant changes were noted. In contrast, patients who were 'distressed' at T0 showed statistically significant improvements in DT, HADS, FACT-G, and FACT-Br scores over time. 'Not distressed' patients required less psychological sessions over the study duration than 'distressed' patients. Interestingly, 'not distressed' GBM patients survived longer than 'distressed' GBM patients. CONCLUSIONS: Increased psychological support improved distress, mood, and QoL for patients identified as 'distressed', whereas psychological well-being was maintained with typical psychological support in patients who were identified as being 'not distressed'. These results encourage a standardisation of psychological support for all RT patients.

Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach.

BACKGROUND AND AIMS: Wholegrain cereals have been implicated in the reduction of lifestyle-related chronic diseases risk including cardiovascular diseases and type 2 diabetes. Molecular mechanisms responsible for the beneficial health effects are not entirely understood. The aims of this study were 1) to identify new potential plasma biomarker candidate metabolites of wholegrain cereal foods intake and 2) to examine whether some putative metabolites associated with wholegrain foods intake may play a role in the improvement of cardiometabolic risk factors. METHODS AND RESULTS: Analysis have been conducted in 54 individuals with metabolic syndrome of both genders, age 40-65 years, randomly assigned to 2 dietary interventions lasting 12-week: 1) wholegrain enriched diet (n = 28), and 2) refined-wheat cereals diet (control diet) (n = 26). Nontargeted metabolite profiling analysis was performed on fasting plasma samples collected at baseline and at the end of the experimental diets. Our data show that, at the end of the intervention, a higher intake of wholegrain (tertile 3) was significantly associated with a marked increase in several lipid compounds, as PC (20:4/16:1), LPC (20:4), LPC (22:6), LPC (18:3), LPC (22:5), and a phenolic compound (P < .05 for all). In the wholegrain group, higher concentrations of these metabolites (tertile 3 vs tertile 1 of each metabolite) were significantly associated with lower postprandial insulin and triglyceride responses (P < .05) by 29% and 37%, respectively. CONCLUSION: These observations suggest a possible role of lipid and polyphenol metabolites in the postprandial metabolic benefits of wholegrains in subjects at high risk of cardiovascular disease. In addition, they provide insight into the role of these metabolites as potential candidate biomarkers of wholegrain foods. The study was registered on ClinicalTrials.gov (identifier: NCT00945854).

Predicting meningioma consistency and brain-meningioma interface with intraoperative strain ultrasound elastography: a novel application to guide surgical strategy.

OBJECTIVE: Providing new tools to improve surgical planning is considered a main goal in meningioma treatment. In this context, two factors are crucial in determining operating strategy: meningioma-brain interface and meningioma consistency. The use of intraoperative ultrasound (ioUS) elastosonography, a real-time imaging technique, has been introduced in general surgery to evaluate similar features in other pathological settings such as thyroid and prostate cancer. The aim of the present study was to evaluate ioUS elastosonography in the intraoperative prediction of key intracranial meningioma features and to evaluate its application in guiding surgical strategy. METHODS: An institutional series of 36 meningiomas studied with ioUS elastosonography is reported. Elastographic data, intraoperative surgical findings, and corresponding preoperative MRI features were classified, applying a score from 0 to 2 to both meningioma consistency and meningioma-brain interface. Statistical analysis was performed to determine the degree of agreement between meningioma elastosonographic features and surgical findings, and whether intraoperative elastosonography was a better predictor than preoperative MRI in assessing meningioma consistency and slip-brain interface, using intraoperative findings as the gold standard. RESULTS: A significantly high degree of reliability and agreement between ioUS elastographic scores and surgical finding scores was reported (intraclass correlation coefficient = 0.848, F = 12.147, p < 0.001). When analyzing both consistency and brain-tumor interface, ioUS elastography proved to have a rather elevated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive (LR+) and negative likelihood ratio (LR-). This consideration was true especially for meningiomas with a hard consistency (sensitivity = 0.92, specificity = 0.96, PPV = 0.92, NPV = 0.96, LR+ = 22.00, LR- = 0.09) and for those presenting with an adherent slip-brain interface (sensitivity = 0.76, specificity = 0.95, PPV = 0.93, NPV = 0.82, LR+ = 14.3, LR- = 0.25). Furthermore, predictions derived from ioUS elastography were found to be more accurate than MRI-derived predictions, as demonstrated by McNemar's test results in both consistency (p < 0.001) and interface (p < 0.001). CONCLUSIONS: While external validation of the data is needed to transform ioUS elastography into a fully deployable clinical tool, this experience confirmed that it may be integrated into meningioma surgical planning, especially because of its rapidity and cost-effectiveness.