Carotid Restenosis Rate After Stenting for Primary Lesions Versus Restenosis After Endarterectomy With Creation of Risk Index.

PURPOSE: Carotid artery stenting (CAS) is an option for carotid restenosis (CR) treatment with favorable outcomes. However, CAS has also emerged as an alternative to carotid endarterectomy (CEA) for the management of patients with primary carotid stenosis. This study aimed to report CR rates after CAS was performed in patients with primary lesions versus restenosis after CEA, to identify predictors of CR, and to report both neurological and overall outcomes. MATERIALS AND METHODS: From January 2000 to September 2018, a total of 782 patients were divided into 2 groups: The CAS (prim) group consisted of 440 patients in whom CAS was performed for primary lesions, and the CAS (res) group consisted of 342 patients with CAS due to restenosis after CEA. Indications for CAS were symptomatic stenosis/restenosis >70% and asymptomatic stenosis/restenosis >85%. A color duplex scan (CDS) of carotid arteries was performed 6 months after CAS, after 1 year, and annually afterward. Follow-up ranged from 12 to 88 months, with a mean follow-up of 34.6±18.0 months. RESULTS: There were no differences in terms of CR rate between the patients in the CAS (prim) and CAS (res) groups (8.7% vs 7.2%, χ2=0.691, p=0.406). The overall CR rate was 7.9%, whereas significant CR (>70%) rate needing re-intervention was 5.6%, but there was no difference between patients in the CAS (prim) and CAS (res) groups (6.4% vs 4.7%, p=0.351). Six independent predictors for CR were smoking, associated previous myocardial infarction and angina pectoris, plaque morphology, spasm after CAS, the use of FilterWire or Spider Fx cerebral protection devices, and time after stenting. A carotid restenosis risk index (CRRI) was created based on these predictors and ranged from -7 (minimal risk) to +10 (maximum risk); patients with a score >-4 were at increased risk for CR. There were no differences in terms of neurological and overall morbidity and mortality between the 2 groups. CONCLUSIONS: There was no difference in CR rate after CAS between the patients with primary stenosis and restenosis after CEA. A CRRI score >-4 is a criterion for identifying high-risk patients for post-CAS CR that should be tested in future randomized trials.

Systemic Jak1 activation provokes hepatic inflammation and imbalanced FGF23 production and cleavage.

Fibroblast growth factor 23 (FGF23) is a main regulator of mineral homeostasis. Low and high circulating FGF23 levels are associated with bone, renal, cardiovascular diseases, and increased mortality. Understanding the factors and signaling pathways affecting FGF23 levels is crucial for the management of these diseases and their complications. Here, we show that activation of the Jak1/Stat3 signaling pathway leads to inflammation in liver and to an increase in hepatic FGF23 synthesis, a key hormone in mineral metabolism. This increased synthesis leads to massive C-terminal FGF23 circulating levels, the inactive C-terminal fragment, and increased intact FGF23 levels, the active form, resulting in imbalanced production and cleavage. Liver inflammation does not lead to activation of the calcineurin-NFAT pathway, and no signs of systemic inflammation could be observed. Despite the increase of active intact FGF23, excessive C-terminal FGF23 levels block the phosphaturic activity of FGF23. Therefore, kidney function and renal αKlotho expression are normal and no activation of the MAPK pathway was detected. In addition, activation of the Jak1/Stat3 signaling pathway leads to high calcitriol levels and low parathyroid hormone production. Thus, JAK1 is a central regulator of mineral homeostasis. Moreover, this study also shows that in order to assess the impact of high FGF23 levels on disease and kidney function, the source and the balance in FGF23 production and cleavage are critical.

European Association of Cardiothoracic Anesthesiology and Intensive Care Pediatric Cardiac Anesthesia Fellowship Curriculum: First Edition.

Pediatric cardiac anesthesia is a subspecialty of cardiac and pediatric anesthesiology dedicated to the perioperative care of patients with congenital heart disease. Members of the Congenital and Education Subcommittees of the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) agreed on the necessity to develop an EACTAIC pediatric cardiac anesthesia fellowship curriculum. This manuscript represents a consensus on the composition and the design of the EACTAIC Pediatric Cardiac Anesthesia Fellowship program. This curriculum provides a basis for the training of future pediatric cardiac anesthesiologists by clearly defining the theoretical and practical requirements for fellows and host centers.

Ralstonia pickettii bacteremia in a cardiac surgery patient in Belgrade, Serbia.

Ralstonia pickettii is an opportunistic bacterium found in the water environment with an increasing incidence as a nosocomial pathogen. The objectives of this study were to describe R. pickettii bacteremia in a cardiac surgery patient and to evaluate its ability to grow in a saline solution and to form biofilm. The patient in this study underwent mitral and aortic valve replacement surgery with two aortocoronary bypasses. She developed signs of respiratory and renal failure, therefore hemodialysis was started. After 25 days in an intensive care unit, the patient had recurrent episodes of fever with signs of bacteremia. R. pickettii was identified from blood cultures by MALDI-TOF MS. Antimicrobial susceptibility testing was performed using disc diffusion and broth microdilution methods in accordance with EUCAST methodology and results were interpreted following clinical breakpoints for Pseudomonas spp. The isolate was susceptible to all tested antimicrobial agents except aminoglycosides and colistin. Survival of R. pickettii was analyzed in saline solution with four different starting concentrations at 25 °C and 37 °C for six days. Biofilm capacity was tested using the microtiter plate method. R. pickettii showed substantial growth in saline solution, with starting concentration of 2 CFU ml-1 reaching 107 CFU ml-1 after six days. There was no significant difference between growth at 25 °C and 37 °C. This indicates that storage of contaminated solutions at room temperature can enhance the count of R. pickettii. Our strain did not show the capacity to form biofilm. The patient responded well to adequate treatment with ceftazidime, and after 48 days in ICU she was discharged to convalesce.

Predictors of Early Deterioration of Renal Function in Patients Older Than 70 Years Undergoing Valvular Surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is the most common clinically important complication in adult patients undergoing open-heart surgery, with an incidence between 8.9% and 39%. Studies have shown that even a slight increase in serum creatinine levels after cardiac surgery significantly affects the mortality and morbidity of these patients. AIM: This study sought to determine the predictors and incidence of acute kidney injury (AKI) in patients older than 70 years undergoing elective valvular surgery. METHODS: Prospective study included 156 patients scheduled for elective cardiac surgery requiring cardiopulmonary bypass (CPB) at Dedinje Cardiovascular Institute between January and September 2019. Isolated valvular surgery was performed in 87 patients, while the remaining 69 patients underwent combined coronary and valvular surgery. The development and stage of CSA-AKI were diagnosed, according to Kidney Disease Improving Global Outcome (KDIGO) criteria. Predictors and incidence of CSA-AKI development were assessed using univariate binary logistic regression analysis. RESULTS: The incidence of CSA-AKI was 17.3%. CSA-AKI stage 1 was diagnosed in 25 patients  (16.02%). CSA-AKI stage 2 was noted in one patient (0.64%), as well as stage 3 (0.64%). In six patients (3.85%), renal replacement therapy (RRT) was required. Using univariate binary logistic analysis, the following parameters were identified as predictors for CSA-AKI development: duration of cardiopulmonary bypass (OR 1.01; CI 95% (1.01-1.02); P = .002), duration of aortic clamping (OR 1.02; CI 95% (1.01-1.03); P = .002), lactate levels during the intensive care unit (ICU) stay (OR 1.33; CI 95% (1.04-1.70); P = .026), duration of mechanical ventilation (MV) (OR 1.03; CI 95% (1.1-1.07); P = .014), the use of inotropic drugs (adrenaline, dobutamine) (OR 0.38: CI 95% (0.16-0.9); P = .026; and OR 0.23; CI 95% (0.1-0.56); P = .0019, respectively), and the use of diuretics (OR 0.24; CI95% (0.06-095); P = .041). Using Mann-Whitney U test for independent samples show that the group of patients who developed CSA-AKI had significantly longer duration of hospitalization (Z = -2.751); P = .006), prolonged ICU stay (Z = -4.160; P < .001), and need for prolonged mechanical ventilation (Z = -4.411; P < .001). CONCLUSION: Independent predictors for AKI development after valvular surgery in patients older than 70 years are prolonged mechanical ventilation and increased lactate values, while the use of diuretics after surgery reduces the incidence of AKI. Also, the development of CSA-AKI is associated with prolonged ICU stay and a longer duration of hospitalization.

European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia Fellowship Curriculum: First Edition.

This special article summarizes the design and certification process of the European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia (CTVA) Fellowship Program. The CTVA fellowship training includes a two-year curriculum at an EACTA-accredited educational facility. Before fellows are accepted into the program, they must meet a number of requirements, including evidence of a valid license to practice medicine, a specialist degree examination in anesthesiology, and appropriate language skills as required in the host centers. The CVTA Fellowship Program has 2 sequential and complementary levels of training-both with a modular structure that allows for individual planning and also takes into account the differing national healthcare needs and requirements of the 36 countries represented in EACTA. The basic training period focuses on the anesthetic management of patients undergoing cardiac, thoracic, and vascular surgery and related procedures. The advanced training period is intended to deepen and to extend the clinical and nontechnical skills that fellows have acquired during the basic training. The goal of the EACTA fellowship is to produce highly trained and competent perioperative physicians who are able to care for patients undergoing cardiac, thoracic, and vascular anesthesia.

Trends in transfusion practice over 20 years in paediatric liver transplant programme.

BACKGROUND: We investigated changes to transfusion practices over time in paediatric liver transplant centre and evaluated the effect of transfusion practice to mortality. METHODS: A pilot retrospective study included two cohorts each with 101 sequential paediatric LT recipients: an Early group (1994-1998) and a Recent group (2009-2013). Demographic characteristics and data on the intraoperative transfusion of red blood cells (RBC), fresh-frozen plasma (FFP), platelets and cryoprecipitate were collected. Postoperative laboratory results were also obtained, together with donor and data regarding 1- and 5-year survival. Appropriate intergroup comparisons, univariate and multivariate analysis were made and P ≤ 0·05 was considered statistically significant. RESULTS: There were no significant group differences in demographic data (except patient height). Despite the fact that median total blood loss did not differ between groups (111 ml/kg in both groups), the Early group had greater levels of intraoperative RBC transfusion (75 vs. 59 ml/kg, respectively, P = 0·04) and less use of FFP (53 vs. 62 ml/kg, respectively, P = 0·01). Overall we noted a lower 1- and 5-year survival in the Early group (88·2% vs. 96%, P = 0·04 and 82·4% vs. 89·1%, P = 0·01, respectively). Univariate, but not multivariate regression analyses demonstrated that higher PELD score, RBC and FFP transfusion, and inclusion in the Early group were contributing factors to 1-year higher mortality. CONCLUSIONS: This retrospective analysis of blood loss and replacement in paediatric LT patients demonstrates that the majority of our patients suffer major haemorrhage and require large-volume RBC and FFP replacements. In our pilot study, large volume of RBC and FFP replacement did not contribute to mortality. Paediatric LT involves a number of multidisciplinary teams. Thus, all care-related factors and combinations thereof that may contribute to outcome and should be evaluated in the future.

Position paper on screening for breast cancer by the European Society of Breast Imaging (EUSOBI) and 30 national breast radiology bodies from Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Israel, Lithuania, Moldova, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Sweden, Switzerland and Turkey.

EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50-69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1-10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40-49 years and 70-74 years, although with "limited evidence". Thus, we firstly recommend biennial screening mammography for average-risk women aged 50-69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40-45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become "routine mammography" in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged. KEY POINTS: • EUSOBI and 30 national breast radiology bodies support screening mammography. • A first priority is double-reading biennial mammography for women aged 50-69 years. • Extension to 73-75 and from 40-45 to 49 years is also encouraged. • Digital mammography (not film-screen or computer radiography) should be used. • DBT is set to become "routine mammography" in the screening setting in the next future.

Consecutive Observational Study to Validate EuroSCORE II Performances on a Single-Center, Contemporary Cardiac Surgical Cohort.

OBJECTIVE: To compare and validate the original EuroSCORE risk stratification models with the renewed EuroSCORE II model in a contemporary cardiac surgical practice. DESIGN: A consecutive observational study to validate EuroSCORE II performances, conducted as retrospective analysis of prospectively collected data. SETTING: A tertiary university institute for cardiovascular diseases. PARTICIPANTS: Adult patients undergoing cardiac surgery between January and December 2012. METHODS: One thousand eight hundred sixty-four consecutive patients were scored preoperatively using additive and logistic EuroSCORE as well as EuroSCORE II. The discriminative power of the EuroSCORE models was tested by calculating the area under the receiver operating characteristic curve (AUC). The calibration of the models was assessed by Hosmer-Lemeshow statistics and with observed-to-expected mortality ratio. MEASUREMENTS AND MAIN RESULTS: The in-hospital overall mortality was 3.65%, with predicted mortalities according to additive EuroSCORE, logistic EuroSCORE, and EuroSCORE II of 5.14%, 6.60%, and 3.51%, respectively. The observed-to-expected (O/E) mortality ratio confirmed good calibration for the entire cohort only for EuroSCORE II (1.05, 95% confidence interval 0.81 - 1.29). Hosmer-Lemeshow test confirmed overall good calibration only for additive EuroSCORE (p = 0.129). The EuroSCORE II confirmed very good discriminatory power for a prolonged intensive care unit (ICU) stay of>2 days and>5 days (AUCs>0.75). Acceptable discriminatory power was confirmed for a prolonged postoperative stay of>7 days and>12 days (AUCs>0.70). CONCLUSION: EuroSCORE II confirmed very good discriminatory capacity, good calibration ability (O/E mortality ratio), and good capability to predict prolonged ICU and postoperative stays in a contemporary patient cohort undergoing cardiac surgery.

Dirofilariasis of the breast: sonographic appearance.

Human dirofilarial infections characteristically manifest as pulmonary "coin" lesions or as subcutaneous nodules. A case of subcutaneous Dirofilaria infection of the breast involving a 25-year-old woman with a painful breast lump is presented. The patient had not traveled anywhere and did not have any animals, but provided a history of being bitten by mosquitoes. The suspicion of a parasitic infection was raised by the presence of rod-like structures within a hypoechoic nodule on sonography; movement within the nodule was detected during the examination. Histopathological examination revealed viable, adult female Dirofilaria repens, a nematode that is commonly found in dogs, cats, and wild mammals throughout parts of Europe, Africa, and Asia. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:433-435, 2014.

Effect of alpha-lipoic acid supplementation on oxidative stress markers and antioxidative defense in patients with schizophrenia.

BACKGROUND: The purpose of this study was to examine the effects of alpha-lipoic acid (LA) supplementation on oxidative stress markers in patients with schizophrenia. SUBJECTS AND METHODS: Eighteen (18) medicated patients with schizophrenia and 38 healthy controls received daily supplements of LA (500 mg/day) for three months. At baseline, 45th and 90th days of supplementation, venous blood collected for analysis of oxidative stress markers [superoxide anion (O2(•-)), thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPP)] and antioxidative defense markers [superoxide dismutase (SOD), total sulfhydryl groups (-SH) and total antioxidant status (TAS)]. RESULTS: Increased plasma TBARS, TAS, SH groups levels and SOD activity were found in schizophrenic patients compared to control group. LA supplementation significantly reduced TBARS, AOPP and improved TAS levels in healthy subjects, while there were no significant differences in patients group. SH groups increased after 45 days and decreased to baseline levels after 90 days of supplementation in the control group. SOD activity decreased significantly in patients group after 45 days and 90 days of supplementation. After initial rose SOD activity in control group, decreased to baseline levels found after 90 days. CONCLUSION: LA supplementation decreased lipid peroxidation and oxidative damage of proteins and improved non-enzymatic antioxidant capacity in healthy controls. No significant changes were observed on oxidative damage in patients with schizophrenia.

Perioperative management and surgical field optimization in functional endoscopic sinus surgery.

A sound anesthesiologist-surgeon collaboration is crucial for the success of functional endoscopic sinus surgery (FESS). The aim of this narrative review was to describe if and how anesthetic choice can decrease bleeding and improve visibility in the surgical field (VSF) and thus contribute to successful FESS. A literature search was conducted on evidence-based practices published from 2011 to 2021 describing perioperative care, intravenous/inhalation anesthetics, and operative approaches for FESS and their effects on blood loss and VSF. With regards to preoperative care and operative approaches, best clinical practices include topical vasoconstrictors at the time of surgery, medical management (steroids) preoperatively, and patient positioning, as well as anesthetic techniques including controlled hypotension, ventilation settings, and anesthetics choices. Four out of five meta-analyses and six out of 11 randomized controlled trials favored total intravenous anesthesia (TIVA) over inhalation anesthesia (IA) for improved VSF. The effects on VSF were more dependent on adjunct medications used (remifentanil, alpha-2 agonists, etc.), rather than the choice of anesthetic technique (i.e., TIVA vs. IA). The current literature is inconclusive regarding the impact of anesthetic choice on VSF during FESS. We recommend that anesthesiologists use the anesthetic technique with which they are most comfortable to facilitate efficiency, recovery, cost, and collaboration with the perioperative team. Future studies should be designed to consider disease severity, the method for measuring blood loss, and a standardized VSF score. Studies should also investigate the long-term effects of TIVA- and IA- induced hypotension.

The Perioperative Pain Management Bundle is Feasible: Findings From the PAIN OUT Registry.

OBJECTIVES: The quality of postoperative pain management is often poor. A "bundle," a small set of evidence-based interventions, is associated with improved outcomes in different settings. We assessed whether staff caring for surgical patients could implement a "Perioperative Pain Management Bundle" and whether this would be associated with improved multidimensional pain-related patient-reported outcomes (PROs). METHODS: "PAIN OUT," a perioperative pain registry, offers tools for auditing pain-related PROs and obtaining information about perioperative pain management during the first 24 hours after surgery. Staff from 10 hospitals in Serbia used this methodology to collect data at baseline. They then implemented the "Perioperative Pain Management Bundle" into the clinical routine and collected another round of data. The bundle consists of 4 treatment elements: (1) a full daily dose of 1 to 2 nonopioid analgesics (eg, paracetamol and/or nonsteroidal anti-inflammatory drugs), (2) at least 1 type of local/regional anesthesia, (3) pain assessment by staff, and (4) offering patients information about pain management. The primary endpoint was a multidimensional pain composite score (PCS), evaluating pain intensity, interference, and side effects that was compared between patients who received the full bundle versus not. RESULTS: Implementation of the complete bundle was associated with a significant reduction in the PCS ( P < 0.001, small-medium effect size [ES]). When each treatment element was evaluated independently, nonopioid analgesics were associated with a higher PCS (ie, poorer outcome, and negligible ES), and the other elements were associated with a lower PCS (all negligible small ES). Individual PROs were consistently better in patients receiving the full bundle compared with 0 to 3 elements. The PCS was not associated with the surgical discipline. DISCUSSION: We report findings from using a bundle approach for perioperative pain management in patients undergoing mixed surgical procedures. Future work will seek strategies to improve the effect.

Technical strategy in a patient with symptomatic thoracic aneurysm near the origin of the left subclavian artery and left internal thoracic artery coronary graft.

Thoracic endovascular aortic repair (TEVAR) is a safe and reliable technique utilized in the treatment for aortic aneurysms. However, in up to 40% of patients, devices are typically placed over the left subclavian artery (LSA) origin. In this report, we present a case of a successful TEVAR procedure following the transposition of the LSA with protective carotico-axillary/carotid bypass in a patient with a patent left internal thoracic artery (LITA)-left anterior descending (LAD) coronary artery bypass graft and right internal carotid artery (ICA) occlusion.

Benefits, risks and complications of perioperative use of epidural anesthesia.

Use of thoracic epidurals is widespread for intraoperative and postoperative analgesia. Thoracic epidural anaesthesia (TEA) reduces sympathetic activity and thereby influences perioperative function of vital organ systems. A results of recent studies suggest that TEA decreases postoperative morbidity and mortality. There is better pain control with TEA in a wide range of surgical procedures. Use of TEA is associated with the risk of harm, but also the other methods used to control perioperative pain and stress response carry specific risks. Timely diagnosis and treatment of spinal compression or infection are crucial to ensure patient safety with TEA. The benefits of TEA outweigh the risks with respect to the perioperative outcome and organ protection, if basic guidelines are followed.

Direct Ischemic Postconditioning After Carotid Endarterectomy in the Prevention of Postoperative Cerebral Ischemic Complications-Observational Case-Control Study.

INTRODUCTION: Ischemic postconditioning (IPCT) represents one of the several therapeutic strategies to attenuate ischemic reperfusion injury (IR) after carotid endarterectomy (CEA). We here present the first in-human study of IPCT in carotid surgery. METHODS: The study represents an observational case-control study, with the data collected in our Institution carotid database. From December 2015 to December 2020, a total of 300 patients were included in our study; IPCT group consisted of 148 patients in whom ischemic postconditioning was performed while control group consisted of 152 patients in whom IPCT was not performed. Indications for IPCT technique were: severe unilateral internal carotid artery (ICA) stenosis (>90%), severe bilateral ICA stenosis (>80%), severe ICA stenosis (>80%) with contralateral ICA occlusion and ICA subocclusion. IPCT was performed by applying 6 cycles of 30 sec reperfusion (declamping of ICA)/30 sec ischemia (clamping of ICA) after finishing the procedure and initial declamping. Two groups of patients were compared in terms of occurrence of intrahospital and early postoperative stroke, TIA (transient ischemic attack) and neurologic morbidity. RESULTS: Cumulative incidence of intrahospital postoperative stroke or TIA was significantly higher in the control group (5.3% vs 0.7%, P = .036). According to carotid plaque characteristics, patients in the IPCT group had significantly more frequent presence of heterogenous plaque, as well as ulcerated plaque, which was associated with the absence of postoperative stroke and significantly lower cumulative rate of TIA/stroke when compared to the control group (43.9% vs 8% and 47.3% vs 1.5%). During the follow-up period of 1 month after the surgery, there were no cases of stroke, TIA and deaths due to neurological causes in both groups of patients. CONCLUSION: Our results showed that IPCT significantly reduced the incidence of postoperative cerebral ischemic complications after CEA in high-risk patients for IR injury when compared to the control group.

Multivoxel MRS: right frontal parafalcine cortex - area of neurobiochemical gender differentiation?

OBJECTIVE: To determine the presence of gender neurometabolic differences in healthy men and women by multivoxel magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS: We performed multivoxel magnetic resonance imaging and spectroscopy in 50 healthy volunteers (27 women and 23 men) using 1.5T scanner. Spectra from 12 different voxels were obtained, covering frontal, paracentral, and parietal white and gray matter. Three dominant signals were analyzed: NAA, tCr and Cho, and expressed as ratios of Cho/tCr, NAA/tCr, NAA/Cho. RESULTS: There was statistically significant gender difference between Cho/Cr and NAA/Cr metabolites ratio in only one location - the right frontal parafalcine cortex. There was no statistically significant difference in NAA/Cho ratio between men and women. CONCLUSION: Our study suggests that right frontal parafalcine cortex is a sexually dysmorphic area and supports the value of multivoxel MRS as a method able to define spatial biochemical heterogeneity of the cerebral tissue.