Comparación clínica y laboratorial de la fiebre amarilla severa versus dengue grave en Perú / Clinical and laboratory differences between severe yellow fever and severe dengue in emergency patients

En los centros de Emergencia con poco apoyo de laboratorio, es difícil diferenciar a los pacientes con dengue grave y fiebre amarilla severa. El objetivo fue comparar el perfil clínico y de laboratorio de los pacientes con dengue grave y fiebre amarilla severa en Urgencias. Se realizó un estudio observacional retrospectivo de pacientes con diagnóstico confirmado de dengue y fiebre amarilla en el período 2018 a 2020 atendidos en la Unidad de Emergencia del Hospital Carrión, Huancayo-Perú. Se evaluaron un total de 35 pacientes, 11 pacientes (31,4%) fueron diagnosticados con fiebre amarilla severa y 24 pacientes (68,5%) con dengue grave. La media de los resultados de laboratorio con fiebre amarilla severa fueron bilirrubina indirecta 4,7 ml/dL, aspartato transaminasa 4463 UI/L, transaminasa aminotransferasa 4329 UI/L, creatinina 4,9 mg/dl. En pacientes con dengue grave el hematocrito promedio fue 51,8, hemoglobina 17,6 g/dl, plaquetas 24 × 103/mm. En pacientes con síndrome ictérico-febril la presencia de bradicardia, bilirrubina indirecta elevada y transaminasas muy elevadas debe hacer sospechar de fiebre amarilla; mientras que los pacientes que acuden por ascitis, derrame pleural, aumento de hematocrito y deficiencia de plaquetas, se debe tratar como dengue grave sobre todo en Unidades de Emergencia con poco apoyo de laboratorio(AU)

In Emergency centers with little laboratory support, differentiating patients with dengue and yellow fever is difficult. The Aim was to compare the clinical and laboratory profile of patients with severe dengue and severe yellow fever in the Emergency unit. We conducted a retrospective observational study of patients with a confirmed diagnosis of dengue and yellow fever in the period 2018 to 2020 treated in the Emergency Unit of the Carrión hospital, Huancayo-Peru. A total of 35 patients were evaluated, 11 patients (31.4%) were diagnosed with severe yellow fever and 24 patients (68.5%) with severe dengue. The mean laboratory results in patients with severe yellow fever were indirect bilirubin 4.7 ml/dL, aspartate transaminase 4463 IU/L, transaminase aminotransferase 4329 IU/L, creatinine 4.9 mg / dl. In patients with severe dengue were hematocrit 51.8, hemoglobin 17.6 g / dl, platelets 24 × 103 / mm. In patients with syndrome jaundice and fever the presence of bradycardia, elevated indirect bilirubin, and very elevated transaminases should be suspicious for yellow fever; while in patients who come for ascites, pleural effusion, increased hematocrit and platelet deficiency, it should be treated as severe dengue especially in Emergency Units with little laboratory support(AU)

Chemical exchange rotation transfer imaging of phosphocreatine in muscle.

In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate. Correcting for these effects while maintaining reasonable acquisition times is challenging. As an alternative approach to overcome these problems, here we evaluate chemical exchange rotation transfer (CERT) imaging of PCr in muscle at 9.4 T. Specifically, the CERT metric, AREXdouble,cpw at 2.6 ppm, was measured in solutions containing the main muscle metabolites, in tissue homogenates with controlled PCr content, and in vivo in rat leg muscles. PCr dominates CERT metrics around 2.6 ppm (although with nontrivial confounding baseline contributions), indicating that CERT is well-suited to PCr specific imaging, and has the added benefit of requiring a relatively small number of acquisitions.

Short echo-time Magnetic Resonance Spectroscopy in ALS, simultaneous quantification of glutamate and GABA at 3 T.

Cortical hyperexcitability has been found in early Amyotrophic Lateral Sclerosis (ALS) and is hypothesized to be a key factor in pathogenesis. The current pilot study aimed to investigate cortical inhibitory/excitatory balance in ALS using short-echo Magnetic Resonance Spectroscopy (MRS). Patients suffering from ALS were scanned on a 3 T Trio Siemens MR scanner using Spin Echo Full Intensity Acquired Localized (SPECIAL) Magnetic Resonance Spectroscopy in primary motor cortex and the occipital lobe. Data was compared to a group of healthy subjects. Nine patients completed the scan. MRS data was of an excellent quality allowing for quantification of a range of metabolites of interest in ALS. In motor cortex, patients had Glutamate/GABA and GABA/Cr- ratios comparable to healthy subjects. However, Glutamate/Cr (p = 0.002) and the neuronal marker N-acetyl-aspartate (NAA/Cr) (p = 0.034) were low, possibly due to grey-matter atrophy, whereas Glutathione/Cr (p = 0.04) was elevated. In patients, NAA levels correlated significantly with both hand strength (p = 0.027) and disease severity (p = 0.016). In summary SPECIAL MRS at 3 T allows of reliable quantification of a range of metabolites of interest in ALS, including both excitatory and inhibitory neurotransmitters. The method is a promising new technique as a biomarker for future studies on ALS pathophysiology and monitoring of disease progression.

Third Trimester Cerebellar Metabolite Concentrations are Decreased in Very Premature Infants with Structural Brain Injury.

Advanced neuroimaging techniques have improved our understanding of microstructural changes in the preterm supratentorial brain as well as the cerebellum and its association with impaired neurodevelopmental outcomes. However, the metabolic interrogation of the developing cerebellum during the early postnatal period after preterm birth remains largely unknown. Our study investigates the relationship between cerebellar neurometabolites measured by proton magnetic spectroscopy (1H-MRS) in preterm infants with advancing post-menstrual age (PMA) and brain injury during ex-utero third trimester prior to term equivalent age (TEA). We prospectively enrolled and acquired high quality 1H-MRS at median 33.0 (IQR 31.6-35.2) weeks PMA from a voxel placed in the cerebellum of 53 premature infants born at a median gestational age of 27.0 (IQR 25.0-29.0) weeks. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentrations of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr). We noted positive correlations of cerebellar concentrations of NAA, Cho and Cr (Spearman correlations of 0.59, 0.64 and 0.52, respectively, p value < 0.0001) and negative correlation of Cho/Cr ratio (R -0.5, p value 0.0002) with advancing PMA. Moderate-to-severe cerebellar injury was noted on conventional magnetic resonance imaging (MRI) in 14 (26.4%) of the infants and were noted to have lower cerebellar NAA, Cho and Cr concentrations compared with those without injury (p value < 0.001). Several clinical complications of prematurity including necrotizing enterocolitis, systemic infections and bronchopulmonary dysplasia were associated with altered metabolite concentrations in the developing cerebellum. We report for the first time that ex-utero third trimester cerebellar metabolite concentrations are decreased in very preterm infants with moderate-to-severe structural cerebellar injury. We report increasing temporal trends of metabolite concentrations in the cerebellum with advancing PMA, which was impaired in infants with brain injury on MRI and may have early diagnostic and prognostic value in predicting neurodevelopmental outcomes in very preterm infants.

Renal effects of exendin-4 in an animal model of brain death.

Organ transplantation is the gold standard therapy for the majority of patients with terminal organ failure. However, it is still a limited treatment especially due to the low number of brain death (BD) donors in relation to the number of waiting list recipients. Strategies to increase the quantity and quality of donor organs have been studied, and the administration of exendin-4 (Ex-4) to the donor may be a promising approach. Male Wistar rats were randomized into 3 groups: (1) control, without central nervous system injury; (2) BD induced experimentally, and (3) BD induced experimentally + Ex-4 administered immediately after BD induction. After BD induction, animals were monitored for 6 h before blood collection and kidney biopsy. Kidney function was assessed by biochemical quantification of plasma kidney markers. Gene and protein expressions of inflammation- and stress-related genes were evaluated by RT-qPCR and immunoblot analysis. Animals treated with Ex-4 had lower creatinine and urea levels compared with controls. BD induced oxidative stress in kidney tissue through increased expression of Ucp2, Sod2 and Inos, and Ex-4 administration reduced the expression of these genes. Ex-4 also induced increased expression of the anti-apoptotic Bcl2 gene. Nlrp3 and Tnf expressions were up-regulated in the BD group compared with controls, but Ex-4 treatment had no effect on these genes. Our findings suggest that Ex-4 administration in BD rats reduces BD-induced kidney damage by decreasing the expression of oxidative stress genes and increasing the expression of Bcl2.

Myocardial triglycerides in cardiac amyloidosis assessed by proton cardiovascular magnetic resonance spectroscopy.

BACKGROUND: Cardiac involvement of amyloidosis leads to left-ventricular (LV) wall thickening with progressive heart failure requiring rehospitalization. Cardiovascular magnetic resonance (CMR) is a valuable tool to non-invasively assess myocardial thickening as well as structural changes. Proton CMR spectroscopy (1H-CMRS) additionally allows assessing metabolites including triglycerides (TG) and total creatine (CR). However, opposing results exist regarding utilization of these metabolites in LV hypertrophy or thickening. Therefore, the aim of this study was to measure metabolic alterations using 1H-CMRS in a group of patients with thickened myocardium caused by cardiac amyloidosis. METHODS: 1H-CMRS was performed on a 1.5 T system (Achieva, Philips Healthcare, Best, The Netherlands) using a 5-channel receive coil in 11 patients with cardiac amyloidosis (60.5 ± 11.4 years, 8 males) and 11 age- and gender-matched controls (63.2 ± 8.9 years, 8 males). After cardiac morphology and function assessment, proton spectra from the interventricular septum (IVS) were acquired using a double-triggered PRESS sequence. Post-processing was performed using a customized reconstruction pipeline based on ReconFrame (GyroTools LLC, Zurich, Switzerland). Spectra were fitted in jMRUI/AMARES and the ratios of triglyceride-to-water (TG/W) and total creatine-to-water (CR/W) were calculated. RESULTS: Besides an increased LV mass and a thickened IVS concomitant to the disease characteristics, patients with cardiac amyloidosis presented with decreased global longitudinal (GLS) and circumferential (GCS) strain. LV ejection fraction was preserved relative to controls (60.0 ± 13.2 vs. 66.1 ± 4.3%, p = 0.17). Myocardial TG/W ratios were significantly decreased compared to controls (0.53 ± 0.23 vs. 0.80 ± 0.26%, p = 0.015). CR/W ratios did not show a difference between both groups, but a higher standard deviation in patients with cardiac amyloidosis was observed. Pearson correlation revealed a negative association between elevated LV mass and TG/W (R = - 0.59, p = 0.004) as well as GCS (R = - 0.48, p = 0.025). CONCLUSIONS: A decrease in myocardial TG/W can be detected in patients with cardiac amyloidosis alongside impaired cardiac function with an association to the degree of myocardial thickening. Accordingly, 1H-CMRS may provide an additional diagnostic tool to gauge progression of cardiac amyloidosis along with standard imaging sequences. TRIAL REGISTRATION: EK 2013-0132.

Sheathless CE-MS based metabolic profiling of kidney tissue section samples from a mouse model of Polycystic Kidney Disease.

Capillary electrophoresis-mass spectrometry (CE-MS) using a sheathless porous tip interface emerged as an attractive tool in metabolomics thanks to its numerous advantages. One of the main advantages compared to the classical co-axial sheath liquid interface is the increased sensitivity, while maintaining the inherent properties of CE, such as a high separation efficiency and low sample consumption. Specially, the ability to perform nanoliter-based injections from only a few microliters of material in the sample vial makes sheathless CE-MS a well-suited and unique approach for highly sensitive metabolic profiling of limited sample amounts. Therefore, in this work, we demonstrate the utility of sheathless CE-MS for metabolic profiling of biomass-restricted samples, namely for 20 µm-thick tissue sections of kidney from a mouse model of polycystic kidney disease (PKD). The extraction method was designed in such a way to keep a minimum sample-volume in the injection vial, thereby still allowing multiple nanoliter injections for repeatability studies. The developed strategy enabled to differentiate between different stages of PKD and as well changes in a variety of different metabolites could be annotated over experimental groups. These metabolites include carnitine, glutamine, creatine, betaine and creatinine. Overall, this study shows the utility of sheathless CE-MS for biomass-limited metabolomics studies.

Preoperative grading of intracranial meningioma by magnetic resonance spectroscopy (1H-MRS).

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p<0.05); however, there were no differences in age, Cho/Cr, or NAA/Cr. According to conditional inference tree analysis, the optimal cut-off point for the Cho/NAA ration between high-grade and low-grade meningioma was 2.409 (sensitivity = 61.54%; specificity = 86.36%). This analysis of pre-operative 1H-MRS metabolite ratio demonstrated that the Cho/NAA ratio may provide a simple and practical predictive value for high-grade intracranial meningiomas, and may aid neurosurgeons in efforts to design an appropriate surgical plan and treatment strategy before surgery.

3T magnetic resonance spectroscopy as a powerful diagnostic modality for assessment of thyroid nodules.

OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a powerful tool for structural studies of chemical compounds and biomolecules and also documented promising findings as a potential imaging technology in thyroid oncology. This prospective study was to ascertain the clinical significance of 3 Tesla MRS in the evaluation of patients with thyroid nodules (TNs) as an ancillary diagnostic technique for thyroid carcinoma. MATERIALS AND METHODS: Magnetic resonance spectroscopy at 3T at echo- times (TEs) 136 and 270 ms was carried out on 15 patients with total number of 32 TNs larger than 1 cm3, which all were surgically resected. Choline (Chol) to creatine (Cr) ratio was assessed at 136 and 270 TEs on each nodule and a receiver operating characteristic (ROC) curve was used to determine optimal cut-off point. The findings were compared with histopathology of thyroid specimens. RESULTS: There were 23 benign and 9 malignant lesions (7 papillary and 2 follicular thyroid carcinomas). The mean values of Chol/Cr at 136 and 270 TEs was 2.28 ± 3.65 and 1.52 ± 1.67 respectively and the difference between benign and malignant nodules was only significant at 136 TEs. The study revealed that Chol/ Cr ratio cut-off point of 2.5 best correlates with histopathology results (sensitivity = 75%; specificity = 100%; PPV = 100%; NPV= 92%). CONCLUSION: This preliminary study showed that 3T magnetic resonance spectroscopy might be a specific modality for the evaluation of thyroid nodules in differentiation of benign from malignant thyroid tissue. However, a larger series would give much greater confidence that this state-of-the-art technology will worth pursuing in clinical practice.

3T magnetic resonance spectroscopy as a powerful diagnostic modality for assessment of thyroid nodules

ABSTRACT Objective: Magnetic resonance spectroscopy (MRS) is a powerful tool for structural studies of chemical compounds and biomolecules and also documented promising findings as a potential imaging technology in thyroid oncology. This prospective study was to ascertain the clinical significance of 3 Tesla MRS in the evaluation of patients with thyroid nodules (TNs) as an ancillary diagnostic technique for thyroid carcinoma. Materials and methods: Magnetic resonance spectroscopy at 3T at echo- times (TEs) 136 and 270 ms was carried out on 15 patients with total number of 32 TNs larger than 1 cm3, which all were surgically resected. Choline (Chol) to creatine (Cr) ratio was assessed at 136 and 270 TEs on each nodule and a receiver operating characteristic (ROC) curve was used to determine optimal cut-off point. The findings were compared with histopathology of thyroid specimens. Results: There were 23 benign and 9 malignant lesions (7 papillary and 2 follicular thyroid carcinomas). The mean values of Chol/Cr at 136 and 270 TEs was 2.28 ± 3.65 and 1.52 ± 1.67 respectively and the difference between benign and malignant nodules was only significant at 136 TEs. The study revealed that Chol/ Cr ratio cut-off point of 2.5 best correlates with histopathology results (sensitivity = 75%; specificity = 100%; PPV = 100%; NPV= 92%). Conclusion: This preliminary study showed that 3T magnetic resonance spectroscopy might be a specific modality for the evaluation of thyroid nodules in differentiation of benign from malignant thyroid tissue. However, a larger series would give much greater confidence that this state-of-the-art technology will worth pursuing in clinical practice.

Senescence and declining reproductive potential: Insight into molecular mechanisms through testicular metabolomics.

Aging is associated with structural and functional changes in the organism that result in the declining of its functioning. Postponed parenthood has renewed the interest in age-related decline of testicular function and male fertility. Still, little is known about the molecular mechanisms associated with testicular senescence and related decline of fertility. Here we sought to elucidate the molecular basis of metabolic changes associated with testicular aging and reproductive potential using an NMR-based metabolomics approach. Testicular metabolic profiles of rats from 3 to 24 months-of-age were analysed. An age-associated decrease in most antioxidant metabolites, like betaine, creatine and glutathione was observed. Amino acid content changed as early as 6 months-of-age, with an increase in branched chain and aromatic amino acids, accompanied by decrease of nucleotide synthesis (IMP, CMP, ATP). Testicular content of phospholipid precursors (choline, ethanolamine, myo-inositol, glycerol) increased with advanced age and was accompanied by a decrease in the levels of their phosphorylated products, suggesting compromised spermatogenesis. This is the first metabolomics study of testicular tissue of aged rats and we were able to identify metabolites associated with reproductive maturity from the onset to senescence. Our results provide evidence for an influence of aging on global testicular metabolome, as early as 6 months-of-age, with a profound alteration of several key metabolic pathways associated with the male reproductive potential.

Identification of Energy Metabolism Changes in Diabetic Cardiomyopathy Rats Using a Metabonomic Approach.

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. It is therefore crucial to elucidate the characteristic metabolic changes that occur during the development of diabetes to gain an understanding the pathogenesis of this disease and identify potential drug targets involved. METHODS: 1H nuclear magnetic resonance-based metabonomics combined with HPLC measurements were used to determine the metabolic changes in isolated cardiac tissues after 5 weeks, 9 weeks, and 15 weeks in rats treated with streptozotocin. RESULTS: Pattern recognition analysis clearly discriminated the diabetic rats from time-matched control rats, suggesting that the metabolic profile of the diabetic group was markedly different from that of the controls. Quantitative analysis showed that the levels of energy metabolites, such as the high-energy phosphate pool (ATP and creatine), significantly decreased in a time-dependent manner. Correlation analysis revealed the inhibition of glycolysis and the tricarboxylic acid (TCA) cycle, enhanced lipid metabolism, and changes in some amino acids, which may have led to the decline in energy production in the DCM rats. CONCLUSIONS: The results indicated that the administration of energy substances or the manipulation of myocardial energy synthesis induced by increased glucose oxidation may contribute to the amelioration of cardiac dysfunction in diabetes.

Measuring the lactate-to-creatine ratio via 1H NMR spectroscopy can be used to noninvasively evaluate apoptosis in glioma cells after X-ray irradiation.

BACKGROUND: Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. To evaluate the effect of radiotherapy noninvasively, it is vital for oncologists to monitor the effects of X-ray irradiation on glioma cells. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can be used as a biomarker to evaluate apoptosis in glioma cells after X-ray irradiation. In this study, we evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells. METHODS: Cells of the glioma cell lines C6 and U251 were randomly divided into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and 15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA damage. Flow cytometry was performed to measure the cell cycle blockage and apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC-ι (p-PKC-ι) level. 1H NMR spectroscopy was employed to determine the Lac/Cr ratio. RESULTS: The DNA damage increased in a radiation dose-dependent manner (p < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6, p < 0.01; U251, p < 0.05), and the p-PKC-ι level decreased (C6, p < 0.01; U251, p < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level. CONCLUSION: The Lac/Cr ratio decreases with an increase in X-ray irradiation and thus can be used as a biomarker to reflect the effects of X-ray irradiation in glioma cells.

Effects of guanidinoacetic acid on growth performance, creatine and energy metabolism, and carcass characteristics in growing-finishing pigs.

The aim of this study was to investigate the effects of dietary supplementation with guanidinoacetic acid (GAA) on the growth performance, creatine and energy metabolism, and carcass characteristics in growing-finishing pigs. In Exp. 1, Duroc × Landrace × Yorkshire pigs (n = 180, 33.61 ± 3.91 kg average BW) were blocked by weight and sex, and allotted to 5 treatments with 6 replicates (3 gilts and 3 barrows per replicate pen). Diets were corn-soybean meal-basal diets supplemented with 0, 300, 600, 900, and 1,200 mg/kg of GAA and fed to the pigs for 98 d. From days 1 to 98, G:F increased (linear, P < 0.05) with increasing addition of dietary GAA. Using a broken-line model, the optimum level of dietary GAA was 300 mg/kg during the overall experimental period (days 1 to 98) to maximize G:F. Hot carcass weight, carcass length, and lean percentage showed a tendency to increase (quadratic, 0.05 < P < 0.10) with increasing addition of dietary GAA. On day 98, serum GAA and liver creatine tended to increase (linear, P = 0.10, 0.07) as dietary GAA increased. In addition, serum ATP on day 98 increased linearly (linear, P < 0.01), and muscle ATP and adenosine monophosphate increased quadratically (quadratic, P = 0.05) with incremental GAA supplementation. In Exp. 2, Duroc × Landrace × Yorkshire pigs (n = 180, 53.19 ± 5.63 kg average BW) were blocked by weight and sex, and allotted to 5 treatments with 6 replicates (3 gilts and 3 barrows per replicate pen). Diets were corn-soybean meal-basal diets supplemented with 0, 150, 300, 600, and 1,200 mg/kg of GAA for 35 d. As dietary GAA increased, final BW, ADG, and G:F increased quadratically (quadratic, P < 0.01), and 300 mg/kg of GAA maximized ADG and final BW (P < 0.05).The results indicate that dietary GAA could increase the creatine and ATP load in the tissues of pigs and accordingly improve growth performance. Dietary supplementation with 300 mg/kg of GAA was suitable to maximize the growth performance of growing-finishing pigs.

Bladder necrosis: 'A man without a bladder'.

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function.

A pilot study of cortical glutathione in youth with depression.

AIM: This study used proton magnetic resonance spectroscopy (1H MRS) to measure in vivo brain glutathione (GSH) in adolescents with major depressive disorder (MDD), and explored the relationship between GSH and illness severity and chronicity. Secondarily, associations between GSH and anhedonia, a key symptom of MDD in adolescents, were investigated. METHODS: Occipital cortex GSH levels were obtained in 19 psychotropic medication-free adolescents with MDD (ages 12-21) and compared to those in eight healthy control adolescents. Correlations between GSH levels and anhedonia severity were examined both in the full participant sample and within the MDD group. Within the MDD group, correlations between GSH levels and illness severity and chronicity were assessed. RESULTS: Occipital GSH levels were lower in adolescents with MDD compared to controls, but did not correlate with anhedonia (either within the MDD group or the full sample), MDD severity, or onset. There were also no group differences in levels of total choline, creatine, and N-acetylaspartate - all neurometabolites that were simultaneously detected with 1H MRS. CONCLUSIONS: Although preliminary, findings add new data to support the role of oxidative stress in MDD and suggest that lower GSH may be a potential marker of MDD early on in the course of illness.

Major Metabolite Levels of Preoperative Proton Magnetic Resonance Sectroscopy and Intraoperative Fluorescence Intensity in Glioblastoma.

Objective To compare the intraoperative major metabolite level of preoperative proton magnetic resonance spectroscopy(1H-MRS)and fluorescence intensity marked with fluorescein sodium(FLs)in glioblastoma(GBM)and thus provide an objective basis for fluorescence surgical treatment of GBM. Methods All newly diagnosed patients by plain and enhanced magnetic resonance imaging from the April 1,2014 to December 31,2015 were enrolled in this study.All of them received 1H-MRS and marked with FLs.The expression of Ki67 in tumor boundary were confirmed by postoperative pathology and determined by immunostaining assay.The relationship between 1H-MRS metabolite levels and tumor fluorescence intensity was analyzed. Results Totally 33 patients were included in the study.Preoperative 1H-MRS revealed high-grade gliomas in 25 cases.The N-acetylaspartate(NAA)decreased significantly and choline(Cho)increased significantly in high-grade gliomas.The ratios of Cho/NAA,NAA/creatine(Cr),and Cho/Cr significantly differed in different tumor regions(P=0.02,P=0.01,and P=0.00,respectively).Surgical results were marked with FLs intraoperatively.Tissue fluorescence were clearly seen.There were 29 patients undergoing total resection and 4 cases undergoing subtotal resection.No acute encephalocele occured after operation,while 2 patients suffered from epilepsy.Postoperative pathology results included:28 cases were diagnosed as GBM(22 cases consistent with 1H-MRS diagnosis).The results of GBM fluorescence imaging included:the level of fluorescence intensity in tumor parenchyma was significantly higher than that in tumor boundary and peritumoral edema(P=0.01).The result of 1H-MRS metabolite analysis included:The kurtosis of NAA and of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor parenchyma(P=0.01,P=0.02,and P=0.01).While there was no difference in the kurtosis of NAA,the kurtosis of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor boundary(P=0.02, P=0.00).In peritumoral edema,there was no significant different in kurtosis of NAA and of Cho and in the ratio of Cho/NAA(P=0.23,P=0.09,P=0.14).Immunohistochemistry in GBM tumor boundary showed different Ki67 expressions according to different fluorescence imaging(P=0.03). Conclusions The fluorescence intensity in GBM parenchyma is higher than that in other tumor regions,and there are different metabolic levels in different fluorescence intensity.The metabolic information marked by FLs and provided by 1H-MRS before operationis are important,and the correlation between them should be further investigated.

Metabolic profiles by 1H-magnetic resonance spectroscopy in natalizumab-associated post-PML lesions of multiple sclerosis patients who survived progressive multifocal leukoencephalopathy (PML).

PURPOSE: Early diagnosis and treatment of multiple sclerosis-related progressive multifocal leukoencephalopathy (PML) significantly improve clinical outcomes. However, there is a lack of information regarding the restart of immunomodulatory therapy in the post-PML setting, when multiple sclerosis activity reappears. We aimed at the examination of metabolic differences using 1H-magnetic resonance spectroscopy (1H-MRS) in multiple sclerosis patients at various post-PML stages and at the exploration of differences according to their disease and JC virus (JCV) status. METHODS: 1H-MRS of PML lesions was carried out on 15 relapsing-remitting multiple sclerosis patients with natalizumab-associated PML. Patients were grouped according to their stage after PML infection as early post-PML, less than 19 months after PML onset (n = 5), or late post-PML group, more than 23 months after PML onset (n = 10). The latter group was further categorized according to persisting JCV load in the cerebrospinal fluid. RESULTS: Early post-PML patients showed significantly higher Lipid/Creatine ratios within PML lesions than late post-PML (p = 0.036). Furthermore, N-Acetyl-Aspartate/Creatine and N-Acetyl-Aspartate/Choline were significantly reduced in early post-PML and late post-PML lesions relative to normal-appearing white matter. In late post-PML, virus-positive patients showed significantly higher ratios of Choline/Creatine (p = 0.019) and consequently a reduced N-Acetyl- Aspartate/Choline ratio (p = 0.010) in contrast to virus-negative patients. In late post-PML patients with persisting viral load, an elevated Choline/Creatine ratio correlated significantly with higher disability. CONCLUSIONS: 1H-MRS may provide additional information related to underlying PML disease activity in various post-PML stages. In particular, Choline/Creatine levels, Lipid levels, and N-Acetyl- Aspartate/Choline are relevant markers in the post-PML setting, taking also the JCV status into account.

MR Spectroscopy in Prostate Cancer: New Algorithms to Optimize Metabolite Quantification.

Prostate cancer (PCa) is the most common non-cutaneous cancer in male subjects and the second leading cause of cancer-related death in developed countries. The necessity of a non-invasive technique for the diagnosis of PCa in early stage has grown through years. Proton magnetic resonance spectroscopy (1H-MRS) and proton magnetic resonance spectroscopy imaging (1H-MRSI) are advanced magnetic resonance techniques that can mark the presence of metabolites such as citrate, choline, creatine and polyamines in a selected voxel, or in an array of voxels (in MRSI) inside prostatic tissue. Abundance or lack of these metabolites can discriminate between pathological and healthy tissue. Although the use of magnetic resonance spectroscopy (MRS) is well established in brain and liver with dedicated software for spectral analysis, quantification of metabolites in prostate can be very difficult to achieve, due to poor signal to noise ratio and strong J-coupling of the citrate. The aim of this work is to develop a software prototype for automatic quantification of citrate, choline and creatine in prostate. Its core is an original fitting routine that makes use of a fixed step gradient descent minimization algorithm (FSGD) and MRS simulations developed with the GAMMA libraries in C++. The accurate simulation of the citrate spin systems allows to predict the correct J-modulation under different NMR sequences and under different coupling parameters. The accuracy of the quantifications was tested on measurements performed on a Philips Ingenia 3T scanner using homemade phantoms. Some acquisitions in healthy volunteers have been also carried out to test the software performance in vivo.

Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas.

OBJECTIVE: A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis. METHODS: A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13-85 years). Oedema and viable tumour measurements were acquired using regions of interest in T1 weighted, T2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan-Meier curves and obtained Cox's proportional hazards. RESULTS: During the follow-up period (3-98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287-8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χ2 (3) = 9.098, p = 0.028. CONCLUSION: MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids-lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM.