Mediastinal paraganglioma detected by 111in-Pentetreotide scintigraphy and SPECT/TC. A case report

Introduction: Mediastinal paragangliomas are low incidence tumors that arise from neural crest. Its diferential diagnosis include several malignant diseases, so its correct characterization is mandatory for an adecuate therapeutic management. 111In-Pentetreotide scintigraphy/SPECT-CT can detect paraganglioma, mainly in those cases of atypical or unsuspected location, and may have a significant role in follow-up of those patients diagnosed with multifocal and familiar paraganglioma. Case: Here we report a case of an extremely rare middle mediastinal paraganglioma, detected by scintigraphy and SPECT-CT with 111In-Pentetreotide in a patient diagnosed of multifocal and family history of paraganglioma. Surgery was carried out by median sternotomy and extracorporeal circulation. The pathological examination of the surgical specimen showed a para-aortic low-grade tumor, positive for chromogranin and synaptophysin, cytokeratin AE1-AE3 negative and Ki67 lower than 5%, compatible with paraganglioma. Currently, the patient is tumor free, under clinical monitoring. Conclusions: 111In- Pentetreotide scan proved to be a helpful diagnostic method because of its potential to explore full body, so It allows us to locate unsuspected and atypical location paragangliomas. This finding suggests that patients diagnosed with multifocal head and neck paraganglioma should undergo periodical follow-up with 111In-Pentetreotide scan to detect unsuspected paraganglioma.Introducción: Los paragangliomas mediastínicos son tumores de baja incidencia que surgen de la cresta neural. Su diagnóstico diferencial incluye varias enfermedades malignas, por lo que su correcta caracterización es obligatoria para un adecuado tratamiento. La gammagrafía SPECT-CT con 111In-pentetreótida puede detectar paragangliomas, principalmente en aquellos casos de localización atípica o no sospechada, y puede tener un papel significativo en el seguimiento de los pacientes diagnosticados con paraganglioma multifocal y familiar. Caso clínico: Se presenta un caso de un paraganglioma mediastínico medio extremadamente raro, detectado por gammagrafía y SPECT-CT con 111In-pentetreótida en un paciente diagnosticado de historia multifocal y familiar de paraganglioma. La cirugía se realizó mediante esternotomía media y circulación extracorpórea. El examen patológico de la muestra quirúrgica mostró un tumor paraórtico de bajo grado, positivo para cromogranina y sinaptofisina, citoqueratina AE1-AE3 negativo y Ki67 menor de 5%, compatible con paraganglioma. Actualmente, el paciente está libre de tumores, bajo supervisión clínica. Conclusiones: La exploración con 111In-pentetreótida demostró ser un método de diagnóstico útil debido a su potencial para explorar todo el cuerpo, por lo que permite localizar paragangliomas insospechados y de localización atípica. Este hallazgo sugiere que los pacientes diagnosticados con paraganglioma multifocal de cabeza y cuello deben someterse a un seguimiento periódico con 111In-pentetreótida para detectar paraganglioma no sospechado

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region – either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.This work was supported by RETICC RD06/0020/0035, RD06/0020/0059 and RD12/0036/0048 grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER), AES PI16/000476 (Instituto de Salud Carlos III, Madrid, Spain and FONDOS FEDER), GRS909A14 (JCYL) and CB16/12/00400 grant (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER)

Searching for massive galaxies at z>=3.5 in GOODS-North

We constrain the space density and properties of massive galaxy candidates at redshifts of z>=3.5 in the GOODS-N field. By selecting sources in the Spitzer+IRAC bands, a highly stellar mass-complete sample is assembled,including massive galaxies which are very faint in the optical/near-IR bands that would be missed by samples selected at shorter wavelengths. The z>=3.5 sample was selected down to 23 mag at 4.5 micron using photometric redshifts that have been obtained by fitting the galaxies SEDs at optical, near-IR and IRAC bands. We also require that the brightest band in which candidates are detected is the IRAC 8 micron band in order to ensure that the near-IR 1.6 micron (rest-frame) peak is falling in or beyond this band. We found 53 z>=3.5 candidates, with masses in the range of M~10^10-10^11M_sun. At least ~81% of these galaxies are missed by traditional Lyman Break selection methods based on UV light. Spitzer+MIPS emission is detected for 60% of the sample of z>=3.5 galaxy candidates. Although in some cases this might suggest a residual contamination from lower redshift star-forming galaxies or AGN, 37% of these objects are also detected in the sub-mm/mm bands in recent SCUBA,AzTEC and MAMBO surveys, and have properties fully consistent with vigorous starburst galaxies at z>=3.5. The comoving number density of galaxies with stellar masses >= 5x10^10M_sun(a reasonable stellar mass completeness limit for our sample) is 2.6x10^-5Mpc^-3 (using the volume within 3.5<z<5), and the corresponding stellar mass density is ~2.9x10^6M_sunMpc^-3, or~3% of the local density above the same stellar mass limit.For the sub-sample of MIPS-undetected galaxies,we find a number density of ~0.97x10^-5Mpc^-3 and a stellar mass density of ~1.15x10^6M_sun Mpc^-3.[abridged]Comment: Accepted by A&A; 35 pages, 15 figures, references update

Tracing the cosmic growth of supermassive black holes to z~3 with Herschel

We study a sample of Herschel selected galaxies within the Great Observatories Origins Deep Survey-South and the Cosmic Evolution Survey fields in the framework of the Photodetector Array Camera and Spectrometer (PACS) Evolutionary Probe project. Starting from the rich multiwavelength photometric data sets available in both fields, we perform a broad-band spectral energy distribution decomposition to disentangle the possible active galactic nucleus (AGN) contribution from that related to the host galaxy. We find that 37 per cent of the Herschel-selected sample shows signatures of nuclear activity at the 99 per cent confidence level. The probability of revealing AGN activity increases for bright (L 1−1000 > 10 11 L ? ) star-forming galaxies at z > 0.3, becoming about 80 per cent for the brightest (L 1−1000 > 10 12 L ? ) Infrared (IR) galaxies at z≥1. Finally, we reconstruct the AGN bolometric luminosity function and the supermassive black hole growth rate across cosmic time up to z ∼ 3 from a far-IR perspective. This work shows general agreement with most of the panchromatic estimates from the literature, with the global black hole growth peaking at z ∼ 2 and reproducing the observed local black hole mass density with consistent values of the radiative efficiency Erad (∼0.07)

Evolution of the Far-Infrared-Radio Correlation and Infrared SEDs of Massive Galaxies over z = 0 - 2

We investigate the far-infrared-radio correlation (FRC) of stellar-mass-selected galaxies in the Extended Chandra Deep Field South using far-infrared imaging from Spitzer and radio imaging from the Very Large Array and Giant Metre-Wave Radio Telescope. We stack in redshift bins to probe galaxies below the noise and confusion limits. Radio fluxes are K-corrected using observed flux ratios, leading to tentative evidence for an evolution in spectral index. We compare spectral energy distribution (SED) templates of local galaxies for K-correcting FIR fluxes, and show that the data are best fit by a quiescent spiral template (M51) rather than a warm starburst (M82) or ULIRG (Arp220), implying a predominance of cold dust in massive galaxies at high redshift. In contrast we measure total infrared luminosities that are consistent with high star-formation rates. We observe that the FRC index (q) does not evolve significantly over z=0-2 when computed from K-corrected 24 or 160-mum photometry, but that using 70-mum fluxes leads to an apparent decline in q beyond z~1. This suggests some change in the SED at high redshift, either a steepening of the spectrum at rest-frame ~25-35mum or a deficiency at ~70mum leading to a drop in the total infrared/radio ratios. We compare our results to other work in the literature and find synergies with recent findings on the high-redshift FRC, high specific star-formation rates of massive galaxies and the cold dust temperatures in these galaxies.Comment: 21 pages, 13 figures, accepted for publication in MNRA

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (β = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression

Characterization of participants adolescents in the clinical trial with Abdala vaccine

Introduction: The clinical evaluation of anti-COVID-19 vaccines in pediatric population, is a challenge in times of pandemic, to respond to the urgency of representative samples that contribute to the reproducibility of the study in the real population. Objective: To characterize the adolescents participating in the clinical trial with the Abdala anti-COVID-19 vaccine, to evaluate compliance with the vaccination schedule and to estimate whether they are representative of this population group. Methods: Data from a phase II trial with Abdala vaccine were used. A total of 703 subjects were included, 207 (29.4 %) of them were adolescents, between 12 and 18 years of age, with apparently healthy or controlled chronic diseases, nutritional assessment between 10 and 90 percentiles, and willingness to participate in the study. Sociodemographic data, personal pathological history, toxic habits and compliance with the vaccination scheme of 3 doses every 14 days were the variables studied. Results: The average age was 15 years, it was predominant female sex (51.7 %), white skin color (55.6 %) and nutritional assessment above 75 to 90 percentiles (40.6 %). The 9.6 % had toxic habits such as smoking and ingestion of alcoholic beverages. Some personal pathological history was in 51.2 % with a higher prevalence for bronchial asthma, rhinitis and other allergies. The vaccination scheme was fulfilled for 95.8 % of individuals. Conclusions: Sociodemographic characteristics, pathological history and toxic habits described for adolescents on the study are representative for this population group in Cuba. The vaccination schedule had an optimal compliance

Staging Parkinson’s Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life

Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL: 1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Four hundred and thirty-nine PD patients (62.05 +/- 7.84 years old; 59% males) were included. MNCD stage was: stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advanced MNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p < 0.0001) and EUROHIS-QOL8 (p < 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

Introduction: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. Materials and methods: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). Conclusion: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the HΨ Patients with a lower H&Y stage may be more affected if they have a greater NMS burden