Mango Fruit Detachment of Trees after Applying a Blend Composed of HNO3 and Charcoal Activated.

As young workers prefer urban labors and migrate to USA and Canada, mango harvesting is becoming scarce on Mexican coasts. This seasonal labor is becoming expensive and when many orchards produce fruit simultaneously, grower losses increase. In this research, an innovative fruit detachment method was tested after applying a viscous paste to the pedicel of mango fruits hanging in the tree. Activated carbon or charcoal (AC), was mixed with different amounts of nitric acid to provide three AC composite blends named: light, medium, and dense. The nanomaterial was applied with a brush to the fruit pedicel/peduncle taking up to 4 h before the mango fruits felt to a net below the tree canopy. Mango detachment experiments indicated that the medium blend was the most efficient in releasing the fruit, taking an average of 2 h. The dense nano-material decreased latex exudation to 7% of the fruits. Fruit maturity emerged as a crucial factor for detachment time, followed by mango weight.

Bibliometric analysis of peer-reviewed literature on perinatal depression in Mexico / Análisis bibliométrico de la literatura revisada por pares sobre depresión perinatal en México

Abstract Background Perinatal depression (PND) is a clinical disease developed in any stage during the pregnancy and postpartum period with serious health and economic implications. Objective The aim of this work was to analyze via bibliometrics indicators Mexico's production on PND to provide a view of the academic landscape and a comprehensive reference for subsequent research in the country. Method The Scopus and Web of Science (WoS) databases were used to perform a search for peer reviewed papers related to PND in México. The search was made following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The extracted data were processed with VOS Viewer to examine link strength and clusters associations of diverse bibliometrics variables. Results A total of 132 records were retrieved and we included 70 studies in the bibliometric analysis after application of the exclusion criteria. The authors with more papers were Navarrete L., and Asunción Lara M. The institutions with more papers were the National Institute of Perinatology, Ramón de la Fuente National Institute of Psychiatry, and National Institute of Public Health of Mexico. A diminution of the research considered in PND is observed in the last two years. Four keyword clusters were identified related to PND: symptoms, prevalence, pregnancy. Discussion and conclusion The scarce literature concerning PND in Mexico compared with other countries could be due the limited collaboration between the health institutes. An urgent need to increase research on PND in Mexico is evident to be applicable in the management of resources in the healthcare system.

Resumen Antecedentes La depresión perinatal (PND) es una enfermedad clínica que se desarrolla en cualquier etapa del embarazo y posparto con graves implicaciones sanitarias y económicas. Objetivo El objetivo de este trabajo fue analizar a través de indicadores bibliométricos la producción de México sobre PND, para brindar una visión del panorama académico y un referente integral para investigaciones posteriores en el país. Método Se utilizaron las bases de datos Scopus y Web of Science (WoS) para realizar una búsqueda de artículos revisados por pares relacionados con la PND en México. La búsqueda se realizó siguiendo los elementos de informes preferidos para revisiones sistemáticas y metaanálisis (PRISMA). Los datos extraídos se procesaron con VOS Viewer para examinar la fuerza de los enlaces y las asociaciones de grupos de diversas variables bibliométricas. Resultados Se recuperaron un total de 132 registros y se incluyeron 70 estudios en el análisis bibliométrico después de la aplicación de los criterios de exclusión. Los autores con más artículos fueron Navarrete L. y Asunción Lara M. Las instituciones con más artículos fueron el Instituto Nacional de Perinatología, el Instituto Nacional de Psiquiatría Ramón de la Fuente y el Instituto Nacional de Salud Pública de México. Se observa una disminución de las investigaciones consideradas en el PND en los últimos dos años. Se identificaron cuatro grupos de palabras clave relacionadas con la PND: síntomas, prevalencia y embarazo. Discusión y conclusión La escasa literatura sobre PND en México en comparación con otros países podría deberse a la limitada colaboración entre los institutos de salud. Se evidencia una necesidad urgente de realizar más investigaciones sobre PND en México que sean aplicables y útiles en la gestión de recursos en el sistema de salud.

Diagnostic and Prognostic Potential of Multiparametric Renal MRI in Kidney Transplant Patients.

BACKGROUND: Multiparametric MRI provides assessment of functional and structural parameters in kidney allografts. It offers a non-invasive alternative to the current reference standard of kidney biopsy. PURPOSE: To evaluate the diagnostic and prognostic utility of MRI parameters in the assessment of allograft function in the first 3-months post-transplantation. STUDY TYPE: Prospective. SUBJECTS: 32 transplant recipients (54 ± 17 years, 20 females), divided into two groups according to estimated glomerular filtration rate (eGFR) at 3-months post-transplantation: inferior graft function (IGF; eGFR<45 mL/min/1.73 m2 , n = 10) and superior graft function (SGF; eGFR ≥ 45 mL/min/1.73 m2 , n = 22). Further categorization was based on the need for hemodialysis (C1) and decrease in s-creatinine (C2) at 1-week post-transplantation: delayed-graft-function (DGF: n = 4 C1, n = 10 C2) and early graft-function (EGF: n = 28 C1, n = 22 C2). FIELD STRENGTH/SEQUENCE: 3-T, pseudo-continuous arterial spin labeling, T1-mapping, and diffusion-weighted imaging. ASSESSMENT: Multiparametric MRI was evaluated at 1-week in all patients and 3-months after transplantation in 28 patients. Renal blood flow (RBF), diffusion coefficients (ADC, ΔADC, D, ∆ $$ \Delta $$ D, D*, flowing fraction f), T1 and ∆ $$ \Delta $$ T1 were calculated in cortex and medulla. The diagnostic and prognostic value of these parameters, obtained at 3-months and 1-week post-transplantation, respectively, was evaluated in the cortex to discriminate between DGF and EGF, and between SGF and IGF. STATISTICAL TESTS: Logistic regression, receiver-operating-characteristics, area-under-the-curve (AUC), confidence intervals (CIs), analysis-of-variance, t-test, Wilcoxon-Mann-Whitney test, Fisher's exact test, Pearson's correlation. P-value<0.05 was considered significant. RESULTS: DGF patients exhibited significantly lower cortical RBF and f and higher D*. The diagnostic value of MRI for detecting DGF was excellent (AUC = 100%). Significant differences between patients with IGF and SGF were found in RBF, ∆T1 , and ∆D. Multiparametric MRI showed higher diagnostic (AUC = 95.32%; CI: 88%-100%) and prognostic (AUC = 97.47%, CI: 92%-100%) values for detecting IGF than eGFR (AUC = 89.50%, CI: 79%-100%). DATA CONCLUSION: Multiparametric MRI may show high diagnostic and prognostic value in transplanted patients, yielding better results compared to eGFR measurements. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Facemask analyses for the non-invasive detection of chronic and acute P. aeruginosa lung infections using nanoparticle-based immunoassays.

Pseudomonas aeruginosa (P. aeruginosa) is a pathogen that persistently colonizes the respiratory tract of patients with chronic lung diseases. The risk of acquiring a chronic P. aeruginosa infection can be minimized by rapidly detecting the pathogen in the patient's airways and promptly administrating adequate antibiotics. However, the rapid detection of P. aeruginosa in the lungs involves the analysis of sputum, which is a highly complex matrix that is not always available. Here, we propose an alternative diagnosis based on analyzing breath aerosols. In this approach, nanoparticle immunosensors identify bacteria adhered to the polypropylene layer of a surgical facemask that was previously worn by the patient. A polypropylene processing protocol was optimized to ensure the efficient capture and analysis of the target pathogen. The proposed analytical platform has a theoretical limit of detection of 105 CFU mL-1 in aerosolized mock samples, and a dynamic range between 105 and 108 CFU mL-1. When tested with facemasks worn by patients, the biosensors were able to detect chronic and acute P. aeruginosa lung infections, and to differentiate them from respiratory infections caused by other pathogens. The results shown here pave the way to diagnose Pseudomonas infections at the bedside, as well as to identify the progress from chronic to acute infection.

Colostrum Quality Assessment in Dairy Goats: Use of an On-Farm Optical Refractometer.

Failure of passive immunity transfer is one of the main causes of increased susceptibility to infectious agents in newborn kids. To ensure successful transfer of passive immunity, kids need to be fed high-quality colostrum, containing an adequate concentration of IgG. This work evaluated the quality of colostrum obtained in the first 3 days postpartum from Malagueña dairy goats. The IgG concentration in colostrum was measured using an ELISA as a reference method, and it was estimated by optical refractometer. Colostrum composition in terms of fat and protein was also determined. The mean concentration of IgG was 36.6 ± 2.3 mg/mL, 22.4 ± 1.5 mg/mL and 8.4 ± 1.0 mg/mL on days 1, 2 and 3 after parturition, respectively. Brix values obtained using the optical refractometer were 23.2%, 18.6% and 14.1% for days 1, 2 and 3, respectively. In this population, 89% of goats produced high-quality colostrum with IgG concentrations of >20 mg/mL on the day of parturition, but this percentage declined dramatically over the following 2 days. The quality of the fresh colostrum estimated with the optical refractometer was positively correlated with those obtained using ELISA (r = 0.607, p = 0.001). This study highlights the importance of feeding first-day colostrum to newborn kids and demonstrates that the optical Brix refractometer is suitable for the on-farm estimation of IgG content in colostrum.

Patient-reported outcome measures after thrombectomy in patients with acute stroke: fine-tuning the modified Rankin Scale.

BACKGROUND: In patients with stroke undergoing endovascular treatment (EVT), long-term outcome is usually only evaluated by the modified Rankin Scale (mRS). Patient-reported outcomes (PROMs) are standardized assessments that consider clinical outcomes from the perspective of the patient. We aimed to evaluate PROMs through a smartphone-based communication platform in patients with stroke who received EVT. METHODS: Consecutive patients with stroke who underwent EVT were offered to participate in the PROMs-through-App program (NORA). A set of standardized PROMs were collected at 7, 30 and 90 days after discharge. Disability was determined by clinicians (mRS) at 90 days. To characterize the potential ceiling effect of mRS in the assessment of different domains, the rate of abnormal PROMs among patients with excellent outcome (mRS 0-1) was calculated. RESULTS: From June 2020 to October 2021, 186 patients were included. The median PROMs collection rate per patient was 80% (50-100%). A correlation was consistently seen between disability measured by mRS and the different PROMs. The rate of abnormal PROMs ranged from 20.83% (HADS at 7 days) to 59.61% (Mental PROMIS at 7 days). At 90 days, among patients with an excellent outcome, the rate of abnormal PROMs ranged from 8.7% (HADS) to 47.83% (Physical PROMIS). CONCLUSIONS: A specifically designed digital platform allows a high collection rate of PROMs among stroke patients who underwent EVT. The mRS score shows a ceiling effect and seems insufficient to fine-tune long-term clinical results. The use of PROMs may allow a better characterization of long-term outcome profiles after EVT.

Multiparametric renal magnetic resonance imaging: A reproducibility study in renal allografts with stable function.

Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f ), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f , and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques.

Redefining Disability: Patient-Reported Outcome Measures After Minor Stroke and Transient Ischemic Attack.

BACKGROUND: Long-term outcome assessment patients with stroke is not fully captured by usual clinical scales such as the modified Rankin Scale (mRS). Patient-reported outcome measures (PROMs) are standardized and validated assessments that consider clinical outcomes from the patient perspective. We aim to analyze the added value of PROMs in patients with transient ischemic attack and minor stroke. METHODS: We included consecutive patients with minor stroke or transient ischemic attack (National Institutes of Health Stroke Scale score 0-5) from April 2020 to October 2021 that participated in the PROMs-through-App program (NORA, NoraHealth Barcelona Spain). Clinician and self-evaluated outcomes were assessed at 90 days: clinician-evaluated mRS, self-reported mRS, the 10-item patient-reported outcome measures questionnaire global health survey (v1.2), Hospital Anxiety and Depression Scale, and the Fatigue Assessment Scale. We evaluated the acceptability (response rate), reliability (internal consistency), and construct validity (correlation with mRS and between scales) of each questionnaire. RESULTS: We included 355 patients in the analysis, response rate was patient-reported outcome measures questionnaire 71.3% (253), Hospital Anxiety and Depression Scale 70.7% (251), Fatigue Assessment Scale 71.8% (255), and self-assessed mRS 66.8% (237). PROMS internal consistency was good or excellent, while agreement between clinician and self-reported mRS was fair (k=0.34). Rate of abnormal PROMS scores were as follows (all responders versus clinician-reported mRS score 0-2): patient-reported outcome measures questionnaire mental health (43.1% versus 36.3%), physical health (48.6% versus 43.6%); Hospital Anxiety and Depression Scale-anxiety (21.9% versus 17.7%) and depression (17.1% versus 13.3%); and Fatigue Assessment Scale (40.8% versus 36.4%). PROMs scores correlated with clinician and self-reported mRS at 90 days. CONCLUSIONS: Evaluation of PROMs using a mobile-app-based communication system is a reliable and valid strategy to assess the outcome of patients from their perspective after a mild stroke or transient ischemic attack.

[Irreversible electroporation: present and future in the treatment of hepatocellular carcinoma].

Currently, among the possible treatments for hepatocellular carcinoma there is group of minimally invasive ablation techniques with wide clinical acceptance due to their greater efficacy and safety in comparison to traditional therapies, low cost, and no need of being admitted to hospital (outpatient treatment program). Irreversible electroporation is a non-thermal ablation technique in which electrical fields are used to create nanopores in the cell membrane that induce tumor cell death. Irreversible electroporation has shown promising results in numerous clinical trials; however, its control on long-term tumor growth and recurrence is inferior in comparison to that of radiofrequency. Combining irreversible electroporation with immunological agents may increase its efficacy in the treatment of focal lesions and metastases. In this work, we present an update on IRE including procedure, mechanism of action, application as a treatment for HCC, and the improvements that have been made in the past few years.

Electroporación irreversible: presente y futuro en el tratamiento del carcinoma hepatocelular / Irreversible electroporation: present and future in the treatment of hepatocellular carcinoma

Entre los tratamientos actuales para el carcinoma hepatocelular se encuentra un grupo de técnicas de ablación mínimamente invasivas con gran aceptación clínica por su mayor eficacia y seguridad respecto a las terapias tradicionales, bajo coste económico y aplicación ambulatoria. La electroporación irreversible es una técnica de ablación no térmica que crea nanoporos en la membrana celular mediante administración de campos eléctricos, induciendo la muerte de las células tumorales. Aunque la electroporación irreversible presenta resultados prometedores en numerosos ensayos clínicos, su control a largo plazo del crecimiento y de las recidivas tumorales es inferior al de la radiofrecuencia. La combinación de electroporación irreversible con agentes inmunológicos podría aumentar su eficacia tanto en el tratamiento de lesiones focales como de metástasis. Esta revisión realiza una actualización sobre la electroporación irreversible: procedimiento, mecanismo de acción, aplicación como tratamiento del carcinoma hepatocelular y alternativas de mejora que están aflorando en los últimos años.(AU)

Currently, among the possible treatments for hepatocellular carcinoma there is group of minimally invasive ablation techniques with wide clinical acceptance due to their greater efficacy and safety in comparison to traditional therapies, low cost, and no need of being admitted to hospital (outpatient treatment program). Irreversible electroporation is a non-thermal ablation technique in which electrical fields are used to create nanopores in the cell membrane that induce tumor cell death. Irreversible electroporation has shown promising results in numerous clinical trials; however, its control on long-term tumor growth and recurrence is inferior in comparison to that of radiofrequency. Combining irreversible electroporation with immunological agents may increase its efficacy in the treatment of focal lesions and metastases. In this work, we present an update on IRE including procedure, mechanism of action, application as a treatment for HCC, and the improvements that have been made in the past few years.(AU)

Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease.

CONTEXT: Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse. OBJECTIVES: This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas. METHODS: A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years' follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery. RESULTS: Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P < .001). CONCLUSION: This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas.

Sex Hormone Receptor Expression in Craniopharyngiomas and Association with Tumor Aggressiveness Characteristics.

Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality of life. Previous studies have reported that CPs express sex hormone receptors, including estrogen and progesterone receptors. Here, we systematically analyzed estrogen receptor α (ERα) and progesterone receptor (PR) expression by immunohistochemistry in a well-characterized series of patients with CP (n = 41) and analyzed their potential association with tumor aggressiveness features. A substantial proportion of CPs displayed a marked expression of PR. However, most CPs expressed low levels of ERα. No major association between PR and ERα expression and clinical aggressiveness features was observed in CPs. Additionally, in our series, ß-catenin accumulation was not related to tumor recurrence.

GATA4 induces liver fibrosis regression by deactivating hepatic stellate cells.

In response to liver injury, hepatic stellate cells activate and acquire proliferative and contractile features. The regression of liver fibrosis appears to involve the clearance of activated hepatic stellate cells, either by apoptosis or by reversion toward a quiescent-like state, a process called deactivation. Thus, deactivation of active hepatic stellate cells has emerged as a novel and promising therapeutic approach for liver fibrosis. However, our knowledge of the master regulators involved in the deactivation and/or activation of fibrotic hepatic stellate cells is still limited. The transcription factor GATA4 has been previously shown to play an important role in embryonic hepatic stellate cell quiescence. In this work, we show that lack of GATA4 in adult mice caused hepatic stellate cell activation and, consequently, liver fibrosis. During regression of liver fibrosis, Gata4 was reexpressed in deactivated hepatic stellate cells. Overexpression of Gata4 in hepatic stellate cells promoted liver fibrosis regression in CCl4-treated mice. GATA4 induced changes in the expression of fibrogenic and antifibrogenic genes, promoting hepatic stellate cell deactivation. Finally, we show that GATA4 directly repressed EPAS1 transcription in hepatic stellate cells and that stabilization of the HIF2α protein in hepatic stellate cells leads to liver fibrosis.

Detection of high heteroplasmy in complete loggerhead and hawksbill sea turtles mitochondrial genomes using RNAseq.

Sea turtle populations around the world face rapid decline due to the effect of anthropogenic and environmental factors. Among the affected populations are those of hawksbill turtles (Eretmochelys imbricata) and loggerhead turtles (Caretta caretta), which is why a greater effort is currently being made in their monitoring and tracing. The intragenic degree of heteroplasmic mutations, commonly associated with diseases of variable symptoms, has not been analyzed in these species. In this study, heteroplasmy in the complete mitogenome (mtDNA) of three loggerhead turtles and one hawksbill turtle was identified from data obtained by RNAseq. Individuals Cc3, Ei1, Cc1 and Cc2 presented 0.3, 1.7, 1.8 and 7.1% of heteroplasmic mutations in all their mtDNA, respectively. The protein-coding genes that presented the highest percentage of heteroplasmy were ND4 and ND5 in individual Cc2 with 16 and 38.6%, respectively. Of the tRNA genes, only tRNATyr was heteroplasmic in the four individuals with 5.63% (Cc1), 25.35% (Ei1 and Cc2) and 49.3% (Cc3). In this study, we identified the critical sites of heteroplasmy in each individual and the genetic variability of their mitogenomes. The data obtained represents the baseline for future projects that evaluate the population status of these species.

Intratumoral STING Agonist Injection Combined with Irreversible Electroporation Delays Tumor Growth in a Model of Hepatocarcinoma.

BACKGROUND/AIM: Irreversible electroporation (IRE) showed promising results for small-size tumors and very early cancers. However, further development is needed to evolve this procedure into a more efficient ablation technique for long-term control of tumor growth. In this work, we show that it is possible to increase the antitumor efficiency of IRE by simmultaneously injecting c-di-GMP, a STING agonist, intratumorally. MATERIALS AND METHODS: Intratumoral administration of c-di-GMP simultaneously to IRE was evaluated in murine models of melanona (B16.OVA) and hepatocellular carcinoma (PM299L). RESULTS: The combined therapy increased the number of tumor-infiltrating IFN-γ/TNF-α-producing CD4 and CD8 T cells and delayed tumor growth, as compared to the effect observed in groups treated with c-di-GMP or IRE alone. CONCLUSION: These results can lead to the development of a new therapeutic strategy for the treatment of cancer patients refractory to other therapies.

Our experience in prolactinomas larger than 60mm / Nuestra experiencia en prolactinomas mayores de 60mm

INTRODUCTION: Giant prolactinomas (tumor size larger than 40mm) are a rare entity of benign nature. Prolactinomas larger than 60mm are usually underrepresented in published studies and their clinical presentation, outcomes and management might be different from smaller giant prolactinomas. PATIENTS AND METHODS: We retrospective collected data from patients with prolactinomas larger than 60mm in maximum diameter and prolactin (PRL) serum levels higher than 21,200μIU/mL in our series of prolactinomas (283). Data were collected from January 2012 to December 2017. We included three patients with prolactinomas larger than 60mm. RESULTS: At diagnosis, two patients presented neurological symptoms and one nasal protrusion. All patients received medical treatment with dopamine agonists. No surgical procedure was performed. Median prolactin levels at diagnosis was 108,180 [52,594-514,984]μIU/mL. Medical treatment achieved a marked reduction (>99%) in prolactin levels in all cases. Tumor size reduction (higher than 33%) was observed in all cases. In one patient cerebrospinal fluid (CSF) leak was observed after tumor shrinkage. CONCLUSIONS: Dopamine agonists appear to be an effective and safe first-line treatment in prolactinomas larger than 60mm even in life-threatening situations. More studies with a higher number of patients are necessary to obtain enough data to make major recommendations

INTRODUCCIÓN: Los prolactinomas gigantes (de tamaño superior a 40mm) son una entidad rara de naturaleza benigna. Los prolactinomas mayores de 60mm suelen estar infrarrepresentados en los estudios publicados, y su presentación clínica, resultados y tratamiento podrían ser diferentes de los de prolactinomas gigantes más pequeños. PACIENTES Y MÉTODOS: Recogimos retrospectivamente datos de pacientes con prolactinomas de más de 60mm de diámetro máximo y con concentraciones séricas de prolactina (PRL) superiores a 21.200μIU/ml de nuestra serie de prolactinomas (283). Los datos se recogieron entre enero de 2012 y diciembre de 2017. Se incluyeron 3 pacientes con prolactinomas mayores de 60mm. RESULTADOS: En el momento del diagnóstico, 2 pacientes presentaban síntomas neurológicos, y uno protrusión nasal. Todos los pacientes recibieron tratamiento médico con agonistas dopaminérgicos. No se realizó ninguna intervención quirúrgica. La mediana de las concentraciones de PRL al diagnóstico fue de 108.180 (52.594-514.984)μIU/ml. El tratamiento médico logró una reducción notable (>99%) de los valores de prolactina en todos los casos. En todos los casos se observó una reducción del tamaño del tumor (superior al 33%). En un paciente se observó una fuga de líquido cefalorraquídeo (LCR) tras la reducción del tumor. CONCLUSIÓN: Los agonistas dopaminérgicos parecen ser un tratamiento de primera línea eficaz y seguro en los prolactinomas mayores de 60mm incluso en situaciones peligrosas para la vida. Se necesitan más estudios con un mayor número de pacientes para obtener datos suficientes para hacer recomendaciones importantes

Our experience in prolactinomas larger than 60mm.

INTRODUCTION: Giant prolactinomas (tumor size larger than 40mm) are a rare entity of benign nature. Prolactinomas larger than 60mm are usually underrepresented in published studies and their clinical presentation, outcomes and management might be different from smaller giant prolactinomas. PATIENTS AND METHODS: We retrospective collected data from patients with prolactinomas larger than 60mm in maximum diameter and prolactin (PRL) serum levels higher than 21,200µIU/mL in our series of prolactinomas (283). Data were collected from January 2012 to December 2017. We included three patients with prolactinomas larger than 60mm. RESULTS: At diagnosis, two patients presented neurological symptoms and one nasal protrusion. All patients received medical treatment with dopamine agonists. No surgical procedure was performed. Median prolactin levels at diagnosis was 108,180 [52,594-514,984]µIU/mL. Medical treatment achieved a marked reduction (>99%) in prolactin levels in all cases. Tumor size reduction (higher than 33%) was observed in all cases. In one patient cerebrospinal fluid (CSF) leak was observed after tumor shrinkage. CONCLUSIONS: Dopamine agonists appear to be an effective and safe first-line treatment in prolactinomas larger than 60mm even in life-threatening situations. More studies with a higher number of patients are necessary to obtain enough data to make major recommendations.

A Silent Corticotroph Pituitary Carcinoma: Lessons From an Exceptional Case Report.

Nowadays, neither imaging nor pathology evaluation can accurately predict the aggressiveness or treatment resistance of pituitary tumors at diagnosis. However, histological examination can provide useful information that might alert clinicians about the nature of pituitary tumors. Here, we describe our experience with a silent corticothoph tumor with unusual pathology, aggressive local invasion and metastatic dissemination during follow-up. We present a 61-year-old man with third cranial nerve palsy at presentation due to invasive pituitary tumor. Subtotal surgical approach was performed with a diagnosis of silent corticotroph tumor but with unusual histological features (nuclear atypia, frequent multinucleation and mitotic figures, and Ki-67 labeling index up to 70%). After a rapid regrowth, a second surgical intervention achieved successful debulking. Temozolomide treatment followed by stereotactic fractionated radiotherapy associated with temozolomide successfully managed the primary tumor. However, sacral metastasis showed up 6 months after radiotherapy treatment. Due to aggressive distant behavior, a carboplatine-etoposide scheme was decided but the patient died of urinary sepsis 31 months after the first symptoms. Our case report shows how the presentation of a pituitary tumor with aggressive features should raise a suspicion of malignancy and the need of follow up by multidisciplinary team with experience in its management. Metastases may occur even if the primary tumor is well controlled.

Optimization of pseudo-continuous arterial spin labeling for renal perfusion imaging.

PURPOSE: To evaluate labeling efficiency of pseudo-continuous arterial spin labeling (PCASL) and to find the gradient parameters that increase PCASL robustness for renal perfusion measurements. METHODS: Aortic blood flow was characterized in 3 groups: young healthy volunteers (YHV1), chronic kidney disease (CKD) patients (CKDP), and healthy controls (HCO). PCASL inversion efficiency was evaluated through numeric simulations considering the measured pulsatile flow velocity profiles and off-resonance effects for a wide range of gradient parameters, and the results were assessed in vivo. The most robust PCASL implementation was used to measure renal blood flow (RBF) in CKDP and HCO. RESULTS: Aortic blood velocities reached peak values of 120 cm/s in YHV1, whereas for elderly subjects values were lower by approximately a factor of 2. Simulations and experiments showed that by reducing the gradient average (Gave ) and the selective to average gradient ratio (Gmax /Gave ), labeling efficiency was maximized and PCASL robustness to off-resonance was improved. The study in CKDP and HCO showed significant differences in RBF between groups. CONCLUSION: An efficient and robust PCASL scheme for renal applications requires a Gmax /Gave ratio of 6-7 and a Gave value that depends on the aortic blood flow velocities (0.5 mT/m being appropriate for CKDP and HCO).

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features.

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST1-5 expression was also evaluated by immunohistochemistry. SST3 was the predominant SST subtype detected, followed by SST2, SST5, and SST1. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST2 and SST5. No major association between SSTs and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs.