CXCR4: From Signaling to Clinical Applications in Neuroendocrine Neoplasms.

There are several well-described molecular mechanisms that influence cell growth and are related to the development of cancer. Chemokines constitute a fundamental element that is not only involved in local growth but also affects angiogenesis, tumor spread, and metastatic disease. Among them, the C-X-C motif chemokine ligand 12 (CXCL12) and its specific receptor the chemokine C-X-C motif receptor 4 (CXCR4) have been widely studied. The overexpression in cell membranes of CXCR4 has been shown to be associated with the development of different kinds of histological malignancies, such as adenocarcinomas, epidermoid carcinomas, mesenchymal tumors, or neuroendocrine neoplasms (NENs). The molecular synapsis between CXCL12 and CXCR4 leads to the interaction of G proteins and the activation of different intracellular signaling pathways in both gastroenteropancreatic (GEP) and bronchopulmonary (BP) NENs, conferring greater capacity for locoregional aggressiveness, the epithelial-mesenchymal transition (EMT), and the appearance of metastases. Therefore, it has been hypothesized as to how to design tools that target this receptor. The aim of this review is to focus on current knowledge of the relationship between CXCR4 and NENs, with a special emphasis on diagnostic and therapeutic molecular targets.

Bictegravir/Emtricitabine/Tenofovir Alafenamide in a Multicentre Cohort: Real-Life Experience From Spain.

BACKGROUND: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce. OBJECTIVE: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort. METHODS: This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy. RESULTS: We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA <50 copies/mL in the OT, mITT, and ITT groups were 94%, 80%, and 62%, respectively, after 12 months of BIC/FTC/TAF treatment. Rates of TE PLWH with HIV-RNA <50 copies/mL were 91%, 88%, and 75% at month 12. The multivariate analysis revealed that neither age, sex, CD4 cell count <200 cells/µL, or viral load >100 000 copies/mL were associated with therapeutic failure. CONCLUSION AND RELEVANCE: Our real-life data showed that BIC/FTC/TAF is effective and safe for use in the treatment of both TN and TE patients in clinical practice.

1-L polyethylene glycol + ascorbic acid versus sodium picosulfate + magnesium citrate bowel preparations for colonoscopy: effectiveness and safety

Background: adequate bowel preparation is crucial for the protective effect of colonoscopy. Commonly used preparation regimens like polyethylene glycol (PEG) or sodium picosulfate with magnesium citrate (SPMC) have shown similar results in clinical trials, but low-volume PEG + ascorbic acid (1-L PEG + ASC) versus SPMC have never been compared in a real-life setting. Aim: to evaluate the effectiveness and safety of 1-L PEG + ASC versus SPMC in a real-life setting for the overall population, for patients aged ≥ 65 years, and males versus females. Methods: out-patients aged ≥ 18 years who underwent colonoscopy for any indication were randomly assigned to the 1-L PEG + ASC or SPMC group. Using the Boston Bowel Preparation Scale (BBPS), the primary endpoints were the bowel cleansing success of the overall colon and right colon, as well as high-quality (HQ) cleansing. Furthermore, the effectiveness and safety outcomes for age groups and males versus females were compared. Results: 1-L PEG + ASC showed significantly better bowel cleansing success than SPMC. Particularly remarkable is the HQ cleansing reached with 1-L PEG + ASC compared with SPMC (55.5 % versus 25.4 % in the overall colon, and 58.7 % versus 27.2 % in the right colon). 1-L PEG + ASC was equally effective for men and women while SPMC showed significant differences between genders (men had worse bowel cleansing). Age did not affect the cleansing effectiveness. 1-L PEG + ASC versus SPMC showed significant differences in tolerance and safety; women also had significantly worse tolerance than men for both solutions, but these did not affect the quality of bowel cleansing. Conclusions: in our real-life setting, 1-L PEG + ASC offered better adequate and HQ bowel cleansing than SPMC, achieving excellent cleansing quality, regardless of gender or tolerance. (AU)

Acceso para cirugía de catarata en diabetes. Un estudio cualitativo con enfoque gerencial / Access for cataract surgery in patients with diabetes. A qualitative study with a managerial approach

Resumen Objetivo: Explorar las brechas que existen para el acceso a la cirugía de catarata en personas con diabetes tipo 2. Materiales y métodos: Se realizó una investigación cualitativa de tipo fenomenológica con enfoque gerencial. Se emplearon herramientas y técnicas de gestión por procesos en salud y metodología Lean- sanidad. El trabajo de campo se realizó en los municipios La Lisa, Marianao y Playa donde se exploraron las experiencias y expectativas de 46 pacientes en seis grupos de discusión, se obtuvo el criterio de nueve médicos de familia y seis oftalmólogos del nivel primario de salud, en dos grupos de discusión. Resultados: Las experiencias de pacientes, médicos de familia y oftalmólogos, organizadas por categorías (diagnóstico, continuidad y comunicación, apoyo social y carga laboral) tienen en su contenido las brechas presentes en el proceso asistencial. Conclusión: Las brechas identificadas en este estudio son suficientes para explicar por qué muchos pacientes no acceden de manera oportuna a la cirugía de catarata.

Abstract Objective: To explore the gaps that exist for access to cataract surgery in people with type 2 diabetes. Materials and methods: A qualitative research of a phenomenological type with a managerial approach was carried out. Management tools and techniques by health processes and Lean-health methodology were used. The field work was carried out in the municipalities of La Lisa, Marianao and Playa where the experiences and expectations of 46 patients were explored in six discussion groups, the criteria of nine family doctors and six ophthalmologists from the primary health level were obtained, in two discussion groups. Results: The experiences of patients, family doctors and ophthalmologists, organized by categories (diagnosis, continuity and communication, social support and workload) have in their content the gaps present in the care process. Conclusion: The gaps identified in this study are sufficient to explain why many patients do not access cataract surgery in a timely manner.

Síndrome fronto-subcortical: cuando la red falla, a propósito de un caso / Frontal-subcortical syndrome: When the network fails, about a case

La depresión y el parkinsonismo son consecuencias directas de una lesión, por lo general vascular, que compromete alguna estructura del circuito fronto-subcortical. Su detección representa un desafío diagnóstico, y tiene importantes repercusiones en el manejo terapéutico. Se presenta el caso de un paciente varón de 79 años con buena situación basal global, que ingresa a una unidad de psicogeriatría tras un intento autolítico. Inicialmente se objetiva una depresión franca no psicótica, y llama la atención un aumento de la base de sustentación a la marcha y bradicinesia. Tras el ajuste de tratamiento antidepresivo se evidencia una notable mejoría de la sintomatología afectiva, pero no motora, por lo que se decide solicitar una resonancia magnética que objetiva lesiones isquémicas en ganglios basales. Este caso representa un claro soporte del modelo de circuitos fronto-subcorticales, en el que la presentación clínica, la evaluación neuropsiquiátrica, los datos de neuroimagen y la respuesta terapéutica contribuyen a la comprensión de los déficits que siguen a la lesión de estas estructuras Consideramos que con este artículo se podrá contar con una información breve y precisa con relación a los mecanismos fisiopatológicos, evaluación, planteamiento diagnóstico y tratamiento del síndrome fronto-subcortical (AU)

Depression and parkinsonism are direct consequences of a lesion, usually vascular, that affects some structure of the frontal-subcortical circuit. Their detection represents a diagnostic challenge and has important repercussions in therapeutic management. The case is presented of a 79-year-old male patient with good overall baseline status, who was admitted to a Psychogeriatric Unit after an autolytic attempt. Initially, a non-psychotic frank depression is observed, and an increase in the base of support for walking and bradykinesia is noted. After adjustment of antidepressant treatment, a notable improvement in affective symptoms is evidenced but not in motor symptoms, so it is decided to request a magnetic resonance imaging that shows ischemic lesions in the basal ganglia. This case provides clear support for the frontal-subcortical circuit model, in which the clinical presentation, neuropsychiatric evaluation, neuroimaging data and therapeutic response contribute to understanding the deficits following these types of lesions. We believe that this article will provide brief and accurate information on the pathophysiological mechanisms, evaluation, diagnostic approach, and treatment of the frontal-subcortical syndrome (AU)

[Frontal-subcortical syndrome: When the network fails, about a case]. / Síndrome fronto-subcortical: cuando la red falla, a propósito de un caso.

Depression and parkinsonism are direct consequences of a lesion, usually vascular, that affects some structure of the frontal-subcortical circuit. Their detection represents a diagnostic challenge and has important repercussions in therapeutic management. The case is presented of a 79-year-old male patient with good overall baseline status, who was admitted to a Psychogeriatric Unit after an autolytic attempt. Initially, a non-psychotic frank depression is observed, and an increase in the base of support for walking and bradykinesia is noted. After adjustment of antidepressant treatment, a notable improvement in affective symptoms is evidenced but not in motor symptoms, so it is decided to request a magnetic resonance imaging that shows ischemic lesions in the basal ganglia. This case provides clear support for the frontal-subcortical circuit model, in which the clinical presentation, neuropsychiatric evaluation, neuroimaging data and therapeutic response contribute to understanding the deficits following these types of lesions. We believe that this article will provide brief and accurate information on the pathophysiological mechanisms, evaluation, diagnostic approach, and treatment of the frontal-subcortical syndrome.

Cobalt-Iron Oxyhydroxide Obtained from the Metal Phosphide: A Highly Effective Electrocatalyst for the Oxygen Evolution Reaction at High Current Densities.

The development of high current density anodes for the oxygen evolution reaction (OER) is fundamental to manufacturing practical and reliable electrochemical cells. In this work, we have developed a bimetallic electrocatalyst based on cobalt-iron oxyhydroxide that shows outstanding performance for water oxidation. Such a catalyst is obtained from cobalt-iron phosphide nanorods that serve as sacrificial structures for the formation of a bimetallic oxyhydroxide through phosphorous loss concomitantly to oxygen/hydroxide incorporation. CoFeP nanorods are synthesized using a scalable method using triphenyl phosphite as a phosphorous precursor. They are deposited without the use of binders on nickel foam to enable fast electron transport, a highly effective surface area, and a high density of active sites. The morphological and chemical transformation of the CoFeP nanoparticles is analyzed and compared with the monometallic cobalt phosphide in alkaline media and under anodic potentials. The resulting bimetallic electrode presents a Tafel slope as low as 42 mV dec-1 and low overpotentials for OER. For the first time, an anion exchange membrane electrolysis device with an integrated CoFeP-based anode was tested at a high current density of 1 A cm-2, demonstrating excellent stability and Faradaic efficiency near 100%. This work opens up a way for using metal phosphide-based anodes for practical fuel electrosynthesis devices.

Evaluation of the quality of life in children and adolescents with type 1 diabetes in two health institutions, Bogotá, D. C., Colombia / Evaluación de la calidad de vida en niños y adolescentes con diabetes de tipo 1 en dos instituciones de salud, Bogotá, D. C., Colombia

Introduction: Diabetes mellitus is one of the most prevalent chronic diseases in the pediatric and juvenile population that affects the quality of life of patients. Objective: To evaluate the quality of life of a pediatric population under 18 years of age diagnosed with type 1 diabetes from two pediatric institutions in the city of Bogotá. Material and methods: We collected of sociodemographic data and clinical variables and application of the PedsQL 4.0™ questionnaire, and the diabetes module 3.2 version validated in Spanish. The sociodemographic data, the clinical variables and the PedsQL™ were processed in the statistical software Stata 17™. Results: In the global score of the PedsQL™ 3.2, diabetes version, men presented better quality of life compared to women. The correlation between the hemoglobin A1c (HbA1c) values and the PedsQL scale in the global score was evaluated. Patients with HbA1c values below 9% presented a better health-related quality of life, while in the group with HbA1c greater than 9% a perception of low quality of life was observed (p=0.025). Regarding the type of therapy and the relationship with the domains of the PedsQL 3.2, diabetes version, patients who used insulin pumps had better scores in the domains barriers, adherence, concern, communication and in the global score compared to patients who used multiple daily injections of insulin as treatment (p=0.0363). Conclusions: In our patients, a better metabolic control (measured by the HbA1c value) and the use of an insulin pump contribute to a better perception of quality of life.

Introducción. La diabetes mellitus es una de las enfermedades crónicas con mayor prevalencia en la población pediátrica y juvenil, con efectos en la calidad de vida de los pacientes. Objetivo. Evaluar la calidad de vida de una población pediátrica menor de 18 años con diagnóstico de diabetes de tipo 1, de dos instituciones pediátricas de la ciudad de Bogotá. Materiales y métodos. Se recolectaron los datos sociodemográficos, y se emplearon la versión validada en español del cuestionario PedsQL 4.0™ y el módulo 3.2 sobre diabetes. Los datos se procesaron en el software estadístico STATA 17™. Resultados. Con el puntaje global del módulo 3.2 sobre diabetes, de la versión validada del PedsQL™, se evaluó la correlación entre los valores de la hemoglobina A1c (HbA1c) y los del cuestionario. Los pacientes con valores por debajo del 9 % de HbA1c presentaron una mejor calidad de vida relacionada con la salud, mientras que, en el grupo con HbA1c mayor de 9 %, se observó una baja percepción de calidad de vida (p=0,025). En cuanto el tipo de terapia y la relación con los dominios del PedsQL™ 3.2, versión diabetes, los pacientes que utilizaban la bomba de insulina o microinfusor presentaban mejor puntaje en los dominios barreras, cumplimiento, preocupación y comunicación, y en el puntaje global, respecto a quienes usaban múltiples inyecciones de insulina como tratamiento (p=0,0363). Conclusiones. En nuestros pacientes, un mejor control metabólico (medido por el valor de HbA1c) y el uso de microinfusora contribuyen a una percepción de mejor calidad de vida.

Evaluación de la calidad de vida en niños y adolescentes con diabetes de tipo 1 en dos instituciones de salud, Bogotá, D. C., Colombia / Evaluation of the quality of life in children and adolescents with type 1 diabetes in two health institutions, Bogotá, D. C., Colombia

Introducción. La diabetes mellitus es una de las enfermedades crónicas con mayor prevalencia en la población pediátrica y juvenil, con efectos en la calidad de vida de los pacientes. Objetivo. Evaluar la calidad de vida de una población pediátrica menor de 18 años con diagnóstico de diabetes de tipo 1, de dos instituciones pediátricas de la ciudad de Bogotá. Materiales y métodos. Se recolectaron los datos sociodemográficos, y se emplearon la versión validada en español del cuestionario PedsQL 4.0™ y el módulo 3.2 sobre diabetes. Los datos se procesaron en el software estadístico STATA 17™. Resultados. Con el puntaje global del módulo 3.2 sobre diabetes, de la versión validada del PedsQL™, se evaluó la correlación entre los valores de la hemoglobina A1c (HbA1c) y los del cuestionario. Los pacientes con valores por debajo del 9 % de HbA1c presentaron una mejor calidad de vida relacionada con la salud, mientras que, en el grupo con HbA1c mayor de 9 %, se observó una baja percepción de calidad de vida (p=0,025). En cuanto el tipo de terapia y la relación con los dominios del PedsQL™ 3.2, versión diabetes, los pacientes que utilizaban la bomba de insulina o microinfusor presentaban mejor puntaje en los dominios barreras, cumplimiento, preocupación y comunicación, y en el puntaje global, respecto a quienes usaban múltiples inyecciones de insulina como tratamiento (p=0,0363). Conclusiones. En nuestros pacientes, un mejor control metabólico (medido por el valor de HbA1c) y el uso de microinfusora contribuyen a una percepción de mejor calidad de vida.

Introduction: Diabetes mellitus is one of the most prevalent chronic diseases in the pediatric and juvenile population that affects the quality of life of patients. Objective: To evaluate the quality of life of a pediatric population under 18 years of age diagnosed with type 1 diabetes from two pediatric institutions in the city of Bogotá. Materials and methods: We collected of sociodemographic data and clinical variables and application of the PedsQL 4.0™ questionnaire, and the diabetes module 3.2 version validated in Spanish. The sociodemographic data, the clinical variables and the PedsQL™ were processed in the statistical software Stata 17™. Results: In the global score of the PedsQL™ 3.2, diabetes version, men presented better quality of life compared to women. The correlation between the hemoglobin A1c (HbA1c) values and the PedsQL scale in the global score was evaluated. Patients with HbA1c values below 9% presented a better health-related quality of life, while in the group with HbA1c greater than 9% a perception of low quality of life was observed (p=0.025). Regarding the type of therapy and the relationship with the domains of the PedsQL 3.2, diabetes version, patients who used insulin pumps had better scores in the domains barriers, adherence, concern, communication and in the global score compared to patients who used multiple daily injections of insulin as treatment (p=0.0363). Conclusions: In our patients, a better metabolic control (measured by the HbA1c value) and the use of an insulin pump contribute to a better perception of quality of life.

Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma.

The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.

Same-day comparative protocol PET/CT-PET/MRI [68 Ga]Ga-DOTA-TOC in paragangliomas and pheochromocytomas: an approach to personalized medicine.

BACKGROUND: PET/MRI is an emerging imaging modality which enables the evaluation and quantification of biochemical processes in tissues, complemented with accurate anatomical information and low radiation exposure. In the framework of theragnosis, PET/MRI is of special interest due to its ability to delineate small lesions, adequately quantify them, and therefore to plan targeted therapies. The aim of this study was to validate the diagnostic performance of [68 Ga]Ga-DOTA-TOC PET/MRI compared to PET/CT in advanced disease paragangliomas and pheochromocytomas (PGGLs) to assess in which clinical settings, PET/MRI may have a greater diagnostic yield. METHODS: We performed a same-day protocol with consecutive acquisition of a PET/CT and a PET/MRI after a single [68 Ga]Ga-DOTA-TOC injection in 25 patients. Intermodality agreement, Krenning Score (KS), SUVmax (Standard Uptake Value), target-to-liver-ratio (TLR), clinical setting, location, and size were assessed. RESULTS: The diagnostic accuracy with PET/MRI increased by 14.6% compared to PET/CT especially in bone and liver locations (mean size of new lesions was 3.73 mm). PET/MRI revealed a higher overall lesion uptake than PET/CT (TLR 4.12 vs 2.44) and implied an upward elevation of the KS in up to 60% of patients. The KS changed in 30.4% of the evaluated lesions (mean size 11.89 mm), in 18.4% of the lesions it increased from KS 2 on PET/CT to a KS ≥ 3 on PET/MRI and 24.96% of the lesions per patient with multifocal disease displayed a KS ≥ 3 on PET/MR, that were not detected or showed lower KS on PET/CT. In 12% of patients, PET/MRI modified clinical management. CONCLUSIONS: PET/MRI showed minor advantages over conventional PET/CT in the detection of new lesions but increased the intensity of SSRs expression in a significant number of them, opening the door to select which patients and clinical settings can benefit from performing PET/MRI.

Medicamentos genéricos ¿buenos y usables? La percepción de los estudiantes de medicina en un estado mexicano

Introducción: el conocimiento y la percepción hacia los medicamentos genéricos son temas que surgen como un factor importante a explorar en los estudiantes de medicina. Objetivo: determinar las diferencias entre los estudiantes de medicina de universidades públicas y privadas sobre la percepción y el uso de las Especialidades Farmacéuticas Genéricas (EFG). Materiales y métodos: se realizó un estudio cuantitativo de tipo observacional, transversal, analítico y comparativo en un universo de 858 estudiantes matriculados durante 2019-2020 en cinco escuelas de medicina del estado mexicano de Tabasco. A través de Google Forms se recolectaron los datos de un formulario auto aplicado con base a un cuestionario previamente validado. Se emplearon estadísticas descriptivas para evaluar las percepciones de los estudiantes y pruebas no paramétricas a través de un modelo de análisis de diferencia de medias para comparar el resultado entre las universidades. Resultados: la percepción de las dimensiones de calidad (8= 12,51) y eficacia (8=6,06) muestran una postura indecisa en general. En la fiabilidad (8=6,99), los alumnos estuvieron de acuerdo. Las dimensiones de preferencia-experiencia (8=10,649) y la de accesibilidad (X=7,01), colocan a los alumnos en el grupo de indecisos. En la comparación de medias de la escala de percepción de EFG (prueba t de estudent), la universidad pública presentó una media baja (8=24,72), mientras que en el grupo de universidades privadas fue mayor (8=26,06). En cuanto al uso de EFG, la universidad pública presentó una media 8=38,22, mientras que el grupo de universidades privadas fue menor (8=36,70). Conclusiones: se requiere incluir en los contenidos curriculares de los futuros profesionales de la medicina, mayor información sobre calidad, seguridad y eficacia de las EFG, lo que contribuirá a elevar el nivel de confianza en su prescripción.

Introduction: Knowledge and perception towards generic drugs are topics that emerge as an important factor to explore in medica students. Objective: To determine the differences between medical students from public and private universities on the perception and use of Generic Pharmaceutical Specialties (GFE). Materials and methods: A quantitative observational, cross-sectional, analytica and comparative study was conducted in a universe of 858 students enrolled during 2019-2020 in five medical schools in the Mexican state of Tabasco. Through Google Forms, data were collected from a self-applied form based on a previously validated questionnaire Descriptive statistics were used to assess student perceptions, and nonparametric tests through an analysis model for difference of means to compare the result between universities. Results: The perception of the dimensions of quality (8= 12,51) and efficacy (8=6,06) shows an indecisive position in general. On reliability (8=6,99), students agreed. The dimensions of preference-experience (8=10.649) and accessibility (8=7,01), place students in the group of undecideds. In the comparison of means of the GFE perception scale (student's t test), the public university presented a low mean (8=24,72), while in the group of private universities it was higher (8=26,06). Regarding the use of GFE, the public university presented a mean 8=38,22, while the group of private universities was lower (8=36,70). Conclusions: It is necessary to include in the curricular contents of future medical professionals more information on quality, safety and efficacy of GFE, which will contribute to raising the level of confidence in their prescription.

Response to targeted radionuclide therapy with [131I]MIBG AND [177Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review.

Purpose: Targeted radionuclide therapy (TRT) with [131I]MIBG and [177Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable paraganglioma (PGL) and pheochromocytoma (PHEO). There is no consensus on which treatment to administer and/or the best sequence in patients who are candidates for both therapies. To clarify these questions, this systematic review assesses the prognostic value of [131I]MIBG and [177Lu]Lu-DOTA-TATE (PRRT-Lu) treatments in terms of progression-free survival (PFS) both globally and considering the primary location. Methods: This review was developed according to the PRISMA Statement with 27 final studies (608 patients). Patient characteristics, treatment procedure, and follow-up criteria were evaluated. In addition, a Bayesian linear regression model weighted according to its sample size and an alternative model, which also included an interaction between the treatment and the proportion of PHEOs, were carried out, adjusted by a Student's t distribution. Results: In linear regression models, [131I]MIBG overall PFS was, on average, 10 months lower when compared with PRRT-Lu. When considering the interaction between treatment responses and the proportion of PHEOs, PRRT-Lu showed remarkably better results in adrenal location. The PFS of PRRT-Lu was longer when the ratio of PHEOs increased, with a decrease in [131I]MIBG PFS by 1.9 months for each 10% increase in the proportion of PHEOs in the sample. Conclusion: Methodology, procedure, and PFS from the different studies are quite heterogeneous. PRRT-Lu showed better results globally and specifically in PHEOs. This fact opens the window to prospective trials comparing or sequencing [131I]MIBG and PRRT-Lu.

Impact of Diabetes Mellitus in Patients with Pancreatic Neuro-Endocrine Tumors: Causes, Consequences, and Future Perspectives.

Diabetes mellitus (DM) and pancreatic neuroendocrine tumors (pNETs) are two entities closely linked together. DM has been described as a risk factor for the development of pNETs and for the aggressiveness of the disease. On the other hand, DM due to pNETs is frequently undiagnosed or misclassified as type 2 DM when it is due to type 3 DM. In addition, metformin, a commonly prescribed drug for type 2 DM, has an antiproliferative property and is gaining increasing attention as an antitumor agent. This review article presents the findings published in the last few years on pNETs and DMs. Emphasis will be placed on DM as a risk factor, pNET as a risk factor for the development of type 3 DM, the management of type 3 DM on pNET, and DM as a prognostic factor in patients with pNET, as well as the future clinical implications of DM in these patients. The coexistence of DM and pNET is extensively presented. It is important to perform future clinical trials, which are necessary to establish the role of metformin on pNET disease. Increasing awareness among professionals managing pNET on the importance of a correct DM diagnosis and management of the disease must be a priority due to the implications on mortality and comorbidities it may have in these patients.

Management of incidentally discovered appendiceal neuroendocrine tumors after an appendicectomy.

Appendiceal neuroendocrine tumors (aNETs) are an uncommon neoplasm that is relatively indolent in most cases. They are typically diagnosed in younger patients than other neuroendocrine tumors and are often an incidental finding after an appendectomy. Although there are numerous clinical practice guidelines on management of aNETs, there is continues to be a dearth of evidence on optimal treatment. Management of these tumors is stratified according to risk of locoregional and distant metastasis. However, there is a lack of consensus regarding tumors that measure 1-2 cm. In these cases, some histopathological features such as size, tumor grade, presence of lymphovascular invasion, or mesoappendix infiltration must also be considered. Computed tomography or magnetic resonance imaging scans are recommended for evaluating the presence of additional disease, except in the case of tumors smaller than 1 cm without additional risk factors. Somatostatin receptor scintigraphy or positron emission tomography with computed tomography should be considered in cases with suspected residual or distant disease. The main point of controversy is the indication for performing a completion right hemicolectomy after an initial appendectomy, based on the risk of lymph node metastases. The main factor considered is tumor size and 2 cm is the most common threshold for indicating a colectomy. Other factors such as mesoappendix infiltration, lymphovascular invasion, or tumor grade may also be considered. On the other hand, potential complications, and decreased quality of life after a hemicolectomy as well as the lack of evidence on benefits in terms of survival must be taken into consideration. In this review, we present data regarding the current indications, outcomes, and benefits of a colectomy.

Transformación integral del sistema de salud de la República Democrática de Timor Leste (2013-2016) / Comprehensive transformation of the health system of the Democratic Republic of Timor Leste (2013-2016)

Resumen Objetivo: Implementar un proyecto de reformas al sistema de salud de la República Democrática de Timor Leste, en el periodo 2013-2016. Materiales y métodos: Se realizó un estudio de tipo investigación/acción desde una perspectiva gerencial. Se incluyó muestra no probabilística por conveniencia de usuarios, proveedores y funcionarios, se emplearon técnicas cualitativas como grupos focales y entrevistas abiertas, así como el uso de herramientas gerenciales. Resultados: En una primera fase se realizó el análisis situacional a escala de país. Con estos elementos se definieron sucesivamente las prioridades estratégicas, los objetivos, indicadores y metas por cada perspectiva. Finalmente, el programa de cambios se organizó, se ejecutó el proceso de transformaciones y se fueron determinando los resultados. Se diseñaron y quedaron funcionando el Programa Nacional de Cáncer y el Programa Nacional de Atención Primaria; se introdujeron especialidades médicas y servicios asistenciales con los que no se contaba; se crearon nuevos enfoques para la gestión de los recursos humanos y, se elevó el nivel del trabajo científico, entre otros beneficios. Conclusiones: Se produjeron mejoras sustanciales en el Sistema de Salud y además se dejó creada una capacidad potencial para que dichos efectos sigan creciendo en cantidad y calidad.

Abstract Objective: Implement a Project to reform the health system of the Democratic Republic of Timor Leste in the period 2013-2016. Materials and methods: A research / action type study was carried out from a managerial perspective. A non-probabilistic sample was included for the convenience of users, suppliers and officials, qualitative techniques such as focus groups and open interviews were used, as well as the use of management tools. Results: In a first phase, the situational analysis was carried out at the country level. With these elements, the strategic priorities, objectives, indicators and goals were successively defined for each perspective. Finally, the change program was organized, the transformation process was carried out and the results were determined. The National Cancer Program and the National Primary Care Program were designed and kept functioning; Missing medical specialties and care services were introduced; New approaches to human resource management were created and the level of scientific work was raised, among other benefits. Conclusions: There were substantial improvements in the health system and in addition, a potential capacity was created so that these effects continue to grow in quantity and quality.

[177Lu]Lu-DOTA-TATE and [131I]MIBG Phenotypic Imaging-Based Therapy in Metastatic/Inoperable Pheochromocytomas and Paragangliomas: Comparative Results in a Single Center.

Purpose: The aim of the study is to assess phenotypic imaging patterns and the response to treatment with [177Lu]Lu-DOTA-TATE and/or [131I]MIBG in paragangliomas (PGLs) and pheochromocytomas (PHEOs), globally and according to the primary location. Methods: This is a 17-patient retrospective observational study, with 9 cases treated with [177Lu]Lu-DOTA-TATE and 8 with [131I]MIBG (37 total treatments). Functional imaging scans and treatment responses were studied in order to choose the best therapeutic option and to define the progression-free survival (PFS) and disease control rate (DCR) according to treatment modality and primary location. Results: All patients were studied with phenotypic nuclear medicine images. Twelve of 17 patients were tested with both [123I]MIBG and somatostatin receptor images, and 6/12 showed appropriate expression of both targets to treatment in the phenotypic images. The rest of the patients were tested with one of the image modalities or only showed suitable uptake of a single radiotracer and were treated with the corresponding therapeutic option. [177Lu]Lu-DOTA-TATE PFS was 29 months with a DCR of 88.8%. [131I]MIBG PFS was 18.5 months with a 62.5% DCR. According to the primary location, the best PFS was in PHEOs treated with [177Lu]Lu-DOTA-TATE. Although the series are small due to the low disease prevalence and do not allow to yield statistically significant differences, this first study comparing [177Lu]Lu-DOTA-TATE and [131I]MIBG displays a trend to an overall longer PFS with [177Lu]Lu-DOTA-TATE, especially in the adrenal primary location. When both radionuclide targets are expressed, the patients' comorbidity and treatment effectiveness should be valued together with the intensity uptake in the phenotypic image in order to choose the best therapeutic option. These preliminary retrospective results reinforce the need for a prospective, multicentric trial to be confirmed.

Evaluation of procalcitonin elevation during ICU stay and its relationship with mortality in ICU patients for COVID-19 with respiratory involvement. A multicenter prospective cohort study.

Introduction: A multicenter prospective cohort study studied patients admitted to the intensive care unit (ICU) by coronavirus-19 (COVID-19) with respiratory involvement. We observed the number of occasions in which the value of procalcitonin (PCT) was higher than 0.5 ng/ml. Objective: Evaluation of PCT elevation and influence on mortality in patients admitted to the ICU for COVID-19 with respiratory involvement. Measurements and main results: We studied 201 patients. On the day of admission, acute physiology and chronic health evaluation (APACHE)-II was 13 (10-16) points. In-hospital mortality was 36.8%. During ICU stay, 104 patients presented 1 or more episodes of PCT elevation and 60 (57.7%) died and 97 patients did not present any episodes of PCT elevation and only 14 (14.4%) died (p < 0.001). Multivariable analysis showed that mortality was associated with APACHE-II: [odds ratio (OR): 1.13 (1.04-1.23)], acute kidney injury [OR: 2.21 (1.1-4.42)] and with the presentation of one or more episodes of escalating PCT: [OR: 5.07 (2.44-10.53)]. Of 71 patients who died, 59.2% had an elevated PCT value on the last day, and of the 124 patients who survived, only 3.2% had an elevated PCT value on the last day (p < 0.001). On the last day of the ICU stay, the sequential organ failure assessment (SOFA) score of those who died was 9 (6-11) and 1 (0-2) points in survivors (p < 0.001). Of the 42 patients who died and in whom PCT was elevated on the last day, 71.4% were considered to have a mainly non-respiratory cause of death. Conclusion: In patients admitted to the ICU by COVID-19 with respiratory involvement, numerous episodes of PCT elevation are observed, related to mortality. PCT was elevated on the last day in more than half of the patients who died. Serial assessment of procalcitonin in these patients is useful because it alerts to situations of high risk of death. This may be useful in the future to improve the treatment and prognosis of these patients.

Somatostatin and Somatostatin Receptors: From Signaling to Clinical Applications in Neuroendocrine Neoplasms.

Neuroendocrine neoplasms (NENs) are heterogeneous neoplasms which arise from neuroendocrine cells that are distributed widely throughout the body. Although heterogenous, many of them share their ability to overexpress somatostatin receptors (SSTR) on their cell surface. Due to this, SSTR and somatostatin have been a large subject of interest in the discovery of potential biomarkers and treatment options for the disease. The aim of this review is to describe the molecular characteristics of somatostatin and somatostatin receptors and its application in diagnosis and therapy on patients with NENs as well as the use in the near future of somatostatin antagonists.

Prognostic Value of Variations in Serum Biomarkers and Prognostic Scores Values Between Admission and Second Day in Intensive Care Unit Septic Patients.

Objective To determinate the prognostic value of procalcitonin (PCT) and C-reactive protein (CRP) changes during the first two days of admission to the ICU with sepsis and/or septic shock, and to compare it with changes in Acute Physiology And Chronic Health Evaluation II (APACHE-II) and Sepsis-related Organ Failure Assessment (SOFA) prognostic scores. Methods A single-center prospective observational study was performed. Fifty consecutive patients admitted to the ICU, diagnosed of severe sepsis/septic shock were included. We considered risk factors for infection: diabetes mellitus, chronic obstructive pulmonary disease (COPD), previous antibiotic treatment, central intravascular catheter, bladder catheter, active neoplasia. Results Median aged 67(52-75) years with median APACHE-II 19(14-25) points and SOFA scores 7(5-11) points on admission, and 28-day mortality of 42%. When we studied the relationship between mortality and the changes between the day of admission and the second day of the variables studied, we found that APACHE-II (p = 0.001) and SOFA (p = 0.002) between admission and second day raised significantly in no survivors, with no significant changes in CRP and PCT. Multivariate analysis showed that mortality was significantly associated to changes in SOFA score (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.18-3.86) and to the presence of one or more risk factors for infection (OR, 6.01; 95% CI, 1.01-35.78) but not with PCT changes. Mortality was also related to the variations between the day of admission and the fifth day on APACHE-II (p = 0.002), SOFA (p < 0.001) and PCT (p = 0.012). Conclusions Changes in SOFA and APACHE-II scores between admission and second day in ICU septic patients are more sensitive mortality predictors than the observed changes in CRP and PCT values. Changes in PCT levels between the day of ICU admission and the fifth day are significantly related to mortality and may be useful as an additional marker in patient outcome.