[X-linked intellectual disability syndrome with macrocephaly due to BRWD3 gene deletion]. / Síndrome de discapacidad intelectual ligada a X con macrocefalia por deleción del gen BRWD3.

INTRODUCTION: Pathogenic variants in BRWD3 gene have been described as a rare cause of syndromic X-linked intellectual disability. Its phenotype shows neurodevelopmental delay with intellectual disability in all reported patients, facial dysmorphic features, macrocephaly, overgrowth and obesity. The great majority of cases yield point variants in the gene, only three large deletions including only the BRWD3 gene have been reported. The BRWD3 protein is an epigenetic reader that regulates chromatin remodeling. We report a boy with a compatible phenotype and a deletion including only this gene. CASE REPORT: Boy, without family and perinatal pathological background, with neurodevelopmental delay: psychomotor delay, speech delay and intellectual disability, macrocephaly (p > 99) and obesity. Phenotype with facial dysmorphic features: wide forehead, deep set eyes, bulbous nose, prominent ears and pointed chin. The array-CGH analysis showed a 586 kb deletion at Xq21.1 including only one gene with associated disorder, BRWD3. Afterwards, the deletion was also identified in his asymptomatic mother and sister. CONCLUSIONS: Our patient confirms that the haploinsufficiency due to BRWD3 deletion is a causal genetic mechanism of the BRWD3-related syndromic X-linked intellectual disability. It is important to recognize the phenotype for the diagnosis and follow up of the patients, and also to carry out the family genetic analysis in order to identify and give genetic counselling to the women who also have the genetic defect, because the majority of them are asymptomatic, as the mother and sister of our patient.

TITLE: Síndrome de discapacidad intelectual ligada a X con macrocefalia por deleción del gen BRWD3.Introducción. Variantes patógenas en el gen BRWD3 son la causa de un tipo poco frecuente de discapacidad intelectual sindrómica ligada a X. Su fenotipo se asocia a la alteración neuroconductual con discapacidad intelectual, dismorfia facial, macrocefalia, sobrecrecimiento y obesidad. La gran mayoría de los pacientes presenta variantes puntuales en el gen y sólo se han descrito tres casos con deleciones parciales que incluyen únicamente al gen BRWD3. Funcionalmente es un lector epigenético que regula la remodelación de la cromatina. Presentamos un varón con fenotipo compatible con una deleción que incluye sólo este gen asociado a patología. Caso clínico. Varón sin antecedentes familiares ni perinatales de interés con alteración en el neurodesarrollo: retraso psicomotor, retraso del lenguaje y discapacidad cognitiva, macrocefalia (p > 99) y obesidad. Fenotipo con dismorfia facial: frente amplia, ojos hundidos, nariz bulbosa, pabellones auriculares despegados y mentón afilado. Array de hibridación genómica comparada con deleción de 586 kb en Xq21.1, que incluye un único gen asociado a la patología, BRWD3. Posteriormente se realizó un estudio a la madre y a la hermana, asintomáticas, y ambas portan la deleción. Conclusiones. Nuestro caso confirma que la haploinsuficiencia debida a la deleción del gen BRWD3 es un mecanismo genético causal de la discapacidad intelectual sindrómica ligada a X asociada al gen BRWD3. Es importante reconocer el fenotipo para el diagnóstico y el seguimiento, así como la realización del estudio familiar para asesoramiento genético a las mujeres que porten la alteración, puesto que en la mayoría de los casos son asintomáticas, como la madre y la hermana de este paciente.

Functional imaging in neuroendocrine tumors: assessment of molecular heterogeneity using [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT.

OBJECTIVE: The aim of the study was evaluate the diagnostic performance of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT in patients with histologically proven neuroendocrine tumors (NETs), as well as the correlation of the visualized findings with the tumor grade. MATERIAL AND METHODS: We included 50 patients with NETs who underwent both [68Ga]Ga-DOTA-TOC and [18F]FDG PET/TC. The pooled sensitivity of both scans was compared, as well as [68Ga]Ga-DOTA-TOC and [18F]FDG for each tumor grade (grade 1/G1, grade 2/G2 and grade 3/G3). Also, the sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG as a function of the continuous variable Ki-67 was investigated. Finally, the number of lesions detected by both PET radiopharmaceuticals for each tumor grade was compared. RESULTS: The pooled sensitivity of both PET/CT (96%) was higher than [68Ga]Ga-DOTA-TOC (84%) and [18F]FDG (44%) separately, with statistically significant differences. The sensitivity of [68Ga]Ga-DOTA-TOC was higher than [18F]FDG in both G1 (p = 0.004) and G2 (p < 0.001). In G3 the performance of both scans detected disease in 100% of this subgroup. The sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT correlated significantly with the Ki-67 proliferative index. In G2 patients the number of lesions detected with [68Ga]Ga-DOTA-TOC was higher than [18F]FDG. CONCLUSIONS: The performance of both PET/CT, particularly in G2 and G3, demonstrates the molecular heterogeneity of metastatic NETs and contributes to the selection of a more appropriate treatment, particularly in those high-grade patients who may benefit from radionuclide therapy (PRRT).

First report of frequencies of Y chromosome microdeletions at a reproductive medicine center in Peru.

Objective: Y chromosome Microdeletions are the second genetic cause of infertility in men. Despite its importance for infertility treatment, there is no previous research in Peru. The aim of this study was to determine the frequencies and characteristics of Y chromosome microdeletions in a group of men who sought infertility consultation at a specialized reproductive medicine center in Peru. Methods: In this study, 201 semen samples were analyzed. The samples were obtained from Niu Vida's fertility program. Each seminal sample was analyzed according to the recommendations of the Laboratory Manual of the World Health Organization (WHO) 2010. A buccal swab and a 500 µL aliquot of seminal sample were used for the molecular study of Y chromosome microdeletions in each patient. The frequencies and the type of Y chromosome microdeletion in the AZFa, AZFb and AZFc regions were evaluated. Results: The prevalence of Y chromosome microdeletions in the AZF region was 6.45% in oligozoospermic and azoospermic patients, and a prevalence of 20% was observed specifically in azoospermic patients. No microdeletions of AZFb type were detected. A partial region microdeletion of AZFa was detected in a teratozoospermic patient with a normal sperm count. Conclusions: The study represents the first report on the incidence of Y chromosome microdeletions in Peru. Our results indicate a high prevalence of microdeletions in azoospermic patients compared to similar studies. It is suggested to assess the presence of AZFa microdeletions and to evaluate additional genetic markers in this region to identify specific mutations that may cause impaired sperm production and male infertility in the Peruvian male population.

Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis.

AIM: Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). METHODS: We conducted an observational, retrospective, multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020. The systemic inflammatory markers were calculated as follows: neutrophil to lymphocyte ratio (NLR)=neutrophil count/lymphocyte count, monocyte to lymphocyte ratio (MLR)=monocyte count/lymphocyte count, platelet to lymphocyte ratio (PLR)=platelet count/lymphocyte count, albumin to lymphocyte ratio (ALR)=albumin levels/lymphocyte count and derived Neutrophil to Lymphocyte ratio (dNLR)=neutrophil count/(leucocytes count - neutrophils count). Baseline analysis and after the second dose were used for the calculation of different ratios. RESULTS: The median age was 63 years (range 41-85), 55% were male. The baseline cut-off values for NLR were 2.61, for MLR 0.31, for PLR 110.14, for ALR 2.39 and for dNLR 1.71. The cut-off values after the 2° dose were, for NLR 2.3, for MLR 0.3, for PLR 131.61, ALR 4.16, and dNLR 1.48. Median progression-free survival (PFS) was 21.7 months (95% CI 10.7-32.8 months) and overall survival (OS) was 32.1 months (95% CI 19.6-44.7 months), PFS was shorter in patients with elevated NLR (p=0.001), ALR (0.03), and dNLR (p=0.001) in baseline analysis. DCR was 81% and ORR 18%. CONCLUSIONS: In GEP or unknown origin NETs treated with PRRT, we have identified the predictive and prognostic impact of baseline systemic inflammatory factors.

[Warsaw breakage syndrome: an etiology for congenital microcephaly and sensorineural deafness]. / Síndrome de rotura de Varsovia: una causa de microcefalia congénita y sordera neurosensorial.

INTRODUCTION: Warsaw breakage syndrome is a very rare genetic disorder due to biallelic pathogenic variants in DDX11 gene, with a role in the sister chromatid cohesion process, and classified in the cohesinophaties group. It is characterized by the clinical triad of growth restriction, microcephaly and sensorineural deafness. Additional, but less frequent features, are facial dysmorphism, and skeletal, heart, skin and genitourinary anomalies. CASE REPORT: We report a boy with the cardinal features of the syndrome: prenatal growth restriction, severe congenital microcephaly, and sensorineural deafness with cochlear nerves agenesis. He also has a cardiac anomaly, hypospadias, cryptorchidism, skin abnormality, and pes planus. The exome yielded two heterozygous likely pathogenic variants in the DDX11 gene, c.1403dup; p.(Ser469Valfs*32) and c.2371C>T; p.(Arg791Trp), inherited in trans from the parents. CONCLUSION: We review the clinical and genetic data of the 23 reported cases with the syndrome in the literature and analyze the etiopathogenic interpretation of our case variants based on the molecular and cellular functions of DDX11 described. Due to the clinical overlap with the chromosomal breakage syndromes and cohesinopathies we must make the differential diagnosis with these entities, overall, with Fanconi anemia, Nijmegen breakage syndrome, Cornelia de Lange syndrome and Roberts syndrome. In clinical practice we must think in Warsaw breakage syndrome in the neonatal period in a patient with intrauterine growth restriction, severe microcephaly, and sensorineural deafness.

TITLE: Síndrome de rotura de Varsovia: una causa de microcefalia congénita y sordera neurosensorial.Introducción. El síndrome de rotura de Varsovia es una alteración genética muy poco frecuente originada por variantes patógenas bialélicas en el gen DDX11, implicado en la cohesión de las cromátidas hermanas, que pertenece al grupo de las cohesinopatías. Clínicamente se caracteriza por retraso del crecimiento, microcefalia y sordera neurosensorial, con otras manifestaciones menos frecuentes: dismorfia facial, anomalías esqueléticas, cardíacas, cutáneas y genitourinarias. Caso clínico. Presentamos a un varón con las manifestaciones cardinales del síndrome: bajo peso en el nacimiento, microcefalia congénita grave y sordera neurosensorial con agenesia de los nervios cocleares. También presenta cardiopatía, hipospadias, criptorquidia, anomalía cutánea y pies planos. En el exoma se han identificado dos variantes en heterocigosis probablemente patógenas en el gen DDX11, c.1403dup; p.(Ser469Valfs*32) y c.2371C>T; p.(Arg791Trp), heredadas cada una de un progenitor. Conclusión. Revisamos a los 23 pacientes descritos con el síndrome en la bibliografía, tanto desde el punto de vista clínico como desde el genético. Analizamos el significado etiopatógeno de las variantes de nuestro caso basándonos en los datos moleculares y las funciones celulares de DDX11 de los estudios publicados. Debido al solapamiento clínico con los síndromes con rotura cromosómica y las cohesinopatías, debemos realizar el diagnóstico diferencial con estas entidades, fundamentalmente la anemia de Fanconi, el síndrome de rotura de Nijmegen, el síndrome de Cornelia de Lange y el síndrome de Roberts. En la práctica clínica, debemos sospechar este síndrome en el período neonatal en un paciente con retraso del crecimiento intrauterino, microcefalia grave y sordera neurosensorial.

Immunohistochemical expression of VEGFR1 in non small cell lung carcinomas: Lower VEGFR1 expression is asociated with squamous cell carcinoma subtype and high SUV max values in 18F-FDG PET.

BACKGROUND: To study the possible relation between immunohistochemical expression of vascular endothelial growth factor receptor 1 (VEGFR1) and the maximum standardised uptake value (SUV max) of 18F-FDG PET in patients with non small cell lung cancer (NSCLC). MATERIAL AND METHODS: The study included 39 patients with NSCLC (24 squamous cell carcinomas and 15 adenocarcinomas). According to the clinical stage, the patients were distributed as follows: 8 stage I, 7 stage II, 15 stage III and 9 stage IV. Immunohistochemical expression of VEGFR1 was studied through the technique of tissue-matrix using Tissue Arrayer Device (Beecher Instruments, Sun Prairie, WI), using the polyclonal antibody against VEGFR1 (Santa Cruz Biotechnology, California, USA). RESULTS: Positive VEGFR1 immunohistochemical expression was noted in 23 cases (59%). The number of positive tumours was not related with clinical stage but there was a different statistically significant association (p:0,0009) between VEGFR1 positivity and histological type, corresponding the greater percentages of positive results to adenocarcinomas (93,3%) versus in squamous cell carcinomas (37,5%). Likewise, SUV max values were higher (p: 0,039) in negative VEGFR1 carcinomas than in positive VEGFR1 tumors (r: 4-32,1; 16,4+/-6,4 (median 16,1) vs r: 3-47; 14,5+/-8,6 (12,8)). CONCLUSIONS: Our results led us to consider that in NSCLC, the negative VEGFR1 immunohistochemical expression is associated significantly with squamous cell carcinomas subtype and with higher SUV max values in 18F-FDG-PET.

18F-FDG PET/CT in cardiovascular infection and inflammation.

The diagnosis of cardiovascular infection and inflammation by [18F]FDG PET/CT in Nuclear Cardiology is of growing interest, because with respect to echocardiography this technique has improved the certainty in the diagnosis of infective endocarditis in patients with prosthetic valves, the increasing number of patients with implantable cardiac devices because of the progressive ageing of the population, as well as in patients with suspected large vessel vasculitis. All are serious clinical situations which require correct diagnosis and appropriate treatment as soon as possible, because they can cause severe complications, high mortality and also increased health care costs. We review the use of [18F]FDG PET/CT in cardiovascular infection and inflammation, including the clinical point of view and the contribution of other image modalities. We focus on the appropriate methodology for this exploration, patient preparation, image acquisition and correct interpretation and the quantification possibilities, defining the specific characteristics of the diagnosis in patients with prosthetic valves, implantable cardiac devices and large vessel vasculitis in the initial diagnosis as well as during follow-up to assess treatment response. We analyze the possible causes of false positive and false negative results and emphasize the special value of a multidisciplinary team for optimal management of these patients.

Checklist of the cestode parasites of wild birds of Argentina.

An annotated checklist of the cestode parasites of Argentinean wild birds is presented, as the result of a compilation of parasitological papers published between 1900 and April 2021. This review provides data on hosts, geographical distribution, sites of infection, location of material deposited in helminthological collections, references and taxonomic comments. A host/parasite list is also provided. During this period, 38 papers were published that gather information about 34 cestode nominal species and 11 taxa identified at generic level, belonging to three orders, ten families and 35 genera. The highest number of cestode taxa was recorded in the family Hymenolepididae, with 12 nominal species and two taxa identified at generic level, followed by Dilepididae, with eight nominal species and three taxa identified at generic level. Of the 1042 species of birds reported in Argentina, only 29 (2.8%) were reported as hosts of adult cestodes. The families of birds with the highest number of reported taxa were Laridae and Anatidae, with 20 and 14 taxa, respectively.

Immunohistochemical expression of VEGFR1 in non small cell lung carcinomas: Lower VEGFR1 expression is asociated with squamous cell carcinoma subtype and high max SUV values in 18F-FDG PET. / Expresión inmunohistoquímica de VEGFR1 en carcinomas de pulmón de células no pequeñas: La expresión inferior de VEGFR1 se asocia con el subtipo de carcinoma de células escamosas y los valores elevados en SUVmáx en PET de 18F-FDG.

BACKGROUND: To study the possible relation between immunohistochemical expression of vascular endothelial growth factor receptor 1 (VEGFR1) and the maximum standardised uptake value (maxSUV) of 18F-FDG PET in patients with non small cell lung cancer. MATERIAL AND METHODS: The study included 39 patients with NSCLC (24 squamous cell carcinomas and 15 adenocarcinomas). According to the clinical stage, the patients were distributed as follows: 8 stage I, 7 stage II, 15 stage III and 9 stage IV. Immunohistochemical expression of VEGFR1 was studied through the technique of tissue-matrix using tissue arrayer device (Beecher Instruments, Sun Prairie, WI), using the polyclonal antibody against VEGFR1 (Santa Cruz Biotechnology, California, USA). RESULTS: Positive VEGFR1 immunohistochemical expression was noted in 23 cases (59%). The number of positive tumours was not related with clinical stage but there was a different statistically significant association (p:.0009) between VEGFR1 positivity and histological type, corresponding the greater percentages of positive results to adenocarcinomas (93.3%) versus in squamous cell carcinomas (37.5%). Likewise, maxSUV values were higher (p: .039) in negative VEGFR1 carcinomas than in positive VEGFR1 tumors (r: 4-32.1; 16.4+/-6.4 [median 16.1] vs. r: 3-47; 14.5+/-8.6 [12.8]). CONCLUSIONS: Our results led us to consider that in NSCLC, the negative VEGFR1 immunohistochemical expression is associated significantly with squamous cell carcinomas subtype and with higher maxSUV values in 18F-FDG-PET.

Two-dimensional Weyl points and nodal lines in pentagonal materials and their optical response.

Two-dimensional pentagonal structures based on the Cairo tiling are the basis of a family of layered materials with appealing physical properties. In this work we present a theoretical study of the symmetry-based electronic and optical properties of these pentagonal materials. We provide a complete classification of the space groups that support pentagonal structures for binary and ternary systems. By means of first-principles calculations, the electronic band structures and the local spin textures in momentum space are analyzed for four examples of these materials, namely, PdSeTe, PdSeS, InP5 and GeBi2, all of which are dynamically stable. Our results show that pentagonal structures can be realized in chiral and achiral lattices with Weyl nodes pinned at high-symmetry points and nodal lines along the Brillouin zone boundary; these degeneracies are protected by the combined action of crystalline and time-reversal symmetries. Additionally, we computed the linear and nonlinear optical features of the proposed pentagonal materials and discuss some particular features such as the shift current, which shows an enhancement due to the presence of nodal lines and points, and their possible applications.

Fungal volatiles emitted by members of the microbiome of desert plants are diverse and capable of promoting plant growth.

Fungi represent a group of eukaryotic microorganisms that are an important part of the plant microbiome. They produce a vast array of metabolites, including fungal volatile organic compounds (fVOCs). However, the diversity and biological activities of fVOCs emitted by the mycobiota of plants native to arid and semi-arid environments remain under-explored. We characterized the chemical diversity of fVOCs produced by 22 representative members of the microbiome of agaves and cacti using SPME-GC-MS. We further tested the effects of pure compounds on the growth and development of Arabidopsis thaliana and host plants. Members of the Sordariomycetes (nine strains), Eurotiomycetes (three), Dothideomycetes (eight), Saccharomycetes (one) and Mucoromycetes (one) were included in our study. We identified 94 fungal organic volatiles classified into nine chemical classes. Terpenes showed the greatest chemical diversity, followed by alcohols and aliphatic compounds. We discovered that camphene and benzyl benzoate, together with the widely distributed and already tested benzyl alcohol, 2-phenylethyl alcohol and 3-methyl-1-butanol, improved plant growth and development of A. thaliana, Agave tequilana and Agave salmiana. Our studies on the fungal VOCs from desert plants underscore an untapped chemical diversity with promising biotechnological applications.

Caracterización de lesiones duodenales y su sobrevida / Characterization of duodenal lesions and their survival

Resumen Introducción: Las lesiones duodenales son infrecuentes. Objetivo: Caracterizar a los pacientes con lesiones duodenales observados entre enero de 2008 y diciembre de 2013 en el Servicio de Salud Metropolitano Sur, en Santiago de Chile. Materiales y Método: Se obtuvieron los datos de los registros del Hospital Barros Luco Trudeau y Hospital El Pino. Los pacientes incluidos fueron los observados entre enero de 2008 y diciembre de 2013. Se analizaron edad, género, características clínicas, localización, métodos diagnósticos, hallazgos anatomopatológicos y tratamiento. El 24 de abril de 2019 se obtuvo la fecha de fallecimiento de todos los pacientes del Registro Civil. El análisis estadístico se realizó con el software STATA 15.1. Resultados: Se encontraron 157 pacientes con lesiones duodenales, 65 presentaron adenocarcinoma duodenal y 71 pacientes pólipos duodenales, 25 de ellos fueron adenomas. Análisis univariado de sobrevida evidenció que los pacientes con pólipos asociado a carcinoma y los adenocarcinomas duodenales, presentaron una sobrevida inferior (p = 0,013, HR 6,584 y p < 0,001, HR 7,604, respectivamente). En los pacientes con adenocarcinoma duodenal, aquellos que se sometieron a una cirugía con intención curativa, y aquellos que recibieron quimioterapia tuvieron una sobrevida global mejor que aquellos que no recibieron terapia (p < 0,001, HR 0,351 y p = 0,001, HR 0,276, respectivamente. Discusión: La incidencia estimada del adenocarcinoma duodenal en nuestra población es de 1,1 por cada 100.000 habitantes, la que es más alta que otras publicadas. Proponemos estudio endoscópico en poblaciones de riesgo y tratamiento con intención curativa para los pacientes con adenocarcinoma duodenal sin metástasis a distancia.

Introduction: Duodenal lesions are infrequent. Aim: To characterize patients with duodenal lesions observed between January 2008 and December 2013 at the Southern Metropolitan Health Service, in Santiago, Chile. Materials and Method: Data were obtained from the Barros Luco Trudeau Hospital and El Pino Hospital records. The patients included were those observed between January 2008 and December 2013. Age, gender, clinical characteristics, location, diagnostic methods, anatomopathological findings and treatment were analyzed. On April 24th 2019 was obtained the date of death of all patients at the National Civil Registry. The statistical analysis was performed with the software STATA 15.1. Results: 157 patients with duodenal lesions were found, 65 presented duodenal adenocarcinoma and 71 patients had duodenal polyps, 25 of them were adenomas. Univariate analysis of survival showed that patients with polyps associated with carcinoma and duodenal adenocarcinomas had a lower survival rate (p = 0.013, HR 6.584 y p < 0.001, HR 7.604, respectively). In patients with duodenal adenocarcinoma, those who underwent surgery with curative intent, and those who receive chemotherapy had a better overall survival than those who did not received therapy (p < 0.001, HR 0.351 y p = 0.001, HR 0.276, respectively). Discussion: We propose endoscopic study in at-risk populations and treatment with curative intent for patients with duodenal adenocarcinoma without distant metastases. The estimated incidence of duodenal adenocarcinoma in our population is 1.1 per 100,000 inhabitants and seem to be higher than other published.

Cardiac scintigraphy with 99mTc-diphosphonates in cardiac amyloidosis. / Gammagrafía cardíaca con 99mTc-difosfonatos en la amiloidosis cardíaca.

Transthyretin cardiac amyloidosis (ATTR) has traditionally been considered a rare, difficult-to-diagnose and untreatable disease. However, its prevalence is known to be greater than what was previously thought, non-invasive diagnostic methods are available, and that effective treatments are emerging. In this context, cardiac scintigraphy (CS) with 99mTc-labelled diphosphonates has aroused a noticeable surge in interest by demonstrating high sensitivity and specificity for the reliable, non-invasive diagnosis of ATTR. By way of a guide, this article aims to identify the critical components in the performance of CS that are useful in everyday clinical practice and, thus, help specialists use optimal radiopharmaceuticals, obtain the most appropriate images, interpret the results thereof, and acquaint themselves with those clinical scenarios in which it is convenient to perform CS.

Cardiac sympathetic innervation scintigraphy with 123I-meta-iodobenzylguanidine. Basis, protocols and clinical applications in Cardiology. / Gammagrafía de inervación simpática cardiaca con 123I-metayodobencilguanidina. Fundamento, protocolos y aplicaciones clínicas en Cardiología.

Imaging of cardiac sympathetic innervation is only possible by nuclear cardiology techniques and its assessment is key in the evaluation of and decision-making for patients with cardiac sympathetic impairment. This review includes the basis of cardiac sympathetic scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG), recommended protocols, patient preparation, image acquisition and quantification, reproducibility, dosimetry, etc., and also the clinical indications for cardiac patients, mainly with regard to heart failure, arrhythmia, coronary artery disease, cardiotoxicity, including its contribution to establishing the indication for and monitoring the response to implantable cardiac devices, pharmacological treatment, heart transplantation and other.

Outcome of drug-induced sleep endoscopy-directed surgery for persistent obstructive sleep apnea after adenotonsillar surgery.

PURPOSE: Drug-induced sleep endoscopy (DISE) is suitable for evaluating persistent obstructive sleep apnea syndrome (OSAS) after adenotonsillar surgery as a means to guide surgical intervention, yet few studies demonstrate its usefulness in resolving the syndrome. We describe our experience of DISE-directed surgery in children with persistent OSAS by analysing objective and subjective outcomes of this treatment. METHODS: Prospective study of 20 otherwise healthy 2-12 year-old children with OSAS persisting after adenotonsillar surgery. All patients underwent DISE-directed surgery and were followed up clinically and with a polysomnogram at 12 ±â€¯3 months. RESULTS: All 20 children had an apnea-hypopnea index (AHI) score ≥1 (mean: 6.1 ±â€¯4.9) and 75% had AHI>3 before surgery. We performed a total of 14 total tonsillectomies (70%), 7 with associated pharyngoplasties; 5 radiofrequency turbinate reductions (25%); 7 radiofrequency lingual tonsil reductions (35%); and 10 revision adenoidectomies (50%). No surgery-related complications were observed. AHI scores at follow-up were significantly lower than AHI scores before surgery (1.895 ±â€¯1.11 vs 6.143 ±â€¯4.88; p < 0.05) and, in 85% (n = 17) of patients, AHI was below 3. There was a significant reduction in the number of children with AHI>3 in follow-up at 12 ±â€¯3 months (15%; n = 3) compared to before surgery (75%; n = 15) (p < 0.005). CONCLUSION: DISE-directed surgery for otherwise healthy children with persistent OSAS is a useful and safe technique to decide a therapeutic strategy and to obtain good objective and subjective results regarding resolution of the syndrome.

[Pulmonary lobectomy in children: the sooner the better?] / Lobectomía pulmonar en niños: ¿cuanto antes mejor?

AIM OF THE STUDY: Recommendation of early pulmonary resection in asymptomatic congenital pulmonary airway malformations (CPAMs) is based on the presumed compensatory lung growth during the first months of life. Our aim is to analyze the long-term pulmonary function after lobectomy before and after one year of age using spirometry. METHODS: We performed a retrospective review of children who underwent pulmonary lobectomy for CPAM between 2001 and 2016. Patients who were old enough (>5 years) to carry out a spirometry were included in the study and were divided into 2 groups (surgery before or after 12 months of age). Pulmonary function testing values were considered normal if they were >80% of predicted. MAIN RESULTS: Forty-seven patients underwent pulmonary lobectomy for CPAM, 23 of them met the inclusion criteria and prospectively performed a spirometry. Among them, 7 had surgery before and 16 after one year of age (0.1 vs. 2); being both groups comparable in terms of sex, type of CPAM and surgical approach. Time from surgery until pulmonary function testing was longer in patients who had surgery before one year of age (9.1 vs. 4.6 years, p = 0.003). After correcting results by time from surgery until spirometry, a better FEV1/FVC was found in patients who had surgery after one year of age (90% vs. 77%, p = 0.043). CONCLUSION: Although spirometry may be influenced by many other variables, these preliminary results do not support the current recommendation of performing early lobectomy in CPAMs. Further studies are required in order to resolve the best age to perform pulmonary lobectomy.

INTRODUCCION/OBJETIVO: La resección temprana de las malformaciones pulmonares asintomáticas ofrece el beneficio teórico de optimizar el crecimiento pulmonar compensatorio durante la infancia. El objetivo de este estudio es determinar si la lobectomía antes del año de vida se asocia con mejor función pulmonar a largo plazo. MATERIALES Y METODOS: Revisión de pacientes en los que se realizó lobectomía pulmonar desde 2001, incluyendo los que tenían edad suficiente para realizar una espirometría (>5 años). Fueron divididos en dos grupos: lobectomía antes o después de 12 meses de vida. Los parámetros espirométricos se consideraron normales cuando eran mayores del 80% esperado. RESULTADOS: Veintitrés de los 47 pacientes intervenidos cumplieron los criterios de inclusión. Siete fueron intervenidos antes (0,1 ± 0,4 años) y 16 después del año de vida (2 ± 3,6 años), siendo ambos grupos comparables en sexo, tipo de malformación y abordaje quirúrgico. El tiempo de seguimiento desde la cirugía hasta que se realizó la espirometría fue mayor en los pacientes intervenidos antes del año de vida (9,1 vs. 4,6 años, p = 0,003). Tras corregir los resultados por el tiempo de seguimiento, se objetivó un mejor cociente FEV1/FVC en los pacientes intervenidos después del año de vida (90% vs. 77%, p = 0,043). CONCLUSION: Aunque la espirometría puede estar influenciada por otras variables, los datos de nuestro estudio no apoyan la recomendación actual de realizar resección temprana en las malformaciones pulmonares congénitas asintomáticas. Se necesitan estudios prospectivos con mayor número de pacientes para determinar la mejor edad para realizar la lobectomía.

[The role of fetal magnetic resonance imaging in the study of congenital diaphragmatic hernia]. / El papel de la resonancia magnética fetal en el estudio de la hernia diafragmática congénita.

INTRODUCTION AND OBJECTIVES: Different echographic and fetal magnetic resonance (MRI) measurements have been described in the diagnosis of associated malformations and the prognosis of congenital diaphragmatic hernia (CDH). We have reviewed our experience searching for useful isolated or combined parameters and how MRI can complement ultrasound. MATERIAL AND METHODS: We evaluated 29 fetuses with CDH. We examined ultrasonography: Lung to Head (LHR o/e) and in MRI: ipsilateral lung volume (IPV) and total expressed as percentage of observed / expected lung volume (VPT o/e) and percentage of herniated liver (PHH). We studied: survival, ECMO and associated malformations. RESULTS: LHR o/e was the measure that best predicted survival (p< 0.05). VPT o/e did not predict survival or the need of ECMO (p> 0.05). PHH ≥19% was related to the need of ECMO. IPV < 2 cc required ECMO more frequently (p< 0.018) and when it was 0 cc in all cases. No combination of MR measurements was superior to LHR o/e in prediction of survival. MRI complemented the ultrasound in 4 cases: diaphragmatic eventration diagnosed with HDC, right HDC with fluid in the sac that suggested thoracic cyst, differentiation between spleen and lung that measured together overestimated the LHR and/or suspicion of Cornelia de Lange due to facial malformations. CONCLUSIONS: Not a single or combined MRI measurement exceeds LHR o/e in survival prediction. MRI is related to prognosis and can be used to support ultrasound in making decisions. MRI occasionally provides complementary morphological information.

INTRODUCCION Y OBJETIVOS: Distintas medidas ecográficas y de resonancia magnética fetal (RM) han sido descritas en el diagnóstico de malformaciones asociadas y el pronóstico de la hernia diafragmática congénita (HDC). Hemos revisado nuestra experiencia buscando parámetros aislados o combinados útiles y cómo la RM puede complementar a la ecografía. MATERIAL Y METODOS: Evaluamos 29 fetos con HDC. Revisamos en ecografía: Lung to Head Ratio observado/esperado (LHR o/e) y en RM: volumen pulmonar ipsilateral (VPI) y total expresado como porcentaje del volumen pulmonar observado/esperado (VPT o/e) y porcentaje de hígado herniado (PHH). Estudiamos: supervivencia, oxigenación con membrana extracorpórea (ECMO) y malformaciones asociadas. RESULTADOS: El LHR o/e fue la medida que mejor predijo supervivencia (p< 0,05). El VPT o/e no predijo supervivencia ni la necesidad de ECMO (p> 0,05). El PHH ≥19% se relacionó con necesidad de ECMO. El VPI menor de 2 cc requirió ECMO más frecuentemente (p< 0,018) y cuando fue de 0 cc en todos los casos. Ninguna combinación de medidas de RM fue superior al LHR o/e en predicción de supervivencia. La RM complementó a la ecografía en 4 casos: eventración diafragmática diagnosticada como HDC, HDC derecha con líquido en el saco que sugería quiste torácico, diferenciación entre bazo y pulmón que medidos juntos sobreestimaba el LHR o/e y sospecha de síndrome de Cornelia de Lange por malformaciones faciales. CONCLUSIONES: Ninguna medida aislada o combinada de RM supera al LHR o/e en la predicción de supervivencia. La RM se relaciona con el pronóstico y puede usarse como apoyo de la ecografía en la toma de decisiones. La RM aporta ocasionalmente información morfológica complementaria.

A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for Malaria Venture Open-Access Malaria Box.

Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5 years and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to the need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report the identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization. The identification of MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose-response studies, in vitro toxicity studies, and structure-activity relationship studies using commercial analogues. The potency of this compound against Cryptosporidium parvum Iowa and field isolates was comparable to that against Cryptosporidium hominis Furthermore, unlike nitazoxanide, clofazimine, and paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this mouse model of chronic infection might relate to whether compounds are parasiticidal or parasitistatic for C. parvum, we developed a novel in vitro parasite persistence assay. This assay suggested that MMV665917 was parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also enabled determination of the concentration of the compound required to maximize the rate of parasite elimination. This time-kill assay can be used to prioritize early-stage Cryptosporidium drug leads and may aid in planning in vivo efficacy experiments. Collectively, these results identify MMV665917 as a promising lead and establish a new method for characterizing potential anticryptosporidial agents.