The association between thyroid differentiation score and survival outcomes in papillary thyroid carcinoma.

BACKGROUND: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in PTC. The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts. METHODS: Two independent cohorts of PTC patients were used: 1) the Cancer Genome Atlas (TCGA) thyroid cancer study (N=372), 2) MD Anderson Cancer Center (MDACC) cohort (N=111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was also explored. The Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. RESULTS: In both cohorts, TDS was associated with tumor and nodal stage at diagnosis as well as tumor driver mutation status. High TDS was associated with longer PFI on univariable analyses across cohorts. After adjusting for overall stage, TDS remained significantly associated with PFI in the MDACC cohort only (aHR 0.67, 95%CI 0.52-0.85). In subgroup analyses stratified by tumor driver mutation status, higher TDS was most consistently associated with longer PFI in BRAFV600E-mutated tumors across cohorts after adjusting for overall stage (TCGA: aHR 0.60, 95% CI: 0.33-1.07; MDACC: aHR 0.59, 95% CI: 0.42-0.82). For OS, increasing TDS was associated with longer OS in the overall MDACC cohort (aHR=0.78, 95% CI:0.63-0.96), where the median duration of follow-up was 12.9 years. CONCLUSION: TDS quantifies the spectrum of differentiation status in PTC and may serve as a potential prognostic biomarker in PTC, mostly promisingly in BRAFV600E-mutated tumors.

Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer: The FAST Multidisciplinary Group Consensus Statement.

Importance: BRAF/MEK inhibitors revolutionized the treatment of BRAF V600E-variant anaplastic thyroid carcinoma (BRAFv-ATC), offering improved outcomes for patients with this previously incurable disease. Observations: Anaplastic thyroid carcinoma (ATC) accounts for approximately half of thyroid cancer-related deaths. It presents as a rapidly growing tumor that often invades locoregional structures and spreads to distant sites early; therefore, prompt diagnosis, staging, and treatment initiation are of the essence in the treatment of ATC. Although most oncologists will encounter a patient with ATC in their practice, the rarity of this disease makes treatment challenging, particularly because those with BRAFv-ATC no longer have a dismal prognosis. BRAF/MEK kinase inhibitors have transformed the outlook and treatment of BRAFv-ATC. Therefore, molecular profiling to identify these patients is critical. More recently, the addition of immunotherapy to BRAF/MEK inhibitors as well as the use of the neoadjuvant approach were shown to further improve survival outcomes in BRAFv-ATC. Many of these recent advances have not yet been incorporated in the currently available guidelines, allowing for disparities in the treatment of patients with BRAFv-ATC across the US. With the increasing complexity in the management of BRAFv-ATC, this Consensus Statement aims to formulate guiding recommendations from a group of experts to facilitate therapeutic decision-making. Conclusions and Relevance: This Consensus Statement from the FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment) group at MD Anderson Cancer Center emphasizes that rapid identification of a BRAF V600E pathogenic variant and timely initiation of sequential therapy are critical to avoid excess morbidity and mortality in patients with BRAFv-ATC. In the past decade, remarkable progress has been made in the treatment of patients with BRAFv-ATC, justifying these new evidence-based recommendations reached through a consensus of experts from a high-volume center.

Molecular Perspectives in Radioactive Iodine Theranostics: Current Redifferentiation Protocols for Mis-Differentiated Thyroid Cancer.

Thyroid cancer molecular oncogenesis involves functional dedifferentiation. The initiating genomic alterations primarily affect the MAPK pathway signal transduction and generate an enhanced ERK output, which in turn results in suppression of the expression of transcription of the molecules of iodine metabolomics. The clinical end result of these molecular alterations is an attenuation in theranostic power of radioactive iodine (RAI). The utilization of RAI in systemic therapy of metastatic disease requires restoration of the functional differentiation. This concept has been accomplished by modulation of MAPK signaling. Objective responses have been demonstrated in metastatic disease settings. RAI-refractoriness in "differentiated thyroid cancers" remains a clinical problem despite optimized RAI administration protocols. Functional mis-differentiation and associated RAI-indifference are the underlying primary obstacles. MAPK pathway modulation offers a potential for reversal of RAI-indifference and combat refractoriness. This review presents the latest clinical experience and protocols for the redifferentiation of radioiodine-refractory mis-differentiated thyroid cancer, providing a comprehensive overview of the current protocols and intervention strategies used by leading institutions. Timing and techniques of imaging, thyrotropin (TSH) stimulation methods, and redifferentiation agents are presented. The efficacy and limitations of various approaches are discussed, providing an overview of the advantages and disadvantages associated with each of the protocols.

Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy.

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also been thoroughly studied and has shown promise in selected cases. In this review, we summarize the progress in the understanding of the genetic landscape and the cellular and molecular basis of radioiodine refractory-DTC and ATC, as well as discuss the current treatment options and future therapeutic avenues.

Next-Generation Sequencing in Sporadic Medullary Thyroid Cancer Patients: Mutation Profile and Disease Aggressiveness.

Context: Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including RET M918T, which has been considered a negative prognostic indicator. Objective: This study aimed to determine the association between clinicopathologic behavior and somatic mutation identified on clinically motivated NGS. Methods: In this retrospective cohort study, patients with sMTC who underwent NGS to identify somatic mutations for treatment planning were identified. Clinicopathologic factors, time to distant metastatic disease (DMD), disease-specific survival (DSS), and overall survival (OS) were compared between somatic mutations. Results: Somatic mutations were identified in 191 sMTC tumors, including RET M918T (53.4%), other RET codons (10.5%), RAS (18.3%), somatic RET indels (8.9%), and RET/RAS wild-type (WT) status (8.9%). The median age at diagnosis was 50 years (range, 11-83); 46.1% were female. When comparing patients with RET M918T, RET-Other, and RET WT (which included RAS and RET/RAS WT), there were no differences in sex, TNM category, systemic therapy use, time to DMD, DSS, or OS. On multivariate analysis, older age at diagnosis (HR 1.05, P < .001; HR 1.06, P< .001) and M1 stage at diagnosis (HR 3.17, P = .001; HR 2.98, P = .001) were associated with decreased DSS and OS, respectively, but mutation cohort was not. When comparing RET M918T to RET indels there was no significant difference in time to DMD, DSS, or OS between the groups. Conclusion: Somatic RET mutations do not portend compromised DSS or OS in a cohort of sMTC patients who underwent clinically motivated NGS.

RAF inhibitor re-challenge therapy in BRAF-aberrant pan-cancers: the RE-RAFFLE study.

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable responses with PR and SD lasting > 6 months. The median progression-free survival on therapy with second RAF inhibitor in the rechallenge setting either as monotherapy or combination was shorter at 2.7 months (0.9-30.1 m) compared to 8.6 months (6.5-11.5 m) with RAF-1i. However, the median PFS with RAF-2i responders (PFS-2) improved at 12.8 months compared to 11.4 months with RAF-1i responders. The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF-aberrant cancers.

Adaptive Darwinian off-target resistance mechanisms to selective RET inhibition in RET driven cancer.

Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment. The selpercatinib-responsive MTC progressed with an acquired ETV6::NTRK3 fusion, which was controlled by selpercatinib plus the NTRK inhibitor larotrectinib. Subsequently, tumor progressed with an acquired EML4::ALK fusion. Combination of selpercatinib with the dual NTRK/ALK inhibitor entrectinib reduced the tumor burden, which was followed by appearance of NTRK3 solvent-front G623R mutation. Preclinical experiments validated selpercatinib plus larotrectinib or entrectinib inhibited RET/NTRK3 dependent cells, whereas selpercatinib plus entrectinib was necessary to inhibit cells with RET/NTRK3/ALK triple alterations or a mixture of cell population carrying these genetic alterations. Thus, RET-altered MTC adapted to selpercatinib and larotrectinib with acquisition of ETV6::NTRK3 and EML4::ALK oncogenes can be managed by combination of selpercatinib and entrectinib providing proof-of-concept of urgency of incorporating molecular profiling in real-time and personalized N-of-1 care transcending one-size-fits-all approach.

Analytical Validation of a Telomerase Reverse Transcriptase (TERT) Promoter Mutation Assay.

CONTEXT: Telomerase reverse transcriptase (TERT) promoter-mutated thyroid cancers are associated with a decreased rate of disease-free and disease-specific survival. High-quality analytical validation of a diagnostic test promotes confidence in the results that inform clinical decision-making. OBJECTIVE: This work aimed to demonstrate the analytical validation of the Afirma TERT promoter mutation assay. METHODS: TERT promoter C228T and C250T variant detection in genomic DNA (gDNA) was analyzed by assessing variable DNA input and the limit of detection (LOD) of variant allele frequency (VAF). The negative and positive percentage agreement (NPA and PPA) of the Afirma TERT test was examined against a reference primer pair as was the analytical specificity from potential interfering substances (RNA and blood gDNA). Further, the intrarun, interrun, and interlaboratory reproducibility of the assay were tested. RESULTS: The Afirma TERT test is tolerant to variation in DNA input amount (7-13 ng) and can detect expected positive TERT promoter variants down to 5% VAF LOD at 7 ng DNA input with greater than 95% sensitivity. Both NPA and PPA were 100% against the reference primer pair. The test remains accurate in the presence of 20% RNA or 80% blood gDNA for an average patient sample that typically has 30% VAF. The test also demonstrated a 100% confirmation rate when compared with an external next-generation sequencing-based reference assay executed in a non-Veracyte laboratory. CONCLUSION: The analytical robustness and reproducibility of the Afirma TERT test support its routine clinical use among thyroid nodules with indeterminate cytology that are Afirma Genomic Sequencing Classifier suspicious or among Bethesda V/VI nodules.

Thyroid Cancer: A Review.

Importance: Approximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer. Observations: Papillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma. Conclusions: Approximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.

Checkpoint Inhibition in Addition to Dabrafenib/Trametinib for BRAFV600E-Mutated Anaplastic Thyroid Carcinoma.

Background: The dabrafenib plus trametinib combination (DT) has revolutionized the treatment of BRAFV600E-mutated anaplastic thyroid carcinoma (BRAFm-ATC). However, patients eventually develop resistance and progress. Single-agent anti-PD-1 inhibitor spartalizumab has shown a median overall survival (mOS) of 5.9 months. Combination of immunotherapy with BRAF/MEK inhibitors (BRAF/MEKi) seems to improve outcomes compared with BRAF/MEKi alone, although no direct comparison is available. BRAF-targeted therapy before surgery (neoadjuvant approach) has also shown improvement in survival. We studied the efficacy and safety of DT plus pembrolizumab (DTP) compared with current standard-of-care DT alone as an initial treatment, as well as in the neoadjuvant setting. Methods: Retrospective single-center study of patients with BRAFm-ATC treated with first-line BRAF-directed therapy between January 2014 and March 2023. Three groups were evaluated: DT, DTP (pembrolizumab added upfront or at progression), and neoadjuvant (DT before surgery, and pembrolizumab added before or after surgery). The primary endpoint was mOS between DT and DTP. Secondary endpoints included median progression-free survival (mPFS) and response rate with DT versus DTP as initial treatments, and the exploratory endpoint was mOS in the neoadjuvant group. Results: Seventy-one patients were included in the primary analysis: n = 23 in DT and n = 48 in DTP. Baseline demographics were similar between groups, including the presence of metastatic disease at start of treatment (p = 0.427) and prior treatments with surgery (p = 0.864) and radiation (p = 0.678). mOS was significantly longer with DTP (17.0 months [confidence interval CI, 11.9-22.1]) compared with DT alone (9.0 months [CI, 4.5-13.5]), p = 0.037. mPFS was also significantly improved with DTP as the initial treatment (11.0 months [CI, 7.0-15.0]) compared with DT alone (4.0 months [CI, 0.7-7.3]), p = 0.049. Twenty-three patients were in the exploratory neoadjuvant group, where mOS was the longest (63.0 months [CI, 15.5-110.5]). No grade 5 adverse events (AEs) occurred in all three cohorts, and 32.4% had immune-related AEs, most frequently hepatitis and colitis. Conclusions: Our results show that in BRAFm-ATC, addition of pembrolizumab to dabrafenib/trametinib may significantly prolong survival. Surgical resection of the primary tumor after initial BRAF-targeted therapy in selected patients may provide further survival benefit. However, conclusions are limited by the retrospective nature of the study. Additional prospective data are needed to confirm this observation.

Strategies for mitigating adverse events related to selective RET inhibitors in patients with RET-altered cancers.

The US Food and Drug Administration (FDA) approval of the selective RET inhibitors selpercatinib and pralsetinib has led to a paradigm change in the treatment of RET-altered lung and thyroid cancers through a higher response rate and a more tolerable safety and toxicity profile than multi-kinase inhibitors. Recently, selpercatinib has received a tissue-agnostic FDA approval for all RET-fusion-positive cancers, and pralsetinib has shown pan-cancer activity as well. Given the anticipated increase in the use of both drugs across multiple tumor types, it is crucial to recognize the possible side effects and approaches for their optimal management in order to maximize the clinical benefit for treated patients. In this review, we underscore potential toxicities associated with selective RET inhibitors and discuss strategies to mitigate them.

Rehabilitación vestibular con posturografía dinámica / Vestibular rehabilitation with Dynamic posturography

La rehabilitación vestibular es fundamental en el tratamiento de la inestabilidad puesto que actúa sobre la compensación, mejorando el equilibrio y la calidad de vida del paciente. El objetivo de este artículo es presentar la utilidad y aspectos prácticos de la posturografía dinámica computarizada en el diseño de un programa de rehabilitación vestibular

Vestibular rehabilitation is essential in the treatment of unsteadiness as it works on compensation improving patient balance and quality of life. The objective of this article is to introduce the usefulness and practical aspects of computerized dynamic posturography in the vestibular rehabilitation program design

Design of a nursing objective structured clinical examination of a first-year clinical practice program / Projeto de um exame clínico estruturado objetivo de enfermagem de um programa de prática clínica do primeiro ano / Diseño de una prueba de evaluación clínica objetiva estructurada de cuidados de enfermería del primer curso de prácticas clínicas

ABSTRACT Objective: The aim of the present study was to design a content-valid nursing objective structured clinical examination attending a first-year clinical nursing practice program. Method: The examination was designed following a procedure based on the consensus of experts which was comprised of three phases: selection of the activities in which students should be competent according to the learning outcomes of the course, clinical case design, and integration of the clinical cases designed into the stations of the test. Results: Of the 44 surveys submitted for the design of the stations, 37 were answered, of which 31 respondents met the inclusion criteria of the panel of experts. The activities on which the experts reached the highest degrees of consensus were: basic physical assessment and monitoring of vital signs, assessment of hygiene and skin status, ability to develop care plans, management of safety principles in administration of medication and administration of oral medication. Based on the selected activities, the experts developed 20 clinical cases, from which a four-station nursing objective structured clinical examination was designed. Conclusion: The structured methodology based on the design of experts enabled the design of a content-valid objective structured clinical examination appropriate for the evaluation of the learning outcomes achieved by the students attending a clinical practice program.

RESUMO Objetivo: O objetivo do presente estudo foi elaborar um exame clínico estruturado de objetivos de enfermagem com conteúdo válido, participando de um programa de prática clínica de enfermagem do primeiro ano. Método: O exame foi elaborado seguindo um procedimento baseado no consenso de especialistas que compreendeu três fases: seleção das atividades nas quais os alunos deveriam ser competentes de acordo com os resultados de aprendizagem do curso, desenho do caso clínico e integração do quadro clínico casos projetados para as estações do teste. Resultados: Das 44 pesquisas submetidas para a concepção das estações, 37 foram respondidas, das quais 31 respondentes atenderam aos critérios de inclusão do painel de especialistas. As atividades nas quais os especialistas alcançaram maior grau de consenso foram: avaliação física básica e monitoramento dos sinais vitais, avaliação da higiene e do estado da pele, capacidade de desenvolver planos de cuidados, gestão dos princípios de segurança na administração de medicamentos e administração de medicamentos orais. Com base nas atividades selecionadas, os especialistas desenvolveram 20 casos clínicos, a partir dos quais foi elaborado um exame clínico estruturado objetivo de enfermagem em quatro estações. Conclusão: A metodologia estruturada baseada na concepção de especialistas permitiu a concepção de um exame clínico estruturado objetivo válido e de conteúdo adequado para a avaliação dos resultados de aprendizagem alcançados pelos alunos que frequentam um programa de prática clínica.

RESUMEN Objetivo: El objetivo de este estudio fue diseñar una Evaluación Clínica Objetiva Estructurada con validez de contenido para evaluar el nivel de competencias de estudiantes de primer curso de formación practico-clínica enfermera. Método: Se diseñó la prueba siguiendo un procedimiento basado en consenso de expertos con tres fases: selección de las actividades en la que los alumnos debían ser competentes en base a los resultados de aprendizaje de la asignatura, diseño de casos clínicos, e integración de los casos clínicos diseñados en las estaciones de la prueba. Resultados: Las actividades que alcanzaron mayor consenso por parte de los expertos fueron: valoración física básica y monitorización de signos vitales, valoración de la higiene y estado de la piel, capacidad para elaborar planes de cuidados, manejo de los principios de seguridad en la administración de medicación y administración de medicación oral. En base a las actividades seleccionadas, los expertos elaboraron 20 casos clínicos, a partir de los cuales se diseñó una evaluación clínica objetiva estructurada de cuidados de enfermería formada por cuatro estaciones. Conclusión: La metodología estructurada basada en el diseño de expertos permitió el diseño de una evaluación clínica objetiva estructurada adecuada para evaluar los resultados de aprendizaje alcanzados por los estudiantes de primer curso de formación práctico-clínica.

Efectos de la administración de calostro orofaríngeo en recién nacidos prematuros sobre los niveles de inmunoglobulina A / Effect of oropharyngeal colostrum administration on immunoglobulin A levels in preterm newborns

Introducción: el recién nacido prematuro de muy bajo peso (RNMBP) es inmunológicamente inmaduro y además presenta una alteración de las barreras naturales de defensa. Objetivo: evaluar los efectos que pueda tener la administración de calostro orofaríngeo, administrado durante los primeros 15 días posnatales, sobre los niveles de inmunoglobulina A (IgA) sérica en recién nacidos prematuros de muy bajo peso durante el primer mes de vida. Material y métodos: se desarrolló un estudio de intervención no aleatorizado con grupo control, en el que se incluyeron 38 recién nacidos con ≤ 32 + 6 semanas de gestación y/o menores de 1.500 g de peso. Los sujetos recibieron 0,2 ml de calostro de su madre cada 4 h, iniciándose el procedimiento en las primeras 24 h de vida hasta el 15.º día postnatal. Se midieron los niveles de IgA en la sangre al nacimiento, 3.er, 15.º y 30.º días de vida. Se registraron datos perinatales al nacimiento y durante el periodo de seguimiento. Resultados: IgA sérica aumentó de forma estadísticamente significativa en el grupo de intervención (M1 15,84 µg/ml, M2 20,07 µg/ml, M3 23,65 µg/ml, M4 30,34 µg/ml, p 0,001) y en el grupo control (M1 12,48 µg/ml, M2 16,48 µg/ml, p 0,018; M3 19,41 µg/ml, M4 22,48 µg/ml, p 0,001). Al mes de vida, los niveles de IgA sérica fueron significativamente mayores en el grupo de intervención que en el grupo control (p 0,026). Conclusiones: este estudio sugiere que la administración de calostro orofaríngeo favorecería el desarrollo del sistema inmunológico de los recién nacidos prematuros y RNMBP a través del aumento de IgA al mes de vida (AU)

Introduction: Very low birth weight (VLBW) newborns have an immature immune system and also disrupted defense natural barriers. Objective: To evaluate the immunologic effects of oropharyngeal colostrum administration to VLBW infants in their first two weeks of life, by assessing IgA serum levels evolution up to one month of life. Material and methods: We conducted an interventional, no randomized, controlled trial recruiting 38 newborns under ≤ 32 + 6 gestational weeks and/or under 1,500 g at birth. Subjects received 0,2 ml of their mother colostrum every 4 hours, starting in the first 24 hours of life, and for a 15 days period. IgA serum levels were measured at birth, 3, 15 and 30 days of life. Perinatal data for the first month of life were registered. Results: Along the first month of life an increase in IgA levels was found in colostrum group (M1 15.84 µg/ml, M2 20.07 µg/ml, M3 23.65 µg ml, M4 30.34 µg/ml, p 0.001) and in control group (M1 12.48 µg/ml, M2 16.48 µg/ml, p 0.018; M3 19.41 µg/ml, M4 22.48 µg/ml, p 0.001). IgA serum levels were statistically increased in colostrum group, in respect to control group at one month of age (p 0.026). Conclusions: Our data suggest that oropharyngeal colostrum administration might facilitate the development of immune system in VLWB infants at one month of age, by increasing IgA serum levels (AU)

Infecciones cervicales profundas. Revisión de 286 casos / Deep neck infection. Review of 286 cases

Introducción: Las infecciones cervicales profundas (ICP) son afecciones potencialmente letales y susceptibles de complicaciones graves. En este estudio se constata el aumento de la incidencia y se trata de buscar las causas. Más del 30% son idiopáticas, pero suelen relacionarse con infecciones dentarias y orofaríngeas. Material y métodos: Se presentan 286 ICP consecutivas en un estudio retrospectivo de los últimos 11 años en nuestro centro y se analizan antecedentes y enfermedades concomitantes y aspectos diagnósticos y terapéuticos de los pacientes que pueden influir en el desarrollo de las ICP. Resultados: Se objetiva un repunte de la incidencia de las ICP en nuestro medio. Las complicaciones más frecuentes fueron mediastinitis, shock séptico con coagulación intravascular diseminada, fascitis necrotizante y compromiso respiratorio agudo. Las secuelas más frecuentes observadas fueron la disfagia por parálisis de pares craneales bajos y neuroencefalopatía. Se produjeron un 10% de neumonías aspirativas. La mortalidad por ICP en los adultos es del 5,9% y en los niños del 6,2%. Conclusiones: Las ICP debe ser consideradas una urgencia médicoquirúrgica. Son susceptibles de complicaciones graves en cuestión de horas. Debemos estar atentos a la aparición de síntomas de alarma como: disnea, estridor, dolor a la palpación en el suelo de la boca, sialorrea, trismus, etc.El avance en los diversos procedimientos diagnósticos (imagen, microbiología) y terapéuticos (antibióticos, cirugía), así como la mejor atención del paciente crítico (UCI- REA), han sido decisivos en el diagnóstico y tratamiento precoz, identificar y tratar las complicaciones y mejorar el pronóstico y la mortalidad de los pacientes (AU)

Introduction: Deep neck infections (DNI) are potentially lethal processes and are susceptible to severe complications. This study shows an increment of the incidence and investigated the cause. More than 30% of cases are idiopathic, but they are commonly related to a dental or oropharyngeal infection. Material and methods: We present 286 consecutive cases in a retrospective 11-year study. We analysed the clinical picture, antecedents and concurrent diseases, and diagnostic and therapeutic approaches that could be related to developing a DNI. Results: A mayor increase in DNI incidence in our setting was seen in the last few years. The mayor complications were mediastinitis, septic shock with disseminated intravascular coagulation syndrome, necrotising fasciitis and acute respiratory failure. A lower cranial nerve palsy that develops into dysphagia and leukoencephalopathy are the most frequent sequela. We found 10% of aspiration pneumonia. Mortality in adults was 5.9% and in children, 6.2%. Conclusions: Deep neck infections constitute a medical and surgical emergency. Severe complications may arise in a short time. We must be vigilant to alarm symptoms such as dyspnea, stridor, pain in the floor of the mouth, sialohrrea, trismus, etc. Improvements in antibiotic therapy, diagnostic imaging and critical patient support modalities have decreased mortality and there is a better prognosis, with complications being identified and treated earlier (AU)

Remisión del hipercortisolismo tras suprarrenalectomía unilateral en paciente con enfermedad de Cushing persistente e hiperplasia adrenal macronodular / Remission of hypercortisolism after unilateral adrenalectomy in a patient with persistent Cushing’s disease and macronodular adrenal hyperplasia

Mujer de 22 años remitida en enero de 1997 a nuestro servicio con síntomas y signos de hipercortisolismo. El estudio hormonal y las pruebas funcionales y de imagen orientan a un origen hipofisario. Se realizó un cateterismo de senos petrosos inferiores que confirmó el diagnóstico de enfermedad de Cushing. Tras cirugía transesfenoidal se produjo remisión del cuadro, con recidiva a los 3 años, por lo que se realizó nueva cirugía hipofisaria y se remitió a la paciente para radioterapia. En años sucesivos persistió la hipersecreción de cortisol, lo que obligó al tratamiento adrenolítico continuado. En su evolución, las concentraciones de corticotropina mostraban tendencia a reducirse y una tomografía computarizada de abdomen mostró una masa hipodensa de 21 × 41 mm en la suprarrenal izquierda. La gammagrafía con yodocolesterol presentaba también una mayor captación a ese nivel. Basándonos en estos hallazgos y dada la persistencia del hipercortisolismo clínico y analítico, se decidió realizar una suprarrenalectomía izquierda vía laparoscópica. Tras esta nueva intervención, se hizo evidente una progresiva mejoría clínica y analítica, e incluso fue necesario el tratamiento sustitutivo con glucocorticoides. Aunque en el presente caso la autonomía funcional del nódulo no queda sólidamente demostrada, la eficacia de la suprarrenalectomía unilateral plantea con más firmeza esa hipótesis (AU)

A 22 years old female patient was initially referred to our department in January 1997 with symptoms and signs consistent with hypercortisolism. The basal hormonal study and functional testing and imaging oriented towards a pituitary origin. An inferior sinus petrosus venous sampling after CRH stimulus confirmed the pituitary origin of ACTH hypersecretion. After transsphenoidal resection of a pituitary microadenoma, analytical and clinical remission was achieved, with relapse three years later, so a new transsphenoidal surgery was performed and stereotactic fractionated radiation therapy was administered. In subsequent years, cortisol hypersecretion persisted, requiring continued medical treatment with increasing doses of adrenolitic drugs. In its evolution, ACTH levels showed a downward trend and abdominal CT scan showed a hypodense mass of 21 × 41 mm in the left adrenal. Iodocholesterol scan also showed increased uptake at this level. Based on these findings and given the persistence of hypercortisolism, left adrenalectomy was ultimately carried out by laparoscopic surgery in May 2008. After this new surgery, sings and symtomps of hypercortisolism improved markedly, and glucocorticoid replacement was needed. Although in this case the functional autonomy of the nodule is not firmly established, the efficacy of unilateral adrenalectomy is clear (AU)