Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD). Trajectory inference identifies three phases of control tissue fibroblast activation, leading to myofibroblast enrichment in tumour samples: initial upregulation of inflammatory cytokines, followed by stress-response signalling and ultimately increased expression of fibrillar collagens. Myofibroblasts correlate with poor overall survival rates in LUAD, associated with loss of epithelial differentiation, TP53 mutations, proximal molecular subtypes and myeloid cell recruitment. In squamous carcinomas myofibroblasts were not prognostic despite being transcriptomically equivalent. These findings have important implications for developing fibroblast-targeting strategies for cancer therapy.

ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.

Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance. SIGNIFICANCE: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors.

¿Supuración crónica o pseudoquiste infectado? Una complicación de la eventroplastia con malla / Chronic suppuration or infected pseudocyst? A complication of incisional hernia repair with mesh

RESUMEN Las infecciones crónicas posteriores a reparaciones de la pared abdominal pueden presentarse como colecciones que involucran a la malla y suelen obligar a su extracción, mientras que los pseudoquistes son colecciones estériles con una gruesa pared fibrótica que debe ser extirpada para lograr la curación. Presentamos una paciente de 75 años con antecedente de eventroplastia, que consultó por un tumor abdominal de 6 meses de evolución, con características imagenológicas de pseudoquiste parietal. Durante la operación se encontró una malla preperitoneal no integrada a los tejidos y rodeada de "biofilm" y líquido turbio. La prótesis se retiró fácilmente y la aponeurosis, muy engrosada, se cerró borde a borde. El posoperatorio transcurrió sin incidentes y el cultivo desarrolló estafilococo aureus sensible a trimetoprima-sufametoxazol. Seis meses después, la evolución fue favorable y sin signos de recidiva.

ABSTRACT Chronic infections after abdominal wall repairs may present as collections involving the mesh which usually require removing the mesh, while pseudocysts are sterile collections with a thick fibrotic wall that must be removed to achieve healing. We report the case of a 75-year-old female patient with a history incisional hernia repair who sought medical advice due to an abdominal tumor which appeared 6 months before consultation with imaging tests suggestive of an abdominal wall pseudocyst. Surgery revealed a preperitoneal mesh without tissue integration surrounded by biofilm and cloudy fluid. The mesh was easily removed and the edges of the thick aponeurosis were sutured. The postoperative period evolved uneventful and the fluid culture was positive for staphylococcus aureus sensitive to trimethoprim-sufamethoxazole. Six months later the patient evolved with favorable outcome without recurrence.

Non-pharmacologic direct cost of a simplified strategy with glecaprevir/pibrentasvir for 8 weeks in naïve non-cirrhotic patients with hepatitis C implemented in clinical practice. The Just SIMPLE Study / Costes directos no farmacológicos de una estrategia simplificada con glecaprevir/pibrentasvir durante 8 semanas en pacientes naïve, no cirróticos, con hepatitis C, implementada en la práctica clínica. Estudio Just SIMPLE

Background and objective: The emergence of highly tolerable, effective, and shorter duration direct-acting antivirals (DAAs) regimens offers the opportunity to simplify hepatitis C virus management but medical costs are unknown. Thus, we aimed to determine the direct medical costs associated with a combo-simplified strategy (one-step diagnosis and low monitoring) to manage HCV infection within an 8-week glecaprevir/pibrentasvir (GLE/PIB) regimen in clinical practice in Spain. Patients and methods: Healthcare resources and clinical data were collected retrospectively from medical charts of 101 eligible patients at 11 hospitals. Participants were adult, treatment naïve subjects with HCV infection without cirrhosis in whom a combo-simplified strategy with GLE/PIB for 8 weeks were programmed between Apr-2018 and Nov-2018. Results: The GLE/PIB effectiveness was 100% (CI95%: 96.2–100%) in the mITT population and 94.1% (CI95%: 87.5–97.8%) in the ITT population. Three subjects discontinued the combo-simplified strategy prematurely, none of them due to safety reasons. Five subjects reported 8 adverse events, all of mild-moderate intensity. Combo-simplified strategy mean direct costs were 754.35±103.60€ compared to 1689.42€ and 2007.89€ of a theoretical 12-week treatment with 4 or 5 monitoring visits, respectively; and 1370.95€ and 1689.42€ of a theoretical 8-week with 3 or 4 monitoring visits, respectively. Only 4.9% of the subjects used unexpected health care resources. Conclusions: 8-week treatment with GLE/PIB combined with a combo simplified strategy in real-life offers substantial cost savings without affecting the effectiveness and safety compared to traditional approaches.(AU)

Antecedentes y objetivo: La aparición de regímenes antivirales de acción directa altamente tolerables, eficaces y de corta duración permite simplificar el manejo de la hepatitis C, pero los costes médicos se desconocen. Así, se pretende determinar los costes médicos directos asociados a una estrategia simplificada (diagnóstico en un solo paso y monitorización reducida) para controlar la infección por VHC con un régimen de 8 semanas de glecaprevir/pibrentasvir (GLE/PIB) en la práctica clínica en España. Pacientes y métodos: Los recursos sanitarios y los datos clínicos se recopilaron retrospectivamente de las historias médicas de 101 pacientes elegibles en 11 hospitales. Los participantes fueron sujetos adultos, sin tratamiento previo de la infección por VHC y sin cirrosis, en los que se programó una estrategia combinada simplificada con GLE/PIB durante 8 semanas entre abril y noviembre de 2018. Resultados: La eficacia de GLE/PIB fue del 100% (IC 95% 96,2-100) en la población mITT y del 94,1% (IC 95% 87,5-97,8) en la población ITT. Tres sujetos suspendieron prematuramente la estrategia combinada simplificada, ninguno de ellos por razones de seguridad. Cinco sujetos reportaron 8 acontecimientos adversos de intensidad leve-moderada. Los costes directos fueron de 754,35±103,60€ frente a 1.689,42€ y 2.007,89€ de un tratamiento teórico de 12 semanas con 4 o 5 visitas de monitorización, respectivamente; y 1.370,95€ y 1.689,42€ de un tratamiento teórico de 8 semanas con 3 o 4 visitas de monitorización, respectivamente. El 4,9% de los sujetos utilizaron recursos de atención médica inesperados. Conclusiones: En la vida real, el tratamiento de 8 semanas con GLE/PIB junto con una estrategia simplificada ofrece ahorros sustanciales de costos, sin afectar la eficacia y seguridad, en comparación con abordajes tradicionales.(AU)

Analysis of Immune Landscape in Pancreatic and Ileal Neuroendocrine Tumours Demonstrates an Immune Cold Tumour Microenvironment.

INTRODUCTION: Neuroendocrine tumours (NETs) are rare tumours with an increasing incidence. While low- and intermediate-grade pancreatic NET (PanNET) and small intestinal NET (siNET) are slow growing, they have a relatively high rate of metastasizing to the liver, leading to substantially worse outcomes. In many solid tumours, the outcome is determined by the quality of the antitumour immune response. However, the quality and significance of antitumour responses in NETs are incompletely understood. This study provides clinico-pathological analyses of the tumour immune microenvironment in PanNET and siNETs. METHODS: Formalin-fixed paraffin-embedded tissue from consecutive resected PanNETs (61) and siNETs (131) was used to construct tissue microarrays (TMAs); 1-mm cores were taken from the tumour centre, stroma, tumour edge, and adjacent healthy tissue. TMAs were stained with antibodies against CD8, CD4, CD68, FoxP3, CD20, and NCR1. T-cell counts were compared with counts from lung cancers. RESULTS: For PanNET, median counts were CD8+ 35.4 cells/mm2, CD4+ 7.6 cells/mm2, and CD68+ macrophages 117.7 cells/mm2. For siNET, there were CD8+ 39.2 cells/mm2, CD4+ 24.1 cells/mm2, and CD68+ 139.2 cells/mm2. The CD8+ cell density in the tumour and liver metastases were significantly lower than in the adjacent normal tissues, without evidence of a cell-rich area at the tumour edge that might have suggested immune exclusion. T-cell counts in lung cancer were significantly higher than those in PanNET and siNETs: CD8+ 541 cells/mm2 and CD4+ 861 cells/mm2 (p ≤ 0.0001). CONCLUSION: PanNETs and siNETs are immune cold with no evidence of T cell exclusion; the low density of immune infiltrates indicates poor antitumour immune responses.

Non-pharmacologic direct cost of a simplified strategy with glecaprevir/pibrentasvir for 8 weeks in naïve non-cirrhotic patients with hepatitis C implemented in clinical practice. The Just SIMPLE Study.

BACKGROUND AND OBJECTIVE: The emergence of highly tolerable, effective, and shorter duration direct-acting antivirals (DAAs) regimens offers the opportunity to simplify hepatitis C virus management but medical costs are unknown. Thus, we aimed to determine the direct medical costs associated with a combo-simplified strategy (one-step diagnosis and low monitoring) to manage HCV infection within an 8-week glecaprevir/pibrentasvir (GLE/PIB) regimen in clinical practice in Spain. PATIENTS AND METHODS: Healthcare resources and clinical data were collected retrospectively from medical charts of 101 eligible patients at 11 hospitals. Participants were adult, treatment naïve subjects with HCV infection without cirrhosis in whom a combo-simplified strategy with GLE/PIB for 8 weeks were programmed between Apr-2018 and Nov-2018. RESULTS: The GLE/PIB effectiveness was 100% (CI95%: 96.2-100%) in the mITT population and 94.1% (CI95%: 87.5-97.8%) in the ITT population. Three subjects discontinued the combo-simplified strategy prematurely, none of them due to safety reasons. Five subjects reported 8 adverse events, all of mild-moderate intensity. Combo-simplified strategy mean direct costs were 754.35±103.60€ compared to 1689.42€ and 2007.89€ of a theoretical 12-week treatment with 4 or 5 monitoring visits, respectively; and 1370.95€ and 1689.42€ of a theoretical 8-week with 3 or 4 monitoring visits, respectively. Only 4.9% of the subjects used unexpected health care resources. CONCLUSIONS: 8-week treatment with GLE/PIB combined with a combo simplified strategy in real-life offers substantial cost savings without affecting the effectiveness and safety compared to traditional approaches.

Diet Quality Is Associated with a High Newborn Size and Reduction in the Risk of Low Birth Weight and Small for Gestational Age in a Group of Mexican Pregnant Women: An Observational Study.

A high-quality diet during pregnancy may have positive effects on fetal growth and nutritional status at birth, and it may modify the risk of developing chronic diseases later in life. The aim of this study was to evaluate the association between diet quality and newborn nutritional status in a group of pregnant Mexican women. As part of the ongoing Mexican prospective cohort study, OBESO, we studied 226 healthy pregnant women. We adapted the Alternated Healthy Eating Index-2010 for pregnancy (AHEI-10P). The association between maternal diet and newborn nutritional status was investigated by multiple linear regression and logistic regression models. We applied three 24-h recalls during the second half of gestation. As the AHEI-10P score improved by 5 units, the birth weight and length increased (ß = 74.8 ± 35.0 g and ß = 0.3 ± 0.4 cm, respectively, p < 0.05). Similarly, the risk of low birth weight (LBW) and small for gestational age (SGA) decreased (OR: 0.47, 95%CI: 0.27-0.82 and OR: 0.55, 95%CI: 0.36-0.85, respectively). In women without preeclampsia and/or GDM, the risk of stunting decreased as the diet quality score increased (+5 units) (OR: 0.62, 95%IC: 0.40-0.96). A high-quality diet during pregnancy was associated with a higher newborn size and a reduced risk of LBW and SGA in this group of pregnant Mexican women.

Inserción laboral del cirujano joven en la Ciudad de Buenos Aires. Necesidad de reestructuración del sistema de formación del cirujano general / Young surgeons entering the workforce in the City of Buenos Aires. Need for restructuring of the general surgery training system

RESUMEN Antecedentes: la formación en cirugía se mantuvo uniforme desde la instauración del modelo de re sidencias. El avance de la ciencia ha llevado a la superespecialización y un 70% de los cirujanos conti núan en formación con una especialidad posbásica. Objetivos: identificar la proporción de cirujanos que derivan horas a otra actividad y analizar la inser ción laboral del cirujano. Material y métodos: estudio prospectivo, descriptivo, de corte transversal. 1) Encuesta, 2) Registros de la Dirección General de Docencia e Investigación, 3) Concursos y Perfiles profesionales de acceso público. Resultados: sobre 435 encuestados, al finalizar la residencia, un 73,3% continuó su formación en una posbásica. Solamente un 24,7% se insertó inmediatamente en el mercado como cirujano general. En cuanto a la inserción laboral actual de aquellos que finalizaron la formación como cirujano general, apenas un 17,4% se desempeña de manera exclusiva como cirujano general. Conclusiones: la falta de confianza para actuar de manera independiente y la necesidad de completar 4 años de formación para ingresar en el campo de interés aparecen como las problemáticas para resol ver. Se propone un programa de 5 años con formato 2+3. El período de formación básica abordará en 24 meses las generalidades de la práctica quirúrgica. El segundo, de formación avanzada, desarrollará en profundidad la subespecialidad elegida. El quinto año otorgará a todos la posibilidad de actuar a modo de cirujano independiente. Planteada como una subespecialidad, la Cirugía General volvería a ser un fin en sí misma y no un medio para llegar a una subespecialidad.

ABSTRACT Background: Training in surgery has remained relatively uniform since the residency programs were introduced. The continuous advances in science have led to the progressive super-specialization of surgeons; 70% of them continue their training with a subspecialty. Objectives: The aim of this study was to identify the proportion of surgeons who dedicate hours of their practice in another activity and to analyze how surgeons enter the workforce. Material and methods: We conducted a prospective and descriptive cross-sectional study with data from a survey, records of the General Directorate of Teaching and Research, and records of competitive selection processes and professional profiles available online. Results: Of 435 survey respondents, 73.3% of the resident graduates continued postresidency training in a surgical subspecialty. Only 24.7% immediately started working in general surgery. Among the graduate trainees in general surgery, only 17.4% were exclusively dedicated to general surgery. Conclusions: The lack of confidence to perform procedures independently and the need for completing 4 years of training in the residency program in general surgery to start training in the professional field of interest, appear as the issued to be solved. We propose a 5-year program with a 2+3 model. The initial period comprises 24 months of basic training covering the general aspects of surgical practice. The second period of advanced training will provide thorough training in the subspecialty chosen. In the last year of the 5-year program trainees will have the opportunity to act as attending surgeons. General surgery, conceived as a subspecialty, would regain its status as an objective and no longer a pathway to become a subspecialist.

Prevalence and associated factors of iron deficiency in Spanish children aged 1 to 11 years.

Iron deficiency (ID) is the most common nutritional deficiency affecting children worldwide. Most traditional laboratory parameters to assess ID can be altered by infections or other inflammatory states, including obesity. The aims of this study were to determine the prevalence of ID in healthy children and to analyse associated factors, avoiding potential confounding factors through the use of serum transferrin receptor (sTfR), reticulocyte haemoglobin content and sTfR/log ferritin index. A cross-sectional population-based study was conducted on 951 children aged 1 to 11 years in Almería (Spain). ID was detected in 7.7% of children and iron deficiency anaemia in 0.9%. Multivariate analysis identified the following as independent risk factors: age under 5 years (OR: 2.2, 95% CI: 1.35-3.6); excessive consumption of cow's milk and dairy products (OR: 1.87, 95% CI: 1.13-3.1); and insufficient consumption of vegetables (OR: 2.7, 95% CI: 1.2-6.1).Conclusions: Using a combination of iron status parameters with greater discriminatory power than classical measures, this study detected a considerable iron deficiency prevalence in Spanish children. Younger children and specific dietary habits exhibit a particular risk for ID, so special attention should be paid to this population. What is Known: • Iron deficiency remains the most prevalent nutritional deficit worldwide, and children aged under 3 years are the most vulnerable to this condition. • Accurate assessment of iron status, based on a combination of biochemical indicators, can often be complicated. What is New: • Iron deficiency continues to present a health problem in Spanish children aged 1 to 11 years, considering the serum transferrin receptor and reticulocyte haemoglobin content for diagnosis. • Excessive consumption of dairy products and low consumption of vegetables are independent risk factors for iron deficiency.

Co-ordination between xylem anatomy, plant architecture and leaf functional traits in response to abiotic and biotic drivers in a nurse cushion plant.

BACKGROUND AND AIMS: Plants in dry Mediterranean mountains experience a double climatic stress: at low elevations, high temperatures coincide with water shortage during summer, while at high elevations temperature decreases and water availability increases. Cushion plants often act as nurses by improving the microclimate underneath their canopies, hosting beneficiary species that may reciprocally modify their benefactors' microenvironment. We assess how the nurse cushion plant Arenaria tetraquetra subsp. amabilis adjusts its hydraulic system to face these complex abiotic and biotic constraints. METHODS: We evaluated intra-specific variation and co-ordination of stem xylem anatomy, leaf functional traits and plant architecture in response to elevation, aspect and the presence of beneficiary species in four A. tetraquetra subsp. amabilis populations in the Sierra Nevada mountains, southern Spain. KEY RESULTS: Xylem anatomical and plant architectural traits were the most responsive to environmental conditions, showing the highest mutual co-ordination. Cushions were more compact and had smaller, more isolated conductive vessels in the southern than in the northern aspect, which allow minimization of the negative impacts of more intense drought. Only vessel size, leaf mass per area and terminal branch length varied with elevation. Nurse cushions co-ordinated plant architecture and xylem traits, having higher canopy compactness, fewer leaves per branch and fewer, more isolated vessels than non-nurse cushions, which reflects the negative effects of beneficiary plants on nurse water status. In non-nurse cushions, plant architecture co-ordinated with leaf traits instead. The interacting effects of aspect and elevation on xylem traits showed that stress due to frost at high elevation constrained xylem anatomy in the north, whereas stress due to drought had a parallel effect in the south. CONCLUSIONS: Trait co-ordination was weaker under more demanding environmental conditions, which agrees with the hypothesis that trait independence allows plants to better optimize different functions, probably entailing higher adjustment potential against future environmental changes.

Status of folate in healthy children in Almeria.

The objective of this study is to establish reference values for folic acid in a healthy population of children aged 4-11 years and to examine related epidemiological, dietary and analytical factors. A cross-sectional study of 658 healthy children aged 4-11 years was made. Epidemiological, socioeconomic and dietary variables were analysed, the BMI Z-score was obtained, levels of serum folate and serum vitamin B12 were determined and haematological, iron status and erythropoietic activity parameters were examined. The study data were analysed by non-parametric tests and linear multiple regression. The mean folate value was 8.6 ± 4.6 ng/mL (95% reference interval: 2.8-20 ng/mL). A level < 3 ng/mL (5th percentile) was considered as folate deficiency (4.6% of subjects). No child reported symptoms related to this deficiency. Folate values were significantly lower with age (p < 0.01), low NSE and low parental educational level (p: 0.0001). No relationship was found between folates and the analytical variables. According to multivariate linear regression, the variables significantly associated with serum folate were age, socioeconomic level and vitamin B12.Conclusions: Serum folate levels in healthy school children are described. Age, socioeconomic level and serum vitamin B12 are factors associated with folate status. Specific cut-off values for a paediatric population should be defined. What is Known: • Folic acid is an essential micronutrient for optimal growth and development; its deficit is associated with adverse health effects. • The studies on their status and deficit are not comparable due to a lack of agreement on appropriate indicators and reference values. What is New: • This study reports the levels of serum folate in a large population of healthy schoolchildren, with strict inclusion criteria in a developed country and identifies the associated sociodemographic, dietary and analytical (vitamin B12, iron parameters and erythropoietic activity) factors, avoiding potential confusion.

Cardiovascular mortality and cardiovascular event rates in patients with inflammatory rheumatic diseases in the CARdiovascular in rheuMAtology (CARMA) prospective study-results at 5 years of follow-up.

OBJECTIVES: To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. METHODS: This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. RESULTS: Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. CONCLUSIONS: Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

Compulsory admissions and preferences in decision-making in patients with psychotic and bipolar disorders.

PURPOSE: Participation in medical decisions and taking into account patients' values and preferences are especially important for psychiatric patients who may be treated against their will. The increasing rates of coercive measures and the underlying clinical, ethical, and legal issues highlight the need to examine their use in psychiatry. Although limited congruence in decision-making preferences may be on the basis of these coercive practices, this issue has not been adequately addressed. We explore the relationship between compulsory admissions and congruence in decision-making preferences in mental health settings. METHODS: Cross-sectional study among 107 outpatients with DSM diagnoses of schizophrenia of bipolar disorder using the Control Preference Scale to assess congruence in decision-making experienced and preferred style. History of compulsory admissions was obtained through review of available records. Descriptive statistics and multivariate analyses were used. RESULTS: 70% of patients reported experiencing their preferred style of decision-making and 44% patients had history of compulsory admissions. These patients were more autonomous and preferred to take a more active role. The degree of congruence was lower in patients with previous compulsory admissions. The best predictors of compulsory admissions were not having a regular doctor and the unmatched participation preferences. CONCLUSIONS: Patients who experienced a different level of participation in decision-making than desired more frequently had compulsory admissions. We propose to assess participation preferences each time a relevant treatment decision is about to be made and tailor care accordingly. We identified several factors leading to compulsory admissions that can be modified to prevent further coercive measures.

Prediction of hypocalcemia after total thyroidectomy using indocyanine green angiography of parathyroid glands: A simple quantitative scoring system.

BACKGROUND: Hypocalcemia is one of the most common complications after total thyroidectomy. Recently, indocyanine green (ICG) angiography of the parathyroid glands (PGs) has been suggested as a reliable tool for predicting postoperative hypocalcemia. The aim of our study was to evaluate the performance of a simple quantitative score based on ICG angiography of the PGs (4-ICG score) for predicting postoperative hypocalcemia. METHODS: Thirty nine consecutive patients who underwent total thyroidectomy for multinodular goiter were included. For each patient, the 4-ICG score was calculated, adding the individual viability value of the four PGs. Discrimination and correlation analyses were performed. RESULTS: In 32/39 patients, the four PGs were identified. Patients with postoperative hypocalcemia (n = 6, 19%) had a lower 4-ICG score (2.5 [1.8-3.3] vs. 4.0 [3.0-6.0]; p = 0.003). The 4-ICG score showed good discrimination in terms of predicting postoperative hypocalcemia (AUC = 0.875 (0.710-0.965); p = 0.001) and a good correlation with postoperative parathyroid function. CONCLUSIONS: The 4-ICG score predicts postoperative hypocalcemia and correlates well with postoperative parathyroid function in patients undergoing total thyroidectomy for multinodular goiter.

The usefulness of reticulocyte haemoglobin content, serum transferrin receptor and the sTfR-ferritin index to identify iron deficiency in healthy children aged 1-16 years.

This cross-sectional study, conducted on a population-based representative sample, evaluates the usefulness of reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) to recognise iron deficiency (ID) without anaemia, provides specific cut-off points for age and gender, and proposes a new definition of ID. A total of 1239 healthy children and adolescents aged 1-16 years were included. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, CHr, sTfR, and sTfR-F index were determined. ROC curves were obtained and sensitivity, specificity, predictive values, likelihood ratios, and accuracy for each specific cut-off points were calculated. Seventy-three had ID without anaemia. Area under the curve for sTfR-F index, sTfR and CHr were 0.97 (CI95% 0.95-0.99), 0.87 (CI95% 0.82-0.92) and 0.68 (CI95% 0.61-0.74), respectively. The following cut-off points defined ID: sTfR-F Index > 1.5 (1-5 years and 12-16 years boys) and > 1.4 (6-11 years and 12-16 years girls); sTfR (mg/L) > 1.9 (1-5 years), > 1.8 (6-11 years), > 1.75 (12-16 years girls) and > 1.95 (12-16 years boys); and CHr (pg) < 27 (1-5 years) and < 28.5 (6-16 years).Conclusions: CHr, sTfR and the sTfR-F index are useful parameters to discriminate ID without anaemia in children and adolescents, and specific cut-off values have been established. The combination of these new markers offers an alternative definition of ID with suitable discriminatory power. What is Known: • In adults, reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) have been evaluated and recognised as reliable indicators of iron deficiency (ID). • Clinical manifestations of ID may be present in stages prior to anaemia, and the diagnosis of ID without anaemia continues to pose problems. What is New: • CHr, sTfR and the sTfR-F index are useful parameters in diagnosis of ID in childhood and adolescence when anaemia is not present. • We propose a new strategy for the diagnosis of ID in childhood and adolescence, based on the combination of these measures, which offer greater discriminatory power than the classical parameters.

Reference Values of Reticulocyte Hemoglobin Content in Healthy Adolescents.

Assessing iron status in a pediatric population is not easy, as it is based on parameters that undergo physiological variations in childhood and adolescence. Analysis of the reticulocyte hemoglobin content (CHr) to screen for iron deficiency may increase the accuracy of diagnosis, but, to date, reference values in healthy adolescents have not been adequately determined. A cross-sectional study was conducted on a population-based representative sample in the city of Almería (Spain), with 253 healthy non-iron-deficient (ID) subjects, aged 12 to 16 years. The mean CHr value was 31.6±1.3 pg. The CHr 2.5 percentile was 28.7 pg. There were no significant differences as regards age or sex. In the multivariate linear regression analysis, sex did not influence the variability of CHr, but it was related to age. CHr was influenced by hemoglobin and the Mentzer index, as well as by functional iron indicators such as erythrocyte protoporphyrin and serum transferrin receptor. These independent variables predicted two thirds of the variability in healthy adolescents (R=0.55). This study provides CHr reference ranges in healthy adolescents for use in clinical practice for the early detection of ID states. In populations with similar sociodemographic characteristics, values above the 2.5 percentile rule out ID, as values under the 2.5 percentile could be suggestive of functional ID.

Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children.

Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross-sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9±1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability.

Reference values of serum transferrin receptor (sTfR) and sTfR/log ferritin index in healthy children.

ABSTARCT The aims of this study were to determine appropriate reference ranges for serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) in healthy children and their relationship with iron parameters, erythropoiesis, and other conditions presented by the subject. A total of 902 children with normal iron status, aged 1-11 years, were included in a cross-sectional study. A physical examination was conducted and z-score of body mass index (zBMI) obtained. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, sTfR, and sTfR/log ferritin were determined. Linear multiple regression was applied to identify the factors that determined sTfR and sTfR-F index variability. Mean values for sTfR and sTfR-F index were 1.22 ± 0.28 mg/L (95% confidence interval [CI]: 1.2-1.23) and 0.87 ± 0.25 (95% CI: 0.85-0.88). The reference intervals (2.5th to 97.5th percentiles [P2.5-P97.5]) were 0.78-1.9 mg/L and 0.49-1.46, respectively. sTfR and sTfR-F values decreased with age (P <.03 and P <.0001, respectively). No changes were observed with sex. Changes in sTfR and sTfR-F index were consistent with ferritin and erythropoietin variations. Iron biomarkers, erythropoietin, and zBMI predicted 19% and 18.1% of the sTfR and sTfR-F index variability. The results provide reference ranges for sTfR and sTfR-F index in healthy children for clinical use in the assessment of body iron status. Both biomarkers are predicted by iron parameters, erythropoietin, and zBMI.

Thyroid Function and Thyroid Autoimmunity in Relation to Weight Status and Cardiovascular Risk Factors in Children and Adolescents: A Population-Based Study.

OBJECTIVE: In obese subjects, slight increases have been observed in thyrotropin [thyroid-stimulating hormone (TSH)] levels, but data in children are scarce. The aim of this study was to evaluate whether thyroid function and autoimmunity vary with weight status in a healthy population of children and adolescents and to determine whether hyperthyrotropinemia is associated with any cardiovascular risk factor. METHODS: This cross-sectional epidemiological study was conducted in Almería (Spain) on a representative sample of 1317 healthy subjects aged 2-16 years. Thyroid function, thyroid autoimmunity and cardiovascular risk factors were measured. Chi-square test, analysis of variance and multiple linear regression were used in the statistical analyses. RESULTS: The obese children and adolescents had thyrotropin levels (mean ± standard deviation) of 3.12±2.44 mU/L. These levels were higher than those of overweight subjects (2.79±1.51 mU/L) and of normal weight subjects (2.73±1.30 mU/L) (p=0.02). Levels of free thyroxine and urinary iodine did not differ significantly between the groups. The prevalence (95% confidence interval) of thyroid autoimmunity was lower in the individuals with normal weight (2.9%; 2.0-4.2) than in the overweight (6.3%; 3.9-9.9) and obese subjects (5.6%, 2.5-11.3) (p=0.02). TSH levels were associated with obesity (ß=0.36; p<0.001) and thyroid autoimmunity (ß=1.10; p<0.001). They were not associated with any cardiovascular risk factor. CONCLUSION: Obese children and adolescents had higher levels of thyrotropin than those who were overweight and of normal weight. The differences among the groups were of very little clinical significance and could possibly be linked to the higher prevalence of thyroid autoimmunity in obese subjects. The hyperthyrotropinemia in these subjects was not associated with any cardiovascular risk factor.

Counting 241Am in the BfS human skull phantom on contact-evaluation in the human monitoring laboratory.

Skull counting can be used to assess the activity of radionuclides internally deposited in the bone. The Human Monitoring Laboratory (HML) at Health Canada conducted the measurement of 241Am in the BfS (Bundesamt für Strahlenschuts) skull phantom on contact with the skull for various positions. By placing the detector in contact, the HML can improve the counting efficiency by over 20% compared to placing the detector 1 cm above the surface of the skull. Among all the positions tested, the forehead position is the preferred counting geometry due to the design of HML's counting facility and the comfort it would provide to the individual being counted, although this counting position did not offer the highest counting efficiency for the gamma rays (either the 59.5 keV or the 26.3 keV) emitted by 241Am.