Estudio de las alteraciones ecográficas y del estado nutricional de yodo en el espectro de la disfunción tiroidea en el embarazo en el departamento de Salud de Castellón

INTRODUCCIÓN La disfunción tiroidea es el segundo trastorno endocrinológico por su prevalencia que puede afectar a la mujer en edad reproductiva, por lo que es frecuente encontrar gestantes con el diagnóstico previo de hipo o hipertiroidismo. El hipotiroidismo está asociado a infertilidad, abortos de repetición, pre-eclampsia, retardo del crecimiento intrauterino, abruptio placentae, prematuridad y secuelas en los neonatos como alteraciones en el desarrollo neurológico y motor, siendo su máxima expresión el cretinismo. (2) Actualmente, los rangos de referencia de TSH (en ausencia de valores de referencia propios de cada región) en el embarazo, según la guía de la American Thyroid Association (ATA) del 2012 son: (8) Primer trimestre: 0,1-2,5 mUI/l Segundo trimestre: 0,2-3,0 mUI/l Tercer trimestre: 0,3-3,0 mUI/l Según las guías de la American Thyroid Association del 2012 como la Endocrine Society del 2012, (8) es recomendable tratar el hipotiroidismo clínico en gestantes con hormona tiroidea de forma precoz con un nivel de evidencia A para disminuir los efectos adversos sobre la salud materno-fetal. Sin embargo, en gestantes con hipotiroidismo subclínico, con ó sin anticuerpos antiperoxidasa positivos, la recomendación de tratar con hormona tiroidea para disminuir estas complicaciones, tiene un nivel de evidencia E. En este grupo las evidencias parecen ir más a favor de tratar aquellas con anticuerpos TPO positivos. (15) El yodo es un oligoelemento esencial para el organismo que interviene en la síntesis de hormonas tiroideas. Se adquiere exclusivamente por la dieta, siendo los alimentos con mayor contenido en yodo los procedentes del mar. (16)La dosis de suplemento recomendada de forma preconcepcional es de 150 µg/día, 200 µg/día durante la gestación y 300 ug/día en la lactancia. (19,39) La ecografía tiroidea constituye la prueba ¿gold standard¿ para la evaluación del volumen tiroideo y para la detección de nódulos Las alteraciones morfológicas tiroideas durante el embarazo han sido poco estudiadas, ya que hay escasos trabajos que estimen su prevalencia y además, existen algunas discrepancias en cuanto al abordaje y manejo de la enfermedad nodular en esta fase de la vida de la mujer. (42,43,44,45,46,47) JUSTIFICACION La controversia del tratamiento con hormona tiroidea en este grupo de pacientes, particularmente en aquellas con TSH > 2,5-10 mUI/l o < 10 mUI/l, con presencia o no de Ac TPO, hace necesario que se establezcan nuevos protocolos de actuación conjunta en los distintos centros hospitalarios. Nuestro trabajo pretende aportar nuevos datos que permitan una mejor comprensión del heterogéneo espectro clínico englobado bajo el término de disfunción tiroidea del embarazo (DTE). Consideramos que los datos aportados por la ecografía tiroidea en el primer trimestre de la gestación en los diferentes subgrupos de TSH (¿ 2,5 mUI/l, entre 2,5- 4 mUI/l y ¿ 4 mUI/l) pueden ser relevantes en este sentido. CONCLUSIONES 1. El Departamento de Salud de Castellón presenta un adecuado estado nutricional de yodo con los datos obtenidos en las yodurias en mujeres sanas no embarazadas según las recomendaciones de la OMS. 2. La población gestante del Departamento de Salud de Castellón es yodo-suficiente, según las recomendaciones de la OMS. Sin embargo la toma de un suplemento de yoduro potásico de 200 ug /día es fundamental para mantener un adecuado nivel de yoduria durante el embarazo. 3. La ecografía es el método de elección para valorar el volumen tiroideo en estudios poblacionales. El discreto aumento de volumen tiroideo observado en embarazadas en el primer trimestre de la gestación respecto a controles sanas no embarazadas es el esperado en regiones yodo-suficientes. 4. No hemos hallado diferencias estadísticamente significativas en el estado nutricional de yodo, en el volumen tiroideo, en la prevalencia de bocio ni en la prevalencia de nódulos en gestantes según sus niveles de TSH. 5. El volumen tiroideo en el grupo de gestantes se relaciona con los Ac TPO positivos. 6. En el grupo de gestantes con disfunción tiroidea, el volumen tiroideo se relaciona además con el IMC. 7. La presencia de nódulos tiroideos en las embarazadas se correlaciona de forma significativa positiva además de con la presencia de Ac TPO positivos con el IMC sin hallar ninguna relación con los niveles de TSH. 8. Las gestantes con nódulos tiroideos detectados mediante ecografía tiroidea en el primer trimestre no presentaron cambios significativos ni en su volumen ni en su diámetro máximo al final de la gestación. 9. El hallazgo ecográfico de una ecoestructura tiroidea heterogénea tiene un elevado valor diagnóstico para la detección de gestantes y controles con Ac TPO positivos y enfermedad tiroidea autoinmune. La especificidad fue del 100 %. 10. La sensibilidad de la ecografía sin embargo ha sido superior en mujeres no embarazadas. 11. La presencia de una ecoestructura tiroidea heterogénea en gestantes con anticuerpos antiperoxidasa positivos fue superior en el subgrupo con niveles de TSH ¿ 4 mUI/l. En este subgrupo, la especificidad del patrón ecográfico heterogéneo se mantuvo en el 100 %, igualándose la sensibilidad a la observada en mujeres no embarazadas, un 80 %. 12. La presencia de una ecoestructura tiroidea heterogénea al realizar una ecografía tiroidea en primer trimestre de embarazo, debería considerarse como un factor de riesgo para el cribado de TSH y Ac TPO. 13. En el grupo de mujeres control no embarazadas, la presencia de anticuerpos antiperoxidasa positivos se relacionó de forma significativa con el número de abortos, nivel de TSH, nódulos y ecoestructura tiroidea heterogénea. 14. No hemos hallado correlación positiva entre el número de abortos y los niveles de TSH ni en gestantes ni en controles. 15. La presencia de anticuerpos antiperoxidasa positivos sí se correlacionaba con una mayor tasa de abortos en controles, no así en gestantes. 16. La positividad de los Ac antiperoxidasa en gestantes se relacionó con el resto de variables ecográficas estudiadas: un mayor volumen tiroideo, mayor prevalencia de bocio, de nódulos tiroideos y de ecoestructura tiroidea heterogénea

Oligomeric enteral nutrition in undernutrition, due to oncology treatment-related diarrhea. Systematic review and proposal of an algorithm of action

Oncology treatment-related diarrhea and malnutrition appear together in oncological patients because of the disease itself, or the treatments that are administered for it. Therefore it is essential to carry out a nutritional treatment. Enteral nutrition formulas, containing peptides and medium chain triglycerides, can facilitate absorption in cases of malabsorption. There are few references to the use of enteral nutrition in the clinical society guidelines of patient management with oncology treatment-related diarrhea (OTRD). A bibliographic review of the studies with oligomeric enteral nutrition in OTRD found only nine studies with chemotherapy (all with the same oligomeric formula in which oral mucositis improves, while the rest of the outcomes show different results), and eight studies with radiotherapy (with different products and very heterogeneous results). We hereby present our action algorithm to supplement the diet of OTRD patients with an oligomeric enteral nutrition formula. The first step is the nutritional assessment, followed by the assessment of the functional capacity of the patient’s intestine. With these two aspects evaluated, the therapeutic possibilities available vary in degrees of complexity: These will range from the usual dietary recommendations, to supplementation with oral oligomeric enteral nutrition, along with complete enteral nutrition with oligomeric formula, and up to potentially total parenteral nutrition

A cross-sectional study examining the parametric thyroid feedback quantile index and its relationship with metabolic and cardiovascular diseases

The usual inverse correlation between thyrotropin (TSH) and thyroid hormone disappears in syndromes of central resistance to thyroid hormone, where both are high. TSH and thyroid hormone are also simultaneously high when there is an elevation of the set point of the thyroid regulation axis. This can be estimated with indices, such as the Parametric Thyroid Feedback Quantile-based Index (PTFQI), which was designed for the general population. The PTFQI is positively associated with diabetes prevalence, but association with other pathologies has not been yet explored. The aim of this project was to explore the potential relationship of the PTFQI with metabolic and cardiovascular disease in a sample of ambulatory adult patients from Spain

Multimorbidity patterns in patients with heart failure: an observational Spanish study based on electronic health records

Objectives To characterise the comorbidities of heart failure (HF) in men and women, to explore their clustering into multimorbidity patterns, and to measure the impact of such patterns on the risk of hospitalisation and mortality. Design Observational retrospective population study based on electronic health records. Setting EpiChron Cohort (Aragón, Spain). Participants All the primary and hospital care patients of the EpiChron Cohort with a diagnosis of HF on 1 January 2011 (ie, 8488 women and 6182 men). We analysed all the chronic diseases registered in patients’ electronic health records until 31 December 2011. Primary outcome We performed an exploratory factor analysis to identify the multimorbidity patterns in men and women, and logistic and Cox proportional-hazards regressions to investigate the association between the patterns and the risk of hospitalisation in 2012, and of 3-year mortality. Results Almost all HF patients (98%) had multimorbidity, with an average of 7.8 chronic diseases per patient. We identified six different multimorbidity patterns, named cardiovascular, neurovascular, coronary, metabolic, degenerative and respiratory. The most prevalent were the degenerative (64.0%) and cardiovascular (29.9%) patterns in women, and the metabolic (49.3%) and cardiovascular (43.2%) patterns in men. Every pattern was associated with higher hospitalisation risks; and the cardiovascular, neurovascular and respiratory patterns significantly increased the likelihood of 3-year mortality. Conclusions Multimorbidity is the norm rather than the exception in patients with heart failure, whose comorbidities tend to cluster together beyond simple chance in the form of multimorbidity patterns that have different impact on health outcomes. This knowledge could be useful to better understand common pathophysiological pathways underlying this condition and its comorbidities, and the factors influencing the prognosis of men and women with HF. Further large scale longitudinal studies are encouraged to confirm the existence of these patterns as well as their differential impact on health outcomes

Point-of-care lung ultrasound assessment for risk stratification and therapy guiding in COVID-19 patients. A prospective non-interventional study.

Background Lung ultrasound is feasible for assessing lung injury caused by coronavirus disease 2019 (COVID-19). However, the prognostic meaning and time-line changes of lung injury assessed by lung ultrasound in COVID-19 hospitalised patients are unknown. Methods Prospective cohort study designed to analyse prognostic value of lung ultrasound in COVID-19 patients by using a quantitative scale (lung ultrasound Zaragoza (LUZ)-score) during the first 72 h after admission. The primary end-point was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow and escalation of medical treatment during the first 72 h were secondary end-points. Results 130 patients were included in the final analysis; mean±sd age was 56.7±13.5 years. Median (interquartile range) time from the beginning of symptoms to admission was 6 (4–9) days. Lung injury assessed by LUZ-score did not differ during the first 72 h (21 (16–26) points at admission versus 20 (16–27) points at 72 h; p=0.183). In univariable logistic regression analysis, estimated arterial oxygen tension/inspiratory oxygen fraction ratio (PAFI) (hazard ratio 0.99, 95% CI 0.98–0.99; p=0.027) and LUZ-score >22 points (5.45, 1.42–20.90; p=0.013) were predictors for the primary end-point. Conclusions LUZ-score is an easy, simple and fast point-of-care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated by PAFI) to further refine risk stratification

Molecular characterization of multidrug resistant Enterobacterales strains isolated from liver and kidney transplant recipients in Spain

The objective of this study was to analyse the mechanisms of resistance to carbapenems and other extended-spectrum-?-lactams and to determine the genetic relatedness of multidrug-resistant Enterobacterales (MDR-E) causing colonization or infection in solid-organ transplantation (SOT) recipients. Prospective cohort study in kidney (n= 142), liver (n= 98) or kidney/pancreas (n= 7) transplant recipients between 2014 and 2018 in seven Spanish hospitals. We included 531 MDR-E isolates from rectal swabs obtained before transplantation and weekly for 4?6 weeks after the procedure and 10 MDR-E from clinical samples related to an infection. Overall, 46.2% Escherichia coli, 35.3% Klebsiella pneumoniae, 6.5% Enterobacter cloacae, 6.3% Citrobacter freundii and 5.7% other species were isolated. The number of patients with MDR-E colonization post-transplantation (176; 71.3%) was 2.5-fold the number of patients colonized pre-transplantation (71; 28.7%). Extended spectrum ?-lactamases (ESBLs) and carbapenemases were detected in 78.0% and 21.1% of MDR-E isolates respectively. In nine of the 247 (3.6%) transplant patients, the microorganism causing an infection was the same strain previously cultured from surveillance rectal swabs. In our study we have observed a low rate of MDR-E infection in colonized patients 4?6 weeks post-transplantation. E. coli producing blaCTX-M-G1 and K. pneumoniae harbouring blaOXA-48 alone or with blaCTX-M-G1 were the most prevalent MDR-E colonization strains in SOT recipients.Acknowledgements The authors thank Mª Jesús Lecea and Laura Álvarez for technical assistance. Tis research was supported by ‘Plan Nacional de I+D+i and Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias 13/01191), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, and the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0007, RD16/0016/0010, RD16/0016/0012, RD16/0016/0011, RD16/0016/0008, RD16/0016/0002). Te study was co-fnanced by the European Development Regional Fund “A way to achieve Europe” and the Operative Program Intelligent Growth 2014‐2020

Mediterranean diet and invasive breast cancer risk in the predimed trial

Trabajo presentado en el X Congreso Internacional de la Dieta Mediterránea, celebrado en Barcelona (España) del 02 al 03 de abril de 2014.[Introduction]: Rates of breast cancer incidence have been rising over the past 3 decades. Dietary factors may play a role in the risk of breast cancer. Some observational cohort studies have suggested that the Mediterranean diet may reduce the risk of breast cancer but no randomized controlled trial had investigated this issue. We aimed to evaluate the effect of two interventions with Mediterranean diet on the primary prevention of breast cancer in a randomized controlled trial. [Methods]: The PREDIMED study (Prevención con Dieta Mediterránea) is a randomized, singleblind, and controlled trial conducted in Spanish primary healthcare centres. Out of 4,282 women recruited (aged 60 to 80 years), 1,478 were assigned to a Mediterranean diet supplemented with extra-virgin olive oil, 1,288 to a Mediterranean diet supplemented with mixed nuts and 1,393 to a control diet (advice to reduce dietary fat). Primary analyses were performed on an intention-to-treat basis. Poisson regression analyses were used to assess the relationship between the nutritional intervention and the incidence of confirmed invasive breast cancer. [Results]: After a median of 4.3 years after randomization, participants in both Mediterranean diet groups (extra-virgin olive oil or nuts) had a 55% relative reduction (95%CI: 9% to 78%) in the risk of invasive breast cancer compared with participants assigned to a control group (with the recommendation to follow a low-fat diet). Observed rates (per 1000 person-years) were 1.14, 1.82 and 2.90 for the Mediterranean diet with extra-virgin olive oil group, the Mediterranean diet supplemented with nuts group and the control group, respectively. The multivariable-adjusted rate ratios versus the control group were 0.34 (95% CI: 0.14 to 0.83) for the Mediterranean diet with extra-virgin olive oil group, and 0.60 (95% CI: 0.26 to 1.35) for the Mediterranean diet supplemented with nuts group. [Conclusions]: This is the first large randomized trial assessing the role of a dietary pattern on breast cancer incidence. Our results suggest that an intervention promoting adherence to the Mediterranean dietary pattern, specially when it is supplemented with extra-virgin olive oil, may contribute to a substantial reduction in the incidence of invasive breast cancer risk in women 60 years and older. However, a longer follow-up of our participants is needed to obtain more precise estimates

Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma

PURPOSE: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance. METHODS: We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance. RESULTS: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance. CONCLUSIONS: We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer

Background. Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. Patients and Methods. A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. Results. A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. Conclusions. In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections