CRISPR loss of function screening to identify genes involved in human primordial germ cell-like cell development.

Despite our increasing knowledge of molecular mechanisms guiding various aspects of human reproduction, those underlying human primordial germ cell (PGC) development remain largely unknown. Here, we conducted custom CRISPR screening in an in vitro system of human PGC-like cells (hPGCLCs) to identify genes required for acquisition and maintenance of PGC fate. Amongst our candidates, we identified TCL1A, an AKT coactivator. Functional assessment in our in vitro hPGCLCs system revealed that TCL1A played a critical role in later stages of hPGCLC development. Moreover, we found that TCL1A loss reduced AKT-mTOR signaling, downregulated expression of genes related to translational control, and subsequently led to a reduction in global protein synthesis and proliferation. Together, our study highlights the utility of CRISPR screening for human in vitro-derived germ cells and identifies novel translational regulators critical for hPGCLC development.

APC and P53 mutations synergise to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with the majority of cases initiated by inactivation of the APC tumour suppressor. This results in the constitutive activation of canonical WNT pathway transcriptional effector ß-catenin, along with induction of WNT feedback inhibitors, including the extracellular palmitoleoyl-protein carboxylesterase NOTUM which antagonises WNT-FZD receptor-ligand interactions. Here, we sought to evaluate the effects of NOTUM activity on CRC as a function of driver mutation landscape. DESIGN: Mouse and human colon organoids engineered with combinations of CRC driver mutations were used for Notum genetic gain-of-function and loss-of-function studies. In vitro assays, in vivo endoscope-guided orthotopic organoid implantation assays and transcriptomic profiling were employed to characterise the effects of Notum activity. Small molecule inhibitors of Notum activity were used in preclinical therapeutic proof-of-principle studies targeting oncogenic Notum activity. RESULTS: NOTUM retains tumour suppressive activity in APC-null adenomas despite constitutive ß-catenin activity. Strikingly, on progression to adenocarcinoma with P53 loss, NOTUM becomes an obligate oncogene. These phenotypes are Wnt-independent, resulting from differential activity of NOTUM on glypican 1 and 4 in early-stage versus late-stage disease, respectively. Ultimately, preclinical mouse models and human organoid cultures demonstrate that pharmacological inhibition of NOTUM is highly effective in arresting primary adenocarcinoma growth and inhibiting metastatic colonisation of distal organs. CONCLUSIONS: Our findings that a single agent targeting the extracellular enzyme NOTUM is effective in treating highly aggressive, metastatic adenocarcinomas in preclinical mouse models and human organoids make NOTUM and its glypican targets therapeutic vulnerabilities in advanced CRC.

Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

Effect of sainfoin proanthocyanidins on milk fatty acids from ewes rearing suckling lambs.

Proanthocyanidins (PAC) can modulate the fatty acid (FA) profile of animal products and make them healthier for human consumption, but their effects are highly variable depending on several factors such as PAC chemical structure or dose. The present experiment aimed to evaluate the effect of PAC on the milk FA profile of Rasa Aragonesa ewes fed fresh sainfoin (PAC-containing forage legume) during the rearing period of suckling lambs (4 weeks postlambing). Twenty lactating ewes rearing a single male lamb were fed fresh sainfoin ad libitum plus 200 g/d of barley. Half the ewes were orally dosed with 100 mL of water (Sainfoin Group; n = 10) and the other half with polyethylene glycol (50 g PEG4000/100 mL water, Sainfoin + PEG Group; n = 10) to block PAC effects. Sainfoin and milk samples were collected weekly to determine their FA profile by gas chromatography. Fresh sainfoin contents of C18:3n-3 decreased from week 1 to week 2, C16:0 and C18:0 increased from week 1 to week 3, and C18:2n-6 did not change. Regarding milk FA, there were minor effects of PAC on milk-saturated FA. During the whole study, the presence of PAC increased C18:0, C18:2n-6, C18:3n-3 and total polyunsaturated FA (PUFA) n-6 and n-3, and decreased C18:1 t11, branched- and odd-chain FA. However, the decrease of milk concentrations of trans-monounsaturated FA, C18:1 t10, and total conjugated linoleic acid (CLA) and the increase of total PUFA due to the presence of PAC occurred only in week 1, while CLA c9,t11 was lower during weeks 1 and 2. The canonical analyses confirmed the differences between treatments in the FA profile of milk. Overall, the use of fresh sainfoin in the diet of lactating ewes resulted in a beneficial modification of the concentration of several milk FAs, suggesting some changes in ruminal biohydrogenation.

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Protection of Regulatory T Cells from Fragility and Inactivation in the Tumor Microenvironment.

Fragility of regulatory T (Treg) cells manifested by the loss of neuropilin-1 (NRP1) and expression of IFNγ undermines the immune suppressive functions of Treg cells and contributes to the success of immune therapies against cancers. Intratumoral Treg cells somehow avoid fragility; however, the mechanisms by which Treg cells are protected from fragility in the tumor microenvironment are not well understood. Here, we demonstrate that the IFNAR1 chain of the type I IFN (IFN1) receptor was downregulated on intratumoral Treg cells. Downregulation of IFNAR1 mediated by p38α kinase protected Treg cells from fragility and maintained NRP1 levels, which were decreased in response to IFN1. Genetic or pharmacologic inactivation of p38α and stabilization of IFNAR1 in Treg cells induced fragility and inhibited their immune suppressive and protumorigenic activities. The inhibitor of sumoylation TAK981 (Subasumstat) upregulated IFNAR1, eliciting Treg fragility and inhibiting tumor growth in an IFNAR1-dependent manner. These findings describe a mechanism by which intratumoral Treg cells retain immunosuppressive activities and suggest therapeutic approaches for inducing Treg fragility and increasing the efficacy of immunotherapies.

Dual-energy CT: Technical considerations and clinical applications.

Although dual-energy CT was initially described by Hounsfield in 1973, it remains underused in clinical practice. It is therefore important to emphasize the clinical benefits and limitations of this technique. Iodine mapping makes it possible to quantify the uptake of iodine, which is very important in characterizing tumors, lung perfusion, pulmonary nodules, and the tumor response to new treatments. Dual-energy CT also makes it possible to obtain virtual single-energy images and virtual images without iodinated contrast or without calcium, as well as to separate materials such as uric acid or fat and to elaborate hepatic iron overload maps. In this article, we review some of the clinical benefits and technical limitations to improve understanding of dual-energy CT and expand its use in clinical practice.

Predictors of Rehabilitation Referral Among Cardiovascular Surgical Patients.

Objective: Cardiovascular disease (CVD) continues to be the leading cause of mortality globally. Cardiac rehabilitation (CR) programs act by modifying the evolution of CVD and mortality; however, CR programs are under-used. The aim was to determine the profile of patients that received rehabilitation after cardiac surgery. Patients and Methods: A retrospective observational study was conducted from January 2017 to December 2017 at a single center. The study sample was chosen among patients admitted to the Intensive Care Unit of the Hospital Gregorio Marañón/Gregorio Marañón General University Hospital. Socio-demographic and clinical variables were collected. Results: In the present study, 336 patients underwent cardiac surgery of which 63.8% were men and 87.1% had ≥1 cardiovascular risk factors. Of the total cohort, 24.7% were operated for ischemic heart disease, 47.9% valvulopathy, 11% underwent combined surgery, 3.6% cardiac transplantation, 6.5% aneurysms, and 3.9% congenital disease. In-hospital respiratory rehabilitation was prescribed to all patients. Only 4.8% of the patients received motor rehabilitation and 13.8% were referred to CR. We found higher referral rates among patients with more cardiovascular risk factors, <65 years of age, and those undergoing coronary surgery and heart transplantation. Age, ischemic heart disease, and overweight were independent predictors of CR referral. Conclusion: The benefit of CR programs after cardiac surgery is widely described; however, the referral rate to CR remains low. It is crucial to optimize referral protocols for these patients.

Identification of extraocular extension in uveal melanoma by ophthalmological ultrasound.

BACKGROUND AND PURPOSE: Uveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound. MATERIAL AND METHODS: A descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study. RESULTS: Ten patients with an average age of 72.3 years were included. The largest proportion of them were medium-sized tumours, followed by large and small ones. The most frequent morphology of the primary tumour was cupuliform. All the EE presented lower internal reflectivity compared to the primary tumour. No trans-scleral connection bridges were found between the primary tumour and the EE in the ultrasound studies. 50% of patients underwent primary enucleation at the time of diagnosis of intraocular MU due to the presence of the EE, and the remaining 50% presented the EE after initial treatment of the primary tumour with I125 brachytherapy. Sixty percent of the patients presented with posterior EE, and were therefore diagnosed with ultrasound A and B. The most frequent histopathological pattern with 87.5% of patients was the epithelioid pattern. DISCUSSION: Ultrasound scanning in patients with MU is mandatory for diagnosis and follow-up of EE. BMU and A and B ultrasound are the test of choice for anterior and posterior EE, respectively. EE have particular ultrasound characteristics such as low internal reflectivity, regularity of their contour and their location usually adjacent to the base of the primary intraocular tumor.

Effects of feeding sainfoin proanthocyanidins to lactating ewes on intake, milk production and plasma metabolites.

There is increasing interest in using sainfoin (Onobrychis viciifolia) to feed sheep, but it contains proanthocyanidins (PACs), and the associated effects of PAC on sheep production are not well-known. The aim of the study was to assess the effect of the presence of PAC from sainfoin, through the inclusion of polyethylene glycol (PEG), on the intake and productive parameters of local ewes bearing one male lamb. For the experiment, 20 ewes and their newborn male lambs were placed in individual indoor cages. All ewes were fed ad libitum fresh sainfoin plus 200 g/d barley. Twice daily, half of the ewes were orally dosed with only water (Sainfoin Group; n = 10), and the other half were orally dosed with 100 g/d PEG 4000 per ewe (Sainfoin + PEG Group; n = 10). Sucking lambs were permanently housed with their dams until they reached 10-12 kg BW. The intake of sainfoin was recorded daily, and its chemical composition was analysed. Weekly, the BW, body condition score (BCS), milk yields and individual milk and blood samples were recorded. At the beginning and end of the experiment, faecal samples were collected from ewes and analysed for the anthelmintic role of PAC. The chemical composition, polyphenol content and antioxidant capacity of the diet and milk were analysed. The presence of PAC did not affect the intake, BW, BCS or milk yield of the dams (P > 0.05); however, all parameters were affected by the week of lactation (P < 0.05). Milk components were affected by the week of lactation (P < 0.001), but only the polyphenol and urea contents were reduced in the presence of PAC (P < 0.01). Similarly, the presence of PAC decreased the plasma urea concentration (P < 0.01) without effect on the rest of metabolites, polyphenols and antioxidant activity (P > 0.05). The presence of PAC had no effect on parasitism (P > 0.05). In conclusion, the presence of PAC had no relevant effects on milk production, although it affected protein metabolism, as indicated by the urea contents in milk and plasma.

[Prevalence of diabesity in the Spanish working population: influence of sociodemographic variables and tobacco consumption].

BACKGROUND: Obesity predisposes to type 2 diabetes so often that the combination is called diabesity. The aim of this study was to determine the prevalence of diabesity in the working population and to analyze the variables associated with it. METHOD: Cross-sectional study between January 2019 and June 2020 by 418,343 workers from 18 to 67 year-old, from different professions and Spanish geographic areas. The prevalence of diabesity was determined with six different for-mulae for obesity: BMI (body mass index), CUN BAE (Clínica Universidad de Navarra Body Adiposity Estimator), ECORE-BF (Equation Córdoba for Estimation of Body Fat), Formula Palafolls, FMI (fat mass index) of Deuremberg and RFM (relative fat mass). The association between diabetes and age, sex, social class and tobacco was analyzed. RESULTS: The global prevalence of diabetes ranged from 2.6% for BMI to 5.8% for the Palafolls formula. The variable most related to diabesity was age over 50 years (OR?=?5.9; 95%CI: 5.7-6.2 for BMI, and OR?=?8.1; 95%CI: 7.9-8.4 for FMI of Deuremberg). Male sex and social class III related with diabesity estimated by all formulas, while being a smoker was only related with the Palafolls formula. CONCLUSION: Diabesity prevalence varies depending on the formula used, with much lower prevalence among women and increased with age independent of the formula used. Its prevalence is higher in the lower social classes.

KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs.

Epigenetic programs are dysregulated in acute myeloid leukemia (AML) and help enforce an oncogenic state of differentiation arrest. To identify key epigenetic regulators of AML cell fate, we performed a differentiation-focused CRISPR screen in AML cells. This screen identified the histone acetyltransferase KAT6A as a novel regulator of myeloid differentiation that drives critical leukemogenic gene-expression programs. We show that KAT6A is the initiator of a newly described transcriptional control module in which KAT6A-catalyzed promoter H3K9ac is bound by the acetyl-lysine reader ENL, which in turn cooperates with a network of chromatin factors to induce transcriptional elongation. Inhibition of KAT6A has strong anti-AML phenotypes in vitro and in vivo, suggesting that KAT6A small-molecule inhibitors could be of high therapeutic interest for mono-therapy or combinatorial differentiation-based treatment of AML. SIGNIFICANCE: AML is a poor-prognosis disease characterized by differentiation blockade. Through a cell-fate CRISPR screen, we identified KAT6A as a novel regulator of AML cell differentiation. Mechanistically, KAT6A cooperates with ENL in a "writer-reader" epigenetic transcriptional control module. These results uncover a new epigenetic dependency and therapeutic opportunity in AML. This article is highlighted in the In This Issue feature, p. 587.

A primary lesion of advanced melanoma in pregnancy: case report and review of literature of the advanced cases in the last ten years.

INTRODUCTION: Pregnancy- associated melanoma (PAM) is reported between 2.8 and 5.0 per 100,000 pregnancies and approximately 35% of women with melanoma are of childbearing age. The diagnosis and treatment of melanoma during pregnancy needs a balance of risks and benefits for both maternal and fetal well-being. It is a type of malignancy, which requires a multidisciplinary approach, not limited to the obstetrician, but also to oncologists, neonatologists, pharmacists and psychologists. MATERIAL AND METHODS: We present a case of a 36-year-old pregnant woman, who was admitted to our 3rd level Unit of Obstetrics and Gynecology (ARNAS Garibaldi Nesima) at 27 weeks and 2 days of gestation, with a diagnosis of suspected infection, then diagnosed as an advanced melanoma, which caused a premature delivery. A review of the literature of the last ten years from the international electronic bibliographic databases PUBMED was performed following the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The search was limited to studies reported in the English language. We only included articles that followed our eligibility criteria, represented by: pregnant women with a diagnosis of advanced melanoma in pregnancy, with special reference to maternal, fetal or perinatal outcomes. RESULTS: The patient was affected by an 11 cm pregnancy-associated melanoma in the lower part back, with 2 hepatic metastasis. Due to the quickly development of general symptoms of sepsis it was decided to perform an urgent C-section. For the systematic review, we found 11 articles of advanced clinical melanoma, providing data from 12 patients. Maternal-perinatal outcomes is different depending on gestational age, general clinical condition, stage at diagnosis. CONCLUSION: Advanced melanoma is usually associated with a higher rate of termination of pregnancy, If the pregnancy continues, for the mother is associated with an higher risk of Cesarean section, sepsis, maternal progression of disease; for the baby is associated with prematurity, low birth weight, neonatal metastatic disease, neonatal morbidity and mortality. The future aim of clinicians should be the creation of an international database of the clinical cases of pregnancy-associated melanoma, to evaluate the same data, to improve treatments, to develop common protocols, and, finally, to improve the obstetric and perinatal outcomes.

Chromatin-state barriers enforce an irreversible mammalian cell fate decision.

Stem and progenitor cells have the capacity to balance self-renewal and differentiation. Hematopoietic myeloid progenitors replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions and can increase this output in response to stress or infection. At what point along the spectrum of maturation do progenitors lose capacity for self-renewal and become irreversibly committed to differentiation? Using a system of conditional myeloid development that can be toggled between self-renewal and differentiation, we interrogate determinants of this "point of no return" in differentiation commitment. Irreversible commitment is due primarily to loss of open regulatory site access and disruption of a positive feedback transcription factor activation loop. Restoration of the transcription factor feedback loop extends the window of cell plasticity and alters the point of no return. These findings demonstrate how the chromatin state enforces and perpetuates cell fate and identify potential avenues for manipulating cell identity.

Tyrosine kinases regulate chondrocyte hypertrophy: promising drug targets for Osteoarthritis.

Osteoarthritis (OA) is a major health problem worldwide that affects the joints and causes severe disability. It is characterized by pain and low-grade inflammation. However, the exact pathogenesis remains unknown and the therapeutic options are limited. In OA articular chondrocytes undergo a phenotypic transition becoming hypertrophic, which leads to cartilage damage, aggravating the disease. Therefore, a therapeutic agent inhibiting hypertrophy would be a promising disease-modifying drug. The therapeutic use of tyrosine kinase inhibitors has been mainly focused on oncology, but the Food and Drug Administration (FDA) approval of the Janus kinase inhibitor Tofacitinib in Rheumatoid Arthritis has broadened the applicability of these compounds to other diseases. Interestingly, tyrosine kinases have been associated with chondrocyte hypertrophy. In this review, we discuss the experimental evidence that implicates specific tyrosine kinases in signaling pathways promoting chondrocyte hypertrophy, highlighting their potential as therapeutic targets for OA.

Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia.

A hallmark of acute myeloid leukemia (AML) is the inability of self-renewing malignant cells to mature into a non-dividing terminally differentiated state. This differentiation block has been linked to dysregulation of multiple cellular processes, including transcriptional, chromatin, and metabolic regulation. The transcription factor HOXA9 and the histone demethylase LSD1 are examples of such regulators that promote differentiation blockade in AML. To identify metabolic targets that interact with LSD1 inhibition to promote myeloid maturation, we screened a small molecule library to identify druggable substrates. We found that differentiation caused by LSD1 inhibition is enhanced by combined perturbation of purine nucleotide salvage and de novo lipogenesis pathways, and identified multiple lines of evidence to support the specificity of these pathways and suggest a potential basis of how perturbation of these pathways may interact synergistically to promote myeloid differentiation. In sum, these findings suggest potential drug combination strategies in the treatment of AML.

Thyroid surgery in pediatric patients: causes and results. / Cirugía tiroidea en la edad pediátrica: causas y resultados.

OBJECTIVE: Even though thyroid surgery is rare in pediatric patients, frequency has increased in the last years. The objective of this study was to analyze the causes and results of these procedures in a pediatric surgical facility. PATIENTS AND METHODS: Retrospective study including all patients requiring thyroid surgery in our department from 2000 to 2019. Demographic data, diagnostic data, associated pathology, type of surgical procedure, pathological results, and intraoperative and postoperative complications were recorded. RESULTS: 47 patients with a mean age of 8.9 ± 3.9 years at surgery were included. The most frequent diagnosis was MEN syndrome (n = 30, 29 MEN 2A and 1 MEN 2B), followed by thyroid papillary carcinoma (n = 5), follicular adenoma (n = 5), multinodular goiter (n = 4), follicular carcinoma (n = 1), thyroglossal duct papillary carcinoma (n = 1), and Graves-Basedow syndrome (n = 1). 38 total thyroidectomies (73.7% of which were prophylactic), 3 double hemithyroidectomies, 5 hemithyroidectomies, and 5 lymphadenectomies were performed. No intraoperative complications or recurrent laryngeal nerve lesions were noted. Mean postoperative hospital stay was 1.3 ± 0.6 days. 7 patients had transitory asymptomatic hypoparathyroidism, and 1 patient had persistent symptomatic hypoparathyroidism. Pathological results of prophylactic thyroidectomies were: 18 C cell hyperplasias, 7 microcarcinomas, and 3 cases without histopathological disorders. CONCLUSIONS: Thyroid surgery in pediatric patients is safe if performed by specialized personnel. Even though it remains rare, frequency has increased in the last years.

OBJETIVO: La cirugía tiroidea es poco frecuente en la edad pediátrica, aunque ha aumentado su frecuencia en los últimos años. El objetivo de este estudio es analizar las causas y los resultados de estos procedimientos en un centro quirúrgico pediátrico. METODOS: Estudio retrospectivo que incluyó a todos los pacientes que necesitaron cirugía tiroidea en nuestro servicio entre 2000-2019. Se recogieron datos demográficos, diagnóstico, patología asociada, tipo de procedimiento quirúrgico realizado, resultados anatomopatológicos y complicaciones intra y posoperatorias. RESULTADOS: Se incluyeron 47 pacientes con una edad media en el momento de la intervención de 8,9 ± 3,9 años. El diagnóstico más frecuente fue síndrome MEN2 (n = 30, 29 MEN2A y 1 MEN2B), seguido de carcinoma papilar de tiroides (n = 5), adenoma folicular (n = 5), bocio multinodular (n = 4), carcinoma folicular (n = 1), carcinoma papilar del conducto tirogloso (n = 1) y síndrome de Graves-Basedow (n = 1). Se realizaron 38 tiroidectomías totales (el 73,7% fueron profilácticas), tres dobles hemitiroidectomías, cinco hemitiroidectomías y en cinco casos fue necesario realizar una linfadenectomía. No se presentaron complicaciones intraoperatorias ni lesiones de nervio laríngeo recurrente. La estancia media posoperatoria fue de 1,3 ± 0,6 días. Siete pacientes presentaron hipoparatiroidismo transitorio asintomático y en un caso, persistente sintomático. Los resultados anatomopatológicos de las tiroidectomías profilácticas fueron: 18 hiperplasias de células C, 7 microcarcinomas y 3 sin alteraciones histopatológicas. CONCLUSIONES: La cirugía tiroidea en la edad pediátrica es segura en manos de equipos especializados. Aunque sigue siendo un procedimiento poco habitual, su frecuencia está aumentando en los últimos años.

Pediatric surgical activity during the SARS-CoV-2 pandemic: experience at a tertiary hospital. / Cirugía pediátrica durante la pandemia de SARS-CoV-2. Experiencia en un hospital de tercer nivel.

OBJECTIVES: The primary objective was to describe the characteristics and demographics of the surgical procedures carried out at a tertiary hospital during the SARS-CoV-2 pandemic. The secondary objective was to study the impact of the pandemic on the acute appendicitis cases treated at our healthcare facility and to compare them with a pre- SARS-CoV-2 period. MATERIAL AND METHODS: A retrospective study of all patients undergoing surgery at the pediatric surgery department in the pandemic period, from the beginning of the state of emergency in Spain until the first restrictions were removed, was conducted. RESULTS: A total of 61 patients underwent surgery in 58 days vs. 406 patients in the same 2019 period (p < 0.00001). 59.01% of surgeries were urgent. 5.1% of patients had a positive SARS-CoV-2 diagnostic test. 30 different procedures were carried out, with appendectomy being the most frequent one (n = 13, 19.6% of patients). 61.5% of appendicitis cases were complicated vs. 42.4% in the non-COVID period (p = 0.17). Surgical approach was open in 46.1% of patients vs. 6.1% in the non-COVID period (p = 0.004). No statistically significant differences were found in terms of complication rate or hospital stay. CONCLUSIONS: During the SARS-CoV-2 pandemic, a significant decrease in the number of daily procedures was noted, with more than half being urgent. Appendicular pathologies were in a more advanced stage than usual, with a clear trend towards open surgery vs. laparoscopy.

OBJETIVOS: Describir las características y demografía de los procedimientos quirúrgicos realizados en un hospital de tercer nivel durante la pandemia del SARS-CoV-2. Como objetivo secundario se estudia el impacto de la pandemia en las apendicitis agudas tratadas en nuestro centro y su comparación con un periodo previo al SARS-CoV-2. MATERIAL Y METODOS: Estudio retrospectivo incluyendo a todos los pacientes intervenidos por parte del Servicio de Cirugía Pediátrica durante el periodo de pandemia. Abarca desde el primer día del estado de alarma hasta la desescalada de las restricciones. RESULTADOS: Se intervinieron un total de 61 pacientes en 58 días frente a 406 pacientes durante el mismo periodo de 2019 (p < 0,00001). El 59,01% de las intervenciones eran de carácter urgente. Un 5,1% de los pacientes tuvieron un test diagnóstico de SARS-CoV-2 positivo. Se realizaron 30 procedimientos distintos, siendo el más frecuente la apendicectomía (n = 13, 19,6% de los pacientes). El 61,5% de las apendicitis fueron complicadas frente a un 42,4% en periodo no COVID (p = 0,17). El abordaje quirúrgico fue abierto en un 46,1% de los pacientes frente al 6,1% no COVID (p = 0,004). No hubo diferencias estadísticamente significativas en la tasa de complicaciones o la estancia hospitalaria. CONCLUSIONES: Durante la pandemia por SARS-CoV-2 se ha producido una importante disminución del número de procedimientos diarios, pasando a ser más de la mitad de carácter urgente. La patología apendicular se ha presentado más evolucionada de lo habitual, habiendo una clara tendencia a la cirugía abierta frente a la laparoscopia.