Case report: A familial B-acute lymphoblastic leukemia associated with a new germline pathogenic variant in PAX5. The first report in Mexico.

B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common childhood cancers worldwide. Although most cases are sporadic, some familial forms, inherited as autosomal dominant traits with incomplete penetrance, have been described over the last few years. Germline pathogenic variants in transcription factors such as PAX5, IKZF1, and ETV6 have been identified as causal in familial forms. The proband was a 7-year-old Mexican girl diagnosed with high-risk B-ALL at five years and 11 months of age. Family history showed that the proband's mother had high-risk B-ALL at 16 months of age. She received chemotherapy and was discharged at nine years of age without any evidence of recurrence of leukemia. The proband's father was outside the family nucleus, but no history of leukemia or cancer was present up to the last contact with the mother. We performed exome sequencing on the proband and the proband's mother and identified the PAX5 variant NM_016734.3:c.963del: p.(Ala322LeufsTer11), located in the transactivation domain of the PAX5 protein. The variant was classified as probably pathogenic according to the ACMG criteria. To the best of our knowledge, this is the first Mexican family with an inherited increased risk of childhood B-ALL caused by a novel germline pathogenic variant of PAX5. Identifying individuals with a hereditary predisposition to cancer is essential for modern oncological practice. Individuals at high risk of leukemia would benefit from hematopoietic stem cell transplantation, but family members carrying the pathogenic variant should be excluded as hematopoietic stem cell donors.

IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia.

Background: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL. Methods: A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation. Results: We identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed. Discussion: Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.

Clinical Evaluation of an Artificial Intelligence-Based Decision Support System for the Diagnosis and American College of Radiology Thyroid Imaging Reporting and Data System Classification of Thyroid Nodules.

Background: This study aimed to evaluate the clinical impact of an artificial intelligence (AI)-based decision support system (DSS), Koios DS, on the analysis of ultrasound imaging and suspicious characteristics for thyroid nodule risk stratification. Methods: A retrospective ultrasound study was conducted on all thyroid nodules with histological findings from June 2021 to December 2022 in a thyroid nodule clinic. The diagnostic performance of ultrasound imaging was evaluated by six readers on the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) before and after the use of the AI-based DSS and by AI itself. Results: A total of 172 patients (83.1% women) with a mean age of 52.3 ± 15.3 years were evaluated. The mean maximum nodular diameter was 2.9 ± 1.2 cm, with 11.0% being differentiated thyroid carcinomas. Among the nodules initially classified as ACR TI-RADS 3 and 4, AI reclassified 81.4% and 24.5% into lower risk categories, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the readers and the AI-based DSS versus histological diagnosis. There was an increase in the area under the ROC curve (AUROC) after the use of AI (0.776 vs. 0.817, p < 0.001). The AI-based DSS improved the mean sensitivity (Sens) (82.3% vs. 86.5%) and specificity (Spe) (38.3% vs. 54.8%), produced a high negative predictive value (94.5% vs. 96.4%), and increased the positive predictive value (PPV) (14.0% vs. 16.1%) and diagnostic precision (43.0% vs. 49.3%). Based on the ACR TI-RADS score, there was significant improvement in interobserver agreement after the use of AI (r = 0.741 for ultrasound imaging alone vs. 0.981 for ultrasound imaging and the AI-based DSS, p < 0.001). Conclusions: The use of an AI-based DSS was associated with overall improvement in the diagnostic efficacy of ultrasound imaging, based on the AUROC, as well as an increase in Sens, Spe, negative and PPVs, and diagnostic accuracy. There was also a reduction in interobserver variability and an increase in the degree of concordance with the use of AI. AI reclassified more than half of the nodules with intermediate ACR TI-RADS scores into lower risk categories.

Multifunctional polymeric guanidine and hydantoin halamines with broad biocidal activity.

Prolonged and excessive use of biocides during the coronavirus disease era calls for incorporating new antiviral polymers that enhance the surface design and functionality for existing and potential future pandemics. Herein, we investigated previously unexplored polyamines with nucleophilic biguanide, guanidine, and hydantoin groups that all can be halogenated leading to high contents of oxidizing halogen that enables enhancement of the biocidal activity. Primary amino groups can be used to attach poly(N-vinylguanidine) (PVG) and poly(allylamine-co-4-aminopyridine-co-5-(4-hydroxybenzylidene)hydantoin) (PAH) as well as a broad-spectrum commercial biocide poly(hexamethylene biguanide) (PHMB) onto a solid support. Halogenation of polymer suspensions was conducted through in situ generation of excess hypobromous acid (HBrO) from bromine and sodium hydroxide or by sodium hypochlorite in aqueous solutions, resulting in N-halamines with high contents of active > N-Br or > N-Cl groups. The virucidal activity of the polymers against human respiratory coronavirus HCoV-229E increased dramatically with their halogenation. Brominated PHMB-Br showed activation activity value > 5 even at 1 mg/L, and complete virus inhibition was observed with either PHMB-Br or PAH-Br at 10 mg/mL. Brominated PVG-Br and PAH-Br possessed fungicidal activity against C. albicans, while PHMB was fungistatic. PHMB, PHMB-Br and PAH polymers demonstrated excellent bactericidal activity against the methicillin-resistant S. aureus and vancomycin-resistant E. faecium. Brominated polymers (PHMB-Br, PVG-Br, PAH-Br) were not toxic to the HeLa monolayers, indicating acceptable biocompatibility to cultured human cells. With these features, the N-halamine polymers of the present study are a worthwhile addition to the arsenal of biocides and are promising candidates for development of non-leaching coatings.

A renal clearable fluorogenic probe for in vivo ß-galactosidase activity detection during aging and senolysis.

Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for ß-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, ß-galactosidase cleaves the O-glycosidic bond, releasing the fluorophore that is ultimately excreted by the kidneys and can be measured in urine. The intensity of the recovered fluorophore reliably reflects an experimentally controlled load of cellular senescence and correlates with age-associated anxiety during aging and senolytic treatment. Interestingly, our findings with the probe indicate that the effects of senolysis are temporary if the treatment is discontinued. Our strategy may serve as a basis for developing fluorogenic platforms designed for easy longitudinal monitoring of enzymatic activities in biofluids.

Association between the genetic variant in the vitamin D pathway (rs2282679), circulating 25-hydroxyvitamin D levels, insulin resistance and metabolic syndrome criteria / Asociación entre la variante genética en la vía de la vitamina D (rs2282679), niveles circulantes de 25-hidroxivitamina D, resistencia a la insulina y criterios de síndrome metabólico

Background and aims: some studies have reported links between 25-hydroxyvitamin D levels and the presence of metabolic syndrome. The aim of the present study was to evaluate whether an association exists among 25-hydroxyvitamin D, rs2282679 of the GC gene and metabolic syndrome (MS). Methods: the study involved a population of 134 postmenopausal obese females. Measurements of anthropometric parameters, blood pressure, bone turnover markers, fasting blood glucose, insulin resistance (HOMA-IR), lipid profile, C-reactive protein and prevalence of MS were recorded. Genotype of CG gene polymorphism (rs2282679) was evaluated. Results: insulin (delta: 4.6 ± 0.9 mUI/l; p = 0.02), triglycerides (delta: 21.6 ± 2.9 mg/dl; p = 0.04) and HOMA-IR (delta: 1.1 ± 0.9 unit; p = 0.02) were lower in TT subjects than TG + GG patients. The percentages of individuals who had MS (OR = 2.80, 95 % CI = 1.39-5.65; p = 0.02), hypertriglyceridemia (OR = 2.39, 95 % CI = 1.44-5.96; p = 0.01), and hyperglycemia (OR = 2.72, 95 % CI = 1.23-6.00; p = 0.43) were higher in G allele carriers. Logistic regression analysis showed an increased risk of MS in G allele carriers (OR = 2.36, 95 % CI = 1.11-5.91, p = 0.02) and an increased risk of 25-hydroxyvitamin D deficiency (< 20 ng/ml) (OR = 2.43, 95 % CI = 1.13-6.69, p = 0.02), too. Conclusions: a negative association among G allele and insulin resistance, hypertriglyceridemia, deficiency of 25 hydroxyvitamin D levels and MS was reported in this population. (AU)

Antecedentes y objetivos: algunos estudios han demostrado una relación entre los niveles de 25-hidroxivitamina D y la presencia del síndrome metabólico. El objetivo de este estudio fue evaluar si existe una asociación entre la 25-hidroxivitamina D, la variante rs2282679 del gen GC y el síndrome metabólico (SM). Métodos: el estudio involucró a una población de 134 mujeres obesas posmenopáusicas. Se registraron parámetros antropométricos, presión arterial, marcadores de recambio óseo, glucemia en ayunas, resistencia a la insulina (HOMA-IR), perfil lipídico, proteína C reactiva y prevalencia de SM. Se evaluó el genotipo del polimorfismo del gen CG (rs2282679). Resultados: los niveles de insulina (delta: 4,6 ± 0,9 mUI/l; p = 0.02), triglicéridos (delta: 21,6 ± 2,9 mg/dl; p = 0,04) y HOMA-IR (delta: 1,1 ± 0,9 unidades; p = 0,02) fueron menores en los sujetos TT que en los pacientes TG + GG. Los porcentajes de individuos que tenían SM (OR = 2,80, IC 95 % = 1,39-5,65; p = 0,02), hipertrigliceridemia (OR = 2,39, IC 95 % = 1,44-5,96; p = 0,01) e hiperglucemia (OR = 2,72, IC 95 % = 1,23-6,00; p = 0,43) fueron mayores en los portadores del alelo G. El análisis de regresión logística mostró un mayor riesgo de SM en los portadores del alelo G (OR = 2,36, IC 95 % = 1,11-5,91; p = 0,02) y un mayor riesgo de deficiencia de 25-hidroxivitamina D (< 20 ng/ml) (OR = 2,43, IC 95 % = 1,13-6,69; p = 0,02). Conclusiones: en esta población hemos detectado una asociación negativa entre el alelo G y la resistencia a la insulina, hipertrigliceridemia, deficiencia niveles de 25-hidroxivitamina D y SM. (AU)

Association between the genetic variant in the vitamin D pathway (rs2282679), circulating 25-hydroxyvitamin D levels, insulin resistance and metabolic syndrome criteria.

Introduction: Background and aims: some studies have reported links between 25-hydroxyvitamin D levels and the presence of metabolic syndrome. The aim of the present study was to evaluate whether an association exists among 25-hydroxyvitamin D, rs2282679 of the GC gene and metabolic syndrome (MS). Methods: the study involved a population of 134 postmenopausal obese females. Measurements of anthropometric parameters, blood pressure, bone turnover markers, fasting blood glucose, insulin resistance (HOMA-IR), lipid profile, C-reactive protein and prevalence of MS were recorded. Genotype of CG gene polymorphism (rs2282679) was evaluated. Results: insulin (delta: 4.6 ± 0.9 mUI/l; p = 0.02), triglycerides (delta: 21.6 ± 2.9 mg/dl; p = 0.04) and HOMA-IR (delta: 1.1 ± 0.9 unit; p = 0.02) were lower in TT subjects than TG + GG patients. The percentages of individuals who had MS (OR = 2.80, 95 % CI = 1.39-5.65; p = 0.02), hypertriglyceridemia (OR = 2.39, 95 % CI = 1.44-5.96; p = 0.01), and hyperglycemia (OR = 2.72, 95 % CI = 1.23-6.00; p = 0.43) were higher in G allele carriers. Logistic regression analysis showed an increased risk of MS in G allele carriers (OR = 2.36, 95 % CI = 1.11-5.91, p = 0.02) and an increased risk of 25-hydroxyvitamin D deficiency (< 20 ng/ml) (OR = 2.43, 95 % CI = 1.13-6.69, p = 0.02), too. Conclusions: a negative association among G allele and insulin resistance, hypertriglyceridemia, deficiency of 25 hydroxyvitamin D levels and MS was reported in this population.

Introducción: Antecedentes y objetivos: algunos estudios han demostrado una relación entre los niveles de 25-hidroxivitamina D y la presencia del síndrome metabólico. El objetivo de este estudio fue evaluar si existe una asociación entre la 25-hidroxivitamina D, la variante rs2282679 del gen GC y el síndrome metabólico (SM). Métodos: el estudio involucró a una población de 134 mujeres obesas posmenopáusicas. Se registraron parámetros antropométricos, presión arterial, marcadores de recambio óseo, glucemia en ayunas, resistencia a la insulina (HOMA-IR), perfil lipídico, proteína C reactiva y prevalencia de SM. Se evaluó el genotipo del polimorfismo del gen CG (rs2282679). Resultados: los niveles de insulina (delta: 4,6 ± 0,9 mUI/l; p = 0.02), triglicéridos (delta: 21,6 ± 2,9 mg/dl; p = 0,04) y HOMA-IR (delta: 1,1 ± 0,9 unidades; p = 0,02) fueron menores en los sujetos TT que en los pacientes TG + GG. Los porcentajes de individuos que tenían SM (OR = 2,80, IC 95 % = 1,39-5,65; p = 0,02), hipertrigliceridemia (OR = 2,39, IC 95 % = 1,44-5,96; p = 0,01) e hiperglucemia (OR = 2,72, IC 95 % = 1,23-6,00; p = 0,43) fueron mayores en los portadores del alelo G. El análisis de regresión logística mostró un mayor riesgo de SM en los portadores del alelo G (OR = 2,36, IC 95 % = 1,11-5,91; p = 0,02) y un mayor riesgo de deficiencia de 25-hidroxivitamina D (< 20 ng/ml) (OR = 2,43, IC 95 % = 1,13-6,69; p = 0,02). Conclusiones: en esta población hemos detectado una asociación negativa entre el alelo G y la resistencia a la insulina, hipertrigliceridemia, deficiencia niveles de 25-hidroxivitamina D y SM.

Clinical Trials on Advanced Therapy Investigational Medicinal Products in Spain (2004-2022): Experience and Challenges for the Future.

Clinical investigation is the basis for establishing how useful advanced therapy investigational medicinal products (ATiMP) are for the treatment of serious diseases.In Spain, clinical trials (CT) on ATiMP need to follow the general European legislation on CT with medicinal products plus some specific legislation and guidance depending on the type of ATiMP.This chapter describes the characteristics of CT on ATiMP authorized in Spain in the period 2004-2022 and the legislation applicable along this period. There are clear differences in the clinical trials conducted by non commercial and commercial sponsors: the first have been more involved in CT on somatic cell therapy medicinal products (sCTMP) and tissue-engineered products (TEP), while the second drive more the CT on gene therapy medicinal products (GTMP) in the last years. Difficulties of budget and resources especially by non-commercial sponsors to meet the regulatory requirements are highlighted. The importance of complying with transparency rules with respect to CT on ATiMP is also discussed.

A Machine Learning Method to Identify the Risk Factors for Liver Fibrosis Progression in Nonalcoholic Steatohepatitis.

AIM: Nonalcoholic fatty liver disease (NAFLD) is a silent epidemy that has become the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD, which is linked to a high risk of cirrhosis and hepatocellular carcinoma. The aim of this study is to develop a predictive model to identify the main risk factors associated with the progression of hepatic fibrosis in patients with NASH. METHODS: A database from a multicenter retrospective cross-sectional study was analyzed. A total of 215 patients with NASH biopsy-proven diagnosed were collected. NAFLD Activity Score and Kleiner scoring system were used to diagnose and staging these patients. Noninvasive tests (NITs) scores were added to identify which one were more reliable for follow-up and to avoid biopsy. For analysis, different Machine Learning methods were implemented, being the eXtreme Gradient Booster (XGB) system the proposed algorithm to develop the predictive model. RESULTS: The most important variable in this predictive model was High-density lipoprotein (HDL) cholesterol, followed by systemic arterial hypertension and triglycerides (TG). NAFLD Fibrosis Score (NFS) was the most reliable NIT. As for the proposed method, XGB obtained higher results than the second method, K-Nearest Neighbors, in terms of accuracy (95.05 vs. 90.42) and Area Under the Curve (0.95 vs. 0.91). CONCLUSIONS: HDL cholesterol, systemic arterial hypertension, and TG were the most important risk factors for liver fibrosis progression in NASH patients. NFS is recommended for monitoring and decision making.

Treatment of Peritoneal Surface Malignancies by Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Spain: Results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP).

INTRODUCTION: Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide. METHODS: This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients. RESULTS: 66% are women and 34% are men with a median age of 59 years (range 17-86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0-39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo-Clavien grade III-IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0-259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients. CONCLUSIONS: large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM.

Diagnosis of malnutrition and its relationship with prognosis in hospitalized patients with oncological pathology.

BACKGROUND AND AIMS: Medical oncology inpatients are at a very high risk of malnutrition, and the presence of complications associated with malnutrition is significant in their evolution. It is necessary to have adequate tools in the diagnosis of malnutrition. OBJECTIVES: This study is aimed to assess the nutritional status of cancer inpatients and compare the incidence of complications based on the nutritional diagnosis with different tools. METHODS: An observational, longitudinal, and retrospective study was designed on 149 patients admitted to the Oncology Service who were requested nutritional and medical treatment between January 2014 and June 2017. Epidemiological, clinical, anthropometric, and nutritional data were collected. Nutritional status was assessed using the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), and the Global Leadership Initiative on Malnutrition (GLIM) criteria. RESULTS: The age of the patients was 61.61 (15.96) years. 67.8% of the patients were men. Most of the patients were in advanced tumor stages (stage III (15.3%); stage IV (77.1%)). The median of the MUST was 2 (0-3) (High risk: 83 (55.7%)). The median MNA was 17 (14-20) (poor nutritional status: 65 (43.6%); risk of malnutrition 71 (47.7%)). According to the GLIM criteria, 115 (77.2%) had malnutrition, and 97 (65.1%) had severe malnutrition. According to MNA, an increase in mortality was observed (MNA <17: 24.6% vs. MNA >17: 7.9%; pvalue <0.01). Multivariate analysis showed that poor nutritional status measured with MNA is related to an increased probability of mortality regardless of the stage of the disease and the patient's age OR: 4.19 95% CI (1.41-12.47); p-value = 0.02. CONCLUSIONS: Malnutrition among cancer patients in whom a nutritional assessment is requested during admission is very high. In hospitalized patients with oncological pathology, it was observed that malnutrition measured by MNA acts as a mortality risk factor.

Predictive value and dynamic risk stratification of high sensitive basal or stimulated thyroglobulin assay in a long-term thyroid carcinoma cohort.

PURPOSE: To evaluate the predictive value of the rhTSH thyroglobulin stimulation test (rhTSH-Tg) compared to basal high-sensitive thyroglobulin (hs-Tg) under TSH suppressive therapy at 12 months after the completion of initial treatment to predict the long-term response and Dynamic Risk Stratification (DRS) at the last follow-up visit in a long-term DTC cohort. METHODS: Prospective study in 114 DTC patients (77.2% women, mean age 46.4 ± 14.1 years old, median/IQR evolution 6.7[3.1-8.0] years) from 2013 to 2020 undergoing total thyroidectomy and radioiodine ablation in whom hs-Tg and rhTSH-Tg was performed 12 months after completing initial treatment. Pearson correlation, receiving operating characteristics (ROC) and DRS at initial and last follow-up visit were analyzed. RESULTS: hs-Tg and rhTSH-Tg show a strong positive linear correlation (r = 0.864, p < 0.001). The diagnostic performance of initial hs-Tg and rhTSH-Tg levels were evaluated via ROC-AUC as a predictor of excellent response (ER) in the last follow-up visit. Hs-Tg showed a better AUC (0.969, 95%CI = 0.941-0.997) than rhTSH-Tg (0.944, 95%IC = 0.905-0.984; p < 0.001). The hs-Tg and rhTSH-Tg cutoff point of highest sensitivity (S) and specificity (E) was 0.110 and 0.815 ng/dl, respectively. Hs-Tg showed a higher diagnostic accuracy than rhTSH-Tg (S = 100% vs 96.8%, E = 84.3% vs 84.3%, NPV = 100% vs 98.6%, PPV = 70.5% vs 69.7%; p < 0.05). The DRS based on initial hs-Tg showed better ability to predict ER (93.3% vs 86.7%) and biochemical incomplete response (53.3%vs13.3%) in the last follow-up visit compared to rhTSH-Tg. CONCLUSIONS: Both initial hs-Th and rhTSH-Tg were good predictors of long-term ER. In patients with hs-Tg, the rhTSH-test did not provide relevant prognosis information. An ER after initial treatment was associated with a very high NPV at subsequent follow-up.

Differences When Classifying Small for Gestational Age Preterm Infants According to the Growth Chart Applied.

OBJECTIVE: Consensus around the ideal chart to classify preterm babies is scant. It is particularly relevant in small for gestational age (SGA) infants due to its clinical and therapeutic implications. The aim of the study was to compare Olsen, Intergrowth-21st, and Fenton growth charts, regarding the classification at birth and incidence of SGA preterm infants. STUDY DESIGN: Retrospective study of 529 preterm infants ≤ 32 weeks of gestational age. Birth weight Z-score was calculated applying the three growth charts and ponderal index (PI) was also estimated. Incidence of SGA (birth weight < 10th percentile) and clinical outcome were compared according to the chart used. RESULTS: Incidence of SGA was significantly higher (p < 0.001) with Olsen (101 cases, 19.1%) compared with Intergrowth-21st (75 cases, 14.2%) and Fenton (53 cases, 10%). Differences were also found with PI of SGA preterm infants, as those infants classified by Olsen were mostly symmetric (PI > 10th percentile), while Fenton and Intergrowth-21st identified less symmetric SGA infants. Kappa concordance between Intergrowth-21st and Fenton was 0.805, Intergrowth-21st versus Olsen 0.824, and Fenton versus Olsen 0.641. No differences were observed on neonatal morbidities or mortality. CONCLUSION: Significant differences were detected when classifying very preterm infants at birth according to the growth chart, mainly among symmetric SGA. Concordance between Fenton and Olsen was poor, but Intergrowth-21st showed high concordance with Fenton and Olsen. However, further research is needed to select the ideal chart. Variability in the population selected to create the curves and the accuracy dating the pregnancy are factors that may have explained differences. KEY POINTS: · Very preterm infants are differently classified at birth with various growth charts.. · Higher incidence of small for gestational age infants with Olsen compared with Fenton or Intergrowth.. · Variability in population selection and accuracy in dating pregnancy may have explained differences..

Lipofuscin labeling through biorthogonal strain-promoted azide-alkyne cycloaddition for the detection of senescent cells.

A new method for senescent cell detection is described, which is based on lipofuscin labeling with a fluorescent reporter through a biorthogonal strain-promoted azide-alkyne cycloaddition. The sensing protocol involves a first step where the interaction of lipofuscin with a Sudan Black B derivative containing an azide moiety (SBB-N3 ) is carried out. In the final step, the azide moiety reacts with a fluorophore containing a cyclooctene ring (BODIPY). The efficacy of this two-step protocol is assessed in senescent melanoma SK-MEL-103 cells, senescent triple-negative breast cancer MDA-MB-231 cells and senescent WI-38 fibroblasts. In all cases, a clear fluorescence pattern was observed in senescent cells, compared to proliferative cells, only when the SBB-N3 -BODIPY probe was formed. Our results provide an alternative tool for the detection of senescent cells, based on an in situ bio-orthogonal reaction for lipofuscin labeling.

ß-Galactosidase-Activatable Nile Blue-Based NIR Senoprobe for the Real-Time Detection of Cellular Senescence.

Cellular senescence is a stable cell cycle arrest in response to stress or other damage stimuli to maintain tissue homeostasis. However, the accumulation of senescent cells can lead to the progression of various senescence-related disorders. In this paper, we describe the development of a ß-galactosidase-activatable near-infrared (NIR) senoprobe, NBGal, for the detection of senescent cells based on the use of the FDA-approved Nile blue (NB) fluorophore. NBGal was validated in chemotherapeutic-induced senescence cancer models in vitro using SK-Mel 103 and 4T1 cell lines. In vivo monitoring of cellular senescence was evaluated in orthotopic triple-negative breast cancer-bearing mice treated with palbociclib to induce senescence. In all cases, NBGal exhibited a selective tracking of senescent cells mainly ascribed to the overexpressed ß-galactosidase enzyme responsible for hydrolyzing the NBGal probe generating the highly emissive NB fluorophore. In this way, NBGal has proven to be a qualitative, rapid, and minimally invasive probe that allows the direct detection of senescent cells in vivo.

Metabolic control and satisfaction in a diabetes education programme in flash glucose monitoring through telemedicine in type 1 diabetes.

OBJECTIVE: To evaluate metabolic control and satisfaction with a telemedicine diabetes education programme for the initiation of flash glucose monitoring (FGM) in type 1 diabetes. MATERIAL AND METHODS: Prospective study in 48 patients (52.1% women, 22.9% on insulin pump) who started FGM. They were analysed at baseline and 3 months after the beginning of the FGM. The results were compared with an on-site learning cohort matched by age, sex and HbA1c. RESULTS: At the beginning and 3 months after the MFG, HbA1c improvement was observed (7.9±1.4 vs 7.3±1.1%), p<0.01; with a decrease in time below range - TBR - (4.7±4.9 vs 3.5±3.5%), p<0.05 and number of hypoglycaemic events (9.4±8.7 vs 6.9±5.7/15 days), p<0.05, associated with a worsening in time above range - TAR - (33.5±19.9 vs 37.0±20.9%), p<0.05. No significant differences were observed in the TIR 70-180mg/dl (61.7±18.6 vs 59.4±20.0%), glycemic variability or the use of FGM. Patient satisfaction with telemedicine training was 4.8±0.3 out of 5. No significant differences were observed in the follow-up, either in HbA1c or other glucometer parameters between on-site and online training. In a multivariate analysis adopting the HbA1c at follow-up as the dependent variable, only the TIR (ß=-0.034; p<0.001) and the initial HbA1c (ß=0.303; p<0.001) maintained statistical significance, unrelated to the on-site or online training (ß=0.136; p=ns). CONCLUSIONS: A telemedicine programme is an adequate tool for training in FGM, with results similar to on-site training, and it was associated with a high degree of satisfaction.

A rare endoscopic finding: primary esophageal melanoma.

We report a case of a patient accidentally diagnosed with an esophageal lesion compatible (histologically and immunohistochemically) with epithelioid melanoma. The skin examination did not reveal any evidence of melanoma and the patient was diagnosed with primary malignant melanoma of the esophagus. It's a very rare tumour. The majority of melanocytic lesions of the gastrointestinal tract are presumably secondary to a cutaneous melanoma and in order to discard this, a thorough skin examination is needed. Diagnosis is based on endoscopic image, histological data and especially on immunohistochemical evaluation. Primary malignant melanoma has a very poor prognosis as it usually presents distant metastasis when diagnosed. Surgery (with or without associated immunotherapy) remains the base of treatment in absence of advanced disease.

Evolution of suppressing TSH therapy at diagnosis and in the long-term follow-up in a cohort of differentiated thyroid cancer.

INTRODUCTION: To evaluate the adequacy of TSH suppression therapy (TSHst) at the first disease assessment and the last follow-up visit. METHODS: Retrospective observational study of those patients under follow-up of DTC in a reference hospital. RESULTS: 216 patients (79.2% women) were evaluated, with a mean age 59.0 ±â€¯13.1 years-old and a mean follow-up of 6.9 ±â€¯4.3 years. 88.4% were papillary carcinomas. At diagnosis, 69.2% had a low risk of recurrence (RR) compared to 13.6% with a high RR. Dynamic risk stratification (DRS) classified patients at first disease assessment and the last visit as excellent response (ER) in 60.0% and 70.7%, respectively. Those patients with ER in the first and last follow-up control maintained TSHst in 30.7% and 16.3% of the cases, respectively (p < 0.001). The factors associated with maintaining TSHst at the last control were younger age, higher RR at diagnosis, DRE at follow-up, presence of multifocality and histological vascular invasion (p < 0.05). In a logistic regression analysis adopting tsTSH at follow-up as the dependent variable, exclusively age (ß = -0.062; p < 0.001), RR at diagnosis (ß = 1.074; p < 0.05) and EDR during follow-up (ß = 1.237; p < 0.05) maintained statistical significance. CONCLUSIONS: Despite the current recommendations, 30.7% of patients with low RR and initial ER are under TSHst. This percentage reduced to 16.3% in those patients with ER after a mean follow-up of 6.9 years. Age, baseline RR, and DRE during follow-up were associated to maintaining tsTSH.