Altered RNA export by SF3B1 mutants confers sensitivity to nuclear export inhibition.

SF3B1 mutations frequently occur in cancer yet lack targeted therapies. Clinical trials of XPO1 inhibitors, selinexor and eltanexor, in high-risk myelodysplastic neoplasms (MDS) revealed responders were enriched with SF3B1 mutations. Given that XPO1 (Exportin-1) is a nuclear exporter responsible for the export of proteins and multiple RNA species, this led to the hypothesis that SF3B1-mutant cells are sensitive to XPO1 inhibition, potentially due to altered splicing. Subsequent RNA sequencing after XPO1 inhibition in SF3B1 wildtype and mutant cells showed increased nuclear retention of RNA transcripts and increased alternative splicing in the SF3B1 mutant cells particularly of genes that impact apoptotic pathways. To identify novel drug combinations that synergize with XPO1 inhibition, a forward genetic screen was performed with eltanexor treatment implicating anti-apoptotic targets BCL2 and BCLXL, which were validated by functional testing in vitro and in vivo. These targets were tested in vivo using Sf3b1K700E conditional knock-in mice, which showed that the combination of eltanexor and venetoclax (BCL2 inhibitor) had a preferential sensitivity for SF3B1 mutant cells without excessive toxicity. In this study, we unveil the mechanisms underlying sensitization to XPO1 inhibition in SF3B1-mutant MDS and preclinically rationalize the combination of eltanexor and venetoclax for high-risk MDS.

Risk stratification model for the pharmaceutical care of oncology patients with solid or hematologic neoplasms. / [Artículo traducido] Modelo de estratificación de riesgo de atención farmacéutica para pacientes oncológicos con neoplasias sólidas o hematológicas.

OBJECTIVE: We aimed to develop of a risk stratification model for the pharmaceutical care (PC) of patients with solid or hematologic neoplasms who required antineoplastic agents or supportive treatments. METHOD: The risk stratification model was collaboratively developed by oncology pharmacists from the Spanish Society of Hospital Pharmacy (SEFH). It underwent refinement through three workshops and a pilot study. Variables were defined, grouped into four dimensions, and assigned relative weights. The pilot study collected and analyzed data from participating centers to determine priority levels and evaluate variable contributions. The study followed the Kaiser Permanente pyramid model, categorizing patients into three priority levels: Priority 1 (intensive PC, 90th percentile), Priority 2 (60th-90th percentiles), and Priority 3 (60th percentile). Cut-off points were determined based on this stratification. Participating centers recorded variables in an Excel sheet, calculating mean weight scores for each priority level and the total risk score. RESULTS: The participants agreed to complete a questionnaire that comprised 22 variables grouped into 4 dimensions: demographic (maximum score =11); social and health variables and cognitive and functional status (maximum = 19); clinical and health services utilization (maximum = 25); and treatment-related (maximum = 41). From the results of applying the model to the 199 patients enrolled, the cutoff points for categorization were 28 or more points for priority 1, 16 to 27 points for priority 2 and less than 16 for priority 3; more than 80% of the total score was based on the dimensions of 'clinical and health services utilization' and 'treatment-related'. Interventions based on the pharmaceutical care model were recommended for patients with solid or hematological neoplasms, according to their prioritization level. CONCLUSION: This stratification model enables the identification of cancer patients requiring a higher level of pharmaceutical care and facilitates the adjustment of care capacity. Validation of the model in a representative population is necessary to establish its effectiveness.

Abdominal wall surgery units accreditation. The Spanish model.

The Spanish Association of Surgeons (AEC) deems it essential to define and regulate the acquisition of high-specialization competencies within General Surgery and Gastrointestinal Surgery and proposes the Regulation for the accreditation of specialized surgical units. The AEC aims to define specialized surgical units as those functional elements of the health system that meet the defined requirements regarding their provision, solvency, and specialization in care, teaching, and research. In this paper we present the proposed accreditation model for Abdominal Wall Surgery Units, as well as the results of a survey conducted to assess the status of such units in our country. The model presented represents one of the pioneering initiatives worldwide concerning the accreditation of Abdominal Wall Surgery Units.

EHS guidelines for inguinal hernia repair. The reality of the current situation in Spain. A proposal to standardize its implementation during surgical training.

Laparoscopic inguinal hernia repairs are underused in our country and do not fulfil to the recommendations of the European Hernia Society (EHS) guidelines. Thus, it is essential to establish measures that increase its use. We propose that the Spanish Association of Surgeons (AEC) promote these actions and that they should be incorporated into the specialty program. The proposed measures include Standardization of learning; reinforce anatomical knowledge; regulated practices with simulators; promote the use of the open posterior approach; rotations through centers of excellence; accreditation of specialized units and use a registry of activity as quality control.

Protocolization of multicenter clinical studies in the digital era. Is useful data centralization by a data-manager?

INTRODUCTION: In multicenter studies, the protocolization of data is a critical phase that can generate biases.The objective is to analyze the concordance and reliability of the data obtained in a clinical multicenter study between the protocolization in the center of origin and the centralized protocolization of the data by a data -manager. METHODS: National multicenter clinical study about an infrequent carcinoma. A double protocolization of the data is carried out: (a) center of origin; and (b) centralized by a data manager: The concordance between the data is analyzed for the global data and for the two groups of the project: (a) study group (Familiar carcinoma, 30 researchers protocolize); (b) control group (Sporadic carcinoma, 4 people protocolize). Interobserver variability is evaluated using Cohen's kappa coefficient. RESULTS: The study includes a total of 689 patients with carcinoma, 252 in the study group and 437 in the control group. Regarding the concordance analysis of the tumor stage, 2.5% of disagreements were observed and the concordance between people who protocolize was near perfect (Kappa = 0.931). Regarding the evaluation of the recurrence risk, disagreements occurred in 7% of the cases and the concordance was near perfect (Kappa = 0.819). Regarding the sonography evaluation (TIRADS), the disagreements were 6.9% and the concordance was near perfect (Kappa = 0.922). Also, 4.6% of transcription errors were detected. CONCLUSIONS: In multicenter clinical studies, the centralized data protocolization o by a data-manager seems to present similar results to the direct protocolization in the database in the center of origin.

Risk stratification model for the pharmaceutical care of oncology patients with solid or hematologic neoplasms.

OBJECTIVE: We aimed to develop of a risk stratification model for the pharmaceutical care of patients with solid or hematologic neoplasms who required antineoplastic agents or supportive treatments. METHOD: The risk stratification model was collaboratively developed by oncology pharmacists from the Spanish Society of Hospital Pharmacy (SEFH). It underwent refinement through 3 workshops and a pilot study. Variables were defined, grouped into 4 dimensions, and assigned relative weights. The pilot study collected and analyzed data from participating centers to determine priority levels and evaluate variable contributions. The study followed the Kaiser Permanente pyramid model, categorizing patients into 3 priority levels: Priority 1 (intensive PC, 90th percentile), Priority 2 (60th-90th percentiles), and Priority 3 (60th percentile). Cut-off points were determined based on this stratification. Participating centers recorded variables in an Excel sheet, calculating mean weight scores for each priority level and the total risk score. RESULTS: The participants agreed to complete a questionnaire that comprised 22 variables grouped into 4 dimensions: demographic (maximum score=11); social and health variables and cognitive and functional status (maximum=19); clinical and health services utilization (maximum=25); and treatment-related (maximum=41). From the results of applying the model to the 199 patients enrolled, the cut-off points for categorization were 28 or more points for priority 1, 16-27 points for priority 2, and less than 16 for priority 3; more than 80% of the total score was based on the dimensions of "clinical and health services utilization" and "treatment-related." Interventions based on the pharmaceutical care model were recommended for patients with solid or hematological neoplasms, according to their prioritization level. CONCLUSION: This stratification model enables the identification of cancer patients requiring a higher level of pharmaceutical care and facilitates the adjustment of care capacity. Validation of the model in a representative population is necessary to establish its effectiveness.

High Throughput Fluorescence-Based In Vitro Experimental Platform for the Identification of Effective Therapies to Overcome Tumour Microenvironment-Mediated Drug Resistance in AML.

The interactions between Acute Myeloid Leukaemia (AML) leukemic stem cells and the bone marrow (BM) microenvironment play a critical role during AML progression and resistance to drug treatments. Therefore, the identification of novel therapies requires drug-screening methods using in vitro co-culture models that closely recreate the cytoprotective BM setting. We have developed a new fluorescence-based in vitro co-culture system scalable to high throughput for measuring the concomitant effect of drugs on AML cells and the cytoprotective BM microenvironment. eGFP-expressing AML cells are co-cultured in direct contact with mCherry-expressing BM stromal cells for the accurate assessment of proliferation, viability, and signaling in both cell types. This model identified several efficacious compounds that overcome BM stroma-mediated drug resistance against daunorubicin, including the chromosome region maintenance 1 (CRM1/XPO1) inhibitor KPT-330. In silico analysis of genes co-expressed with CRM1, combined with in vitro experiments using our new methodology, also indicates that the combination of KPT-330 with the AURKA pharmacological inhibitor alisertib circumvents the cytoprotection of AML cells mediated by the BM stroma. This new experimental model and analysis provide a more precise screening method for developing improved therapeutics targeting AML cells within the cytoprotective BM microenvironment.

EIT Ambivium, Linea Semilunaris, and Fulcrum Abdominalis.

Building upon the recent advancements in posterior component separation techniques for complex abdominal wall hernia repair, highlights the critical importance of a thorough understanding of the abdominal wall anatomy. To address anatomical concepts with a pivotal role in hernia repair, we propose two new terminologies: "EIT Ambivium" referring to the lateral border of the rectus sheath, and "Fulcrum Abdominalis" demarcating the point where the Linea Arcuata intersects with the EIT Ambivium.

Complicaciones de la esofagectomía por cáncer de esófago / Complications of Esophagectomy for Esophageal Cancer

Introducción: La esofagectomía es uno de los procedimientos con más alta morbilidad posoperatoria en cirugía oncológica digestiva. Objetivo: Describir las complicaciones relacionadas con la esofagectomía subtotal programada según variables de interés. Métodos: Se realizó un estudio descriptivo y transversal en los Servicios de Cirugía General de los hospitales "Saturnino Lora" y "Juan Bruno Zayas" de Santiago de Cuba, desde 2010 hasta 2019. La población estuvo conformada por 81 pacientes, de la cual se reclutó una muestra aleatoria de 68 enfermos sometidos a esofagectomía subtotal programada por cáncer de esófago. Fueron investigadas las siguientes variables: presencia de complicaciones posoperatorias y tipo de técnica quirúrgica utilizada. Además, se clasificaron en grados según Dindo Clavien. Resultados: Todos los enfermos fueron operados por técnica abierta mediante esofagectomía subtotal programada, donde la resección mediante la técnica de Ivor-Lewis se realizó en el 69,2 por ciento. Para todas las técnicas quirúrgicas empleadas predominó la atelectasia (39,7 por ciento) como complicación posquirúrgica, y entre las infecciosas la neumonía en 30 enfermos (44,1 por ciento), mientras que para las complicaciones quirúrgicas no infecciosas el neumotórax fue mayormente incidente, para el 25,0 por ciento. El mayor número de complicaciones se ubicó en el grado II de Dindo Clavien. Conclusiones: La presencia de complicaciones posquirúrgicas de la enfermedad es notable, en correspondencia a lo reflejado por la literatura médica. Existió relación significativa entre la presencia del hábito de fumar, de enfermedad pulmonar obstructiva crónica y la de toracotomía con algunas de las complicaciones encontradas(AU)

Introduction: Esophagectomy is one of the procedures with the highest postoperative morbidity in digestive cancer surgery. Objective: To describe the complications related to scheduled subtotal esophagectomy according to variables of interest. Methods: A descriptive and cross-sectional study was carried out in the General Surgery Services at Saturnino Lora and Juan Bruno Zayas hospitals in Santiago de Cuba, from 2010 to 2019. The population consisted of 81 patients, out of which a random sample of 68 patients undergoing elective subtotal esophagectomy for esophageal cancer was selected. The variables investigated were presence of postoperative complications and type of surgical technique used. In addition, they were classified in grades according to Clavien-Dindo. Results: All the patients were operated by open technique by programmed subtotal esophagectomy, the resection by the Ivor-Lewis technique was performed in 69.2 percent. For all the surgical techniques used, atelectasis (39.7 percent) prevailed as a postsurgical complication, and among the infectious complications, pneumonia prevailed in 30 patients (44.1 percent), while for non-infectious surgical complications, pneumothorax was mostly incidental for 25.0 percent. The highest number of complications was in Clavien-Dindo grade II. Conclusions: The presence of post-surgical complications of the disease is notable, corresponding to what is reflected in the medical literature. There was significant relationship between the presence of smoking, chronic obstructive pulmonary disease and thoracotomy with some of the complications found(AU)

Umbilical incisional hernias (M3): are trocar-site hernias different? Comparative analysis of the EVEREG registry⋆.

BACKGROUND: Incisional hernia (HI), in open and laparoscopic surgery, is a very frequent complication. HI located in the umbilical region are called M3. The main aim of this study is to compare HI produced by the placement of an umbilical laparoscopic trocar (M3T) with those located in M3 in open surgery (M3O) in terms of basal characteristics, complications and recurrences; and secondarily the identification of risk factors. METHOD: Cross-sectional observational study based on the national prospective registry EVEREG during the period of July 2012-June 2018. The main variables were recurrences and postoperative complications. Both groups (M3T and M3O) were compared. Multiple logistic regression was performed to identify the risk factors of the entire cohort. RESULTS: 882 had a follow-up time longer than 12 months. M3O group presented superior ASA-Class, more complex HI and previous repair. It also presented a higher recurrence rate at 12 and 24 months (8.6% vs. 2.5%; P < 0,0001 and 9.3% vs. 2.9%; P < 0.0001) and higher postoperative complications rate (21.9% vs. 14.6 %; P = 0.02). Previous repair, intervention length and associated procedures requirement were identified as risk factors for postoperative complications. Absence of a specialist present during surgery, previous repair, and the absence of complications were identified as risk factors for recurrence. In the PSM analysis no differences were detected in of complications and recurrences. CONCLUSIONS: HI M3O is more complex than M3T. The complexity is not related to the origin of the hernia but to its characteristics and those of the patient.

Predictores de complicaciones y muerte en pacientes con esofagectomía por cáncer de esófago / Predictors of complications and death in patients with esophagectomy due to esophagus cancer

Introducción: La morbilidad y la mortalidad continúan siendo altas a escala mundial como consecuencia de la esofagectomía programada por cáncer de esófago. Objetivo: Identificar los factores predictores de complicaciones posquirúrgicas y de muerte, la estadía hospitalaria y las causas de muerte en la población estudiada. Método: Se efectuó un estudio de cohorte de 81 pacientes con diagnóstico de cáncer de esófago, atendidos en los hospitales Saturnino Lora y Dr. Juan Bruno Zayas Alfonso de la provincia de Santiago de Cuba desde enero de 2010 hasta diciembre de 2019, de los cuales se escogió una muestra aleatoria de 68. Para identificar los factores predictivos asociados con las complicaciones y la mortalidad se definieron 2 cohortes de enfermos: los expuestos y los no expuestos a los factores de interés, tales como la realización de toracotomía, las reintervenciones, además de las complicaciones médicas y quirúrgicas infecciosas. Se utilizó el método estadístico de bondad de ajuste de Hosmer-Lemeshow con un nivel de significación α= 0,10. Resultados: Si se realiza toracotomía, la probabilidad de que se desarrollen complicaciones quirúrgicas infecciosas es 2,3 veces mayor que si no se lleva a cabo el proceder; asimismo, el riesgo de fallecer por dichas complicaciones (p=0,024), en contraposición a cuando no se presentan, asciende a 370,0 % (IC 90 %: 1,5-14,8). Conclusión: La realización de toracotomía se establece como factor predictor de complicaciones y la presencia de reintervenciones y de complicaciones médicas y quirúrgicas infecciosas como predictores de muerte en la esofagectomía programada.

Introduction: Morbidity and mortality continue being high worldwide as consequence of the esophagectomy programmed due to esophagus cancer. Objective: To identify the predictor factors of postsurgical and death complications, hospitalization and death causes in the studied population. Method: A cohort study of 81 patients with diagnosis of esophagus cancer was carried out. They were assisted in Saturnino Lora and Dr. Juan Bruno Zayas Alfonso hospitals in the province of Santiago de Cuba from January, 2010 to December, 2019, of which a random sample of 68 was chosen. To identify the prediction factors associated with the complications and mortality 2 cohorts of sick patients were defined: the exposed and those not exposed to interest factors, such as the thoracotomy realization, reinterventions, besides the infectious medical and surgical complications. The statistical method of Hosmer-Lemeshow was used with a significance level of α = 0,10. Results: If thoracotomy is carried out, the probability that infectious surgical complications are developed is 2.3 times more that if it is not carried out; also, the risk of dying due to this complications (p=0.024), in opposition to when they are not presented, ascends to 370.0 % (IC 90 %: 1.5-14.8). Conclusion: The thoracotomy realization is established as predictor factor of complications and the presence of reinterventions and infectious medical and surgical complications as death predictors in the programmed esophagectomy.

Susceptibility Genes and Chromosomal Regions Associated With Non-Syndromic Familial Non-Medullary Thyroid Carcinoma: Some Pathogenetic and Diagnostic Keys.

Thyroid cancer is the malignant tumor that is increasing most rapidly in the world, mainly at the expense of sporadic papillary thyroid carcinoma. The somatic alterations involved in the pathogenesis of sporadic follicular cell derived tumors are well recognized, while the predisposing alterations implicated in hereditary follicular tumors are less well known. Since the genetic background of syndromic familial non-medullary carcinoma has been well established, here we review the pathogenesis of non-syndromic familial non-medullary carcinoma emphasizing those aspects that may be useful in clinical and pathological diagnosis. Non-syndromic familial non-medullary carcinoma has a complex and heterogeneous genetic basis involving several genes and loci with a monogenic or polygenic inheritance model. Most cases are papillary thyroid carcinoma (classic and follicular variant), usually accompanied by benign thyroid nodules (follicular thyroid adenoma and/or multinodular goiter). The possible diagnostic and prognostic usefulness of the changes in the expression and/or translocation of various proteins secondary to several mutations reported in this setting requires further confirmation. Given that non-syndromic familial non-medullary carcinoma and sporadic non-medullary thyroid carcinoma share the same morphology and somatic mutations, the same targeted therapies could be used at present, if necessary, until more specific targeted treatments become available.

Caracterización de pacientes con cáncer de esófago operados mediante esofagectomía programada

RESUMEN Introducción: El cáncer de esófago es la octava neoplasia diagnosticada con más frecuencia a nivel mundial, con 456 mil nuevos casos al año. Objetivo: Caracterizar a pacientes con cáncer de esófago que se les realiza esofagectomía subtotal programada. Métodos: Se realizó un estudio observacional, descriptivo de una serie de casos en los servicios de cirugía general de los Hospitales Provincial "Saturnino Lora" y General "Juan B. Zayas" de Santiago de Cuba desde 2010 al 2019. El universo estuvo conformado por 81 pacientes con diagnóstico de cáncer de esófago, de los cuales se seleccionaron 68 por cumplir con los criterios de inclusión. Fueron investigadas variables epidemiológicas, clínicas y quirúrgicas. Se calcularon porcentajes, media aritmética y desviación estándar. Resultados: Se observó predominio de los hombres (88,2 %); dentro de los factores epidemiológicos hubo predominio del hábito alcohólico (75,0 %) y del tabaquismo (58,8 %), la disfagia fue el síntoma más frecuente (48 enfermos). Las lesiones tumorales localizadas en el tercio medio e inferior fueron las más frecuentes. Predominó el carcinoma epidermoide en 52 pacientes y la localización del tumor en el tercio medio esofágico. En cuanto al tipo de resección quirúrgica la más utilizada fue la de McKeown (87,2 %). Conclusión: El cáncer de esófago es más frecuente en varones de la tercera década de la vida, fumadores, consumidores de alcohol y con mal estado nutricional. El patrón histológico predominante es el carcinoma epidermoide vegetante. La esofagectomía transhiatal es la variante técnica más utilizada en su tratamiento quirúrgico.

ABSTRACT Introduction: Esophageal cancer is the eighth most frequently diagnosed neoplasm worldwide with 456 thousand new cases per year. Objective: To characterize patients with esophageal cancer who undergo programmed subtotal esophagectomy. Methods: An observational, descriptive study of a case series was carried out in the general surgery services of the Provincial Hospital "Saturnino Lora" and General "Juan B. Zayas" of Santiago de Cuba from 2010 to 2019. The universe was made up of 81 patients diagnosed with esophageal cancer, of which 68 were selected agreeing inclusion criteria. Epidemiological, clinical and surgical variables were investigated. Percentages, arithmetic mean and standard deviation were calculated. Results: A predominance of men was observed (88.2 %); among the epidemiological factors, there was a predominance of alcoholic habit (75.0 %) and smoking (58.8 %), dysphagia in 48 patients was the most frequent symptom. Tumor lesions located in the middle and lower third were the most frequent. Squamous cell carcinoma predominated in 52 patients and the tumor was located in the middle third of the esophagus. Regarding the type of surgical resection, the most used was that of McKeown (87.2 %). Conclusion: Esophageal cancer is more frequent in men in the third decade of life, smokers, chronic alcoholics and poor nutritional status. The predominant histological pattern is vegetative squamous cell carcinoma. Transhiatal esophagectomy is the most widely used technical variant in its surgical treatment.

Studying the ubiquitin code through biotin-based labelling methods.

Post-translational modifications of cellular substrates by members of the ubiquitin (Ub) and ubiquitin-like (UbL) family are crucial for regulating protein homeostasis in organisms. The term "ubiquitin code" encapsulates how this diverse family of modifications, via adding single UbLs or different types of UbL chains, leads to specific fates for substrates. Cancer, neurodegeneration and other conditions are sometimes linked to underlying errors in this code. Studying these modifications in cells is particularly challenging since they are usually transient, scarce, and compartment-specific. Advances in the use of biotin-based methods to label modified proteins, as well as their proximally-located interactors, facilitate isolation and identification of substrates, modification sites, and the enzymes responsible for writing and erasing these modifications, as well as factors recruited as a consequence of the substrate being modified. In this review, we discuss site-specific and proximity biotinylation approaches being currently applied for studying modifications by UbLs, highlighting the pros and cons, with mention of complementary methods when possible. Future improvements may come from bioengineering and chemical biology but even now, biotin-based technology is uncovering new substrates and regulators, expanding potential therapeutic targets to manipulate the Ub code.

Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cells.

OBJECTIVES: Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5'UTR of XPO1 in the inflammatory environment characteristic of the coeliac intestinal epithelium. DESIGN: The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (m6A)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD. RESULTS: Individuals harbouring the risk allele had higher m6A methylation in the 5'UTR of XPO1 RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall m6A methylation in humans as well as in in vitro and in vivo models. CONCLUSION: We identify a novel m6A-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at m6A proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.

Effectiveness and safety of eribulin for human epidermal growth factor receptor 2 negative metastatic breast cancer in a real-world population.

BACKGROUND: Eribulin's clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. PATIENTS AND METHODS: This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. RESULTS: A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1-11.4) and 2.8 months (95% confidence interval: 2.5-3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3-4.5) versus triple negative: 2.0 (95%confidence interval: 1.7-2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6-12.5 vs. 4.8 months, 95% confidence interval: 3.4-6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1-16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8-5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. CONCLUSION: Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.

Apical approach in periodontal reconstructive surgery with enamel matrix derivate and enamel matrix derivate plus bone substitutes: a randomized, controlled clinical trial.

OBJECTIVES: This parallel, randomized controlled clinical trial evaluated the influence of bone substitutes (BS) on the efficacy of the non-incised papillae surgical approach (NIPSA) with enamel matrix derivate (EMD) in resolving deep, isolated, combined non-contained intrabony and supra-alveolar periodontal defects, preserving the soft tissue. MATERIAL AND METHODS: Twenty-four patients were randomized to treatment with NIPSA and EMD or NIPSA plus EMD and BS. Bleeding on probing (BoP), interproximal clinical attachment level (CAL), interproximal probing depth (PD), recession (REC), location of the tip of the papilla (TP), and width of the keratinized tissue (KT) were evaluated before surgery and at 1 year post-surgery (primary outcomes). Wound closure was assessed at 1 week post-surgery, and supra-alveolar attachment gain (SUPRA-AG) was recorded at 1 year post-surgery. RESULTS: At 1 week, 87.5% of cases registered complete wound closure and there were no cases of necrosis, without differences between groups (p > .05). At 1 year, all cases showed negative BoP. A significant PD reduction (NIPSA + EMD 8.25 ± 2.70 mm vs. NIPSA + EMD + BS 6.83 ± 0.81 mm) and CAL gain (NIPSA + EMD 8.33 ± 2.74 mm vs. NIPSA + EMD + BS 7.08 ± 2.68 mm) were observed (p < .001) in both groups, without significant between-group differences (p > .05). The residual PD was < 5 mm in all defects (NIPSA + EMD 2.50 ± 0.67 mm vs. NIPSA + EMD + BS 2.67 ± 0.78 mm). Soft tissues were preserved without significant between-group differences (REC: NIPSA + EMD 0.25 ± 0.45 mm vs. NIPSA + EMD + BS 0.17 ± 0.58 mm, p > .05; KT: 0.00 ± 0.43 mm vs. 0.08 ± 0.67 mm, p > .05). There were improvements in the papilla in both groups (TP: NIPSA + EMD 0.33 ± 0.49 mm vs. NIPSA + EMD + BS 0.45 ± 0.52 mm, p > .05), which was only significant in the NIPSA EMD + BS group (0.45 ± 0.52 mm; p < .05). In both groups, CAL gain was recorded in the supra-alveolar component, showing full resolution of the intrabony component of the defect in all cases (SUPRA-AG: NIPSA + EMD 1.83 ± 1.11 mm vs. NIPSA + EMD + BS 2.00 ± 1.76 mm, p > .05). CONCLUSIONS: NIPSA and EMD with or without BS seem to be a valid surgical approach in the treatment of isolated, deep non-contained periodontal defects. In our study, both treatments resulted in significant PD reduction and CAL gain, that extended in the supra-alveolar component, without differences with the use of BS. Both treatments resulted in soft tissue preservation. However, the addition of BS may improve interdental papillary tissue. CLINICAL RELEVANCE: NIPSA, with or without bone substitutes, resulted in significant periodontal improvement, with soft tissue preservation in isolated, deep non-contained periodontal defects. The application of bone substitutes may provide interproximal soft tissue gain. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT04712630.

Modulating factors of fibromyalgia in women during the COVID-19 pandemic: A protocol for systematic review.

BACKGROUND: Fibromyalgia is a disease that affects mostly women and is related to stressors. The aim of this study was to assess how the Coronavirus disease 2019 pandemic has affected women with fibromyalgia. METHODS: A systematic review was conducted in the PubMed, ScienceDirect, and Springer Link databases, following the recommendations of the preferred reporting items for systematic reviews and meta-analyses statement. The methodological quality was assessed using the Joanna Briggs Institute critical appraisal tools for non-randomized studies. RESULTS: A total of 6 studies were included. Most results indicated a worsening in the mental health of women with fibromyalgia during the pandemic, and this in turn impacted on physical health. CONCLUSION: The mental health of women with fibromyalgia was more affected during the Coronavirus disease 2019 pandemic period than that of non-fibromyalgia sufferers. This was also reflected in the worsening of symptoms and weakness in performing daily activities.

Algunas consideraciones en torno al cáncer de esófago / Some specificities around esophageal cancer

RESUMEN Introducción: El cáncer de esófago es una enfermedad presente a escala mundial, sobre todo en naciones en vías de desarrollo. Se realizó una revisión bibliográfica en bases de datos biomédicas mediante el motor de búsqueda de información Google académico. Se seleccionaron 24 de 62 artículos; 22 (91,6 %) del último quinquenio, publicados en español e inglés, relacionados con el objetivo propuesto. Objetivo: Describir algunos aspectos del cáncer de esófago, con énfasis en los epidemiológicos, etiopatogénicos y del tratamiento quirúrgico. Desarrollo: El cáncer de esófago es más frecuente en varones, con proporción hombre/mujer de 6:1, aunque en poblaciones de alto riesgo la incidencia es igual en ambos sexos; aunque algunos refieren que la relación es de 3 a 10 hombres por cada mujer, en dependencia de la zona geográfica. Las áreas de alta frecuencia son: Asia, África Central y del Sur. El carcinoma epidermoide y el adenocarcinoma representan el 95,0 % de todos los tumores esofágicos. La esofagectomía abierta o mínimamente invasiva constituye el pilar básico del tratamiento quirúrgico. Conclusiones: En la etiología del cáncer de esófago, los factores moleculares, genéticos y ambientales juegan un papel importante. El diagnóstico en etapas avanzadas predomina debido a lo tardío de la aparición de los síntomas y a las insuficiencias en el cribaje. El tratamiento quirúrgico constituye un pilar fundamental para los tres primeros estadios de la enfermedad, acompañada o no de quimio-radioterapia adyuvante o de neoadyuvancia (en el estadio II).

ABSTRACT Introduction: Esophageal cancer is a disease present worldwide, especially in developing nations. A bibliographic review was carried out in biomedical databases using the Google Scholar search engine. 24 of 62 articles were selected; 22 (91.6 %) of the last five years, published in Spanish and English, related to the proposed objective. Objective: To describe some aspects of esophageal cancer, with emphasis on the epidemiological, etiopathogenic and surgical treatment. Development: Esophageal cancer is more common in men, with a male/female ratio of 6:1, although in high-risk populations the incidence is the same in both sexes; although some report that the ratio is between 3 and 10 men for every woman, depending on the geographical area. High frequency areas are: Asia, Central and South of Africa. Squamous cell carcinoma and adenocarcinoma represent 95.0 % of all esophageal tumors. Open or minimally invasive esophagectomy is the basic pillar of surgical treatment. Conclusions: In the etiology of esophageal cancer, molecular, genetic and environmental factors play an important role. Diagnosis in advanced stages predominates due to the late onset of symptoms and insufficient screening. Surgical treatment is a fundamental pillar for the first three stages of the disease, accompanied or not by adjuvant or neoadjuvant chemo-radiotherapy (in stage II).