Molecular profile in endometrial carcinoma: can we predict the lymph node status? A systematic review and meta-analysis.

PURPOSE: Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of lymph node metastases (LNM) in patients with EC according to molecular profile. METHODS: A systematic review and meta-analysis were performed according to PRISMA guidelines by searching in two major electronic databases (PubMed and Scopus), including original articles reporting lymph node metastases according to the molecular classification of EC as categorized in the ESGO-ESMO-ESP guidelines. RESULTS: Fifteen studies enrolling 3056 patients were included. Pooled prevalence LNM when considering only patients undergoing lymph node assessment was 4% for POLE-mutated (95%CI: 0-12%), 22% for no specific molecular profile (95% CI: 9-39%), 23% for Mismatch repair-deficiency (95%CI: 10-40%) and 31% for p53-abnormal (95%CI: 24-39%). CONCLUSIONS: The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.

Effectiveness of family metacognitive training in mothers with psychosis and their adolescent children: a multicenter study protocol.

Background: More than half of women with psychosis take care of their children despite the difficulties caused by the disease. Additionally, these kids have a higher risk of developing a mental health disorder. However, no interventions have been developed to meet these needs. Metacognitive Training (MCT) is a psychological intervention that has demonstrated its efficacy in improving cognitive insight, symptom management and social cognition in people with first-episode psychosis (FEP). Additionally, MCT has shown better results in women than men with FEP. This study aims to adapt and evaluate the efficacy of MCT-F in mothers and adolescent children in an online group context with the main purpose of improving family relationships, cognitive awareness and symptoms in women with psychosis and increase their children's knowledge of the disease and their functioning. As secondary objectives, it also aims to evaluate improvements in metacognition, social cognition, symptoms, protective factors and self-perception of stigma. Materials and methods: A quasi-experimental design with participants acting as their own control will be carried out. Forty-eight mothers with psychosis and their adolescent children (between 12 and 20 years old) recruited from a total of 11 adult mental health care centers will receive MCT-F. Participants will be evaluated 11 weeks before the intervention (T1), at baseline (T2), and post-intervention (T3) with a cognitive insight scale, as a primary outcome. Measures of metacognitive and social cognition, symptoms, cognitive functioning, family and social functioning, protective factors (self-esteem, resilience, and coping strategies) and self-perceived stigma will be addressed as secondary outcomes. Assessment will also address trauma and attachment in mothers and, lastly, the feasibility and acceptability of MCT-F in both participant groups. Discussion: This will be the first investigation of the efficacy, acceptability, and viability of the implementation of MCT-F. The results of this study may have clinical implications, contributing to improving mothers' with psychosis and adolescents' functioning and better understanding of the disease, in addition to the possible protective and preventive effect in adolescents, who are known to be at higher risk of developing severe mental disorders.Clinical trial registration:https://clinicaltrials.gov/, identifier [NCT05358457].

Family Metacognitive Training (MCT-F): Adapting MCT to Mothers with Psychosis and Their Adolescent Children.

Over half of women with psychosis are mothers. Research suggests that mothers with psychosis face unique challenges affecting both their mental health prognosis and their relationship with their children. Moreover, those children have a higher risk of developing a mental disorder. Notwithstanding, interventions specifically tailored to these families remain largely uncovered. Metacognitive Training (MCT) has demonstrated its efficacy in improving cognitive insight, symptom management, and social cognition in people with psychosis. However, there is no evidence of the efficacy of MCT in a family setting (MCT-F). This study describes the first adaptation of MCT for mothers with psychosis and their adolescent children in an online group setting. The phases (assessment, decision, adaptation, production, topical experts' integration) of the ADAPT-ITT model were systematically applied through a participatory approach (n = 22), including a first-person perspective and involving qualitative (e.g., topical expert literature review and consensus groups, interviews, thematic analyses) and quantitative methods. While MCT's core components were retained, participants guided adaptations both in content and delivery. The findings suggest the importance of community engagement and sharing decision-making processes to demonstrate the acceptability and feasibility of the adapted intervention. Employing a structured approach such as the ADAPT-ITT model ensures readiness of the new training for efficacy trials.

Molecular profile is a strong predictor of the pattern of recurrence in patients with endometrial cancer.

OBJECTIVES: To investigate the pattern of first recurrence of disease in patients with endometrial cancer according to molecular classification, and to assess the independent role of molecular profiling in each type of failure. METHODS: Retrospective single-center study including patients diagnosed with endometrial cancer stage I-IVB (International Federation of Gynecology and Obstetrics 2009) between December 1994 and May 2022, who underwent primary surgical treatment and had a complete molecular profile. First recurrence was classified as isolated or multiple, and as vaginal, pelvic, peritoneal, nodal, and distant according to its location. The log-rank test and univariate and multivariate adjusted Cox regression models were used for comparison between groups. RESULTS: A total of 658 patients were included. Recurrence was observed in 122 patients (18.5%) with a recurrence rate of 12.4% among mismatch-repair deficient tumors, 14.5% among non-specific molecular profile, 2.1% among POLE-mutated, and 53.7% among p53-abnormal tumors. Recurrences were found to be isolated in 80 (65.6%) and multiple in 42 (34.4%) patients, with no differences in molecular subtype (p=0.92). Patients with p53-abnormal tumors had a recurrence mainly as distant (28.4%) and peritoneal (21.1%) disease, while patients with non-specific molecular profile tumors presented predominantly with distant failures (10.3%), and mismatch-repair deficient tumors with locoregional recurrences (9.4%).On multivariate analysis, p53-abnormal molecular profile was the only independent risk factor for peritoneal failure (OR=8.54, 95% CI 2.0 to 36.3). Vaginal recurrence was independently associated with p53-abnormal molecular profile (OR=6.51, 95% CI 1.1 to 37.4) and lymphovascular space invasion. p53-abnormal and non-specific molecular profiles were independent predictors for distant recurrence (OR=3.13, 95% CI 1.1 to 8.7 and OR=2.35, 95% CI 1.1 to 5.0, respectively), along with lymphovascular space invasion and high-grade tumors. Molecular profile was not independently associated with pelvic and nodal recurrences. CONCLUSIONS: Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.

Endometrial adenocarcinoma recurring in the lung: impact of molecular profile and role of local therapies on prognosis.

OBJECTIVES: The objective of our study was to describe the characteristics of patients with endometrial cancer diagnosed with a first recurrence involving the lung, and to describe the prognostic role of the molecular profile. We also aimed to describe the prognostic outcomes after local treatment of recurrence (resection of lung metastases or stereotactic body radiation therapy) in a group of patients with isolated lung recurrence. METHODS: This was a retrospective, single-center study between June 1995 and July 2021. The study included patients diagnosed with a first recurrence of endometrial cancer involving the lung. We defined two groups of patients: patients with isolated lung recurrence (confined to the lung) and patients with multisystemic recurrence (in the lung and other locations). RESULTS: Among 1413 patients diagnosed with endometrial cancer in stage IA to IVA of the International Federation of Gynecology and Obstetrics (FIGO) 2009, 64 (4.5%) patients had a first recurrence involving the lung. Of these, 15 (39.1%) were of a non-specific molecular profile, 16 (25%) were p53-abnormal, 15 (23.4%) were mismatch-repair deficient, and 0% POLE-mutated. P53-abnormal patients had the shortest 3 year progression-free survival after recurrence and those with mismatch-repair deficient had the longest 3 year progression-free survival (14.3% (range; 1.6-40.3) and 47.6% (range; 9.1-79.5) respectively, p=0.001). We found no differences on overall survival after recurrence by molecular profile. Thirty-one of 64 (48.4%) patients had an isolated recurrence in the lung, and 16 (25%) patients received local treatment. When comparing patients with isolated lung recurrence, locally treated patients had a longer median progression-free survival than patients treated systemically (41.9 (range, 15.4-NA) vs 7.8 (range, 7.2-10.6) months respectively, p=0.029), a complete response rate of 80% for stereotactic body radiation therapy and a complete resection of 90.9% for surgery. CONCLUSION: Although few patients will benefit from local treatment (stereotactic body radiation therapy or resection) after a recurrence involving the lung, local therapies might be considered as an option in oligometastatic lung recurrences as they achieve high local control rates and better oncological outcomes than systemic treatment alone.

Is moral disgust socially learned?

The present study examined mother-child talk about disgust. A total of 68 mothers and their 4-, (Mage = 55.72 months, SD = 4.13), 6- (Mage = 77.70 months, SD = 5.45), and 8- (Mage = 100.90 months, SD = 4.61) year-old children discussed four tasks relating to moral and pathogen disgust. Tasks comprised labeling facial expressions of emotions, generating items that would make participants disgusted or angry, identifying moral and pathogen transgressions as either causing anger or disgust, and finally rating the degree to which moral and pathogen transgressions were disgusting and justifying their responses. Mother-child dyads recognized the facial expression of happiness more accurately than that of disgust, but disgust was recognized equally well as expressions of sadness and anger across all age groups. Dyads associated moral transgressions with anger, whereas they associated pathogen transgressions with disgust. Finally, mothers and children and mothers individually rated pathogen transgressions as more disgusting than moral transgressions. Taken together, findings show that moral disgust is understood at a later age and is only used metaphorically, if at all, in children as old as 8 years old. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium.

CDK8 and CDK19 form a conserved cyclin-dependent kinase subfamily that interacts with the essential transcription complex, Mediator, and also phosphorylates the C-terminal domain of RNA polymerase II. Cells lacking either CDK8 or CDK19 are viable and have limited transcriptional alterations, but whether the two kinases redundantly control cell proliferation and differentiation is unknown. Here, we find in mice that CDK8 is dispensable for regulation of gene expression, normal intestinal homeostasis, and efficient tumourigenesis, and is largely redundant with CDK19 in the control of gene expression. Their combined deletion in intestinal organoids reduces long-term proliferative capacity but is not lethal and allows differentiation. However, double-mutant organoids show mucus accumulation and increased secretion by goblet cells, as well as downregulation of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and functionality of the CFTR pathway. Pharmacological inhibition of CDK8/19 kinase activity in organoids and in mice recapitulates several of these phenotypes. Thus, the Mediator kinases are not essential for cell proliferation and differentiation in an adult tissue, but they cooperate to regulate specific transcriptional programmes.

Surgical treatment in older patients with endometrial cancer: A retrospective study.

INTRODUCTION: Older patients (OP) diagnosed with endometrial cancer (EC) are less likely to receive an optimal surgical treatment compared with non-older patients (NOP). This undertreatment along with the presence of more aggressive tumours at diagnosis can explain the worse prognosis of EC in OP. There is limited evidence comparing perioperative outcomes between OP and NOP, and the benefit of applying complex procedures to OP is still controversial. The primary objective of the study was to compare intraoperative and postoperative complications between NOP and OP with EC that underwent primary surgery. Secondary objectives were to compare surgical management and survival rates. METHODS: This is a retrospective single-centre observational study including women undergoing surgery for EC between 2010 and 2019. Patients were classified according to age as NOP (younger than 75 years) or OP (75 years or older). Basal characteristics and surgical outcomes of groups were compared using Chi-square, Fisher's exact tests, student T-tests or Mann Whitney tests. Kaplan Meier analysis was used to evaluate survival. RESULTS: In total 281 patients underwent primary surgery for EC between 2010 and 2019 in our centre. At diagnosis, 184 patients were younger than 75 years while 97 were 75 and older. No differences were found in disease characteristics. Most of our patients (83,3%) underwent laparoscopic surgery. Pelvic (58,2% vs. 37,1%, p = 0,001) and para-aortic (46,7% vs. 23,7%, p < 0,001) lymphadenectomies were performed more frequently in NOP compared with OP. Rates of intra-operative (6,5% vs. 12,4%, p = 0,116) and post-operative (13,0% vs. 20,6%, p = 0,120) complications were not statistically different between NOP and OP, and neither was the rate of severe complications according to Clavien-Dindo classification (5,4% vs. 8,2% of complications grade III-V respectively, p = 0,387). The 5-year disease-specific survival (DSS) rate tended to be lower in the OP than in the NOP (74,8% vs. 82,5%, p = 0,071). Considering only patients in whom complete surgical staging was performed, OP presented similar DSS to NOP, with comparable complication rate. CONCLUSIONS: OP do not present a significantly higher rate of perioperative complications compared to NOP. However, they underwent fewer lymphadenectomies and tended to present poorer DSS. Further studies are needed to standardize the surgical management of these patients.

Laparoscopic approach for symptomatic pelvic and para-aortic lymphoceles

Description and demonstration of the feasibility of laparoscopic management of symptomatic pelvic lymphocele after surgical staging in gynecological cancer surgery. Step-by-step description of the surgical procedure using pictures and an educational video. Patient gave informed consent for the use of images and the full video article was approved by the Institutional Review Board of the Hospital of Sant Pau. Lymphocele is one of the most common complications of pelvic or lumbo-aortic lymphadenectomy. Although the incidence is variable at 1-58%, around 5-18% of cases are symptomatic. Only symptomatic lymphocele requires treatment, which can be medical or interventional. Drainage is usuallyperformed by guided radiology although a surgical approach has shown a lower rate of recurrence. A 64-years-old woman diagnosed withendometrial carcinosarcoma was staged laparoscopically by pelvic and para-aortic lymphadenectomy. Para-aortic lymphadenectomy wasperformed using an extraperitoneal approach. Three weeks later she presented with an intense and persistent burning pain, radiating towardsthe left leg. Computed tomography imaging suggested the presence of a 10x7.6 cm lymphocele adjacent to the left external iliac vessels.Laparoscopy was performed with four-port placement configuration, enabling the identification of a large, bilobed lymphocele, adjacent to theleft pelvic wall and left paracolic gutter. Adhesiolysis and identification of main landmarks in the left paracolic gutter and left paravesical fossawas performed as a first step. Peritoneum of each lymphocele was opened in the caudal region and the opening was broadened to facilitatelymph drainage. Owing to the low morbidity and excellent results, we suggest that laparoscopic drainage should be performed as a feasible anduseful treatment for pelvic symptomatic lymphoceles.

Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis.

Ki-67 is a nuclear protein that is expressed in all proliferating vertebrate cells. Here, we demonstrate that, although Ki-67 is not required for cell proliferation, its genetic ablation inhibits each step of tumor initiation, growth, and metastasis. Mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumorigenesis. In established cancer cells, Ki-67 knockout causes global transcriptome remodeling that alters the epithelial-mesenchymal balance and suppresses stem cell characteristics. When grafted into mice, tumor growth is slowed, and metastasis is abrogated, despite normal cell proliferation rates. Yet, Ki-67 loss also down-regulates major histocompatibility complex class I antigen presentation and, in the 4T1 syngeneic model of mammary carcinoma, leads to an immune-suppressive environment that prevents the early phase of tumor regression. Finally, genes involved in xenobiotic metabolism are down-regulated, and cells are sensitized to various drug classes. Our results suggest that Ki-67 enables transcriptional programs required for cellular adaptation to the environment. This facilitates multiple steps of carcinogenesis and drug resistance, yet may render cancer cells more susceptible to antitumor immune responses.

Gender differences in response to metacognitive training in people with first-episode psychosis.

INTRODUCTION: The study aimed to assess gender differences in the efficacy of metacognitive training (MCT) in people with first-episode psychosis in terms of symptoms and cognitive insight as a primary outcome and other metacognitive and social cognition measures as a secondary outcome. METHOD: A multicenter, controlled, randomized clinical trial was performed including 122 patients with first-episode psychosis. A total of 8 weekly group sessions of MCT or a psychoeducational intervention were performed. Patients were assessed at baseline, posttreatment, and follow-up. Symptoms were assessed with the Positive and Negative Syndrome Scale and cognitive insight with the Beck Cognitive Insight Scale. A battery of questionnaires on metacognition and social cognition variables was included to assess secondary outcomes. A regression model for repeated measures was performed by gender. RESULTS: Women of the MCT group improved more in general symptoms (p = .046), self-certainty (p = .010), and a composite index of the cognitive insight (p = .031). Moreover, women in the MCT group showed a reduction in personalizing bias (p = .021) and irrational beliefs related to dependence (p = .024), while men in the MCT group showed an improvement in intolerance to frustration (p = .017). In the Jumping to Conclusions task, men in the MCT group improved in the affective task (p = .021) while no differences were found in women. CONCLUSIONS: Our results suggest that MCT is more effective in reducing symptoms and improving cognitive insight for women than men. Moreover, different irrational beliefs and cognitive biases were reduced differently considering gender. MCT could be a gender-sensitive intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Young people's reasoning about exclusion in novel groups.

This study examined children's and adolescents' reasoning about the exclusion of others in peer and school contexts. Participants (80 8-year-olds, 85 11-year-olds, 74 14-year-olds, and 73 20-year-olds) were asked to judge and reason about the acceptability of exclusion from novel groups by children and school principals. Three contexts for exclusion between two groups were systematically varied: unequal economic status, geographical location, and a control (no reason provided for group differences). Regardless of condition, participants believed that exclusion was less acceptable in peer contexts than in school contexts and when children were excluded rather than principals. Participants also used more moral and less social conventional reasoning for peer contexts than for school contexts. In terms of condition, whereas 8-year-olds rated exclusion based on unequal economic status as less acceptable than exclusion based on geographical location or no reason when enacted by a principal, 14-year-olds rated the unequal economic condition as more acceptable than the other two contexts. The 11- and 20-year-olds did not distinguish economic status differences. The findings suggest that children and adolescents are sensitive to context and take multiple variables into account, including the type of group difference (socioeconomic status or other reasons), authority status of the perpetrator of exclusion, and setting (school or peer group). Patterns may have differed from past research because of the sociocultural context in which exclusion was embedded and the contexts of group differences.

Are There Gender Differences in Emotion Comprehension? Analysis of the Test of Emotion Comprehension.

This article examines whether there are gender differences in understanding the emotions evaluated by the Test of Emotion Comprehension (TEC). The TEC provides a global index of emotion comprehension in children 3-11 years of age, which is the sum of the nine components that constitute emotion comprehension: (1) recognition of facial expressions, (2) understanding of external causes of emotions, (3) understanding of desire-based emotions, (4) understanding of belief-based emotions, (5) understanding of the influence of a reminder on present emotional states, (6) understanding of the possibility to regulate emotional states, (7) understanding of the possibility of hiding emotional states, (8) understanding of mixed emotions, and (9) understanding of moral emotions. We used the answers to the TEC given by 172 English girls and 181 boys from 3 to 8 years of age. First, the nine components into which the TEC is subdivided were analysed for differential item functioning (DIF), taking gender as the grouping variable. To evaluate DIF, the Mantel-Haenszel method and logistic regression analysis were used applying the Educational Testing Service DIF classification criteria. The results show that the TEC did not display gender DIF. Second, when absence of DIF had been corroborated, it was analysed for differences between boys and girls in the total TEC score and its components controlling for age. Our data are compatible with the hypothesis of independence between gender and level of comprehension in 8 of the 9 components of the TEC. Several hypotheses are discussed that could explain the differences found between boys and girls in the belief component. Given that the Belief component is basically a false belief task, the differences found seem to support findings in the literature indicating that girls perform better on this task.

Left cheek bias for emotion perception, but not expression, is established in children aged 3-7 years.

As the left hemiface is controlled by the emotion-dominant right hemisphere, emotion is expressed asymmetrically. Portraits showing a model's left cheek consequently appear more emotive. Though the left cheek bias is well established in adults, it has not been investigated in children. To determine whether the left cheek biases for emotion perception and expression are present and/or develop between the ages of 3 and 7 years, 145 children (71 male, 74 female; M age = 65.49 months) completed two experimental tasks: one assessing biases in emotion perception, and the other assessing biases in emotion expression. Regression analysis confirmed that children aged 3-7 years find left cheek portraits happier than right cheek portraits, and age does not predict the magnitude of the bias. In contrast when asked to pose for a photo expressing happiness children did not show a left cheek bias, with logistic regression confirming that age did not predict posing orientations. These findings indicate that though the left cheek bias for emotion perception is established by age 3, a similar bias for emotion expression is not evident by age 7. This implies that tacit knowledge of the left cheek's greater expressivity is not innate but develops in later childhood/adolescence.

Parent-Child Positive Touch: Gender, Age, and Task Differences.

This study examined gender, age, and task differences in positive touch and physical proximity during mother-child and father-child conversations. Sixty-five Spanish mothers and fathers and their 4- (M = 53.50 months, SD = 3.54) and 6-year-old (M = 77.07 months, SD = 3.94) children participated in this study. Positive touch was examined during a play-related storytelling task and a reminiscence task (conversation about past emotions). Fathers touched their children positively more frequently during the play-related storytelling task than did mothers. Both mothers and fathers were in closer proximity to their 6-year-olds than their 4-year-olds. Mothers and fathers touched their children positively more frequently when reminiscing than when playing. Finally, 6-year-olds remained closer to their parents than did 4-year-olds. Implications of these findings for future research on children's socioemotional development are discussed.

Gender and age differences in parent-child emotion talk.

This study examined gender differences in emotion word use during mother-child and father-child conversations. Sixty-five Spanish mothers and fathers and their 4- (M = 53.50, SD = 3.54) and 6-year-old (M = 77.07, SD = 3.94) children participated in this study. Emotion talk was examined during a play-related storytelling task and a reminiscence task (conversation about past experiences). Mothers mentioned a higher proportion of emotion words than did fathers. During the play-related storytelling task, mothers of 4-year-old daughters mentioned a higher proportion of emotion words than did mothers of 4-year-old sons, whereas fathers of 4-year-old daughters directed a higher proportion of emotion words than did fathers of 4-year-old sons during the reminiscence task. No gender differences were found with parents of 6-year-old children. During the reminiscence task daughters mentioned more emotion words with their fathers than with their mothers. Finally, mothers' use of emotion talk was related to whether children used emotion talk in both tasks. Fathers' use of emotion talk was only related to children's emotion talk during the reminiscence task.

The use of emotions in narratives in Williams syndrome.

UNLABELLED: Although individuals with Williams syndrome are very sociable, they tend to have limited contact and friendships with peers. In typically developing children the use of positive emotions (e.g., happy) has been argued to be related to peer relationships and popularity. The current study investigated the use and development of emotion words in Williams syndrome using cross-sectional developmental trajectories and examined children's use of different types of emotion words. Nineteen children with Williams syndrome (WS) and 20 typically developing (TD) children matched for chronological age told a story from a wordless picture book. Participants with WS produced a similar number of emotion words compared to the control group and the use of emotion words did not change when plotted against chronological age or vocabulary abilities in either group. However, participants with WS produced more emotion words about sadness. Links between emotion production and friendships as well as future studies are discussed. LEARNING OUTCOMES: After reading this article, readers will be able to: explain the development of positive and negative emotions in Williams syndrome and recognize that emotion production is atypical in this population.