Management of Medullary Thyroid Cancer: Patterns of Recurrence and Outcomes of Reoperative Surgery.

BACKGROUND: There remains uncertainty regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer (MTC). We aim to describe the patterns of disease recurrence and outcomes of the reoperative surgery in a cohort of consecutively treated patients at a specialized tertiary referral center. PATIENTS AND METHODS: A retrospective cohort study of 235 surgically treated patients with MTC at a tertiary referral center was performed using prospectively collected data. RESULTS: In the study period 1986-2022, 235 patients underwent surgery for MTC. Of these, 45 (19%) patients had reoperative surgery for cervical nodal recurrence at a median (range) 2.1 (0.3-16) years following the index procedure. After a median follow-up of 4 years, 38 (84%) patients remain free of structural cervical recurrence, although 15 (33%) underwent 2 or more reoperative procedures. No long-term complications occurred after reoperative surgery. Local cervical recurrence was independently predicted by pathologically involved nodal status (OR 5.10, P = .01) and failure to achieve biochemical cure (OR 5.0, P = .009). Local recurrence did not adversely affect overall survival and was not associated with distant recurrence (HR 0.93, P = .83). Overall survival was independently predicted by high pathological grade (HR 10.0, P = .002) and the presence of metastatic disease at presentation (HR 8.27, P = 0018). CONCLUSION: Loco-regional recurrence in MTC does not impact overall survival, or the development of metastatic disease, demonstrating the safety of the staged approach to the clinically node-negative lateral neck. When recurrent disease is technically resectable, reoperative surgery can be undertaken with minimal morbidity in a specialized center and facilitates structural disease control.

Among high responders, is oocyte development potential different in Rotterdam consensus PCOS vs non-PCOS patients undergoing IVF?

PURPOSE: To evaluate the oocyte potential to develop to blastocyst in Rotterdam consensus PCOS in women with hyper-responses requiring freeze-all embryos. METHODS: Retrospective, single-academic center, cohort study of 205 patients who underwent freeze-all antagonist IVF cycles for OHSS risk between 2013 and 2019. Women in the PCOS group (n = 88) were diagnosed per the 2003 Rotterdam criteria. Control patients (n = 122) had no evidence of hyperandrogenism or menstrual disturbance. Data was compared by t-tests, chi-squared tests, or multivariate logistic regression (SPSS). Frozen blastocysts were Gardner's grade BB or better. RESULTS: There was no difference in terms of number of oocytes collected (PCOS vs non-PCOS 27.7 ± 9.4 vs 25.9 ± 8.2, p = 0.157), number of MII (20.7 ± 8.0 vs 19.1 ± 6.6, p = 0.130), number of 2PN fertilized (15.6 ± 7.4 vs 14.4 ± 5.9, p = 0.220), and number of frozen blastocysts (7.8 ± 4.9 vs 7.1 ± 3.8, p = 0.272). In addition, fertilization rates (74 ± 17% vs 75 ± 17%, p = 0.730), blastulation rates per 2PN (51 ± 25% vs 51 ± 25%, p = 0.869), and blastulation rates per mature oocytes (37 ± 18% vs 37 ± 15%, p = 0.984) were all comparable between PCOS and controls, respectively. Moreover, there was no difference when comparing PCOS and controls in pregnancy rates (45/81 vs 77/122, p = 0.28) and clinical pregnancy rates (34/81 vs 54/122, p = 0.75), respectively. Multivariate logistic regression controlling for confounders failed to alter these results. CONCLUSION: PCOS subjects do not seem to have altered oocyte potential as measured by number of MII oocytes collected, fertilization, and blastulation rates when compared to high-responder controls, with similar magnitude of stimulation.

Leveraging the social network for treatment of social anxiety: Pilot study of a youth-specific digital intervention with a focus on engagement of young men.

OBJECTIVE: The primary objective was to determine the acceptability, feasibility and safety of a novel digital intervention (Entourage) for young people with prominent social anxiety symptoms, with a particular focus on the engagement of young men. The secondary aim was to explore whether the intervention was associated with clinically significant improvements to clinical and social variables known to co-occur with social anxiety. METHOD: A multidisciplinary team comprising of mental health clinicians, researchers, young adult fiction writers, a comic artist and young people with a lived experience of social anxiety developed the Entourage platform in collaboration. Entourage combines evidence-based therapeutic techniques for social anxiety with an engaging, social-media-based interface that allows users to build social connections, while also receiving expert clinical moderation and support from peer workers. Acceptability, feasibility and safety outcomes of Entourage were tested in a 12-week pilot study with 89 young people (48.3% male; age M = 19.8 years, SD = 3.3 years). Eligible participants were recruited via liaison with four headspace early-intervention centres in north-western Melbourne. RESULTS: 56.8% of the sample reported social anxiety symptoms in the severe or very severe range at baseline. Results demonstrated the Entourage intervention was feasible, safe, and potentially acceptable, with 98.6% of participants reporting they would recommend Entourage to another young person experiencing social anxiety. Usage results were also comparable across male and non-male participants. Results showed that young people reliably and significantly improved on clinical and social variables. In particular, young males showed a clinically significant improvement on social anxiety symptoms (d = 0.79, p < .001), depression (d = 0.71, p < .001), belongingness (d = 0.58, p = .001), increased feelings of social connectedness (d = 0.46, p = .004) and decreased loneliness (d = 0.46, p = .006). Non-male participants also experienced a significant increase in social connectedness (d = 0.76, p < .001), alongside reduced social anxiety (d = 0.78, p < .001) and experiential avoidance (d = 0.81, p < .001). CONCLUSIONS: Entourage is a highly engaging and potentially effective intervention that represents a novel combination of features designed both to reduce social anxiety symptoms and improve social connection among young people. Entourage demonstrated some acceptability, feasibility and safety, with encouraging benefits to clinical and social variables. Entourage also showed favorable results for the engagement and support of young men with social anxiety symptoms.

An Enhanced Social Networking Intervention for Young People with Active Suicidal Ideation: Safety, Feasibility and Acceptability Outcomes.

Online social networking interventions have potential to support young people who experience suicidal thoughts by specifically addressing interpersonal risk factors for suicide, but may also pose a risk of harm. This uncontrolled, single-group pilot study aimed to evaluate the safety, feasibility, and acceptability of an enhanced online social networking intervention ("Affinity") among a sample of young people who experienced active suicidal ideation, and to explore potential changes in clinical outcomes and the therapeutic targets of the intervention. Twenty young people with current or recent suicidal ideation who were receiving treatment for depression at a tertiary-level mental health service were given access to Affinity for two months. Participants were assessed at baseline and 8-week follow-up; 90 percent reported clinical suicidal ideation at baseline. A priori criteria related to feasibility, safety and acceptability were satisfied. In terms of potential clinical effects, significant and reliable pre-post improvements were found on self-report outcomes including suicidal ideation. This study provides initial world-first evidence to support the use of an online intervention incorporating social networking as an adjunct to treatment for young people who experience suicidal ideation. The effectiveness of Affinity needs to be evaluated in a randomised controlled trial.

Social communication deficits and restricted repetitive behavior symptoms in Tourette syndrome.

Background: Autism spectrum disorders (ASD) have been found to occur more frequently in individuals with Tourette syndrome (TS) than in the general population. Similarities exist between ASD and TS clinically, which suggests a potential relationship between the two conditions. Purpose: The purpose of this study was to explore the occurrence of autism-related features in ASD and TS, focusing on areas of overlap and difference. Patients and methods: This study examined the nature and extent of autistic traits as measured by the Social Communication Questionnaire (SCQ) in a sample with a diagnosis of TS, a sample diagnosed to have ASD, and a normative general population sample. Results: The TS sample had significantly higher mean SCQ scores than the general population, but generally lower scores than the ASD sample. The group differences in mean SCQ scores between the TS and ASD sample were significant except in the domain of restricted repetitive behaviours (RRB). Conclusion: This suggests that ASD traits occur commonly in the TS population, with a significant overlap in certain clinical features. This was especially the case for complex movements or repetitive behaviours, which may represent either: i) a shared phenotype which is subclinical, ii) a phenocopy where some clinical symptoms mimic each other, or iii) a co-morbidity. Awareness of this association can be useful in identifying these symptoms as part of the comprehensive assessment of TS and addressing these to improve the overall clinical outcomes in these patients.

Current status of biological treatment options in Autism Spectrum Disorder.

Autism Spectrum Disorders (ASDs) are characterised by deficits in social communication and restricted and repetitive behaviours. With an onset in early childhood, ASDs are thought to be heterogeneous, both genetically and clinically. This has led to the notion that "autism" is "autisms", however, there has been limited progress in understanding the different subgroups and the unique pathogenesis that would then allow targeted intervention. Although existing treatments are mainly symptom focussed, research is beginning to unravel the underlying genetic and molecular pathways, structural and functional neuronal circuitry involvement and the associated neurochemicals. This paper will review selected biological models with regard to pharmacological targets while also covering some of the non-pharmacological treatments such as neuro-stimulation.

Screen time of infants in Sydney, Australia: a birth cohort study.

OBJECTIVES: To determine the amount of daily screen time in children 18 months of age and ascertain correlations that may be contributing to excessive screen use. DESIGN: A birth cohort was followed with telephone interviews at 6, 12 and 18 months of age. Information about screen time was collected at 18 months. SETTING: Parents were recruited from postnatal wards of 2 major public hospitals and at home visits conducted for new mothers within 4 weeks of birth in South Western Sydney (SWS). PARTICIPANTS: Parents of 500 children with infants 18 months of age residing in SWS. PRIMARY AND SECONDARY OUTCOMES: Screen time in infants 18 months of age and associated correlations. RESULTS: A large percentage of children 18 months of age (40%) had screen times >2 hours daily. There were significant associations between more than 2 hours of screen time daily and mothers without a partner (OR 4.32 (95% CI 1.67 to 11.15)); having <3 siblings (no siblings: OR 2.44 (95% CI 1.20 to 4.94); 1-2 siblings: OR 2.08 (95% CI 1.06 to 4.08)); an employed father (OR 1.96 (95% CI 1.09 to 3.52)); no outdoor equipment at home (OR 1.89 (95% CI 1.08 to 3.34)) and fewer than 5 outings per week (OR 2.08 (95% CI 1.37 to 3.17)). CONCLUSIONS: There is emerging evidence that excess screen time in children causes adverse cognitive, developmental and health outcomes. This study has shown that a large proportion of very young children residing in SWS have screen exposures for >2 hours per day. Factors contributing to excess screen time have also been identified in this study; however, a greater understanding of risk factors needs to be ascertained in order to facilitate greater public health efforts to reduce screen exposure.

Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome.

BACKGROUND: MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies. METHODS: Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays. RESULTS: We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain. CONCLUSIONS: The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis.

Parental encouragement of healthy behaviors: adolescent weight status and health-related quality of life.

BACKGROUND: Obesity is a major health concern for adolescents, with one in four being overweight or obese in Australia. The purpose of this study was to examine the moderation effect of parental encouragement of healthy behaviors on the relationship between adolescent weight status and Health-Related Quality of Life (HRQoL). METHODS: Baseline data were collected from 3,040 adolescents participating in the It's Your Move project, conducted in the Barwon South-West region of Victoria, in 2005. The Paediatric Quality of Life Inventory was used to measure HRQoL, and parental encouragement was derived from purposely designed self-report items. Weight status was calculated according to World Health Organization growth standards from measured weight and height. Linear regression analyses modeled direct relationships and interaction terms. Analyses were adjusted for age, sex, physical activity level, nutrition and school attended. RESULTS: Higher levels of parental encouragement, as compared to low encouragement, were positively associated with higher global HRQoL scores, particularly in the physical functioning domain. To a lesser degree, high parental encouragement was also associated with higher scores on the psychosocial domain. Obese weight status showed a significant association with lower HRQoL on all scales. Parental encouragement significantly moderated the inverse relationship between overweight status and physical wellbeing. CONCLUSIONS: Findings suggest that parental encouragement of healthy behavior is associated with increased HRQoL scores for adolescents. Whilst more research is needed to validate the significant interaction effect, main effects suggest that parental encouragement of healthy behavior is an important factor in adolescent wellbeing and should be considered when developing prevention and clinical interventions for obesity.