Intrusive thoughts and memories in adolescents with major depressive disorder or post-traumatic stress disorder.

OBJECTIVES: Research in adults suggests that intrusive memories and intrusive thoughts (often referred to as intrusive cognitions) are common in members of the general population and are often seen in clinical disorders. However, little is known about the experience of intrusive cognitions in adolescents, particularly in adolescents with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The present study sought to gather fundamental data on these phenomena (i.e., frequency, characteristics and appraisals of intrusive cognitions) in adolescents with MDD and PTSD. METHODS: Adolescents aged 11-18 with MDD (n = 11), PTSD (n = 13) and a non-clinical control group (n = 25) completed structured interviews concerning their intrusive memories and thoughts. RESULTS: Intrusive thoughts were common in all three groups but were particularly frequently experienced in the MDD group. Intrusive memories were expectedly very common in the PTSD group but also experienced by over half of the adolescents with MDD. Both clinical groups reported more negative emotions in response to their intrusive thoughts or memories and appraised these cognitions more negatively than the non-clinical group. CONCLUSION: Intrusive memories and thoughts are common experiences in adolescents with MDD and PTSD. Emotions and appraisals relating to these cognitions may be targets for psychological intervention in this age group. However, small sample sizes limit the conclusions that can be drawn. Replication is needed with larger numbers of clinical participants.

The Difference in Clinical Behavior of Gene Fusions Involving RET/PTC Fusions and THADA/IGF2BP3 Fusions in Thyroid Nodules.

BACKGROUND: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules. This study investigated the impact of two gene fusions, RET/PTC and THADA/IGF2BP3, that have been described as oncogenic events in thyroid neoplasms. METHODS: We performed a retrospective, single-centered study at a McGill University teaching hospital in Montreal, Canada, from January 2016 to August 2021. We included patients who underwent surgery for thyroid nodules that pre-operatively underwent molecular testing showing either RET/PTC or THADA/IGF2BP3 gene fusion. RESULTS: This study included 697 consecutive operated thyroid nodules assessed using molecular testing, of which five had the RET/PTC fusion and seven had the THADA/IGF2BP3 fusion. Of the five nodules in the RET/PTC group, 100% were malignant and presented as Bethesda V/VI. Eighty percent (4/5) were found to have lymph node metastasis. Twenty percent (1/5) had extrathyroidal extensions. Sixty percent (3/5) were a diffuse sclerosing variant of papillary thyroid carcinoma, and the rest were the classical variant. Of the seven THADA/IGF2BP3 nodules, all presented as Bethesda III/IV and 71.4% (5/7) were malignant based on the final pathology analysis, and 28.6% (2/7) were NIFTP. All the THADA/IGF2BP3 fusion malignancies were a follicular variant of papillary thyroid carcinoma. None had lymph node metastasis or displayed extrathyroidal extensions. CONCLUSIONS: RET/PTC nodules presented as Bethesda V/VI and potentially had more aggressive features, whereas THADA/IGF2BP3 nodules presented as Bethesda III/IV and had more indolent behavior. This understanding may allow clinicians to develop more targeted treatment plans, such as the extent of surgery and adjuvant radioactive iodine treatment.

Effect of Having Concurrent Mutations on the Degree of Aggressiveness in Patients with Thyroid Cancer Positive for TERT Promoter Mutations.

This study aimed to examine whether concurrent mutations with a TERT promoter mutation are associated with a greater likelihood of more aggressive disease than a TERT promoter mutation alone. The medical records of 1477 patients who underwent thyroid surgery at two tertiary hospitals between 2017 and 2022 were reviewed. Twenty-four patients had TERT promoter mutations based on molecular profile testing. Clinicodemographic data, mutational profiles, and histopathological features were assessed. Descriptive analysis, Fisher's exact test, and binary logistic regression were performed. Seven patients had single-gene TERT promoter mutations, and 17 had concurrent mutations, including BRAF V600E, HRAS, NRAS, PIK3CA, and EIF1AX. The overall prevalence of malignancy was 95.8%, of which 78.3% were aggressive thyroid cancers. There was a statistically significant association between concurrent mutations and disease aggressiveness. The odds of having aggressive disease were 10 times higher in patients with a TERT promoter mutation and a concurrent molecular alteration than in those with a TERT promoter mutation alone. This is an important finding for thyroid specialists to consider when counseling patients concerning risk stratification and management options.

Risk Factors Associated With Reoperative Surgery for Thyroid Malignancies: A Retrospective Cohort Study.

OBJECTIVE: To examine various factors associated with an increased risk of reoperation for persistent or recurrent malignant thyroid cancers. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic hospital centers. METHODS: Patients undergoing surgery for thyroid cancer at 2 tertiary academic institutions from 2006 to 2020 were included. Those who underwent a reoperative procedure were compared with patients only requiring 1 procedure. The Pearson chi-square and independent t test were used to compare group data accordingly. Furthermore, a binomial logistic regression was performed, while machine learning models were used to construct a predictive algorithm. RESULTS: This study included 2266 patients with surgically managed thyroid malignancy, of which 54 (2.4%) necessitated reoperations. Those requiring a second surgical procedure were more likely to be male (40.7% vs 20.9%, P < .001), undergo bilateral (24.1% vs 3.3%, P < .001) and lateral (16.7% vs 1.8%, P < .001) neck dissections, and have a greater number of metastatic lymph nodes (mean, 9.1 vs 3.5; P < .001) and a larger tumor size (mean, 3.0 vs 2.0 cm; P < .001). According to the binomial logistic regression model, lateral neck dissection, greater number of metastatic lymph nodes, and larger tumor size significantly increased the odds of necessitating a second procedure by 7.8 (95% CI, 2.523-24.083), 1.1 (95% CI, 1.032-1.152), and 1.3 (95% CI, 1.064-1.559), respectively. Last, machine learning models could not significantly predict the occurrence of reoperation. CONCLUSION: This study identified patient- and cancer-related characteristics associated with an increased risk of requiring reoperation for thyroid malignancies.

EIF1AX mutation in thyroid tumors: a retrospective analysis of cytology, histopathology and co-mutation profiles.

BACKGROUND: The EIF1AX mutation has been identified in various benign and malignant thyroid lesions, with a higher prevalence in poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma, especially when combined with RAS or TP53 mutation. However, data and clinical significance of EIF1AX mutations in thyroid nodules is still limited. We investigated the prevalence of EIF1AX mutations and co-mutations in cytologically indeterminate thyroid nodules at our institution. METHODS: A 5-year retrospective analysis was performed on surgically resected thyroid nodules with identified EIF1AX mutations on molecular testing with ThyroseqV3®. Mutation type and presence of co-mutations were correlated with histopathologic diagnosis and clinical characteristics. Histopathology diagnoses were subsequently categorized as benign, borderline, malignant or aggressive malignant (≥ 10% PDTC component). Chi-square test was used to compare the malignancy associations of the: 1) A113_splice mutation compared to non-A113_splice mutations 2) singular A113_splice mutations compared to singular non-A113_splice mutations. Fisher's Exact Test was used to determine the association of A113_splice mutation with aggressive malignancies compared to non-A113_splice mutations. A p value of 0.05 or less was considered statistically significant. RESULTS: Out of 1583 patients who underwent FNA, 621 had further molecular testing. 31 cases (5%) harbored EIF1AX mutations. Of these cases, 12 (38.7%) were malignant, 2 (6.5%) were borderline, and 17 (55%) were benign. 4/31 cases (13%) were aggressive malignant (≥ 10% PDTC component). The most prevalent mutation was the A113_splice mutation at the junction of intron 5 and exon 6 (48%). All other mutations, except one, were located at the N-terminal in exon 2. 7/31 cases (22.6%) harbored ≥ 1 co-mutation(s), including 4 RAS, 3 TP53, 1 TERT and 1 PIK3CA, with 86% of them being malignant. All 4 nodules with RAS co-mutations were malignant including one PDTC. CONCLUSION: Our study reports the largest cohort of EIF1AX mutations in Bethesda III/IV FNA samples with surgical follow-up to our knowledge. The presence of the EIF1AX mutation confers a 45.2% risk of malignancy (ROM) or borderline after surgery. However, the coexistence of EIF1AX mutations with other driver mutations such as RAS, TERT or TP53 conferred an 86% ROM. While 55% of thyroid nodules were benign at the time of surgery, the possible malignant transformation of these nodules, had they not been resected, is unknown. Finally, 13% of the nodules with EIF1AX mutations were aggressive with a significant PDTC component. These findings can further aid in clinical decisions for patients with thyroid nodules.

Patient-Reported Financial Burden Following Stereotactic Body Radiation Therapy for Localized Prostate Cancer.

Introduction and Objectives: In patients with localized prostate cancer, 5-fraction, stereotactic body radiation therapy (SBRT) has been found to offer comparable oncologic outcomes and potential for improved treatment compliance compared to conventional, 40-plus fraction radiation therapy (RT). Recent studies of oncologic patient experiences have highlighted both the impact of therapy-associated financial toxicity (FT) on treatment adherence and health-related quality of life (HRQOL). Methods: A cross-sectional assessment of FT after SBRT was performed using the 12-item COST questionnaire. The total questionnaire score (range 0-44) was used to evaluate the FT grade (0-3), with a higher COST value representing lower grade. The patient zip code was used to approximate the distance from the index hospital. Univariate and multivariate analyses of the average COST score (0-4) are performed. Results: The response rate was 57.5% (332 of 575 consented patients) with 90.7%, 8.2%, and 1.1% experiencing grade 0, 1, and 2 FT, respectively, with no grade 3. Unemployment or disability, non-white race, low income, and concurrent hormonal therapy were associated with a statistically significant worse FT (lower COST value) on univariate and multivariate analyses (p < 0.05). Education level and insurance status significant were evaluated on univariate analysis only. There was a non-statistically significant difference in age, marital status, time since treatment, and distance from the index hospital. Conclusions: SBRT was associated with low FT. However, statistically significant socioeconomic disparities in FT remain despite ultra-hypofractionated treatment.

Mutational status may supersede tumor size in predicting the presence of aggressive pathologic features in well differentiated thyroid cancer.

BACKGROUND: In clinical practice, thyroid tumor size plays a critical role in the staging of thyroid malignancies and in the selection of nodules that should undergo ultrasound-guided fine-needle aspiration. Thyroid tumor size is influenced by the elapsed time since the beginning of oncogenesis and by the presence of somatic mutations driving growth, such as BRAFV600E mutations, associated with aggressive phenotypes, and RAS-like mutations, associated with more indolent behavior. Although large nodules are often considered to be more alarming, the true impact of tumor size on prognosis remains controversial. The aim of this study was to assess the relationship between mutational status, tumor size and aggressiveness, with emphasis on BRAFV600E and RAS-like mutations. METHOD: We conducted a multicentric retrospective chart review in Montréal, Canada, of all patients who underwent thyroid surgery between January 2016 and December 2020, with well-differentiated thyroid cancer on final pathology, and who had undergone molecular testing revealing the presence of BRAFV600E mutations or RAS-like mutations (NRAS, HRAS or KRAS). RESULTS: We included 214 cases. There were 117 (54.7%) cases of BRAFV600E and 97 (45.3%) cases of RAS-like mutations. The BRAFV600E group was statistically associated with a smaller mean tumor size when compared with the RAS group of 1.55 cm and 2.04 cm, respectively. In a multivariate model, tumors with BRAFV600E mutations were also more likely to display aggressive pathological features, including extra-thyroidal extension, lymph node metastasis, columnar cell features, tall cell histology, or hobnail histology (OR 26.69; 95% CI 11.15-70.81). In contrast, tumor size was not associated with pathologic aggressive features on multivariate analysis (OR 0.81; 95% CI 0.54-1.22). CONCLUSION: This study demonstrates that thyroid tumors expressing BRAFV600E mutations correlate with aggressive pathologic features more than tumors expressing RAS-like mutations. When comparing tumors with BRAFV600E and RAS-like mutations, the former were found to be smaller. As a result of this finding, this study suggests that molecular alterations may better predict aggressive pathologic features than the size of the tumor.

Evaluation of cytomegalovirus "Blips" in high-risk kidney/kidney-pancreas transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality after solid organ transplantation. While guidelines suggest using highly sensitive QNAT assays for CMV detection, there is no defined viral load to guide initiation of preemptive therapy. This study evaluates the progression to quantifiable CMV (DNAemia) following a CMV "blip" in high-risk (D+/R) kidney/kidney-pancreas (KP) transplant recipients. METHODS: This is a single center, retrospective study. A CMV "blip" was defined as the first positive QNAT assay below the level of quantification (<1.37 × 102 IU/ml or <200 viral copies). Subsequent CMV QNAT assays were followed to assess the progression from blip to CMV DNAemia for 1 year following transplant. RESULTS: A total of 134 patients were included in the study. Fifty-three (39.6%) patients had their first positive CMV QNAT value below the level of quantification, a "CMV blip." Of these 53 patients, 69.8% (n = 37) progressed to DNAemia while 30.2% (n = 16) did not. The median time from transplant to the first CMV blip was 68 (46-97) days and most patients with viral blips (71.1%) were on prophylaxis. No differences in patient characteristics were found among those who progressed from blip to DNAemia and those who only had a blip. CONCLUSIONS: In CMV high-risk kidney/KP transplant recipients, CMV blips progressed to CMV DNAemia in the majority of cases. This progression typically occurred 2-3 weeks following the initial blip. CMV blips are common early posttransplant despite prophylaxis and likely represent an early marker of CMV infection.

Longitudinal trajectories of adiposity-related measures from age 2-5 years in a population of low-income Hispanic children.

BACKGROUND: We estimated longitudinal trajectories of body mass index (BMI) z-score and percentile, weight for height (WFH) z-score and percentile, and percentage of the 95th BMI percentile (BMIp95) among low-income Hispanic children ages 2-5 years to provide normative data for this population and compare the behavior of different measures. METHODS: Longitudinal height and weight measurements obtained from 18,072 Hispanic children aged 2-5 years enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children in Los Angeles County were analyzed. Trajectories of adiposity-related measures were estimated using mixed models, stratified by sex and BMI percentile at age 2 years. RESULTS: For children in the 5th-85th BMI percentile at age 2 years, all adiposity-related measures rose during ages 2-3.5 years; during ages 3.5-5 years, BMI-based measures increased, BMIp95 decreased, and WFH-based measures were stable. For children exceeding the 85th BMI percentile at age 2 years, measures generally trended downward during ages 2-5 years, except for BMIp95, which had variable trends. CONCLUSIONS: Adiposity measures changed at different rates as children grew during ages 2-3.5 years compared to ages 3.5-5 years, and different measures displayed different trends. Studies should consider examining multiple measures and focusing on change relative to a comparison group. IMPACT: To address the childhood obesity epidemic, information on normative trajectories of adiposity-related measures in at-risk populations of young children is needed. Longitudinal analysis of data collected from low-income Hispanic children during ages 2-5 years revealed different patterns for different adiposity measures and for ages 2-3.5 years versus 3.5-5 years. Child obesity studies should consider examining multiple adiposity measures and focus on change relative to a comparison group to avoid misinterpreting longitudinal patterns.

Widespread cryptic viral infections in lotic biofilms.

Viruses have important impacts on aquatic microbial ecology and have been studied at length in the global ocean. However, the roles of bacteriophages in lotic ecosystems, particularly in benthic biofilms, have been largely under-studied. The main goals of this work were to determine whether viruses are consistent members of natural benthic biofilm communities of freshwater streams; whether temperate phages are present and active in such biofilms; and whether community profiling approaches like RAPD-PCR can be adapted to characterize biofilm virus communities. Results from both field and laboratory experiments suggest that viruses are consistent members of lotic biofilm communities. Interestingly, prophage induction was statistically significant but only a small percentage of the total bacterial population appeared to harbor prophage or engaged in induction. Finally, while the use of RAPD-PCR for the community level profiling of biofilm viral communities suggests temporal change in response to biofilm maturity, further refinements are required for broad-scale quantitative application.

The prevalence of intrusive memories in adult depression: A meta-analysis.

BACKGROUND: Intrusive memories have typically been associated with post-traumatic stress disorder (PTSD) but some studies have suggested they can also occur in depression-alone. OBJECTIVE: This meta-analysis aimed to estimate the prevalence of intrusive memories in adult depression and to explore methodological and other factors that may moderate this prevalence. METHOD: The databases PsycINFO, PsycARTICLES, MedLine, PubMed, CINAHL and Embase were searched for relevant articles, published up to and including July 2016. Studies measuring point prevalence of intrusive memories in adults aged 18 years or above with depression were included and assessed for quality. Meta-analysis was completed under a random effects model. RESULTS: Seven studies measuring point prevalence of intrusive memories in adult depression were included. The overall pooled prevalence estimate calculated was 76.0% (95% CI 59.4-89.4%), reducing to 66.0% (95% CI 51.0-79.5%) when restricted to intrusive memories experienced within the week prior to assessment. Heterogeneity was high. Between-groups analyses indicated that adults with depression are as likely to experience intrusive memories as adults with PTSD, and more likely to experience intrusive memories than healthy controls (risk ratio of 2.94, 95% CI 1.53-5.67). LIMITATIONS: The strength of conclusions is limited by the small number of studies included. Consideration of the relationship between depression, intrusive memories and trauma exposure is required. CONCLUSIONS: Intrusive memories are experienced by a large majority of adults with depression and may therefore be an important target for cognitive intervention. Larger scale measurement of clinical outcome is needed with identification of individual factors predicting treatment response.

Peer relations in childhood.

We present a developmental model that describes normal peer relations and highlights processes that underlie the emergence of problems with peers in childhood. We propose that children's relationships with peers begin in the first years of life, with stable individual differences and preferences for particular peers emerging by three years of age. Social skills that facilitate peer relationships consolidate in the preschool years, during which time peer groups become structured with respect to friendship groups, gender, and dominance relations; some children begin to be rejected by their peers. In later childhood some children develop entrenched problems with peer relationships, in terms of loneliness, bullying and victimisation. Underlying cognitive and emotional processes that facilitate successful peer relationships at all ages are identified, and the extent to which peer relations play a causal role in the genesis of disorder is evaluated. A review of the evidence suggests that, rather than a simple pathway from problematic peer relations to disorder, there is a reciprocal relationship between children's problems with peers and their psychological problems from infancy to adolescence.