OBJECTIVE: Bipolar disorder (BD) is a highly heritable disorder characterized by emotion dysregulation and recurrent oscillations between mood states. Despite the proven efficacy of early interventions, vulnerability markers in high-risk individuals are still lacking. BD patients present structural alterations of the hippocampus, a pivotal hub of emotion regulation networks composed of multiple subregions with different projections. However, the hippocampal dynamic functional connectivity (dFC) in BD remains unclear. We aim to investigate whether the dFC of hippocampal subdivisions differentiates BD patients, offspring of BD patients (BDoff), and healthy controls (HC); and whether it correlates with symptoms differently between these groups.
METHODS: We studied for the first time the dFC of the hippocampus through a cutting-edge micro-co-activation patterns (μCAPs) analysis of resting-state functional MRI data of 97 subjects (26 BD, 18 BDoff, 53 HC). μCAPs allow a data-driven differentiation within the seed region.
RESULTS: dFC between the hippocampal body and a somatomotor-μCAP was lower both in BD patients (p-valueFDR:0.00015) and in BDoff (p-valueFDR:0.020) than in HC. Inversely, dFC between the hippocampal head and a limbic-μCAP was higher in BD patients than in HC (p-valueFDR: 0.005). Furthermore, the correlations between a frontoparietal-μCAP and both depression and emotion dysregulation symptoms were significantly higher in BD than HC (p-valueFDR <0.02).
CONCLUSIONS: Overall, we observed alterations of large-scale functional brain networks associated with decreased cognitive control flexibility and disrupted somatomotor, saliency, and emotion processing in BD. Interestingly, BDoff presented an intermediate phenotype between BD and HC, suggesting that dFC of hippocampal subregions might represent a marker of vulnerability to BD.

The real-world benefits of adding androgen-deprivation therapy (ADT) and its optimal duration when combined with current standard high-dose radiation therapy (RT) remain unknown. We aimed to assess the efficacy of and toxicities associated with ADT in the setting of combination with high-dose RT for intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). This article is a modified and detailed version of the commentary on Clinical Question 8 described in the Japanese Clinical Practice Guidelines for Prostate Cancer (ver. 2023). A qualitative systematic review was performed according to the Minds Guide. All relevant published studies between September 2010 and August 2020, which assessed the outcomes of IR or HR PCa treated with high-dose RT, were screened using two databases (PubMed and ICHUSHI). A total of 41 studies were included in this systematic review, mostly consisting of retrospective studies (N = 34). The evidence basically supports the benefit of adding ADT to high-dose RT to improve tumor control. Regarding IR populations, many studies suggested the existence of a subgroup for which adding ADT had no impact on either overall survival or the BF-free duration. On the other hand, regarding HR populations, several studies suggested the positive impact of adding ADT for ≥1 year on overall survival. Adding ADT increases not only the risk of sexual dysfunction but also that of cardiovascular toxicities or bone fracture. Although the benefit of adding ADT was basically suggested for both IR and HR populations, further investigations are warranted to identify subgroups of patients for whom ADT has no benefit, as well as the appropriate duration of ADT for those who do derive benefit.

BACKGROUND: The performance of serum galactomannan (GM) for the diagnosis of invasive aspergillosis (IA) has been studied mainly in adults. Paediatric data are scarce and based on small and heterogeneous cohorts.
OBJECTIVE: To evaluate the performance of serum GM for the diagnosis of IA in a paediatric oncologic population at high risk of IA and to clarify the impact of antifungal prophylaxis on this test.
METHODS: We performed a retrospective study from January 2014 to December 2020 in the paediatric oncologic haematologic department of the University Hospital of Bordeaux. The diagnosis of IA was made using the recommendations of the EORTC and the MSGERC.
RESULTS: Among the 329 periods at high risk of IA in 222 patients, the prevalence of IA was 1.8% (3 proven and 3 probable IA). In the total population, the sensitivity, and the positive predictive value (PPV) were respectively 50% and 17.6%. Under antifungal prophylaxis, the sensitivity and PPV dropped, respectively, to 33.3% and 14.3%. In this group, the post-test probability of IA was 2% for a negative serum GM and only 14%.
CONCLUSIONS: In this large cohort of children at high risk of IA, the incidence of IA is low and the diagnostic performance of GM is poor, especially in the case of mould-active prophylaxis. Screening should be targeted rather than systematic and should be reserved for patients at highest risk for IA without mould-active prophylaxis. Combination with other tests such as Aspergillus PCR would increase the accuracy of GM in screening setting.

Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of \"+\", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.

This study aimed to assess the effectiveness and optimal dosage of aspirin in preventing preeclampsia in high-risk pregnant women. Traditional and network meta-analyses were conducted on data from 23 randomized controlled trials involving 10 547 pregnant women. The findings demonstrated that aspirin significantly reduced the incidence of preeclampsia (OR = 0.66, 95%CI [0.58, 0.75]), with the best preventive effect observed at a dosage of 80-100 mg/day (OR = 0.51, 95%CI [0.36, 0.72]). No significant differences were found in the occurrence of postpartum hemorrhage (OR = 1.03, 95%CI [0.79, 1.33]), small for gestational age (OR = 0.83, 95%CI [0.50, 1.35]), placental abruption (OR = 0.96, 95%CI [0.53, 1.73]), and intrauterine growth restriction (OR = 0.63, 95%CI [0.45, 1.86]) between women taking aspirin and those taking placebos. Different doses of aspirin showed a reduction in preeclampsia incidence, but there was no significant difference in efficacy between the dosage groups. Side effects did not significantly differ between placebo and different aspirin dosage groups. SUCRA analysis suggested that 80-100 mg/day may be the optimal dosage, prioritizing both effectiveness and minimizing side effects. Sensitivity analysis confirmed the robustness of the findings. However, improvements are needed in addressing issues like loss to follow-up, reporting bias, and publication bias. In conclusion, a dosage of 80-100 mg/day is recommended for preventing preeclampsia in high-risk pregnant women, although individual circumstances should be considered for optimizing the balance between effectiveness and safety.

For patients with gastric cancer, a well-balanced treatment that considers both oncological aspects and surgical risk is demanded. This study aimed to explore the optimal extent of lymph node dissection (LND) for patients with gastric cancer according to surgical risk, stratified by the risk calculator system produced by the Japan National Clinical Database (NCD).
We retrospectively evaluated 187 patients who underwent radical gastrectomy for gastric cancer. Using the median predicted anastomotic leak rate obtained by the NCD risk calculator as the cutoff value, we classified 97 and 90 patients as having high and low risks, respectively.
In low-risk patients, although limited LND reduced the postoperative intraabdominal infectious complications (IAIC), multivariate analysis revealed standard LND as an independent prognostic factor that improved Relapse-free survival (RFS). In high-risk patients, the rates of postoperative IAIC and RFS were similar between standard and limited LND. Pancreatic fistula was not observed in the limited dissection group.
Limited LND might be the optimal treatment strategy for patients with gastric cancer with high surgical risk.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2.
METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL).
RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms.
CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

OBJECTIVE: To obtain evidence of the clinical validity of the nursing diagnosis (ND) risk for disturbed maternal-fetal dyad in high-risk pregnancy.
METHODS: Causal validation of the ND through a case-control study performed in a university hospital with 155 high-risk pregnant women: 31 cases and 124 controls. A causal association was found between the ND etiological factors and the occurrence of disruption of the symbiotic maternal-fetal dyad; an association was verified when the etiological factor presented a p-value <0.05 and odds ratio >1.
RESULTS: The risk factor absent-inadequate prenatal care; populations at risk, such as young-advanced maternal age and economically disadvantaged pregnant women; and association conditions, such as maternal conditions and compromised fetal oxygen transport, increased the outcome likelihood. The associated condition maternal illnesses appeared as a protective factor.
CONCLUSIONS: Evidence of clinical validity of the ND risk for disturbed maternal-fetal dyad was obtained, and an association between etiological factors and disruption of the symbiotic maternal-fetal dyad was found.
CONCLUSIONS: The results contribute to advance scientific knowledge in nursing teaching, research, and practice and support the nursing process in high-risk pregnancies.

UNASSIGNED: Studies regarding the risk factors of prenatal anxiety disorders are inconclusive and sometimes contradictory. The current study aimed to define the prevalence and risk factors for anxiety disorders in women during pregnancy.
UNASSIGNED: This is a cross-sectional and hospital-based survey of two public hospitals (Ayatollah Rohani and Yahyanejad) of inpatients/outpatients, obstetric wards/clinics, and four private outpatient obstetric clinics in the city of Babol. Convenience sampling was utilized to recruit 432 pregnant women. A trained clinical psychologist conducted the Structured Clinical Interview for DSM-5 (SCID-5) to diagnose anxiety disorders. In addition, the Brief Symptom Inventory 18 (BSI-18) was completed by the participants to assess the severity of psychological distress.
UNASSIGNED: Of 432 pregnant women, 132 (30.5%) were diagnosed with anxiety disorders. Anxiety disorders included 61 cases of pregnancy adjustment disorder (47.7%), 52 cases of generalized anxiety disorder (40.6%), and 15 cases of specific phobia (to delivery) (11.7%). The logistic regression results showed that the age, pregnancy, education, parity, and high-risk pregnancy variables predicted 28% of the variance of anxiety disorders. Furthermore, as the age (β = 0.94, p = 0.003) and gestational age (β = 0.9, p < 0.001) increased, the probability of anxiety disorders in pregnancy decreased. Moreover, university education (β = 1.65, p = 0.049) and high-risk pregnancy (β = 1.72, p = 0.02) were recognized as risk factors for developing anxiety disorders during pregnancy.
UNASSIGNED: The high incidence of anxiety disorders in pregnant women suggests that obstetricians should pay more attention to identifying and treating anxiety disorders in all pregnant women, especially in high-risk pregnancies.

UNASSIGNED: Current literature suggests that axial skeleton magnetic resonance imaging (AS-MRI) is more sensitive than Tc 99m bone scintigraphy (BS) for detecting bone metastases (BM) in high-risk prostate cancer (PCa). However, BS is still widely performed. Its diagnostic accuracy has been studied; however, its feasibility and cost implications are yet to be examined.
UNASSIGNED: We reviewed all patients with high risk PCa undergoing AS-MRI over a 5-year period. AS-MRI was performed on patients with histologically confirmed PCa and either PSA > 20 ng/ml, Gleason ≥8, or TNM Stage ≥T3 or N1 disease. All AS-MRI studies were obtained using a 1.5-T AchievaPhilips™MRI scanner. We compared the AS-MRI positivity and equivocal rate with that of BS. Data were analysed according to Gleason score, T-stage and PSA. Multivariate logistic regression analyses were used to quantify the strength of association between positive scans and clinical variables. Feasibility and burden of expenditure was also evaluated.
UNASSIGNED: Five hundred three patients with a median age of 72 and a mean PSA of 34.8 ng/ml were analysed. Eighty-eight patients (17.5%) were positive for BM on AS-MRI (mean PSA 99 [95% CI 69.1-129.9]). Comparatively 409 patients (81.3%) were negative for BM on AS-MRI (mean PSA 24.7 (95% CI [21.7-27.7]) (p = 0.007); 1.2% (n = 6) of patients had equivocal results (mean PSA 33.4 [95% CI 10.5-56.3]). There was no significant difference in age (p = 0.122) between this group and patients with a positive scan, but there was a significant difference in PSA (p = 0.028), T stage (p = 0.006) and Gleason score (p = 0.023). In comparison with BS, AS-MRI detection rate was equivalent or higher compared with the literature. Based on NHS tariff calculations, there would be a minimum cost saving of £8406.89. All patients underwent AS-MRI within 14 days.
UNASSIGNED: The use of AS-MRI to stage BM in high-risk PCa is both feasible and results in a reduced burden of expenditure.