BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC.
METHODS: A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed.
RESULTS: Among the 63 patients with high-risk UTUC, the median age was 66 years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26 months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers.
CONCLUSIONS: The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.

UNASSIGNED: Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder. Nevertheless, some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.
UNASSIGNED: To examine the prevalence rates of sleep and circadian dysfunctions, mental disorders and their symptoms in the offspring of parents with (O-BD) and without bipolar disorder (O-control).
UNASSIGNED: The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area, China. The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders, and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, respectively. Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.
UNASSIGNED: Adjusting for age, sex and region of recruitment, there was a significantly higher risk of delayed sleep phase symptoms (9.55% vs 2.58%, adjusted OR: 4.04) in O-BD than in O-control. O-BD had a nearly fivefold higher risk of mood disorders (11.70% vs 3.47%, adjusted OR: 4.68) and social anxiety (6.28% vs 1.49%, adjusted OR: 4.70), a fourfold higher risk of depressive disorders (11.17% vs 3.47%, adjusted OR: 3.99) and a threefold higher risk of mood symptoms (20.74% vs 10.40%, adjusted OR: 2.59) than O-control. Subgroup analysis revealed that O-BD children (aged under 12 years) had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control, while there was a nearly 4-fold higher risk of delayed sleep phase symptoms, a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents (aged 12 years and over).
UNASSIGNED: There was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts, confirming the central role of circadian rhythm dysfunction in bipolar disorder. The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.
UNASSIGNED: NCT03656302.

The iBerry Study, a Dutch population-based high-risk cohort (n = 1022) examines the transition from subclinical symptoms to psychiatric disorders in adolescents. Here, we present the first follow-up measurement, approximately 3 years after baseline assessment and 5 years after the screening based on self-reported emotional and behavioral problems (SDQ-Y). We give an update on the data collection, details on the (non)response, and the results on psychopathology outcomes. The first follow-up (2019-2022) had a response rate of 79% (n = 807). Our results at baseline (mean age 15.0 years) have shown the effectiveness of using the SDQ-Y to select a cohort oversampled for the risk of psychopathology. At first follow-up (mean age 18.1 years), the previously administered SDQ-Y remains predictive for selecting adolescents at risk. At follow-up, 47% of the high-risk adolescents showed significant mental health problems based on self- and parent reports and 46% of the high-risk adolescents met the criteria for multiple DSM-5 diagnoses. Compared to low-risk adolescents, high-risk adolescents had a sevenfold higher odds of significant emotional and behavioral problems at follow-up. Comprehensive assessment on psychopathology, substance abuse, psychotic symptoms, suicidality, nonsuicidal self-injury, addiction to social media and/or video gaming, and delinquency, as well as social development, and the utilization of healthcare and social services were conducted. This wave, as well as the ones to follow, track these adolescents into their young adulthood to identify risk factors, elucidate causal mechanisms, and discern pathways leading to both common and severe mental disorders. Results from the iBerry Study will provide leads for preventive interventions.

OBJECTIVE: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER.
METHODS: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS).
RESULTS: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43).
CONCLUSIONS: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up.

OBJECTIVE: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients.
METHODS: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes.
RESULTS: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.\'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision.
CONCLUSIONS: Our findings endorse the algorithm\'s commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients.
METHODS: In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles.
RESULTS: Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p < 0.001). Furthermore, PFS was notably extended in the HAIC-LEN-PD1 group compared to the LEN-PD1 group (9.6 months vs. 4.9 months, HR = 0.48, p < 0.001). Patients in the HAIC-LEN-PD1 group had a higher ORR and DCR according to the modified RECIST (76.7% vs. 23.0%, p < 0.001; 92.2% vs. 72.1%, p = 0.001). HAIC-LEN-HAIC group led to more adverse events than LEN-PD1 group, most of which were tolerable and controllable.
CONCLUSIONS: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.

BACKGROUND: Birth asphyxia is a leading cause of neonatal mortality in sub-Saharan Africa. The relationship to grand multiparity (GM), a controversial pregnancy risk factor, remains largely unexplored, especially in the context of large multinational studies. We investigated birth asphyxia and its association with GM and referral in Benin, Malawi, Tanzania and Uganda.
METHODS: This was a prospective cross-sectional study. Data were collected using a perinatal e-Registry in 16 hospitals (four per country). The study population consisted of 80 663 babies (>1000 g, >28 weeks\' gestational age) delivered between July 2021 and December 2022. The primary outcome was birth asphyxia, defined by 5-minute appearance, pulse, grimace, activity and respiration score <7. A multilevel and stratified multivariate logistic regression was performed with GM (parity ≥5) as exposure, and birth asphyxia as outcome. An interaction between referral (none, prepartum, intrapartum) and GM was also evaluated as a secondary outcome. All models were adjusted for confounders.
BACKGROUND: Pan African Clinical Trial Registry 202006793783148.
RESULTS: Birth asphyxia was present in 7.0% (n = 5612) of babies. More babies with birth asphyxia were born to grand multiparous women (11.9%) than to other parity groups (≤7.6%). Among the 76 850 cases included in the analysis, grand multiparous women had a 1.34 times higher odds of birth asphyxia (95% confidence interval [CI] 1.17-1.54) vs para one to two. Grand multiparous women referred intrapartum had the highest probability of asphyxiation (13.02%, 95% CI 9.34-16.69). GM increased odds of birth asphyxia in Benin (odds ratio [OR] 1.37, 95% CI 1.13-1.68) and Uganda (OR 1.29, 95% CI 1.02-1.64), but was non-significant in Tanzania (OR 1.44, 95% CI 0.81-2.56) and Malawi (OR 0.98, 95% CI 0.67-1.44).
CONCLUSIONS: There is some evidence of an increased risk of birth asphyxia for grand multiparous women having babies at hospitals, especially following intrapartum referral. Antenatal counseling should recognize grand multiparity as higher risk and advise appropriate childbirth facilities. Findings in Malawi suggest an advantage of health systems configuration requiring further exploration.

BACKGROUND: The benefit of adding rituximab to standard lymphomes malins B (LMB) chemotherapy for children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL) has previously been demonstrated in an international randomized phase III trial, to which the Japanese Pediatric Leukemia/Lymphoma Study Group could not participate.
METHODS: To evaluate the efficacy and safety of rituximab in combination with LMB chemotherapy in Japanese patients, we conducted a single-arm multicenter trial.
RESULTS: In this study, 45 patients were enrolled between April 2016 and September 2018. A total of 33 (73.3%), 5 (11.1%), and 6 (13.3%) patients had Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma, and aggressive mature B-NHL, not otherwise specified, respectively. Ten (22.2%) and 21 (46.7%) patients had central nervous system disease and leukemic disease, respectively. The median follow-up period was 47.5 months. Three-year event-free survival and overall survival were 97.7% (95% confidence interval, 84.9-99.7) and 100%, respectively. The only event was relapse, which occurred in a patient with diffuse large B-cell lymphoma. Seven patients (15.6%) developed Grade 4 or higher non-hematologic adverse events. Febrile neutropenia was the most frequent Grade 3 or higher adverse event after the pre-phase treatment, with a frequency of 54.5%.
CONCLUSIONS: The efficacy and safety of rituximab in combination with LMB chemotherapy in children with high-risk mature B-NHL was observed in Japan.

Offspring of parents with schizophrenia spectrum disorders (SSD) have an increased risk of neurodevelopmental disturbances. However, the ability to provide very early interventions to support these children and their families requires profound knowledge regarding characteristic features of both the parents and their offspring. Information on this subject is currently sparse. The aim of the present study is to investigate clinical and sociodemographic variables in offspring in the age range of 0-3 years of mothers diagnosed with SSD.
The study is descriptive with a cross-sectional design and includes parent-child dyads consisting of mothers diagnosed with SSD (ICD-10: F20-29) and their offspring aged 0-3 years, who were referred for examination and intervention at the infant and toddler psychiatric units, at the Mental Health Services, Capital Region, Copenhagen University Hospitals in two locations (Bispebjerg and Glostrup). Clinical and sociodemographic data were extracted from the Copenhagen \"Infant Psychiatric Database\" and processed by descriptive analysis.
Out of 95 parent-child dyads considered for the study population, 85 were included. 27.8% of the mothers had psychiatric comorbidities, and 18.9% of the fathers had a psychiatric diagnosis at the time of investigation. Of the children, 89.7% were born full term (≥37th week) and most of them had a birth weight of ≥2500 g (81.8%). Of the mothers, 50% had experienced pregnancy complications of varying severity. Birth complications were seen in 62.9% of the dyads. Psychopathology was identified in 50% of the children at age 0-3 years, and 62.2% of the parent-child dyads appeared to have an affected relationship.
Results show widespread psychopathology in offspring aged 0-3 years of mothers with SSD. Moreover, several psychosocial stressors, clinical parental features, and relational disturbances are identified. These results contribute to a better understanding and identification of early risk markers of long-term psychopathology in this infant patient group, and hence serve as potential targets for early interventions.

OBJECTIVE: Performing restaging transurethral bladder resection (reTURB) for high-risk non-muscle invasive bladder cancer (NMIBC) reduces the risk of recurrence and tumour understaging. Management of residual high-grade papillary Ta or T1 after reTURB has changed this last 10years in international recommendations. This study aimed to compare the recurrence free survival according to the different management procedures performed.
METHODS: Patients who underwent reTURB for initial high-risk NMIBC between 2011 and 2020 were included. Patients with residual high-grade papillary Ta or T1 tumour after reTURB were divided into two groups: BCG instillations upfront versus BCG following a third-look resection (3TURB). Patient and tumour characteristics, BCG instillations, recurrence-free survival were retrospectively analysed.
RESULTS: A total of 162 high-risk patients were included. Sixty-one (37.7%) had residual high-grade papillary Ta or T1 at reTURB: 35 (21.6%) had BCG instillations upfront, 18 (11.2%) had a 3TURB and 8 (5%) had other management. The mean follow-up was 34.2weeks±20.2. Recurrence-free survival was significantly better in patients who underwent BCG instillations upfront (P<0.0043). Recurrence after BCG therapy following reTURB was significantly lower in patients with no residual NMIBC at 6 (92.5% vs. 72.4%, P<0.004) and 12months (85% vs. 67.3%, P<0.03).
CONCLUSIONS: The efficacy of intravesical BCG is compromised in case of residual tumour following TURB. The role of a 3TURB following a positive reTURB is not yet determined. This study has confirmed that residual tumor following reTURB is a negative predictive factor but could not demonstrate the value of a 3TURB compared to upfront BCG.
METHODS: