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Objectives Methods Results Conclusions The objective of this study is to evaluate the safety and efficacy of neoadjuvant degarelix acetate and low‐dose estramustine phosphate for high−/very high‐risk prostate cancer.Overall, 187 patients diagnosed with National Comprehensive Cancer Network high−/very high‐risk cTanyN0M0 localized prostate cancer who consented to undergo robot‐assisted radical prostatectomy after receiving neoadjuvant chemohormonal therapy for 6 months were prospectively enrolled between December 2017 and March 2023. Adverse events, perioperative and histopathological outcomes, and biochemical recurrence‐free survival rates were examined. Survival analysis compared the estramustine phosphate completion and reduction groups.Thirty‐six patients discontinued neoadjuvant therapy in <5 months owing to adverse events (n = 34) or other reasons (n = 2). Eleven were excluded for being in the postoperative castration range. Of the 140 patients who underwent surgery, 124 continued with two tablets of estramustine phosphate and 16 with one tablet. Overall, 82 patients were very high‐risk. Histopathological outcomes were significantly worse in the very high‐risk group than those in the high‐risk group. Very high‐risk status and estramustine phosphate reduction were significant factors in biochemical recurrence in multivariate analysis. The biochemical recurrence‐free survival rate in very high‐risk patients was significantly lower in the estramustine phosphate dose reduction group than in the completion group but not significant in high‐risk patients. Major adverse events were anemia (n = 174), elevated transaminase levels (n = 68), and deep vein thrombosis (n = 24). Severe adverse events included acute coronary syndrome (n = 4) and pulmonary embolism (n = 3).Dose compliance with estramustine phosphate predicted biochemical recurrence in patients with very high‐risk prostate cancer undergoing robot‐assisted radical prostatectomy with neoadjuvant chemohormonal therapy. [ABSTRACT FROM AUTHOR]

The prognosis of thyroid cancer in patients varies significantly based on different pathological types or distinct clinical situations. Investigating the expression of immune checkpoint molecules PD-L1 and B7-H3 in high-risk thyroid cancer and their correlation with clinicopathological features and prognosis will contribute to the development of novel therapeutic strategies. A retrospective sample of 202 patients with thyroid cancer who underwent surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences was collected, including 33 cases of anaplastic thyroid cancer (ATC), 21 cases of differentiated thyroid cancer (DTC) with distant metastasis (DM), 7 cases of differentiated high-grade thyroid carcinoma (DHGTC), and 109 cases of aggressive subtypes of papillary thyroid carcinoma (PTC) (including 28 cases of tall cell PTC, 31 cases of diffuse sclerosing PTC, 20 cases of solid PTC, 15 cases of columnar cell PTC, and 15 cases of hobnail PTC). In the control group, there were 32 cases of classic PTC. The differences in protein expression between PD-L1 and B7-H3 in several high-risk thyroid cancers and normal tissues and controls were compared by immunohistochemical staining, and the clinicopathological features and prognostic relevance were statistically analyzed. The expression of PD-L1 in ATC (P < 0.001), tall cell PTC (P = 0.031), and DHGTC (P = 0.003) was significantly higher than that in classic PTC. The expression of B7-H3 in ATC (P < 0.001), DTC with DM (P = 0.001), diffuse sclerosing PTC (P = 0.013), columnar cell PTC (P = 0.007), solid PTC (P < 0.001), hobnail PTC (P < 0.001), and DHGTC (P < 0.001) was significantly higher than that in classic PTC. In ATC, PD-L1 expression correlated significantly with extrathyroidal extension (ETE) (P = 0.027) and B7-H3 expression correlated significantly with male patients (P = 0.031) and lymph node metastasis (LNM) (P = 0.026). The positive expression of B7-H3 (P = 0.041) was an independent risk factor for disease progression in ATC. B7-H3 positive expression (P = 0.049), PD-L1 positive expression (P = 0.015), and tumor diameter ≥ 2 cm (P = 0.038) were independent risk factors for disease progression in patients with DTC with DM. PD-L1 positive expression (P = 0.019) and tumor diameter ≥ 2 cm (P = 0.018) were independent risk factors for disease progression in patients with aggressive subtypes of PTC. B7-H3 and PD-L1 are expected to be effective prognostic indicators for patients with aggressive thyroid cancer, which can help in optimization of individualized treatment strategies. Immunotherapy targeting these two molecules may provide new and complementary ideas for the treatment of high-risk/refractory thyroid cancer. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion 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.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.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).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. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy (HDP) pose a substantial public health concern, ranking among the primary contributors to maternal and perinatal morbidity and mortality, impacting around 5–10% of pregnancies. This study aimed to determine the prevalence of HDP and its associated factors among mothers aged 15–49 who recently gave birth within the last two years, throughout Malaysia, informing effective public health and primary care interventions. Methods: This study was a part of the national survey on maternal and child health (MCH) also known as the National Health and Morbidity Survey (NHMS) 2022: MCH. This was a cross-sectional study using two stage stratified random sampling design. Data of mothers aged 15–49 years old who recently gave birth within the last two years were selected in this study. This survey utilised a set of structured validated questionnaires administered via face-to-face interviews (using a mobile device). Multiple logistic regression analysis was employed to identify the associated factors for hypertension. Results: Among 6 335 participants recruited for this study with an estimated population of 782, 550, the prevalence of HDP among Malaysian mothers aged 15–49 years old who recently gave birth within the last two years was 6.5% (95% CI: 5.76, 7.37). Multiple logistic regression showed that maternal age and ethnicity were significantly associated with hypertension. Advanced maternal age had higher odds of hypertension, with an aOR of 2.18 (95% CI = 1.75, 2.71). In addition, Other Bumiputera had higher odds of hypertension (aOR = 2.71, 95% CI = 1.25, 5.87). Conclusion: This study reveals the prevalence of HDP among Malaysian women with children under 2 years old, emphasizing advanced maternal age (above 35) and ethnicity as notable risk factors. It improves understanding of the epidemiology of HDP in Malaysia, offering valuable insights for the development of effective public health strategies and clinical interventions that can help with the control of HDP. [ABSTRACT FROM AUTHOR]

Basal Cell Carcinoma (BCC) is the most prevalent skin cancer and continues to witness a surge in incidence rates. The categorization of BCC subtypes into low or high risk, guided by recurrence and invasiveness metrics, underscores the need for precise differentiation. While the punch biopsy remains the gold standard for diagnosis, its invasiveness prompts a need for non-invasive alternatives. Ultrasound (US) has emerged as a noteworthy candidate, gaining momentum in its potential to offer a less intrusive diagnostic approach. We conducted a systematic review regarding features of the high-risk subtypes of BCC on US. A thorough literature search of PubMed Medline, Embase, and CINAHL databases was conducted according to PRISMA guidelines and a total of nine studies meeting our inclusion criteria were included in this review. Evidence is still nascent but US features such as lesional shape, depth, hyperechoic spots, and color doppler may be helpful in differentiating high-risk BCC subtypes. However, further prospective studies with standardized interventions and outcome measures are required. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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%. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Purpose: To obtain evidence of the clinical validity of the nursing diagnosis (ND) risk for disturbed maternal–fetal dyad in high‐risk pregnancy. Method: 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. Findings: 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. Implications for nursing practice: The results contribute to advance scientific knowledge in nursing teaching, research, and practice and support the nursing process in high‐risk pregnancies. [ABSTRACT FROM AUTHOR]

Abstract Background Hypertensive disorders of pregnancy (HDP) pose a substantial public health concern, ranking among the primary contributors to maternal and perinatal morbidity and mortality, impacting around 5–10% of pregnancies. This study aimed to determine the prevalence of HDP and its associated factors among mothers aged 15–49 who recently gave birth within the last two years, throughout Malaysia, informing effective public health and primary care interventions. Methods This study was a part of the national survey on maternal and child health (MCH) also known as the National Health and Morbidity Survey (NHMS) 2022: MCH. This was a cross-sectional study using two stage stratified random sampling design. Data of mothers aged 15–49 years old who recently gave birth within the last two years were selected in this study. This survey utilised a set of structured validated questionnaires administered via face-to-face interviews (using a mobile device). Multiple logistic regression analysis was employed to identify the associated factors for hypertension. Results Among 6 335 participants recruited for this study with an estimated population of 782, 550, the prevalence of HDP among Malaysian mothers aged 15–49 years old who recently gave birth within the last two years was 6.5% (95% CI: 5.76, 7.37). Multiple logistic regression showed that maternal age and ethnicity were significantly associated with hypertension. Advanced maternal age had higher odds of hypertension, with an aOR of 2.18 (95% CI = 1.75, 2.71). In addition, Other Bumiputera had higher odds of hypertension (aOR = 2.71, 95% CI = 1.25, 5.87). Conclusion This study reveals the prevalence of HDP among Malaysian women with children under 2 years old, emphasizing advanced maternal age (above 35) and ethnicity as notable risk factors. It improves understanding of the epidemiology of HDP in Malaysia, offering valuable insights for the development of effective public health strategies and clinical interventions that can help with the control of HDP.

Although rarely diagnosed in the pediatric population, deep vein thrombosis (DVT) is experiencing a growing incidence, while continuously acquiring different nuances due to the widening range of risk factors and lifestyle changes in children and adolescents.

Background & aim: Spirituality is among prominent strategies to minimize negative emotions in different circumstances. Clarifying the concept of spiritual well-being in high-risk pregnancies enables healthcare providers to address and support their patients' spiritual needs. This study aimed to explore the perceptions and experiences of spiritual well-being among women with high-risk pregnancy.Methods: This qualitative content analysis was conducted from December 2017 to March 2019 in public and private hospitals and health centers in Mashhad, Iran. The participants included 26 women with high-risk pregnancy, who selected using a purposive sampling. Data was collected through semi-structured and face-to-face individual interviews using the interview guide. The data analysis was carried out concurrently with the data collection, using the conventional content analysis based on the Graneheim and Lundman's method. Results: Following data analysis, "Spiritual well-being in high-risk pregnancies” was characterized by two main categories including “Meaning-seeking and belief in purposeful pregnancy” and" Relying on spirituality in achieving health."Conclusion: Searching for meaning and purposefulness in pregnancy and relying on spirituality to achieve health are among the components of spiritual well-being in high-risk pregnancy; hence, understanding women’s spiritual well-being could help tailoring strategies to reduce their tensions and discomforts caused by high-risk pregnancy. Thus, it is highly recommended that women with high-risk pregnancy receive spiritual care as part of their comprehensive care.

While renal biopsy remains the preferred diagnostic method for assessing proteinuria, hematuria, or renal failure, laparoscopic renal biopsy (LRB) can serve as an alternative for high-risk patients when percutaneous kidney biopsy (PKB) is not recommended. This study was aimed to evaluate the safety of LRB. In study 1, Fourteen patients from January 2021 to January 2023 had a LRB taken for various indications, such as morbid obesity, abnormal kidney construction, uncontrolled hypertension, and coagulopathy. We also conducted a Meta-analysis of the success rate and complication rate of previous LRB in study 2. All the patients completed biopsies and adequate renal tissues were obtained. The success rate was 100%. The median number of glomeruli obtained was 22.5 (range:12.0, 45.0). The complication rate was 7.1% (urinary tract infection). There were no significant differences between levels of hemoglobin, serum creatinine, and urinary NAGL before and after surgery. In the meta-analysis, the success rate of operation, satisfactory rate of sample, and complication rate of surgery were 99.9%, 99.1%, and 2.6% respectively. LRB can achieve a good success rate and specimen retrieval and does not increase the risk of complications for high-risk patients. It can present as one of the alternative methods for patients with glomerular diseases. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract 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

Background and aims: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

We compared recruitment of participants at high risk for glaucoma and other eye diseases in three community-based studies designed to improve access to eye care in underserved populations in New York City, Alabama, and Michigan. We used (1) participant data collected at enrollment (e.g. demographic, medical conditions, healthcare access, and method of hearing about study) and (2) interviews with study staff to assess effective recruitment strategies in enrolling people at high risk for eye disease. We analyzed participant data using descriptive statistics and interview data using content analysis to categorize responses to questions. In these community-based studies, all sites recruited greater proportions of populations with increased risk of eye disease compared to their estimates in the US population. High-risk characteristics varied based on the setting (i.e. Federally Qualified Health Centers or affordable housing buildings). Older adults represented 35% to 57%; 43% to 56% identified as Black; 1% to 40% as Hispanic/Latino; 20% to 42% reported a family history of glaucoma; 32% to 61% reported diabetes; and 50% to 67% reported high blood pressure. Social risk factors for under-utilization of eye care due to poverty included that 43% to 70% of participants had high school or lower education; 16% to 40% were employed; and 7% and 31% had no health insurance. From a qualitative perspective, active, personalized, culturally sensitive methods were most effective in recruiting participants. Implementing eye disease detection interventions in community-based settings facilitated recruiting individuals at high risk for glaucoma and other eye diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. This phase 2 study investigated 6 versus 18 months of perioperative androgen‐deprivation therapy in men with localized, unfavorable intermediate‐risk or high‐risk prostate cancer. Because patients dropped out of part 2 randomization postprostatectomy, the study was underpowered to detect differences in 3‐year biochemical progression‐free survival between treatment arms. [ABSTRACT FROM AUTHOR]

Background: 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). Patients and Methods: 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. Results: 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. Conclusion: Limited LND might be the optimal treatment strategy for patients with gastric cancer with high surgical risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The care of patients undergoing low-volume, high-risk emergency procedures such as bedside laparotomy (BSL) remains a challenge for surgical trauma critical care nurses. OBJECTIVES: This study evaluates simulation and microlearning on trauma nurse role ambiguity, knowledge, and confidence in caring for patients during emergency BSL. METHODS: The study is a single-center, prospective pretest-posttest design conducted from September to November 2022 at a Level I trauma center in the Mid-Atlantic United States using simulation and microlearning to evaluate role clarity, knowledge, and confidence among surgical trauma intensive care unit (STICU) nurses. Participants, nurses from a voluntary convenience sample within a STICU, attended a simulation and received three weekly microlearning modules. Instruments measuring role ambiguity, knowledge, and confidence were administered before the simulation, after, and again at 30 days. RESULTS: From the pretest to the initial posttest, the median (interquartile range [IQR]) Role Ambiguity scores increased by 1.0 (1.13) (p < .001), and at the 30-day posttest, improved by 1.33 (1.5) (p < .001). The median (IQR) knowledge scores at initial posttest improved by 4.0 (2.0) (p < .001) and at the 30-day posttest improved by 3.0 (1.75) (p < .001). The median (IQR) confidence scores at initial posttest increased by 0.08 (0.33) (p = .009) and at the 30-day posttest improved by 0.33 (0.54) (p = .01). CONCLUSIONS: We found that simulation and microlearning improved trauma nurse role clarity, knowledge, and confidence in caring for patients undergoing emergency BSL. [ABSTRACT FROM AUTHOR]

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. Conclusion: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features. Key points: • HAIC-LEN-PD1 combination treatment for HCC. • HAIC-LEN-PD1 is a safe and effective treatment for high-risk patients with HCC. • HAIC-LEN-PD1 is more effective than LEN-PD1 in prolonging patient survival. [ABSTRACT FROM AUTHOR]

To examine the risk of anxiety disorders in offspring of parents with mood disorders. We conducted a systematic review and meta-analysis. We searched 4 electronic databases (Medline, Embase, PsycINFO, and Web of Science [core collection]) to identify cross-sectional and cohort studies that examined the association between parental mood disorders (including bipolar disorder and unipolar depression) and risk of anxiety disorders in offspring. Pooled risk ratios (RRs) of overall and specific anxiety disorders were synthesized using a random effects model. Subgroup analyses and meta-regression were performed to identify moderation factors. A total of 35 studies were included in the final analysis. Our results showed higher risks of all types of anxiety disorders in the offspring of parents with mood disorders (any anxiety disorder, RR = 1.82, 95% CI = 1.47-2.26), except for agoraphobia (RR = 1.08, 95% CI = 0.56-2.08), and with an especially elevated risk of panic disorder (RR = 3.07, 95% CI = 2.19-4.32). Subgroup analysis demonstrated no significant difference between the risks of anxiety disorders across the offspring of parents with bipolar disorder as opposed to unipolar depression. The absence of anxiety disorders in control parents, younger offspring age, and specific parent/offspring sex were associated with higher RRs for some anxiety disorders in offspring of parents with mood disorders. Our findings suggest a robust relationship between parental mood disorders and offspring anxiety disorders, and highlight the potential value of prevention and early intervention for anxiety disorders in this context. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. Anxiety Disorders in Offspring of Parents with Mood Disorders: A Systematic Review; https://www.crd.york.ac.uk/prospero/ ; CRD42021215058. [ABSTRACT FROM AUTHOR]

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%. Conclusion: The efficacy and safety of rituximab in combination with LMB chemotherapy in children with high‐risk mature B‐NHL was observed in Japan. [ABSTRACT FROM AUTHOR]

MM is non-curable cancer that arises from plasma cells and is the second most common type of blood cancer. Drug-refractory relapses are inevitable, making it essential to sustain long-lasting remissions as part of therapy. Lenalidomide maintenance until progression is a standard of care for transplant-eligible newly-diagnosed patients. However, poor outcomes of high-risk patients and the risk of secondary primary malignancies associated with maintenance underline the need for novel approaches. Significant changes in frontline treatment maintenance are expected, with the increasing importance of minimal residual disease monitoring and the development of novel drug combinations for maintenance. This article explores current standards and prospects for maintaining response after upfront in ASCT in MM. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives: to develop and evaluate a Middle-Range Theory for the nursing diagnosis “Disrupted Mother-Fetus Dyad Risk” in high-risk pregnancies. Methods: this methodological study was conducted in two stages: theory development and evaluation. Dorothea Orem’s General Nursing Model was used as the theoretical-conceptual foundation. Evaluation was conducted using the Delphi method with seven judges, and consensus was achieved when the Content Validity Index of the evaluated items was ≥ 0.80. Results: the theory identified 20 elements of the nursing diagnosis “Disrupted Mother-Fetus Dyad Risk” (10 risk factors, 4 at-risk populations, and 6 associated conditions), 14 propositions, and 1 pictogram. After two rounds of evaluation, the theory was considered consistent, with consensus reached for all items, each achieving a Content Validity Index ≥ 0.80. Conclusions: the Middle-Range Theory included biopsychosocial factors explaining the nursing phenomenon “Disrupted Mother-Fetus Dyad Risk,” which aids in nurses’ diagnostic reasoning.

Mucocele-like lesions of the breast are rare, usually presenting themselves as suspicious findings on imaging, warranting biopsies. It can be associated with several degrees of hyperplasia, including atypical ductal hyperplasia and ductal carcinoma in situ, historically being considered a high-risk lesion. It also can be an underestimated invasive carcinoma in a percutaneous biopsy. When facing a histologic diagnosis of a mucocele-lesion in a percutaneous biopsy, it is important to be aware of these lesions' significance to make the most appropriate interpretation, recommendation, and management. The purpose of this work is to present some cases of breast mucocele-like lesions from our Institution and perform a review of the literature.

Background: The rate of preterm birth is increasing globally. It causes significant short-term and long-term health care burdens. A comprehensive recognition of the risk factors related to preterm births is important in the prevention of preterm birth. Our study is to investigate the incidence and maternal risk factors of preterm birth from a nationwide population-based perspective. Methods: This is a retrospective cohort study. All live births from 2004 to 2014 in Taiwan enrolled. The main data source was Taiwan’s Birth Certificate Application (BCA) database. The BCA database was linked with the National Health Insurance Research Database (NHIRD) to establish any links between information on newborns and maternal underlying disease. Results: A total of 1,385,979 births were included in the analysis. The incidence of preterm birth increased gradually in Taiwan from 8.85% in 2004 to 10.73% in 2014. Maternal age, socioeconomic status, maternal allergy and autoimmune diseases, gynecological diseases, and pregnancy-related complications were significant risk factors for preterm birth. Conclusion: The overall incidence of preterm births has gradually increased in Taiwan. Maternal age, socioeconomic status, certain underlying diseases, and pregnancy-related complications were risk factors for preterm birth.

Background While renal biopsy remains the preferred diagnostic method for assessing proteinuria, hematuria, or renal failure, laparoscopic renal biopsy (LRB) can serve as an alternative for high-risk patients when percutaneous kidney biopsy (PKB) is not recommended. This study was aimed to evaluate the safety of LRB.Methods In study 1, Fourteen patients from January 2021 to January 2023 had a LRB taken for various indications, such as morbid obesity, abnormal kidney construction, uncontrolled hypertension, and coagulopathy. We also conducted a Meta-analysis of the success rate and complication rate of previous LRB in study 2.Results All the patients completed biopsies and adequate renal tissues were obtained. The success rate was 100%. The median number of glomeruli obtained was 22.5 (range:12.0, 45.0). The complication rate was 7.1% (urinary tract infection). There were no significant differences between levels of hemoglobin, serum creatinine, and urinary NAGL before and after surgery. In the meta-analysis, the success rate of operation, satisfactory rate of sample, and complication rate of surgery were 99.9%, 99.1%, and 2.6% respectively.Conclusion LRB can achieve a good success rate and specimen retrieval and does not increase the risk of complications for high-risk patients. It can present as one of the alternative methods for patients with glomerular diseases.

Introduction: 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. Material and 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. Clinical Trial: 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. [ABSTRACT FROM AUTHOR]

An easy-to-use preparation-related model (PRM) predicting inadequate bowel preparation (BP) was developed and proved superior to traditional models in our previous study. Here we aimed to investigate whether PRM-based individualized intervention can improve BP adequacy. Patients undergoing morning colonoscopy were prospectively enrolled in 5 endoscopic centers in China. After standard BP of split-dose polyethylene glycol (PEG) was completed, patients were randomized (1:1) to the individualized group or standard group. High-risk patients predicted by PRM score ≥3 were instructed to drink an additional 1.5 L PEG in the individualized group while not in standard group. The primary endpoint was the rate of adequate BP, defined by segmental Boston bowel preparation scale ≥2. Secondary outcomes included adenoma detection rate (ADR) and adverse events. 900 patients were randomly allocated to the individualized group (n = 449) and the control (n = 451). Baseline characteristics were similar between the two groups. The rates of high-risk patients were 19.6 % in individualized group and 19.7 % in standard group. In intention-to-treat analysis, adequate BP was 91.8 % in individualized group and 84.7 % in the standard group (p = 0.001). Among high-risk patients, adequate BP rate was 94.3 % in individualized group and 49.3 % in standard group (p < 0.001), and ADR were 40.9 % vs 16.9 %, respectively (p < 0.001). No significant differences were found regarding the adverse events and willingness to repeat BP (all p >0.05). The individualized intervention using an additional dose of PEG to high-risk patients predicted by PRM, significantly improved BP quality. The intervention significantly improved ADR in high-risk patients. (ClinicalTrials.gov number: NCT04434625) [ABSTRACT FROM AUTHOR]

The regulation of artificial intelligence (AI) should strike a balance between addressing the risks of the technology and its benefits through enabling useful innovation whilst remaining adaptable to evolving risks. The European Union's (EU) overarching risk-based regulation subjects AI systems across industries to a set of regulatory standards depending on where they fall in the risk bucket, whilst the UK's sectoral approach advocates for an incremental regulation. By demonstrating the EU AI Act's inability to adapt to evolving risks and regulate the technology proportionately, this article argues that the UK should avoid the EU AI Act's compartmentalized high-risk classification system. The UK should refine its incremental regulation by adopting a generic principle for risk classification that allows for contextual risk assessment whilst adapting to evolving risks. The article contends that if refined appropriately, the UK's incremental approach that relies on coordinate sectionalism encourages innovation without undermining the UK technology sector's competitiveness in the global market of compliant AI, while also mitigating the potential risks presented by the technology. [ABSTRACT FROM AUTHOR]

Objective: To compare neurofunctional responses in emotional and attentional networks of psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder (BD). Methods: ADHD youth with (high-risk, HR, n = 48) and without (low-risk, LR, n = 50) a first-degree relative with BD and healthy controls (n = 46) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional distracters. Region-of-interest analyses were performed for bilateral amygdala (AMY), ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, and anterior (ACC) and posterior cingulate cortex (PCC). Results: Compared with HC, HR, but not LR, exhibited predominantly left-lateralized AMY, VLPFC, DLPFC, PCC, and rostral ACC hyperactivation to emotional distractors, whereas LR exhibited right VLPFC and bilateral dorsal ACC hypoactivation to attentional targets. Regional responses correlated with emotional and attention symptoms. Conclusion: Aberrant neurofunctional responses during emotional and attentional processing differentiate ADHD youth with and without a family history of BD and correlate with relevant symptoms ratings. [ABSTRACT FROM AUTHOR]

Purpose: Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. Methods and materials: A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan--Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. Results: A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Conclusion: Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow- up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity. [ABSTRACT FROM AUTHOR]

Background: Management for locally advanced rectal cancer (LARC) conventionally comprises long‐course chemoradiotherapy (LCCRT), total mesorectal excision (TME), and adjuvant chemotherapy. However, the RAPIDO study published in 2021 showed that total neoadjuvant therapy (TNT) led to better oncological outcomes without increased toxicity. We review the surgical and short‐term oncological outcomes of patients with high‐risk LARC who underwent TNT or LCCRT before TME. Methods: Patients with high‐risk LARC who underwent TNT or LCCRT before TME between 2021 and 2022 were reviewed. Results: Thirty‐five patients (66%) had TNT as per RAPIDO whilst 18 underwent LCCRT. Median follow‐up was 16 months (range 5–25). Of the patients who had TNT, median age was 65 years old (range 44–79), 34 (97%) had clinical Stage 3 LARC and median height FAV was 5 cm (range 0.5–14). Nine (26%) required a dose delay/reduction due to treatment toxicity. Seven (50%) showed resolution of previously enlarged lateral nodes. Three (9%) had pathological complete response. Postoperative major morbidity was 23%, of which 4 patients required a reoperation. Six (17%) patients had disease‐related treatment failure, with two having disease progression during TNT, two developed local recurrence, and two developed distal metastasis following surgery. Median duration to surgery following completion of chemotherapy was significantly shorter with TNT (36 days versus 74 days) (P < 0.001). There were no other significant differences in outcomes. Conclusion: TNT is clinically safe in high‐risk LARC patients with no significant difference to surgical and short‐term oncological outcomes compared to LCCRT, although a higher incidence of early surgical morbidity was observed. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor differentiation therapy using retinoids has a long history of clinical development and an established role as a part of the standard treatment for high-risk neuroblastoma. However, basic and clinical science related to this treatment is still immature in multiple respects. In the present review, we systematically expand on the basic and clinical science of retinoids for neuroblastoma treatment, off-label issues related to the treatment and possible countermeasures, and finally, prospects for this therapy. Retinoids are vitamin A derivatives and include trans-retinoic acid, isotretinoin, tamibarotene, and bexarotene, all of which are currently available for clinical use. The clinical development of retinoid therapy for neuroblastoma has a history spanning more than four decades. The most promising agent is isotretinoin, which can contribute to improving event-free survival in patients with high-risk neuroblastoma by approximately 10% when administered over six months as maintenance therapy. Although isotretinoin is regarded as an essential component in the standard clinical management of high-risk neuroblastoma, its use for this purpose in the US and EU is off-label. To promote isotretinoin use in Japan as a treatment for neuroblastoma, our clinical research team is planning to launch an investigator-initiated, registration-directed clinical trial. The present review article discusses the basic science behind retinoid therapy, pre-clinical/clinical evidence on neuroblastoma, the concept of the proposed clinical trial, and prospects for this therapy. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Non-metastatic castration-resistant prostate cancer (nmCRPC) represents a challenging disease state in prostate cancer care. nmCRPC patients with a high risk of progression to metastatic disease who are identified by a prostate-specific antigen doubling time (PSADT) =10 months are eligible for treatment with the novel androgen receptor inhibitors (ARIs), shown to delay disease progression and extend survival. However, nmCRPC is often unexploited in clinical practice due to a lack of standardization in the methodology and in the tools used for its identification. In this article, a group of Urology and Oncology specialists with acknowledged expertise in prostate cancer reviews the state of the art in the management of high-risk nmCRPC patients, identifies gaps and unmet needs, and proposes strategies to optimize the identification of this patient subgroup in the clinical practice and improve their health outcomes. [ABSTRACT FROM AUTHOR]

Background: There is limited data with regard to the use of modified 5-fluoroural-leucovorin-irinotecan-oxaliplatin (mFOLFIRINOX) in terms of tolerance and enabling total mesorectal excision (TME) of locally advanced rectal adenocarcinomas (LARC) with highrisk characteristics (T4b status, signet ring histology etc) post standard neoadjuvant long course chemoradiation (NACTRT) or short course radiation (SCRT) and chemotherapy. Materials and Methods: Patients with LARC from January 2018 to December 2020 receiving mFOLFIRINOX post NACTRT/SCRT to facilitate TME were evaluated. The primary endpoint was assessment of grade 3 and grade 4 treatment related toxicity and TME rates. Event free survival (EFS), where event was defined as disease progression or recurrence post resection after mFOLFIRINOX, was calculated by Kaplan Meier method. Results: Forty-seven patients were evaluated with a median age of 33 years (Range:18-59), 45% T4b status, 96% radiological circumferential margin (CRM) involved (79% CRM positive post NACTRT/SCRT), 43% extramural venous invasion (n=33) and 36% signet ring histology. 62% had received prior NACTRT and 38% had received SCRT with chemotherapy before receiving mFOLFIRINOX. The most common grade 3 and grade 4 treatment related side effects included diarrhoea (7%), anaemia (4%) and infections (4%). Intended duration of mFOLFIRINOX or beyond was completed in 94% of patients. 60% of patients underwent curative local resection with R0 resection rates of 100% (n=28) and pathological complete response rates of 21%. The most common surgeries done were exenterations and abdominoperineal in 22% and 17% patients respectively. With a median follow up of 19 months, 24 patients had recurred or progressed for a median EFS of 20 months [95% confidence interval (CI): 15-24]. Conclusions: Locally advanced rectal cancers with high-risk characteristics are a niche group of cancers with less-than-optimal outcomes post standard neoadjuvant strategies. mFOLFIRINOX appears to be well tolerated and enables TME in a significant proportion of these patients. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of cerebral palsy is possible by 5 months corrected age for 'at‐risk' infants, using diagnostic tools such as the Hammersmith Infant Neurological Examination (HINE), Prechtl's General Movements Assessment (GMA) and magnetic resonance imaging (MRI). This is an uncertain and stressful time for parents where provision of appropriate information and support is essential. Aim: To explore parents' views and experiences in relation to the new early neurodevelopmental follow‐up of 'at‐risk' infants. Methods: Thirteen in‐depth one‐to‐one qualitative interviews were conducted by the primary researcher, with eight parents (six mothers and two fathers) of 'at‐risk' infants eligible for a follow‐up clinic where the GMA and HINE were performed at 12‐week corrected age. Interviews used a pre‐piloted topic guide and took place before and after the clinic. Interviews were audio‐recorded, transcribed verbatim and analysed using inductive coding and thematic analysis using the framework approach. Findings: Seven themes were identified: (1) attempting to manage uncertainty, (2) taking priority, (3) trusting professionals, (4) independence in the parent role, (5) feeling understood, (6) patterns of care and (7) individuality. Parents reported experiencing uncertainty about their current situation and future. Adequate preparation for and timing of information are vital. When uncertainty is poorly managed, parents' wellbeing suffers. Individual parents' perspectives and infants' developmental trajectories differ, and information should be tailored specifically for this. Conclusion: A parent's understanding of the journey through neurodevelopmental care for their high risk infants is initially very limited. Implementing a counselling service for parents to access psychological support and digital reminder system for clinic appointments, as well as providing more tailored information through trusted professionals, could all improve future parents' experiences. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The phase III trial, Japan Clinical Oncology Group 0802, illustrated the superiority of sublobar resection for early-stage lung cancer in terms of overall survival, with more non-lung cancer-related deaths after a lobectomy. The advantages of sublobar resection may be more pronounced in high-risk patients. The goal of this study was to elucidate the prognoses of high-risk patients. METHODS Patients with a risk of being ineligible for Japan Clinical Oncology Group 0802 for general conditions were classified as the high-risk group, and those who were not at risk of being ineligible were classified as the normal-risk group. Overall survival and prognostic factors were analysed in the high-risk group. RESULTS There were 254 (19.4%) and 1054 patients in the high- and normal-risk groups, respectively. Five-year survival rates were 94.5% and 79.1% in the normal-risk and high-risk groups, respectively (P  < 0.001). More patients in the high-risk group died of lung cancer (P  < 0.001) and non-lung cancer deaths (P  < 0.001) than patients in the normal-risk group. In the high-risk group, 151 lobectomies and 103 sublobar resections were performed. There was no significant difference in the numbers of lung cancer deaths and of non-lung cancer deaths between the procedures. Stratified survival analyses showed that the diffusing capacity of the lungs for carbon monoxide  < 40% tended to favour sublobar resection; being female and having a high carcinoembryonic antigen level tended to favour a lobectomy. CONCLUSIONS Sublobar resection is not always superior for early-stage lung cancer. Even in such cases, the surgical method should be determined by taking into consideration the patient's background and lung cancer surveillance. [ABSTRACT FROM AUTHOR]

Purpose: 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. Conclusion: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients. [ABSTRACT FROM AUTHOR]

Purpose: Treatment intensification of external beam radiotherapy (EBRT) plays a crucial role in the treatment of high-risk prostate cancer. Methods: We performed a critical narrative review of the relevant literature and present new developments in evidence-based treatment intensification strategies. Results: For men with high-risk prostate cancer, there is strong evidence to support prolonging androgen deprivation therapy (ADT) to 18–36 months and escalating the dose to the prostate using a brachytherapy boost. A potentially less toxic alternative to a brachytherapy boost is delivering a focal boost to dominant intraprostatic lesions using EBRT. In patients who meet STAMPEDE high-risk criteria, there is evidence to support adding a second-generation anti-androgen agent, such as abiraterone acetate, to long-term ADT. Elective pelvic lymph node irradiation may be beneficial in select patients, though more prospective data is needed to elucidate the group of patients who may benefit the most. Tumor genomic classifier (GC) testing and advanced molecular imaging will likely play a role in improving patient selection for treatment intensification as well as contribute to the evolution of treatment intensification strategies for future patients. Conclusion: Treatment intensification using a combination of EBRT, advanced hormonal therapies, and brachytherapy may improve patient outcomes and survival in men with high-risk prostate cancer. Shared decision-making between patients and multidisciplinary teams of radiation oncologists, urologists, and medical oncologists is essential for personalizing care in this setting and deciding which strategies make sense for individual patients. [ABSTRACT FROM AUTHOR]

The rate of preterm birth is increasing globally. It causes significant short-term and long-term health care burdens. A comprehensive recognition of the risk factors related to preterm births is important in the prevention of preterm birth. Our study is to investigate the incidence and maternal risk factors of preterm birth from a nationwide population-based perspective. This is a retrospective cohort study. All live births from 2004 to 2014 in Taiwan enrolled. The main data source was Taiwan's Birth Certificate Application (BCA) database. The BCA database was linked with the National Health Insurance Research Database (NHIRD) to establish any links between information on newborns and maternal underlying disease. A total of 1,385,979 births were included in the analysis. The incidence of preterm birth increased gradually in Taiwan from 8.85% in 2004 to 10.73% in 2014. Maternal age, socioeconomic status, maternal allergy and autoimmune diseases, gynecological diseases, and pregnancy-related complications were significant risk factors for preterm birth. The overall incidence of preterm births has gradually increased in Taiwan. Maternal age, socioeconomic status, certain underlying diseases, and pregnancy-related complications were risk factors for preterm birth. [ABSTRACT FROM AUTHOR]

Opinion statement: Localized high-risk (HR) prostate cancer (PCa) is a heterogenous disease state with a wide range of presentations and outcomes. Historically, non-surgical management with radiotherapy and androgen deprivation therapy was the treatment option of choice. However, surgical resection with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) is increasingly utilized as a primary treatment modality for patients with HRPCa. Recent studies have demonstrated that surgery is an equivalent treatment option in select patients with the potential to avoid the side effects from androgen deprivation therapy and radiotherapy combined. Advances in imaging techniques and biomarkers have also improved staging and patient selection for surgical resection. Advances in robotic surgical technology grant surgeons various techniques to perform RP, even in patients with HR disease, which can reduce the morbidity of the procedure without sacrificing oncologic outcomes. Clinical trials are not only being performed to assess the safety and oncologic outcomes of these surgical techniques, but to also evaluate the role of surgical resection as a part of a multimodal treatment plan. Further research is needed to determine the ideal role of surgery to potentially provide a more personalized and tailored treatment plan for patients with localized HR PCa. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: to learn the meanings attributed to pregnancy loss by women with Lupus. Method: qualitative research, based on Symbolic Interactionism and Grounded Theory. Data collection took place between January and August 2022 through in-depth interviews. Data analysis went through the stages of initial and focused coding. Results: seventeen women participated. The central phenomenon “The climb to motherhood: falls and overcoming” was constructed, consisting of three categories: “Falling to the ground during the climb: the experience of pregnancy loss”; “Getting up and following the path: new attempts to conceive”; and “Remembering the journey: meanings attributed to pregnancy losses”. Final considerations: experiencing pregnancy is, analogously, like climbing a mountain, where obstacles need to be overcome to reach the summit. The experience of pregnancy loss is seen as complex, especially when there is fragility in healthcare and a lack of awareness regarding feelings of loss and grief.