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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.

ObjectiveTo assess the impact of automated algorithms on the trainees’ decision-making capacity and confidence for individualized surgical planning.MethodsAt Chinese PLA General Hospital, trainees were enrolled to undergo decision-making capacity and confidence training through three alternative visual tasks of the inferior clivus model formed from an automated algorithm and given consecutively in three exemplars. The rationale of automated decision-making was used to instruct each trainee.ResultsFollowing automated decision-making calculation in 50 skull base models, we screened out three optimal plans, infra-tubercle approach (ITA), trans-tubercle approach (TTA), and supra-tubercle approach (STA) for 41 (82.00%), 8 (16.00%), and 1 (2.00%) subject, respectively. From September 1, 2023, through November 17, 2023, 62 trainees (median age [range]: 27 [26–28]; 28 [45.16%] female; 25 [40.32%] neurosurgeons) made a decision among the three plans for the three typical models (ITA, TTA, and STA exemplars). The confidence ratings had fine test-retest reliability (Spearman's rho: 0.979; 95% CI: 0.970 to 0.988) and criterion validity with time spent (Spearman's rho: −0.954; 95%CI: −0.963 to −0.945). Following instruction of automated decision-making, time spent (initial test: 24.02 vs. 7.13 in ITA; 30.24 vs. 7.06 in TTA; 34.21 vs. 12.82 in STA) and total hits (initial test: 30 vs. 16 in ITA; 37 vs. 17 in TTA; 42 vs. 28 in STA) reduced significantly; confidence ratings (initial test: 2 vs. 4 in ITA; 2 vs. 4 in TTA; 1 vs. 3 in STA) increased correspondingly. Statistically significant differences (P

Abstract Background Intraoperative pulmonary embolism (PE) with cardiac arrest (CA) represents a critical and potentially fatal condition. Available treatments include systemic thrombolysis, catheter-based thrombus fragmentation or aspiration, and surgical embolectomy. However, limited studies are focused on the optimal treatment choice for this critical condition. We present a case series and an updated review of the management of intraoperative CA secondary to PE. Methods A retrospective review of patients who developed high-risk intraoperative PE was performed between June 2012 and June 2022. For the updated review, a literature search on PubMed and Scopus was conducted which resulted in the inclusion of a total of 46 articles. Results A total of 196 174 major non-cardiac surgeries were performed between 2012 and 2022. Eight cases of intraoperative CA secondary to high-risk PE were identified. We found a mortality rate of 75%. Anticoagulation therapy was administered to one patient (12.5%), while two patients (25%) underwent thrombolysis, and one case (12.5%) underwent mechanical thrombectomy combined with thrombus aspiration. Based on the literature review and our 10-year experience, we propose an algorithm for the management of intraoperative CA caused by PE. Conclusion The essential components for adequate management of intraoperative PE with CA include hemodynamic support, cardiopulmonary resuscitation, and the implementation of a primary perfusion intervention. The prompt identification of the criteria for each specific treatment modality, guided by the individual patient’s characteristics, is necessary for an optimal approach.

Abstract Background The progressive multimorbidity explosion has challenged Chile’s health systems and worldwide. The Centro de Innovación en Salud ANCORA UC implemented a new Multimorbidity Patient-Centered Care Model in Chile. Objective Evaluate the perspective of high-risk patients about the core elements of the model. Methodology We conducted a cross sectional telephone-based survey that considered the application of a 13 items questionnaire. Of them, nine were Likert scale questions with scores from 1 to 7, one dichotomic question, and three open-ended questions. 231 high-risk patients who received care through the model at primary care centers participated in the study. Quantitative data were encoded, consolidated, and analyzed with the SPSS software. We performed descriptive and analytic statistics techniques to assess different variables and their potential associations. Thematic analysis was conducted for qualitative data. Results The overall score was 5.84 (range: 1 to 7), with a standard deviation of 1.25. Questions with the best scores were those related with personalized care and the primary care teams. The lowest scored was for the item regarding the continuity of care between primary nurses and inpatient care at the hospital. There was a difference in patient outcomes depending on their health center. Regarding sociodemographic characteristics, age did not significantly affect the results. Conclusions The study reveals the perceptions about a complex multimorbidity intervention from the patient’s perspective. It complements the impact on health services utilization evaluation that supports decision-makers currently scaling up a similar strategy in our country and could be considered in other countries dealing with non-communicable diseases.

Introduction: Diabetes has emerged as a global pandemic of the 21st century, with approximately 463 million adults (aged 20- 79 years) living with diabetes worldwide in 2019. Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes compared to Type 1 and other forms. The burden of diabetes in India is expected to increase in the coming years. The Indian Diabetes Risk Score (IDRS) is a validated and cost-effective tool used to identify the risk of developing diabetes among the population. Aim: To estimate the risk of T2DM using the IDRS in adults aged 25 years and above. Additionally, the study aimed to explore the association between the risk of diabetes and other factors. Materials and Methods: An observational, community-based, cross-sectional study was conducted in the field practice area of Kurnool Medical College, Kurnool, Andhra Pradesh, India. Data collection took place from December 2022 to February 2023, using a simple random sampling technique. The study included residents aged over 25. A sample size of 100 participants was selected. The IDRS, developed by the Madras Diabetic Research Foundation (MDRF), was used as a validated tool to screen individuals at high-risk of developing T2DM. Data was collected using a semistructured questionnaire that included socio-demographic information, the IDRS tool to detect the risk of developing diabetes, and other risk factors such as Body Mass Index (BMI), family history of diabetes, physical activity, smoking, alcohol consumption, and hypertension. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) version 23.0. The Chi-square test was used to determine significance, with a p-value of

Objective To investigate the clinical efficacy of peripheral blood stem cell transplantation from haploidentical and matched sibling donors for treatment of high-risk and refractory/relapsed acute myeloid leukemia (AML). Methods Data on the efficacy of haploidentical peripheral blood stem cell transplantation (Haplo-HSCT) with myeloablative conditioning regimen were retrospectively analyzed and compared with that of matched sibling donors' peripheral blood stem cell transplantation (MSD-HSCT) for treatment of high-risk refractory/relapsed AML in our center from January 1st, 2010 to June 30th, 2020. Results A total of 98 patients were enrolled, including 62 patients in the Haplo-HSCT group and 36 patients in MSD-HSCT group. The median age, conditioning regimen, and infusion doses of MNC and CD34+ cells were significantly different between the two groups, but no significant differences in other baseline parameters were found. Transplantation-related infectious complications and the incidence of acute and chronic graft-versus-host disease (GVHD) were also not significantly different between the two groups. The 3-year cumulative relapse in the Haplo-HSCT group was significantly lower than that in the MSD-HSCT group (16.2% vs. 41.1%, P=0.036). The 3-year DFS of the Haplo-HSCT and MSD-HSCT groups were 66.98% and 41.8%, respectively (P=0.140), and their OS were 73.37% and 51.41%, respectively (P=0.105). Conclusion The clinical efficacy of Haplo-HSCT for the treatment of high-risk and refractory/relapsed AML is similar to that of MSD-HSCT, and Haplo-HSCT may have better GVL effect.

Abstract Background As a result of increased life expectancy and improved care for patients suffering from chronic disease, the number of patients with multimorbidity requiring surgical intervention is increasing. For complex surgical patients, it is essential to balance the potential benefits of surgical treatment against the risk of permanent loss of functional capacity and quality of life due to complications. European and US guidelines on perioperative care recommend preoperative multidisciplinary team (MDT) discussions for high-risk noncardiac surgical patients. However, the evidence underlying benefits from preoperative MDT meetings with all relevant perioperative specialties present is limited. The current study aims to investigate the effect of implementation of preoperative MDT discussions for high-risk patients undergoing noncardiac surgery on serious adverse events. Methods/design PREPARATION is a stepped-wedge cluster randomized trial in 14 Dutch hospitals without currently established preoperative MDT meeting. The intervention, preoperative MDT meetings, will be implemented sequentially with seven blocks of 2 hospitals switching from control (preoperative screening as usual) to the intervention every 3 months. Each hospital will be randomized to one of seven blocks. We aim to include 1200 patients. The primary outcome is the incidence of serious adverse events at 6 months. Secondary outcomes include (cost)effectiveness, functional outcome, and quality of life for up to 12 months. Discussion PREPARATION is the first study to assess the effectiveness of a preoperative MDT meeting for high-risk noncardiac surgical patients in the presence of an anesthesiologist. If the results suggest that preoperative MDT discussions for high-risk patients are (cost)-effective, the current study facilitates implementation of preoperative MDT meetings in clinical practice. Trial registration ClinicalTrials.gov NCT05703230. Registered on 11/09/2022.

Abstract Background and objective For high-risk elderly patients with chronic diseases, endoscopic stone removal for large common bile duct stones is associated with a high risk of adverse events and incomplete stone removal. The aim of this study was to investigate whether the treatment strategy of short-term biliary plastic stent placement followed by elective endoscopic stone removal is more effective and safer than immediate endoscopic stone removal. Methods The data of 262 high-risk elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) for large common bile duct (CBD) stones from 2017 to 2022 were retrospectively analyzed. The patients were divided into group A (immediate stone removal) and group B (stent drainage + elective stone removal). The baseline data of the 2 groups were matched 1:1 by propensity score matching. The stone clearance rate, ERCP procedure time, total hospital stay, and procedure-related adverse events were compared between the matched groups. In group B, stone size before and after stent placement, hospital stay, procedure time and adverse events of two ERCPs were compared. Results A total of 57 pairs of patients were successfully matched between the 2 groups. The stone clearance rate in group B was higher than that in group A (89.5% vs. 75.3, P = 0.049). The total hospital stay in group B was longer than that in group A (11.86 ± 3.912 d vs. 19.14 ± 3.176 d, P

Objective: To determine if nirmatrelvir-ritonavir 300mg/100mg treatment for 5 days in high-risk outpatients with mild to moderate COVID-19 symptoms was associated with a reduction in hospitalization, intensive care unit (ICU) admission, and death. Methods: This 1:1 propensity score matched cohort study from 647 public health clinics in Malaysia included all patients with COVID-19 with positive tests aged 18 years and older, who were eligible for nirmatrelvir-ritonavir treatment within 5 days of illness from July 14, 2022, to November 14, 2022. The exposed group was patients with COVID-19 initiated with nirmatrelvir-ritonavir treatment, whereas those not initiated with the drug served as the control group. Data was analyzed from July 14, 2022 to December 31, 2022. Results: A total of 20,966 COVID-19 high-risk outpatients (n = 10,483 for nirmatrelvir-ritonavir group and n = 10,483 for control group) were included in the study. Nirmatrelvir-ritonavir treatment was associated with a 36% reduction (adjusted hazard ratio 0.64 [95% CI 0.43, 0.94]) in hospitalization compared with those not given the drug. There was a single ICU admission for the control group and one death each was reported in the nirmatrelvir-ritonavir and control group, respectively. Conclusions: Nirmatrelvir-ritonavir treatment was associated with reduced hospitalization in high-risk patients with COVID-19 even in highly vaccinated populations.

Background: Intraoperative pulmonary embolism (PE) with cardiac arrest (CA) represents a critical and potentially fatal condition. Available treatments include systemic thrombolysis, catheter-based thrombus fragmentation or aspiration, and surgical embolectomy. However, limited studies are focused on the optimal treatment choice for this critical condition. We present a case series and an updated review of the management of intraoperative CA secondary to PE. Methods: A retrospective review of patients who developed high-risk intraoperative PE was performed between June 2012 and June 2022. For the updated review, a literature search on PubMed and Scopus was conducted which resulted in the inclusion of a total of 46 articles. Results: A total of 196 174 major non-cardiac surgeries were performed between 2012 and 2022. Eight cases of intraoperative CA secondary to high-risk PE were identified. We found a mortality rate of 75%. Anticoagulation therapy was administered to one patient (12.5%), while two patients (25%) underwent thrombolysis, and one case (12.5%) underwent mechanical thrombectomy combined with thrombus aspiration. Based on the literature review and our 10-year experience, we propose an algorithm for the management of intraoperative CA caused by PE. Conclusion: The essential components for adequate management of intraoperative PE with CA include hemodynamic support, cardiopulmonary resuscitation, and the implementation of a primary perfusion intervention. The prompt identification of the criteria for each specific treatment modality, guided by the individual patient's characteristics, is necessary for an optimal approach. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a highly heterogenous plasma cell malignancy, commonly seen in older patients. Age is one of the important prognostic factors. However, nearly all the prognostic staging systems are based on clinical trials, where patients were relatively fit and young. It is unknown how the presence of biochemical or cytogenetic prognostic factors and their risk weights changes with older age. To further investigate this question, we retrospectively analyzed the data from a consecutive cohort of patients treated with either bortezomib or thalidomide-based therapy. This retrospective study was carried out on a cohort of 1125 newly diagnosed multiple myeloma patients, from January 2008 to December 2019. Patients received bortezomib or thalidomide-based induction and maintenance therapy. Patients accepted hematopoietic stem cell transplantation if eligible. Statistical analysis was conducted by Stata/MP 16.0 and SPSS 26.0. With age increasing, the proportion of patients with ISS 3, performance status score ≥2, and the incidence rate of gain(1q) significantly increased. We also found that ISS became less important in older patients. However, cytogenetic abnormalities exerted a consistently adverse impact on survival, both in young and old patients. Older patients had an inferior outcome than their young counterparts. All patients in our cohort benefitted more from bortezomib than thalidomide-based induction therapy, except for patients ≥71 years old. ISS may lose prognostic value in patients ≥71 years old. Older patients had an inferior outcome and needed more effective and less toxic treatment. Plain Language Summary Multiple myeloma is a type of blood cancer commonly seen in older people. To treat this disease, genetic abnormality, the poor physical status of patients and the abundance of tumor cells are the main difficulties. We often draw these conclusions from clinical trials. However, clinical trials always enrolled relatively younger patients, so the presence and significance of these factors may vary from clinical trials to the real world. We conducted the study to find out the real risk in both young and old patients. We found that older patients were more likely to have anemia, poor nutritional status and renal function. We also found older patients had more risk of relapse, progression or death than young patients. Frail physical status is the key obstacle to treating older patients, and tumor burden no longer impacts the outcome of these people. Bortezomib is a powerful drug to treat this disease, but patients ≥71 years old had less benefit than younger ones. More studies should focus on older or frail patients as these patients need more effective and less toxic treatment. [ABSTRACT FROM AUTHOR]

Background: The progressive multimorbidity explosion has challenged Chile's health systems and worldwide. The Centro de Innovación en Salud ANCORA UC implemented a new Multimorbidity Patient-Centered Care Model in Chile. Objective: Evaluate the perspective of high-risk patients about the core elements of the model. Methodology: We conducted a cross sectional telephone-based survey that considered the application of a 13 items questionnaire. Of them, nine were Likert scale questions with scores from 1 to 7, one dichotomic question, and three open-ended questions. 231 high-risk patients who received care through the model at primary care centers participated in the study. Quantitative data were encoded, consolidated, and analyzed with the SPSS software. We performed descriptive and analytic statistics techniques to assess different variables and their potential associations. Thematic analysis was conducted for qualitative data. Results: The overall score was 5.84 (range: 1 to 7), with a standard deviation of 1.25. Questions with the best scores were those related with personalized care and the primary care teams. The lowest scored was for the item regarding the continuity of care between primary nurses and inpatient care at the hospital. There was a difference in patient outcomes depending on their health center. Regarding sociodemographic characteristics, age did not significantly affect the results. Conclusions: The study reveals the perceptions about a complex multimorbidity intervention from the patient's perspective. It complements the impact on health services utilization evaluation that supports decision-makers currently scaling up a similar strategy in our country and could be considered in other countries dealing with non-communicable diseases. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of refractory pulmonary arterial hypertension (PAH) is challenging and rarely the focus of reviews. The purpose of this review is to discuss current treatment options of refractory PAH, along with the state of research of several new medications. Areas covered: We conducted a comprehensive PubMed search on the relevant literature on treating PAH, with a focus on approved and investigational interventions for high-risk patients. Our strategy used keywords 'Treatment' AND 'Pulmonary Hypertension,' without date restrictions, ensuring a thorough survey of available literature for our review. Expert opinion: By utilizing serial risk assessment to identify patients remaining intermediate or highrisk, more patients are likely to survive longer. This is done by earlier use of combination or triple therapy with prostacyclin drugs. Current medications for PAH are all essentially vasodilators that improve physiology, but do not truly modify the disease process. The potential application of new investigational medications is exciting as they work by novel pathways likely to change the landscape of refractory PAH treatment. [ABSTRACT FROM AUTHOR]

Interest in the applications of mindfulness practice in education is growing in the scientific community. Recent research has shown that mindfulness practice in schools may be beneficial for executive functions (EFs) which are abilities crucial for healthy development. The study of the effects of mindfulness practices on children's neural correlates of EFs, particularly inhibitory control, may provide relevant information about the impact and mechanisms of mindfulness‐based interventions (MBIs) in children. The aim of the present study was to investigate the effects of a MBI in elementary school children on the neural correlates of inhibitory control via a randomized controlled trial. Children from two 4th grade classrooms and two 5th grade classrooms located in a school identified as having low socioeconomic status in Santiago de Chile were randomly assigned to either receive a MBI or serve as active controls and receive a social skills program. Both before and after the interventions, electroencephalographic activity was recorded during a modified version of the Go/Nogo task in a subsample of children in each group. Additionally, teachers completed questionnaires of students' EFs and students completed self‐report measures. Results revealed increases in EFs assessed by questionnaires together with improved P3 amplitude associated with successful response inhibition in children who received the MBI compared to active controls. These results contribute to the understanding of the ways in which mindfulness practices can promote the development of inhibitory control together with EF improvement, factors identified as critical for children's social and emotional development and positive mental health. Research Highlights: This study investigated the effects of a mindfulness‐based intervention in children from a low socioeconomic status school on neural correlates of EFs.Children performed a Go/Nogo task while electroencephalographic activity was recorded and completed questionnaires before and after a MBI or an active control program.Improvements in EFs assessed by questionnaires together with an increased Nogo‐P3 activity associated with successful inhibition in children who received the MBI were found.The results could contribute to understand how mindfulness practice can promote the development of inhibitory control in children from vulnerable populations. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes has emerged as a global pandemic of the 21st century, with approximately 463 million adults (aged 20-79 years) living with diabetes worldwide in 2019. Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes compared to Type 1 and other forms. The burden of diabetes in India is expected to increase in the coming years. The Indian Diabetes Risk Score (IDRS) is a validated and cost-effective tool used to identify the risk of developing diabetes among the population. Aim: To estimate the risk of T2DM using the IDRS in adults aged 25 years and above. Additionally, the study aimed to explore the association between the risk of diabetes and other factors. Materials and Methods: An observational, community-based, cross-sectional study was conducted in the field practice area of Kurnool Medical College, Kurnool, Andhra Pradesh, India. Data collection took place from December 2022 to February 2023, using a simple random sampling technique. The study included residents aged over 25. A sample size of 100 participants was selected. The IDRS, developed by the Madras Diabetic Research Foundation (MDRF), was used as a validated tool to screen individuals at high-risk of developing T2DM. Data was collected using a semistructured questionnaire that included socio-demographic information, the IDRS tool to detect the risk of developing diabetes, and other risk factors such as Body Mass Index (BMI), family history of diabetes, physical activity, smoking, alcohol consumption, and hypertension. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) version 23.0. The Chi-square test was used to determine significance, with a p-value of <0.05 considered significant. Results: A total of 100 residents aged over 25 years were included in the study. IDRS categorisation revealed that 14 (14%) were at low risk, 43 (43%) at moderate risk, and 43 (43%) at high-risk for developing T2DM, respectively. A statistically significant association was observed between diabetes risk score and individuals who smoked (p=0.04), consumed alcohol (p=0.04), and had hypertension (p<0.001). BMI showed a positive correlation with IDRS score (p=0.031), family history score (p=0.028), and waist circumference score (p=0.034). Conclusion: Early detection of the risk of diabetes through periodic screening and effective behavioural change communication could be instrumental in controlling the diabetes crisis. [ABSTRACT FROM AUTHOR]

Traditional prognostic models for newly diagnosed patients with multiple myeloma (MM), including International Staging System criteria and number of high-risk chromosomal abnormalities, are based on disease characteristics at diagnosis. However, the identification of patients at risk of more rapidly progressive MM is inherently a dynamic assessment. In a subset of patients with MM, adverse disease biology only becomes evident after the failure of firstline therapy. We define this entity as functional high-risk MM (FHRMM), encompassing relapse within 18 months of treatment initiation and/or within 12 months of frontline autologous stem cell transplantation. FHRMM is not adequately captured by traditional prognostic models, and there is a need for better understanding of mechanisms or risk factors for early relapse or progression. In this review, we explore potential definitions of FHRMM before delving into its underlying drivers based on genetic, transcriptomic, and immune cell profiling studies. Emerging data suggest that specific features of both myeloma cells and immune cells can enable the FHRMM phenotype. We conclude our review by discussing ongoing and future studies that seek to identify and intervene upon patients with FHRMM preemptively. [ABSTRACT FROM AUTHOR]

Background: As a result of increased life expectancy and improved care for patients suffering from chronic disease, the number of patients with multimorbidity requiring surgical intervention is increasing. For complex surgical patients, it is essential to balance the potential benefits of surgical treatment against the risk of permanent loss of functional capacity and quality of life due to complications. European and US guidelines on perioperative care recommend preoperative multidisciplinary team (MDT) discussions for high-risk noncardiac surgical patients. However, the evidence underlying benefits from preoperative MDT meetings with all relevant perioperative specialties present is limited. The current study aims to investigate the effect of implementation of preoperative MDT discussions for high-risk patients undergoing noncardiac surgery on serious adverse events. Methods/design: PREPARATION is a stepped-wedge cluster randomized trial in 14 Dutch hospitals without currently established preoperative MDT meeting. The intervention, preoperative MDT meetings, will be implemented sequentially with seven blocks of 2 hospitals switching from control (preoperative screening as usual) to the intervention every 3 months. Each hospital will be randomized to one of seven blocks. We aim to include 1200 patients. The primary outcome is the incidence of serious adverse events at 6 months. Secondary outcomes include (cost)effectiveness, functional outcome, and quality of life for up to 12 months. Discussion: PREPARATION is the first study to assess the effectiveness of a preoperative MDT meeting for high-risk noncardiac surgical patients in the presence of an anesthesiologist. If the results suggest that preoperative MDT discussions for high-risk patients are (cost)-effective, the current study facilitates implementation of preoperative MDT meetings in clinical practice. Trial registration: ClinicalTrials.gov NCT05703230. Registered on 11/09/2022. [ABSTRACT FROM AUTHOR]

Background and objective: For high-risk elderly patients with chronic diseases, endoscopic stone removal for large common bile duct stones is associated with a high risk of adverse events and incomplete stone removal. The aim of this study was to investigate whether the treatment strategy of short-term biliary plastic stent placement followed by elective endoscopic stone removal is more effective and safer than immediate endoscopic stone removal. Methods: The data of 262 high-risk elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) for large common bile duct (CBD) stones from 2017 to 2022 were retrospectively analyzed. The patients were divided into group A (immediate stone removal) and group B (stent drainage + elective stone removal). The baseline data of the 2 groups were matched 1:1 by propensity score matching. The stone clearance rate, ERCP procedure time, total hospital stay, and procedure-related adverse events were compared between the matched groups. In group B, stone size before and after stent placement, hospital stay, procedure time and adverse events of two ERCPs were compared. Results: A total of 57 pairs of patients were successfully matched between the 2 groups. The stone clearance rate in group B was higher than that in group A (89.5% vs. 75.3, P = 0.049). The total hospital stay in group B was longer than that in group A (11.86 ± 3.912 d vs. 19.14 ± 3.176 d, P<0.001). The total adverse event rate in group A was higher than that in group B (29.8% vs. 12.3%, P = 0.005). The incidence of cholangitis/cholecystitis after ERCP was significantly higher in group A than in group B (7.0% vs. 0.9% P = 0.029). There was no significant difference in the incidence of post-ERCP pancreatitis, bleeding, pneumonia, and cardio-cerebrovascular events between the 2 groups. There were no perforation cases in either group. After plastic biliary stent placement in group B, the stone size was significantly smaller than before stent placement (1.59 ± 0.544 cm vs. 1.95 ± 0.543 cm, P < 0.001), and there was no significant difference in the total adverse event incidence between the two ERCP procedures (18.8% vs. 10.9%, P = 0.214). Conclusion: For high-risk elderly patients with large CBD stones, the treatment strategy involving temporary placement of plastic stent and elective endoscopic stone removal is safer and more effective than immediate stone removal. [ABSTRACT FROM AUTHOR]

Gaining insight into the prenatal care experiences and expectations of high-risk pregnant women is crucial for offering holistic care that aligns with their individualized needs. This study aimed at determining the care experiences and expectations of women with high-risk pregnancies. We adopted a descriptive qualitative approach in the research. The data were collected through in-depth interviews between March and June 2022. The participants included 27 high-risk pregnant women selected by purposive sampling. We analyzed the data using inductive content analysis. We utilized the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist to report data. The participants' ages ranged from 22 to 40 years. The participants' gestational ages ranged from 29 to 38 weeks. We identified three themes, namely "Emotions felt in the course of pregnancy", "Care experiences; satisfaction and dissatisfaction", and "Expectations for ideal care". The findings showed that women experienced fear, stress, and anxiety while expecting supportive, attentive, and understanding care during the course of pregnancy. Our results revealed that high-risk pregnant women have some unmet care needs. Healthcare professionals should strive to provide individualized and holistic care for high-risk pregnant women. [ABSTRACT FROM AUTHOR]

High-risk pregnant women experience stress and anxiety. Anxiety may affect prenatal attachment. This study aimed to examine the effect of anxiety on prenatal attachment in high-risk pregnant women. The study was cross-sectional and conducted on 290 high-risk pregnant women who applied to the perinatology outpatient clinic of a university hospital between February and July 2022. The data were collected with the descriptive information sheet, Prenatal Attachment Inventory (PAI), and Perinatal Anxiety Screening Scale (PASS). Mann-Whitney U, Kruskal Wallis-H, and Spearman's Correlation tests were used to analyze the data. The mean age of the examined pregnant women was 28.12 ± 5.36, and most of them were multigravida (65.5 percent) and in the third trimester (80.7 percent). The PAI and PASS mean scores were 64.09 ± 11.31 and 27.98 ± 16.52, respectively. There was a weak positive correlation between anxiety and prenatal attachment (r =.227, p <.001). The levels of prenatal attachment were higher in primigravidas and women with no children. Also, the anxiety levels of pregnant women in the third trimester were lower. Health professionals should evaluate the prenatal attachment and anxiety levels of high-risk pregnant women, and consider obstetrical factors that may influence both prenatal attachment and anxiety levels. [ABSTRACT FROM AUTHOR]

Background: The Trauma and Injury Severity Score (TRISS) uses anatomic/physiologic variables to predict outcomes. The National Surgical Quality Improvement Program Surgical Risk Calculator (NSQIP-SRC) includes functional status and comorbidities. It is unclear which of these tools is superior for high-risk trauma patients (American Society of Anesthesiologists Physical Status (ASA-PS) class IV or V). This study compares risk prediction of TRISS and NSQIP-SRC for mortality, length of stay (LOS), and complications for high-risk operative trauma patients. Methods: This is a prospective study of high-risk (ASA-PS IV or V) trauma patients (≥18 years-old) undergoing surgery at 4 trauma centers. We compared TRISS vs NSQIP-SRC vs NSQIP-SRC + TRISS for ability to predict mortality, LOS, and complications using linear, logistic, and negative binomial regression. Results: Of 284 patients, 48 (16.9%) died. The median LOS was 16 days and number of complications was 1. TRISS + NSQIP-SRC best predicted mortality (AUROC:.877 vs.723 vs.843, P =.0018) and number of complications (pseudo-R2/median error (ME) 5.26%/1.15 vs 3.39%/1.33 vs 2.07%/1.41, P <.001) compared to NSQIP-SRC or TRISS, but there was no difference between TRISS + NSQIP-SRC and NSQIP-SRC with LOS prediction (P =.43). Discussion: For high-risk operative trauma patients, TRISS + NSQIP-SRC performed better at predicting mortality and number of complications compared to NSQIP-SRC or TRISS alone but similar to NSQIP-SRC alone for LOS. Thus, future risk prediction and comparisons across trauma centers for high-risk operative trauma patients should include a combination of anatomic/physiologic data, comorbidities, and functional status. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to identify clinical predictors of early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). A total of 670 high-risk PCa patients treated with CIRT and ADT were included in the study. Early BCR was defined as recurrence occurring during adjuvant ADT after CIRT or within 2 years after completion of ADT. Univariate and multivariate analyses were performed to identify clinical predictors of early BCR. Patients were also classified according to the Systemic Therapy in Advancing or Metastatic Prostate cancer (STAMPEDE) PCa classification. Early BCR was observed in 5.4% of the patients. Multivariate analysis identified clinical T3b stage and ≥75% positive biopsy cores as clinical predictors of early BCR after CIRT and ADT. The STAMPEDE PCa classification was also significantly associated with early BCR based on univariate analysis. These predictors can help clinicians identify patients who are at risk of early BCR. In the future, combination therapy of ADT with abiraterone may be an option for high-risk PCa patients who are at risk of early BCR, based on the results of the STAMPEDE study. [ABSTRACT FROM AUTHOR]

• We assess the effectiveness of nirmatrelvir-ritonavir treatment. • Hospitalization rate was low in BA.4, BA.5, and XBB predominant Omicron period. • Nirmatrelvir-ritonavir treatment reduced hospitalization in patients with COVID-19. To determine if nirmatrelvir-ritonavir 300mg/100mg treatment for 5 days in high-risk outpatients with mild to moderate COVID-19 symptoms was associated with a reduction in hospitalization, intensive care unit (ICU) admission, and death. This 1:1 propensity score matched cohort study from 647 public health clinics in Malaysia included all patients with COVID-19 with positive tests aged 18 years and older, who were eligible for nirmatrelvir-ritonavir treatment within 5 days of illness from July 14, 2022, to November 14, 2022. The exposed group was patients with COVID-19 initiated with nirmatrelvir-ritonavir treatment, whereas those not initiated with the drug served as the control group. Data was analyzed from July 14, 2022 to December 31, 2022. A total of 20,966 COVID-19 high-risk outpatients (n = 10,483 for nirmatrelvir-ritonavir group and n = 10,483 for control group) were included in the study. Nirmatrelvir-ritonavir treatment was associated with a 36% reduction (adjusted hazard ratio 0.64 [95% CI 0.43, 0.94]) in hospitalization compared with those not given the drug. There was a single ICU admission for the control group and one death each was reported in the nirmatrelvir-ritonavir and control group, respectively. Nirmatrelvir-ritonavir treatment was associated with reduced hospitalization in high-risk patients with COVID-19 even in highly vaccinated populations. [ABSTRACT FROM AUTHOR]

In 2050 two-thirds of the world's population is predicted to live in cities, which asks for a better understanding of how the urban environment affects mental health. Urbanicity has repeatedly been found to be a risk factor, in particular for psychosis. Here, we explored what factors of the urban exposome underlie the association between urban characteristics and psychotic experiences (PE) in adolescents. Participants were 815 adolescents (mean age 14.84 years, SD 0.78) from an at-risk cohort (greater Rotterdam area, the Netherlands) oversampled on their self-reported emotional and behavioral problems. We used linear regression analysis to examine the association with detailed geodata on urbanicity (surrounding address density), green space density (high and low vegetation), and mixed noise levels (road, rail, air, industry, and wind power) with PE in adolescents. Analyses were adjusted for multiple socio-economic and parental confounders. Furthermore, we explored sex-interaction effects. Higher surrounding address density and low greenspace density were each independently associated with more PE (B = 0.18, 95 % CI 0.02; 0.34 and B = 0.17, 95 % CI 0.01; 0.32, respectively). High mixed noise levels were only associated with more PE in boys (B = 0.23, 95 % CI 0.01; 0.46). A sex-interaction effect was found for high urbanicity (B = −0.46, 95 % CI −0.77; −0.14) and low greenspace density (B = −0.49, 95 % CI −0.73; −0.11), illustrating that these associations with PE were specific for boys. Multiple characteristics of living in an urban area are associated with more PE in adolescent boys. Our observations provide leads for prevention of mental health problems via urban designing. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical efficacy of peripheral blood stem cell transplantation from haploidentical and matched sibling donors for treatment of high-risk and refractory/relapsed acute myeloid leukemia (AML). Methods Data on the efficacy of haploidentical peripheral blood stem cell transplantation (Haplo-HSCT) with myeloablative conditioning regimen were retrospectively analyzed and compared with that of matched sibling donors’ peripheral blood stem cell transplantation (MSD-HSCT) for treatment of highrisk refractory/relapsed AML in our center from January 1st, 2010 to June 30th, 2020. Results A total of 98 patients were enrolled, including 62 patients in the Haplo-HSCT group and 36 patients in MSD-HSCT group. The median age, conditioning regimen, and infusion doses of MNC and CD34+ cells were significantly different between the two groups, but no significant differences in other baseline parameters were found. Transplantation-related infectious complications and the incidence of acute and chronic graft-versus-host disease (GVHD) were also not significantly different between the two groups. The 3-year cumulative relapse in the Haplo-HSCT group was significantly lower than that in the MSD-HSCT group (16.2% vs. 41.1%, P=0.036). The 3-year DFS of the Haplo-HSCT and MSD-HSCT groups were 66.98% and 41.8%, respectively (P=0.140), and their OS were 73.37% and 51.41%, respectively (P=0.105). Conclusion The clinical efficacy of Haplo-HSCT for the treatment of high-risk and refractory/relapsed AML is similar to that of MSD-HSCT, and Haplo-HSCT may have better GVL effect. [ABSTRACT FROM AUTHOR]

Objective: Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula (POPF). Summary Background Data: TP is mentioned as an alternative to PD in patients at high risk for POPF, but a systematic review is lacking. Methods: Systematic review and meta-analyses using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published up to October 2022, comparing elective single-stage TP for any indication versus PD in patients at high risk for POPF. The primary endpoint was short-term mortality. Secondary endpoints were major morbidity (i.e., Clavien- Dindo grade ≥IIIa) on the short-term and quality of life. Results: After screening 1212 unique records, five studies with 707 patients (334 TP and 373 high-risk PD) met the eligibility criteria, comprising one randomized controlled trial and four observational studies. The 90-day mortality after TP and PDdid not differ (6.3% vs. 6.2%; RR=1.04 [95%CI 0.56-1.93]). Major morbidity rate was lower after TP compared to PD (26.7% vs. 38.3%; RR=0.65 [95%CI 0.48-0.89]), but no significance was seen in matched/randomized studies (29.0% vs. 36.9%; RR = 0.73 [95%CI 0.48-1.10]). Two studies investigated quality of life (EORTC QLQ-C30) at a median of 30-52 months, demonstrating comparable global health status after TP and PD (77% [±15] vs. 76% [±20]; P=0.857). Conclusions: This systematic review and meta-analysis found no reduction in short-term mortality and major morbidity after TP as compared to PD in patients at high risk for POPF. However, if TP is used as a bailout procedure, the comparable long-term quality of life is reassuring. [ABSTRACT FROM AUTHOR]

Background. Dyslipidaemia and hypertension care have not been reported in large samples of community-based participants with known diabetes (KD) nor compared with individuals at high risk for diabetes. Objectives. To describe the management and associations of dyslipidaemia and hypertension in adults with KD, newly diagnosed diabetes (NDD) and normoglycaemia. Methods. This urban population-based cross-sectional study comprised participants with KD, NDD and normoglycaemia. Participants at high risk for diabetes but without KD underwent oral glucose tolerance tests; those who were subsequently classified as NDD or normoglycaemic were included in this study. Data collection comprised administered questionnaires, clinical measurements and biochemical analyses. Multivariable logistic regressions determined the associations with hypertension and dyslipidaemia management in separate models. Results. Among 618 participants (82% women), aged median 58 years, there were 339 participants with KD, 70 with NDD and 209 with normoglycaemia. Prevalence of hypertension (BP ≥140/90 mmHg or on treatment) and dyslipidaemia (raised low-density lipoprotein cholesterol >3 mmol/L or on treatment) was highest in KD (89% and 83%) compared with NDD (64% and 74%) and normoglycaemia (66% for both) (p

PurposeModern 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 materialsA 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.ResultsA 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.ConclusionUtilization 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.

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.

Objectives: Although factors related to a return visit to the emergency department (ED) have been reported, only few studies have examined “high-risk” ED revisits with serious adverse outcomes. This study aimed to describe the incidence and trend of high-risk ED revisits in United States EDs and to investigate factors associated with these revisits.Methods: Data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS), 2010–2018. Adult ED revisits within 72 hours of a previous discharge were identified using a mark on the Patient Record Form. High-risk revisits were defined as revisits with serious adverse outcomes, including intensive care unit admissions, emergency surgery, cardiac catheterization, or cardiopulmonary resuscitation (CPR) during the return visit. Analyses used descriptive statistics and multivariable logistic regression accounting for NHAMCS's complex survey design.Results: Over the 9-year study period, there were an estimated 37,700,000 revisits, and the proportion of revisits in the entire ED population decreased slightly from 5.1% in 2010 to 4.5% in 2018 (P for trend = 0.02). By contrast, there were an estimated 827,000 high-risk ED revisits, and the proportion of high-risk revisits in the entire ED population remained stable at approximately 0.1%. The mean age of these high-risk revisit patients was 57 years, and 43% were men. Approximately 6% of the patients were intubated, and 13% received CPR. Most of them were hospitalized, and 2% died in the ED. Multivariable analysis showed older age (65+ years), Hispanic ethnicity, daytime visits, and arrival by ambulance during the revisit were independent predictors of high-risk revisits.Conclusions: High-risk revisits accounted for a relatively small fraction (0.1%) of the ED visits. Over the time period of NHAMCS survey between 2010-2018, this fraction remained stable. We identified factors during the return visit that could be used to label high-risk revisits for timely intervention.

The aim of this retrospective study was to identify clinical predictors of early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). A total of 670 high-risk PCa patients treated with CIRT and ADT were included in the study. Early BCR was defined as recurrence occurring during adjuvant ADT after CIRT or within 2 years after completion of ADT. Univariate and multivariate analyses were performed to identify clinical predictors of early BCR. Patients were also classified according to the Systemic Therapy in Advancing or Metastatic Prostate cancer (STAMPEDE) PCa classification. Early BCR was observed in 5.4% of the patients. Multivariate analysis identified clinical T3b stage and ≥75% positive biopsy cores as clinical predictors of early BCR after CIRT and ADT. The STAMPEDE PCa classification was also significantly associated with early BCR based on univariate analysis. These predictors can help clinicians identify patients who are at risk of early BCR. In the future, combination therapy of ADT with abiraterone may be an option for high-risk PCa patients who are at risk of early BCR, based on the results of the STAMPEDE study.

Abstract Background Outcomes for patients with relapsed acute lymphoblastic leukemia (ALL) are poor and there is a need for novel therapies to improve outcomes. Targeted inhibition of WEE1 with small-molecule inhibitor adavosertib (AZD1775) has emerged as a therapeutic strategy to sensitize cancer cells to DNA-damaging chemotherapeutics, particularly in the context of TP53-mutated tumors. However, WEE1 inhibition as a potential therapeutic strategy for patients with high-risk and relapsed ALL, including those with TP53 mutations, has not been definitively evaluated. Methods Anti-leukemic effects of adavosertib were investigated using a relapsed TP53 isogenic cell model system, primary patient, and patient-derived ALL samples (n = 27) in an ex vivo co-culture model system with bone marrow-derived mesenchymal stem cells. Combination effects with drugs currently used for relapsed ALL were quantified by Excess over Bliss analyses. Investigations for alterations of cell cycle and apoptosis as well as related proteins were examined by flow cytometry and Western blot, respectively. Results Our study demonstrates the potent anti-leukemic activity of the clinically advanced WEE1 inhibitor adavosertib in a large majority (n = 18/27) of high-risk and relapsed ALL specimens at lower than clinically attainable concentrations, independent of TP53 mutation status. We show that treatment with adavosertib results in S-phase disruption even in the absence of DNA-damaging agents and that premature mitotic entry is not a prerequisite for its anti-leukemic effects. We further demonstrate that WEE1 inhibition additively and synergistically enhances the anti-leukemic effects of multiple conventional chemotherapeutics used in the relapsed ALL treatment setting. Particularly, we demonstrate the highly synergistic and cytotoxic combination of adavosertib with the nucleoside analog cytarabine and provide mechanistic insights into the combinational activity, showing preferential engagement of apoptotic cell death over cell cycle arrest. Our findings strongly support in vivo interrogation of adavosertib with cytarabine in xenograft models of relapsed and high-risk ALL. Conclusions Together, our data emphasize the functional importance of WEE1 in relapsed ALL cells and show WEE1 as a promising p53-independent therapeutic target for the improved treatment of high-risk and relapsed ALL.

Abstract Introduction The objective of this systematic review is to identify tuberculosis (TB) high-risk among the general population globally. The review was conducted using the following steps: elaboration of the research question, search for relevant publications, selection of studies found, data extraction, analysis, and evidence synthesis. Methods The studies included were those published in English, from original research, presented findings relevant to tuberculosis high-risk across the globe, published between 2017 and 2023, and were based on geospatial analysis of TB. Two reviewers independently selected the articles and were blinded to each other`s comments. The resultant disagreement was resolved by a third blinded reviewer. For bibliographic search, controlled and free vocabularies that address the question to be investigated were used. The searches were carried out on PubMed, LILACS, EMBASE, Scopus, and Web of Science. and Google Scholar. Results A total of 79 published articles with a 40-year study period between 1982 and 2022 were evaluated. Based on the 79 studies, more than 40% of all countries that have carried out geospatial analysis of TB were from Asia, followed by South America with 23%, Africa had about 15%, and others with 2% and 1%. Various maps were used in the various studies and the most used is the thematic map (32%), rate map (26%), map of temporal tendency (20%), and others like the kernel density map (6%). The characteristics of the high-risk and the factors that affect the hotspot’s location are evident through studies related to poor socioeconomic conditions constituting (39%), followed by high population density (17%), climate-related clustering (15%), high-risk spread to neighbouring cities (13%), unstable and non-random cluster (11%). Conclusion There exist specific high-risk for TB which are areas that are related to low socioeconomic conditions and spectacular weather conditions, these areas when well-known will be easy targets for intervention by policymakers. We recommend that more studies making use of spatial, temporal, and spatiotemporal analysis be carried out to point out territories and populations that are vulnerable to TB.

AIM: To investigate whether the two-step strategy [conjunctival flap covering surgery (CFCS) combined with secondary deep anterior lamellar keratoplasty (DALK)] is effective for patients with high-risk fungal keratitis (FK). METHODS: In this noncomparative, retrospective case series, 10 subjects (6 males, 4 females) with a mean age of 56.5±7.1 (range 47-72)y with high-risk FK undergone the two-step strategy were included. Reported outcome measures were healing of the corneal ulcer, recurrence of FK, reject reaction, improvement in best corrected visual acuity (BCVA) and relevant complications. RESULTS: The average diameter of corneal infiltrates was 7.50±0.39 mm, ranging from 6.94 to 8.13 mm. The mean depth of corneal infiltrates was 422.4±77.1 μm, ranging from 350 to 535 μm. The mean corneal thickness was 597.4±117.3 μm, ranging from 458 to 851 μm. Hypopyon and endothelial plaques were presented in all patients. The period between the two steps was 3.65±0.9 (ranging from 3 to 5)mo. The graft diameter was 7.75±0.39 mm. At the last follow-up (average 9.25±3.39, ranging from 5.5 to 17mo), no fungal recurrence or graft rejection appeared, and all patients showed improvement of BCVA. One patient suffered from liver function impairment due to oral voriconazole for 4wk and recovered spontaneously after 1wk of drug withdrawal. CONCLUSION: The two-step strategy is safe and effective in the treatment of high-risk FK by transforming intentional therapeutic penetrating keratoplasty during acute infection to later optical DALK. It is a practical strategy, especially in areas lacking fresh donor corneas and eye bank services.

We evaluated repetitive behavior with objects in infants at risk for autism spectrum disorder (ASD) from 9 to 36 months of age, and associations between early repetitive behavior and social engagement. Infant siblings of children with ASD (high-risk) or typical development (low-risk) were administered a task eliciting repetitive object use at 9, 12, 15, 18, 24, and 36 months of age. Infants (n = 147) were classified into 1 of 3 outcome groups at 36 months: Low-Risk Non-ASD (n = 58), High-Risk Non-ASD (n = 72), and ASD (n = 17). Behavior was coded from video for frequencies of unusual visual inspection, spinning, and rotating behaviors. Differences in unusual visual inspection were most prominent, consistent, and present earliest: At 9 months, the ASD group engaged in this behavior more frequently than both other groups, persisting through 36 months. Differences in frequencies of spinning and rotating were later-appearing, more time-limited, and/or related to familial ASD risk rather than ultimate diagnosis. Sensitivity and specificity estimates for the presence of unusual visual inspection at 9 months of age were in the moderate range (.60 and .68, respectively) for ASD versus Low-Risk Non-ASD comparisons, generally increasing over time. Unusual visual inspection at 9 months predicted 12-month social behavior controlling for 9-month social behavior, but not vice versa, with no evidence of moderation by ASD diagnosis. In summary, unusual visual inspection of objects is present and stable by 9 months of age in infants developing ASD and predicts reduced social engagement three-months later. Close monitoring of this behavior may aid early detection. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Abstract Background Challenges in recruiting appropriately trained obstetricians and gynaecologists have been identified across the world. Given well documented staff shortages within obstetrics and gynaecology in Ireland, it is increasingly important to understand the factors which influence medical students to choose or reject a career in the speciality. The aim of this study was to ascertain the perceptions of final year graduate entry medical students of obstetrics and gynaecology, including the factors which may influence a student’s decision to pursue in a career in the speciality. Methods Paper-based surveys of graduate entry medical students (n = 146) were conducted at the beginning and end of a six week rotation in obstetrics and gynaecology in Ireland. Responses to the surveys pre- and post-rotation were matched and changes in career choices, merits and demerits over time were analysed. All analysis was conducted using SPSS for Windows version 25. Results The responses of 72 students to both questionnaires could be matched (response rate of 49.3%). No male students expressed an interest in obstetrics, gynaecology or both as a first choice of career in the pre rotation survey. Obstetrics as a first choice of career increased from 6.9% pre rotation to 19.4% post rotation (p = 0.04) and this increase was seen in male and female students. Gynaecology as a first choice increased slightly from 1.4 to 4.2% (p = 0.50) and the dual speciality increased from 6.9 to 13.9% (p = 0.23). Students identified many merits of obstetrics pre-rotation with more than 60% identifying it as exciting, interesting fulfilling and challenging. However, incompatibility with family life was cited as a demerit by 72% of respondents and 68.1% identified fear of litigation as a demerit. Participants were less positive overall about the merits of a career in gynaecology with less than 40% viewing it as exciting, fulfilling, and varied. Conclusions While respondents were positive about the merits of a career in obstetrics and gynecology, concerns remain about work-life balance, career opportunities, and the high-risk nature of the specialty. These concerns should be addressed by the profession and policy makers if they wish to attract sufficient numbers to address anticipated need in the coming years. Gender differences in speciality choice were also evident. If males are to be recruited into obstetrics and gynaecology, consideration should be given to the positive impact of internship.

Abstract Background In a parallel randomized controlled trial the effectiveness of the family- and group-based cognitive-behavioural “Gug-Auf” intervention in preventing depression in children of depressed parents was evaluated. We hypothesized that the intervention would be associated with reduced incidence of depression at 15 months as well as with reduced symptom severity at 6, 9, and 15 months. We also explored the role of a number of mediators and moderators. Methods Families were included if a parent (n = 100, mean age = 46.06, 61% female) had experienced depression and children (n = 135, aged 8–17 years, 53% female) had no mental illness. Families (91.5% German) were randomly allocated (50:50 block-wise; stratified by child age and parental depression) to the 12-session “GuG-Auf” intervention or no intervention. Outcomes were assessed (on an intention-to-treat basis) at 0-(T1), 6-(T2), 9-(T3) and 15-months (T4) after baseline. Primary outcome (onset of depression; T4) was assessed with standardized (blinded) clinical interviews. Secondary (unblinded) outcome was risk of depression (at T2-T4) indicated by self- and parent-reported symptoms of internalizing, externalizing and depressive disorder. Potential mediators were emotion regulation, attributional style, knowledge of depression and parenting style. Potential moderators were parental depression severity and negative life events. Results None of the children who received the intervention developed depression, whereas two of those in the control group did. The intervention significantly reduced depression risk (indicated by severity of self-reported internalizing symptoms) at T3 (p = .027, d = -0.45) and T4 (p = .035, d = -0.44). Both groups showed reduced depressive symptoms (p = .029, d = -0.44). Cognitive problem-solving and negative parenting emerged as mediators. There was no evidence that the intervention was associated with parent-reported internalizing symptoms or externalizing symptoms. No adverse events were observed. Conclusions Children of parents with depression showed an increase in self-reported (but not parent-reported) internalizing symptoms over time. This increase was not present in children who received the GuG-Auf intervention. The intervention was not associated with changes in externalizing symptoms. Conclusions regarding prevention of the onset of depression were not possible. Despite some limitations in the generalizability, these findings contribute to reducing the burden of youth depression. Registration The trial was registered on 16/04/2014 at ClinicalTrials.gov ( NCT02115880 ) and study protocol published in BMC Psychiatry ( https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-014-0263-2 ).

Objective To compare the efficacy of common clinical interventions in the treatment of cervical high-risk (HR) HPV infection based on Bayesian network meta-analysis. Methods Randomized controlled trials (RCTs) about common clinical interventions for cervical HR-HPV infection were searched in PubMed, Web of Science, Embase, The Cochrane Library, CBM, CNKI, Wanfang Data, and VIP databases from inception to July 31, 2021 using specific inclusion and exclusion criteria. The quality of the included studies was evaluated in accordance with the Cochrane systematic review manual. Meta-analysis was performed with Stata16 and RevMan5.3 software. Results Seventy-three RCTs were included, involving 3642 patients and eight treatment methods. Network meta-analysis showed that in the three months after treatment, the negative conversion rate was in the order: PTL > anti-HPV BPD > ALA-PDT > Nr-CWS > BFKS > CSJZS > rhIFNα-2b > FUO. In the six months after treatment, the negative conversion rate was in the order: Nr-CWS > ALA-PDT > PTL > anti-HPV BPD > BFKS > rhIFNα-2b > FUO > CSJZS. In the nine months after treatment, the negative conversion rate was in the order: PTL > ALA-PDT > BFKS > anti-HPV BPD > rhIFNα-2b > FUO. IN the 12 months after treatment, the negative conversion rate was in the order: Nr-CWS > ALA-PDT > anti-HPV BPD > PTL > BFKS > rhIFNα-2b > FUO > CSJZS. Conclusion In terms of HPV negative conversion rate, Nr-CWS and PTL are more effective and currently ideal compared with the other treatments. Owing to the quality of the evidence, the above conclusions must be confirmed by future high-quality studies.

Abstract Background EAU guidelines strongly recommend kidney sparing surgery (KSS) as the primary treatment option for the low-risk UTUC patients. While there are few reports involving the KSS treated for the high-risk counterparts, especially the ureteral resection. Objective To evaluate the effectiveness and safety of the segmental ureterectomy (SU) for the patients with high-risk ureteral carcinoma. Materials and methods We included 20 patients from May 2017 to December 2021 who underwent segmental ureterectomy (SU) in Henan Provincial People’s Hospital. The overall survival (OS) and progression free survival (PFS) were evaluated. Besides, the ECOG scores and postoperative complications were also included. Results As of December 2022, the mean OS was 62.1months (95%CI:55.6-68.6months) and the mean PFS was 45.0months (95%CI:35.9-54.1months). The median OS and median PFS were not reached. The 3-year OS rate was 70% and the 3-year PFS rate was 50%. The percentage of Clavien I and II complications was 15%. Conclusion For the selected patients with high-risk ureteral carcinoma, the efficacy and safety of segmental ureterectomy were satisfactory. But we still need to conduct prospective or randomized study to validate the value of SU in patients with high-risk ureteral carcinoma.