International Society Research Articles

Rivaroxaban for 18 Months Versus 6 Months in Patients With Cancer and Acute Low-Risk Pulmonary Embolism: An Open-Label, Multicenter, Randomized Clinical Trial (ONCO PE Trial)

Background: The optimal duration of anticoagulation therapy for patients with cancer and acute low-risk pulmonary embolism (PE) is clinically relevant, but evidence is lacking. Prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. Methods: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 32 institutions in Japan, we randomly assigned patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, in a 1:1 ratio, to receive either an 18-month or a 6-month rivaroxaban treatment. The primary end point was recurrent venous thromboembolism (VTE) at 18 months. The major secondary end point was major bleeding at 18 months according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that an 18-month treatment was superior to a 6-month treatment in terms of the primary end point. Results: From February 2021 to March 2023, 179 patients were randomized, and after the exclusion of one patient who withdrew consent, 178 were included in the intention-to-treat population: 89 patients in the 18-month rivaroxaban group and 89 in the 6-month rivaroxaban group. The mean age was 65.7 years; 47% of the patients were men, and 12% had symptoms of PE at baseline. The primary end point of recurrent VTE occurred in 5 of the 89 patients (5.6%) in the 18-month rivaroxaban group and in 17 of the 89 (19.1%) in the 6-month rivaroxaban group (odds ratio, 0.25 [95% CI, 0.09–0.72]; P =0.01). Among 22 recurrent VTE, 5 patients presented with a symptomatic recurrent VTE; recurrent PE occurred in 11 patients, including 2 with main and 4 with lobar PEs; and recurrent deep vein thrombosis was seen in 11 patients, including 3 with proximal deep vein thromboses. The major secondary end point of major bleeding occurred in 7 of the 89 patients (7.8 %) in the 18-month rivaroxaban group and in 5 of the 89 patients (5.6%) in the 6-month rivaroxaban group (odds ratio, 1.43 [95% CI, 0.44–4.70]; P =0.55). Conclusions: In patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, the 18-month rivaroxaban treatment was superior to the 6-month rivaroxaban treatment with respect to recurrent VTE events.

Insights From ISASS Webinar Series on Current and Emerging Techniques in Endoscopic Spine Surgery | Part 3: A Polytomous Rasch Analysis on Surgeons' Endorsement of Multiportal Access, Treatment of Lumbar Facet Cyst, Grade I Spondylolisthesis, and Interbody Fusion.

The International Society for the Advancement of Spine Surgery hosted the third in a series of webinars focused on innovative endoscopic spine surgery techniques. This session aimed to discuss and evaluate advanced treatments for lumbar spinal stenosis and related conditions utilizing multiportal endoscopic approaches; articulating instruments; unilateral biportal endoscopy; transforaminal techniques for facet cysts, herniated disc, and spinal stenosis; as well as percutaneous endoscopic lumbar interbody fusion (PELIF). To analyze the level of surgeon endorsement for the presented endoscopic spine surgery techniques before and after the webinar, utilizing polytomous Rasch analysis, and to evaluate the potential for these insights to inform clinical guideline recommendations. An online survey was administered to 868 surgeons during a sponsored webinar hosted by the International Society for the Advancement of Spine Surgery. The survey used Likert-scale ratings to evaluate 5 main topics and additional surgical experiences and was distributed before and after the webinar. Survey responses were analyzed using descriptive statistics and Polytomous Rasch analysis to evaluate shifts in acceptance and perception. Of the 793 surgeons who attended the webinar, 229 accessed the prewebinar survey, 154 began it, and 119 completed it, yielding a completion rate of 77.3%. The respondents included 52.9% orthopedic surgeons, 37.0% neurosurgeons, 1.7% fellows, 0.8% residents, and 0.8% medical students. In the postwebinar phase, engagement remained high, with 298 accessing the survey, 169 starting it, and 128 completing it, resulting in a 75.7% completion rate. The postwebinar participant demographics closely resembled the initial distribution, consisting of 53.1% orthopedic surgeons, 35.9% neurosurgeons, 6.2% residents, 3.1% fellows, and 1.6% medical students. The confidence in various endoscopic techniques saw notable changes, particularly for procedures involving transforaminal lateral canal decompression for stenosis, herniated disc, and low-grade spondylolisthesis. Unilateral biportal endoscopy facet joint decompression and PELIF saw an increase in high-level endorsements after the webinar. Polytomous Rasch analysis provided insights into procedural techniques. The study showed consensus on the effectiveness of percutaneous endoscopic decompression of low-grade spondylolisthesis, reflecting evolving surgeon preferences and consensus on best practices. Infit and outfit statistics from the Rasch analysis suggested a good fit between the survey responses and the Rasch model both before and after the webinar, indicating minimal data distortion due to bias except for transforaminal decompression for posterolateral and central herniated nucleus pulposus. Differential item functioning analysis showed no significant bias in item responses between orthopedic surgeons and neurosurgeons in the prewebinar survey but identified potential bias for 1 item postwebinar in PELIF and articulating instruments. The webinar influenced surgeon perceptions and endorsements of advanced endoscopic techniques, substantially impacting professional practice. Continued use of Rasch analysis in evaluating educational interventions offered a nuanced understanding of changes in surgical practice toward more complex and controversial issues such as central and migrated herniated nucleus pulposus, facet cyst, low-grade spondylolisthesis, and fusion while potentially guiding future clinical guidelines and training programs to align with evolving endoscopic techniques. Assessing surgeon confidence and acceptance of endoscopic spinal surgeries using polytomous Rasch analysis. Level 2 (inferential) and 3 (observational) evidence because Rasch analysis provides statistical validation of instruments rather than direct clinical outcomes.

Key Takeaways From the ISASS Webinar Series on Current and Emerging Techniques in Endoscopic Spine Surgery | Part 2: Polytomous Rasch Analysis of Learning Curve and Surgeon Endorsement of Biportal, Interlaminar, and Transforaminal Endoscopic Stenosis Decompression, Discectomy, and Laminectomy in Combination With Interspinous Process Spacers.

The International Society for the Advancement of Spine Surgery hosted the second of a series of 4 webinars on endoscopic spine surgery techniques. The second webinar focused on the application of unilateral biportal endoscopy for discectomy and laminectomy in combination with interbody fusion and interspinous process spacers. This series was intended to identify current trends with contemporary modern endoscopic spine surgery techniques. To analyze the level of surgeon endorsement for the presented endoscopic spine surgery techniques before and after the webinar utilizing polytomous Rasch analysis, as well as to evaluate the potential for these insights to inform clinical guideline recommendations. A survey was available to 667 potential respondents during the Zoom webinar, collecting data on surgeon endorsements using a Likert scale. The polytomous Rasch model was employed to analyze responses while considering the complexity of decisions against surgeon expertise, developing a logarithmic measurement scale, allowing objective statistical analysis of categorical variables, highlighting incongruent or out of order items vs congruent and in order items, and driving improvement in clinical guidelines. Of the 667 surgeons who participated in the webinar, 224 accessed, 122 started, and 61 completed the prewebinar survey, achieving a 50.0% completion rate. Respondents comprised primarily orthopedic surgeons (70.5%) and neurosurgeons (24.6%), with fellows and medical students each making up 1.6%. These surgeons estimated that mastering the learning curve of endoscopic spine surgery required an average of 18.08 cases corroborated by postwebinar responses averaging 15.78 cases. Descriptive statistics revealed an acknowledgment of a learning curve in mastering endoscopic spine surgery, with a slight increase in recognition postwebinar (81.8% up from 80.3%). The data underscored the importance of cadaver courses and high-volume surgical practice before the webinar and highlighted the value of mentorship afterward, indicating a preference shift toward more interactive learning. The confidence in various endoscopic techniques saw notable changes, particularly for procedures involving interlaminar lateral canal decompression and the combined use of transforaminal endoscopic decompression with interspinous process spacers, which saw an increase in high-level endorsements postwebinar. Polytomous Rasch analysis provided insights into training methods and procedural techniques, with mentorship and cadaver courses emerging as key elements for mastering the learning curve. The analysis also highlighted a general consensus on the effectiveness of percutaneous endoscopic interlaminar decompression for lateral canal stenosis, reflecting evolving surgeon preferences and consensus on best practices. Infit and outfit statistics from the Rasch analysis suggested a good fit between the survey responses and the Rasch model both before and after the webinar, indicating minimal data distortion due to bias. Differential item functioning analysis showed no significant bias in item responses between orthopedic surgeons and neurosurgeons in the prewebinar survey, but it identified potential bias for one item postwebinar-unilateral biportal endoscopic laminectomy for central stenosis. This webinar highlighted the importance of hands-on training methods such as cadaver courses and mentorship in mastering the complex spinal endoscopy procedures. The application of polytomous Rasch analysis provided a detailed understanding of surgeons' current preferences and perceptions, as well as the evolving consensus on best practices in endoscopic spine surgery, displaying wide acceptance of the percutaneous interlaminar endoscopic decompression for lateral canal stenosis decompression and a growing interest in integrating endoscopic techniques for more comprehensive spinal care, including wide decompression and spinal stabilization. Assessing surgeon confidence and acceptance of endoscopic spinal surgeries using polytomous Rasch analysis. Level 2 (inferential) and 3 (observational) evidence because Rasch analysis provides statistical validation of instruments rather than direct clinical outcomes.

Status Hierarchies and Stigma Shifting in International Relations

Abstract How do states as social actors cope with stigma-induced status anxiety? I propose the concept of “stigma shifting” as a way in which status-anxious states overcompensate for their stigma-induced inferiority and reaffirm their place in the world: by seeking identification with higher-status states and differentiation from lower-status states. In identifying with the desired group of states, stigmatized states engage in approval-seeking behavior and reaffirm their in-group status in areas where they feel discredited. In differentiating themselves from the undesired group, stigmatized states engage in distinction-seeking behavior, claiming their superiority over this “lesser” group in areas that gave rise to their status anxiety in the first place. Stigma shifting, in other words, allows a stigmatized state to take the role of a stigmatizer. To demonstrate the concept's depth and analytical utility, I draw on the case of East Asia in three disparate issue areas: colonial redress, nuclear disaster, and international order making. Japan, stigmatized in all three areas, has reaffirmed its status by shifting the stigma onto its significant but “lesser” others: China and Korea. Ultimately, stigma shifting solidifies status hierarchies in the world—not just the hierarchy as represented by the “Western” dominance of international society but also the regional hierarchies of the non-Western world.

Using Time in Tight Glucose Range as a Health-Promoting Strategy in Preschoolers With Type 1 Diabetes.

Children who develop diabetes in their first years of life risk being exposed to many decades of hyperglycemia, hence having a high risk of early complications and premature death. An additional age-dependent risk is that dysglycemia, especially hyperglycemia, negatively affects the developing brain. In evaluating the outcome of insulin treatment at an individual and group level, cutoff thresholds for glucose values are needed. Time in tight range (TITR) was defined as a measurement of time spent in a state of normoglycemia. The International Society of Pediatric and Adolescent Diabetes recommended that for preschoolers with type 1 diabetes (T1D), either >70% of time with glucose in range 70-180 mg/dL (3.9-10 mmol/L) or >50% of time in a tighter range 70-140 mg/dL (TITR) can be used as continuous glucose monitoring targets. In Sweden, over the past two decades, pediatric diabetes teams set glycemic targets to 70-140 mg/dL (3.9-7.8 mmol/L). Swedish registry data show that >50% of children <7 years old have >50% TITR. The purpose of this review is to share and discuss international knowledge and experiences of working with TITR as a health-promoting strategy in preschoolers with T1D on a structural and individual level. We conclude that as insulin treatment improves, a reasonable goal is to strive for as much time in a state of normoglycemia as possible, and this can easily be explained to families of children with diabetes. For children with access to an experienced health care team and diabetes technologies a currently realistic target can be at least half of the time in normoglycemic range, i.e., TITR >50%.

Enhancing bone metastasis prediction in prostate cancer using quantitative mpMRI features, ISUP grade and PSA density: a machine learning approach.

Bone metastasis is a critical complication in prostate cancer, significantly impacting patient prognosis and quality of life. This study aims to enhance bone metastasis prediction using machine learning (ML) techniques by integrating dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion features, International Society of Urological Pathology (ISUP) grade, and prostate-specific antigen (PSA) density. A retrospective analysis was conducted on 122 patients with histopathologically confirmed prostate cancer who underwent multiparametric prostate magnetic resonance imaging (mpMRI). Quantitative mpMRI features, PSA density, and ISUP grades were extracted and normalized. The dataset was balanced using oversampling and divided into training (70%) and test (30%) sets. Various ML models were developed and evaluated using area under the curve (AUC) metrics. Bone metastases were present in 26 patients (21.3%) at diagnosis. IAUGC and MaxSlope showed a statistically significant association with bone metastasis (p = 0.035, p = 0.050 respectively). The optimal PSA density cut-off value of 0.24 yielded a sensitivity of 0.88, specificity of 0.60, and AUC of 0.77. Machine learning models were developed using the dataset created with IAUGC, MaxSlope, ISUP grade, and PSA density values. Among the ML models, XGBoost demonstrated superior performance with validation and test AUCs of 91.5% and 92.6%, respectively, along with high precision (93.3%) and recall (93.1%). Integrating quantitative mpMRI features, ISUP grade, and PSA density through machine learning algorithms, particularly XGBoost, significantly improves the accuracy of bone metastasis prediction in prostate cancer patients. This approach can potentially reduce the need for additional imaging modalities and associated radiation exposure.

Key Takeaways From ISASS Webinar Series on Endoscopic Spine Surgery Techniques | Part 4: Advancing the Curve on Surgeons' Experience With Complex Lumbar Revision Scenarios, Grades 1 to 3 Spondylolytic Spondylolisthesis, Cervical Foraminotomy, and Cervical Spondylotic Myelopathy.

The fourth webinar in a 4-part series hosted by the International Society for the Advancement of Spine Surgery explored contemporary endoscopic spine surgery techniques. This session covered complex revision strategies, endoscopic management of grades 1-3 spondylolytic spondylolisthesis, cervical foraminotomy, and decompression techniques for cervical spondylotic myelopathy (CSM). The aim was to assess surgeon endorsement of the discussed endoscopic spine surgery techniques both before and after the webinar using polytomous Rasch analysis. Additionally, the analysis sought to determine how these insights might shape clinical guideline recommendations. Before the webinar, which was attended by 868 potential participants, a survey was distributed to collect data on the level of support for various techniques using a Likert scale. The polytomous Rasch model analyzed these responses by evaluating decision complexity relative to surgeon expertise. This approach helped develop a logarithmic scale to objectively analyze categorical responses, distinguish between congruent and incongruent items, and contribute to the enhancement of clinical guidelines. Of the 868 surgeons, 263 accessed, 150 started, and 118 completed the prewebinar survey, with a completion rate of 78.7%. The participants were mainly orthopedic surgeons (59.3%) and neurosurgeons (34.7%) but also included residents (2.5%), fellows (1.7%), and interventional radiologists (1.7%). In the postwebinar phase, 298 participants accessed the survey, 169 started it, and 128 completed it, achieving a 75.7% completion rate. The demographics of postwebinar participants closely mirrored the initial group: 66.4% orthopedic surgeons, 23.4% neurosurgeons, 3.6% residents, 2.9% fellows, 0.7% medical students, and 2.9% interventional radiologists. The Rasch analysis confirmed high surgeon confidence for the posterior cervical foraminotomy and endoscopic treatment of spondylolytic spondylolisthesis grades 1 to 3 and posterior endoscopic decompression for CSM. Both pre- and postwebinar responses showed a good fit to the Rasch model for these endoscopic techniques, indicating minimal bias, supported by differential item functioning analysis. The application of the endoscopic surgery platform for procedures such as lumbar revision surgery for adjacent segment disease or failed interbody fusion cages and posterior decompression of CSM saw little shift in endorsement, as evidenced both in descriptive and the logarithmically transformed Rasch statistics. This webinar highlighted the evolving consensus on best practices in endoscopic spine surgery, displaying wide acceptance of endoscopic debridement of spondylolytic spondylolisthesis, cervical foraminotomy for herniated disc and bony stenosis, and posterior endoscopic decompression for CSM. Assessing surgeon confidence and acceptance of endoscopic spinal surgeries using polytomous Rasch analysis. Level 2 (inferential) and 3 (observational) evidence because Rasch analysis provides statistical validation of instruments rather than direct clinical outcomes.

Insights on High-Value Procedures From the ISASS 4-Part Webinar Series on Current and Emerging Techniques in Endoscopic Spine Surgery Based on Surgeon Experience.

The authors conducted a comprehensive review and integration of insights from 4 webinars hosted by the International Society for the Advancement of Spine Surgery (ISASS) to arrive at recommendations for best clinical practices for guideline development for endoscopic spine surgery. This perspective article discusses the limitations of traditional surgical trials and amalgamates surgeons' experience and research on various cutting-edge techniques. Data were extracted from surveys conducted during each webinar session involving 3639 surgeons globally. The polytomous Rasch model was employed to analyze responses, ensuring a robust statistical assessment of surgeon endorsements and educational impacts and focusing on operative nuances and experience-based outcomes. Bias detection was performed using the differential item functioning test. The ISASS webinars provided a dynamic platform for discussing advances in endoscopic spine surgery, identifying a range of high-value procedures from basic discectomies to complex lumbar interbody fusions. Each high-value endoscopic spine surgery was highlighted in separate peer-reviewed publications, which form the basis for this summary document that synthesizes key takeaways from these webinars. High-value clinical applications of endoscopic spine surgery, primarily defined as higher-intensity endorsement transformation from the pre- to postwebinar survey with a shift to higher mean logit locations of test items both with unbiased and orderly threshold progression, were: (a) Percutaneous interlaminar endoscopic decompression for lateral canal stenosis, (b) transforaminal debridement of low-grade degenerative spondylolisthesis, (c) transforaminal full-endoscopic interbody fusion for hard disc herniation, (d) endoscopic standalone lumbar interbody fusion, (e) endoscopic debridement of spondylolytic spondylolisthesis, and (f) posterior cervical foraminotomy for herniated disc and bony stenosis. The ISASS webinar series has significantly impacted surgeons' education and contributed to the identification of high-value endoscopic spine surgery practices that may serve as a cornerstone for surgeon training standards, policy, and guidelines development. Ongoing research on technological advancements and expansions of clinical indications combined with systematic review is expected to refine the recommendations on high-value endoscopic spinal surgeries recommended for enhanced reimbursement. Assessing surgeon confidence and acceptance of endoscopic spinal surgeries using polytomous Rasch analysis. Level 2 (inferential) and 3 (observational) evidence because Rasch analysis provides statistical validation of instruments rather than direct clinical outcomes.

Identification and outcomes of acute kidney disease in patients presenting in Bolivia, Brazil, South Africa, and Nepal.

The International Society of Nephrology proposes an acute kidney disease (AKD) management strategy that includes a risk score to aid AKD identification in low- and low-middle-income countries (LLMICs). We investigated the performance of the risk score and determined kidney and patient outcomes from AKD at multiple LLMIC sites. Adult patients presenting to healthcare facilities in Bolivia, Brazil, South Africa, and Nepal were screened using a symptom-based risk score and clinical judgment. Those at AKD risk underwent serum creatinine testing, predominantly with a point-of-care (POC) device. Clinical data were collected prospectively between September 2018 and November 2020. We analyzed risk score performance and determined AKD outcomes at discharge and over follow-up of 90 days. A total of 4,311 patients were at increased risk of AKD, and 2,922 (67.8%) had AKD confirmed. AKD prevalence was 80.2% in patients enrolled based on the risk score and 32.5% when enrolled on clinical judgment alone (p < 0.0001). The area under the receiver operating characteristic curve was 0.73 for the risk score to detect AKD. Death during admission occurred in 84 (2.9%) patients with AKD and 3 (0.2%) patients without kidney disease (p < 0.0001). Death after discharge occurred in 206 (9.7%) AKD patients, and 1865 AKD patients underwent reassessment of kidney function after discharge; 902 (48.4%) patients had persistent kidney disease including 740 (39.7%) patients reclassified with de novo or previously undiagnosed chronic kidney disease (CKD). The study was pragmatically designed to assess outcomes as part of routine healthcare, and there was heterogeneity in clinical practice and outcomes between sites, in addition to selection bias during cohort identification. The use of a risk score can aid AKD identification in LLMICs. High rates of persistent kidney disease and mortality after discharge highlight the importance of AKD follow-up in low-resource settings.

EasyFlow: An open-source, user-friendly cytometry analyzer with graphic user interface (GUI).

Flow cytometry enables quantitative measurements of fluorescence in single cells. The technique was widely used for immunology to identify populations with different surface protein markers. More recently, the usage of flow cytometry has been extended to additional readouts, including intracellular proteins and fluorescent protein transgenes, and is widely utilized to study developmental biology, systems biology, microbiology, and many other fields. A common file format (FCS format, defined by the International Society for Advancement of Cytometry (ISAC)) has been universally adopted, facilitating data exchange between different machines. A diverse spectrum of software packages has been developed for the analysis of flow cytometry data. However, those are either 1) costly proprietary softwares, 2) open source packages with prerequisite installation of R or Python and sometimes require users to have experience in coding, or 3) online tools that are limiting for analysis of large data sets. Here, we present EasyFlow, an open-source flow cytometry analysis graphic user interface (GUI) based on Matlab or Python, that can be installed and run locally across platforms (Windows, MacOS, and Linux) without requiring previous coding knowledge. The Python version (EasyFlowQ) is also developed on a popular plotting framework (Matplotlib) and modern user interface toolkit (Qt), allowing more advanced users to customize and keep contributing to the software, as well as its tutorials. Overall, EasyFlow serves as a simple-to-use tool for inexperienced users with little coding experience to use locally, as well as a platform for advanced users to further customize for their own needs.

A framework for developing Generic Implant Safety Procedures (GISPs) for scanning patients with medical implants and devices in MRI.

UK guidelines for MR safety recommend that MRI departments refer to the implant manufacturer for advice regarding the MRI safety of scanning patients with an implantable medical device prior to scanning [1]. This process of assuring safety can be time consuming, leading to delays and potential cancellations of a patient's MRI. Furthermore, at times the implant cannot be identified, or the implant manufacturers cannot provide up to date MRI safety information. The purpose of generic implant safety procedures (GISPs) is to define a process for managing patients with certain types of implants where the risk from scanning is low. This process incorporates scope for an evidence-based risk-benefit decision to scan some groups of patients under locally-approved conditions, without seeking to identify the exact make and model of the implant and subsequent assurance of MR safety from the implant manufacturer. This publication provides best practice recommendations from a multi-professional working group for the development of these procedures. It is supported by The Institute of Physics and Engineering in Medicine, The Society of Radiographers, The Royal College of Radiologists, The British institute of Radiology, The British Association of MR Radiographers, The International Society of Magnetic Resonance in Medicine British and Irish Chapter and the NHS Scotland MRI Physics Group.

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research.

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross-cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.

Visualization of caudothalamic groove at expert fetal neurosonography.

To describe the sonographic features of the caudothalamic groove in the third trimester of pregnancy in a group of structurally normal fetuses and to report a small series of cases with abnormal appearance of the caudothalamic groove at antenatal cranial ultrasound. This was an observational study conducted at two fetal medicine referral units in Italy. A non-consecutive cohort of pregnant women with a singleton non-anomalous pregnancy were recruited prospectively and underwent three-dimensional (3D) ultrasound assessment of the fetal brain at 28-32 weeks' gestation. At offline analysis, the ultrasound volumes were adjusted in the multiplanar mode, according to a standardized methodology, until the caudothalamic groove was visible in the parasagittal plane. To evaluate interobserver agreement, two operators were asked independently to indicate if the caudothalamic groove was visible unilaterally or bilaterally on each volume and Cohen's kappa (κ) coefficient was calculated. The digital archives of the two centers were also searched retrospectively to retrieve cases with abnormal findings at the level of the caudothalamic groove on antenatal cranial ultrasound that were confirmed postnatally. A total of 180 non-consecutive cases were included. At offline analysis of the 3D ultrasound volumes, the caudothalamic groove was identified in the parasagittal plane by both operators at least unilaterally in 176 (97.8%) cases and bilaterally in 174 (96.7%) cases. The κ-coefficient for the agreement between the two independent operators in recognizing the caudothalamic groove was 0.89 and 0.83 for one and both hemispheres, respectively. The retrospective search of our archives yielded five cases with an abnormal appearance of the caudothalamic groove at antenatal cranial ultrasound, including two cases of hemorrhage and three cases of cyst. The caudothalamic groove is consistently seen in normal fetuses on multiplanar neurosonography in the third trimester, and abnormal findings in this region may be detected antenatally. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Expert Opinion for Defining a Severe Bleeding Phenotype to Guide Prophylaxis in Patients with Nonsevere Hemophilia.

Prophylaxis is the standard of care for patients with severe hemophilia, patients with moderate hemophilia, or those with another congenital bleeding disorder that is associated with a severe bleeding phenotype and/or a high risk of spontaneous life-threatening bleeding. Patients with nonsevere hemophilia (factor VIII [FVIII] ≥ 1%) may also have a bleeding phenotype that requires prophylaxis. To date, however, there are no clear criteria as to when prophylaxis is indicated in these patients. Also, the term "severe bleeding phenotype (SBPT)" is neither included in the definitions of the International Society on Thrombosis and Haemostasis (ISTH) nor specified in the World Federation of Hemophilia (WFH) guidelines. Based on our personal experience and available evidence, we propose the criteria we use to define an SBPT and when we consider offering prophylaxis in patients with nonsevere hemophilia. Our proposals can be the basis for discussions in the community about the assessment of SBPT and the initiation of prophylaxis in patients with nonsevere hemophilia without inhibitors.

Current status of ultrasound training in obstetrics and gynecology: a scoping literature review

IntroductionAs a widely accessible, cost-effective, and safe imaging tool, obstetric and gynecologic (OB/GYN) ultrasound (ULS) plays a vital role in diagnostics and patient care. With its growing relevance, the demand for comprehensive education in this field increases. The objective of this work was to outline the current state of OB/GYN ULS education.MethodsA scoping literature search was performed until May 2023 using the medical database PubMed according to PRISMA guidelines. Using specific keywords, relevant publications were filtered. Subsequently, abstracts were independently reviewed by two authors and the inclusion of each publication was assessed against pre-defined key search terms. Full-text versions of the included publications were scrutinized and pertinent information was extracted.ResultsIn this review, 126 articles from the literature search matched the inclusion criteria and were investigated. Our findings revealed a diverse range of course concepts and programs, a lot of them not meeting the expectations of trainees and international guidelines. OB/GYN ULS training primarily targets residents, yet opportunities for early exposure and continuing education are underexplored. International organizations, such as the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and the German Society for Ultrasound in Medicine (DEGUM) have proposed guidelines and curricula for standardized training. However, adoption remains varied. There is an emergent need to innovate teaching methods.ConclusionThere is consensus that standardizing OB/GYN ULS curricula could enhance training quality and streamline the creation of new programs, ultimately improving patient care. Further research is needed to define the most effective strategies for curriculum development and implementation.

Relationship between maltreatment and mental health in adolescents: A school-based study in Indonesia.

Maltreatment affects emotional development in adolescents and inhibits social adjustment. This study aimed to analyze the relationship between maltreatment and mental health among adolescents. A cross-sectional study was conducted on adolescents in the first and second grades of middle school (12-14 years old) and high school (15-17 years old) in eight cities and municipalities in the province, selected through several stages of simple random sampling (N = 1837). The International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tool for Children (ICAST-C) questionnaire for detecting maltreatment was translated, simplified, and validated by an expert based on a theoretical framework that involved pediatricians, public health, and medicolegal perspectives. The Strengths and Difficulties Questionnaire (SDQ) was used to assess emotional states. ICAST-C and SDQ scores were transformed to logit values using Rasch model analysis. Distribution frequency and linear regression were used for data analysis. The results indicated that 85.6% of adolescents aged 12-14 and 83% of those aged 15-17 experienced physical maltreatment, while 89.4% of the 12-14 age group and 82.9% of the 15-17 age group experienced psychological maltreatment. The emotional states of the two groups were 52.8% and 59.2%, respectively. There was a significant correlation between the experience of physical maltreatment and emotions among 12-14 (r1 = 0.148 (0.190-0.257)) and 15-17 years old (r1 = 0.047 (0.084-0.156)). There was a significant correlation between the experience of psychological maltreatment and emotions among 12-14 years old '(r2 = 0.191 (0.270-0.350)) and 15 to 17 years old (r2 = 0.097 (0.167-0.252)). In conclusion, physical and psychological maltreatment were correlated with mental health states among adolescent students in West Java, Indonesia.

Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis refractory to biologic therapy: 2-year clinical and radiographic results from the open-label extension of the SELECT-AXIS 2 study.

The efficacy and safety of upadacitinib in patients with ankylosing spondylitis (AS) and inadequate response/intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR) were evaluated through 1 year in the SELECT-AXIS 2 study. Here, we assess 2-year efficacy, safety, and imaging outcomes in SELECT-AXIS 2. Patients who received continuous upadacitinib, and those who switched from placebo to upadacitinib at week 14, could enter the open-label extension (OLE). Efficacy endpoints included Assessment of SpondyloArthritis international Society (ASAS) and Axial Spondyloarthritis Disease Activity Score (ASDAS) responses, and changes from baseline in measures of disease activity, back pain, function, and quality of life. Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). As observed (AO) and AO with non-responder imputation (AO-NRI) analyses were used for binary endpoints; AO with mixed-effects model for repeated measures (AO-MMRM) for continuous endpoints; and AO-analysis of covariance for mSASSS. Treatment-emergent adverse events (TEAEs) in patients receiving ≥ 1 upadacitinib dose through week 104 are presented as events (E)/100 patient-years (PY). Subgroup analyses were performed by prior tumor necrosis factor/interleukin-17 inhibitor exposure and bDMARD lack of efficacy/intolerance. Of 420 patients who entered the bDMARD-IR AS study, 409 entered the OLE, and 331 (continuous upadacitinib, n = 163; placebo to upadacitinib, n = 168) completed week 104. Improvements in efficacy measures were sustained through the OLE, with similar response rates between the continuous upadacitinib and placebo to upadacitinib groups at week 104. At week 104, 64.9% and 61.7% of patients, respectively, had achieved ASAS 40% response (AO-NRI). Mean changes from baseline were similar between the two groups at week 104 across measures (ASDAS: -2.1 and -2.0; total back pain: -4.9 and -4.6, respectively; AO-MMRM). Over 93.0% of patients showed no radiographic progression (mSASSS mean change from baseline < 2) at week 104. The overall TEAE rate was 165.2 E/100 PY, with low rates of major adverse cardiovascular and venous thromboembolic events (0.3 E/100 PY each). Upadacitinib efficacy, including very low rates of radiographic progression, was demonstrated through 104 weeks in treatment-refractory patients with active AS. Treatment was well tolerated, with no newly identified safety signals. NCT04169373.

Transabdominal sonographic sliding signs for preoperative prediction of dense intra-abdominal adhesions in women undergoing repeat Cesarean delivery.

To assess the accuracy and utility of transabdominal sonographic paraumbilical and suprapubic sliding signs in predicting intra-abdominal adhesions in women undergoing repeat Cesarean section (CS) and the association of repeat CS with short-term maternal and neonatal outcomes. This was a prospective observational study of pregnant women with a history of CS who were scheduled for third-trimester elective or emergency CS at a tertiary referral and teaching hospital between July 2021 and June 2022. In order to evaluate the role of transabdominal sonographic paraumbilical and suprapubic sliding signs in the prediction of intra-abdominal adhesions, participants underwent a high-resolution transabdominal ultrasound scan prior to repeat CS. Free cephalad and caudad gliding of the uterus under the abdominal wall during deep inhalation and exhalation in each area was considered a positive sliding sign, suggesting a low risk of intra-abdominal adhesions. The absence of such movement was considered a negative sliding sign, suggesting a high risk of intra-abdominal adhesions. The presence or absence of intra-abdominal adhesions was then confirmed during surgery by physicians who were blinded to the sonographic sliding-sign findings. The type of adhesion, structures involved, method of adhesiolysis, incision-to-delivery time, 1-min and 5-min Apgar scores, maternal and neonatal injury and other short-term complications were also reported. Of 419 women with a history of at least one previous CS who underwent repeat CS, the preoperative sonographic paraumbilical and suprapubic sliding signs were negative in 173 (41.3%) and 178 (42.5%) women, respectively. On repeat CS, 224 (53.5%) women had intra-abdominal adhesions, of which 165 (39.4%) had dense adhesions and 59 (14.1%) had only filmy adhesions. The sensitivity and specificity of a negative preoperative paraumbilical sliding sign in predicting the presence of dense intra-abdominal adhesions in women undergoing repeat CS were 94.6% (95% CI, 92.4-96.7%) and 93.3% (95% CI, 90.9-95.7%), respectively. A negative suprapubic sliding sign also showed high sensitivity (95.2% (95% CI, 93.1-97.2%)) and specificity (91.7% (95% CI, 89.1-94.4%)). Additionally, a negative sliding sign at both locations in the same patient had robust sensitivity (90.2% (95% CI, 87.3-93.0%)) and specificity (96.3% (95% CI, 94.5-98.1%)). We found that the risk of dense intra-abdominal adhesions increased with parity and the number of previous CS. Dense intra-abdominal adhesions were associated with increased incision-to-delivery time, higher risk of maternal bladder injury, intraoperative bleeding and postpartum hemorrhage. Dense intra-abdominal adhesions are common in women with a previous history of CS and are associated with delayed delivery of the neonate and increased risk of adverse maternal outcomes. The transabdominal sonographic paraumbilical and suprapubic sliding signs are robust methods for the accurate preoperative prediction of dense intra-abdominal adhesions in patients with a history of CS. As the techniques are easy to learn and perform, the sliding sign should be used more widely for triaging patients at high risk of dense intra-abdominal adhesions for appropriate preoperative planning. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

NCOG-13. ASSESSING CAREGIVER OUTCOMES OF PRIMARY BRAIN TUMOR PATIENTS: A SYSTEMATIC REVIEW OF THE LITERATURE

Abstract BACKGROUND Family caregivers in neuro-oncology are known to have high levels of unmet support needs. Intervention trials and effective support options are scarce. The Response Assessment in Neuro-Oncology (RANO-) Cares working group has been established to determine standards of caregiver outcomes (CO) research reporting in neuro-oncology. We present the current state of methodological quality of reporting on neuro-oncology caregiver outcomes in randomized controlled trials (RCTs). METHODS A systematic literature review (PubMed/Medline, Embase, Web of Science, Emcare, Cochrane Library, PsycINFO; July 2023) was performed to assess to what degree RCTs assessing outcomes of family caregivers of adult primary brain tumor patients adhere to established reporting standards. Using Covidence, screening and data extraction was independently performed by two researchers, with a third guiding consensus. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life (ISOQOL) Research criteria for patient-reported outcome reporting was utilized to assess reporting standards. Risk of bias was assessed per RCT. RESULTS Fifteen publications (12 unique RCTs) included 684 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on COs as a primary aim and eight (80%) of these satisfied ≥2/3 of the key methodological criteria. Of the five secondary analysis reports (33%) two met ≥2/3 of applicable key criteria. Criteria often missed are related to sample size calculations, details on statistical approaches, discussion of limitations and clinical significance of studies. Only three of the 12 RCTs were definitive trials aimed at improving COs and five should be considered as pilot or feasibility studies. CONCLUSION RCTs investigating neuro-oncology COs have high reporting standards and risk of bias was low. Future studies should focus on specific caregiver interventions to reduce high caregiver burden and with that patients’ quality of life.

A 2-year Review of the Diagnostic Performance of Serum and Bronchoalveolar Lavage Galactomannan Testing in Lung Transplant Recipients in a National Heart and Lung Transplant Centre.

The 2015 International Society for Heart and Lung Transplant (ISHLT) fungal guidelines recommend the use of bronchoalveolar lavage (BAL) galactomannan over serum galactomannan for the diagnosis of invasive aspergillosis (IA) in lung transplant (LTx) recipients, based on limited evidence. Galactomannan testing is costly. A single-center, retrospective cohort study reviewing all 814 serum and BAL galactomannan samples received from 184 LTx recipients in our center between 2021 and 2022 and assessing their diagnostic performance in the diagnosis of IA. Over the study period, 394 serum galactomannan samples were received from 144 patients and 420 BAL galactomannan samples from 143 patients. Using a cut-off of ≥ 1.0 for BAL galactomannan, the sensitivity and specificity were 65.9% and 98.4%, respectively. In total, 30 patients had positive BAL galactomannan. Antifungal therapy was commenced or continued in 29 of these patients either as targeted or pre-emptive treatment. Using a cut-off of ≥ 0.5 for serum galactomannan, the sensitivity and specificity were 9.7% and 99.7%, respectively. In total, four patients had a positive serum galactomannan. All four patients were either already on antifungal treatment for IA or were started before the serum galactomannan result was available, supported by laboratory, clinical, and radiological findings. A positive serum galactomannan was used to monitor treatment response in one patient. Serum galactomannan is not a valuable test in the diagnosis of IA in our LTx recipients, is costly, and does not remove the need for bronchoscopy and BAL galactomannan. This supports the ISHLT recommendation.