Search

Purpose: Less invasive decision support tools are desperately needed to identify occult high-risk disease in men with prostate cancer (PCa) on active surveillance (AS). For a variety of reasons, many men on AS with low- or intermediate-risk disease forgo the necessary repeat surveillance biopsies needed to identify potentially higher-risk PCa. Here, we describe the development of a blood-based immunocyte transcriptomic signature to identify men harboring occult aggressive PCa. We then validate it on a biopsy-positive population with the goal of identifying men who should not be on AS and confirm those men with indolent disease who can safely remain on AS. This model uses subtraction-normalized immunocyte transcriptomic profiles to risk-stratify men with PCa who could be candidates for AS., Materials and Methods: Men were eligible for enrollment in the study if they were determined by their physician to have a risk profile that warranted prostate biopsy. Both training (n = 1017) and validation cohort (n = 1198) populations had blood samples drawn coincident to their prostate biopsy. Purified CD2 + and CD14 + immune cells were obtained from peripheral blood mononuclear cells, and RNA was extracted and sequenced. To avoid overfitting and unnecessary complexity, a regularized regression model was built on the training cohort to predict PCa aggressiveness based on the National Comprehensive Cancer Network PCa guidelines. This model was then validated on an independent cohort of biopsy-positive men only, using National Comprehensive Cancer Network unfavorable intermediate risk and worse as an aggressiveness outcome, identifying patients who were not appropriate for AS., Results: The best final model for the AS setting was obtained by combining an immunocyte transcriptomic profile based on 2 cell types with PSA density and age, reaching an AUC of 0.73 (95% CI: 0.69-0.77). The model significantly outperforms ( P < .001) PSA density as a biomarker, which has an AUC of 0.69 (95% CI: 0.65-0.73). This model yields an individualized patient risk score with 90% negative predictive value and 50% positive predictive value., Conclusions: While further validation in an intended-use cohort is needed, the immunocyte transcriptomic model offers a promising tool for risk stratification of individual patients who are being considered for AS.

Chronic obstructive pulmonary disease (COPD), particularly following acute exacerbations (AE-COPD), significantly heightens the risks and mortality associated with acute myocardial infarction (AMI). The intersection of COPD and AMI is characterised by a considerable overlap in inflammatory mechanisms, which play a crucial role in the development of both conditions. Although extensive research has been conducted on individual inflammatory pathways in AMI and COPD, the understanding of thrombo-inflammatory crosstalk in comorbid settings remains limited. The effectiveness of various inflammatory components in reducing AMI infarct size or slowing COPD progression has shown promise, yet their efficacy in the context of comorbidity with COPD and AMI is not established. This review focuses on the critical importance of both local and systemic inflammation, highlighting it as a key pathophysiological connection between AMI and COPD/AE-COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Marriott, Singanayagam and El-Awaisi.)

Purpose: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning., Methods: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains., Results: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI., Conclusion: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders., Methods: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition., Results: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses., Conclusion: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent., Methods: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www., Clinicaltrials: gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase., Results: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65-1.23]; I 2 =0%). Among patients treated with low dose (<0.2 mg/kg; 4 studies), medium dose (0.2-0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22-2.82]; I 2 =0%), 0.77 ([95% CI, 0.53-1.14]; I 2 =0%), and 2.31 ([95% CI, 0.69-7.75]; I 2 =40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%-3.49%]; I 2 =0%, 7 studies), 1.69% ([95% CI, 1.14%-2.32%]; I 2 =1%, 23 studies), and 4.19% ([95% CI, 1.92%-7.11%]; I 2 =52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents., Conclusions: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.