Citations

Abstract Accurate response assessment in patients with high-grade gliomas (HGGs) is complicated by post-treatment radiographic changes that are equivocal for treatment effect versus progression. Plasma-based liquid biopsy assays for circulating tumor DNA (ctDNA) have had limited sensitivity to date, due in part to the presence of the blood-brain barrier that limits the diffusion of tumor-derived analytes out of the central nervous system. To address this challenge, we developed a ctDNA plasma-based assay to detect individualized tumor-derived amplified junctions in patients with HGGs. These junctions occur due to large-scale chromosomal rearrangements, such as those associated with epidermal growth factor receptor (EGFR) or cyclin-dependent kinase 4 (CDK4) amplification. To identify these amplified junctions, whole genome sequencing was performed on resected tissue. Primers were designed to flank junction breakpoints and were then utilized on each patient’s plasma samples to detect the amplified junction via qPCR. Tumor-specific amplified junctions were robustly detected in plasma from 14/14 (100%) patients with IDH-mutant or wild-type grade 4 astrocytomas whose tumor genomes demonstrated amplification-related junctions, located at chromosomes 7, 11, or 12. In comparison, ctDNA could not be detected in three control cases that did not have an amplification or did not have high copy number junctions. Importantly, serial plasma samples obtained prior to and at disease recurrence in 4 patients demonstrated an increasing abundance of amplified junctions that accurately correlated with disease progression in 4/4 patients (100%). In two of these patients, increasing abundance of amplified junctions preceded radiographic changes compatible with disease progression by approximately 2 or 4 months, respectively. In conclusion, tumor-specific amplified junctions could reliably be detected in plasma from patients with IDH-mutant or wild-type grade 4 astrocytomas and correlated with changes in disease burden. Further work is currently ongoing to evaluate these promising results in a larger cohort of patients with serial plasma samples.

Context.— Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance. Objective.— To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists’ roles in their continuing care. Design.— At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our “ On My Path ” program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience. Results.— One hundred fifty-eight interactions have been documented (2017–2022) at our institution, including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program. Conclusions.— Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients.

Solitary myofibromas are rare, benign, mesenchymal tumors typically found in the head and neck regions. We report an exceptionally rare case of a solitary cardiac myofibroma and its short-term management and outcome. A two-month-old infant was referred due to a murmur. Echocardiography revealed a 2 × 1 cm solitary mass originating from a mitral papillary muscle, causing severe regurgitation. Magnetic resonance imaging showed the mass to be homogeneous on T1, hyperintense on T2, and hypointense on first-pass perfusion imaging with no enhancement on delayed postcontrast imaging. The mass was surgically excised partially due to its involvement with the mitral valve. Postoperative recovery was uneventful, with echocardiography four months later showing no tumor recurrence and trivial mitral regurgitation. This report provides valuable imaging and pathology examples to aid in the recognition of this rare tumor and demonstrates that successful surgical excision is possible, even with significant cardiac involvement.

Abstract Background Delirium, an acute brain dysfunction, is proposed to be highly prevalent in clinical care and shown to significantly increase the risk of mortality and dementia. Objectives To report on the global prevalence of clinically documented delirium and delirium-related clinical practices in wards caring for paediatric and adult patients in healthcare facilities. Design A prospective, cross-sectional, 39-question survey completed on World Delirium Awareness Day, 15 March 2023. Participants Clinicians or researchers with access to clinical data. Main Outcome and Measure The primary outcome was the prevalence of clinically documented delirium at 8:00 a.m. (4 h) and 8:00 p.m. (±4 h). Secondary outcomes included delirium-related care practices and barriers to use. Descriptive statistics were calculated and multilevel modelling was completed. Results 1664 wards submitted surveys from 44 countries, reporting on delirium assessments at 8:00 a.m. (n = 36 048) and 8:00 p.m. (n = 32 867); 61% reported use of validated delirium assessment tools. At 8:00 a.m., 18% (n = 2788/15 458) and at 8:00 p.m., 17.7% (n = 2454/13 860) were delirium positive. Top prevention measures were pain management (86.7%), mobilisation (81.4%) and adequate fluids (80.4%). Frequently reported pharmacologic interventions were benzodiazepines (52.7%) and haloperidol (46.2%). Top barriers included the shortage of staff (54.3%), lack of time to educate staff (48.6%) and missing knowledge about delirium (38%). Conclusion and Relevance In this study, approximately one out of five patients were reported as delirious. The reported high use of benzodiazepines needs further evaluation as it is not aligned with best-practice recommendations. Findings provide a benchmark for future quality improvement projects and research.

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children, including sensorineural hearing loss. There is interest in developing a pre-conception vaccine that could confer protective immunity on a woman of child-bearing age, hence resulting in a reduced cCMV disease burden. Other populations, including solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients, could also benefit from CMV vaccination. To review and discuss vaccines that are in clinical development, a workshop, sponsored by the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID), was empaneled. At this workshop, correlates of protective immunity against CMV, epidemiologic features of CMV transmission, and vaccine platforms in development were reviewed. Representatives from academia, pharma, and the NIH engaged in discussion on the current state-of-the-art in CMV vaccinology. A summary of the presentations from this is provided in this report.

Abstract Background Patients with lower extremity peripheral arterial disease (PAD) have a higher risk of cardiovascular events. Stress echocardiography (SE) based on regional wall motion abnormality (RWMA) is imperfect for risk stratification in PAD, but it can be complemented with an assessment of coronary flow velocity reserve (CFVR) in the mid-distal left anterior descending coronary artery. Purpose To assess the value of SE with RWMA and CFVR to predict survival in PAD. Methods In a retrospective analysis of prospectively acquired data in an observational, multicenter study, we recruited 359 patients (age 69±8 years, 240 [67%] males) with PAD referred for dipyridamole SE in 3 accredited laboratories. We assessed RWMA and CFVR (abnormal value <2.0). All patients were followed up for a median of 4.7 (interquartile range: 2.0 to 8.2 years). All-cause death was the outcome end-point. Results The positivity rate was 37/359 (10%) for RWMA and 159/359 (44%) for CFVR. During follow-up, 97 (27%) deaths were registered. At multivariable analysis, inducible RWMA and/or CFVR <2.0 (HR 2.58, 95% CI 1.65-4.04; p<0.0001), age ≥70 years, diabetes, dialysis treatment, and ejection fraction ≤50% were associated with decreased survival. The annual mortality was 7.4% in patients with RWMA and/or CFVR <2.0 and 2.7% in those with no RWMA and CFVR >2.0 (Figure, p<0.0001). Conclusion In patients with PAD, SE shows more than 4-fold higher prevalence of abnormal CFVR compared to RWMA. The prognostic value of CFVR outperforms RWMA, showing the importance of coronary microvascular dysfunction and diffuse, subcritical coronary atherosclerosis in determining the outcome.

Background: Delivering ethical care in global plastic surgery is challenging due to the unique complexities of resource-limited settings. Additionally, the rise of medical tourism has highlighted the importance of informed consent and awareness of the potential risks that are associated with seeking medical care in foreign countries. This article aims to consider core medical ethics principles and apply them in the context of delivering global plastic surgery. Methods: This article examines the application of the four core medical ethics principles in a framework set forth by Beauchamp and Childress, namely autonomy, beneficence, nonmaleficence, and justice, in the context of delivering plastic surgery in international settings. A literature review was performed, where all potential global plastic surgery articles were reviewed to better understand the application of the four core medical ethics framework in this context. Results: Increased communication between visiting surgeons and local healthcare providers; heightened education of surgeons traveling to low-to-middle-income countries regarding local medical practices, resource availability, and cultural norms before providing surgical education; and a greater emphasis on collecting and publishing data analyzing short- and long-term outcomes in low-to-middle-income countries are all likely to improve the success of international medical missions, ensuring that all patients receive medical treatment in a manner that upholds Beauchamp and Childress’ four core medical ethics principles. Conclusion: Providing plastic and reconstructive surgery abroad can be done ethically if the four main principles of medical ethics (respect for autonomy, beneficence, nonmaleficence, and justice) are used.