Citations

ABSTRACT Disease Overview POEMS syndrome is a life‐threatening syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnosis The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. Risk Stratification Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR. Risk‐Adapted Therapy For those patients with a dominant plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement should receive systemic therapy. Corticosteroids are temporizing, but alkylators and lenalidomide are the mainstays of treatment, the former either in the form of low dose conventional therapy or as high‐dose conditioning for stem cell transplantation. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Daratumumab combinations also appear promising based on case series. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.

Abstract Aims Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). While CKD is known to give rise to systemic inflammation, its inciting factors remain poorly defined. Oxalate, long implicated in rare genetic kidney disorders, accumulates with decreased kidney function and has emerged as a driver of inflammation and independent risk factor for CVD. Here, we investigate the immunological mechanisms linking oxalate nephropathy to systemic inflammation, cardiac damage and kidney injury. Methods and results Oxalate nephropathy was induced in C57BL6/N mice through an oxalate-enriched diet. Oxalate induced systemic immune activation, renal fibrosis, and adverse cardiac remodelling, including pulmonary congestion with systolic and diastolic dysfunction. Flow cytometry analysis identified interleukin (IL)-17A as a dominant inflammatory effector, with expansion of Th17 and Th17-like Treg in the kidney, intestine, and spleen. Bulk mRNA sequencing confirmed these findings in kidney and heart. In line, plasma IL-17A was increased in oxalate-fed mice. Confirming the oxalate-IL-17A relationship, plasma IL-17A was elevated in patients with primary hyperoxaluria. Gut microbiome analysis by 16S amplicon sequencing showed only mild oxalate-induced alterations in mice. However, soluble oxalate directly enhanced Th17 polarization and disrupted mitochondrial respiration in vitro. In vivo, antibody-mediated IL-17A blockade improved kidney function, cardiac fibrosis, reduced neutrophil infiltration, and partially restored cardiac function in oxalate-fed mice. Conclusion Our study identifies oxalate as a systemic immunometabolic stressor and IL-17A as a central mediator of oxalate-induced cardiorenal injury. These findings establish the oxalate-IL-17A axis as a mechanistic link between CKD and CVD and suggest IL-17A inhibition as a potential therapeutic strategy to reduce cardiovascular damage in CKD.

Abstract Grey matter network topology is altered in Alzheimer’s disease and these alterations are related to cognitive decline. Understanding the biological underpinnings of loss of brain connectivity may provide insights into mechanisms related to developing Alzheimer’s dementia (i.e. dementia A+). We investigated which biological processes as measured in CSF proteomics were associated with loss of brain connections across the Alzheimer’s disease continuum. We included 347 individuals with abnormal CSF amyloid [mean age ± standard deviation (SD) 66 ± 8; 98 cognitively unimpaired—A+, 88 mild cognitive impairment—A+, 161 dementia A+] and 146 cognitively unimpaired individuals with normal CSF amyloid (mean age ± SD 62 ± 8) and available T1w MRI-scans and CSF proteomic data (3097 proteins using tandem mass tag spectrometry) from the Amsterdam Dementia Cohort. We used an automated pipeline to construct grey matter networks from 3D-T1 sequences and for each network, calculated the small-worldness coefficient, which we previously found to be robustly related to cognitive decline. Linear models were applied to test associations between CSF protein levels and connectivity measures using an interaction term for clinical stage while controlling for connectivity density, age and sex. We validated our results in data from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Pathway enrichment analysis was performed for proteins associated with loss of brain connectivity (P < 0.05) using the Gene Ontology database. Individuals across the Alzheimer’s disease continuum had lower small-worldness coefficients compared with controls (ANOVA P < 0.001). In amyloid positive individuals, higher levels of 222 proteins and lower levels of 482 proteins were associated with lower small-worldness coefficients and were enriched for innate immune system and neuroplasticity pathways, respectively. Stratified for disease stage, most protein associations with lower small-worldness coefficients were found in mild cognitive impairment A+ (n = 527 proteins) and dementia A+ (n = 799 proteins) with considerable overlap (n = 239 proteins). Proteins in these stages were enriched for complement activation and synaptic integrity. In cognitive unimpairment A+, we found proteins enriched for processes involved in apoptosis. We did not find any enriched biological processes in controls. Repeating analyses in ADNI indicated that similar biological processes were associated with altered grey matter network connectivity. Higher CSF levels of proteins involved in immune responses and lower levels of proteins related to neuroplasticity were associated with lower small-worldness coefficients across the Alzheimer’s disease continuum. This suggests that preserving cognitive function in the presence of amyloid and prevention of dementia A+ may require therapies that strengthen synapses and targets the innate immune system in addition to amyloid and tau.

Civic health equity is the principle that all people deserve a fair and just opportunity to participate in their communities and to have a voice in the systems that shape their lives. Yet despite its importance to population health, civic engagement remains inconsistently addressed in health professions education. Inequities in civic participation contribute to unequal political representation and policy responsiveness, disproportionately affecting historically marginalized communities, and limit the ability of future health professionals to engage with the structural and policy drivers of health. This paper describes the development and implementation of a civic health equity metric within the Planetary Health Report Card (PHRC), an international, student-led, faculty-supported initiative that evaluates how health professional schools integrate planetary health and social accountability into educational practice. First introduced in the 2026 PHRC assessment cycle, the metric was developed through iterative leadership discussions informed by existing frameworks. It assesses whether health professional curricula prepare students to understand civic participation and advocacy as mechanisms for addressing environmental and structural determinants of health. The metric is part of the PHRC curriculum domain and uses a standardized scoring system ranging from 0 to 3 points, with required qualitative justification from participating institutions. To promote feasibility and broad adoption, it is explicitly nonpartisan and educational in nature, aligning with 501(c)(3) requirements. By embedding civic health equity within an established assessment framework, this metric provides educators with a practical tool to identify curricular gaps, support equitable access to civic learning, and strengthen health promotion–oriented training.

Background: Patients with spontaneous coronary artery dissection (SCAD) are at increased risk of cardiovascular events, including dissection in other arterial territories such as cervical arteries. Those with combined coronary and cervical arterial dissection (CACAD) may have more widespread arterial abnormalities and worse outcomes, underscoring the need for better risk stratification and personalized care. Objective: This study examined the prevalence of cervical artery dissection (CvAD) in patients diagnosed with SCAD, evaluated potential risk factors for developing CvAD, and assessed their impact on clinical outcomes, including all-cause mortality, SCAD recurrence, and stroke. The goal was to enhance risk stratification by identifying SCAD patients at increased risk for CvAD. Design: In this retrospective cohort study, patients diagnosed with SCAD between 2018 and 2024 across Mayo Clinic sites were identified using ICD-10 codes. Manual chart review confirmed CvAD diagnoses. Patients were stratified based on the presence or absence of CvAD. Chi-square and independent t-tests were used to compare risk factors and comorbidities. Univariate screening and multivariable logistic regression were used to identify predictors of CvAD. Results: Among 1380 patients with SCAD, 131 (9.5%) had CvAD. The median follow-up was 2.02 years (IQR: 1.1–5.2 years). All CvAD diagnoses were identified after the index SCAD event through systematic post-SCAD vascular imaging. The mean age was similar between groups (51.5 ± 11.3 years in CACAD vs. 50.9 ± 10.7 years in SCAD-only, p = 0.540), and the majority were female (93.9% vs. 91.9%, p = 0.529). Multivariable regression identified extremity arterial dissection (OR: 8.13, 95% CI: 3.41–19.36, p < 0.001), fibromuscular dysplasia (FMD) (OR: 7.52, 95% CI: 4.67–12.10, p < 0.001), connective tissue disorders (CTDs) (OR: 6.85, 95% CI: 2.35–19.98, p < 0.001), and anxiety (OR: 1.69, 95% CI: 1.01–2.81, p = 0.044) as significant predictors of CvAD. CvAD was a strong independent predictor of stroke (OR: 6.37, 95% CI: 2.93–13.87, p < 0.001). Mortality and SCAD recurrence did not differ significantly between groups. Conclusions: Patients with CACAD demonstrate a systemic vascular phenotype with significantly higher rates of FMD, connective tissue disease, extremity arterial dissection, and stroke. These findings highlight the importance of comprehensive vascular screening and individualized monitoring in at-risk SCAD patients.

ABSTRACT Objectives Tongue base obstruction is a cause of persistent sleep apnea after adenotonsillectomy in pediatric patients. The internet is the most used tool by patients for gathering healthcare information. This study aims to assess the quality and readability of websites directed to patients regarding tongue base procedures for pediatric obstructive sleep apnea. Methods Queries for the terms “lingual tonsillectomy,” “posterior midline glossectomy,” “tongue reduction,” “tongue base suspension,” and “hypoglossal nerve stimulator” were entered into Google on September 11, 2023. Thirty sites were pulled for each, and up to 10 sites per query meeting inclusion criteria were included for analysis. The DISCERN tool was used to evaluate quality. Flesch Reading Ease Score (FRES) and Flesch–Kincaid Grade Level (FKGL) were used to measure readability. Sites were analyzed for mention of pediatrics. Results Thirty‐five unique sites were analyzed. The mean DISCERN score was 44.7 (range 28.5–64.0) or “fair.” The mean FRES was 46.3 (range 9.6–66.6) and FKGL 11.5 (range 7.4–19.2), indicating college and 12th‐grade reading levels. Only 8/35 sites mentioned pediatrics. The average number per query of relevant sites directed towards patients on the first search engine page was 3.6. Despite tongue base procedures being relevant to pediatrics, only one in five sites mentioned children. Conclusion Websites directed at patients regarding tongue base procedures are of “fair” quality and at readability grade levels far above what is recommended. The majority of sites available for tongue base procedures are geared to professionals rather than patients. This study demonstrates a need for high‐quality information for patients about these procedures.

ABSTRACT This case highlights the diagnostic challenges posed by rare oropharyngeal neurofibromas, their potential to mimic other conditions, and the novel application of transoral robotic surgery (TORS) for the management of an oropharyngeal neurofibroma. A 47‐year‐old female presented with a 1‐year history of a left tonsillar mass. Clinical evaluation, imaging, and biopsy results were inconclusive but raised suspicion for a neoplasm. The patient underwent robotic‐assisted tonsillectomy and mass resection. Subsequent histopathological evaluation confirmed a benign spindle cell tumor consistent with neurofibroma. Oropharyngeal neurofibromas may present diagnostic challenges due to their resemblance to common tonsillar pathologies. Imaging and biopsies may not always provide definitive diagnoses, necessitating surgical excision for accurate characterization. This case demonstrates the utility of TORS, offering improved visualization and access while minimizing patient morbidity.

ABSTRACT Background Artificial intelligence (AI) and automation offer opportunities to enhance the efficiency, timeliness, and sustainability of living guidelines (LGs). However, how AI and automation have been integrated into existing LG development frameworks remains unclear. This scoping review represents the first step in a broader programme of work aimed at developing a framework which aims to guide responsible and coordinated AI adoption across all phases of LG development. Objective To identify existing frameworks, methods, and approaches that integrate AI or automation into any stage of LG development. Methods We conducted a structured search of PubMed, Embase, Web of Science, Scopus, Cochrane Database for Systematic Review and Cochrane Central Register of Controlled Trials from inception to March 12, 2026. We included peer‐reviewed articles describing frameworks, models, or methods that applied AI or automation in the development of LGs. We extracted data into a standardised form, capturing study characteristics, AI methods, targeted guideline processes, and key findings and synthesised findings using a thematic narrative approach. Results Of 1090 records identified, three studies met the inclusion criteria. The included studies described AI or automation applied to select components of the LG process, to support continuous evidence surveillance, to semi‐automate study screening, and incremental updating of living systematic reviews. None addressed multiple stages of LG development in an integrated manner. Conclusions Current evidence demonstrates fragmented and narrowly focused AI or automation applications within LG development processes. Our findings highlight opportunities for future work to develop and evaluate more comprehensive frameworks that span multiple stages of the LG lifecycle.