Citations

ABSTRACT Objective With regulatory approval of HPV‐specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. Data Sources and Methods RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. Results Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case‐by‐case basis. HPV ‐specific immunotherapy that induces an HPV ‐specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first‐line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second‐line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally‐administered adjuvant should be considered. Conclusion This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options. Level of Evidence 5

Background: Large language models (LLMs) are increasingly integrated into clinical documentation, decision support, and patient-facing applications across healthcare, including plastic and reconstructive surgery. Yet, their evaluation remains bottlenecked by costly, time-consuming human review. This has given rise to LLM-as-a-judge, in which LLMs are used to evaluate the outputs of other AI systems. Methods: This review examines LLM-as-a-judge in healthcare with particular attention to judging architectures, validation strategies, and emerging applications. A narrative review of the literature was conducted, synthesizing LLM judge methodologies as well as judging paradigms, including those applied to clinical documentation, medical question-answering systems, and clinical conversation assessment. Results: Across tasks, LLM judges align most closely with clinicians on objective criteria (e.g., factuality, grammaticality, internal consistency), benefit from structured evaluation and chain-of-thought prompting, and can approach or exceed inter-clinician agreement, but remain limited for subjective or affective judgments and by dataset quality and task specificity. Conclusions: The literature indicates that LLM judges can enable efficient, standardized evaluation in controlled settings; however, their appropriate role remains supportive rather than substitutive, and their performance may not generalize to complex plastic surgery environments. Their safe use depends on rigorous human oversight and explicit governance structures.

ABSTRACT Advanced chronic diseases, or multicomplexity in older adults presents unique challenges. Transthyretin cardiac amyloidosis (ATTR‐CA) is one such scenario where heart failure is a common presentation, and management remains challenging. We describe the challenges involved in the diagnosis of ATTR‐CA in older adults, which has implications on treatment options. We discuss the application of comprehensive geriatric assessment (CGA) and shared decision making (SDM) in the context of these challenges. Based on geriatric medicine principles, an innovative framework for applying SDM in ATTR‐CA patients is proposed, including consideration of the patient priorities care approach. The proposed framework emphasizes assessing functionality, frailty, and life expectancy to help categorize risk. This framework can be applied in various advanced chronic diseases or multicomplexity. Based on risk categorization, treatment burden, and alignment with values and preferences, management pathways are suggested for each risk category. Incorporating CGA and SDM, the proposed framework supports patient‐centered care, ensuring that clinical recommendations are tailored to each older adult's unique needs and goals. In ATTR‐CA, a collaboration between cardiology and geriatric medicine provides significant value in managing older adults. The need to prevent age‐related bias in clinical decision‐making exists across all health conditions, and the proposed framework allows for a thorough evaluation of multimorbidity, frailty, disability, and patient preferences. While ATTR‐CA is used as a prototype, this integrated approach can be applied across all health conditions and is essential for delivering holistic care, improving communication, and aligning treatment plans with patient values.

Abstract Background Fever and worsening rigidity in Parkinson's disease (PD) may resemble neuroleptic malignant syndrome (NMS). We examined PD patients diagnosed with NMS—regardless of whether diagnostic criteria were used—to establish the clinical characteristics and etiology. Cases Among 15 cases, 40% (6/15) required ICU admission, 27% (4/15) required mechanical ventilation, 80% (12/15) recovered, and 20% (3/15) died. 27% (4/15) had a reduction in carbidopa‐levodopa as the primary trigger, 27% (4/15) had sepsis in addition to concurrent reductions in carbidopa‐levodopa, 7% (1/15) had sepsis alone, 33% (5/15) were exposed to new or increased antidopaminergic drugs, and 7% (1/15) had deep brain stimulator (DBS) malfunction. Literature Review Several terms to describe exacerbation of parkinsonism including NMS‐like state and parkinsonism hyperpyrexia syndrome (PHS) have been proposed over the years but may be restrictive in their definitions and confounders exist. Conclusions Acute parkinsonism dopamine depletion syndrome (APDDS) might be a more encompassing term to describe to an acute exacerbation of preexisting parkinsonism resulting from recent reduction in dopaminergic or other Parkinson's therapy (eg, DBS failure), or exposure to antidopaminergics. Symptoms include increased rigidity, encephalopathy, hyperthermia, or autonomic instability. Sepsis is a frequent confounder and may be associated with concurrent reduction or discontinuation of carbidopa‐levodopa.

ABSTRACT Introduction/Aims Scapular winging occurs as an abnormal protrusion of the scapula due to nerve injury, muscle weakness, bone, or joint pathology. The main muscular stabilizers of the scapula include the serratus anterior, trapezius, rhomboid major and minor, levator scapulae, and pectoralis minor. Needle electromyography (EMG) has historically been used as one of the primary diagnostic tests for evaluating this finding. However, sampling of these muscles can be technically difficult and carries risks for complications. Muscle ultrasound (MUS) can also reliably identify abnormalities in the muscles involved in scapular stabilization while offering the benefit of rapid side‐to‐side comparison and improved patient comfort. This study aims to highlight the concordance of ultrasound and EMG findings using our published MUS protocol in patients with scapular winging. Methods A retrospective analysis was performed of 13 patients who presented to an electrodiagnostic (EDX) laboratory with the referral diagnosis of “scapular winging” or “scapular dyskinesis.” All patients underwent MUS testing of scapular muscles according to a previously published protocol followed by EMG of muscles deemed relevant by the clinician. Results Seven patients were found to have a neurogenic cause of their scapular winging and in those patients, all had both EMG and MUS abnormalities. MUS was found to have a sensitivity of 87.5%, specificity of 95.7%, and individual muscle concordance with EMG of 90.6%. Discussion There is high concordance between EMG and MUS in patients with scapular winging. This combined with potential advantages of the MUS modality supports their concurrent use in patients with scapular winging.

Introduction Placental inflammation is a major contributor to preterm birth (PTB), and there are currently few targeted strategies to prevent PTB and its associated adverse neonatal outcomes. Serum amyloid A (SAA), particularly the isoforms SAA1 and SAA2, are well-recognized inflammatory markers, but their functional roles in placental inflammation remain poorly defined. Methods Using a translational mouse model of sub-chronic maternal inflammation, we investigated the immune mechanisms and therapeutic potential of siRNA-mediated targeting of Saa2 (siSaa2). Placental expression patterns of SAA2 were examined in vivo , and macrophage responses to extracellular SAA2 were modeled in vitro using RAW264.7 cells to assess downstream P2X7R-dependent signaling and functional outcomes. Results SAA2 is primarily induced in placental trophoblast and endothelial compartments during inflammation, where it acts as an extracellular inflammatory mediator. In vitro , we model macrophage responses to extracellular SAA2 using RAW264.7 cells to examine downstream P2X7R-dependent signaling and functional outcomes. Maternal administration of siSaa2 improved PTB rates, placental morphology and fetal brain development. Additionally, SAA1 and SAA2 exhibited distinct expression patterns in the mouse and human placenta. Discussion These findings identify placental SAA2 as a key inflammatory mediator in inflammation-associated PTB and demonstrate that targeted silencing of Saa2 represents a potential therapeutic strategy to mitigate placental injury and adverse fetal outcomes.

Abstract Here, we examine immune signaling pathways affecting the duration of primary nasopharyngeal colonization by Streptococcus pneumoniae ( Spn ), the first step in its pathogenesis. Spn colonization which lasts days to weeks in WT mice was persistent ( > 6 months) in the absence of IL-17RA-signaling. RNA-seq analysis confirmed the role of IL-17RA signaling in neutrophil-associated pathways. Rather than driving neutrophil specific chemokine expression, IL-17RA-signaling was required to replenish neutrophils in nasal tissue that were otherwise depleted during infection. Enhanced neutrophil trafficking correlated with IL-17RA-dependent expression of endothelial cell adhesion molecules that promote neutrophil trafficking from the circulation into nasal tissue. Persistent colonization was also observed in mice lacking IL-1R-signaling. Recognition of IL-1-family cytokines, however, was not necessary for the expression of IL-17A or neutrophil recruitment. Instead, IL-1R-signaling was associated with the activation of neutrophils in nasal tissue that displayed increased levels of the surface marker CD11b, an important receptor for the complement-opsonized phagocytosis of Spn . Our findings provide insight into the requirement for sustained neutrophil presence and activity to prevent persistent mucosal infection by a leading opportunistic mucosal pathogen. Author Summary Colonization of the upper airway by Streptococcus pneumoniae ( Spn ) is common and often asymptomatic, particularly in early life, yet prolonged colonization increases the risk of transmission and invasive disease. Despite its importance, the immune mechanisms that prevent long-term persistence of Spn in the upper airway are not fully understood. In this study, we investigated how two immune signaling pathways, the IL-17RA and IL-1R pathways, contribute to preventing persistent Spn colonization. Using a mouse model, we found that the IL-17RA pathway supports continued replenishment of neutrophils into nasal tissue by promoting expression of molecules that allow these cells to exit the bloodstream and enter the nasal tissue. In contrast, the IL-1R pathway activates neutrophils in a way that makes them more effective at clearing Spn . Loss of either pathway resulted in persistent Spn colonization, with an additive effect seen when both pathways were removed. Collectively, our results highlight how two distinct immune pathways cooperate to control pneumococcal colonization by sustaining neutrophil recruitment and function.

Abstract Radiation therapy (RT) has long been included in the treatment of glioblastoma (GBM). However, radioresistance in cancer cells as well as toxicity in normal tissues are major obstacles to clinical efficacy. Improved understanding of the mechanisms of tumor microenvironment-induced radioresistance during and after radiation therapy can provide fundamental insights to improve clinical outcomes in GBM. Here, using three-dimensional engineered hydrogel models in vitro, we report the influence of extracellular matrix, hypoxia, and adjacent neuronal cells in radiotherapeutic sensitivity. We find that mechanical cues and oxygen availability regulate cellular response to radiation, with softer matrices allowing for more DNA damage. Hyaluronan fragments from the extracellular matrix also modulate rapid metabolic response to radiation, especially in hypoxic environments. We show that neuronal networks influence tumor metabolic activity and the inflammatory response. Overall, we demonstrate here that alternative radiation strategies, such as low dose rate radiation therapy and microenvironmental regulation, have the potential to be more effective in a specific subset of radiosensitive GBM tumors.

ABSTRACT Background Systemic infections are a leading cause of hospitalization and death among patients with cirrhosis. Timely and accurate infection identification is essential for both clinical care and the development of predictive models. However, existing methods such as ICD-10 coding are unreliable, and manual chart review is resource-intensive and difficult to scale. This study aimed to develop and validate an automated large language model (LLM)-based approach for infection classification and subtyping in patients with cirrhosis presenting to the emergency department (ED). Method We developed INFEHR (INfection identification and subtyping using Free-text EHR analysis), an LLM-powered pipeline utilizing Claude 3.5 Sonnet to analyze clinical notes from the first 72 hours of admission. Model outputs were compared against a physician-adjudicated gold standard in a cohort of 1,000 encounters from patients with cirrhosis who presented to the ED. Performance was benchmarked against ICD-10 code–based labeling and CDC Adult Sepsis Event criteria. Results INFEHR achieved 94.7% overall accuracy, with 99.5% sensitivity and 92.8% positive predictive value for identifying infection presence, outperforming ICD-10–based classification across all metrics ( p < 0.0001). The model also demonstrated strong performance in classifying pathogen type and infection site. This pipeline processed notes within seconds, offering improvements in efficiency and scalability over manual review. Conclusion INFEHR offers a scalable, reproducible, and accurate method for infection phenotyping in cirrhosis. By overcoming limitations of traditional coding and manual review, it supports high-throughput infection surveillance, improves cohort construction for clinical research, and enables future integration into real-time decision-support tools in hepatology.