Citations

Background Caregiver burden assessments lack clinical uniformity in palliative care. Existing evidence-based interventions often impose resource demands that are prohibitive for smaller programs. Objectives (1) Demonstrate the practical utility of routine caregiver screening paired with an interdisciplinary team (IDT) response protocol. (2) Identify patient and caregiver factors influencing burden. Design Setting: Cross-sectional study in a US outpatient palliative care clinic. Measure ments: The 12-item Zarit Burden Interview (ZBI-12) was administered by a nurse or social worker. Scores guided immediate, point-of-care IDT interventions. Results Of 81 approached caregivers, 74 completed the ZBI-12 (72% female; median age 56). Burden was stratified into mild (n = 37), mild-moderate (n = 22), and high (n = 15) tiers, with median scores increasing significantly (6 vs 16 vs 28; P < 0.001). General counseling was consistent across tiers (∼54%). However, high-intensity supportive interventions rose significantly with burden severity: social work telephone follow-ups increased (0% vs 13.6% vs 33.3%; P < 0.001), support group referrals rose (2.7% vs 31.8% vs 46.7%; P < 0.001), and psychotherapy referrals increased (0% vs 4.5% vs 13.3%; P = 0.030). Multivariable linear regression showed lower patient Palliative Performance Scale (PPS) scores independently predicted higher caregiver burden. Each 10-point decrease in PPS correlated with a 2.4-point increase in total ZBI-12 score (β = −0.240; 95% CI, −0.433 to −0.048; P = 0.015). Conclusion This workflow provides a replicable roadmap to transition caregivers from “invisible patients” to actively supported extensions of the care unit, reinforcing dyadic assessments as standard practice in outpatient palliative medicine.

Introduction There is uncertainty about the number of shark bites on humans in Florida (FL). Methods The International Shark Attack File (ISAF) and Global Shark Attack File (GSAF) databases (2016–2024) were compared with the non-inpatient FL Ambulatory and Emergency Department Patient Data database (AHCA) (2018–2023) and the National Emergency Medical Services (EMS) Information System (NEMSIS) (2016–2024). Results Between 2016–2024 there were 244 FL shark encounters reported in ISAF (mean 27.1 per year), 214 in GSAF (mean 23.8 per year), and 293 in a merged ISAF and GSAF (mean 32.6 per year). Between 2020–2023, there were 373 FL shark encounters reported in AHCA (mean 62.2 per year) compared with 114 encounters reported in NEMSIS (mean 22.8 per year) for 2020–2024. The rate ratio for AHCA FL shark encounters compared to the merged ISAF and GSAF was 1.91 (95% CI 1.64–2.23); p < .001. The percentage of shark encounters in Volusia County, FL, compared with all of FL shark encounters showed no significant differences between the ISAF and GSAF (40.2% and 33.6%, respectively) ( p = .16) and between the AHCA and NEMSIS (7.2% and 7.5%, respectively) ( p = 1.0). However, when comparing either ISAF or GSAF with either AHCA or NEMSIS, there were significant differences ( p < .001 for all). Discussion The AHCA dataset identified about twice as many shark bites as either the ISAF or GSAF. Many FL shark encounters did not require EMS or admission to the hospital. The discrepancy in the number of shark encounters attributed to Volusia County, FL, varied based on the dataset being examined.

ABSTRACT Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty that can be challenging to diagnose and treat. Neutrophils are a prominent feature in PJI, with neutrophil extracellular traps (NETs) known to be present; little is known, however, about the physiology of PJI-associated NETs. Here, the proteomes of PJI and non-infectious arthroplasty failure (NIAF), analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS) and proximity extension assay (PEA)-based profiling of fluids derived from sonication of arthroplasty components removed from patients who had undergone revision arthroplasty, were compared, with a focus on NET formation. In addition, in vitro effects of synovial fluid components on Staphylococcus aureus- induced NET formation were characterized. LC-MS/MS (PJI n = 85, NIAF n = 26) and PEA (PJI n = 95, NIAF n = 39) showed NET formation and neutrophil degranulation to be associated with PJI, with the complement cascade and platelet activation pathways identified as potential contributors. In vitro studies showed delayed NET formation in artificial synovial fluid compared to standard cell culture media conventionally used to evaluate NETs. Together, these results demonstrate the presence of NETs in PJI, identify potential pathways involved in PJI-associated NETosis, and point to an influence of synovial components on NET formation during PJI. IMPORTANCE Periprosthetic joint infection (PJI) is a major complication of joint replacement, placing a significant burden on patients and the healthcare system. Our research reveals that neutrophils and their antimicrobial “traps” are dominant features of the immune response at the infection joint site. Importantly, we found that the unique environment of the joint delays the formation of these traps, potentially contributing to the pathogenesis of PJI. By establishing a new experimental platform tailored for the infected joint, this work provides a foundational platform for probing these mechanisms and supports the development of improved diagnostic and therapeutic strategies.

Purpose: This study examined whether phoneme-level posterior probabilities generated by an articulatory-informed deep learning model (Phonet) can serve as interpretable and sensitive markers of articulatory impairment in motor speech disorders (MSDs). The goal was to determine whether these features distinguish individuals with and without MSDs and reflect varying severity levels of articulatory impairment. Method: A total of 676 participants (199 with MSDs, 477 without MSDs) completed a remotely captured word repetition task. Speech recordings were phonetically aligned, and posterior probabilities were extracted using a retrained version of the Phonet model, which estimates frame-level probabilities for 23 phonological classes. Segment-level posterior values were computed and compared across groups and severity levels using linear mixed-effects regression models. Results: Posterior probabilities were significantly reduced in the MSD group across all phoneme types. Within the MSD group, posterior probabilities decreased progressively with greater clinical severity, as measured by both perceptual sound distortion ratings and a cumulative articulation error score. Segment-specific analyses revealed systematic differences across phoneme classes, indicating that posterior probabilities capture distinct patterns of articulatory degradation associated with motor speech impairment. Conclusions: Phoneme-level posterior probabilities serve as interpretable, segment-specific indicators of articulatory impairment in MSDs. These features differentiate clinical status and reflect gradations of severity, making them promising tools for augmenting traditional perceptual speech assessments. Their linguistic transparency and scalability support future clinical applications in diagnosis, monitoring, and targeted intervention.

Abstract Globe-sparing surgery for orbit-involving sinonasal neoplasms (OISNs) is increasingly an option since the introduction of effective neoadjuvant treatments. Even if vision is preserved, loss of orbital support structures can cause major ocular sequelae. This study analyzed long-term ophthalmic outcomes following globe-sparing maxillectomy (GSM). We retrospectively reviewed all cases of GSM for OISNs with at least 1 year of ophthalmology follow-up at a tertiary care multisite institution from 2005 to 2024. Patient demographics, surgical details, ophthalmic findings, and final oncologic status were recorded. Orbital involvement was graded based on preoperative computed tomography imaging, and outcomes were compared across orbital involvement grades. Thirty-three patients (39% female) were included, with a mean age of 56 ± 18 years and a median follow-up of 2 years (range 1–12 years). Eleven patients (33%) had Grade I, 19 (58%) had Grade II, and 3 (9%) had Grade III involvement. With higher grades of orbital involvement, patients had a higher likelihood of receiving a preoperative ophthalmic exam (p < 0.001) and experiencing preoperative globe malposition (p = 0.015). Patients with higher-grade orbital involvement had a greater frequency of most ophthalmic symptoms postoperatively. Final best visual acuity was 20/40 or better in 82% of Grade I patients and 71% of Grade II/III patients (p = 0.681). GSM for OISNs offers a favorable visual prognosis. Ocular structural and functional impairment were observed at high frequency after surgery, even with lower-grade orbital involvement. Establishing ophthalmic care for all OISN patients is critical to adequately manage ocular sequelae.

Abstract To quantify lateral extension over the optic canal (OC) through endoscopic endonasal approaches (EEAs) and present techniques to maximize lateral extension. On 20 sides of 10 specimens, transplanum EEAs were performed. The OC roof was drilled maximally laterally. The lateral anterior cranial fossa (ACF) dura accessed was marked; its distance from lateral OC was measured at the proximal and distal OC. To enhance lateral drilling, we performed a posteromedial orbital decompression (POD)—removal of the posteromedial lamina papyracea and orbital apex bone—and continued lateral drilling. New lateral limits were marked and measured. At proximal OC, the transplanum approach accessed the full width of ACF dura overlying OC in 55% of sides; POD addition provided access in 100% of sides (p < 0.01). At proximal OC, the transplanum approach provided access to ACF dura an average of 0.7 mm lateral to OC; POD addition provided an average access of 6.0 mm lateral to OC (p < 0.01). At distal OC, the transplanum approach accessed the full width of ACF dura overlying OC in 30% of sides dissected; POD addition afforded access in 100% of sides (p < 0.01). At distal OC, the transplanum approach provided access to ACF dura an average of 1.1 mm medial to OC; adjunct POD provided an average access of 6.4 mm lateral to OC (p < 0.01). A transplanum approach affords inconsistent access to the full width of ACF dura overlying OC; adjunct POD consistently affords access to ACF dura lateral to OC and significantly increases lateral reach.

Background : Diabetic-foot osteomyelitis (DFO) is a severe complication of diabetic-foot ulcers associated with delayed healing, amputation, and increased mortality. Machine learning (ML) has increasingly been explored for diagnosis and clinical decision-making in diabetic-foot care; however, the current evidence specific to DFO has not been systematically synthesized. Methods : We performed systematic searches of MEDLINE, Embase, Scopus, and Web of Science for studies published between January 2000 and May 2026. Studies that developed or evaluated ML models for DFO diagnosis, prediction, or outcomes were included. Data extraction was performed using the CHARMS framework, reporting followed PRISMA 2020 and TRIPOD-SRMA recommendations, and methodological quality was evaluated using PROBAST + AI. Due to considerable heterogeneity, narrative synthesis was performed. Results : A total of 10 studies published from 2022 to 2026 met the inclusion criteria. Five studies developed or evaluated ML models with a direct DFO diagnostic endpoint, one additional study evaluated model explainability, and four evaluated complementary DFO-relevant diabetic-foot applications. Reported discrimination ranged from 0.879 to 0.998, but comparisons were limited by differences in clinical endpoints, reference standards, input modalities and validation strategies. Only one direct DFO model was externally validated, and no study developed a multimodal model combining clinical and imaging data. Conclusion : Current evidence is limited by heterogeneous methodologies, limited external validation, and inconsistent reporting despite promising discrimination reported by several models. Future studies should evaluate whether multimodal models integrating clinical and imaging data provide incremental value over unimodal approaches, with external validation, calibration, and clinical utility assessment before clinical implementation.

ABSTRACT Background and Objectives Among patient with early‐stage breast cancer, breast conservation surgery (BCS) is the most performed surgery, utilized in approximately two‐thirds of patients. While 5‐year overall‐survival rates are strong—typically above 90%—additional re‐excisions can occur in up to 25% of patients who undergo index BCS and some patients will require subsequent surgery for new breast cancer or recurrences. As such, these additional procedures can complicate patients’ pathway to survivorship, negatively impact quality of life, and lead to excess healthcare costs. Methods This retrospective cohort study used linked claims and an electronic healthcare record database to (1) characterize patients at higher risk for additional breast oncologic surgery (aBOS) following BCS, and (2) quantify the long‐term financial impact of aBOS after BCS. In total, 87,190 patients with breast cancer, who had an index BCS between January 1, 2012, to March 31, 2023, were followed for up to 5‐years post‐operatively. Patients with and without aBOS were analyzed, comparing demographics, tumor characteristics, healthcare utilization, and per‐person‐per‐month (PPPM) costs. Results Twenty‐three percent ( n = 20,212) of patients underwent aBOS. These patients were younger, had higher tumor grades and larger tumor sizes, and incurred greater healthcare costs compared to patients who did not undergo a secondary surgery. Conclusion This study highlights significant factors influencing BCS outcomes and healthcare utilization, underscoring the need for tailored therapeutic strategies for patients with breast cancer.

PURPOSE Patients with breast cancer requiring postmastectomy radiation therapy (PMRT) often desire breast reconstruction. Reconstructions can be adversely affected by PMRT, and fear of reconstruction complications has discouraged adoption of short-course radiation therapy used after lumpectomy. To fill the evidence gap, we conducted a noninferiority trial of hypofractionated versus conventional PMRT in patients undergoing breast reconstruction. The primary outcome was reconstruction complication rate, a composite of wound healing, readmission, capsular contracture, unplanned reoperation, and reconstruction failure. METHODS Women with unilateral invasive breast cancer with planned immediate or delayed reconstruction and PMRT were randomly assigned (1:1) to 50 Gy (25 fractions/5 weeks) or 42.56 Gy (16 fractions/3 weeks). This study was designed with a noninferiority margin of 10%, assuming a 2-year reconstruction complication rate of 25% with conventional PMRT. Randomization was stratified by immediate versus delayed and autologous versus implant-only reconstruction. RESULTS Between 2018 and 2021, 898 patients enrolled with a median follow-up of 3.9 years; 825 patients were evaluable for the primary end point. The 24-month reconstruction complication rates were 12.3% (52/422) with hypofractionated PMRT and 10.2% (41/403) with conventional PMRT, corresponding to an estimated difference of -2.1% (95% CI, -6.5 to 2.2). The complication rate was higher (regardless of arm) with implant-only versus autologous reconstruction (odds ratio = 1.65). There was no statistically significant difference in 36-month locoregional recurrence rates: 1.5% (95% CI, 0.7 to 3.2) with hypofractionated and 2.2% (95% CI, 1.1 to 4.3) with conventional PMRT. Acute and late toxicity rates were not statistically different. CONCLUSION A 16-fraction course of hypofractionated PMRT is safe and noninferior to conventional PMRT in women undergoing breast reconstruction after mastectomy.

In recent years, lipid nanoparticles (LNPs) have shown great promise as highly flexible delivery systems for cancer vaccines, which enable effective cargo delivery and allow for controlling their distribution, cell-targeting ability and immunogenicity. Innovations in ionizable lipid chemistry, biodegradable formulations, RNA engineering and LNP design resulted in improvements in RNA encapsulation, endosomal escape, delivery outside the liver, and targeting of lymphoid organs and antigen-presenting cells. All these achievements led to an expansion of strategies for developing cancer vaccines from using only mRNA to personal neoantigen vaccines, self-amplifying RNA (saRNA), circular RNA (circRNA), peptide/protein vaccines, and multi-purpose platforms that combine antigen delivery and modulation of the immune system. LNPs are also studied as tools for altering the tumor microenvironment (TME) and boosting anti-tumor immunity through local delivery of cytokines and innate immune modulators. Preliminary clinical results with personalized mRNA neoantigen vaccines show strong potential for this approach. However, inflammatory toxicity, suitability for repeated dosing, off-target delivery, difficulties with large-scale production, formulation stability, personalized production schedule and regulatory issues are still significant challenges. New biodegradable and PEG-free formulations, innovations in manufacturing and lyophilization technology, and AI-based approaches in lipid screening could help overcome some of these problems.