Citations

Abstract Accurate endoscopic marking of suspicious lesions and polyps is essential for the effective surgical management of gastrointestinal (GI) diseases, including colorectal cancer and inflammatory bowel disease. Currently, lesion localization relies on submucosal injection of a carbon-based tattoo ink; however, this ink exhibits extensive tissue diffusion and extravasation, leading to poor spatial fidelity, compromised precision, and risk for fibrotic responses. Given the need for contrast relative to endoscopic white light and biocompatibility, we report here the design and evaluation of melanin-inspired nanoparticle tattoo (MINT) inks, formulated from synthetic melanin nanoparticles and biopolymer-encapsulated synthetic melanin. MINT inks are designed to be durable, high-contrast, easily injectable, and colloidally stable for at least 2 months and to elicit minimal macrophage-mediated inflammatory responses in vitro. In live porcine colon studies, submucosal injection of MINT inks resulted in highly localized tattoos with minimal lateral spread over 9 weeks of follow-up, which is a significant advantage over the extensive diffusion observed with clinical carbon ink. MINT tattoo markings were distinctly visible from both mucosal and serosal surfaces of the intestine and enabled reproducible multipoint and quadrant-based marking, which enhanced spatial orientation. Collectively, these findings demonstrate that MINT inks are biocompatible and capable of providing precise, long-lasting, high-contrast marking of lesions in the colon. By overcoming the limitations of conventional carbon-particle-based tattoos, MINT inks represent a promising next-generation contrast agent for improving endoscopic localization and surgical outcomes in GI diseases.

BACKGROUND Acral lentiginous melanoma (ALM) is a biologically distinct, inherently aggressive, and understudied melanoma subtype without a unified surgical approach. OBJECTIVE To provide an updated review of ALM and offer practical, surgeon-focused guidance on diagnosis, biopsy, margin-controlled excision, and Mohs micrographic surgery (MMS)-based management of ALM. METHODS & MATERIALS A PubMed/MEDLINE search of ALM, with an emphasis on articles published after 2015. RESULTS ALM demonstrates inherent biological aggressiveness characterized by extensive subclinical spread, delayed diagnosis, and higher stage-adjusted recurrence compared with nonacral cutaneous melanomas. Anatomic constraints additionally necessitate specialized surgical approaches, although current management is extrapolated from nonacral melanoma data. Retrospective data support MMS and margin-controlled excision and tissue preservation in ALM, with the benefit of digit-sparing surgery and functional preservation. No randomized trials have included ALM, highlighting a key evidence gap. CONCLUSION Margin-controlled approaches such as MMS may improve local control and tissue preservation in select ALM patients. Prospective ALM-specific research and standardized diagnostic and surgical protocols are strongly needed.

Objective: Patients with limited English proficiency often face barriers to accessing timely care. We evaluated whether Spanish-language Fast Pass messaging, combined with two-way Short Message Service (SMS) functionality, increased appointment acceptance rates among Spanish-preferring patients while maintaining equitable outcomes for English-preferring patients. Methods: A pre/post-quality improvement project was conducted at Mayo Clinic from November 2023 to June 2025. Epic’s Fast Pass, an automated appointment waitlist system, was enhanced with Spanish-language templates and bidirectional SMS in lieu of patient portal utilization. The primary outcome was the Fast Pass acceptance rate for Spanish-preferring patients. Balancing measures included acceptance among English-preferring patients. Secondary outcomes included scheduler efficiency and cost savings. Results: Prior to implementation, Spanish-preferring patients accepted 4.69% of Fast Pass offers compared with 7.57% for English-preferring patients. Post-implementation, acceptance rates for Spanish-preferring patients increased from 4.69% to 8.05%, a 71.6% improvement in the acceptance rate, exceeding the initial target of a 7.57% acceptance rate. Acceptance rates for English-preferring patients also improved, rising from 7.57% to 9.5%, or a 25.5% improvement in the acceptance rate. The intervention resulted in 344 additional Spanish-language accepted appointments and 29,883 additional English-language accepted appointments, both measured by unique patient appointments. The intervention also improved operational efficiency, saving more than 4,000 hours of scheduler time and reducing scheduling-related costs. Conclusions: Spanish-language concordant and SMS-enabled Fast Pass messages improved patient equity in appointment access while increasing scheduling efficiency and reducing operational costs. Health systems should adopt language-concordant digital communication strategies. Future research should expand to include additional languages and explore artifical intelligence–based scheduling support.

Importance Timely identification of aortic stenosis (AS) is essential for appropriate clinical management, yet screening remains limited by dependence on comprehensive echocardiography and trained imaging personnel. Objective To develop and validate a deep learning algorithm for detection of moderate or greater AS and prospectively evaluate its performance using artificial intelligence (AI)–guided focused cardiac ultrasound (FoCUS) acquired by novice operators. Design, Setting, and Participants This diagnostic study included retrospective algorithm development and validation and prospective evaluation of AI-guided FoCUS across Mayo Clinic sites in the Midwest, Arizona, and Florida. The model was developed using 6753 patients and evaluated in internal validation (n = 852), internal test (n = 844), and validation (n = 1912) cohorts. Performance was assessed on FoCUS acquired by experienced sonographers (n = 602) and prospectively by novice operators (n = 1302). The retrospective model development and validation cohorts comprised studies performed from January 2005 through September 2022. Prospective study was conducted in 2 enrollment periods from June to August 2024 and from June to September 2025. Participants from both periods were combined to comprise the final prospective cohort. Exposure AI-guided FoCUS acquisition and automated deep learning–based assessment for detection of moderate or greater AS. Main Outcomes and Measures Detection of moderate or greater AS. Performance was assessed using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and positive predictive value. Results The model demonstrated excellent discrimination in the internal test cohort (AUROC, 0.99; 95% CI, 0.98-1.00) and geographically distinct validation cohorts in Arizona (AUROC, 0.99; 95% CI, 0.97-1.00) and Florida (AUROC, 0.99; 95% CI, 0.96-1.00). Among FoCUS examinations acquired by experienced sonographers, sensitivity was 95% (95% CI, 82-99) and specificity was 97% (95% CI, 95-98). In the prospective novice-operator cohort, 1258 of 1302 examinations (96.6%) were suitable for automated analysis. Sensitivity was 93% (95% CI, 82-99) and specificity was 96% (95% CI, 95-97). Expert review of AI-positive and uninterpretable examinations increased the positive predictive value from 49.4% to 91.1%, with sensitivity of 85.4%. Conclusions and Relevance A deep learning algorithm accurately detected moderate or greater AS across validation cohorts in this study. In prospective evaluation, novice operators were able to acquire AI-guided FoCUS examinations that enabled accurate detection of moderate or greater AS. These findings support a scalable strategy that may expand access to AS detection in settings with limited echocardiography resources.

Abstract Background. Cardiovascular disease is a leading cause of death among women with breast cancer, and the 2026 ACC/AHA dyslipidemia guideline endorses coronary artery calcium (CAC) scoring to guide statin therapy before cardiotoxic treatment. Breast cancer patients routinely undergo staging 18 F-fluorodeoxyglucose PET/CT, whose low- dose CT visualizes the coronary arteries, thus enabling CAC quantification at no additional cost or radiation. Methods In this single-center retrospective study, consecutive women with newly diagnosed breast cancer undergoing staging 18 F-FDG PET/CT (2009–2021) had semi- automated Agatston CAC scoring performed on the low-dose CT and were stratified by CAC presence (CAC-P) versus absence (CAC-A). We assessed a composite of cardiac diagnostic testing (stress testing, coronary CT angiography, invasive angiography), clinical events, and reclassification of statin eligibility per ACC/AHA guideline thresholds in a prevention-eligible subgroup. Results Among 276 women (mean age 55.5 years; median follow-up 7.1 years), CAC was present in 68 (25%) but was clinically reported in only 5.4%. CAC-P was associated with more cardiac testing (34% vs 12%; age-adjusted hazard ratio 2.75, 95% CI 1.43–5.28) and, though underpowered, with more atherosclerotic events (7.4% vs 1.4%), but not with the all-cause composite. In the prevention-eligible subgroup (n=39), CAC scoring would have changed statin eligibility in 64%, initiating therapy in 62% of CAC-P women and supporting de-prescribing in 67% of CAC-A women. Conclusions CAC can be feasibly quantified from staging PET/CT in women with breast cancer and would frequently reclassify statin eligibility at no additional cost or radiation, yet is rarely reported.

Background Cardiac involvement by extranodal natural killer/T-cell lymphoma (ENKTL) and aggressive NK-cell leukaemia (ANKL) is exceedingly rare and presents with heterogeneous manifestations, often leading to diagnostic uncertainty and delay. We contribute three additional biopsy- or autopsy-proven cases and place them in the context of a literature review of previously reported cases classified according to the 5th edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors. Case series Three men (ages 58–72) presented with diverse cardiac manifestations. A 72-year-old with progressive dyspnoea and cardiogenic shock had cMRI findings interpreted as myocarditis on an infiltrative substrate; endomyocardial biopsy confirmed cardiac infiltration by ENKTL. Despite brentuximab vedotin (BV)-based therapy he died shortly thereafter. A 60-year-old with encephalopathy, biventricular dysfunction, and widespread nodal/multiorgan disease had nodal pathology consistent with EBV-negative ANKL according to the criteria of the 5th edition of the WHO Classification of Hematolymphoid Tumors; he declined chemotherapy and died within six days, with autopsy confirming multiorgan (including myocardial and bone marrow) infiltration. A 58-year-old with prior sinonasal ENKTL treated with four cycles of SMILE developed a new right atrial mass one month later; the mass was diagnosed by cMRI/PET-CT concordance and an extracardiac (EBUS-lung) tissue confirmation of the same recurrence. BV followed by gemcitabine/oxaliplatin failed to control progression and he died approximately one month after cardiac spread. Across cases, CD56 was positive in all, EBER in two, and CD30 was expressed variably. Conclusions Cardiac ENKTL/ANKL is a rapidly fatal entity with protean features. Multimodal imaging aids early recognition and tissue targeting, but definitive diagnosis rests on tissue confirmation. L-asparaginase-based chemotherapy remains the treatment backbone; CD30- and PD-L1-guided agents such as BV, PD-1 blockade, and daratumumab may offer transient control after biomarker-guided selection but lack randomized data in cardiac disease. Across the reported experience, survival after cardiac involvement was uniformly short, typically days to a few months. Our three cases add to this literature by illustrating the diversity of cardiac presentations, the variable CD30 expression relevant to brentuximab vedotin use, and the contribution of multimodal imaging to diagnosis. Findings from our series and the pooled literature are descriptive rather than constituting a formal survival analysis, and underscore the need for earlier diagnosis and prospective investigation.

ACCESS is a prospective, multicenter phase II trial evaluating peripheral blood stem cell (PBSC) transplantation using 4-7/8 HLA-mismatched unrelated donors (MMUD) with post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first HCT with myeloablative (MAC) or reduced-intensity/nonmyeloablative (RIC/NMA) conditioning were enrolled, with donors aged 18-35 years and matched at 4/8-7/8 HLA loci by high-resolution typing. This expanded analysis includes all enrolled adult PBSC recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA match level. Among 268 adults, 183 received 7/8 and 85 received <7/8 MMUD grafts; 82.4% of the <7/8 cohort received 6/8 grafts. Median follow-up among survivors was 11.9 months. At 1-year, overall survival was 78.6% (95% CI, 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the <7/8 cohort. One-year relapse, non-relapse mortality, and GVHD-free relapse-free survival were 17.1%, 13.7%, and 51.1% versus 22.8%, 8.4%, and 54.6%, respectively. The cumulative incidence of grade II-IV and grade III-IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort versus 28.3% and 5.9% in the <7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% versus 7.7%, respectively. Among adult ACCESS recipients treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. (Registered as NCT04904588 at CT.gov)

Background and Purpose Stroke is a frequent manifestation of non-bacterial thrombotic endocarditis (NBTE), yet current knowledge largely stems from case reports and small case series. This systematic review summarizes stroke presentation, imaging features, management, and outcomes in patients with NBTE-related stroke. Methods We conducted a patient-level systematic review of published case reports and case series. PubMed, MEDLINE, Embase, Web of Science, and PsycINFO were searched from inception through August 2025 for studies reporting individual patients with NBTE-related stroke. Extracted data included demographics, vascular risk factors, stroke presentation, imaging features, NBTE etiology, treatment (unfractionated heparin/low-molecular-weight heparin [UFH/LMWH], vitamin K antagonists [VKA], direct oral anticoagulants [DOACs], and/or valvular surgery), and outcomes. Multivariable regression was used to explore factors associated with recurrent stroke and mortality. Results We included 236 patients with NBTE and stroke from 218 studies (median age 56 years [IQR: 43–63], 63% female). Left hemispheric stroke syndromes predominated among clinical presentations (27%), and multi-vessel territory ischemic infarcts (>2 territories) were observed in 65%. Conventional vascular risk factors were infrequent (0%−21%), whereas deep vein thrombosis (43%) and systemic embolism (41%) frequently preceded or coincided with stroke onset. Malignancy (70%) and autoimmune disease (25%) were the main NBTE etiologies. Anticoagulation was initiated in 70%, and 21% underwent valvular surgery. Over a median follow-up of 2.0 months, stroke recurred in 43% and death occurred in 49% of patients. Malignant etiology (aOR 10.3, P < 0.001) and metastases (aOR 3.9, P < 0.001) were associated with increased mortality, while VKA use (aOR 0.08, P < 0.001) and autoimmune etiology (aOR 0.1, P < 0.001) were associated with lower mortality. Malignancy (aOR 2.8, P < 0.001) and DOAC use (aOR 5.2, P = 0.012) were associated with increased risk of recurrent stroke. Conclusion NBTE should be considered in stroke patients lacking conventional vascular risk factors, particularly those with malignancy or autoimmune disease. Malignancy and DOAC use were associated with higher recurrent stroke risk, while VKA use was associated with lower mortality; however, these anticoagulant-class findings should be considered hypothesis-generating and interpreted cautiously given the case-report evidence base, small treatment subgroups, potential confounding, and limited follow-up. What this study adds By synthesizing patient-level data from published case reports and case series, this review provides a stroke-focused characterization of NBTE, including clinical presentation, infarct topography, underlying etiologies, management strategies, recurrent cerebrovascular events, and mortality. The findings highlight multifocal infarction, malignancy-associated NBTE, and recurrent stroke despite anticoagulation as key clinical concerns, while emphasizing that observed associations with anticoagulant class should be viewed as hypothesis-generating rather than definitive treatment guidance