Publications by Year: 2026

BACKGROUND: The prevalence and prognostic significance of liver biomarkers in heart failure (HF) with mildly reduced or preserved ejection fraction are uncertain, with both potential hemodynamic and metabolic contributions to liver dysfunction in these patients. We evaluated the prevalence and prognostic value of liver biomarkers and assessed the effects of the nonsteroidal mineralocorticoid receptor antagonist finerenone on these biomarkers and clinical outcomes in FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure).

METHODS: FINEARTS-HF was a randomized, double-blind, placebo-controlled trial that enrolled 6001 patients with left ventricular ejection fraction ≥40%, evidence of structural heart disease, and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Liver biomarkers examined were total bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase.

RESULTS: Among 5873 patients with available baseline bilirubin measurements, 11.9% had elevated levels (>1.0 mg/dL). Higher bilirubin levels were associated with a greater risk of total worsening HF events and cardiovascular death. Compared with placebo, finerenone rapidly reduced bilirubin and alkaline phosphatase levels (but not transaminase levels), with effects sustained over time. Finerenone reduced the risk of total worsening HF events and cardiovascular death across all bilirubin tertiles (T1 [<0.4 mg/dL], rate ratio 0.94 [95% CI, 0.75-1.17]; T2 [0.5-0.6 mg/dL], 0.83 [0.66-1.05]; T3 [≥0.7 mg/dL], 0.77 [0.62-0.97]), with no significant interaction by bilirubin level (Pinteraction=0.43). Consistent effects were observed for the components of the primary outcome, all-cause death, and improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score.

CONCLUSIONS: Baseline bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of finerenone on morbidity and mortality in HF with mildly reduced or preserved ejection fraction. Finerenone reduced bilirubin and alkaline phosphatase, suggesting a possible decongestive effect in HF with mildly reduced or preserved ejection fraction.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04435626.

BACKGROUND: Medial dished (MD) liner designs for cruciate-retaining (CR) total knee arthroplasty (TKA) are a relatively novel development. MD tibial inserts have a more constraining medial side, which allows for more similar kinematics and function to a native knee.

AIM: To evaluate the clinical results and patient-reported outcomes after CR TKA procedures utilizing a kinematically designed medial dish system.

METHODS: A multicenter, retrospective cohort review of 139 primary elective TKAs utilizing a kinematically designed CR Knee System (JOURNEY™ II CR MD; Smith and Nephew, Memphis, TN, United States) at three different institutions with a minimum of two years of follow-up. Demographic information, clinical outcomes, and patient-reported outcome measures were collected and analyzed.

RESULTS: With up to 3.7 years from surgery, overall implant survivorship was 98.6%. There were significant postoperative increases in the average Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores (17.4 at 6 months, 26.1 points at two years or more, P < 0.001).

CONCLUSION: The combination of high implant survivorship and substantial improvements in patient-reported outcome measures suggests that the medial dish tibial insert represents a safe and effective option within TKA. Additional investigation is necessary to evaluate the long-term survivorship of this design.

Immunoglobulin A (IgA) nephropathy is a common cause of kidney failure and can recur after kidney transplantation, increasing the risk of allograft loss. Effective treatments for recurrent IgA nephropathy in kidney transplant recipients are urgently needed. Iptacopan is a complement factor B inhibitor that received accelerated approval by the US Food and Drug Administration in August 2024 for the treatment of high-risk native IgA nephropathy based on trials that excluded transplant recipients. In this case series, we report our early experience with iptacopan in three individuals with biopsy-confirmed recurrent IgA nephropathy after kidney transplant. All received iptacopan for ≥3 months in combination with a short course of systemic corticosteroids. Two individuals demonstrated significant reductions in proteinuria and resolution of microscopic hematuria. One individual developed progressive graft dysfunction; repeat biopsy showed persistent active glomerulonephritis with codeposition of IgG, suggesting a more aggressive or atypical disease phenotype. These early data suggest that iptacopan, in combination with short-term corticosteroids, may offer therapeutic benefit in selected kidney transplant recipients with recurrent IgA nephropathy, warranting further investigation.

BACKGROUND: While varices and variceal bleeds are well-known and feared complications of advanced cirrhosis and portal hypertension, omental variceal bleed are a rare sequala even in patients with known esophageal or gastric varices. While rare, omental varices pose a risk for hemoperitoneum if ruptured, which is a life-threatening complication with high mortality rates despite surgical intervention.

CASE SUMMARY: This report reviews the case of a patient 36-year-old female with alcohol related cirrhosis decompensated by ascites, but no history of varices admitted for hemorrhagic shock from spontaneous rupture of omental varices requiring emergency surgery. She underwent the first documented successful orthotopic liver transplantation the same admission.

CONCLUSION: This case report and literature review stresses the importance of early consideration and identification of intraabdominal variceal sources in cirrhotic patients with refractory shock.

BACKGROUND: Accessing brain magnetic resonance imaging (MRI) can be challenging, especially for underserved patients, which may lead to disparities in neurological diagnosis.

METHOD: This mixed-methods study enrolled adults with one of four neurological disorders: mild cognitive impairment or dementia of the Alzheimer type, multiple sclerosis (MS), Parkinson disease (PD), or stroke. Participants were enrolled at the Massachusetts General Hospital outpatient clinic in Boston (01/2021-08/2025) and underwent a point-of-care, low-field portable MRI (pMRI) using a 0.064 T scanner (Hyperfine) and pre- and post-scan surveys. For comparison, all participants had received a standard clinical brain MRI of at least 1.5T.

RESULTS: Of the 130 participants (54% male, 46% female), the mean age was 60.6 years (standard deviation (SD) = 17.5). 71% reported at least one barrier to MRI care. The median interval between pMRI and standard MRI brain imaging was 48.5 days (25th, 75th percentiles: 26, 112.5). Participants rated pMRI as highly tolerable, with 93% reporting comfort scores ≥ 7 (on a 10-point scale), and 78% indicating willingness to undergo future pMRI. Mean comfort ratings were significantly higher for pMRI (8.4) compared to traditional MRI (7.5; p < 0.05), though the effect size was moderate (η2 = 0.096). No differences in tolerability or comfort were observed across disease, age, or sex groups. Common barriers to standard MRI access included transportation, cost, and scheduling, particularly among low-income or unemployed participants. Qualitative feedback emphasized the need for better physical accommodations but broadly supported the acceptability and potential uses of pMRI.

CONCLUSION: These findings support the feasibility, tolerability, and high patient acceptability of pMRI.

BACKGROUND: Field observation is a valuable but underused methodological approach in patient-reported outcomes (PRO) implementation research, particularly in low-resourced settings such as community cancer centers (CCCs). Rooted in ethnographic tradition, field observations allow researchers to assess clinical environments in real time, capturing workflow processes, communication patterns, and contextual factors not readily accessible through interviews or surveys. When applied through implementation science frameworks such as the Consolidated Framework for Implementation Research (CFIR), this method supports systematic assessment of organizational structures, implementation climate, and readiness for change. The objective of this study was to develop and apply a structured field observation protocol to inform context-specific PRO implementation workflows in CCCs providing breast cancer care.

METHODS: Structured field observations were conducted at five CCCs during the pre-implementation phase of a larger initiative to integrate imPROVE, a web-based PRO data collection platform, into routine care. The protocol followed three phases: (1) pre-visit planning with site leads to gather contextual and logistical data; (2) in-clinic observations by two trained researchers documenting clinic layout, patient flow, staff roles, and communication; and (3) post-visit data processing using structured templates and CFIR-guided analysis. Field notes were triangulated with insights from staff, patient and community leader interviews (reported elsewhere) to generate site-specific implementation strategies.

RESULTS: Observations uncovered key contextual differences across sites, including clinic layout, staffing stability, patient volume, caregiver presence, and digital literacy. These variations influenced feasibility and shaped tailored implementation plans. For example, sites with long waiting periods between check-in and exam were better suited for waiting-room PRO collection, while others required provider-facilitated approaches. Language diversity and caregiver engagement also emerged as critical determinants. Sites with strong leadership continuity and clear workflows demonstrated higher implementation readiness.

CONCLUSION: Field observation was instrumental in identifying real-world barriers and facilitators that shaped site-specific PRO workflows. This approach enhanced ecological validity, stakeholder engagement, and the feasibility of PRO integration in CCCs. Embedding field observation in early implementation planning strengthens the methodological rigor of PRO research and supports sustainable, context-aligned interventions in resource-constrained settings.

BACKGROUND AND OBJECTIVES: Accurate visualization of thermal damage zone (TDZ) in the dermis is critical for energy-based device (EBD) and burn research. While nitroblue tetrazolium chloride (NBTC) staining and birefringence imaging are commonly used, both rely on detecting loss-of-signal, thereby only inferring TDZ indirectly. Other methods, such as hematoxylin and eosin and Masson's trichrome, are protocol-sensitive and limited in sufficiency and consistency for TDZ visualization. This study aims to validate a novel staining protocol optimized for direct and selective visualization of thermally denatured collagen, termed Ahn-van Gieson stain (AVG).

METHODS: Protocol analysis was performed to identify sources of inconsistency in the iron hematoxylin-based Verhoeff-van Gieson stain, followed by comparison of multiple versions of modifications for optimization. Horizontal sections of the human dermis were irradiated with a defocused CO₂ laser beam under thermal recording with a 10.6 μm notch filter. Thermal data were processed to generate peak temperature and Arrhenius integral maps for collagen denaturation. Slides stained with the optimized AVG protocol were overlaid with thermal maps for validation.

RESULTS: Iron-hematoxylin stained both TDZ and surrounding collagen regions, but subsequent differentiation using FeCl3 led to partial loss of staining within TDZ, contributing to inconsistent results. Replacing the FeCl3 differentiation step with 1 min 1% acid alcohol treatment produced the most consistent and high-contrast visualization of TDZ. The protocol required approximately 40 min, functioned reliably on both frozen and paraffin-embedded samples, and was compatible with birefringence imaging. The stained areas corresponded well with thermal maps for collagen denaturation, supporting the specificity of AVG for thermally denatured collagen.

CONCLUSIONS: The novel protocol enables direct, high-contrast, and reproducible visualization of thermally denatured collagen using standard equipment in a short time. It holds promise as a practical histological tool in EBD and burn research, where precise collagen damage visualization is essential.

Heparan sulfate proteoglycans (HSPGs) have been recognized as key plasma membrane-tethered co-receptors for a broad range of growth factors and cytokines containing cationic heparan-binding domains1,2. However, how HSPGs mechanistically mediate signalling at the cell surface-particularly in the context of cell surface RNA-remain poorly understood. During developmental and disease processes, vascular endothelial growth factor (VEGF-A), a heparan sulfate-binding factor, regulates endothelial cell growth and angiogenesis3. The regulatory paradigm for endothelial cell-mediated selectively of VEGF-A binding and activity has largely been focused on understanding the selective sulfation of the anionic heparan sulfate chains4-8. Here we examine the organizational rules of a new class of anionic cell surface conjugates, glycoRNAs9,10, and cell surface RNA-binding proteins (csRBPs11,12). Leveraging genome-scale knockout screens, we discovered that heparan sulfate biosynthesis and specifically the 6-O-sulfated forms of heparan sulfate chains are critical for the assembly of clusters of glycoRNAs and csRBPs (cell surface ribonucleoproteins (csRNPs)). Mechanistically, we show that these clusters antagonize heparan sulfate-mediated activation of ERK signalling downstream of VEGF-A. We demonstrate that the heparan sulfate-binding domain of VEGF-A165 is responsible for binding RNA, and that disrupting this interaction enhances ERK signalling and impairs vascular development both in vitro and in vivo and is conserved across species. Our study thus uncovers a previously unrecognized regulatory axis by which csRNPs negatively modulate heparan sulfate-mediated signalling in the context of angiogenesis driven by VEGF-A.

AIMS: Scarce literature exists regarding the spectrum of vascular neoplasms of the distal female genital tract. Herein, we describe the clinicopathologic features of a cohort of intermediate to malignant endothelial neoplasms of the vulva and vagina.

METHODS AND RESULTS: Specimens were identified retrospectively from in-house and consultation files at our institution. Clinicopathologic data was obtained from review of the chart and available histologic material. Nineteen cases were identified in total. Kaposi sarcoma (n = 2) was of the enigmatic 'sporadic' form in elderly non-HIV females. Kaposiform haemangioendothelioma (n = 1) presented at an older (rather than paediatric) age and was negative for HHV-8 by IHC; both Kaposi sarcomas were positive. Pseudomyogenic haemangioendothelioma (n = 2) presented in elderly females (rather than young males) with positivity for both FOSB and AE1/AE3. Epithelioid haemangioendothelioma (n = 8), showed variably well-developed chondromyxoid matrix and consistent positivity for CAMTA1 IHC. Angiosarcomas were disproportionately of the epithelioid subtype, with high-grade cytologic atypia, destructive infiltration and rare EMA positivity.

CONCLUSIONS: While many morphologic features of vascular lesions at this site are shared with those of extra-genital soft tissues, pathologists must be aware that these tumours may occur in the vulvovaginal area and display unconventional clinical profiles. As such, a broad differential for epithelioid and spindle cell neoplasms at this site is prudent.