Publications

BACKGROUND: The efficacy and safety of intravenous thrombolysis with tenecteplase within 24 h after stroke onset due to basilar artery occlusion are not well studied. We aimed to assess whether intravenous tenecteplase administered within 24 h after symptom onset improved functional outcome compared with standard medical treatment in patients with basilar artery occlusion.

METHODS: TRACE-5 was a prospective, randomised, open-label, blinded-endpoint, superiority, phase 3 trial conducted at 66 stroke centres in China. We included patients aged 18 years or older with stroke due to basilar artery occlusion who were eligible for intravenous thrombolytics within 24 h of stroke onset or the time they were last known to be well and had a pre-stroke modified Rankin scale (mRS) score of 3 or less (scores range from 0 to 6, with higher scores indicating greater disability). Patients were randomly assigned to receive a single intravenous bolus of tenecteplase (0·25 mg/kg; maximum 25 mg) within 24 h after symptom onset or standard medical treatment (which could include intravenous alteplase at 0·9 mg/kg, maximum 90 mg, within 4·5 h of symptom onset; anticoagulation; or antiplatelets), with or without endovascular thrombectomy. The primary outcome was a score of 0-1 on the mRS or return to the baseline mRS score (if the baseline pre-stroke mRS score was 2-3) at 90 days. Safety outcomes were symptomatic intracranial haemorrhage and death. The primary outcome and safety outcomes were assessed in all randomly assigned participants included in their originally assigned groups. This trial is registered with ClinicalTrials.gov, NCT06196320.

FINDINGS: Between Jan 24, 2024, and June 20, 2025, 452 patients were enrolled (mean age 66·4 years [SD 11·2], 321 [71%] males, and 131 [29%] females), of whom 222 (49%) subsequently underwent thrombectomy; 221 were randomly assigned to receive tenecteplase and 231 to receive standard medical treatment. Alteplase was used in 80 (35%) of the patients in the standard medical treatment group. An mRS score of 0-1 or return to the baseline mRS score occurred in 83 (38%) patients in the tenecteplase group and 66 (29%) patients in the standard medical treatment group (adjusted relative rate 1·50 [95% CI 1·09-2·08], p=0·014). Symptomatic intracranial haemorrhage within 36 h occurred in four (2%) patients in the tenecteplase group and seven (3%) patients in the standard medical treatment group (adjusted relative rate 0·58 [95% CI 0·17-1·99]). All-cause mortality at 90 days was similar between groups (65 [29%] patients in the tenecteplase group and 71 [31%] patients in the standard medical treatment group; adjusted relative rate 0·87 [95% CI 0·62-1·22]), as was the proportion of patients with an mRS score of 5-6 at 90 days (82 [37%] vs 89 [39%]; 0·87 [0·65-1·18]).

INTERPRETATION: In this trial involving Chinese patients with ischaemic stroke due to basilar artery occlusion, tenecteplase within 24 h after stroke onset improved functional outcome compared with standard medical treatment. The incidence of symptomatic intracranial haemorrhage and death was similar.

FUNDING: Noncommunicable Chronic Diseases-National Science and Technology Major Project, Beijing Municipal Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

PURPOSE: The optimal excitation flip angle (FA) for short-TR spin-echo acquisitions can be well above 90°, far beyond the small FAs suited for commonly-used sinc RF pulses. The goal of this study was to characterize the benefits of Shinnar-Le Roux (SLR) over sinc pulses for these acquisitions, which may lead to improvements in the temporal and spatial specificity of fMRI.

METHODS: Slice profiles were obtained either through Bloch simulation or from scans of an oil phantom at 7 T (T1/TR = 1500/300 ms). Spatial integrals of the slice profiles were used as measures of the resulting (relative) SNR. We also measured the spatial profile of spin-echo "linescan" acquisitions, which are of increasing interest for in vivo studies of cortical layers.

RESULTS: For 2D acquisitions with the parameter values used here, the high-quality slice profiles provided by the SLR pulses resulted in an SNR gain of ∼100% relative to sinc pulses. For 1D linescan acquisitions, the SNR gains were even higher: ∼150%.

CONCLUSIONS: The large gains in SNR described here should enhance any studies using short-TR spin-echo acquisitions; in particular, we anticipate application of these SLR pulses to fMRI studies that target the microvasculature with both high spatial and high temporal resolution. Potential limitations, due to high SAR or B1+ inhomogeneity, should however be kept in mind, especially at ultra-high field strengths.

BACKGROUND & AIMS: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and high cardiovascular risk often have advanced liver fibrosis, but data on associations and outcomes are limited. The aim of this study was to evaluate the relationships between cardiovascular risk categories and liver fibrosis severity, liver fibrosis progression, and liver-related events (LREs) in MASLD.

METHODS: Patients with MASLD from the VCTE-Prognosis cohort were stratified into low, intermediate, and high cardiovascular risk categories using the Framingham Risk Score (FRS), Primary Care Equivalents (PCE), or Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) scores. Outcomes included the prevalence of advanced fibrosis (liver stiffness ≥10 kPa), liver stiffness progression (≥20% increase and Baveno category upshift), and LRE (hepatocellular carcinoma, hepatic decompensation, liver transplantation, or liver-related mortality). Associations were assessed using multivariable logistic regression and Fine-Gray competing-risks models.

RESULTS: Among 9312 patients with MASLD (mean age, 54.4 ± 11.0 years; 56.8% male; 87.4% Asian), advanced fibrosis prevalence increased with cardiovascular risk: adjusted odds ratios (ORs) were 2.72 (95% confidence interval [CI], 2.25-3.28; P < .001) for FRS, 1.83 (95% CI, 1.46-2.29; P < .001) for PCE, and 2.93 (95% CI, 2.33-3.69; P < .001) for PREVENT. Over a median follow-up of 4.5 years, liver stiffness progression occurred in 5.0% of patients, more frequently in high-risk groups (adjusted subdistribution hazard ratio [SHR], 1.56; 95% CI, 1.14-2.15; P = .006 for PCE and adjusted SHR, 1.85; 95% CI, 1.33-2.56; P < .001 for PREVENT). LREs occurred in 1.4% of patients, with higher incidence in high-risk groups (adjusted SHR, 2.12; 95% CI, 1.19-3.77; P = .010 for FRS; adjusted SHR, 2.01; 95% CI, 1.08-3.74; P = .027 for PCE; and adjusted SHR, 2.80; 95% CI, 1.40-5.61; P = .004 for PREVENT).

CONCLUSIONS: Higher cardiovascular risk is associated with greater prevalence of advanced liver fibrosis, liver stiffness progression, and LRE incidence in MASLD.

PURPOSE: The reported incidence of subsequent malignant neoplasms (SMNs) in long-term survivors of pediatric classic Hodgkin lymphoma (cHL) is based on patients treated with outdated radiation therapy (RT) doses and techniques. The risk associated with modern mediastinal RT in pediatric cHL is unknown.

METHODS AND MATERIALS: We modeled the risk of SMN in children with cHL who enrolled in the multi-institutional Children's Oncology Group AHOD1331 trial (2015-2019) and received mediastinal RT.

RESULTS: Among 587 trial patients, 296 (50%) received mediastinal RT and were eligible for this analysis. Proton therapy was used for 25%, photon intensity modulated RT (IMRT) for 46%, and photon 3-dimensional conformal RT (3D-CRT) for 28%. The RT prescription dose was 21 Gy in 83% and 30 Gy in 16%. The estimated mean lifetime attributable risk at 70 years of age of breast carcinoma (females) was 2.92% (1.45% proton; 4.36% IMRT; 1.82% 3D-CRT; P < .0001), lung carcinoma was 5.37% (4.15% proton; 6.24% IMRT; 5.07% 3D-CRT; P < .0001), and thyroid carcinoma was 0.17% (0.25% proton; 0.17% IMRT; 0.12% 3D-CRT; P = .271). The predicted risk of breast carcinoma was higher among female patients treated with their arms raised versus arms down (P < .0001).

CONCLUSIONS: Normal tissue doses associated with contemporary mediastinal RT produce lower predicted SMN risks than were observed in cohorts treated with historical RT approaches, with substantial variation among individuals. On average, proton therapy is associated with a lower predicted risk. These findings have implications for the selection of therapies, counseling of patients, planning of RT, and recommendations for SMN screening.

PURPOSE: To report on the presentation, treatment, and visual outcome of stromal keratitis (SK) in the Zoster Eye Disease Study (ZEDS).

DESIGN: Secondary analysis of SK end point of randomized clinical trial.

SUBJECTS: Patients with herpes zoster ophthalmicus (HZO) were randomized in a double-masked clinical trial of oral valacyclovir 1 g daily or placebo for 1 year. They were followed prospectively every 3 months for 18 months for end points of SK, iritis (IR), endothelial keratitis (EK), or dendritiform epithelial keratitis (DEK).

METHODS: Presentation of recurrent, new, or worsening SK was evaluated retrospectively by treatment assignment, randomization strata, and use of topical steroids. Investigators had been allowed discretionary treatment of end points including open-label valacyclovir and topical steroids. Visual outcome and treatment with open-label oral valacyclovir and topical steroids were evaluated.

MAIN OUTCOME MEASURES: Use of open-label valacyclovir and topical steroid treatment of recurrent, new, or worsening SK, and visual acuity at 12 months.

RESULTS: Recurrent, new, or worsening SK occurred in 105 of 527 participants (20%). The randomization group was not associated with this complication. Mean best-corrected visual acuity at enrollment was logMAR 0.10 ± 0.14 with no difference at 1 year, logMAR 0.13 ± 0.2, and no difference between valacyclovir and placebo groups at enrollment or at 1 year. Among the 105 instances of SK, 79 (75%) were recognized at scheduled study visits rather than at episodic visits. In only 11 of 105 (10%) of recurrent, new, or worsening SK did masked investigators opt to treat with open-label oral antiviral. At the time of SK complication, 52 of 105 participants (50%) were receiving topical steroids, but 47 of 52 participants (90%) receiving topical steroids were using 1× daily or less, 21 of 47 participants (45%) were using high potency, and 26 of 47 participants (55%) were using low potency (P = .47). Of 48 of 105 participants (47%) receiving no topical steroids at recurrent, new, or worsening SK, 18 of 48 (38%) had discontinued steroids in the prior 3 months. A total of 38 of 48 participants (75%) receiving no topical steroids at complication SK were subsequently treated with high-potency steroids 2× daily or more. Of 26 of 52 participants (50%) receiving low-potency steroids at SK complication, 23 of 26 (88%) were treated with increase in frequency only.

CONCLUSIONS: Individuals with ocular complications of HZO who develop SK generally maintain very good vision without the use of oral antiviral therapy when monitored closely and SK is recognized and treated. Low-potency topical steroids should be considered for treatment and ongoing suppression of SK in HZO.

BACKGROUND: Spironolactone is widely used in dermatology. While routine potassium monitoring is no longer recommended in young, healthy females taking spironolactone for acne, hyperkalemia incidence, risk factors, and monitoring necessity in older females is unclear.

OBJECTIVE: To determine hyperkalemia incidence in females aged ≥45 taking spironolactone for dermatologic conditions.

METHODS: In this retrospective cohort study, 1197 Mass General Brigham medical records from January 1, 2015 through February 25, 2025 were reviewed; 398 cases were analyzed.

RESULTS: Hyperkalemia incidence was 10.1% (40/398) and more commonly observed in older patients (age ≥65: 22.4% versus ages 45-64: 7.9%) and those with ≥1 predisposing comorbidity (medically complex: 14.7% versus healthy: 7.3%). Healthy females aged 45-64 were least affected (6.3%). Patients age ≥65 with ≥1 predisposing comorbidity had the highest incidence (28.1%). Hyperkalemia was generally mild (97.5%), asymptomatic (85%), and did not impact clinical management (62.5%).

LIMITATIONS: Limitations include retrospective design and lack of comparator group.

CONCLUSION: Overall hyperkalemia risk in females aged ≥45 is higher than in younger patients and increased further in specific subpopulations. Hyperkalemia is generally mild and prescription modification is uncommon. While spironolactone use is safe for most patients, monitoring guidelines should be clarified to ensure optimal management in this population.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) offer cardiorenal benefits in patients with type 2 diabetes mellitus (T2DM).

OBJECTIVE: To evaluate safety and effectiveness of SGLT2i in improving clinical outcomes in patients with psoriasis and comorbid T2DM, compared with dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 receptor agonists (GLP1RA).

METHODS: This emulated target trial included adults with psoriasis and T2DM initiating SGLT2i, DPP4i, or GLP1RA between 2013 and 2025. SGLT2i initiators were propensity score-matched to DPP4i initiators and GLP1RA initiators, respectively. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the outcomes.

RESULTS: A total of 8799 SGLT2i initiators and 8799 matched DPP4i initiators with psoriasis and comorbid T2DM, and 11,550 SGLT2i initiators and 11,550 matched GLP1RA initiators, were included. Compared with DPP4i, treatment with SGLT2i was associated with significantly lower all-cause mortality (HR = 0.633, 95% CI = 0.564-0.711) and reduced risks of emergency visits (HR = 0.915, 95% CI = 0.871-0.961), acute kidney injury (HR = 0.834, 95% CI = 0.759-0.916), chronic kidney disease (HR = 0.866, CI = 0.791-0.949), end-stage renal disease (HR = 0.555, 95% CI = 0.438-0.703), and severe sepsis (HR = 0.689, CI = 0.594-0.799). Compared with GLP1RA, treatment with SGLT2i was associated with reduced risks of asthma (HR = 0.822, 95% CI = 0.713-0.946), depression (HR = 0.887, CI = 0.801-0.983), sleep disorders (HR = 0.856, CI = 0.783-0.936), and malignancies (HR = 0.852, 95% CI = 0.764-0.951).

LIMITATIONS: Retrospective design.

CONCLUSION: Treatment with SGLT2i was associated with favorable clinical outcomes in patients with psoriasis and comorbid T2DM. These findings support investigation of SGLT2i as an adjunct therapy in this population.

Myelin-weighted imaging with inversion-recovery ultrashort-echo-time (IR-UTE) is highly motion-sensitive, yet extra hardware or longer scans are impractical. We evaluated whether a 1D superior–inferior (SI) navigator with bit-reversed spoke-angles mitigates motion artifacts without extending acquisition. Dual-echo IR-UTE was implemented at 3T. After an adiabatic inversion pulse, 21 spokes were acquired per segment around the white-matter null point, and dual-echo subtraction suppressed residual long-T2 signals. Adding SI-navigators at the end of each segment allows motion detection without lengthening TR. And bit-reversal is used to pseudo-randomize the spoke-angles. Bloch simulations of a 2D synthetic brain removed 10% of spokes to mimic gating. Three volunteers were scanned: (i) sequential-ordering, no-motion; (ii) bit-reversed, no-motion; (iii) bit-reversed with deliberate head nods. The navigator rejected 1,280 of 12,000 spokes (10.7%) during nodding, and the same gating was reconstructed on motion-free data. Simulation showed coherent streaks for sequential ordering but an isotropic point-spread function for bit-reversal. In vivo, gating degraded only the sequential dataset. bit-reversal preserved subcortical and deep-white-matter detail. During intentional nodding, gating with bit-reversal enhanced myelin contrast, outperforming the image reconstructed from the ungated data. The SI-navigator plus bit-reversal enables effective motion gating without hardware or time penalty, supporting routine motion-robust myelin mapping.

OBJECTIVE: To determine whether frailty, as quantified using the Five-Item Modified Frailty Index (mFI-5), independently predicts postoperative complications in patients undergoing surgery for diabetic foot ulcers (DFUs), and to assess its utility as a clinical risk stratification tool.

APPROACH: A retrospective cohort analysis was conducted using the American College of Surgeons National Surgical Quality Improvement Program database (2015-2021). Adults with type 2 diabetes and International Classification of Diseases, 10th Revision-coded DFUs (E11.621) undergoing elective surgery were identified and stratified into frail (mFI-5 >2) and prefrail (mFI-5 ≤2) groups. Preoperative variables, perioperative characteristics, and 30-day postoperative outcomes were compared using univariate tests, followed by multivariable logistic regression adjusting for clinically relevant confounders. The study design, reporting, and analysis followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for observational cohort studies.

RESULTS: Among 2,819 patients, 714 (25.3%) were classified as frail. Frail patients had significantly higher rates of overall complications (50.6% vs. 32.9%), mortality (4.1% vs. 1.6%), and medical complications, including reintubation and urinary tract infection. In adjusted models, frailty independently predicted any postoperative complication (odds ratio [OR] = 1.34, 95% confidence interval [CI] 1.05-1.70, p = 0.02) and medical complications (OR = 1.53, 95% CI: 1.12-2.07, p = 0.007).

INNOVATION: This is the first large-scale study applying the mFI-5 to DFU surgery, demonstrating that frailty provides prognostic information beyond traditional comorbidity-based assessments and offers a rapid, objective tool for perioperative risk evaluation.

CONCLUSION: Frailty, as measured by the mFI-5, independently predicts postoperative morbidity and mortality after DFU surgery. Incorporating preoperative frailty screening may improve surgical decision making, resource allocation, and enhance outcomes in this high-risk population.