Citations

Background The optimal imaging guidance for percutaneous coronary intervention (PCI) in complex coronary lesions remains a matter of debate. This meta-analysis compares the efficacy and safety of optical coherence tomography (OCT)-guided PCI versus angiography-guided PCI. Methods Following PRISMA guidelines, we systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov from inception to December 2024. Randomized controlled trials (RCTs) comparing OCT-guided PCI to angiography-guided PCI were included. Data analysis was performed using RevMan 5.4, with risk ratios (RR) and 95% confidence intervals (CI) calculated for dichotomous outcomes using a random-effects model. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results Eleven RCTs involving 6432 participants were included. OCT-guided PCI showed no statistically significant reduction in all-cause mortality compared to angiography-guided PCI (RR 0.72, 95% CI 0.51–1.01, P = 0.06, I 2 = 0%). However, OCT-guided PCI was associated with a significant reduction in cardiac death (RR 0.52, 95% CI 0.30–0.90, P = 0.02, I 2 = 0%), major adverse cardiovascular events (MACE) (RR 0.70, 95% CI 0.55–0.89, P = 0.003, I 2 = 0%), stent thrombosis (RR 0.53, 95% CI 0.33–0.87, P = 0.01, I 2 = 0%), and major edge dissection (RR 0.47, 95% CI 0.34–0.65, P < 0.00001, I 2 = 0%). Upon stratification of studies on the basis of follow-up duration, similar results were noted. Conclusion OCT-guided PCI demonstrated significant benefits in reducing cardiac death, MACE, and procedural complications compared to angiography-guided PCI. These findings support the integration of OCT in complex PCI, although further studies are warranted to assess its impact on long-term mortality.

Background: Resistant hypertension represents a significant clinical challenge, often driven by dysregulated aldosterone production. Aldosterone synthase inhibitors (ASIs) are a novel therapeutic class designed to directly suppress aldosterone biosynthesis. This study aimed to synthesize evidence regarding the comparative efficacy, optimal dosing, and dose–response relationships of three ASIs—baxdrostat, lorundrostat, and osilodrostat—for the treatment of resistant hypertension. Methods: A systematic review and network meta-analysis (NMA) were conducted following PRISMA 2020 guidelines. We searched PubMed, Web of Science, and CENTRAL for randomized controlled trials (RCTs) published up to 31 October 2025. The primary outcome was the mean change in systolic blood pressure (SBP) compared to placebo. We utilized a frequentist random-effects model, characterized dose–response relationships via meta-regression, and ranked treatments using the Surface Under the Cumulative Ranking Curve (SUCRA). Results: The analysis included 8 RCTs comprising 3253 participants. Baxdrostat 2 mg once daily demonstrated the greatest antihypertensive efficacy with a mean SBP reduction of −13.8 mmHg (95% CI: −17.5 to −10.1) versus placebo, followed by Lorundrostat 100 mg (−12.5 mmHg) and Baxdrostat 1 mg (−11.5 mmHg). SUCRA analysis identified Baxdrostat as the highest-ranked treatment (83.0%), followed by Lorundrostat (67.8%) and Osilodrostat (55.5%). Dose–response meta-regression revealed strong linear correlations for Baxdrostat (R2 = 0.91), Osilodrostat (R2 = 0.81), and Lorundrostat (R2 = 0.80). Conclusions: ASIs, particularly Baxdrostat and Lorundrostat, offer robust blood pressure reductions in patients with resistant hypertension. The strong linear dose–response relationships suggest these agents have a favorable therapeutic window for titration. While effective, clinical implementation requires careful monitoring for adverse events.

ABSTRACT Background This study aimed to explore the effect of family history (FH) and polygenic risk scores (PRS) for multiple psychiatric disorders on lithium response in bipolar disorder (BD). Method The sample included patients from the Mayo Clinic BD Biobank. FH in first‐degree relatives was obtained via the patient questionnaire. Linear regression models tested the association of FH and PRS for BD, major depressive disorder (MDD), schizophrenia (SCZ), alcohol use disorder (AUD), anxiety disorder (ANX), and attention‐deficit/hyperactivity disorder (ADHD) with lithium response measured by the Alda A score adjusted for the Alda B sum score. Post hoc models additionally adjusted for clinical covariates (age at onset, rapid cycling, and BD subtype). Results 716 patients had Alda scores for lithium response (61.9% females, mean age = 43.4 years). FH‐BD ( β = −0.57, p = 0.015), AUD ( β = −0.44, p = 0.045), and ANX ( β = −0.61, p = 0.050) were associated with worse lithium response. After adjusting for clinical covariates, associations for FH‐BD and FH‐ANX were no longer significant. PRS‐BD was associated with better response ( β = 0.22, p = 0.041), while PRS‐MDD ( β = −0.28, p = 0.01) and PRS‐ADHD ( β = −0.24, p = 0.028) were associated with worse response, with effects largely unchanged after adjusting for clinical covariates. In the combined model considering all FHs simultaneously, only FH‐BD remained significantly associated with worse lithium response ( β = −0.71, p = 0.039). In the combined model for PRS, only PRS‐BD ( β = 0.31, p = 0.008; better response) and PRS‐MDD ( β = −0.29, p = 0.020; worse response) showed significant associations. Conclusions In this exploratory study, FH‐BD, AUD, and ANX were associated with poor response, though only FH‐AUD remained significant after adjusting for clinical factors. PRS‐BD predicted better response, while PRS‐MDD was associated with worse response. These findings suggest independent and potentially complementary roles of FH and PRS. Integrating both familial and genetic risk measures may improve personalized treatment strategies and outcomes for BD patients.

Cutaneous metastases occur in up to 20% of patients with advanced melanoma and can be difficult to manage with systemic therapy alone. Pembrolizumab is a standard therapy with limited local treatment options for cutaneous manifestations. Imiquimod has shown activity in other skin cancers but is less well studied in melanoma. We conducted a pilot trial to evaluate the feasibility, safety, and preliminary efficacy of combining topical imiquimod with intravenous pembrolizumab in patients with unresectable melanoma with cutaneous metastases. This was a single-center, open-label, non-randomized interventional study (NCT03276832). Eligible patients received pembrolizumab IV every 21 days plus topical imiquimod 5% applied Monday–Friday each cycle. The primary endpoint was objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, and safety. In this study, seven patients were enrolled, five were male and two females; one was Hispanic and six were non-Hispanic White. Median treatment exposure was 8 cycles. ORR was 57.1%, with 3 patients (42.9%) achieving complete response, 1 partial response, and 2 stable disease. The 7-month PFS rate was 57.1%. At study closure, 4 patients remained alive without progression, 2 were alive following progression, and 1 had died of disease. Toxicities were mostly grade 1, with fatigue and anemia most common with minimal grade 2 events. The combination of topical imiquimod and pembrolizumab was feasible, safe, and demonstrated promising antitumor activity in unresectable cutaneous melanoma. A 42.9% CR rate in this small elderly cohort supports further evaluation of local immune modulation with systemic PD-1 blockade for cutaneous melanoma.

OBJECTIVE Ruptured, large pediatric arteriovenous malformations (AVMs) pose a significant management challenge due to high rerupture risk and the morbidity of conventional treatments. Volume-staged stereotactic radiosurgery (VS-SRS) has emerged as an alternative; however, evidence for its use in this specific population is limited. This study aimed to evaluate the long-term efficacy and safety of VS-SRS for ruptured, large AVMs in a dedicated pediatric cohort. METHODS This international, multicenter, retrospective cohort study from 21 centers analyzed outcomes for 42 pediatric patients (age < 18 years) with previously ruptured, large AVMs treated with VS-SRS. The primary outcome was complete AVM obliteration, and secondary outcomes included post-SRS hemorrhage, radiation-induced changes (RICs), and favorable outcome. Favorable outcome in this study was defined as obliteration without post-SRS hemorrhage or permanent RIC. RESULTS At the initial SRS, the median patient age was 14.5 years, and the median AVM volume was 15.0 cm 3 ; most AVMs were high grade (Spetzler-Martin grades IV and V). With a median follow-up of 41.5 months, complete AVM obliteration was achieved in 21 patients (50.0%). The cumulative obliteration rate was 37% at 5 years and 56% at 10 years. Patients with a nidus volume of ≤ 10 cm 3 had significantly higher cumulative obliteration rates than those with a nidus volume > 10 cm 3 (log-rank test, p = 0.021). Similarly, patients treated with a prescription dose > 17 Gy showed significantly higher cumulative obliteration rates compared to those treated with a dose ≤ 17 Gy (log-rank test, p = 0.012). The cumulative 5-year incidences of hemorrhage and RICs following VS-SRS were 19% and 7%, respectively. In multivariable analysis, only larger total AVM volume was an independent predictor of a lower likelihood of favorable outcome (hazard ratio 0.89, 95% CI 0.80–0.99; p = 0.036). CONCLUSIONS In this multicenter pediatric cohort, VS-SRS for ruptured, large AVMs provides a reasonable chance of long-term obliteration, but generally acceptable risks of post-SRS hemorrhage and RICs exist. VS-SRS should be considered as an option for pediatric patients with large, ruptured AVMs.

Abstract Newer approaches to control alloreactivity may produce similar transplant outcomes using HLA-mismatched donors vs HLA-matched unrelated donors (MUD). However, prospective comparisons are lacking. BMT CTN 1702 used a donor search prognosis score to assign patients to an 8/8 HLA MUD or the center’s preference of haploidentical related donors (HAPLO), mismatched unrelated donors (MMUD), or umbilical cord blood (UCB). Outcomes of MUD were compared to HAPLO, MMUD, and UCB transplantation after adjusting for covariates. Patients (n = 1179 [93% adults]) underwent transplantation with MUD (n = 772), HAPLO (n = 254), MMUD (n = 112), and UCB (n = 41) at a median of 3.7, 3.4, 3.9, and 3.8 months from enrollment. Posttransplant cyclophosphamide (PTCy) was used in 23.9%, 83.9%, 65.2%, and 0% of MUD, HAPLO, MMUD, and UCB. In multivariate analyses, compared to MUD, survival was lower for UCB (hazard ratio [HR], 2.65; P&lt; .001) but not statistically different for HAPLO and MMUD (HRs, 1.08 and 1.18, respectively). Relapse risk was not significantly different by donor, but treatment-related mortality (HR, 3.31; P&lt; .001) and disease-free survival (HR, 1.99; P = .002) were inferior for UCB but not different for HAPLO and MMUD than MUD. In patients who received PTCy, HAPLO and MMUD were associated with increased grade 3 or 4 acute graft-versus-host disease (GVHD; HR, 2.39 [P = .017] and 2.53 [P = .038], respectively) and chronic GVHD (HR, 1.71 for both; P = .028 and .080) than MUD, but other outcomes were not different. HAPLO or MMUD may be used to expedite transplantation when finding MUD is unlikely. This study was registered at www.clinicaltrials.gov as NCT03904134.

Abstract Genetic loss of the mitochondrial control enzyme PINK1 leads to Parkinson’s disease, characterized by dopaminergic neuron degeneration and neuroinflammation, yet its role in glia remains poorly understood. To address this gap, we investigated how the function of astrocytes and their ability to support neurons is influenced by PINK1 deficiency. For the first time, we demonstrate that human astrocytes exhibit robust PINK1 activity. Next, the first bulk transcriptomic study of human PINK1 mutant astrocytes was performed followed by biochemical validation at the protein level, uncovering homeostatic collapse. Co-culture experiments demonstrated that this astrocyte dysfunction drives neuronal damage through non-cell-autonomous mechanisms. Notably, pharmacological enhancement of autophagy successfully mitigated this inflammatory secretome, indicating that mitochondrial quality control deficits are reversible. These findings establish an unexpected role for PINK1 in glial biology, reveal that astrocytes are vulnerable to mitophagy deficits, and highlight a novel mechanistic link connecting mitochondrial dysfunction, neuroinflammation, and neurodegeneration.

Abstract Foreign body response is a common yet serious challenge for biomedical implants. It can trigger inflammation and eventually lead to the formation of a fibrotic capsule, which compromises device function. Although significant efforts have been made to develop antifibrotic surface coatings for implantable materials, developing broadly applicable solutions remains challenging due to the diversity of materials used in biomedical implants. Here, we propose a simple and versatile strategy to develop antifibrotic coatings for biomedical implants. Photoreactive benzophenone groups are incorporated into designer polymers to enable covalent attachment to various substrates. The effect of benzophenone group density within polymer chains on surface coating efficiency was investigated, and an optimal BP incorporation ratio was identified. Polymers incorporating varying ratios of an anti-fibrotic small molecule and anti-fouling zwitterionic moieties were synthesized and successfully attached to silicone implants. In vivo evaluation of these implants in C57BL/6 mice identified an optimized polymer composition that reduced fibrotic capsule thickness by around 60%. Coating of commercial medical catheters with this optimized polymer reduced collagen deposition by over 3.5-fold following 4 weeks of implantation in the peritoneal space of C57BL/6 mice. Finally, we demonstrated that the optimized polymer coating can be readily applied to a variety of commonly used biomedical materials using this straightforward method, highlighting the versatility of the approach. This work provides a facile and broadly applicable strategy for developing antifibrotic coatings, which has the potential to expand the design of surface modifications aimed at improving the performance of biomedical implants.