Citations

Abstract Rationale Chronic thromboembolic disease (CTED), which is the result of persistent pulmonary vascular obstruction despite 3 months of anticoagulation, can present with significant functional limitations and exercise intolerance despite normal resting hemodynamics. These patients may experience functional impairment due to exercise-induced pulmonary hypertension, impaired stroke volume augmentation with exercise, ventilatory inefficiency, and/or preload insufficiency. Such exercise-induced pathophysiological abnormalities can significantly impair quality of life and contribute to poor long-term outcomes. Although balloon pulmonary angioplasty (BPA) has shown benefit in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its role in CTED patients with normal resting hemodynamics remains uncertain. This systematic review and meta-analysis evaluated the efficacy of BPA in this population. Methods A systematic search of PubMed, Cochrane, Embase, and Scopus was performed from inception through March 1, 2025. A total of 763 studies were screened, of which 42 full-text articles were assessed: six met the inclusion criteria (four retrospective, two prospective), comprising 98 patients. Results Across the included studies, baseline mean values were 20.81 +/- 3.62 mmHg for mean pulmonary arterial pressure (mPAP), 3.49 +/- 1.42 Wood units for pulmonary vascular resistance (PVR), and 405.72 +/- 108.40 m for the 6-minute walk distance (6MWD). Balloon Pulmonary Angioplasty (BPA) was consistently associated with significant improvements in hemodynamic and functional outcomes; BPA reduced mPAP by 3.40 mmHg and PVR by 0.90 WU, while increasing 6MWD by 31.90 m. These changes were also statistically robust across studies, with pooled standardized mean changes (SMC) of -0.88 for mPAP (95% CI, -1.10 to -0.67; P < .05), -0.68 for PVR (95% CI, -0.87 to -0.49; P < .05), and 0.29 for 6MWD (95% CI, 0.13 to 0.45; P < .05). Study-level effect sizes for 6MWD ranged from 0.19 to 0.54 (Figure 1A). Functional improvements were further demonstrated by shifts in NYHA class distribution (Figure 1B). Conclusion BPA was associated with meaningful reductions in mPAP and PVR and significant improvements in functional capacity among patients with CTED. These results indicate that BPA could be an effective treatment for certain patients with CTED, though more research is necessary. This abstract is funded by: None

Abstract Rationale Chronic thromboembolic disease (CTED) is characterized by persistent pulmonary vascular obstruction due to unresolved thromboemboli despite at least three months of anticoagulation. Although resting hemodynamics often remain normal, affected patients frequently develop functional limitation due to exercise-induced pulmonary hypertension, ventilatory inefficiency, limited stroke volume augmentation, or preload insufficiency. Such exercise-induced pathophysiological dysregulation can significantly impair quality of life and contribute to poor long-term outcomes. Pulmonary endarterectomy (PEA) is an established treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH), offering significant improvements in hemodynamics and survival. Its role in CTED, however, remains unclear. While CTED has traditionally been managed with anticoagulation and supportive therapy, emerging evidence suggests PEA may provide symptomatic and functional benefit in selected CTED patients. Given the ongoing uncertainty regarding the role of PEA in CTED, we performed a systematic review and meta-analysis to define its safety profile and clinical efficacy in this patient subset. Methods A systematic search of PubMed, Cochrane, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar was conducted from database inception to March 1, 2025. Of 2,244 records screened, 34 full-text articles were assessed, and seven met the inclusion criteria. Results Across the included studies, the pooled baseline mean values were 20.48 ± 3.03 mm Hg for mean pulmonary arterial pressure (mPAP), 2.83 ± 1.11 Wood units for pulmonary vascular resistance (PVR), and 397 ± 100.08 m for the 6-minute walk distance (6MWD). Pulmonary Endarterectomy (PEA) was consistently associated with significant improvements in hemodynamic and functional outcomes; PEA reduced mPAP by 3.58 mmHg (pooled Standardized Mean Change (SMC)=-1.03; 95% CI, -1.23 to -0.83; P < .05), PVR by 0.86 Woods units (pooled SMC=-0.86; 95% CI, -1.05 to -0.67; P < .05), while, conversely, increased 6MWD by 37.49 m (pooled SMC, 0.49; 95% CI, 0.32 to 0.67; P < .05). Study-level effect sizes for 6MWD ranged from 0.21 to 1.47 (Figure 1A). This clinical improvement is further reflected in the enhancement of the NYHA functional class, as illustrated in Figure 1B. Conclusion PEA was associated with significant reductions in mPAP and PVR, as well as a considerable improvement in functional capacity in patients with CTED, with robust results across multiple tests for bias, influence, and sensitivity analyses. These findings support PEA as a viable therapeutic option for selected patients with CTED, although further research is warranted. This abstract is funded by: None

OBJECTIVES We aimed to characterize the frequency of major complications of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) and adolescents present at 6 months after initial presentation. METHODS The Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM) study was a prospective cohort at 20 US pediatric academic medical centers. Individuals aged younger than 21 years meeting any of the following were enrolled: SARS-CoV-2 detection within 7 days, Centers for Disease Control and Prevention (CDC) MIS-C criteria, or CDC MIS-C criteria except having involvement of 1 organ system. The study was designed to assess the proportion of children with major complications (cardiovascular, pulmonary, gastrointestinal/hepatic, renal, and/or neurologic) 6 months after presentation. RESULTS Data were analyzed on 229 hospitalized participants: 59 with COVID-19 (mean age 10.4 years; SD, 5.5) and 170 with MIS-C (mean age 10.1 years; SD, 4.8). Overall, 42.8% were female, making up 55.9% and 38.2% of the COVID-19 and MIS-C groups, respectively. Overall, the frequencies of major complications at 6 months after initial presentation were: 16/195 (8.2%) cardiovascular, 11/154 (7.1%) pulmonary, 11/154 (7.1%) gastrointestinal/hepatic, 3/152 (2.0%) renal, and 3/189 (1.6%) neurologic. Organ system complications did not differ significantly between the COVID-19 and MIS-C groups. Six of 14 (42.9%) COVID-19 and 21/26 (80.7%) MIS-C participants with at least 1 six-month complication had no underlying medical condition that may have been associated with their complication(s). CONCLUSIONS Major complications were infrequent but observed in children without underlying medical conditions, underscoring the importance of prospective follow-up to optimize management and elucidate the complications associated with severe SARS-CoV-2 infection in children.

ABSTRACT Background and Objective Despite growing interest in mindfulness‐based interventions for adolescents with chronic pain, the data have not been systematically summarized. We conducted a systematic review and meta‐analyses to estimate the effect of mindfulness‐based interventions on pain intensity, catastrophizing, acceptance and interference; functioning, quality of life, and anxiety and depression in youth with chronic pain. Databases and Data Treatment Electronic databases CINAHL, CCTR, Embase, Medline, PsycINFO, Scopus and Web of Science were systematically searched to January 2, 2025. Studies were included if they were in English, included > 5 patients, were not part of intensive interdisciplinary pain treatment and included pre‐post outcomes from mindfulness‐based interventions delivered to adolescents with chronic pain. Risk of bias was assessed with the Newcastle–Ottawa Scale. Results Fourteen studies including a total of 323 adolescents were identified. There were significant within group improvements in pain intensity, pain catastrophizing, pain acceptance, pain interference, functioning, depression, anxiety, and quality of life, with results maintained or increased at follow‐up effect sizes at follow‐up were moderate to large (e.g., quality of life SMD = 0.33; pain intensity SMD = −0.73; pain interference SMD = −1.44). Heterogeneity of results was generally moderate to high. Compared to standardized long interventions, variable length interventions showed greater pre‐post changes in functioning, pain intensity, and pain catastrophizing. The certainty in the estimates was generally low, due to risk of bias and pre‐post designs. Conclusions Although adolescents with chronic pain report improvements after participating in mindfulness‐based interventions, rigorous RCTs are needed to substantiate these results. Significance Statement Chronic pain in youth is common and difficult to treat. Previous interventions have largely been based on cognitive‐behavioural therapy and not successful for all. This is the first systematic review and meta‐analysis in paediatric chronic pain to focus on mindfulness‐based interventions, highlighting an alternative and potentially effective intervention approach. This study informs clinicians about an effective intervention approach and assists researchers in identifying gaps for further research.

BACKGROUND Patients with severe aortic stenosis (AS) exhibit heterogeneous flow-gradient hemodynamics and ventricular remodeling, which may influence symptomatic, functional, and structural responses to transcatheter aortic valve implantation (TAVI). Thus, we evaluated differences in functional recovery and reverse remodeling after transfemoral TAVI across flow-gradient phenotypes. METHODS In this sub-study of the COMPARE-TAVI 1 trial, 975 patients undergoing transfemoral TAVI were classified as classical low-flow low-gradient (cLFLG, 9.1%), paradoxical low-flow low-gradient (pLFLG, 7.7%), low-flow high-gradient (24.7%), normal-flow low-gradient (NFLG, 13.0%), and normal-flow high-gradient (45.4%). The primary functional outcome was longitudinal change in six-minute walk test distance (6MWTD) from baseline to 1 year follow-up. Secondary endpoints included changes in NYHA functional class and reverse remodeling from baseline to 1 year follow-up along with the incidence and risk of all-cause death and a composite MACE-endpoint. RESULTS Mean 6MWTD increased by 59±4 meters at 1-month (p=0.000) with no additional improvement at 1-year, but with heterogeneity between groups (p=0.000). Improvements among NFLG, cLFLG and low-flow high-gradient AS were comparable with normal-flow high-gradient AS, while pLFLG AS exhibited significantly increments at 1-year (−28±15 meters, p=0.007). Patients with NFLG, cLFLG and pLFLG were more symptomatic at baseline (NYHA ≥III: 40.5%, 57.3% and 50.6%, respectively, p=0.000). NYHA improved in all groups at 1-year follow-up (p=0.000), although persistent symptoms at 1-year were most frequent in pLFLG (NYHA ≥II; 38.7%, p=0.012). Reverse remodeling was also comparable between normal-flow high-gradient AS and NFLG, cLFLG, and low-flow high-gradient AS, respectively, but attenuated in pLFLG AS in both unadjusted and adjusted analyses. No differences were observed in the incidence and risk of all-cause death or the composite MACE-endpoint. CONCLUSION TAVI associates with functional recovery across all flow-gradient phenotypes, although with heterogeneous responses. Patients with NFLG showed comparable functional recovery and reverse remodeling at 1-year follow-up compared with normal-flow high-gradient AS, whereas pLFLG demonstrated attenuated benefits across all parameters.

Summary Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine. 1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions. 1–3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres. 4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

Background Large vessel occlusion (LVO) stroke is associated with a high risk of permanent disability. There are no reliable tools providing periprocedural information on clot characteristics, such as composition and length, that may impact first pass effect, which has been shown to improve functional outcomes. In the first study of a novel technology, we evaluated whether the Clotild Smart Guidewire System (Clotild), an impedance-based device, can provide in situ information on clot characteristics during a mechanical thrombectomy procedure. Methods This is the first-in-human, international, multicentric, single-arm trial involving LVO stroke patients. Of 45 enrolled subjects, 41 constituted the safety population; 39 was the per protocol population, of which 26 subjects with complete impedance data comprised the performance population. The latter was divided into development (11 subjects) and validation (15 subjects) populations for prediction model development and assessment. The safety endpoint assessed Clotild-related intracranial vessel perforation/dissection. Performance endpoints evaluated Clotild’s ability to perform classification of impedance measurements distinguishing substantial versus negligible local content in red blood cells (RBCs) and platelets, to detect the arterial wall and the distal end of the clot. Results The safety endpoint was met in all subjects. Performance analysis comparing the agreement between Clotild’s output and impedance experts’ readings showed an area under the receiver operating characteristic curve (AUC) of 0.97 (95% CI 0.93 to 0.99) for RBC, and 0.94 (95% CI 0.89 to 0.98) for platelet clot composition. Regarding detection, Clotild’s performance showed an AUC of 0.69 (95% CI 0.59 to 0.77) for the arterial wall, and 0.83 (95% CI 0.59 to 1.00) for the distal end of the clot. Conclusions Clotild was proven safe to acquire impedance data and to provide information on in situ clot characteristics in large vessel occlusions.

The diagnosis of coccidioidomycosis is often achieved serologically by the detection of antibodies against fungal antigens. While several serologic tests are available for coccidioidomycosis, all of them are performed in a laboratory setting causing delays in diagnosis and therapeutic intervention. Point-of-care testing offers the ability to provide a shorter time to result by avoiding specimen send-out, minimizing processing steps, and employing expeditious immunochemical techniques. A preliminary trial of a rapid anti-coccidioidal antibody lateral flow assay (LFA) using fingerstick blood was performed on 22 patients with coccidioidomycosis at the point of care during outpatient clinic visits. Patients were tested longitudinally over the course of one year. An LFA reader was implemented to provide an objective result by quantifying the intensity of the test line band. There was close qualitative concordance observed between positive LFA results with send-out immunodiffusion (89.5%) and complement fixation (78.4%) standard of care clinical laboratory assays. Additionally, the relationship between LFA test line density values and traditional complement fixation antibody titers was assessed.

Abstract Background Anxiety is a common symptom experienced by patients with cancer, who are increasingly interested in non-pharmacologic symptom management. Acupressure, a noninvasive intervention thought to impact the neurohormonal axis, has shown promise in reducing anxiety. However, research on acupressure for anxiety in patients with cancer has been limited. Methods Individuals receiving chemotherapy, who reported baseline anxiety, were eligible for this study. Consenting participants received one 15-minute nurse-led acupressure session and completed pre- and post-intervention surveys. The primary endpoint was a change in anxiety. Participants were also asked about symptoms of nausea, pain, well-being, relaxation, worry, and distress. Participants were invited to learn self-acupressure techniques. These participants were asked to complete a final survey 1-week post-intervention. Results Thirty adult patients participated in this study. Mean baseline anxiety was 5 on a 0 to 10 Likert scale. Immediate post-intervention anxiety scores significantly improved for all thirty patients to an average of 2.0 (P < .001). Mean nausea scores improved from 1.5 at baseline to 0 post-intervention (P < .001), and pain scores improved from 2.0 at baseline to 1.0 post-intervention (P = .001). Participants reported significant improvement in sense of wellbeing (P = .0004), distress (P < .001), ability to achieve relaxation (P < .001), and ability to control their worries (P < .001). The improvement in anxiety, well-being, and relaxation was sustained at one week. 100% of participants stated that they would recommend acupressure for symptom management. Conclusion Acupressure is a promising non-pharmacologic intervention for the management of cancer-associated anxiety.