Citations

Background: Spontaneous coronary artery dissection (SCAD) is a rare and often underdiagnosed cause of acute coronary syndrome (ACS), predominantly affecting younger women without traditional cardiovascular risk factors. The management of SCAD remains a subject of debate, likely secondary to inconclusive evidence. This study aims to compare the clinical outcomes of SCAD patients treated with optimal medical therapy (OMT) versus those who underwent percutaneous coronary intervention (PCI) using a national population-based cohort. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) database from 2016 to 2020. The study included patients identified with SCAD using the ICD-10-CM (the International Classification of Diseases, Tenth Revision, Clinical Modification) code I25.42. We excluded individuals who did not receive PCI or coronary angiography, those who underwent coronary artery bypass grafting, and patients with incomplete records. The primary outcome was in-hospital mortality, while secondary outcomes included acute kidney injury, cardiac arrest, cardiogenic shock, use of temporary mechanical circulatory support, cost of hospitalization, and length of stay. National estimates were obtained using discharge weights, and statistical comparisons were performed using chi-square tests and linear regression. Multivariate logistic regression was employed to identify predictors of mortality and other outcomes. Results: A total of 31,105 SCAD patients were included in the study, with 10,480 receiving OMT and 20,625 undergoing PCI. Patients in the PCI group were older (mean age 64 vs. 54 years) and had higher comorbidities compared to those in the OMT group. The proportion of SCAD patients receiving PCI declined from 72% in 2016 to 60% in 2020. In multivariable analysis, PCI was associated with increased in-hospital mortality (odds ratio (OR) 1.89, 95% confidence interval (CI) 1.24–2.90, p = 0.0003), cardiogenic shock (OR 2.29, 95% CI 1.71–3.07, p < 0.0001), use of a left ventricular assist device (LVAD) (OR 3.97, 95% CI 2.42–6.53, p < 0.0001), and an intra-aortic balloon pump (IABP) (OR 2.24, 95% CI 1.63–3.09, p < 0.0001). Trends also suggested an association between PCI and cardiac arrest, extracorporeal membrane oxygenation (ECMO), and acute kidney injury (AKI). The PCI group had significantly higher hospitalization costs and longer lengths of stay compared to the OMT group (both p < 0.001). Conclusions: In this large, national cohort study, SCAD patients who underwent PCI had significantly higher risks of adverse in-hospital outcomes, including mortality, compared to those treated with OMT. These findings underscore the importance of careful patient selection and the potential advantages of conservative management in SCAD, particularly in patients without severe or unstable presentations. Further research is needed to develop evidence-based guidelines for the optimal management of SCAD.

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have become increasingly utilized in patients undergoing percutaneous coronary intervention (PCI). Despite these purported advantages, prior reports regarding the use of IVUS and OCT have indicated that contemporary use of intravascular imaging remains low with significant regional variation. Here, we present the findings of an updated contemporary analysis regarding the use of IVUS/OCT-guided PCI versus angiography-guided PCI in the United States. We also evaluated in-hospital mortality and clinical outcomes between IVUS/OCT-guided PCI versus angiography-guided PCI-only over million patients in the United States. There has been a significant decrease in the number of PCIs performed, while there has been increasing in the trend of IVUS/OCT-guided PCI over this period. Most importantly, we found that IVUS/OCT-guided PCI was associated with better clinical outcomes in terms of in-hospital mortality, compared with angiography-guided PCI.

Abstract The DNA damage response (DDR) and the blood tumor barrier (BTB) restrict chemotherapeutic success for primary brain tumors like glioblastoma (GBM). Coherently, GBM almost invariably relapse with fatal outcome. We here show that interaction of GBM and myeloid cells simultaneously induces chemoresistance on the genetic and the vascular level by activating GP130 receptor signaling, which can be addressed therapeutically. We performed transcriptomic and immunohistochemical screens with human brain material, pharmacological experiments with a humanized organotypic GBM model, proteomics and cell-based assays and observed that nanomolar concentrations of the signaling peptide Humanin promoted TMZ resistance through DDR activation. GBM mouse models recapitulating intratumoral Humanin-release showed accelerated BTB formation. Genetic analysis of pericyte to endothelial cell signaling in transgenic mice revealed increased GP130 activation in Humanin releasing tumors as compared to controls. GP130 blockade attenuated both DDR activity and BTB formation resulting in improved preclinical chemotherapeutic efficacy. Altogether, we describe an overarching mechanism for TMZ resistance and outline a translatable strategy with predictive markers to improve chemotherapy for GBM.

ABSTRACT Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host’s immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428–e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8 ], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, “rhinocerebral mucormycosis.” A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

BackgroundMultiparametric MRI may cause overdiagnosis of clinically significant prostate cancer (csPCa) with the Prostate Imaging Reporting and Data System version 2.1 (PI‐RADS v2.1).ObjectivesTo investigate the diagnostic performance of stiffness as a standalone and complementary marker to PI‐RADS v2.1 for diagnosing csPCa.Study TypeProspective.SubjectsOne hundred forty‐seven participants with pathologically confirmed prostate lesions (≥1 cm), including 71 with csPCa.Field Strength/SequenceT1‐weighted fast spin‐echo, T2‐weighted fast spin‐echo, single‐shot echo‐planar diffusion‐weighted imaging, fast 3D gradient‐echo T1‐weighted dynamic contrast‐enhanced imaging, and 3D single‐shot spin‐echo based echo‐planar MR elastography at 3.0 T.AssessmentThe PI‐RADS v2.1 score was assessed by three radiologists independently. Lesion shear stiffness (SS) values at 60 Hz and 90 Hz were measured. A modified PI‐RADS integrating stiffness with PI‐RADS v2.1 was developed. Diagnostic performance for csPCa was compared between stiffness, PI‐RADS v2.1 and the modified PI‐RADS.Statistical TestSpearman's correlation, Fleiss κ and intraclass correlation, Pearson correlation, one‐way analysis of variance, area under the receiver operating characteristic curve (AUC), and the Delong test. Significance level was P < 0.05.ResultsIn the peripheral zone, csPCa (N = 35) had significantly higher SS than non‐csPCa at 60 Hz (3.22 ± 0.66 kPa vs. 2.56 ± 0.56 kPa) and at 90 Hz (5.64 ± 1.30 kPa vs. 4.48 ± 0.84 kPa). PI‐RADS v2.1 showed 100% sensitivity, 58% specificity, and 0.79 AUC for detecting csPCa. SS achieved 97% sensitivity, 52% specificity, and 0.80 AUC at 60 Hz, while SS had 63% sensitivity, 87% specificity, and 0.78 AUC at 90 Hz. The modified PI‐RADS, combing SS at 60 Hz with PI‐RADS v2.1, resulted in a significantly increased AUC (0.86) compared to that of PI‐RADS v2.1, with a sensitivity of 97% and specificity of 75%.Data ConclusionStiffness can help identifying csPCa in the peripheral zone. Combining stiffness with the PI‐RADS v2.1 improved the diagnostic accuracy and specificity for csPCa.Evidence Level1Technical EfficacyStage 2

Abstract Purpose: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS). Experimental Design: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort. Results: Germline PV were observed in 6.5% and 4.6% of women with DCIS in the clinical testing and population-based cohorts, respectively. BRCA1, BRCA2, and PALB2 PV frequencies were significantly lower among women with DCIS than those with IDC (clinical cohort: 2.8% vs. 5.7%; population-based cohort: 1.7% vs. 3.7%), whereas the PV frequencies for ATM and CHEK2 were similar. ATM, BRCA1, BRCA2, CHEK2, and PALB2 PV were significantly associated with an increased risk of DCIS (OR &gt; 2.0), but only BRCA2 PV were associated with high risk (OR &gt; 4) in both cohorts. The cumulative incidence of CBC among carriers of PV in high-penetrance genes with DCIS was 23% over 15 years. Conclusions: The enrichment of PV in ATM, BRCA1, BRCA2, CHEK2, and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of CBC in carriers of PV in high-penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.

Collaboration between military and civilian investigators is necessary to develop strategies for optimizing treatments to diminish the sequelae of non–battle-related musculoskeletal injuries, which are highly prevalent among servicemembers. The 2024 Extremity War Injuries Symposium provided a forum whereby a diverse group of clinicians and researchers could develop strategies for optimizing treatments and diminishing the sequelae of conditions that are highly prevalent among active individuals. Key points were as follows: 1. The value of collaborations between military and civilian investigators cannot be overemphasized. These synergies can leverage the capabilities of established infrastructures in order to answer important questions pertaining to short-term outcomes—for example, warrior readiness of anterior cruciate ligament reconstructions among servicemembers and long-term posttraumatic osteoarthritis (PTOA) outcomes among civilian cohorts. 2. Current and future prospective trials will inform future treatment decisions related to multiligamentous knee injuries and glenohumeral instability. 3. Novel approaches to addressing PTOA in the acute postinjury period will need longitudinal surveillance to measure their impact on improving clinical outcomes and diminishing residual functional deficits.

Abstract 3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health‐related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D‐printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state‐of‐the‐art in 3D‐printed functional polymeric health‐related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D‐printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self‐powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.