Citations

Meniscal lesions in skeletally immature patients can lead to joint degradation and knee instability. Meniscal allograft transplant (MAT) surgery is a solution to maintain knee stability. There is a lack of consensus on MAT surgery outcomes in pediatric patients. A systematic review was conducted according to the PRISMA guidelines. PubMed, Scopus and EMBASE databases were searched from 1965 to June 2022. Studies were evaluated using the Newcastle–Ottawa Scale (NOS). Three studies were selected, and 58 patients were included (mean age 15.9 years) in total. The lateral meniscus was involved in 82.8% of all MAT surgeries. Post-meniscectomy syndrome and discoid meniscus were the main indications for MAT surgery. All studies reported improved subjective clinical scores and levels of sport after the surgery. The complication rate was 27.5%. Partial meniscectomy, meniscus knot removal, chondral defect treatment and lysis of adhesions were the most frequent procedures performed during reoperation. MAT surgery can improve clinical outcomes in pediatric patients with strictly selected indications. MAT surgery is safe when there are no limb asymmetries or malalignments, but it remains a challenging procedure with a high complication rate. Long-term follow-up is needed for definitive statements on the use of MAT in skeletally immature patients.

Abstract Glioblastoma (GBM) is the most malignant form of gliomas and is the most common and lethal primary brain tumor in adults. Within the tumor, there is a subtype of cells deemed brain tumor initiating cells (BTICs), which contribute to tumor progression, therapy resistance, and tumoral heterogeneity. The tumor microenvironment, surrounding tumors, contains an ecosystem of cells in which BTICs can interact with and further promote tumor progression. In the lateral wall of the lateral ventricles, the neurogenic niche of the subventricular zone (SVZ), contains neural stem cells (NSCs) that self-renew and generate highly migratory neural progenitor cells (NPCs). Interestingly, GBM tumors proximal to the SVZ are more proliferative, migratory, and negatively impact the survival of patients. We have previously observed that the presence of GBM induces reciprocal changes to the SVZ altering its neurogenic capacity and resulting in a more proliferative tumor. BTICs share the similar self-renewal capacity to NPCs and may exert intercellular communication resulting in increase malignancy features. However, the exact mechanisms of how GSCs communicate with NPCs is not well understood. Cancer cells release higher amounts of extracellular vesicles (EVs) than non-malignant cells. Cancer EVs help communicate with other nearby cells, leading to promotion of tumorigenesis. EVs are a heterogenous group of cell-derived membranous structures that serve as means of intercellular communication, allowing for cells to exchange proteins, lipids, RNA, and other genetic material. They can be further characterized into two main subtypes, small EVs, that range from 30-150nm, and large EVs, that range from 50-1000nm. EVs derived from gliomas or non-glioma cells in the tumor microenvironment are involved in tumor cell proliferation, invasion, malignancy, and drug resistance. The overarching goal of this project is to characterize BTIC-derived small EV cargo to identify proteins and RNAs that modify the GBM tumor microenvironment. We hypothesize that GBM-derived small extracellular vesicles alter the phenotype of non-cancer cells in the tumor microenvironment through distinct cargo contained in small extracellular vesicles. The results of these experiments will help us to elucidate what exact small EV cargo impacts the tumor microenvironment, with the potential of revealing possible therapeutic targets for GBM.The optimized protocol gives us the ability to enrich our desired EV population of small EVs from BTICs. BTIC-derived small EVs influence recipient NPCs by significantly upregulating markers for stemness, tumor aggressiveness, and invasion, as well as increasing NPC migration. Future experiments will include trying to establish a cell-specific labeling system in vitro to label EVs from BTICs, to allow for direct co-culture of BTICs with NPCs and other cells in the tumor microenvironment. Citation Format: Marissa Russo. The role of extracellular vesicles in the glioblastoma tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2370.

Background Women with atrial fibrillation (AF) demonstrate more AF‐related symptoms and worse quality of life (QOL). Whether increased use of ablation in women reduces sex‐related QOL differences is unknown. Sex‐related outcomes for ablation versus drug therapy was a prespecified analysis in the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial. Methods and Results Symptoms were assessed periodically over 60 months with the Mayo AF‐Specific Symptom Inventory (MAFSI) frequency score, and QOL was assessed with the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary and component scores. Women had lower baseline QOL scores than men (mean AFEQT scores 55.9 and 65.6, respectively). Ablation patients improved more than drug therapy patients with similar treatment effect by sex: AFEQT 12‐month mean adjusted treatment difference in women 6.1 points (95% CI, 3.5–8.6) and men 4.9 points (95% CI, 3.0–6.9). Participants with baseline AFEQT summary scores <70 had greater QOL improvement, with a mean treatment difference at 12 months of 7.6 points for women (95% CI, 4.3–10.9) and 6.4 points for men (95% CI, 3.3–9.4). The mean adjusted difference in MAFSI frequency score between women randomized to ablation versus drug therapy at 12 months was −2.5 (95% CI, −3.4 to −1.6); for men, the difference was −1.3 (95% CI, −2.0 to −0.6). Conclusions Compared with drug therapy for AF, ablation resulted in more QOL improvement in both sexes, primarily driven by improvements in those with lower baseline QOL. Ablation did not eliminate the AF‐related QOL gap between women and men. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00911508.

Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic to guide the management of these patients.

Importance Only modest attention has been paid to the contributions of social determinants of health to atrial fibrillation (AF) risk factors, diagnosis, symptoms, management, and outcomes. The diagnosis of AF provides unique challenges exacerbated by the arrhythmia’s often paroxysmal nature and individuals’ disparate access to health care and technologies that facilitate detection. Social determinants of health affect access to care and management decisions for AF, increasing the likelihood of adverse outcomes among individuals who experience systemic disadvantages. Developing effective approaches to address modifiable social determinants of health requires research to eliminate the substantive inequities in health care delivery and outcomes in AF. Observations The National Heart, Lung, and Blood Institute convened an expert panel to identify major knowledge gaps and research opportunities in the field of social determinants of AF. The workshop addressed the following social determinants: (1) socioeconomic status and access to care; (2) health literacy; (3) race, ethnicity, and racism; (4) sex and gender; (5) shared decision-making in systemically disadvantaged populations; and (6) place, including rurality, neighborhood, and community. Many individuals with AF have multiple adverse social determinants, which may cluster in the individual and in systemically disadvantaged places (eg, rural locations, urban neighborhoods). Cumulative disadvantages may accumulate over the life course and contribute to inequities in the diagnosis, management, and outcomes in AF. Conclusions and Relevance Workshop participants identified multiple critical research questions and approaches to catalyze social determinants of health research that address the distinctive aspects of AF. The long-term aspiration of this work is to eradicate the substantive inequities in AF diagnosis, management, and outcomes across populations.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Transcatheter aortic valve replacement is now indicated across all risk categories of patients with symptomatic severe aortic stenosis and has been proposed as first line option for the majority of patients >74 years old. However, median age of patients enrolled in the transcatheter aortic valve replacement low-risk trials is 74 years and transcatheter aortic valve replacement has never been systematically investigated in young low risk patients. Although the long-term data in surgical aortic valve replacement in young patients (age <75) are well known, such data remain lacking in transcatheter aortic valve replacement. In the absence of clear guideline recommendations in patients with challenging anatomies (eg, hostile calcium, bicuspid), it is important to know the potential advantages and disadvantages of each treatment and to consider how they might integrate with each other in the lifetime management of such patients. In this review, we discuss current outstanding issues on the management of severe aortic stenosis from a lifetime management perspective, particularly in terms of initial intervention and future reinterventions.

Abstract Glioblastoma (GBM) is the most common and aggressive primary neoplasm of the central nervous system. The location of GBM contributes significantly to patient outcomes, where tumors contacting the lateral ventricles (LVs) have increased expression of stem cell genes, increased incidence of distal recurrence, and decreased overall survival. While the reasons for these findings are not fully understood, we hypothesize they arise due to interactions with the subventricular zone (SVZ), the largest neurogenic niche in mammals. We examined bidirectional signals between GBM cells and neural progenitor cells (NPCs) in vitro and in vivo using a combination of patient-derived intraoperative samples, preclinical animal models, and the methionine tRNA synthetase L274G (MetRS*) nascent proteomic labeling system, which allows for cell-specific proteomics analysis from complex in vivo systems. In co-culture with NPCs, GBM cells increase their viability, proliferation, migration, and expression of malignancy-promoting proteins, including migratory proteins such as TAGLN, PALLD, and STAT1. In vivo, tumor proximity to the SVZ results in increased proliferation, increased expression of stemness markers, decreased survival, and altered tumor-specific proteome. We then examined the reciprocal effect of GBM cells on NPC biology. In vitro and in vivo, GBM cells decreased NPC proliferation and induced decreased neuronal maturation of NPCs. To determine NPC proteomic changes in vivo, we created a transgenic mouse line Nestin-CreERT2; STOPflox R26-MetRS L274G, where upon tamoxifen administration Nestin+ NPCs express GFP and MetRS*. Our results indicate that LV-proximal GBM induces decreased expression of neuronal maturation proteins such as Eml1, VGLUT1, and EAAT2, and an increase in pro-migratory factors such as Lamc1 in NPCs. In conclusion, there are bidirectional proteomic interactions between GBM cells and NPCs that contributes to altered neurogenesis and increased tumor malignancy of LV-proximal GBM. The signaling factors identified in our studies will result in identification of novel therapeutic targets for GBM.

AbstractIntroductionData on utilization, major complications, and in‐hospital mortality of catheter ablation (CA) for sarcoidosis‐related ventricular tachycardia (VT) are limited. We sought to determine the outcomes of sarcoidosis‐related VT, and incidence and predictors of complications associated with the CA procedure.MethodsWe queried the 2002–2018 National Inpatient Sample database to identify patients aged ≥18 years with sarcoidosis admitted with VT. A 1:3 propensity score‐matched (PSM) analysis was used to compare patient outcomes between CA and medically managed groups. Multivariable regression was performed to determine independent predictors of in‐hospital mortality and procedural complications associated with the CA procedure.ResultsOf 3220 sarcoidosis patients with VT, 132 (4.1%) underwent CA. Patients who underwent CA were younger, male predominant, more likely Caucasian, had differences in baseline comorbidities including more likely to have heart failure, less likely to have prior myocardial infarction, COPD, or severe renal disease, had a higher mean household income, and more likely admitted to a larger/urban teaching hospital. After PSM, we examined 106 CA cases and 318 medically managed cases. There was a trend toward a lower in‐hospital mortality rate in the CA group when compared to the medically managed group (1.9% vs. 6.6%, p = 0.08). The most common complications were pericardial drainage (5.3%), postoperative hemorrhage (3.8%), accidental puncture periprocedure (3.0%), and cardiac tamponade (2.3%). Independent predictors of in‐hospital mortality and procedural complications among the CA group included congestive heart failure (odds ratio [OR], 13.2; 95% confidence interval [CI], 1.7–104.2) and mild to moderate renal disease (OR, 3.9; 95% CI, 1.1–13.3).ConclusionsCompared to patients with sarcoidosis‐related VT who received medical therapy alone, those who underwent CA have a trend for a lower mortality rate despite procedure‐related complications occurring as high as 9.1%. Additional studies are recommended to better evaluate the benefits and risks of VT ablation in this group.